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7/5/23, 9:15 AM Mechanisms of thrombogenesis in atrial fibrillation - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Mechanisms of thrombogenesis in atrial fibrillation : Gregory YH Lip, MD, FRCPE, FESC, FACC : Bradley P Knight, MD, FACC : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Mar 02, 2022. INTRODUCTION Atrial fibrillation (AF) is associated with substantial mortality and morbidity, largely due to thromboembolism, particularly stroke. This complication can occur with either paroxysmal (intermittent) or chronic (permanent) AF. A number of randomized trials have demonstrated the efficacy of warfarin in reducing this risk both during the course of chronic AF and in the period prior to and after the restoration of sinus rhythm. (See "Atrial fibrillation in adults: Use of oral anticoagulants" and "Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation".) The factors that promote thromboembolism in AF will be reviewed here. FACTORS PROMOTING THROMBOEMBOLISM Almost 150 years ago, Virchow proposed that three conditions should be present for development of thrombosis [1]: Abnormalities in blood flow Abnormalities in the blood vessel wall Interaction with blood constituents Each of these abnormalities may contribute to thromboembolism in AF [2,3]. https://www.uptodate.com/contents/mechanisms-of-thrombogenesis-in-atrial-fibrillation/print 1/20 7/5/23, 9:15 AM Mechanisms of thrombogenesis in atrial fibrillation - UpToDate As an example, dilated atria, poorly contracting dilated left ventricles, valvular heart disease (particularly mitral stenosis), and congestive heart failure are clinical features commonly associated with stroke and thromboembolism in patients with AF [2]. These abnormalities in blood flow and vessels (the first two components of Virchow's triad) can be related to the presence of structural heart disease or extrinsic interventions such as cardioversion. As will be described below, AF also may confer a hypercoagulable or prothrombotic state [3]. Pooled data from a meta-analysis have demonstrated that independent clinical risk factors for stroke in nonvalvular AF include a history of hypertension and diabetes [4]. Patients with heart failure are also at high risk, particularly those with left ventricular systolic dysfunction or aneurysm formation [5-7]. (See "Atrial fibrillation in adults: Selection of candidates for anticoagulation".) These clinical criteria are complemented by echocardiographic findings, which have demonstrated that a dilated left atrium, impaired left atrial function, and impaired left ventricular systolic function are independent risk factors for stroke in patients with AF ( table 1 and table 2) [7]. (See "Role of echocardiography in atrial fibrillation".) Left atrial abnormalities A dilated left atrium and reduced left atrial and left atrial appendage (LAA) blood flow on echocardiography are independent risk factors for thromboembolism. Patients with these abnormalities are more likely to have stasis of blood as demonstrated by the presence of spontaneous echo contrast or "smoke" on transesophageal echocardiography; this increase in echogenicity is thought to represent aggregation of red cells at low shear stress ( image 1 and movie 1 and movie 2) [8]. Spontaneous echo contrast has been related to hemodynamic and hemostatic abnormalities and an increased risk of stroke and thromboembolism [8-13]. The presence of both left atrial spontaneous echo contrast and chamber enlargement among patients with nonrheumatic AF is strongly associated with an increased risk for cerebral ischemic events (odds ratio 33.7 in one report) [11]. Left atrial spontaneous echo contrast does not appear to be affected by anticoagulant therapy [14]. (See "Role of echocardiography in atrial fibrillation".) The fibrosis and inflammation seen in the left atrium of patients with AF are particularly intense in the LAA and may predispose to adjacent thrombosis. In addition, the fibrillating LAA is the only area within the left atrium that is comprised of pectinate muscle and can create an appropriate milieu for blood stasis and thrombus formation. Atrial stunning after cardioversion Cardioversion of AF leads to an increased risk of thromboembolism, particularly if patients are not anticoagulated before, during, and after cardioversion. In addition to dislodgement of pre-existing thrombi, embolization may result https://www.uptodate.com/contents/mechanisms-of-thrombogenesis-in-atrial-fibrillation/print 2/20 7/5/23, 9:15 AM Mechanisms of thrombogenesis in atrial fibrillation - UpToDate from de novo thrombus formation induced by impaired left atrial systolic function. (See "Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation".) The transient atrial contractile dysfunction is also known as atrial "stunning," and can occur whether sinus rhythm is restored spontaneously, by external or internal DC (electric) cardioversion, or by drugs. The duration of the left atrial dysfunction appears to be related in part to the duration of AF. In one report, full recovery of atrial mechanical function was attained within 24 hours in patients with AF for 2 weeks, within one week in patients with AF for two to six weeks, and within one month with more prolonged AF [15]. The time course of recovery of left atrial function could explain why the great majority of embolic events in patients who remain in sinus rhythm occur within the first 10 days after cardioversion [16,17]. (See "Hemodynamic consequences of atrial fibrillation and cardioversion to sinus rhythm", section on 'Atrial stunning'.) Paroxysmal atrial fibrillation The risk of thromboembolic events in patients with paroxysmal AF and relationship to AF burden (percentage of time in AF) is discussed separately. (See "Paroxysmal atrial fibrillation", section on 'Risk of embolization'.) Paroxysmal AF is associated with abnormalities in atrial function, as evidenced by the appearance of spontaneous echo contrast on transesophageal echocardiography [18], and in hemostasis which presumably contribute to the increase in thrombotic risk. One report supported the importance of AF duration as levels of beta-thromboglobulin and platelet factor 4 (markers of platelet activation) were significantly increased during episodes more than 12 hours in duration; there was also a trend toward an elevation in fibrinogen levels in these patients [19]. In another series, patients with paroxysmal AF had intermediate values of fibrinogen and fibrin D-dimer between normals and elevations seen in patients with chronic AF [20]. In contrast, patients with paroxysmal supraventricular tachycardia, who retain active atrial contraction and have a low risk of stroke, had levels of hemostatic markers that were similar to controls in sinus rhythm. Left ventricular dysfunction Heart failure by itself confers a risk of stroke and thromboembolism; the risk is additive to that of AF [5,7,21]. A report from the SAVE trial, for example, found a progressive increase in stroke risk during a 42-month follow-up in patients with left ventricular dysfunction; furthermore, every 5 percentage point decrease in left ventricular ejection fraction (LVEF) was associated with an 18 percent increase in the risk of stroke [21]. In addition, there was a significant reduction in longitudinal stroke risk associated with the use of warfarin (relative risk 0.19) or aspirin (relative risk 0.44). (See "Antithrombotic therapy in patients with heart failure".) https://www.uptodate.com/contents/mechanisms-of-thrombogenesis-in-atrial-fibrillation/print 3/20 7/5/23, 9:15 AM Mechanisms of thrombogenesis in atrial fibrillation - UpToDate Similar findings were noted in a prospective study of 1066 patients entered into three clinical trials evaluating the role of anticoagulation in nonvalvular AF (BAATAF, SPINAF, and SPAF) [22]. The incidence of a stroke was 9.3 percent per year in patients with moderate to severe left ventricular dysfunction, even in the absence of congestive heart failure, compared to 4.4 percent per year in those with normal or mildly abnormal left ventricular function ( figure 1). The presence of a poorly contracting, dilated left ventricle is likely to promote stasis of blood and lead to an increased risk of intracardiac thrombus formation and subsequent embolism. A left ventricular aneurysm has both diastolic and systolic bulging or dyssynergy which result in severe stasis of blood [5]. The incidence of thrombi within left ventricular aneurysms ranges from 14 to 68 percent at postmortem, an observation that is consistent with a 50 to 95 percent incidence at the time of aneurysmectomy [23]. The reported incidence of systemic embolism in patients with a left ventricular aneurysm ranges widely, from 0 to 52 percent [23-26]. Patients with heart failure, particularly those with a left ventricular aneurysm, also demonstrate abnormalities of blood rheology, coagulation, and endothelial function, suggesting the presence of a prothrombotic or hypercoagulable state. As an example, both plasma fibrinogen and von Willebrand factor concentrations may be elevated in heart failure, and platelet abnormalities are evident [27,28]. Since AF also confers a hypercoagulable state, this may be additive to the hemodynamic and hemostatic abnormalities conferred by heart failure [29]. Hypertension Hypertension is a risk factor for stroke (usually thrombotic) and it increases the risk of stroke associated with AF twofold [2,4,6]. How this occurs is unclear. Hypertension may be associated with a hypercoagulable state due in part to abnormalities in blood rheology and endothelial function [30]. Valvular disease Valvular heart disease, especially mitral stenosis, increases the risk of stroke in AF 17-fold [31]. There is some evidence that the presence of mitral regurgitation is protective against the development of intracardiac thrombi in chronic AF, presumably due to enhanced turbulence and decreased stasis within the left atrium [5]. As an example, one transesophageal echocardiography study of 169 patients with rheumatic heart disease, 63 percent of whom were in AF, found a preoperative incidence of left atrial spontaneous contrast echo of 1, 30, and 54 percent and of thrombus of 1, 13 and 17 percent for those with mitral regurgitation, combined mitral regurgitation and stenosis, and isolated mitral stenosis, respectively [32]. Further support for this observation comes from a report of 32 patients with mitral regurgitation undergoing mitral valve repair; atrial indexes of hypercoagulability were significantly lower than peripheral venous levels, consistent with the clinical observations of reduced echo contrast and left atrial thrombosis [33]. https://www.uptodate.com/contents/mechanisms-of-thrombogenesis-in-atrial-fibrillation/print 4/20 7/5/23, 9:15 AM Mechanisms of thrombogenesis in atrial fibrillation - UpToDate These findings correlate with a reduced incidence of embolism in mitral regurgitation. The Stroke Prevention in Atrial Fibrillation (SPAF) study, for example, reported that the annual rate of clinical thromboembolism in patients with an enlarged left atrium and abnormal left ventricular wall motion was lower in those with than in those without mitral regurgitation (7.2 versus 15.4 percent) [34]. Chronic mitral regurgitation often leads to left atrial dilatation and dysfunction and associated complications. However, even in the presence of left atrial enlargement, severe mitral regurgitation is associated with a lower incidence of embolism (9 versus 25 percent at 7.4 years in those in whom regurgitation was absent or mild) [35]. Hypercoagulable state A number of studies that measured indices of coagulability suggest that AF confers a hypercoagulable state, increasing the risk of thromboembolism and stroke [3,12,29,36]. One report of 109 patients with AF fibrillation evaluated the relationship between hemostatic and hemodynamic parameters obtained with transesophageal echocardiography (TEE) and the presence of left atrial thrombus [12]. Compared to patients without evidence of thrombus, those with thrombus had spontaneous echo contrast, reduced LAA velocity, increased plasma concentrations of markers of platelet activation (beta-thromboglobulin and platelet factor 4), increased plasma markers of thrombogenesis (thrombin-antithrombin complexes, D- dimers), and evidence of endothelial damage/dysfunction (elevated plasma and endocardial levels of von Willebrand factor, which is released from damaged endothelium) [37]. (See "Coronary endothelial dysfunction: Clinical aspects".) A multiple logistic model identified LAA velocity, beta-thromboglobulin, and von Willebrand factor, but not spontaneous echo contrast, as independent associates of left atrial thromboembolism [12]. Activation of the coagulation system has been identified in other reports of both paroxysmal [19,20] and chronic AF [38-44]. This effect is independent of the presence or absence of underlying structural heart disease. As noted above, reversion to sinus rhythm results in normalization of hemostatic markers within two to four weeks [45,46]. Anticoagulation in patients with AF also alters the hypercoagulable state as illustrated by the following observations: Fibrin D-dimer levels are increased in patients with AF. In one study, fibrin D-dimer levels were highest in patients who were not receiving any antithrombotic therapy, intermediate in those on aspirin, and lowest in those treated with warfarin [41]. Similar findings were noted in another report in which patients with AF treated with warfarin had lower levels of prothrombin fragment F1 + 2 and thrombin-antithrombin complex than those treated with aspirin or no antithrombotic therapy [42]. https://www.uptodate.com/contents/mechanisms-of-thrombogenesis-in-atrial-fibrillation/print 5/20 7/5/23, 9:15 AM Mechanisms of thrombogenesis in atrial fibrillation - UpToDate High fibrin D-dimer levels have been associated with an increased rate of embolic events in patients with AF on oral anticoagulant therapy [47]. In one study, elevated D-dimer levers ( 0.5 mcg/mL) were associated with more thromboembolic events compared to those with low D-dimer levels (hazard ratio 15.8, 95% CI 3.33-75.5) [48] In a substudy from the AFASAK trial, 100 patients with chronic AF were randomized to treatment with fixed minidose warfarin 1.25 mg daily alone or in combination with aspirin 300 mg/day, conventional warfarin therapy with dose adjusted to maintain an International Normalized Ratio (INR) between 2.0 and 3.0 or aspirin 300 mg daily. Patients treated with warfarin at any dose demonstrated a significant rise in the INR with a corresponding reduction in prothrombin fragment F1 + 2 [49]. The degree of anticoagulation with warfarin appears to be important. In one report, ultra low-dose warfarin (1 mg/day) did not significantly alter plasma fibrin D-dimer or beta- thromboglobulin levels [50]. A second study found that treatment with aspirin (300 mg daily) plus low-dose warfarin (1 or 2 mg daily) or low-dose warfarin alone (2 mg daily) did not significantly reduce any of the hemostatic markers; in contrast, there was a significant reduction of fibrinogen and fibrin D-dimer with dose-adjusted warfarin [51]. Evidence of endothelial damage/dysfunction in AF is provided by the following observations: Endocardial damage and disorganization of the LAA endocardium has been described in the setting of mitral valve disease, especially where AF is present [52]. Abnormal plasma indices of endothelial damage/dysfunction, such as vWf, which have been related to thrombogenesis [41], stroke risk [53], and adverse prognosis [54]. (See 'Left ventricular dysfunction' above.) Increased levels of circulating endothelial cells (CECs), an index of endothelial damage in the setting of AF and target organ damage (heart failure, stroke, myocardial infarction) [55]. Mechanisms Although these observations suggest that AF is associated with a hypercoagulable state and endothelial dysfunction, the precise mechanisms by which this might occur are uncertain [3,12,56]. Abnormalities in cardiac blood flow (sluggish, slow flow within the atria) may be partly responsible, adding to an endothelial disturbance in the pulmonary vasculature [41,43]. The latter effect may stimulate lung macrophages to produce hepatocyte stimulating factor (now known to be interleukin IL-6), increasing the hepatic synthesis of fibrinogen, perhaps in a similar manner to smoking [57]. https://www.uptodate.com/contents/mechanisms-of-thrombogenesis-in-atrial-fibrillation/print 6/20 7/5/23, 9:15 AM Mechanisms of thrombogenesis in atrial fibrillation - UpToDate Other data suggest that inflammation may contribute to the hypercoagulable state in AF [58]. As an example, high plasma levels of C-reactive protein (CRP) and interleukin-6 (IL-6) among patients with AF are independently related to indices of the prothrombotic state in AF (eg, CRP to fibrinogen, IL-6 to tissue factor) [59]. CRP has also been related to the presence of dense spontaneous echo contrast (SEC) in the left atrium or LAA on transesophageal echocardiography [60]. SEC is a well-recognized independent predictor for stroke and thromboembolism in AF. Indices of the prothrombotic state and inflammatory markers (IL-6, but not CRP) may predict stroke and vascular events in AF [54,61]. In a larger series of 880 AF patients, CRP was positively correlated to stroke risk and related to stroke risk factors and prognosis (mortality, vascular events) [62]. Other mechanisms stimulating the prothrombotic state in AF that have been explored include matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of matrix metalloproteinases [TIMPs]) as well as growth factors. In one report, plasma levels of MMP-1 were lower and plasma levels of TIMP-1 were higher in 48 consecutive patients with permanent nonvalvular AF compared with controls [63]. However, these values were not independently associated with the presence of AF on multivariate analysis. Instead, clinical factors (that is, age, ischemic heart disease, or hypertension) and echocardiographic variables (end-diastolic left ventricular diameter or left ventricular mass index) were found to be independently associated with MMP system. Abnormal growth factors, such as vascular endothelial growth factor (VEGF, also a marker of angiogenesis) have been related to tissue factor (TF) upregulation and therefore coagulation at least in cancer pathophysiology. Among AF patients, TF levels have been shown to be significantly correlated with plasma VEGF levels [64]. In separate studies, plasma levels of TF and VEGF have also been shown to be increased in atherosclerosis, a condition whose pathophysiology involves a tendency to thrombosis and angiogenesis [65,66]. Similar observations have been noted for angiopoietin, another index of angiogenesis [67]. Other possible mechanisms that have been proposed for the hemostatic abnormalities include neuroendocrine activation [68], slow flow itself [69], increased expression of markers of platelet activation including P-selectin and CD63 [70,71], and elevated serum levels of lipoprotein(a) which is structurally similar to plasminogen and may have antifibrinolytic action [72]. In a series that included 121 patients with AF, 78 with a history of AF but in sinus rhythm at the time of the study, and 65 control subjects, markers of platelet activation were increased in patients with AF and in those with a history of AF [71]. However, multivariable analysis suggested that the degree of platelet activation was probably due to the underlying cardiovascular diseases https://www.uptodate.com/contents/mechanisms-of-thrombogenesis-in-atrial-fibrillation/print 7/20 7/5/23, 9:15 AM Mechanisms of thrombogenesis in atrial fibrillation - UpToDate associated with AF rather than the AF itself. Indeed, another marker of platelet activation, soluble CD40 ligand levels, was not related to the risk of stroke nor to prognosis [62]. Prognostic value of elevated biomarkers Measures of the prothrombotic state in patients with AF, using biomarkers such as von Willebrand factor (vWF) or D-dimer (both of which are discussed in the section above), have been evaluated for their prognostic value. (See "Clinical use of coagulation tests", section on 'Fibrin D-dimer'.) With regard to vWF, the following observations have been made: Among 1321 patients with AF, there was a significant stepwise increase in plasma vWf levels as the risk of stroke increased [53]. Two studies have suggested that the addition of plasma vWf levels to traditional risk predictors may improve the ability to predict stroke and vascular events [54,73]. In a study of 229 patients with permanent AF who were stabilized on warfarin therapy for at least six months, high plasma vWF levels (>221 international units/dl) were an independent predictor for adverse events, including death, stroke, and bleeding during two years of follow-up [74]. Two studies have found that D-dimer levels added to the ability of traditional risk factors to predict adverse outcomes [47,48], while one did not [74]. Other biomarkers have been tested in highly selected clinical trial cohorts to predict the risk of stroke, thromboembolism, or bleeding. These have included troponin, natriuretic peptides, and growth differential factor 15 (GDF15) [75-77]. These have led to proposals of biomarker-based stroke and bleeding risk scores, ABC-stroke, and ABC-bleeding, respectively [78]. In the real world clinical setting, the ABC-stroke and ABC-bleeding scores did not offer any advantage over clinical factor-based scores, such as CHA DS -VASc and HAS-BLED [79,80]. Also, the small 2 2 incremental value of improved prediction of high risk (at least statistically) should be balanced against the simplicity and practicality for everyday clinical use [78]. In another study, addition of multiple biomarkers enhanced the predictive value of CHA DS - 2 2 VASc and HAS-BLED, although the overall improvement was modest, the added predictive advantage over original scores was marginal, and decision curve analyses found lower net benefit compared with the original clinical scores [81]. Many of these biomarkers are predictive of thromboembolism, bleeding, death, heart failure, and hospitalizations, as well as noncardiovascular conditions, such as glaucoma progression. This may lead to confusion amongst clinicians over which end point to focus on. https://www.uptodate.com/contents/mechanisms-of-thrombogenesis-in-atrial-fibrillation/print 8/20 7/5/23, 9:15 AM Mechanisms of thrombogenesis in atrial fibrillation - UpToDate Use of indices of a prothrombotic or hypercoagulable state to test anticoagulation therapies Indices such as fibrin D-dimer are indicative of a prothrombotic state in AF. They have been used as biomarker surrogates of thrombogenesis in AF when testing anticoagulation regimes in Phase 2 clinical trials and to help with dose selection for large Phase 3 clinical trials [82-85]. SUMMARY The mechanisms leading to an increased risk of stroke, thrombus, and embolism in atrial fibrillation (AF) are multiple, complex, and closely interact with each other. 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Fibrin D-dimer: a useful clinical marker of thrombogenesis? Clin Sci (Lond) 1995; 89:205. 45. Lip GY, Rumley A, Dunn FG, Lowe GD. Plasma fibrinogen and fibrin D-dimer in patients with atrial fibrillation: effects of cardioversion to sinus rhythm. Int J Cardiol 1995; 51:245. 46. Abe, Y, Kim, et al. Evidence for the intravascular hyperclotting state induced by atrial fibrillation itself (abstract). J Am Coll Cardiol 1996; 27(Suppl A):35A. 47. Vene N, Mavri A, Kosmelj K, Stegnar M. High D-dimer levels predict cardiovascular events in patients with chronic atrial fibrillation during oral anticoagulant therapy. Thromb Haemost 2003; 90:1163. 48. Sadanaga T, Sadanaga M, Ogawa S. Evidence that D-dimer levels predict subsequent thromboembolic and cardiovascular events in patients with atrial fibrillation during oral anticoagulant therapy. J Am Coll Cardiol 2010; 55:2225. 49. Petersen P, Kastrup J, Helweg-Larsen S, et al. Risk factors for thromboembolic complications in chronic atrial fibrillation. The Copenhagen AFASAK study. Arch Intern Med 1990; 150:819. 50. Lip GY, Lip PL, Zarifis J, et al. Fibrin D-dimer and beta-thromboglobulin as markers of thrombogenesis and platelet activation in atrial fibrillation. Effects of introducing ultra-low- dose warfarin and aspirin. Circulation 1996; 94:425. https://www.uptodate.com/contents/mechanisms-of-thrombogenesis-in-atrial-fibrillation/print 12/20 7/5/23, 9:15 AM Mechanisms of thrombogenesis in atrial fibrillation - UpToDate 51. Li-Saw-Hee FL, Blann AD, Lip GY. Effects of fixed low-dose warfarin, aspirin-warfarin combination therapy, and dose-adjusted warfarin on thrombogenesis in chronic atrial fibrillation. Stroke 2000; 31:828. 52. Goldsmith I, Kumar P, Carter P, et al. Atrial endocardial changes in mitral valve disease: a scanning electron microscopy study. Am Heart J 2000; 140:777. 53. Conway DS, Pearce LA, Chin BS, et al. Plasma von Willebrand factor and soluble p-selectin as indices of endothelial damage and platelet activation in 1321 patients with nonvalvular atrial fibrillation: relationship to stroke risk factors. Circulation 2002; 106:1962. 54. Conway DS, Pearce LA, Chin BS, et al. Prognostic value of plasma von Willebrand factor and soluble P-selectin as indices of endothelial damage and platelet activation in 994 patients with nonvalvular atrial fibrillation. Circulation 2003; 107:3141. 55. Freestone B, Lip GY, Chong AY, et al. Circulating endothelial cells in atrial fibrillation with and without acute cardiovascular disease. Thromb Haemost 2005; 94:702. 56. Lip GY. Does paroxysmal atrial fibrillation confer a paroxysmal thromboembolic risk? Lancet 1997; 349:1565. 57. Ritchie DG, Levy BA, Adams MA, Fuller GM. Regulation of fibrinogen synthesis by plasmin- derived fragments of fibrinogen and fibrin: an indirect feedback pathway. Proc Natl Acad Sci U S A 1982; 79:1530. 58. Boos CJ, Anderson RA, Lip GY. Is atrial fibrillation an inflammatory disorder? Eur Heart J 2006; 27:136. 59. Conway DS, Buggins P, Hughes E, Lip GY. Relationship of interleukin-6 and C-reactive protein to the prothrombotic state in chronic atrial fibrillation. J Am Coll Cardiol 2004; 43:2075. 60. Conway DS, Buggins P, Hughes E, Lip GY. Relation of interleukin-6, C-reactive protein, and the prothrombotic state to transesophageal echocardiographic findings in atrial fibrillation. Am J Cardiol 2004; 93:1368. 61. Conway DS, Buggins P, Hughes E, Lip GY. Prognostic significance of raised plasma levels of interleukin-6 and C-reactive protein in atrial fibrillation. Am Heart J 2004; 148:462. 62. Lip GY, Patel JV, Hughes E, Hart RG. High-sensitivity C-reactive protein and soluble CD40 ligand as indices of inflammation and platelet activation in 880 patients with nonvalvular atrial fibrillation: relationship to stroke risk factors, stroke risk stratification schema, and prognosis. Stroke 2007; 38:1229. 63. Mar n F, Rold n V, Climent V, et al. Is thrombogenesis in atrial fibrillation related to matrix metalloproteinase-1 and its inhibitor, TIMP-1? Stroke 2003; 34:1181. https://www.uptodate.com/contents/mechanisms-of-thrombogenesis-in-atrial-fibrillation/print 13/20 7/5/23, 9:15 AM Mechanisms of thrombogenesis in atrial fibrillation - UpToDate 64. Chung NA, Belgore F, Li-Saw-Hee FL, et al. Is the hypercoagulable state in atrial fibrillation mediated by vascular endothelial growth factor? Stroke 2002; 33:2187. 65. Blann AD, Belgore FM, McCollum CN, et al. Vascular endothelial growth factor and its receptor, Flt-1, in the plasma of patients with coronary or peripheral atherosclerosis, or Type II diabetes. Clin Sci (Lond) 2002; 102:187. 66. Makin AJ, Chung NA, Silverman SH, Lip GY. Vascular endothelial growth factor and tissue factor in patients with established peripheral artery disease: a link between angiogenesis and thrombogenesis? Clin Sci (Lond) 2003; 104:397. 67. Freestone B, Chong AY, Lim HS, et al. Angiogenic factors in atrial fibrillation: a possible role in thrombogenesis? Ann Med 2005; 37:365. 68. Sbarouni E, Bradshaw A, Andreotti F, et al. Relationship between hemostatic abnormalities and neuroendocrine activity in heart failure. Am Heart J 1994; 127:607. 69. Lip GY, Lowe GD, Metcalfe MJ, et al. Is diastolic dysfunction associated with thrombogenesis? A study of circulating markers of a prothrombotic state in patients with coronary artery disease. Int J Cardiol 1995; 50:31. 70. Minamino T, Kitakaze M, Sanada S, et al. Increased expression of P-selectin on platelets is a risk factor for silent cerebral infarction in patients with atrial fibrillation: role of nitric oxide. Circulation 1998; 98:1721. 71. Choudhury A, Chung I, Blann AD, Lip GY. Platelet surface CD62P and CD63, mean platelet volume, and soluble/platelet P-selectin as indexes of platelet function in atrial fibrillation: a comparison of "healthy control subjects" and "disease control subjects" in sinus rhythm. J Am Coll Cardiol 2007; 49:1957. 72. Igarashi Y, Yamaura M, Ito M, et al. Elevated serum lipoprotein(a) is a risk factor for left atrial thrombus in patients with chronic atrial fibrillation: a transesophageal echocardiographic study. Am Heart J 1998; 136:965. 73. Lip GY, Lane D, Van Walraven C, Hart RG. Additive role of plasma von Willebrand factor levels to clinical factors for risk stratification of patients with atrial fibrillation. Stroke 2006; 37:2294. 74. Rold n V, Mar n F, Mui a B, et al. Plasma von Willebrand factor levels are an independent risk factor for adverse events including mortality and major bleeding in anticoagulated atrial fibrillation patients. J Am Coll Cardiol 2011; 57:2496. 75. Hijazi Z, Siegbahn A, Andersson U, et al. High-sensitivity troponin I for risk assessment in patients with atrial fibrillation: insights from the Apixaban for Reduction in Stroke and other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial. Circulation 2014; 129:625. https://www.uptodate.com/contents/mechanisms-of-thrombogenesis-in-atrial-fibrillation/print 14/20 7/5/23, 9:15 AM Mechanisms of thrombogenesis in atrial fibrillation - UpToDate 76. Hijazi Z, Wallentin L, Siegbahn A, et al. High-sensitivity troponin T and risk stratification in patients with atrial fibrillation during treatment with apixaban or warfarin. J Am Coll Cardiol 2014; 63:52. 77. Hijazi Z, Wallentin L, Siegbahn A, et al. N-terminal pro-B-type natriuretic peptide for risk

fibrillation: effects of warfarin treatment. Br Heart J 1995; 73:527. 42. Asakura H, Hifumi S, Jokaji H, et al. Prothrombin fragment F1 + 2 and thrombin- antithrombin III complex are useful markers of the hypercoagulable state in atrial fibrillation. Blood Coagul Fibrinolysis 1992; 3:469. 43. Lip GY, Blann A. von Willebrand factor: a marker of endothelial dysfunction in vascular disorders? Cardiovasc Res 1997; 34:255. 44. Lip GY, Lowe GD. Fibrin D-dimer: a useful clinical marker of thrombogenesis? Clin Sci (Lond) 1995; 89:205. 45. Lip GY, Rumley A, Dunn FG, Lowe GD. Plasma fibrinogen and fibrin D-dimer in patients with atrial fibrillation: effects of cardioversion to sinus rhythm. Int J Cardiol 1995; 51:245. 46. Abe, Y, Kim, et al. Evidence for the intravascular hyperclotting state induced by atrial fibrillation itself (abstract). J Am Coll Cardiol 1996; 27(Suppl A):35A. 47. Vene N, Mavri A, Kosmelj K, Stegnar M. High D-dimer levels predict cardiovascular events in patients with chronic atrial fibrillation during oral anticoagulant therapy. Thromb Haemost 2003; 90:1163. 48. Sadanaga T, Sadanaga M, Ogawa S. Evidence that D-dimer levels predict subsequent thromboembolic and cardiovascular events in patients with atrial fibrillation during oral anticoagulant therapy. J Am Coll Cardiol 2010; 55:2225. 49. Petersen P, Kastrup J, Helweg-Larsen S, et al. Risk factors for thromboembolic complications in chronic atrial fibrillation. The Copenhagen AFASAK study. Arch Intern Med 1990; 150:819. 50. Lip GY, Lip PL, Zarifis J, et al. Fibrin D-dimer and beta-thromboglobulin as markers of thrombogenesis and platelet activation in atrial fibrillation. Effects of introducing ultra-low- dose warfarin and aspirin. Circulation 1996; 94:425. https://www.uptodate.com/contents/mechanisms-of-thrombogenesis-in-atrial-fibrillation/print 12/20 7/5/23, 9:15 AM Mechanisms of thrombogenesis in atrial fibrillation - UpToDate 51. Li-Saw-Hee FL, Blann AD, Lip GY. Effects of fixed low-dose warfarin, aspirin-warfarin combination therapy, and dose-adjusted warfarin on thrombogenesis in chronic atrial fibrillation. Stroke 2000; 31:828. 52. Goldsmith I, Kumar P, Carter P, et al. Atrial endocardial changes in mitral valve disease: a scanning electron microscopy study. Am Heart J 2000; 140:777. 53. Conway DS, Pearce LA, Chin BS, et al. Plasma von Willebrand factor and soluble p-selectin as indices of endothelial damage and platelet activation in 1321 patients with nonvalvular atrial fibrillation: relationship to stroke risk factors. Circulation 2002; 106:1962. 54. Conway DS, Pearce LA, Chin BS, et al. Prognostic value of plasma von Willebrand factor and soluble P-selectin as indices of endothelial damage and platelet activation in 994 patients with nonvalvular atrial fibrillation. Circulation 2003; 107:3141. 55. Freestone B, Lip GY, Chong AY, et al. Circulating endothelial cells in atrial fibrillation with and without acute cardiovascular disease. Thromb Haemost 2005; 94:702. 56. Lip GY. Does paroxysmal atrial fibrillation confer a paroxysmal thromboembolic risk? Lancet 1997; 349:1565. 57. Ritchie DG, Levy BA, Adams MA, Fuller GM. Regulation of fibrinogen synthesis by plasmin- derived fragments of fibrinogen and fibrin: an indirect feedback pathway. Proc Natl Acad Sci U S A 1982; 79:1530. 58. Boos CJ, Anderson RA, Lip GY. Is atrial fibrillation an inflammatory disorder? Eur Heart J 2006; 27:136. 59. Conway DS, Buggins P, Hughes E, Lip GY. Relationship of interleukin-6 and C-reactive protein to the prothrombotic state in chronic atrial fibrillation. J Am Coll Cardiol 2004; 43:2075. 60. Conway DS, Buggins P, Hughes E, Lip GY. Relation of interleukin-6, C-reactive protein, and the prothrombotic state to transesophageal echocardiographic findings in atrial fibrillation. Am J Cardiol 2004; 93:1368. 61. Conway DS, Buggins P, Hughes E, Lip GY. Prognostic significance of raised plasma levels of interleukin-6 and C-reactive protein in atrial fibrillation. Am Heart J 2004; 148:462. 62. Lip GY, Patel JV, Hughes E, Hart RG. High-sensitivity C-reactive protein and soluble CD40 ligand as indices of inflammation and platelet activation in 880 patients with nonvalvular atrial fibrillation: relationship to stroke risk factors, stroke risk stratification schema, and prognosis. Stroke 2007; 38:1229. 63. Mar n F, Rold n V, Climent V, et al. Is thrombogenesis in atrial fibrillation related to matrix metalloproteinase-1 and its inhibitor, TIMP-1? Stroke 2003; 34:1181. https://www.uptodate.com/contents/mechanisms-of-thrombogenesis-in-atrial-fibrillation/print 13/20 7/5/23, 9:15 AM Mechanisms of thrombogenesis in atrial fibrillation - UpToDate 64. Chung NA, Belgore F, Li-Saw-Hee FL, et al. Is the hypercoagulable state in atrial fibrillation mediated by vascular endothelial growth factor? Stroke 2002; 33:2187. 65. Blann AD, Belgore FM, McCollum CN, et al. Vascular endothelial growth factor and its receptor, Flt-1, in the plasma of patients with coronary or peripheral atherosclerosis, or Type II diabetes. Clin Sci (Lond) 2002; 102:187. 66. Makin AJ, Chung NA, Silverman SH, Lip GY. Vascular endothelial growth factor and tissue factor in patients with established peripheral artery disease: a link between angiogenesis and thrombogenesis? Clin Sci (Lond) 2003; 104:397. 67. Freestone B, Chong AY, Lim HS, et al. Angiogenic factors in atrial fibrillation: a possible role in thrombogenesis? Ann Med 2005; 37:365. 68. Sbarouni E, Bradshaw A, Andreotti F, et al. Relationship between hemostatic abnormalities and neuroendocrine activity in heart failure. Am Heart J 1994; 127:607. 69. Lip GY, Lowe GD, Metcalfe MJ, et al. Is diastolic dysfunction associated with thrombogenesis? A study of circulating markers of a prothrombotic state in patients with coronary artery disease. Int J Cardiol 1995; 50:31. 70. Minamino T, Kitakaze M, Sanada S, et al. Increased expression of P-selectin on platelets is a risk factor for silent cerebral infarction in patients with atrial fibrillation: role of nitric oxide. Circulation 1998; 98:1721. 71. Choudhury A, Chung I, Blann AD, Lip GY. Platelet surface CD62P and CD63, mean platelet volume, and soluble/platelet P-selectin as indexes of platelet function in atrial fibrillation: a comparison of "healthy control subjects" and "disease control subjects" in sinus rhythm. J Am Coll Cardiol 2007; 49:1957. 72. Igarashi Y, Yamaura M, Ito M, et al. Elevated serum lipoprotein(a) is a risk factor for left atrial thrombus in patients with chronic atrial fibrillation: a transesophageal echocardiographic study. Am Heart J 1998; 136:965. 73. Lip GY, Lane D, Van Walraven C, Hart RG. Additive role of plasma von Willebrand factor levels to clinical factors for risk stratification of patients with atrial fibrillation. Stroke 2006; 37:2294. 74. Rold n V, Mar n F, Mui a B, et al. Plasma von Willebrand factor levels are an independent risk factor for adverse events including mortality and major bleeding in anticoagulated atrial fibrillation patients. J Am Coll Cardiol 2011; 57:2496. 75. Hijazi Z, Siegbahn A, Andersson U, et al. High-sensitivity troponin I for risk assessment in patients with atrial fibrillation: insights from the Apixaban for Reduction in Stroke and other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial. Circulation 2014; 129:625. https://www.uptodate.com/contents/mechanisms-of-thrombogenesis-in-atrial-fibrillation/print 14/20 7/5/23, 9:15 AM Mechanisms of thrombogenesis in atrial fibrillation - UpToDate 76. Hijazi Z, Wallentin L, Siegbahn A, et al. High-sensitivity troponin T and risk stratification in patients with atrial fibrillation during treatment with apixaban or warfarin. J Am Coll Cardiol 2014; 63:52. 77. Hijazi Z, Wallentin L, Siegbahn A, et al. N-terminal pro-B-type natriuretic peptide for risk assessment in patients with atrial fibrillation: insights from the ARISTOTLE Trial (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation). J Am Coll Cardiol 2013; 61:2274. 78. Lip GY. Stroke and bleeding risk assessment in atrial fibrillation: when, how, and why? Eur Heart J 2013; 34:1041. 79. Esteve-Pastor MA, Rivera-Caravaca JM, Roldan V, et al. Long-term bleeding risk prediction in 'real world' patients with atrial fibrillation: Comparison of the HAS-BLED and ABC-Bleeding risk scores. The Murcia Atrial Fibrillation Project. Thromb Haemost 2017; 117:1848. 80. Rivera-Caravaca JM, Rold n V, Esteve-Pastor MA, et al. Long-Term Stroke Risk Prediction in Patients With Atrial Fibrillation: Comparison of the ABC-Stroke and CHA2DS2-VASc Scores. J Am Heart Assoc 2017; 6. 81. Rold n V, Rivera-Caravaca JM, Shantsila A, et al. Enhancing the 'real world' prediction of cardiovascular events and major bleeding with the CHA2DS2-VASc and HAS-BLED scores using multiple biomarkers. Ann Med 2018; 50:26. 82. Lip GY, Rasmussen LH, Olsson SB, et al. Oral direct thrombin inhibitor AZD0837 for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation: a randomized dose-guiding, safety, and tolerability study of four doses of AZD0837 vs. vitamin K antagonists. Eur Heart J 2009; 30:2897. 83. Weitz JI, Connolly SJ, Patel I, et al. Randomised, parallel-group, multicentre, multinational phase 2 study comparing edoxaban, an oral factor Xa inhibitor, with warfarin for stroke prevention in patients with atrial fibrillation. Thromb Haemost 2010; 104:633. 84. Connolly SJ, Eikelboom J, Dorian P, et al. Betrixaban compared with warfarin in patients with atrial fibrillation: results of a phase 2, randomized, dose-ranging study (Explore-Xa). Eur Heart J 2013; 34:1498. 85. Ezekowitz MD, Reilly PA, Nehmiz G, et al. Dabigatran with or without concomitant aspirin compared with warfarin alone in patients with nonvalvular atrial fibrillation (PETRO Study). Am J Cardiol 2007; 100:1419. Topic 981 Version 14.0 https://www.uptodate.com/contents/mechanisms-of-thrombogenesis-in-atrial-fibrillation/print 15/20 7/5/23, 9:15 AM Mechanisms of thrombogenesis in atrial fibrillation - UpToDate GRAPHICS Clinical and echocardiographic predictors of stroke in atrial fibrillation Clinical factors History of hypertension Recent (within 3 months) HF Previous cerebrovascular event (stroke or TIA) Echocardiographic factors Global left ventricular dysfunction Dilated atrium on M-mode ( 4.7 cm or 2.4 cm/m2) Stroke risk (per year) based on clinical factors No risk factors 2.5 percent 1 risk factor 7.2 percent 1 or 2 risk factors 17.6 percent Stroke risk (per year) based on clinical and echocardiographic factors No risk factors 1.0 percent 1 risk factor 6.0 percent 2 or 3 risk factors 18.6 percent Adapted from: Stroke Prevention in Atrial Fibrillation Investigators. Ann Intern Med 1992; 116:1 and 1992; 116:6. Graphic 64291 Version 3.0 https://www.uptodate.com/contents/mechanisms-of-thrombogenesis-in-atrial-fibrillation/print 16/20 7/5/23, 9:15 AM Mechanisms of thrombogenesis in atrial fibrillation - UpToDate Indicators of thromboembolic risk on transesophageal echocardiography in patients with atrial fibrillation Left atrial appendage size and function Left atrial size and function Spontaneous echo contrast Left atrial or atrial appendage thrombus Intraatrial septal aneurysm Patent foramen ovale Aortic atherosclerosis with plaque in ascending aorta Graphic 72745 Version 1.0 https://www.uptodate.com/contents/mechanisms-of-thrombogenesis-in-atrial-fibrillation/print 17/20 7/5/23, 9:15 AM Mechanisms of thrombogenesis in atrial fibrillation - UpToDate Spontaneous echo contrast seen in the left atrium on transesophageal echocardiogram Transesophageal echocardiography showing spontaneous echo contrast (or "smoke") in an enlarged left atrium (LA). This finding is a marker for stasis and is associated with a higher risk of thrombus formation and thromboembolism. Courtesy of Warren Manning, MD. Graphic 66980 Version 5.0 https://www.uptodate.com/contents/mechanisms-of-thrombogenesis-in-atrial-fibrillation/print 18/20 7/5/23, 9:15 AM Mechanisms of thrombogenesis in atrial fibrillation - UpToDate Significant left ventricular dysfunction predicts stroke in AF In a prospective study of 1066 patients entered into three clinical trials evaluating the role of anticoagulation in nonvalvular AF (BAATAF, SPINAF, and SPAF), the incidence of a stroke was 9.3 percent per year in patients with moderate to severe left ventricular dysfunction compared with 4.4 percent per year in those with normal or mildly abnormal left ventricular function. Data from: Atrial Fibrillation Investigators, Arch Intern Med 1998; 158:1316. Graphic 70244 Version 4.0 https://www.uptodate.com/contents/mechanisms-of-thrombogenesis-in-atrial-fibrillation/print 19/20 7/5/23, 9:15 AM Mechanisms of thrombogenesis in atrial fibrillation - UpToDate Contributor Disclosures Gregory YH Lip, MD, FRCPE, FESC, FACC Consultant/Advisory Boards: BMS/Pfizer [Atrial fibrillation and thrombosis]; Boehringer Ingelheim [Atrial fibrillation and thrombosis]; Daiichi-Sankyo [Atrial fibrillation and thrombosis]. Speaker's Bureau: BMS/Pfizer [Atrial fibrillation and thrombosis]; Boehringer Ingelheim [Atrial fibrillation and thrombosis]; Daiichi-Sankyo [Atrial fibrillation and thrombosis]. All of the relevant financial relationships listed have been mitigated. Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/mechanisms-of-thrombogenesis-in-atrial-fibrillation/print 20/20

7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Overview of the acute management of tachyarrhythmias : Jordan M Prutkin, MD, MHS, FHRS : James Hoekstra, MD, Hugh Calkins, MD : Todd F Dardas, MD, MS All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Feb 03, 2023. INTRODUCTION Tachyarrhythmias, defined as abnormal heart rhythms with a ventricular rate of 100 or more beats per minute, are frequently symptomatic and often result in patients seeking care at their provider's office or the emergency department. Signs and symptoms related to the tachyarrhythmia may include shock, hypotension, heart failure, shortness of breath, chest pain, acute myocardial infarction, palpitations, and/or decreased level of consciousness. An overview of the management of these various arrhythmias will be presented here. More complete reviews of the individual arrhythmias are discussed separately. INITIAL DIAGNOSTIC AND TREATMENT DECISIONS In patients who present with a symptomatic tachyarrhythmia, a 12-lead electrocardiogram (ECG) should be obtained while a brief initial assessment of the patient's overall clinical assessment is performed. If the patient is hemodynamically unstable, it may be preferable to obtain only a rhythm strip prior to urgent cardioversion and not wait for a 12-lead ECG. The information acquired from these initial assessments is crucial for subsequent management of the patient. Is the patient clinically (or hemodynamically) unstable? The most important clinical determination in a patient presenting with a tachyarrhythmia is whether or not the patient is experiencing signs and symptoms related to the rapid heart rate. These can include hypotension, shortness of breath, chest pain suggestive of coronary ischemia, shock, and/or decreased level of consciousness. https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 1/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate Determining whether a patient's symptoms are related to the tachycardia depends upon several factors, including age and the presence of underlying cardiac disease. Hemodynamically unstable and not sinus rhythm If a patient has clinically significant hemodynamic instability potentially due to the tachyarrhythmia, an attempt should be made as quickly as possible to determine whether the rhythm is sinus tachycardia ( algorithm 1). If the rhythm is not sinus tachycardia, or if there is any doubt that the rhythm is sinus tachycardia, urgent conversion to sinus rhythm is recommended. (See "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'Similar to sinus rhythm' and "Basic principles and technique of external electrical cardioversion and defibrillation" and "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'Assessment of hemodynamic stability'.) Hemodynamically stable If the patient is not experiencing hemodynamic instability, a nonemergent approach to the diagnosis of the patient's rhythm can be undertaken [1-3]. A close examination of the 12-lead ECG should permit the correct identification of the arrhythmia in 80 percent of cases [4]. (See 'Is the QRS complex narrow or wide? Regular or irregular?' below and "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'Evaluation' and "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'Evaluation of the electrocardiogram'.) Is the QRS complex narrow or wide? Regular or irregular? Treatment of any tachyarrhythmia depends on a variety of clinical factors. However, most treatment decisions are made based on the width, morphology, and regularity of the QRS complex ( algorithm 2). In most patients, the differentiation between narrow and wide QRS complex tachyarrhythmias requires only a surface ECG. Narrow QRS complex tachyarrhythmias have a QRS complex <120 milliseconds in duration Wide QRS complex tachyarrhythmias have a QRS complex 120 milliseconds in duration The various types of narrow and wide QRS complex tachyarrhythmias are discussed below. (See 'Narrow QRS complex tachyarrhythmias' below and 'Wide QRS complex tachyarrhythmias' below.) NARROW QRS COMPLEX TACHYARRHYTHMIAS Discussion of the treatment of narrow QRS complex tachycardias will be divided into those with a regular ventricular response and those with an irregular ventricular response ( algorithm 3 and algorithm 1). https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 2/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate Regular narrow QRS complex tachyarrhythmias The regular narrow QRS complex tachycardias include ( algorithm 2) [3]: Sinus tachycardia (see "Sinus tachycardia: Evaluation and management") Inappropriate sinus tachycardia (see "Sinus tachycardia: Evaluation and management", section on 'Inappropriate sinus tachycardia') Sinoatrial nodal reentrant tachycardia (SANRT) (see "Sinoatrial nodal reentrant tachycardia (SANRT)") Atrioventricular nodal reentrant tachycardia (AVNRT) (see "Atrioventricular nodal reentrant tachycardia") Atrioventricular reentrant (or reciprocating) tachycardia (AVRT) (see "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway") Atrial tachycardia (AT) (see "Focal atrial tachycardia") Atrial flutter (see "Overview of atrial flutter") Intraatrial reentrant tachycardia (IART) (see "Intraatrial reentrant tachycardia") Junctional ectopic tachycardia Nonparoxysmal junctional tachycardia Because the vast majority of regular narrow QRS complex tachycardias are due to sinus tachycardia, AVNRT, AVRT, AT, and atrial flutter, these conditions will be presented here. Discussions regarding the treatment of the other less common types of regular narrow QRS complex tachycardias are presented separately. (See "Sinus tachycardia: Evaluation and management", section on 'Inappropriate sinus tachycardia' and "Sinoatrial nodal reentrant tachycardia (SANRT)", section on 'Treatment' and "Intraatrial reentrant tachycardia", section on 'Treatment' and "Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome", section on 'Permanent junctional reciprocating tachycardia'.) Sinus tachycardia The most common tachycardia is sinus tachycardia. If it is certain that the patient's rhythm is sinus tachycardia and clinically significant cardiac symptoms are present, management should be focused on the underlying disorder and on treating any contributing cause of the rapid heart rate (eg, coronary ischemia, pulmonary embolism, respiratory or cardiac failure, hypovolemia, anemia, hyperthyroidism, fever, pain, or anxiety). This may include volume replacement or diuresis, antibiotics, anti-pyretics, oxygen, pain control, or other treatments as appropriate. In patients with sinus tachycardia and certain forms of heart disease, such as coronary disease or aortic stenosis, treatment may need to be directed at the heart rate itself. In such cases, cautious use of an intravenous beta blocker is appropriate. (See "Sinus tachycardia: Evaluation and management" and "Acute myocardial infarction: Role of beta blocker therapy" and "Medical management of symptomatic aortic stenosis".) https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 3/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate Atrioventricular nodal reentrant tachycardia (AVNRT) Patients with AVNRT associated with hemodynamic compromise or severe symptoms due to the tachycardia (eg, angina, hypotension, or heart failure) require rapid termination of the arrhythmia. (See "Atrioventricular nodal reentrant tachycardia", section on 'Initial management'.) For patients with AVNRT who are hemodynamically unstable related to their arrhythmia, we recommend immediate DC cardioversion. Consideration for using vagal maneuvers (Valsalva maneuver or carotid sinus massage) is also reasonable if it does not delay cardioversion. (See "Vagal maneuvers".) For patients with AVNRT associated with severe symptoms due to the tachycardia (eg, angina, hypotension, heart failure, or mental status changes) in whom intravenous access is available, we suggest an initial attempt at termination with adenosine ( algorithm 4) rather than cardioversion. If adenosine cannot be administered or is ineffective, patients should undergo immediate DC cardioversion. For patients with AVNRT that is not associated with severe symptoms or hemodynamic collapse, including patients without symptoms, we suggest the following sequential approach to acute termination: Vagal maneuvers (see "Vagal maneuvers") IV adenosine ( algorithm 4) IV non-dihydropyridine calcium channel blocker or an IV beta blocker Atrioventricular reentrant tachycardia (AVRT) Patients with any arrhythmia (ie, orthodromic AVRT, antidromic AVRT, atrial fibrillation/flutter) involving an accessory pathway should have a prompt initial assessment of hemodynamic status. AVRT may result in either a narrow QRS complex tachycardia or a wide QRS complex tachycardia depending on the direction of conduction across the accessory pathway and also the presence of aberrant conduction. (See 'Antidromic AVRT' below and "Treatment of arrhythmias associated with the Wolff-Parkinson- White syndrome", section on 'Acute treatment of symptomatic arrhythmias'.) For patients with AVRT who are hemodynamically unstable related to their arrhythmia, we recommend immediate DC cardioversion. Consideration for using vagal maneuvers is reasonable if it does not delay cardioversion. (See "Vagal maneuvers".) For patients with acute symptomatic orthodromic AVRT (usually narrow QRS complex in the absence of an underlying conduction delay) who are hemodynamically stable, our approach is as follows ( table 1): https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 4/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate We recommend initial treatment with one or more vagal maneuvers rather than pharmacologic therapy. (See "Vagal maneuvers".) If vagal maneuvers are ineffective, pharmacologic therapy with an AV nodal blocking agent (ie, adenosine, verapamil, beta blockers) should be instituted. We suggest intravenous adenosine ( algorithm 4) rather than intravenous verapamil as the initial choice based on its high efficacy and short half-life. If adenosine is ineffective, we proceed with intravenous verapamil as the second-line agent. If orthodromic AVRT persists, intravenous procainamide and beta blockers approved for intravenous administration (propranolol, metoprolol, and esmolol) are additional therapeutic options. Amiodarone may also be considered. Because most patients with acute symptomatic antidromic AVRT have a wide QRS complex, the approach to this arrhythmia is discussed below. (See 'Antidromic AVRT' below.) Atrial tachycardia Focal atrial tachycardias (AT), usually paroxysmal and self-limited, arise from a single site or area of microreentry or enhanced automaticity outside of the sinus node. (See "Focal atrial tachycardia", section on 'Acute treatment'.) For patients with AT who are felt to be hemodynamically unstable related to their arrhythmia, we recommend immediate DC cardioversion. For a hemodynamically stable patient with symptomatic AT, we suggest acute treatment with an oral or intravenous beta blocker or non-dihydropyridine calcium channel blocker (ie, diltiazem or verapamil). Such treatment may slow the ventricular response and/or terminate the arrhythmia. Intravenous amiodarone is an acceptable alternative that may be preferred in a patient with borderline hypotension as amiodarone may slow the rate or convert the rhythm back to normal sinus. Atrial flutter Atrial flutter usually presents as a regular narrow complex tachycardia, though it occasionally may have an irregular ventricular response. Atrial flutter should always be considered high on the differential diagnosis when a patient presents with a regular narrow complex tachycardia with a ventricular response of approximately 150 beats per minute. As with atrial fibrillation, the early steps in the management of a patient with new onset atrial flutter involve an assessment of the need for cardioversion, ventricular rate slowing therapy, and antithrombotic therapy. Our initial approach to the management of patients with atrial flutter is the same as our approach for atrial fibrillation. (See 'Atrial fibrillation' below.) Irregular narrow QRS complex tachyarrhythmias The irregular narrow QRS complex tachycardias include ( algorithm 2): https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 5/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate Atrial fibrillation (AF) (see "Atrial fibrillation: Overview and management of new-onset atrial fibrillation") Atrial flutter with variable conduction (see "Overview of atrial flutter") Focal atrial tachycardia with variable conduction (see "Focal atrial tachycardia") Multifocal atrial tachycardia (MAT) (see "Multifocal atrial tachycardia") Atrial fibrillation Most patients with new onset (ie, first detected or diagnosed) AF with a rapid rate present with symptoms related to the arrhythmia. Except for embolization, the symptoms associated with new onset AF are primarily due to a rapid and/or irregular ventricular response. The early steps in the management of a patient with new onset rapid AF involve an assessment of the need for cardioversion, ventricular rate slowing therapy, and antithrombotic therapy. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation".) Urgent or emergent cardioversion should be considered for patients with active ischemia, significant hypotension, severe heart failure, or the presence of a preexcitation syndrome associated with rapid conduction using the accessory pathway. (See 'Atrioventricular reentrant tachycardia (AVRT)' above.) For all patients who do not require urgent or emergent cardioversion, we recommend rate control to improve symptoms and to reduce the risk of tachycardia-mediated cardiomyopathy. We believe a goal of less than 110 beats per minute is reasonable for an asymptomatic patient with a normal ejection fraction. Beta blockers and non- dihydropyridine calcium channel blockers are preferred as first-line agents in most patients, and digoxin should only rarely be used. Intravenous preparations are preferred to oral preparations when rapid control of rate is necessary. For patients with AF less than 48 hours in duration in whom cardioversion is planned, the use of antithrombotic therapy pre-cardioversion to reduce the risk of embolization can be considered. For patients with AF longer than 48 hours in duration (or of unknown duration), we recommend four weeks of therapeutic oral anticoagulation prior to cardioversion, as opposed to immediate cardioversion. Transesophageal echocardiography-based (TEE) screening for the presence of atrial thrombi is recommended if cardioversion is desired earlier than four weeks. Anticoagulation must be continued for a minimum of four weeks after cardioversion. Whether long-term anticoagulation is indicated depends on assessment of the patient's thromboembolic risk profile. (See "Atrial fibrillation in adults: Selection of candidates for anticoagulation".) https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 6/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate Atrial flutter As with atrial fibrillation, the early steps in the management of a patient with new onset atrial flutter involve an assessment of the need for cardioversion, ventricular rate slowing therapy, and antithrombotic therapy. Our initial approach to the management of patients with atrial flutter is the same as our approach for atrial fibrillation. (See 'Atrial fibrillation' above.) Multifocal atrial tachycardia Multifocal atrial tachycardia (MAT) is an arrhythmia with organized atrial activity yielding P waves with three or more different morphologies. MAT is commonly associated with significant underlying pulmonary or cardiac illness. (See "Multifocal atrial tachycardia", section on 'Treatment'.) Most episodes of MAT do not precipitate hemodynamic compromise or limiting symptoms. Thus, therapy in patients with MAT should be aimed at the inciting underlying disease. Patients with MAT and associated hypokalemia or hypomagnesemia should undergo electrolyte repletion prior to the initiation of additional medical therapy for MAT. Medical therapy for MAT is indicated only if MAT causes a sustained rapid ventricular response that causes or worsens myocardial ischemia, heart failure, peripheral perfusion, or oxygenation. Options for medical therapy for patients with symptomatic MAT requiring ventricular rate control include non-dihydropyridine calcium channel blockers and beta blockers. For patients without heart failure or bronchospasm, we suggest initial therapy with a beta blocker, usually metoprolol, before calcium channel blockers. Conversely, for patients with severe bronchospasm, we suggest initial therapy with a non-dihydropyridine calcium channel blocker, usually verapamil, rather than a beta blocker. Beta blockers may be used cautiously in patients with stable heart failure. Rate control therapy is typically unsuccessful, however, without treating the underlying disorder. WIDE QRS COMPLEX TACHYARRHYTHMIAS Discussion of the treatment of wide QRS complex tachycardias, similar to narrow QRS complex tachycardias, can be divided into those with a regular or irregular ventricular rate. Regular wide QRS complex tachyarrhythmias The regular wide QRS complex tachycardias include ( algorithm 2): Monomorphic ventricular tachycardia (VT). (See "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis" and "Ventricular tachycardia in the absence of apparent structural heart disease".) https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 7/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate Supraventricular tachycardia with aberrant conduction, underlying conduction delay, conduction over an accessory pathway (eg, AVNRT with right bundle branch block), or a paced ventricular response. Supraventricular tachycardia in a patient on certain antiarrhythmic medications or with significant electrolyte abnormalities. Antidromic AVRT. The most concerning potential cause of a wide QRS complex tachycardia is VT, and, in the majority of patients, the arrhythmia should be assumed to be VT until proven otherwise. Immediate assessment of patient stability takes precedence over any further diagnostic evaluation. (See "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'Summary and recommendations'.) A patient who is unresponsive or pulseless should be treated according to standard advance cardiac life support (ACLS) algorithms ( algorithm 5). In a patient who is unstable but conscious, we recommend immediate synchronized cardioversion with appropriate sedation when possible. In a stable patient, a focused diagnostic evaluation may proceed to determine the etiology of the arrhythmia and guide specific therapy. Ventricular tachycardia In stable patients with known or presumed VT, we recommend the following approach (see "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'Summary and recommendations'): We recommend synchronized external cardioversion, following appropriate sedation, as the initial therapy for most patients with stable VT. If the patient has an implantable cardioverter-defibrillator, it may be possible to terminate the arrhythmia by antitachycardia pacing prior to an attempted cardioversion. In patients with refractory or recurrent wide complex tachycardia (WCT), we suggest an intravenous class I or III antiarrhythmic drug ( table 2), such as amiodarone, lidocaine, or procainamide. In selected patients known to have one of the syndromes of VT in the setting of a structurally normal heart, we suggest calcium channel blockers or beta blockers be used for arrhythmia termination or suppression. However, the decision to use these drugs in this https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 8/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate setting should be made in consultation with a cardiologist experienced in arrhythmia management. Supraventricular tachycardia with aberrant conduction The narrow complex supraventricular tachycardia (SVT) rhythms may present with a wide complex in the setting of aberrant conduction or conduction over an accessory pathway (not including AVRT). In stable patients with a WCT that is known to be an SVT, initial management is similar to that of an SVT with a narrow QRS complex. A continuous rhythm strip should be obtained during any intervention that is intended to slow or terminate the arrhythmia. (See 'Regular narrow QRS complex tachyarrhythmias' above.) For AVNRT or AVRT, or an SVT in which the specific arrhythmia is unknown, we suggest the following sequence of interventions in order to terminate the arrhythmia or to slow ventricular response and facilitate diagnosis in stable patients: Vagotonic maneuvers (eg, valsalva or carotid sinus pressure) Intravenous adenosine ( algorithm 4) Intravenous calcium channel blockers or beta blockers Cardioversion in selected persistent cases, or if the patient is unstable Supraventricular tachycardia with a pacemaker Regular wide QRS complex tachycardias in patients with a pacemaker may be due to tracking of one of the typical supraventricular tachycardias (eg, sinus tachycardia, atrial flutter, etc) or may be due to endless loop tachycardia (ELT, also referred to as pacemaker-mediated tachycardia [PMT]). (See "Unexpected rhythms with normally functioning dual-chamber pacing systems", section on 'Pacemaker-mediated tachycardia'.) In patients with tracking of a native supraventricular tachyarrhythmia, the pacemaker usually should automatically mode switch to a non-tracking mode. If it does not, placing a magnet on the pacemaker will lead to asynchronous pacing at a fixed and lower rate, and the pacemaker settings can be adjusted to prevent rapid pacing. If the rhythm is due to ELT, retrograde conduction from the ventricle to the atrium is sensed by the pacemaker and serves as a trigger to pace the ventricle, which again conducts back to the atrium and perpetuates the tachycardia. Placing a magnet on the pacemaker leads to asynchronous pacing and will stop the tachycardia. Most pacemakers have algorithms to prevent or treat ELT, but pacemaker settings can usually be reprogrammed if they are ineffective. https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 9/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate Antidromic AVRT For patients with acute symptomatic antidromic AVRT (regular and wide QRS complex) who are hemodynamically stable, our approach is as follows (see "Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome", section on 'Antidromic AVRT'): We treat with intravenous procainamide in an effort to terminate the tachycardia or, if the tachycardia persists, slow the ventricular response. This is because it is often difficult to correctly determine that the rhythm is due to antidromic AVRT and not ventricular tachycardia. If the rhythm is definitely known to be antidromic AVRT, then adenosine ( algorithm 4), verapamil, or IV beta blockers may be considered, but monitoring should be continued to ensure that there is not a rapid ventricular rate if atrial fibrillation (AF) subsequently develops after SVT termination. Irregular wide QRS complex tachyarrhythmias The irregular wide QRS complex tachycardias include ( algorithm 2): Polymorphic VT, including torsades de pointes. (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes".) Irregular narrow complex tachycardias with aberrant conduction, antegrade conduction over an accessory pathway (eg, preexcited AF), or underlying conduction delay (eg, AF with right bundle branch block). Ventricular fibrillation. Polymorphic ventricular tachycardia Polymorphic (or polymorphous) ventricular tachycardia (VT) is defined as an unstable rhythm with a continuously varying QRS complex morphology in any recorded electrocardiographic (ECG) lead. Polymorphic VT is generally a rapid and hemodynamically unstable rhythm, and urgent defibrillation is usually necessary. In addition to immediate defibrillation, further therapy is intended to treat underlying disorders and to prevent recurrences. The specific approach depends upon whether or not the QT interval on the baseline ECG is prolonged. Polymorphic VT that occurs in the setting of QT prolongation in sinus rhythm is considered as a distinct arrhythmia, called torsades de pointes. (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes".) Prompt defibrillation is indicated in patients with hemodynamically unstable torsades de pointes. In the conscious patient with recurrent episodes of torsades de pointes: https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 10/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate Intravenous magnesium sulfate (initial dose of 1 to 2 grams IV over 15 minutes, may be followed by an infusion) is first-line therapy, as it is highly effective for both treatment and prevention of recurrence of long QT-related ventricular ectopic beats that trigger torsades de pointes. The benefit is seen even in patients with normal serum magnesium concentrations at baseline. Temporary transvenous overdrive pacing (atrial or ventricular) at about 100 beats per minute is generally reserved for patients who do not respond to intravenous magnesium. In those with congenital long QT syndrome, beta blockers may be used to reduce the frequency of premature ventricular contractions and shorten the QT interval. For patients with polymorphic VT triggered by pauses or bradycardia, isoproterenol (initial dose 0.05 to 0.1 mcg/kg per minute in children and 2 mcg/minute in adults, then titrated to achieve a heart rate of 100 beats per minute) can be used as a temporizing measure to achieve a heart rate of 100 beats per minute prior to pacing. For patients with polymorphic VT and a normal baseline QT interval, the most likely cause is myocardial ischemia. Treatments may include: Prompt defibrillation in the hemodynamically unstable patient. Beta-blockers if blood pressure tolerates. Metoprolol 5 mg intravenously every five minutes, to a total of 15 mg, may be given. IV amiodarone may prevent a recurrent episode. Urgent coronary angiography and possible revascularization. Short-term mechanical circulatory support. Magnesium is less likely to be effective for polymorphic VT if the baseline QT interval is normal. If the polymorphic VT is due to catecholaminergic polymorphic ventricular tachycardia (CPVT), beta blockers should be used. If it is due to Brugada syndrome, isoproterenol should be initiated. (See "Catecholaminergic polymorphic ventricular tachycardia", section on 'Acute management' and "Brugada syndrome or pattern: Management and approach to screening of relatives".) https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 11/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate Preexcited atrial fibrillation For patients with acute symptomatic preexcited AF who are hemodynamically stable, our approach is as follows: We suggest initial medical therapy with rhythm control versus rate control. While there is no clear first-line medication for rhythm control, options include ibutilide and procainamide. (See "Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome", section on 'Atrial fibrillation with preexcitation'.) For all patients with preexcited AF, we recommend not using standard AV nodal blocking medications (ie, beta blockers, non-dihydropyridine calcium channel blockers [verapamil and diltiazem], digoxin, adenosine). Blocking the AV node may result in increased conduction of atrial impulses to the ventricle by way of the accessory pathway, increasing the ventricular rate and potentially resulting in hemodynamic instability and development of ventricular fibrillation. While preexcited AF conducts down a bypass pathway, in contrast to AVRT, the rhythm is irregularly irregular and wide complex. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Atrial fibrillation" and "Society guideline links: Arrhythmias in adults" and "Society guideline links: Ventricular arrhythmias" and "Society guideline links: Basic and advanced cardiac life support in adults" and "Society guideline links: Supraventricular arrhythmias".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 12/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Tachycardia (The Basics)" and "Patient education: Ventricular tachycardia (The Basics)" and "Patient education: Supraventricular tachycardia (SVT) (The Basics)") SUMMARY AND RECOMMENDATIONS Initial diagnostic and treatment decisions In patients who present with a symptomatic tachyarrhythmia, a 12-lead ECG should be obtained while a brief initial assessment of the patient's overall clinical assessment is performed. If the patient is hemodynamically unstable, it may be preferable to obtain only a rhythm strip prior to urgent cardioversion and not wait for a 12-lead ECG. The information acquired from these initial assessments is crucial for subsequent management of the patient (see 'Initial diagnostic and treatment decisions' above): Narrow QRS complex tachycardias If the QRS complex is narrow ( algorithm 2), the approach to acute management is based on whether the patient is stable ( algorithm 3) or unstable ( algorithm 1). (See 'Narrow QRS complex tachyarrhythmias' above.) Wide QRS complex tachycardias If the QRS complex is wide ( algorithm 2), the approach to acute management is based on whether the patient is stable or unstable; pulseless patients should be treated according to the adult cardiac life support algorithm ( algorithm 5). (See 'Wide QRS complex tachyarrhythmias' above.) ACKNOWLEDGMENTS The UpToDate editorial staff acknowledges Philip Podrid, MD, FACC, and Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 13/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate 1. Link MS. Clinical practice. Evaluation and initial treatment of supraventricular tachycardia. N Engl J Med 2012; 367:1438. 2. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2016; 67:e27. 3. Brugada J, Katritsis DG, Arbelo E, et al. 2019 ESC Guidelines for the management of patients with supraventricular tachycardiaThe Task Force for the management of patients with supraventricular tachycardia of the European Society of Cardiology (ESC). Eur Heart J 2020; 41:655. 4. Kalbfleisch SJ, el-Atassi R, Calkins H, et al. Differentiation of paroxysmal narrow QRS complex tachycardias using the 12-lead electrocardiogram. J Am Coll Cardiol 1993; 21:85. Topic 936 Version 43.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 14/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate GRAPHICS Algorithm for the evaluation of narrow QRS complex tachycardias in unstable patients IV: intravenous. Graphic 109811 Version 2.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 15/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate Algorithm for the initial ECG review and differential diagnosis of tachycardia ECG: electrocardiogram; AVNRT: atrioventricular nodal reentrant tachycardia; AVRT: atrioventricular reciprocating (bypass-tract mediated) tachycardia; AT: atrial tachycardia; SANRT: sinoatrial nodal reentrant tachycardia; AF: atrial fibrillation; AV: atrioventricular; VT: ventricular tachycardia; SVT: supraventricular tachycardia; WPW: Wolff-Parkinson-White. A narrow QRS complex is <120 milliseconds in duration, whereas a wide QRS complex is 120 milliseconds duration. Refer to UpToDate topic reviews for additional details on specific ECG findings and management of individu arrhythmias. Monomorphic VT accounts for 80% of wide QRS complex tachycardias; refer to UpToDate topic on diagnosi wide QRS complex tachycardias for additional information on discriminating VT from SVT. Graphic 117571 Version 3.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 16/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate Algorithm for the evaluation of narrow QRS complex tachycardias in stable pati AVNRT: atrioventricular nodal reentrant tachycardia; AVRT: atrioventricular reentrant tachycardia (due to an a electrocardiogram; SANRT: sinoatrial nodal reentrant tachycardia. Graphic 76920 Version 3.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 17/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate Approach to adenosine dosing in stable adults with suspected supraventricular tachyarrhythmia This figure summarizes the initial dosing, administration, and need for repeat dosing of adenosine in a hemo stable adult with suspected AV node-dependent SVT. Adenosine can be used as a diagnostic aid to identify th rhythm or as a therapy to terminate SVTs that rely on AV node conduction. AV node-dependent SVTs include A reentrant tachycardia (AVNRT) and AV reentrant (or reciprocating) tachycardia (AVRT). The management of su node-dependent SVT in hemodynamically stable adults commonly starts with a trial of 1 or more vagal mane proceeding to adenosine therapy. If the patient has hemodynamically unstable SVT, cardioversion is indicate UpToDate content for details on management of SVTs. https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 18/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate AV: atrioventricular; SVT: supraventricular tachycardia; IV: intravenous; ACC: American College of Cardiology; American Heart Association; HRS: Heart Rhythm Society; ECG: electrocardiogram. Lower adenosine doses are indicated in certain clinical settings. If central venous administration is perform adenosine dose is 3 mg; if needed (SVT persists and there is no AV block), the dose may be increased to 6 mg mg for subsequent doses. For heart transplant recipients, the initial adenosine dose is 1 mg; if needed (SVT p there is no AV block), the dose may be increased to 2 mg and then 3 mg for subsequent doses. An 18 mg dose is more likely to be required to produce AV block in patients with a body weight >70 kg, par [1] those weighing >110 kg. When a third dose is indicated, an alternative approach is to administer 12 mg (in mg) as described in the 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients with Supraventr Tachycardia. [2] SVT termination in response to adenosine includes SVT termination closely followed by SVT recurrence. Refer to UpToDate content on treatment of SVT for dosing of second-line AV nodal blockers. If the SVT pers second-line AV nodal blocker therapy, electrical cardioversion is performed, as discussed in UpToDate conten treatment of SVT. SVTs that are not AV node dependent include atrial flutter, atrial fibrillation, and atrial tachycardia. When AV is induced by adenosine, the ECG may reveal atrial activity diagnostic of these rhythms. References: 1. Prabhu S, Mackin V, McLellan AJA, et al. Determining the optimal dose of adenosine for unmasking dormant pulmonary vein co following atrial brillation ablation: Electrophysiological and hemodynamic assessment. DORMANT-AF study. J Cardiovasc Electr 28:13. 2. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Hea Society. Circulation 2016; 133:e506. Graphic 141417 Version 3.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 19/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate Medical therapy of arrhythmias associated with Wolff-Parkinson-White syndrome Arrhythmia Treatment options Contraindicated therapies Orthodromic AV reentrant tachycardia Acute termination* Unstable patients: Synchronized cardioversion Stable patients: First line: Vagal maneuvers Second line: IV adenosine Third line: IV verapamil OR IV diltiazem Other therapies: IV procainamide OR IV beta blocker; synchronized cardioversion if other therapies are ineffective or not feasible Chronic prevention First line: Catheter ablation of the accessory pathway Second line: Oral flecainide or

crucial for subsequent management of the patient (see 'Initial diagnostic and treatment decisions' above): Narrow QRS complex tachycardias If the QRS complex is narrow ( algorithm 2), the approach to acute management is based on whether the patient is stable ( algorithm 3) or unstable ( algorithm 1). (See 'Narrow QRS complex tachyarrhythmias' above.) Wide QRS complex tachycardias If the QRS complex is wide ( algorithm 2), the approach to acute management is based on whether the patient is stable or unstable; pulseless patients should be treated according to the adult cardiac life support algorithm ( algorithm 5). (See 'Wide QRS complex tachyarrhythmias' above.) ACKNOWLEDGMENTS The UpToDate editorial staff acknowledges Philip Podrid, MD, FACC, and Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 13/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate 1. Link MS. Clinical practice. Evaluation and initial treatment of supraventricular tachycardia. N Engl J Med 2012; 367:1438. 2. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2016; 67:e27. 3. Brugada J, Katritsis DG, Arbelo E, et al. 2019 ESC Guidelines for the management of patients with supraventricular tachycardiaThe Task Force for the management of patients with supraventricular tachycardia of the European Society of Cardiology (ESC). Eur Heart J 2020; 41:655. 4. Kalbfleisch SJ, el-Atassi R, Calkins H, et al. Differentiation of paroxysmal narrow QRS complex tachycardias using the 12-lead electrocardiogram. J Am Coll Cardiol 1993; 21:85. Topic 936 Version 43.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 14/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate GRAPHICS Algorithm for the evaluation of narrow QRS complex tachycardias in unstable patients IV: intravenous. Graphic 109811 Version 2.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 15/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate Algorithm for the initial ECG review and differential diagnosis of tachycardia ECG: electrocardiogram; AVNRT: atrioventricular nodal reentrant tachycardia; AVRT: atrioventricular reciprocating (bypass-tract mediated) tachycardia; AT: atrial tachycardia; SANRT: sinoatrial nodal reentrant tachycardia; AF: atrial fibrillation; AV: atrioventricular; VT: ventricular tachycardia; SVT: supraventricular tachycardia; WPW: Wolff-Parkinson-White. A narrow QRS complex is <120 milliseconds in duration, whereas a wide QRS complex is 120 milliseconds duration. Refer to UpToDate topic reviews for additional details on specific ECG findings and management of individu arrhythmias. Monomorphic VT accounts for 80% of wide QRS complex tachycardias; refer to UpToDate topic on diagnosi wide QRS complex tachycardias for additional information on discriminating VT from SVT. Graphic 117571 Version 3.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 16/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate Algorithm for the evaluation of narrow QRS complex tachycardias in stable pati AVNRT: atrioventricular nodal reentrant tachycardia; AVRT: atrioventricular reentrant tachycardia (due to an a electrocardiogram; SANRT: sinoatrial nodal reentrant tachycardia. Graphic 76920 Version 3.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 17/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate Approach to adenosine dosing in stable adults with suspected supraventricular tachyarrhythmia This figure summarizes the initial dosing, administration, and need for repeat dosing of adenosine in a hemo stable adult with suspected AV node-dependent SVT. Adenosine can be used as a diagnostic aid to identify th rhythm or as a therapy to terminate SVTs that rely on AV node conduction. AV node-dependent SVTs include A reentrant tachycardia (AVNRT) and AV reentrant (or reciprocating) tachycardia (AVRT). The management of su node-dependent SVT in hemodynamically stable adults commonly starts with a trial of 1 or more vagal mane proceeding to adenosine therapy. If the patient has hemodynamically unstable SVT, cardioversion is indicate UpToDate content for details on management of SVTs. https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 18/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate AV: atrioventricular; SVT: supraventricular tachycardia; IV: intravenous; ACC: American College of Cardiology; American Heart Association; HRS: Heart Rhythm Society; ECG: electrocardiogram. Lower adenosine doses are indicated in certain clinical settings. If central venous administration is perform adenosine dose is 3 mg; if needed (SVT persists and there is no AV block), the dose may be increased to 6 mg mg for subsequent doses. For heart transplant recipients, the initial adenosine dose is 1 mg; if needed (SVT p there is no AV block), the dose may be increased to 2 mg and then 3 mg for subsequent doses. An 18 mg dose is more likely to be required to produce AV block in patients with a body weight >70 kg, par [1] those weighing >110 kg. When a third dose is indicated, an alternative approach is to administer 12 mg (in mg) as described in the 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients with Supraventr Tachycardia. [2] SVT termination in response to adenosine includes SVT termination closely followed by SVT recurrence. Refer to UpToDate content on treatment of SVT for dosing of second-line AV nodal blockers. If the SVT pers second-line AV nodal blocker therapy, electrical cardioversion is performed, as discussed in UpToDate conten treatment of SVT. SVTs that are not AV node dependent include atrial flutter, atrial fibrillation, and atrial tachycardia. When AV is induced by adenosine, the ECG may reveal atrial activity diagnostic of these rhythms. References: 1. Prabhu S, Mackin V, McLellan AJA, et al. Determining the optimal dose of adenosine for unmasking dormant pulmonary vein co following atrial brillation ablation: Electrophysiological and hemodynamic assessment. DORMANT-AF study. J Cardiovasc Electr 28:13. 2. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Hea Society. Circulation 2016; 133:e506. Graphic 141417 Version 3.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 19/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate Medical therapy of arrhythmias associated with Wolff-Parkinson-White syndrome Arrhythmia Treatment options Contraindicated therapies Orthodromic AV reentrant tachycardia Acute termination* Unstable patients: Synchronized cardioversion Stable patients: First line: Vagal maneuvers Second line: IV adenosine Third line: IV verapamil OR IV diltiazem Other therapies: IV procainamide OR IV beta blocker; synchronized cardioversion if other therapies are ineffective or not feasible Chronic prevention First line: Catheter ablation of the accessory pathway Second line: Oral flecainide or propafenone in the absence of structural or ischemic heart disease Third line: Oral IA antiarrhythmic agent OR oral amiodarone Antidromic AV reentrant tachycardia Acute termination* Unstable patients: Adenosine, verapamil, diltiazem, Synchronized cardioversion beta blockers, digoxin should all be avoided if NOT certain of diagnosis Stable patients (if CERTAIN of the diagnosis): Same progression of therapies as acute termination of orthodromic AVRT Stable patients (if NOT certain of the diagnosis): IV procainamide, synchronized cardioversion if procainamide is ineffective or not available https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 20/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate Chronic prevention First line: Catheter ablation of the accessory pathway Digoxin Beta blockers Second line: Oral flecainide or propafenone in the absence of Verapamil, diltiazem structural or ischemic heart disease Other therapies: Oral IA antiarrhythmic agent OR oral amiodarone Pre-excited atrial fibrillation Acute termination* Unstable patients: Amiodarone Synchronized cardioversion Stable patients: Digoxin Beta blockers First line: IV ibutilide or IV procainamide Adenosine Other therapies: IC antiarrhythmic agent or dofetilide; synchronized cardioversion if other therapies are ineffective or not available Verapamil, diltiazem Chronic prevention First line: Catheter ablation or the accessory pathway Oral digoxin Second line: Oral flecainide or propafenone in the absence of structural or ischemic heart disease Third line: Oral IA antiarrhythmic agent OR oral amiodarone AVRT: atrioventricular reciprocating tachycardia; IV: intravenous; class IC: flecainide, propafenone; class IA: quinidine, procainamide, disopyramide. Cardioversion is indicated if hemodynamically unstable or drugs are ineffective. Ablation of the accessory pathway is generally preferred to cure the arrhythmia. Procainamide is the intravenous drug of choice for acute termination of suspected antidromic AVRT. If the tachycardia is definitely known to be antidromic AVRT, and it has been verified that the AV node (rather than a second accessory pathway) is acting as the retrograde limb of the circuit, one could consider treatment with an agent such as adenosine similar to therapy for orthodromic AVRT, https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 21/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate but it is rare to have all of the necessary data in the acute setting to justify use of AV nodal blocking agents. Graphic 62762 Version 7.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 22/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate Adult cardiac arrest algorithm https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 23/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 24/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate Reprinted with permission. Highlights of the 2020 American Heart Association Guidelines for CPR and ECC. Copyright 2020 American Association, Inc. Graphic 129983 Version 9.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 25/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate Revised (2018) Vaughan Williams classification of antiarrhythmic drugs abridged table Class 0 (HCN channel blockers) Ivabradine Class I (voltage-gated Na+ channel blockers) Class Ia (intermediate dissociation): Quinidine, ajmaline, disopyramide, procainamide Class Ib (rapid dissociation): Lidocaine, mexilitine Class Ic (slow dissociation): Propafenone, flecainide Class Id (late current): Ranolazine Class II (autonomic inhibitors and activators) Class IIa (beta blockers): Nonselective: carvedilol, propranolol, nadolol Selective: atenolol, bisoprolol, betaxolol, celiprolol, esmolol, metoprolol Class IIb (nonselective beta agonists): Isoproterenol Class IIc (muscarinic M2 receptor inhibitors): Atropine, anisodamine, hyoscine, scopolamine Class IId (muscarinic M2 receptor activators): Carbachol, pilocarpine, methacholine, digoxin Class IIe (adenosine A1 receptor activators): Adenosine Class III (K+ channel blockers and openers) Class IIIa (voltage dependent K+ channel blockers): Ambasilide, amiodarone, dronedarone, dofetilide, ibutilide, sotalol, vernakalant Class IIIb (metabolically dependent K+ channel openers): https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 26/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate Nicorandil, pinacidil Class IV (Ca++ handling modulators) Class IVa (surface membrane Ca++ channel blockers): Bepridil, diltiazem, verapamil Class IVb (intracellular Ca++ channel blockers): Flecainide, propafenone Class V (mechanosensitive channel blockers): No approved medications Class VI (gap junction channel blockers) No approved medications Class VII (upstream target modulators) Angiotensin converting enzyme inhibitors Angiotensin receptor blockers Omega-3 fatty acids Statins HCN: hyperpolarization-activated cyclic nucleotide-gated; Na: sodium; K: potassium; Ca: calcium. Graphic 120433 Version 3.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 27/28 7/5/23, 10:17 AM Overview of the acute management of tachyarrhythmias - UpToDate Contributor Disclosures Jordan M Prutkin, MD, MHS, FHRS No relevant financial relationship(s) with ineligible companies to disclose. James Hoekstra, MD No relevant financial relationship(s) with ineligible companies to disclose. Hugh Calkins, MD Grant/Research/Clinical Trial Support: Adagio Medical [Atrial fibrillation]; Boston Scientific [ARVC]; Farapulse [Atrial fibrillation]; Medtronic [Atrial fibrillation]. Consultant/Advisory Boards: Abbott [Atrial fibrillation]; Atricure [Atrial fibrillation]; Biosense Webster [Catheter ablation]; Boston Scientific [ARVC and atrial fibrillation]; Medtronic [Atrial fibrillation]; Sanofi [Atrial fibrillation]. Other Financial Interest: Atricure [Lecture honoraria]; Biosense Webster [Lecture honoraria]; Boston Scientific [Lecture honoraria]; Medtronic [Lecture honoraria]. All of the relevant financial relationships listed have been mitigated. Todd F Dardas, MD, MS No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 28/28

7/5/23, 10:17 AM Paroxysmal atrial fibrillation - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Paroxysmal atrial fibrillation : David Spragg, MD, FHRS, Kapil Kumar, MD : Bradley P Knight, MD, FACC : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Feb 14, 2022. INTRODUCTION Atrial fibrillation (AF) is the most common treated arrhythmia. Its prevalence in the population increases with age, and it is estimated to affect over 4 percent of the population above the age of 60 [1-3]. (See "Epidemiology, risk factors, and prevention of atrial fibrillation", section on 'Epidemiology'.) This topic will discuss the clinical presentation, etiology, natural history, and management for paroxysmal AF (PAF; also known as intermittent AF) highlighting differences and similarities compared with more sustained forms of AF. Perioperative AF is discussed separately. (See "Atrial fibrillation in patients undergoing noncardiac surgery" and "Atrial fibrillation and flutter after cardiac surgery".) DEFINITION AND PREVALENCE PAF is defined as AF that terminates spontaneously or with intervention within seven days of onset [4]. "Persistent," "longstanding persistent," and "permanent" are terms used for types of AF with episode durations longer than one week. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation", section on 'Classification and terminology'.) PAF has been reported as comprising 25 to 62 percent of AF cases [5]. The prevalence of PAF may be underestimated, as many episodes (including some lasting more than 48 hours) are asymptomatic [6,7]. Also, the duration of recurrent AF episodes vary over time in each individual, https://www.uptodate.com/contents/paroxysmal-atrial-fibrillation/print 1/18 7/5/23, 10:17 AM Paroxysmal atrial fibrillation - UpToDate and progression to persistent or permanent AF is common. (See 'Recurrence of AF' below and 'Progression to persistent AF' below.) Risk factors for developing PAF are similar to those associated with sustained AF and include age, hypertension, structural heart disease including valve disease, and obstructive sleep apnea. (See "Epidemiology, risk factors, and prevention of atrial fibrillation".) PATHOGENESIS Factors that precipitate PAF, particularly in patients without apparent structural heart disease, are incompletely understood, but are thought to be linked to premature atrial complexes (PACs; also referred to a premature atrial beats, premature supraventricular complexes, or premature supraventricular beats) and alterations in autonomic nervous system activity. (See "Mechanisms of atrial fibrillation", section on 'Mechanisms of atrial fibrillation: triggers and substrates' and "Epidemiology, risk factors, and prevention of atrial fibrillation", section on 'Potentially reversible triggers'.) Substrate alterations that may contribute to sustained AF are discussed separately. (See "Mechanisms of atrial fibrillation", section on 'Mechanisms of atrial fibrillation: triggers and substrates'.) Premature atrial complexes Studies have shown that the majority of episodes of PAF are triggered by PACs [8-10], and greater frequency of PACs is associated with greater risk of AF [11]. PAF episodes are less commonly preceded by atrial flutter, atrial tachycardia, or paroxysmal supraventricular tachycardias [10,12]. Most PACs triggering PAF originate near the ostia of the pulmonary veins (eg, in 89 and 94 percent of cases in two series [8,9]). Less commonly, foci occur in the right/left atria, the vein of Marshall, and the superior vena cava [9,13,14]. The importance of the pulmonary veins in the genesis of PAF is further demonstrated by the beneficial effect of pulmonary vein isolation. (See "Atrial fibrillation: Catheter ablation".) PACs appear to be most important as triggers of PAF in patients who have structurally normal or near-normal hearts. However, it is unclear if modification of the PAC burden can reduce AF risk. The relative importance of PAC and other triggers versus an abnormal substrate is less clear in patients with significant structural heart disease. (See "Mechanisms of atrial fibrillation", section on 'Mechanisms of atrial fibrillation: triggers and substrates'.) Autonomic nervous system The autonomic nervous system may be involved, as both parasympathetic (vagal) and sympathetic (adrenergic) tone [15] promote the development and https://www.uptodate.com/contents/paroxysmal-atrial-fibrillation/print 2/18 7/5/23, 10:17 AM Paroxysmal atrial fibrillation - UpToDate maintenance of AF [16]. (See "Mechanisms of atrial fibrillation", section on 'Role of the autonomic nervous system'.) The frequency of autonomic stimuli as a trigger for PAF has not been well studied. In a report from the European Heart Survey on AF, 1517 patients with PAF were categorized according to trigger pattern: adrenergic, vagal, or both (6, 15, and 12 percent of the total group, respectively) [17]. The prevalence of underlying heart disease (heart failure, coronary artery disease, valvular heart disease, or hypertension) was similar in the three groups. In a report of patients referred for radiofrequency ablation due to symptomatic drug-refractory PAF, the prevalence of vagal, adrenergic, or other AF was found 27, 7, and 66 percent of the time, respectively [18]. Parasympathetic tone Vagally-mediated AF commonly occurs at night or in the early morning when vagal tone is normally predominant, and it is often seen in athletic young men without apparent heart disease who have slow heart rates during rest or sleep [16,19]. The induction of AF by vagal stimulation may result from shortening of the atrial refractory period in only some areas of the atrial myocardium, thus producing heterogeneity of atrial refractoriness [20]. Acetylcholine and increased vagal tone shorten the atrial myocardial refractory period but vagal innervation of the atria is heterogeneous. Vagal stimulation and associated hypotension may rarely contribute to the development of syncope in association with episodes of AF [21]. (See 'Evaluation' below.) Sympathetic tone Increased adrenergic tone may be associated with AF in patients with underlying heart disease, associated with hyperthyroidism, and during exercise or other activity [16]. Increased sympathetic tone shortens the atrial myocardial refractory period and increases atrial myocardial conduction velocity. However, AF during exercise testing is a rare event; in a retrospective review of 3000 exercise tests, there were only four episodes of AF [22]. Sympathetic stimulation has also been suggested as the cause for AF associated with surgery, particularly cardiac surgery. (See "Cardiovascular effects of hyperthyroidism" and "Atrial fibrillation and flutter after cardiac surgery".) There is no evidence suggesting that selection of therapy based upon the type of autonomic dysfunction improves outcomes, with the exception of perioperative therapy (such as beta blockers) in patients undergoing cardiac surgery. (See "Atrial fibrillation and flutter after cardiac surgery".) CLINICAL PRESENTATION General symptoms and signs As for more sustained AF, PAF may or may not be accompanied by symptoms, and the spectrum of symptoms is broad. The most common https://www.uptodate.com/contents/paroxysmal-atrial-fibrillation/print 3/18 7/5/23, 10:17 AM Paroxysmal atrial fibrillation - UpToDate complaints include palpitations, often accompanied by dyspnea (ranging from dyspnea with exertion to dyspnea at rest), a sensation of lightheadedness, fatigue, weakness, or generalized malaise. The severity and extent of symptoms and signs are affected by the patient s underlying cardiac condition, age, and rapidity and regularity of the ventricular response. In patients with preexisting heart failure or at risk for heart failure, the loss of atrial contraction and rapid ventricular rate associated with PAF may precipitate heart failure (which may manifest as dyspnea, peripheral edema, and weight gain). (See "The management of atrial fibrillation in patients with heart failure", section on 'mechanisms of cardiac dysfunction'.) In some patients, a rapid ventricular rate may precipitate angina and/or ischemic electrocardiogram (ECG) changes which may be accompanied by troponin elevation; the presentation may be consistent with an acute coronary syndrome or demand ischemia. (See "Acute coronary syndrome: Terminology and classification" and "Elevated cardiac troponin concentration in the absence of an acute coronary syndrome".) Syncope is rare PAF rarely causes syncope [23]. In some case, syncope and PAF are both triggered by another disorder (eg, pulmonary embolism or vagal stimulus) [23,24]. The termination of PAF is occasionally associated with lightheadedness, presyncope or syncope due to a prolonged sinus pause, which may be caused by sinus node dysfunction ( waveform 1). Sinus node dysfunction is commonly associated with AF, including PAF [25]. Some patients have progressive atrial structural remodeling that may cause both sinus node dysfunction and AF, while others may develop sinus node dysfunction secondary to electrical remodeling caused by AF. (See "Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation", section on 'Symptoms' and "Sinus node dysfunction: Epidemiology, etiology, and natural history", section on 'Etiology'.) Rapid ventricular response in AF alone is rarely the cause of syncope except for patients with Wolff-Parkinson-White syndrome and a rapidly conducting accessory pathway. (See "Syncope in adults: Epidemiology, pathogenesis, and etiologies", section on 'Cardiac arrhythmias' and "Wolff- Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis", section on 'Clinical manifestations'.) EVALUATION The evaluation of patients with AF includes history, physical examination, ECG, echocardiography, and laboratory tests, as described separately. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation", section on 'Evaluation'.) https://www.uptodate.com/contents/paroxysmal-atrial-fibrillation/print 4/18 7/5/23, 10:17 AM Paroxysmal atrial fibrillation - UpToDate The ECG in AF displays rapid, low-amplitude, continuously varying fibrillatory (f) waves and no discrete p waves. The ventricular rhythm is generally irregularly irregular (lacking a repetitive pattern); however, AF can have a regular rhythm in the setting of complete heart block. The ECG in patients with AF is described in detail separately ( algorithm 1). (See "The electrocardiogram in atrial fibrillation".) NATURAL HISTORY Recurrence of AF The recurrence rate for PAF is high and has varied among studies. The incidence of recurrence in various reports has ranged from 70 percent at one year (without antiarrhythmic therapy) [26] to 60 to 90 percent at four to six years [27-30]. These reported rates likely underestimate the actual rate of recurrence, since most episodes (including some that last more than 48 hours) are asymptomatic [6,7]; such prolonged asymptomatic episodes occurred in 17 percent of patients in a report using continuous monitoring [6]. That study also showed that 40 percent of patients had episodes of AF-like symptoms in the absence of AF [6]. Risk factors for recurrent AF in patients with PAF are similar to those for recurrence after cardioversion to sinus rhythm in patients with persistent AF. In the Stroke Prevention in Atrial Fibrillation (SPAF) trial, patients with any AF recurrence were more likely to have heart failure (17 versus 8 percent) or a prior myocardial infarction (15 versus 5 percent) than patients without recurrence [31]. Echocardiographic factors associated with AF recurrence included moderate to severe left ventricular dysfunction (12 versus 3 percent in those without recurrence) and larger left atrial diameter. Compared with a normal left atrial diameter of less than 4.0 cm, the relative risk of recurrent AF was 1.6 with a left atrial diameter between 4.1 and 5.0 cm and 4.5 above 5.0 cm. Progression to persistent AF By definition, PAF spontaneously reverts to sinus rhythm within seven days of onset. The percent of patients with PAF who progress to persistent or permanent AF increases with time. In different reports, the rate of progression to persistent or permanent AF was 8, 12, 18, and 25 percent at one, two, four, and five years, respectively [30-32]. In a 2016 registry report, approximately 36 percent of patients with PAF had progressed to persistent AF within 10 years [33]. A study of patients with AF and cardiac devices found that in a minority of patients with AF, persistent AF reverted to PAF without any therapeutic intervention, underscoring our limited understanding of the natural history of AF [34]. A number of studies have attempted to identify predictors of progression to persistent AF [30,31]. In the report from SPAF cited above, the following differences were noted between the patients with paroxysmal and persistent AF [31]: patients with PAF were younger, had lower https://www.uptodate.com/contents/paroxysmal-atrial-fibrillation/print 5/18 7/5/23, 10:17 AM Paroxysmal atrial fibrillation - UpToDate rates of hypertension and heart failure, had smaller left atrial diameters (4.3 versus 4.8 cm), and were less likely to have moderate to severe left ventricular systolic dysfunction (6 versus 18 percent). For every 1 cm increase in left ventricular systolic dimension, there was a 1.8-fold greater risk of developing persistent AF. The risk of progression to persistent AF with older age was quantified in two reports showing a hazard ratio (HR) of 1.41 to 1.82 for each 10-year increase in age [30,32]. The risk of transition from PAF to persistent AF also depends upon the underlying etiology for the arrhythmia. Progression has been reported in approximately 66 percent of patients with rheumatic mitral stenosis, 40 percent with hypertension, and 27 percent with ischemic heart disease [35,36]. Risk of embolization Studies suggest that the risk of thromboembolic events is higher in patients with permanent or persistent AF, with higher AF burden (ie, daily duration or percentage of time in AF), and in the days immediately after an episode of AF. A potential limitation of prior studies is that they have been conducted in patients with implantable cardiac monitors and/or devices, potentially limiting generalizability to other patient groups. Patients with PAF and long periods of apparent sinus rhythm still may be at significant risk for thromboembolism; PAF episodes and stroke are not always temporally associated [37]. Recurrent episodes of PAF are common and may be asymptomatic [6,7,38]. Also, the surface ECG may not reflect left atrial appendage mechanical function [39]. The relationship between subclinical AF and cryptogenic stroke is discussed separately. (See "Cryptogenic stroke and embolic stroke of undetermined source (ESUS)", section on 'Occult atrial fibrillation'.) PAF versus permanent or persistent AF A 2015 meta-analysis of 12 studies of 100,000 persons stratified clinical outcomes by AF type (paroxysmal and persistent or permanent) [40]. The incidences of thromboembolism and all-cause mortality were higher with non- paroxysmal AF than with PAF (adjusted HRs 1.38 [95% CI 1.19-1.61] and 1.22 [95% CI 1.09- 1.36], respectively). In a community-based (Japan) study (not included in the above meta- analysis) of 1588 patients with PAF and 1716 with sustained AF, PAF was an independent predictor of lower stroke/systemic embolism risk (HR of approximately 0.50 in multiple models) compared with sustained AF [41]. AF burden Evidence suggests that AF burden is associated with risk of thromboembolic events, independent of CHADS -VASC or ATRIA risk scores. However, the available data do 2 not provide a clear threshold of AF burden or duration for elevated thromboembolic risk. https://www.uptodate.com/contents/paroxysmal-atrial-fibrillation/print 6/18 7/5/23, 10:17 AM Paroxysmal atrial fibrillation - UpToDate The data suggest that AF episodes lasting longer than 17 to 24 hours impart significant risk, but the risk associated with shorter AF episodes is uncertain. Daily duration of AF Studies have come to different conclusions as to a possible threshold of daily AF duration that confers a long-term risk of embolization. A pooled analysis of data on individuals with AF from five prospective studies (n = 10,016) evaluated the risk of ischemic stroke over a median follow-up of two years with the following cut-off points of AF daily duration: 5 minutes, and 1, 6, 12, and 23 hours [42]. The stroke risks were over twofold for AF duration 1 hour compared with shorter durations (HR 2.11, 95% CI 1.22-3.64). The prospective ASSERT study included 2580 subjects [43]. The initial report indicated that asymptomatic (subclinical) episodes of AF lasting >6 minutes, as compared with no episodes or episodes lasting 6 minutes, were associated with an increased risk of ischemic stroke or systemic embolism (adjusted HR 2.50; 95% CI 1.28-4.89). However, a follow-up study reporting on 2455 patients (mean follow-up of 2.5 years) found that only patients with episodes of subclinical AF lasting longer than 24 hours, compared with patients with no subclinical episodes, were at increased risk of subsequent stroke or systemic embolism (adjusted HR 3.24, 95% CI 1.51-6.95) [44]. Percentage of time in AF A retrospective study in 1900 adults with PAF who were not on anticoagulation found that the burden of AF was associated with risk of thromboembolism independent of ATRIA or CHA DS -VASc risk scores [45]. The median burden of AF 2 2 was 4.4 percent (interquartile range 1.1 to 17.2 percent). The unadjusted incidence of thromboembolism while not taking anticoagulation was 1.51 per 100 person- years. The highest tertile of AF burden ( 11.4 percent) was associated with a higher risk of thromboembolism (3.16 [95% CI 1.51-6.62]) compared with the lower tertiles. In the RATE registry, 5379 patients with pacemakers or implantable cardioverter- defibrillators were followed for a median duration of 22.9 months. Over 37,000 ECGs were adjudicated for the presence of atrial tachycardia (AT) and/or AF [46]. Runs of 3 consecutive premature atrial complexes (PACs) were defined as AT/AF and short episodes were defined as runs <15 to 20 seconds. Patients with clinical events (emergency department visits/hospitalizations for heart failure, atrial or ventricular arrhythmia, stroke or transient ischemic attack [TIA], and syncope) were significantly more likely than those without to have long AT/AF episodes. In addition, patients with clinical events were no more likely than those without to https://www.uptodate.com/contents/paroxysmal-atrial-fibrillation/print 7/18 7/5/23, 10:17 AM Paroxysmal atrial fibrillation - UpToDate have short AT/AF. The risk of stroke plus TIA was lower, but not statistically significantly so, in patients with only short compared with only long duration AT/AF. Temporal association between AF presentation and stroke onset Two case-cross-over studies have examined the association between time in AF since onset and stroke risk. One study linked a commercial database of continuous rhythm recording to Veterans Administration clinical records. Stroke risk was highest during the five days immediately after an episode of AF and waned over the 30 days following the episode [47]. Another study linked a large health insurance database with implantable cardiac device data in 890 patients with stroke [48]. This study had similar findings to the above Veterans study in that five hours or more of AF was associated with increased stroke risk (odds ratio [OR], 3.71 95% CI 2.06-6.70). This study also showed that stroke risk was highest during days 1 to 5 following the start of AF (OR 5.00; 95% CI, 2.62-9.55). Furthermore, AF >23 hours per day on a given day was associated with a high risk of stroke (OR 5.00, 95% CI 2.08-12.01). MANAGEMENT The management for patients with PAF is similar to that for the general population of patients with AF. Important considerations are the duration of AF and the presence or absence of symptoms during episodes. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation".) Prevention of recurrence The decision to start antiarrhythmic drug therapy in patients with PAF is similar to that in the general population of patients with AF. (See "Management of atrial fibrillation: Rhythm control versus rate control".) Patients with frequent or highly symptomatic PAF may require pharmacologic or nonpharmacologic therapy to prevent recurrence. The choice between these therapies is discussed separately (See "Maintenance of sinus rhythm in atrial fibrillation: Catheter ablation versus antiarrhythmic drug therapy".): The choice of drug therapy is determined by associated clinical conditions as well as patient preference. (See "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations".) Catheter ablation is the primary nonpharmacologic approach to prevent recurrent AF. Surgical-based ablation techniques such as the Maze procedure are generally reserved for PAF patients undergoing other cardiac surgical procedures (See "Atrial fibrillation: Catheter ablation" and "Atrial fibrillation: Surgical ablation".) https://www.uptodate.com/contents/paroxysmal-atrial-fibrillation/print 8/18 7/5/23, 10:17 AM Paroxysmal atrial fibrillation - UpToDate Rate control Daily use of a rate-controlling agent such as a beta blocker, calcium channel blocker, or digoxin is generally not needed for PAF. However, for patients with highly symptomatic episodes, such drugs can be used for acute episodes, and some patients are maintained on one of these drugs to control the ventricular rate when PAF occurs. (See "Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy".) Anticoagulation For patients with PAF, the approach for deciding whether to anticoagulate to reduce the risk of thromboembolism is similar to that for patients with persistent or permanent AF. The burden of AF (duration and frequency of episodes) is a factor for decision-making only for selected patients in whom the balance of benefit versus risk of anticoagulation is uncertain, recognizing that it may not be possible to accurately estimate AF burden, as discussed separately. (See "Atrial fibrillation in adults: Selection of candidates for anticoagulation", section on 'Paroxysmal AF'.) Sinus node dysfunction Patients with frequent AF episodes and long, symptomatic post- conversion pauses due to sinus dysfunction are commonly treated with a pacemaker (along with rate or rhythm control) (see "Sinus node dysfunction: Treatment", section on 'Permanent pacing'). A possible alternative option for selected patients with PAF and minimally symptomatic sinus node dysfunction with relatively short pauses (eg, 2 to 3 seconds) is catheter ablation to minimize AF episodes and associated post-conversion pauses. However, since ablation is not a cure for AF, a pacemaker may still be required if there are symptomatic pauses. (See "Sinus node dysfunction: Treatment", section on 'Catheter ablation'.) The management of sinus node dysfunction is discussed further separately. (See "Sinus node dysfunction: Treatment", section on 'Treatment'.) Management of heart failure Management of heart failure in patients with AF is discussed separately. (See "The management of atrial fibrillation in patients with heart failure".) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Atrial fibrillation" and "Society guideline links: Arrhythmias in adults".) SUMMARY AND RECOMMENDATIONS https://www.uptodate.com/contents/paroxysmal-atrial-fibrillation/print 9/18 7/5/23, 10:17 AM Paroxysmal atrial fibrillation - UpToDate Definition Paroxysmal atrial fibrillation (PAF; also known as intermittent AF) is defined as AF that terminates spontaneously or with intervention within seven days of onset. (See 'Definition and prevalence' above.) Precipitants Factors that precipitate PAF are incompletely understood but are thought to be premature atrial complexes (PACs) and alterations in autonomic nervous system activity. (See 'Pathogenesis' above.) Symptoms Like sustained AF, PAF may or may not be accompanied by symptoms, and the spectrum of symptoms is broad. The most common complaints include palpitations, often accompanied by dyspnea, a sensation of lightheadedness, fatigue, weakness, or generalized malaise. PAF may precipitate angina and/or ischemic electrocardiogram changes. PAF rarely causes syncope. (See 'Clinical presentation' above.) Recurrence Most patients with PAF have one or more recurrences in the next year. Over one-third of patients with PAF may progress to persistent AF in 10 years, but the risk of progression increases with older age and presence of cardiovascular conditions such as rheumatic mitral stenosis and hypertension. (See 'Natural history' above.) Thromboembolic risk Studies suggest that the risk of thromboembolic events in patients with PAF is lower than the risk in patients with persistent or permanent AF, is associated with AF burden (ie, percentage of time in AF), and is highest in the days soon after an episode of AF. However, the available data do not provide a clear threshold of AF burden or duration for elevated thromboembolic risk. The data suggest that AF episodes lasting longer than 17 to 24 hours impart significant risk, but the risk associated with shorter AF episodes is uncertain. (See 'Risk of embolization' above.) Management The management of the arrhythmia in patients with PAF is similar to that for the general population of patients with AF. Important considerations are the duration of AF and the presence or absence of symptoms during episodes. (See 'Management' above and "Atrial fibrillation: Overview and management of new-onset atrial fibrillation".) Anticoagulation For patients with PAF, the approach for deciding whether to anticoagulate to reduce the risk of thromboembolism is similar to that for patients with persistent or permanent AF. (See "Atrial fibrillation in adults: Selection of candidates for anticoagulation", section on 'Paroxysmal AF'.) The burden of AF (duration and frequency of episodes) is a factor for decision-making only for selected patients in whom the balance of benefit versus risk of anticoagulation is https://www.uptodate.com/contents/paroxysmal-atrial-fibrillation/print 10/18 7/5/23, 10:17 AM Paroxysmal atrial fibrillation - UpToDate uncertain, recognizing that it may not be possible to accurately estimate AF burden, as discussed separately. (See 'Anticoagulation' above.) ACKNOWLEDGMENT The UpToDate editorial staff thank Alan Cheng, MD, and Philip J Podrid, MD, FACC, who contributed to earlier versions of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Halperin JL, Hart RG. Atrial fibrillation and stroke: new ideas, persisting dilemmas. Stroke 1988; 19:937. 2. Kannel WB, Abbott RD, Savage DD, McNamara PM. Epidemiologic features of chronic atrial fibrillation: the Framingham study. N Engl J Med 1982; 306:1018. 3. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation: a major contributor to stroke in the elderly. The Framingham Study. Arch Intern Med 1987; 147:1561. 4. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2014; 64:e1. 5. Lip GY, Hee FL. Paroxysmal atrial fibrillation. QJM 2001; 94:665. 6. Israel CW, Gr nefeld G, Ehrlich JR, et al. Long-term risk of recurrent atrial fibrillation as documented by an implantable monitoring device: implications for optimal patient care. J Am Coll Cardiol 2004; 43:47. 7. Page RL, Wilkinson WE, Clair WK, et al. Asymptomatic arrhythmias in patients with symptomatic paroxysmal atrial fibrillation and paroxysmal supraventricular tachycardia. Circulation 1994; 89:224. 8. Chen SA, Hsieh MH, Tai CT, et al. Initiation of atrial fibrillation by ectopic beats originating from the pulmonary veins: electrophysiological characteristics, pharmacological responses, and effects of radiofrequency ablation. Circulation 1999; 100:1879. 9. Ha ssaguerre M, Ja s P, Shah DC, et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med 1998; 339:659. https://www.uptodate.com/contents/paroxysmal-atrial-fibrillation/print 11/18 7/5/23, 10:17 AM Paroxysmal atrial fibrillation - UpToDate 10. Kolb C, N rnberger S, Ndrepepa G, et al. Modes of initiation of paroxysmal atrial fibrillation from analysis of spontaneously occurring episodes using a 12-lead Holter monitoring system. Am J Cardiol 2001; 88:853. 11. Dewland TA, Vittinghoff E, Mandyam MC, et al. Atrial ectopy as a predictor of incident atrial fibrillation: a cohort study. Ann Intern Med 2013; 159:721. 12. Sauer WH, Alonso C, Zado E, et al. Atrioventricular nodal reentrant tachycardia in patients referred for atrial fibrillation ablation: response to ablation that incorporates slow-pathway modification. Circulation 2006; 114:191. 13. Hwang C, Wu TJ, Doshi RN, et al. Vein of marshall cannulation for the analysis of electrical activity in patients with focal atrial fibrillation. Circulation 2000; 101:1503. 14. Lin WS, Tai CT, Hsieh MH, et al. Catheter ablation of paroxysmal atrial fibrillation initiated by non-pulmonary vein ectopy. Circulation 2003; 107:3176. 15. Coumel P. Cardiac arrhythmias and the autonomic nervous system. J Cardiovasc Electrophysiol 1993; 4:338. 16. Coumel P. Autonomic influences in atrial tachyarrhythmias. J Cardiovasc Electrophysiol 1996; 7:999. 17. de Vos CB, Nieuwlaat R, Crijns HJ, et al. Autonomic trigger patterns and anti-arrhythmic treatment of paroxysmal atrial fibrillation: data from the Euro Heart Survey. Eur Heart J 2008; 29:632. 18. Rosso R, Sparks PB, Morton JB, et al. Vagal paroxysmal atrial fibrillation: prevalence and ablation outcome in patients without structural heart disease. J Cardiovasc Electrophysiol 2010; 21:489. 19. Herweg B, Dalal P, Nagy B, Schweitzer P. Power spectral analysis of heart period variability of preceding sinus rhythm before initiation of paroxysmal atrial fibrillation. Am J Cardiol 1998; 82:869. 20. Elvan A, Pride HP, Eble JN, Zipes DP. Radiofrequency catheter ablation of the atria reduces inducibility and duration of atrial fibrillation in dogs. Circulation 1995; 91:2235. 21. Brignole M, Gianfranchi L, Menozzi C, et al. Role of autonomic reflexes in syncope associated with paroxysmal atrial fibrillation. J Am Coll Cardiol 1993; 22:1123. 22. Wright RF, Graboys TB. Provocation of supraventricular tachycardia during exercise stress testing. Cardiovasc Rev Rep 1980; 1:57. 23. Hussain S, Jerry C, Luck . Syncope And Atrial Fibrillation: Which Is The Chicken And Which Is The Egg? J Atr Fibrillation 2015; 8:1175. https://www.uptodate.com/contents/paroxysmal-atrial-fibrillation/print 12/18 7/5/23, 10:17 AM Paroxysmal atrial fibrillation - UpToDate 24. Keller K, Hobohm L, M nzel T, Ostad MA. Syncope in the German Nationwide inpatient sample - Syncope in atrial fibrillation/flutter is related to pulmonary embolism and is accompanied by higher in-hospital mortality. Eur J Intern Med 2019; 62:29. 25. John RM, Kumar S. Sinus Node and Atrial Arrhythmias. Circulation 2016; 133:1892. 26. Coplen SE, Antman EM, Berlin JA, et al. Efficacy and safety of quinidine therapy for maintenance of sinus rhythm after cardioversion. A meta-analysis of randomized control trials. Circulation 1990; 82:1106. 27. Rostagno C, Bacci F, Martelli M, et al. Clinical course of lone atrial fibrillation since first symptomatic arrhythmic episode. Am J Cardiol 1995; 76:837. 28. Davidson E, Weinberger I, Rotenberg Z, et al. Atrial fibrillation. Cause and time of onset. Arch Intern Med 1989; 149:457. 29. Takahashi N, Seki A, Imataka K, Fujii J. Clinical features of paroxysmal atrial fibrillation. An observation of 94 patients. Jpn Heart J 1981; 22:143. 30. Kerr CR, Humphries KH, Talajic M, et al. Progression to chronic atrial fibrillation after the initial diagnosis of paroxysmal atrial fibrillation: results from the Canadian Registry of Atrial Fibrillation. Am Heart J 2005; 149:489. 31. Flaker GC, Fletcher KA, Rothbart RM, et al. Clinical and echocardiographic features of intermittent atrial fibrillation that predict recurrent atrial fibrillation. Stroke Prevention in Atrial Fibrillation (SPAF) Investigators. Am J Cardiol 1995; 76:355. 32. Al-Khatib SM, Wilkinson WE, Sanders LL, et al. Observations on the transition from intermittent to permanent atrial fibrillation. Am Heart J 2000; 140:142. 33. Padfield GJ, Steinberg C, Swampillai J, et al. Progression of paroxysmal to persistent atrial fibrillation: 10-year follow-up in the Canadian Registry of Atrial Fibrillation. Heart Rhythm 2017; 14:801. 34. Sugihara C, Veasey R, Freemantle N, et al. The development of AF over time in patients with permanent pacemakers: objective assessment with pacemaker diagnostics demonstrates distinct patterns of AF. Europace 2015; 17:864. 35. Godtfredsen J. Atrial fibrillation Etiology, course and prognosis: A followup of 1212 patien ts, University of Denmark, Copenhagen 1975. 36. Aboaf AP, Wolf PS. Paroxysmal atrial fibrillation. A common but neglected entity. Arch Intern Med 1996; 156:362. 37. Daoud EG, Glotzer TV, Wyse DG, et al. Temporal relationship of atrial tachyarrhythmias, cerebrovascular events, and systemic emboli based on stored device data: a subgroup analysis of TRENDS. Heart Rhythm 2011; 8:1416. https://www.uptodate.com/contents/paroxysmal-atrial-fibrillation/print 13/18 7/5/23, 10:17 AM Paroxysmal atrial fibrillation - UpToDate 38. Diederichsen SZ, Haugan KJ, Brandes A, et al. Natural History of Subclinical Atrial Fibrillation Detected by Implanted Loop Recorders. J Am Coll Cardiol 2019; 74:2771. 39. Warraich HJ, Gandhavadi M, Manning WJ. Mechanical discordance of the left atrium and appendage: a novel mechanism of stroke in paroxysmal atrial fibrillation. Stroke 2014; 45:1481. 40. Ganesan AN, Chew DP, Hartshorne T, et al. The impact of atrial fibrillation type on the risk of thromboembolism, mortality, and bleeding: a systematic review and meta-analysis. Eur Heart J 2016; 37:1591. 41. Takabayashi K, Hamatani Y, Yamashita Y, et al. Incidence of Stroke or Systemic Embolism in Paroxysmal Versus Sustained Atrial Fibrillation: The Fushimi Atrial Fibrillation Registry. Stroke 2015; 46:3354. 42. Boriani G, Glotzer TV, Santini M, et al. Device-detected atrial fibrillation and risk for stroke: an analysis of >10,000 patients from the SOS AF project (Stroke preventiOn Strategies based on Atrial Fibrillation information from implanted devices). Eur Heart J 2014; 35:508. 43. Healey JS, Connolly SJ, Gold MR, et al. Subclinical atrial fibrillation and the risk of stroke. N Engl J Med 2012; 366:120. 44. Van Gelder IC, Healey JS, Crijns HJGM, et al. Duration of device-detected subclinical atrial fibrillation and occurrence of stroke in ASSERT. Eur Heart J 2017; 38:1339. 45. Go AS, Reynolds K, Yang J, et al. Association of Burden of Atrial Fibrillation With Risk of Ischemic Stroke in Adults With Paroxysmal Atrial Fibrillation: The KP-RHYTHM Study. JAMA Cardiol 2018; 3:601. 46. Swiryn S, Orlov MV, Benditt DG, et al. Clinical Implications of Brief Device-Detected Atrial Tachyarrhythmias in a Cardiac Rhythm Management Device Population: Results from the Registry of Atrial Tachycardia and Atrial Fibrillation Episodes. Circulation 2016; 134:1130. 47. Turakhia MP, Ziegler PD, Schmitt SK, et al. Atrial Fibrillation Burden and Short-Term Risk of Stroke: Case-Crossover Analysis of Continuously Recorded Heart Rhythm From Cardiac Electronic Implanted Devices. Circ Arrhythm Electrophysiol 2015; 8:1040. 48. Singer DE, Ziegler PD, Koehler JL, et al. Temporal Association Between Episodes of Atrial Fibrillation and Risk of Ischemic Stroke. JAMA Cardiol 2021; 6:1364. Topic 956 Version 36.0 https://www.uptodate.com/contents/paroxysmal-atrial-fibrillation/print 14/18 7/5/23, 10:17 AM Paroxysmal atrial fibrillation - UpToDate GRAPHICS Long pause after episode of paroxysmal atrial fibrillation An example of a long postconversion pause after spontaneous conversion of an episode of paroxysmal atrial fibrillation. Graphic 132571 Version 2.0 https://www.uptodate.com/contents/paroxysmal-atrial-fibrillation/print 15/18 7/5/23, 10:17 AM Paroxysmal atrial fibrillation - UpToDate Approach to diagnosis of an irregularly irregular supraventricular rhythm* This graphic describes an approach to distinguishing atrial fibrillation (identified with a thick border) from other causes of an irregularly irregular supraventricular rhythm. While atrial fibrillation is the rhythm most commonly described as irregularly irregular, mimics of atrial fibrillation should be excluded when an irregularly irregular rhythm is identified. Of note, atrial fibrillation uncommonly occurs with a regular ventricular rhythm, as described in UpToDate content on the electrocardiogram in atrial fibrillation. ECG: electrocardiogram; AV: atrioventricular; PVCs: premature ventricular complexes; PACs: premature atrial complexes. Refer to UpToDate content on distinguishing supraventricular from ventricular rhythms. If no atrial activity is detected or the morphology of atrial activity is unclear, use ECG amplification (digital magnification or increase in gain for the entire ECG signal). https://www.uptodate.com/contents/paroxysmal-atrial-fibrillation/print 16/18 7/5/23, 10:17 AM Paroxysmal atrial fibrillation - UpToDate The ventricular rhythm associated with Mobitz I or II second-degree AV block is not irregularly irregular since there is a pattern to the variation in ventricular rate, but this pattern may not be immediately recognized. Graphic 132103 Version 1.0 https://www.uptodate.com/contents/paroxysmal-atrial-fibrillation/print 17/18 7/5/23, 10:17 AM Paroxysmal atrial fibrillation - UpToDate Contributor Disclosures

of preceding sinus rhythm before initiation of paroxysmal atrial fibrillation. Am J Cardiol 1998; 82:869. 20. Elvan A, Pride HP, Eble JN, Zipes DP. Radiofrequency catheter ablation of the atria reduces inducibility and duration of atrial fibrillation in dogs. Circulation 1995; 91:2235. 21. Brignole M, Gianfranchi L, Menozzi C, et al. Role of autonomic reflexes in syncope associated with paroxysmal atrial fibrillation. J Am Coll Cardiol 1993; 22:1123. 22. Wright RF, Graboys TB. Provocation of supraventricular tachycardia during exercise stress testing. Cardiovasc Rev Rep 1980; 1:57. 23. Hussain S, Jerry C, Luck . Syncope And Atrial Fibrillation: Which Is The Chicken And Which Is The Egg? J Atr Fibrillation 2015; 8:1175. https://www.uptodate.com/contents/paroxysmal-atrial-fibrillation/print 12/18 7/5/23, 10:17 AM Paroxysmal atrial fibrillation - UpToDate 24. Keller K, Hobohm L, M nzel T, Ostad MA. Syncope in the German Nationwide inpatient sample - Syncope in atrial fibrillation/flutter is related to pulmonary embolism and is accompanied by higher in-hospital mortality. Eur J Intern Med 2019; 62:29. 25. John RM, Kumar S. Sinus Node and Atrial Arrhythmias. Circulation 2016; 133:1892. 26. Coplen SE, Antman EM, Berlin JA, et al. Efficacy and safety of quinidine therapy for maintenance of sinus rhythm after cardioversion. A meta-analysis of randomized control trials. Circulation 1990; 82:1106. 27. Rostagno C, Bacci F, Martelli M, et al. Clinical course of lone atrial fibrillation since first symptomatic arrhythmic episode. Am J Cardiol 1995; 76:837. 28. Davidson E, Weinberger I, Rotenberg Z, et al. Atrial fibrillation. Cause and time of onset. Arch Intern Med 1989; 149:457. 29. Takahashi N, Seki A, Imataka K, Fujii J. Clinical features of paroxysmal atrial fibrillation. An observation of 94 patients. Jpn Heart J 1981; 22:143. 30. Kerr CR, Humphries KH, Talajic M, et al. Progression to chronic atrial fibrillation after the initial diagnosis of paroxysmal atrial fibrillation: results from the Canadian Registry of Atrial Fibrillation. Am Heart J 2005; 149:489. 31. Flaker GC, Fletcher KA, Rothbart RM, et al. Clinical and echocardiographic features of intermittent atrial fibrillation that predict recurrent atrial fibrillation. Stroke Prevention in Atrial Fibrillation (SPAF) Investigators. Am J Cardiol 1995; 76:355. 32. Al-Khatib SM, Wilkinson WE, Sanders LL, et al. Observations on the transition from intermittent to permanent atrial fibrillation. Am Heart J 2000; 140:142. 33. Padfield GJ, Steinberg C, Swampillai J, et al. Progression of paroxysmal to persistent atrial fibrillation: 10-year follow-up in the Canadian Registry of Atrial Fibrillation. Heart Rhythm 2017; 14:801. 34. Sugihara C, Veasey R, Freemantle N, et al. The development of AF over time in patients with permanent pacemakers: objective assessment with pacemaker diagnostics demonstrates distinct patterns of AF. Europace 2015; 17:864. 35. Godtfredsen J. Atrial fibrillation Etiology, course and prognosis: A followup of 1212 patien ts, University of Denmark, Copenhagen 1975. 36. Aboaf AP, Wolf PS. Paroxysmal atrial fibrillation. A common but neglected entity. Arch Intern Med 1996; 156:362. 37. Daoud EG, Glotzer TV, Wyse DG, et al. Temporal relationship of atrial tachyarrhythmias, cerebrovascular events, and systemic emboli based on stored device data: a subgroup analysis of TRENDS. Heart Rhythm 2011; 8:1416. https://www.uptodate.com/contents/paroxysmal-atrial-fibrillation/print 13/18 7/5/23, 10:17 AM Paroxysmal atrial fibrillation - UpToDate 38. Diederichsen SZ, Haugan KJ, Brandes A, et al. Natural History of Subclinical Atrial Fibrillation Detected by Implanted Loop Recorders. J Am Coll Cardiol 2019; 74:2771. 39. Warraich HJ, Gandhavadi M, Manning WJ. Mechanical discordance of the left atrium and appendage: a novel mechanism of stroke in paroxysmal atrial fibrillation. Stroke 2014; 45:1481. 40. Ganesan AN, Chew DP, Hartshorne T, et al. The impact of atrial fibrillation type on the risk of thromboembolism, mortality, and bleeding: a systematic review and meta-analysis. Eur Heart J 2016; 37:1591. 41. Takabayashi K, Hamatani Y, Yamashita Y, et al. Incidence of Stroke or Systemic Embolism in Paroxysmal Versus Sustained Atrial Fibrillation: The Fushimi Atrial Fibrillation Registry. Stroke 2015; 46:3354. 42. Boriani G, Glotzer TV, Santini M, et al. Device-detected atrial fibrillation and risk for stroke: an analysis of >10,000 patients from the SOS AF project (Stroke preventiOn Strategies based on Atrial Fibrillation information from implanted devices). Eur Heart J 2014; 35:508. 43. Healey JS, Connolly SJ, Gold MR, et al. Subclinical atrial fibrillation and the risk of stroke. N Engl J Med 2012; 366:120. 44. Van Gelder IC, Healey JS, Crijns HJGM, et al. Duration of device-detected subclinical atrial fibrillation and occurrence of stroke in ASSERT. Eur Heart J 2017; 38:1339. 45. Go AS, Reynolds K, Yang J, et al. Association of Burden of Atrial Fibrillation With Risk of Ischemic Stroke in Adults With Paroxysmal Atrial Fibrillation: The KP-RHYTHM Study. JAMA Cardiol 2018; 3:601. 46. Swiryn S, Orlov MV, Benditt DG, et al. Clinical Implications of Brief Device-Detected Atrial Tachyarrhythmias in a Cardiac Rhythm Management Device Population: Results from the Registry of Atrial Tachycardia and Atrial Fibrillation Episodes. Circulation 2016; 134:1130. 47. Turakhia MP, Ziegler PD, Schmitt SK, et al. Atrial Fibrillation Burden and Short-Term Risk of Stroke: Case-Crossover Analysis of Continuously Recorded Heart Rhythm From Cardiac Electronic Implanted Devices. Circ Arrhythm Electrophysiol 2015; 8:1040. 48. Singer DE, Ziegler PD, Koehler JL, et al. Temporal Association Between Episodes of Atrial Fibrillation and Risk of Ischemic Stroke. JAMA Cardiol 2021; 6:1364. Topic 956 Version 36.0 https://www.uptodate.com/contents/paroxysmal-atrial-fibrillation/print 14/18 7/5/23, 10:17 AM Paroxysmal atrial fibrillation - UpToDate GRAPHICS Long pause after episode of paroxysmal atrial fibrillation An example of a long postconversion pause after spontaneous conversion of an episode of paroxysmal atrial fibrillation. Graphic 132571 Version 2.0 https://www.uptodate.com/contents/paroxysmal-atrial-fibrillation/print 15/18 7/5/23, 10:17 AM Paroxysmal atrial fibrillation - UpToDate Approach to diagnosis of an irregularly irregular supraventricular rhythm* This graphic describes an approach to distinguishing atrial fibrillation (identified with a thick border) from other causes of an irregularly irregular supraventricular rhythm. While atrial fibrillation is the rhythm most commonly described as irregularly irregular, mimics of atrial fibrillation should be excluded when an irregularly irregular rhythm is identified. Of note, atrial fibrillation uncommonly occurs with a regular ventricular rhythm, as described in UpToDate content on the electrocardiogram in atrial fibrillation. ECG: electrocardiogram; AV: atrioventricular; PVCs: premature ventricular complexes; PACs: premature atrial complexes. Refer to UpToDate content on distinguishing supraventricular from ventricular rhythms. If no atrial activity is detected or the morphology of atrial activity is unclear, use ECG amplification (digital magnification or increase in gain for the entire ECG signal). https://www.uptodate.com/contents/paroxysmal-atrial-fibrillation/print 16/18 7/5/23, 10:17 AM Paroxysmal atrial fibrillation - UpToDate The ventricular rhythm associated with Mobitz I or II second-degree AV block is not irregularly irregular since there is a pattern to the variation in ventricular rate, but this pattern may not be immediately recognized. Graphic 132103 Version 1.0 https://www.uptodate.com/contents/paroxysmal-atrial-fibrillation/print 17/18 7/5/23, 10:17 AM Paroxysmal atrial fibrillation - UpToDate Contributor Disclosures David Spragg, MD, FHRS No relevant financial relationship(s) with ineligible companies to disclose. Kapil Kumar, MD No relevant financial relationship(s) with ineligible companies to disclose. Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/paroxysmal-atrial-fibrillation/print 18/18

7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Perioperative management of patients receiving anticoagulants : James D Douketis, MD, FRCPC, FACP, FCCP, Gregory YH Lip, MD, FRCPE, FESC, FACC : Lawrence LK Leung, MD : Jennifer S Tirnauer, MD All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Nov 18, 2022. INTRODUCTION The management of anticoagulation in patients undergoing surgical procedures is challenging, since interrupting anticoagulation for a procedure transiently increases the risk of thromboembolism. At the same time, surgery and invasive procedures have associated bleeding risks that are increased by the anticoagulant(s) administered for thromboembolism prevention. If the patient bleeds from the procedure, their anticoagulant may need to be discontinued for a longer period, resulting in a longer period of increased thromboembolic risk. A balance between reducing the risk of thromboembolism and preventing excessive bleeding must be reached for each patient. Other clinical issues are anticoagulant specific. For those taking a vitamin K antagonist, it takes several days until the anticoagulant effect is reduced and then re-established perioperatively; the risks and benefits of "bridging" with a shorter acting agent, such as heparin, during this time are unclear. The direct oral anticoagulants (DOACs; dabigatran, factor Xa inhibitors [rivaroxaban, apixaban, edoxaban]) have shorter half-lives, making them easier to discontinue and resume rapidly. Our approach to managing ongoing anticoagulation in patients undergoing surgery or an invasive procedure is discussed here. Additional details regarding the use of specific anticoagulants and antiplatelet agents are presented separately. Vitamin K antagonists (See "Warfarin and other VKAs: Dosing and adverse effects".) https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 1/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Heparins (See "Heparin and LMW heparin: Dosing and adverse effects".) Direct thrombin inhibitors and direct factor Xa inhibitors (See "Direct oral anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing and adverse effects".) Antiplatelet agents (See "Perioperative medication management", section on 'Medications affecting hemostasis'.) Specific recommendations for individuals with prosthetic heart valves are discussed separately. (See "Anticoagulation for prosthetic heart valves: Management of bleeding and invasive procedures".) Perioperative venous thromboembolism prevention in patients not receiving ongoing anticoagulation is also discussed separately. (See "Prevention of venous thromboembolic disease in adult nonorthopedic surgical patients" and "Prevention of venous thromboembolism in adults undergoing hip fracture repair or hip or knee replacement" and "Prevention of venous thromboembolism (VTE) in adults undergoing non-major extremity orthopedic surgery".) OVERVIEW OF OUR APPROACH General approach Interruption of anticoagulation temporarily increases thromboembolic risk, and continuing anticoagulation increases the risk of bleeding associated with invasive procedures; both of these outcomes can increase mortality rates [1-6]. Our approach to perioperative management of anticoagulation takes into account and balances these risks, along with specific features of the anticoagulant the patient is taking [7]. Much of our approach is based on nonrandomized and observational studies and expert opinion, as there are few large, well-designed, randomized, placebo-controlled trials in this clinical domain. In addition, thrombotic and bleeding risks may vary depending on individual circumstances, and data from randomized trials or well-designed observational studies are not available to guide practice in many settings. Thus, our approach discussed herein should be used as clinical guidance and should not substitute for clinician judgment in decisions about perioperative anticoagulant management for individual patients. Our approach to decision-making is outlined as follows; this is presented in an interactive format at Thrombosis Canada; a similar approach is provided on the IPRO-MAPPP website in the United States: Estimate thromboembolic risk The higher the thromboembolic risk, the greater the importance of minimizing the interval without anticoagulation ( table 1). We estimate https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 2/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate thromboembolic risk for patients with atrial fibrillation based on age and comorbidities. For those with a recent deep vein thrombosis (DVT) or pulmonary embolism (PE), we estimate the risk based on the interval since diagnosis. For patients with a recent (within the previous one to three months) stroke, PE or DVT, in whom the risk of recurrent thromboembolism is markedly increased, we prefer to delay surgery when possible until the risk lessens and is close to baseline. (See 'Estimating thromboembolic risk' below.) Estimate bleeding risk A higher bleeding risk confers a greater need for perioperative hemostasis and hence a longer period of anticoagulant interruption. Bleeding risk is dominated by the type and urgency of surgery; some patient comorbidities also contribute. Procedures with a low bleeding risk (eg, dental extractions, minor skin surgery) often can be performed without interruption of anticoagulation. (See 'Estimating procedural bleeding risk' below and 'Deciding whether to interrupt anticoagulation' below.) Determine the timing of anticoagulant interruption The timing of anticoagulant interruption depends on the specific agent the patient is receiving. Warfarin requires earlier discontinuation than the DOACs (dabigatran, rivaroxaban, apixaban, edoxaban). Additional considerations may be required in individuals with reduced kidney and/or liver function. (See 'Timing of anticoagulant interruption' below.) Determine whether to use bridging anticoagulation For most patients, we do not use bridging anticoagulation (use of a short-acting parenteral agent to reduce the interval without anticoagulation), because it increases bleeding risk without reducing the rate of thromboembolism. However, some patients on warfarin with an especially high thromboembolic risk (eg, mechanical heart valve, recent stroke) may benefit from bridging. (See 'Bridging anticoagulation' below.) Example cases The following examples illustrate our decision-making process using this approach in general terms; management of every case must be individualized based on the judgment of the treating clinicians: A 76-year-old female with nonvalvular atrial fibrillation, hypertension, and prior stroke three months ago, receiving warfarin, requires elective hip replacement with neuraxial anesthesia; kidney function is normal, and weight is 75 kg. This patient has a very high thromboembolic risk ( table 1) and a high bleeding risk ( table 2). Omit warfarin for five days before the procedure (last dose on preoperative day minus 6). https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 3/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Preoperative bridging with therapeutic-dose low molecular weight (LMW) heparin (eg, dalteparin, 100 units/kg [7500 units] subcutaneously twice daily) starting on preoperative day minus 3, with last dose on the morning of day minus 1. Resume warfarin within 24 hours after surgery (usual dose). Postoperative low-dose LMW heparin for venous thromboembolism (VTE) prevention (eg, dalteparin, 5000 units subcutaneously once daily) within 24 hours after surgery until postoperative bridging is started. Postoperative bridging on postoperative day 2 or 3, when hemostasis is secured (eg, dalteparin, 100 units/kg [7500 units] subcutaneously twice daily); continue for at least four to five days, until the international normalized ratio (INR) is therapeutic. A 70-year-old male with nonvalvular atrial fibrillation, diabetes, and hypertension (CHA DS -VASc score = 3) receiving dabigatran who requires a colon resection for cancer; 2 2 kidney function is normal. This patient has a moderate thrombotic risk ( table 1) and a high bleeding risk ( table 2). Omit dabigatran for two days before the procedure (last dose of dabigatran on day minus 3). No bridging. Resume dabigatran on postoperative day 2 or 3, when patient is able to take medication by mouth. Use prophylactic-dose LMW heparin for VTE prophylaxis for the first two to three postoperative days. A 55-year-old male with an unprovoked DVT four months ago, receiving apixaban 5 mg twice daily, who requires a colonoscopy because of a personal history of premalignant colorectal polyps; kidney function is normal. This patient has a high thrombotic risk ( table 1) and a low bleeding risk ( table 2). Omit apixaban for one day before the procedure (last dose of apixaban on day minus 2). No bridging. Resume apixaban the day after the procedure, after at least 24 hours have elapsed and when hemostasis is secured. If the patient requires polyp removal, delay resumption of apixaban for one to two more days. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 4/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate A 68-year-old female with nonvalvular atrial fibrillation, hypertension, and congestive heart failure (CHA DS -VASc score = 4), receiving rivaroxaban 15 mg daily in the morning, 2 2 requires a dental cleaning and two dental extractions; creatinine clearance (CrCl) is 35 mL/min. This patient has a moderate thrombotic risk ( table 1) and a low bleeding risk ( table 2). Omit rivaroxaban on the day of the procedure. Use oral tranexamic acid mouthwash just before the procedure and two to three times that day after the procedure. Resume rivaroxaban the day after the procedure, after at least 24 hours have elapsed (assuming the dental extractions were uneventful). ESTIMATING THROMBOEMBOLIC RISK The major factors that increase thromboembolic risk are atrial fibrillation, prosthetic heart valves, and recent venous or arterial thromboembolism (eg, within the preceding three months). Atrial fibrillation Atrial fibrillation accounts for the highest percentage of patients for whom perioperative anticoagulation questions arise. Patients with atrial fibrillation are a heterogeneous group; risk can be further classified according to clinical variables such as age, hypertension, congestive heart failure, diabetes, prior stroke, and other vascular disease ( table 1) [2,8]. The CHA DS -VASc score ( table 3) (calculator 1), which incorporates these 2 2 variables, is discussed in detail separately, but use of risk scores has not been prospectively validated in the perioperative setting. The magnitude of this issue was illustrated in three large trials: RE-LY (Randomized Evaluation of Long-Term Anticoagulant Therapy), ROCKET AF (Rivaroxaban Once daily, oral direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation), and ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) [9-11]. In these trials, a total of 15,000 to 20,000 patients were randomly assigned to warfarin versus one of the direct oral anticoagulants (dabigatran, rivaroxaban, or apixaban, respectively). Surgical or other invasive procedures were required in one-fourth of patients in RE-LY and one-third of patients in ROCKET AF and ARISTOTLE. RE-LY (dabigatran versus warfarin) Of the 4591 patients who underwent elective procedures in RE-LY, the perioperative thromboembolic risk was 1.2 percent, based on a https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 5/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate composite endpoint of stroke, cardiovascular death, and pulmonary embolus (PE) [9]. There were no differences in thromboembolic risk with dabigatran versus warfarin, or with the high versus the low dabigatran dose. However, urgent surgery was associated with a higher risk of ischemic stroke or systemic embolism than elective surgery (warfarin: 1.8 versus 0.4 percent; dabigatran 150 mg twice daily: 1.4 versus 0.4 percent; dabigatran 110 mg twice daily: 2.8 versus 0.3 percent). ROCKET AF (rivaroxaban versus warfarin) Of the 4692 anticoagulant interruptions in this trial, 40 percent were for surgery or invasive procedures [11]. The thromboembolic risk during anticoagulant interruption was similar for rivaroxaban and warfarin (0.3 and 0.4 percent). ARISTOTLE (apixaban versus warfarin) During 9260 procedures performed on patients in the ARISTOTLE trial, the perioperative thromboembolic risk was 0.57 percent for warfarin and 0.35 percent for apixaban [10]. Bleeding risk in these trials and registries are presented below. (See 'Overview of whether to interrupt' below.) Prosthetic heart valve The risks of thromboembolism and perioperative management of patients with prosthetic heart valves are discussed separately. (See "Anticoagulation for prosthetic heart valves: Management of bleeding and invasive procedures", section on 'Planning for invasive procedures' and "Diagnosis of mechanical prosthetic valve thrombosis or obstruction".) Recent thromboembolism Thromboembolic risk is greater in the immediate period following a thromboembolic event and declines over time. Individuals with a recent thromboembolic event (eg, within the previous three months) are likely to benefit from delaying surgery, if possible. There are no high-quality data to determine when risk declines to baseline. If emergency surgery is required (eg, acute cholecystectomy), bridging anticoagulation may be used to reduce the interval without an anticoagulant. (See 'Bridging anticoagulation' below.) Venous The perioperative risk of venous thromboembolism (VTE) is greatest in individuals with an event (eg, deep vein thrombosis [DVT], PE) within the prior three months and those with a history of VTE associated with a high-risk inherited thrombophilia ( table 1). However, many patients with VTE do not require thrombophilia testing, and we do not perform this testing specifically to evaluate perioperative thrombotic risk in patients who otherwise do not warrant screening. Appropriate use of thrombophilia screening is discussed separately. (See "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity".) https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 6/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Individuals with cancer have a moderate risk, and those with a thromboembolic event more than one year ago have a low risk of VTE complications. Thus, patients who require surgery within the first three months following an episode of VTE are likely to benefit from delaying elective surgery, even if the delay is only for a few weeks. This approach is supported by data showing that the recurrence risk for individuals with a recent VTE is highest within the initial three to four weeks and diminishes over the following two months [12-14]. Without anticoagulation, the early risk of recurrent VTE was approximately 50 percent; treatment with warfarin for one month reduced this risk to 8 to 10 percent, and after three months of warfarin therapy the risk declined to 4 to 5 percent [14-16]. Arterial The risk of recurrent arterial embolism from any cardiac source is approximately 0.5 percent per day in the first month after an acute event [17]. Thus, patients with a recent arterial embolism are likely to benefit from delaying elective surgery, if such a delay is possible. The vast majority of cases are due to atrial fibrillation; other less common cardiac sources include paradoxical embolism, nonbacterial thrombotic endocarditis in a patient with malignancy, dilated or poorly contractile left ventricle, or left ventricular aneurysm [18-20]. ESTIMATING PROCEDURAL BLEEDING RISK The risk of bleeding is dominated by the type of surgery or procedure. Comorbidities (eg, older age, reduced kidney function) and medications that affect hemostasis (eg, aspirin) may also contribute [3,21,22]. As a general guideline, we divide procedures into high and low bleeding risk (two-day risk of major bleeding 2 to 4 percent or 0 to 2 percent, respectively); examples of high bleeding risk procedures include coronary artery bypass surgery, kidney biopsy, and any procedure lasting >45 minutes; low bleeding risk procedures include cholecystectomy, carpal tunnel repair, and abdominal hysterectomy ( table 2) [2]. These categories do not substitute for clinical judgment or consultation between the surgeon and other treating clinicians. Neuraxial, intracranial, and cardiac procedures are especially concerning because the location of potential bleeding increases the risk of serious complications. (See "Neuraxial anesthesia/analgesia techniques in the patient receiving anticoagulant or antiplatelet medication".) Major bleeding is generally defined as bleeding that is fatal, involves a critical anatomic site (eg, intracranial, pericardial), requires surgery to correct, lowers the hemoglobin by 2 g/dL, or requires transfusion of 2 units packed red cells; however, there is heterogeneity in definitions used by different clinicians [23]. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 7/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate The risks of some specific types of procedures are also discussed in detail separately in the following topic reviews, along with management issues specific to those procedures: Neuraxial anesthesia (See "Neuraxial anesthesia/analgesia techniques in the patient receiving anticoagulant or antiplatelet medication".) Gastrointestinal procedures (See "Management of anticoagulants in patients undergoing endoscopic procedures", section on 'Elective procedures'.) Percutaneous coronary intervention (eg, angioplasty, atherectomy, stenting) (See "Periprocedural management of antithrombotic therapy in patients receiving long-term oral anticoagulation and undergoing percutaneous coronary intervention", section on 'Elective patients' and "Coronary artery disease patients requiring combined anticoagulant and antiplatelet therapy", section on 'Prevention'.) Ophthalmologic procedures (See "Diabetic retinopathy: Prevention and treatment", section on 'Patients taking antiplatelet or anticoagulant medication' and "Cataract in adults", section on 'Management of antithrombotic agents'.) Dental and cutaneous procedures are generally associated with a low risk of bleeding. (See 'Settings in which continuing the anticoagulant may be preferable' below.) Patient factors can also contribute to bleeding risk; these patient-related risks can be quantified using bleeding risk scores. An example is the HAS-BLED score (calculator 2), which was used in the BNK Online Bridging Registry (BORDER), an observational registry that assessed perioperative outcomes in outpatients undergoing invasive cardiac procedures (cardiac catheterization, pacemaker implantation, cardiac surgery) [24]. The HAS-BLED score assigns one point each for hypertension, abnormal kidney or liver function (two points for both), stroke, bleeding tendency, labile INRs, elderly age, and antiplatelet drugs or alcohol ( table 4). Nearly all of the patients in the BORDER study were receiving a vitamin K antagonist, which was interrupted for the procedure and replaced with a bridging agent, usually a low molecular weight (LMW) heparin. There were 35 clinically relevant bleeding episodes during 1000 procedures (3.5 percent). A HAS-BLED bleeding risk score 3 was the most predictive variable for bleeding (hazard ration [HR] 11.8, 95% CI 5.6-24.9) [24]. DECIDING WHETHER TO INTERRUPT ANTICOAGULATION Overview of whether to interrupt Once the thromboembolic and bleeding risks have been estimated, a decision can be made about whether the anticoagulant should be interrupted or https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 8/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate continued. Data comparing the relative benefits of continuing anticoagulation versus interrupting an anticoagulant are limited, and decisions that balance thromboembolic and bleeding risks must be made on a case-by-case basis. No scoring system can substitute for clinical judgment in this decision making. Our approach is illustrated in the algorithm ( algorithm 1) and summarized as follows: In general, the anticoagulant must be discontinued if the surgical bleeding risk is high. Those at very high or high thromboembolic risk should limit the period without anticoagulation to the shortest possible interval; in some cases, this involves the use of a bridging agent. (See 'Settings requiring anticoagulant interruption' below.) In contrast, individuals undergoing selected low bleeding risk surgery often can continue their anticoagulant; in certain cases, continuation of the anticoagulant may be preferable. (See 'Settings in which continuing the anticoagulant may be preferable' below.) Practices to reduce bleeding and thromboembolic risks should be employed regardless of whether the patient's anticoagulant is interrupted or continued. Examples include the following: Agents that interfere with platelet function (nonsteroidal antiinflammatory drugs [NSAIDs], aspirin) should be avoided for routine analgesia unless the benefit outweighs the increased risk of bleeding; routine perioperative use of aspirin should be avoided due to an increased risk of bleeding and lack of benefit. By contrast, if these agents are administered for a separate indication (eg, recent stroke, acute coronary syndromes, implanted coronary stent), they can (and generally should) be continued [25]. Perioperative aspirin use is discussed in detail separately. (See "Perioperative medication management", section on 'Medications affecting hemostasis' and "Periprocedural management of antithrombotic therapy in patients receiving long-term oral anticoagulation and undergoing percutaneous coronary intervention".) For those not receiving an anticoagulant in the immediate postoperative period, thromboprophylaxis to reduce the risk of venous thromboembolism (VTE) should be used when appropriate. (See "Prevention of venous thromboembolic disease in adult nonorthopedic surgical patients".) Settings requiring anticoagulant interruption Individuals undergoing surgery with a high risk of bleeding will require interruption of their usual anticoagulant perioperatively, putting them at higher risk of thromboembolic complications related to their underlying condition. If the very high risk of thromboembolism is transient (eg, ischemic stroke within the previous three months), attempts should be made to delay elective surgery, if possible, https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 9/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate until the thromboembolic risk has returned to baseline. It may also be advisable to delay elective surgery in a patient with atrial fibrillation who has had inadequate anticoagulation in the preceding month. This is based on the observation that among patients with nonvalvular atrial fibrillation, over 85 percent of thrombi resolve after four weeks of warfarin therapy [26]. Individuals with a temporarily very high or high thromboembolic risk in whom surgery cannot be delayed (eg, potentially curative cancer surgery in a patient who just had an acute VTE) should limit the interval without an anticoagulant to minimize the risk of VTE recurrence. This generally involves stopping the usual anticoagulant as close to surgery as possible, restarting it as soon as possible, and, for those on warfarin, using a bridging agent before and/or after surgery while the usual anticoagulant is not therapeutic. A temporary inferior vena cava (IVC) filter may also be appropriate in selected individuals. (See 'Timing of anticoagulant interruption' below and 'Bridging anticoagulation' below and 'Temporary IVC filters' below.) For individuals with a chronically elevated thromboembolic risk who are receiving warfarin, we often use bridging anticoagulation to minimize the period when anticoagulation is not being used. (See 'Limited indications for bridging' below.) Individuals with a moderate thromboembolic risk generally can interrupt their anticoagulant for surgery without bridging. The bleeding risk from bridging may outweigh any potential benefit, especially in those with low-risk nonvalvular atrial fibrillation [27,28]. Temporary IVC filters Placement of a temporary inferior vena cava (IVC) filter is indicated in patients with a very recent (within the prior three to four weeks) acute VTE who require interruption of anticoagulation for a surgery or major procedure in which it is anticipated that therapeutic-dose anticoagulation will need to be delayed for more than 12 hours postoperatively. As an example, most patients who require surgery using general or neuraxial anesthesia that must be performed within three to four weeks of an acute VTE would require placement of an IVC filter. Further information about the placement of IVC filters is presented separately. (See "Placement of vena cava filters and their complications".) In contrast, patients who require temporary interruption of anticoagulation for a minor procedure such as central venous catheter placement, which may be performed with omission of one dose of an anticoagulant, would not require an IVC filter. Individuals with a VTE more than four weeks prior to the intended surgery do not require placement of an IVC filter, and other clinical situations such as prior perioperative VTE or high-risk thrombophilia are not routine indications for perioperative placement of an IVC filter. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 10/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Settings in which continuing the anticoagulant may be preferable For individuals undergoing selected surgery that confers a low risk of bleeding (eg, cataract extraction) it may be preferable for them to continue their anticoagulant, depending on patient factors and the judgment of the treating clinician. Continuing the anticoagulant likely reduces the risk of thromboembolism, and in some settings (eg, cardiac implantable electronic device) it actually reduces the risk of bleeding as well. For those receiving warfarin or another vitamin K antagonist, it is important to confirm that the international normalized ratio (INR) is not above the therapeutic range at the time of the procedure. Dental procedures Dental procedures are generally considered to confer a low risk of bleeding, and anticoagulation can be continued in most patients during these procedures. The evidence for the safety of continuing anticoagulation comes from patients receiving warfarin with an INR in the therapeutic range [29-35]. In the ARISTOTLE trial, which included patients anticoagulated with warfarin versus apixaban for atrial fibrillation, perioperative bleeding rates were approximately 1 percent in patients undergoing dental and other low bleeding risk procedures. Bleeding can be further reduced with the use of topical hemostatic agents (eg, tranexamic acid mouthwash, used three to four times daily for one to two days) [8,34,36-39]. An exception is multiple tooth extractions, which we consider high bleeding risk. (See 'Settings requiring anticoagulant interruption' above.) Cutaneous procedures Cutaneous procedures (eg, skin biopsy, tumor excision) are also generally considered to confer a low risk of bleeding; the potential for local control measures further reduces concerns about bleeding risk. Selected cardiac procedures For certain cardiac procedures, there is evidence that continuing anticoagulation is safe (and in some cases associated with better outcomes) compared with stopping and restarting the anticoagulant. Cardiac implantable devices We agree with a position document from the European Heart Rhythm Association (EHRA) that states the majority of patients undergoing implantation of a cardiac electronic device (pacemaker, cardioverter-defibrillator) should continue their anticoagulant perioperatively [40]. This is based on data from the BRUISE CONTROL trial, which randomly assigned patients on warfarin undergoing implantation of a cardiac implantable electronic device to continuation of warfarin or heparin bridging, as well as other smaller trials [41]. This trial found a lower risk of bleeding in patients who continued warfarin. Potential explanations for the increased bleeding in the heparin-bridging arm include initiation of post-procedure bridging too early (eg, https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 11/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate within 24 hours after the procedure) or better identification of surgical bleeding sites that could be addressed during the procedure in patients receiving continued warfarin. An exception is a patient with a low risk of thromboembolic events, in whom warfarin may be discontinued, or a patient receiving a direct oral anticoagulant (DOAC), for whom temporary discontinuation is likely to be appropriate; bridging anticoagulation is not recommended in such individuals [40]. In an analysis of 611 patients from the RE-LY trial (dabigatran versus warfarin in atrial fibrillation) who underwent implantable device surgery, pocket hematomas occurred at a similar frequency in those who had interruption of dabigatran and those who had interruption of warfarin without bridging [42]. It is not clear whether uninterrupted dabigatran would be associated with lower risks of bleeding and/or thrombosis. (See "Cardiac implantable electronic devices: Periprocedural complications".) Endovascular procedures and catheter ablation Endovascular procedures include a variety of venous and arterial interventions, such as angioplasty, catheter ablation, and atherectomy. In a meta-analysis of randomized trials involving over 20,000 patients undergoing these procedures, uninterrupted warfarin therapy was associated with equivalent or lower rates of complications compared with interruption of warfarin [43]. As an example, a benefit of warfarin continuation rather than discontinuation with bridging was reported in the COMPARE trial, which randomly assigned patients with atrial fibrillation undergoing catheter ablation to continued warfarin or discontinuation of warfarin with bridging [44]. In this trial, patients randomized to continue warfarin had a lower risk of stroke and less bleeding. We also agree with the EHRA position document statement that all patients undergoing catheter ablation for atrial fibrillation should receive full anticoagulation with heparin in addition to continuing their oral anticoagulant [40]. If a decision is made to discontinue the anticoagulant (eg, patient with impaired kidney function), bridging is reserved for those with a high to very high thromboembolic risk and not used for those with a moderate thromboembolic risk. (See 'Limited indications for bridging' below.) TIMING OF ANTICOAGULANT INTERRUPTION If a decision has been made to interrupt the anticoagulant for surgery with high or moderate bleeding risk, the agent should be stopped in sufficient time to allow anticoagulation to resolve. For some agents such as warfarin, laboratory testing is a reliable indicator that the https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 12/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate anticoagulant effect has resolved after discontinuation; for direct oral anticoagulants (DOACs), well-validated and easily accessible testing is not always available. Data to guide the timing of anticoagulant interruption are evolving, especially for DOACs, and much of our practice is based on expert opinion and observational studies as we await results from ongoing trials [45]. Validated approaches have been developed to guide the timing of DOAC interruption. (See 'DOAC interruptions (overview)' below.) If a moderate or high bleeding risk surgery is required urgently or immediately, reversal of the anticoagulant may also be required. (See 'Urgent/emergency invasive procedure' below.) Risks of bleeding with neuraxial anesthesia and risks of thrombosis in patients with prosthetic heart valves are especially concerning; these issues are discussed in detail separately. (See "Neuraxial anesthesia/analgesia techniques in the patient receiving anticoagulant or antiplatelet medication" and "Antithrombotic therapy for mechanical heart valves".) Typical durations of anticoagulant interruption are illustrated by the RE-LY trial, which randomly assigned individuals with nonvalvular atrial fibrillation to warfarin or dabigatran for prevention of thromboembolism [9]. In this trial, nearly half of patients treated with dabigatran had surgery within 48 hours of stopping the drug, whereas only approximately 1 in 10 patients treated with warfarin had surgery within 48 hours of drug discontinuation. The incidence of thromboembolism was low (<1 percent), and bleeding rates were similar for those receiving warfarin or either dabigatran dose. Similar findings were reported in the PAUSE study, which focused on individuals with atrial fibrillation receiving a DOAC. (See 'Atrial fibrillation' above and 'DOAC interruptions (overview)' below.) Warfarin interruption Warfarin blocks a vitamin K-dependent step in clotting factor production; it impairs coagulation by interfering with the functions of factors II (prothrombin), VII, IX, and X. Resolution of warfarin effect is determined by measurement of the prothrombin time (PT), which is standardized across institutions using an international normalized ratio (INR). Discontinuation If warfarin discontinuation is appropriate, we typically omit warfarin for five days before an elective surgery (the last dose of warfarin is given on day minus 6); this duration of warfarin interruption should lead to normalization of the INR by the time of surgery and obviates the need for routine INR testing one to two days before the surgery [8,14,46,47]. This approach also appears to be safe, without exposing patients to an increased risk for perioperative bleeding [48,49]. When INR testing is not routinely done, routine use of vitamin K is avoided. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 13/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate There may be circumstances when preoperative INR testing is warranted, such as in patients who have a <5 day warfarin interruption or a recent high INR (>4.5). In such cases, we check the INR one to two days before the surgery, and, if the INR is >1.5, a low dose of oral vitamin K (eg, 1 to 2 mg) can be given for selected patients and/or procedures in which a normalized INR is required; this can be followed by re-checking an INR the following day. An INR in the normal (<1.3) or near-normal (1.3 to 1.4) range is important in patients undergoing surgery associated with a high bleeding risk (eg, intracranial, spinal, urologic) or if neuraxial anesthesia is to be used. (See 'Estimating procedural bleeding risk' above and 'Neuraxial anesthesia' below.) This timing of warfarin discontinuation is based on the biologic half-life of warfarin (36 to 42 hours) and the observed time for the PT/INR to return to normal after stopping warfarin (two to three days for the INR to fall to below 2; four to six days to normalize) [46]. Normalization of the INR may take longer in patients receiving higher-intensity anticoagulation (INR 2.5 to 3.5) and in older individuals [50]. Half-lives of other vitamin K antagonists also differ (eg, 8 to 11 hours for acenocoumarol; approximately four to six days for phenprocoumon [51]; approximately three days for fluindione). (See "Warfarin and other VKAs: Dosing and adverse effects", section on 'Warfarin administration'.) For a procedure that requires more rapid normalization of the INR, additional interventions may be needed to actively reverse the anticoagulant. (See 'Urgent/emergency invasive procedure' below.) This discontinuation schedule will produce a period of several days with subtherapeutic anticoagulation. As an example, it is estimated that if warfarin is withheld for five days before surgery and is restarted as soon as possible afterwards, patients would have a subtherapeutic INR for approximately eight days (four days before and four days after surgery) [14]. Thus, for patients at very high or high thromboembolic risk, bridging may be appropriate. Use of bridging preoperatively We generally reserve bridging for individuals considered at very high or high risk of thromboembolism (eg, recent [within the prior three months] stroke, mechanical heart valve, CHA DS -VASc score of 7 or 8 ( table 3) (calculator 1), 2 2 CHADS score of 5 or 6) if they require interruption of warfarin. In these cases, the bridging 2 agent (eg, therapeutic-dose subcutaneous low molecular weight [LMW] heparin) is started three days before surgery. (See 'Bridging anticoagulation' below.) A bridging agent may also be appropriate if there is a prolonged period during which the patient cannot take oral medications (eg, postoperative ileus) and in patients who have had https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 14/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate a thromboembolic event during a prior episode of perioperative anticoagulant interruption. This practice is based on expert opinion and has not been formally evaluated in a clinical trial. Restarting warfarin and postoperative bridging We resume warfarin 12 to 24 hours after surgery, typically the evening of the day of surgery or the evening of the day after surgery, assuming there were no unexpected surgical issues that would increase bleeding risk and the patient is taking adequate oral fluids [8]. We use the same dose the patient was receiving preoperatively.

atrial fibrillation undergoing catheter ablation to continued warfarin or discontinuation of warfarin with bridging [44]. In this trial, patients randomized to continue warfarin had a lower risk of stroke and less bleeding. We also agree with the EHRA position document statement that all patients undergoing catheter ablation for atrial fibrillation should receive full anticoagulation with heparin in addition to continuing their oral anticoagulant [40]. If a decision is made to discontinue the anticoagulant (eg, patient with impaired kidney function), bridging is reserved for those with a high to very high thromboembolic risk and not used for those with a moderate thromboembolic risk. (See 'Limited indications for bridging' below.) TIMING OF ANTICOAGULANT INTERRUPTION If a decision has been made to interrupt the anticoagulant for surgery with high or moderate bleeding risk, the agent should be stopped in sufficient time to allow anticoagulation to resolve. For some agents such as warfarin, laboratory testing is a reliable indicator that the https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 12/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate anticoagulant effect has resolved after discontinuation; for direct oral anticoagulants (DOACs), well-validated and easily accessible testing is not always available. Data to guide the timing of anticoagulant interruption are evolving, especially for DOACs, and much of our practice is based on expert opinion and observational studies as we await results from ongoing trials [45]. Validated approaches have been developed to guide the timing of DOAC interruption. (See 'DOAC interruptions (overview)' below.) If a moderate or high bleeding risk surgery is required urgently or immediately, reversal of the anticoagulant may also be required. (See 'Urgent/emergency invasive procedure' below.) Risks of bleeding with neuraxial anesthesia and risks of thrombosis in patients with prosthetic heart valves are especially concerning; these issues are discussed in detail separately. (See "Neuraxial anesthesia/analgesia techniques in the patient receiving anticoagulant or antiplatelet medication" and "Antithrombotic therapy for mechanical heart valves".) Typical durations of anticoagulant interruption are illustrated by the RE-LY trial, which randomly assigned individuals with nonvalvular atrial fibrillation to warfarin or dabigatran for prevention of thromboembolism [9]. In this trial, nearly half of patients treated with dabigatran had surgery within 48 hours of stopping the drug, whereas only approximately 1 in 10 patients treated with warfarin had surgery within 48 hours of drug discontinuation. The incidence of thromboembolism was low (<1 percent), and bleeding rates were similar for those receiving warfarin or either dabigatran dose. Similar findings were reported in the PAUSE study, which focused on individuals with atrial fibrillation receiving a DOAC. (See 'Atrial fibrillation' above and 'DOAC interruptions (overview)' below.) Warfarin interruption Warfarin blocks a vitamin K-dependent step in clotting factor production; it impairs coagulation by interfering with the functions of factors II (prothrombin), VII, IX, and X. Resolution of warfarin effect is determined by measurement of the prothrombin time (PT), which is standardized across institutions using an international normalized ratio (INR). Discontinuation If warfarin discontinuation is appropriate, we typically omit warfarin for five days before an elective surgery (the last dose of warfarin is given on day minus 6); this duration of warfarin interruption should lead to normalization of the INR by the time of surgery and obviates the need for routine INR testing one to two days before the surgery [8,14,46,47]. This approach also appears to be safe, without exposing patients to an increased risk for perioperative bleeding [48,49]. When INR testing is not routinely done, routine use of vitamin K is avoided. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 13/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate There may be circumstances when preoperative INR testing is warranted, such as in patients who have a <5 day warfarin interruption or a recent high INR (>4.5). In such cases, we check the INR one to two days before the surgery, and, if the INR is >1.5, a low dose of oral vitamin K (eg, 1 to 2 mg) can be given for selected patients and/or procedures in which a normalized INR is required; this can be followed by re-checking an INR the following day. An INR in the normal (<1.3) or near-normal (1.3 to 1.4) range is important in patients undergoing surgery associated with a high bleeding risk (eg, intracranial, spinal, urologic) or if neuraxial anesthesia is to be used. (See 'Estimating procedural bleeding risk' above and 'Neuraxial anesthesia' below.) This timing of warfarin discontinuation is based on the biologic half-life of warfarin (36 to 42 hours) and the observed time for the PT/INR to return to normal after stopping warfarin (two to three days for the INR to fall to below 2; four to six days to normalize) [46]. Normalization of the INR may take longer in patients receiving higher-intensity anticoagulation (INR 2.5 to 3.5) and in older individuals [50]. Half-lives of other vitamin K antagonists also differ (eg, 8 to 11 hours for acenocoumarol; approximately four to six days for phenprocoumon [51]; approximately three days for fluindione). (See "Warfarin and other VKAs: Dosing and adverse effects", section on 'Warfarin administration'.) For a procedure that requires more rapid normalization of the INR, additional interventions may be needed to actively reverse the anticoagulant. (See 'Urgent/emergency invasive procedure' below.) This discontinuation schedule will produce a period of several days with subtherapeutic anticoagulation. As an example, it is estimated that if warfarin is withheld for five days before surgery and is restarted as soon as possible afterwards, patients would have a subtherapeutic INR for approximately eight days (four days before and four days after surgery) [14]. Thus, for patients at very high or high thromboembolic risk, bridging may be appropriate. Use of bridging preoperatively We generally reserve bridging for individuals considered at very high or high risk of thromboembolism (eg, recent [within the prior three months] stroke, mechanical heart valve, CHA DS -VASc score of 7 or 8 ( table 3) (calculator 1), 2 2 CHADS score of 5 or 6) if they require interruption of warfarin. In these cases, the bridging 2 agent (eg, therapeutic-dose subcutaneous low molecular weight [LMW] heparin) is started three days before surgery. (See 'Bridging anticoagulation' below.) A bridging agent may also be appropriate if there is a prolonged period during which the patient cannot take oral medications (eg, postoperative ileus) and in patients who have had https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 14/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate a thromboembolic event during a prior episode of perioperative anticoagulant interruption. This practice is based on expert opinion and has not been formally evaluated in a clinical trial. Restarting warfarin and postoperative bridging We resume warfarin 12 to 24 hours after surgery, typically the evening of the day of surgery or the evening of the day after surgery, assuming there were no unexpected surgical issues that would increase bleeding risk and the patient is taking adequate oral fluids [8]. We use the same dose the patient was receiving preoperatively. After warfarin is restarted in the perioperative setting, it takes 5 to 10 days to attain a full anticoagulant effect as measured by an INR above 2. Thus, we generally treat individuals at very high risk and some individuals with a high risk of thromboembolism with a heparin bridging agent during this period. (See 'Bridging anticoagulation' below.) DOAC interruptions (overview) Individuals who interrupt therapy with a direct oral anticoagulant (DOAC) will have a shorter period without anticoagulation than those who interrupt therapy with warfarin, due to the rapid resolution of anticoagulant effect when a DOAC is discontinued preoperatively and the rapid resumption of effect when a DOAC is restarted postoperatively. The PAUSE (Perioperative Anticoagulation Use for Surgery Evaluation) study, which prospectively evaluated outcomes in 3007 individuals who were taking a DOAC for atrial fibrillation and underwent an elective surgery or procedure and followed a simple, standardized management approach for interruption of their anticoagulant [52]. There was no preoperative coagulation testing and no heparin bridging. Rates of thromboembolic and hemorrhagic complications associated with this management were low (major bleeding in <2 percent; ischemic stroke in <0.5 percent), thereby supporting the safety of this approach. In addition, there was approximately 94 percent adherence to the preoperative and postoperative DOAC interruption and resumption protocols, thereby supporting the generalizability of this approach. The PAUSE approach is illustrated in the figure ( figure 1) and summarized as follows: Low/moderate bleed risk For low/moderate bleeding risk surgery, omit the DOAC one day before and resume one day (approximately 24 hours) after the procedure, provided hemostasis is secure. The total duration of interruption is two days. High bleed risk For high bleeding risk surgery, omit the DOAC two days before and resume two days (approximately 48 hours) after the procedure, provided hemostasis is https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 15/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate secure. The total duration of interruption is four days. Waiting an additional one day before resumption may be appropriate in some cases. Impaired kidney function For individuals with impaired kidney function (creatinine clearance [CrCl] <30 to 50 mL/min) who are taking dabigatran, there is an additional one day interruption before low/moderate bleeding risk procedures and an additional two days interruption before high bleeding risk procedures. Direct factor Xa inhibitors (apixaban, edoxaban, rivaroxaban) do not require adjustments for kidney function. Using this approach, residual DOAC levels (not required in routine practice) were in a low range (<50 ng/mL) in most patients overall, and in 99 percent of patients having a high bleeding risk surgery [52]. This approach is outlined in more detail in the following sections. The population in the PAUSE study was exclusively individuals with atrial fibrillation. The perioperative management from PAUSE can also be applied to patients who are receiving DOAC therapy for venous thromboembolism (VTE) and require treatment interruption for an elective procedure ( algorithm 1). For individuals in whom the VTE was >30 days prior, management can be followed in the same manner as individuals with atrial fibrillation. For those who had a recent VTE (within the prior 30 days), perioperative management should be individualized and may include placement of a temporary inferior vena cava (IVC) filter or shorter periods of DOAC interruption. (See 'Temporary IVC filters' above.) Dabigatran Dabigatran is a direct thrombin inhibitor; it reversibly blocks the enzymatic function of thrombin in converting fibrinogen to fibrin. Discontinuation Dabigatran can be omitted for one day before a low/moderate bleeding risk surgical procedure and for two days before a high bleeding risk procedure, in individuals with normal or mildly impaired kidney function (CrCl >50 mL/min) ( figure 1). For those with impaired kidney function (CrCl 30 to 50 mL/min), dabigatran can be omitted for two days before a low/moderate bleeding risk procedure and four days before a high bleeding risk procedure. As an example, in a patient on dabigatran with a CrCl >50 mL/min undergoing a high bleeding risk procedure, the patient will skip four doses of dabigatran (no drug on surgical day minus 2 and day minus 1) and no drug on the day of surgery ( table 5). In dabigatran-treated patients with a CrCl 30 to 50 mL/min undergoing a high bleeding risk procedure such as neuraxial anesthesia, a longer interval for interruption is required. (See 'Neuraxial anesthesia' below.) https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 16/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate The last preoperative day on which dabigatran is administered can be more closely estimated based on the elimination half-life of dabigatran, which varies according to kidney function (eg, 12 to 14 hours in patients with normal kidney function) [2,53-56]. A protocol incorporating bleeding risk and CrCl was tested in a prospective cohort of 541 dabigatran- treated patients undergoing surgery and was associated with low rates of bleeding and thrombotic complications [56]. Routine coagulation tests have not been validated for ensuring that dabigatran effect has resolved. A normal or near-normal activated partial thromboplastin time (aPTT) may be used in selected patients to evaluate whether dabigatran has been adequately cleared from the circulation prior to surgery (eg, patients at high risk of surgical bleeding) ( table 6). Importantly, the reliability of aPTT testing may depend on the specific assay used; if available, a diluted plasma thrombin time may be preferable [54,57,58]. (See "Direct oral anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing and adverse effects", section on 'Dabigatran' and "Clinical use of coagulation tests".) Use of bridging In general, the rapid offset and onset of dabigatran activity makes bridging anticoagulation unnecessary. We reserve bridging anticoagulation for selected individuals who are at very high risk for postoperative thromboembolism and require extended interruption of dabigatran. Examples include postoperative bridging in patients who are unable to take oral medications postoperatively due to intestinal ileus from gastrointestinal surgery. (See 'Bridging anticoagulation' below.) Restarting dabigatran Dabigatran should be resumed postoperatively when hemostasis has been achieved, at the same dose the patient was receiving preoperatively. In general, dabigatran can be restarted one day (approximately 24 hours) after a low/moderate bleeding risk surgery/procedure and two days (approximately 48 hours) after a high bleeding risk surgery/procedure. Since dabigatran has a rapid onset of action, with peak effects occurring two to three hours after intake, caution should be used in patients who have had major surgery or other procedures associated with a high bleeding risk. In cases where the resumption of dabigatran is delayed for two to three days and there is concern about patients being exposed to an increased risk for VTE, we usually administer a low- dose LMW heparin regimen (eg, enoxaparin 40 mg daily) until the DOAC is resumed. If this schedule is used, most patients will omit dabigatran for two total days for a low/moderate bleeding risk procedure and four total days for a high bleeding risk procedure. An additional one to two days of dabigatran interruption is done in patients with moderately impaired kidney function (CrCl 30 to 50 mL/min). https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 17/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Rivaroxaban Rivaroxaban is a direct factor Xa inhibitor; it reversibly blocks the enzymatic function of factor Xa in converting prothrombin to thrombin. Discontinuation Rivaroxaban can be omitted for one day in patients who are having a low/moderate bleeding risk surgical procedure and for two days before a high bleeding risk procedure ( figure 1). Thus, for low/moderate bleeding risk procedures, the patient will omit one dose of rivaroxaban on the one day before the procedure; for high bleeding risk procedures, the patient will omit two doses of rivaroxaban on the two days before the procedure. These intervals are based on an elimination half-life of 7 to 11 hours and apply to individuals with normal kidney function or mildly impaired kidney function (CrCl >50 mL/min), who are likely to be receiving the 20 mg once daily dose; and to those with moderately reduced kidney function (CrCl 30 to 50 mL/min), who are likely to be receiving the 15 mg once daily dose. Longer intervals for interruption may be required for situations in which the bleeding risk is very high, such as neuraxial anesthesia. (See 'Neuraxial anesthesia' below.) Rivaroxaban interacts with dual inhibitors of CYP-3A4 and P-glycoprotein (eg, systemic ketoconazole, ritonavir); dose adjustment or substitution of heparin may be appropriate if these dual CYP-3A4 and P-glycoprotein inhibitors are used perioperatively. Interactions with drugs that inhibit only one of these enzymes do not seem to alter rivaroxaban anticoagulant effect. Routine coagulation tests have not been validated for ensuring that the rivaroxaban anticoagulant effect has resolved. A normal or near-normal anti-factor Xa activity level may be used in selected patients to evaluate whether rivaroxaban has been adequately cleared from the circulation prior to surgery (eg, patients at high risk of surgical bleeding) ( table 6) [2]. The reliability of anti-factor Xa activity testing may depend on the specific assay used, and clinicians are advised to speak with their clinical laboratory to determine whether this assay is available at their institution and whether it has been validated for direct factor Xa inhibitors. Use of bridging In general, the rapid offset and onset of rivaroxaban makes bridging anticoagulation unnecessary. In rare cases bridging may be required, such as the use of postoperative bridging in individuals who have a very high thromboembolic risk and are unable to take oral medications postoperatively due to intestinal ileus from gastrointestinal surgery. (See 'Bridging anticoagulation' below.) Restarting rivaroxaban Rivaroxaban can be resumed postoperatively when hemostasis has been achieved, at the same dose the patient was receiving preoperatively. In general, https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 18/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate rivaroxaban can be restarted one day after a low/moderate bleeding risk procedure and two days after a high bleeding risk procedure. Since rivaroxaban has a rapid onset of action, caution should be used in patients who have had major surgery or other procedures associated with a high bleeding risk. We generally restart rivaroxaban one day after low bleeding risk surgery and two to three days after high bleeding risk surgery. In cases where the resumption of rivaroxaban is delayed for two to three days and there is concern about patients being exposed to an increased risk for VTE, we usually administer a low-dose LMW heparin regimen (eg, enoxaparin 40 mg daily) until the DOAC is resumed. If this schedule is used, most patients will omit rivaroxaban for two total days for a low/moderate bleeding risk procedure and four total days for a high bleeding risk procedure. Adjustments are not made routinely for patients with moderately impaired kidney function (CrCl 30 to 50 mL/min). Apixaban Apixaban is a direct factor Xa inhibitor; it reversibly blocks the enzymatic function of factor Xa in converting prothrombin to thrombin. Discontinuation Apixaban can be omitted for one day before a low/moderate bleeding risk procedure and for two days before a high bleeding risk procedure ( figure 1). Thus, for low/moderate bleeding risk procedures, the patient will omit two dose of apixaban on the one day before the procedure; for high bleeding risk procedures, the patient will omit four doses of apixaban on the two days before the procedure. These intervals are based on an apixaban elimination half-life of 8 to 12 hours. These intervals apply to individuals with normal kidney function or mildly impaired kidney function (CrCl >50 mL/min), who are likely to be receiving the 5 mg twice daily dose; and to those with moderate to severe kidney insufficiency (CrCl 30 to 50 mL/min), who are likely to be receiving the 2.5 mg twice daily dose. Longer intervals for interruption may be required for situations in which the bleeding risk is very high, such as neuraxial anesthesia. (See 'Neuraxial anesthesia' below.) Routine coagulation tests have not been validated for ensuring that apixaban effect has resolved. A normal or near-normal anti-factor Xa activity level may be used in selected patients to evaluate whether apixaban has been adequately cleared from the circulation prior to surgery (eg, patients at high risk of surgical bleeding) ( table 6). The reliability of anti-factor Xa activity testing may depend on the specific assay used, and clinicians are advised to speak with their clinical laboratory to determine whether this assay is available at their institution and whether it has been validated for direct factor Xa inhibitors. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 19/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Use of bridging In general, the rapid offset and onset of apixaban makes bridging anticoagulation unnecessary. In rare cases, bridging may be required, such as the use of postoperative bridging in individuals who have a very high thromboembolic risk and are unable to take oral medications postoperatively due to intestinal ileus from gastrointestinal surgery. (See 'Bridging anticoagulation' below.) Restarting apixaban Apixaban can be resumed postoperatively when hemostasis has been achieved, at the same dose the patient was receiving preoperatively. In general, apixaban can be restarted one day after a low/moderate bleeding risk procedure and two days after a high bleeding risk procedure. Since apixaban has a rapid onset of action, caution should be used in patients who have had major surgery or other procedures associated with a high bleeding risk. We generally restart apixaban one day after low/moderate bleeding risk surgery and two days after a high bleeding risk surgery. In cases where the resumption of apixaban is delayed for two to three days and there is concern about patients being exposed to an increased risk for VTE, we usually administer a low-dose LMW heparin regimen (eg, enoxaparin 40 mg daily) until the DOAC is resumed. If this schedule is used, most patients will omit apixaban for two total days for a low/moderate bleeding risk procedure and four total days for a high bleeding risk procedure. Adjustments are not made routinely for patients with moderately impaired kidney function (CrCl 30 to 50 mL/min). Edoxaban Edoxaban is a direct factor Xa inhibitor; it reversibly blocks the enzymatic function of factor Xa in converting prothrombin to thrombin. Discontinuation Edoxaban can be omitted for one day before a low/moderate bleeding risk procedure and for two days before a high bleeding risk procedure ( figure 1). Thus, for low/moderate bleeding risk procedures, the patient will omit one dose of edoxaban on the one day before the procedure; for high bleeding risk procedures, the patient will omit two doses of edoxaban on the two days before the procedure. These intervals are based on an edoxaban elimination half-life of 10 to 14 hours. These intervals apply to individuals with normal kidney function or mildly impaired kidney function(CrCl >50 mL/min) and those with moderately impaired kidney function (CrCl 30 to 50 mL/min), who are likely to be receiving the 60 mg once daily or the 30 mg once daily doses, respectively. Longer intervals for interruption may be considered for those undergoing major surgery, neuraxial anesthesia or manipulation, or other situations in which complete hemostatic function may be required. (See 'Neuraxial anesthesia' below.) https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 20/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Routine coagulation tests have not been validated for ensuring that edoxaban effect has resolved. A normal or near-normal anti-factor Xa activity level may be used in selected patients to evaluate whether edoxaban has been adequately cleared from the circulation prior to surgery (eg, patients at high risk of surgical bleeding) ( table 6). The reliability of anti-factor Xa activity testing may depend on the specific assay used, and clinicians are advised to speak with their clinical laboratory to determine whether this assay is available at their institution and whether it has been validated for direct factor Xa inhibitors. Use of bridging In general, the rapid offset and onset of edoxaban makes bridging anticoagulation unnecessary. In rare cases, bridging may be required, such as the use of postoperative bridging in individuals who have a very high thromboembolic risk and are unable to take oral medications postoperatively due to intestinal ileus from gastrointestinal surgery. (See 'Bridging anticoagulation' below.) Restarting edoxaban Edoxaban can be resumed postoperatively when hemostasis has been achieved, at the same dose the patient was receiving preoperatively. In general, edoxaban can be restarted one day after a low/moderate bleeding risk procedure and two days after a high bleeding risk procedure. Since edoxaban has a rapid onset of action, caution should be used in patients who have had major surgery or other procedures associated with a high bleeding risk. We generally restart edoxaban one day after low bleeding risk surgery and two to three days after high bleeding risk surgery. In cases where the resumption of edoxaban is delayed for two to three days and there is concern about patients being exposed to an increased risk for VTE, we usually administer a low- dose LMW heparin regimen (eg, enoxaparin 40 mg daily) until the DOAC is resumed. If this schedule is used, most patients will omit edoxaban for two total days for a low/moderate bleeding risk procedure and four total days for a high bleeding risk procedure. BRIDGING ANTICOAGULATION Bridging anticoagulation involves the administration of a short-acting anticoagulant, typically a low molecular weight (LMW) heparin, during the interruption of a longer-acting agent, typically warfarin. Limited indications for bridging The intent of bridging is to minimize the time the patient is not anticoagulated, thereby minimizing the risk for perioperative thromboembolism. However, this needs to be balanced with the importance of mitigating the risk of postoperative bleeding. Accumulating evidence suggests that in the vast majority of patients, bridging does not provide a benefit in lowering thromboembolic risk, whereas most data show a consistent increase in https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 21/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate bleeding risk. Our approach to the use of bridging is depicted in the algorithm ( algorithm 1) and summarized as follows: Avoid bridging in individuals who have low thromboembolic risk with anticoagulant interruption [59]: Individuals receiving a direct oral anticoagulant (DOAC), unless they have a high thromboembolic risk and a prolonged period during which they cannot take the DOAC postoperatively (eg, due to intestinal ileus) Routine prophylactic anticoagulation in atrial fibrillation Secondary prophylaxis following venous thromboembolism (VTE) (more than three months prior) Bridging may be appropriate during warfarin discontinuation in the following individuals, shown below; however, it may also be considered in other individuals in whom the clinician deems bridging appropriate based on individual patient characteristics and the type of surgery or procedure [1,59]: Mechanical mitral valve (exceptions may include those with newer-generation On-X valves or without any additional stroke risk factors) (see "Antithrombotic therapy for mechanical heart valves", section on 'Lower INR target for On-X aortic valve') Mechanical aortic valve with major additional stroke risk factors (eg, prior stroke or TIA) Embolic stroke within the previous three months or very high stroke risk (eg, CHADS 2 score of 5 or 6) VTE within the previous three months (except those with a calf deep vein thrombosis (DVT) and no evidence of DVT on repeat ultrasound, who may not require bridging) Possibly in selected individuals with recent coronary stenting (eg, within the previous three months) (see "Periprocedural management of antithrombotic therapy in patients receiving long-term oral anticoagulation and undergoing percutaneous coronary intervention") Previous thromboembolism during interruption of chronic anticoagulation (based on presumed increased risk; not addressed in clinical trials) Individuals with valvular atrial fibrillation (or associated with mitral valvular heart disease) have not been included in large trials, and there may be cases in which the clinician who best knows https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 22/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate the patient may have greater concerns about thrombosis and may decide that bridging is appropriate. We feel more strongly about avoiding bridging the lower the patient's baseline thromboembolic risk (eg, lower CHADS or CHA DS -VASc score ( table 3)) and the higher the 2 2 2 risk of bleeding. Evidence to support the limited use of bridging to selected individuals with very high thromboembolic risk comes from several meta-analyses. As an example, a 2020 meta-analysis that included six randomized trials and 12 cohort studies found that bridging was associated with an increased risk of bleeding (relative risk [RR] 2.83; 95% CI 2.00-4.01) with no statistical reduction in thromboembolic risk (RR 1.26; 95% CI 0.61-2.58) [60]. Supporting evidence for the practice of avoiding bridging in most individuals with atrial fibrillation includes the following: In the BRIDGE trial (Bridging Anticoagulation in Patients who Require Temporary Interruption of Warfarin Therapy for an Elective Invasive Procedure or Surgery), which randomly assigned 1884 patients with atrial fibrillation who required interruption of warfarin for an invasive procedure to receive bridging anticoagulation with the LMW heparin dalteparin versus placebo, the incidence of arterial thromboembolic events 30 days after the procedure was similar in those who received dalteparin or placebo (0.3 versus 0.4 percent) [48]. The incidence of major bleeding (a secondary outcome) was higher in those who received dalteparin (3.2 versus 1.3 percent), although none of the bleeds were fatal. Patients were excluded from the trial if they had a mechanical heart valve or a recent (within previous 12 weeks) stroke, embolism, or transient ischemic attack. The PERIOP-2 trial assessed 1471 patients with atrial fibrillation or a mechanical heart valve who required warfarin interruption for an elective surgery/procedure [49]. A mechanical heart valve was present in 21 percent (mitral in 9 percent; aortic in 12 percent). Before the surgery/procedure, all patients received bridging with the LMW heparin dalteparin, 200 IU/kg daily (100 IU/kg daily on the day before the surgery/procedure). After the surgery/procedure, patients were randomly assigned to receive dalteparin 200 IU/kg daily (fixed-dose 5,000 IU daily in patients at high-bleed-risk) or placebo until the INR was 2.0 and were followed for 12 weeks. There was no significant difference in the risk of major thromboembolism (for atrial fibrillation, 1.41 versus 0.75 percent, p = 0.27; for mechanical valves, 0 versus 0.67 percent, p = 0.49) or for major bleeding (for atrial fibrillation, 2.62 versus 1.64 percent, p = 0.25; for mechanical valves, 1.96 versus 0.67 percent, p = 0.62). Bridging versus no bridging did not affect major outcomes in patients who required a major procedure during participation in large anticoagulation trials for atrial fibrillation, https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 23/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate including the RE-LY (warfarin versus dabigatran), ROCKET-AF (warfarin versus rivaroxaban), and ARISTOTLE (warfarin versus apixaban) trials [9-11]. In the RE-LY trial, patients receiving warfarin had more thromboembolic events associated with bridging than with non-use of bridging (1.8 versus 0.3 percent); patients who received bridging also had a higher risk of major bleeding (warfarin: 6.8 percent with bridging, 1.6 percent without; dabigatran: 6.5 percent with bridging, 1.8 percent without) [61]. Additional real world data come from the ORBIT-AF and Dresden registries. ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) is a community-based registry of outpatients with atrial fibrillation receiving any oral anticoagulant; in this study, 2200 of 7372 individuals (30 percent) had interruption of anticoagulation for a procedure [62]. Bridging was used in 24 percent of these interruptions, especially in patients with a history of stroke or a mechanical heart valve and/or receiving warfarin; bleeding events were more common in individuals who received bridging compared with those who did not receive bridging (5 versus 1.3 percent). A composite endpoint that included major bleeding, myocardial infarction, stroke, systemic embolism, hospitalization, or death within 30 days was also higher in those who received bridging (13 versus 6.3 percent). In the Dresden NOAC registry, over 800 patients who were receiving dabigatran, rivaroxaban, or apixaban for any indication and underwent an invasive procedure had similar rates of major cardiovascular events if they received bridging, no bridging, or no anticoagulant discontinuation [63]. Bridging was not an independent risk factor for major bleeding; however, individuals undergoing major procedures were more likely to receive bridging and to have major bleeding. Supporting evidence for the practice of avoiding bridging in other groups includes the following: VTE In a systematic review from 2019 that evaluated patients who were receiving a vitamin K antagonist to treat venous thromboembolism (VTE; 28 cohort studies that included nearly 7000 procedures), the pooled incidence of recurrent VTE was similar with and without bridging [64]. The risk of bleeding was generally higher when bridging was used. Any indication for anticoagulation In a large systematic review and meta-analysis involving 34 studies (33 observational and one randomized) in patients receiving a vitamin K antagonist for any indication who were undergoing elective surgery or procedures. there was no significant difference in the rate of thromboembolism in patients who received bridging compared with patients who did not (odds ratio [OR] 0.80; 95% CI 0.42-1.54) [65]. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 24/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Bridging was associated with a threefold increase in major bleeding compared with no bridging (OR 3.60; 95% CI 1.52-8.50); full-dose heparin was associated with an increase in overall bleeding compared with lower heparin doses (OR 2.28; 95% CI 1.27-4.08). (See 'Heparin product and dose' below.) A potential role for bridging in reducing the risk of "rebound hypercoagulability" has also been proposed; however, this premise is not supported by data from the BRIDGE trial discussed above [48]. Heparin product and dose Typically, LMW heparins are used for bridging, as they have similar efficacy compared with unfractionated heparin, are more convenient to use, and generally do not require monitoring. Intravenous unfractionated heparin is less costly and can be reversed more rapidly than subcutaneous LMW heparin; it may be a reasonable alternative in some individuals. We prefer LMW heparin for bridging anticoagulation in individuals with a very high risk of arterial thromboembolism (eg, rheumatic heart disease, atrial fibrillation with recent embolic stroke, high-risk mechanical heart valve) and those with a moderate risk of thromboembolism (eg, active cancer) [27,28,66]. Perioperative anticoagulation management in individuals with prosthetic heart valves is discussed in detail separately. (See "Anticoagulation for prosthetic heart valves: Management of bleeding and invasive procedures", section on 'Planning for invasive procedures'.) For individuals with impaired kidney function and/or those requiring hemodialysis, intravenous or subcutaneous unfractionated heparin can be used more easily because dosing is unaffected by kidney function [67]. (See "Heparin and LMW heparin: Dosing and adverse effects", section on 'LMW heparin standard dosing'.) There are no data on using the direct oral anticoagulants (DOACs) as bridging agents. We do not use any of the DOACs for bridging. Heparins can be dosed at prophylactic doses, therapeutic doses, or doses intermediate between the two. The term "therapeutic dose" refers to doses typically used for treatment of thromboembolic disease, despite the fact that in this case it is being used prophylactically (to prevent thromboembolism). There are no clinical trial data or practice standards to guide dosing, and clinical judgment is required to determine the appropriate dose for each patient [65,68,69]. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 25/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Therapeutic dosing Therapeutic dosing (also called "full dose") is appropriate for bridging anticoagulation for individuals with a potential arterial thromboembolic source (eg, atrial fibrillation, mechanical heart valve) or VTE within the preceding month. Typical regimens include enoxaparin, 1 mg/kg subcutaneously twice daily or dalteparin, 100 units/kg subcutaneously twice daily. Intermediate dosing Intermediate-dose anticoagulation may be appropriate for individuals with atrial fibrillation or VTE within the preceding month when bridging is needed but concerns about bleeding are greater. Typical regimens include enoxaparin, 40 mg twice daily, or dalteparin, 5000 units subcutaneously twice daily. Prophylactic dosing Prophylactic-dose anticoagulation (also called "low dose") generally

bleeds were fatal. Patients were excluded from the trial if they had a mechanical heart valve or a recent (within previous 12 weeks) stroke, embolism, or transient ischemic attack. The PERIOP-2 trial assessed 1471 patients with atrial fibrillation or a mechanical heart valve who required warfarin interruption for an elective surgery/procedure [49]. A mechanical heart valve was present in 21 percent (mitral in 9 percent; aortic in 12 percent). Before the surgery/procedure, all patients received bridging with the LMW heparin dalteparin, 200 IU/kg daily (100 IU/kg daily on the day before the surgery/procedure). After the surgery/procedure, patients were randomly assigned to receive dalteparin 200 IU/kg daily (fixed-dose 5,000 IU daily in patients at high-bleed-risk) or placebo until the INR was 2.0 and were followed for 12 weeks. There was no significant difference in the risk of major thromboembolism (for atrial fibrillation, 1.41 versus 0.75 percent, p = 0.27; for mechanical valves, 0 versus 0.67 percent, p = 0.49) or for major bleeding (for atrial fibrillation, 2.62 versus 1.64 percent, p = 0.25; for mechanical valves, 1.96 versus 0.67 percent, p = 0.62). Bridging versus no bridging did not affect major outcomes in patients who required a major procedure during participation in large anticoagulation trials for atrial fibrillation, https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 23/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate including the RE-LY (warfarin versus dabigatran), ROCKET-AF (warfarin versus rivaroxaban), and ARISTOTLE (warfarin versus apixaban) trials [9-11]. In the RE-LY trial, patients receiving warfarin had more thromboembolic events associated with bridging than with non-use of bridging (1.8 versus 0.3 percent); patients who received bridging also had a higher risk of major bleeding (warfarin: 6.8 percent with bridging, 1.6 percent without; dabigatran: 6.5 percent with bridging, 1.8 percent without) [61]. Additional real world data come from the ORBIT-AF and Dresden registries. ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) is a community-based registry of outpatients with atrial fibrillation receiving any oral anticoagulant; in this study, 2200 of 7372 individuals (30 percent) had interruption of anticoagulation for a procedure [62]. Bridging was used in 24 percent of these interruptions, especially in patients with a history of stroke or a mechanical heart valve and/or receiving warfarin; bleeding events were more common in individuals who received bridging compared with those who did not receive bridging (5 versus 1.3 percent). A composite endpoint that included major bleeding, myocardial infarction, stroke, systemic embolism, hospitalization, or death within 30 days was also higher in those who received bridging (13 versus 6.3 percent). In the Dresden NOAC registry, over 800 patients who were receiving dabigatran, rivaroxaban, or apixaban for any indication and underwent an invasive procedure had similar rates of major cardiovascular events if they received bridging, no bridging, or no anticoagulant discontinuation [63]. Bridging was not an independent risk factor for major bleeding; however, individuals undergoing major procedures were more likely to receive bridging and to have major bleeding. Supporting evidence for the practice of avoiding bridging in other groups includes the following: VTE In a systematic review from 2019 that evaluated patients who were receiving a vitamin K antagonist to treat venous thromboembolism (VTE; 28 cohort studies that included nearly 7000 procedures), the pooled incidence of recurrent VTE was similar with and without bridging [64]. The risk of bleeding was generally higher when bridging was used. Any indication for anticoagulation In a large systematic review and meta-analysis involving 34 studies (33 observational and one randomized) in patients receiving a vitamin K antagonist for any indication who were undergoing elective surgery or procedures. there was no significant difference in the rate of thromboembolism in patients who received bridging compared with patients who did not (odds ratio [OR] 0.80; 95% CI 0.42-1.54) [65]. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 24/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Bridging was associated with a threefold increase in major bleeding compared with no bridging (OR 3.60; 95% CI 1.52-8.50); full-dose heparin was associated with an increase in overall bleeding compared with lower heparin doses (OR 2.28; 95% CI 1.27-4.08). (See 'Heparin product and dose' below.) A potential role for bridging in reducing the risk of "rebound hypercoagulability" has also been proposed; however, this premise is not supported by data from the BRIDGE trial discussed above [48]. Heparin product and dose Typically, LMW heparins are used for bridging, as they have similar efficacy compared with unfractionated heparin, are more convenient to use, and generally do not require monitoring. Intravenous unfractionated heparin is less costly and can be reversed more rapidly than subcutaneous LMW heparin; it may be a reasonable alternative in some individuals. We prefer LMW heparin for bridging anticoagulation in individuals with a very high risk of arterial thromboembolism (eg, rheumatic heart disease, atrial fibrillation with recent embolic stroke, high-risk mechanical heart valve) and those with a moderate risk of thromboembolism (eg, active cancer) [27,28,66]. Perioperative anticoagulation management in individuals with prosthetic heart valves is discussed in detail separately. (See "Anticoagulation for prosthetic heart valves: Management of bleeding and invasive procedures", section on 'Planning for invasive procedures'.) For individuals with impaired kidney function and/or those requiring hemodialysis, intravenous or subcutaneous unfractionated heparin can be used more easily because dosing is unaffected by kidney function [67]. (See "Heparin and LMW heparin: Dosing and adverse effects", section on 'LMW heparin standard dosing'.) There are no data on using the direct oral anticoagulants (DOACs) as bridging agents. We do not use any of the DOACs for bridging. Heparins can be dosed at prophylactic doses, therapeutic doses, or doses intermediate between the two. The term "therapeutic dose" refers to doses typically used for treatment of thromboembolic disease, despite the fact that in this case it is being used prophylactically (to prevent thromboembolism). There are no clinical trial data or practice standards to guide dosing, and clinical judgment is required to determine the appropriate dose for each patient [65,68,69]. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 25/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Therapeutic dosing Therapeutic dosing (also called "full dose") is appropriate for bridging anticoagulation for individuals with a potential arterial thromboembolic source (eg, atrial fibrillation, mechanical heart valve) or VTE within the preceding month. Typical regimens include enoxaparin, 1 mg/kg subcutaneously twice daily or dalteparin, 100 units/kg subcutaneously twice daily. Intermediate dosing Intermediate-dose anticoagulation may be appropriate for individuals with atrial fibrillation or VTE within the preceding month when bridging is needed but concerns about bleeding are greater. Typical regimens include enoxaparin, 40 mg twice daily, or dalteparin, 5000 units subcutaneously twice daily. Prophylactic dosing Prophylactic-dose anticoagulation (also called "low dose") generally is not used for bridging in patients with atrial fibrillation, because there is no evidence that prophylactic-dose heparin prevents stroke in this setting. This dose level may be reasonable in patients who have had a VTE event within the preceding 3 to 12 months. Typical prophylactic regimens include enoxaparin, 40 mg once daily, or dalteparin, 5000 units subcutaneously once daily. The use of prophylactic-dose heparin for postoperative VTE prevention in patients not receiving ongoing anticoagulation is discussed separately. (See "Prevention of venous thromboembolic disease in adult nonorthopedic surgical patients".) Additional details regarding heparin products, including dose adjustments for obesity and impaired kidney function, are provided separately. (See "Heparin and LMW heparin: Dosing and adverse effects".) Timing of bridging Once a decision to use bridging has been made, the next decision is whether to use bridging before the procedure, after the procedure, or both ( table 7). Sample bridging protocols are provided on the Thrombosis Canada website. Atrial fibrillation As noted above, we suggest not using bridging for most patients with atrial fibrillation. (See 'Limited indications for bridging' above.) However, for individuals for whom bridging is used due to a very high risk of thromboembolism, we use bridging both preoperatively and postoperatively [14]. Warfarin is usually resumed 12 to 24 hours after surgery, typically the evening of the day of surgery or the evening of the day after surgery, as long as adequate hemostasis has been achieved. (See 'Warfarin interruption' above.) Venous thromboembolism https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 26/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate First three months For individuals within the first three months after an acute episode of VTE, we use bridging both preoperatively and postoperatively, typically with therapeutic-dose LMW heparin (eg, enoxaparin 1 mg/kg twice daily) [14]. This practice is based on the high incidence of recurrence without anticoagulation. While postoperative intravenous heparin doubles the rate of bleeding, there is a net reduction in serious morbidity in such patients because the risk of postoperative recurrent VTE is high. (See 'Preoperative timing of bridging' below and 'Postoperative timing of bridging' below.) In selected patients in whom surgery cannot be delayed beyond the first month after the diagnosis of an acute VTE, it may be appropriate to use a temporary inferior vena cava (IVC) filter, especially if bridging anticoagulation cannot be used postoperatively due to high bleeding risk. (See "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)", section on 'Patients at high risk of bleeding' and "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Inferior vena cava filters'.) Greater than three months For individuals greater than three months after an acute episode of VTE, we generally use postoperative bridging, typically with a low-dose LMW heparin regimen (eg, enoxaparin 40 mg daily), but not preoperative bridging [70]. For patients who are undergoing a minor procedure or day surgery, bridging is probably not justified. This practice is based on the significantly reduced risk of VTE recurrence after the first month [71,72]. (See 'Postoperative timing of bridging' below.) Preoperative timing of bridging We generally initiate heparin bridging three days before a planned procedure (ie, two days after stopping warfarin), when the prothrombin time/international normalized ratio (PT/INR) has started to drop below the therapeutic range. LMW heparin We discontinue low molecular weight (LMW) heparin 24 hours before the planned surgery or procedure, based on a biologic half-life of most subcutaneous LMW heparins of approximately three to five hours [8,66,73]. If a twice-daily LMW heparin regimen is given, the evening dose the night before surgery is omitted, whereas if a once- daily regimen is given (eg, dalteparin 200 international units/kg), one-half of the total daily dose is given on the morning of the day before surgery. This ensures that no significant residual anticoagulant will be present at the time of surgery, based on studies that have shown a residual anticoagulant effect at 24 hours after stopping therapeutic-dose LMW heparin, and it is consistent with the 2012 American College of Chest Physicians (ACCP) Guidelines [8,12,74,75]. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 27/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Unfractionated heparin For therapeutic-dose unfractionated heparin, we continue the intravenous infusion until four to five hours before the procedure, based on the biologic half-life of intravenous unfractionated heparin of approximately 45 minutes [8,73,74]. If subcutaneous unfractionated heparin is used, typically with a dose of approximately 250 international units/kg twice daily, the last dose can be given the evening before the procedure. Postoperative timing of bridging Postoperative resumption of unfractionated heparin and LMW heparin is similar, based on the onset of anticoagulation at approximately one hour after administration for both forms of heparin, and peak anticoagulant activity at approximately three to five hours. The resumption of bridging, especially when given as a therapeutic-dose regimen, should be delayed until there is adequate hemostasis based on a clinical assessment of the wound site, drainage fluid amount, and expected postoperative bleeding; coupled, where appropriate, with hemoglobin levels [76]. This assessment will vary depending on the surgery type and individual patient considerations, and it may be difficult for surgery where ongoing bleeding is not readily apparent (eg, cardiac, intracranial). A slight delay in resumption of postoperative anticoagulation is preferable to premature initiation of postoperative bridging that results in bleeding, which ultimately will lengthen the period without an anticoagulant and thus increase thromboembolic risk. For those undergoing major surgery or those with a high bleeding risk procedure, therapeutic-dose unfractionated heparin or LMW heparin should be delayed for 48 to 72 hours after hemostasis has been secured [8]. For most minor procedures associated with a low bleeding risk in which bridging is used (eg, laparoscopic hernia repair), therapeutic-dose unfractionated heparin or LMW heparin can usually be resumed 24 hours after the procedure. Resumption of bridging anticoagulation too early, especially the use of therapeutic-dose heparin within 24 hours after surgery, is associated with a two- to fourfold increased risk for major bleeding compared with no bridging or prophylactic-dose heparin. The increased bleeding risk was demonstrated in the Prospective peri-operative enoxaparin cohort trial (PROSPECT), which evaluated bleeding risk in a cohort of 260 patients undergoing major surgery whose treating clinicians used bridging anticoagulation [77]. In this trial, nine patients had major postoperative bleeding (3.5 percent), most on postoperative day 0, and 19 (7.3 percent) had minor bleeding. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 28/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Postoperatively, warfarin is generally resumed on the same postoperative day as the heparin. Heparin can be discontinued when the INR reaches the therapeutic range for individuals at moderate thromboembolism risk. Individuals with heparin-induced thrombocytopenia Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening condition in which heparin-induced antibodies to platelets can cause thrombocytopenia and/or venous or arterial thrombosis. (See "Clinical presentation and diagnosis of heparin-induced thrombocytopenia".) Patients with HIT should not receive any heparin (eg, they should not receive heparin flushes, unfractionated heparin, or LMW heparin). Non-heparin anticoagulants that can be used in patients with HIT are discussed separately. (See "Management of heparin-induced thrombocytopenia", section on 'Anticoagulation'.) URGENT/EMERGENCY INVASIVE PROCEDURE Reversal of the patient's usual anticoagulant may be required for more urgent or emergency surgery or procedures or to treat perioperative bleeding. Agents with a potential prothrombotic effect (eg, prothrombin complex concentrates [PCCs], plasma products, immediate reversal agents) should be reserved for the treatment of severe, life-threatening bleeding or anticipated severe bleeding (eg, intracranial hemorrhage, emergency major surgery with elevated prothrombin time/international normalized ratio [PT/INR]). Agent-specific strategies include the following: Warfarin For individuals who require reversal of warfarin or other vitamin K antagonists, the appropriate reversal strategy is determined by the degree of anticoagulation (eg, PT/INR, clinical bleeding), urgency of the procedure, and degree of bleeding risk ( table 8). If semi-urgent reversal of warfarin is required (eg, within one to two days), warfarin should be withheld and vitamin K administered (eg, 2.5 to 5 mg of oral or intravenous vitamin K). (See "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Urgent surgery/procedure'.) If immediate reversal is required (eg, for emergency surgery or active bleeding), this can be achieved via the use of PCCs or plasma products (eg, Fresh Frozen Plasma [FFP], Plasma Frozen Within 24 Hours After Phlebotomy [PF24]) along with vitamin K ( table 9) [78,79]. The 4-factor PCCs contain adequate amounts of all vitamin K- dependent clotting factors, whereas 3-factor PCCs may require supplementation with https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 29/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate FFP for adequate factor VII ( table 10). Of note, there is a thrombotic risk associated with these products, and they should be used only if there is life-threatening bleeding and prolongation of the INR by a vitamin K antagonist [79]. (See "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Serious/life- threatening bleeding'.) Dabigatran Dabigatran is an oral direct thrombin inhibitor; it can be reversed by idarucizumab ( table 11). In an open-label study involving 503 patients who had bleeding or required emergency surgery, idarucizumab effectively reversed the anticoagulant effect of dabigatran [80]. The use of this agent as well as other potential strategies for individuals receiving dabigatran who are at great risk of serious bleeding with an emergency procedure are presented separately. (See "Management of bleeding in patients receiving direct oral anticoagulants".) Rivaroxaban, apixaban, and edoxaban Rivaroxaban, apixaban, and edoxaban are oral direct factor Xa inhibitors; these anticoagulants can be reversed by andexanet alfa or a PCC ( table 11). These and other potential strategies for individuals receiving these agents who are at great risk of serious bleeding with an urgent/emergency procedure are presented separately. (See "Management of bleeding in patients receiving direct oral anticoagulants".) Algorithms for anticoagulant reversal depending on the severity of bleeding are provided by various societies and groups such as Thrombosis Canada. Additional discussions of postoperative bleeding are presented separately. (See "Postoperative complications among patients undergoing cardiac surgery", section on 'Hematologic dysfunction'.) NEURAXIAL ANESTHESIA Neuraxial (ie, spinal or epidural) anesthesia should not be used in anticoagulated individuals, due to the risk of potentially catastrophic bleeding into the epidural space. The increased risk of bleeding applies both at the time of catheter placement and the time of removal. If neuraxial anesthesia is considered for surgical anesthesia or postoperative pain control, the timing of anesthesia and anticoagulant administration should be coordinated to optimize the safe use of both. Early consultation with the anesthesiologist is advised. This subject is discussed in detail separately. (See "Neuraxial anesthesia/analgesia techniques in the patient receiving anticoagulant or antiplatelet medication".) https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 30/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate The timing of anticoagulant use in patients receiving neuraxial anesthesia is illustrated by evidence-based guidelines from the American Society of Regional Anesthesia (ASRA), which suggest the following [81,82]: Prophylactic-dose low molecular weight (LMW) heparin (eg, enoxaparin, 40 mg once daily): Before surgery, wait at least 10 to 12 hours after the last dose of LMW heparin is administered before a spinal/epidural catheter is placed. After surgery, when there is adequate surgical site hemostasis, wait at least six to eight hours after catheter removal before resuming treatment with LMW heparins. Therapeutic-dose LMW heparin (eg, enoxaparin, 1 mg/kg twice daily): Before surgery, wait at least 24 hours after the last dose of LMW heparin is administered before a spinal/epidural catheter is placed. After surgery, when there is adequate surgical site hemostasis, for twice daily dosing, wait at least 24 hours after catheter removal before resuming therapeutic-dose LMW heparin. For once daily dosing, wait at least six to eight hours after catheter removal before the first dose; the second postoperative dose should occur no sooner than 24 hours after the first dose. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Anticoagulation".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 31/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Taking oral medicines for blood clots (The Basics)" and "Patient education: Choosing an oral medicine for blood clots (The Basics)") Beyond the Basics topics (see "Patient education: Warfarin (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS Balancing thromboembolic and bleeding risk Interruption of anticoagulation temporarily increases thromboembolic risk, and continuing anticoagulation increases the risk of bleeding. We take into account these risks, along with specific features of the anticoagulant the patient is taking. Internet-based resources and case examples are provided above. (See 'Overview of our approach' above.) Thromboembolic risk Those at very high or high thromboembolic risk should limit the period without anticoagulation to the shortest possible interval ( table 1). If thromboembolic risk is transiently increased (eg, recent stroke, recent pulmonary embolism), we prefer to delay surgery until the risk returns to baseline, if possible. (See 'Estimating thromboembolic risk' above.) Atrial fibrillation We estimate thromboembolic risk for patients with atrial fibrillation based on clinical variables including age and comorbidities. In the RE-LY (Randomized Evaluation of Long-Term Anticoagulant Therapy) trial, the perioperative thromboembolic risk was 1.2 percent based on a composite endpoint of stroke, cardiovascular death, and pulmonary embolus. The risk of recurrent arterial embolism from any cardiac source is approximately 0.5 percent per day in the first month after an acute event. (See 'Atrial fibrillation' above and "Atrial fibrillation in adults: Use of oral anticoagulants".) Prosthetic heart valve The risks of thromboembolism and perioperative management of patients with bioprosthetic and mechanical heart valves are discussed separately. (See "Anticoagulation for prosthetic heart valves: Management of bleeding and invasive procedures", section on 'Planning for invasive procedures' and "Diagnosis of mechanical prosthetic valve thrombosis or obstruction".) https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 32/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Recent thromboembolism The perioperative risk of venous thromboembolism (VTE) is greatest in individuals with an event within the prior three months, and those with a history of VTE associated with a high-risk inherited thrombophilia. Patients who require surgery within the first three months following an episode of VTE are likely to benefit from delaying elective surgery, even if the delay is only for a few weeks. (See 'Recent thromboembolism' above.) Bleeding risk A higher bleeding risk confers a greater need for perioperative hemostasis, and hence a longer period of anticoagulant interruption. Bleeding risk is dominated by the type and urgency of surgery ( table 2); some patient comorbidities (eg, older age, decreased kidney function) and medications that affect hemostasis also contribute. (See 'Estimating procedural bleeding risk' above and 'Deciding whether to interrupt anticoagulation' above.) High risk High bleeding risk procedures include coronary artery bypass surgery, kidney biopsy, and any procedure lasting >45 minutes. In general, the anticoagulant must be discontinued if the surgical bleeding risk is high. (See 'Settings requiring anticoagulant interruption' above.) Low risk Low bleeding risk procedures include dental extractions, minor skin surgery, cholecystectomy, carpal tunnel repair, and abdominal hysterectomy. Individuals undergoing selected low bleeding risk surgery often can continue their anticoagulant. (See 'Settings in which continuing the anticoagulant may be preferable' above.) Cardiac implantable device or catheter ablation for atrial fibrillation Continuing warfarin was associated with a lower risk of bleeding in patients on the BRUISE CONTROL trial who were undergoing implantation of a cardiac implantable electronic device (eg, pacemaker, implantable cardioverter-defibrillator) and patients on the COMPARE trial who were undergoing catheter ablation for atrial fibrillation. (See 'Overview of whether to interrupt' above and "Cardiac implantable electronic devices: Periprocedural complications".) Timing of interruption The timing of interruption depends on the periprocedural bleeding risk and the specific anticoagulant. The algorithm summarizes our approach ( algorithm 1). The figure illustrates the timing of direct oral anticoagulant (DOAC) interruption ( figure 1). (See 'Timing of anticoagulant interruption' above.) Bridging Bridging anticoagulation involves the administration of a short-acting anticoagulant, typically a low molecular weight (LMW) heparin, during the interruption of a https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 33/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate longer-acting agent, typically warfarin. The intent is to minimize the risk of perioperative thromboembolism. For most individuals, bridging increases bleeding risk without lowering thromboembolic risk, and we suggest not using bridging (Grade 2B). We feel more strongly about avoiding bridging the lower the baseline thromboembolic risk and the higher the bleeding risk. We generally do not use bridging for DOACs. (See 'Limited indications for bridging' above.) For selected patients on warfarin (eg, stroke, systemic embolism, or transient ischemic attack within the previous three months; atrial fibrillation and very high risk of stroke [eg, CHADS score of 5 or 6]; VTE within the previous three months; recent coronary stenting; 2 previous thromboembolism during interruption of chronic anticoagulation), we suggest the use of bridging (Grade 2C). Agent When bridging is used, we prefer LMW heparin for most patients. An exception is an individual with impaired kidney function and/or hemodialysis requirement, for whom intravenous or subcutaneous unfractionated heparin can be used more easily. We do not use DOACs for bridging. Non-heparin anticoagulants that can be used in patients with heparin-induced thrombocytopenia are discussed separately. (See 'Heparin product and dose' above.) Timing Bridging can be used preoperatively, postoperatively, or both, depending on the underlying condition for which the patient is being anticoagulated ( table 7). The timing depends on the heparin product used and the procedural bleeding risk. Importantly, resumption of bridging anticoagulation too early is associated with an increased risk for major bleeding. (See 'Timing of bridging' above.) The role of bridging in individuals with mechanical heart valves is discussed separately. (See "Anticoagulation for prosthetic heart valves: Management of bleeding and invasive procedures".) Urgent/Emergency procedure Reversal of the patient's usual anticoagulant may be required for more urgent or emergency procedures or to treat perioperative bleeding. Agents with a potential prothrombotic effect (eg, immediate reversal agents, prothrombin complex concentrates, plasma products) should be reserved for the treatment of life- threatening, severe bleeding or anticipated severe bleeding (intracranial hemorrhage, emergency major surgery). (See 'Urgent/emergency invasive procedure' above and "Management of bleeding in patients receiving direct oral anticoagulants".) Use of UpToDate is subject to the Terms of Use. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 34/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate REFERENCES 1. Douketis JD. Perioperative management of patients who are receiving warfarin therapy: an evidence-based and practical approach. Blood 2011; 117:5044. 2. Spyropoulos AC, Douketis JD. How I treat anticoagulated patients undergoing an elective procedure or surgery. Blood 2012; 120:2954. 3. Torn M, Rosendaal FR. Oral anticoagulation in surgical procedures: risks and recommendations. Br J Haematol 2003; 123:676. 4. Kakkar VV, Cohen AT, Edmonson RA, et al. Low molecular weight versus standard heparin for prevention of venous thromboembolism after major abdominal surgery. The Thromboprophylaxis Collaborative Group. Lancet 1993; 341:259. 5. Jaffer AK. Perioperative management of warfarin and antiplatelet therapy. Cleve Clin J Med 2009; 76 Suppl 4:S37. 6. Gallego P, Apostolakis S, Lip GY. Bridging evidence-based practice and practice-based evidence in periprocedural anticoagulation. Circulation 2012; 126:1573. 7. Bell BR, Spyropoulos AC, Douketis JD. Perioperative Management of the Direct Oral Anticoagulants: A Case-Based Review. Hematol Oncol Clin North Am 2016; 30:1073. 8. Douketis JD, Spyropoulos AC, Spencer FA, et al. Perioperative management of antithrombotic therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e326S. 9. Healey JS, Eikelboom J, Douketis J, et al. Periprocedural bleeding and thromboembolic events with dabigatran compared with warfarin: results from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) randomized trial. Circulation 2012; 126:343. 10. Garcia D, Alexander JH, Wallentin L, et al. Management and clinical outcomes in patients treated with apixaban vs warfarin undergoing procedures. Blood 2014; 124:3692. 11. Sherwood MW, Douketis JD, Patel MR, et al. Outcomes of temporary interruption of rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation: results from the rivaroxaban once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation (ROCKET AF). Circulation 2014; 129:1850. 12. Coon WW, Willis PW 3rd. Recurrence of venous thromboembolism. Surgery 1973; 73:823. 13. Douketis JD, Foster GA, Crowther MA, et al. Clinical risk factors and timing of recurrent venous thromboembolism during the initial 3 months of anticoagulant therapy. Arch Intern Med 2000; 160:3431. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 35/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate 14. Kearon C, Hirsh J. Management of anticoagulation before and after elective surgery. N Engl J Med 1997; 336:1506. 15. Levine MN, Hirsh J, Gent M, et al. Optimal duration of oral anticoagulant therapy: a randomized trial comparing four weeks with three months of warfarin in patients with proximal deep vein thrombosis. Thromb Haemost 1995; 74:606. 16. Optimum duration of anticoagulation for deep-vein thrombosis and pulmonary embolism. Research Committee of the British Thoracic Society. Lancet 1992; 340:873. 17. Cardiogenic brain embolism. Cerebral Embolism Task Force. Arch Neurol 1986; 43:71. 18. Lip GY. Intracardiac thrombus formation in cardiac impairment: the role of anticoagulant therapy. Postgrad Med J 1996; 72:731. 19. Loh E, Sutton MS, Wun CC, et al. Ventricular dysfunction and the risk of stroke after myocardial infarction. N Engl J Med 1997; 336:251. 20. Nixon JV. Left ventricular mural thrombus. Arch Intern Med 1983; 143:1567. 21. Nieuwenhuis HK, Albada J, Banga JD, Sixma JJ. Identification of risk factors for bleeding during treatment of acute venous thromboembolism with heparin or low molecular weight heparin. Blood 1991; 78:2337. 22. Levine MN, Raskob G, Landefeld S, Hirsh J. Hemorrhagic complications of anticoagulant treatment. Chest 1995; 108:276S. 23. Mehran R, Rao SV, Bhatt DL, et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation 2011; 123:2736. 24. Omran H, Bauersachs R, R benacker S, et al. The HAS-BLED score predicts bleedings during bridging of chronic oral anticoagulation. Results from the national multicentre BNK Online bRiDging REgistRy (BORDER). Thromb Haemost 2012; 108:65. 25. Armstrong MJ, Gronseth G, Anderson DC, et al. Summary of evidence-based guideline: periprocedural management of antithrombotic medications in patients with ischemic cerebrovascular disease: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 2013; 80:2065. 26. Collins LJ, Silverman DI, Douglas PS, Manning WJ. Cardioversion of nonrheumatic atrial fibrillation. Reduced thromboembolic complications with 4 weeks of precardioversion anticoagulation are related to atrial thrombus resolution. Circulation 1995; 92:160. 27. Singer DE, Albers GW, Dalen JE, et al. Antithrombotic therapy in atrial fibrillation: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:546S. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 36/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate 28. Salem DN, O'Gara PT, Madias C, Pauker SG. Valvular and structural heart disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:593S. 29. McIntyre H. Management, during dental surgery, of patients on anticoagulants. Lancet 1966; 2:99. 30. Wahl MJ. Dental surgery in anticoagulated patients. Arch Intern Med 1998; 158:1610. 31. Malden N. Dental procedures can be undertaken without alteration of oral anticoagulant regimen. Evid Based Dent 2005; 6:11. 32. Blinder D, Manor Y, Martinowitz U, Taicher S. Dental extractions in patients maintained on oral anticoagulant therapy: comparison of INR value with occurrence of postoperative bleeding. Int J Oral Maxillofac Surg 2001; 30:518. 33. Garcia-Darennes F, Darennes J, Freidel M, Breton P. [Protocol for adapting treatment with vitamin K antagonists before dental extraction]. Rev Stomatol Chir Maxillofac 2003; 104:69. 34. Perry DJ, Noakes TJ, Helliwell PS, British Dental Society. Guidelines for the management of patients on oral anticoagulants requiring dental surgery. Br Dent J 2007; 203:389. 35. Svensson R, Hallmer F, Englesson CS, et al. Treatment with local hemostatic agents and primary closure after tooth extraction in warfarin treated patients. Swed Dent J 2013; 37:71. 36. Sindet-Pedersen S, Ramstr m G, Bernvil S, Blomb ck M. Hemostatic effect of tranexamic acid mouthwash in anticoagulant-treated patients undergoing oral surgery. N Engl J Med 1989; 320:840. 37. Webster K, Wilde J. Management of anticoagulation in patients with prosthetic heart valves undergoing oral and maxillofacial operations. Br J Oral Maxillofac Surg 2000; 38:124. 38. Souto JC, Oliver A, Zuazu-Jausoro I, et al. Oral surgery in anticoagulated patients without reducing the dose of oral anticoagulant: a prospective randomized study. J Oral Maxillofac Surg 1996; 54:27. 39. Patatanian E, Fugate SE. Hemostatic mouthwashes in anticoagulated patients undergoing dental extraction. Ann Pharmacother 2006; 40:2205. 40. Sticherling C, Marin F, Birnie D, et al. Antithrombotic management in patients undergoing electrophysiological procedures: a European Heart Rhythm Association (EHRA) position document endorsed by the ESC Working Group Thrombosis, Heart Rhythm Society (HRS), and Asia Pacific Heart Rhythm Society (APHRS). Europace 2015; 17:1197. 41. Birnie DH, Healey JS, Wells GA, et al. Pacemaker or defibrillator surgery without interruption of anticoagulation. N Engl J Med 2013; 368:2084. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 37/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate 42. Essebag V, Proietti R, Birnie DH, et al. Short-term dabigatran interruption before cardiac rhythm device implantation: multi-centre experience from the RE-LY trial. Europace 2017. 43. Shahi V, Brinjikji W, Murad MH, et al. Safety of Uninterrupted Warfarin Therapy in Patients

for prevention of venous thromboembolism after major abdominal surgery. The Thromboprophylaxis Collaborative Group. Lancet 1993; 341:259. 5. Jaffer AK. Perioperative management of warfarin and antiplatelet therapy. Cleve Clin J Med 2009; 76 Suppl 4:S37. 6. Gallego P, Apostolakis S, Lip GY. Bridging evidence-based practice and practice-based evidence in periprocedural anticoagulation. Circulation 2012; 126:1573. 7. Bell BR, Spyropoulos AC, Douketis JD. Perioperative Management of the Direct Oral Anticoagulants: A Case-Based Review. Hematol Oncol Clin North Am 2016; 30:1073. 8. Douketis JD, Spyropoulos AC, Spencer FA, et al. Perioperative management of antithrombotic therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e326S. 9. Healey JS, Eikelboom J, Douketis J, et al. Periprocedural bleeding and thromboembolic events with dabigatran compared with warfarin: results from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) randomized trial. Circulation 2012; 126:343. 10. Garcia D, Alexander JH, Wallentin L, et al. Management and clinical outcomes in patients treated with apixaban vs warfarin undergoing procedures. Blood 2014; 124:3692. 11. Sherwood MW, Douketis JD, Patel MR, et al. Outcomes of temporary interruption of rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation: results from the rivaroxaban once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation (ROCKET AF). Circulation 2014; 129:1850. 12. Coon WW, Willis PW 3rd. Recurrence of venous thromboembolism. Surgery 1973; 73:823. 13. Douketis JD, Foster GA, Crowther MA, et al. Clinical risk factors and timing of recurrent venous thromboembolism during the initial 3 months of anticoagulant therapy. Arch Intern Med 2000; 160:3431. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 35/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate 14. Kearon C, Hirsh J. Management of anticoagulation before and after elective surgery. N Engl J Med 1997; 336:1506. 15. Levine MN, Hirsh J, Gent M, et al. Optimal duration of oral anticoagulant therapy: a randomized trial comparing four weeks with three months of warfarin in patients with proximal deep vein thrombosis. Thromb Haemost 1995; 74:606. 16. Optimum duration of anticoagulation for deep-vein thrombosis and pulmonary embolism. Research Committee of the British Thoracic Society. Lancet 1992; 340:873. 17. Cardiogenic brain embolism. Cerebral Embolism Task Force. Arch Neurol 1986; 43:71. 18. Lip GY. Intracardiac thrombus formation in cardiac impairment: the role of anticoagulant therapy. Postgrad Med J 1996; 72:731. 19. Loh E, Sutton MS, Wun CC, et al. Ventricular dysfunction and the risk of stroke after myocardial infarction. N Engl J Med 1997; 336:251. 20. Nixon JV. Left ventricular mural thrombus. Arch Intern Med 1983; 143:1567. 21. Nieuwenhuis HK, Albada J, Banga JD, Sixma JJ. Identification of risk factors for bleeding during treatment of acute venous thromboembolism with heparin or low molecular weight heparin. Blood 1991; 78:2337. 22. Levine MN, Raskob G, Landefeld S, Hirsh J. Hemorrhagic complications of anticoagulant treatment. Chest 1995; 108:276S. 23. Mehran R, Rao SV, Bhatt DL, et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation 2011; 123:2736. 24. Omran H, Bauersachs R, R benacker S, et al. The HAS-BLED score predicts bleedings during bridging of chronic oral anticoagulation. Results from the national multicentre BNK Online bRiDging REgistRy (BORDER). Thromb Haemost 2012; 108:65. 25. Armstrong MJ, Gronseth G, Anderson DC, et al. Summary of evidence-based guideline: periprocedural management of antithrombotic medications in patients with ischemic cerebrovascular disease: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 2013; 80:2065. 26. Collins LJ, Silverman DI, Douglas PS, Manning WJ. Cardioversion of nonrheumatic atrial fibrillation. Reduced thromboembolic complications with 4 weeks of precardioversion anticoagulation are related to atrial thrombus resolution. Circulation 1995; 92:160. 27. Singer DE, Albers GW, Dalen JE, et al. Antithrombotic therapy in atrial fibrillation: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:546S. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 36/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate 28. Salem DN, O'Gara PT, Madias C, Pauker SG. Valvular and structural heart disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:593S. 29. McIntyre H. Management, during dental surgery, of patients on anticoagulants. Lancet 1966; 2:99. 30. Wahl MJ. Dental surgery in anticoagulated patients. Arch Intern Med 1998; 158:1610. 31. Malden N. Dental procedures can be undertaken without alteration of oral anticoagulant regimen. Evid Based Dent 2005; 6:11. 32. Blinder D, Manor Y, Martinowitz U, Taicher S. Dental extractions in patients maintained on oral anticoagulant therapy: comparison of INR value with occurrence of postoperative bleeding. Int J Oral Maxillofac Surg 2001; 30:518. 33. Garcia-Darennes F, Darennes J, Freidel M, Breton P. [Protocol for adapting treatment with vitamin K antagonists before dental extraction]. Rev Stomatol Chir Maxillofac 2003; 104:69. 34. Perry DJ, Noakes TJ, Helliwell PS, British Dental Society. Guidelines for the management of patients on oral anticoagulants requiring dental surgery. Br Dent J 2007; 203:389. 35. Svensson R, Hallmer F, Englesson CS, et al. Treatment with local hemostatic agents and primary closure after tooth extraction in warfarin treated patients. Swed Dent J 2013; 37:71. 36. Sindet-Pedersen S, Ramstr m G, Bernvil S, Blomb ck M. Hemostatic effect of tranexamic acid mouthwash in anticoagulant-treated patients undergoing oral surgery. N Engl J Med 1989; 320:840. 37. Webster K, Wilde J. Management of anticoagulation in patients with prosthetic heart valves undergoing oral and maxillofacial operations. Br J Oral Maxillofac Surg 2000; 38:124. 38. Souto JC, Oliver A, Zuazu-Jausoro I, et al. Oral surgery in anticoagulated patients without reducing the dose of oral anticoagulant: a prospective randomized study. J Oral Maxillofac Surg 1996; 54:27. 39. Patatanian E, Fugate SE. Hemostatic mouthwashes in anticoagulated patients undergoing dental extraction. Ann Pharmacother 2006; 40:2205. 40. Sticherling C, Marin F, Birnie D, et al. Antithrombotic management in patients undergoing electrophysiological procedures: a European Heart Rhythm Association (EHRA) position document endorsed by the ESC Working Group Thrombosis, Heart Rhythm Society (HRS), and Asia Pacific Heart Rhythm Society (APHRS). Europace 2015; 17:1197. 41. Birnie DH, Healey JS, Wells GA, et al. Pacemaker or defibrillator surgery without interruption of anticoagulation. N Engl J Med 2013; 368:2084. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 37/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate 42. Essebag V, Proietti R, Birnie DH, et al. Short-term dabigatran interruption before cardiac rhythm device implantation: multi-centre experience from the RE-LY trial. Europace 2017. 43. Shahi V, Brinjikji W, Murad MH, et al. Safety of Uninterrupted Warfarin Therapy in Patients Undergoing Cardiovascular Endovascular Procedures: A Systematic Review and Meta- Analysis. Radiology 2016; 278:383. 44. Di Biase L, Burkhardt JD, Santangeli P, et al. Periprocedural stroke and bleeding complications in patients undergoing catheter ablation of atrial fibrillation with different anticoagulation management: results from the Role of Coumadin in Preventing Thromboembolism in Atrial Fibrillation (AF) Patients Undergoing Catheter Ablation (COMPARE) randomized trial. Circulation 2014; 129:2638. 45. Godier A, Dincq AS, Martin AC, et al. Predictors of pre-procedural concentrations of direct oral anticoagulants: a prospective multicentre study. Eur Heart J 2017; 38:2431. 46. White RH, McKittrick T, Hutchinson R, Twitchell J. Temporary discontinuation of warfarin therapy: changes in the international normalized ratio. Ann Intern Med 1995; 122:40. 47. Larson BJ, Zumberg MS, Kitchens CS. A feasibility study of continuing dose-reduced warfarin for invasive procedures in patients with high thromboembolic risk. Chest 2005; 127:922. 48. Douketis JD, Spyropoulos AC, Kaatz S, et al. Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation. N Engl J Med 2015; 373:823. 49. Kovacs MJ, Wells PS, Anderson DR, et al. Postoperative low molecular weight heparin bridging treatment for patients at high risk of arterial thromboembolism (PERIOP2): double blind randomised controlled trial. BMJ 2021; 373:n1205. 50. Hylek EM, Regan S, Go AS, et al. Clinical predictors of prolonged delay in return of the international normalized ratio to within the therapeutic range after excessive anticoagulation with warfarin. Ann Intern Med 2001; 135:393. 51. Douketis JD, Berger PB, Dunn AS, et al. The perioperative management of antithrombotic therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:299S. 52. Shaw JR, Li N, Vanassche T, et al. Predictors of preprocedural direct oral anticoagulant levels in patients having an elective surgery or procedure. Blood Adv 2020; 4:3520. 53. Stangier J, Rathgen K, St hle H, Mazur D. Influence of renal impairment on the pharmacokinetics and pharmacodynamics of oral dabigatran etexilate: an open-label, parallel-group, single-centre study. Clin Pharmacokinet 2010; 49:259. 54. van Ryn J, Stangier J, Haertter S, et al. 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Regional anaesthesia in the patient receiving antithrombotic and antiplatelet therapy. Br J Anaesth 2011; 107 Suppl 1:i96. 82. Horlocker TT, Vandermeuelen E, Kopp SL, et al. Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (Fourth Edition). Reg Anesth Pain Med 2018; 43:263. Topic 1312 Version 84.0 https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 41/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate GRAPHICS Perioperative thrombotic risk Indication for anticoagulant therapy Thrombotic risk Mechanical heart valve Atrial fibrillation VTE High thrombotic risk* Any mitral valve CHADS score 5-6 Recent (within 3 2 prosthesis months) VTE CHA DS -VASc 2 2 score 7-9 Any caged-ball or Severe thrombophilia tilting disc aortic valve prosthesis (eg, deficiency of protein C, protein S, or Recent (within 3 months) stroke or antithrombin; antiphospholipid antibodies; multiple abnormalities) Recent (within 6 months) stroke or transient ischemic attack transient ischemic attack Rheumatic valvular heart disease Moderate thrombotic risk Bileaflet aortic valve prosthesis and 1 or more of the of following risk factors: atrial fibrillation, prior CHADS score 3-4 VTE within the past 3 to 12 months 2 CHA DS -VASc 2 2 score 4-6 Nonsevere thrombophilia (eg, heterozygous factor V Leiden or prothrombin gene mutation) stroke or transient ischemic attack, hypertension, diabetes, congestive heart failure, age >75 years Recurrent VTE Active cancer (treated within 6 months or palliative) Low thrombotic risk Bileaflet aortic valve prosthesis without CHADS score 0-2 VTE >12 months previous and no other 2 CHA DS -VASc 2 2 atrial fibrillation and no risk factors score 0-3 (assuming no prior stroke or other risk factors for stroke transient ischemic attack) The risk classification is largely based on indirect evidence and is intended to be used as a starting point to estimate risk. Patient-specific factors and clinical judgment should also be incorporated into the risk estimate. The source guideline used CHADS scores for risk estimation; additional information from CHA DS -VASc scores may also inform risk, but these scores have not been directly 2 2 2 https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 42/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate compared in a clinical trial. Refer to UpToDate topics on perioperative anticoagulation management for details. VTE: venous thromboembolism; CHADS : congestive heart failure, hypertension, age 75 years, diabetes mellitus, and stroke or transient ischemic attack; CHA DS -VASc: congestive heart failure, hypertension, age 75 years (2 points), diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism (2 points), vascular disease (peripheral artery disease, myocardial infarction, or aortic plaque), age 65 to 74 years, sex category female. 2 2 2 Very high-risk patients may also include those with a prior stroke or transient ischemic attack occurring <3 months before the planned surgery and a CHADS score >5 or CHA DS -VASc score >6 2 2 2 (those with prior thromboembolism during temporary interruption of anticoagulation, or those undergoing certain types of surgery associated with an increased risk for stroke or other thromboembolism [eg, cardiac valve replacement, carotid endarterectomy, major vascular surgery]). Modi ed from Douketis JD, Spyropoulos AC, Spencer FA, et al. Perioperative management of antithrombotic therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141(2 Suppl):e326S. Copyright 2012. Reproduced with permission from the American College of Chest Physicians. Graphic 86930 Version 7.0 https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 43/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Procedural bleeding risk High bleeding risk procedure (two-day risk of major bleed 2 to 4%) Any major operation of duration >45 minutes Abdominal aortic aneurysm repair Coronary artery bypass Endoscopically guided fine-needle aspiration Foot/hand/shoulder surgery Heart valve replacement Hip replacement Kidney biopsy Knee replacement Laminectomy Neurosurgical/urologic/head and neck/abdominal/breast cancer surgery Polypectomy, variceal treatment, biliary sphincterectomy, pneumatic dilatation Transurethral prostate resection Vascular and general surgery Low bleeding risk procedure (two-day risk of major bleed 0 to 2%) Abdominal hernia repair Abdominal hysterectomy Arthroscopic surgery lasting <45 minutes Axillary node dissection Bronchoscopy with or without biopsy Carpal tunnel repair Cataract and noncataract eye surgery Central venous catheter removal Cholecystectomy Cutaneous and bladder/prostate/thyroid/breast/lymph node biopsies Dilatation and curettage Gastrointestinal endoscopy biopsy, enteroscopy, biliary/pancreatic stent without sphincterotomy, endosonography without fine-needle aspiration Hemorrhoidal surgery https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 44/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Hydrocele repair Noncoronary angiography Pacemaker and cardiac defibrillator insertion and electrophysiologic testing Paracentesis Thoracentesis Tooth extractions (multiple tooth extractions is an exception that may be higher risk) This table is based on definitions derived from surgical/subspecialty societies in anticoagulant bridging or anticoagulant bridging management studies. Refer to UpToDate content on management of anticoagulants in patients undergoing gastrointestinal procedures for information on bleeding risks of additional gastrointestinal procedures. Adapted from research originally published in Blood. Spyropoulos AC, Douketis JD. How I treat anticoagulated patients undergoing an elective procedure or surgery. Blood 2012; 120:2954. Copyright 2012 the American Society of Hematology. Graphic 86929 Version 7.0 https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 45/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Clinical risk factors for stroke, transient ischemic attack, and systemic embolism in the CHA DS -VASc score 2 2 (A) The risk factor-based approach expressed as a point based scoring system, with the acronym CHA DS -VASc 2 2 (NOTE: maximum score is 9 since age may contribute 0, 1, or 2 points) CHA DS -VASc risk factor Points 2 2 Congestive heart failure +1 Signs/symptoms of heart failure or objective evidence of reduced left ventricular ejection fraction Hypertension +1 Resting blood pressure >140/90 mmHg on at least 2 occasions or current antihypertensive treatment Age 75 years or older +2 Diabetes mellitus +1 Fasting glucose >125 mg/dL (7 mmol/L) or treatment with oral hypoglycemic agent and/or insulin Previous stroke, transient ischemic attack, or thromboembolism +2 Vascular disease +1 Previous myocardial infarction, peripheral artery disease, or aortic plaque Age 65 to 74 years +1 Sex category (female) +1 (B) Adjusted stroke rate according to CHA DS -VASc score 2 2 CHA DS -VASc score Patients Stroke and 2 2 (n = 73,538) thromboembolism event rate at 1-year follow-up (%) 0 6369 0.78 1 8203 2.01 2 12,771 3.71 3 17,371 5.92 4 13,887 9.27 5 8942 15.26 https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 46/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate 6 4244 19.74 7 1420 21.50 8 285 22.38 9 46 23.64 CHA DS -VASc: Congestive heart failure, Hypertension, Age ( 75; doubled), Diabetes, Stroke (doubled), Vascular disease, Age (65 to 74), Sex. 2 2 Part A from: Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial brillation developed in collaboration with EACTS. Europace 2016; 18(11):1609-1678. By permission of Oxford University Press on behalf of the European Society of Cardiology. Copyright 2016 Oxford University Press. Available at: www.escardio.org/. Graphic 83272 Version 29.0 https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 47/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Clinical characteristics comprising the HAS-BLED bleeding risk score Letter Clinical characteristic* Points H Hypertension (ie, uncontrolled blood pressure) 1 A Abnormal renal and liver function (1 point each) 1 or 2 S Stroke 1 B Bleeding tendency or predisposition 1 L Labile INRs (for patients taking warfarin) 1 E Elderly (age greater than 65 years) 1 D Drugs (concomitant aspirin or NSAIDs) or excess alcohol use (1 point each) 1 or 2 Maximum 9 points HAS-BLED score (total points) Bleeds per 100 patient-years 0 1.13 1 1.02 2 1.88 3 3.74 4 8.70 5 to 9 Insufficient data The HAS-BLED bleeding risk score has only been validated in patients with atrial fibrillation receiving warfarin. Refer to UpToDate topics on anticoagulation in patients with atrial fibrillation and on specific anticoagulants for further information and other bleeding risk scores and their performance relative to clinical judgment. INR: international normalized ratio; NSAIDs: nonsteroidal antiinflammatory drugs. Hypertension is defined as systolic blood pressure >160 mmHg. Abnormal renal function is defined as the presence of chronic dialysis, renal transplantation, or serum creatinine 200 micromol/L. Abnormal liver function is defined as chronic hepatic disease (eg, cirrhosis) or biochemical evidence of significant hepatic derangement (eg, bilirubin more than 2 times the upper limit of normal, plus 1 or more of aspartate transaminase, alanine transaminase, and/or alkaline phosphatase more than 3 times the upper limit of normal). Bleeding predisposition includes chronic bleeding disorder or https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 48/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate previous bleeding requiring hospitalization or transfusion. Labile INRs for a patient on warfarin include unstable INRs, excessively high INRs, or <60% time in therapeutic range. Based on initial validation cohort from Pisters R. A novel-user-friendly score (HAS-BLED) to assess 1- year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest 2010; 138:1093. Actual rates of bleeding in contemporary cohorts may vary from these estimates. Original gure modi ed for this publication. Lip GY. Implications of the CHA2DS2-VASc and HAS-BLED Scores for thromboprophylaxis in atrial brillation. Am J Med 2011; 124:111. Table used with the permission of Elsevier Inc. All rights reserved. Graphic 75259 Version 16.0 https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 49/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Algorithm for anticoagulant discontinuation in individuals undergoing elective Refer to UpToDate for further information on the bleeding risk of common procedures and the thromboemb risk of common underlying conditions. High thromboembolic risk includes mechanical heart valve, high risk stroke, or recent venous thromboembolism (within the prior 3 months). DOAC: direct oral anticoagulant; VKA: vitamin K antagonist; CrCl: creatinine clearance; VTE: venous thromboembolism; IVC: inferior vena cava; LMW: low molecular weight. Anticoagulants: Direct oral anticoagulants (DOACs) include dabigatran, apixaban, edoxaban, and rivaroxaban. Vitamin K antagonists include warfarin, acenocoumarol, phenprocoumon, and fluindione. The following applies to DOAC interruption: These intervals are for individuals with normal kidney function and factor Xa inhibitors regardless of ki function. For individuals with CrCl 30 to 50 mL/min receiving dabigatran, longer intervals are used (omit from 2 before a low/moderate bleeding risk procedure; omit from 4 days before a high bleeding risk procedu The perioperative management from the PAUSE study (a population with atrial fibrillation) can be appl individuals who are receiving a DOAC for VTE that was >30 days prior. If the individual had a VTE within prior 30 days, DOAC interruption should be individualized and may include placement of a temporary filter or shorter periods of DOAC interruption. Bridging is not used for DOACs. The following applies to VKA interruption: For warfarin, discontinue 5 days before the procedure. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 50/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate If bridging is needed for a high thromboembolic risk patient, start LMW heparin at therapeutic dose approximately 3 days before surgery, with the last preoperative dose approximately 24 hours before s Resume warfarin postoperatively once hemostasis is assured (typically the evening of the day of surge the day after surgery). Resume LMW heparin approximately 2 to 3 days after surgery (determined by t bleeding risk of the procedure) and discontinue LMW heparin after stable warfarin anticoagulation. The overlap period between LMW heparin and warfarin depends on the patient's thromboembolic risk Based on guidance from A Tafur, J Douketis. Perioperative management of anticoagulant and antiplatelet therapy. Heart 2018; 104:14 Graphic 129999 Version 2.0 https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 51/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Timing for interruption of a direct oral anticoagulant (DOAC) before and after elective surgery This strategy applies to all DOACs in individuals with normal kidney function (eg, CrCl >50 mL/min) and individuals taking apixaban, edoxaban, or rivaroxaban with CrCl 30 to 50 mL/min. For individuals taking dabigatran who have CrCl of 30 to 50 mL/min, omit an additional dose before the procedure. For any DOAC and a high bleeding risk procedure, it may be reasonable to omit the DOAC for an additional postoperative day (5 days total interruption). Refer to UpToDate for additional details. DOAC: direct oral anticoagulant; CrCl: creatinine clearance. Graphic 130000 Version 1.0 https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 52/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Perioperative management of oral direct thrombin inhibitors and factor Xa inhibitors Interval between last dose and procedure Resumption after NOTE: No anticoagulant procedure Kidney is administered the day Anticoagulant function of the procedure and dose High Low High Low bleeding risk bleeding risk bleeding risk bleeding risk https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 53/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Dabigatran CrCl >50 mL/minute Give last dose 3 days before Give last dose 2 days before procedure (ie, skip 4 doses procedure (ie, skip 2 doses Dose 150 mg twice daily on the 2 days on the day before the procedure) before the procedure) CrCl 30 to 50 Give last dose Give last dose mL/minute 5 days before procedure (ie, 3 days before procedure (ie, Dose 150 mg skip 8 doses skip 4 doses twice daily on the 4 days before the procedure) on the 2 days before the procedure) Rivaroxaban CrCl >50 mL/minute Give last dose 3 days before procedure (ie, skip 2 doses on the 2 days before the procedure) Give last dose 2 days before procedure (ie, skip 1 dose on the day before the procedure) Dose 20 mg once daily Resume 48 to 72 hours after surgery (ie, postoperative day 2 to 3) Resume 24 hours after surgery (ie, postoperative day 1) CrCl 30 to 50 mL/minute Dose 15 mg once daily Apixaban CrCl >50 mL/minute Give last dose 3 days before procedure (ie, Give last dose 2 days before procedure (ie, Dose 5 mg twice daily skip 4 doses on the 2 days before the procedure) skip 2 doses on the day before the procedure) CrCl 50 mL/minute Dose 2.5 mg twice daily Edoxaban CrCl 51 to 95 Give the last Give the last mL/minute dose 3 days dose 2 days before the procedure (ie, before the procedure (ie, Dose 60 mg once daily skip 2 doses on the 2 days skip 2 dose on the day CrCl 50 mL/minute* before the before the procedure) procedure) Dose 30 mg once daily Bleeding risk is determined primarily by the type of surgery; patient comorbidities may also play a role. In patients undergoing neuraxial anesthesia or a very high bleeding risk procedure, a longer https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 54/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate period of interruption may be warranted. In many low bleeding risk procedures, the anticoagulant does not need to be interrupted. Bridging anticoagulation may be appropriate preoperatively in patients with a very high thromboembolic risk who require more prolonged interruption of the anticoagulant (eg, for renal insufficiency) and/or postoperatively in patients who are unable to resume the anticoagulant (eg, unable to take oral medication due to intestinal ileus). Refer to the UpToDate topics on perioperative management of patients receiving anticoagulants for further details. CrCl: creatinine clearance. Product information varies in different countries regarding a lower limit of CrCl below which the drug should not be used. As an example, product information in the United States specifies avoiding use with CrCl <15 mL/minute. Graphic 93260 Version 12.0 https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 55/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Expected effects of anticoagulant drugs on commonly used coagulation tests Brand Anti-factor Drug class Drug PT aPTT name(s) Xa activity / * Vitamin K Warfarin Jantoven antagonists / * Acenocoumarol Sintrom Heparins Unfractionated heparin / LMW heparins Enoxaparin Lovenox Dalteparin Fragmin Nadroparin Fraxiparine / Fondaparinux Arixtra Direct thrombin inhibitors Argatroban Acova / Dabigatran Pradaxa / / Direct factor Xa inhibitors Rivaroxaban Xarelto / / Apixaban Eliquis Edoxaban Lixiana, Savaysa PT and aPTT are measured in seconds; anti-factor Xa activity is measured in units/mL. Upward arrow ( ) signifies an increase above normal due to the anticoagulant (prolongation of PT or aPTT; increase in anti-factor Xa activity). The effect magnitude will vary depending on the reagent formulation and instrument used. Dash ( ) signifies no appreciable effect. Normal ranges for the PT, aPTT, and anti-factor Xa activity vary among laboratories and should be reported from the testing laboratory along with the patient result. Refer to the UpToDate topic on coagulation testing for details. PT: prothrombin time; aPTT: activated partial thromboplastin time; LMW heparin: low molecular weight heparin. Warfarin has a weak effect on most aPTT reagents. However, warfarin use will increase the sensitivity of the aPTT to heparin effect. While heparin, LMW heparin, and fondaparinux should, in theory, prolong the PT as indirect thrombin inhibitors, in practice most PT reagents contain heparin-binding chemicals that block any heparin effect below a concentration of 1 unit/mL. Above concentrations of 1 unit/mL, heparin effect on the PT may be observed. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 56/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Anti-factor Xa activity testing must be calibrated for the specific anticoagulant; this information should be verified with the clinical laboratory. Some of the data are from: Samuelson BT, Cuker A, Crowther M, Garcia DA. Laboratory assessment of the anticoagulant activity of direct oral anticoagulants: A systematic review. Chest 2017; 151:127. Graphic 91267 Version 9.0 https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 57/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Recommendations for preoperative and postoperative anticoagulation in patients on a vitamin K antagonist Indication Before surgery After surgery Venous thromboembolism Within first month IV heparin or SQ LMWH IV heparin or SQ LMWH Second/third month No change* IV heparin or SQ LMWH 3 months No change* SQ heparin or LWMH Arterial thromboembolism Recent, within one month IV heparin or SQ LMWH IV heparin or SQ LMWH Prophylaxis (eg, non-valvular AF, mechanical heart valve) No change* Resume oral anticoagulation NOTE: Warfarin should be withheld to allow the INR to fall spontaneously to 1.5 to 2 before surgery is performed. IV: intravenous; SQ: subcutaneous; LMWH: low molecular weight heparin; AF: atrial fibrillation; INR: international normalized ratio. If the patient is hospitalized, SQ heparin or LMWH should be administered, but hospitalization is not recommended solely for this purpose. Can use SQ heparin or SQ LMWH if the surgery carries a high risk of postoperative thromboembolism. Graphic 81389 Version 4.0 https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 58/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Reversing anticoagulation in warfarin-associated bleeding Management Time to anticoagulation Comments and cautions option reversal Discontinuing 5 to 14 days Five days is typical for patients with an warfarin therapy INR in the therapeutic range Vitamin K* 6 to 24 hours to correct the INR, longer to fully reverse anticoagulation Recovery of factors X and II (prothrombin) takes longer than 24 hours Risk of anaphylaxis with intravenous injection Impaired response to warfarin lasting up to one week may occur after large doses (ie, >5 mg) Fresh frozen Depends on the time it takes to Effect is transient and concomitant plasma complete the infusion; typically 12 to 32 hours for complete reversal vitamin K must be administered Potential for volume overload (2 to 4 L to normalize INR) Potential for TRALI Potential for viral transmission Prothrombin complex 15 minutes after 10-minute to 1-hour infusion Effect is transient, and concomitant vitamin K must be administered; concentrate limited availability Cost

53/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Dabigatran CrCl >50 mL/minute Give last dose 3 days before Give last dose 2 days before procedure (ie, skip 4 doses procedure (ie, skip 2 doses Dose 150 mg twice daily on the 2 days on the day before the procedure) before the procedure) CrCl 30 to 50 Give last dose Give last dose mL/minute 5 days before procedure (ie, 3 days before procedure (ie, Dose 150 mg skip 8 doses skip 4 doses twice daily on the 4 days before the procedure) on the 2 days before the procedure) Rivaroxaban CrCl >50 mL/minute Give last dose 3 days before procedure (ie, skip 2 doses on the 2 days before the procedure) Give last dose 2 days before procedure (ie, skip 1 dose on the day before the procedure) Dose 20 mg once daily Resume 48 to 72 hours after surgery (ie, postoperative day 2 to 3) Resume 24 hours after surgery (ie, postoperative day 1) CrCl 30 to 50 mL/minute Dose 15 mg once daily Apixaban CrCl >50 mL/minute Give last dose 3 days before procedure (ie, Give last dose 2 days before procedure (ie, Dose 5 mg twice daily skip 4 doses on the 2 days before the procedure) skip 2 doses on the day before the procedure) CrCl 50 mL/minute Dose 2.5 mg twice daily Edoxaban CrCl 51 to 95 Give the last Give the last mL/minute dose 3 days dose 2 days before the procedure (ie, before the procedure (ie, Dose 60 mg once daily skip 2 doses on the 2 days skip 2 dose on the day CrCl 50 mL/minute* before the before the procedure) procedure) Dose 30 mg once daily Bleeding risk is determined primarily by the type of surgery; patient comorbidities may also play a role. In patients undergoing neuraxial anesthesia or a very high bleeding risk procedure, a longer https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 54/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate period of interruption may be warranted. In many low bleeding risk procedures, the anticoagulant does not need to be interrupted. Bridging anticoagulation may be appropriate preoperatively in patients with a very high thromboembolic risk who require more prolonged interruption of the anticoagulant (eg, for renal insufficiency) and/or postoperatively in patients who are unable to resume the anticoagulant (eg, unable to take oral medication due to intestinal ileus). Refer to the UpToDate topics on perioperative management of patients receiving anticoagulants for further details. CrCl: creatinine clearance. Product information varies in different countries regarding a lower limit of CrCl below which the drug should not be used. As an example, product information in the United States specifies avoiding use with CrCl <15 mL/minute. Graphic 93260 Version 12.0 https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 55/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Expected effects of anticoagulant drugs on commonly used coagulation tests Brand Anti-factor Drug class Drug PT aPTT name(s) Xa activity / * Vitamin K Warfarin Jantoven antagonists / * Acenocoumarol Sintrom Heparins Unfractionated heparin / LMW heparins Enoxaparin Lovenox Dalteparin Fragmin Nadroparin Fraxiparine / Fondaparinux Arixtra Direct thrombin inhibitors Argatroban Acova / Dabigatran Pradaxa / / Direct factor Xa inhibitors Rivaroxaban Xarelto / / Apixaban Eliquis Edoxaban Lixiana, Savaysa PT and aPTT are measured in seconds; anti-factor Xa activity is measured in units/mL. Upward arrow ( ) signifies an increase above normal due to the anticoagulant (prolongation of PT or aPTT; increase in anti-factor Xa activity). The effect magnitude will vary depending on the reagent formulation and instrument used. Dash ( ) signifies no appreciable effect. Normal ranges for the PT, aPTT, and anti-factor Xa activity vary among laboratories and should be reported from the testing laboratory along with the patient result. Refer to the UpToDate topic on coagulation testing for details. PT: prothrombin time; aPTT: activated partial thromboplastin time; LMW heparin: low molecular weight heparin. Warfarin has a weak effect on most aPTT reagents. However, warfarin use will increase the sensitivity of the aPTT to heparin effect. While heparin, LMW heparin, and fondaparinux should, in theory, prolong the PT as indirect thrombin inhibitors, in practice most PT reagents contain heparin-binding chemicals that block any heparin effect below a concentration of 1 unit/mL. Above concentrations of 1 unit/mL, heparin effect on the PT may be observed. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 56/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Anti-factor Xa activity testing must be calibrated for the specific anticoagulant; this information should be verified with the clinical laboratory. Some of the data are from: Samuelson BT, Cuker A, Crowther M, Garcia DA. Laboratory assessment of the anticoagulant activity of direct oral anticoagulants: A systematic review. Chest 2017; 151:127. Graphic 91267 Version 9.0 https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 57/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Recommendations for preoperative and postoperative anticoagulation in patients on a vitamin K antagonist Indication Before surgery After surgery Venous thromboembolism Within first month IV heparin or SQ LMWH IV heparin or SQ LMWH Second/third month No change* IV heparin or SQ LMWH 3 months No change* SQ heparin or LWMH Arterial thromboembolism Recent, within one month IV heparin or SQ LMWH IV heparin or SQ LMWH Prophylaxis (eg, non-valvular AF, mechanical heart valve) No change* Resume oral anticoagulation NOTE: Warfarin should be withheld to allow the INR to fall spontaneously to 1.5 to 2 before surgery is performed. IV: intravenous; SQ: subcutaneous; LMWH: low molecular weight heparin; AF: atrial fibrillation; INR: international normalized ratio. If the patient is hospitalized, SQ heparin or LMWH should be administered, but hospitalization is not recommended solely for this purpose. Can use SQ heparin or SQ LMWH if the surgery carries a high risk of postoperative thromboembolism. Graphic 81389 Version 4.0 https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 58/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Reversing anticoagulation in warfarin-associated bleeding Management Time to anticoagulation Comments and cautions option reversal Discontinuing 5 to 14 days Five days is typical for patients with an warfarin therapy INR in the therapeutic range Vitamin K* 6 to 24 hours to correct the INR, longer to fully reverse anticoagulation Recovery of factors X and II (prothrombin) takes longer than 24 hours Risk of anaphylaxis with intravenous injection Impaired response to warfarin lasting up to one week may occur after large doses (ie, >5 mg) Fresh frozen Depends on the time it takes to Effect is transient and concomitant plasma complete the infusion; typically 12 to 32 hours for complete reversal vitamin K must be administered Potential for volume overload (2 to 4 L to normalize INR) Potential for TRALI Potential for viral transmission Prothrombin complex 15 minutes after 10-minute to 1-hour infusion Effect is transient, and concomitant vitamin K must be administered; concentrate limited availability Cost Variable factor VII content depending on the product: a 4-factor PCC is preferred Potentially prothrombotic Recombinant 15 minutes after bolus infusion Effect is transient, and concomitant factor VIIa vitamin K must be administered Cost Potentially prothrombotic Please refer to the UpToDate topic on warfarin reversal in intracerebral hemorrhage for further details of management. INR: international normalized ratio; TRALI: transfusion-related acute lung injury; PCC: prothrombin complex concentrate. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 59/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate A total of 10 mg intravenously by slow infusion given over 10 minutes. Adapted with permission from: Aguilar MI, Hart RG, Kase CS, et al. Treatment of warfarin-associated intercerebral hemorrhage: Literature review and expert opinion. Mayo Clin Proc 2007; 82:82. Copyright 2007 Dowden Health Media. Graphic 79151 Version 16.0 https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 60/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Emergency reversal of anticoagulation from warfarin for life-threatening hemorrhage in adults: Suggested approaches based upon available resources A. If 4-factor prothrombin complex concentrate (4F PCC) is available (preferred approach): 1. Give 4F PCC* 1500 to 2000 units IV over 10 minutes. Check INR 15 minutes after completion of the infusion. If INR is not 1.5, give additional 4F PCC (refer to topic or drug reference for details). 2. Give vitamin K 10 mg IV over 10 to 20 minutes. B. If 3-factor prothrombin complex concentrate (3F PCC) is available but 4F PCC is not available: 1. Give 3F PCC* 1500 to 2000 units IV over 10 minutes. Check INR 15 minutes after completion of the infusion. If INR is not 1.5, give additional 3F PCC (refer to topic or drug reference for details). 2. Give Factor VIIa 20 mcg/kg IV OR give FFP 2 units IV by rapid infusion. Factor VIIa may be preferred if volume overload is a concern. 3. Give vitamin K 10 mg IV over 10 to 20 minutes. C. If neither 3F PCC nor 4F PCC is available: 1. Give FFP 2 units IV by rapid infusion. Check INR 15 minutes after completion of infusion. If INR 1.5, administer 2 additional units of FFP IV rapid infusion. Repeat process until INR 1.5. May wish to administer loop diuretic between FFP infusions if volume overload is a concern. 2. Give vitamin K 10 mg IV over 10 to 20 minutes. These products and doses are for use in life-threatening bleeding only. Evidence of life-threatening bleeding and over-anticoagulation with a vitamin K antagonist (eg, warfarin) are required. Anaphylaxis and transfusion reactions can occur. It may be reasonable to thaw 4 units of FFP while awaiting the PT/INR. The transfusion service may substitute other plasma products for FFP (eg, Plasma Frozen Within 24 Hours After Phlebotomy [PF24]); these products are considered clinically interchangeable. PCC will reverse anticoagulation within minutes of administration; FFP administration can take hours due to the volume required; vitamin K effect takes 12 to 24 hours, but administration of vitamin K is needed to counteract the long half-life of warfarin. Subsequent monitoring of the PT/INR is needed to guide further therapy. Refer to topics on warfarin reversal in individual situations for further management. PCC: unactivated prothrombin complex concentrate; 4F PCC: PCC containing coagulation factors II, VII, IX, X, protein S and protein C; 3F PCC: PCC containing factors II, IX, and X and only trace factor VII; FFP: fresh frozen plasma; PT: prothrombin time; INR: international normalized ratio; FEIBA: factor eight inhibitor bypassing agent. Before use, check product label to confirm factor types (3 versus 4 factor) and concentration. Activated complexes and single-factor IX products (ie, FEIBA, AlphaNine, Mononine, Immunine, BeneFix) are NOT used for warfarin reversal. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 61/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate PCC doses shown are those suggested for initial treatment of emergency conditions. Subsequent treatment is based on INR and patient weight if available. Refer to topic and Lexicomp drug reference included with UpToDate for INR-based dosing. Graphic 89478 Version 10.0 https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 62/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate PCC products available in the United States* Unactivated prothrombin complex concentrates (PCCs) 4 factor: Contains inactive forms of 4 factors: Factors II, VII, IX, and X Kcentra Also contains heparin 3 factor: Contains inactive forms of 3 factors: Factors II, IX, and X Profilnine Contains little or no factor VII Does not contain heparin Activated prothrombin complex concentrate (aPCC) 4 factor: Contains 4 factors: Factors II, VII, IX, and X. Of these, only factor VII is mostly the activated form FEIBA Does not contain heparin The table lists 4-factor and 3-factor PCC products available in the United States. Kcentra is available as Beriplex in Canada. Bebulin (a 3-factor PCC) was discontinued in 2018 due to decreased demand for the product. Potency is determined differently for different products; refer to product information. All PCCs are plasma derived and contain other proteins, including anticoagulant proteins (proteins C and S). Unactivated factors are proenzymes (inactive precursor proteins). Activated factors have higher enzymatic activity. Refer to UpToDate topics for use of these products. US: United States; PCC: prothrombin complex concentrate; FEIBA: factor eight inhibitor bypassing activity. Other 4-factor PCCs available outside the US include Octaplex and Cofact Proplex. Single-factor recombinant activated factor VII (rFVIIa) products are also available. Graphic 94210 Version 8.0 https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 63/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Direct oral anticoagulant reversal agents for life-threatening bleeding (imminent risk of death from bleeding) Reversal agent (all are given Anticoagulant intravenously) Dabigatran (Pradaxa; oral thrombin inhibitor) Idarucizumab (Praxbind). Dose: 5 grams* Oral factor Xa inhibitors: Andexanet alfa (AndexXa). Dosing for the initial bolus and subsequent infusion depend Apixaban (Eliquis) on the dose level of the factor Xa inhibitor and the interval since it was last taken. Edoxaban (Lixiana, Savaysa) Rivaroxaban (Xarelto) OR- 4-factor PCC (Kcentra, Beriplex P/N, Octaplex). Dosing can be done with a fixed dose of 2000 units OR a weight-based dose of 25 to 50 units per kg. Reversal agents carry a risk of life-threatening thrombosis and should only be used under the direction of a specialist with expertise in their use and/or in a patient at imminent risk of death from bleeding. In general, a single dose is given; dosing may be repeated in rare situations in which the oral anticoagulant persists for longer in the circulation, such as severe kidney dysfunction. Andexanet dosing is as follows: If the patient took rivaroxaban >10 mg, apixaban >5 mg, or dose unknown within the previous 8 hours: Andexanet 800 mg bolus at 30 mg/minute followed by 960 mg infusion at 8 mg/minute for up to 120 minutes. OR- If the patient took rivaroxaban 10 mg or apixaban 5 mg, or if 8 hours have elapsed since the last dose of a factor Xa inhibitor: Andexanet 400 mg bolus at 30 mg/minute followed by 480 mg infusion at 4 mg/minute for up to 120 minutes. Refer to UpToDate topics on treatment of bleeding in patients receiving a DOAC or perioperative management of patients receiving a DOAC for additional information on administration, risks, and alternative therapies. DOAC: direct oral anticoagulant; PCC: prothrombin complex concentrate; FEIBA: factor eight inhibitor bypassing activity. If idarucizumab is unavailable, an activated PCC (FEIBA, 50 to 80 units per kg intravenously) may be a reasonable alternative. Graphic 112299 Version 9.0 https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 64/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Contributor Disclosures James D Douketis, MD, FRCPC, FACP, FCCP Consultant/Advisory Boards: AstraZeneca [Reversal of anticoagulants for bleeding and perioperative management]; CytoSorb [Reversal of anticoagulants for bleeding and perioperative management]; PhaseBio [Reversal of anticoagulants for bleeding and perioperative management]; Servier [Anticoagulants for atrial fibrillation and cancer-associated thrombosis]. Other Financial Interest: Leo Pharma [Anticoagulants for the treatment of cancer-associated thrombosis]; Pfizer [Anticoagulants (LMWH, DOACs), management of COVID-19]. All of the relevant financial relationships listed have been mitigated. Gregory YH Lip, MD, FRCPE, FESC, FACC Consultant/Advisory Boards: BMS/Pfizer [Atrial fibrillation and thrombosis]; Boehringer Ingelheim [Atrial fibrillation and thrombosis]; Daiichi-Sankyo [Atrial fibrillation and thrombosis]. Speaker's Bureau: BMS/Pfizer [Atrial fibrillation and thrombosis]; Boehringer Ingelheim [Atrial fibrillation and thrombosis]; Daiichi-Sankyo [Atrial fibrillation and thrombosis]. All of the relevant financial relationships listed have been mitigated. Lawrence LK Leung, MD No relevant financial relationship(s) with ineligible companies to disclose. Jennifer S Tirnauer, MD No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 65/65

7/5/23, 10:17 AM Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation : Robert Phang, MD, FACC, FHRS, Warren J Manning, MD : Bradley P Knight, MD, FACC, Brian Olshansky, MD, N A Mark Estes, III, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Feb 02, 2022. INTRODUCTION Spontaneous or intended conversion of atrial fibrillation (AF) to sinus rhythm (SR) is associated with a short-term increase from the baseline risk of clinical thromboembolism. This topic will discuss management strategies that attempt to decrease this thromboembolic risk, based on the duration of the AF episode, prior anticoagulant therapy, and the patient s individualized risk of stroke (CHA DS -VASc score ( 2 table 1)). 2 The modalities used to perform cardioversion, long-term anticoagulation in patients with AF, and an overview of the management of AF are presented separately. (See "Atrial fibrillation: Cardioversion" and "Atrial fibrillation in adults: Selection of candidates for anticoagulation" and "Atrial fibrillation in adults: Use of oral anticoagulants" and "Atrial fibrillation: Overview and management of new-onset atrial fibrillation".) EXTREMELY HIGH-RISK PATIENTS Patients with AF and certain types of valvular heart disease (rheumatic mitral stenosis or a mechanical valve), are at extremely high risk of thromboembolic complications at all times, not only at the time of cardioversion. The approach to antithrombotic therapy in such patients is discussed in other UpToDate topics. (See "Rheumatic mitral stenosis: Overview of management", section on 'Prevention of thromboembolism' and "Antithrombotic therapy for mechanical heart valves".) https://www.uptodate.com/contents/prevention-of-embolization-prior-to-and-after-restoration-of-sinus-rhythm-in-atrial-fibrillation/print 1/27 7/5/23, 10:17 AM Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation - UpToDate RATIONALE FOR ANTICOAGULATION All patients with AF, whether paroxysmal, persistent, or permanent, have an increased risk of embolization compared with those without AF. (See "Atrial fibrillation in adults: Selection of candidates for anticoagulation".) At the time of reversion to SR, whether pharmaceutical, electrical, or spontaneous, there is a transient incremental increase from the baseline risk. Most embolic events occur within 10 days of reversion to SR [1-5]. Patients undergoing cardioversion of AF of more than 48 hours duration represent a particularly high-risk group (compared with AF of less than 48 hours duration), with an embolic risk from as low as 1 to as high as 5 percent in the first month after reversion to SR in the absence of anticoagulation [2-4,6-8]. This rate is substantially higher than the rate that would be calculated for the general population of patients with AF, in whom the yearly rate is between 1.3 and 5.1 (or higher) percent, depending on age and additional comorbidities. The most common source of stroke associated with cardioversion in these patients is embolism of a thrombus from the left atrial appendage during or in the first two weeks after the procedure. Possible causes include embolism of a left atrial thrombus that was already present at the time of conversion to SR, embolism of a thrombus that formed after conversion due to depressed left atrial appendage ejection velocity postconversion, or delay in recovery of left atrial mechanical function after conversion, and thrombus formation during subsequent episodes of AF: Precardioversion left atrial thrombus. Embolization after return of synchronous atrial contraction is due to the dislodgement of left atrial thrombi present at the time of cardioversion. This is felt to be the dominant cause of postcardioversion thromboembolism and the rationale for performing transesophageal echocardiogram (TEE) prior to cardioversion. The prevalence of left atrial thrombus in nonanticoagulated patients with AF of less than 72 hours undergoing TEE is 12 and 14 percent [9,10]. This value is similar to that found among AF patients with a duration of unknown or more than two days duration [11,12]. The prevalence of left atrial appendage thrombus is increased in high-risk patients with severe left ventricular systolic dysfunction, left atrial enlargement, depressed left atrial appendage ejection velocity, or left atrial appendage spontaneous echo contrast (a marker of blood stasis). https://www.uptodate.com/contents/prevention-of-embolization-prior-to-and-after-restoration-of-sinus-rhythm-in-atrial-fibrillation/print 2/27 7/5/23, 10:17 AM Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation - UpToDate Postcardioversion atrial mechanical dysfunction creates a milieu that promotes new (postcardioversion) thrombus formation. The transient atrial contractile dysfunction after cardioversion is referred to as atrial "stunning" and can occur whether SR is restored spontaneously, by external or internal direct current cardioversion, or by antiarrhythmic medications. The duration of the left atrial contractile dysfunction appears to be related in part to the duration of AF prior to cardioversion. Recovery of atrial mechanical function may be delayed for several weeks [13] for those who have been in AF for a few months prior to cardioversion. In comparison, for those with AF for only a few days, left atrial mechanical recovery occurs within a day (but may still be associated with more pronounced but transient dysfunction immediately after cardioversion). (See "Hemodynamic consequences of atrial fibrillation and cardioversion to sinus rhythm", section on 'Atrial stunning'.) In support of the atrial stunning after cardioversion hypothesis, there have been case reports and small series of patients developing TEE evidence for de novo left atrial appendage thrombi (primarily in the setting of no anticoagulation) immediately following cardioversion, when the precardioversion TEE showed no left atrial appendage thrombus [9,14-16]. (See "Role of echocardiography in atrial fibrillation", section on 'Spontaneous echo contrast' and "Mechanisms of thrombogenesis in atrial fibrillation".) Recurrent AF is common during the first month after conversion [17]. Up to 90 percent of these episodes are asymptomatic [18], and asymptomatic episodes lasting more than 48 hours are not uncommon, occurring in 17 percent of patients in a report using continuous monitoring [17]. Anticoagulation during the four weeks postcardioversion thereby provides prophylaxis against new thrombus formation and facilitates early cardioversion without a screening TEE should recurrent AF occur. The rationale and indications for chronic anticoagulation after the period of postconversion anticoagulation are similar to those for the broad population of patients with AF and are discussed separately. (See "Atrial fibrillation in adults: Use of oral anticoagulants", section on 'Summary and recommendations'.) PATIENTS WITH SPONTANEOUS CONVERSION Some patients with AF have spontaneous conversion prior to planned cardioversion. The risk of thromboembolism after spontaneous conversion or electrical cardioversion is relatively low, but the risk during this time is likely higher than the ambient rate of thromboembolic events associated with AF. There is no evidence that risk of embolization in the first few weeks after https://www.uptodate.com/contents/prevention-of-embolization-prior-to-and-after-restoration-of-sinus-rhythm-in-atrial-fibrillation/print 3/27 7/5/23, 10:17 AM Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation - UpToDate spontaneous conversion differs from that for patients with AF undergoing electrical or chemical cardioversion. In a study of 1041 patients who were anticoagulated prior to and after cardioversion, 16 percent experienced spontaneous conversion (prior to planned electrical cardioversion) [19]. The rate of thromboembolism was similar in patients with spontaneous conversion compared with patients who underwent electrical cardioversion (<1 percent in both groups) although this comparison is limited by the small number of events). Though of unproven efficacy, some of our contributors recommend anticoagulation for four weeks after reversion to SR (either spontaneous or via cardioversion) for patients with AF of less than 48 hours duration, even for those with a low CHA DS -VASc score ( table 1). The rationale 2 2 for this approach is concern regarding the high likelihood of AF recurrence in the first month after reversion to SR, as well as transient postcardioversion atrial stunning in the immediate pericardioversion period. This approach may be modified in patients at very high bleeding risk. (See "Atrial fibrillation in adults: Selection of candidates for anticoagulation".) Management of long-term anticoagulation (after the initial four weeks) including the role of CHA DS -VASc score is discussed separately. (See "Atrial fibrillation in adults: Selection of 2 2 candidates for anticoagulation" and "Atrial fibrillation in adults: Use of oral anticoagulants", section on 'Approach to anticoagulation'.) URGENT CARDIOVERSION Patients with new onset AF in whom the ventricular rate is rapid may require urgent (or emergent) cardioversion to prevent adverse clinical consequences such as hemodynamic decompensation. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation", section on 'Symptom and hemodynamic management'.) The indications for urgent cardioversion of AF are uncommon, but in the setting of hemodynamic instability due to rapid AF that is refractory to pharmacologic support, such as in patients with Wolff-Parkinson-White syndrome, the need for restoration of SR may take precedence over the need for protection from thromboembolism. When possible, the patient should receive precardioversion anticoagulation (eg, bolus of unfractionated heparin or dose of direct oral anticoagulant [DOAC; also referred to as non-vitamin K oral anticoagulant [NOAC]) as soon as possible due to the risk of postcardioversion left atrial appendage stunning. Anticoagulation should be considered for four weeks postcardioversion, unless it is contraindicated [20] (see 'AF duration less than 48 hours' below). Management of long-term anticoagulation (after the initial four weeks) is discussed separately. (See "Atrial fibrillation in adults: Selection of candidates for anticoagulation" and "Atrial https://www.uptodate.com/contents/prevention-of-embolization-prior-to-and-after-restoration-of-sinus-rhythm-in-atrial-fibrillation/print 4/27 7/5/23, 10:17 AM Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation - UpToDate fibrillation in adults: Use of oral anticoagulants", section on 'Approach to anticoagulation'.) AF DURATION LESS THAN 48 HOURS Anticoagulation prior to cardioversion If conversion to SR (either spontaneous or via cardioversion) occurs within 48 hours of the onset of AF, the thromboembolic risk appears to be very low [21-23]. However, many, and perhaps most, patients cannot accurately define the onset of AF. As a result, we categorize a patient as having AF of less than 48 hours duration only if we have a high level of confidence in the patient s history. Otherwise, we approach the patient as if AF has been present for more than 48 hours. (See 'AF duration uncertain or 48 or more hours' below.) For most patients in whom cardioversion will take place less than 48 hours after the onset of AF, we start a DOAC prior to cardioversion rather than no anticoagulant. Intravenous heparin is a reasonable alternative for hospitalized patients. When a DOAC is used, the specific choice of DOAC should be individualized for each patient. We generally choose the agent that will be given at the time of discharge. Of note, the approach presented here is in contrast to the historical approach of some cardiologists proceeding to early cardioversion without anticoagulation if the duration was less than 24 hours. I(See "Atrial fibrillation in adults: Use of oral anticoagulants".) We generally wait at least three hours after the first dose of a DOAC to cardiovert. For patients at very high bleeding risk, some of our experts suggest cardioversion without anticoagulation if normal SR can be restored within 48 hours of documented onset. Other experts recommend anticoagulation prior to cardioversion even in these high-bleeding-risk patients. If cardioversion needs to take place within three hours, whether for patient instability or convenience (see 'Urgent cardioversion' above), we start intravenous unfractionated heparin (bolus and continuous drip goal partial thromboplastin time 1.5 to 2.0 times control) or a low molecular weight heparin (1 mg/kg subcutaneously every 12 hours); we do not give DOAC and heparin together. However, if warfarin is the agent selected for longer term anticoagulation, warfarin is started while heparin therapy is continued until the international normalized ratio exceeds 2.0. For extremely high-risk patients (eg, those with rheumatic mitral stenosis, mechanical valves, prior thromboembolism, severe left ventricular dysfunction, heart failure, or diabetes), we anticoagulate for at least three weeks or initiate therapeutic anticoagulation (with heparin or DOAC) in combination with TEE prior to an attempt at cardioversion as described above for AF of more than 48 hours duration. (See 'AF duration uncertain or 48 or more hours' below.) https://www.uptodate.com/contents/prevention-of-embolization-prior-to-and-after-restoration-of-sinus-rhythm-in-atrial-fibrillation/print 5/27 7/5/23, 10:17 AM Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation - UpToDate The 48 hour cut point is based on limited evidence and is somewhat arbitrary. For example, the prevalence of left atrial thrombus on TEE is substantially lower when the duration of AF is less than 48 hours (1.4 percent) [24]. Among patients with a history of AF of less than 48 hours in duration, there is likely a range of risk based on CHA DS -VASc score ( table 1). A retrospective 2 2 study of 3143 patients with AF of less than 48 hours duration demonstrated that patients with heart failure and diabetes were at high risk for clinical thromboembolism (up to 10 percent if both risk factors were present). The absence of both risk factors and age <60 years conveyed a very low risk of 0.2 percent [23]. (See 'AF duration uncertain or 48 or more hours' below and 'Rationale for anticoagulation' above.) No randomized trial has evaluated anticoagulation compared with no anticoagulation in AF patients undergoing cardioversion with a definite duration of AF <48 hours. Observational data suggest that the risk of stroke/thromboembolism is very low (0 to 0.2 percent) in patients with a definite AF duration of <12 hours and a very low stroke risk (CHA DS -VASc 0 in men, 1 in 2 2 women), in whom the benefit of four-week anticoagulation after cardioversion is undefined. The 2020 European Society of Cardiology guidelines for the diagnosis and management of AF suggest that prescription of anticoagulants can be optional, based on an individualized approach [25]. With regard to the question as to whether to anticoagulate these patients or not, there are no studies comparing heparin with no heparin in patients with AF of less than 48 hours duration. However, data regarding the rate of clinical thromboembolization after cardioversion in patients with AF of less than 48 hours duration have raised a concern about the safety of cardioversion without anticoagulation in this population. In an observational study of 2481 such individuals (5116 successful cardioversions) who were not treated with peri- or postprocedural anticoagulant, definite thromboembolic events occurred in 38 (0.7 percent) within 30 days (median of two days); of these, 31 were strokes [23]. Four additional patients suffered a transient ischemic attack. Age greater than 60 years, female sex, heart failure, and diabetes were the strongest predictors of embolization, with nearly 10 percent of those with both heart failure and diabetes experiencing a stroke. The risk of stroke in those without heart failure and age less than 60 years was 0.2 percent. An observational study of 16,274 patients undergoing direct current cardioversion with and without oral anticoagulant therapy also demonstrated that the absence of postcardioversion anticoagulation was associated with a high risk of thromboembolism, regardless of CHA DS -VASc scores [26]. There was a greater-than-twofold 2 2 increased risk of thromboembolism in those not treated with postcardioversion anticoagulation (hazard ratio 2.21; 95% CI 0.79-6.77 and 2.40; 95% CI 1.46-3.95 with CHA DS -VASc score 0 to 1 2 2 and CHA DS -VASc score 2 or more, respectively). The rationale for lack of postcardioversion 2 2 anticoagulation could not be exactly discerned in this trial but was deemed to be multifactorial, https://www.uptodate.com/contents/prevention-of-embolization-prior-to-and-after-restoration-of-sinus-rhythm-in-atrial-fibrillation/print 6/27 7/5/23, 10:17 AM Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation - UpToDate including presumed short-duration AF, perceived low thromboembolic risk, and lack of guideline adherence. With regard to the question of which anticoagulant to use, there are no studies comparing differing forms of heparin in patients with AF of short duration nor are there studies comparing a DOAC with heparin. Indirect evidence comparing the two heparins comes from a trial of 496 patients with AF of more than 48 hours duration who were randomly assigned to either low molecular weight heparin or unfractionated heparin followed by oral anticoagulation [27]. Patients were cardioverted after either 21 days of anticoagulation or after a TEE that was negative for thrombus; anticoagulation continued for 28 days after cardioversion. Low molecular weight heparin was noninferior to unfractionated heparin followed by oral anticoagulation in terms of the combined primary end point of ischemic neurologic events, major hemorrhage, or death by the end of study treatment (2.8 versus 4.8 percent). Low molecular weight heparin also has a safety and efficacy profile similar to unfractionated heparin when used as a bridge to oral anticoagulation in patients undergoing TEE-based therapy [28]. Anticoagulation after reversion to sinus rhythm Though of unproven in efficacy, some of our contributors recommend anticoagulation for four weeks after reversion to SR (either spontaneous or intended) for patients with AF of less than 48 hours duration, even for those with a low CHA DS -VASc score. The rationale for this approach is a concern regarding the high 2 2 likelihood of AF recurrence in the first month after reversion to SR, as well as transient postcardioversion atrial stunning in the immediate pericardioversion period. This decision may be modified in patients at very high bleeding risk. Some of our contributors do not anticoagulate patients with a low CHA DS -VASc score (0 in men 2 2 or 1 in women) after restoration of SR if AF was less than 48 hours duration [23,29]. Management of long-term anticoagulation (after the initial four weeks) is discussed separately. (See "Atrial fibrillation in adults: Selection of candidates for anticoagulation" and "Atrial fibrillation in adults: Use of oral anticoagulants", section on 'Approach to anticoagulation'.) AF DURATION UNCERTAIN OR 48 OR MORE HOURS Patients with AF of more than 48 hours or of unknown duration should receive at least three weeks of therapeutic anticoagulation prior to cardioversion and four weeks of anticoagulation after cardioversion. In this setting, this treatment regimen can reduce the risk of thromboembolism during the four weeks after cardioversion from 6 percent to less than 1 percent [2-4,6,7,30-32]. https://www.uptodate.com/contents/prevention-of-embolization-prior-to-and-after-restoration-of-sinus-rhythm-in-atrial-fibrillation/print 7/27 7/5/23, 10:17 AM Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation - UpToDate For patients in whom there is a reason to not wait three weeks, an option for management is precardioversion therapeutic anticoagulation in conjunction with a screening TEE to guide early cardioversion. This strategy can be used for patients in whom cardioversion needs to be performed before at least three weeks of therapeutic anticoagulation have been completed [12]. While the TEE approach shortens the precardioversion duration of anticoagulation, it does not change our recommendation for four weeks of anticoagulation after cardioversion or the need to be therapeutically anticoagulated at the time of the cardioversion due to the risk associated with postcardioversion atrial appendage stunning. (See 'Transesophageal echocardiography- based approach' below.) Prospective studies have shown that the risk of clinical stroke or systemic embolism ranges from 0 to 0.9 percent if preceded by at least three weeks of therapeutic anticoagulation with warfarin (target international normalized ratio [INR] 2.0 to 3.0) or one of the DOACs [2-4,12], or shorter- term anticoagulation with TEE-guided approach discussed directly above. Retrospective data demonstrated that the thromboembolism risk is 4 to 7 percent in nonanticoagulated patients [7,8,33]. Anticoagulant approach Since many patients will require long-term anticoagulation, we prefer the DOACs to warfarin before and after cardioversion (see "Atrial fibrillation in adults: Use of oral anticoagulants", section on 'Choice of anticoagulant'). While there has been longer experience with use of warfarin than DOACs prior to cardioversion, we believe there is sufficient evidence that DOACs are as effective and as safe as warfarin in this setting. Advantages of DOAC therapy include convenience (no INR testing required) and the possibility of a shorter duration of precardioversion anticoagulation in reliably adherent patients, since it often takes five or more weeks for a patient to have at least three continuous weeks of therapeutic anticoagulation with warfarin (INR 2.0 to 3.0). In patients in whom adherence to DOAC therapy is questionable, with possible missed doses leading up to the cardioversion, we often obtain precardioversion TEE to exclude an atrial (appendage) thrombus. Routine precardioversion TEE is not recommended for patients who have been therapeutically anticoagulated (INR 2.0 or greater) with warfarin for three weeks or who have been compliant with their daily DOAC. (See 'Transesophageal echocardiography-based approach' below.) Compliance with warfarin can be ascertained with INR monitoring. For patients started on warfarin, the target INR should be 2.5 (range 2.0 to 3.0), and cardioversion should not take place until an INR of 2.0 or greater has been documented for at least three consecutive weeks ( figure 1 and figure 2) [34,35]. https://www.uptodate.com/contents/prevention-of-embolization-prior-to-and-after-restoration-of-sinus-rhythm-in-atrial-fibrillation/print 8/27 7/5/23, 10:17 AM Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation - UpToDate The following data are available for the DOACs: Dabigatran In a post-hoc analysis of the RE-LY trial, which compared dabigatran with warfarin, in which there were 1983 cardioversions in 1270 participants, there was no significant difference in the rate of thromboembolism and stroke within 30 days between those who received at least three weeks of dabigatran 110 or 150 mg twice daily or warfarin (0.8, 0.3, and 0.6 percent, respectively) [2]. Apixaban In a post-hoc analysis of the ARISTOTLE trial, which compared apixaban with warfarin, 743 cardioversions were performed in 540 patients. No strokes or systemic embolism occurred during the 30-day follow-up period of both warfarin and apixaban groups [3]. (See "Atrial fibrillation in adults: Use of oral anticoagulants", section on 'Choice of anticoagulant'.) Rivaroxaban In the X-VeRT study, 1504 patients with AF of unknown or longer than 48 hours duration were randomly assigned in a 2:1 manner to cardioversion after at least three weeks of rivaroxaban or a vitamin K antagonist. There was no significant difference in the rate of the primary efficacy outcome (a composite of stroke, transient ischemic attack, peripheral embolism, myocardial infarction, and cardiovascular death) or the safety outcome of major bleeding (0.51 versus 1.02 percent and 0.6 percent versus 0.8 percent, respectively) [4]. Similarly, in a post-hoc analysis of the ROCKET-AF trial, which compared rivaroxaban with warfarin, 143 patients underwent 181 electric cardioversions, 142 patients underwent 194 pharmacologic cardioversions, and 79 patients underwent 85 catheter ablations. There was no significant difference in the long-term rate of stroke or systemic embolism (hazard ratio 1.38; 95% CI 0.61-3.11) [36]. (See "Atrial fibrillation in adults: Use of oral anticoagulants", section on 'Choice of anticoagulant'.) Edoxaban In the ENSURE-AF trial, 2199 patients were randomly assigned to receive edoxaban or enoxaparin and warfarin with discontinuation of enoxaparin when the INR was >2.0 [5]. There was no significant difference in the primary efficacy end point (0.5 percent in the edoxaban group versus 1 percent in the enoxaparin warfarin group; odds ratio [OR] 0.46, 95% CI 0.12-1.43). The primary safety end point occurred in 1.6 percent of the edoxaban group versus 1.1 percent in the enoxaparin warfarin group (OR 1.48, 95% CI 0.64-3.55). The results were independent of the TEE-guided strategy and anticoagulation status. Therapeutic anticoagulation prior to cardioversion appears to be effective largely due to thrombus resolution, rather than organization and adherence of left atrial thrombi [37,38]. (See https://www.uptodate.com/contents/prevention-of-embolization-prior-to-and-after-restoration-of-sinus-rhythm-in-atrial-fibrillation/print 9/27 7/5/23, 10:17 AM Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation - UpToDate 'Rationale for anticoagulation' above.) Transesophageal echocardiography-based approach We suggest a TEE-based approach ( table 2A-B) for symptomatic patients and for patients for whom there is a concern about a three-week (or more) delay to cardioversion. Such a concern might arise from a preference to not have ongoing symptoms of AF or a possible lower likelihood of successful cardioversion with a longer period of AF. Other individuals for whom this strategy may be reasonable include those at high bleeding risk, as the TEE-guided approach shortens the total precardioversion anticoagulation time for those without thrombus; and those at highest risk for a cardioversion- related thromboembolic event, including prior thromboembolism and elderly women with diabetes and heart failure. Patients who require hospitalization are also candidates for this approach [39,40]. This recommendation for a focused use of the TEE-based approach is based on our concerns about cost, the small potential for complications, and the possibility of worse outcomes. We also recommend precardioversion TEE for all patients with a percutaneous left atrial appendage occlusion device in place (eg, Watchman, Lariat, Amulet,) or who have undergone surgical LAA exclusion (eg, by stapling, suture or approved device closure). Following LAA occlusion, adjacent thrombus may occur (with or without incomplete closure) with associated risk of thromboembolism. Limited data are available to guide the anticoagulation strategy in this setting [41]. (See "Atrial fibrillation: Left atrial appendage occlusion".) In a TEE-based approach, the imaging study is performed after therapeutic anticoagulation (of short duration) and prior to anticipated cardioversion. Patients without evidence of left and right atrial (specifically the left atrial appendage, which is the site for the vast majority of thrombi) thrombus proceed to cardioversion. If thrombus is found (or cannot be confidently excluded) on TEE, cardioversion should not be performed, and therapeutic anticoagulation should be continued for at least four weeks after which time we recommend that a TEE be repeated (to screen for residual thrombus, which would be a contraindication to cardioversion) if cardioversion is desired. The TEE approach should include the following sequential steps before cardioversion: For inpatients, the options include using heparin plus warfarin or using an DOAC. With the former, we administer either low molecular weight or unfractionated heparin (bolus and continuous drip with a goal partial thromboplastin time 1.5 to 2 times control) and simultaneously initiate oral warfarin (target INR 2.0 to 3.0). With the latter, we give at least two doses of a DOAC. As the pharmacokinetics of the DOACs are different than warfarin, https://www.uptodate.com/contents/prevention-of-embolization-prior-to-and-after-restoration-of-sinus-rhythm-in-atrial-fibrillation/print 10/27 7/5/23, 10:17 AM Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation - UpToDate the combination of a heparin plus DOAC may lead to supratherapeutic anticoagulation. We do not recommend overlap of or combined use of heparin and a DOAC. For most outpatients, we prefer DOAC to warfarin. There are multiple factors that determine whether a DOAC or warfarin would be used, including cost and patient preference, but DOACs have the advantage of faster onset of action and ease of dosing. A strategy of at least two days of DOAC prior to TEE-guided cardioversion can be used. As an alternative, oral warfarin can be started five days before TEE with the target INR 2.0 to 3.0 [12]. A minimal precardioversion INR of 2.0 is acceptable, though 2.5 may be preferred. Obtain a TEE to assess for the presence of atrial thrombi. The use of an endocardial border definition echo contrast agent may help in cases where there is uncertainty about the presence or absence of thrombus [42]. If no thrombus is seen, proceed with cardioversion. Continue therapeutic anticoagulation from the time of TEE through cardioversion and extend for another four weeks. If a thrombus is seen on TEE, the patient should receive a minimum of four weeks of therapeutic anticoagulation and a repeat TEE to document thrombus resolution if cardioversion is desired [37]. If no cardioversion is desired, a follow-up TEE is not needed, as the patient should receive lifelong antithrombotic therapy. If thrombus is absent on repeat TEE, cardioversion may be performed. If thrombus is still evident, the rhythm control strategy may be changed to a rate control strategy, especially when AF-related symptoms are controlled, since there is a high risk of thromboembolism if cardioversion is performed. However, the evidence supporting this latter recommendation of avoidance of cardioversion with a residual thrombus is minimal. It is best to be conservative with at least three weeks of precardioversion oral anticoagulant if an atrial thrombus cannot be confidently excluded on TEE. Continuous oral anticoagulation (warfarin INR 2.0 to 3.0 or full-dose DOAC) for at least four weeks after cardioversion in all eligible patients, regardless of the cardioversion method, CHA DS -VASc score, or apparent maintenance of SR. In patients who have not achieved 2 2 therapeutic anticoagulation with warfarin at the time of cardioversion, unfractionated or low molecular weight heparin should be continued until the INR is therapeutic. Observational studies have suggested that patients with AF of more than 48 hours duration can be acutely anticoagulated with heparin/oral anticoagulant and proceed directly to cardioversion without prolonged anticoagulation if no atrial thrombus is seen on precardioversion TEE ( table 2A-B) [11,43-45]. The ACUTE trial compared a TEE-guided strategy with a conventional https://www.uptodate.com/contents/prevention-of-embolization-prior-to-and-after-restoration-of-sinus-rhythm-in-atrial-fibrillation/print 11/27 7/5/23, 10:17 AM Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation - UpToDate strategy (including therapeutic warfarin [INR 2.0 to 3.0] anticoagulation for at least three weeks prior to electrical cardioversion) in 1222 patients with AF of more than two days duration (median duration 13 days) who were undergoing electrical cardioversion [12,46]. Patients assigned to the TEE-guided strategy were anticoagulated with heparin before TEE if they were inpatients or with oral warfarin for five days (target INR 2.0 to 3.0) before TEE if they were outpatients. TEE was then followed by cardioversion if no atrial thrombi were identified. With both approaches, warfarin therapy was continued for four weeks after cardioversion. If the initial TEE demonstrated thrombus (which was present in 12 percent), cardioversion was postponed and patients received therapeutic (INR 2.0 to 3.0) anticoagulation for three weeks, at which time a repeat TEE was performed. Patients assigned to conventional strategy received three weeks of therapeutic anticoagulation before cardioversion. The following findings were noted: Within the eight weeks after study enrollment, there was no significant difference between the TEE and conventional groups in the incidence of ischemic stroke (0.6 versus 0.3 percent, respectively; relative risk [RR] 1.95, 95% CI 0.36-10.60) or all embolic events, including stroke, transient ischemic attack, and peripheral embolism (0.8 versus 0.5 percent, respectively; RR 1.62, 95% CI 0.39-6.76). One important difference is that the majority of thromboembolic events in the TEE arm occurred in patients who had reverted back to AF and/or had a subtherapeutic INR at the time of the event, while the thromboembolic events in the warfarin arm occurred in patients with SR with a therapeutic INR. There were significantly fewer hemorrhagic events with the TEE strategy (2.9 versus 5.5 percent), but no significant difference in the incidence of major bleeding (0.8 versus 1.5 percent) [12,47]; in addition, there was no significant difference in all-cause mortality (2.4 versus 1 percent) or cardiac deaths (1.3 versus 0.7). The TEE strategy led to a shorter mean time to cardioversion (3 versus 31 days) and a greater incidence of successful restoration of SR (71 versus 65 percent). Thromboembolism has been reported after a negative precardioversion TEE in some patients who were not therapeutically anticoagulated at the time of TEE and continuing for one month after cardioversion [9,14,15]. These adverse events may be related to the limited sensitivity of TEE for small thrombi, or to new thrombus formation that has been reported during the period between TEE and cardioversion or after cardioversion [9,14,15]. Thus, we recommend therapeutic anticoagulation for all patients undergoing a TEE-based approach to cardioversion. https://www.uptodate.com/contents/prevention-of-embolization-prior-to-and-after-restoration-of-sinus-rhythm-in-atrial-fibrillation/print 12/27 7/5/23, 10:17 AM Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation - UpToDate The development of impaired left atrial mechanical function and of new thrombi after cardioversion provides the rationale for four weeks of therapeutic anticoagulation after cardioversion (INR 2.0 to 3.0 or daily DOAC), even when the precardioversion TEE shows no thrombus [15,16]. There is suggestive evidence that such an approach reduces the incidence of embolic events [16]. (See 'Rationale for anticoagulation' above.) Although the results of the ACUTE study discussed above raise concerns about possible worse outcomes in patients treated with this strategy [39], some experts have suggested that the TEE strategy is a reasonable alternative to a conventional approach in some patients, such as those with a strong preference for early cardioversion, those with AF of less than three to four weeks duration who would benefit most from left atrial mechanical recovery, and those at increased risk of hemorrhagic complications (as the duration of precardioversion anticoagulation may be shortened). Another potential reason to consider this strategy is that a shorter period of AF may increase the likelihood of successful cardioversion and long-term maintenance of SR. (See "Atrial fibrillation: Cardioversion", section on 'Electrical cardioversion'.) RECOMMENDATIONS OF OTHERS Our recommendations are in broad agreement with those from the American Heart Association/American College of Cardiology/Heart Rhythm Society, the European Society of Cardiology, and the European Heart Rhythm Association [20,25,48,49]. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Atrial fibrillation" and "Society guideline links: Arrhythmias in adults".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and Beyond the Basics. th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading https://www.uptodate.com/contents/prevention-of-embolization-prior-to-and-after-restoration-of-sinus-rhythm-in-atrial-fibrillation/print 13/27 7/5/23, 10:17 AM Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation - UpToDate level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on patient info and the keyword(s) of interest.) Beyond the Basics topic (see "Patient education: Atrial fibrillation (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS Conversion of atrial fibrillation (AF) to sinus rhythm (SR), either spontaneously or intended, is associated with a clinically important transient increase in the risk of thromboembolism, particularly stroke. This risk increases significantly after 48 hours of AF and can be lowered by therapeutic anticoagulation before cardioversion. (See 'Rationale for anticoagulation' above.)

cardioversion with a residual thrombus is minimal. It is best to be conservative with at least three weeks of precardioversion oral anticoagulant if an atrial thrombus cannot be confidently excluded on TEE. Continuous oral anticoagulation (warfarin INR 2.0 to 3.0 or full-dose DOAC) for at least four weeks after cardioversion in all eligible patients, regardless of the cardioversion method, CHA DS -VASc score, or apparent maintenance of SR. In patients who have not achieved 2 2 therapeutic anticoagulation with warfarin at the time of cardioversion, unfractionated or low molecular weight heparin should be continued until the INR is therapeutic. Observational studies have suggested that patients with AF of more than 48 hours duration can be acutely anticoagulated with heparin/oral anticoagulant and proceed directly to cardioversion without prolonged anticoagulation if no atrial thrombus is seen on precardioversion TEE ( table 2A-B) [11,43-45]. The ACUTE trial compared a TEE-guided strategy with a conventional https://www.uptodate.com/contents/prevention-of-embolization-prior-to-and-after-restoration-of-sinus-rhythm-in-atrial-fibrillation/print 11/27 7/5/23, 10:17 AM Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation - UpToDate strategy (including therapeutic warfarin [INR 2.0 to 3.0] anticoagulation for at least three weeks prior to electrical cardioversion) in 1222 patients with AF of more than two days duration (median duration 13 days) who were undergoing electrical cardioversion [12,46]. Patients assigned to the TEE-guided strategy were anticoagulated with heparin before TEE if they were inpatients or with oral warfarin for five days (target INR 2.0 to 3.0) before TEE if they were outpatients. TEE was then followed by cardioversion if no atrial thrombi were identified. With both approaches, warfarin therapy was continued for four weeks after cardioversion. If the initial TEE demonstrated thrombus (which was present in 12 percent), cardioversion was postponed and patients received therapeutic (INR 2.0 to 3.0) anticoagulation for three weeks, at which time a repeat TEE was performed. Patients assigned to conventional strategy received three weeks of therapeutic anticoagulation before cardioversion. The following findings were noted: Within the eight weeks after study enrollment, there was no significant difference between the TEE and conventional groups in the incidence of ischemic stroke (0.6 versus 0.3 percent, respectively; relative risk [RR] 1.95, 95% CI 0.36-10.60) or all embolic events, including stroke, transient ischemic attack, and peripheral embolism (0.8 versus 0.5 percent, respectively; RR 1.62, 95% CI 0.39-6.76). One important difference is that the majority of thromboembolic events in the TEE arm occurred in patients who had reverted back to AF and/or had a subtherapeutic INR at the time of the event, while the thromboembolic events in the warfarin arm occurred in patients with SR with a therapeutic INR. There were significantly fewer hemorrhagic events with the TEE strategy (2.9 versus 5.5 percent), but no significant difference in the incidence of major bleeding (0.8 versus 1.5 percent) [12,47]; in addition, there was no significant difference in all-cause mortality (2.4 versus 1 percent) or cardiac deaths (1.3 versus 0.7). The TEE strategy led to a shorter mean time to cardioversion (3 versus 31 days) and a greater incidence of successful restoration of SR (71 versus 65 percent). Thromboembolism has been reported after a negative precardioversion TEE in some patients who were not therapeutically anticoagulated at the time of TEE and continuing for one month after cardioversion [9,14,15]. These adverse events may be related to the limited sensitivity of TEE for small thrombi, or to new thrombus formation that has been reported during the period between TEE and cardioversion or after cardioversion [9,14,15]. Thus, we recommend therapeutic anticoagulation for all patients undergoing a TEE-based approach to cardioversion. https://www.uptodate.com/contents/prevention-of-embolization-prior-to-and-after-restoration-of-sinus-rhythm-in-atrial-fibrillation/print 12/27 7/5/23, 10:17 AM Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation - UpToDate The development of impaired left atrial mechanical function and of new thrombi after cardioversion provides the rationale for four weeks of therapeutic anticoagulation after cardioversion (INR 2.0 to 3.0 or daily DOAC), even when the precardioversion TEE shows no thrombus [15,16]. There is suggestive evidence that such an approach reduces the incidence of embolic events [16]. (See 'Rationale for anticoagulation' above.) Although the results of the ACUTE study discussed above raise concerns about possible worse outcomes in patients treated with this strategy [39], some experts have suggested that the TEE strategy is a reasonable alternative to a conventional approach in some patients, such as those with a strong preference for early cardioversion, those with AF of less than three to four weeks duration who would benefit most from left atrial mechanical recovery, and those at increased risk of hemorrhagic complications (as the duration of precardioversion anticoagulation may be shortened). Another potential reason to consider this strategy is that a shorter period of AF may increase the likelihood of successful cardioversion and long-term maintenance of SR. (See "Atrial fibrillation: Cardioversion", section on 'Electrical cardioversion'.) RECOMMENDATIONS OF OTHERS Our recommendations are in broad agreement with those from the American Heart Association/American College of Cardiology/Heart Rhythm Society, the European Society of Cardiology, and the European Heart Rhythm Association [20,25,48,49]. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Atrial fibrillation" and "Society guideline links: Arrhythmias in adults".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and Beyond the Basics. th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading https://www.uptodate.com/contents/prevention-of-embolization-prior-to-and-after-restoration-of-sinus-rhythm-in-atrial-fibrillation/print 13/27 7/5/23, 10:17 AM Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation - UpToDate level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on patient info and the keyword(s) of interest.) Beyond the Basics topic (see "Patient education: Atrial fibrillation (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS Conversion of atrial fibrillation (AF) to sinus rhythm (SR), either spontaneously or intended, is associated with a clinically important transient increase in the risk of thromboembolism, particularly stroke. This risk increases significantly after 48 hours of AF and can be lowered by therapeutic anticoagulation before cardioversion. (See 'Rationale for anticoagulation' above.) The following recommendations apply to patients with AF of clearly less than 48 hours duration (See 'AF duration less than 48 hours' above.): For patients one or more high risk factors for thromboembolism (eg, prior thromboembolism, heart failure, or diabetes mellitus), we suggest deferral of cardioversion to allow for three weeks of effective therapeutic precardioversion anticoagulation rather than early cardioversion (Grade 2C). Anticoagulation with heparin or a direct-acting oral anticoagulant (DOAC) before, during, and after cardioversion along with precardioversion transesophageal echocardiography (TEE) is an alternative approach for these high-risk patients. For patients not at high risk of thromboembolism (listed in the above bulleted recommendation), we anticoagulate most patients with a CHA DS -VASc score 1 2 2 (Grade 2C). We start either DOAC or a combination of heparin and warfarin prior to cardioversion. For patients with low risk of thromboembolism (CHA DS -VASc score 0 in men, 1 in 2 2 women), our experts have differing approaches regarding postcardioversion anticoagulation, with some using four weeks of postcardioversion warfarin or DOAC anticoagulation and others not. The following recommendations apply to patients with AF of more than 48 hours duration or when the duration is unknown (see 'AF duration uncertain or 48 or more https://www.uptodate.com/contents/prevention-of-embolization-prior-to-and-after-restoration-of-sinus-rhythm-in-atrial-fibrillation/print 14/27 7/5/23, 10:17 AM Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation - UpToDate hours' above): We recommend a minimum of three consecutive weeks of therapeutic anticoagulation (warfarin with an international normalized ratio [INR] greater than 2.0 or DOAC) prior to cardioversion, rather than proceeding directly to cardioversion (Grade 1B). We recommend a DOAC prior to elective cardioversion rather than warfarin irrespective of whether the anticoagulant will be given long term (Grade 1B). (See 'Anticoagulant approach' above.) For symptomatic patients in whom there is a strong preference to not delay cardioversion, or in whom there is a concern about bleeding with prolonged oral anticoagulation, or who are not likely to tolerate AF despite adequate rate slowing, a TEE strategy is a reasonable approach using therapeutic anticoagulation with heparin/warfarin or DOAC throughout the pericardioversion period. (See 'Transesophageal echocardiography-based approach' above.) We recommend therapeutic oral anticoagulation (with a DOAC or warfarin with target INR of 2.0 to 3.0) for four weeks after cardioversion in all patients, rather than discontinuing anticoagulation after cardioversion (Grade 1B). Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Berger M, Schweitzer P. Timing of thromboembolic events after electrical cardioversion of atrial fibrillation or flutter: a retrospective analysis. Am J Cardiol 1998; 82:1545. 2. Nagarakanti R, Ezekowitz MD, Oldgren J, et al. 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Thromboembolic complications after cardioversion of acute atrial fibrillation: the FinCV (Finnish CardioVersion) study. J Am Coll Cardiol 2013; 62:1187. 24. Kleemann T, Becker T, Strauss M, et al. Prevalence of left atrial thrombus and dense spontaneous echo contrast in patients with short-term atrial fibrillation < 48 hours undergoing cardioversion: value of transesophageal echocardiography to guide cardioversion. J Am Soc Echocardiogr 2009; 22:1403. 25. Hindricks G, Potpara T, Dagres N, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J 2021; 42:373. 26. Hansen ML, Jepsen RM, Olesen JB, et al. Thromboembolic risk in 16 274 atrial fibrillation patients undergoing direct current cardioversion with and without oral anticoagulant therapy. Europace 2015; 17:18. 27. Stellbrink C, Nixdorff U, Hofmann T, et al. Safety and efficacy of enoxaparin compared with unfractionated heparin and oral anticoagulants for prevention of thromboembolic complications in cardioversion of nonvalvular atrial fibrillation: the Anticoagulation in Cardioversion using Enoxaparin (ACE) trial. Circulation 2004; 109:997. https://www.uptodate.com/contents/prevention-of-embolization-prior-to-and-after-restoration-of-sinus-rhythm-in-atrial-fibrillation/print 17/27 7/5/23, 10:17 AM Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation - UpToDate 28. Klein AL, Jasper SE, Katz WE, et al. The use of enoxaparin compared with unfractionated heparin for short-term antithrombotic therapy in atrial fibrillation patients undergoing transoesophageal echocardiography-guided cardioversion: assessment of Cardioversion Using Transoesophageal Echocardiography (ACUTE) II randomized multicentre study. Eur Heart J 2006; 27:2858. 29. Garg A, Khunger M, Seicean S, et al. Incidence of Thromboembolic Complications Within 30 Days of Electrical Cardioversion Performed Within 48 Hours of Atrial Fibrillation Onset. JACC Clin Electrophysiol 2016; 2:487. 30. Pritchett EL. Management of atrial fibrillation. N Engl J Med 1992; 326:1264. 31. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361:1139. 32. Botkin SB, Dhanekula LS, Olshansky B. Outpatient cardioversion of atrial arrhythmias: efficacy, safety, and costs. Am Heart J 2003; 145:233. 33. Weinberg DM, Mancini J. 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Efficacy of anticoagulation in resolving left atrial and left atrial appendage thrombi: A transesophageal echocardiographic study. Am Heart J 2000; 140:150. 39. Silverman DI, Manning WJ. Strategies for cardioversion of atrial fibrillation time for a change? N Engl J Med 2001; 344:1468. 40. Seto TB, Taira DA, Tsevat J, Manning WJ. Cost-effectiveness of transesophageal echocardiographic-guided cardioversion: a decision analytic model for patients admitted to the hospital with atrial fibrillation. J Am Coll Cardiol 1997; 29:122. https://www.uptodate.com/contents/prevention-of-embolization-prior-to-and-after-restoration-of-sinus-rhythm-in-atrial-fibrillation/print 18/27 7/5/23, 10:17 AM Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation - UpToDate 41. Sharma SP, Turagam MK, Gopinathannair R, et al. Direct Current Cardioversion of Atrial Fibrillation in Patients With Left Atrial Appendage Occlusion Devices. J Am Coll Cardiol 2019; 74:2267. 42. Jung PH, Mueller M, Schuhmann C, et al. Contrast enhanced transesophageal echocardiography in patients with atrial fibrillation referred to electrical cardioversion improves atrial thrombus detection and may reduce associated thromboembolic events. Cardiovasc Ultrasound 2013; 11:1. 43. Klein AL, Murray RD, Grimm RA. Role of transesophageal echocardiography-guided cardioversion of patients with atrial fibrillation. J Am Coll Cardiol 2001; 37:691. 44. Manning WJ, Silverman DI, Gordon SP, et al. Cardioversion from atrial fibrillation without prolonged anticoagulation with use of transesophageal echocardiography to exclude the presence of atrial thrombi. N Engl J Med 1993; 328:750. 45. Manning WJ, Silverman DI, Keighley CS, et al. Transesophageal echocardiographically facilitated early cardioversion from atrial fibrillation using short-term anticoagulation: final results of a prospective 4.5-year study. J Am Coll Cardiol 1995; 25:1354. 46. Klein AL, Grimm RA, Jasper SE, et al. Efficacy of transesophageal echocardiography-guided cardioversion of patients with atrial fibrillation at 6 months: a randomized controlled trial. Am Heart J 2006; 151:380. 47. Klein AL, Murray RD, Grimm RA, et al. Bleeding complications in patients with atrial fibrillation undergoing cardioversion randomized to transesophageal echocardiographically guided and conventional anticoagulation therapies. Am J Cardiol 2003; 92:161. 48. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation 2014; 130:e199. 49. Heidbuchel H, Verhamme P, Alings M, et al. Updated European Heart Rhythm Association practical guide on the use of non-vitamin-K antagonist anticoagulants in patients with non- valvular atrial fibrillation: Executive summary. Eur Heart J 2016. Topic 906 Version 62.0 https://www.uptodate.com/contents/prevention-of-embolization-prior-to-and-after-restoration-of-sinus-rhythm-in-atrial-fibrillation/print 19/27 7/5/23, 10:17 AM Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation - UpToDate GRAPHICS Clinical risk factors for stroke, transient ischemic attack, and systemic embolism in the CHA DS -VASc score 2 2 (A) The risk factor-based approach expressed as a point based scoring system, with the acronym CHA DS -VASc (NOTE: maximum score is 9 since age may contribute 0, 1, or 2 points) 2 2 CHA DS -VASc risk factor Points 2 2 Congestive heart failure +1 Signs/symptoms of heart failure or objective evidence of reduced left ventricular ejection fraction Hypertension +1 Resting blood pressure >140/90 mmHg on at least 2 occasions or current antihypertensive treatment Age 75 years or older +2 Diabetes mellitus +1 Fasting glucose >125 mg/dL (7 mmol/L) or treatment with oral hypoglycemic agent and/or insulin Previous stroke, transient ischemic attack, or thromboembolism +2 Vascular disease +1 Previous myocardial infarction, peripheral artery disease, or aortic plaque Age 65 to 74 years +1 Sex category (female) +1 (B) Adjusted stroke rate according to CHA DS -VASc score 2 2 CHA DS -VASc score Patients (n = 73,538) Stroke and thromboembolism event 2 2 rate at 1-year follow-up (%) 0 6369 0.78 1 8203 2.01 2 12,771 3.71 3 17,371 5.92 4 13,887 9.27 https://www.uptodate.com/contents/prevention-of-embolization-prior-to-and-after-restoration-of-sinus-rhythm-in-atrial-fibrillation/print 20/27 7/5/23, 10:17 AM Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation - UpToDate 5 8942 15.26 6 4244 19.74 7 1420 21.50 8 285 22.38 9 46 23.64 CHA DS -VASc: Congestive heart failure, Hypertension, Age ( 75; doubled), Diabetes, Stroke (doubled), Vascular disease, Age (65 to 74), Sex. 2 2 Part A from: Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial brillation developed in collaboration with EACTS. Europace 2016; 18(11):1609-1678. By permission of Oxford University Press on behalf of the European Society of Cardiology. Copyright 2016 Oxford University Press. Available at: www.escardio.org/. Graphic 83272 Version 29.0 https://www.uptodate.com/contents/prevention-of-embolization-prior-to-and-after-restoration-of-sinus-rhythm-in-atrial-fibrillation/print 21/27 7/5/23, 10:17 AM Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation - UpToDate Optimal INR to minimize both bleeding and thromboembo lism in patients with atrial fibrillation (A) ORs for TE (396 cases, 1581 controls) and ICH (164 cases, 656 controls) by INR level in adults with nonvalvular AF, with 8 INR categories using INR 2.0 to 2.5 as the referent. Vertical bars indicate 95% CI. The numbers of cases and controls for each INR category are given below the figure. (B) ORs for TE (396 cases, 1581 controls) and ICH (164 cases, 656 controls) by INR level in adults with nonvalvular AF, with 6 INR categories using INR 2.0 to https://www.uptodate.com/contents/prevention-of-embolization-prior-to-and-after-restoration-of-sinus-rhythm-in-atrial-fibrillation/print 22/27 7/5/23, 10:17 AM Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation - UpToDate 2.5 as the referent. Vertical bars indicate 95% CI. The numbers of cases and controls for each INR category are given below the figure. AF: atrial fibrillation; INR: international normalized ratio; OR: odds ratio; TE: thromboembolism; ICH: intracranial hemorrhage; CI: confidence interval. Reproduced with permission from: Singer DE, Chang Y, Fang MC, et al. Should patient characteristics in uence target anticoagulation intensity for stroke prevention in nonvalvular atrial brillation? The ATRIA study. Circ Cardiovasc Qual Outcomes 2009; 2:297. Copyright 2009 Lippincott Williams & Wilkins. Graphic 65373 Version 13.0 https://www.uptodate.com/contents/prevention-of-embolization-prior-to-and-after-restoration-of-sinus-rhythm-in-atrial-fibrillation/print 23/27 7/5/23, 10:17 AM Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation - UpToDate Odds ratios for ischemic stroke and intracranial bleeding in relation to intensity of anticoagulation Adjusted odds ratios for ischemic stroke and intracranial bleeding in relation to intensity of anticoagulation. Reproduced with permission from: Fuster V, Ryden LE, Cannom DS, et al. 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 Guidelines for the management of patients with atrial brillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in partnership with the European Society of Cardiology and in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation 2011; 123:e269. Copyright 2011 Lippincott Williams & Wilkins. Graphic 87025 Version 4.0 https://www.uptodate.com/contents/prevention-of-embolization-prior-to-and-after-restoration-of-sinus-rhythm-in-atrial-fibrillation/print 24/27 7/5/23, 10:17 AM Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation - UpToDate Advantages and disadvantages of the conventional approach to cardioversion (one month of pretreatment with warfarin) in patients with atrial fibrillation Advantages Disadvantages Use of warfarin for one month before Delaying cardioversion to normal sinus rhythm for one cardioversion may lower the stroke rate month potentially decreases functional capacity. from 5.6 percent to a very low stroke rate of <2 percent. Relatively easy to administer with regular Prolonging treatment for seven to eight weeks one monitoring of INRs. month prior to and one month after cardioversion increases the risk of bleeding complications. Suitable for community hospitals. Not followed by routine clinical practice, especially in the elderly. The conventional approach has withstood the "test of time" since the 1960s. Patients who are at the highest risk for developing systemic embolization who should receive more prolonged or intensive anticoagulation are not routinely identified. Reprinted with permission from the American College of Cardiology. J Am Coll Cardiol 2001; 37:691. https://www.journals.elsevier.com/journal-of-the-american-college-of-cardiology. Graphic 72971 Version 6.0 https://www.uptodate.com/contents/prevention-of-embolization-prior-to-and-after-restoration-of-sinus-rhythm-in-atrial-fibrillation/print 25/27 7/5/23, 10:17 AM Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation - UpToDate Advantages and disadvantages of the transesophageal echocardiography- guided approach to cardioversion of patients with atrial fibrillation undergoing cardioversion Advantages Disadvantages Transesophageal echocardiography (TEE) should be able to detect left atrial appendage thrombi, TEE is performed without any definitive guidelines about who should receive the which increase the risk of embolic stroke after procedure (high versus low risk) electrical cardioversion, thus sparing patients with thrombi from undergoing cardioversion In the majority of patients without left atrial Residual thrombus on repeat TEE may diminish appendage thrombi, earlier cardioversion may shorten the period of anticoagulation and lower the cost-effectiveness of the TEE-guided approach the corresponding risk of bleeding complications A TEE-guided approach may prove more cost- effective owing to the reduction in laboratory Transesophageal echocardiography requires a level III-trained physician and availability of monitoring costs and the reduction in bleeding complications expensive echocardiographic machines Earlier cardioversion is believed to increase the Transesophageal echocardiography may miss likelihood of a successful return to and thrombi that may embolize after cardioversion. In maintenance of sinus rhythm contrast, TEE may render false positive results by erroneously identifying spontaneous echocardiographic contrast, sludge, multilobed appendages or pectinate muscles as thrombus. Reprinted with permission from: The American College of Cardiology. J Am Coll of Cardiol 2001; 37:691-704. https://www.journals.elsevier.com/journal-of-the-american-college-of-cardiology. Graphic 54077 Version 6.0 https://www.uptodate.com/contents/prevention-of-embolization-prior-to-and-after-restoration-of-sinus-rhythm-in-atrial-fibrillation/print 26/27 7/5/23, 10:17 AM Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation - UpToDate Contributor Disclosures Robert Phang, MD, FACC, FHRS No relevant financial relationship(s) with ineligible companies to disclose. Warren J Manning, MD Equity Ownership/Stock Options: Pfizer [Anticoagulants]. All of the relevant financial relationships listed have been mitigated. Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Brian Olshansky, MD Other Financial Interest: AstraZeneca [Member of the DSMB for the DIALYZE trial]; Medtelligence [Cardiovascular disease]. All of the relevant financial relationships listed have been mitigated. N A Mark Estes, III, MD Consultant/Advisory Boards: Boston Scientific [Arrhythmias]; Medtronic [Arrhythmias]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/prevention-of-embolization-prior-to-and-after-restoration-of-sinus-rhythm-in-atrial-fibrillation/print 27/27

7/5/23, 10:18 AM Role of echocardiography in atrial fibrillation - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Role of echocardiography in atrial fibrillation : Warren J Manning, MD : Bradley P Knight, MD, FACC : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Feb 03, 2023. INTRODUCTION Atrial fibrillation (AF) is the most common treated arrhythmia. Echocardiography plays a key role in evaluation and management of patients with AF. The topic will review the use of echocardiography in evaluating patients with AF. An overview of AF is presented separately. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation".) OBJECTIVES The role of echocardiographic imaging among patients with AF can be divided into two main categories: Assessment of cardiac chamber sizes and function, the atrial contribution to left ventricular filling, the pericardium, and valvular function. This information may be helpful in determining the conditions associated with AF, the risk for recurrent AF following cardioversion, and the hemodynamic benefit of maintaining sinus rhythm. This information is generally obtained from transthoracic echocardiography (TTE), with moderately invasive transesophageal echocardiography (TEE) generally reserved for assessment of the left atrial appendage for thrombus prior to cardioversion. (See "Epidemiology, risk factors, and prevention of atrial fibrillation" and "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations".) https://www.uptodate.com/contents/role-of-echocardiography-in-atrial-fibrillation/print 1/16 7/5/23, 10:18 AM Role of echocardiography in atrial fibrillation - UpToDate Identification of patients at increased risk for thromboembolic complications of AF before cardioversion and in patients with chronic AF. (See "Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation" and "Atrial fibrillation in adults: Selection of candidates for anticoagulation".) INDICATIONS Nearly all patients presenting with their first episode of AF will benefit from transthoracic (surface) echocardiographic (TTE) evaluation of left atrial size, left ventricular cavity size and regional/global systolic function, and mitral valve morphology and function. Examination of prior TTE data (if available) may allow for assessment of the atrial contribution to left ventricular filling (transmitral Doppler peak A wave velocity) when the patient is in sinus rhythm so as to have an assessment of the atrial contribution to ventricular filling. (See 'Transthoracic echocardiography' below.) A more selected subgroup may benefit from the additional information obtained from transesophageal echocardiographic (TEE) evaluation for left atrial thrombi to allow for early cardioversion if no thrombi are identified. (See 'Transesophageal echocardiography' below and "Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation".) TRANSTHORACIC ECHOCARDIOGRAPHY TTE provides detailed information about cardiac anatomy and function. In comparison to TEE, TTE is less useful for the detection of atrial thrombus, especially thrombus in the right atrial appendage or left atrial appendage (LAA), which is better detected by TEE. (See 'Left atrial thrombi' below.) Left atrial size TTE is particularly helpful in assessing the size of the body of the left atrium. 2 The normal left atrial dimension in adults is less than 4.0 cm (or less than 2.0 cm/m body 2 surface area) or biplane derived left atrial volume index of less than 34 mL/m body surface area. Left atrial enlargement is common in AF, particularly in patients with mitral valve disease (both stenosis and regurgitation), left ventricular cavity dilation, annular calcification, or hypertension [1]. In addition, sustained AF itself can lead to a further increase in left atrial size [2], an effect that is reversible after cardioversion and maintenance of sinus rhythm [3]. Pulsed Doppler studies have shown that the time to recovery of atrial mechanical function is directly related to the duration of AF (eg, within 24 hours in patients with AF for less than 2 weeks; up to a week for patients who have been in AF for two to six weeks; and up to a month for patients https://www.uptodate.com/contents/role-of-echocardiography-in-atrial-fibrillation/print 2/16 7/5/23, 10:18 AM Role of echocardiography in atrial fibrillation - UpToDate with sustained AF for more than six weeks) [4]. However, the routine serial assessment of atrial mechanical function recovery is not recommended and TTE Doppler assessment of atrial recovery does not predict long term maintenance of sinus rhythm. (See "Echocardiographic evaluation of the atria and appendages".) Regardless of the mechanism, left atrial enlargement is important prognostically. It decreases the probability that long-term maintenance of sinus rhythm will be successful [5-7]. Patients with chronic (more than one year) AF, rheumatic mitral valve disease, or severe left atrial 2 enlargement (dimension greater than 6.0 cm or left atrial volume greater than 48 mL/m ) are at greatest risk for recurrent AF [7]. If, however, the duration of AF is brief, an attempt at cardioversion is reasonable for most patients regardless of absolute left atrial size. (See "Atrial fibrillation: Cardioversion".) Although TTE can provide anatomic imaging of the body of the left atrium, TEE is preferred when looking for left atrial thrombi and assessing LAA and right atrial appendage anatomy and function (abnormalities of which predispose to the thrombus formation), as these areas are not well seen on TTE. Few data are known regarding the impact of AF on atrial appendage anatomy, though sustained AF does lead to progressively more impaired LAA ejection velocity. (See 'Transesophageal echocardiography' below.) Mitral valve function TTE is quite useful in the assessment of mitral valve anatomy and function, which can influence the risk of thrombus formation. As an example, occult mitral stenosis in the adult may initially present with AF, often in the setting of acute thromboembolism. In this setting, long-term oral anticoagulation is indicated even if cardioversion to sinus rhythm is successful and independent of CHA DS -VASc score (these 2 2 clinical thromboembolism scores were derived from non-valvular AF populations). Long-term maintenance of sinus rhythm is unlikely unless the mitral stenosis (by surgery or percutaneous balloon mitral valvuloplasty) or severe mitral regurgitation (surgical repair or replacement) is corrected. (See "Surgical and investigational approaches to management of mitral stenosis" and "Percutaneous mitral balloon commissurotomy in adults".) Mitral regurgitation is commonly found among patients with AF. More than moderate mitral regurgitation appears to protect against clinical thromboembolism in chronic AF, presumably by minimized stasis in the left atrium and LAA [8-11] (see "Mechanisms of thrombogenesis in atrial fibrillation"). However, mitral regurgitation does not appear to protect from the formation of LAA thrombus as identified on TEE. As mentioned, examination of a prior TTE when the patient is in sinus rhythm (if available) will provide useful information on the relative atrial contribution to total left ventricular filling by https://www.uptodate.com/contents/role-of-echocardiography-in-atrial-fibrillation/print 3/16 7/5/23, 10:18 AM Role of echocardiography in atrial fibrillation - UpToDate examining the transmitral peak A wave velocity or peak E to peak A wave ratio. For those patients with a relatively high/large transmitral A wave, the contribution of left atrial systole to left ventricular filling is greater. Thus, these patients may derive greater hemodynamic benefit from rhythm control. Left ventricular function All patients with newly discovered AF should have a TTE to assess for LV size and function and other structural cardiac conditions that may impact treatment. TTE assessment of left ventricular systolic function helps to guide the choice of pharmacologic therapy for ventricular rate control in chronic AF. (See "Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy".) TTE can also detect left ventricular hypertrophy, focal wall motion abnormalities suggestive of myocardial infarction, and conditions less frequently associated with AF, including pericarditis (pericardial effusion), pulmonary embolus (dilated and poorly functioning right ventricle), and aortic stenosis (AF is generally poorly tolerated in this disorder and does not occur until very late in the disease). (See "Medical management of asymptomatic aortic stenosis in adults", section on 'Atrial fibrillation'.) Left ventricular dysfunction, as determined from the TTE, independently predicts an increased risk of a stroke in patients with AF. Analysis of 1066 patients entered into three prospective clinical trials evaluating the role of anticoagulation in nonvalvular AF (BAATAF, SPINAF, and SPAF) found that, among patients in the placebo or control groups, the incidence of a stroke was 9.3 percent per year in patients with moderate to severe left ventricular dysfunction compared with 4.4 percent per year in those with normal or mildly abnormal left ventricular systolic function ( figure 1) [12]. The predictive value of left ventricular dysfunction for thromboembolic risk has been confirmed in many other studies. (See "Atrial fibrillation in adults: Selection of candidates for anticoagulation", section on 'CHA2DS2-VASc score'.) While TTE is recommended for all patients presenting with their first episode of AF, repeated TTE is not indicated when the patient has recurrent episodes unless there is a concern that the clinical situation has changed (eg, new heart failure). TRANSESOPHAGEAL ECHOCARDIOGRAPHY The preceding observations provide the rationale for the performance of TTE in all patients presenting with their first episode of AF. On the other hand, TEE should be reserved for patients in whom the diagnostic information will lead to alterations in therapy. It is a moderately invasive imaging technique that provides superior visualization of posterior structures, such as the left atrium and left atrial appendage (LAA). https://www.uptodate.com/contents/role-of-echocardiography-in-atrial-fibrillation/print 4/16 7/5/23, 10:18 AM Role of echocardiography in atrial fibrillation - UpToDate TEE has particular value in estimating thromboembolic risk in different clinical settings: It can detect LAA and right atrial appendage thrombi ( movie 1 and movie 2) for patients being considered for early cardioversion. In this setting, there is little additional benefit from TTE prior to TEE, as most of the necessary information can be derived from the TEE with its superior assessment of both appendages. (See "Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation".) While data suggest a role of TEE for patients who have not received a full month of therapeutic anticoagulation prior to cardioversion, there does not appear to be a role for routine TEE prior to cardioversion in patients who have been adequately anticoagulated with warfarin or direct oral anticoagulant (DOAC) for at least four weeks prior to cardioversion. However, TEE immediately prior to elective cardioversion should be considered for those patients at increased risk for left atrial thrombi (eg, rheumatic mitral valve disease, recent/prior thromboembolism, severe left ventricular systolic dysfunction) or those with a transiently subtherapeutic international normalized ratio (INR) or who have missed doses of DOAC in the month prior to elective cardioversion. (See "Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation".) Among patients in paroxysmal or chronic AF, abnormalities in the LAA (thrombus, dense spontaneous echo contrast, or flow velocity 20 cm/s) or the presence of a complex aortic plaque increases the risk of a thromboembolic event and are more likely in patients with clinical risk factors for thromboembolism ( figure 2) [13]. Another role of TEE is for assessment of the adequacy of complete exclusion of the LAA for those undergoing surgical or percutaneous (eg, Watchman device) LAA occlusion. This assessment is helpful in determining the duration of anticoagulation following LAA occlusion. (See "Atrial fibrillation: Left atrial appendage occlusion".) Left atrial thrombi A main advantage of TEE is that it provides superior visualization of posterior structures, such as the left atrium and LAA as well as the anterior right atrial appendage. This is particularly important for the detection of thrombi, spontaneous echocontrast (a precursor to thrombus), and depressed atrial appendage ejection velocities as these metrics are not assessable with TTE. The ability of TTE to identify or exclude left atrial or atrial appendage thrombi (as well as right atrial appendage thrombi) is quite limited, with a reported sensitivity of 39 to 63 percent, due largely to poor visualization of the LAA [14,15]. By contrast, TEE permits detection of thrombus in both the left atrium ( movie 3 and movie 4) and the LAA ( movie 1 and movie 2). https://www.uptodate.com/contents/role-of-echocardiography-in-atrial-fibrillation/print 5/16 7/5/23, 10:18 AM Role of echocardiography in atrial fibrillation - UpToDate TEE evidence of thrombus in the body of the left atrium is very uncommon. The vast majority of thrombi are seen in the LAA with thrombi seen in approximately 13 percent of patients presenting with nonrheumatic AF of more than three days duration [16-18]. The prevalence is increased in high-risk patients with mitral stenosis (33 percent in one series) [19], left ventricular systolic dysfunction, enlargement of the left atrium or LAA, spontaneous echo contrast, a recent thromboembolic event (43 percent in one report) [20], and CHADS2 score [21]. Recurrent embolization in the last setting may be due to migration of the residual thrombus. On the other hand, the apparent lack of atrial thrombi in 57 percent of these patients probably reflects migration of the entire thrombus during the embolic event, a thrombus not visualized by TEE due to its small size, or another source for the embolus. Thrombus in the right atrial appendage is far less common. The sensitivity and specificity of TEE for left atrial thrombi (in patients in whom the left atrium was directly examined at surgery) are 93 to 100 percent and 99 to 100 percent, respectively [14,15]. In a review of 231 patients in whom only 5.2 percent had a left atrial thrombus, TEE has a positive and negative predictive value of 86 and 100 percent, respectively [14]. For patients who are not candidates for TEE due to esophageal stricture or another contraindication, intracardiac echocardiography with the catheter in the main pulmonary artery has been shown to be at least as efficacious as TEE for identifying atrial appendage thrombi [22]. One potential limitation of these studies is that they were performed by experienced operators and the accuracy may not be replicable at all institutions. Additionally, the complementary role of three-dimension real-time TEE for atrial appendage thrombus is unknown. The use of an endocardial border definition echocontrast agent may help define small thrombi in the atrial appendage [23]. (See "Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation".) Studies from the Stroke Prevention in Atrial Fibrillation (SPAF) investigators confirmed the usefulness of TEE for predicting thromboembolism [13,24]. This study involved 786 patients with nonrheumatic AF, 382 of whom were at high clinical risk for a thromboembolism (eg, women >75 years of age and patients with systolic blood pressure >160 mmHg or a history of previous thromboembolism, impaired left ventricular function, or recent congestive heart failure). The rate of stroke was increased over threefold when TEE evidence of dense spontaneous echo contrast was present, increased by threefold for reduced (<20 cm/second) LAA peak ejection velocity and for LAA thrombus, and increased by fourfold by complex aortic plaque. Spontaneous echo contrast Spontaneous echo contrast (SEC or "smoke") refers to the presence of dynamic, smoke-like echoes seen during TEE in the left atrium or atrial appendage https://www.uptodate.com/contents/role-of-echocardiography-in-atrial-fibrillation/print 6/16 7/5/23, 10:18 AM Role of echocardiography in atrial fibrillation - UpToDate ( movie 3 and movie 2). Although most widely studied in the left atrium, SEC also occurs in the right atrium [16,25]. (See 'Right atrial thrombi' below.) SEC is thought to reflect increased erythrocyte aggregation caused by low shear rate due to altered atrial flow dynamics and uncoordinated atrial systole [26,27]. Erythrocyte aggregation is mediated by plasma proteins, especially fibrinogen, which promotes red cell rouleaux formation by moderating the normal electrostatic forces (due to negatively charged membranes) which keep erythrocytes from aggregating [28]. SEC is a strong risk factor for and may be the preceding stage to thrombus formation and thromboembolic events [13,24,29,30]. The following clinical characteristics of SEC have been identified: SEC is present in over 50 percent of all patients with AF and in over 80 percent of those with LAA thrombi or a recent thromboembolic event [12,13,20,24,25,29,30]. Furthermore, serial TEE studies have shown that SEC subsequently develops in many patients with chronic AF (44 percent in one report) who do not have SEC on their initial TEE [29]. The LAA peak outflow velocity can be estimated by TEE and SEC semiquantitatively graded as marked or dense if present throughout the entire cardiac cycle, or faint when intermittent [24,29]. The risk of thromboembolism increases as these parameters worsen [24]. SEC is associated with clinical risk factors for thromboembolism, including a prior thromboembolic event, left ventricular systolic dysfunction, and hypertension ( figure 2) [24,31] as well as CHADS2 risk score. On the other hand, it is less common in patients with mitral regurgitation [29] which, as noted above, appears to protect against clinical thromboembolism in chronic AF, presumably by minimized stasis in the left atrium and atrial appendage [8-11]. Warfarin, which leads to thrombus resolution and a lower incidence of thromboembolism, does not affect the presence of SEC, since it does not change the underlying hemodynamic abnormality [28,30,32]. (See "Atrial fibrillation in adults: Use of oral anticoagulants".) Blood flow velocity The ability to estimate blood flow velocity in the left or right atrium and left and right atrial appendage permits a more quantifiable measure of stasis. A low LAA blood flow velocity (less than 20 cm/second) is associated with the presence of appendage thrombus [25,29,33] and with denser SEC [24,29]. The risk of stroke increases sharply with marked reductions in blood flow velocity (<15 cm/sec), particularly in the LAA or posterior left atrium [34]. https://www.uptodate.com/contents/role-of-echocardiography-in-atrial-fibrillation/print 7/16 7/5/23, 10:18 AM Role of echocardiography in atrial fibrillation - UpToDate It has been suggested that left atrial blood flow velocity also may be a predictor of the likelihood of maintaining sinus rhythm after cardioversion. In one report, a high peak LAA blood flow velocity (>40 cm/sec) identified patients with an increased likelihood of remaining in sinus rhythm one year after cardioversion [35]. In comparison, low blood velocity was of limited predictive value. Other reports have been conflicting on the predictive value of low LAA blood flow velocity for the maintenance of sinus rhythm [36,37]. An explanation for ongoing thromboembolism in patients with paroxysmal AF and apparently maintained sinus rhythm may be related to a mechanical discordance between the body of the left atrium and the LAA (ie, an AF LAA pulse wave Doppler phenotype with sinus rhythm electrocardiogram and body of the left atrium motion) [38]. The reproducibility and consistency of this finding are unknown, but retrospective data suggest a discordance in up to 25 percent of patients with paroxysmal AF. Right atrial thrombi Few data are available comparing the sensitivity, specificity, and accuracy of TTE and TEE for right atrial and right atrial appendage thrombi, but the right atrial appendage is rarely seen by TTE. By contrast, right atrial or atrial appendage thrombi are also easily seen by TEE ( image 1). They are much less common than left atrial thrombi in patients in AF, occurring in 3 to 6 percent of cases (versus 15 to 20 percent for left atrial thrombi) [16,25]. The majority of patients with right atrial thrombi also have markedly depressed right ventricular systolic function, rheumatic tricuspid stenosis or prosthetic valve, or left atrial thrombi [12]. Cardioversion should be deferred even if patients have isolated right atrial thrombi. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Atrial fibrillation".) SUMMARY AND RECOMMENDATIONS Routine performance of transthoracic echocardiography is suggested for all patients presenting with their first episode of atrial fibrillation (AF) to obtain information regarding atrial size, ventricular function, valvular function, and possible pericardial effusion. Repeated transthoracic echocardiographic examinations for recurrent presentations of AF are not necessary unless the clinical presentation has changed. If available, data from prior transthoracic echocardiography (TTE) when the patient was in sinus rhythm is useful to https://www.uptodate.com/contents/role-of-echocardiography-in-atrial-fibrillation/print 8/16 7/5/23, 10:18 AM Role of echocardiography in atrial fibrillation - UpToDate determine the patient's relative dependence on sinus rhythm/atrial contribution to total left ventricular filling. (See 'Indications' above and 'Transthoracic echocardiography' above.) The main advantage of moderately invasive transesophageal echocardiography (TEE) is its ability to detect left and right atrial appendage thrombi and patients at risk for thrombi because of the presence of spontaneous echo contrast or reduced left atrial appendage (LAA) blood flow velocity as well as aortic plaque. The main clinical use of TEE for AF is in the management of early cardioversion in patients with AF of more than 48 hours or high- risk patients with AF of shorter duration who are candidates for cardioversion. (See 'Indications' above and 'Transesophageal echocardiography' above and "Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation".) There does not appear to be a role for routine TEE prior to cardioversion in patients who have been adequately anticoagulated with warfarin or direct oral anticoagulant (DOAC) for at least four weeks prior to cardioversion. However, TEE immediately prior to elective cardioversion should be considered for those patients at increased risk for left atrial thrombi (eg, rheumatic mitral valve disease, recent/prior thromboembolism, severe left ventricular systolic dysfunction) or those with a transiently subtherapeutic international normalized ratio (INR) or who have missed doses of DOAC in the month prior to elective cardioversion. (See 'Indications' above and 'Transesophageal echocardiography' above and "Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation", section on 'Transesophageal echocardiography-based approach'.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Dittrich HC, Pearce LA, Asinger RW, et al. Left atrial diameter in nonvalvular atrial fibrillation: An echocardiographic study. Stroke Prevention in Atrial Fibrillation Investigators. Am Heart J 1999; 137:494. 2. Sanfilippo AJ, Abascal VM, Sheehan M, et al. Atrial enlargement as a consequence of atrial fibrillation. A prospective echocardiographic study. Circulation 1990; 82:792. 3. Manning WJ, Leeman DE, Gotch PJ, Come PC. Pulsed Doppler evaluation of atrial mechanical function after electrical cardioversion of atrial fibrillation. J Am Coll Cardiol 1989; 13:617. 4. Manning WJ, Silverman DI, Katz SE, et al. Impaired left atrial mechanical function after cardioversion: relation to the duration of atrial fibrillation. J Am Coll Cardiol 1994; 23:1535. 5. H glund C, Rosenhamer G. Echocardiographic left atrial dimension as a predictor of maintaining sinus rhythm after conversion of atrial fibrillation. Acta Med Scand 1985; https://www.uptodate.com/contents/role-of-echocardiography-in-atrial-fibrillation/print 9/16 7/5/23, 10:18 AM Role of echocardiography in atrial fibrillation - UpToDate 217:411. 6. Dittrich HC, Erickson JS, Schneiderman T, et al. Echocardiographic and clinical predictors for outcome of elective cardioversion of atrial fibrillation. Am J Cardiol 1989; 63:193. 7. Brodsky MA, Allen BJ, Capparelli EV, et al. Factors determining maintenance of sinus rhythm after chronic atrial fibrillation with left atrial dilatation. Am J Cardiol 1989; 63:1065. 8. Blackshear JL, Pearce LA, Asinger RW, et al. Mitral regurgitation associated with reduced thromboembolic events in high-risk patients with nonrheumatic atrial fibrillation. Stroke Prevention in Atrial Fibrillation Investigators. Am J Cardiol 1993; 72:840. 9. Ozkan M, Kaymaz C, Kirma C, et al. Predictors of left atrial thrombus and spontaneous echo contrast in rheumatic valve disease before and after mitral valve replacement. Am J Cardiol 1998; 82:1066. 10. Nakagami H, Yamamoto K, Ikeda U, et al. Mitral regurgitation reduces the risk of stroke in patients with nonrheumatic atrial fibrillation. Am Heart J 1998; 136:528. 11. Goldsmith IR, Blann AD, Patel RL, Lip GY. Reduced indexes of left atrial hypercoagulability in patients with severe mitral regurgitation. Am J Cardiol 2000; 86:234. 12. Echocardiographic predictors of stroke in patients with atrial fibrillation: a prospective study of 1066 patients from 3 clinical trials. Arch Intern Med 1998; 158:1316. 13. Zabalgoitia M, Halperin JL, Pearce LA, et al. Transesophageal echocardiographic correlates of clinical risk of thromboembolism in nonvalvular atrial fibrillation. Stroke Prevention in Atrial Fibrillation III Investigators. J Am Coll Cardiol 1998; 31:1622. 14. Manning WJ, Weintraub RM, Waksmonski CA, et al. Accuracy of transesophageal echocardiography for identifying left atrial thrombi. A prospective, intraoperative study. Ann Intern Med 1995; 123:817. 15. Hwang JJ, Chen JJ, Lin SC, et al. Diagnostic accuracy of transesophageal echocardiography for detecting left atrial thrombi in patients with rheumatic heart disease having undergone mitral valve operations. Am J Cardiol 1993; 72:677. 16. Manning WJ, Silverman DI, Keighley CS, et al. Transesophageal echocardiographically facilitated early cardioversion from atrial fibrillation using short-term anticoagulation: final results of a prospective 4.5-year study. J Am Coll Cardiol 1995; 25:1354. 17. Weigner MJ, Thomas LR, Patel U, et al. Early cardioversion of atrial fibrillation facilitated by transesophageal echocardiography: short-term safety and impact on maintenance of sinus rhythm at 1 year. Am J Med 2001; 110:694. 18. Klein AL, Grimm RA, Murray RD, et al. Use of transesophageal echocardiography to guide cardioversion in patients with atrial fibrillation. N Engl J Med 2001; 344:1411. https://www.uptodate.com/contents/role-of-echocardiography-in-atrial-fibrillation/print 10/16 7/5/23, 10:18 AM Role of echocardiography in atrial fibrillation - UpToDate 19. Srimannarayana J, Varma RS, Satheesh S, et al. Prevalence of left atrial thrombus in rheumatic mitral stenosis with atrial fibrillation and its response to anticoagulation: a transesophageal echocardiographic study. Indian Heart J 2003; 55:358. 20. Manning WJ, Silverman DI, Waksmonski CA, et al. Prevalence of residual left atrial thrombi among patients with acute thromboembolism and newly recognized atrial fibrillation. Arch Intern Med 1995; 155:2193. 21. Ayirala S, Kumar S, O'Sullivan DM, Silverman DI. Echocardiographic predictors of left atrial appendage thrombus formation. J Am Soc Echocardiogr 2011; 24:499. 22. Anter E, Silverstein J, Tschabrunn CM, et al. Comparison of intracardiac echocardiography and transesophageal echocardiography for imaging of the right and left atrial appendages. Heart Rhythm 2014; 11:1890. 23. Jung PH, Mueller M, Schuhmann C, et al. Contrast enhanced transesophageal echocardiography in patients with atrial fibrillation referred to electrical cardioversion improves atrial thrombus detection and may reduce associated thromboembolic events. Cardiovasc Ultrasound 2013; 11:1. 24. Transesophageal echocardiographic correlates of thromboembolism in high-risk patients with nonvalvular atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators Committee on Echocardiography. Ann Intern Med 1998; 128:639. 25. de Divitiis M, Omran H, Rabahieh R, et al. Right atrial appendage thrombosis in atrial fibrillation: its frequency and its clinical predictors. Am J Cardiol 1999; 84:1023. 26. Black IW, Chesterman CN, Hopkins AP, et al. Hematologic correlates of left atrial spontaneous echo contrast and thromboembolism in nonvalvular atrial fibrillation. J Am Coll Cardiol 1993; 21:451. 27. Fatkin D, Herbert E, Feneley MP. Hematologic correlates of spontaneous echo contrast in patients with atrial fibrillation and implications for thromboembolic risk. Am J Cardiol 1994; 73:672. 28. Fatkin D, Loupas T, Low J, Feneley M. Inhibition of red cell aggregation prevents spontaneous echocardiographic contrast formation in human blood. Circulation 1997; 96:889. 29. Fatkin D, Kelly RP, Feneley MP. Relations between left atrial appendage blood flow velocity, spontaneous echocardiographic contrast and thromboembolic risk in vivo. J Am Coll Cardiol 1994; 23:961. 30. Black IW, Hopkins AP, Lee LC, Walsh WF. Left atrial spontaneous echo contrast: a clinical and echocardiographic analysis. J Am Coll Cardiol 1991; 18:398. https://www.uptodate.com/contents/role-of-echocardiography-in-atrial-fibrillation/print 11/16 7/5/23, 10:18 AM Role of echocardiography in atrial fibrillation - UpToDate 31. Puwanant S, Varr BC, Shrestha K, et al. Role of the CHADS2 score in the evaluation of thromboembolic risk in patients with atrial fibrillation undergoing transesophageal echocardiography before pulmonary vein isolation. J Am Coll Cardiol 2009; 54:2032. 32. Tsai LM, Chen JH, Lin LJ, Teng JK. Natural history of left atrial spontaneous echo contrast in nonrheumatic atrial fibrillation. Am J Cardiol 1997; 80:897. 33. Santiago D, Warshofsky M, Li Mandri G, et al. Left atrial appendage function and thrombus formation in atrial fibrillation-flutter: a transesophageal echocardiographic study. J Am Coll Cardiol 1994; 24:159. 34. Shively BK, Gelgand EA, Crawford MH. Regional left atrial stasis during atrial fibrillation and flutter: determinants and relation to stroke. J Am Coll Cardiol 1996; 27:1722. 35. Antonielli E, Pizzuti A, P link s A, et al. Clinical value of left atrial appendage flow for prediction of long-term sinus rhythm maintenance in patients with nonvalvular atrial fibrillation. J Am Coll Cardiol 2002; 39:1443. 36. Verhorst PM, Kamp O, Welling RC, et al. Transesophageal echocardiographic predictors for maintenance of sinus rhythm after electrical cardioversion of atrial fibrillation. Am J Cardiol 1997; 79:1355. 37. P rez Y, Duval AM, Carville C, et al. Is left atrial appendage flow a predictor for outcome of cardioversion of nonvalvular atrial fibrillation? A transthroacic and transesophageal echocardiographic study. Am Heart J 1997; 134:745. 38. Warraich HJ, Gandhavadi M, Manning WJ. Mechanical discordance of the left atrium and appendage: a novel mechanism of stroke in paroxysmal atrial fibrillation. Stroke 2014; 45:1481. Topic 908 Version 19.0 https://www.uptodate.com/contents/role-of-echocardiography-in-atrial-fibrillation/print 12/16 7/5/23, 10:18 AM Role of echocardiography in atrial fibrillation - UpToDate GRAPHICS Significant left ventricular dysfunction predicts stroke in AF In a prospective study of 1066 patients entered into three clinical trials evaluating the role of anticoagulation in nonvalvular AF (BAATAF, SPINAF, and SPAF), the incidence of a stroke was 9.3 percent per year in patients with moderate to severe left ventricular dysfunction compared with 4.4 percent per year in those with normal or mildly abnormal left ventricular function. Data from: Atrial Fibrillation Investigators, Arch Intern Med 1998; 158:1316. Graphic 70244 Version 4.0 https://www.uptodate.com/contents/role-of-echocardiography-in-atrial-fibrillation/print 13/16 7/5/23, 10:18 AM Role of echocardiography in atrial fibrillation - UpToDate Left atrial abnormalities and complex aortic plaque correlate with the risk of thromboembolism in atrial fibrillation Correlation of clinical risk for thromboembolism (TE) and transesophageal echocardiographic (TEE) findings in 786 patients with atrial fibrillation. Patients were deemed to be at high risk if they had one or more of the following clinical features: prior TE, women >75 years of age, systolic blood pressure >160 mmHg, and heart failure or poor left ventricular function. Patients with none of these features were either at low risk or, if they had a history of hypertension, moderate risk. Panel A: There was an increasing incidence of a left atrial appendage (LAA) abnormality (thrombus, dense spontaneous echo contrast, or flow velocity 20 cm/s) or a complex aortic plaque risk with increasing clinical risk of TE. Panel B: The frequency of LAA abnormalities and complex aortic plaque in patients with a single high risk factor. Redrawn from: Zabalgoitia M, Halperin JL, Pearce LA, et al. for the Stroke Prevention in Atrial Fibrillation III Investigators. J Am Coll Cardiol 1998; 31:1622. Graphic 55452 Version 3.0 https://www.uptodate.com/contents/role-of-echocardiography-in-atrial-fibrillation/print 14/16 7/5/23, 10:18 AM Role of echocardiography in atrial fibrillation - UpToDate Apical 4 chamber echocardiogram showing right atrial thrombus The apical four chamber view show a thrombus that was in transit from the lower extremities and temporarily became lodged in the right atrium (RA). Additionally, the right ventricle (RV) is enlarged, implying that other emboli have reached the pulmonary circulation, resulting in raised pulmonary vascular resistance. LV: left ventricle; LA: left atrium. Graphic 68756 Version 4.0 https://www.uptodate.com/contents/role-of-echocardiography-in-atrial-fibrillation/print 15/16 7/5/23, 10:18 AM Role of echocardiography in atrial fibrillation - UpToDate Contributor Disclosures Warren J Manning, MD Equity Ownership/Stock Options: Pfizer [Anticoagulants]. All of the relevant financial relationships listed have been mitigated. Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/role-of-echocardiography-in-atrial-fibrillation/print 16/16

7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Stroke in patients with atrial fibrillation : Warren J Manning, MD : Peter J Zimetbaum, MD, Scott E Kasner, MD : Nisha Parikh, MD, MPH, John F Dashe, MD, PhD All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Apr 18, 2023. INTRODUCTION An ischemic stroke may occur in patients with atrial fibrillation (AF) either as the initial presenting manifestation of AF or despite appropriate antithrombotic prophylaxis. In such patients, a cardiac embolus, most commonly a thrombus originating from the left atrial appendage (LAA), is the cause of the ischemic stroke. (See "Clinical diagnosis of stroke subtypes", section on 'Brain ischemia'.) Issues specific to stroke in patients with AF will be reviewed here. The risk of atheroembolism (including stroke), the role of anticoagulant prophylaxis (primary prevention) in patients with AF, and the general evaluation and management of the patient with stroke are presented elsewhere. (See "Atrial fibrillation in adults: Use of oral anticoagulants" and "Overview of the evaluation of stroke" and "Approach to reperfusion therapy for acute ischemic stroke" and "Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack".) STROKE CHARACTERISTICS Strokes due to embolization of thrombus, most commonly from the left atrial appendage (LAA) in patients with AF, present with the characteristics of ischemic stroke. (See "Clinical diagnosis of stroke subtypes", section on 'Distinguishing stroke subtypes'.) Features suggestive of cardioembolic stroke https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 1/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate Increased clinical severity AF is associated with more severe ischemic strokes and "longer" transient ischemic attacks (TIAs) than emboli from carotid disease, presumably due to embolization of larger thrombi with AF [1,2]. This relationship was illustrated in a report comparing ischemic brain events in patients with AF with those with carotid disease in two major trials. The ratio of hemispheric events to retinal events was 25:1 with AF compared with 2:1 with carotid disease [1]. As a result, patients with AF who suffer an ischemic stroke appear to have a worse outcome (more disability, greater mortality) than those who have an ischemic stroke in the absence of AF, even after adjustment for the advanced age of patients with AF-related stroke [3-5]. The "longer" TIAs typical in AF patients are more often associated with abnormal magnetic resonance diffusion imaging and would be classified as strokes by the revised American Heart Association definition [6]. (See "Definition, etiology, and clinical manifestations of transient ischemic attack".) Radiologic patterns Cardioembolic stroke from AF may affect any vascular territory or multiple vascular territories of the brain with one or more wedge-shaped infarcts involving the cortex and the underlying subcortical white matter. Other patterns include striatocapsular infarction from a middle cerebral artery stem occlusion and/or borderzone infarcts [7]. Silent cerebral infarction In addition to causing symptomatic stroke with major deficits, AF is also associated with silent cerebral infarctions (SCIs) and TIA [8-13]. SCI is characterized by brain lesions that have a radiographic appearance consistent with cerebral infarction in the absence of clinical complaints or findings. In a 2014 systematic review and meta-analysis of 17 studies, the prevalence of SCI lesions on magnetic resonance imaging and computed tomography among patients with AF was 40 and 22 percent, respectively [12]. In this review, AF was associated with more than a twofold increased risk of SCI in patients with no history of symptomatic stroke (odds ratio 2.62, 95% CI 1.81-3.80) in 11 studies. However, most studies pooled in this meta- analysis were cross-sectional, making the causal link between AF and silent cerebral infarction uncertain. ACUTE ISCHEMIC STROKE The initial rapid evaluation of acute ischemic stroke for patients with known or suspected AF is similar to the approach for patients with other known or suspected causes of stroke. Is reperfusion therapy indicated? All patients with acute ischemic stroke should be evaluated for possible reperfusion therapy, including urgent brain and neurovascular imaging. The immediate goal of reperfusion therapy is to restore blood flow to the regions of brain that https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 2/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate are ischemic but not yet infarcted. (See "Approach to reperfusion therapy for acute ischemic stroke".) Intravenous thrombolysis (IVT) improves functional outcome at three to six months when given within 4.5 hours of ischemic stroke onset. (See "Intravenous thrombolytic therapy for acute ischemic stroke: Therapeutic use".) However, contraindications to IVT may be relevant for patients with AF and acute ischemic stroke ( table 1): Current vitamin K antagonist (VKA) use (eg, warfarin) with evidence of anticoagulant effect (eg, an international normalized ratio [INR] >1.7 or prothrombin time >15 seconds). Direct-acting oral anticoagulant (DOAC; also referred to as non-vitamin K oral anticoagulants [NOAC]) use, unless the patient has not received a DOAC dose for more than 48 hours, assuming normal renal function or laboratory tests such as partial thromboplastin time, INR, platelet count, ecarin clotting time, thrombin time, or appropriate direct factor Xa activity assays are normal. In most cases, only the INR is readily available for clinical decision-making. Evidence of intracranial hemorrhage on neuroimaging. Mechanical thrombectomy is indicated for select patients with acute ischemic stroke caused by an intracranial large artery occlusion in the proximal anterior circulation who can be treated within 24 hours of the time last known to be well ( algorithm 1). (See "Mechanical thrombectomy for acute ischemic stroke".) Specific data on the effectiveness of thrombolytic therapy in ischemic stroke are limited for patients with AF, although such patients account for 20 to 30 percent of those participating in clinical trials [14,15]. As an example, the National Institute of Neurological Disorders and Stroke (NINDS) trial included 115 patients with AF (18 percent) [14]. No subgroup analysis of these patients has been reported, although there was no evidence of a treatment interaction between history of AF and benefit from alteplase. The large size and worse prognosis of AF-associated acute ischemic stroke accentuate both the risks and the benefits of fibrinolysis [15]. (See "Approach to reperfusion therapy for acute ischemic stroke".) Diagnostic approach Comprehensive evaluation Patients with AF who suffer an ischemic stroke are likely to have had a cardioembolic event. On the other hand, AF is common in older adults, who often are at https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 3/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate risk for other types of stroke. Thus, the presence of AF in a stroke patient does not always mean that there is a causal relationship [16]. As a result, all patients with a stroke, even in the setting of AF, need a complete evaluation for other causes of stroke, especially if they would result in different treatment. The evaluation is generally the same as the evaluation in other patients with acute stroke, including brain and neurovascular imaging, cardiac rhythm monitoring during the acute phase, and echocardiography. As for other patients with a suspected embolic stroke, transesophageal echocardiography (TEE) may be used to identify embolic sources (intracardiac or aortic), which may be particularly helpful for patients at increased risk for complications of anticoagulation. However, a TEE is not used to exclude AF as the cause of embolic stroke, since residual atrial thrombi may or may not be present. (See "Overview of the evaluation of stroke", section on 'Ischemia' and "Overview of the evaluation of stroke", section on 'Confirming the diagnosis'.) Source of embolism For those patients with AF in whom an embolic stroke seems likely, other sources than the left atrial appendage (LAA) need to be considered. Embolism refers to particles of debris originating elsewhere that block arterial access to a particular brain region. Embolic strokes may arise from a source in the heart, aorta, or large vessels ( table 2). (See "Stroke: Etiology, classification, and epidemiology", section on 'Embolism' and "Clinical diagnosis of stroke subtypes", section on 'Brain ischemia'.) Thromboembolism of aortic atheroma is discussed separately. (See "Thromboembolism from aortic plaque".) Brain and neurovascular imaging Neuroimaging should be obtained for all patients suspected of having acute ischemic stroke or transient ischemic attack (TIA). Brain and neurovascular imaging play an essential role in acute stroke by: Differentiating ischemia from hemorrhage Excluding stroke mimics, such as tumor Assessing the status of large cervical and intracranial arteries Estimating the volume of brain tissue that is irreversibly infarcted (ie, infarction "core") Estimating the extent of potentially salvageable brain tissue that is at risk for infarction (ie, ischemic "penumbra") Guiding acute interventions, including patient selection for reperfusion therapies (ie, intravenous thrombolysis and mechanical thrombectomy) Imaging of acute ischemic stroke is reviewed in detail elsewhere. (See "Neuroimaging of acute stroke".) https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 4/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate Cardiac monitoring For patients in sinus rhythm without a history of AF, cardiac rhythm monitoring is recommended for at least the first 24 to 48 hours after the onset of ischemic stroke to identify AF or atrial flutter [17]. However, paroxysmal AF may not be detected on short- term cardiac monitoring such as continuous telemetry and 24- or 48-hour Holter monitors. To increase the likelihood of detecting AF, ambulatory cardiac monitoring for several weeks is suggested for all adult patients with a cryptogenic ischemic stroke or cryptogenic TIA. (See "Overview of the evaluation of stroke", section on 'Monitoring for subclinical atrial fibrillation'.) Echocardiography Transthoracic echocardiographic (TTE) evaluation is recommended for most patients presenting with ischemic stroke, primarily to investigate the conditions associated with AF. Because chronic anticoagulation with warfarin or one of the DOACs is recommended in all eligible patients with AF and stroke, echocardiography often will not have a significant impact on anticoagulant management decisions. (See "Role of echocardiography in atrial fibrillation" and "Epidemiology, risk factors, and prevention of atrial fibrillation" and "Atrial fibrillation in adults: Use of oral anticoagulants".) The LAA and thus LAA thrombus are rarely seen on TTE but are easily visualized/detected by TEE. Approximately 45 percent of patients presenting with an acute embolic event in the setting of new-onset AF will have residual LAA thrombus [18,19]. Even when not seen on TEE, an intracardiac thrombus is presumed to have been present in all patients with AF who have had a recent thromboembolic event independent of anticoagulation status. This hypothesis is based in part upon the observations that microscopic thrombus can be identified in most patients with chronic sustained AF at autopsy [20] and that patients with a recent thromboembolism and newly recognized AF are significantly more likely to have spontaneous echocardiography contrast (a marker of stasis) than similar patients without a thromboembolic event (87 versus 48 percent) [19]. Thus, for patients with AF, diagnostic evaluation by TEE to search for a residual intraatrial thrombus is not essential since the absence of a thrombus will not alter the long-term clinical (anticoagulation) management. However, TEE to confirm absence of residual thrombus prior to cardioversion may be reasonable for those in whom a rhythm strategy is going to be pursued. (See "Role of echocardiography in atrial fibrillation" and "Management of atrial fibrillation: Rhythm control versus rate control".) Managing antithrombotic therapy acutely Stop anticoagulation temporarily For most patients on anticoagulant therapy at the time of stroke onset, anticoagulation is temporarily withheld during the acute phase of ischemic stroke due to the risk of hemorrhagic transformation of the brain infarction. https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 5/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate Acute antiplatelet therapy In patients with AF who experience an ischemic stroke, acute antiplatelet therapy ( algorithm 2) may be warranted to reduce both disability and the risk of early recurrent stroke, which is 3 to 5 percent in the first two weeks [21,22]. These benefits must be balanced against the risk of intracranial bleeding with antithrombotic therapy. Starting or resuming oral anticoagulation Once the stroke evaluation is complete, antithrombotic therapy may be modified according to the ischemic stroke mechanism ( algorithm 3). For patients with AF, long-term oral anticoagulation is started (or resumed) once the risk of hemorrhagic transformation has diminished, usually within the first days to two weeks after stroke onset, as guided mainly by the size of the ischemic infarct. (See 'Timing after acute ischemic stroke' below.) The management of acute antithrombotic therapy in patients with stroke is discussed in detail elsewhere. (See "Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack".) RISK OF RECURRENT STROKE Patients who have had a prior embolic event already have the most potent risk factor for subsequent stroke. The risk of recurrent stroke in the first few weeks after the initial event is 3 to 5 percent based upon large numbers of patients observed in the control arms of randomized trials [21,22]. In addition, a risk of up to 12 percent per year has been reported in nonanticoagulated patients in the first two to three years after a stroke [23,24]. Due to the high risk of recurrent embolism, lifelong anticoagulation is recommended for secondary prevention (these patients have a minimum CHA DS -VASc score (calculator 1) of 2 for 2 2 which chronic anticoagulation is strongly recommended). LONG-TERM ANTICOAGULATION Indications For most patients with ischemic stroke and AF, chronic oral anticoagulation is recommended to reduce the risk of thromboembolism and recurrent ischemic stroke, independent of the cause of the stroke. Patients with a previous intracranial hemorrhage may be candidates for anticoagulation, depending upon their risk of recurrent ischemic stroke and intracranial bleeding. (See https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 6/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate "Spontaneous intracerebral hemorrhage: Secondary prevention and long-term prognosis", section on 'Anticoagulation'.) Benefit Randomized trials have shown that therapeutic oral anticoagulant with a vitamin K antagonist (VKA) or a direct-acting oral anticoagulant (DOAC) reduces the risk of ischemic stroke and other embolic events by approximately two-thirds compared with placebo irrespective of baseline risk. (See "Atrial fibrillation in adults: Selection of candidates for anticoagulation", section on 'General efficacy'.) DOACs Randomized trials have demonstrated that DOACs are either superior (apixaban and dabigatran) or noninferior (edoxaban or rivaroxaban) to VKAs for stroke prevention. Studies have also shown that DOACs have less bleeding side effects than VKAs among patients with AF and ischemic stroke or transient ischemic attack (TIA). DOACS are also preferred over VKAs for patients with AF and other indications for anticoagulation. (See "Atrial fibrillation in adults: Use of oral anticoagulants".) In the ARISTOTLE trial, among 3436 participants with stroke or systemic embolism, apixaban was found to be superior to adjusted-dose warfarin in preventing recurrent stroke or systemic embolism (2.5 versus 3.2 percent; hazard ratio [HR] 0.79, 95% CI 0.66- 0.95) [25]. Apixaban also caused less major bleeding compared with warfarin (2.1 versus 3.1 percent; HR 0.69, 95% CI 0.60-0.80) and resulted in lower overall mortality (3.5 versus 3.9 percent). In a separate trial, among patients with prior stroke, dabigatran had a larger protective effect on stroke as compared with warfarin but had similar rates of major hemorrhage [26]. In other clinical trials of patients with prior stroke or TIA, both edoxaban [27] and rivaroxaban [28] were found to be noninferior to warfarin with respect to future stroke prevention. Warfarin Aspirin alone offers inadequate protection, with a stroke risk that averaged 10 percent per year in a pooled analysis of individual participants from six randomized trials [29]. Compared with aspirin, treatment with adjusted-dose warfarin (international normalized ratio 2 to 3) reduced this risk to 4 percent per year. In an analysis from the EAFT and SPAF III trials of 834 patients with prior nondisabling ischemic stroke or prior TIA at study entry, the long-term risk of recurrent stroke was lower in patients with a prior TIA than in those with a prior ischemic stroke [30]. However, the reduction in recurrent stroke risk with warfarin therapy was comparable in both groups: 3 versus 7 percent per year with aspirin in patients with a TIA and 4 versus 11 percent per year in those with ischemic stroke. https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 7/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate In addition, anticoagulated patients with AF who experience ischemic stroke typically have smaller infarcts with a lower mortality rate compared with patients with AF and stroke who are not anticoagulated [31,32]. This is likely explained by a higher fraction of nonembolic strokes among anticoagulated AF patients and small size of embolic strokes. Anticoagulation greatly reduced the likelihood of large stroke due to left atrial emboli, so that the remaining strokes are from cerebral small artery disease or other mechanisms [31]. Risk The most feared complication of anticoagulant therapy is the risk of major bleeding, as reviewed separately. (See "Atrial fibrillation in adults: Selection of candidates for anticoagulation", section on 'Bleeding risk' and "Risks and prevention of bleeding with oral anticoagulants".) The decision of whether to use chronic oral anticoagulants must take both benefit and risk into account through shared decision-making with the patient. However, the benefit of oral anticoagulants far outweighs the risk for nearly all patients with ischemic stroke and AF [33]. (See "Atrial fibrillation in adults: Selection of candidates for anticoagulation".) Choosing between direct-acting oral anticoagulants and warfarin For most patients with stroke or TIA and AF who do not have a specific indication for warfarin or another VKA, a DOAC is preferred to a VKA. (See "Atrial fibrillation in adults: Use of oral anticoagulants" and "Atrial fibrillation in adults: Use of oral anticoagulants", section on 'Approach to anticoagulation'.) Situations where a VKA is indicated (rather than a DOAC) include the following [33]: Moderate to severe mitral stenosis Mechanical heart valve in any location Warfarin is generally preferred for patients with severely impaired kidney function, since all DOACs are excreted by the kidney to some degree. (See "Direct oral anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing and adverse effects", section on 'Chronic kidney disease'.) Dosing Dosing recommendations for DOACs ( table 3) are reviewed in detail elsewhere. (See "Direct oral anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing and adverse effects".) Note that there are legitimate reasons for DOAC dose reductions, which differ according to the specific agent. In general, clinical settings in which dose modification may be indicated include older age, low body weight, renal insufficiency, and/or concomitant use of interacting drugs. (See "Direct oral anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing and adverse effects".) https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 8/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate For patients with AF treated with a VKA (eg, warfarin), an INR between 2 and 3 is recommended, with an average annual time in the therapeutic range >70 percent. (See "Atrial fibrillation in adults: Use of oral anticoagulants", section on 'Vitamin K antagonist'.) Timing after acute ischemic stroke For medically stable patients with AF and a small- or moderate-sized infarct with no intracranial bleeding, warfarin can be initiated soon (after 24 hours) after admission with minimal risk of transformation to hemorrhagic stroke. We prefer to wait 48 hours to start a DOAC in these patients, as DOACs have a more rapid anticoagulant effect. Withholding anticoagulation for one to two weeks is generally recommended for those with large ischemic stroke, symptomatic hemorrhagic transformation, or poorly controlled hypertension [34-38]. Patients may benefit from aspirin until therapeutic anticoagulation is achieved [39]. (See "Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack".) Although once widely practiced, early treatment with heparin for patients with AF who have an acute cardioembolic stroke should generally be avoided, as studies have shown that such treatment causes more harm than good. (See "Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack", section on 'Atrial fibrillation'.) Specific patient groups Patients with another potential stroke mechanism In some patients with ischemic stroke and AF, the work-up will identify a noncardioembolic stroke mechanism (eg, large artery atherosclerosis, small vessel disease, other determined etiology) as the potential cause of the stroke. Lacunar infarction The optimal therapy is not known for patients with AF who experience a small subcortical "lacunar" infarct deemed as likely to be due to cerebral small artery disease as opposed to a cardiac embolus [40]. Anticoagulation is recommended for these patients even though the stroke mechanism is uncertain. This is because in randomized trials, these patients would have been categorized as having a history of stroke; these trials have consistently shown that patients with a history of stroke benefit from VKA and DOACs. Large artery stenosis Some patients with AF have a significant ipsilateral stenosis of a large artery that supplies the territory of the acute ischemic stroke. In such cases, it is usually impossible to determine with certainty which mechanism was causative. Anticoagulation for AF is recommended, and the large artery stenosis should be treated https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 9/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate appropriately (eg, revascularization for cervical internal carotid artery stenosis) as a separate cause. Older age Older age is generally cited as a risk factor for bleeding; the risk increase with age is approximately linear. However, the risk of bleeding attributable to older age is often overestimated, and anticoagulants are underused in older individuals who are at the highest risk of stroke and may derive more benefit than younger individuals [33]. (See "Risks and prevention of bleeding with oral anticoagulants", section on 'Age, race, and sex'.) Fall risk Among patients with a history of falls or at high risk of falling, the risk of intracranial hemorrhage is increased among patients on anticoagulation, aspirin, or no antithrombotic therapy, but the absolute increased risk of intracranial hemorrhage related to anticoagulation is small. In particular, anticoagulation increases the risk of subdural hemorrhage (SDH), which is often due to falls, but the absolute risk with VKA therapy is approximately two additional SDHs per 1000 patients [41], which is much lower compared with the risk of cardioembolic stroke due to AF [33]. Nonrandomized studies suggest that for patients with AF and high risk of falls, the benefit of anticoagulation (ie, a reduced risk of ischemic stroke and consequent disability) outweighs the risk of intracranial bleeding from a fall. (See "Risks and prevention of bleeding with oral anticoagulants", section on 'Risk factors for bleeding in specific sites'.) Anticoagulant-intolerant patients Left atrial appendage (LAA) occlusion or dual antiplatelet therapy may be reasonable alternatives to therapy with aspirin alone in high-risk patients with AF who cannot be treated with long-term warfarin or DOAC, or because of strong patient preference following careful consideration of the advantages of oral anticoagulation. LAA occlusion is discussed separately. (See "Atrial fibrillation: Left atrial appendage occlusion".) ANTICOAGULATION FAILURE Determining the cause of recurrent stroke All patients with AF who have an ischemic stroke despite oral anticoagulation with a vitamin K antagonist (VKA) or a direct-acting oral anticoagulant (DOAC) should have a thorough evaluation to determine if the most likely stroke mechanism is cardioembolic due to AF or noncardioembolic due to large artery atherosclerosis, small vessel disease, or another cause of ischemic stroke. Note that patients with ischemic stroke and AF will still need chronic oral anticoagulation even if a competing stroke mechanism is found. https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 10/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate Transesophageal echocardiogram (TEE) is useful to assess for left atrial appendage (LAA) thrombus and other potential cardiac sources of embolism. (See "Overview of the evaluation of stroke", section on 'Ischemia' and "Overview of the evaluation of stroke", section on 'Confirming the diagnosis'.) Missed doses should be suspected in patients taking a DOAC, and subtherapeutic intensity of anticoagulation is a very common cause of treatment failure for patients taking a VKA [42-44]. For patients with stroke on DOACs with good compliance or while on warfarin anticoagulation with a therapeutic international normalized ratio (INR), a noncardioembolic stroke mechanism (eg, lacunar, large artery stenosis, malignancy) is often the cause, although cardioembolism may account for the majority [44,45]. In an analysis of patients with ischemic stroke despite oral anticoagulation, the stroke etiology for 1674 patients taking a DOAC was due to the following factors [44]: Cardioembolism - 49 percent Poor adherence or insufficient dose 23 percent A competing mechanism 28 percent For 1274 patients taking a VKA, the stroke etiology was due to the following factors [44]: Cardioembolism 37 percent Poor adherence or insufficient dose 43 percent A competing mechanism 20 percent Direct-acting oral anticoagulant treatment failure While data are limited, ischemic stroke that occurs during therapy with a DOAC (eg, apixaban, dabigatran, edoxaban, or rivaroxaban) for AF has been associated with several factors, including treatment at doses lower than recommended and/or poor adherence. LAA thrombus, if present, suggests the need to reassess dosing and compliance. One study compared 713 cases of ischemic stroke or transient ischemic attack (TIA) during DOAC treatment with unmatched controls (consecutive outpatients with AF) who did not have cerebrovascular events during DOAC treatment [46]. In multivariable analysis, ischemic cerebrovascular events were associated with off-label under-dosing of DOAC, atrial enlargement, hyperlipidemia, and higher CHA DS -VASc score. 2 2 It is important to verify that the correct DOAC dose was prescribed and that the patient was compliant. If a thrombus is present despite appropriate dosing and compliance, it is reasonable to change to another DOAC, but optimal treatment is uncertain, and no consensus exists. A retrospective study suggested that for patients with left ventricular thrombus, warfarin may be https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 11/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate superior to DOAC for reducing the risk of stroke or systemic embolism [47]. Analogous data for AF patients with LAA thrombi are not available. Regardless, resuming oral anticoagulation therapy for patients with AF is generally indicated after one to two weeks of temporary interruption with large infarcts or shorter interruption with small infarcts. Warfarin treatment failure In patients with AF who suffer ischemic stroke during warfarin anticoagulation, the intensity of anticoagulation is most often subtherapeutic (INR less than 2), and continuing warfarin after one to two weeks of temporary interruption for patients with large infarcts or shorter interruption with small infarcts with renewed efforts to keep the INR in the 2 to 3 therapeutic range or consideration of a change to a DOAC is advised. When ischemic stroke occurs with a therapeutic INR (2 to 3), we favor increasing the target INR to 2.5 to 3.5, or switching from warfarin to a DOAC rather than routine addition of antiplatelet therapy. The addition of antiplatelet therapy is known to increase major hemorrhage (and particularly brain hemorrhage), and the benefit is less well defined. HEMORRHAGIC STROKE For patients with AF on anticoagulation who develop a hemorrhagic stroke, anticoagulation and antiplatelet drugs should be discontinued, and medications to reverse the effects of anticoagulant drugs should be given immediately. These and other management issues are discussed separately.(See "Reversal of anticoagulation in intracranial hemorrhage" and "Spontaneous intracerebral hemorrhage: Acute treatment and prognosis".) ADDITIONAL SECONDARY PREVENTION STRATEGIES Early rhythm control One trial suggested a benefit of early rhythm control among patients with AF who had a stroke [48]. In this study, 300 patients with AF and acute ischemic stroke were randomly assigned to early rhythm control or usual care. The rate of ischemic stroke was lower in the rhythm control group at 12 months (1.7 versus 6.3 percent); rates of mortality and hospitalizations did not differ. Rates of sustained AF were lower in the early rhythm control group compared with usual care (34 versus 63 percent) at 12 months. A potential limitation of this study was that it was non-blinded. Further randomized studies in other populations are needed before we can recommend the widespread use of early rhythm control in patients with stroke and AF. https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 12/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate Control of hypertension Blood pressure control is an important component of the management of patients with AF who have had a stroke. Antihypertensive therapy, preferably including an angiotensin-converting enzyme inhibitor, reduces the risk of vitamin K antagonist (VKA)-associated intracranial hemorrhage and may reduce the rate of recurrent stroke. (See "Reversal of anticoagulation in intracranial hemorrhage".) The latter benefit was suggested in a secondary analysis from the PROGRESS trial, which demonstrated the benefit of blood pressure lowering (using perindopril-indapamide) among both hypertensive and nonhypertensive patients who had a previous stroke or transient ischemic attack (TIA) [49]. (See "Antihypertensive therapy for secondary stroke prevention".) Among the subset of 476 patients with AF, perindopril-based therapy produced a mean 7.3/3.4 mmHg reduction in blood pressure compared with placebo and a 34 percent reduction in the incidence of recurrent stroke (13.6 versus 18.9 percent), a difference that was not statistically significant because of the small number of recurrent events [50]. However, there was a significant 38 percent reduction in all major vascular events (one major vascular event prevented in every 11 patients treated for five years), providing a strong rationale for blood pressure lowering. Revascularization for carotid artery stenosis About 10 percent of patients with AF with ischemic stroke or TIA have a cervical carotid stenosis of 50 percent or greater diameter, slightly more than half of which are ipsilateral to the neurological symptoms. Based on estimates of attributable risk, ipsilateral stenosis of at least 70 percent stenosis is equally likely to be the cause of cerebral ischemia as is cardiogenic embolism. Consequently, carotid revascularization with endarterectomy or stenting seems reasonable for AF patients with high-grade ipsilateral stenosis, followed by chronic anticoagulation and antiplatelet therapy, although this approach is empiric, without good supporting evidence, and the use of combined antiplatelet and anticoagulant therapy increases bleeding risk. The management of symptomatic carotid artery disease is discussed elsewhere. (See "Management of symptomatic carotid atherosclerotic disease".) Statin therapy For most patients with ischemic stroke, we start statin therapy. Statin therapy reduces the risk of recurrent ischemic stroke and cardiovascular events among patients with stroke of atherosclerotic origin, although the efficacy of statin therapy specifically for patients with ischemic stroke attributed to AF has not been well studied. However, a report of 6116 patients with ischemic stroke who were discharged on a statin found that outpatient adherence to statin therapy was associated with a reduced risk of recurrent ischemic stroke for patients with AF as well as those without AF, even after https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 13/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate adjustment for time in the therapeutic range of the international normalized ratio (INR) among patients with AF taking warfarin [51]. Many patients with AF have concomitant atherosclerotic disease, and statin therapy is recommended for patients with atherosclerotic cardiovascular disease (such as prior acute coronary syndrome, myocardial infarction, stable or unstable angina, coronary or other arterial revascularization, ischemic stroke, TIA, or peripheral arterial disease) (see "Overview of secondary prevention of ischemic stroke", section on 'LDL-C lowering therapy'). In addition, and in the absence of defined atherosclerotic cardiovascular disease, many patients are at high risk for a cardiovascular disease event due to age and the presence of hypertension. (See "Low- density lipoprotein cholesterol-lowering therapy in the primary prevention of cardiovascular disease", section on 'Age >75 years'.) Lifestyle modification A number of behavioral and lifestyle modifications may be beneficial for reducing the risk of ischemic stroke and cardiovascular disease. These include smoking cessation, limited alcohol consumption, weight control, regular aerobic physical activity, salt restriction, and a Mediterranean diet. (See "Overview of secondary prevention of ischemic stroke", section on 'Lifestyle modification'.) SUMMARY AND RECOMMENDATIONS Features suggestive of cardioembolic stroke Cardioembolic stroke from atrial fibrillation (AF) is generally associated with increased severity compared with embolic stroke from carotid disease. Cardioembolic stroke may affect single or multiple vascular territories of the brain and appear as wedge-shaped infarcts involving cortex and adjacent white matter. (See 'Features suggestive of cardioembolic stroke' above.) Evaluation for reperfusion therapy All patients with acute ischemic stroke should be assessed to see if they are eligible for reperfusion therapy. (See 'Is reperfusion therapy indicated?' above.) Comprehensive stroke evaluation All patients with acute stroke, even in the setting of AF, need a complete evaluation for other causes of stroke; the work-up should include brain and neurovascular imaging, cardiac rhythm monitoring, and echocardiography. Paroxysmal AF may not be detected on short-term cardiac monitoring; thus, ambulatory cardiac monitoring for several weeks is suggested for all adult patients with a cryptogenic ischemic stroke or cryptogenic transient ischemic attack (TIA). (See 'Diagnostic approach' above.) https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 14/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate Antithrombotic therapy during the acute phase of stroke Anticoagulation is usually temporarily withheld immediately after ischemic stroke, due to the risk of hemorrhagic transformation, and restarted within the first days to two weeks, as guided mainly by the size of the ischemic infarct. (See 'Timing after acute ischemic stroke' above.) For patients with AF and large acute infarctions, symptomatic hemorrhagic transformation, or poorly controlled hypertension, we suggest withholding oral anticoagulation for one to two weeks (Grade 2C). (See 'Timing after acute ischemic stroke' above.) However, early acute antiplatelet therapy ( algorithm 2) may be warranted to reduce both disability and the risk of early recurrent stroke, which is 3 to 5 percent in the first two weeks. (See 'Managing antithrombotic therapy acutely' above.) Long-term anticoagulation For most patients with an ischemic stroke or TIA and AF, we recommend a direct-acting oral anticoagulant (DOAC) rather than a vitamin K antagonist (VKA) (Grade 1A). DOACs are more efficacious at preventing recurrent stroke and have lower rates of major hemorrhage. However, a VKA is indicated for patients with moderate to severe mitral stenosis or any mechanical heart valve and is generally preferred for patients with severely impaired kidney function. (See 'Long-term anticoagulation' above.) Anticoagulation treatment failure Determining the cause For patients with AF who develop an ischemic stroke while on anticoagulation, subtherapeutic intensity of anticoagulation (eg, inappropriate low-dose DOAC, missed DOAC doses, or low international normalized ratio [INR] on warfarin) at the time of stroke is the most common cause of treatment failure. Nevertheless, all such patients should have a thorough evaluation (including brain and neurovascular

randomized studies in other populations are needed before we can recommend the widespread use of early rhythm control in patients with stroke and AF. https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 12/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate Control of hypertension Blood pressure control is an important component of the management of patients with AF who have had a stroke. Antihypertensive therapy, preferably including an angiotensin-converting enzyme inhibitor, reduces the risk of vitamin K antagonist (VKA)-associated intracranial hemorrhage and may reduce the rate of recurrent stroke. (See "Reversal of anticoagulation in intracranial hemorrhage".) The latter benefit was suggested in a secondary analysis from the PROGRESS trial, which demonstrated the benefit of blood pressure lowering (using perindopril-indapamide) among both hypertensive and nonhypertensive patients who had a previous stroke or transient ischemic attack (TIA) [49]. (See "Antihypertensive therapy for secondary stroke prevention".) Among the subset of 476 patients with AF, perindopril-based therapy produced a mean 7.3/3.4 mmHg reduction in blood pressure compared with placebo and a 34 percent reduction in the incidence of recurrent stroke (13.6 versus 18.9 percent), a difference that was not statistically significant because of the small number of recurrent events [50]. However, there was a significant 38 percent reduction in all major vascular events (one major vascular event prevented in every 11 patients treated for five years), providing a strong rationale for blood pressure lowering. Revascularization for carotid artery stenosis About 10 percent of patients with AF with ischemic stroke or TIA have a cervical carotid stenosis of 50 percent or greater diameter, slightly more than half of which are ipsilateral to the neurological symptoms. Based on estimates of attributable risk, ipsilateral stenosis of at least 70 percent stenosis is equally likely to be the cause of cerebral ischemia as is cardiogenic embolism. Consequently, carotid revascularization with endarterectomy or stenting seems reasonable for AF patients with high-grade ipsilateral stenosis, followed by chronic anticoagulation and antiplatelet therapy, although this approach is empiric, without good supporting evidence, and the use of combined antiplatelet and anticoagulant therapy increases bleeding risk. The management of symptomatic carotid artery disease is discussed elsewhere. (See "Management of symptomatic carotid atherosclerotic disease".) Statin therapy For most patients with ischemic stroke, we start statin therapy. Statin therapy reduces the risk of recurrent ischemic stroke and cardiovascular events among patients with stroke of atherosclerotic origin, although the efficacy of statin therapy specifically for patients with ischemic stroke attributed to AF has not been well studied. However, a report of 6116 patients with ischemic stroke who were discharged on a statin found that outpatient adherence to statin therapy was associated with a reduced risk of recurrent ischemic stroke for patients with AF as well as those without AF, even after https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 13/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate adjustment for time in the therapeutic range of the international normalized ratio (INR) among patients with AF taking warfarin [51]. Many patients with AF have concomitant atherosclerotic disease, and statin therapy is recommended for patients with atherosclerotic cardiovascular disease (such as prior acute coronary syndrome, myocardial infarction, stable or unstable angina, coronary or other arterial revascularization, ischemic stroke, TIA, or peripheral arterial disease) (see "Overview of secondary prevention of ischemic stroke", section on 'LDL-C lowering therapy'). In addition, and in the absence of defined atherosclerotic cardiovascular disease, many patients are at high risk for a cardiovascular disease event due to age and the presence of hypertension. (See "Low- density lipoprotein cholesterol-lowering therapy in the primary prevention of cardiovascular disease", section on 'Age >75 years'.) Lifestyle modification A number of behavioral and lifestyle modifications may be beneficial for reducing the risk of ischemic stroke and cardiovascular disease. These include smoking cessation, limited alcohol consumption, weight control, regular aerobic physical activity, salt restriction, and a Mediterranean diet. (See "Overview of secondary prevention of ischemic stroke", section on 'Lifestyle modification'.) SUMMARY AND RECOMMENDATIONS Features suggestive of cardioembolic stroke Cardioembolic stroke from atrial fibrillation (AF) is generally associated with increased severity compared with embolic stroke from carotid disease. Cardioembolic stroke may affect single or multiple vascular territories of the brain and appear as wedge-shaped infarcts involving cortex and adjacent white matter. (See 'Features suggestive of cardioembolic stroke' above.) Evaluation for reperfusion therapy All patients with acute ischemic stroke should be assessed to see if they are eligible for reperfusion therapy. (See 'Is reperfusion therapy indicated?' above.) Comprehensive stroke evaluation All patients with acute stroke, even in the setting of AF, need a complete evaluation for other causes of stroke; the work-up should include brain and neurovascular imaging, cardiac rhythm monitoring, and echocardiography. Paroxysmal AF may not be detected on short-term cardiac monitoring; thus, ambulatory cardiac monitoring for several weeks is suggested for all adult patients with a cryptogenic ischemic stroke or cryptogenic transient ischemic attack (TIA). (See 'Diagnostic approach' above.) https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 14/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate Antithrombotic therapy during the acute phase of stroke Anticoagulation is usually temporarily withheld immediately after ischemic stroke, due to the risk of hemorrhagic transformation, and restarted within the first days to two weeks, as guided mainly by the size of the ischemic infarct. (See 'Timing after acute ischemic stroke' above.) For patients with AF and large acute infarctions, symptomatic hemorrhagic transformation, or poorly controlled hypertension, we suggest withholding oral anticoagulation for one to two weeks (Grade 2C). (See 'Timing after acute ischemic stroke' above.) However, early acute antiplatelet therapy ( algorithm 2) may be warranted to reduce both disability and the risk of early recurrent stroke, which is 3 to 5 percent in the first two weeks. (See 'Managing antithrombotic therapy acutely' above.) Long-term anticoagulation For most patients with an ischemic stroke or TIA and AF, we recommend a direct-acting oral anticoagulant (DOAC) rather than a vitamin K antagonist (VKA) (Grade 1A). DOACs are more efficacious at preventing recurrent stroke and have lower rates of major hemorrhage. However, a VKA is indicated for patients with moderate to severe mitral stenosis or any mechanical heart valve and is generally preferred for patients with severely impaired kidney function. (See 'Long-term anticoagulation' above.) Anticoagulation treatment failure Determining the cause For patients with AF who develop an ischemic stroke while on anticoagulation, subtherapeutic intensity of anticoagulation (eg, inappropriate low-dose DOAC, missed DOAC doses, or low international normalized ratio [INR] on warfarin) at the time of stroke is the most common cause of treatment failure. Nevertheless, all such patients should have a thorough evaluation (including brain and neurovascular imaging, and echocardiography) to determine if the most likely cause of stroke is cardioembolic due to AF, or noncardioembolic due to another mechanism. (See 'Determining the cause of recurrent stroke' above.) DOAC treatment failure In this setting, it is important to verify that the correct DOAC dose is prescribed and that the patient is compliant. If a thrombus is present despite appropriate dosing and compliance, it is reasonable to change to another DOAC, but optimal treatment is uncertain. (See 'Direct-acting oral anticoagulant treatment failure' above.) Warfarin treatment failure In this setting, options include increasing the target INR to 2.5 to 3.5, switching to a DOAC, or considering LAA occlusion. For patients with a subtherapeutic INR at the time of the stroke, an attempt should be made to identify the https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 15/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate cause (eg, poor compliance, drug or food interaction) and to consider switching to a DOAC if the annual time in therapeutic range has been less than 70 percent. Hemorrhagic stroke on anticoagulation For patients on anticoagulation who develop a hemorrhagic stroke, anticoagulation and antiplatelet drugs should be discontinued, and medications to reverse the effects of anticoagulant drugs should be given immediately. These and other measures are reviewed separately. (See "Reversal of anticoagulation in intracranial hemorrhage" and "Spontaneous intracerebral hemorrhage: Acute treatment and prognosis".) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Anderson DC, Kappelle LJ, Eliasziw M, et al. Occurrence of hemispheric and retinal ischemia in atrial fibrillation compared with carotid stenosis. Stroke 2002; 33:1963. 2. Harrison MJ, Marshall J. Atrial fibrillation, TIAs and completed strokes. Stroke 1984; 15:441. 3. Lin HJ, Wolf PA, Kelly-Hayes M, et al. Stroke severity in atrial fibrillation. The Framingham Study. Stroke 1996; 27:1760. 4. J rgensen HS, Nakayama H, Reith J, et al. Acute stroke with atrial fibrillation. 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The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. International Stroke Trial Collaborative Group. Lancet 1997; 349:1569. 22. Saxena R, Lewis S, Berge E, et al. Risk of early death and recurrent stroke and effect of heparin in 3169 patients with acute ischemic stroke and atrial fibrillation in the https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 17/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate International Stroke Trial. Stroke 2001; 32:2333. 23. Secondary prevention in non-rheumatic atrial fibrillation after transient ischaemic attack or minor stroke. EAFT (European Atrial Fibrillation Trial) Study Group. Lancet 1993; 342:1255. 24. Sandercock P, Bamford J, Dennis M, et al. Atrial fibrillation and stroke: prevalence in different types of stroke and influence on early and long term prognosis (Oxfordshire community stroke project). BMJ 1992; 305:1460. 25. Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365:981. 26. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361:1139. 27. Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013; 369:2093. 28. Hankey GJ, Patel MR, Stevens SR, et al. Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF. Lancet Neurol 2012; 11:315. 29. van Walraven C, Hart RG, Singer DE, et al. Oral anticoagulants vs aspirin in nonvalvular atrial fibrillation: an individual patient meta-analysis. JAMA 2002; 288:2441. 30. Hart RG, Pearce LA, Koudstaal PJ. Transient ischemic attacks in patients with atrial fibrillation: implications for secondary prevention: the European Atrial Fibrillation Trial and Stroke Prevention in Atrial Fibrillation III trial. Stroke 2004; 35:948. 31. Hylek EM, Go AS, Chang Y, et al. Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N Engl J Med 2003; 349:1019. 32. Rizos T, Meid AD, Huppertz A, et al. Low Exposure to Direct Oral Anticoagulants Is Associated with Ischemic Stroke and Its Severity. J Stroke 2022; 24:88. 33. Best JG, Bell R, Haque M, et al. Atrial fibrillation and stroke: a practical guide. Pract Neurol 2019; 19:208. 34. Paciaroni M, Agnelli G, Ageno W, Caso V. Timing of anticoagulation therapy in patients with acute ischaemic stroke and atrial fibrillation. Thromb Haemost 2016; 116:410. 35. Smythe MA, Parker D, Garwood CL, et al. Timing of Initiation of Oral Anticoagulation after Acute Ischemic Stroke in Patients with Atrial Fibrillation. Pharmacotherapy 2020; 40:55. 36. Lansberg MG, O'Donnell MJ, Khatri P, et al. Antithrombotic and thrombolytic therapy for ischemic stroke: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e601S. https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 18/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate 37. Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014; 45:2160. 38. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016; 37:2893. 39. Chen ZM, Sandercock P, Pan HC, et al. Indications for early aspirin use in acute ischemic stroke : A combined analysis of 40 000 randomized patients from the chinese acute stroke trial and the international stroke trial. On behalf of the CAST and IST collaborative groups. Stroke 2000; 31:1240. 40. Evans A, Perez I, Yu G, Kalra L. Should stroke subtype influence anticoagulation decisions to prevent recurrence in stroke patients with atrial fibrillation? Stroke 2001; 32:2828. 41. Connolly BJ, Pearce LA, Hart RG. Vitamin K antagonists and risk of subdural hematoma: meta-analysis of randomized clinical trials. Stroke 2014; 45:1672. 42. Gladstone DJ, Bui E, Fang J, et al. Potentially preventable strokes in high-risk patients with atrial fibrillation who are not adequately anticoagulated. Stroke 2009; 40:235. 43. Yaghi S, Liberman AL, Henninger N, et al. Factors associated with therapeutic anticoagulation status in patients with ischemic stroke and atrial fibrillation. J Stroke Cerebrovasc Dis 2020; 29:104888. 44. Polymeris AA, Meinel TR, Oehler H, et al. Aetiology, secondary prevention strategies and outcomes of ischaemic stroke despite oral anticoagulant therapy in patients with atrial fibrillation. J Neurol Neurosurg Psychiatry 2022; 93:588. 45. Freedman B, Martinez C, Katholing A, Rietbrock S. Residual Risk of Stroke and Death in Anticoagulant-Treated Patients With Atrial Fibrillation. JAMA Cardiol 2016; 1:366. 46. Paciaroni M, Agnelli G, Caso V, et al. Causes and Risk Factors of Cerebral Ischemic Events in Patients With Atrial Fibrillation Treated With Non-Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention. Stroke 2019; 50:2168. 47. Robinson AA, Trankle CR, Eubanks G, et al. Off-label Use of Direct Oral Anticoagulants Compared With Warfarin for Left Ventricular Thrombi. JAMA Cardiol 2020; 5:685. 48. Park J, Shim J, Lee JM, et al. Risks and Benefits of Early Rhythm Control in Patients With Acute Strokes and Atrial Fibrillation: A Multicenter, Prospective, Randomized Study (the RAFAS Trial). J Am Heart Assoc 2022; 11:e023391. 49. PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure- lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet 2001; 358:1033. https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 19/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate 50. Arima H, Hart RG, Colman S, et al. Perindopril-based blood pressure-lowering reduces major vascular events in patients with atrial fibrillation and prior stroke or transient ischemic attack. Stroke 2005; 36:2164. 51. Flint AC, Conell C, Ren X, et al. Statin Adherence Is Associated With Reduced Recurrent Stroke Risk in Patients With or Without Atrial Fibrillation. Stroke 2017; 48:1788. Topic 1059 Version 46.0 https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 20/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate GRAPHICS Eligibility criteria for the treatment of acute ischemic stroke with intravenous thrombolysis (recombinant tissue plasminogen activator or tPA) Inclusion criteria Clinical diagnosis of ischemic stroke causing measurable neurologic deficit Onset of symptoms <4.5 hours before beginning treatment; if the exact time of stroke onset is not known, it is defined as the last time the patient was known to be normal or at neurologic baseline Age 18 years Exclusion criteria Patient history Ischemic stroke or severe head trauma in the previous three months Previous intracranial hemorrhage Intra-axial intracranial neoplasm Gastrointestinal malignancy Gastrointestinal hemorrhage in the previous 21 days Intracranial or intraspinal surgery within the prior three months Clinical Symptoms suggestive of subarachnoid hemorrhage Persistent blood pressure elevation (systolic 185 mmHg or diastolic 110 mmHg) Active internal bleeding Presentation consistent with infective endocarditis Stroke known or suspected to be associated with aortic arch dissection Acute bleeding diathesis, including but not limited to conditions defined under 'Hematologic' Hematologic 3 Platelet count <100,000/mm * Current anticoagulant use with an INR >1.7 or PT >15 seconds or aPTT >40 seconds* Therapeutic doses of low molecular weight heparin received within 24 hours (eg, to treat VTE and ACS); this exclusion does not apply to prophylactic doses (eg, to prevent VTE) Current use (ie, last dose within 48 hours in a patient with normal renal function) of a direct thrombin inhibitor or direct factor Xa inhibitor with evidence of anticoagulant effect by laboratory tests such as aPTT, INR, ECT, TT, or appropriate factor Xa activity assays Head CT https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 21/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate Evidence of hemorrhage Extensive regions of obvious hypodensity consistent with irreversible injury Warnings Only minor and isolated neurologic signs or rapidly improving symptoms Serum glucose <50 mg/dL (<2.8 mmol/L) Serious trauma in the previous 14 days Major surgery in the previous 14 days History of gastrointestinal bleeding (remote) or genitourinary bleeding Seizure at the onset of stroke with postictal neurologic impairments Pregnancy** Arterial puncture at a noncompressible site in the previous seven days Large ( 10 mm), untreated, unruptured intracranial aneurysm Untreated intracranial vascular malformation Additional warnings for treatment from 3 to 4.5 hours from symptom onset Age >80 years Oral anticoagulant use regardless of INR Severe stroke (NIHSS score >25) Combination of both previous ischemic stroke and diabetes mellitus ACS: acute coronary syndrome; aPTT: activated partial thromboplastin time; ECT: ecarin clotting time; INR: international normalized ratio; PT: prothrombin time; NIHSS: National Institutes of Health Stroke Scale; tPA: intravenous alteplase; TT: thrombin time; VTE: venous thromboembolism. Although it is desirable to know the results of these tests, thrombolytic therapy should not be delayed while results are pending unless (1) there is clinical suspicion of a bleeding abnormality or thrombocytopenia, (2) the patient is currently on or has recently received anticoagulants (eg, heparin, warfarin, a direct thrombin inhibitor, or a direct factor Xa inhibitor), or (3) use of anticoagulants is not known. Otherwise, treatment with intravenous tPA can be started before availability of coagulation test results but should be discontinued if the INR, PT, or aPTT exceed the limits stated in the table, or 3 if platelet count is <100,000 mm . With careful consideration and weighting of risk-to-benefit, patients may receive intravenous alteplase despite one or more warnings. Patients who have a persistent neurologic deficit that is potentially disabling, despite improvement of any degree, should be treated with tPA in the absence of other contraindications. Any of the following should be considered disabling deficits: Complete hemianopia: 2 on NIHSS question 3, or Severe aphasia: 2 on NIHSS question 9, or Visual or sensory extinction: 1 on NIHSS question 11, or https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 22/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate Any weakness limiting sustained effort against gravity: 2 on NIHSS question 5 or 6, or Any deficits that lead to a total NIHSS >5, or Any remaining deficit considered potentially disabling in the view of the patient and the treating practitioner using clinical judgment Patients may be treated with intravenous alteplase if glucose level is subsequently normalized. The potential risks of bleeding with alteplase from injuries related to the trauma should be weighed against the anticipated benefits of reduced stroke-related neurologic deficits. The increased risk of surgical site bleeding with alteplase should be weighed against the anticipated benefits of reduced stroke-related neurologic deficits. There is a low increased risk of new bleeding with alteplase in the setting of past gastrointestinal or genitourinary bleeding. However, alteplase administration within 21 days of gastrointestinal bleeding is not recommended. Alteplase is reasonable in patients with a seizure at stroke onset if evidence suggests that residual impairments are secondary to acute ischemic stroke and not to a postictal phenomenon. * Alteplase can be given in pregnancy when the anticipated benefits of treating moderate or severe stroke outweigh the anticipated increased risks of uterine bleeding. The safety and efficacy of administering alteplase is uncertain for these relative exclusions. Although these were exclusions in the trial showing benefit in the 3 to 4.5 hour window, intravenous alteplase appears to be safe and may be beneficial for patients with these criteria, including patients taking oral anticoagulants with an INR <1.7. Adapted from: 1. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008; 359:1317. 2. Del Zoppo GJ, Saver JL, Jauch EC, et al. Expansion of the time window for treatment of acute ischemic stroke with intravenous tissue plasminogen activator. A science advisory from the American Heart Association/American Stroke Association. Stroke 2009; 40:2945. 3. Re-examining Acute Eligibility for Thrombolysis (TREAT) Task Force:, Levine SR, Khatri P, et al. Review, historical context, and clari cations of the NINDS rt-PA stroke trials exclusion criteria: Part 1: rapidly improving stroke symptoms. Stroke 2013; 44:2500. 4. Demaerschalk BM, Kleindorfer DO, Adeoye OM, et al. Scienti c rationale for the inclusion and exclusion criteria for intravenous alteplase in acute ischemic stroke: A statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2016; 47:581. 5. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2019; 50:e344. Graphic 71462 Version 26.0 https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 23/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate Indications for mechanical thrombectomy to treat patients with acute ischemic IV: intravenous; tPA: tissue plasminogen activator (alteplase or tenecteplase); CTA: computed tomography an artery occlusion; MT: mechanical thrombectomy; ASPECTS: Alberta Stroke Program Early CT Score; NIHSS: Na tomography; MRI: magnetic resonance imaging; mRS: modified Rankin Scale; MCA: middle cerebral artery; IC recovery. Patients are not ordinarily eligible for IV tPA unless the time last known to be well is <4.5 hours. However, im that is diffusion positive and FLAIR negative) is an option at expert stroke centers to select patients with wake associated UpToDate topics for details. Usually assessed with MRA or CTA, less often with digital subtraction angiography. There is intracranial arterial occlusion of the distal ICA, middle cerebral (M1/M2), or anterior cerebral (A1/A2 MT may be a treatment option for patients with acute ischemic stroke caused by occlusion of the basilar ar stroke centers, but benefit is uncertain. [1] Based upon data from the Aurora study . Reference: https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 24/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate 1. Albers GW, Lansberg MG, Brown S, et al. Assessment of Optimal Patient Selection for Endovascular Thrombectomy Beyond 6 Hou Neurol 2021; 78:1064. Graphic 117086 Version 3.0 https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 25/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate Pathophysiologic ischemic stroke classification Large vessel atherothrombotic stroke More common Bifurcation of the common carotid artery Siphon portion of the common carotid artery Middle cerebral artery stem Intracranial vertebral arteries proximal to middle basilar artery Origin of the vertebral arteries Less common Origin of the common carotid artery Posterior cerebral artery stem Origin of the major branches of the basilar-vertebral arteries Origin of the branches of the anterior, middle, and posterior cerebral arteries Small vessel (lacunar) stroke Mechanism Lipohyalinotic occlusion Less frequently proximal atherothrombotic occlusion Least likely embolic occlusion Most common locations Penetrating branches of the anterior, middle, and posterior cerebral and basilar arteries Cardioaortic embolic stroke Cardiac sources definite - antithrombotic therapy generally used Left atrial thrombus Left ventricular thrombus Atrial fibrillation and paroxysmal atrial fibrillation Sustained atrial flutter Recent myocardial infarction (within one month) Rheumatic mitral or aortic valve disease Bioprosthetic and mechanical heart valve Chronic myocardial infarction with ejection fraction <28 percent https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 26/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate Symptomatic heart failure with ejection fraction <30 percent Dilated cardiomyopathy Cardiac sources definite - anticoagulation hazardous Bacterial endocarditis (exception nonbacterial) Atrial myxoma Cardiac sources possible Mitral annular calcification Patent foramen ovale Atrial septal aneurysm Atrial septal aneurysm with patent foramen ovale Left ventricular aneurysm without thrombus Isolated left atrial spontaneous echo contrast ("smoke") without mitral stenosis or atrial fibrillation Mitral valve strands Ascending aortic atheromatous disease (>4 mm) True unknown source embolic stroke Other Dissection Moyamoya Binswanger's disease Primary thrombosis Cerebral mass Graphic 55099 Version 4.0 https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 27/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate Immediate antithrombotic treatment of acute ischemic stroke This algorithm is intended to provide basic guidance regarding the immediated use of antithrombotic therapy for patients with an acute ischemic stroke. For further details, including scoring of the NIHSS and suggested dosing regimens of antithrombotic agents, refer to the relevant UpToDate topic reviews. OA: oral anticoagulants; IVT: intravenous thrombolysis; MT: mechanical thrombectomy; NIHSS: National Institutes of Health Stroke Scale; DAPT: dual antiplatelet therapy (eg, aspirin and clopidogrel, or aspirin and ticagrelor). Refer to text and associated algorithm for details. Brain and large vessel imaging, cardiac evaluation, and (for select patients) other laboratory tests. https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 28/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate For severe systemic or symptomatic intracranial bleeding, withhold all anticoagulant and antiplatelet therapy for one to two weeks or until the patient is stable. Graphic 131697 Version 2.0 https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 29/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate Antithrombotic therapy according to cause of acute ischemic stroke This algorithm is intended to provide basic guidance regarding the immediate use of antithrombotic therapy with an acute ischemic stroke. For further details, including scoring of the NIHSS and suggested dosing regim antithrombotic agents, refer to the relevant UpToDate topic reviews. https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 30/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate HTN: hypertension; SBP: systolic blood pressure; DBP: diastolic blood pressure; ICA: internal carotid artery; C endarterectomy; OA: oral anticoagulation; CAS: carotid artery stenting; DAPT: dual antiplatelet therapy (eg, a clopidogrel, or aspirin and ticagrelor); NIHSS: National Institutes of Health Stroke Scale; CT: computed tomog magnetic resonance imaging. Brain and neurovascular imaging, cardiac evaluation, and (for select patients) other laboratory tests. Indications for long-term oral anticoagulation include atrial fibrillation, ventricular thrombus, mechanical h treatment of venous thromboembolism. "Large" infarcts are defined as those that involve more than one-third of the middle cerebral artery territor one-half of the posterior cerebral artery territory based upon neuroimaging with CT or MRI. Though less relia infarct size can also be defined clinically (eg, NIHSS score >15). Long-term aspirin therapy is alternative (though less effective) if OA contraindicated or refused. Direct oral anticoagulant agents have a more rapid anticoagulant effect than warfarin, a factor that may inf choice of agent and timing of OA initiation. Some experts prefer DAPT, based upon observational evidence. Long-term single-agent antiplatelet therapy for secondary stroke prevention with aspirin, clopidogrel, or as release dipyridamole. Graphic 131701 Version 2.0 https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 31/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate Standard dosing of direct oral anticoagulants Nonvalvular AF - VTE primary Anticoagulant stroke VTE treatment prophylaxis prophylaxis* Dabigatran (Pradaxa) 150 mg twice daily Parenteral 110 mg for the first anticoagulation for 5 to day, then 220 mg once 10 days; then dabigatran 150 mg twice daily daily Apixaban (Eliquis) 5 mg twice daily 10 mg twice daily for one week, then 5 mg 2.5 mg twice daily twice daily Edoxaban (Savaysa, Lixiana) 60 mg once daily Parenteral anticoagulation for 5 to 10 days; then edoxaban 60 mg once daily Rivaroxaban (Xarelto) 20 mg once daily with the evening meal 15 mg twice daily with food for three weeks; then 20 mg once daily with food 10 mg once daily, with or without food This is a simplified table that lists the most common dosing in individuals with normal renal function, normal weight, and lack of concomitant interacting medications (eg, P-glycoprotein inhibitors or inducers). Refer to UpToDate topics on AF, VTE treatment, VTE prophylaxis, and DOAC dosing for possible changes based on impaired renal function or extremes of weight. Other factors may influence dosing in individual patients. AF: atrial fibrillation; VTE: venous thromboembolism, includes deep vein thrombosis and pulmonary embolism; DOAC: direct oral anticoagulant. Dosing may be reduced for certain drugs in certain settings (eg, use of dabigatran 110 mg twice daily for individuals who are at increased risk of bleeding; refer to UpToDate topic on anticoagulation for atrial fibrillation for other examples). Treatment for acute VTE typically refers to the first three to six months of administration; continued treatment beyond six months may be done with a lower dose for some anticoagulants (eg, apixaban, rivaroxaban); the dose is not lowered when therapy is continued using dabigatran or edoxaban. Refer to the latest prescribing information for each individual anticoagulant. Prophylaxis refers to primary prophylaxis in settings such as after knee or hip surgery. https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 32/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate Graphic 112514 Version 5.0 https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 33/34 7/5/23, 10:18 AM Stroke in patients with atrial fibrillation - UpToDate Contributor Disclosures Warren J Manning, MD Equity Ownership/Stock Options: Pfizer [Anticoagulants]. All of the relevant financial relationships listed have been mitigated. Peter J Zimetbaum, MD Consultant/Advisory Boards: Abbott Medical [Lead extraction]. All of the relevant financial relationships listed have been mitigated. Scott E Kasner, MD Grant/Research/Clinical Trial Support: Bayer [Stroke]; Bristol Meyers Squibb [Stroke]; Medtronic [Stroke]; WL Gore and Associates [Stroke]. Consultant/Advisory Boards: Abbvie [Stroke]; AstraZeneca [Stroke]; BMS [Stroke]; Diamedica [Stroke]; Medtronic [Stroke]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. John F Dashe, MD, PhD No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/stroke-in-patients-with-atrial-fibrillation/print 34/34

7/5/23, 10:18 AM Supraventricular arrhythmias after myocardial infarction - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Supraventricular arrhythmias after myocardial infarction : David Spragg, MD, FHRS, Kapil Kumar, MD : Brian Olshansky, MD, Bernard J Gersh, MB, ChB, DPhil, FRCP, MACC, James Hoekstra, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Jul 28, 2022. INTRODUCTION Supraventricular arrhythmias, other than atrial fibrillation (AF) or flutter, are relatively uncommon in the periinfarction period. Their occurrence often indicates myocardial dysfunction and they may, by themselves, cause congestive heart failure or exacerbate ongoing myocardial ischemia. The incidence, mechanism, and treatment of supraventricular arrhythmias (particularly sinus bradycardia, sinus tachycardia, and AF) occurring after myocardial infarction (MI) will be reviewed here. The focus of the discussion here is on supraventricular arrhythmias in the setting of MI caused by acute atherothrombotic coronary artery disease. However, there are some clinical settings in which supraventricular arrhythmia may cause MI (such as when AF causes left atrial thrombus that embolizes to a coronary artery, or in the setting of a supraventricular tachycardia causing demand ischemia and MI). (See "Diagnosis of acute myocardial infarction" and "Diagnosis of acute myocardial infarction", section on 'Definitions'.) The following related topics are discussed separately: conduction disturbances after MI, ventricular arrhythmias during MI, and risk stratification of patients after MI. (See "Conduction abnormalities after myocardial infarction" and "Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features" and "Risk stratification after acute ST- elevation myocardial infarction".) SINUS BRADYCARDIA https://www.uptodate.com/contents/supraventricular-arrhythmias-after-myocardial-infarction/print 1/12 7/5/23, 10:18 AM Supraventricular arrhythmias after myocardial infarction - UpToDate Sinus bradycardia, defined as less than 50 to 60 beats per minute (bpm), occurs in 15 to 25 percent of patients after acute MI [1-3]. It has the following clinical characteristics [1,2,4]: It is frequently seen with inferior wall infarctions, since the right coronary artery supplies the sinoatrial node (SA) in approximately 60 percent of people. It is most often transient, particularly for sinus bradycardia occurring within the first six hours; such arrhythmias typically resolve within 24 hours. It is usually caused by increased vagal tone, often seen with inferior MI. In some cases, this may be the result of diaphragmatic irritation. Other less common causes include ischemia of the SA node and as a reperfusion arrhythmia following fibrinolysis [5]. It is due to medications (beta blockade, calcium channel blocker, or digoxin). Treatment If therapy is necessary due to hemodynamic compromise or ischemia, sinus bradycardia following an acute MI usually responds well to intravenous atropine (0.6 to 1.0 mg in the majority of cases) [6,7]. Persistent bradycardia with hemodynamic compromise despite intravenous atropine warrants consideration of temporary cardiac pacing [6,7]. Atrial or sequential atrioventricular (AV) pacing is superior to ventricular pacing, particularly if there is an associated right ventricular MI [8]. Permanent pacing is not typically necessary in patients with sinus bradycardia after an MI, because in most cases the bradyarrhythmia is transient [7]. Any decision to implant a permanent cardiac pacemaker should be delayed for several days of observation. (See "Permanent cardiac pacing: Overview of devices and indications".) Mortality as a result of periinfarction sinus bradycardia is rare [1]. Its significance is related to the associated reduction in cardiac output and coronary perfusion, thereby exacerbating ischemia, and to the possible development of an escape rhythm with possible AV dissociation causing hemodynamic compromise [9]. SINUS TACHYCARDIA Sinus tachycardia occurs in approximately 30 to 40 percent of acute MIs [10]. Although this is seen on presentation, the heart rate usually declines over time to a level that reflects the degree of activation of the sympathetic nervous system. Patients with persistent sinus tachycardia usually have larger infarcts that are more often anterior [10] and a marked impairment in left ventricular (LV) function, which is associated with substantial morbidity, a high early mortality, and an increased 30-day mortality [10,11]. In addition, sinus tachycardia may increase the size of https://www.uptodate.com/contents/supraventricular-arrhythmias-after-myocardial-infarction/print 2/12 7/5/23, 10:18 AM Supraventricular arrhythmias after myocardial infarction - UpToDate ischemic injury and infarction due at least in part to increased oxygen consumption. In some cases, sinus tachycardia may be the result of associated pericarditis. Therapeutic efforts should be targeted at identification and management of the underlying cause. However, most patients will receive such therapy independent of the tachycardia since early beta blocker administration is part of routine management of acute MI. Care should be exercised in the utilization of beta blockers early in an infarction, especially in the presence of large anterior MIs, hypotension, or pulmonary congestion. (See "Acute myocardial infarction: Role of beta blocker therapy".) ATRIAL FIBRILLATION The following section will review the incidence, pathophysiology, clinical characteristics, and treatment of the atrial tachyarrhythmias that occur after acute MI. AF is the most common of these. The overall incidence of atrial tachyarrhythmias in the periinfarction period ranges from 6 to 20 percent [9,10,12-17]. These arrhythmias primarily occur within the first 72 hours after infarction; however, only 3 percent are noted in the very early (less than three-hour) phase [12]. AF is common both during hospitalization and after discharge for acute MI and in both time periods has prognostic significance. The incidence during hospitalization has been reported to be between 5 and 18 percent and is more likely in individuals with heart failure, kidney disease, hypertension, diabetes, and pulmonary disease [13,14,18]. As expected with these risk factors, 30-day mortality in patients who develop AF is increased [13]. Long-term mortality is also increased in patients with in-hospital AF compared to those without [9,13,15,16,19-22]. Information concerning the longer-term incidence and prognosis of patients who develop AF after discharge comes from the CARISMA study, which evaluated the long-term development of arrhythmias in 271 patients with acute MI and an LV ejection fraction less than 40 percent [18]. These individuals underwent placement of an insertable cardiac monitor (ICM; also sometimes referred to as implantable cardiac monitor or implantable loop recorder) and were monitored for the development of AF lasting more than 16 beats. (See "Ambulatory ECG monitoring", section on 'Insertable cardiac monitor' and "Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features", section on 'Late arrhythmias'.) The following findings were noted during two years of follow-up: https://www.uptodate.com/contents/supraventricular-arrhythmias-after-myocardial-infarction/print 3/12 7/5/23, 10:18 AM Supraventricular arrhythmias after myocardial infarction - UpToDate Ninety-five individuals (39 percent) developed AF. Nearly half of these occurred by two months and nearly 80 percent by one year. Most of the AF events were asymptomatic. The duration of the AF event(s) was more than 30 seconds in slightly more than half of these. New onset AF was associated with a significantly increased risk of major cardiovascular events (Unadjusted hazard ratio [HR] 2.04). AF remained a significant predictor of adverse outcomes even after adjustment. The risk was significantly increased in those individuals whose duration of AF was more than 30 seconds (HR 2.73, 95% CI 1.25-5.50), but not in those with episodes lasting less than 30 seconds (HR 1.17, 95% CI 0.35-3.92). Pathophysiology The increase in the prevalence of AF during an acute MI has been ascribed to one or more of the following factors: atrial dysfunction (due to atrial ischemia, which is rare; infarction, which is rare; or atrial stretching due to heart failure with elevation in left atrial pressures, which is the most common etiology) [23], sympathetic stimulation, pericarditis [24], inflammatory state [25], atheromatous disease of the arteries supplying the sinoatrial (SA) and AV nodes and the left atrium (which is a rare cause for AF) [10,12,21,26], and iatrogenic factors such as positive inotropic agents. Prevention Statin therapy, possibly due to an antiinflammatory effect, has been associated with a reduction in AF recurrences in patients with lone AF, ischemic heart disease, and after cardiac bypass surgery. (See "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Clinical trials", section on 'Statins'.) In a retrospective study of over 3300 patients presenting with acute MI and in sinus rhythm, statin therapy (prescription within 48 hours of hospitalization) was associated with a reduced risk of AF (odds ratio 0.64, 95% CI 0.45-0.92) [27]. However, we do not recommend initiation of statin therapy in patients with MI to solely prevent AF. Almost all such patients should be on statin therapy for other reasons. (See "Low density lipoprotein-cholesterol (LDL-C) lowering after an acute coronary syndrome", section on 'Summary and recommendations'.) Treatment The management of periinfarction atrial tachyarrhythmias is important, because tachycardia can increase myocardial oxygen demand, thereby exacerbating ischemia and possibly decreasing cardiac output. Atrial tachyarrhythmias may also induce or exacerbate heart failure, especially when associated with a rapid ventricular response. For sustained AF or atrial flutter that is of new onset after the MI and is associated with hemodynamic compromise, we make the following recommendations: https://www.uptodate.com/contents/supraventricular-arrhythmias-after-myocardial-infarction/print 4/12 7/5/23, 10:18 AM Supraventricular arrhythmias after myocardial infarction - UpToDate Initial treatment should consist of rate control. The first-line treatment is beta blockade. One option is intravenous metoprolol (2.5 to 5.0 mg every two to five minutes to a total of 15 mg over 10 to 15 minutes). If ineffective, intravenous calcium channel blockade (verapamil or diltiazem) should be considered. For unstable patients, synchronized direct current cardioversion should be considered. (See "Atrial fibrillation: Cardioversion" and "Atrial fibrillation: Cardioversion", section on 'Indications'.) For episodes of AF with hemodynamic compromise that do not respond to electrical cardioversion or that recur after a brief period of sinus rhythm, the use of intravenous followed by oral amiodarone to help control rate and help maintain sinus is indicated. The use of amiodarone or digoxin in the setting of hemodynamic compromise is recommended because these drugs are associated with less risk of worsening myocardial dysfunction than some other drugs (although some preparations of intravenous amiodarone can cause hypotension, which is the result of Tween 80, the detergent used to get amiodarone into aqueous solution) and have not been associated with increased risk of mortality post-infarction. However, in many patients hemodynamic compromise during AF is a result of the rapid ventricular rate. In such cases, amiodarone and digoxin, which slow AV conduction only gradually and after a long period of time, may not be as effective as other agents. We recommend the use of either an intravenous beta blocker or intravenous verapamil in this setting. Dofetilide is also an effective drug for long-term management of AF after MI to help maintain sinus rhythm. The DIAMOND-MI trial found that this drug had no effect on all- cause, cardiac, or total arrhythmic mortality compared to placebo [28]. However, dofetilide was better than placebo for reverting AF or flutter to sinus rhythm (42.3 versus 12.5 percent for placebo). For patients with sustained AF or atrial flutter without ongoing ischemia or hemodynamic compromise, rate control is indicated. Consideration should be given to cardioversion to sinus rhythm in patients without a history of AF or atrial flutter prior to MI. (See "Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy" and "Atrial fibrillation in adults: Use of oral anticoagulants".) Long-term antiarrhythmic therapy may not be necessary if factors associated with recurrent AF, such as moderate to severe LV systolic dysfunction or heart failure, are absent [16,22,29]. We suggest reassessment of the patient s rhythm status in one to two months after MI. If there is no https://www.uptodate.com/contents/supraventricular-arrhythmias-after-myocardial-infarction/print 5/12 7/5/23, 10:18 AM Supraventricular arrhythmias after myocardial infarction - UpToDate evidence of recurrent AF and if risk factors for recurrence are absent, antiarrhythmic therapy can be discontinued. The role of anticoagulation in these patients is discussed elsewhere. (See 'Anticoagulation' below and "Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation".) Anticoagulation The optimal anticoagulation strategy for patients with MI who develop AF for the first time is unknown. With regard to intravenous heparin, most of our experts use it in patients who will be cardioverted prior to discharge. For patients who will not be cardioverted, some of our experts use intravenous heparin until such time as the patient is successfully anticoagulated with an oral agent while others do not use heparin (particularly in patients with a low CHA DS-VASc score) 2 prior to oral anticoagulation. Most of our experts recommend at least three to four weeks of oral anticoagulant, assuming the patient is not at high bleeding risk. (See "Atrial fibrillation in adults: Use of oral anticoagulants", section on 'Summary and recommendations'.) For those patients who are discharged on anticoagulant therapy after one episode of AF, the optimal duration is unknown [30]. As the risk of bleeding is very high in patients on triple antithrombotic therapy (ie, antiplatelet therapy for those receive a stent along with anticoagulation), practitioners should carefully and repeatedly reassess the need for continued anticoagulation (and thienopyridine). This issue is discussed in detail elsewhere. (See "Coronary artery disease patients requiring combined anticoagulant and antiplatelet therapy".) Patients with recurrent episodes of AF, especially if persistent or permanent (which is often the result of LV dysfunction and heart failure post-MI), should be treated with oral anticoagulants long term. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation", section on 'Classification and terminology' and "Atrial fibrillation in adults: Use of oral anticoagulants" and "Acute coronary syndrome: Oral anticoagulation in medically treated patients".) PSVT Paroxysmal supraventricular tachycardia (PSVT) occurs in less than 10 percent of patients after an acute MI, but may require aggressive management due to a rapid ventricular rate [31]. We suggest the following sequence of therapeutic measures [7]: https://www.uptodate.com/contents/supraventricular-arrhythmias-after-myocardial-infarction/print 6/12 7/5/23, 10:18 AM Supraventricular arrhythmias after myocardial infarction - UpToDate Carotid sinus massage or a valsalva maneuver (both of which increase vagal tone and alter AV nodal properties). (See "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'Carotid sinus massage'.) Intravenous adenosine (6 mg over one to two seconds; if no response, 12 mg one to two minutes later; may repeat 12 mg dose if needed). We suggest adenosine be used only in patients who have been revascularized. An external defibrillator should be available since a small percentage of patients develop ventricular fibrillation from adenosine likely related to a coronary steal phenomenon. Intravenous beta blockade with metoprolol (2.5 to 5.0 mg every two to five minutes to a total of 15 mg over 10 to 15 minutes) or esmolol. Our authors and reviewers also suggest that either intravenous verapamil, amiodarone, diltiazem, or cardioversion may be considered. NONPAROXYSMAL JUNCTIONAL TACHYCARDIA Junctional tachycardia (or an accelerated junctional tachycardia) is an arrhythmia arising from a discrete focus within the AV node or His bundle. The mechanism is thought to be one of enhanced automaticity rather than reentry. In adults, this rhythm, generally called nonparoxysmal junctional tachycardia, and is an uncommon arrhythmia associated with acute MI [32-34]. The same arrhythmia may also be seen with digitalis intoxication [35,36]. Atrial activity during junctional tachycardia is variable. Retrograde atrial activation may occur, with a P wave that either follows each QRS complex or is concealed in the QRS complex, as with AV nodal reentrant tachycardia. If retrograde conduction does not occur, independent atrial activity may be seen, with complete AV dissociation that must be distinguished from AV dissociation due to complete heart block (in complete heart block, the atrial rate exceeds the ventricular rate, while with an accelerated junctional tachycardia the atrial rate is slower than the ventricular rate). (See "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'Undetectable P waves'.) Nonparoxysmal junctional tachycardia is typically transient, occurring within the first 48 hours of infarction and developing and terminating gradually. The rate of a junctional tachycardia is generally slightly above 100 bpm, whereas reentrant paroxysmal supraventricular tachycardias (PSVTs) are generally faster. No specific antiarrhythmic therapy is indicated [7]. https://www.uptodate.com/contents/supraventricular-arrhythmias-after-myocardial-infarction/print 7/12 7/5/23, 10:18 AM Supraventricular arrhythmias after myocardial infarction - UpToDate SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Non-ST-elevation acute coronary syndromes (non-ST-elevation myocardial infarction)" and "Society guideline links: ST- elevation myocardial infarction (STEMI)".) SUMMARY Supraventricular arrhythmias, other than atrial fibrillation (AF) or atrial flutter, are relatively uncommon in the periinfarction period. The incidence of in-hospital AF after myocardial infarction (MI) ranges from 5 to 18 percent. The development of AF is associated with a worse prognosis. Sinus bradycardia, defined as less than 50 to 60 beats per minute, occurs in 15 to 25 percent of patients after acute MI and is most often due to increased vagal tone. (See 'Sinus bradycardia' above.) Sinus tachycardia occurs in approximately 30 to 40 percent of acute MIs. Patients with persistent sinus tachycardia usually have larger infarcts that are more often anterior, associated with a marked impairment in left ventricular function, and a high, early, and 30- day mortality. (See 'Sinus tachycardia' above.) Paroxysmal supraventricular tachycardia (PSVT) occurs in less than 10 percent of patients after an acute MI, but may require aggressive management due to a rapid ventricular rate. (See 'PSVT' above.) Nonparoxysmal junctional tachycardia is typically transient, occurring within the first 48 hours of infarction and developing and terminating gradually. No specific antiarrhythmic therapy is indicated. ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Philip J Podrid, MD, FACC, who contributed to earlier versions of this topic review. Use of UpToDate is subject to the Terms of Use. https://www.uptodate.com/contents/supraventricular-arrhythmias-after-myocardial-infarction/print 8/12 7/5/23, 10:18 AM Supraventricular arrhythmias after myocardial infarction - UpToDate REFERENCES 1. Marks R, Beard RJ, Clark ML, et al. Gastrointestinal observations in rosacea. Lancet 1967; 1:739. 2. Adgey AA, Geddes JS, Mulholland HC, et al. Incidence, significance, and management of early bradyarrhythmia complicating acute myocardial infarction. Lancet 1968; 2:1097. 3. Rotman M, Wagner GS, Wallace AG. Bradyarrhythmias in acute myocardial infarction. Circulation 1972; 45:703. 4. Zimetbaum PJ, Josephson ME. Use of the electrocardiogram in acute myocardial infarction. N Engl J Med 2003; 348:933. 5. Goldberg S, Greenspon AJ, Urban PL, et al. 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The incidence and prognostic significance of new-onset atrial fibrillation in patients with acute myocardial infarction and left ventricular systolic dysfunction: a CARISMA substudy. Heart Rhythm 2011; 8:342. 19. Pedersen OD, Bagger H, K ber L, Torp-Pedersen C. The occurrence and prognostic significance of atrial fibrillation/-flutter following acute myocardial infarction. TRACE Study group. TRAndolapril Cardiac Evalution. Eur Heart J 1999; 20:748. 20. Behar S, Zahavi Z, Goldbourt U, Reicher-Reiss H. Long-term prognosis of patients with paroxysmal atrial fibrillation complicating acute myocardial infarction. SPRINT Study Group. Eur Heart J 1992; 13:45. 21. Hod H, Lew AS, Keltai M, et al. Early atrial fibrillation during evolving myocardial infarction: a consequence of impaired left atrial perfusion. Circulation 1987; 75:146. 22. Sakata K, Kurihara H, Iwamori K, et al. Clinical and prognostic significance of atrial fibrillation in acute myocardial infarction. Am J Cardiol 1997; 80:1522. 23. Celik S, Erd l C, Baykan M, et al. Relation between paroxysmal atrial fibrillation and left ventricular diastolic function in patients with acute myocardial infarction. Am J Cardiol 2001; 88:160. 24. Nagahama Y, Sugiura T, Takehana K, et al. The role of infarction-associated pericarditis on the occurrence of atrial fibrillation. Eur Heart J 1998; 19:287. 25. Zahler D, Merdler I, Rozenfeld KL, et al. C-Reactive Protein Velocity and the Risk of New Onset Atrial Fibrillation among ST Elevation Myocardial Infarction Patients. Isr Med Assoc J 2021; 23:169. 26. Kramer RJ, Zeldis SM, Hamby RI. Atrial fibrillation a marker for abnormal left ventricular function in coronary heart disease. Br Heart J 1982; 47:606. 27. Danchin N, Fauchier L, Marijon E, et al. Impact of early statin therapy on development of atrial fibrillation at the acute stage of myocardial infarction: data from the FAST-MI register. Heart 2010; 96:1809. https://www.uptodate.com/contents/supraventricular-arrhythmias-after-myocardial-infarction/print 10/12 7/5/23, 10:18 AM Supraventricular arrhythmias after myocardial infarction - UpToDate 28. K ber L, Bloch Thomsen PE, M ller M, et al. Effect of dofetilide in patients with recent myocardial infarction and left-ventricular dysfunction: a randomised trial. Lancet 2000; 356:2052. 29. Cameron A, Schwartz MJ, Kronmal RA, Kosinski AS. Prevalence and significance of atrial fibrillation in coronary artery disease (CASS Registry). Am J Cardiol 1988; 61:714. 30. Axelrod M, Gilutz H, Plakht Y, et al. Early Atrial Fibrillation During Acute Myocardial Infarction May Not Be an Indication for Long-Term Anticoagulation. Angiology 2020; 71:559. 31. Ganz LI, Friedman PL. Supraventricular tachycardia. N Engl J Med 1995; 332:162. 32. Konecke LL, Knoebel SB. Nonparoxysmal junctional tachycardia complicating acute myocardial infarction. Circulation 1972; 45:367. 33. Knoebel SB, Rasmussen S, Lovelace DE, Anderson GJ. Nonparoxysmal junctional tachycardia in acute myocardial infarction: computer-assisted detection. Am J Cardiol 1975; 35:825. 34. Berisso MZ, Ferroni A, Molini D, Vecchio C. [Supraventricular tachyarrhythmias during acute myocardial infarction: short- and mid-term clinical significance, therapy and prevention of relapse]. G Ital Cardiol 1991; 21:49. 35. Bigger JT Jr. Digitalis toxicity. J Clin Pharmacol 1985; 25:514. 36. Kastor JA, Yurchak PM. Recognition of digitalis intoxication in the presence of atrial fibrillation. Ann Intern Med 1967; 67:1045. Topic 82 Version 19.0 Contributor Disclosures David Spragg, MD, FHRS No relevant financial relationship(s) with ineligible companies to disclose. Kapil Kumar, MD No relevant financial relationship(s) with ineligible companies to disclose. Brian Olshansky, MD Other Financial Interest: AstraZeneca [Member of the DSMB for the DIALYZE trial]; Medtelligence [Cardiovascular disease]. All of the relevant financial relationships listed have been mitigated. Bernard J Gersh, MB, ChB, DPhil, FRCP, MACC Consultant/Advisory Boards: Bain Institute [CRO for trials involving Edwards percutaneous valve devices]; Cardiovascular Research Foundation [Data safety monitoring board (RELIEVE-HF Trial)]; Caristo Diagnostics Limited [Imaging and inflammation/atherosclerosis]; Philips Image Guided Therapy Corporation [Imaging]; Sirtex Med Limited [General consulting]; Thrombosis Research Institute [Data safety monitoring board (GARFIELD study)]. All of the relevant financial relationships listed have been mitigated. James Hoekstra, MD No relevant financial relationship(s) with ineligible companies to disclose. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. https://www.uptodate.com/contents/supraventricular-arrhythmias-after-myocardial-infarction/print 11/12 7/5/23, 10:18 AM Supraventricular arrhythmias after myocardial infarction - UpToDate Conflict of interest policy https://www.uptodate.com/contents/supraventricular-arrhythmias-after-myocardial-infarction/print 12/12

7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. The electrocardiogram in atrial fibrillation : Brian Olshansky, MD, Zachary D Goldberger, MD, FACC, FHRS, Steven M Pogwizd, MD : Bradley P Knight, MD, FACC : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Sep 10, 2021. INTRODUCTION Atrial fibrillation (AF) can cause significant symptoms; impair functional status, hemodynamics, and quality of life; and increase the risk of stroke and death. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation".) Diagnosis of AF has important implications for acute and long-term management. A missed diagnosis of AF may result in a failure to appropriately anticoagulate for stroke prophylaxis or effectively treat symptoms due to AF, while overdiagnosis of AF may lead to inappropriate testing and therapy including unwarranted anticoagulation with associated risk of major bleeding. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation".) This topic will review the electrocardiographic (ECG) features of AF. The mechanisms of AF are presented separately. (See "Mechanisms of atrial fibrillation".) DIAGNOSIS OF ATRIAL FIBRILLATION AF is diagnosed by interpretation of the 12-lead ECG. In most patients, a single 12-lead ECG, recorded while the patient is in AF, is sufficient to secure the diagnosis. Examination of prior ECGs may be helpful, but prior diagnosis (or misdiagnosis) of AF should not influence interpretation of a current ECG. In some patients, AF is detected on ECG recordings from cardiac telemetry, ambulatory ECG monitor (eg, Holter monitor or loop recorder), or cardiac implantable electronic device (permanent pacemaker [PPM] or implantable cardioverter-defibrillator [ICD]). (See "Ambulatory ECG monitoring" and "Permanent cardiac pacing: Overview of devices and https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 1/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate indications" and "Implantable cardioverter-defibrillators: Overview of indications, components, and functions".) Our approach While the ECG diagnosis of AF with typical features can be straightforward in patients with characteristic features of AF (see 'Key features of atrial fibrillation' below), misdiagnosis of AF is common, as there are a significant number of AF mimics that should be excluded. (See 'Differential diagnosis' below.) The following is our approach to ECG identification of the cause of an irregularly irregular ventricular rhythm (or regular rhythm with fibrillatory or absent P waves) ( algorithm 1): Exclude artifact If artifact may be present, examine all 12 leads and examine atrial activity in the leads with the least amount of artifact-related oscillations ( waveform 1 and waveform 2). If atrial activity cannot be adequately assessed, address the cause of the artifact to the extent possible and repeat the ECG. (See 'Differential diagnosis' below.) Identify atrial activity Examine all 12 leads of the ECG closely for the presence of atrial activity, particularly the inferior leads and lead V1. Focus on areas with longer R-R intervals that display longer periods of isoelectric baseline. Increase amplitude, if needed If no atrial activity is detected or the morphology of atrial activity is not well visualized, use ECG amplification (either digital magnification or an increase in gain for the entire ECG signal) ( waveform 3). Examine atrial activity The morphology, frequency, and timing of atrial activity in relationship to QRS complexes should be assessed. Exclude AF mimics. (See 'Differential diagnosis' below.) If AF mimics are excluded, and there are fibrillatory waves or no P waves (despite ECG amplification), AF is diagnosed. Common and uncommon ECG characteristics of AF are described below. (See 'Key features of atrial fibrillation' below.) Key features of atrial fibrillation Common findings The following findings are commonly seen with AF: Atrial activity (see 'Atrial activity' below): Lack of discrete P waves ( waveform 4). https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 2/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Rapid, low-amplitude fibrillatory (or f) waves vary continuously in amplitude, morphology, and rate. The rate may be between 350 to 600 beats per minute (bpm) or unmeasurable. If present, f waves usually are best seen in the inferior leads and in V1. The f waves may be identified between QRS complexes and are sometimes visible superimposed on the ST segment and T waves. Ventricular activity (see 'Ventricular activation' below): The ventricular rhythm is described as "irregularly irregular," meaning lacking a repetitive, predictable pattern. (See 'General features' below.) The ventricular rate (especially in absence of atrioventricular [AV] nodal blocking drugs or intrinsic conduction disease) is usually 90 to 170 bpm, with higher rates seen in younger individuals (see 'General features' below). Based on the ventricular rate, AF is often characterized as having "slow" (<60 bpm), "moderate" (60 to 100 bpm), or "rapid" (>100 bpm) ventricular response ( waveform 5). The QRS complexes are narrow unless conduction through the His-Purkinje system is abnormal due to preexisting right or left bundle branch ( waveform 6), fascicular block, functional (rate-related) aberration, or ventricular preexcitation with anterograde conduction via an AV accessory pathway. (See 'With aberrant conduction' below and 'With Wolff-Parkinson-White syndrome' below.) Uncommon findings The following findings are less commonly identified in patients with AF: A regular (rather than an irregularly irregular) ventricular rhythm: Regular ventricular escape complexes in patients with complete or high-grade AV block are referred to as "regularization of AF." Complete or high-grade AV block may be caused by conduction system disease, AV node ablation, or drugs (including digoxin toxicity). (See "Etiology of atrioventricular block" and "Atrial fibrillation: Atrioventricular node ablation" and "Third-degree (complete) atrioventricular block" and "Cardiac arrhythmias due to digoxin toxicity", section on 'Digoxin-induced arrhythmias'.) Junctional escape Most commonly, the escape pacemaker is located in the AV junction above the bifurcation of the bundle branches, leading to a QRS complex that has the same morphology as if it had conducted from the atria through the AV node ( waveform 7). This pacemaker generally has a characteristic rate of approximately 60 bpm, unless it is accelerated or depressed due to pathology, ischemia, or drugs (eg, digoxin). https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 3/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Ventricular escape With less commonly seen ventricular (subjunctional or fascicular) escape rhythms, the QRS is wide and, unless accelerated, the ventricular rate is generally 30 to 50 bpm ( waveform 7). Ventricular pacing produces a regular paced ventricular rhythm with wide QRS. (See "Permanent cardiac pacing: Overview of devices and indications" and "Modes of cardiac pacing: Nomenclature and selection".) The ventricular rhythm is typically regular when there is ventricular tachycardia in the presence of AF. With very fast rates of AV conduction, the ventricular rate may appear regular. If there is conversion between AF and atrial flutter with a fixed ratio of conduction, the ventricular rate will be regular during periods of atrial flutter. Variable (rather than consistent) QRS morphology may result from varying combinations of AV conduction and native or paced ventricular beats ( waveform 8). In these unusual cases, there may be AV conduction and fusion beats (hybrid complexes produced by coincident AV conduction and ventricular or paced beats) or pseudofusion beats (QRS complexes with morphology of AV conducted beats but with superimposed pacemaker stimuli). An example is the occurrence of AF with rapid ventricular response in concert with a "competing" tachycardia (eg, ventricular tachycardia) ( waveform 9). (See "ECG tutorial: Miscellaneous diagnoses", section on 'Fusion and capture beats' and "ECG tutorial: Pacemakers", section on 'Ventricular pacing only'.) Differential diagnosis When there are no recognizable atrial deflections in any ECG lead, turning up the gain on the ECG may enable identification of f or P waves and thus help distinguish fine AF from sinus rhythm with irregularity (due to ectopy or sinus arrhythmia) ( waveform 3). AF can be confused with a number of other supraventricular arrhythmias that exhibit atrial activity (ie, sinus P waves, ectopic P waves, or flutter waves). "Coarse" AF (large-amplitude f waves, especially in lead V1) should be distinguished from atrial flutter and multifocal atrial tachycardia, as discussed below. Specific AF mimics can be subdivided based on the type of atrial activity present. One or more of the following types of rhythms may be present: Artifact Artifact from tremor, shivering, or loose lead connection superimposed on sinus rhythm (or any other non-AF rhythm) can mimic AF ( waveform 1 and waveform 2). https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 4/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial flutter Atrial flutter is characterized by flutter waves on the isoelectric baseline between longer R-R intervals and on the ST segments and/or T waves, usually best seen in inferior leads or V1 ( waveform 10). Both typical and atypical atrial flutter can mimic AF. In atrial flutter, atrial rates are generally 250 to 350 bpm (but are sometimes as low as 190 to 200 bpm). While atrial flutter with a constant degree of AV block (2:1, 3:1, 4:1) typically results in regular rhythms, atrial flutter with variable AV conduction is irregular. Some patients with AF also have episodes of atrial flutter. (See "Overview of atrial flutter", section on 'Electrocardiogram'.) We avoid use of the term "atrial fibrillation/flutter," which is commonly used when the precise type of atrial activity is unclear. The term is inaccurate and may impact care as there are differences in the short- and long-term management for AF and atrial flutter. When it is difficult to distinguish these conditions, we use alternate language such as "The atrial activity is unclear and coarse, but the likely diagnosis is AF. However, atrial flutter with variable conduction cannot be excluded." Some patients have both of these conditions. If an ECG catches a transition between AF and atrial flutter, this transition should be noted and not labeled as "atrial fibrillation/flutter." The presence of sinus P waves (upright in II, inverted in aVR, and biphasic in V1) suggests an underlying sinus rhythm. Sinus arrhythmia If all P waves are sinus, variation in PP (by >0.16 seconds) with a relatively constant PR suggests sinus arrhythmia ( waveform 11). There is progressive increase and decrease in the P-P interval (See "ECG tutorial: Rhythms and arrhythmias of the sinus node", section on 'Sinus arrhythmia' and "Normal sinus rhythm and sinus arrhythmia", section on 'Sinus arrhythmia'.) Sinus arrhythmia with competing junctional escape rhythm If there is variation in PP and there is one or more QRS complex without a preceding P wave or preceded by a shorter than normal PR interval, consider sinus arrhythmia with a competing junctional escape rhythm (also known as isorhythmic AV dissociation) ( waveform 12). This occurs when the sinus rate intermittently drops below that of the junctional escape rhythm. The inconsistent P-QRS relationship is more challenging for the standard AF algorithms of ECG machines, and the rhythm is often misinterpreted as AF. (See "ECG tutorial: Rhythms and arrhythmias of the sinus node", section on 'Types' and "ECG tutorial: Atrial and atrioventricular nodal (supraventricular) arrhythmias", section on 'Junctional escape beats'.) https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 5/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Sinus rhythm with second-degree AV block Sinus rhythm with second-degree AV block can result in an irregular rhythm with occasional dropped beats (nonconducted P waves) which may (Mobitz I) or may not (Mobitz II) be preceded by progressive PR prolongation ( waveform 13). (See "Second-degree atrioventricular block: Mobitz type I (Wenckebach block)" and "Second-degree atrioventricular block: Mobitz type II" and "ECG tutorial: Atrioventricular block".) Sinus rhythm with premature ventricular complexes (PVCs) Sinus rhythm with PVCs can result in an irregular rhythm that may be mistaken as AF when P wave amplitude is diminished or in the setting of artifact. One morphology of nonsinus P waves (along with sinus P waves): Sinus rhythm with premature atrial complexes (PACs) The combination of sinus rhythm and PACs results in an irregular rhythm that can resemble AF, especially when the P waves of sinus beats and/or PACs are superimposed on the ST segment or T waves of preceding beats . To distinguish this rhythm from AF, magnification of digitized ECG tracings may facilitate recognition of sinus and ectopic P waves and demonstrate a consistent one-to-one relationship between P waves and QRS complexes ( waveform 3). (See "ECG tutorial: Atrial and atrioventricular nodal (supraventricular) arrhythmias", section on 'Premature atrial complex'.) Runs of nonsinus P waves A shift in atrial activation arising from the sinus node to that from an ectopic atrial site (or vice versa) can lead to a sudden change in P wave morphology and, often, some irregularity that could mimic AF. Ectopic atrial rhythm Atrial rate is 100; generally, 30 to 60 bpm ( waveform 14). (See "ECG tutorial: Atrial and atrioventricular nodal (supraventricular) arrhythmias", section on 'Ectopic atrial rhythm'.) Focal atrial tachycardia Atrial tachycardia (AT) is characterized by atrial rates in the 140 to 180 bpm range ( waveform 15). In the presence of AV block, the ventricular response can be irregular and mimic AF. While AT with block has been commonly described with digoxin toxicity, it can occur in the absence of digoxin. (See "Cardiac arrhythmias due to digoxin toxicity", section on 'Digoxin-induced arrhythmias'.) Three or more P wave morphologies: Wandering atrial pacemaker or multifocal atrial rhythm is an irregular rhythm that is also characterized by P waves of at least three morphologies and is characterized by https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 6/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate ventricular rates <100 bpm ( waveform 16). (See "ECG tutorial: Atrial and atrioventricular nodal (supraventricular) arrhythmias" and "ECG tutorial: Atrial and atrioventricular nodal (supraventricular) arrhythmias", section on 'Wandering atrial pacemaker'.) Multifocal atrial tachycardia (MAT) MAT is a rapid irregularly irregular rhythm (ventricular rate 100 bpm) characterized by P waves of at least three different morphologies and with a one-to-one correspondence of P waves to QRS complexes ( waveform 17). (See "ECG tutorial: Atrial and atrioventricular nodal (supraventricular) arrhythmias", section on 'Multifocal atrial tachycardia' and "Multifocal atrial tachycardia", section on 'Clinical manifestations and diagnosis'.) Ventricular tachycardia AF with aberrant conduction may include consecutive runs of aberrantly conducted beats with wide QRS complexes, which may appear similar to ventricular tachycardia. The ventricular rate with AF is generally irregular. (See 'With aberrant conduction' below.) EXPLANATION OF ECG FEATURES Atrial activity In AF, there is no regular or organized atrial activity ( waveform 4). Numerous apparent microreentrant circuits within the atria may generate multiple waves of impulses that compete with or extinguish each other in what is termed "fibrillatory conduction." The sinus node is suppressed and cannot activate the atrium. Mechanisms causing this abnormal pattern of atrial electrical activity are discussed elsewhere. (See "Mechanisms of atrial fibrillation".) Rapid, irregular, and variable fibrillatory (f) waves may be coarse (amplitude 1 mm) or fine (<1 mm) and may not be identified. Some studies have found that fine AF is associated with older age, but age ranges for coarse and fine AF overlap widely [1,2]. The amplitude of f waves does not correlate with left atrial size [1,3]. The differential diagnosis for AF is discussed above. (See 'Differential diagnosis' above.) Ventricular activation General features In AF, the ventricular response rate is dependent on properties of the AV conduction system. As rapid and irregular atrial impulses bombard the AV node, some impulses occur in such rapid succession that they are blocked due to the refractoriness of the AV node, resulting in irregular impulse conduction through the AV node to the ventricular myocardium via https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 7/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate the His-Purkinje system. High frequency of atrial stimuli reaching the AV node does not lead to high frequency of AV conduction, as frequent impulses may cause "concealed" depolarization (ie, not evident on the surface ECG) impairing AV conduction. The large number of atrial impulses arriving at the AV node compete with each other, interfering with their penetration into and through the node, leaving this tissue variably refractory. While the ventricular rate in adults with AF is usually 90 to 170 bpm, in young, untreated individuals, rates are 160 to 200 bpm, reflecting the maximal rate at which the AV node can conduct (as determined by its refractory period in lieu of concealed conduction). Increases in the ventricular response rate to over 200 bpm may occur if the refractory period of the AV node is shortened, as with an increase in circulating catecholamines (eg, sympathetic stimulation or pheochromocytoma, hyperthyroidism, or conduction down a manifest accessory pathway). A decrease in the ventricular response rate occurs when the refractory period of the AV node is increased (eg, with aging, conduction system disease, drugs, or enhanced vagal tone) or AV conduction otherwise slows. With aberrant conduction A common cause for QRS widening during AF is aberrant conduction, which is a rate-related change in conduction. Most aberrancy is tachycardia- dependent, although bradycardia-dependent aberrancy does occur [4]. The aberrant conduction in AF involves a rate-related (tachycardia-induced) change in conduction, typically a functional bundle branch block; right bundle branch block (RBBB) is more common than left bundle branch block (LBBB), as the RBBB has a longer refractory period than the LBBB. An important property of the conducting system and myocardium is that refractoriness is longer at slow rates and shorter at faster rates. The refractoriness of the conducting system varies on a beat-by-beat basis and is related to the coupling interval of the preceding beat. As such, a long coupling interval leads to prolongation of bundle branch refractoriness (typically R>L), and if the next beat comes in early (ie, a long-short cycle), the refractoriness of the RBBB leads to a RBBB configuration and QRS widening that resembles a premature ventricular complex (PVC). This pattern of long-short cycle typically leads to RBBB morphology (known as Ashman phenomenon [5]) and can occur during sinus rhythm with appropriately timed premature atrial complexes (PACs) ( waveform 18) as well as during AF ( waveform 19). Aberrancy with LBBB morphology is less common but can occur. The QRS of aberrant beats typically exhibits an upstroke similar to those of other native supraventricular beats in leads other than V1 to V2, while PVCs typically exhibit markedly different morphology from supraventricular beats in multiple leads, as shown for sinus rhythm ( waveform 18). The approach to evaluating wide QRS complex tachycardia to distinguish supraventricular tachycardia from ventricular tachycardia is discussed separately. (See "Wide QRS complex tachycardias: Approach to the diagnosis".) https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 8/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate During AF, Ashman phenomenon is associated with frequent isolated wide-complex aberrantly conducted beats. However, aberrantly conducted beats can also occur in couplets or longer nonsustained runs that can resemble ventricular tachycardia ( waveform 19). In these situations, there is no longer a long-short cycle but rather short-short cycles of rapid AF. In this case, the functional RBBB and activation down the LBBB is followed by partial penetration up the right bundle, leading to RBBB of the subsequent beat. This represents "concealed conduction" up the right bundle (ie, not evident on the surface ECG, which solely reflects atrial and ventricular activity). This can continue for a number of consecutive beats until functional BBB resolves either despite continued short cycle length or when the cycle length lengthens. As such, AF with aberrant conduction can resemble ventricular tachycardia, and it is critical to distinguish between ventricular tachycardia and sustained aberrancy . (See 'Differential diagnosis' above.) With Wolff-Parkinson-White syndrome When AF is associated with ventricular preexcitation due to anterograde conduction down an accessory pathway in patients with Wolff- Parkinson-White syndrome (WPW), the ventricular response rate may be very rapid and may exceed 280 to 300 bpm ( waveform 20), since impulse activation bypasses the AV node. Preexcited AF is facilitated when the refractory period of the accessory pathway is very short. Accessory pathway tissue differs from that of the AV node. Specifically, the accessory pathway does not exhibit postrepolarization refractoriness but rather conducts rapidly as the tissue is dependent on sodium (rather than calcium) channel activity. Conduction down the accessory pathway typically results in a slurred QRS upstroke (ie, "delta" wave), and the QRS morphology depends on the location of the pathway and its insertion into the ventricular myocardium. The QRS complex is usually wide, with rapid activation down the accessory pathway into ventricular muscle, often in concert with some conduction down the AV node and His-Purkinje system. The more conduction proceeds through the accessory pathway, the wider and more slurred the QRS complex. (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis", section on 'Electrocardiographic findings'.) A distinguishing feature of AF with preexcitation is the relationship between heart rate and QRS duration; the faster the rate, the wider the QRS. At times, it can resemble ventricular tachycardia (based on its appearance and, often, the presence of precordial concordance). While the rhythm is irregularly irregular, variations may be difficult to measure at extremely fast rates. The clinical significance of AF with rapid ventricular response in patients with WPW is discussed separately. (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis", section on 'Ventricular fibrillation and sudden death'.) ROLE OF COMPUTER TECHNOLOGY https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 9/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Computer interpretation Each ECG computer interpretation should be overread by a trained clinician as an essential requirement for patient care and safety. Automatic computer interpretation of the ECG is common practice, with over 100 million automatic ECG interpretations yearly. Limited data are available on the accuracy of automatic computer interpretation for AF, but an estimated 10 to 30 percent of the computer ECG interpretations may misdiagnose AF, and such misdiagnosis may be frequently missed by clinicians [6,7]. Such misdiagnosis can lead to inappropriate interventions and therapies. The methodological approaches that computers utilize to determine whether or not AF is present are not well clarified. Insufficient overreading may be a growing problem as formal ECG interpretation becomes less of a focus in many training programs. Wearable consumer devices While ambulatory ECG monitoring (Holter, event, or patch- based monitors, and implantable loop recorders) is a commonly employed clinical method to detect occult AF (see "Ambulatory ECG monitoring"), there has been growing use of wearable consumer devices such as smart watches and other devices that can connect to smart phones [8,9] to monitor heart rate and rhythm [10,11]. While these widely used electronic devices have potential capabilities for detecting AF, and algorithms are improving, they are subject to limitations. Generally, the methodology (often proprietary) monitors the irregularity in ventricular response rates but does not monitor the presence and type of atrial activation. Also, some devices may require a threshold episode duration (eg, 30 seconds) to detect an arrhythmia. These limitations are likely to limit the sensitivity and specificity of these devices in detecting and diagnosing AF. Thus, all patients with suspected AF require clinician review of recordings on clinically approved ECG equipment, as described above . (See 'Our approach' above.) SUMMARY AND RECOMMENDATIONS Atrial fibrillation (AF) is diagnosed by interpretation of the 12-lead electrocardiogram (ECG). AF should be considered in patients with an irregularly irregular ventricular rhythm (or regular rhythm with fibrillatory or absent P waves). (See 'Diagnosis of atrial fibrillation' above and 'Differential diagnosis' above.) In some patients, AF is detected on ECG recordings from cardiac telemetry, ambulatory ECG monitor (eg, Holter monitor or loop recorder), or cardiac implantable electronic device (permanent pacemaker [PPM] or implantable cardioverter-defibrillator [ICD]). (See "Ambulatory ECG monitoring" and "Permanent cardiac pacing: Overview of devices and indications" and "Implantable cardioverter-defibrillators: Overview of indications, components, and functions".) https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 10/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Our approach to diagnosis of AF involves exclusion of artifact, ECG amplification (if no atrial activity is detected or the morphology of atrial activity is not well-visualized), and exclusion of AF mimics ( algorithm 1). (See 'Our approach' above and 'Differential diagnosis' above.) Common features of AF include lack of discrete P waves, presence of fibrillatory (f) waves, and irregularly irregular ventricular rhythm. QRS complexes are narrow unless there is a right or left bundle branch block, fascicular block, functional (rate-related) aberration, or antegrade conduction via an AV accessory pathway. (See 'Common findings' above.) ECG features that are uncommonly associated with AF include a regular ventricular rhythm and variable QRS morphology. (See 'Uncommon findings' above.) The differential diagnosis of AF includes artifact, atrial flutter, sinus rhythm (with sinus arrhythmia, second-degree AV block, or premature atrial complexes [PACs]), ectopic atrial rhythm, multifocal atrial tachycardia (MAT), wandering atrial pacemaker, focal atrial tachycardia with block, sinus rhythm with competing junctional rhythm, and ventricular tachycardia. (See 'Differential diagnosis' above.) Each ECG computer interpretation should be overread by a trained clinician as an essential requirement for patient care and safety. Limited data on the accuracy of automatic computer interpretation for AF suggest that 10 to 30 percent of the computer ECG interpretations may misdiagnose AF. (See 'Computer interpretation' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Pourafkari L, Baghbani-Oskouei A, Aslanabadi N, et al. Fine versus coarse atrial fibrillation in rheumatic mitral stenosis: The impact of aging and the clinical significance. Ann Noninvasive Electrocardiol 2018; 23:e12540. 2. Yilmaz MB, Guray Y, Guray U, et al. Fine vs. coarse atrial fibrillation: which one is more risky? Cardiology 2007; 107:193. 3. Li YH, Hwang JJ, Tseng YZ, et al. Clinical significance of fibrillatory wave amplitude. A clue to left atrial appendage function in nonrheumatic atrial fibrillation. Chest 1995; 108:359. 4. Fisch C, Miles WM. Deceleration-dependent left bundle branch block: a spectrum of bundle branch conduction delay. Circulation 1982; 65:1029. https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 11/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate 5. GOUAUX JL, ASHMAN R. Auricular fibrillation with aberration simulating ventricular paroxysmal tachycardia. Am Heart J 1947; 34:366. 6. Bogun F, Anh D, Kalahasty G, et al. Misdiagnosis of atrial fibrillation and its clinical consequences. Am J Med 2004; 117:636. 7. Lindow T, Kron J, Thulesius H, et al. Erroneous computer-based interpretations of atrial fibrillation and atrial flutter in a Swedish primary health care setting. Scand J Prim Health Care 2019; 37:426. 8. https://www.forbes.com/sites/paullamkin/2018/02/22/smartwatch-popularity-booms-with-fi tness-trackers-on-the-slide/#6ebca2b97d96 (Accessed on April 15, 2021). 9. http://www.pewresearch.org/fact-tank/2017/01/12/evolution-of-technology (Accessed on Ap ril 15, 2021). 10. Perez MV, Mahaffey KW, Hedlin H, et al. Large-Scale Assessment of a Smartwatch to Identify Atrial Fibrillation. N Engl J Med 2019; 381:1909. 11. D rr M, Nohturfft V, Brasier N, et al. The WATCH AF Trial: SmartWATCHes for Detection of Atrial Fibrillation. JACC Clin Electrophysiol 2019; 5:199. Topic 1014 Version 27.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 12/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate GRAPHICS Approach to diagnosis of an irregularly irregular supraventricular rhythm* This graphic describes an approach to distinguishing atrial fibrillation (identified with a thick border) from other causes of an irregularly irregular supraventricular rhythm. While atrial fibrillation is the rhythm most commonly described as irregularly irregular, mimics of atrial fibrillation should be excluded when an irregularly irregular rhythm is identified. Of note, atrial fibrillation uncommonly occurs with a regular ventricular rhythm, as described in UpToDate content on the electrocardiogram in atrial fibrillation. ECG: electrocardiogram; AV: atrioventricular; PVCs: premature ventricular complexes; PACs: premature atrial complexes. Refer to UpToDate content on distinguishing supraventricular from ventricular rhythms. https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 13/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate If no atrial activity is detected or the morphology of atrial activity is unclear, use ECG amplification (digital magnification or increase in gain for the entire ECG signal). The ventricular rhythm associated with Mobitz I or II second-degree AV block is not irregularly irregular since there is a pattern to the variation in ventricular rate, but this pattern may not be immediately recognized. Graphic 132103 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 14/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Normal sinus rhythm with artifact Normal sinus rhythm with artifact: 12-lead ECG showing sinus rhythm (best seen in lead V1) along with baseline artifact that resembles AF (most evident in leads II, III, and aVF). The best way to avoid misinterpretation of this AF mimic is to carefully review all leads of the 12-lead tracing, noting any leads with evidence of regular P waves, a consistent PR interval, and a one-to-one correspondence of P waves to QRS complexes (in this case, lead V1 along with the occasional concurrent P waves in lead II demonstrates sinus rhythm). ECG: electrocardiogram; AF: atrial fibrillation. Graphic 132168 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 15/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Normal sinus rhythm with tremor Normal sinus rhythm with tremor: Lead V1 and lead II rhythm strips show sinus rhythm, evident from typical sinus P waves in leads V1 and lead II, with superimposed 3 to 5 Hz oscillations consistent with tremor activity. Graphic 132169 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 16/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Value of increasing ECG gain with possible AF Value of increasing ECG gain with possible AF. (A) Lead V1 and lead II rhythm strips show an irregularly irregular rhythm. At first glance, the rhythm looks li with moderate ventricular response. (B) However, when the gain is increased twofold, it is now apparent that there are P waves preceding each QR th (*). Some P waves (eg, the 1 , 2 5 , 10 , 11 , 12 , and 13 P waves appear to be nonsinus, suggesting frequent atrial premature complex st nd th th th th th rd , 6 , 7 , 8 , 9 , and 14 ) appear to be sinus P waves, while the 3 , 4 th th th th th In this case, magnification of the ECG tracing facilitates recognition of a common AF mimic that could be associated with a preliminary ECG machine interpretation of AF. ECG: electrocardiogram; AF: atrial fibrillation. Graphic 132167 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 17/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate ECG atrial fibrillation Atrial fibrillation. 12-lead ECG shows an irregularly irregular rhythm. Discrete P waves are not seen, and there is fibrillatory atrial activity, best seen in lead V1. The average heart rate is 102 bpm, with a normal axis, QRS duration, and QTc interval, and with nonspecific ST-T changes. ECG: electrocardiogram; bpm: beats per minute. Graphic 132160 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 18/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial fibrillation with a slow, moderate, and rapid ventricular response Atrial fibrillation with a slow (A), moderate (B), and rapid (C) ventricular response. Lead V1 and lead II rhythm strips show irregularly irregular rhythms without discrete P waves and with fibrillatory atrial activity. Graphic 132159 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 19/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial fibrillation with left bundle branch block Atrial fibrillation with LBBB. Rhythm strip shows an irregularly irregular rhythm. Discrete P waves are not seen, and there is fibrillatory atrial activity. The QRS duration is approximately 120 ms, and a complete LBBB is seen with a QS complex in lead V1. LBBB: left bundle branch block. Graphic 132162 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 20/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial fibrillation with complete heart block AF with complete heart block. Lead V1 and lead II rhythm strips show AF with complete heart block with a na complex junctional escape rhythm (A) or with a wide complex ventricular escape rhythm (B). AF: atrial fibrillation. Graphic 132164 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 21/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial fibrillation with fully paced QRS complexes Atrial fibrillation with fully paced QRS complexes (beats 1 ,5, 6, 7, 8). Native ventricular conduction is present (beats 2, 3, 4), and there are complexes (beats 9, 10) where the pacer stimulus occurs while the native complex is being conducted, resulting in a complex that has the same morphology as the native QRS complex (pacemaker pseudofusion). Graphic 132165 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 22/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial fibrillation with ventricular tachycardia AF with ventricular tachycardia. Lead V1 and lead II rhythm strips show AF with rapid ventricular response and the onset of monomorphic ventricular tachycardia at approximately 170 bpm. AF: atrial fibrillation; bpm: beats per minute. Graphic 132166 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 23/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial flutter Atrial flutter. (A) Lead V1 and lead II ECG tracings show AFL with a moderate ventricular response and variable AV conduct with flutter waves discernable in lead II. They are uniform, and occur at a rate of 300/min. Inferiorly directed flutter waves that are positive in V1 are suggestive of typical (cavotricuspid isthmus-dependent), countercloc AFL. (B) Lead V1 and lead II ECG tracings show AFL with moderate ventricular response and variable AV conductio with flutter waves in lead II at a rate of 272 bpm, consistent with typical AFL. ECG: electrocardiogram; AFL: atrial flutter; AV: atrioventricular; bpm: beats per minute. Graphic 132170 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 24/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Sinus rhythm with sinus arrhythmia Sinus rhythm with sinus arrhythmia. Lead V1 and lead II rhythm strips show an irregular rhythm with a ventricular rate that gradually increases, and with each QRS preceded by a sinus P wave, indicating sinus rhythm with sinus arrhythmia. This can mimic AF, especially if the P wave amplitude is low. AF: atrial fibrillation. Graphic 132171 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 25/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate ECG: Sinus arrhythmia and a junctional escape rhythm Sinus arrhythmia and a junctional escape rhythm. Lead V1 and lead II rhythm strips show an irregular

ECG: electrocardiogram; AV: atrioventricular; PVCs: premature ventricular complexes; PACs: premature atrial complexes. Refer to UpToDate content on distinguishing supraventricular from ventricular rhythms. https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 13/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate If no atrial activity is detected or the morphology of atrial activity is unclear, use ECG amplification (digital magnification or increase in gain for the entire ECG signal). The ventricular rhythm associated with Mobitz I or II second-degree AV block is not irregularly irregular since there is a pattern to the variation in ventricular rate, but this pattern may not be immediately recognized. Graphic 132103 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 14/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Normal sinus rhythm with artifact Normal sinus rhythm with artifact: 12-lead ECG showing sinus rhythm (best seen in lead V1) along with baseline artifact that resembles AF (most evident in leads II, III, and aVF). The best way to avoid misinterpretation of this AF mimic is to carefully review all leads of the 12-lead tracing, noting any leads with evidence of regular P waves, a consistent PR interval, and a one-to-one correspondence of P waves to QRS complexes (in this case, lead V1 along with the occasional concurrent P waves in lead II demonstrates sinus rhythm). ECG: electrocardiogram; AF: atrial fibrillation. Graphic 132168 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 15/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Normal sinus rhythm with tremor Normal sinus rhythm with tremor: Lead V1 and lead II rhythm strips show sinus rhythm, evident from typical sinus P waves in leads V1 and lead II, with superimposed 3 to 5 Hz oscillations consistent with tremor activity. Graphic 132169 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 16/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Value of increasing ECG gain with possible AF Value of increasing ECG gain with possible AF. (A) Lead V1 and lead II rhythm strips show an irregularly irregular rhythm. At first glance, the rhythm looks li with moderate ventricular response. (B) However, when the gain is increased twofold, it is now apparent that there are P waves preceding each QR th (*). Some P waves (eg, the 1 , 2 5 , 10 , 11 , 12 , and 13 P waves appear to be nonsinus, suggesting frequent atrial premature complex st nd th th th th th rd , 6 , 7 , 8 , 9 , and 14 ) appear to be sinus P waves, while the 3 , 4 th th th th th In this case, magnification of the ECG tracing facilitates recognition of a common AF mimic that could be associated with a preliminary ECG machine interpretation of AF. ECG: electrocardiogram; AF: atrial fibrillation. Graphic 132167 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 17/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate ECG atrial fibrillation Atrial fibrillation. 12-lead ECG shows an irregularly irregular rhythm. Discrete P waves are not seen, and there is fibrillatory atrial activity, best seen in lead V1. The average heart rate is 102 bpm, with a normal axis, QRS duration, and QTc interval, and with nonspecific ST-T changes. ECG: electrocardiogram; bpm: beats per minute. Graphic 132160 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 18/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial fibrillation with a slow, moderate, and rapid ventricular response Atrial fibrillation with a slow (A), moderate (B), and rapid (C) ventricular response. Lead V1 and lead II rhythm strips show irregularly irregular rhythms without discrete P waves and with fibrillatory atrial activity. Graphic 132159 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 19/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial fibrillation with left bundle branch block Atrial fibrillation with LBBB. Rhythm strip shows an irregularly irregular rhythm. Discrete P waves are not seen, and there is fibrillatory atrial activity. The QRS duration is approximately 120 ms, and a complete LBBB is seen with a QS complex in lead V1. LBBB: left bundle branch block. Graphic 132162 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 20/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial fibrillation with complete heart block AF with complete heart block. Lead V1 and lead II rhythm strips show AF with complete heart block with a na complex junctional escape rhythm (A) or with a wide complex ventricular escape rhythm (B). AF: atrial fibrillation. Graphic 132164 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 21/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial fibrillation with fully paced QRS complexes Atrial fibrillation with fully paced QRS complexes (beats 1 ,5, 6, 7, 8). Native ventricular conduction is present (beats 2, 3, 4), and there are complexes (beats 9, 10) where the pacer stimulus occurs while the native complex is being conducted, resulting in a complex that has the same morphology as the native QRS complex (pacemaker pseudofusion). Graphic 132165 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 22/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial fibrillation with ventricular tachycardia AF with ventricular tachycardia. Lead V1 and lead II rhythm strips show AF with rapid ventricular response and the onset of monomorphic ventricular tachycardia at approximately 170 bpm. AF: atrial fibrillation; bpm: beats per minute. Graphic 132166 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 23/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial flutter Atrial flutter. (A) Lead V1 and lead II ECG tracings show AFL with a moderate ventricular response and variable AV conduct with flutter waves discernable in lead II. They are uniform, and occur at a rate of 300/min. Inferiorly directed flutter waves that are positive in V1 are suggestive of typical (cavotricuspid isthmus-dependent), countercloc AFL. (B) Lead V1 and lead II ECG tracings show AFL with moderate ventricular response and variable AV conductio with flutter waves in lead II at a rate of 272 bpm, consistent with typical AFL. ECG: electrocardiogram; AFL: atrial flutter; AV: atrioventricular; bpm: beats per minute. Graphic 132170 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 24/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Sinus rhythm with sinus arrhythmia Sinus rhythm with sinus arrhythmia. Lead V1 and lead II rhythm strips show an irregular rhythm with a ventricular rate that gradually increases, and with each QRS preceded by a sinus P wave, indicating sinus rhythm with sinus arrhythmia. This can mimic AF, especially if the P wave amplitude is low. AF: atrial fibrillation. Graphic 132171 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 25/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate ECG: Sinus arrhythmia and a junctional escape rhythm Sinus arrhythmia and a junctional escape rhythm. Lead V1 and lead II rhythm strips show an irregular rhythm that initiates with sinus rhythm with sinus arrhythmia and a gradual slowing of heart rate. When the heart rate slows below a rate of approximately 35 bpm, a junctional escape beat appears followed by an atrial premature complex (note the different P wave morphology in lead V1 compared with initial sinus beats). The variation in rate and the presence of some QRS complexes not preceded by a P wave contribute to this rhythm being incorrectly labeled as atrial fibrillation by a preliminary ECG machine interpretation. ECG: electrocardiogram; bpm: beats per minute. Graphic 132172 Version 3.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 26/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Normal sinus rhythm with Mobitz I second-degree AV block Normal sinus rhythm with Mobitz I second-degree AV block. Lead V1 and lead II rhythm strips show a regularly irregular rhythm with group beat. There are distinct P waves before each QRS as well as during the relative pauses. The P-P interval is constant, consistent with a sinus rhythm at a rate of 80 bpm. There is progressive prolongation of the PR interval followed by a dropped beat (nonconducted sinus P wave), reflective of Mobitz I second-degree AV block. AV: atrioventricular; bpm: beats per minute. Graphic 132173 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 27/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Normal sinus rhythm with an ectopic atrial rhythm Normal sinus rhythm with an ectopic atrial rhythm. Lead V1 and lead II rhythm strips show a somewhat irregular narrow QRS complex rhythm that starts off (first 3 beats) with sinus P waves, which then shift to a different (nonsinus) focus, evident by the change in P wave morphology in subsequent beats. Graphic 132174 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 28/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial tachycardia with block Atrial tachycardia with block. Lead V1 and lead II rhythm strips show regular atrial activity at a rate of 160 bpm with variable AV block, consistent with atrial tachycardia with AV block. bpm: beats per minute; AV: atrioventricular. Graphic 132175 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 29/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Wandering atrial pacemaker Wandering atrial pacemaker. Lead V1 and lead II rhythm strips show an irregularly irregular rhythm. On close examination there are more than 3 different P wave morphologies preceding each QRS complex. As the rate is <100 beats per minute, the rhythm is wandering atrial pacemaker (rather than multifocal atrial tachycardia). Graphic 132176 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 30/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Multifocal atrial tachycardia Multifocal atrial tachycardia. Lead V1 and lead II rhythm strips show an irregularly irregular narrow QRS complex rhythm that, on first glance, looks like AF with rapid ventricular response. On closer examination, there are P waves preceding each QRS complex, and, overall, there are more than 3 different P wave morphologies, consistent with the diagnosis of multifocal atrial tachycardia. AF: atrial fibrillation. Graphic 132177 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 31/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Sinus rhythm with frequent PACs with aberrant conduction Sinus rhythm with frequent PACs with aberrant conduction. st rd th th th th (A) Lead V1 and lead II rhythm strips show sinus rhythm with the 1 , 3 , 5 , 7 , 9 , and 11 beats preced t by normal sinus P waves. The 2 nd th th th th th th , 4 , 6 , 8 , 10 , and 12 beats are all PACs. However, while the 4 , 10 th nd th th th and 12 beats conduct normally, the 2 aberrant conduction with a RBBB morphology evident in lead V1. In lead II, the aberrantly conducted PACs ha similar appearance to normally conducted PACs except for a deep terminal S wave and some QRS widening d to the rate-related RBBB. , 6 , 8 , and 12 beats conduct with a wide QRS complex due to rd (B) Lead V1 and lead II rhythm strips show sinus rhythm with a PAC with aberrant conduction (3 beat) and w an interpolated PVC (8 beat). th PACs: premature atrial complexes; RBBB: right bundle branch block; PVC: premature ventricular complex. Graphic 132178 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 32/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate AF with aberrant conduction and concealed conduction AF with aberrant conduction and concealed conduction. Lead V1 and lead II rhythm strips show AF with th rapid ventricular response. Note that the 5 and 6 QRS complexes, as well as the 18 and the 20 to th th th th the 30 QRS complexes, are wide with a right bundle branch pattern apparent in lead V1, while the QRS complexes for these beats in lead II are similar to native AF beats. These are all aberrantly conducted beats. th While the initial or isolated aberrant beats (5 , 18 , and 20 ) occur after a relative long-short interval th th th st th (Ashman phenomenon), the subsequent beats (6 and 21 to 30 ) occur with a short-short sequence but are aberrant due to concealed conduction. For more detail, refer to UpToDate content on the electrocardiogram in atrial fibrillation. AF: Atrial fibrillation. Graphic 132179 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 33/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate AF with Wolff-Parkinson-White syndrome AF with Wolff-Parkinson-White syndrome. 12-lead ECG showing AF with preexcitation. There is an irregular, wide-complex tachycardia, with many QRS complexes showing a slurred upstroke (delta wave). At times, the ventricular rate can be as high as 300 bpm. AF: atrial fibrillation; ECG: electrocardiogram; bpm: beats per minute. Reproduced with permission from: Nathanson LA, McClennen S, Safran C, Goldberger AL. ECG Wave-Maven: Self-Assessment Program for Students and Clinicians. Copyright 2021 Beth Israel Deaconess Medical Center. Available at: http://ecg.bidmc.harvard.edu (Accessed on August 2, 2021). Graphic 132180 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 34/35 7/5/23, 10:18 AM The electrocardiogram in atrial fibrillation - UpToDate Contributor Disclosures Brian Olshansky, MD Other Financial Interest: AstraZeneca [Member of the DSMB for the DIALYZE trial]; Medtelligence [Cardiovascular disease]. All of the relevant financial relationships listed have been mitigated. Zachary D Goldberger, MD, FACC, FHRS Other Financial Interest: Elsevier [Book royalties from Goldberger s Clinical Electrocardiography]. All of the relevant financial relationships listed have been mitigated. Steven M Pogwizd, MD No relevant financial relationship(s) with ineligible companies to disclose. Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 35/35

7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. The management of atrial fibrillation in patients with heart failure : Brian Olshansky, MD : Wilson S Colucci, MD, Bradley P Knight, MD, FACC : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Sep 30, 2022. INTRODUCTION Atrial fibrillation (AF) is common among patients with heart failure (HF). This topic will focus on the acute and long-term management and prognosis of AF in patients with HF, including those with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). Our recommendations are similar to those made in the 2014 American Heart Association/American College of Cardiology/Heart Rhythm Society guideline, its 2019 focused update, the 2021 guideline for AF management in HFrEF, and the joint European Heart Rhythm Association/Heart Failure Association consensus document on AF [1-5]. The general management of patients with HFrEF and HFpEF is discussed separately: (See "Overview of the management of heart failure with reduced ejection fraction in adults".) (See "Treatment and prognosis of heart failure with preserved ejection fraction".) The management of AF in HF for patients with specific cardiomyopathies and valvular disease are discussed separately: Hypertrophic cardiomyopathy. (See "Hypertrophic cardiomyopathy in adults: Supraventricular tachycardias including atrial fibrillation", section on 'Treatment'.) Amyloid cardiomyopathy. (See "Amyloid cardiomyopathy: Treatment and prognosis".) https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 1/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate Valvular heart disease. (See "Rheumatic mitral stenosis: Overview of management", section on 'Management of atrial fibrillation' and "Medical management of asymptomatic aortic stenosis in adults", section on 'Atrial fibrillation' and "Indications for intervention for chronic severe primary mitral regurgitation".) EPIDEMIOLOGY The prevalence of AF in patients with HF varies from less than 10 to 57 percent, depending in part upon the severity of HF [6-11]. For instance, the prevalence of AF increases from 4 to 50 percent as the New York Heart Association functional class increases from I to IV [12-19]. (See "Predictors of survival in heart failure with reduced ejection fraction", section on 'NYHA functional class'.) However, AF was recently associated with heart failure with reduced ejection fraction (HFrEF) and HF with preserved EF (HFpEF) events, with no significant difference in the strength of association among these subtypes, and many comorbidities (eg, anemia, renal failure, hypertension, valvular disease, coronary artery disease, etc) may also contribute to the development of AF in HF patients [20]. The presence of either HF or AF increases the likelihood that the other will develop over time [21]. The temporal associations of AF and HF were studied in over 10,000 individuals in the Framingham Heart Study [22]: Among 1737 persons with new AF, 37 percent had HF. Among 1166 persons with new HF, 57 percent had AF. Of these, 41 percent had HFpEF and 44 percent had HFrEF (15 percent could not be classified). The presence of both AF and HF predicted greater mortality risk compared with having neither condition, particularly among individuals with HFrEF. (See 'Prognosis' below.) In the investigation from the Framingham Heart Study, prevalent AF was more strongly associated with incident HFpEF than HFrEF (hazard ratios [HRs] 2.34 versus 1.48) [21]. However, a more recent study of over 25,000 participants in the REGARDS cohort did not show differential associations between AF and the development of HFpEF compared with HFrEF (HR 1.87 and 1.67 respectively, p interaction = 0.58) [20]. MECHANISMS OF CARDIAC DYSFUNCTION https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 2/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate AF can impair myocardial function by multiple mechanisms that cause or worsen HF [23]. (See "Hemodynamic consequences of atrial fibrillation and cardioversion to sinus rhythm".) Specific mechanisms include: Tachycardia, bradycardia, abrupt heart rate change, and irregular rhythm may decrease cardiac output. Persistent tachycardia may lead to arrhythmia-induced cardiomyopathy or can worsen a preexisting cardiomyopathy [24-26]. (See "Arrhythmia-induced cardiomyopathy" and "Arrhythmia-induced cardiomyopathy", section on 'Atrial fibrillation and atrial flutter'.) Loss of atrial systole prevents optimal ventricular filling. Patients with diastolic HF are especially symptomatic in AF since left ventricular (LV) filling is more dependent on atrial contraction. (See "Pathophysiology of heart failure with preserved ejection fraction".) AF can lead to maladaptive vasoconstriction from angiotensin II, norepinephrine, and other procoagulant biochemicals. The left atrial remodeling that occurs in AF can lead to atrial fibrosis, dilation and dysfunction (this is sometimes referred to as an atriopathy ). This can cause mitral and/or tricuspid regurgitation, which exacerbate HF. HF is also a risk factor for AF, possibly mediated by left atrial stretch. (See "Mechanisms of atrial fibrillation", section on 'Triggers of AF'.) GOALS OF THERAPY For patients with AF and HF, we set the following goals of therapy: Manage acute HF exacerbation Control symptoms; prevent cardiac dysfunction and subsequent HF and/or hemodynamic compromise Prevent arterial thromboembolism, particularly stroke Reduce mortality and cardiac hospitalization ACUTE DECOMPENSATION The general approach to managing acute HF decompensation with AF involves anticoagulation, treating the acute HF exacerbation, rate control to <120 beats per minute, correction of https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 3/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate reversible causes, and (only in rare instances) cardioversion. To manage acute decompensated HF with uncontrolled rates in AF, hospitalization is generally required. AF can precede an acute HF exacerbation, and uncontrolled HF can accelerate the ventricular response of AF or precipitate AF in patients in sinus rhythm. Symptoms Patients can present with sudden pulmonary congestion and an increase in the ventricular rate of AF, causing palpitations and shortness of breath and hypotension leading to dizziness or even syncope. Anticoagulation Prior to or concurrent with treating the acute HF exacerbation, we anticoagulate patients with AF and HF; if the patient has acute HF symptoms, we prioritize HF treatment. Because of the high risk of thromboembolism in these patients, we anticoagulate irrespective of ejection fraction (EF), whether or not a long-term rate or rhythm control management strategy is employed, and even if patient has a CHA DS -VASc score of 1 [27]. 2 2 However, if a patient has contraindications to anticoagulation such as a high risk of bleeding, we do not anticoagulate them. (See "Atrial fibrillation in adults: Selection of candidates for anticoagulation".) In addition, effective anticoagulation is required prior to, during, and after cardioversion, whether it be pharmacological or electrical. Details regarding anticoagulation and the role of transesophageal echocardiography prior to cardioversion in patients with AF are discussed separately. (See "Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation".) Acute heart failure management We treat HF with diuretics, vasodilators, and other measures as appropriate. This is discussed separately. (See "Treatment of acute decompensated heart failure: Specific therapies", section on 'Initial therapy'.) As part of acute HF management in patients with AF, we also slow the ventricular response. Acute rate control We aim to reduce the ventricular rate to <120 beats per minute. We do not rate control to lower ventricular rates until the acute HF exacerbation is stabilized, as patients may need a higher heart rate to maintain their cardiac output. Our specific approach to acute rate control differs for patients with HFrEF and HFpEF. HF with reduced EF (HFrEF) For patients with HFrEF, we use intravenous (IV) amiodarone, IV digoxin, (and rarely IV diltiazem) to acutely control the heart rate. After starting the medication, we continually reassess the heart rate and titrate the medication https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 4/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate to achieve the goal heart rate of <120 beats per minute. Usually, we try the medication for one to two days, and if the heart rate remains elevated, we attempt another agent. The choice of medications is usually influenced by practitioner familiarity. Amiodarone has very little negative inotropic activity and is usually more effective than digoxin. However, amiodarone and IV diltiazem can both cause hypotension. Amiodarone is associated with conversion to sinus rhythm in a small percent of patients, which is of concern if the patient is not anticoagulated. We usually avoid diltiazem due to its negative inotropic effect that might further compromise cardiac contractility. (See "Amiodarone: Clinical uses".) Amiodarone dosing for AF rate control in all patients and among critically ill patients is presented separately. Dosing is similar for AF in patients with HF. (See "Amiodarone: Clinical uses", section on 'Ventricular rate control in critically ill patients with atrial fibrillation and rapid ventricular response'.) Digoxin dosing for AF rate control usually includes IV loading followed by a maintenance oral dose. Oral loading is also possible. (See "Treatment with digoxin: Initial dosing, monitoring, and dose modification", section on 'Rapid digoxin loading'.) Diltiazem dosing in the acute setting is discussed separately. We generally avoid beta blocker therapy in patients with AF and acute decompensated HF. In such patients, the negative inotropic properties of a beta blocker may worsen the clinical condition. The use of beta blockers for long-term control of heart rate in AF is discussed separately. (See "Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy", section on 'Urgent therapy' and 'Rate control in heart failure with reduced ejection fraction' below and 'Rate control in heart failure with preserved ejection fraction' below and "Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy".) HF with preserved EF (HFpEF) In HFpEF patients who present with congestion or hypotension, rate control can be attempted first with IV diltiazem (which may be better tolerated in patients with borderline hypotension) or IV beta blockade. We consider these agents to be equally effective at rate control of AF in patients with HFpEF. With both medications, hypotension is a potential side effect. Diltiazem dosing in the acute setting is discussed separately. For the acute control of ventricular rate, IV beta blockade with metoprolol, propranolol, or esmolol can be effective. Specific dosing information for these medications is presented separately. Specific dosing information is discussed separately. https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 5/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate Correction of reversible causes In some patients, there is a reversible cause of AF, HF, or both. These are reviewed separately. (See "Pathophysiology of heart failure with preserved ejection fraction", section on 'Decompensated HFpEF' and "Overview of the management of heart failure with reduced ejection fraction in adults", section on 'Management of causes and associated conditions' and "Atrial fibrillation: Overview and management of new-onset atrial fibrillation", section on 'Triggers'.) Etiologies that are specific to AF and HF include: If a patient with existing AF develops new HF, a possible diagnosis to consider is arrythmia- induced cardiomyopathy from inadequate rate control. (See "Arrhythmia-induced cardiomyopathy".) If a patient develops new-onset AF and HF concurrently, thyrotoxicosis should be considered as a diagnostic possibility. (See "Cardiovascular effects of hyperthyroidism", section on 'Heart failure' and "Cardiovascular effects of hyperthyroidism", section on 'Atrial fibrillation'.) Role of cardioversion We rarely consider an initial cardioversion for treatment of patients with acute decompensated HF; there is a low probability of successful or durable cardioversion unless the HF decompensation is first corrected. However, cardioversion (generally electrical) may be helpful in the following circumstances: Initial attempts to decrease pulmonary congestion with diuretics, vasodilators, and rate control have failed. AF is thought to be the cause of acute HF decompensation, ie, the onset of AF has recently preceded the HF exacerbation. In such patients, even if the rate is well controlled, cardioversion may be helpful in managing HF. Patients with persistent evidence of myocardial ischemia. This scenario assumes that the patient does not require urgent reperfusion or other stabilizing therapies for acute coronary syndrome. (See "Overview of the acute management of ST-elevation myocardial infarction", section on 'Choosing and initiating reperfusion with PCI or fibrinolysis' and "Overview of the acute management of non-ST-elevation acute coronary syndromes", section on 'Choosing a revascularization strategy'.) In patients with HFpEF, it can be difficult to tell if the HF is predominantly due to AF or some other cause. https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 6/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate An important potential harm of cardioversion in this setting is the risk of a thromboembolic event in nonanticoagulated patients. We almost always avoid cardioversion (even in patients with hemodynamic instability or cardiogenic shock) if the patient is not adequately anticoagulated (ie, has not been on therapeutic, uninterrupted, chronic anticoagulation for at least one month prior). For patients in whom urgent cardioversion is being considered despite inadequate anticoagulation, a transesophageal echocardiogram should be considered to evaluate for a left atrial or left atrial appendage thrombus. (See 'Anticoagulation' above and "Role of echocardiography in atrial fibrillation", section on 'Transesophageal echocardiography'.) We avoid cardioversion in patients with long-standing persistent or permanent AF, who have failed cardioversion, or who have had early recurrence of AF after cardioversion with additional antiarrhythmic therapy. LONG-TERM MANAGEMENT Long-term anticoagulation We continue anticoagulation that was started during acute management, transitioning to oral anticoagulation as appropriate. If anticoagulation was not started during the acute management phase, and if there are no contraindications, we start anticoagulation. Because of the high risk of thromboembolism in these patients, we anticoagulate irrespective of ejection fraction (EF), whether or not a long-term rate or rhythm control management strategy is employed, and even if a patient has a CHA DS -VASc score of 1 2 2 [27]. (See "Atrial fibrillation in adults: Use of oral anticoagulants".) Novel oral anticoagulants, instead of warfarin, are often used for effective anticoagulation. There is increased risk of bleeding when these anticoagulants are used concomitantly with amiodarone or other medications [28-31]. Preference for rhythm over rate control Although the first management approach in acute decompensated AF with HF is often rate control, rhythm control is our preferred long-term management strategy for most patients. This includes patients with recent-onset AF, persistent HF even when rate controlled, or inadequate rate control. (See 'Acute decompensation' above.) Potential exceptions to this approach are noted below. (See 'Exceptions' below.) Evidence for cardiovascular benefit Specific reasons for returning the patient to sinus rhythm are to establish a symptom-rhythm correlation; this helps to establish if AF is a specific trigger or contributing factor for a patient's HF symptoms and/or worsening HF. A return to sinus rhythm can also improve cardiac function, increase exercise tolerance, and alleviate HF symptoms. https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 7/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate Some evidence suggests that early rhythm control (ie, within one year) is beneficial for improved five-year cardiovascular outcomes in patients with HF (either HF with preserved EF [HFpEF] or reduced EF [HFrEF]). In a prespecified subanalysis of the EAST-AFNET 4 randomized trial, over 750 patients with symptomatic HF were randomly assigned to early rhythm control or usual care (which included rhythm control for symptoms) [32]. The following was observed: The composite outcome of cardiovascular death, stroke, or hospitalization for HF or acute coronary syndrome occurred less often in patients in the early rhythm control versus usual care group (5.7 versus 7.9 per 100 patient-years; hazard ratio [HR] 0.74, 95% CI 0.56-0.97). Kaplan-Meier curves showed that event rates in the two treatment groups began to separate at six months. The two treatment groups had similar rates of all-cause mortality (9.9 versus 11.8 percent). Left ventricular EF (LVEF) improved in both groups (approximately 5 percent increase). The primary safety outcome (death, stroke, or serious adverse events related to rhythm control therapy) was similar between treatment groups (17.9 versus 21.6 percent, HR 0.85, 95% CI 0.62-1.17). Some limitations of EAST-AFNET 4 should be mentioned. The usual care assigned to the control group in EAST-AFNET 4 may not be generalizable, as it may not reflect standard treatment of AF in patients with HF. Also, patients assigned to rhythm control received a variety of therapies; only 19 percent received catheter ablation (CA). In the subsequent RAFT-AF trial, results were similar, although the trial was stopped early for futility and did not have statistically significant findings. Four hundred and eleven patients with HF and a high burden of AF were randomly assigned to either CA-based rhythm control or rate control and followed for mortality and HF events [33]. Patients assigned to rhythm control had a lower mortality and HF events compared with the rate control group, but the results were not statistically significant (23.4 versus 32.5 percent; HR 0.71, 95% CI 0.49-1.03). Patients in the rhythm control group also had greater improvements in LVEF (increase of 10 versus 4 percent), six-minute walk test, and HF- and AF-related quality of life. The CA-related adverse event rate was high at 11 percent. An additional limitation of this study was the lack of statistical power to detect a potential protective effect of therapy; the study was unable to recruit the anticipated number of participants due to restrictions on clinical research during the COVID-19 pandemic. Four small randomized trials, each with methodological limitations, and one observational study have compared CA with rate control in patients with HF and also found benefit [34-38]. (See "Atrial fibrillation: Catheter ablation", section on 'Efficacy' and 'Catheter ablation' below.) https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 8/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate A previous trial (AF-CHF) did not find a significant benefit for long-term pharmacologic rhythm control compared with rate control in patients with HFrEF and AF [39,40]. It is important to recognize that CA was not a strategy tested in the AF-CHF trial, whereas 19 percent of patients in the rhythm control arm had CA in the EAST-AFNET 4 trial. Furthermore, in AF-CHF, the patients all had severe LV systolic dysfunction. These key differences may underline why the results in AF- CHF were null in contrast to the EAST-AFNET 4 trial described above, in which early rhythm control was beneficial. Exceptions A rate control strategy may be preferred in patients with longstanding AF or severe left atrial enlargement. In these cases, the cardioversion is much less likely to be successful or durable. Also, for patients with severe valvular disease (such as severe mitral regurgitation), cardioversion is less likely to be successful in maintaining sinus rhythm and reducing symptoms. A rate control strategy may also be reasonable in an older patient who is unwilling to undergo the burdens of a rhythm control strategy, particularly if they tolerate AF well. Some patients will not want to be placed on antiarrhythmic medications or undergo invasive procedures. In these patients, a rate control strategy may be pursued. If a patient has a contraindication to anticoagulation, a rate control strategy may also be preferred. Heart failure with reduced ejection fraction Rhythm control Conversion to and maintenance of sinus rhythm can be achieved with electrical cardioversion, antiarrhythmic drug therapy, CA, or surgical ablation [21]. Generally, we approach attempts at rhythm control in a step-wise fashion as outlined in the sections that follow. (See 'Preference for rhythm over rate control' above.) Rhythm control is less effective in patients with persistent AF (which is common among patients with HF) or with severe left atrial enlargement (a marker of AF chronicity). Electrical cardioversion For nearly all patients, we first try electrical cardioversion (this can be done in conjunction with antiarrhythmic medication, which can increase the likelihood of maintaining sinus rhythm, or it can be performed without such a medication). We generally perform the initial electrical cardioversion without an antiarrhythmic medication if this is the first episode of AF, if AF is well tolerated, if HF is not difficult to manage, and if there is no hemodynamically significant mitral regurgitation or left atrial enlargement. Patients require appropriate anticoagulation prior to, during, and after cardioversion. (See 'Anticoagulation' above.) https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 9/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate Electrical cardioversion is not appropriate in those who have short episodes of paroxysmal AF and for those in whom HF exacerbation is unlikely to be due to the AF. However, we use cardioversion if paroxysmal AF episodes last days, if there is precipitous change in condition, and if patients do not respond to an antiarrhythmic drug. After initial cardioversion, the majority of patients will have recurrent AF unless it was due to an acute precipitant that is no longer present (eg, acute pulmonary edema, myocardial infarction, pulmonary embolus, cardiac surgery). If a patient reverts to AF after cardioversion, we may try another cardioversion, this time with an antiarrhythmic medication (initiated prior to cardioversion) in order to help the patient maintain sinus rhythm. In some patients, we attempt cardioversion multiple times. Considerations include the likelihood of maintaining sinus rhythm, the time course of AF recurrence, patient symptom burden, and need for improvement of patient hemodynamics. We also try to balance these with the patient's overall preference to be in sinus rhythm. For example, if AF seems to be related to acute HF decompensation or other adverse event, repeat cardioversions are appropriate. If repeat cardioversions are not successful, we may use antiarrhythmic drugs and/or CA to maintain sinus rhythm. Antiarrhythmic drugs In nearly all patients with HFrEF who have recurrent AF after cardioversion, we use an antiarrhythmic drug to help maintain sinus rhythm or to facilitate cardioversion if the cardioversion is not successful in achieving sinus rhythm. We always ensure the patient is appropriately anticoagulated. (See 'Anticoagulation' above.) We use dofetilide, sotalol, or amiodarone as the initial antiarrhythmic medication in patients with persistent AF and HF. Some experts prefer to try dofetilide first, especially in patients who are younger and have preserved kidney dysfunction. Other experts prefer to use amiodarone, given its ease of use. Dofetilide is more likely to cause the potentially life-threatening ventricular arrhythmia "torsades de pointes" in patients with HF with severe systolic dysfunction than amiodarone and in those with acute decompensation. Therefore, dofetilide is safer to use in patients with HF and milder systolic dysfunction, as well as those patients who have an implantable cardiac defibrillator, as these devices can prevent sudden cardiac arrest from ventricular arrhythmia. Prior to using dofetilide, during its initiation, and subsequent to initiation, measurements of QT intervals are necessary. (See "Clinical use of dofetilide", section on 'Safety' and "Acquired long QT syndrome: Definitions, pathophysiology, and causes".) Sotalol can worsen HF in those with HFrEF due to the beta-blocking effects and is not recommended for patients with markedly impaired LV function and acute decompensated https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 10/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate HF. Sotalol can cause the potentially life-threatening arrythmia torsade de pointes, and thus prior to using the drug and after it is initiated, measurements of QT intervals are necessary. If the baseline QTc is greater than 450 msec, sotalol is contraindicated. Other details regarding sotalol initiation and QTc monitoring are discussed separately. (See "Clinical uses of sotalol", section on 'Dosing' and "Clinical uses of sotalol", section on 'Proarrhythmia'.) We avoid propafenone, dronedarone, and flecainide because of worse outcomes in HFrEF patients. The following provides evidence for the efficacy of specific pharmacotherapy in AF and HF: Dofetilide Dofetilide, a class III antiarrhythmic drug, can be effective and safe for preventing recurrent persistent AF in patients with HF. It may also be used to convert patients to sinus rhythm. The recommended dose of dofetilide is 500 micrograms twice daily in the absence of renal insufficiency, but it is adjusted based on renal function. Patients need to be hospitalized for dofetilide initiation. Further information regarding the initiation protocol and safety of dofetilide is discussed separately. (See "Clinical use of dofetilide".) In the DIAMOND-CHF trial, 390 patients with AF and symptomatic HF were randomly assigned to dofetilide or placebo [41]. Dofetilide was more likely to be associated with conversion to sinus rhythm at one month (12 versus 1 percent) and maintenance of sinus rhythm at one year (44 versus 13 percent; HR 0.35, 95% CI 0.22-0.57). Mortality did not differ between treatment groups (41 versus 42 percent; HR 0.95, 95% CI 0.81-1.11). In a separate investigation, among 500 patients with HFrEF and AF in the DIAMOND-HF and DIAMOND-MI studies, dofetilide was more likely than placebo to lead to conversion to sinus rhythm (59 versus 34 percent) and to maintain sinus rhythm at one year (79 versus 42 percent; relative risk 0.30, 95% CI 0.19-0.48) [42]. (See "Clinical use of dofetilide".) The most important side effect of dofetilide was torsades de pointes, which was seen in 25 cases (3.3 percent); three-quarters of episodes occurred within the first three days while the patient was in the hospital [42]. (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes", section on 'Definitions'.) Amiodarone When used for preventing recurrence of AF, advantages of low-dose amiodarone include no negative inotropic effect and little or no proarrhythmia. Advantages of amiodarone compared with dofetilide include the ability to start therapy as an outpatient (for AF), once-a-day dosing, and a lower risk of torsades de pointes. In addition, https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 11/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate since amiodarone has non-competitive beta-blocking and calcium channel antagonist activity, the ventricular rate is usually slow and well tolerated if AF does recur. The recommended dose of amiodarone is 400 mg/day. Occasionally, less than 200 mg/day is used (eg, for patients at high risk of side effects or toxicities). (See "Amiodarone: Adverse effects, potential toxicities, and approach to monitoring", section on 'Adverse drug interactions'.) Its use in HF patients does not necessarily require hospitalization, but careful monitoring of the prothrombin time international normalized ratio is necessary, as amiodarone can potentiate the effects of warfarin. (See "Amiodarone: Adverse effects, potential toxicities, and approach to monitoring", section on 'Adverse drug interactions'.) The efficacy of amiodarone in AF and HF was illustrated in a subset analysis from the CHF- STAT trial of over 660 patients in which 15 percent of patients had AF at baseline [43]. Among these 103 patients, 51 were randomly assigned to amiodarone and 52 to placebo. Patients assigned to amiodarone had a higher likelihood of converting to sinus rhythm (31 versus 8 percent). Patients who converted to sinus rhythm with amiodarone had a lower mortality than those who did not. However, it is not clear if reductions in mortality were because patients who converted were less sick to begin with or if restoration of sinus rhythm was causative. Complications associated with amiodarone loading and long-term therapy in patients with HFrEF and AF include bradycardia requiring permanent pacemaker, hypothyroidism, and neurotoxicity [44]. Side effects with maintenance therapy are less likely with lower doses but still occur. Sotalol Sotalol should be used with caution in patients with HF who have poor LV function (LVEF <30 percent) based on increased risk for torsades de pointes [45]. This is especially true if there are marked fluctuations in electrolyte levels, acute or decompensated HF, or renal dysfunction. (See "Drugs that should be avoided or used with caution in patients with heart failure", section on 'Antiarrhythmic agents' and "Clinical uses of sotalol", section on 'Heart failure'.) Sotalol can be used if the QT is not prolonged, if there is no renal dysfunction, if there are normal electrolytes (specifically normal potassium), if there is no acute decompensation, and if the LVEF is no more than modestly impaired (ie, if LVEF is >30 percent). However, sotalol can cause marked bradycardia and worsen HF in HFrEF in some instances. https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 12/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate Beta blockers Chronic beta blocker therapy may reduce the likelihood of development of AF in patients with HF due to systolic dysfunction. Likewise, in people with paroxysmal AF, beta blockers may help maintain sinus rhythm. Using beta blockers as antiarrhythmic therapy can serve a dual purpose because these medications are also an important component of optimal medical therapy for HF. (See "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Clinical trials", section on 'Beta blockers'.) Medications we do not suggest using in AF and HF patients include: Dronedarone In general, dronedarone has no role in the management of AF in a HF patient. In particular, dronedarone should not be used in patients with New York Heart Association class III to IV HF or LV systolic dysfunction (LVEF <0.40), as efficacy is low, and safety is a concern. It should also not be used in patients with longstanding persistent AF. This recommendation is consistent with that made by the European Medicines Agency in September of 2011 and the U S Food and Drug Administration in December of 2011. Strong evidence for an adverse effect of dronedarone use in patients with HFrEF comes from the ANDROMEDA trial (patients in this study had an LVEF 35 percent) [46] . The trial was discontinued early due to a significant increase in the incidence of death in the patients assigned to dronedarone versus placebo (8.1 versus 3.8 percent; HR 2.13, 95% CI 1.07-4.25). The primary cause of death among patients receiving dronedarone was worsening HF [46]. Dronedarone is likely less efficacious than amiodarone at AF rhythm control [47]. (See "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Clinical trials", section on 'Dronedarone'.) Class IC drugs Class IC drugs (flecainide, propafenone) are associated with an increased risk for proarrhythmia and sudden cardiac death and should not be used in patients with AF and HF ( table 1). Ibutilide We do not use this medication in decompensated HF due to the substantial risks of torsades de pointes. (See "Therapeutic use of ibutilide", section on 'Proarrhythmia'.) Catheter ablation For patients with symptomatic AF who have HFrEF that is not decompensated and recurrent AF despite electrical cardioversion and antiarrhythmic drug therapy (or side effect or intolerance to antiarrhythmic therapy), we perform CA of AF rather than continued attempts at cardioversion with or without antiarrhythmic drug therapy. In some patients, repeat CA is pursued if the first CA is unsuccessful. (See "Maintenance of sinus rhythm in atrial fibrillation: Catheter ablation versus antiarrhythmic drug therapy".) https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 13/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate Rarely, if a patient has a contraindication to all antiarrhythmic medications and there is new AF and/or paroxysmal AF, we will pursue CA as the initial therapy. An example is a patient with HF and AF who has a contraindication to dofetilide and/or sotalol (eg, kidney disease, a long QT interval) and propensity to develop amiodarone toxicity (eg, underlying thyroid, lung, or liver disease). Patients HFrEF and AF who are unlikely to benefit from CA If the patient has one or more of the following factors, they may be unsuitable for CA: Some patients with advanced HF (including those with LV assist device destination therapy or on ionotropic support). Severe comorbidities or medical instability. Patients asymptomatic on optimal HF therapy. Longstanding AF that is unrelated to progressive symptoms or concerns. Older-aged persons including those with frailty. We do not generally perform CA in persons >age 80 years of age. Markedly enlarged left atrial size and longstanding persistent and drug-resistant AF. There is no evidence that suggests a specific left atrial dimension cut point beyond which CA may not be useful. Patients with complete heart block (either spontaneous or related to an atrioventricular node ablation) and permanent ventricular pacing. If the patient is deemed unsuitable for CA for one or more of these reasons and has failed other attempts at rhythm control, we pursue a rate control strategy. (See 'Rate control in heart failure with reduced ejection fraction' below.) Efficacy of CA versus medical therapy The CASTLE-AF trial randomly assigned 363 patients with implantable cardioverter-defibrillators, symptomatic paroxysmal or persistent AF, New York Heart Association class II or higher, and an LVEF 35 percent to CA or medical therapy [48]. Death from any cause or hospitalization for HF occurred in fewer patients in the CA compared with medical therapy group (29 versus 45 percent; HR 0.62; 95% CI 0.43- 0.87). The time in AF was also lower with CA versus medical therapy (25 versus 60 percent). Several important limitations of the CASTLE-AF trial include patients lost to follow-up (particularly in the group assigned implantable cardioverter-defibrillator), lack of blinding, small sample size, and limited generalizability given that 85 percent of participants were https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 14/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate male (females have less successful CAs) and that all patients had defibrillators and/or cardiac resynchronization therapy. A greater number of patients in the ablation group than in the medical therapy group crossed over to the other treatment group (15.6 versus 9.8). Finally, although medical therapy (for both AF and HF) was managed per study protocol, it is possible that a nontraditional or more aggressive approach to medical management might have influenced the trial results. In a 2019 meta-analysis of six trials (775 patients), of which CASTLE-AF was the largest [49], CA reduced all-cause mortality compared with drug therapy (9 versus 18 percent). Studies have also shown that CA can increase exercise ability, LVEF, quality of life, and is associated with a decrease in pro-brain natriuretic peptide levels [34,36,37,50]. Efficacy of CA versus atrioventricular node ablation with biventricular pacing In a randomized trial of 81 patients with HF and symptomatic, drug-refractory AF, CA was associated with modest improvements in LVEF (35 versus 28 percent), six-minute walk distance (340 versus 297 meters), and score on the Minnesota Living With Heart Failure questionnaire [35]. The role of atrioventricular ablation and biventricular pacing in patients with AF is discussed in detail elsewhere. (See 'Atrioventricular node ablation with pacing' below and "Cardiac resynchronization therapy in atrial fibrillation", section on 'Cardiac resynchronization therapy outcomes in patients with atrial fibrillation'.) Rate control in heart failure with reduced ejection fraction Indications We pursue a rate control strategy for patients in whom rhythm control is not tolerated or has been unsuccessful. A rate control strategy is sometimes the preferred initial

heart failure", section on 'Antiarrhythmic agents' and "Clinical uses of sotalol", section on 'Heart failure'.) Sotalol can be used if the QT is not prolonged, if there is no renal dysfunction, if there are normal electrolytes (specifically normal potassium), if there is no acute decompensation, and if the LVEF is no more than modestly impaired (ie, if LVEF is >30 percent). However, sotalol can cause marked bradycardia and worsen HF in HFrEF in some instances. https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 12/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate Beta blockers Chronic beta blocker therapy may reduce the likelihood of development of AF in patients with HF due to systolic dysfunction. Likewise, in people with paroxysmal AF, beta blockers may help maintain sinus rhythm. Using beta blockers as antiarrhythmic therapy can serve a dual purpose because these medications are also an important component of optimal medical therapy for HF. (See "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Clinical trials", section on 'Beta blockers'.) Medications we do not suggest using in AF and HF patients include: Dronedarone In general, dronedarone has no role in the management of AF in a HF patient. In particular, dronedarone should not be used in patients with New York Heart Association class III to IV HF or LV systolic dysfunction (LVEF <0.40), as efficacy is low, and safety is a concern. It should also not be used in patients with longstanding persistent AF. This recommendation is consistent with that made by the European Medicines Agency in September of 2011 and the U S Food and Drug Administration in December of 2011. Strong evidence for an adverse effect of dronedarone use in patients with HFrEF comes from the ANDROMEDA trial (patients in this study had an LVEF 35 percent) [46] . The trial was discontinued early due to a significant increase in the incidence of death in the patients assigned to dronedarone versus placebo (8.1 versus 3.8 percent; HR 2.13, 95% CI 1.07-4.25). The primary cause of death among patients receiving dronedarone was worsening HF [46]. Dronedarone is likely less efficacious than amiodarone at AF rhythm control [47]. (See "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Clinical trials", section on 'Dronedarone'.) Class IC drugs Class IC drugs (flecainide, propafenone) are associated with an increased risk for proarrhythmia and sudden cardiac death and should not be used in patients with AF and HF ( table 1). Ibutilide We do not use this medication in decompensated HF due to the substantial risks of torsades de pointes. (See "Therapeutic use of ibutilide", section on 'Proarrhythmia'.) Catheter ablation For patients with symptomatic AF who have HFrEF that is not decompensated and recurrent AF despite electrical cardioversion and antiarrhythmic drug therapy (or side effect or intolerance to antiarrhythmic therapy), we perform CA of AF rather than continued attempts at cardioversion with or without antiarrhythmic drug therapy. In some patients, repeat CA is pursued if the first CA is unsuccessful. (See "Maintenance of sinus rhythm in atrial fibrillation: Catheter ablation versus antiarrhythmic drug therapy".) https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 13/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate Rarely, if a patient has a contraindication to all antiarrhythmic medications and there is new AF and/or paroxysmal AF, we will pursue CA as the initial therapy. An example is a patient with HF and AF who has a contraindication to dofetilide and/or sotalol (eg, kidney disease, a long QT interval) and propensity to develop amiodarone toxicity (eg, underlying thyroid, lung, or liver disease). Patients HFrEF and AF who are unlikely to benefit from CA If the patient has one or more of the following factors, they may be unsuitable for CA: Some patients with advanced HF (including those with LV assist device destination therapy or on ionotropic support). Severe comorbidities or medical instability. Patients asymptomatic on optimal HF therapy. Longstanding AF that is unrelated to progressive symptoms or concerns. Older-aged persons including those with frailty. We do not generally perform CA in persons >age 80 years of age. Markedly enlarged left atrial size and longstanding persistent and drug-resistant AF. There is no evidence that suggests a specific left atrial dimension cut point beyond which CA may not be useful. Patients with complete heart block (either spontaneous or related to an atrioventricular node ablation) and permanent ventricular pacing. If the patient is deemed unsuitable for CA for one or more of these reasons and has failed other attempts at rhythm control, we pursue a rate control strategy. (See 'Rate control in heart failure with reduced ejection fraction' below.) Efficacy of CA versus medical therapy The CASTLE-AF trial randomly assigned 363 patients with implantable cardioverter-defibrillators, symptomatic paroxysmal or persistent AF, New York Heart Association class II or higher, and an LVEF 35 percent to CA or medical therapy [48]. Death from any cause or hospitalization for HF occurred in fewer patients in the CA compared with medical therapy group (29 versus 45 percent; HR 0.62; 95% CI 0.43- 0.87). The time in AF was also lower with CA versus medical therapy (25 versus 60 percent). Several important limitations of the CASTLE-AF trial include patients lost to follow-up (particularly in the group assigned implantable cardioverter-defibrillator), lack of blinding, small sample size, and limited generalizability given that 85 percent of participants were https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 14/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate male (females have less successful CAs) and that all patients had defibrillators and/or cardiac resynchronization therapy. A greater number of patients in the ablation group than in the medical therapy group crossed over to the other treatment group (15.6 versus 9.8). Finally, although medical therapy (for both AF and HF) was managed per study protocol, it is possible that a nontraditional or more aggressive approach to medical management might have influenced the trial results. In a 2019 meta-analysis of six trials (775 patients), of which CASTLE-AF was the largest [49], CA reduced all-cause mortality compared with drug therapy (9 versus 18 percent). Studies have also shown that CA can increase exercise ability, LVEF, quality of life, and is associated with a decrease in pro-brain natriuretic peptide levels [34,36,37,50]. Efficacy of CA versus atrioventricular node ablation with biventricular pacing In a randomized trial of 81 patients with HF and symptomatic, drug-refractory AF, CA was associated with modest improvements in LVEF (35 versus 28 percent), six-minute walk distance (340 versus 297 meters), and score on the Minnesota Living With Heart Failure questionnaire [35]. The role of atrioventricular ablation and biventricular pacing in patients with AF is discussed in detail elsewhere. (See 'Atrioventricular node ablation with pacing' below and "Cardiac resynchronization therapy in atrial fibrillation", section on 'Cardiac resynchronization therapy outcomes in patients with atrial fibrillation'.) Rate control in heart failure with reduced ejection fraction Indications We pursue a rate control strategy for patients in whom rhythm control is not tolerated or has been unsuccessful. A rate control strategy is sometimes the preferred initial strategy in a subset of patients as outlined above. (See 'Exceptions' above.) Among patients with HF, rate control to prevent rapid AF usually leads to an improvement in symptoms. Slowing of the ventricular rate often leads to a moderate or even marked improvement in LV function [9,25,26]. (See 'mechanisms of cardiac dysfunction' above.) Rate control goal The broad goal of rate control is to minimize symptoms with exercise and rest. Thus, the adequacy of rate control should be assessed in both circumstances [21]. (See "Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy".) The optimal heart rate in patients with AF and HF has not been well studied and is not certain. Our authors generally start with a heart rate goal of <85 beats per minute at rest and <110 beats per minute during moderate exercise (the strict approach). If this is not possible, the goal becomes <110 beats per minute at rest (the lenient approach). https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 15/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate In a symptomatic patient in whom the ventricular rate varies markedly with minimal changes in activity, a rhythm control strategy may be necessary. Medications Although we prefer to use just one rate-slowing medication, sometimes more than one medication is required to achieve adequate heart rate control. When titrating therapy, we measure the patient's ventricular rates at rest and with moderate exertion. (See 'Rate control goal' above.) Beta blocker We usually select a beta blocker as first therapy due to their superior safety profile in both AF and HF. We would avoid starting a beta blocker if the patient had decompensated HF. Most patients with preexisting HFrEF are already on a beta blocker for treatment of HF, and if possible, we increase the dosage of their medication. The alternatives of digoxin (lesser efficacy) and amiodarone (more side effects) have significant limitations. We start with carvedilol, extended-release metoprolol succinate, or bisoprolol. The doses should be optimized before considering a second agent. These drugs are discussed in detail separately. (See "Primary pharmacologic therapy for heart failure with reduced ejection fraction", section on 'Evidence' and "Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy", section on 'Elective and long-term management' and "Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy".) Carvedilol is started at an oral dose of 3.125 mg twice daily. The usual dosage range is 3.125 to 25 mg twice daily but may be titrated higher for the purpose of treating HFrEF (up to 25 to 50 mg, depending on the patient's weight). A possible adverse effect of carvedilol is hypotension since this beta blocker also has alpha-adrenergic-receptor- blocking action [51]. Metoprolol succinate is started at an oral dose of 25 mg daily. This can be titrated up to a target dose of 200 mg daily in patients with HFrEF. Even if AF rate control is achieved at lower doses, the target for metoprolol succinate is higher for HFrEF. Bisoprolol is started at an oral dose of 2.5 mg once daily; the dose is increased gradually as tolerated to achieve ventricular rate control, and in patients with HFrEF, the target dose is 10 mg daily. Beta blockers have been shown to improve symptoms but not survival in AF and HF. In a meta-analysis of AF patients in 11 randomized trials of over 3000 patients, beta blockers reduced the ventricular rate (by 12 beats per minute) but did not decrease mortality when https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 16/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate compared with placebo (overall death rate 20 percent; HR 0.96, 95% CI 0.81-1.12) [52]. This finding was consistent with a prior study [53]. Digoxin In patients who cannot receive a beta blocker or are not adequately rate controlled despite their maximal-tolerated dose, and in whom rhythm control will not be attempted, digoxin may be considered. This may be relevant for patients with decompensated HF, in whom initiation or increase of beta blockers is contraindicated. If such a patient also has rapid AF requiring rate control, use of digoxin is suggested. However, digoxin is often ineffective when used alone. If two drugs are needed to control for long-term rate, we suggest adding digoxin to a beta blocker. Dosing and administration of digoxin are described separately. (See "Treatment with digoxin: Initial dosing, monitoring, and dose modification" and "Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy".) Amiodarone In the event of inadequate rate control with beta blockers and/or digoxin, amiodarone can be used either alone or in combination with other rate control medications. We do not generally use amiodarone as a long-term rate control medication, but in the acute setting, it can assist with rate control as it is being loaded or can be used as a temporary rate control agent in patients who are unable to tolerate other therapies [43]. We exercise care when using amiodarone, especially in those without adequate anticoagulation since there is the possibility of pharmacologically restoring sinus rhythm. The usual maintenance dose of amiodarone from AF is 100 to 200 mg daily after a loading dose. Therapies that should be avoided for AF rate control and HFrEF include dronedarone, class IC drugs, and nondihydropyridine calcium channel blockers (verapamil and diltiazem). (See "Calcium channel blockers in heart failure with reduced ejection fraction" and "Drugs that should be avoided or used with caution in patients with heart failure".) Atrioventricular node ablation with pacing Rate control can also be achieved with radiofrequency ablation of the atrioventricular node and permanent pacemaker placement. This strategy may be useful in patients in whom rate control with antiarrhythmic drug or CA has failed or is contraindicated. Atrioventricular node ablation with pacing can be particularly helpful for patients with permanent AF. (See "Atrial fibrillation: Atrioventricular node ablation".) https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 17/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate If the LVEF is 45 percent or less and there is an expectation that ventricular pacing will occur more than 25 percent of the time, a biventricular, His bundle, or left bundle pacing system (also called cardiac resynchronization therapy) should be considered instead of a standard right ventricular pacing system. (See "Atrial fibrillation: Atrioventricular node ablation", section on 'Cardiac resynchronization therapy'.) In addition, atrioventricular node ablation may be necessary for some patients with HF and AF who are referred for cardiac resynchronization therapy for treatment of HF. This is because intact atrioventricular conduction may "override" pace and thus reduce efficacy of the cardiac resynchronization therapy device. In particular, atrioventricular node ablation may be beneficial for patients who are not pacing at least 90 percent with cardiac resynchronization therapy [54]. (See "Cardiac resynchronization therapy in atrial fibrillation", section on 'Role of atrioventricular node ablation in patients with heart failure and atrial fibrillation'.) Left bundle or His bundle pacing have also become options, although randomized controlled clinical trials have yet to definitively demonstrate an advantage of this approach versus a cardiac resynchronization therapy approach. Heart failure with preserved ejection fraction Our long-term management approach to patients with AF and HFpEF is similar to that of patients with AF and HFrEF. The main differences are with respect to the choice of specific rhythm and rate control medications. Rhythm control Rhythm control is the preferred long-term strategy for most patients. (See 'Evidence for cardiovascular benefit' above.) Antiarrhythmic therapy and CA approaches are similar in HFpEF and HFrEF. Some medication such as dofetilide and sotalol tend to have fewer complications in patients with preserved LVEF (See 'Rhythm control' above.) The efficacy and safety of CA have been evaluated in patients with diastolic HF. A meta-analysis of 12 retrospective cohort studies confirmed the safety of CA for patients with HFpEF; over a one- to three-year follow up, complications occurred in <1 percent of patients [55]. Fifty-eight percent of patients maintained sinus rhythm without using an antiarrhythmic medication. Admission for HF and all-cause mortality each occurred in 6 percent of patients. Rate control in heart failure with preserved ejection fraction For patients with AF and HFpEF, we attempt to maintain a resting heart rate of 80 bpm or less ("strict rate control"). Whereas some data indicate that faster rates may be acceptable (lenient rate control), this is not generally recommended. Exceptions include: https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 18/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate A patient with paroxysmal AF with frequent episodes of fast AF and slow, symptomatic rates when in sinus rhythm. A patient with permanent AF who is asymptomatic with resting rates as fast as 110 beats per minute. However, this group of patients has not been well studied. We typically start with a beta blocker. (See 'Medications' above.) In patients with HFpEF (but not HFrEF), we use a nondihydropyridine calcium channel blocker if a beta blocker is not tolerated. We use digoxin cautiously in HFpEF, but it can be helpful in combination with a beta blocker to control ventricular response rate, especially in older patients. Other strategies are similar to rate control strategies in patients with AF and HFrEF. (See 'Rate control in heart failure with reduced ejection fraction' above.) PROGNOSIS Observational studies present conflicting data as to whether AF is an independent predictor of mortality in patients with HF [6-8,56-59]. Most were performed several years ago and may not be as generalizable to current patients. However, two more recent studies suggest AF may be associated with increased mortality among patients with HF. A meta-analysis of 16 studies with nearly 54,000 patients showed that among patients with HF, AF was associated with modestly increased mortality (odds ratio of 1.4 among seven randomized trials of HF therapy; 1.15 among nine observational studies) [60]. A registry study of nearly one million patients with HF suggested that new-onset AF was associated with worse mortality than long-standing AF, over a follow-up period of over 13 years [61]. In this analysis, patients who developed new-onset AF had greater mortality than patients with long-standing AF (59 versus 49 percent). Among persons with HF and AF compared with persons with neither condition, the adjusted odds of death was 8.76 (95% CI 8.31 9.23). A post-hoc analysis of a beta blocker trial of nearly 2400 participants with HF showed that new- onset AF (in 190 patients) predicted worse HF-related outcomes [62]. In this study, participants with new-onset AF were at a higher risk of HF mortality (28 versus 23 percent, HR 2.0, 95% CI 1.50-2.67) and had more HF hospitalization days (average of 15 versus 7 days per patient) than those who did not develop AF. SOCIETY GUIDELINE LINKS https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 19/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Atrial fibrillation" and "Society guideline links: Arrhythmias in adults" and "Society guideline links: Heart failure in adults".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and Beyond the Basics. th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on patient info and the keyword(s) of interest.) Basics topic (see "Patient education: Heart failure and atrial fibrillation (The Basics)") SUMMARY AND RECOMMENDATIONS Background and epidemiology Comorbid atrial fibrillation (AF) and heart failure (HF) is common. The prevalence of AF in patients with HF increases from 4 to 50 percent as HF functional class declines. (See 'Introduction' above and 'Epidemiology' above.) AF can impair myocardial atrial and ventricular function, which can both cause and worsen HF. (See 'mechanisms of cardiac dysfunction' above.) Acute management In all patients, we anticoagulate (irrespective of ejection fraction [EF] or whether a long-term rate or rhythm control management strategy is employed), treat acute HF decompensation with diuretics and vasodilators, and correct potential reversible causes of AF and HF. (See 'Acute decompensation' above.) In patients with AF and acute HF, we target rate control to <120 beats per minute; digoxin, amiodarone, and diltiazem are appropriate agents in this setting. (See 'Acute rate control' above.) https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 20/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate Cardioversion is rarely employed in the setting of AF with acute HF decompensation. (See 'Role of cardioversion' above.) Long-term management For most patients with AF and compensated HF, we suggest rhythm rather than rate control as an initial treatment strategy (Grade 2B). (See 'Long-term management' above.) A rate control strategy may be preferred in patients with long-standing AF or severe left atrial enlargement, as cardioversion is less likely to be successful or durable in these patients. A rate control strategy may also be reasonable for those unwilling to undergo the burdens of a rhythm control strategy, particularly if they tolerate AF well. (See 'Preference for rhythm over rate control' above and 'Rhythm control' above.) We employ a stepwise approach, including the following: Long-term anticoagulation Patients require anticoagulation prior to, during, and after electrical or pharmacologic cardioversion and catheter ablation (CA). (See "Atrial fibrillation in adults: Use of oral anticoagulants".) Cardioversion After acute stabilization, for nearly all patients with AF and HF, we suggest electrical cardioversion as initial treatment (Grade 2C). This can be done without an antiarrhythmic medication if this is the first episode of AF, AF is well tolerated, HF is not difficult to manage, and there is no hemodynamically significant mitral regurgitation or left atrial enlargement. (See 'Electrical cardioversion' above.) Antiarrhythmics For patients who return to persistent AF after electrical cardioversion or fail cardioversion, we suggest dofetilide (Grade 2C). Contraindications to dofetilide include QT prolongation, potassium fluctuations, and renal dysfunction. Amiodarone is a reasonable alternative for older individuals and sotalol for patients with mild renal dysfunction. (See 'Rhythm control' above.) Catheter ablation For patients with symptomatic AF who have HF without acute decompensation, and failure of antiarrhythmic drug therapy, we suggest CA of AF (Grade 2B). This recommendation assumes that the patient is a reasonable candidate. (See 'Catheter ablation' above.) Rate control If a rate control strategy is chosen in patients with HF with reduced EF (HFrEF), we recommend beta blockers rather than calcium channel blockers or digoxin as initial therapy (Grade 1B). (See 'Rate control in heart failure with reduced ejection fraction' above.) https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 21/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate We also suggest beta blocker therapy for rate control in patients with HF with preserved EF (HFpEF) (Grade 2C). Nondihydropyridine calcium channel blocker therapy is an alternative in patients with HFpEF who cannot tolerate or do not respond to beta blocker therapy. We use a heart rate goal of <85 beats per minute at rest and <110 beats per minute during moderate exercise (the strict approach). If this is not possible, the goal becomes <110 beats per minute at rest (the lenient approach). Lenient rate control goal is used more in patients with HFpEF. (See 'Rate control goal' above.) Atrioventricular node ablation with pacing For patients who fail a rate control strategy using medication and are either not candidates for or have failed a rhythm control strategy, atrioventricular node ablation with pacing is an effective therapeutic option. (See 'Atrioventricular node ablation with pacing' above and "Atrial fibrillation: Atrioventricular node ablation".) Prognosis AF is associated with an increased mortality and increased risk of HF progression. (See 'Prognosis' above.) ACKNOWLEDGMENT The UpToDate editorial staff thank Dr. Alan Cheng for his contributions as an author to prior versions of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Lip GY, Heinzel FR, Gaita F, et al. 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Predictors of primary atrial fibrillation and concomitant clinical and hemodynamic changes in patients with chronic heart failure: a prospective study in 344 patients with baseline sinus rhythm. J Am Coll Cardiol 1998; 32:197. 24. Grogan M, Smith HC, Gersh BJ, Wood DL. Left ventricular dysfunction due to atrial fibrillation in patients initially believed to have idiopathic dilated cardiomyopathy. Am J Cardiol 1992; 69:1570. 25. Kieny JR, Sacrez A, Facello A, et al. Increase in radionuclide left ventricular ejection fraction after cardioversion of chronic atrial fibrillation in idiopathic dilated cardiomyopathy. Eur Heart J 1992; 13:1290. 26. Redfield MM, Kay GN, Jenkins LS, et al. Tachycardia-related cardiomyopathy: a common cause of ventricular dysfunction in patients with atrial fibrillation referred for atrioventricular ablation. Mayo Clin Proc 2000; 75:790. 27. Sobue Y, Watanabe E, Lip GYH, et al. Thromboembolisms in atrial fibrillation and heart failure patients with a preserved ejection fraction (HFpEF) compared to those with a reduced https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 24/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate ejection fraction (HFrEF). Heart Vessels 2018; 33:403. 28. Li A, Li MK, Crowther M, Vazquez SR. Drug-drug interactions with direct oral anticoagulants associated with adverse events in the real world: A systematic review. Thromb Res 2020; 194:240. 29. Mar PL, Gopinathannair R, Gengler BE, et al. Drug Interactions Affecting Oral Anticoagulant Use. Circ Arrhythm Electrophysiol 2022; 15:e007956. 30. Chang SH, Chou IJ, Yeh YH, et al. Association Between Use of Non-Vitamin K Oral Anticoagulants With and Without Concurrent Medications and Risk of Major Bleeding in Nonvalvular Atrial Fibrillation. JAMA 2017; 318:1250. 31. Hill K, Sucha E, Rhodes E, et al. Amiodarone, Verapamil, or Diltiazem Use With Direct Oral Anticoagulants and the Risk of Hemorrhage in Older Adults. CJC Open 2022; 4:315. 32. Rillig A, Magnussen C, Ozga AK, et al. Early Rhythm Control Therapy in Patients With Atrial Fibrillation and Heart Failure. Circulation 2021; 144:845. 33. Parkash R, Wells GA, Rouleau J, et al. Randomized Ablation-Based Rhythm-Control Versus Rate-Control Trial in Patients With Heart Failure and Atrial Fibrillation: Results from the RAFT-AF trial. Circulation 2022; 145:1693. 34. Jones DG, Haldar SK, Hussain W, et al. A randomized trial to assess catheter ablation versus rate control in the management of persistent atrial fibrillation in heart failure. J Am Coll Cardiol 2013; 61:1894. 35. Khan MN, Ja s P, Cummings J, et al. Pulmonary-vein isolation for atrial fibrillation in patients with heart failure. N Engl J Med 2008; 359:1778. 36. Hunter RJ, Berriman TJ, Diab I, et al. A randomized controlled trial of catheter ablation versus medical treatment of atrial fibrillation in heart failure (the CAMTAF trial). Circ Arrhythm Electrophysiol 2014; 7:31. 37. Prabhu S, Taylor AJ, Costello BT, et al. Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction: The CAMERA-MRI Study. J Am Coll Cardiol 2017; 70:1949. 38. Joy PS, Gopinathannair R, Olshansky B. Effect of Ablation for Atrial Fibrillation on Heart Failure Readmission Rates. Am J Cardiol 2017; 120:1572. 39. Roy D, Talajic M, Nattel S, et al. Rhythm control versus rate control for atrial fibrillation and heart failure. N Engl J Med 2008; 358:2667. 40. Suman-Horduna I, Roy D, Frasure-Smith N, et al. Quality of life and functional capacity in patients with atrial fibrillation and congestive heart failure. J Am Coll Cardiol 2013; 61:455. https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 25/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate 41. Torp-Pedersen C, M ller M, Bloch-Thomsen PE, et al. Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group. N Engl J Med 1999; 341:857. 42. Pedersen OD, Bagger H, Keller N, et al. Efficacy of dofetilide in the treatment of atrial fibrillation-flutter in patients with reduced left ventricular function: a Danish investigations of arrhythmia and mortality on dofetilide (diamond) substudy. Circulation 2001; 104:292. 43. Deedwania PC, Singh BN, Ellenbogen K, et al. Spontaneous conversion and maintenance of sinus rhythm by amiodarone in patients with heart failure and atrial fibrillation: observations from the veterans affairs congestive heart failure survival trial of antiarrhythmic therapy (CHF-STAT). The Department of Veterans Affairs CHF-STAT Investigators. Circulation 1998; 98:2574. 44. Weinfeld MS, Drazner MH, Stevenson WG, Stevenson LW. Early outcome of initiating amiodarone for atrial fibrillation in advanced heart failure. J Heart Lung Transplant 2000; 19:638. 45. Lehmann MH, Hardy S, Archibald D, et al. Sex difference in risk of torsade de pointes with d,l-sotalol. Circulation 1996; 94:2535. 46. K ber L, Torp-Pedersen C, McMurray JJ, et al. Increased mortality after dronedarone therapy for severe heart failure. N Engl J Med 2008; 358:2678. 47. Piccini JP, Hasselblad V, Peterson ED, et al. Comparative efficacy of dronedarone and amiodarone for the maintenance of sinus rhythm in patients with atrial fibrillation. J Am Coll Cardiol 2009; 54:1089. 48. Marrouche NF, Brachmann J, Andresen D, et al. Catheter Ablation for Atrial Fibrillation with Heart Failure. N Engl J Med 2018; 378:417. 49. Turagam MK, Garg J, Whang W, et al. Catheter Ablation of Atrial Fibrillation in Patients With Heart Failure: A Meta-analysis of Randomized Controlled Trials. Ann Intern Med 2019; 170:41. 50. Anselmino M, Matta M, D'Ascenzo F, et al. Catheter ablation of atrial fibrillation in patients with left ventricular systolic dysfunction: a systematic review and meta-analysis. Circ Arrhythm Electrophysiol 2014; 7:1011. 51. Taniguchi T, Ohtani T, Mizote I, et al. Switching from carvedilol to bisoprolol ameliorates adverse effects in heart failure patients with dizziness or hypotension. J Cardiol 2013; 61:417. 52. Kotecha D, Flather MD, Altman DG, et al. Heart Rate and Rhythm and the Benefit of Beta- Blockers in Patients With Heart Failure. J Am Coll Cardiol 2017; 69:2885. https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 26/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate 53. Rienstra M, Damman K, Mulder BA, et al. Beta-blockers and outcome in heart failure and atrial fibrillation: a meta-analysis. JACC Heart Fail 2013; 1:21. 54. Gasparini M, Regoli F, Galimberti P, et al. Cardiac resynchronization therapy in heart failure patients with atrial fibrillation. Europace 2009; 11 Suppl 5:v82. 55. Androulakis E, Sohrabi C, Briasoulis A, et al. Catheter Ablation for Atrial Fibrillation in Patients with Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta- Analysis. J Clin Med 2022; 11. 56. Wang TJ, Larson MG, Levy D, et al. Temporal relations of atrial fibrillation and congestive heart failure and their joint influence on mortality: the Framingham Heart Study. Circulation 2003; 107:2920.

reduced versus preserved ejection fraction. Heart 2022; 108:353. 21. Cha YM, Redfield MM, Shen WK, Gersh BJ. Atrial fibrillation and ventricular dysfunction: a vicious electromechanical cycle. Circulation 2004; 109:2839. 22. Santhanakrishnan R, Wang N, Larson MG, et al. Atrial Fibrillation Begets Heart Failure and Vice Versa: Temporal Associations and Differences in Preserved Versus Reduced Ejection Fraction. Circulation 2016; 133:484. 23. Pozzoli M, Cioffi G, Traversi E, et al. Predictors of primary atrial fibrillation and concomitant clinical and hemodynamic changes in patients with chronic heart failure: a prospective study in 344 patients with baseline sinus rhythm. J Am Coll Cardiol 1998; 32:197. 24. Grogan M, Smith HC, Gersh BJ, Wood DL. Left ventricular dysfunction due to atrial fibrillation in patients initially believed to have idiopathic dilated cardiomyopathy. Am J Cardiol 1992; 69:1570. 25. Kieny JR, Sacrez A, Facello A, et al. Increase in radionuclide left ventricular ejection fraction after cardioversion of chronic atrial fibrillation in idiopathic dilated cardiomyopathy. Eur Heart J 1992; 13:1290. 26. Redfield MM, Kay GN, Jenkins LS, et al. Tachycardia-related cardiomyopathy: a common cause of ventricular dysfunction in patients with atrial fibrillation referred for atrioventricular ablation. Mayo Clin Proc 2000; 75:790. 27. Sobue Y, Watanabe E, Lip GYH, et al. Thromboembolisms in atrial fibrillation and heart failure patients with a preserved ejection fraction (HFpEF) compared to those with a reduced https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 24/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate ejection fraction (HFrEF). Heart Vessels 2018; 33:403. 28. Li A, Li MK, Crowther M, Vazquez SR. Drug-drug interactions with direct oral anticoagulants associated with adverse events in the real world: A systematic review. Thromb Res 2020; 194:240. 29. Mar PL, Gopinathannair R, Gengler BE, et al. Drug Interactions Affecting Oral Anticoagulant Use. Circ Arrhythm Electrophysiol 2022; 15:e007956. 30. Chang SH, Chou IJ, Yeh YH, et al. Association Between Use of Non-Vitamin K Oral Anticoagulants With and Without Concurrent Medications and Risk of Major Bleeding in Nonvalvular Atrial Fibrillation. JAMA 2017; 318:1250. 31. Hill K, Sucha E, Rhodes E, et al. Amiodarone, Verapamil, or Diltiazem Use With Direct Oral Anticoagulants and the Risk of Hemorrhage in Older Adults. CJC Open 2022; 4:315. 32. Rillig A, Magnussen C, Ozga AK, et al. Early Rhythm Control Therapy in Patients With Atrial Fibrillation and Heart Failure. Circulation 2021; 144:845. 33. Parkash R, Wells GA, Rouleau J, et al. Randomized Ablation-Based Rhythm-Control Versus Rate-Control Trial in Patients With Heart Failure and Atrial Fibrillation: Results from the RAFT-AF trial. Circulation 2022; 145:1693. 34. Jones DG, Haldar SK, Hussain W, et al. A randomized trial to assess catheter ablation versus rate control in the management of persistent atrial fibrillation in heart failure. J Am Coll Cardiol 2013; 61:1894. 35. Khan MN, Ja s P, Cummings J, et al. Pulmonary-vein isolation for atrial fibrillation in patients with heart failure. N Engl J Med 2008; 359:1778. 36. Hunter RJ, Berriman TJ, Diab I, et al. A randomized controlled trial of catheter ablation versus medical treatment of atrial fibrillation in heart failure (the CAMTAF trial). Circ Arrhythm Electrophysiol 2014; 7:31. 37. Prabhu S, Taylor AJ, Costello BT, et al. Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction: The CAMERA-MRI Study. J Am Coll Cardiol 2017; 70:1949. 38. Joy PS, Gopinathannair R, Olshansky B. Effect of Ablation for Atrial Fibrillation on Heart Failure Readmission Rates. Am J Cardiol 2017; 120:1572. 39. Roy D, Talajic M, Nattel S, et al. Rhythm control versus rate control for atrial fibrillation and heart failure. N Engl J Med 2008; 358:2667. 40. Suman-Horduna I, Roy D, Frasure-Smith N, et al. Quality of life and functional capacity in patients with atrial fibrillation and congestive heart failure. J Am Coll Cardiol 2013; 61:455. https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 25/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate 41. Torp-Pedersen C, M ller M, Bloch-Thomsen PE, et al. Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group. N Engl J Med 1999; 341:857. 42. Pedersen OD, Bagger H, Keller N, et al. Efficacy of dofetilide in the treatment of atrial fibrillation-flutter in patients with reduced left ventricular function: a Danish investigations of arrhythmia and mortality on dofetilide (diamond) substudy. Circulation 2001; 104:292. 43. Deedwania PC, Singh BN, Ellenbogen K, et al. Spontaneous conversion and maintenance of sinus rhythm by amiodarone in patients with heart failure and atrial fibrillation: observations from the veterans affairs congestive heart failure survival trial of antiarrhythmic therapy (CHF-STAT). The Department of Veterans Affairs CHF-STAT Investigators. Circulation 1998; 98:2574. 44. Weinfeld MS, Drazner MH, Stevenson WG, Stevenson LW. Early outcome of initiating amiodarone for atrial fibrillation in advanced heart failure. J Heart Lung Transplant 2000; 19:638. 45. Lehmann MH, Hardy S, Archibald D, et al. Sex difference in risk of torsade de pointes with d,l-sotalol. Circulation 1996; 94:2535. 46. K ber L, Torp-Pedersen C, McMurray JJ, et al. Increased mortality after dronedarone therapy for severe heart failure. N Engl J Med 2008; 358:2678. 47. Piccini JP, Hasselblad V, Peterson ED, et al. Comparative efficacy of dronedarone and amiodarone for the maintenance of sinus rhythm in patients with atrial fibrillation. J Am Coll Cardiol 2009; 54:1089. 48. Marrouche NF, Brachmann J, Andresen D, et al. Catheter Ablation for Atrial Fibrillation with Heart Failure. N Engl J Med 2018; 378:417. 49. Turagam MK, Garg J, Whang W, et al. Catheter Ablation of Atrial Fibrillation in Patients With Heart Failure: A Meta-analysis of Randomized Controlled Trials. Ann Intern Med 2019; 170:41. 50. Anselmino M, Matta M, D'Ascenzo F, et al. Catheter ablation of atrial fibrillation in patients with left ventricular systolic dysfunction: a systematic review and meta-analysis. Circ Arrhythm Electrophysiol 2014; 7:1011. 51. Taniguchi T, Ohtani T, Mizote I, et al. Switching from carvedilol to bisoprolol ameliorates adverse effects in heart failure patients with dizziness or hypotension. J Cardiol 2013; 61:417. 52. Kotecha D, Flather MD, Altman DG, et al. Heart Rate and Rhythm and the Benefit of Beta- Blockers in Patients With Heart Failure. J Am Coll Cardiol 2017; 69:2885. https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 26/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate 53. Rienstra M, Damman K, Mulder BA, et al. Beta-blockers and outcome in heart failure and atrial fibrillation: a meta-analysis. JACC Heart Fail 2013; 1:21. 54. Gasparini M, Regoli F, Galimberti P, et al. Cardiac resynchronization therapy in heart failure patients with atrial fibrillation. Europace 2009; 11 Suppl 5:v82. 55. Androulakis E, Sohrabi C, Briasoulis A, et al. Catheter Ablation for Atrial Fibrillation in Patients with Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta- Analysis. J Clin Med 2022; 11. 56. Wang TJ, Larson MG, Levy D, et al. Temporal relations of atrial fibrillation and congestive heart failure and their joint influence on mortality: the Framingham Heart Study. Circulation 2003; 107:2920. 57. Crijns HJ, Tjeerdsma G, de Kam PJ, et al. Prognostic value of the presence and development of atrial fibrillation in patients with advanced chronic heart failure. Eur Heart J 2000; 21:1238. 58. Olsson LG, Swedberg K, Ducharme A, et al. Atrial fibrillation and risk of clinical events in chronic heart failure with and without left ventricular systolic dysfunction: results from the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) program. J Am Coll Cardiol 2006; 47:1997. 59. Wasywich CA, Whalley GA, Gamble GD, et al. Does rhythm matter? The prognostic importance of atrial fibrillation in heart failure. Heart Lung Circ 2006; 15:353. 60. Mamas MA, Caldwell JC, Chacko S, et al. A meta-analysis of the prognostic significance of atrial fibrillation in chronic heart failure. Eur J Heart Fail 2009; 11:676. 61. Ziff OJ, Carter PR, McGowan J, et al. The interplay between atrial fibrillation and heart failure on long-term mortality and length of stay: Insights from the, United Kingdom ACALM registry. Int J Cardiol 2018; 252:117. 62. Aleong RG, Sauer WH, Davis G, Bristow MR. New-onset atrial fibrillation predicts heart failure progression. Am J Med 2014; 127:963. Topic 977 Version 71.0 https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 27/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate GRAPHICS Revised (2018) Vaughan Williams classification of antiarrhythmic drugs abridged table Class 0 (HCN channel blockers) Ivabradine Class I (voltage-gated Na+ channel blockers) Class Ia (intermediate dissociation): Quinidine, ajmaline, disopyramide, procainamide Class Ib (rapid dissociation): Lidocaine, mexilitine Class Ic (slow dissociation): Propafenone, flecainide Class Id (late current): Ranolazine Class II (autonomic inhibitors and activators) Class IIa (beta blockers): Nonselective: carvedilol, propranolol, nadolol Selective: atenolol, bisoprolol, betaxolol, celiprolol, esmolol, metoprolol Class IIb (nonselective beta agonists): Isoproterenol Class IIc (muscarinic M2 receptor inhibitors): Atropine, anisodamine, hyoscine, scopolamine Class IId (muscarinic M2 receptor activators): Carbachol, pilocarpine, methacholine, digoxin Class IIe (adenosine A1 receptor activators): Adenosine Class III (K+ channel blockers and openers) Class IIIa (voltage dependent K+ channel blockers): https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 28/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate Ambasilide, amiodarone, dronedarone, dofetilide, ibutilide, sotalol, vernakalant Class IIIb (metabolically dependent K+ channel openers): Nicorandil, pinacidil Class IV (Ca++ handling modulators) Class IVa (surface membrane Ca++ channel blockers): Bepridil, diltiazem, verapamil Class IVb (intracellular Ca++ channel blockers): Flecainide, propafenone Class V (mechanosensitive channel blockers): No approved medications Class VI (gap junction channel blockers) No approved medications Class VII (upstream target modulators) Angiotensin converting enzyme inhibitors Angiotensin receptor blockers Omega-3 fatty acids Statins HCN: hyperpolarization-activated cyclic nucleotide-gated; Na: sodium; K: potassium; Ca: calcium. Graphic 120433 Version 3.0 https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 29/30 7/5/23, 10:19 AM The management of atrial fibrillation in patients with heart failure - UpToDate Contributor Disclosures Brian Olshansky, MD Other Financial Interest: AstraZeneca [Member of the DSMB for the DIALYZE trial]; Medtelligence [Cardiovascular disease]. All of the relevant financial relationships listed have been mitigated. Wilson S Colucci, MD Grant/Research/Clinical Trial Support: Merck [Heart failure]. All of the relevant financial relationships listed have been mitigated. Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/the-management-of-atrial-fibrillation-in-patients-with-heart-failure/print 30/30

7/5/23, 10:19 AM The role of pacemakers in the prevention of atrial fibrillation - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. The role of pacemakers in the prevention of atrial fibrillation : Rod Passman, MD, MSCE : Bradley P Knight, MD, FACC : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Jun 14, 2022. INTRODUCTION The principal reason to place a pacemaker in a patient with atrial fibrillation (AF) is to treat symptomatic bradycardia. Pacing has not been shown to prevent the development of AF. This topic will review the role of pacemakers in the prevention of AF. Brief mention will be given to implantable cardioverter defibrillators. The utility of other nonpharmacologic strategies for preventing AF is discussed separately. (See "Atrial fibrillation: Catheter ablation" and "Atrial fibrillation: Surgical ablation".) PATIENTS WITHOUT AN INDICATION FOR A PACEMAKER In patients with a history of atrial fibrillation (AF), pacing from one or both atria has been suggested as a means to reduce AF recurrences. There is no conclusive evidence to support the implantation of an atrial pacemaker to prevent AF in patients with a history of AF but no indication for pacing [1]. Similar to societal guidelines, we do not recommend the insertion of an atrial pacemaker for this purpose [2]. (See 'Overdrive (antitachycardia) atrial pacing' below.) PATIENTS WITH SYMPTOMATIC BRADYCARDIA https://www.uptodate.com/contents/the-role-of-pacemakers-in-the-prevention-of-atrial-fibrillation/print 1/13 7/5/23, 10:19 AM The role of pacemakers in the prevention of atrial fibrillation - UpToDate Many patients with atrial fibrillation (AF) have sinus node dysfunction with symptomatic bradycardia requiring pacemaker placement. Moreover, antiarrhythmic drug treatment may lead to sinus or atrioventricular nodal dysfunction that may require pacing in order to permit up- titration of drug dose. The appropriate pacing modes for patients with sinus node dysfunction are discussed separately. (See "Sinus node dysfunction: Treatment", section on 'Treatment'.) In patients who require permanent pacing, only physiologic pacing from the right atrium has been shown to prevent episodes of AF. Physiologic pacing Background The term "physiologic pacing" has historically been used to describe the maintenance of atrioventricular (AV) synchrony. For patients with non-permanent AF who require permanent pacing, we place a dual chamber pacemaker and program it to physiologic pacing, which is discussed below. Physiologic pacing results in a significantly lower rate of AF. Sinus rhythm leads to a predictable myocardial activation sequence of different regions of the heart. This sequence optimizes cardiac output. Several mechanisms may contribute to the benefit of physiologic pacing in preventing AF in patients who are treated with standard dual- chamber pacing. (See "The electrocardiogram in atrial fibrillation".) Types of physiologic pacing and their benefits are summarized as follows: Maintenance of AV synchrony This lowers the potential for AF by preventing the development of right atrial electrical and left atrial mechanical remodeling [3-5]. His bundle pacing Compared with right ventricular (RV) pacing, His bundle pacing may reduce left atrial dysfunction by preventing left ventricular (LV) dyssynchrony and reducing LV compliance [6]. Reductions in the dispersion of refractoriness These reductions may be in part due to lowering average atrial pressure and therefore stretch-related changes [7]. Another factor may be suppression of ectopic atrial premature beats that can initiate AF [8,9]. There are several adverse physiologic effects of pacing the RV. Isolated RV pacing disrupts the normal sequence of activation of the atria and ventricles in patients in normal sinus rhythm. This can cause both AV and RV dyssynchrony, which are both described below: AV dyssynchrony The failure to activate the atria before the ventricles with RV pacing is termed AV dyssynchrony. AV dyssynchrony may promote AF. Preventing AV dyssynchrony is https://www.uptodate.com/contents/the-role-of-pacemakers-in-the-prevention-of-atrial-fibrillation/print 2/13 7/5/23, 10:19 AM The role of pacemakers in the prevention of atrial fibrillation - UpToDate part of the rationale for atrial pacing in patients with paroxysmal AF. Ventricular dyssynchrony RV pacing causes the RV to contract before the LV and causes the septum to contract before the lateral wall of the LV; this sequence for activation is similar to that of a native left bundle branch block. The phenomenon is referred to as ventricular dyssynchrony or asynchrony and can also lead to AF. Therefore, the risk of AF with pacing can be reduced by maintaining AV synchrony (physiologic pacing) and by minimizing the amount of ventricular pacing [10]. Evidence for efficacy of physiologic pacing His bundle versus RV pacing There may be a beneficial role of His bundle pacing in the prevention of AF or for reduction of AF burden in those with pacing indications; however, this has not been definitively established [11,12]. A retrospective study of 410 patients without AF who were referred for permanent pacemaker and followed for an average of 1.6 years showed that those with left bundle branch area pacing had less new-onset AF compared with those with RV pacing (5.2 versus 18 percent; hazard ratio [HR] 0.33, 95% CI 0.16-0.67) [6]. (See "Modes of cardiac pacing: Nomenclature and selection", section on 'Physiologic pacing' and "Modes of cardiac pacing: Nomenclature and selection", section on 'Modes to minimize ventricular pacing'.) Atrial versus ventricular pacing The potential benefit of physiologic pacing on the development of AF has been evaluated in a number of clinical trials [13-23]. Physiologic pacing may be accomplished with atrial or AV pacing, which is also referred to as dual-chamber pacing. A 2006 meta-analysis of randomized trials of physiologic versus ventricular pacing included 7231 patients and over 35,000 patient-years of follow-up [13]. Most patients assigned to physiologic pacing received a dual-chamber (DDD) pacemaker, and some received AAI pacing. Physiologic pacing resulted in a significantly lower rate of AF (HR 0.80, 95% CI 0.72-0.89). However, there was no significant reduction in mortality or heart failure. Another trial not included in the meta- analysis has come to similar conclusions [18]. Site of atrial pacing The impact of the site of atrial pacing was evaluated in the SAFE study of 385 patients with paroxysmal AF and sinus node dysfunction with an indication for long- term pacing [24]. Individuals were randomly assigned to pacing at the right atrial appendage or the right septum. After a mean follow-up of 3.1 years, there was no difference in the rate of occurrence of persistent AF between the two sites. Alternate strategies As discussed above, we place a dual chamber pacemaker in patients with non-permanent AF who have symptomatic bradycardia and no indication for biventricular pacing. When possible, we pace from the right atrium only. While attempting physiologic pacing https://www.uptodate.com/contents/the-role-of-pacemakers-in-the-prevention-of-atrial-fibrillation/print 3/13 7/5/23, 10:19 AM The role of pacemakers in the prevention of atrial fibrillation - UpToDate has been standard of care for decades, data suggests a physiologic benefit of His bundle pacing when feasible [11]. (See "Sinus node dysfunction: Treatment", section on 'Long-term management'.) The ability of other atrial pacing systems to suppress AF recurrences has been evaluated in several studies and has not been found to prevent the development of AF. Alternative-site, dual-site right atrial, and biatrial pacing Based on the available evidence, we do not perform alternative site, dual-site right atrial, or biatrial pacing to prevent episodes of AF. The atria can be paced at sites other than the right atrial appendage, such as at the high interatrial septum near Bachman s bundle, or at two sites simultaneously to provide greater synchronization of atrial tissue, which might protect against AF. Biatrial pacing usually involves pacing simultaneously from a lead in the right atrial appendage to stimulate the right atrium and a lead in the coronary sinus to stimulate the left atrium [25]. Alternatively, two sites in the right atrium can be paced simultaneously (eg, the high right atrium and low on the interatrial septum near the coronary sinus ostium) [26]. The following summarizes the lack of robust evidence for efficacy of alternative pacing strategies: Dual versus single site atrial pacing Possible mechanisms by which arrhythmia recurrence rates are lowered with dual-site pacing include a reduction in atrial conduction delay and a smaller increase in the width of the atrial electrogram caused by an early premature beat, measured at the right posterior interatrial septum. Whereas smaller observational studies suggested a benefit of dual-site versus single-site pacing [27-31], in the larger DAPPAF trial [26], no benefit was observed. In the DAPPAF trial, 118 patients with paroxysmal symptomatic AF and a bradyarrhythmic indication for pacing were randomly assigned to each of three pacing modes: right atrial, dual-site right atrial, and support (DDI or VDI) pacing [26]. Although there were no overall differences in incident AF among patients assigned to these pacing groups, subgroup analysis suggested that dual-site pacing was more effective than single-site or support pacing in patients receiving a class I or III antiarrhythmic drug and in those with 1 symptomatic AF episode per week. Pacing from specific sites in right atrium and coronary sinus In the PASTA trial 142 patients with pacing indications were randomly assigned to pacing from either the free right atrial wall, right atrial appendage, coronary sinus ostium, or dual site right atrial pacing from the coronary sinus ostium and the right atrial appendage [31]. There was no https://www.uptodate.com/contents/the-role-of-pacemakers-in-the-prevention-of-atrial-fibrillation/print 4/13 7/5/23, 10:19 AM The role of pacemakers in the prevention of atrial fibrillation - UpToDate statistically significant difference with respect to the occurrence of AF between the four groups after 24 months. Intraatrial septal versus right atrial pacing A meta-analysis of 12 randomized controlled trials enrolling 1146 patients compared right atrial appendage pacing with interatrial septum pacing. Compared with right atrial appendage pacing, interatrial septum pacing was associated with a reduction in the number of AF episodes and burden. However, the development of permanent AF and the prevalence of recurrent AF were similar between the two pacing modes [32]. Overdrive (antitachycardia) atrial pacing We consider using overdrive atrial pacing in patients with frequent, symptomatic episodes of AF whose episodes have been difficult to manage with rate or rhythm control. (See 'Patients without an indication for a pacemaker' above.) The rationale for overdrive or antitachycardia pacing that predominates over intrinsic atrial activity is that triggering of AF might be reduced by affecting the pattern of atrial depolarization and suppressing atrial premature beats. Initial studies produced variable results [25]. This was followed by the development of complex algorithms that keep the pacing rate slightly faster than the intrinsic atrial rate in an attempt to minimize the sudden rate change that occurs after premature beats. Proprietary pacing algorithms Some combinations of proprietary pacing algorithms designed to both prevent AF by overdrive pacing and to pace-terminate AF at its onset have been shown to have a statistically significant positive impact on AF burden. However, their impact is clinically small, often leads to symptoms such as palpitations related to overdrive pacing, and should not be considered as a treatment option in patients who do not have a bradycardia indication for pacing. In addition, overdrive atrial pacing is not as efficacious as antiarrhythmic drug therapy or catheter ablation for preventing AF. Some [33-36], but not all [24], of these algorithms appear to more effectively reduce the total number of episodes of AF or the burden of symptomatic AF compared to DDDR alone [33-36]. We do not routinely use any of these algorithms for overdrive atrial pacing. The following studies are representative: POT trial The Prevention Or Termination trial studied the effect of antitachycardia pacing on AF burden when added to preventive pacing algorithms (PPA) [37]. The study consisted of 85 patients who received a DDDR (rate-adaptive dual-chamber pacemaker) with antitachycardia pacing (ATP) algorithms who had greater than 30 minutes per week of AF. They were randomly assigned either to PPA or to PPA with ATP for three months, https://www.uptodate.com/contents/the-role-of-pacemakers-in-the-prevention-of-atrial-fibrillation/print 5/13 7/5/23, 10:19 AM The role of pacemakers in the prevention of atrial fibrillation - UpToDate and then they were crossed to the alternative therapy for the same amount of time with a one-month washout period. Both groups showed a significant decrease in AF burden at the end of the first period (64 versus 81 percent), but there was no further decrease in AF burden of the number of episodes when adding ATP to PPA. SAFARI trial The Study of Atrial Fibrillation Reduction (SAFARI) was designed to determine the impact of preventive pacing algorithms on patients with pacing indications and a history of paroxysmal AF. The study randomized 240 patients to receive either continuous overdrive and triggered overdrive pacing therapies (PPTs) or standard pacing. The primary efficacy end point was post-randomization AF burden, defined as the average number of hours per day spent in atrial tachyarrhythmia during the longest period of at least 90 days between the 4- and 10-month visits. There was no difference in the development of permanent AF between the PPTs ON group (0 percent) compared with the OFF group (2.5 percent). Patients randomized to the PPTs ON group had a median reduction in AF burden to 0.08 hours/day compared with no change in the OFF group [38]. ADOPT-A trial The randomized Atrial Dynamic Overdrive Pacing Trial (ADOPT-A) trial assessed the efficacy of a pacemaker algorithm designed to pace the atrium at rates slightly faster than intrinsic in patients with a history of symptomatic paroxysmal or persistent AF and an indication for dual chamber pacing. The primary end points of the study were symptomatic AF burden and adverse events. A total of 319 patients were randomized. The burden of symptomatic atrial arrhythmias (defined as AF, atrial flutter, and atrial tachyarrhythmias) was reduced by 26.5 percent, from 2.6 percent in the control group to 1.9 percent in the treatment group. The mean number of AF episodes (4.3 11.5 control versus 3.2 8.6 treatment) and adverse event rates were not statistically different between groups. ASSERT trial The main objective of the Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial (ASSERT) was to evaluate the risk of stroke in patients with dual chamber pacemakers and ICDs and subclinical AF episodes lasting >six minutes. Patients with pacemakers were also randomly assigned to receive or not to receive continuous atrial overdrive pacing to evaluate long-term atrial arrhythmia risk. Of the 2451 pacemaker patients randomized, there was no difference in the annual rate of atrial tachyarrhythmia development (1.96 percent per year in patients randomized to receive atrial overdrive pacing versus 1.44 percent per year in control patients) and no difference in the combined end point of stroke, systemic embolism, myocardial infarction, death from vascular causes, or hospitalization for heart failure [39]. https://www.uptodate.com/contents/the-role-of-pacemakers-in-the-prevention-of-atrial-fibrillation/print 6/13 7/5/23, 10:19 AM The role of pacemakers in the prevention of atrial fibrillation - UpToDate MINERVA trial This trial evaluated a novel atrial antitachycardia pacing feature (DDDRP). In the study, DDDRP alone was compared with DDDRP with managed ventricular pacing (MVP) or with MVP alone in patients with bradycardia and previous atrial arrhythmias [40]. The reactive antitachycardia pacing algorithm used in the study continually monitors the atrial rhythm and delivers tiered pacing therapies based on atrial rate. The primary AF objective was to assess rates of permanent AF in the 1166 enrolled patients. At two years, permanent or persistent AF occurred in 19 percent of patients in the control DDDRP arm, 25 percent in the MVP arm, and 15.1 percent in the DDDRP + MVP arm [2]. PATIENTS WHO REQUIRE ICD OR RESYNCHRONIZATION THERAPY The number of patients with atrial fibrillation (AF) who are receiving an implantable cardioverter defibrillator (ICD) or who require cardiac resynchronization therapy is increasing. Many patients who have ICD indications (eg, low left ventricular ejection fraction) may have a history of AF or may have subclinical AF detected on routine follow-up. In patients with a history of non-permanent AF and both pacing and ICD indications, we place a dual-chamber ICD. In patients with no known AF history in whom an ICD is indicated, we place a single-chamber device. An atrial sensing only (VDD) ICD lead is also available and may be useful in the diagnosis of AF in a patient with a single lead ICD. A stand-alone atrial defibrillator was previously evaluated but is no longer available due to the high risk of recurrent AF and the pain associated with shocks. These devices are capable of sensing within and defibrillating the right atrium. However, we do not recommend their placement to terminate AF nor do we use them for AF outside the hospital setting. The use of cardiac resynchronization in patients with AF is discussed separately. (See "Cardiac resynchronization therapy in atrial fibrillation", section on 'Our approach'.) RECOMMENDATIONS OF OTHERS We agree with recommendations made by the American College of Cardiology Foundation/American Heart Association/Heart Rhythm Society guidelines and their focused updates [2,41,42]. SOCIETY GUIDELINE LINKS https://www.uptodate.com/contents/the-role-of-pacemakers-in-the-prevention-of-atrial-fibrillation/print 7/13 7/5/23, 10:19 AM The role of pacemakers in the prevention of atrial fibrillation - UpToDate Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Atrial fibrillation" and "Society guideline links: Arrhythmias in adults".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and Beyond the Basics. th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on patient info and the keyword(s) of interest.) Basics topic (see "Patient education: Pacemakers (The Basics)") Beyond the Basics topic (see "Patient education: Pacemakers (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS Patients without an indication for a pacemaker Patients with atrial fibrillation (AF) should not receive a permanent pacemaker to prevent or reduce the frequency of AF in the absence of another indication for pacing. (See 'Alternate strategies' above.) Avoiding right ventricular (RV) apical pacing In patients without chronic AF who require a pacemaker for bradycardia, we recommend dual-chamber or atrial pacing, rather than ventricular pacing (Grade 1A). RV pacing can increase the risk of AF. Conduction system pacing, particularly left bundle area pacing, may be superior to RV apical pacing in those expected to require a high degree of ventricular pacing. (See 'Patients with symptomatic bradycardia' above.) Similarly, in patients with intact atrioventricular (AV) conduction who receive a dual- chamber device, we recommend the use of pacing modes/parameters that minimize RV pacing (Grade 1B). (See 'Patients with symptomatic bradycardia' above.) https://www.uptodate.com/contents/the-role-of-pacemakers-in-the-prevention-of-atrial-fibrillation/print 8/13 7/5/23, 10:19 AM The role of pacemakers in the prevention of atrial fibrillation - UpToDate Ineffective strategies We do not use alternative-site, dual-right atrial, or biatrial pacing to prevent AF, as available evidence does not support the efficacy of these approaches. (See 'Alternate strategies' above.) No role for overdrive pacing to prevent AF We do not use overdrive pacing (antitachycardia pacing) to prevent AF in patients who do not have a bradycardia indication for pacing, as available evidence does not support the efficacy of this approach in all patients. We consider using overdrive atrial pacing in patients with frequent, symptomatic episodes of AF whose episodes have been difficult to manage with rate or rhythm control. (See 'Overdrive (antitachycardia) atrial pacing' above.) Patients with implantable cardioverter-defibrillator (ICD) indications who also have AF In patients with a history of non-permanent AF and both pacing and ICD indications, we place a dual-chamber ICD. An atrial sensing only (VDD) ICD lead is also available and may be useful in the diagnosis of AF in a patient with a single-lead ICD. (See 'Patients who require ICD or resynchronization therapy' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Ellenbogen KA. Pacing therapy for prevention of atrial fibrillation. Heart Rhythm 2007; 4:S84. 2. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2014; 64:e1. 3. Sparks PB, Mond HG, Vohra JK, et al. 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N Engl J Med 2007; 357:1000. https://www.uptodate.com/contents/the-role-of-pacemakers-in-the-prevention-of-atrial-fibrillation/print 10/13 7/5/23, 10:19 AM The role of pacemakers in the prevention of atrial fibrillation - UpToDate 19. Andersen HR, Thuesen L, Bagger JP, et al. Prospective randomised trial of atrial versus ventricular pacing in sick-sinus syndrome. Lancet 1994; 344:1523. 20. Andersen HR, Nielsen JC, Thomsen PE, et al. Long-term follow-up of patients from a randomised trial of atrial versus ventricular pacing for sick-sinus syndrome. Lancet 1997; 350:1210. 21. Kristensen L, Nielsen JC, Mortensen PT, et al. Incidence of atrial fibrillation and thromboembolism in a randomised trial of atrial versus dual chamber pacing in 177 patients with sick sinus syndrome. Heart 2004; 90:661. 22. Nielsen JC, Kristensen L, Andersen HR, et al. A randomized comparison of atrial and dual- chamber pacing in 177 consecutive patients with sick sinus syndrome: echocardiographic and clinical outcome. J Am Coll Cardiol 2003; 42:614. 23. Stambler BS, Ellenbogen KA, Orav EJ, et al. Predictors and clinical impact of atrial fibrillation after pacemaker implantation in elderly patients treated with dual chamber versus ventricular pacing. Pacing Clin Electrophysiol 2003; 26:2000. 24. Lau CP, Tachapong N, Wang CC, et al. Prospective randomized study to assess the efficacy of site and rate of atrial pacing on long-term progression of atrial fibrillation in sick sinus syndrome: Septal Pacing for Atrial Fibrillation Suppression Evaluation (SAFE) Study. Circulation 2013; 128:687. 25. Cooper JM, Katcher MS, Orlov MV. Implantable devices for the treatment of atrial fibrillation. N Engl J Med 2002; 346:2062. 26. Saksena S, Prakash A, Ziegler P, et al. Improved suppression of recurrent atrial fibrillation with dual-site right atrial pacing and antiarrhythmic drug therapy. J Am Coll Cardiol 2002; 40:1140. 27. Delfaut P, Saksena S, Prakash A, Krol RB. Long-term outcome of patients with drug- refractory atrial flutter and fibrillation after single- and dual-site right atrial pacing for arrhythmia prevention. J Am Coll Cardiol 1998; 32:1900. 28. Levy T, Walker S, Rex S, et al. No incremental benefit of multisite atrial pacing compared with right atrial pacing in patients with drug refractory paroxysmal atrial fibrillation. Heart 2001; 85:48. 29. Lau CP, Tse HF, Yu CM, et al. Dual-site atrial pacing for atrial fibrillation in patients without bradycardia. Am J Cardiol 2001; 88:371. 30. Leclercq JF, De Sisti A, Fiorello P, et al. Is dual site better than single site atrial pacing in the prevention of atrial fibrillation? Pacing Clin Electrophysiol 2000; 23:2101. https://www.uptodate.com/contents/the-role-of-pacemakers-in-the-prevention-of-atrial-fibrillation/print 11/13 7/5/23, 10:19 AM The role of pacemakers in the prevention of atrial fibrillation - UpToDate 31. Spitzer SG, Wacker P, Gazarek S, et al. Primary prevention of atrial fibrillation: does the atrial lead position influence the incidence of atrial arrhythmias in patients with sinus node dysfunction? Results from the PASTA Trial. Pacing Clin Electrophysiol 2009; 32:1553. 32. Zhang L, Jiang H, Wang W, et al. Interatrial septum versus right atrial appendage pacing for prevention of atrial fibrillation : A meta-analysis of randomized controlled trials. Herz 2018; 43:438. 33. Israel CW, Lawo T, Lemke B, et al. Atrial pacing in the prevention of paroxysmal atrial fibrillation: first results of a new combined algorithm. Pacing Clin Electrophysiol 2000; 23:1888. 34. Funck RC, Adamec R, Lurje L, et al. Atrial overdriving is beneficial in patients with atrial arrhythmias: first results of the PROVE Study. Pacing Clin Electrophysiol 2000; 23:1891. 35. Carlson MD, Ip J, Messenger J, et al. A new pacemaker algorithm for the treatment of atrial fibrillation: results of the Atrial Dynamic Overdrive Pacing Trial (ADOPT). J Am Coll Cardiol 2003; 42:627. 36. Wiberg S, L nnerholm S, Jensen SM, et al. Effect of right atrial overdrive pacing in the prevention of symptomatic paroxysmal atrial fibrillation: a multicenter randomized study, the PAF-PACE study. Pacing Clin Electrophysiol 2003; 26:1841. 37. Mont L, Ruiz-Granell R, Mart nez JG, et al. Impact of anti-tachycardia pacing on atrial fibrillation burden when added on top of preventive pacing algorithms: results of the prevention or termination (POT) trial. Europace 2008; 10:28. 38. Gold MR, Adler S, Fauchier L, et al. Impact of atrial prevention pacing on atrial fibrillation burden: primary results of the Study of Atrial Fibrillation Reduction (SAFARI) trial. Heart Rhythm 2009; 6:295. 39. Healey JS, Connolly SJ, Gold MR, et al. Subclinical atrial fibrillation and the risk of stroke. N Engl J Med 2012; 366:120. 40. Boriani G, Tukkie R, Manolis AS, et al. Atrial antitachycardia pacing and managed ventricular pacing in bradycardia patients with paroxysmal or persistent atrial tachyarrhythmias: the MINERVA randomized multicentre international trial. Eur Heart J 2014; 35:2352. 41. Tracy CM, Epstein AE, Darbar D, et al. 2012 ACCF/AHA/HRS focused update of the 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. [corrected]. Circulation 2012; 126:1784. 42. January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical https://www.uptodate.com/contents/the-role-of-pacemakers-in-the-prevention-of-atrial-fibrillation/print 12/13 7/5/23, 10:19 AM The role of pacemakers in the prevention of atrial fibrillation - UpToDate Practice Guidelines and the Heart Rhythm Society in Collaboration With the Society of Thoracic Surgeons. Circulation 2019; 140:e125. Topic 1044 Version 32.0 Contributor Disclosures Rod Passman, MD, MSCE Grant/Research/Clinical Trial Support: Abbott [Ablation]; AHA [Ablation]; NIH [Stroke prevention]. Consultant/Advisory Boards: Abbott [Ablation]; iRhythm [Monitoring]; Janssen [Atrial fibrillation detection]; Medtronic [Implantable cardiac monitors]. Speaker's Bureau: iRhythm [Monitoring]. All of the relevant financial relationships listed have been mitigated. Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/the-role-of-pacemakers-in-the-prevention-of-atrial-fibrillation/print 13/13

7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Atrial fibrillation and flutter after cardiac surgery : Richard Lee, MD, MBA : Gabriel S Aldea, MD, Bradley P Knight, MD, FACC, John Pepper, MA, MChir, FRCS, FESC : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Feb 28, 2022. INTRODUCTION Atrial fibrillation (AF) and atrial flutter occur frequently after cardiac surgery. The development of these atrial arrhythmias prolongs hospital stay and is associated with worse long-term prognosis. Other supraventricular arrhythmias, including atrial arrhythmias such as atrioventricular nodal re-entrant tachycardia, are not common in this setting. (See "Atrioventricular nodal reentrant tachycardia".) This topic will review the pathogenesis, predictors, clinical course, prevention, and management of AF and atrial flutter occurring after cardiac surgery. Most of the observations on atrial arrhythmias come from patients who developed atrial fibrillation. Our approach to patients with atrial flutter is similar, unless otherwise specified. Ventricular tachyarrhythmias after cardiac surgery and arrhythmias after cardiac transplantation are discussed separately. (See "Early cardiac complications of coronary artery bypass graft surgery", section on 'Ventricular tachyarrhythmias' and "Heart transplantation in adults: Arrhythmias".) PATHOGENESIS Atrial fibrillation (AF) and atrial flutter can occur early in the postoperative period or as a late complication of cardiac surgery. A discussion of the mechanisms of AF in the general population is found elsewhere. (See "Mechanisms of atrial fibrillation".) https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 1/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate Postoperative AF is likely related to a combination of perioperative factors. These include pre- existing degenerative changes in the atrial myocardium and perioperative conditions that result in abnormalities of several electrophysiologic parameters that promote the development of AF, such as dispersion of atrial refractoriness, increase in phase 3 depolarization, enhanced automaticity, increased interatrial conduction time, and decreased conduction velocity, atrial transmembrane potentials, and fluid and electrolyte shifts [1-5]. (See "The electrocardiogram in atrial fibrillation".) RISK FACTORS Although some patients develop atrial fibrillation (AF) after cardiac surgery without any apparent predisposing factors, most patients have at least one clinical predictor. Preoperative risk factors include [2,6-17]: Increasing age [6-12]. Previous history of AF. Mitral valvular disease, particularly mitral stenosis. Increased left atrial size or cardiomegaly. Previous cardiac surgery. Chronic obstructive pulmonary disease (COPD). Elevated preoperative hemoglobin A1c [18]. Low-intensity physical activity in the year prior to surgery [19]. Being a White person [20]. Obesity [17,21]. Absence of beta blocker or angiotensin converting enzyme inhibitor (ACE inhibitor) treatment or withdrawal of previous treatment. (See 'Prevention of atrial fibrillation and complications' below.) Preoperative digoxin use in some [7,13] but not all studies [14]. Higher preoperative plasma concentration of brain natriuretic peptide (BNP) [15]. (See "Natriuretic peptide measurement in heart failure".) https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 2/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate Low-dose dopamine [22]. Severe right coronary artery stenosis [12]. Preoperative increase in P wave duration on surface (>116 msec) [16] or on signal averaged (>140 msec) ECG ( figure 1) [9,23]. (See "Signal-averaged electrocardiogram: Overview of technical aspects and clinical applications".) Hypokalemia and hypomagnesemia. (See 'Pathogenesis' above.) Alcohol use disorder. (See "Epidemiology, risk factors, and prevention of atrial fibrillation", section on 'Alcohol'.) PERIOPERATIVE RISK FACTORS Perioperative factors that have been implicated in the creation of atrial susceptibility to atrial fibrillation (AF) or atrial flutter include: Atrial injury from surgical handling, or cannulation, atrial suture lines. Acute atrial enlargement from pressure or volume overload. Inadequate myocardial protection during cardiopulmonary bypass. Atrial ischemia. Long bypass and aortic cross-clamp times. Hyperadrenergic state (eg, use of postoperative inotropic medications). Pulmonary complications, hypoxemia. Inflammation [24,25]. (See "Epidemiology, risk factors, and prevention of atrial fibrillation", section on 'Inflammation and infection'.) Hypokalemia and hypomagnesemia [26-29]. Pericardial effusion and pericarditis. Oxidative stress [30]. While mechanisms specific to late AF have not been identified, atrial flutter in these patients is re-entrant and may involve atypical isthmuses between natural barriers, atrial incisions, and scar https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 3/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate as well as the cavotricuspid isthmus [31-33]. Two potential negative risk factors are off-pump coronary artery bypass graft surgery (CABG) and preservation of the anterior fat pad: Off-pump CABG off-pump CABG is associated with a lower rate of postoperative AF than conventional CABG in some [34-36], but not all [37], studies. (See "Off-pump and minimally invasive direct coronary artery bypass graft surgery: Clinical use".) Preservation of the anterior fat pad Some [38], but not all [39], studies have found lower rate of postoperative AF with preservation of the anterior fat pad. However, none of these risk factors has adequate predictive accuracy to identify the individual patient at risk for postoperative atrial arrhythmia. As a result, risk models that use several factors have been created [6,40]. In one study, a multivariable risk model was derived in a cohort of 3093 patients, and then tested in a validation cohort of 1564 patients [6]. Predictors were identified for any postoperative AF as well as for recurrent AF. The risk score for any postoperative AF successfully stratified patients into groups at low risk (AF incidence <17 percent), medium risk (AF incidence 17 to 52 percent), and high risk (AF incidence >52 percent) ( table 1). While we do not routinely use any of these risk models, they highlight the individual risks. INCIDENCE AND TIME COURSE Atrial fibrillation (AF) occurs in 15 to 40 percent of patients in the early postoperative period following coronary artery bypass graft surgery (CABG) [1,6,41,42]. In a 2018 post-hoc analysis of 1812 patients without prior AF in the EXCEL trial, which compared CABG with percutaneous coronary intervention (PCI) for left main coronary artery disease, perioperative AF developed in 18.0 percent of those undergoing CABG (and 0.1 percent of those who received PCI). The incidence increases with increasing age [6-12,43]. (See "Left main coronary artery disease", section on 'Randomized trials' and 'Adverse outcomes following atrial fibrillation' below.) AF occurs in 37 to 50 percent after valve surgery [1,7,8], and in as many as 60 percent undergoing valve replacement plus CABG [1,7]. Atrial arrhythmias occur most often within the first few days after surgery [1,6,9,11]. In a prospective, multicenter study of 4657 patients undergoing surgery, the majority of first episodes of AF occurred by day two, while the majority of recurrent episodes occurred by day three. Forty-three percent of patients with AF had more than one episode [6]. https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 4/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate Among patients with postoperative AF who have no prior history of atrial arrhythmias, the AF is usually self-limited, as 15 to 30 percent convert within two hours and up to 80 percent in 24 hours [1,44,45]. The mean duration of AF in one report was 11 to 12 hours [45] and more than 90 percent are in sinus rhythm six to eight weeks following surgery [1,45-47]. In one report, for example, only 3 of 116 patients who developed AF after CABG were still in AF at six weeks [46]. AF may also occur late after cardiac surgery and the incidence is likely higher than appreciated because many patients may have continued asymptomatic episodes of AF. In a study of over 2000 patients enrolled in cardiac rehabilitation programs after cardiac surgery, 11 percent of patients developed AF (4.4 percent new-onset AF) [48]. Late postoperative AF was associated with adverse outcomes, including heart failure and rehospitalization. Atrial flutter is relatively uncommon compared to atrial fibrillation. CLINICAL MANIFESTATIONS AND DIAGNOSIS The development of atrial fibrillation or flutter after cardiac surgery may or may not lead to symptoms, such as palpitations, or to a change in the hemodynamic status of the patient. In some individuals with rapid ventricular rates, the blood pressure may fall and potentially be associated with a decline in the urine output. We are not aware of any studies that have systematically characterized the clinical manifestations of postoperative atrial fibrillation (AF) in coronary artery bypass graft surgery patients. In our experience, about 90 percent of these individuals are symptomatic and about 15 percent are hemodynamically unstable. The diagnosis of AF in the hospital is usually not difficult as most patients are on continuous monitoring. All patients should have documentation of the rhythm with a 12-lead electrocardiogram. (See "The electrocardiogram in atrial fibrillation".) Longer-term continuous AF screening may detect more episodes in postoperative cardiac surgery patients who are discharged from the hospital, but more studies are needed before we can recommend this as routine practice (see "Atrial fibrillation: Overview and management of new-onset atrial fibrillation", section on 'Screening'). In a randomized trial of 336 cardiac surgical patients with risk factors for stroke, use of continuous cardiac rhythm monitoring with wearable sensors increased the rate of AF detection within 30 days of discharge. In the intent-to-treat analysis, the primary end point of AF for at least six minutes occurred in 32 patients in the intervention group versus 3 patients in the usual care group (absolute difference, 17.9 percent 95% CI 11.5-24.3 percent) [49]. https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 5/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate ADVERSE OUTCOMES FOLLOWING ATRIAL FIBRILLATION Potential adverse outcomes after the development of postoperative atrial fibrillation (AF) include stroke, death, and prolongation of hospital stay: Postoperative AF has been associated with an increased risk of in-hospital stroke in some [7,41,50-55] but not all series [56,57]. In some of these studies, it is possible that underlying comorbidities, such as older age, cerebrovascular or peripheral artery disease, and cardiopulmonary bypass time, are related to in-hospital stroke rather than the arrhythmia itself [43,52,56-59]. At least three studies with differing designs have evaluated the long-term thromboembolic risk of patients with new onset AF after coronary artery bypass graft surgery (CABG) and reached somewhat different conclusions: In the EXCEL trial of patients with left main coronary artery disease, new onset AF was an independent predictor of stroke at three years with a rate of 6.6 percent compared with 2.4 percent in patients without AF [43]. (See 'Incidence and time course' above.) In a cohort study of 2108 patients who developed postoperative AF and 8432 patients with nonvalvular AF, the risk of thromboembolism was lower in the former group (18.3 versus 29.7 events per 1000 person-years; adjusted hazard ratio 0.67, 95% CI 0.55-0.81) [60]. In addition, the risk was similar between the groups of patients with and without postoperative AF. In a post-hoc analysis of the ART randomized trial (see "Coronary artery bypass graft surgery: Graft choices", section on 'Two arterial grafts') comparing bilateral with single internal thoracic artery grafts, the cumulative incidence of cerebrovascular accident was higher in those with postoperative AF relative to those without (6.3 versus 3.7 percent; hazard ratio 1.53, 95% CI 1.06-2.23) [61]. Postoperative AF may identify a subset of patients with increased in-hospital and long-term mortality [6,25,41,42,62,63]. This was suggested by a retrospective study of 6475 patients undergoing CABG at a single institution, 994 (15 percent) of whom developed AF [41]. Patients with AF had significantly greater mortality in-hospital (7.4 versus 3.4 percent) and at four years (26 versus 13 percent). In a case-matched subset of 390 patients, the mortality at five years was significantly higher in those with AF (20 versus 7 percent). On multivariate analysis, postoperative AF was a predictor of long-term mortality in both the retrospective cohort (adjusted odds ratio 1.5) and the case-matched population (odds ratio 3.4). https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 6/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate In the EXCEL trial of patients with left main coronary artery disease, new onset AF was an independent predictor of all-cause death at three years with a rate of 11.4 percent compared with 4.3 percent in patients without AF [43]. (See 'Incidence and time course' above.) In another study of 1832 patients who underwent CABG, patients with postoperative AF had a higher long-term mortality (2.99 versus 1.34 per 100 person-years; adjusted hazard ratio 2.13, 95% CI 1.45-3.15) during a median follow-up of 51 months [42]. Patients with AF were at higher risk of dying from systemic embolism (adjusted hazard ratio 4.33, 95% CI 1.78-10.52), but not from other causes. Postoperative AF is associated with prolongation of the duration of hospitalization, with an increased length of stay between one and six days [7,11,43,50,51,64,65]. New onset AF added approximately six days to the hospital duration in the EXCEL trial of patients with left main coronary artery disease [43]. (See 'Incidence and time course' above.) PREVENTION OF ATRIAL FIBRILLATION AND COMPLICATIONS We recommend therapies to prevent the development of postoperative atrial fibrillation (AF) in patients undergoing cardiac surgery in an attempt to decrease the duration of hospitalization, to possibly decrease the risk of in-hospital stroke and death, and to decrease the need for anticoagulation in some patients. Prevention of atrial fibrillation The use of beta blockers, sotalol, amiodarone, atrial pacing, or antioxidant vitamins lowers the risk of postoperative AF [66]. Beta blockers are the best studied of these therapies and we prefer beta blockers to sotalol or amiodarone based on their ease of use and better safety profile. We do not recommend atrial pacing in most cases. There have been no studies comparing the relative efficacy and safety of the traditional antiarrhythmic drugs to antioxidant vitamins. Beta blockers Beta blocker administration is the most widely used prophylactic strategy based on numerous studies showing benefit, ease of use, and cost considerations [1,6,10,14,64,67-70]. Meta-analyses of randomized trials from 2002 and 2004 found that they reduced the risk of AF compared to placebo or no therapy (odds ratios of 0.35, 95% CI 0.26-0.49 and 0.39, 95% CI 0.28-0.52) [64,71]. However, a larger 2006 meta-analysis of 31 trials including 4452 patients performed separate analyses based on whether non-study beta blocker was allowed to be continued or not [72]. When trials confounded by postoperative non-study beta blocker withdrawal were excluded, the effect of beta blockers, although still significant, was less (OR 0.69, 95% CI 0.54-0.87). In addition, other between-trial differences (heterogeneity), such as https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 7/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate control group event rates which ranged between 5 and 54 percent, lead us to be unsure of the true magnitude of the benefit from beta blockers in patients who have not previously received them. The issue of whether some beta blockers lower the risk of postoperative AF more successfully than others has not been well studied. In a meta-analysis of randomized trials with 601 patients that compared carvedilol to metoprolol (succinate and tartrate), carvedilol reduced the incidence of AF (odds ratio 0.50, 95% CI 0.32-0.80) [73]. The benefit is seen when beta blockers are begun prior to or immediately after surgery. We feel the evidence is not strong enough for us to recommend one beta blocker over another. When possible, we start beta blockers at least 48 hours before surgery, due to concerns about the induction of excessive bradycardia. In addition, some experts are concerned about the increased risk of stroke seen in patients undergoing noncardiac surgery who receive beta blockers soon before surgery. (See "Management of cardiac risk for noncardiac surgery", section on 'Patients who may require preoperative initiation of therapy'.) If a patient is a candidate for initiation of a beta blocker but presents within the 48-hour window, our reviewers have differing approaches. Some will start low dose beta blocker at any time before surgery, while others will wait until after the patient has returned to the intensive care unit and is deemed "stable." The optimal duration of therapy for prevention of postoperative atrial arrhythmias is uncertain, but we often continue the beta blocker until the first postoperative visit. However, many patients who undergo CABG have a clear indication for the long-term use of beta blocker therapy (eg, previous myocardial infarction, left ventricular systolic dysfunction with heart failure, or hypertension). Sotalol Sotalol is a class III antiarrhythmic agent that has beta blocking activity. A 2011 meta-analysis of 15 randomized studies of patients undergoing cardiac surgery found that sotalol lowered the risk of AF compared to placebo (relative risk [RR] 0.55, 95% CI 0.45-0.66) [74]. Compared to beta blocker, sotalol was more effective (14 versus 23 percent; RR=0.64 [CI, 0.50- 0.84]). There was no significant difference in the rates between sotalol and amiodarone. Risks of sotalol include torsade de pointes and bradycardia. (See "Clinical uses of sotalol".) Sotalol is effective when begun 24 to 48 hours before surgery or four hours after surgery [75,76]. Amiodarone Most of our contributors prefer beta blockers to amiodarone for the preoperative prevention of AF. https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 8/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate Amiodarone lowers the incidence of postoperative AF by about 40 to 50 percent [64,71,77-82]. A 2006 meta-analysis of 18 trials that included nearly 3000 patients found that amiodarone lowered the risk of AF or atrial flutter compared to placebo (odds ratio [OR] 0.48, 95% CI 0.40- 0.57) [72]. However, amiodarone is associated with more adverse cardiac events compared to placebo, including bradycardia requiring temporary pacing (5.7 versus 2 percent), and QT prolongation (1.3 versus 0 percent) [82]. (See "Amiodarone: Adverse effects, potential toxicities, and approach to monitoring".) Metoprolol was directly compared to amiodarone in an equivalence trial of 316 hemodynamically stable patients who underwent CABG or valve surgery [83]. The rates of the development of AF were similar (23.9 and 24.8 percent, respectively). A number of different preoperative regimens of amiodarone have been evaluated. It has been given orally one to seven days before surgery [78,79], intravenously immediately after surgery [80], or intravenously for 24 hours followed by oral therapy for four days [81]. The efficacy of these different regimens is illustrated by the following observations: One study randomly assigned 124 patients to oral amiodarone or placebo for a minimum of seven days prior to elective cardiac surgery, continuing the drug until discharge [78]. The mean total dose of amiodarone administered was 4.8 grams over 13 days (600 mg/day for seven days followed by 200 mg/day until discharge). The amiodarone group had a significant reduction in the incidence of postoperative atrial fibrillation (25 versus 53 percent) without any increase in fatal or nonfatal postoperative complications. Other oral regimens that have been effective include those that begin five days before surgery or one day before surgery [79]. The efficacy of postoperative intravenous therapy was documented in the ARCH trial in which 300 patients were randomly assigned to 1 gram of intravenous amiodarone per day for two days or placebo; therapy was begun immediately after CABG [80]. Amiodarone significantly reduced the incidence of atrial fibrillation (35 versus 47 percent for placebo), but did not lower the length of hospitalization (7.6 versus 8.2 days). In another report, intravenous amiodarone begun on call to the operating room and continued for 48 hours, followed by oral amiodarone for three days, also significantly reduced postoperative atrial fibrillation (6 versus 26 percent) [84]. Although some have suggested that amiodarone might be more effective than a beta blocker for the prevention of atrial fibrillation after cardiac surgery [85], this was not confirmed in two https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 9/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate meta-analyses [64,71]. Antioxidant vitamins Oxidative stress plays a role in ischemia-reperfusion injury, which occurs in open heart surgery. It is also involved in the pathogenesis of AF. Based on limited supportive evidence, as well as the absence of side effects in the short term or significant cost, we believe it is reasonable to give antioxidant vitamins to lower the rate of postoperative AF. (See "Reperfusion injury of the heart", section on 'Arrhythmias' and "Reperfusion injury of the heart", section on 'Antioxidant therapy' and 'Pathogenesis' above.) A 2011 meta-analysis evaluating five randomized trials comprising 567 patients found that the prophylactic use of the antioxidant vitamins C and E lowered the rate of postoperative AF (odds ratio 0.43, 95% CI 0.21-0.89) [86]. The conclusion of the meta-analysis is limited by the inclusion of small, low-quality studies. Subsequent to the meta-analysis, a small trial randomly assigned 203 patients scheduled to undergo on-pump cardiac surgery to supplementation with n-3 PUFA (1 gram twice daily), vitamin C (1 g/day), and vitamin E (400 international units/day) or placebo [87]. n-3 PUFA was started approximately seven days and the vitamins two days before surgery; treatment was continued until hospital discharge. The primary outcome of the occurrence of electrocardiographically confirmed postoperative AF occurred significantly less often in the antioxidant therapy group (9.7 versus 32 percent; relative risk 0.28, 95% CI 0.14-0.56). Due to the small number of events (postoperative AF), as well as the unusually low relative risk found, we believe this trial provides weak evidence in favor of antioxidant vitamins. In addition, we do not believe that the trial, which combined n-3 PUFA with vitamins, changes our view that n-3 PUFA are of no benefit in this setting. If antioxidant vitamins are given to prevent postoperative AF, we suggest using them with the timing and dosing used in the above trial and adding them to another preventative therapy. Atrial pacing Atrial pacing to prevent postoperative AF has been examined in a number of studies. Most [88-92], but not all [81,93,94], showed benefit. In a 2006 meta-analysis, pacing was associated with a significant reduction in AF (OR 0.60, 95% CI 0.47-0.77) [72]. With regard to the optimal pacing strategy (eg, left compared to right atrium or pacing from one or both atria), studies are not definitive [89-94]. Atrial pacing is not considered an invasive procedure in these patients because placement of temporary pacing wires is routinely done at the time of surgery. Reducing risk of pericardial effusion There are several methods to reduce the incidence of pericarditis and residual pericardial effusion. One approach we use is placement of a large drain (eg, Blake drain), left in postoperatively until they no longer drain. Colchicine can be added in this setting to prevent pericarditis when a drain is in place. However, outside of this particular https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 10/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate setting, the evidence supporting colchicine's efficacy in reducing postoperative AF is mixed. (See 'Ineffective or possibly effective therapies' below.) Posterior left pericardiotomy can reduce the incidence of pericardial effusions, which are common triggers for postoperative AF. In patients without a known diagnosis of AF, posterior left pericardiotomy was shown to reduce the incidence of postoperative AF after surgery on the coronary arteries, aortic valve, and/or ascending aorta, without additional risk of postoperative complications [95]. Patients undergoing mitral or tricuspid valve surgeries were not studied. In an adaptive randomized trial of 420 patients, patients assigned posterior left pericardiotomy had a lower incidence of postoperative AF compared with controls (17 versus 32 percent). Patients assigned posterior left pericardiotomy also had a lower incidence of pericardial effusion (12 versus 21 percent). Postoperative major events were similar in the intervention and control groups (3 versus 2 percent), and no pericardiotomy-related complications occurred. Factors that limited generalizability of this study were that it was done in a single center, and there were relatively high rates of postoperative AF, even in a study population at lower risk for AF. We await further studies before recommending this approach for all patients undergoing cardiac surgery. Ineffective or possibly effective therapies We do not recommend any of the following preventative strategies to prevent the development of atrial arrhythmias: Digoxin Digoxin, given preoperatively or postoperatively, does not appear to prevent AF [14,68,69,96]. Antiarrhythmic drugs Data about the prophylactic use of class I antiarrhythmic drugs to prevent postoperative AF are limited. Procainamide appears to reduce the number of episodes and duration of AF compared to placebo, but not the incidence of AF [97,98]. Calcium channel blockers Calcium channel blockers have uncertain utility in preventing AF after cardiac surgery [68,99-102]. Intravenous magnesium Based on the fact that hypomagnesia is a risk factor for AF (see 'Risk factors' above), magnesium supplementation has been evaluated as a possible therapy to reduce postoperative atrial arrhythmias [103-108]. In a 2006 meta-analysis of 22 trials including 2896 patients, supraventricular arrhythmias occurred significantly less often in patients treated with magnesium compared to controls (odds ratio 0.57, 95% CI 0.42-0.77) [72]. However, there was no effect on hospital stay, perioperative myocardial infarction, or mortality. There was also significant heterogeneity in the size of the effect among trials, and the possibility of publication bias was suggested. https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 11/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate In a 2012 meta-analysis of seven randomized trials (n = 1028), which were felt to have no 2 heterogeneity (I = 0), intravenous magnesium reduced the incidence of postoperative AF (relative risk 0.64, 95% CI 0.50-0.83) [109]. Angiotensin inhibition Although angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) have not previously been considered a specific therapy in patients with AF, a number of observations suggest benefit in nonsurgical settings. (See "ACE inhibitors, angiotensin receptor blockers, and atrial fibrillation".) A significant reduction in the incidence of postoperative AF (20 versus 34 percent) with ACE inhibitors was seen in an observational study of 4657 patients undergoing CABG [6]. However, in a study of 445 patients randomly assigned to placebo, ramipril, or spironolactone one week to four days prior to cardiac surgery, there was no significant difference in the rate of AF after surgery [110]. In a prospective study of 4657 patients undergoing CABG, postoperative AF occurred significantly less often in patients who were treated preoperatively and postoperatively with ACE inhibitors compared to those who were not (20 versus 34 percent, odds ratio 0.62) [6]. In addition, patients who had previously been taking ACE inhibitors and were withdrawn from therapy had a significant increase in risk (46 percent, odds ratio 1.69). The utility of these agents in preventing AF after cardiac surgery remains controversial, however, as other studies have not found a significant benefit [111-113]. A retrospective analysis of 8889 patients undergoing CABG described an increase in major adverse events, including postoperative renal dysfunction as well as AF, in patients receiving preoperative ACE inhibitors [114]. Given the inconsistency in the results among these studies, we do not recommend preoperative ACE inhibitors specifically for prevention of AF in patients undergoing CABG. Statins Some, but not all, studies have shown that statins lower the rate of postoperative AF [115,116]. A 2015 meta-analysis of 17 randomized trials that compared statin therapy with either placebo or no therapy prior to cardiac surgery (predominantly coronary artery bypass graft surgery) found that such treatment reduced the incidence of postoperative AF (odds ratio 0.54, 95% CI 0.43-0.67), but failed to influence short-term mortality or postoperative stroke [117,118]. However, the meta-analysis pointed out significant limitations of the evidence. The largest randomized trial of preoperative statin therapy was published after the meta- analysis. In the STICS trial, 1922 patients in sinus rhythm scheduled for elective cardiac surgery (87 percent CABG) were randomly assigned to receive perioperative rosuvastatin https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 12/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate (20 mg daily) or placebo up to eight days before surgery [116]. Any previously prescribed statin was stopped. The rate of the primary outcome of postoperative AF within five days of surgery was similar in both groups (21.1 and 20.5 percent, respectively; odds ratio 1.04, 95% CI 0.84-1.30). Of note, there was no difference in the rate of myocardial injury within 120 hours after surgery. In addition, rosuvastatin was associated with a significant absolute excess in the rate of postoperative acute kidney injury (24.7 versus 19.3 percent; p = 0.005). Based upon established benefits of statin therapy in patients with coronary heart disease, all patients should be on long-term statin. However, for patients who have not started statin therapy prior to CABG, we suggest waiting until after surgery, as there is no clear evidence of benefit from preoperative initiation and possible harm. (See "Coronary artery bypass surgery: Perioperative medical management", section on 'Statins'.) N-acetylcysteine N-acetylcysteine (NAC) has the potential to protect against the development of perioperative AF due to its antioxidant and anti-inflammatory properties. (See 'Pathogenesis' above.) This hypothesis was tested in a trial of 115 patients undergoing either CABG or valve surgery who were randomly assigned to either NAC or placebo given one hour before and continued for 48 hours after surgery [119]. The primary end point of an AF episode lasting longer than five minutes during hospitalization was seen in 15 patients and was significantly less common in those who received NAC (5.2 versus 21.2 percent). In a small study designed to evaluate the potential benefit of anti-inflammatory therapy (with NAC or carvedilol), 311 patients undergoing cardiac surgery who had no history of AF were randomly assigned to metoprolol, carvedilol, or carvedilol plus NAC [120]. The incidence of postoperative AF was significantly lower in the carvedilol plus NAC group compared to either of the other two interventions (35.9, 24.0, and 8.7 percent, respectively). Colchicine Colchicine reduces the incidence of the postpericardiotomy syndrome. (See "Post-cardiac injury syndromes", section on 'Prevention'.) The issue of whether colchicine can reduce the incidence of postoperative AF was addressed in a post hoc substudy. In COPPS, 360 patients undergoing cardiac surgery were randomly assigned to either colchicine 1.0 mg given twice daily on day one followed by 0.5 mg twice daily for one month (the dose was halved in patients <70 kg) or placebo [121]. The first dose was given on postoperative day three. The COPPS Prevention of Atrial Fibrillation (POAF) substudy evaluated outcomes in the 336 patients in sinus rhythm on day three. Colchicine significantly reduced the incidence of postoperative AF (12 versus 22 https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 13/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate percent; relative risk reduction 45.5 percent, 95% CI 34.0-94.0 percent) at 30 days. In addition, patients taking colchicine had a significantly shorter in-hospital stay (9.4 versus 10.3 days). There was a trend toward a higher rate of side effects (9.5 versus 4.8 percent) and drug withdrawal (11.8 versus 6.6 percent) with colchicine, but no severe side effects were recorded. In the COPPS-2 trial, 360 patients scheduled for cardiac surgery were randomly assigned to oral colchicine or placebo before surgery [122]. The drug was continued for one month after surgery. At three months, there was no significant difference between the two groups in the secondary end point of postoperative AF (34 versus 41 percent, respectively). (See "Post-cardiac injury syndromes", section on 'Prevention'.) We believe there is insufficient evidence to recommend the routine use of colchicine, in part out of a concern that it may negatively impact wound healing and that it leads to gastrointestinal side effects. The 2014 American Heart Association/American College of Cardiology/Heart Rhythm Society AF guideline states that colchicine may be considered [123,124]. This was not changed in the 2019 focused update [125]. Naproxen The potential benefit from naproxen was evaluated in the NAFARM trial, which randomly assigned 161 patients to either naproxen or placebo [126]. There was no significant difference in the rate of postoperative AF (7 versus 15 percent, respectively). The study was stopped early because of an increase in renal failure in the naproxen group. Glucocorticoid Based upon the hypothesis that perioperative inflammation may contribute to the development of AF, glucocorticoids have been suggested as prophylactic therapy. (See "Glucocorticoid effects on the immune system".) Two meta-analyses of small trials in which glucocorticoid treatment was compared to placebo or no treatment in adult cardiac surgery found 26 and 40 percent reductions in the incidence of AF, irrespective of the dose given [127,128]. However, the large, randomized SIRS trial, published after the meta-analyses, found no difference in the rate of new AF [129]. Due to their potential adverse effects on glucose metabolism, wound healing, infection, and the absence of a lowering of the risk of death, we do not recommend the routine use of glucocorticoid therapy to prevent AF. The potential role for glucocorticoid therapy for other outcomes is discussed separately. (See "Coronary artery bypass surgery: Perioperative medical management", section on 'Glucocorticoid therapy'.) https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 14/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate Prevention of complications of atrial fibrillation While beta blockers, sotalol, amiodarone, and pacing decrease the risk of postoperative AF, the evidence is less robust that the risk of complications such as stroke, death, or length of stay can be prevented. It may be difficult to demonstrate a lowering of the risk of in-hospital stroke with these therapies, as AF is only one risk factor for stroke and as the incidence of stroke is low. (See 'Adverse outcomes following atrial fibrillation' above.) The best available evidence of the impact of these interventions on the complications of AF comes from a 2006 meta-analysis of heterogenous trials, which noted the following [72]: In 29 trials that evaluated length of stay, only amiodarone and pacing shortened the average length of stay (-0.60 days, 95% CI -0.92 to -0.29 and -1.3 days 95% CI -2.55 to -0.08, respectively). In 25 trials that reported on the incidence of postoperative stroke, the risk of stroke was decreased from 1.9 to 1.1 percent with treatment (odds ratio 0.63, 95% CI 0.41-0.98). Amiodarone was the only single intervention that significantly lowered the risk of stroke compared to placebo. Our approach to prevention We recommend preventative therapy to reduce the incidence of postoperative AF, especially in patients at high risk of its development. While the evidence is not robust, prevention of AF may lead to a lowering of the risk of in-hospital stroke and a shortened length of stay. In addition, successful prevention of AF will prevent the need for anticoagulation in some patients. Beta blockers, sotalol, amiodarone, and atrial pacing are significantly more effective than placebo in lowering the rate of postoperative AF [64,71,72]. There is some evidence to support the use of antioxidant vitamins for this purpose. We prefer beta blockers to amiodarone or sotalol due to lower cost and lower risk of potential side effects and to pacing because of its relative complexity and cost. Amiodarone or sotalol is a reasonable alternative in patients who cannot tolerate beta blockade. If possible, we prefer to start beta blockers prior to CABG. We suggest metoprolol 25 mg twice daily; the dose can be

statin was stopped. The rate of the primary outcome of postoperative AF within five days of surgery was similar in both groups (21.1 and 20.5 percent, respectively; odds ratio 1.04, 95% CI 0.84-1.30). Of note, there was no difference in the rate of myocardial injury within 120 hours after surgery. In addition, rosuvastatin was associated with a significant absolute excess in the rate of postoperative acute kidney injury (24.7 versus 19.3 percent; p = 0.005). Based upon established benefits of statin therapy in patients with coronary heart disease, all patients should be on long-term statin. However, for patients who have not started statin therapy prior to CABG, we suggest waiting until after surgery, as there is no clear evidence of benefit from preoperative initiation and possible harm. (See "Coronary artery bypass surgery: Perioperative medical management", section on 'Statins'.) N-acetylcysteine N-acetylcysteine (NAC) has the potential to protect against the development of perioperative AF due to its antioxidant and anti-inflammatory properties. (See 'Pathogenesis' above.) This hypothesis was tested in a trial of 115 patients undergoing either CABG or valve surgery who were randomly assigned to either NAC or placebo given one hour before and continued for 48 hours after surgery [119]. The primary end point of an AF episode lasting longer than five minutes during hospitalization was seen in 15 patients and was significantly less common in those who received NAC (5.2 versus 21.2 percent). In a small study designed to evaluate the potential benefit of anti-inflammatory therapy (with NAC or carvedilol), 311 patients undergoing cardiac surgery who had no history of AF were randomly assigned to metoprolol, carvedilol, or carvedilol plus NAC [120]. The incidence of postoperative AF was significantly lower in the carvedilol plus NAC group compared to either of the other two interventions (35.9, 24.0, and 8.7 percent, respectively). Colchicine Colchicine reduces the incidence of the postpericardiotomy syndrome. (See "Post-cardiac injury syndromes", section on 'Prevention'.) The issue of whether colchicine can reduce the incidence of postoperative AF was addressed in a post hoc substudy. In COPPS, 360 patients undergoing cardiac surgery were randomly assigned to either colchicine 1.0 mg given twice daily on day one followed by 0.5 mg twice daily for one month (the dose was halved in patients <70 kg) or placebo [121]. The first dose was given on postoperative day three. The COPPS Prevention of Atrial Fibrillation (POAF) substudy evaluated outcomes in the 336 patients in sinus rhythm on day three. Colchicine significantly reduced the incidence of postoperative AF (12 versus 22 https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 13/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate percent; relative risk reduction 45.5 percent, 95% CI 34.0-94.0 percent) at 30 days. In addition, patients taking colchicine had a significantly shorter in-hospital stay (9.4 versus 10.3 days). There was a trend toward a higher rate of side effects (9.5 versus 4.8 percent) and drug withdrawal (11.8 versus 6.6 percent) with colchicine, but no severe side effects were recorded. In the COPPS-2 trial, 360 patients scheduled for cardiac surgery were randomly assigned to oral colchicine or placebo before surgery [122]. The drug was continued for one month after surgery. At three months, there was no significant difference between the two groups in the secondary end point of postoperative AF (34 versus 41 percent, respectively). (See "Post-cardiac injury syndromes", section on 'Prevention'.) We believe there is insufficient evidence to recommend the routine use of colchicine, in part out of a concern that it may negatively impact wound healing and that it leads to gastrointestinal side effects. The 2014 American Heart Association/American College of Cardiology/Heart Rhythm Society AF guideline states that colchicine may be considered [123,124]. This was not changed in the 2019 focused update [125]. Naproxen The potential benefit from naproxen was evaluated in the NAFARM trial, which randomly assigned 161 patients to either naproxen or placebo [126]. There was no significant difference in the rate of postoperative AF (7 versus 15 percent, respectively). The study was stopped early because of an increase in renal failure in the naproxen group. Glucocorticoid Based upon the hypothesis that perioperative inflammation may contribute to the development of AF, glucocorticoids have been suggested as prophylactic therapy. (See "Glucocorticoid effects on the immune system".) Two meta-analyses of small trials in which glucocorticoid treatment was compared to placebo or no treatment in adult cardiac surgery found 26 and 40 percent reductions in the incidence of AF, irrespective of the dose given [127,128]. However, the large, randomized SIRS trial, published after the meta-analyses, found no difference in the rate of new AF [129]. Due to their potential adverse effects on glucose metabolism, wound healing, infection, and the absence of a lowering of the risk of death, we do not recommend the routine use of glucocorticoid therapy to prevent AF. The potential role for glucocorticoid therapy for other outcomes is discussed separately. (See "Coronary artery bypass surgery: Perioperative medical management", section on 'Glucocorticoid therapy'.) https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 14/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate Prevention of complications of atrial fibrillation While beta blockers, sotalol, amiodarone, and pacing decrease the risk of postoperative AF, the evidence is less robust that the risk of complications such as stroke, death, or length of stay can be prevented. It may be difficult to demonstrate a lowering of the risk of in-hospital stroke with these therapies, as AF is only one risk factor for stroke and as the incidence of stroke is low. (See 'Adverse outcomes following atrial fibrillation' above.) The best available evidence of the impact of these interventions on the complications of AF comes from a 2006 meta-analysis of heterogenous trials, which noted the following [72]: In 29 trials that evaluated length of stay, only amiodarone and pacing shortened the average length of stay (-0.60 days, 95% CI -0.92 to -0.29 and -1.3 days 95% CI -2.55 to -0.08, respectively). In 25 trials that reported on the incidence of postoperative stroke, the risk of stroke was decreased from 1.9 to 1.1 percent with treatment (odds ratio 0.63, 95% CI 0.41-0.98). Amiodarone was the only single intervention that significantly lowered the risk of stroke compared to placebo. Our approach to prevention We recommend preventative therapy to reduce the incidence of postoperative AF, especially in patients at high risk of its development. While the evidence is not robust, prevention of AF may lead to a lowering of the risk of in-hospital stroke and a shortened length of stay. In addition, successful prevention of AF will prevent the need for anticoagulation in some patients. Beta blockers, sotalol, amiodarone, and atrial pacing are significantly more effective than placebo in lowering the rate of postoperative AF [64,71,72]. There is some evidence to support the use of antioxidant vitamins for this purpose. We prefer beta blockers to amiodarone or sotalol due to lower cost and lower risk of potential side effects and to pacing because of its relative complexity and cost. Amiodarone or sotalol is a reasonable alternative in patients who cannot tolerate beta blockade. If possible, we prefer to start beta blockers prior to CABG. We suggest metoprolol 25 mg twice daily; the dose can be titrated postoperative based on the heart rate and blood pressure. We continue this therapy until the first postoperative visit, unless there is a contraindication. The evidence to support the use of antioxidant vitamins is less robust than that for traditional antiarrhythmic drugs. While awaiting larger randomized trials, we believe it is reasonable to use antioxidant therapy as given in the small randomized trial [87]. MANAGEMENT https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 15/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate While prevention with beta blockers, amiodarone, sotalol, or pacing lowers the risk of postoperative atrial fibrillation (AF), many patients still develop AF (see 'Prevention of atrial fibrillation' above). We are uncertain as to the optimal management of these patients, in part because it is not known whether postoperative AF represents the same arrhythmia as AF occurring without cardiac surgery or if it possesses a similar natural history in terms of portending adverse events. We think the initial management should include correction of predisposing factors such as hypoxemia, electrolyte abnormalities, and hemodynamic instability as well as pain management and withdrawal of stimulating factors such as inotropic agents. Subsequent management relates to the issues of rate control versus rhythm control cardioversion and anticoagulation [130]. Options for management of AF include rate or rhythm control strategies. For patients with atrial flutter, we cardiovert to sinus rhythm prior to discharge in most cases, as this rhythm is more difficult than AF to control medically. Rate control Given the transient nature of the arrhythmia (see 'Incidence and time course' above), initial control of the ventricular response rate is an effective and relatively safe strategy in many patients who develop postoperative AF [44,131]. Rate control is most commonly achieved with beta blockers. The benefit is partly due to blockade of the augmented postoperative sympathetic state and to prevention of beta blocker withdrawal in patients on beta blockers preoperatively. Intravenous esmolol, a beta blocker with a short half-life, can be given for acute rate control if there is a concern for bradyarrhythmias, hypotension, or bronchospasm. Slowing of the ventricular rate in many AF patients receiving inotropic agents postoperatively can be achieved by lowering the dose or discontinuation of these agents. The optimal rate goal for patients with AF after cardiac surgery has not been determined. As these patients vary widely in many clinical features (co-morbidities, need for rapid ventricular rate, etc), we suggest that the optimal ventricular rate be determined on a case by case basis. In many patients, a ventricular rate of less than 110 beats per minute will prevent symptoms such as palpitations and allow for optimal cardiac performance. (See "Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy", section on 'Evaluation and goal ventricular rate'.). Calcium channel blockers and digoxin are other atrioventricular (AV) nodal blockers that can control the ventricular rate in AF, but they are not more effective than beta blockers. In patients in whom alternate agents have not been successful in controlling the rate in atrial fibrillation, intravenous amiodarone can be used to slow the ventricular response. (See "Control of https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 16/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy".) Rhythm control Restoration of sinus rhythm from well-tolerated postoperative AF is usually not necessary but occasionally can be beneficial. (See 'Incidence and time course' above.) Restoration of sinus rhythm is indicated in symptomatic patients or in those when rate control is difficult to achieve. An attempt at the restoration of sinus rhythm can be beneficial in patients with a low ejection fraction. In addition, cardioversion in asymptomatic patients may be reasonable when well-tolerated AF occurs near the time of anticipated hospital discharge or when it does not spontaneously terminate within 24 hours, so that oral anticoagulation can be avoided; this is particularly true in patients at high risk of bleeding. We believe that an attempt at cardioversion with either electrical or pharmacologic therapy is reasonable. The choice between the two should be made on local practice and patient conditions. Electrical therapy of AF involves direct current external transthoracic cardioversion and it is effective in approximately 95 percent of cases [132] (see "Cardioversion for specific arrhythmias"). For patients who are refractory to transthoracic cardioversion or when reversion is desirable but the patient's respiratory status makes anesthesia for electrical conversion potentially difficult, pharmacologic therapy with intravenous sotalol or amiodarone is reasonable. (See 'Sotalol' above and 'Amiodarone' above.) Amiodarone dosing regimens are available in the relevant drug monograph. The efficacy of antiarrhythmic drugs for reversion of postoperative AF is similar to that in AF not related to surgery [133-141]. (See "Atrial fibrillation: Cardioversion".) Rate versus rhythm control For patients who do not spontaneously revert to sinus rhythm within a few hours, rate control and rhythm control (with or without electrical cardioversion) appear to be comparable strategies [45,46,142]. The choice between the two strategies should take into account patient and physician preferences. Advantages of a rate control strategy include the absence of side effects from drug therapy; disadvantages include a slower resolution of AF, thereby leading to a potentially greater need for anticoagulation at discharge. In many patients, we chose a rhythm control strategy. In a study of patients with no history of AF undergoing cardiac surgery, 523 individuals were randomly assigned to either rate or rhythm control [142]. In the rate control group, the heart rate goal was less than 100 beats per minute and in the rhythm control group, amiodarone was given with or without a rate slowing drug. If AF persisted for 24 to 48 hours, electrical cardioversion was recommended. The primary end point was the total number of days of https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 17/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate hospitalization within 60 days after randomization. There was no difference between the two groups in the primary outcome (median, 5.1 and 5 days, respectively; p = 0.76). This study had limitations, such as including heterogenous patients and lacking the power to assess effect on death or serious adverse events. Anticoagulation Patients on long-term anticoagulant For AF patients who are taking warfarin or direct oral anticoagulants, we suggest stopping this therapy at least three days before surgery. We restart oral anticoagulant therapy three to five days after surgery. The role of bridging heparin therapy for patients at high risk of an embolic complication while off oral anticoagulant, such as those with AF and a prior embolic event, is discussed elsewhere. (See "Perioperative management of patients receiving anticoagulants".) Patients not taking anticoagulant prior to cardiac surgery Patients with AF or atrial flutter, regardless of the setting, are at risk for thromboembolic events; the magnitude of that risk varies based upon a number of factors. Thromboembolic risk is primarily limited to AF or atrial flutter of more than 48 hours duration and is greater in patients with certain high risk features (eg, rheumatic mitral valve disease, previous thromboembolism, hypertension, or heart failure) ( table 2) [130]. The general recommendations for anticoagulation in patients with AF are discussed in detail elsewhere. (See "Atrial fibrillation in adults: Use of oral anticoagulants" and "Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation" and "Embolic risk and the role of anticoagulation in atrial flutter".) Patients who develop AF after cardiac surgery are at risk of thromboembolic events, including in- hospital stroke. However, in the individual post-surgical patient with an embolic event, the cause may be unclear, as underlying comorbidities are often responsible for such strokes, rather than the arrhythmia itself [56,64,143]. (See 'Incidence and time course' above.) Based on evidence that oral anticoagulant therapy prevents episodes of systemic embolization in the broad population of patients with atrial fibrillation, we believe that such therapy will lead to fewer embolic events in patients with postoperative AF. However, a reduction of events with anticoagulant therapy in this population has never been well studied. (See "Atrial fibrillation in adults: Use of oral anticoagulants", section on 'Summary and recommendations'.) As factors other than AF contribute to in-hospital stroke rates, it is not clear that aggressive early anticoagulation (eg, intravenous heparin as a bridge to warfarin) will reduce the incidence of stroke. In addition, the bleeding risk associated with anticoagulation in the immediate postoperative period (within the first 48 hours in most patients) makes the overall impact of this approach less certain. The potential complications associated with anticoagulation were https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 18/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate illustrated in several observational series of patients who were treated with intravenous heparin or oral anticoagulants for a variety of indications [144-146]. When closely monitored, complication rates appear to be low [144,145]. However, one report found a significant increase in large pericardial effusions and tamponade in patients treated with warfarin, particularly when the International normalized ratio (INR) was above the therapeutic target [146]. These large effusions all occurred one week or more after surgery. Thus, when anticoagulation is initiated, the patient must be monitored carefully. (See "Perioperative management of patients receiving anticoagulants".) Similarly, the optimal duration of anticoagulation after hospital discharge is unknown. Among patients with new-onset AF after cardiac surgery, many will revert to and maintain sinus rhythm [1,45-47]. Due to the inability to reverse their therapeutic effect, we do not start newer oral anticoagulants in the early postoperative period. There are limited data at present, but this is an evolving strategy that may gain support as our understanding evolves [147]. (See "Direct oral anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing and adverse effects".) Left atrial appendage closure Evidence is emerging that the left atrial appendage may play a major role in the development of stroke, and surgical closure may reduce this risk. Patients who have AF who are undergoing cardiac surgery for other indications may benefit from closure. Specific recommendations are provided separately. (See "Atrial fibrillation: Left atrial appendage occlusion".) Our approach to postoperative anticoagulation Among patients who develop AF following cardiac surgery, we suggest the following approach to anticoagulation: For patients with multiple episodes of AF or one episode that lasts more than 24 to 48 hours, we recommend the initiation of oral anticoagulant therapy, but only if bleeding risks are considered acceptable. As the role of direct thrombin and factor Xa inhibitors has not been established for patients with postoperative AF, we suggest that warfarin be chosen for most patients (International normalized ratio 2 to 3). We suggest continuation of anticoagulation for at least four weeks after return to sinus rhythm, particularly if the patient has risk factors for thromboembolism. Longer duration of anticoagulation is recommended by some of our experts in patients with high CHA DS - 2 2 VASc scores ( table 3), at low risk for bleeding based on the HAS-BLED score ( table 4), or at high risk of AF recurrence. https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 19/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate Long-term anticoagulation should be considered for patients who remain in AF or who have paroxysmal AF at four weeks. (See "Atrial fibrillation in adults: Use of oral anticoagulants", section on 'Summary and recommendations'.) We suggest maintaining oral anticoagulation in patients in which a concomitant Cox-Maze procedure has been performed for at least three months, regardless of no postoperative atrial arrhythmias. (See "Atrial fibrillation: Surgical ablation", section on 'Maze procedure'.) After three months with no AF recurrence, anticoagulation may be interrupted, considering the patient risk profile for stroke by the CHA DS -VASc score ( table 3) [148]. 2 2 In most cases, we do not use intravenous heparin as a bridge to full oral anticoagulation, as the risk of postoperative bleeding outweighs the small benefit from stroke prevention. For patients with prior systemic or pulmonary embolization or those with a mechanical valve, bridging anticoagulation with heparin may be reasonable. Both intravenous and oral anticoagulation should be monitored closely, as bleeding complications, including pericardial effusion and tamponade increase with excessive anticoagulation. RECOMMENDATIONS OF OTHERS Guidelines from the American College of Cardiology Foundation/American Heart Association and the European Society of Cardiology [130,148,149]. Our recommendations are generally consistent with recommendations from these groups. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Atrial fibrillation" and "Society guideline links: Arrhythmias in adults" and "Society guideline links: Coronary artery bypass graft surgery".) SUMMARY AND RECOMMENDATIONS Presentation Atrial fibrillation (AF) and atrial flutter occur frequently after cardiac surgery. Most episodes occur by the third postoperative day. (See 'Incidence and time course' above.) https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 20/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate Adverse outcomes Potential adverse outcomes of these atrial arrhythmias include a longer length of stay, stroke, or death. (See 'Adverse outcomes following atrial fibrillation' above.) Preventive strategies Beta blockers, sotalol, amiodarone, atrial pacing, reducing the risk of pericardial effusion, and antioxidant vitamins lower the risk of the development of AF and atrial flutter after cardiac surgery and may reduce the length of stay and lower the risk of in-hospital stroke. (See 'Prevention of atrial fibrillation and complications' above.) For patients undergoing cardiac surgery, we recommend treatment with beta blockers (Grade 1B). Beta blocker therapy should be started prior to surgery and continued at least until the first postoperative visit unless contraindicated. We prefer oral metoprolol 25 mg twice daily. For patients who cannot take beta blockers, either amiodarone or sotalol may be used, with the decision based on patient characteristics and physician familiarity. (See 'Our approach to prevention' above.) We suggest antioxidant therapy in addition to beta blocker therapy (Grade 2C). We start this therapy two days prior to surgery and continue until discharge. We prefer the regimen of vitamin C (1 gram) and vitamin E (400 international units), each given daily. (See 'Our approach to prevention' above.) Management of postoperative atrial fibrillation Ventricular rate control For hemodynamically stable patients who develop postoperative AF, the optimal ventricular rate range should be determined for each patient. In many patients, this rate will be less than 110 beats per minute. Cardioversion For patients who develop well-tolerated postoperative AF and whose rate is well controlled, we suggest not performing cardioversion within the first 24 hours of its development (Grade 2B). Cardioversion may be required within this time frame for those whose AF is poorly tolerated or whose rate is not well controlled. (See 'Rhythm control' above.) Cardioversion in asymptomatic patients may be reasonable when well-tolerated AF is present near the time of anticipated hospital discharge, or when it does not spontaneously terminate within 24 to 48 hours, so that oral anticoagulation can be avoided. https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 21/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate Anticoagulation For patients with multiple episodes of AF or one episode that lasts more than 24 to 48 hours, and if the perioperative bleeding risks are considered reasonable, we recommend oral anticoagulation (Grade 1B). (See 'Our approach to postoperative anticoagulation' above.) We suggest anticoagulation with warfarin (international normalized ratio 2 to 3) rather than either a direct thrombin or factor Xa inhibitor (Grade 2C). For patients in whom anticoagulation is started and irrespective of the rhythm status at the time of discharge from the hospital, we suggest continuation of anticoagulation for at least four weeks, rather than stopping at the time of discharge (Grade 2C). ACKNOWLEDGMENT The UpToDate editorial staff would like to thank Drs. John M. Stulak, Manuel Castell , and Arie P. Kappetein for their contributions to previous versions of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Maisel WH, Rawn JD, Stevenson WG. Atrial fibrillation after cardiac surgery. Ann Intern Med 2001; 135:1061. 2. Cox JL. A perspective of postoperative atrial fibrillation in cardiac operations. Ann Thorac Surg 1993; 56:405. 3. Tsikouris JP, Kluger J, Song J, White CM. Changes in P-wave dispersion and P-wave duration after open heart surgery are associated with the peak incidence of atrial fibrillation. Heart Lung 2001; 30:466. 4. Dupont E, Ko Y, Rothery S, et al. 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Off-pump coronary artery surgery for reducing mortality and morbidity: meta-analysis of randomized and observational studies. J Am Coll Cardiol 2005; 46:872. 35. Athanasiou T, Aziz O, Mangoush O, et al. Do off-pump techniques reduce the incidence of postoperative atrial fibrillation in elderly patients undergoing coronary artery bypass https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 24/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate grafting? Ann Thorac Surg 2004; 77:1567. 36. Angelini GD, Taylor FC, Reeves BC, Ascione R. Early and midterm outcome after off-pump and on-pump surgery in Beating Heart Against Cardioplegic Arrest Studies (BHACAS 1 and 2): a pooled analysis of two randomised controlled trials. Lancet 2002; 359:1194. 37. Almassi GH, Pecsi SA, Collins JF, et al. Predictors and impact of postoperative atrial fibrillation on patients' outcomes: a report from the Randomized On Versus Off Bypass trial. J Thorac Cardiovasc Surg 2012; 143:93. 38. Cummings JE, Gill I, Akhrass R, et al. Preservation of the anterior fat pad paradoxically decreases the incidence of postoperative atrial fibrillation in humans. J Am Coll Cardiol 2004; 43:994. 39. White CM, Sander S, Coleman CI, et al. Impact of epicardial anterior fat pad retention on postcardiothoracic surgery atrial fibrillation incidence: the AFIST-III Study. J Am Coll Cardiol 2007; 49:298. 40. Amar D, Shi W, Hogue CW Jr, et al. Clinical prediction rule for atrial fibrillation after coronary artery bypass grafting. J Am Coll Cardiol 2004; 44:1248. 41. Villareal RP, Hariharan R, Liu BC, et al. Postoperative atrial fibrillation and mortality after coronary artery bypass surgery. J Am Coll Cardiol 2004; 43:742. 42. Mariscalco G, Klersy C, Zanobini M, et al. 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30. Kim YM, Kattach H, Ratnatunga C, et al. Association of atrial nicotinamide adenine dinucleotide phosphate oxidase activity with the development of atrial fibrillation after cardiac surgery. J Am Coll Cardiol 2008; 51:68. 31. Verma A, Marrouche NF, Seshadri N, et al. Importance of ablating all potential right atrial flutter circuits in postcardiac surgery patients. J Am Coll Cardiol 2004; 44:409. 32. Akar JG, Kok LC, Haines DE, et al. Coexistence of type I atrial flutter and intra-atrial re- entrant tachycardia in patients with surgically corrected congenital heart disease. J Am Coll Cardiol 2001; 38:377. 33. Seiler J, Schmid DK, Irtel TA, et al. Dual-loop circuits in postoperative atrial macro re-entrant tachycardias. Heart 2007; 93:325. 34. Wijeysundera DN, Beattie WS, Djaiani G, et al. Off-pump coronary artery surgery for reducing mortality and morbidity: meta-analysis of randomized and observational studies. J Am Coll Cardiol 2005; 46:872. 35. Athanasiou T, Aziz O, Mangoush O, et al. Do off-pump techniques reduce the incidence of postoperative atrial fibrillation in elderly patients undergoing coronary artery bypass https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 24/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate grafting? Ann Thorac Surg 2004; 77:1567. 36. Angelini GD, Taylor FC, Reeves BC, Ascione R. Early and midterm outcome after off-pump and on-pump surgery in Beating Heart Against Cardioplegic Arrest Studies (BHACAS 1 and 2): a pooled analysis of two randomised controlled trials. Lancet 2002; 359:1194. 37. Almassi GH, Pecsi SA, Collins JF, et al. Predictors and impact of postoperative atrial fibrillation on patients' outcomes: a report from the Randomized On Versus Off Bypass trial. J Thorac Cardiovasc Surg 2012; 143:93. 38. Cummings JE, Gill I, Akhrass R, et al. Preservation of the anterior fat pad paradoxically decreases the incidence of postoperative atrial fibrillation in humans. J Am Coll Cardiol 2004; 43:994. 39. White CM, Sander S, Coleman CI, et al. Impact of epicardial anterior fat pad retention on postcardiothoracic surgery atrial fibrillation incidence: the AFIST-III Study. J Am Coll Cardiol 2007; 49:298. 40. Amar D, Shi W, Hogue CW Jr, et al. Clinical prediction rule for atrial fibrillation after coronary artery bypass grafting. J Am Coll Cardiol 2004; 44:1248. 41. Villareal RP, Hariharan R, Liu BC, et al. Postoperative atrial fibrillation and mortality after coronary artery bypass surgery. J Am Coll Cardiol 2004; 43:742. 42. Mariscalco G, Klersy C, Zanobini M, et al. Atrial fibrillation after isolated coronary surgery affects late survival. Circulation 2008; 118:1612. 43. Kosmidou I, Chen S, Kappetein AP, et al. New-Onset Atrial Fibrillation After PCI or CABG for Left Main Disease: The EXCEL Trial. J Am Coll Cardiol 2018; 71:739. 44. Soucier RJ, Mirza S, Abordo MG, et al. Predictors of conversion of atrial fibrillation after cardiac operation in the absence of class I or III antiarrhythmic medications. Ann Thorac Surg 2001; 72:694. 45. Lee JK, Klein GJ, Krahn AD, et al. Rate-control versus conversion strategy in postoperative atrial fibrillation: a prospective, randomized pilot study. Am Heart J 2000; 140:871. 46. Kowey PR, Stebbins D, Igidbashian L, et al. Clinical outcome of patients who develop PAF after CABG surgery. Pacing Clin Electrophysiol 2001; 24:191. 47. Landymore RW, Howell F. Recurrent atrial arrhythmias following treatment for postoperative atrial fibrillation after coronary bypass operations. Eur J Cardiothorac Surg 1991; 5:436. 48. Ambrosetti M, Tramarin R, Griffo R, et al. Late postoperative atrial fibrillation after cardiac surgery: a national survey within the cardiac rehabilitation setting. 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Demographic determinants and effect of pre-operative angiotensin converting enzyme inhibitors and angiotensin receptor blockers on the occurrence of atrial fibrillation after CABG surgery. BMC Cardiovasc Disord 2010; 10:7. https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 30/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate 112. Coleman CI, Makanji S, Kluger J, White CM. Effect of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers on the frequency of post-cardiothoracic surgery atrial fibrillation. Ann Pharmacother 2007; 41:433. 113. White CM, Kluger J, Lertsburapa K, et al. Effect of preoperative angiotensin converting enzyme inhibitor or angiotensin receptor blocker use on the frequency of atrial fibrillation after cardiac surgery: a cohort study from the atrial fibrillation suppression trials II and III. Eur J Cardiothorac Surg 2007; 31:817. 114. Bandeali SJ, Kayani WT, Lee VV, et al. Outcomes of preoperative angiotensin-converting enzyme inhibitor therapy in patients undergoing isolated coronary artery bypass grafting. Am J Cardiol 2012; 110:919. 115. Patti G, Chello M, Candura D, et al. Randomized trial of atorvastatin for reduction of postoperative atrial fibrillation in patients undergoing cardiac surgery: results of the ARMYDA-3 (Atorvastatin for Reduction of MYocardial Dysrhythmia After cardiac surgery) study. Circulation 2006; 114:1455. 116. Zheng Z, Jayaram R, Jiang L, et al. Perioperative Rosuvastatin in Cardiac Surgery. N Engl J Med 2016; 374:1744. 117. Liakopoulos OJ, Kuhn EW, Slottosch I, et al. Preoperative statin therapy for patients undergoing cardiac surgery. Cochrane Database Syst Rev 2012; :CD008493. 118. Kuhn EW, Slottosch I, Wahlers T, Liakopoulos OJ. Preoperative statin therapy for patients undergoing cardiac surgery. Cochrane Database Syst Rev 2015; :CD008493. 119. Ozaydin M, Peker O, Erdogan D, et al. N-acetylcysteine for the prevention of postoperative atrial fibrillation: a prospective, randomized, placebo-controlled pilot study. Eur Heart J 2008; 29:625. 120. Ozaydin M, Icli A, Yucel H, et al. Metoprolol vs. carvedilol or carvedilol plus N-acetyl cysteine on post-operative atrial fibrillation: a randomized, double-blind, placebo-controlled study. Eur Heart J 2013; 34:597. 121. Imazio M, Brucato A, Ferrazzi P, et al. Colchicine reduces postoperative atrial fibrillation: results of the Colchicine for the Prevention of the Postpericardiotomy Syndrome (COPPS) atrial fibrillation substudy. Circulation 2011; 124:2290. 122. Imazio M, Brucato A, Ferrazzi P, et al. Colchicine for prevention of postpericardiotomy syndrome and postoperative atrial fibrillation: the COPPS-2 randomized clinical trial. JAMA 2014; 312:1016. 123. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 31/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation 2014; 130:e199. 124. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation 2014; 130:2071. 125. January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in Collaboration With the Society of Thoracic Surgeons. Circulation 2019; 140:e125. 126. Horbach SJ, Lopes RD, da C Guaragna JC, et al. Naproxen as prophylaxis against atrial fibrillation after cardiac surgery: the NAFARM randomized trial. Am J Med 2011; 124:1036. 127. Ho KM, Tan JA. Benefits and risks of corticosteroid prophylaxis in adult cardiac surgery: a dose-response meta-analysis. Circulation 2009; 119:1853. 128. Dieleman JM, van Paassen J, van Dijk D, et al. Prophylactic corticosteroids for cardiopulmonary bypass in adults. Cochrane Database Syst Rev 2011; :CD005566. 129. Whitlock RP, Devereaux PJ, Teoh KH, et al. Methylprednisolone in patients undergoing cardiopulmonary bypass (SIRS): a randomised, double-blind, placebo-controlled trial. Lancet 2015; 386:1243. 130. Fuster V, Ryden LE, Cannom DS, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation). J Am Coll Cardiol. 2006; 48:e149. 131. Solomon AJ, Kouretas PC, Hopkins RA, et al. Early discharge of patients with new-onset atrial fibrillation after cardiovascular surgery. Am Heart J 1998; 135:557. 132. European Heart Rhythm Association, European Association for Cardio-Thoracic Surgery, Camm AJ, et al. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J 2010; 31:2369. 133. Geelen P, O'Hara GE, Roy N, et al. Comparison of propafenone versus procainamide for the acute treatment of atrial fibrillation after cardiac surgery. Am J Cardiol 1999; 84:345. 134. McAlister HF, Luke RA, Whitlock RM, Smith WM. Intravenous amiodarone bolus versus oral quinidine for atrial flutter and fibrillation after cardiac operations. J Thorac Cardiovasc Surg https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 32/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate 1990; 99:911. 135. Gavaghan TP, Koegh AM, Kelly RP, et al. Flecainide compared with a combination of digoxin and disopyramide for acute atrial arrhythmias after cardiopulmonary bypass. Br Heart J 1988; 60:497. 136. Di Biasi P, Scrofani R, Paje A, et al. Intravenous amiodarone vs propafenone for atrial fibrillation and flutter after cardiac operation. Eur J Cardiothorac Surg 1995; 9:587. 137. Campbell TJ, Gavaghan TP, Morgan JJ. Intravenous sotalol for the treatment of atrial fibrillation and flutter after cardiopulmonary bypass. Comparison with disopyramide and digoxin in a randomised trial. Br Heart J 1985; 54:86. 138. VanderLugt JT, Mattioni T, Denker S, et al. Efficacy and safety of ibutilide fumarate for the conversion of atrial arrhythmias after cardiac surgery. Circulation 1999; 100:369. 139. Yilmaz AT, Dem rkili U, Arslan M, et al. Long-term prevention of atrial fibrillation after coronary artery bypass surgery: comparison of quinidine, verapamil, and amiodarone in maintaining sinus rhythm. J Card Surg 1996; 11:61. 140. Connolly SJ, Mulji AS, Hoffert DL, et al. Randomized placebo-controlled trial of propafenone for treatment of atrial tachyarrhythmias after cardiac surgery. J Am Coll Cardiol 1987; 10:1145. 141. Hjelms E. Procainamide conversion of acute atrial fibrillation after open-heart surgery compared with digoxin treatment. Scand J Thorac Cardiovasc Surg 1992; 26:193. 142. Gillinov AM, Bagiella E, Moskowitz AJ, et al. Rate Control versus Rhythm Control for Atrial Fibrillation after Cardiac Surgery. N Engl J Med 2016; 374:1911. 143. Kollar A, Lick SD, Vasquez KN, Conti VR. Relationship of atrial fibrillation and stroke after coronary artery bypass graft surgery: when is anticoagulation indicated? Ann Thorac Surg 2006; 82:515. 144. Gohlke H, Gohlke-B rwolf C, St rzenhofecker P, et al. Improved graft patency with anticoagulant therapy after aortocoronary bypass surgery: a prospective, randomized study. Circulation 1981; 64:II22. 145. Weber MA, Hasford J, Taillens C, et al. Low-dose aspirin versus anticoagulants for prevention of coronary graft occlusion. Am J Cardiol 1990; 66:1464. 146. Malouf JF, Alam S, Gharzeddine W, Stefadouros MA. The role of anticoagulation in the development of pericardial effusion and late tamponade after cardiac surgery. Eur Heart J 1993; 14:1451. 147. Anderson E, Johnke K, Leedahl D, et al. Novel oral anticoagulants vs warfarin for the management of postoperative atrial fibrillation: clinical outcomes and cost analysis. Am J https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 33/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate Surg 2015; 210:1095. 148. Dunning J, Nagendran M, Alfieri OR, et al. Guideline for the surgical treatment of atrial fibrillation. Eur J Cardiothorac Surg 2013; 44:777. 149. Hillis LD, Smith PK, Anderson JL, et al. 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, Society of Cardiovascular Anesthesiologists, and Society of Thoracic Surgeons. J Am Coll Cardiol 2011; 58:e123. Topic 1011 Version 56.0 https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 34/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate GRAPHICS Signal averaged electrocardiogram predicts atrial fibrillation after coronary artery bypass graft (CABG) surgery The incidence of atrial fibrillation (AF) after coronary artery bypass graft surgery is directly related to the duration of the P wave on a signal averaged ECG. Data from Zaman AG, Archbold RA, Helft G, et al. Circulation 2000; 101:1403. Graphic 60431 Version 4.0 https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 35/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate Multivariable risk index for postoperative atrial fibrillation Predictor Risk points* Age <30 6 30-39 12 40-49 18 50-59 24 60-69 30 70-79 36 80 42 Medical history AF 7 COPD 4 Concurrent valve surgery 6 Withdrawal of treatment Beta blockers 6 ACE inhibitors 5 Preoperative and postoperative treatment Beta blockers 7 ACE inhibitors 5 Postoperative beta blocker treatment 11 Other treatment Potassium supplementation 5 NSAIDs 7 Sum of risk points Risk rank Postoperative AF risk <14 Low < 17 percent 14-31 Medium 17 to 52 percent >31 High > 52 percent AF: atrial fibrillation; COPD: chronic obstructive pulmonary disease; ACE inhibitors: angiotensin converting enzyme inhibitors; NSAIDs: nonsteroidal antiinflammatory drugs. https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 36/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate To calculate the estimated risk of postoperative atrial fibrillation, the sum of the risk points is determined. Scores are stratified into low risk (<14 points; AF incidence <17 percent), medium risk (14 to 31 points; AF incidence 17 to 52 percent) and high risk (>31 points; AF incidence >52 percent). Data from: Mathew JP, et al. JAMA 2004; 291:1720. Graphic 53732 Version 3.0 https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 37/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate CHADS score, thromboembolic risk, and effect of warfarin anticoagulation 2 Clinical parameter Points Congestive heart failure (any history) 1 Hypertension (prior history) 1 Age 75 years 1 Diabetes mellitus 1 Secondary prevention in patients with a prior ischemic stroke or a transient 2 ischemic attack; most experts also include patients with a systemic embolic event Events per 100 person-years* CHADS score 2 NNT Warfarin No warfarin 0 0.25 0.49 417 1 0.72 1.52 125 2 1.27 2.50 81 3 2.20 5.27 33 4 2.35 6.02 27 5 or 6 4.60 6.88 44 NNT: number needed to treat to prevent 1 stroke per year with warfarin. The CHADS score estimates the risk of stroke, which is defined as focal neurologic signs or symptoms that persist for more than 24 hours and that cannot be explained by hemorrhage, trauma, 2 or other factors, or peripheral embolization, which is much less common. Transient ischemic attacks are not included. All differences between warfarin and no warfarin groups are statistically significant, except for a trend with a CHADS score of 0. Patients are considered to be at low risk with a score of 0, at intermediate risk with a score of 1 or 2, and at high risk with a score 3. One exception is that most experts would consider patients with a prior ischemic stroke, transient ischemic attack, or 2 systemic embolic event to be at high risk, even if they had no other risk factors and, therefore, a score of 2. However, the great majority of these patients have some other risk factor and a score of at least 3. Data from: Go AS, Hylek EM, Chang Y, et al. Anticoagulation therapy for stroke prevention in atrial brillation: how well do randomized trials translate into clinical practice? JAMA 2003; 290:2685; and CHADS2 score from Gage BF, Waterman AD, Shannon W, et al. Validation of clinical classi cation schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA 2001; 285:2864. Graphic 61615 Version 8.0 https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 38/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate Comparison of the CHADS and CHA DS -VASc risk stratification scores for 2 patients with nonvalvular AF 2 2 Definition and scores for CHADS and CHA DS -VASc Stroke risk stratification with the CHADS and CHA DS -VASc scores 2 2 2 2 2 2 Unadjusted [1] CHADS acronym Score CHADS acronym ischemic stroke rate (% per year) 2 2 Congestive HF 1 0 0.6 Hypertension 1 1 3.0 Age 75 years 1 2 4.2 Diabetes mellitus 1 3 7.1 Stroke/TIA/TE 2 4 11.1 Maximum score 6 5 12.5 6 13.0 Unadjusted ischemic stroke rate CHA DS -VASc acronym 2 2 [2] CHA DS -VASc acronym Score 2 2 (% per year) Congestive HF 1 0 0.2 Hypertension 1 1 0.6 Age 75 years 2 2 2.2 Diabetes mellitus 1 3 3.2 Stroke/TIA/TE 2 4 4.8 Vascular disease (prior MI, PAD, or 1 5 7.2 aortic plaque) Age 65 to 74 years 1 6 9.7 Sex category (ie, female sex) 1 7 11.2 Maximum score 9 8 10.8 9 12.2 AF: atrial fibrillation; CHADS : Congestive heart failure, Hypertension, Age 75 years, Diabetes mellitus, prior Stroke or TIA or thromboembolism (doubled); CHA DS -VASc: Congestive heart failure, Hypertension, Age 75 years (doubled), Diabetes mellitus, prior Stroke or TIA or thromboembolism (doubled), Vascular disease, Age 65 to 74 years, Sex category; HF: heart failure; TIA: transient ischemic attack; TE: thromboembolism; MI: myocardial infarction; PAD: peripheral artery disease. 2 2 2 https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 39/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate [3] These unadjusted (not adjusted for possible use of aspirin) stroke rates were published in 2012 . Actual rates of stroke in contemporary cohorts might vary from these estimates. References: 1. Gage BF, Waterman AD, Shannon W, et al. Validation of clinical classi cation schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA 2001; 285:2864. 2. Lip GYH, Nieuwlaat R, Pisters R, et al. Re ning clinical risk strati cation for predicting stroke and thromboembolism in atrial brillation using a novel risk factor-based approach: the euro heart survey on atrial brillation. Chest 2010; 137:263. 3. Friberg L, Rosenqvist M, Lip GY. Evaluation of risk strati cation schemes for ischaemic stroke and bleeding in 182 678 patients with atrial brillation: the Swedish Atrial Fibrillation cohort study. Eur Heart J 2012; 33:1500. Original table and unadjusted ischemic stroke rates, as noted above, have been modi ed for this publication. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2014; 64:e1. Table used with the permission of Elsevier Inc. All rights reserved. Graphic 94752 Version 14.0 https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 40/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate Clinical characteristics comprising the HAS-BLED bleeding risk score Letter Clinical characteristic* Points H Hypertension (ie, uncontrolled blood pressure) 1 A Abnormal renal and liver function (1 point each) 1 or 2 S Stroke 1 B Bleeding tendency or predisposition 1 L Labile INRs (for patients taking warfarin) 1 E Elderly (age greater than 65 years) 1 D Drugs (concomitant aspirin or NSAIDs) or excess alcohol use 1 or 2 (1 point each) Maximum 9 points HAS-BLED score Bleeds per 100 patient-years (total points) 0 1.13 1 1.02 2 1.88 3 3.74 4 8.70 5 to 9 Insufficient data The HAS-BLED bleeding risk score has only been validated in patients with atrial fibrillation receiving warfarin. Refer to UpToDate topics on anticoagulation in patients with atrial fibrillation and on specific anticoagulants for further information and other bleeding risk scores and their performance relative to clinical judgment. INR: international normalized ratio; NSAIDs: nonsteroidal antiinflammatory drugs. Hypertension is defined as systolic blood pressure >160 mmHg. Abnormal renal function is defined as the presence of chronic dialysis, renal transplantation, or serum creatinine 200 micromol/L. Abnormal liver function is defined as chronic hepatic disease (eg, cirrhosis) or biochemical evidence of significant hepatic derangement (eg, bilirubin more than 2 times the upper limit of normal, plus 1 or more of aspartate transaminase, alanine transaminase, and/or alkaline phosphatase more than 3 times the upper limit of normal). Bleeding predisposition includes chronic bleeding disorder or https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 41/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate previous bleeding requiring hospitalization or transfusion. Labile INRs for a patient on warfarin include unstable INRs, excessively high INRs, or <60% time in therapeutic range. Based on initial validation cohort from Pisters R. A novel-user-friendly score (HAS-BLED) to assess 1- year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest 2010; 138:1093. Actual rates of bleeding in contemporary cohorts may vary from these estimates. Original gure modi ed for this publication. Lip GY. Implications of the CHA2DS2-VASc and HAS-BLED Scores for thromboprophylaxis in atrial brillation. Am J Med 2011; 124:111. Table used with the permission of Elsevier Inc. All rights reserved. Graphic 75259 Version 16.0 https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 42/43 7/5/23, 10:20 AM Atrial fibrillation and flutter after cardiac surgery - UpToDate Contributor Disclosures Richard Lee, MD, MBA No relevant financial relationship(s) with ineligible companies to disclose. Gabriel S Aldea, MD No relevant financial relationship(s) with ineligible companies to disclose. Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. John Pepper, MA, MChir, FRCS, FESC No relevant financial relationship(s) with ineligible companies to disclose. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/atrial-fibrillation-and-flutter-after-cardiac-surgery/print 43/43

7/5/23, 10:21 AM Atrial flutter: Maintenance of sinus rhythm - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Atrial flutter: Maintenance of sinus rhythm : Jordan M Prutkin, MD, MHS, FHRS : Bradley P Knight, MD, FACC : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: May 30, 2023. INTRODUCTION Atrial flutter is a relatively common supraventricular arrhythmia that can impact quality of life and cause stroke or systemic embolization. Restoration and maintenance of sinus rhythm improves symptoms and decreases the risk of embolization if atrial flutter recurrence does not occur. (See "Overview of atrial flutter", section on 'Clinical manifestations' and "Embolic risk and the role of anticoagulation in atrial flutter", section on 'Embolic risk'.) Issues related to the indications and therapeutic options for the maintenance of sinus rhythm in atrial flutter will be reviewed here. Causes of atrial flutter, rate control therapy, the restoration of sinus rhythm after cardioversion, and the role of anticoagulation in atrial flutter are discussed separately. (See "Overview of atrial flutter", section on 'Etiology and risk factors' and "Restoration of sinus rhythm in atrial flutter" and "Embolic risk and the role of anticoagulation in atrial flutter" and "Control of ventricular rate in atrial flutter".) INDICATIONS We attempt to keep most patients with recurrent atrial flutter in sinus rhythm to decrease symptoms, unlike atrial fibrillation (AF) in which rhythm control and rate control are reasonable strategies. In addition, the long-term maintenance of sinus rhythm may decrease the risk of stroke. Rhythm control with either radiofrequency (RF) catheter ablation or antiarrhythmic drug therapy is necessary; in most cases, RF catheter ablation is preferred because of the high rate of success and low rate of complications. Exceptions include individuals identified as having https://www.uptodate.com/contents/atrial-flutter-maintenance-of-sinus-rhythm/print 1/17 7/5/23, 10:21 AM Atrial flutter: Maintenance of sinus rhythm - UpToDate reversible triggers such as pneumonia, hyperthyroidism, and other acute medical problems. (See "Management of atrial fibrillation: Rhythm control versus rate control".). Atrial flutter is characterized by rapid, regular atrial depolarizations at a characteristic rate of approximately 300 beats/min. In the absence of rate slowing drugs or atrioventricular (AV) nodal disease, every other depolarization passes through the AV node, and the ventricular rate is usually around 150 beats per minute. Unlike AF, attempts to slow this rate are often unsuccessful or require high doses of rate slowing drugs; thus, the maintenance of sinus rhythm is desirable in most patients to control symptoms. In addition, episodes will often be recurrent unless a reversible cause is present. (See "ECG tutorial: Atrial and atrioventricular nodal (supraventricular) arrhythmias", section on 'Atrial fibrillation and atrial flutter' and "Overview of atrial flutter".) The discussion in this topic pertains primarily to patients with typical atrial flutter. The pathogenesis of typical atrial flutter makes it highly amendable to curative therapy with radiofrequency (RF) catheter ablation, though atypical flutters may also be cured with RF ablation. Typical (also called isthmus-dependent) atrial flutter utilizes a large macroreentrant pathway in the right atrium, with the left atrium following passively. (See "Electrocardiographic and electrophysiologic features of atrial flutter".) The negative deflection of the flutter (F) wave in lead II coincides in time with the impulse activating the low right atrial tissue between the inferior vena cava and the tricuspid valve. Activation then travels anteriorly through the region of the low septum, and superiorly and anteriorly up the medial surface of the right atrium, returning along the lateral wall of the right atrium back to the cavotricuspid isthmus (CTI) [1-6]. The cavotricuspid isthmus between the inferior vena cava and the tricuspid annulus (IVC-TA isthmus) is an obligatory route for typical flutter, and, as such, is the best anatomic target for ablation ( waveform 1A-B) [2-5,7-15]. RF CATHETER ABLATION For patients with typical atrial flutter in whom a decision is made to maintain sinus rhythm, radiofrequency catheter ablation is usually preferred to pharmacologic therapy. Technique The femoral approach is generally used and, under fluoroscopic guidance or using a three-dimensional mapping system, an ablation catheter is placed at the CTI where a large ventricular and small atrial electrogram are recorded. RF energy is applied, and the catheter is slowly withdrawn to create a line of ablation from the annulus to the inferior vena cava. https://www.uptodate.com/contents/atrial-flutter-maintenance-of-sinus-rhythm/print 2/17 7/5/23, 10:21 AM Atrial flutter: Maintenance of sinus rhythm - UpToDate The goal is to create a complete ablation line with the absence of electrical conduction across the CTI both medially to laterally and laterally to medially. This is the best marker for long-term success ( waveform 1A-B). If the patient presents in typical atrial flutter, CTI block should still be assessed with differential pacing on both sides of the ablation line after termination of atrial flutter, since frequently there can still be conduction across the CTI [16,17]. An infusion of isoproterenol during pacing may help to assess the completeness of isthmus block [18]. Alternatively, adenosine may also be given to assess for block across the line [19]. Another method for ablation is the maximum voltage technique [20]. Coronary sinus (CS) ostial pacing is completed and the largest amplitude atrial signal in the CTI is ablated as a point lesion. The next largest signal is then targeted, and the process is repeated until block is seen across the isthmus. Electroanatomic mapping is used in many cases for identifying the appropriate target area for ablation; it is a nonfluoroscopic three-dimensional mapping system. This system permits reconstruction of cardiac anatomy without the use of fluoroscopy. A study of 50 patients with atrial flutter compared isthmus ablation using conventional fluoroscopy for catheter positioning to positioning with electromagnetic mapping [21]. The success rate for complete isthmus blockade after 20 RF pulses or 25 minutes of fluoroscopy time was greater with electromagnetic mapping (96 versus 67 percent). Electromagnetic mapping significantly reduced the overall fluoroscopic time (4 versus 22 minutes) and the fluoroscopic time needed for isthmus mapping (0.2 versus 17.7 minutes). Ablation guided by intracardiac echocardiography (ICE) can also be used, and may be helpful to assess for pouches and ridges in the CTI during difficult cases or repeat procedures [10]. Outcome The initial success rate for RF catheter ablation of typical atrial flutter has ranged from 65 to 100 percent [22,23]. A meta-analysis of a 21 studies examining atrial flutter success rate suggested a single procedure success of 92 percent and multiple procedure success rate of 97 percent [24]. Recurrent atrial flutter or fibrillation Between 7 and 44 percent of patients who undergo flutter ablation have recurrent atrial arrhythmia, though the recurrent arrhythmia is usually AF [22,23]. Thus, some patients should undergo surveillance for recurrent atrial flutter or AF. Our approach to surveillance for recurrent arrhythmia is as follows. For patients who were initially symptomatic and who did not develop a tachycardia mediated cardiomyopathy, we perform testing to document recurrent arrhythmia only for symptoms. If the patient was initially asymptomatic, we perform periodic examinations (every 12 months) at which time we obtain an electrocardiogram, Holter, or event monitor. For those patients who developed tachycardia- https://www.uptodate.com/contents/atrial-flutter-maintenance-of-sinus-rhythm/print 3/17 7/5/23, 10:21 AM Atrial flutter: Maintenance of sinus rhythm - UpToDate mediated cardiomyopathy, standard heart failure therapy is still indicated unless otherwise contraindicated. Follow-up assessment of left ventricular function by imaging techniques such as echocardiography is warranted. We obtain a repeat echocardiogram three to six months after initiation of therapy. The rate of recurrent AF appears to depend upon the presence or absence of AF before the procedure. In a study of 100 patients, 29 of whom had documented AF before the procedure, AF occurred in 36.4 percent of those with complete follow-up after a mean of almost 15 months [25]. However, in another study of approximately 100 patients without pre-existent AF, new onset AF developed in only 12.9 percent during a mean follow-up of 19 months [26]. Most patients (92 percent) who develop AF after flutter ablation do so within six months. The risk may be as low as 10 percent (mean follow-up of 20 months) in those with no prior AF and a left ventricular ejection fraction >50 percent [27]. The likely reasons for the difference in the rates of recurrence likely has to do with differing populations being studied (eg, symptomatic versus asymptomatic patients) and the intensity of follow-up. In a study of 363 patients who underwent RF ablation for typical atrial flutter, 82 percent developed drug refractory AF during a follow-up period of 39 (+/- 11) months [28]. Elimination of atrial flutter may delay, but does not prevent AF and the two may share common triggers. Therefore, patients may derive a better long-term benefit from additional anatomical ablative treatment, lifestyle modifications, and/or pharmacological therapy of AF. (See 'Patients with atrial fibrillation' below.) Improvement in left ventricular function Persistent atrial flutter can result in a tachycardia-mediated left ventricular cardiomyopathy, similar to what has been seen with AF and other arrhythmias. On the other hand, reversal of the arrhythmia can result in improvement in left ventricular ejection fraction and, in 6 of 11 patients in one report, restoration of normal function [29]. (See "Hemodynamic consequences of atrial fibrillation and cardioversion to sinus rhythm" and "Arrhythmia-induced cardiomyopathy", section on 'Atrial fibrillation and atrial flutter'.) Quality of life RF ablation improves the quality of life and reduces symptoms in patients with atrial flutter, particularly if there is no associated AF [23,30]. Other benefits include a reduced frequency of hospitalizations, emergency department visits, need for cardioversion, and the need for antiarrhythmic drugs [31]. Safety RF catheter ablation of atrial flutter is significantly safer than that for atrial fibrillation, in part because the left atrium is not entered and because the procedure is generally shorter due to the fact that ablation in a very limited area that is not adjacent to vulnerable structures https://www.uptodate.com/contents/atrial-flutter-maintenance-of-sinus-rhythm/print 4/17 7/5/23, 10:21 AM Atrial flutter: Maintenance of sinus rhythm - UpToDate such as the esophagus and pulmonary veins [32]. (See "Atrial fibrillation: Catheter ablation", section on 'Complications'.) Pericardial effusion, atrioventricular block, and vascular access complications occur infrequently [33]. Procedure-related mortality is very rare and was 0 percent in a meta-analysis of 12 studies [24]. RF ablation versus pharmacologic therapy With the high success rate of radiofrequency (RF) catheter ablation for treating atrial flutter and its low complication rate, pharmacologic therapy is increasingly being replaced by ablation as the preferred strategy in most patients. Improved outcomes with ablation, compared to drug therapy, were illustrated in a randomized trial of 61 patients with at least two episodes of symptomatic atrial flutter within a four-month period [34]. The patients were assigned to conventional antiarrhythmic drug therapy or catheter ablation as a first line treatment. After a mean follow-up of 21 months, the following significant benefits were noted in the patients undergoing ablation: More were in sinus rhythm (80 versus 36 percent with drugs; P<0.01). Fewer required rehospitalization (22 versus 63 percent). Fewer developed AF (29 versus 53 percent). Sense of well-being and function during daily life activities improved with ablation but did not change with drugs. PHARMACOLOGIC THERAPY For most patients with atrial flutter, pharmacologic therapy is not chosen for the long-term maintenance of sinus rhythm. The success rate at one year has been estimated at only 20 to 30 percent, with the risk of recurrence highest in the patient with an enlarged right atrium who is in heart failure. Good prognostic signs for maintaining sinus rhythm are normal atrial size, recent onset, little or no heart failure, and an underlying reversible disorder such as hyperthyroidism, myocardial infarction, or pulmonary embolism. For patients in whom an attempt will be made to maintain sinus rhythm with antiarrhythmic drug therapy, we use the following drugs (with suggested starting doses): dronedarone 400 mg twice daily; flecainide 50 to 100 mg twice daily with an atrioventricular nodal agent; sotalol 80 mg twice daily; dofetilide 500 microgram twice daily; or amiodarone. Our reviewers have differing preferences as to the order in which these are tried. The drugs that are most likely to maintain sinus rhythm are the same as those used for rhythm control in atrial fibrillation (AF) ( algorithm 1). They act by suppressing triggering beats and https://www.uptodate.com/contents/atrial-flutter-maintenance-of-sinus-rhythm/print 5/17 7/5/23, 10:21 AM Atrial flutter: Maintenance of sinus rhythm - UpToDate arrhythmias and affecting atrial electrophysiologic properties. In a meta-analysis that included 36 patients, flecainide was 50 percent effective in the maintenance of sinus rhythm over variable follow-up [35]. Flecainide can also slow down the atrial flutter rate; thus, atrioventricular (AV) nodal agents should always be used in conjunction to prevent one-to-one atrial flutter. (See "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations", section on 'Selecting an antiarrhythmic drug'.) Oral dofetilide, a class III antiarrhythmic drug available for use in the United States, may be more effective than other agents for maintaining sinus rhythm. In the SAFIRE-D trial, which included 48 patients with atrial flutter, the probability of maintaining sinus rhythm at one year with dofetilide at a dose of 125, 250, or 500 mcg twice daily was 0.40, 0.37, and 0.58 versus 0.25 for placebo [36]. Dronedarone has been studied for the use of atrial flutter, though the major studies all included patients with AF also. In a trial of 2327 patients with AF or atrial flutter who were randomly assigned to either dronedarone 400 mg twice daily or placebo, dronedarone reduced the chances of recurrent AF or flutter by 25 percent and prolonged the time to first recurrence from 498 to 737 days [37]. In those with atrial flutter who had a recurrence, the mean heart rate was reduced by six beats/min, reflecting its rate control properties also. PATIENTS WITH ATRIAL FIBRILLATION Many patients with atrial flutter also have episodes of atrial fibrillation (AF). For many of these patients who have chosen ablation, we recommend atrial fibrillation (with or without atrial flutter ablation) ablation rather than atrial flutter ablation alone. The electrophysiologic substrates of AF and atrial flutter are different, and the addition of atrial flutter ablation to AF ablation adds very little risk. However, in some cases, we believe it is reasonable to perform atrial flutter ablation alone, particularly if atrial flutter is the predominant rhythm and if the rate in flutter is difficult and causing most symptoms. (See "Atrial fibrillation: Catheter ablation".) The optimal approach to ablation in patients with both atrial flutter and atrial fibrillation was evaluated in the single-blind APPROVAL trial, which randomly assigned 360 patients to ablation of AF (with or without atrial flutter ablation) or ablation of flutter alone [38]. Among patients in the first group, 124 received AF ablation only and 58 had both ablation procedures. At nearly 22 months of follow-up, patients assigned to the group that received AF ablation (with or without atrial flutter ablation) had a higher rate of primary end point of freedom from arrhythmia off antiarrhythmic drug therapy during follow-up (64 versus 19 percent). This outcome was similar for the two subpopulations in the first group (AF ablation with or without atrial flutter ablation). https://www.uptodate.com/contents/atrial-flutter-maintenance-of-sinus-rhythm/print 6/17 7/5/23, 10:21 AM Atrial flutter: Maintenance of sinus rhythm - UpToDate Patients in group one had significant improvement in scores on most quality-of-life measures, whereas those in group two did not. The finding in APPROVAL of similar outcomes between patients who received both AF and atrial flutter ablation and those who received AF ablation alone was noted in an earlier study of 108 patients with both AF and typical atrial flutter who were randomly assigned to either a dual ablative procedure (pulmonary vein isolation [PVI] and CTI ablation, 49 patients) or PVI alone (59 patients) [39]. These findings suggest that pulmonary vein triggers appear to initiate atrial flutter as well as AF. This conclusion is consistent with evidence that atrial flutter commonly starts after a transitional rhythm of variable duration, usually AF [40,41]. (See "Electrocardiographic and electrophysiologic features of atrial flutter".) ANTICOAGULATION The discussion of anticoagulation below focuses on patients who undergo radiofrequency (RF) catheter ablation. However, similar issues apply to patients with atrial flutter (and atrial fibrillation) in whom antiarrhythmic drug therapy is to be started. Any therapy that causes conversion of atrial flutter (or fibrillation) to sinus rhythm leads to a measurable increase in the short-term risk of embolization unless proper anticoagulation is in place. (See "Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation".) Anticoagulation before RF catheter ablation For patients in atrial flutter scheduled to under RF ablation, anticoagulation is handled, broadly speaking, in a manner similar to that for patients with atrial fibrillation who undergo cardioversion. Most of these patients require at least three to four weeks of adequate anticoagulation before the procedure. (See "Restoration of sinus rhythm in atrial flutter", section on 'Anticoagulation' and "Embolic risk and the role of anticoagulation in atrial flutter", section on 'Radiofrequency catheter ablation'.) For those patients with atrial flutter of less than 48 hours duration, there is disagreement whether a transesophageal echocardiogram (TEE) is necessary to exclude the presence of a left atrial thrombus, as there is not good quality evidence available. If a TEE is performed and no thrombus is found, RF catheter ablation may be performed without prior anticoagulation. For low-risk patients with atrial flutter of less than 48 hours, it may be reasonable to proceed with ablation without a TEE. (See "Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation", section on 'AF duration less than 48 hours'.) https://www.uptodate.com/contents/atrial-flutter-maintenance-of-sinus-rhythm/print 7/17 7/5/23, 10:21 AM Atrial flutter: Maintenance of sinus rhythm - UpToDate If the patient is not in atrial flutter at the time of the ablation, therapeutic anticoagulation is not necessary and a TEE is not usually performed. Anticoagulation after RF catheter ablation Anticoagulation for the prevention of embolic events may be necessary, at least on a temporary basis, after flutter ablation due to the potential for the development of recurrent atrial flutter or AF within six months. However, there are limited data to support this approach [42]. We use the following approach: We recommend oral anticoagulation for all patients for at least four weeks after atrial flutter ablation if they were in atrial flutter at the start of the ablation. For patients with evidence of recurrent atrial flutter after atrial flutter ablation, with atrial fibrillation before or after the flutter ablation, or for those patients in sinus rhythm at the time of the ablation, we use the CHA2DS2-VASc score to determine the long-term need for anticoagulation. This may include using no anticoagulation in those at low risk. This issue is discussed in detail elsewhere. (See "Atrial fibrillation: Catheter ablation", section on 'Periprocedural embolic events'.) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Atrial fibrillation" and "Society guideline links: Arrhythmias in adults".) SUMMARY AND RECOMMENDATIONS Indications We attempt to maintain sinus rhythm in most patients with recurrent atrial flutter to decrease symptoms and prevent complications. Unlike atrial fibrillation, the alternative strategy of rate control is usually unsuccessful. (See 'Indications' above.) Radio frequency ablation For most patients with typical atrial flutter in whom a rhythm control strategy is desired, we recommend radiofrequency catheter ablation rather than a pharmacologic approach (Grade 1B). (See 'RF catheter ablation' above and 'RF ablation versus pharmacologic therapy' above.) For patients with both atrial flutter and fibrillation, we recommend radiofrequency catheter ablation of the atrial fibrillation and flutter rather than ablation of atrial flutter alone (Grade 1B). (See 'Patients with atrial fibrillation' above.) https://www.uptodate.com/contents/atrial-flutter-maintenance-of-sinus-rhythm/print 8/17 7/5/23, 10:21 AM Atrial flutter: Maintenance of sinus rhythm - UpToDate For those patients in whom atrial flutter is the predominant rhythm, atrial flutter ablation alone is a reasonable strategy. Importance of anticoagulation Anticoagulation around the time of radiofrequency catheter ablation or pharmacologic cardioversion is handled in a manner similar to that for patients with atrial flutter or fibrillation scheduled to undergo cardioversion. Most patients will require effective anticoagulation both before and after the procedure. (See 'Anticoagulation' above.) ACKNOWLEDGMENT The UpToDate editorial staff thank Dr. Jie Cheng, who contributed as an author to prior versions of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Wells JL Jr, MacLean WA, James TN, Waldo AL. Characterization of atrial flutter. 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Further insights into the various types of isthmus block: application to ablation during sinus rhythm. Circulation 1996; 94:3204. 17. Schwartzman D, Callans DJ, Gottlieb CD, et al. Conduction block in the inferior vena caval- tricuspid valve isthmus: association with outcome of radiofrequency ablation of type I atrial flutter. J Am Coll Cardiol 1996; 28:1519. 18. Nabar A, Rodriguez LM, Timmermans C, et al. Isoproterenol to evaluate resumption of conduction after right atrial isthmus ablation in type I atrial flutter. Circulation 1999; 99:3286. 19. Lehrmann H, Weber R, Park CI, et al. "Dormant transisthmus conduction" revealed by adenosine after cavotricuspid isthmus ablation. Heart Rhythm 2012; 9:1942. 20. Jacobsen PK, Klein GJ, Gula LJ, et al. Voltage-guided ablation technique for cavotricuspid isthmus-dependent atrial flutter: refining the continuous line. J Cardiovasc Electrophysiol 2012; 23:672. 21. Kottkamp H, H gl B, Krauss B, et al. Electromagnetic versus fluoroscopic mapping of the inferior isthmus for ablation of typical atrial flutter: A prospective randomized study. Circulation 2000; 102:2082. https://www.uptodate.com/contents/atrial-flutter-maintenance-of-sinus-rhythm/print 10/17 7/5/23, 10:21 AM Atrial flutter: Maintenance of sinus rhythm - UpToDate 22. Scheinman MM, Huang S. The 1998 NASPE prospective catheter ablation registry. Pacing Clin Electrophysiol 2000; 23:1020. 23. Calkins H, Canby R, Weiss R, et al. Results of catheter ablation of typical atrial flutter. Am J Cardiol 2004; 94:437. 24. Spector P, Reynolds MR, Calkins H, et al. Meta-analysis of ablation of atrial flutter and supraventricular tachycardia. Am J Cardiol 2009; 104:671. 25. Anselme F, Saoudi N, Poty H, et al. Radiofrequency catheter ablation of common atrial flutter: significance of palpitations and quality-of-life evaluation in patients with proven isthmus block. Circulation 1999; 99:534. 26. Ng DW, Altemose GT, Wu Q, et al. Typical atrial flutter as a risk factor for the development of atrial fibrillation in patients without otherwise demonstrable atrial tachyarrhythmias. Mayo Clin Proc 2008; 83:646. 27. Paydak H, Kall JG, Burke MC, et al. Atrial fibrillation after radiofrequency ablation of type I atrial flutter: time to onset, determinants, and clinical course. Circulation 1998; 98:315. 28. Ellis K, Wazni O, Marrouche N, et al. Incidence of atrial fibrillation post-cavotricuspid isthmus ablation in patients with typical atrial flutter: left-atrial size as an independent predictor of atrial fibrillation recurrence. J Cardiovasc Electrophysiol 2007; 18:799. 29. Luchsinger JA, Steinberg JS. Resolution of cardiomyopathy after ablation of atrial flutter. J Am Coll Cardiol 1998; 32:205. 30. Lee SH, Tai CT, Yu WC, et al. Effects of radiofrequency catheter ablation on quality of life in patients with atrial flutter. Am J Cardiol 1999; 84:278. 31. O'Callaghan PA, Meara M, Kongsgaard E, et al. 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Am J Cardiol 1992; 70:3A. https://www.uptodate.com/contents/atrial-flutter-maintenance-of-sinus-rhythm/print 11/17 7/5/23, 10:21 AM Atrial flutter: Maintenance of sinus rhythm - UpToDate 36. Singh S, Zoble RG, Yellen L, et al. Efficacy and safety of oral dofetilide in converting to and maintaining sinus rhythm in patients with chronic atrial fibrillation or atrial flutter: the symptomatic atrial fibrillation investigative research on dofetilide (SAFIRE-D) study. Circulation 2000; 102:2385. 37. Page RL, Connolly SJ, Crijns HJ, et al. Rhythm- and rate-controlling effects of dronedarone in patients with atrial fibrillation (from the ATHENA trial). Am J Cardiol 2011; 107:1019. 38. Mohanty S, Mohanty P, Di Biase L, et al. Results from a single-blind, randomized study comparing the impact of different ablation approaches on long-term procedure outcome in coexistent atrial fibrillation and flutter (APPROVAL). Circulation 2013; 127:1853. 39. Wazni O, Marrouche NF, Martin DO, et al. 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Topic 1065 Version 27.0 https://www.uptodate.com/contents/atrial-flutter-maintenance-of-sinus-rhythm/print 12/17 7/5/23, 10:21 AM Atrial flutter: Maintenance of sinus rhythm - UpToDate GRAPHICS Intracardiac and surface ECG recordings during electrophysiologic study and radiofrequency catheter ablation of typical atrial flutter Three surface ECG leads (I, aVF, V1) and intracardiac recordings from the high right atrium (HRA), a mapping catheter in the isthmus between the tricuspid valve and inferior vena cava (TV-IVC) (HBE1-2), eight recordings from a catheter extending from the lateral right atrial wall through the TV-IVC isthmus and into the ostium of the coronary sinus (CS15-1 to CS1-2), and right ventricular apex (RVA3-4) in a patient with typical atrial flutter. The tip of the mapping catheter was initially positioned on the tricuspid annulus, and then dragged through the TV-IVC isthmus to the ostium of the IVC during RF application; atrial flutter terminated. Note that the atrial activation (A) blocks between CS7-8 and CS5-6, which on fluoroscopy corresponded to the position of the mapping catheter. Fl: flutter waves; V: ventricular electrogram. Graphic 69946 Version 4.0 https://www.uptodate.com/contents/atrial-flutter-maintenance-of-sinus-rhythm/print 13/17 7/5/23, 10:21 AM Atrial flutter: Maintenance of sinus rhythm - UpToDate Intracardiac and surface electrocardiogram (ECG) recordings during electrophysiologic study and radiofrequency catheter ablation of atrial flutter showing bidirectional isthmus block Shown are three surface ECG leads (I, aVF, V1) and intracardiac recordings from the high right atrium (HRA), eight recordings from a catheter extending from the lateral right atrial wall through the tricuspid valve-inferior vena cava (TV- IVC) isthmus and into the ostium of the coronary sinus (CS15-16 through CS1- 2), and right ventricular apex (RVA3-4) in a patient who has undergone ablation for atrial flutter. Left panel shows pacing (PA) from the lateral right atrial wall; the impulse is propagated down the lateral wall of the high right atrium, generating an atrial electrogram (A), to the lateral TV-IVC isthmus region (CS13- 14, CS11-12, CS9-10) where conduction is blocked. The medial aspect of the isthmus is not depolarized until a wavefront of activation comes down the interatrial septum or from the low left atrium; the distal poles of the catheter are therefore depolarized late and in the opposite direction, from the coronary sinus ostium back towards the medial TV-IVC isthmus (CS3-4, CS5-6, CS7-8). Right panel shows pacing from the coronary sinus ostium. In this case, the medial isthmus is depolarized promptly (CS3-4, CS5-6), but conduction is blocked within the isthmus (CS7-8). Thus, activation of the lateral wall of the right atrium is delayed until a wavefront travels up the septum and across the roof of the right atrium. Activation of the proximal poles of the catheter is therefore delayed and occurs from high to low (CS15-16, CS13-14, CS11-12, https://www.uptodate.com/contents/atrial-flutter-maintenance-of-sinus-rhythm/print 14/17 7/5/23, 10:21 AM Atrial flutter: Maintenance of sinus rhythm - UpToDate CS9-10). Patients with bidirectional block across the TC-IVC isthmus have a low rate of atrial flutter recurrence. Graphic 60090 Version 4.0 https://www.uptodate.com/contents/atrial-flutter-maintenance-of-sinus-rhythm/print 15/17 7/5/23, 10:21 AM Atrial flutter: Maintenance of sinus rhythm - UpToDate Maintenance of sinus rhythm Therapy to maintain sinus rhythm in patients with recurrent paroxysmal or persistent atrial fibrillation. Drugs are listed alphabetically and not in order of suggested use. The seriousness of heart disease progresses from left to right, and selection of therapy in patients with multiple conditions depends on the most serious condition present. LVH: left ventricular hypertrophy. Reproduced from: Fuster V, Ryden LE, Cannom DS, et al. 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 Guidelines for the management of patients with atrial brillation: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in partnership with the European Society of Cardiology and in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. J Am Coll Cardiol 2011; 57:223. Illustration used with the permission of Elsevier Inc. All rights reserved. Graphic 83173 Version 2.0 https://www.uptodate.com/contents/atrial-flutter-maintenance-of-sinus-rhythm/print 16/17 7/5/23, 10:21 AM Atrial flutter: Maintenance of sinus rhythm - UpToDate Contributor Disclosures Jordan M Prutkin, MD, MHS, FHRS No relevant financial relationship(s) with ineligible companies to disclose. Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/atrial-flutter-maintenance-of-sinus-rhythm/print 17/17

7/5/23, 10:21 AM Control of ventricular rate in atrial flutter - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Control of ventricular rate in atrial flutter : Jordan M Prutkin, MD, MHS, FHRS : Bradley P Knight, MD, FACC : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Jul 19, 2022. INTRODUCTION Atrial flutter is a relatively common supraventricular arrhythmia characterized by rapid, regular atrial depolarizations at a characteristic rate around 300 beats/min and a regular ventricular rate corresponding to one-half or one-quarter of the atrial rate (150 or 75 beats/minute). It may remain as atrial flutter, it may degenerate into atrial fibrillation, or it may revert to sinus rhythm within hours or days. In patients who present with or who have recurrent episodes associated with a rapid ventricular rate, slowing of the rate may be necessary to either reduce symptoms or prevent tachycardia-mediated cardiomyopathy. For the purpose of this topic, rate control means lowering the heart rate, which in the case of atrial flutter is usually difficult to achieve. Thus, for many patients, radiofrequency ablation (and permanent restoration of sinus rhythm) is the preferred long-term approach to patients with atrial flutter. (See "Atrial flutter: Maintenance of sinus rhythm", section on 'RF catheter ablation'.) The physiologic and clinical rationales for ventricular rate control in atrial flutter and the modalities used to achieve this goal will be reviewed here. Other issues such as the causes of atrial flutter, the embolic risk associated with this arrhythmia, and the restoration and maintenance of sinus rhythm are discussed separately. (See "Overview of atrial flutter" and "Restoration of sinus rhythm in atrial flutter" and "Embolic risk and the role of anticoagulation in atrial flutter" and "Atrial flutter: Maintenance of sinus rhythm".) PHYSIOLOGIC BASIS FOR THERAPY https://www.uptodate.com/contents/control-of-ventricular-rate-in-atrial-flutter/print 1/15 7/5/23, 10:21 AM Control of ventricular rate in atrial flutter - UpToDate The ventricular rate in atrial flutter is principally determined by the rate at which impulses exit the atrioventricular (AV) node. With a regular atrial rate of 300 beats/min, the ventricular rate is usually about 150 beats/min. This ventricular rate is determined by the refractory period of a healthy AV node, such that every other impulse (2:1) traverses the AV node and travels to the ventricles. In the absence of drugs that slow AV nodal conduction, a higher degree of AV block (eg, 3:1 or 4:1) suggests AV nodal disease; in these settings, the ventricular rates would be roughly 100 and 75 beats/min, respectively. Even input/output ratios (eg, 2:1 or 4:1 conduction) are more common than odd ratios (eg, 3:1 or 5:1). Odd ratios probably reflect bilevel block in the AV node. Sometimes, variable conduction may occur with alternating or seemingly random patterns of 2:1, 3:1, 4:1, or other conduction patterns, again due to varying levels of block in the AV node. On the other hand, a 1:1 response with typical atrial flutter usually suggests possible hyperthyroidism, catecholamine excess, parasympathetic withdrawal, or the existence of an accessory bypass tract. (See "Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome".) An important exception can occur in patients taking antiarrhythmic drugs, which can slow the atrial flutter rate so that 1:1 conduction occurs. This occurs most commonly with the class IC drugs, particularly when used in the absence of concomitant AV nodal blocking agents, but can also occur with dronedarone or even amiodarone. Also, 1:1 conduction of "slow" atrial flutter can occur in patients with marked right atrial enlargement. The AV node has been called a "slow response" tissue, since its action potential depends on calcium ions flowing through kinetically slow channels ( figure 1). The activation and reactivation characteristics of these channels limit the rate of conduction through the AV node. The autonomic nervous system can modify the rate of conduction, which is increased by sympathetic activity and reduced by parasympathetic activity. It is useful to consider the electrophysiologic differences between atrial fibrillation and atrial flutter, since they can impact therapy: Atrial fibrillation is characterized by multiple wandering wavelets, which result in the AV node being bombarded by 400 to 600 impulses per minute. Some impulses traverse the AV node and reach the specialized infranodal conduction system and then the ventricles. However, most of the atrial impulses penetrate the AV node for varying distances and then are extinguished by encountering the refractoriness of an earlier wavefront; this phenomenon of concealed conduction in turn creates a refractory wave that affects succeeding impulses. The lack of shortening of the refractory period with increasing rate https://www.uptodate.com/contents/control-of-ventricular-rate-in-atrial-flutter/print 2/15 7/5/23, 10:21 AM Control of ventricular rate in atrial flutter - UpToDate (as occurs in the atria) further decreases the likelihood of an impulse traversing the AV node. (See "The electrocardiogram in atrial fibrillation".) In comparison, typical atrial flutter is a macroreentrant arrhythmia, resulting in approximately 300 impulses/min reaching the AV node. This slower rate produces less refractoriness within the AV node and therefore less concealed conduction than in atrial fibrillation. Based upon these observations, it would be expected that atrial fibrillation would be more sensitive than atrial flutter to drugs that affect AV nodal refractoriness; this prediction has been confirmed clinically. Stated another way, control of the ventricular rate in atrial flutter is more difficult than in atrial fibrillation. (See 'Rate control with drugs' below.) INDICATIONS FOR RATE CONTROL There are three principle situations in which rate control should be considered: Immediate rate control to reduce symptoms during a first or subsequent episode in which a patient has not reverted to sinus rhythm (or spontaneously converted to atrial fibrillation); cardioversion should be considered, as it has a high likelihood of success. (See "Restoration of sinus rhythm in atrial flutter", section on 'Indications'.) It should be kept in mind that acute rate control in asymptomatic/minimally symptomatic patients with atrial flutter rarely works in the absence of coincident atrioventricular node disease. In the majority of patients, we focus on restoring sinus rhythm with cardioversion. Chronic therapy to prevent symptoms in patients who are likely to have recurrent atrial flutter and are not scheduled to undergo radiofrequency ablation of the atrial flutter. (See "Atrial flutter: Maintenance of sinus rhythm", section on 'RF catheter ablation'.) Chronic therapy to prevent tachycardia-mediated cardiomyopathy (see "Arrhythmia- induced cardiomyopathy") in the uncommon patient with chronic atrial flutter who does not undergo radiofrequency ablation of the atrial flutter. Atypical atrial flutter may result after an atrial fibrillation ablation procedure. Frequently, these patients may be more symptomatic with faster heart rates than when in atrial fibrillation. It may be difficult to rate control these patients, and antiarrhythmic agents, cardioversion, and/or atrial flutter ablation are frequently necessary. (See "Atrial fibrillation: Catheter ablation", section on 'Arrhythmic complications'.) https://www.uptodate.com/contents/control-of-ventricular-rate-in-atrial-flutter/print 3/15 7/5/23, 10:21 AM Control of ventricular rate in atrial flutter - UpToDate The following two characteristics of atrial flutter render the need to decide about the initiation of rate slowing uncommon: Atrial flutter may be an electrically unstable rhythm, meaning that it may degenerate into the less organized atrial fibrillation or revert to sinus rhythm within hours or days. Spontaneous reversion of paroxysmal atrial flutter to a sinus mechanism may occur after predisposing problems are improved, such as decompensated heart failure and the sequelae of cardiac surgery. Persistent atrial flutter is less common than persistent atrial fibrillation and is frequently associated with structural heart disease, atrial enlargement, prior cardiac surgery or atrial fibrillation ablation, or congenital heart disease. In these patients, chronic therapy to control the ventricular response is generally difficult unless there is concomitant atrioventricular (AV) node dysfunction. Atrial flutter, particularly the typical cavotricuspid-isthmus-dependent variety, is usually curable with catheter ablation. If patients have both atrial flutter and fibrillation, ablation of the cavotricuspid isthmus will not necessarily eliminate recurrent atrial fibrillation. This strategy may still be useful in selected patients in whom rapid rates during atrial flutter are highly symptomatic, but episodes of atrial fibrillation are well tolerated. RATE CONTROL GOALS Although rate control targets have been described for atrial fibrillation [1], they are less useful in atrial flutter since, as noted above, atrioventricular block tends to go in steps (eg, 2:1, 3:1, and 4:1). For most patients, we believe a ventricular rate at rest of less than 80 beats/min is reasonable for symptomatic patients and less than 110 beats/min may be reasonable for asymptomatic patients with normal left ventricular systolic function. Rate control should be assessed both at rest and with exertion. RATE CONTROL WITH DRUGS The goal of therapy with drugs that slow atrioventricular (AV) conduction is to improve symptoms and prevent the development of a tachycardia-mediated cardiomyopathy. For patients who require immediate rate slowing, and for whom cardioversion (and the restoration of sinus rhythm) is not chosen, we prefer intravenous diltiazem or esmolol to other options. For patients who will be placed on long-term oral therapy for rate control, we prefer either diltiazem or verapamil. https://www.uptodate.com/contents/control-of-ventricular-rate-in-atrial-flutter/print 4/15 7/5/23, 10:21 AM Control of ventricular rate in atrial flutter - UpToDate The rate at which impulses from the atria exit the AV node is the principle determinant of the ventricular rate. (See 'Physiologic basis for therapy' above.) Thus, rate control in atrial flutter is achieved principally with drugs that slow conduction through the AV node. The pharmacologic agents for controlling the ventricular rate in atrial flutter are based as follows: Blockade of the calcium channel with the nondihydropyridine calcium channel blockers diltiazem and verapamil. Decrease sympathetic tone using beta-blockers. Enhancement of parasympathetic tone with vagotonic drugs, most frequently digoxin. The use of amiodarone, which slows AV nodal conduction and increases AV nodal refractoriness. However, as discussed above, the smaller amount of concealed conduction in the AV node because of the slower atrial rate in atrial flutter means that greater AV nodal refractoriness must be produced. As a result, higher doses of a single drug are required, and combination therapy at conventional doses is frequently needed to minimize toxicity. Difficulties with pharmacologic rate control make patients with atrial flutter excellent candidates for a catheter ablation procedure, which is often curative. (See "Atrial flutter: Maintenance of sinus rhythm", section on 'RF catheter ablation'.) Nonpharmacologic therapy to convert back to normal sinus rhythm including direct current cardioversion, pace termination, or catheter ablation are reasonable treatments if the patient is having adverse hemodynamic consequences from the arrhythmia, if pharmacologic therapies are unsuccessful or not tolerated, or if the patient has pre-excitation syndrome. Calcium channel blockers The nondihydropyridine calcium channel blockers diltiazem and verapamil may be useful for acute rate control in non-pre-excited atrial flutter when given intravenously and can produce long-term rate slowing when given orally (see "Major side effects and safety of calcium channel blockers" and "Calcium channel blockers in the treatment of cardiac arrhythmias" and "Calcium channel blockers in the treatment of cardiac arrhythmias", section on 'Atrial fibrillation and flutter'): Diltiazem Intravenous diltiazem is often the drug of choice for acutely controlling the rapid ventricular response in atrial flutter [2-4]. Diltiazem increases AV nodal refractoriness and slows conduction velocity in the AV node, thereby decreasing the ventricular response. Diltiazem has a less pronounced negative inotropic effect than verapamil [5]. https://www.uptodate.com/contents/control-of-ventricular-rate-in-atrial-flutter/print 5/15 7/5/23, 10:21 AM Control of ventricular rate in atrial flutter - UpToDate There is a Food and Drug Administration-approved regimen for a continuous 24-hour intravenous diltiazem infusion [2-4]. This regimen consists of an intravenous bolus of 0.25 mg/kg (average adult dose 20 mg) over two minutes followed 15 minutes later by a second bolus of 0.35 mg/kg (average adult dose 25 mg) over two minutes if the first dose is tolerated but does not produce the desired response (20 percent reduction in heart rate from the baseline, conversion to sinus rhythm, or a heart rate less than 100 beats/min); this is followed by a continuous infusion at a rate of 10 to 15 mg/h in responders but not nonresponders; some patients respond to a 5 mg/h infusion [4]. This regimen usually controls the ventricular rate within four to five minutes [2]. Oral diltiazem is used far more commonly than verapamil for chronic rate control. Monotherapy with oral diltiazem can be used to treat patients with persistent atrial flutter, as well as patients who have recurrent or persistent atrial fibrillation with episodic atrial flutter. The initial dose is 30 mg every six hours, and is increased to a maximum of 360 mg/day. Sustained release diltiazem is most commonly used as a once a day drug. Verapamil Intravenous verapamil is very rarely used for acute control. Its use is associated with a higher frequency of hypotension than that with diltiazem. Verapamil, like diltiazem, increases refractoriness and decreases conduction velocity in the AV node, leading to reductions in the ventricular response in atrial flutter [6-10]. Intravenous verapamil can be given acutely in a dose of 5 to 10 mg over two to three minutes; this dose can be repeated every 15 to 30 minutes as necessary. The maintenance infusion rate is approximately 5 mg/hour. The onset of action is within two minutes and the peak effect occurs in 10 to 15 minutes. Control of the ventricular response is lost in roughly 90 minutes if repeated boluses or a maintenance infusion are not given. Similar to diltiazem, oral verapamil may be used to treat patients with persistent atrial flutter or patients with recurrent or persistent atrial fibrillation who have episodic atrial flutter. The initial dose of oral verapamil is 40 to 80 mg every six hours. This dose can be increased to a maximum of 360 mg/day if hepatic function is relatively normal. The sustained-release formulation is used for chronic therapy. Clinical cautions Diltiazem and verapamil should not be given to patients with severe heart failure (New York Heart Association class III or IV) and should be given with caution to patients with sinus node dysfunction, second- or third-degree AV block, the pre-excitation syndrome, hypotension, or the concurrent intake of other drugs that inhibit sinoatrial (SA) nodal function or slow AV nodal conduction. https://www.uptodate.com/contents/control-of-ventricular-rate-in-atrial-flutter/print 6/15 7/5/23, 10:21 AM Control of ventricular rate in atrial flutter - UpToDate Calcium channel blockers have a number of characteristics that need to be considered when they are administered to patients with atrial flutter: The effect on SA nodal function is variable, which is important if the patient has paroxysmal atrial flutter with episodes of normal sinus rhythm also. Although both verapamil and diltiazem have an inhibitory effect on the sinus node (which generates a slow action potential mediated by calcium fluxes), their vasodilator effects cause a reflex release of catecholamines that can maintain or slightly accelerate the SA nodal rate. However, SA nodal function is depressed in patients with the sinus node dysfunction, at least in part due to blockade of calcium channels and an inability of the sinus node to respond to catecholamines. Thus, if the normal reflex mechanism is impaired by therapy with a beta blocker, the addition of a calcium channel blocker can lead to slowing or, rarely, failure of SA nodal function. (See "Sinus node dysfunction: Epidemiology, etiology, and natural history".) Both drugs (verapamil perhaps more than diltiazem) can produce high-degree AV block and therefore should not be given to patients with underlying second- or third-degree AV block. For similar reasons, calcium channel blockers must be used with caution when given with other drugs that slow AV nodal conduction (eg, beta blockers, digoxin). Verapamil has a negative inotropic effect that is more pronounced than that of diltiazem. As a result, it should be used with caution in patients with heart failure and should not be given if the patient is hypotensive. It should also be used cautiously with other negative inotropes, such as beta blockers. Verapamil interacts with digoxin, resulting in an increase in serum digoxin. This interaction is dose-related (often occurring when verapamil doses are over 240 mg/day) and generally occurs after seven days of therapy with both agents. Similar to the digoxin-quinidine interaction, verapamil reduces the renal clearance of digoxin; it may also interfere with its hepatic metabolism [11-13]. Beta blockers There is little literature on the use of intravenous or oral beta blockers (excluding esmolol) as primary therapy for atrial flutter. Anecdotal reports suggest that these drugs can slow the ventricular rate, particularly if given in combination with digoxin or diltiazem. Among the beta blockers, atenolol and nadolol have the advantage of a long half-life, and atenolol, in our experience, has the least adverse effect on the sensorium. Long-acting propranolol and metoprolol preparations are also effective. We generally begin with atenolol, 25 mg/day, and increase the daily dose to 100 mg and sometimes 200 mg if necessary. Beta https://www.uptodate.com/contents/control-of-ventricular-rate-in-atrial-flutter/print 7/15 7/5/23, 10:21 AM Control of ventricular rate in atrial flutter - UpToDate blockers are particularly useful for patients who also have coronary artery disease or chronic heart failure. Beta blockers may have a variety of adverse effects. Some of these complications may be important in patients with atrial flutter, including worsening heart failure, hypotension, bradycardia, bronchospasm, and high-degree AV block. (See "Major side effects of beta blockers".) Esmolol Esmolol, a rapidly acting beta blocker with additional electrophysiologic properties, is administered intravenously, and is useful for rate control in acute non-pre- excited atrial flutter [14,15]. Esmolol is preferred to other intravenous beta blockers in this setting due to its rapid onset of action and a greater clinical experience. Esmolol begins to act in one to two minutes, is metabolized by red blood cell esterase, and has a short duration of action of 10 to 20 minutes. The following esmolol regimen is recommended for acute rate control: A bolus of 0.5 mg/kg is infused over one minute, followed by 50 mcg/kg per min If, after four minutes, the response is inadequate, another bolus is given followed by an infusion of 100 mcg/kg per min. If, after four minutes, the response is still inadequate, a third and final bolus can be given followed by an infusion of 150 mcg/kg per min. If necessary, the infusion can be increased to a maximum of 200 mcg/kg per min after another four minutes Alternatively, an infusion can be started at 50 mcg/kg per min without a bolus, and the rate of administration can be increased by 50 mcg/kg per min every 30 minutes. Digoxin Digoxin historically was the most commonly used drug to control the ventricular rate in atrial flutter in the nonemergent setting. However, calcium channel blockers and beta blockers, singly or in combination, have largely supplanted digoxin for both initial intravenous rate control and chronic oral therapy. The use of digoxin for the treatment of heart failure is discussed separately. (See "Secondary pharmacologic therapy for heart failure with reduced ejection fraction", section on 'Optional therapies'.) We generally reserve digoxin for patients whose rate has not adequately been controlled with the use of a calcium channel blocker, a beta blocker, or both. It is not as effective as these two https://www.uptodate.com/contents/control-of-ventricular-rate-in-atrial-flutter/print 8/15 7/5/23, 10:21 AM Control of ventricular rate in atrial flutter - UpToDate categories of drug, and its use is associated with higher mortality in patients at higher digoxin levels. It may not be appropriate for use in older patients. (See "Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy".) Digoxin can be administered orally, intravenously, or intramuscularly, although we do not use the intramuscular route because absorption is erratic. Intravenous digoxin begins to act within 15 to 30 minutes, with a peak effect attained in one to five hours. The relatively slow onset of action of digoxin is undesirable in patients with a rapid ventricular response. Since digoxin has a slow onset of action, there is rarely a reason for parenteral administration in patients who can take oral medications. A larger dose of digoxin than used in atrial fibrillation is required to control the ventricular rate in atrial flutter; as noted above, the smaller amount of concealed conduction in the AV node because of the slower atrial rate in atrial flutter means that greater AV nodal refractoriness must be produced [16]. Serum digoxin levels should be monitored periodically in patients on persistent therapy. Although the correlation between drug concentration and ventricular rate control is poor, the presence of a low value is useful since it allows a higher dose to be administered. The use of high doses of digoxin is potentially hazardous if electric cardioversion is performed, since this combination increases the risk of serious ventricular arrhythmias. Junctional escape beats (as detected by similarity of the longest observed recurring R-R intervals on the electrocardiogram [ECG]) are common when digoxin has successfully slowed the ventricular rate. Giving additional digoxin in this setting will increase the degree of AV nodal block and produce periods of regular junctional rhythm. The change from single junctional escapes to periodic junctional rhythm suggests the development of digoxin toxicity. If the pulse is palpated but ECG not reviewed, it may be mistakenly assumed that the patient is in sinus rhythm. However, it may be difficult to distinguish on the ECG between digoxin-induced complete heart block during atrial flutter and a slow, regular ventricular rate. In complete heart block, the R-R interval will not be an exact multiple of the atrial cycle length (A-A interval). In addition, the relationship between the QRS complex and flutter wave (ie, the point on the flutter wave where the QRS complex begins) is variable during complete heart block. Amiodarone Amiodarone can be used for rate control, but it should be remembered that intravenous amiodarone can possibly promote reversion to sinus rhythm, albeit infrequently. Since cardioversion is associated with an increased risk of thromboembolism, amiodarone should generally not be used in patients who are not candidates for conversion to sinus rhythm because of inadequate anticoagulation. (See "Prevention of embolization prior to and after https://www.uptodate.com/contents/control-of-ventricular-rate-in-atrial-flutter/print 9/15 7/5/23, 10:21 AM Control of ventricular rate in atrial flutter - UpToDate restoration of sinus rhythm in atrial fibrillation" and "Atrial fibrillation: Cardioversion", section on 'Less effective or ineffective drugs' and "Atrial fibrillation: Cardioversion", section on 'Specific antiarrhythmic drugs'.) Intravenous amiodarone slows conduction through the AV node and prolongs the effective refractory period of the AV node [17]. It has been used for rate control in critically ill patients with atrial tachyarrhythmias, mostly atrial fibrillation with some cases of atrial flutter [18,19]. This includes patients with heart failure, since amiodarone has less negative inotropic activity than beta blockers or calcium channel blockers [20]. (See "The management of atrial fibrillation in patients with heart failure".) The efficacy of slowing of the ventricular rate with amiodarone and diltiazem was compared in a study of 60 critically ill patients with recent onset atrial tachyarrhythmias, almost all atrial fibrillation [19]. Amiodarone was given as a 300 mg bolus, with or without a continuous infusion of 45 mg/h for 24 hours. Diltiazem was given as a 25 mg bolus, followed by a continuous infusion of 20 mg/h for 24 hours. Rate control was achieved with both drugs; the degree of slowing was somewhat better with diltiazem, an effect that was offset by a significantly higher incidence of hypotension that required discontinuation of diltiazem. Amiodarone may promote the appearance of "slow" atrial flutter in patients with atrial tachyarrhythmia. However, 1:1 AV conduction is generally not a problem in this setting due to the inhibitory effect of amiodarone on AV nodal conduction. In summary, amiodarone is an alternative rate control agent in patients with atrial flutter and severe hemodynamic compromise, although it has not been approved by the United States Food and Drug Administration for this purpose. Because of the long-term risk of adverse effects, amiodarone is generally not recommended for persistent rate control in patients with atrial flutter. (See "Amiodarone: Adverse effects, potential toxicities, and approach to monitoring".) RADIOFREQUENCY ABLATION OF THE ATRIOVENTRICULAR NODE Radiofrequency ablation of the AV junction (AV node and/or His bundle) is uncommonly performed in patients with pure atrial flutter because of the high rate of success with radiofrequency ablation of the re-entrant circuit, which maintains sinus rhythm [21,22]. The main indication for AV junction ablation is in patients with atrial flutter who have coincident atrial fibrillation. (See "Atrial flutter: Maintenance of sinus rhythm", section on 'RF catheter ablation'.) PATIENTS WITH PRE-EXCITATION SYNDROME https://www.uptodate.com/contents/control-of-ventricular-rate-in-atrial-flutter/print 10/15 7/5/23, 10:21 AM Control of ventricular rate in atrial flutter - UpToDate Among patients with atrial flutter and pre-excitation, therapy is aimed at reversion to sinus rhythm and subsequent treatment of the accessory pathway rather than rate control. The atrioventricular (AV) nodal blocking drugs (calcium channel blockers, beta blockers, and digoxin) can paradoxically increase the ventricular response in patients with atrial flutter and pre- excitation by impairing conduction via the normal AV node-His-Purkinje system. This decreases retrograde concealed conduction in the accessory pathway, thereby improving antegrade conduction over the pathway. Acute treatment should be directed toward converting to normal sinus rhythm in these patients. (See "Treatment of arrhythmias associated with the Wolff- Parkinson-White syndrome", section on 'When to avoid AV nodal blockers'.) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Atrial fibrillation" and "Society guideline links: Arrhythmias in adults".) SUMMARY AND RECOMMENDATIONS There are three principle clinical situations for which rate control should be considered in patients with atrial flutter: to treat symptoms during a first episode or recurrent episode; to prevent symptoms in patients who are likely to have recurrent atrial flutter; and to prevent tachycardia-mediated cardiomyopathy in the patient with chronic atrial flutter. (See 'Indications for rate control' above.) Rate control in atrial flutter is often more difficult than in atrial fibrillation. For many patients, atrial flutter ablation, which permanently restores sinus rhythm in a high percentage of patients, is the preferred long-term approach. (See 'Indications for rate control' above.) For most patients, we believe a ventricular rate at rest of less than 80 beats/min is reasonable for symptomatic patients and less than 110 beats/min may be reasonable for asymptomatic patients with normal left ventricular systolic function. (See 'Rate control goals' above.) For patients who require immediate rate slowing, and for whom cardioversion is not chosen, we suggest intravenous diltiazem or esmolol rather than other drug options (Grade 2C). The choice between these two should take into account practitioner familiarity. (See 'Rate control with drugs' above.) https://www.uptodate.com/contents/control-of-ventricular-rate-in-atrial-flutter/print 11/15 7/5/23, 10:21 AM Control of ventricular rate in atrial flutter - UpToDate For patients who will be placed on long-term oral therapy for rate control, we suggest oral diltiazem or verapamil rather than other oral agents (Grade 2C). (See 'Rate control with drugs' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Wyse DG, Waldo AL, DiMarco JP, et al. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002; 347:1825. 2. Salerno DM, Dias VC, Kleiger RE, et al. Efficacy and safety of intravenous diltiazem for treatment of atrial fibrillation and atrial flutter. The Diltiazem-Atrial Fibrillation/Flutter Study Group. Am J Cardiol 1989; 63:1046. 3. Ellenbogen KA, Dias VC, Plumb VJ, et al. A placebo-controlled trial of continuous intravenous diltiazem infusion for 24-hour heart rate control during atrial fibrillation and atrial flutter: a multicenter study. J Am Coll Cardiol 1991; 18:891. 4. Ellenbogen KA, Dias VC, Cardello FP, et al. Safety and efficacy of intravenous diltiazem in atrial fibrillation or atrial flutter. Am J Cardiol 1995; 75:45. 5. B hm M, Schwinger RH, Erdmann E. Different cardiodepressant potency of various calcium antagonists in human myocardium. Am J Cardiol 1990; 65:1039. 6. Dominic J, McAllister RG Jr, Kuo CS, et al. Verapamil plasma levels and ventricular rate response in patients with atrial fibrillation and flutter. Clin Pharmacol Ther 1979; 26:710. 7. Tommaso C, McDonough T, Parker M, Talano JV. Atrial fibrillation and flutter. Immediate control and conversion with intravenously administered verapamil. Arch Intern Med 1983; 143:877. 8. Hwang MH, Danoviz J, Pacold I, et al. Double-blind crossover randomized trial of intravenously administered verapamil. Its use for atrial fibrillation and flutter following open heart surgery. Arch Intern Med 1984; 144:491. 9. Plumb VJ, Karp RB, Kouchoukos NT, et al. Verapamil therapy of atrial fibrillation and atrial flutter following cardiac operation. J Thorac Cardiovasc Surg 1982; 83:590. https://www.uptodate.com/contents/control-of-ventricular-rate-in-atrial-flutter/print 12/15 7/5/23, 10:21 AM Control of ventricular rate in atrial flutter - UpToDate 10. Waxman HL, Myerburg RJ, Appel R, Sung RJ. Verapamil for control of ventricular rate in paroxysmal supraventricular tachycardia and atrial fibrillation or flutter: a double-blind randomized cross-over study. Ann Intern Med 1981; 94:1. 11. Klein HO, Lang R, Weiss E, et al. The influence of verapamil on serum digoxin concentration. Circulation 1982; 65:998. 12. Hori R, Okamura N, Aiba T, Tanigawara Y. Role of P-glycoprotein in renal tubular secretion of digoxin in the isolated perfused rat kidney. J Pharmacol Exp Ther 1993; 266:1620. 13. Hedman A, Angelin B, Arvidsson A, et al. Digoxin-verapamil interaction: reduction of biliary but not renal digoxin clearance in humans. Clin Pharmacol Ther 1991; 49:256. 14. Platia EV, Michelson EL, Porterfield JK, Das G. Esmolol versus verapamil in the acute treatment of atrial fibrillation or atrial flutter. Am J Cardiol 1989; 63:925. 15. Schwartz M, Michelson EL, Sawin HS, MacVaugh H 3rd. Esmolol: safety and efficacy in postoperative cardiothoracic patients with supraventricular tachyarrhythmias. Chest 1988; 93:705. 16. Smith TW. Digitalis. Mechanisms of action and clinical use. N Engl J Med 1988; 318:358. 17. Morady F, DiCarlo LA Jr, Krol RB, et al. Acute and chronic effects of amiodarone on ventricular refractoriness, intraventricular conduction and ventricular tachycardia induction. J Am Coll Cardiol 1986; 7:148. 18. Clemo HF, Wood MA, Gilligan DM, Ellenbogen KA. Intravenous amiodarone for acute heart rate control in the critically ill patient with atrial tachyarrhythmias. Am J Cardiol 1998; 81:594. 19. Delle Karth G, Geppert A, Neunteufl T, et al. Amiodarone versus diltiazem for rate control in critically ill patients with atrial tachyarrhythmias. Crit Care Med 2001; 29:1149. 20. Deedwania PC, Singh BN, Ellenbogen K, et al. Spontaneous conversion and maintenance of sinus rhythm by amiodarone in patients with heart failure and atrial fibrillation: observations from the veterans affairs congestive heart failure survival trial of antiarrhythmic therapy (CHF-STAT). The Department of Veterans Affairs CHF-STAT Investigators. Circulation 1998; 98:2574. 21. Scheinman MM, Evans-Bell T. Catheter ablation of the atrioventricular junction: a report of the percutaneous mapping and ablation registry. Circulation 1984; 70:1024. 22. Scheinman MM, Huang S. The 1998 NASPE prospective catheter ablation registry. Pacing Clin Electrophysiol 2000; 23:1020. Topic 1067 Version 32.0 https://www.uptodate.com/contents/control-of-ventricular-rate-in-atrial-flutter/print 13/15 7/5/23, 10:21 AM Control of ventricular rate in atrial flutter - UpToDate GRAPHICS Physiology of the AV node in AF The atrioventricular (AV) node modulates the response between the atrium and the ventricle. In atrial fibrillation, the atrial rate is up to 600 beats per minute while the ventricular rate in response is 90 to 170 beats per minute; this difference in the rate results from several properties of the AV node that impede impulse conduction. The AV node generates a slow action potential (AP) that is mediated by calcium (Ca++) ion currents; the node is therefore slow response tissue. Parasympathetic innervation via the vagus nerve also slows conduction, while activation of the sympathetic nervous system speeds conduction. Graphic 75699 Version 1.0 https://www.uptodate.com/contents/control-of-ventricular-rate-in-atrial-flutter/print 14/15 7/5/23, 10:21 AM Control of ventricular rate in atrial flutter - UpToDate Contributor Disclosures Jordan M Prutkin, MD, MHS, FHRS No relevant financial relationship(s) with ineligible companies to disclose. Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/control-of-ventricular-rate-in-atrial-flutter/print 15/15

7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Electrocardiographic and electrophysiologic features of atrial flutter : Jordan M Prutkin, MD, MHS, FHRS : Peter J Zimetbaum, MD, Ary L Goldberger, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Mar 31, 2023. INTRODUCTION Atrial flutter (AFL) is an abnormal cardiac rhythm characterized by rapid, regular atrial depolarizations at a typical atrial rate of 250 to 350 beats per minute. There is frequently 2:1 conduction across the atrioventricular (AV) node, meaning that every other atrial depolarization reaches the ventricles. As a result, the ventricular rate is usually one-half the AFL rate in the absence of AV node dysfunction. AFL is classified as typical or atypical based on whether the flutter circuit traverses the cavotricuspid isthmus in the right atrium [1]. Other topic reviews discuss the clinical aspects of AFL. (See "Overview of atrial flutter" and "Restoration of sinus rhythm in atrial flutter" and "Control of ventricular rate in atrial flutter" and "Atrial flutter: Maintenance of sinus rhythm" and "Embolic risk and the role of anticoagulation in atrial flutter" and "Atrial fibrillation and flutter after cardiac surgery".) CLASSIFICATION The first classification scheme in 1970 defined atrial flutter (AFL) as "common" or "atypical," depending on whether the flutter wave had a negative sawtooth pattern in the inferior leads [2]. A few years later, the terms types I and II were created to describe flutter [1]. Type I AFL was classified as a macroreentrant atrial tachycardia while type II AFL was considered unclassified because the mechanisms were not fully understood. https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 1/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate A 2001 working group from Europe and North America tried to reconcile new data from electrophysiology studies and activation mapping [3]. Flutter was defined as a regular tachycardia 240 beats/min with no isoelectric baseline between atrial deflections. Typical and reversal typical flutter were characterized, as described below, and all other flutters were atypical. An American College of Cardiology, American Heart Association, and Heart Rhythm Society guideline on the management of supraventricular tachycardia reaffirmed the classification of AFL into cavo-tricuspid-isthmus (CTI)-dependent ("typical") versus non-CTI dependent ("atypical") [4] and this is the methodology currently used. Typical AFL is a macroreentrant atrial tachycardia, with the inferior border of the circuit traversing the isthmus of tissue between the inferior vena cava and tricuspid annulus as a necessary component. AFL involving this cavotricuspid isthmus is referred to as "typical" or "isthmus-dependent" flutter. In the most common form of CTI-dependent flutter, the reentrant circuit rotates around the tricuspid annulus in a counterclockwise direction when the heart is viewed in a left anterior oblique projection, traversing up the septum and down the lateral wall. This is the arrhythmia associated with the classic electrocardiogram finding of sawtooth flutter waves in the inferior leads. (See 'Electrocardiographic features' below.) Less often, the reentrant circuit rotates in the opposite direction. This arrhythmia is called "clockwise" or "reverse" typical flutter. Atypical AFL is an intraatrial reentrant tachycardia or AFL that does not involve the CTI. It may be a lesion macroreentrant tachycardia, upper loop flutter, intra-isthmus reentry, non-atriotomy- related right atrial flutter, left atrial macroreentry, post-Maze or atrial fibrillation ablation left atrial flutters, or mitral annular flutter [5]. It is frequently seen in those who have had prior cardiac surgery, prior intracardiac ablation, congenital heart disease, or cardiomyopathy but may also be idiopathic. Atypical flutter may be in the right or left atrium and usually revolves around a prior incisional or idiopathic scar, ablation lesion set, or other fixed anatomic barriers. If there has been an incomplete ablation line from a prior procedure, this can increase the chances of an atypical flutter. Many patients with congenital heart disease, especially with more complex disease or surgical repairs, will present with atypical flutter, known as intraatrial reentrant tachycardia [6]. Some patients with idiopathic atrial fibrosis will also present with scar- based atypical flutters. ELECTROPHYSIOLOGIC FEATURES https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 2/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Electrophysiologic studies, using entrainment mapping and electroanatomic mapping, have been used to define the atrial flutter (AFL) circuit in the electrophysiology laboratory and at surgery [7-11]. The principal electrophysiologic features of AFL are: Reentry Excitable gap Transient entrainment and termination by rapid atrial pacing Electrophysiologically, AFL is a reentrant arrhythmia in that it excites an area of the atrium and then travels sufficiently slowly in a pathway that is long enough such that the initially excited area recovers its excitability and is reactivated [7-9,12-15]. Either a single premature extrastimulus or rapid atrial pacing can initiate AFL and, because there is an excitable gap, terminate the arrhythmia [13-15]. The excitable gap is the portion of a reentrant circuit that has recovered its excitability and can again be depolarized, allowing for entrainment with overdrive pacing during AFL [13,14,16]. (See "Reentry and the development of cardiac arrhythmias", section on 'Definition and characteristics'.) Typical AFL commonly starts after a transitional rhythm of variable duration, usually atrial fibrillation [17,18]. It has been postulated that a fundamental feature that determines whether an atrial arrhythmia becomes sustained typical AFL or atrial fibrillation is the development of a line of functional refractoriness or block between the vena cavae [18]. In spontaneous typical AFL, the critical line of functional block between the vena cavae may be created by transient atrial fibrillation. This line of block results in unidirectional block and stable AFL follows. According to this theory, if the line of functional block is not created, atrial fibrillation persists or the rhythm reverts back to sinus. Another view, based in part on a small electrophysiologic study of 10 patients, emphasizes the anatomic barriers as well as the properties of conduction and refractoriness during atrial fibrillation to explain the usual pattern observed with typical AFL [19]. In the electrophysiology laboratory, premature electrical stimulation may function in a manner similar to the transitional atrial fibrillation in forming the critical functional line of block between the vena cavae [18]. An additional determinant of whether the transitional atrial tachyarrhythmia becomes AFL or atrial fibrillation may be the cycle length of the flutter [18]. If the cycle length is critically short, it will create fibrillatory conduction and atrial fibrillation. Lastly, the electrical properties of the isthmus may also be a factor in the tendency for AFL to disorganize into atrial fibrillation in some patients [20]. https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 3/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Similar to what has been reported in atrial fibrillation, AFL results in electrical remodeling of the atrial myocardium, perhaps accounting for the observation that untreated AFL can eventually lead to atrial fibrillation [21]. In contrast to the normal situation in which the atrial refractory period shortens with an increase in rate and prolongs when the rate decreases, the refractory period fails to lengthen appropriately at slow rates (eg, with return to sinus rhythm) in patients with AFL present for a mean of 8.5 months (range 1 to 32 months) [22]. This abnormality persists for at least 30 minutes after cardioversion to sinus rhythm; the duration of AFL has no significant impact upon the magnitude of these electrophysiologic changes. Those with a history of AFL, but not fibrillation, have significant changes in the electrophysiologic properties of the right atrium, even when they are in normal sinus rhythm. The right atrium is more likely to be enlarged, have lower voltage suggesting scar, longer P wave duration, and slowed conduction velocity most prominent in the lower right atrium, and sinus node dysfunction [23]. The duration of AFL does impact the time course of electrical remodeling recovery after arrhythmia termination. As an example, one study of 25 patients with paroxysmal or chronic flutter (average duration 17 months) found that, in those with paroxysmal AFL, the refractory period shortened after a 5- to 10-minute period of flutter and reversed within five minutes of restoration of sinus rhythm; atrial fibrillation developed in some patients when the refractory period was at its nadir [24]. In patients with chronic AFL, the atrial refractory period increased during the first three weeks after resumption of sinus rhythm. Typical flutters A large macroreentrant circuit in the right atrium is involved in typical AFL. If one begins the cycle at the end of the negative deflection of the F wave in lead II, the impulse at that point exists in the low right atrial septum between the inferior vena cava (IVC) and the tricuspid valve. In counterclockwise typical flutter, the impulse then travels anteriorly through the region of the low septum, ascends superiorly and anteriorly up the septal and posterior walls of the right atrium, and returns or descends over the anterior and lateral free wall ( figure 1) [25]. This circuit is then completed through the region between the tricuspid valve and IVC (counterclockwise reentry). A reverse direction of rotation (clockwise reentry, ascending the anterior wall, and descending the posterior and septal walls) is seen in reverse typical AFL [3,25]. The crista terminalis (and its continuation as the eustachian ridge) and IVC often form the posterior barrier, while the tricuspid annulus constitutes the anterior barrier of the circuit ( figure 1) [11,26]. This has potential clinical implications, since this region can be a target for ablation therapy in patients with refractory AFL [26,27]. (See "Atrial flutter: Maintenance of sinus rhythm", section on 'RF catheter ablation'.) https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 4/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate The presence of slow conduction in the cavotricuspid isthmus has been confirmed by noncontact mapping [28]. The cavotricuspid isthmus is a part of the circuit most vulnerable to interval-dependent conduction delay [16] and termination of AFL with ibutilide, propafenone, or amiodarone is due in part to failure of impulse conduction through this tissue [22]. (See "Overview of catheter ablation of cardiac arrhythmias", section on 'Noncontact mapping'.) The typical AFL circuit has been thought to run anterior to the superior vena cava (SVC) in most patients [29]. However, a study of 15 patients with typical flutter using noncontact and entrainment mapping showed that the posterior wall was a part of the circuit in seven patients [30]. In a study of 50 patients using entrainment mapping, between one-quarter to one-third did not use the atrial roof anterior to the SVC as part of the circuit [31]. These studies imply that the crista terminalis is not always a fixed barrier to conduction and the circuit can be posterior to the SVC. Partial isthmus atrial flutter is a type of typical flutter where a wavefront goes between the IVC and coronary sinus ostium after conducting through the posterior cavo-tricuspid-isthmus (CTI). This wavefront then conducts around the CS ostium and up the septum, but also goes retrograde back into the anterior CTI. For this circuit to occur, there must either be a pectinate muscle that breaks the CTI into an anterior and posterior portion [32] or rapid conduction through the eustachian ridge [26]. Intra-isthmus reentry is usually seen in those with prior CTI ablation [33]. The circuit is contained entirely within the CTI and may be in the septal, medial, or anterior portions, with areas of long fractionated potentials the best target for ablation [33]. The circuit for lower loop reentry circles around the IVC, on the septal side usually between the IVC and coronary sinus ostium [34]. It exits out on the low lateral wall, with wavefront one conducting up the lateral wall and wavefront two going through the CTI, anterior to the coronary sinus ostium, and up the septal wall in a manner similar to counterclockwise typical flutter. The two wave fronts collide somewhere in the lateral right atrium or septum, but the dominant circuit still encircles the IVC. Lower loop reentry frequently morphs into counterclockwise AFL and may be associated with an atrial myopathy [5]. Atypical right atrial flutters Lesion macroreentrant tachycardia An atriotomy scar or suture line can act as an obstacle to conduction and create reentry. There may also be atrial septal defect patches that can lead to an atypical flutter circuit. In addition, scar from congenital heart disease lesions such as after an atrial level switch surgery (Mustard or Senning repairs) for transposition of the great arteries or https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 5/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate after a Fontan repair may lead to atypical flutters. (See "Management of complications in patients with Fontan circulation", section on 'Arrhythmias'.) Atriotomy scar-related atypical flutters are the most common of this type, where the scar is vertical along the lateral right atrium. The anterior right atrial wall may have ascending or descending activation depending on whether the circuit is clockwise or counterclockwise, while the septum may have more variable conduction [3]. The circuit wraps around the incision, with the upper turnaround point between the scar and SVC and the lower turnaround point between the scar and IVC. Alternatively, one of the turnaround points may be through an area of conduction within the scar. As is true for all flutters, entrainment and activation mapping are helpful for defining the circuit. The atriotomy region will have double potentials and low voltage to denote its location. During flutter, the double potentials are more widely spaced in the center of the scar and usually become one single fractionated electrogram at the turnaround points. Typical flutter may be seen after ablation of this atypical flutter, if a prior cavotricuspid isthmus ablation has not previously been completed. Nonatriotomy-related right atrial flutter For unexplained reasons, some patients will have areas of low voltage in the right atrium. This may lead to a scar similar to an atriotomy lesion, even though there has been no cardiac incision. This leads to a flutter wrapping around the scar, though may also be a figure-8 reentry if there is conduction through the low voltage area [32]. Ablation from the lower border of the scar to the IVC frequently terminates the arrhythmia. Upper loop reentry This circuit crosses through a conduction gap in the crista terminalis in the upper right atrium, which is where the successful site of ablation can be [35]. It can be clockwise or counterclockwise, with activation going up or down the anterior right atrial free wall. At least one patient also demonstrated successful ablation in the region between the fossa ovalis and IVC [32], indicating that this tachycardia circuit may not be as clearly defined as previously thought. Atypical left atrial flutters Post-Maze or atrial fibrillation ablation left atrial flutters These tachycardias are most frequently due to incomplete ablation lines from either a transvenous catheter ablation or a surgical Maze procedure. They may also be related to left atrial fibrosis seen in those with a history of atrial arrhythmias. They are usually seen in the anterior wall, through the roof, or on the septum. Mapping can often be difficult due to low voltages. (See "Atrial fibrillation: Surgical ablation", section on 'Maze procedure'.) https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 6/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Mitral annular flutter wraps around the mitral valve clockwise or counterclockwise [36,37]. Entrainment from a catheter in the coronary sinus will frequently demonstrate concealed entrainment on all poles for mitral annular flutter, but not for other left atrial flutters. It can be difficult to terminate and often needs ablation within the coronary sinus or vein of Marshall to achieve a line of block [38]. Even in the presence of apparent complete block, there may still be recurrence of mitral flutter as there may only be significant conduction slowing rather than block [39]. Left atrial macroreentry Less commonly, atypical flutters can occur in those with no prior ablation or surgery in the left atrium. They may be located on the anterior or posterior wall and are bounded by an anatomic obstacle like the mitral annulus [40]. They may be a single circuit or double loop and are associated with low voltage signals with areas of fractionated signals [41]. Atrioventricular node and the ventricular response The electrophysiologic events in AFL can be viewed as an input (the F waves) and an output (QRS complexes) that is processed through a regulator or black box (the atrioventricular [AV] node). The electrophysiologic characteristics of the AV node, which is a "slow response" tissue in comparison to the atria, primarily determine the ventricular response. (See "The electrocardiogram in atrial fibrillation".) As noted below (see 'Electrophysiologic features' above), the ventricular response in AFL is generally one-half the atrial input, resulting in a ventricular rate of about 150 beats/min. 3:1 and 4:1 input/output ratios are also relatively common, leading to ventricular rates of about 100 and 75 beats/min, respectively. Thus, AFL should be considered whenever the electrocardiogram shows a heart rate of 150, 100, and 75 beats/min. Rarely, the input/output ratio is 1:1, resulting in a ventricular response of nearly 300 beats/min. This may occur in states characterized by marked catecholamine excess and in the presence of AV bypass tracts with preexcitation ( waveform 1). A 1:1 response is more commonly seen when the atrial rate is slowed and AV nodal conduction is enhanced, leading to ventricular rates of 220 to 250 beats/min. This combination can be induced by class IA or IC antiarrhythmic drugs ( table 1) due to: Slowing of the conduction velocity in the reentrant circuit and therefore the flutter rate by inhibition of sodium channels. Increasing AV nodal conduction by their vagolytic effects. These characteristics have implications for management. (See "Control of ventricular rate in atrial flutter".) https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 7/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Partial or complete block in the AV node or in the specialized infranodal conduction system (His bundle, bundle branches and fascicles, and terminal Purkinje fibers) may lead to escape or accelerated rhythms from within the AV node or below to assume control of the ventricles. The ventricular rate in this setting may be normal, faster, or slower than is normal for these lower pacemakers. The diagnosis of complete heart block may be missed if F waves are not carefully matched with R waves or when the lower escape rate approaches an arithmetic divisor of the flutter rate. As is true for atrial fibrillation, there may be a Wenckebach type of exit block around such an escape site, resulting in group beating. ELECTROCARDIOGRAPHIC FEATURES The electrocardiographic features of typical atrial flutter (AFL) in the presence of normal atrioventricular (AV) nodal conduction are ( waveform 2): P waves are absent. For counterclockwise typical AFL, biphasic "sawtooth" flutter waves (F waves) are present at a rate of about 300 beats/min, with the range being 240 to 340 beats/min [1]. The F waves are fairly regular on the surface electrocardiogram with constant amplitude, duration, morphology, and reproducibility throughout the cardiac cycles. There can be very subtle variability, however, as spectral analysis has detected an underlying periodic pattern modulated by an interplay between the autonomic nervous system, respiratory system, and ventricular rate [42]. The F waves usually do not have an isoelectric interval between them (ie, the F waves blend into one another) unless the rate of the AFL is slow. In counterclockwise typical AFL, the F waves have an axis of around 90 and are prominently negative in the inferior leads (II, III, aVF). The F waves often have an initial slowly downsloping segment followed by a sharp negative deflection, then a sharp positive deflection that may have a positive overshoot leading into the next downward deflection ( waveform 2). With 2:1 flutter, there is commonly a negative deflection superimposed on the ST segment, giving the appearance of ST depression related to myocardial ischemia. In clockwise typical AFL (reverse typical AFL), the F waves are usually positive in the inferior leads due to an opposite direction of atrial activation, but there is significant https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 8/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate heterogeneity in the F wave morphology [3]. The F wave may even have a sine wave pattern. The deflection in V1 is often broad and negative ( waveform 3) (panel B). The ventricular response (R-R intervals) is usually one-half the rate of the atrial input (ie, 2:1 AV nodal conduction with a ventricular response of about 150 beats/min). This finding is sufficiently common and the diagnosis of AFL should be considered whenever the ventricular rate is about 150 beats/min. AV block greater than 2:1 in the absence of drugs that slow the ventricular response suggests AV nodal disease and the possibility of associated sinus node disease, which may be part of the tachy-brady syndrome. A 1:1 AV response suggests accessory bypass tracts, sympathetic excess, parasympathetic withdrawal, or class IC antiarrhythmic agents. Even ratios of input to output (eg, 2:1, 4:1) are more common than odd numbers (eg, 3:1, 5:1). Odd ratios and shifting ratios (eg, alteration of 2:1 with 4:1) probably reflect bilevel block in the AV node. The QRS complex is narrow unless there is functional aberration, preexisting bundle branch or fascicular block, preexcitation, or ventricular pacing. The electrocardiographic features of atypical AFL are: P waves are absent. F waves are regular, but in contrast to typical AFL, there may be an isoelectric appearance between F waves if there is an area of significantly slowed conduction. There is no clear F wave morphology to identify the location consistently, as atypical flutters are often associated with atrial scar that can alter conduction velocity and direction. That said, some patterns described below may be seen. Lower loop reentry typically has negative F waves in the inferior leads ( waveform 4). Upper loop reentry has positive F waves in the inferior leads and negative, flat, or barely positive F waves in lead I [43]. Intra-isthmus reentry will appear like typical counterclockwise AFL. If there is a negative F wave in V1, the flutter is usually in the right atrium ( waveform 5). Left atrial flutters have variable morphologies, but may have a positive F wave in V1 or may be isoelectric ( waveform 6) [5]. It is often positive in the inferior leads, but not always ( waveform 7). https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 9/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Counterclockwise mitral annular flutter is positive in V1-6 and the inferior leads and negative in aVL [44]. Clockwise mitral annular flutter is positive in the right precordial leads but usually negative and then positive in the lateral precordial leads ( waveform 8). It is negative in the inferior leads and positive in I and aVL. Morphology of the QRS complex Activation through the AV node and infranodal conduction system is normal in AFL, so the QRS complex is narrow unless: A preexisting conduction defect is present. Functional block occurs in a portion of the infranodal conduction system, leading to a bundle branch or fascicular block. The refractory period of the bundle branches and fascicles is determined by the preceding cycle length. A long preceding cycle lengthens the refractory period in these structures, so a premature beat is more likely to be functionally blocked after a long cycle, known as Ashman's phenomenon. Preexcitation through an AV bypass tract is present. Ventricular pacing is present. Pitfalls The electrocardiographic criteria listed above are usually sufficient to make the proper diagnosis; there are, however, potential pitfalls: One of the F waves may be obscured by the QRS complex or the ST-T wave ( waveform 9) in patients with 2:1 AV nodal conduction. In this setting, AFL may be misdiagnosed as a sinus tachycardia or a paroxysmal supraventricular tachycardia with downsloping ST depression. In clockwise, typical flutter, the F waves may be positive, and if every other F wave is obscured, it may be mistaken for a long RP tachycardia such as sinus tachycardia, ectopic atrial tachycardia, atypical AV nodal reentrant tachycardia, or AV reciprocating tachycardia. The atrial electrical potential may be small and the F waves may be difficult to see in the standard leads. Sometimes it may be necessary to increase the gain of the electrocardiogram to see the F waves more clearly (ie, 20 mm/mV). Atrial fibrillation, especially with coarse fibrillatory waves in lead V1, is often misdiagnosed as AFL [45]. Examination of a rhythm strip will often show that the atrial fibrillatory rate and morphology change over a period of time. We discourage using the term AFL-fibrillation, since the rhythm more closely resembles atrial fibrillation in its response to drugs that slow AV nodal conduction and in the higher energy requirement for direct current cardioversion. https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 10/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Sometimes the negative F wave merges with the beginning or end of the QRS complex, suggesting a pathologic Q wave in the first case and a conduction delay in the second. Likewise, the F wave may appear to cause pathologic ST-segment depression. The F wave morphology may appear atypical in those with congenital heart disease, atrial fibrosis, following cardiac surgery, or after left atrial ablation for atrial fibrillation even though the rhythm is typical flutter [46,47]. Prior extensive ablation in the left atrium may alter the morphology of F waves in typical AFL, due to reductions in left atrial potentials and changes in the atrial activation sequence. This was illustrated in a series of 15 patients who had undergone circumferential left atrial ablation for the treatment of atrial fibrillation and later developed typical AFL (12 counterclockwise, 3 clockwise) [47]. In 9 of 15 cases, the F waves were upright in the inferior leads, including 7 of 12 of typical counterclockwise flutter. Electrocardiography and telemetry artifacts caused by tremor [48] or electromagnetic interference [49,50] may suggest the occurrence of AFL, but this pseudo-atrial flutter will be revealed when the tremor or interference ceases. DIFFERENTIAL DIAGNOSIS The differential diagnosis of atrial flutter (AFL) includes a number of supraventricular tachyarrhythmias. (See "Focal atrial tachycardia" and "Intraatrial reentrant tachycardia" and "Sinoatrial nodal reentrant tachycardia (SANRT)" and "Cardiac arrhythmias due to digoxin toxicity" and "Multifocal atrial tachycardia" and "Atrioventricular nodal reentrant tachycardia" and "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'Types of narrow QRS complex tachycardia'.) As noted above, obscured atrial activity or F waves that resemble normal or inverted P waves may suggest sinus tachycardia, paroxysmal supraventricular tachycardia, or atrial fibrillation. There are four major ways to help establish the correct diagnosis: An earlier electrocardiogram, if available, may allow comparison of the F or presumed P wave with the previous P wave morphology. Scrutiny of the ST-segment and T waves may show a bump or irregularity caused by a second flutter wave. Decreasing atrioventricular (AV) nodal conduction physiologically with a vagotonic maneuver (such as the Valsalva maneuver or carotid sinus massage) or with a rapidly https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 11/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate acting drug (such as adenosine, verapamil, or esmolol) will increase the AV nodal block and reveal the atrial F waves ( waveform 9). Recording from an atrial catheter, atrial pacing wire, or an esophageal electrode will also demonstrate the regular atrial activity ( waveform 10). Even with these maneuvers, ectopic atrial tachycardia and other supraventricular tachycardias with 2:1 block may remain in the differential diagnosis. Furthermore, two types of arrhythmia can occur in the same patient, as a supraventricular tachycardia can initiate AFL or atrial fibrillation. An example of this difficulty occurs when AFL has a slow ventricular response that overlaps with the rate seen in other supraventricular tachycardias. If, for example, the patient is taking digitalis for flutter, then an atrial tachycardia with a 2:1 AV response that reflects a high degree of digitalis toxicity must be excluded. Treatment of these two disorders is clearly different, and atrial morphology may be of little help in identifying the underlying arrhythmia. In this setting, establishment of the correct diagnosis may depend upon the clinical history, plasma digoxin levels, and the response following cessation of digoxin therapy. As noted above, complete heart block may be difficult to recognize in the presence of AFL. The presence of F waves and a regular rate of the lower pacemaker may lead to the appearance of an uncomplicated AFL. MANAGEMENT The control of ventricular rate and the approach to anticoagulant therapy for patient with atrial flutter is discussed elsewhere. (See "Overview of atrial flutter" and "Embolic risk and the role of anticoagulation in atrial flutter".) Cardioversion in patients with atrial flutter is discussed separately. (See "Restoration of sinus rhythm in atrial flutter".) The approach to the maintenance of sinus rhythm and the impact of electrophysiologic type is discussed separately. (See "Atrial flutter: Maintenance of sinus rhythm" and "Atrial flutter: Maintenance of sinus rhythm", section on 'RF catheter ablation'.) SUMMARY https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 12/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Atrial flutter (AFL) is a supraventricular tachycardia with regular flutter waves and usually an absent isoelectric interval. The rhythm is due to macroreentry, has an excitable gap, and can be transiently entrained and terminated by rapid atrial pacing. Electrocardiographic characteristics include: Biphasic, sawtooth F waves, best seen in the inferior electrocardiogram leads (II, III, aVF), at about 300 beats/min are the classic finding for typical, counterclockwise AFL. The ventricular response is a multiple of the atrial rate, though most frequently is 2:1 with a ventricular rate of 150 beats/min. Flutter waves may sometimes be obscured in the QRS complex in 2:1 conduction. Typical AFL most frequently rotates counterclockwise posterior to the tricuspid valve and uses the critical region of the cavotricuspid isthmus within the circuit. Clockwise, typical AFL uses the same circuit, but rotates in the opposite direction. Atypical AFL is any flutter that does not involve the cavotricuspid isthmus. The flutter wave morphology does not have a characteristic pattern to localize the flutter circuit. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Wells JL Jr, MacLean WA, James TN, Waldo AL. Characterization of atrial flutter. Studies in man after open heart surgery using fixed atrial electrodes. Circulation 1979; 60:665. 2. Puech P, Latour H, Grolleau R. [Flutter and his limits]. Arch Mal Coeur Vaiss 1970; 63:116. 3. Saoudi N, Cos o F, Waldo A, et al. A classification of atrial flutter and regular atrial tachycardia according to electrophysiological mechanisms and anatomical bases; a Statement from a Joint Expert Group from The Working Group of Arrhythmias of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Eur Heart J 2001; 22:1162. 4. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2016; 67:e27. 5. Bun SS, Latcu DG, Marchlinski F, Saoudi N. Atrial flutter: more than just one of a kind. Eur Heart J 2015; 36:2356. https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 13/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate 6. Khairy P, Aboulhosn J, Gurvitz MZ, et al. Arrhythmia burden in adults with surgically repaired tetralogy of Fallot: a multi-institutional study. Circulation 2010; 122:868. 7. Peuch P, Gallay P, Grolleau R. Mechanism of atrial flutter in humans. In: Atrial Arrhythmias: C urrent Concepts and Management, Tourboul P, Waldo AL (Eds), Mosby Year Book, St Louis 1 990. p.190. 8. Klein GJ, Guiraudon GM, Sharma AD, Milstein S. Demonstration of macroreentry and feasibility of operative therapy in the common type of atrial flutter. Am J Cardiol 1986; 57:587. 9. Cosio FG, Arribas F, Barbero JM, et al. Validation of double-spike electrograms as markers of conduction delay or block in atrial flutter. Am J Cardiol 1988; 61:775. 10. Tai CT, Chen SA, Chiang CE, et al. Characterization of low right atrial isthmus as the slow conduction zone and pharmacological target in typical atrial flutter. Circulation 1997; 96:2601. 11. Kalman JM, Olgin JE, Saxon LA, et al. Activation and entrainment mapping defines the tricuspid annulus as the anterior barrier in typical atrial flutter. Circulation 1996; 94:398. 12. Disertori M, Inama G, Vergara G, et al. Evidence of a reentry circuit in the common type of atrial flutter in man. Circulation 1983; 67:434. 13. Waldo AL, MacLean WA, Karp RB, et al. Entrainment and interruption of atrial flutter with atrial pacing: studies in man following open heart surgery. Circulation 1977; 56:737. 14. Watson RM, Josephson ME. Atrial flutter. I. Electrophysiologic substrates and modes of initiation and termination. Am J Cardiol 1980; 45:732. 15. Inoue H, Matsuo H, Takayanagi K, Murao S. Clinical and experimental studies of the effects of atrial extrastimulation and rapid pacing on atrial flutter cycle. Evidence of macro-reentry with an excitable gap. Am J Cardiol 1981; 48:623. 16. Callans DJ, Schwartzman D, Gottlieb CD, et al. Characterization of the excitable gap in human type I atrial flutter. J Am Coll Cardiol 1997; 30:1793. 17. Waldo AL, Cooper TB. Spontaneous onset of type I atrial flutter in patients. J Am Coll Cardiol 1996; 28:707. 18. Waldo AL. Mechanisms of atrial flutter and atrial fibrillation: distinct entities or two sides of a coin? Cardiovasc Res 2002; 54:217. 19. Roithinger FX, Karch MR, Steiner PR, et al. Relationship between atrial fibrillation and typical atrial flutter in humans: activation sequence changes during spontaneous conversion. Circulation 1997; 96:3484. https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 14/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate 20. Narayan SM, Bode F, Karasik PL, Franz MR. Alternans of atrial action potentials during atrial flutter as a precursor to atrial fibrillation. Circulation 2002; 106:1968. 21. Morton JB, Byrne MJ, Power JM, et al. Electrical remodeling of the atrium in an anatomic model of atrial flutter: relationship between substrate and triggers for conversion to atrial fibrillation. Circulation 2002; 105:258. 22. Franz MR, Karasik PL, Li C, et al. Electrical remodeling of the human atrium: similar effects in patients with chronic atrial fibrillation and atrial flutter. J Am Coll Cardiol 1997; 30:1785. 23. Stiles MK, Wong CX, John B, et al. Characterization of atrial remodeling studied remote from episodes of typical atrial flutter. Am J Cardiol 2010; 106:528. 24. Sparks PB, Jayaprakash S, Vohra JK, Kalman JM. Electrical remodeling of the atria associated with paroxysmal and chronic atrial flutter. Circulation 2000; 102:1807. 25. Kalman JM, Olgin JE, Saxon LA, et al. Electrocardiographic and electrophysiologic characterization of atypical atrial flutter in man: use of activation and entrainment mapping and implications for catheter ablation. J Cardiovasc Electrophysiol 1997; 8:121. 26. Nakagawa H, Lazzara R, Khastgir T, et al. Role of the tricuspid annulus and the eustachian valve/ridge on atrial flutter. Relevance to catheter ablation of the septal isthmus and a new technique for rapid identification of ablation success. Circulation 1996; 94:407. 27. Cosio FG, L pez-Gil M, Goicolea A, et al. Radiofrequency ablation of the inferior vena cava-

levels, and the response following cessation of digoxin therapy. As noted above, complete heart block may be difficult to recognize in the presence of AFL. The presence of F waves and a regular rate of the lower pacemaker may lead to the appearance of an uncomplicated AFL. MANAGEMENT The control of ventricular rate and the approach to anticoagulant therapy for patient with atrial flutter is discussed elsewhere. (See "Overview of atrial flutter" and "Embolic risk and the role of anticoagulation in atrial flutter".) Cardioversion in patients with atrial flutter is discussed separately. (See "Restoration of sinus rhythm in atrial flutter".) The approach to the maintenance of sinus rhythm and the impact of electrophysiologic type is discussed separately. (See "Atrial flutter: Maintenance of sinus rhythm" and "Atrial flutter: Maintenance of sinus rhythm", section on 'RF catheter ablation'.) SUMMARY https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 12/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Atrial flutter (AFL) is a supraventricular tachycardia with regular flutter waves and usually an absent isoelectric interval. The rhythm is due to macroreentry, has an excitable gap, and can be transiently entrained and terminated by rapid atrial pacing. Electrocardiographic characteristics include: Biphasic, sawtooth F waves, best seen in the inferior electrocardiogram leads (II, III, aVF), at about 300 beats/min are the classic finding for typical, counterclockwise AFL. The ventricular response is a multiple of the atrial rate, though most frequently is 2:1 with a ventricular rate of 150 beats/min. Flutter waves may sometimes be obscured in the QRS complex in 2:1 conduction. Typical AFL most frequently rotates counterclockwise posterior to the tricuspid valve and uses the critical region of the cavotricuspid isthmus within the circuit. Clockwise, typical AFL uses the same circuit, but rotates in the opposite direction. Atypical AFL is any flutter that does not involve the cavotricuspid isthmus. The flutter wave morphology does not have a characteristic pattern to localize the flutter circuit. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Wells JL Jr, MacLean WA, James TN, Waldo AL. Characterization of atrial flutter. Studies in man after open heart surgery using fixed atrial electrodes. Circulation 1979; 60:665. 2. Puech P, Latour H, Grolleau R. [Flutter and his limits]. Arch Mal Coeur Vaiss 1970; 63:116. 3. Saoudi N, Cos o F, Waldo A, et al. A classification of atrial flutter and regular atrial tachycardia according to electrophysiological mechanisms and anatomical bases; a Statement from a Joint Expert Group from The Working Group of Arrhythmias of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Eur Heart J 2001; 22:1162. 4. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2016; 67:e27. 5. Bun SS, Latcu DG, Marchlinski F, Saoudi N. Atrial flutter: more than just one of a kind. Eur Heart J 2015; 36:2356. https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 13/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate 6. Khairy P, Aboulhosn J, Gurvitz MZ, et al. Arrhythmia burden in adults with surgically repaired tetralogy of Fallot: a multi-institutional study. Circulation 2010; 122:868. 7. Peuch P, Gallay P, Grolleau R. Mechanism of atrial flutter in humans. In: Atrial Arrhythmias: C urrent Concepts and Management, Tourboul P, Waldo AL (Eds), Mosby Year Book, St Louis 1 990. p.190. 8. Klein GJ, Guiraudon GM, Sharma AD, Milstein S. Demonstration of macroreentry and feasibility of operative therapy in the common type of atrial flutter. Am J Cardiol 1986; 57:587. 9. Cosio FG, Arribas F, Barbero JM, et al. Validation of double-spike electrograms as markers of conduction delay or block in atrial flutter. Am J Cardiol 1988; 61:775. 10. Tai CT, Chen SA, Chiang CE, et al. Characterization of low right atrial isthmus as the slow conduction zone and pharmacological target in typical atrial flutter. Circulation 1997; 96:2601. 11. Kalman JM, Olgin JE, Saxon LA, et al. Activation and entrainment mapping defines the tricuspid annulus as the anterior barrier in typical atrial flutter. Circulation 1996; 94:398. 12. Disertori M, Inama G, Vergara G, et al. Evidence of a reentry circuit in the common type of atrial flutter in man. Circulation 1983; 67:434. 13. Waldo AL, MacLean WA, Karp RB, et al. Entrainment and interruption of atrial flutter with atrial pacing: studies in man following open heart surgery. Circulation 1977; 56:737. 14. Watson RM, Josephson ME. Atrial flutter. I. Electrophysiologic substrates and modes of initiation and termination. Am J Cardiol 1980; 45:732. 15. Inoue H, Matsuo H, Takayanagi K, Murao S. Clinical and experimental studies of the effects of atrial extrastimulation and rapid pacing on atrial flutter cycle. Evidence of macro-reentry with an excitable gap. Am J Cardiol 1981; 48:623. 16. Callans DJ, Schwartzman D, Gottlieb CD, et al. Characterization of the excitable gap in human type I atrial flutter. J Am Coll Cardiol 1997; 30:1793. 17. Waldo AL, Cooper TB. Spontaneous onset of type I atrial flutter in patients. J Am Coll Cardiol 1996; 28:707. 18. Waldo AL. Mechanisms of atrial flutter and atrial fibrillation: distinct entities or two sides of a coin? Cardiovasc Res 2002; 54:217. 19. Roithinger FX, Karch MR, Steiner PR, et al. Relationship between atrial fibrillation and typical atrial flutter in humans: activation sequence changes during spontaneous conversion. Circulation 1997; 96:3484. https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 14/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate 20. Narayan SM, Bode F, Karasik PL, Franz MR. Alternans of atrial action potentials during atrial flutter as a precursor to atrial fibrillation. Circulation 2002; 106:1968. 21. Morton JB, Byrne MJ, Power JM, et al. Electrical remodeling of the atrium in an anatomic model of atrial flutter: relationship between substrate and triggers for conversion to atrial fibrillation. Circulation 2002; 105:258. 22. Franz MR, Karasik PL, Li C, et al. Electrical remodeling of the human atrium: similar effects in patients with chronic atrial fibrillation and atrial flutter. J Am Coll Cardiol 1997; 30:1785. 23. Stiles MK, Wong CX, John B, et al. Characterization of atrial remodeling studied remote from episodes of typical atrial flutter. Am J Cardiol 2010; 106:528. 24. Sparks PB, Jayaprakash S, Vohra JK, Kalman JM. Electrical remodeling of the atria associated with paroxysmal and chronic atrial flutter. Circulation 2000; 102:1807. 25. Kalman JM, Olgin JE, Saxon LA, et al. Electrocardiographic and electrophysiologic characterization of atypical atrial flutter in man: use of activation and entrainment mapping and implications for catheter ablation. J Cardiovasc Electrophysiol 1997; 8:121. 26. Nakagawa H, Lazzara R, Khastgir T, et al. Role of the tricuspid annulus and the eustachian valve/ridge on atrial flutter. Relevance to catheter ablation of the septal isthmus and a new technique for rapid identification of ablation success. Circulation 1996; 94:407. 27. Cosio FG, L pez-Gil M, Goicolea A, et al. Radiofrequency ablation of the inferior vena cava- tricuspid valve isthmus in common atrial flutter. Am J Cardiol 1993; 71:705. 28. Schilling RJ, Peters NS, Goldberger J, et al. Characterization of the anatomy and conduction velocities of the human right atrial flutter circuit determined by noncontact mapping. J Am Coll Cardiol 2001; 38:385. 29. Shah DC, Ja s P, Ha ssaguerre M, et al. Three-dimensional mapping of the common atrial flutter circuit in the right atrium. Circulation 1997; 96:3904. 30. Dixit S, Lavi N, Robinson M, et al. Noncontact electroanatomic mapping to characterize typical atrial flutter: participation of right atrial posterior wall in the reentrant circuit. J Cardiovasc Electrophysiol 2011; 22:422. 31. Maury P, Duparc A, Hebrard A, et al. Prevalence of typical atrial flutter with reentry circuit posterior to the superior vena cava: use of entrainment at the atrial roof. Europace 2008; 10:190. 32. Yang Y, Cheng J, Bochoeyer A, et al. Atypical right atrial flutter patterns. Circulation 2001; 103:3092. 33. Yang Y, Varma N, Badhwar N, et al. Prospective observations in the clinical and electrophysiological characteristics of intra-isthmus reentry. J Cardiovasc Electrophysiol https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 15/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate 2010; 21:1099. 34. Cheng J, Cabeen WR Jr, Scheinman MM. Right atrial flutter due to lower loop reentry: mechanism and anatomic substrates. Circulation 1999; 99:1700. 35. Tai CT, Huang JL, Lin YK, et al. Noncontact three-dimensional mapping and ablation of upper loop re-entry originating in the right atrium. J Am Coll Cardiol 2002; 40:746. 36. Wasmer K, M nnig G, Bittner A, et al. Incidence, characteristics, and outcome of left atrial tachycardias after circumferential antral ablation of atrial fibrillation. Heart Rhythm 2012; 9:1660. 37. Chae S, Oral H, Good E, et al. Atrial tachycardia after circumferential pulmonary vein ablation of atrial fibrillation: mechanistic insights, results of catheter ablation, and risk factors for recurrence. J Am Coll Cardiol 2007; 50:1781. 38. Bai R, Di Biase L, Mohanty P, et al. Ablation of perimitral flutter following catheter ablation of atrial fibrillation: impact on outcomes from a randomized study (PROPOSE). J Cardiovasc Electrophysiol 2012; 23:137. 39. Miyazaki S, Shah AJ, Hocini M, et al. Recurrent spontaneous clinical perimitral atrial tachycardia in the context of atrial fibrillation ablation. Heart Rhythm 2015; 12:104. 40. Zhang J, Tang C, Zhang Y, et al. Electroanatomic characterization and ablation outcome of nonlesion related left atrial macroreentrant tachycardia in patients without obvious structural heart disease. J Cardiovasc Electrophysiol 2013; 24:53. 41. Fukamizu S, Sakurada H, Hayashi T, et al. Macroreentrant atrial tachycardia in patients without previous atrial surgery or catheter ablation: clinical and electrophysiological characteristics of scar-related left atrial anterior wall reentry. J Cardiovasc Electrophysiol 2013; 24:404. 42. Stambler BS, Ellenbogen KA. Elucidating the mechanisms of atrial flutter cycle length variability using power spectral analysis techniques. Circulation 1996; 94:2515. 43. Yuniadi Y, Tai CT, Lee KT, et al. A new electrocardiographic algorithm to differentiate upper loop re-entry from reverse typical atrial flutter. J Am Coll Cardiol 2005; 46:524. 44. Gerstenfeld EP, Dixit S, Bala R, et al. Surface electrocardiogram characteristics of atrial tachycardias occurring after pulmonary vein isolation. Heart Rhythm 2007; 4:1136. 45. Knight BP, Michaud GF, Strickberger SA, Morady F. Electrocardiographic differentiation of atrial flutter from atrial fibrillation by physicians. J Electrocardiol 1999; 32:315. 46. Khairy P, Stevenson WG. Catheter ablation in tetralogy of Fallot. Heart Rhythm 2009; 6:1069. 47. Chugh A, Latchamsetty R, Oral H, et al. Characteristics of cavotricuspid isthmus-dependent atrial flutter after left atrial ablation of atrial fibrillation. Circulation 2006; 113:609. https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 16/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate 48. Baranchuk A, Kang J. Pseudo-atrial flutter: Parkinson tremor. Cardiol J 2009; 16:373. 49. Chakravarthy M, Mattur K, Raghavan R, et al. Artifactual 'atrial flutter' caused by a continuous passive motion device after total knee replacement. Anaesth Intensive Care 2009; 37:1038. 50. Hoffmayer KS, Goldschlager N. Pseudoatrial flutter. J Electrocardiol 2008; 41:201. Topic 1061 Version 26.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 17/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate GRAPHICS Reentrant circuit of typical atrial flutter within the right atrium Schematic representation of reentrant circuit (red arrow) of typical (type 1) atrial flutter. The reentrant impulse rotates in a counterclockwise direction around the tricuspid annulus. The crista terminalis (CT) and eustacian ridge (ER) serve as lines of block, preventing the impulse from short-circuiting the annulus. Ablation is performed in the isthmus between the IVC and TA, which is an obligatory part of the circuit. SVC: superior vena cava; CS: coronary sinus; IVC: inferior vena cava; FO: foramen ovale Graphic 52904 Version 5.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 18/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate 12-lead electrocardiogram showing atrial flutter in preexcitation syndrome Atrial flutter is generated within the right atrium and the atrial impulses in this case are conducted to the ventricle by an accessory pathway. There is 1:1 conduction with a ventricular rate of 300 beats/min. The QRS complexes are widened or aberrant and have a bundle branch block morphology and a left axis deviation, suggesting the presence of an atriofascicular (Mahaim) accessory pathway. Courtesy of Morton Arnsdorf, MD. Graphic 78602 Version 4.0 Normal ECG https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 19/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Normal electrocardiogram showing normal sinus rhythm at a rate of 75 beats/minute, a PR interval of 0.14 seconds, a QRS interval of 0.10 seconds, and a QRS axis of approximately 75 . Courtesy of Ary Goldberger, MD. Graphic 76183 Version 4.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 20/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Revised (2018) Vaughan Williams classification of antiarrhythmic drugs abridged table Class 0 (HCN channel blockers) Ivabradine Class I (voltage-gated Na+ channel blockers) Class Ia (intermediate dissociation): Quinidine, ajmaline, disopyramide, procainamide Class Ib (rapid dissociation): Lidocaine, mexilitine Class Ic (slow dissociation): Propafenone, flecainide Class Id (late current): Ranolazine Class II (autonomic inhibitors and activators) Class IIa (beta blockers): Nonselective: carvedilol, propranolol, nadolol Selective: atenolol, bisoprolol, betaxolol, celiprolol, esmolol, metoprolol Class IIb (nonselective beta agonists): Isoproterenol Class IIc (muscarinic M2 receptor inhibitors): Atropine, anisodamine, hyoscine, scopolamine Class IId (muscarinic M2 receptor activators): Carbachol, pilocarpine, methacholine, digoxin Class IIe (adenosine A1 receptor activators): Adenosine Class III (K+ channel blockers and openers) Class IIIa (voltage dependent K+ channel blockers): Ambasilide, amiodarone, dronedarone, dofetilide, ibutilide, sotalol, vernakalant Class IIIb (metabolically dependent K+ channel openers): https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 21/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Nicorandil, pinacidil Class IV (Ca++ handling modulators) Class IVa (surface membrane Ca++ channel blockers): Bepridil, diltiazem, verapamil Class IVb (intracellular Ca++ channel blockers): Flecainide, propafenone Class V (mechanosensitive channel blockers): No approved medications Class VI (gap junction channel blockers) No approved medications Class VII (upstream target modulators) Angiotensin converting enzyme inhibitors Angiotensin receptor blockers Omega-3 fatty acids Statins HCN: hyperpolarization-activated cyclic nucleotide-gated; Na: sodium; K: potassium; Ca: calcium. Graphic 120433 Version 3.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 22/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Typical atrial flutter Electrocardiogram in type I counterclockwise typical atrial flutter. The biphasic flutter (F) waves are prominently negative (lead II) in counterclockwise typical flutter. The patient is on a beta-blocker which explains the predominant 4:1 conduction pattern. Graphic 74395 Version 4.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 23/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Reverse typical atrial flutter Electrocardiogram in type I clockwise typical atrial flutter. The flutter waves are positive in the inferior leads (II, III, aVF), with a more sinusoidal appearance and a broad negative F wave in V1. Graphic 81563 Version 3.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 24/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Electrocardiogram in lower loop reentry flutter Arrows point to flutter waves, which are positive in V1 and subtle but negative in the inferior leads. Graphic 106118 Version 1.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 25/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Electrocardiogram from a patient with an atriotomy-related right atrial flutter a mitral valve repair On electrophysiology study, the circuit was found to be wrapping around the atriotomy scar. The arrows poin flutter waves, which are negative in the inferior leads. Graphic 106119 Version 1.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 26/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Electrocardiogram of an atypical left atrial flutter occurring through a scar on t anterior septum in a patient with a prior atrial fibrillation ablation The arrows show the flutters waves, which are positive in V1. Graphic 106120 Version 1.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 27/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Electrocardiogram of an atypical roof dependent left atrial flutter after an atria fibrillation ablation The arrows show positive flutter waves in V1 indicative of a left atrial focus. Flutter waves are isoelectric in th leads. Graphic 106121 Version 2.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 28/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Electrocardiogram of a patient with clockwise mitral annular flutter The arrows show the flutter waves, which are low amplitude and negative in the inferior leads. They are posit 3, but become negative and then positive in V4-6. Graphic 106122 Version 1.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 29/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Atrial flutter at a rate of 250 beats/minute with 2:1 AV conduction in the presence of left bundle branch block Although every other flutter wave can be seen at the end of the T wave in the first part of the tracing (arrows), a sinus mechanism cannot be excluded. The flutter waves become clearly apparent after carotid sinus massage is applied to slow conduction through the AV node, thereby increasing the degree of AV block. AV: atrioventricular Courtesy of Morton Arnsdorf, MD. Graphic 76876 Version 3.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 30/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Atrial flutter RA recording Atrial flutter which is inapparent in lead I (upper panel); suggested by prominent negativity in lead II (arrows, middle panel), which could also represent biphasic T waves; and documented by right atrial recording, which shows prominent negative deflections (arrows, lower panel). Courtesy of Morton Arnsdorf, MD. Graphic 54591 Version 2.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 31/32 7/5/23, 10:22 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Contributor Disclosures Jordan M Prutkin, MD, MHS, FHRS No relevant financial relationship(s) with ineligible companies to disclose. Peter J Zimetbaum, MD Consultant/Advisory Boards: Abbott Medical [Lead extraction]. All of the relevant financial relationships listed have been mitigated. Ary L Goldberger, MD Other Financial Interest: Elsevier book royalties [Clinical electrocardiography]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 32/32

7/5/23, 10:22 AM Embolic risk and the role of anticoagulation in atrial flutter - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Embolic risk and the role of anticoagulation in atrial flutter : Warren J Manning, MD, Jordan M Prutkin, MD, MHS, FHRS : Bradley P Knight, MD, FACC, Scott E Kasner, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: May 11, 2022. INTRODUCTION Most patients with atrial flutter should be considered for chronic anticoagulation in a manner similar to those with atrial fibrillation (AF). This recommendation is based not only on the fact atrial flutter carries a risk for systemic embolization but also that these patients usually have episodes of AF. (See "Atrial fibrillation in adults: Use of oral anticoagulants", section on 'Summary and recommendations'.) Our approach to anticoagulation applies to all types of atrial flutter, whether it is typical or atypical. (See "Electrocardiographic and electrophysiologic features of atrial flutter".) PREVALENCE OF THROMBUS Many patients with atrial flutter have alternating periods of atrial fibrillation (AF) making it difficult to know the exact risk of thrombus formation (and subsequent embolization) specifically attributable to atrial flutter [1]. Atrial mechanical function is not normal in patients with atrial flutter. However, transmitral and left atrial appendage Doppler echocardiography commonly demonstrate more organized atrial and atrial appendage mechanical function with sustained atrial flutter, as opposed to AF, in which organized atrial contraction is absent. One study performed transesophageal https://www.uptodate.com/contents/embolic-risk-and-the-role-of-anticoagulation-in-atrial-flutter/print 1/13 7/5/23, 10:22 AM Embolic risk and the role of anticoagulation in atrial flutter - UpToDate echocardiography (TEE) immediately before and after cardioversion in 19 patients with atrial flutter and 44 patients with AF with the following findings [2]: Prior to cardioversion, patients with atrial flutter had greater left atrial appendage peak ejection velocities and shear rates compared to those with AF. After cardioversion, left atrial appendage peak ejection velocities and shear rates decreased in both groups of patients, but the impaired left atrial appendage function was less pronounced in patients with atrial flutter. New or increased spontaneous echo contrast, a marker of blood stasis, occurred significantly less often in patients with atrial flutter (21 versus 50 percent for AF). Like AF, the vast majority of thrombi among patients with atrial flutter are located in the left atrial appendage. TEE evidence of atrial thrombi has been documented in a number of reports of patients with atrial flutter not receiving chronic anticoagulation [3-8]. As with AF, the thrombi overwhelmingly involve or are exclusively within the left atrial appendage. The frequency with which this occurs may vary with the duration of the arrhythmia and other risk factors (similar to AF) as illustrated by the following observations: Two series evaluated patients with atrial flutter for a mean duration of 33 to 36 days who did not have a history of AF, rheumatic heart disease, or a prosthetic heart valve [3,4]. A left atrial thrombus was found in 1 to 1.6 percent, a right atrial thrombus in 1 percent, and left atrial spontaneous echo contrast in 11 to 13 percent [3,4]. In one of these reports, there was a close correlation between a history of thromboembolism and periods of AF during atrial flutter [4]. Atrial thrombi and spontaneous echo contrast may be more common in patients with atrial flutter of longer duration. In a TEE study of 30 patients with persistent atrial flutter (duration 6.4 months), two patients (7 percent) had thrombus in the left atrial appendage, and 25 percent had spontaneous echo contrast prior to cardioversion [5]. As described below in more depth (see 'Cardioversion' below) and mentioned above, left atrial contractile function (as measured by peak atrial appendage ejection velocity) transiently declines after cardioversion in many patients and is considered a manifestation of atrial "stunning." Left atrial thrombus was present in 5 of 47 consecutive patients (11 percent) with atrial flutter for a mean duration of 28 days who did not have a history of AF or mitral stenosis [6]. https://www.uptodate.com/contents/embolic-risk-and-the-role-of-anticoagulation-in-atrial-flutter/print 2/13 7/5/23, 10:22 AM Embolic risk and the role of anticoagulation in atrial flutter - UpToDate EMBOLIC RISK The risk of embolization in atrial flutter is related to risk factors and the need for cardioversion or ablation. Risk factors and lone atrial flutter Risk factors for clinical thromboembolism include valvular heart disease (eg, rheumatic valve disease, prosthetic valves), increasing age, depressed left ventricular systolic function or heart failure, hypertension, diabetes, vascular disease, and a history of thromboembolism. Atrial flutter without an identifiable risk factor is called lone atrial flutter. It is relatively uncommon, occurring in only 3 of 181 adults with atrial flutter in a population-based study (1.7 percent) [9] and in 8 percent of children and young adults with atrial flutter in a multicenter series [10]. The embolic risk associated with lone atrial flutter was evaluated in a review of 59 mostly elderly patients with lone atrial flutter (mean age at diagnosis 70 years); 75 percent developed recurrent episodes or persistent atrial flutter [11]. At presentation, these patients did not have coronary heart disease, hyperthyroidism, heart failure, valvular heart disease, congenital heart disease, obstructive lung disease, uncontrolled hypertension, or known antecedent atrial fibrillation (AF). At the time of diagnosis, 25 were treated with aspirin and six with warfarin; at last follow-up, 28 were treated with aspirin and 13 with warfarin. The following observations were noted at an average follow-up of 10 years: AF developed in 33 patients (56 percent), which was paroxysmal in 25 and permanent in eight, highlighting the rationale for managing anticoagulation in patients with atrial flutter in a manner similar to AF. One or more ischemic cerebrovascular events occurred in 19 patients (32 percent) at a mean age of 80 years, including six who were in AF at the time of the event. Compared to age- and sex-adjusted expected rates of thromboembolism, the thromboembolic risk was significantly increased in the patients with lone atrial flutter (hazard ratio 5.2 in patients with controlled hypertension and 2.5 in patients without a history of hypertension). When compared with patients with lone AF, the patients with lone atrial flutter had, after adjustment for age and sex, a significantly higher rate of thromboembolism (hazard ratio 2.6). The risk was lower and no longer significant when only patients without a history of hypertension were included (hazard ratio 1.9). (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation", section on 'Classification and terminology'.) https://www.uptodate.com/contents/embolic-risk-and-the-role-of-anticoagulation-in-atrial-flutter/print 3/13 7/5/23, 10:22 AM Embolic risk and the role of anticoagulation in atrial flutter - UpToDate Long-term flutter There is an increased risk for clinical thromboembolism in patients with persistent atrial flutter compared to the general population without atrial arrhythmias [1,12-14]. In a systematic review based upon limited data, the long-term embolic risk in patients with sustained atrial flutter (with varying risk factors) was estimated to be approximately 3 percent per year [12]. For comparison, the rate of thromboembolism in patients with AF <1 percent per year in patients with no risk factors, with the rate increasing with increasing CHA DS -VASc score 2 2 ( table 1). One problem with interpreting these data, as mentioned previously, is that many patients with persistent atrial flutter also have episodes of AF (34 percent in the preceding report [13]) also have episodes of AF. In a review of the Medicare database, the risk of stroke was significantly increased in patients with atrial flutter (relative risk 1.41 compared to a control group). In these patients, the relative risk was 1.56 in patients who subsequently had an episode of AF (similar to the risk with AF alone), while those with isolated atrial flutter had a stroke risk not significantly different from the control population (relative risk 1.11) ( figure 1) [1]. Cardioversion Although the risk of clinical thromboembolization at the time of cardioversion is increased compared to individuals not undergoing cardioversion, the absolute thromboembolism risk of cardioversion for pure atrial flutter is not known with a high degree of confidence due to the fact that many patients included in reports of atrial flutter cardioversion related events also had episodes of AF (but happened to be in atrial flutter at the time of cardioversion) [3,13,15-17]. The studies that have attempted to evaluate the risk at the time of cardioversion studied different populations. Some included patients with a prior history of thromboembolism and were thus more likely to report high event rates, while studies in which at least some patients were anticoagulated or underwent precardioversion transesophageal echocardiography (TEE) to assess for thrombus were more likely to report low event rates [3,12-17]. Three early studies found no embolic events in a total of 314 patients with atrial flutter (and without AF) who underwent elective cardioversion for atrial flutter without anticoagulation prior to or after cardioversion [4,18,19]. However, the overall incidence is 0.6 to 1.0 percent [16,17] with a higher risk in patients with a history of AF or underlying heart disease [13,15]. In a meta- analysis of these studies, the rate of short-term emboli ranged from 0 to 7.3 percent [12]. Embolization may be related to a transient reduction in atrial mechanical function leading to post-cardioversion thrombus formation, referred to as atrial "stunning," and is present after successful cardioversion of atrial flutter [2,5,6,20,21]. In one report, left atrial appendage peak ejection velocity fell by 26 percent within 15 minutes of cardioversion and almost 50 percent of https://www.uptodate.com/contents/embolic-risk-and-the-role-of-anticoagulation-in-atrial-flutter/print 4/13 7/5/23, 10:22 AM Embolic risk and the role of anticoagulation in atrial flutter - UpToDate subjects had new or more pronounced spontaneous echo contrast [5]. These changes predispose to de novo thrombus formation [15]. Similar observations have been made in patients with AF. (See "Hemodynamic consequences of atrial fibrillation and cardioversion to sinus rhythm", section on 'Atrial stunning'.) The severity of atrial stunning appears to be somewhat less pronounced in atrial flutter than in AF, which could explain the lower embolic risk after cardioversion in atrial flutter. In a report that compared 19 patients with atrial flutter with 44 patients with AF, the left atrial appendage peak ejection velocity was significantly higher in the patients with atrial flutter at baseline (42 versus 28 cm/sec in atrial fibrillation) and after cardioversion (27 versus 15 cm/sec) [2]. In addition, new or more pronounced spontaneous echo contrast was significantly less likely in those with atrial flutter (21 versus 50 percent). Radiofrequency catheter ablation Atrial stunning (see 'Cardioversion' above) also occurs after radiofrequency catheter ablation [21,22]. The likelihood of developing atrial stunning and its duration were assessed in a review of 15 patients with persistent atrial flutter (mean duration 17 months) and seven with paroxysmal atrial flutter who underwent radiofrequency catheter ablation [21]. Significant left atrial appendage stunning and spontaneous echo contrast on TEE were observed after ablation in 80 percent of those with persistent flutter but in none with paroxysmal atrial flutter, suggesting that, like AF, left atrial stunning in atrial flutter is related to the duration of the arrhythmia and not the mode of reversion. These changes resolved after three weeks of sustained sinus rhythm. (See "Atrial flutter: Maintenance of sinus rhythm", section on 'RF catheter ablation'.) PREVENTION OF EMBOLIZATION Patients with long-term atrial flutter Patients with persistent or recurrent atrial flutter who also have periods of atrial flutter-fibrillation should be treated in the same manner as those with pure atrial fibrillation (AF) [23,24]. This recommendation also applies to patients with atrial flutter who have a prior history of AF. Though the optimal management of atrial flutter without any history of AF is uncertain and may be more limited ( figure 1) [1], we and others recommend that patients with pure atrial flutter be managed similar to those with AF [25]. (See "Atrial fibrillation in adults: Use of oral anticoagulants", section on 'Summary and recommendations'.) Anticoagulation with warfarin (goal international normalized ratio [INR] between 2.0 and 3.0) has been recommended to prevent embolization in patients with atrial flutter, similar to patients with AF (eg, using CHA DS -VASc criteria for nonvalvular AF). Of the non-vitamin K oral 2 2 https://www.uptodate.com/contents/embolic-risk-and-the-role-of-anticoagulation-in-atrial-flutter/print 5/13 7/5/23, 10:22 AM Embolic risk and the role of anticoagulation in atrial flutter - UpToDate anticoagulants tested for stroke prevention in AF, in the large clinical trials, only apixaban enrolled patients with atrial flutter [26]. It is likely, however, that there is similar efficacy of all the non-vitamin K oral anticoagulants (eg, apixaban, dabigatran, edoxaban, and rivaroxaban) for atrial flutter as well as AF. At the time of cardioversion We and others recommend that anticoagulation leading to, at the time of, and after cardioversion of atrial flutter be managed in a manner similar to that for AF [23,24]. (See "Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation".) Patients presenting with an initial episode of atrial flutter should be treated in a manner similar to those presenting with their first episode of AF, including a transthoracic echocardiogram (TTE) to evaluate for congenital heart disease, valve disease, and left ventricular systolic function. After radiofrequency catheter ablation Anticoagulation recommendations following catheter ablation of AF are discussed separately. (See "Atrial flutter: Maintenance of sinus rhythm", section on 'Anticoagulation after RF catheter ablation'.) RECOMMENDATIONS OF OTHERS The 2016 European Society of Cardiology guidelines for the management of atrial fibrillation, the 2015 American Heart Association/American College of Cardiology/Heart Rhythm Society guideline on the management of adult patient with supraventricular tachycardia, and the 2014 American Heart Association/American College of Cardiology/Heart Rhythm Society guideline on the management of patients with atrial fibrillation (and its 2019 focused update) similarly recommend managing anticoagulation in patients with atrial flutter in a manner similar to those in atrial fibrillation [23,27-31], recognizing that no report has been sufficiently large to accurately define both the risk of embolization and benefit of antithrombotic therapy in a pure atrial flutter population. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Atrial fibrillation" and "Society guideline links: Arrhythmias in adults".) SUMMARY AND RECOMMENDATIONS https://www.uptodate.com/contents/embolic-risk-and-the-role-of-anticoagulation-in-atrial-flutter/print 6/13 7/5/23, 10:22 AM Embolic risk and the role of anticoagulation in atrial flutter - UpToDate The risk of embolization in atrial flutter is related to clinical risk factors and underlying cardiac disease (eg, valve disease). However, the exact rates are not known, in part due to the presence of atrial fibrillation (AF) in most cohorts studied and the coexistence of AF and atrial flutter in most individuals. (See 'Long-term flutter' above.) For patients with atrial flutter, with or without AF, we recommend an anticoagulant strategy identical to that used in patients with AF (Grade 1B). (See 'Prevention of embolization' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Biblo LA, Yuan Z, Quan KJ, et al. Risk of stroke in patients with atrial flutter. Am J Cardiol 2001; 87:346. 2. Grimm RA, Stewart WJ, Arheart K, et al. Left atrial appendage "stunning" after electrical cardioversion of atrial flutter: an attenuated response compared with atrial fibrillation as the mechanism for lower susceptibility to thromboembolic events. J Am Coll Cardiol 1997; 29:582. 3. Corrado G, Sgalambro A, Mantero A, et al. Thromboembolic risk in atrial flutter. The FLASIEC (FLutter Atriale Societ Italiana di Ecografia Cardiovascolare) multicentre study. Eur Heart J 2001; 22:1042. 4. Schmidt H, von der Recke G, Illien S, et al. Prevalence of left atrial chamber and appendage thrombi in patients with atrial flutter and its clinical significance. J Am Coll Cardiol 2001; 38:778. 5. Weiss R, Marcovitz P, Knight BP, et al. 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Incidence and predictors of atrial flutter in the general population. J Am Coll Cardiol 2000; 36:2242. 10. Garson A Jr, Bink-Boelkens M, Hesslein PS, et al. Atrial flutter in the young: a collaborative study of 380 cases. J Am Coll Cardiol 1985; 6:871. 11. Halligan SC, Gersh BJ, Brown RD Jr, et al. The natural history of lone atrial flutter. Ann Intern Med 2004; 140:265. 12. Ghali WA, Wasil BI, Brant R, et al. Atrial flutter and the risk of thromboembolism: a systematic review and meta-analysis. Am J Med 2005; 118:101. 13. Seidl K, Hauer B, Schwick NG, et al. Risk of thromboembolic events in patients with atrial flutter. Am J Cardiol 1998; 82:580. 14. Lanzarotti CJ, Olshansky B. Thromboembolism in chronic atrial flutter: is the risk underestimated? J Am Coll Cardiol 1997; 30:1506. 15. Mehta D, Baruch L. Thromboembolism following cardioversion of "common" atrial flutter. Risk factors and limitations of transesophageal echocardiography. Chest 1996; 110:1001. 16. Elhendy A, Gentile F, Khandheria BK, et al. Thromboembolic complications after electrical cardioversion in patients with atrial flutter. Am J Med 2001; 111:433. 17. Gallagher MM, Hennessy BJ, Edvardsson N, et al. Embolic complications of direct current cardioversion of atrial arrhythmias: association with low intensity of anticoagulation at the time of cardioversion. J Am Coll Cardiol 2002; 40:926. 18. Arnold AZ, Mick MJ, Mazurek RP, et al. Role of prophylactic anticoagulation for direct current cardioversion in patients with atrial fibrillation or atrial flutter. J Am Coll Cardiol 1992; 19:851. 19. Chalasani P, Cambre S, Silverman ME. Direct-current cardioversion for the conversion of atrial flutter. Am J Cardiol 1996; 77:658. 20. Jordaens L, Missault L, Germonpr E, et al. Delayed restoration of atrial function after conversion of atrial flutter by pacing or electrical cardioversion. Am J Cardiol 1993; 71:63. 21. Sparks PB, Jayaprakash S, Vohra JK, et al. Left atrial "stunning" following radiofrequency catheter ablation of chronic atrial flutter. J Am Coll Cardiol 1998; 32:468. 22. Welch PJ, Afridi I, Joglar JA, et al. Effect of radiofrequency ablation on atrial mechanical function in patients with atrial flutter. Am J Cardiol 1999; 84:420. 23. You JJ, Singer DE, Howard PA, et al. Antithrombotic therapy for atrial fibrillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e531S. https://www.uptodate.com/contents/embolic-risk-and-the-role-of-anticoagulation-in-atrial-flutter/print 8/13 7/5/23, 10:22 AM Embolic risk and the role of anticoagulation in atrial flutter - UpToDate 24. American College of Cardiology Foundation, American Heart Association, European Society of Cardiology, et al. Management of patients with atrial fibrillation (compilation of 2006 ACCF/AHA/ESC and 2011 ACCF/AHA/HRS recommendations): a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. Circulation 2013; 127:1916. 25. Singer DE, Albers GW, Dalen JE, et al. Antithrombotic therapy in atrial fibrillation: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:546S. 26. Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365:981. 27. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation 2014; 130:2071. 28. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation 2014; 130:e199. 29. Hindricks G, Potpara T, Dagres N, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J 2021; 42:373. 30. January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in Collaboration With the Society of Thoracic Surgeons. Circulation 2019; 140:e125. 31. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2016; 67:e27. Topic 1066 Version 30.0 https://www.uptodate.com/contents/embolic-risk-and-the-role-of-anticoagulation-in-atrial-flutter/print 9/13 7/5/23, 10:22 AM Embolic risk and the role of anticoagulation in atrial flutter - UpToDate GRAPHICS Clinical risk factors for stroke, transient ischemic attack, and systemic embolism in the CHA DS -VASc score 2 2 (A) The risk factor-based approach expressed as a point based scoring system, with the acronym CHA DS -VASc 2 2 (NOTE: maximum score is 9 since age may contribute 0, 1, or 2 points) CHA DS -VASc risk factor Points 2 2 Congestive heart failure +1 Signs/symptoms of heart failure or objective evidence of reduced left ventricular ejection fraction Hypertension +1 Resting blood pressure >140/90 mmHg on at least 2 occasions or current antihypertensive treatment Age 75 years or older +2 Diabetes mellitus +1 Fasting glucose >125 mg/dL (7 mmol/L) or treatment with oral hypoglycemic agent and/or insulin Previous stroke, transient ischemic attack, or thromboembolism +2 Vascular disease +1 Previous myocardial infarction, peripheral artery disease, or aortic plaque Age 65 to 74 years +1 Sex category (female) +1 (B) Adjusted stroke rate according to CHA DS -VASc score 2 2 CHA DS -VASc score Patients (n = 73,538) Stroke and thromboembolism event 2 2 rate at 1-year follow-up (%) 0 6369 0.78 1 8203 2.01 2 12,771 3.71 3 17,371 5.92 4 13,887 9.27 https://www.uptodate.com/contents/embolic-risk-and-the-role-of-anticoagulation-in-atrial-flutter/print 10/13 7/5/23, 10:22 AM Embolic risk and the role of anticoagulation in atrial flutter - UpToDate 5 8942 15.26 6 4244 19.74 7 1420 21.50 8 285 22.38 9 46 23.64 CHA DS -VASc: Congestive heart failure, Hypertension, Age ( 75; doubled), Diabetes, Stroke (doubled), Vascular disease, Age (65 to 74), Sex. 2 2 Part A from: Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial brillation developed in collaboration with EACTS. Europace 2016; 18(11):1609-1678. By permission of Oxford University Press on behalf of the European Society of Cardiology. Copyright 2016 Oxford University Press. Available at: www.escardio.org/. Graphic 83272 Version 29.0 https://www.uptodate.com/contents/embolic-risk-and-the-role-of-anticoagulation-in-atrial-flutter/print 11/13 7/5/23, 10:22 AM Embolic risk and the role of anticoagulation in atrial flutter - UpToDate Stroke risk in atrial flutter is related to concomitant atrial fibrillation Among 395,147 patients over 65 years of age, the risk of stroke in those with chronic atrial flutter is increased when atrial fibrillation (AF) is also present and is equivalent to the risk associated with only AF. The incidence of stroke in those with isolated atrial flutter is the same as the risk in the control patients who have no atrial arrhythmia. Data from Biblo LA, Yuan Z, Quan KJ, et al. Am J Cardiol 2001; 87:346. Graphic 67382 Version 2.0 https://www.uptodate.com/contents/embolic-risk-and-the-role-of-anticoagulation-in-atrial-flutter/print 12/13 7/5/23, 10:22 AM Embolic risk and the role of anticoagulation in atrial flutter - UpToDate Contributor Disclosures Warren J Manning, MD Equity Ownership/Stock Options: Pfizer [Anticoagulants]. All of the relevant financial relationships listed have been mitigated. Jordan M Prutkin, MD, MHS, FHRS No relevant financial relationship(s) with ineligible companies to disclose. Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Scott E Kasner, MD Grant/Research/Clinical Trial Support: Bayer [Stroke]; Bristol Meyers Squibb [Stroke]; Medtronic [Stroke]; WL Gore and Associates [Stroke]. Consultant/Advisory Boards: Abbvie [Stroke]; AstraZeneca [Stroke]; BMS [Stroke]; Diamedica [Stroke]; Medtronic [Stroke]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/embolic-risk-and-the-role-of-anticoagulation-in-atrial-flutter/print 13/13

7/5/23, 10:22 AM Overview of atrial flutter - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Overview of atrial flutter : Robert Phang, MD, FACC, FHRS, Jordan M Prutkin, MD, MHS, FHRS : Peter J Zimetbaum, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Jun 16, 2022. INTRODUCTION Atrial flutter is an abnormal cardiac rhythm characterized by rapid, regular atrial depolarizations at a characteristic rate of approximately 300 beats/min and a regular ventricular rate of about 150 beats/min in patients not taking atrioventricular (AV) nodal blockers. It can lead to symptoms of palpitations, shortness of breath, fatigue, or lightheadedness, as well as an increased risk of atrial thrombus formation that may cause cerebral and/or systemic embolization. Atrial flutter occurs in many of the same situations as atrial fibrillation, which is much more common. Atrial flutter may be a stable rhythm or a bridge arrhythmia between sinus rhythm and atrial fibrillation, or an organized rhythm in atrial fibrillation patients treated with antiarrhythmic drugs. It may also be associated with a variety of other supraventricular arrhythmias. (See "Epidemiology, risk factors, and prevention of atrial fibrillation".) This topic will summarize key points regarding the causes, clinical presentation, diagnosis, and management approach to patients with atrial flutter. Other topics discuss management issues in detail. (See "Restoration of sinus rhythm in atrial flutter" and "Control of ventricular rate in atrial flutter" and "Atrial flutter: Maintenance of sinus rhythm" and "Embolic risk and the role of anticoagulation in atrial flutter".) ELECTROPHYSIOLOGIC CLASSIFICATION https://www.uptodate.com/contents/overview-of-atrial-flutter/print 1/22 7/5/23, 10:22 AM Overview of atrial flutter - UpToDate Atrial flutter was previously classified as either type I or type II. That terminology is no longer used. Typical atrial flutter The designation of "typical" atrial flutter involves a macroreentrant circuit traversing the cavo-tricuspid isthmus (CTI) ( figure 1). This isthmus is the region of right atrial tissue between the orifice of the inferior vena cava and the tricuspid valve annulus ( figure 2). If this isthmus is involved, it is called "typical" atrial flutter or CTI-dependent atrial flutter. The circuit is usually a counterclockwise rotation around the tricuspid valve ( figure 2), exhibiting a classic sawtooth appearance in the inferior electrocardiogram (ECG) leads (II, III, aVF) ( image 1B). If the circuit is clockwise, it is called "reverse" or "clockwise" typical flutter, exhibiting positive flutter waves in the inferior ECG leads ( image 1C). The clockwise circuit occurs far less frequently than the counterclockwise circuit; rare patients exhibit both circuits at different times. The ECG hallmark of typical atrial flutter is discordance in flutter wave "direction" between the inferior leads and lead V1. In counterclockwise circuits, flutter waves are directly negative in the inferior leads but are positive in lead V1. In clockwise circuits, the opposite is true. These ECG rules are generally less reliable after atrial ablation or surgery. Atypical atrial flutter If the CTI is not involved in the underlying mechanism, then it is called "atypical" atrial flutter. This type of flutter can involve any region of the right or left atria, around areas of scar tissue due to intrinsic heart disease or surgical/ablated scar tissue (see "Electrocardiographic and electrophysiologic features of atrial flutter"). Surgical repair of congenital heart disease may lead to macroreentrant atrial flutter circuits, both typical (cavotricuspid isthmus dependent) and atypical. These circuits are usually right atrial, related to anatomic obstacles and surgical scars (cavotricuspid isthmus, right atriotomy scar, atrial septal defect repair, etc). Left atrial flutters that arise after AF ablation procedures constitute a large fraction of atypical flutters. Incomplete ablation lines created in attempts to cure atrial fibrillation with ablation can promote atypical atrial flutter circuits in the left atrium (mitral isthmus flutter, etc). Focal atrial tachycardias with atrioventricular block may also mimic atypical atrial flutter by ECG appearance, but by electrophysiologic study the focal mechanism can be differentiated from the macroreentry seen in atrial flutter. In atypical atrial flutters, the flutter waves in the inferior leads and lead V1 are often concordant. (See "Focal atrial tachycardia".) ETIOLOGY AND RISK FACTORS Atrial flutter is uncommon in the structurally normal heart [1-3]. A variety of underlying conditions can predispose to the development of atrial flutter. These include: https://www.uptodate.com/contents/overview-of-atrial-flutter/print 2/22 7/5/23, 10:22 AM Overview of atrial flutter - UpToDate After antiarrhythmic drug initiation Atrial flutter may occur after initiation of an antiarrhythmic drug for the suppression of atrial fibrillation. It may occur in up to 15 percent of patients treated with flecainide or propafenone, and is also seen in patients treated with dronedarone or amiodarone. After acute myocardial infarction Atrial flutter is a relatively uncommon complication of an acute myocardial infarction [4,5] and is rarely, if ever, a manifestation of digitalis toxicity [6,7]. (See "Supraventricular arrhythmias after myocardial infarction" and "Cardiac arrhythmias due to digoxin toxicity".) Post-cardiac surgery Atrial flutter can occur after cardiac surgery, both as a postoperative complication and as a late arrhythmia. The atrial flutter in these patients is re-entrant and may be typical or involve atypical isthmuses between natural barriers, atrial incisions, and scar. (See "Atrial fibrillation and flutter after cardiac surgery", section on 'Pathogenesis'.) Post-atrial fibrillation ablation Some patients develop atypical left atrial flutter after atrial fibrillation ablation. These arrhythmias may be due to circuits created by scar from left atrial (LA) ablations, but are often amenable to ablation themselves. This issue is discussed in detail separately. (See "Atrial fibrillation: Catheter ablation", section on 'Arrhythmic complications'.) Other specific triggers Any of the disorders that can cause atrial fibrillation, including thyrotoxicosis, obesity, obstructive sleep apnea, sinus node dysfunction, pericarditis, pulmonary disease, and pulmonary embolism. (See "Epidemiology, risk factors, and prevention of atrial fibrillation".) INCIDENCE In the general population, the development of new onset atrial flutter is uncommon and occurs with significantly less frequency than atrial fibrillation. In a population-based study, lone atrial flutter with neither identifiable recent predisposing events nor chronic preexisting comorbidities occurred in only 3 of 181 patients (1.7 percent) [1]. Sixteen percent of cases were attributable to heart failure and 12 percent to chronic obstructive pulmonary disease [1]. The incidence increased markedly with age, ranging from 5 per 100,000 person years under age 50 to 587 per 100,000 person years over age 80. The rate of lone atrial flutter was 8 percent in another series of 380 children and young adults [3]. https://www.uptodate.com/contents/overview-of-atrial-flutter/print 3/22 7/5/23, 10:22 AM Overview of atrial flutter - UpToDate Much of the information about atrial flutter has been derived from patients referred to tertiary care centers; as a result, the incidence of atrial flutter in the general population has been uncertain. This issue was addressed in a large database of 58,820 residents who obtained their care from one major medical center [1]. The overall incidence of new cases of atrial flutter during a four-year period was 88 per 100,000 person-years, ranging from 5 per 100,000 in those less than 50 and 587 per 100,000 in those more than 80 years of age. Atrial flutter was 2.5 times more common in men. Based upon these data, it was estimated that the incidence of atrial flutter in the United States is 200,000 new cases per year. The incidence of this arrhythmia, as with atrial fibrillation, is greatest when underlying heart disease is associated with left atrial enlargement, or left ventricular or biventricular failure [1,8,9]. CLINICAL MANIFESTATIONS History and physical examination Typical complaints include palpitations, fatigue, lightheadedness, and/or mild shortness of breath. Less common problems include significant dyspnea, angina, hypotension, anxiety, presyncope, or infrequently, syncope. These symptoms are in large part attributable the rapid heart rate. (See 'Hemodynamics' below.) The purpose of the remainder of the history is to define the onset of the arrhythmia as well as its frequency and duration, the precipitating causes and modes of termination, the previous response to drug therapy, and the presence of heart disease or potentially reversible causes. (See 'Etiology and risk factors' above.) The physical examination may reveal tachycardia, hypotension, diaphoresis, and evidence of congestive heart failure. (See "Heart failure: Clinical manifestations and diagnosis in adults", section on 'Physical examination'.) Occasionally, cardiac auscultation may reveal an irregular rhythm, abnormal valve sounds, or a gallop. Flutter waves may be seen in the jugular veins at a rate consistent with the atrial rate. Electrocardiogram For patients in atrial flutter at the time of the electrocardiogram (ECG), it generally shows an atrial rate of about 300 beats per minute (range 240 to 340) ( image 1A-C). Typical P waves are absent, and the atrial activity is seen as a sawtooth pattern (also called F waves) in leads II, III, and aVF. The ECG hallmark of typical atrial flutter is discordance in flutter wave "direction" between the inferior leads and lead V1. In counterclockwise circuits, flutter waves are directly negative in the https://www.uptodate.com/contents/overview-of-atrial-flutter/print 4/22 7/5/23, 10:22 AM Overview of atrial flutter - UpToDate inferior leads but are positive in lead V1. In clockwise circuits, the opposite is true. These ECG rules are generally less reliable after atrial ablation or surgery. There is typically 2:1 conduction across the atrioventricular (AV) node, particularly in counterclockwise typical atrial flutter; as a result, the ventricular rate is usually one-half the flutter rate in the absence of AV node dysfunction. Even atrial to ventricular rate ratios (eg, 2:1 or 4:1 conduction) are much more common than odd ratios (eg, 3:1 or 5:1) (see "Electrocardiographic and electrophysiologic features of atrial flutter"). Odd ratios probably reflect bilevel block in the AV node. On the other hand, a 1:1 response suggests catecholamine excess, parasympathetic withdrawal, the presence of antiarrhythmic drug therapy with Class IA or IC agents ( table 1), or the existence of an accessory bypass tract. The ECG may also identify left ventricular hypertrophy, pre-excitation, bundle branch block, or prior myocardial infarction (MI). Overlapping flutter waves may complicate assessment of the QT interval, repolarization pattern, and even the presence of T waves. Echocardiogram A transthoracic echocardiogram should be obtained in all patients with atrial flutter to evaluate the size of the right and left atria, the size and function of the right and left ventricles, and to detect possible pericardial or valvular heart disease or left ventricular hypertrophy. Transthoracic echocardiography has a low sensitivity for detecting thrombus, and transesophageal echocardiography (TEE) is preferred for this purpose. TEE may play an important role in the selection of patients for cardioversion as it does in atrial fibrillation. (See "Role of echocardiography in atrial fibrillation".) Hemodynamics Several hemodynamic changes occur with atrial flutter; many of these are consequent to the rapid atrial and ventricular rates. These changes include an increase in the mean right and left atrial pressures, a reduction in right and left ventricular end-diastolic pressures, a decrease in systolic blood pressure, and an increase in diastolic pressure. The cardiac index is generally unaltered [10]. The reduction in left ventricular pressure is a result of the rapid heart rate, while the increase in atrial pressure is due, in part, to contraction against closed atrioventricular valves. The hemodynamic changes lead to the symptoms presented below. (See 'History and physical examination' above.) Additional testing Exercise testing is sometimes useful to reproduce exercise-induced atrial flutter, to evaluate for associated ischemic heart disease, or to determine the maximum heart rate with exercise, which can help guide medical therapy. Holter monitoring or event recorders are used to identify the arrhythmia if symptoms are nonspecific, to identify triggering events, to https://www.uptodate.com/contents/overview-of-atrial-flutter/print 5/22 7/5/23, 10:22 AM Overview of atrial flutter - UpToDate detect associated atrial arrhythmias, and to determine average and peak heart rates. (See "Ambulatory ECG monitoring".) Serum electrolytes, renal and hepatic function, and pulmonary and thyroid function tests can be ordered when searching for predisposing causes. DIAGNOSIS The diagnosis of atrial flutter is almost always secured by the observation of a characteristic pattern on the electrocardiogram, which includes the presence of continuous, regular atrial electrical activity. If there are sawtooth negative flutter waves in the leads II, III, and aVF, it is typical atrial flutter ( image 1B), especially at a characteristic atrial rate of approximately 300 beats/min with a regular ventricular rate of about 150 beats/min in patients not taking atrioventricular nodal blockers. (See 'Introduction' above and 'Electrophysiologic classification' above.) DIFFERENTIAL DIAGNOSIS Occasionally, the pattern of atrial activity on the electrocardiogram is not convincing for atrial flutter and raises the possibility of atrial fibrillation, other supraventricular arrhythmia, or even electrical artifact. If the latter has been excluded, an electrophysiology study is necessary to determine if the arrhythmia is atrial flutter. (See "Invasive diagnostic cardiac electrophysiology studies" and "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'Types of narrow QRS complex tachycardia'.) COMPLICATIONS Serious complications of atrial flutter include myocardial ischemia, dizziness or syncope, heart failure (with either preserved or reduced left ventricular systolic function), stroke, or systemic embolism. Control of the ventricular rate or reversion to normal sinus rhythm will improve or prevent the first three; anticoagulation is frequently used to decrease the risk of embolization. (See "Atrial fibrillation in adults: Use of oral anticoagulants".) Atrial flutter with a rapid ventricular response is also an important cause of tachycardia induced cardiomyopathy. Control of the ventricular rate or reversion to normal sinus rhythm will improve many symptoms in these patients. Rate-control is critical to treat heart failure (HF) symptoms, but in patients with tachycardia-mediated cardiomyopathy, rate plus rhythm control may be https://www.uptodate.com/contents/overview-of-atrial-flutter/print 6/22 7/5/23, 10:22 AM Overview of atrial flutter - UpToDate more effective in improving symptoms. Effective treatment of atrial flutter, most commonly with ablation, frequently leads to improvement and sometimes normalization of left ventricular function. (See "Arrhythmia-induced cardiomyopathy".) GENERAL TREATMENT ISSUES As is true for atrial fibrillation, there are four major issues that must be considered in the management of atrial flutter: Control of the ventricular rate Reversion to normal sinus rhythm (NSR) Maintenance of NSR Prevention of systemic embolization The following discussion will provide a brief summary of these four treatment issues, each of which is discussed in detail separately. Rate control in atrial flutter Rate control in atrial flutter, as in atrial fibrillation, usually involves the administration of a non-dihydropyridine calcium channel blocker or a beta blocker. Digoxin is used less often because its major action is an enhancement of vagal tone, which is offset during exertion. The main indication is concurrent heart failure in which it is often given in combination with a beta-blocker. In general, it is more difficult to affect rate control in atrial flutter, as compared with atrial fibrillation. While up-titration of atrioventricular (AV) nodal blocking agents typically lowers the mean rate in atrial fibrillation, patients with atrial flutter are frequently "stuck" at 2:1 AV conduction. Rarely, amiodarone may also be also as a rate control agent, particularly in acutely ill patients, but is not generally used long term due to the risk of potential side effects. Ablation therapy of the AV node and pacemaker implantation ("ablate and pace" strategy) is also rarely indicated, but is a treatment option in drug-refractory cases. (See "Control of ventricular rate in atrial flutter".) Reversion to normal sinus rhythm Due to the high rate of recurrence of atrial flutter in patients without a correctable cause, and because of its high success rate with low rate of complications, definitive treatment with radiofrequency catheter ablation is the preferred treatment for most patients. (See "Atrial flutter: Maintenance of sinus rhythm", section on 'RF catheter ablation'.) https://www.uptodate.com/contents/overview-of-atrial-flutter/print 7/22 7/5/23, 10:22 AM Overview of atrial flutter - UpToDate It is less preferable for most patients to consider antiarrhythmic drugs because of potential for side effects. Class IA and IC drugs ( table 1) risk causing rapidly conducted atrial flutter. These drugs can slow the atrial flutter rate, and in the absence of AV nodal blocking agents, lead to 1:1 A:V conduction and paradoxically faster rates than baseline flutter (generally with 2:1 A:V conduction). Amiodarone and dronedarone can also slow the atrial flutter rate, but rarely lead to 1:1 A:V conduction because they also slow AV nodal conduction. All of these agents can "organize" atrial fibrillation and lead to "slow" atrial flutter, with the risk of 1:1 A:V conduction as described. For hemodynamically stable patients who will not require urgent catheter ablation, watchful waiting under anticoagulation and rate control medicines may be reasonable, as atrial flutter may convert to sinus rhythm spontaneously. Cardioversion is also reasonable if the patient has had no prior episodes of atrial flutter, or if they choose to decline ablation as an invasive first-line strategy. Synchronized internal or external direct current (DC) is preferred to antiarrhythmic drug cardioversion (using quinidine, procainamide, disopyramide, flecainide, propafenone, amiodarone, ibutilide, or dofetilide). If pharmacologic reversion is deemed necessary, ibutilide, which is approved by the United States Food and Drug Administration only for intravenous use, is the drug of choice [11] (see "Restoration of sinus rhythm in atrial flutter"). It can revert atrial flutter to a sinus mechanism in approximately 60 percent of patients and is more effective than procainamide, sotalol, or amiodarone [11-13]. Ibutilide therapy carries a risk of QT prolongation and torsades de pointes. One report noted an 8.3 percent incidence of torsades de pointes [14]. Although torsades de points is usually not sustained, electrical cardioversion was required for sustained arrhythmia in 1.7 percent. As a result, the use of ibutilide requires continuous monitoring, resuscitative equipment including a defibrillator, and personnel trained in the use of electrical cardioversion and resuscitation. (See "Therapeutic use of ibutilide".) In the setting of ventricular preexcitation, patients with atrial flutter and rapid ventricular rates should be treated with intravenous ibutilide or procainamide, as is recommended in the treatment of AF with ventricular preexcitation [15] (see "Restoration of sinus rhythm in atrial flutter"). Administration of intravenous adenosine, beta blockers, digoxin (oral or intravenous), nondihydropyridine calcium channel antagonists (oral or intravenous), or amiodarone in patients with Wolff-Parkinson-White syndrome and pre-excited AF and/or atrial flutter is potentially harmful because these drugs accelerate the ventricular rate [15]. (See "Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome".) https://www.uptodate.com/contents/overview-of-atrial-flutter/print 8/22 7/5/23, 10:22 AM Overview of atrial flutter - UpToDate Atrial overdrive pacing is another method to convert atrial flutter to sinus rhythm. The most frequent settings for this approach are patients with pre-existing permanent pacemakers where pacing can be performed via the programmer or following cardiac surgery when pacing via a temporary epicardial (atrial) wire can be performed. Of course, the usual precautions should be taken with regard to anticoagulation or transesophageal echocardiography (TEE) if the duration of atrial flutter is beyond 24 to 48 hours or of unknown duration. Maintenance of normal sinus rhythm The rate of recurrence of atrial flutter is difficult to determine because most published data combine atrial flutter with atrial fibrillation. However, the recurrence rate is substantial. In one report, for example, 50 patients were followed for a mean of 3.5 years after cardioversion for chronic atrial flutter; prophylactic antiarrhythmic drugs were not given [16]. Sinus rhythm was maintained at six months and five years in 53 and 42 percent of patients, respectively. In a second study of 59 patients with lone atrial flutter, 75 percent developed recurrent or chronic atrial flutter [17]. (See "Atrial flutter: Maintenance of sinus rhythm".) Antiarrhythmic drug mechanisms, as with atrial fibrillation, may suppress triggering premature atrial complex (PAC; also referred to a premature atrial beat, premature supraventricular complex, or premature supraventricular beat), which may require the use of class IA and IC drugs, beta blockers, and amiodarone, and/or to prolong the atrial refractory period with class III drugs. However, because of the high rate of recurrence in patients without a correctable cause, and because of its high success rate, radiofrequency catheter ablation is generally preferable to long- term pharmacologic therapy in patients with typical atrial flutter. The isthmus between the inferior vena cava and the tricuspid annulus (cavotricuspid isthmus) is an obligatory route for typical flutter, and, as such, is the preferred anatomic target for ablation ( figure 1). This applies to the common counterclockwise circuit, as well as the less common clockwise circuit. A meta-analysis of 21 studies demonstrated an ablation success rate for a single procedure of 91.7 percent and for multiple procedures of 97.0 percent [18]. (See "Atrial flutter: Maintenance of sinus rhythm" and "Atrial fibrillation and flutter after cardiac surgery", section on 'Pathogenesis' and "Atrial fibrillation: Catheter ablation", section on 'Arrhythmic complications'.) In a meta-analysis of 48 studies (between 1996 and 2015) of patients undergoing catheter ablation for typical atrial flutter, who were followed for an average of 2.5 years, those without prior atrial fibrillation had a 23 percent incidence of new atrial fibrillation diagnosis. Not surprisingly, those with prior history of paroxysmal atrial fibrillation undergoing atrial flutter ablation had a much higher recurrence rate of 52 percent, highlighting the need for individualized risk assessment for long-term anticoagulation [19]. https://www.uptodate.com/contents/overview-of-atrial-flutter/print 9/22 7/5/23, 10:22 AM Overview of atrial flutter - UpToDate Prevention of systemic embolization Sustained atrial flutter, while much less common than atrial fibrillation, carries an elevated thromboembolic risk. The frequency of thromboembolism and the importance of anticoagulation were illustrated in a report of 100 patients who were referred to an electrophysiology laboratory for cardioversion of atrial flutter that was present for at least six months: Six patients had a thromboembolic event that was attributable to atrial flutter [20]. The event occurred during atrial flutter or after cardioversion and none of the patients were receiving adequate anticoagulation. There were no embolic events in patients on adequate anticoagulation. (See "Embolic risk and the role of anticoagulation in atrial flutter", section on 'Long-term flutter'.) One problem with interpreting these data is that many patients with chronic atrial flutter also have periods of atrial fibrillation. Our approach to anticoagulation in patients with atrial flutter is identical to that for atrial fibrillation [21]. Although the risk of systemic embolism is probably a little lower compared with atrial fibrillation, it is appropriate to use anticoagulation in atrial flutter as similar to atrial fibrillation. Risk stratification using the CHA DS -VASc scoring system should be completed prior 2 2 to deciding on the use of oral anticoagulation. (See "Atrial fibrillation in adults: Use of oral anticoagulants".) Commonly, four weeks after successful ablation of isolated typical atrial flutter (ie, no prior atrial fibrillation history), anticoagulation is discontinued. However, in patients with prior atrial fibrillation history, anticoagulation should be continued long term based on the CHA DS -VASc 2 2 scoring system. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Atrial fibrillation" and "Society guideline links: Arrhythmias in adults".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and Beyond the Basics. th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading https://www.uptodate.com/contents/overview-of-atrial-flutter/print 10/22 7/5/23, 10:22 AM Overview of atrial flutter - UpToDate level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on patient info and the keyword(s) of interest.) Basics topics (see "Patient education: Atrial flutter (The Basics)") SUMMARY AND RECOMMENDATIONS Definition Atrial flutter is an abnormal cardiac rhythm characterized by rapid, regular atrial depolarizations at a characteristic rate of approximately 300 beats/min and a regular ventricular rate of about 150 beats/min ( image 1B). (See 'Introduction' above and 'Electrophysiologic classification' above.) Comorbid conditions Atrial flutter is unusual in patients without heart disease. It frequently coexists with atrial fibrillation and may be associated with valvular heart disease, cardiomyopathy, post-cardiac surgery, pericardial disease including pericardiotomy, prior heart surgery, and acute or chronic pulmonary diseases. (See 'Etiology and risk factors' above.) Electrophysiologic classification Distinguishing typical from atypical atrial flutter has useful treatment implications, particularly the high success rate of catheter ablation in typical atrial flutter. (See 'Electrophysiologic classification' above.) Clinical manifestations The clinical manifestations are similar to those of atrial fibrillation. (See 'Clinical manifestations' above.) Symptoms Typical complaints include palpitations, fatigue, lightheadedness, and/or mild shortness of breath. Physical examination This may reveal tachycardia, hypotension, diaphoresis, and evidence of congestive heart failure. Occasionally, cardiac auscultation may reveal an irregular rhythm, abnormal valve sounds, or a gallop. Flutter waves may be seen in the jugular veins at a rate consistent with the atrial rate. Diagnosis The diagnosis can usually be made from a 12 lead electrocardiogram. (See 'Electrocardiogram' above and 'Diagnosis' above.) https://www.uptodate.com/contents/overview-of-atrial-flutter/print 11/22 7/5/23, 10:22 AM Overview of atrial flutter - UpToDate Treatment strategies The management of rate-control and anticoagulation strategies for prevention of systemic thromboembolism are similar to those used for atrial fibrillation. However, long-term antiarrhythmic medications are infrequently used given the limitations of pharmacologic therapy and high rate of success of ablation for typical atrial flutter. (See 'General treatment issues' above.) Anticoagulation Although the risk of systemic embolism is probably somewhat lower compared with atrial fibrillation, it is still appropriate to use anticoagulation in atrial flutter. Risk stratification using the CHA DS -VASc scoring system should be completed prior to 2 2 deciding on the use of oral anticoagulation. (See 'Prevention of systemic embolization' above and "Atrial fibrillation in adults: Use of oral anticoagulants".) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Granada J, Uribe W, Chyou PH, et al. Incidence and predictors of atrial flutter in the general population. J Am Coll Cardiol 2000; 36:2242. 2. FOSMOE RJ, AVERILL KH, LAMB LE. Electrocardiographic findings in 67,375 asymptomatic subjects. II. Supraventricular arrhythmias. Am J Cardiol 1960; 6:84. 3. Garson A Jr, Bink-Boelkens M, Hesslein PS, et al. Atrial flutter in the young: a collaborative study of 380 cases. J Am Coll Cardiol 1985; 6:871. 4. JULIAN DG, VALENTINE PA, MILLER GG. DISTURBANCES OF RATE, RHYTHM AND CONDUCTION IN ACUTE MYOCARDIAL INFARCTION: A PROSPECTIVE STUDY OF 100 CONSECUTIVE UNSELECTED PATIENTS WITH THE AID OF ELECTROCARDIOGRAPHIC MONITORING. Am J Med 1964; 37:915. 5. Meltzer LE, Kitchell JB. The incidence of arrhythmias associated with acute myocardial infarction. Prog Cardiovasc Dis 1966; 9:50. 6. DELMAN AJ, STEIN E. ATRIAL FLUTTER SECONDARY TO DIGITALIS TOXICITY. REPORT OF THREE CASES AND REVIEW OF THE LITERATURE. Circulation 1964; 29:SUPPL:593. https://www.uptodate.com/contents/overview-of-atrial-flutter/print 12/22 7/5/23, 10:22 AM Overview of atrial flutter - UpToDate 7. FRIEDBERG CK, DONOSO E. Arrhythmias and conduction disturbances due to digitalis. Prog Cardiovasc Dis 1960; 2:408. 8. Friedberg CK. Diseases of the Heart, Saunders, Philadelphia 1966. 9. Lewis T. Diseases of the Heart, MacMillan, London 1948. 10. Alboni P, Scarf S, Fuc G, et al. Atrial and ventricular pressures in atrial flutter. Pacing Clin Electrophysiol 1999; 22:600. 11. Wellens HJ. Contemporary management of atrial flutter. Circulation 2002; 106:649. 12. Vos MA, Golitsyn SR, Stangl K, et al. Superiority of ibutilide (a new class III agent) over DL- sotalol in converting atrial flutter and atrial fibrillation. The Ibutilide/Sotalol Comparator Study Group. Heart 1998; 79:568. 13. Stambler BS, Wood MA, Ellenbogen KA. Antiarrhythmic actions of intravenous ibutilide compared with procainamide during human atrial flutter and fibrillation: electrophysiological determinants of enhanced conversion efficacy. Circulation 1997; 96:4298. 14. Stambler BS, Wood MA, Ellenbogen KA, et al. Efficacy and safety of repeated intravenous doses of ibutilide for rapid conversion of atrial flutter or fibrillation. Ibutilide Repeat Dose Study Investigators. Circulation 1996; 94:1613. 15. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2014; 64:e1. 16. Crijns HJ, Van Gelder IC, Tieleman RG, et al. Long-term outcome of electrical cardioversion in patients with chronic atrial flutter. Heart 1997; 77:56. 17. Halligan SC, Gersh BJ, Brown RD Jr, et al. The natural history of lone atrial flutter. Ann Intern Med 2004; 140:265. 18. Spector P, Reynolds MR, Calkins H, et al. Meta-analysis of ablation of atrial flutter and supraventricular tachycardia. Am J Cardiol 2009; 104:671. 19. Maskoun W, Pino MI, Ayoub K, et al. Incidence of Atrial Fibrillation After Atrial Flutter Ablation. JACC Clin Electrophysiol 2016; 2:682. 20. Lanzarotti CJ, Olshansky B. Thromboembolism in chronic atrial flutter: is the risk underestimated? J Am Coll Cardiol 1997; 30:1506. 21. Writing Group Members, January CT, Wann LS, et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: A https://www.uptodate.com/contents/overview-of-atrial-flutter/print 13/22 7/5/23, 10:22 AM Overview of atrial flutter - UpToDate Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Heart Rhythm 2019; 16:e66. Topic 1048 Version 43.0 https://www.uptodate.com/contents/overview-of-atrial-flutter/print 14/22 7/5/23, 10:22 AM Overview of atrial flutter - UpToDate GRAPHICS Reentrant circuit of typical atrial flutter within the right atrium Schematic representation of reentrant circuit (red arrow) of typical (type 1) atrial flutter. The reentrant impulse rotates in a counterclockwise direction around the tricuspid annulus. The crista terminalis (CT) and eustacian ridge (ER) serve as lines of block, preventing the impulse from short-circuiting the annulus. Ablation is performed in the isthmus between the IVC and TA, which is an obligatory part of the circuit. SVC: superior vena cava; CS: coronary sinus; IVC: inferior vena cava; FO: foramen ovale Graphic 52904 Version 5.0 https://www.uptodate.com/contents/overview-of-atrial-flutter/print 15/22 7/5/23, 10:22 AM Overview of atrial flutter - UpToDate Electrical activation of the right atrium in atrial flutter Electroanatomical (3D) mapping using the CARTO system. The right atrium (RA) is depicted in the LAO projection. The circular "cutout" area in the forefront of the picture represents the tricuspid valve annulus. The red area is the inferolateral RA, the yellow-green area at the bottom of the picture is near the inferior vena cava, the yellow dots are at the region of the His bundle (AV node), and the blue area is the superior RA. The top of the picture is the superior vena cava region. The color (red-orange-yellow-green-blue-purple) represents the direction of electrical activation in the RA during typical (counterclockwise) atrial flutter. Each flutter wave seen on ECG represents a single electrical activation of this entire circuit. Graphic 89570 Version 1.0 https://www.uptodate.com/contents/overview-of-atrial-flutter/print 16/22 7/5/23, 10:22 AM Overview of atrial flutter - UpToDate ECG of counterclockwise typical atrial flutter Sawtooth-like oscillations of baseline between flutter waves, best seen in the inferior leads. Negative flutter waves in II, III, aVF, V6. Positive flutter waves in V1. ECG: electrocardiogram. Graphic 89571 Version 2.0 https://www.uptodate.com/contents/overview-of-atrial-flutter/print 17/22 7/5/23, 10:22 AM Overview of atrial flutter - UpToDate ECG of clockwise typical atrial flutter Sawtooth-like oscillations of baseline between flutter waves, best seen in inferior leads. Positive flutter waves in II, III, aVF, V6. Negative flutter waves in V1. ECG: electrocardiogram. Graphic 89576 Version 2.0 https://www.uptodate.com/contents/overview-of-atrial-flutter/print 18/22 7/5/23, 10:22 AM Overview of atrial flutter - UpToDate ECG of atypical atrial flutter Note the lack of classic sawtooth flutter waves in the inferior leads II, III, and aVF. ECG: electrocardiogram. Graphic 89577 Version 4.0 https://www.uptodate.com/contents/overview-of-atrial-flutter/print 19/22 7/5/23, 10:22 AM Overview of atrial flutter - UpToDate Revised (2018) Vaughan Williams classification of antiarrhythmic drugs abridged table Class 0 (HCN channel blockers) Ivabradine Class I (voltage-gated Na+ channel blockers) Class Ia (intermediate dissociation): Quinidine, ajmaline, disopyramide, procainamide Class Ib (rapid dissociation): Lidocaine, mexilitine Class Ic (slow dissociation): Propafenone, flecainide Class Id (late current): Ranolazine Class II (autonomic inhibitors and activators) Class IIa (beta blockers): Nonselective: carvedilol, propranolol, nadolol Selective: atenolol, bisoprolol, betaxolol, celiprolol, esmolol, metoprolol Class IIb (nonselective beta agonists): Isoproterenol Class IIc (muscarinic M2 receptor inhibitors): Atropine, anisodamine, hyoscine, scopolamine Class IId (muscarinic M2 receptor activators): Carbachol, pilocarpine, methacholine, digoxin Class IIe (adenosine A1 receptor activators): Adenosine Class III (K+ channel blockers and openers) Class IIIa (voltage dependent K+ channel blockers): Ambasilide, amiodarone, dronedarone, dofetilide, ibutilide, sotalol, vernakalant Class IIIb (metabolically dependent K+ channel openers): https://www.uptodate.com/contents/overview-of-atrial-flutter/print 20/22 7/5/23, 10:22 AM Overview of atrial flutter - UpToDate Nicorandil, pinacidil Class IV (Ca++ handling modulators) Class IVa (surface membrane Ca++ channel blockers): Bepridil, diltiazem, verapamil Class IVb (intracellular Ca++ channel blockers): Flecainide, propafenone Class V (mechanosensitive channel blockers): No approved medications Class VI (gap junction channel blockers) No approved medications Class VII (upstream target modulators) Angiotensin converting enzyme inhibitors Angiotensin receptor blockers Omega-3 fatty acids Statins HCN: hyperpolarization-activated cyclic nucleotide-gated; Na: sodium; K: potassium; Ca: calcium. Graphic 120433 Version 3.0 https://www.uptodate.com/contents/overview-of-atrial-flutter/print 21/22 7/5/23, 10:22 AM Overview of atrial flutter - UpToDate Contributor Disclosures

THREE CASES AND REVIEW OF THE LITERATURE. Circulation 1964; 29:SUPPL:593. https://www.uptodate.com/contents/overview-of-atrial-flutter/print 12/22 7/5/23, 10:22 AM Overview of atrial flutter - UpToDate 7. FRIEDBERG CK, DONOSO E. Arrhythmias and conduction disturbances due to digitalis. Prog Cardiovasc Dis 1960; 2:408. 8. Friedberg CK. Diseases of the Heart, Saunders, Philadelphia 1966. 9. Lewis T. Diseases of the Heart, MacMillan, London 1948. 10. Alboni P, Scarf S, Fuc G, et al. Atrial and ventricular pressures in atrial flutter. Pacing Clin Electrophysiol 1999; 22:600. 11. Wellens HJ. Contemporary management of atrial flutter. Circulation 2002; 106:649. 12. Vos MA, Golitsyn SR, Stangl K, et al. Superiority of ibutilide (a new class III agent) over DL- sotalol in converting atrial flutter and atrial fibrillation. The Ibutilide/Sotalol Comparator Study Group. Heart 1998; 79:568. 13. Stambler BS, Wood MA, Ellenbogen KA. Antiarrhythmic actions of intravenous ibutilide compared with procainamide during human atrial flutter and fibrillation: electrophysiological determinants of enhanced conversion efficacy. Circulation 1997; 96:4298. 14. Stambler BS, Wood MA, Ellenbogen KA, et al. Efficacy and safety of repeated intravenous doses of ibutilide for rapid conversion of atrial flutter or fibrillation. Ibutilide Repeat Dose Study Investigators. Circulation 1996; 94:1613. 15. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2014; 64:e1. 16. Crijns HJ, Van Gelder IC, Tieleman RG, et al. Long-term outcome of electrical cardioversion in patients with chronic atrial flutter. Heart 1997; 77:56. 17. Halligan SC, Gersh BJ, Brown RD Jr, et al. The natural history of lone atrial flutter. Ann Intern Med 2004; 140:265. 18. Spector P, Reynolds MR, Calkins H, et al. Meta-analysis of ablation of atrial flutter and supraventricular tachycardia. Am J Cardiol 2009; 104:671. 19. Maskoun W, Pino MI, Ayoub K, et al. Incidence of Atrial Fibrillation After Atrial Flutter Ablation. JACC Clin Electrophysiol 2016; 2:682. 20. Lanzarotti CJ, Olshansky B. Thromboembolism in chronic atrial flutter: is the risk underestimated? J Am Coll Cardiol 1997; 30:1506. 21. Writing Group Members, January CT, Wann LS, et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: A https://www.uptodate.com/contents/overview-of-atrial-flutter/print 13/22 7/5/23, 10:22 AM Overview of atrial flutter - UpToDate Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Heart Rhythm 2019; 16:e66. Topic 1048 Version 43.0 https://www.uptodate.com/contents/overview-of-atrial-flutter/print 14/22 7/5/23, 10:22 AM Overview of atrial flutter - UpToDate GRAPHICS Reentrant circuit of typical atrial flutter within the right atrium Schematic representation of reentrant circuit (red arrow) of typical (type 1) atrial flutter. The reentrant impulse rotates in a counterclockwise direction around the tricuspid annulus. The crista terminalis (CT) and eustacian ridge (ER) serve as lines of block, preventing the impulse from short-circuiting the annulus. Ablation is performed in the isthmus between the IVC and TA, which is an obligatory part of the circuit. SVC: superior vena cava; CS: coronary sinus; IVC: inferior vena cava; FO: foramen ovale Graphic 52904 Version 5.0 https://www.uptodate.com/contents/overview-of-atrial-flutter/print 15/22 7/5/23, 10:22 AM Overview of atrial flutter - UpToDate Electrical activation of the right atrium in atrial flutter Electroanatomical (3D) mapping using the CARTO system. The right atrium (RA) is depicted in the LAO projection. The circular "cutout" area in the forefront of the picture represents the tricuspid valve annulus. The red area is the inferolateral RA, the yellow-green area at the bottom of the picture is near the inferior vena cava, the yellow dots are at the region of the His bundle (AV node), and the blue area is the superior RA. The top of the picture is the superior vena cava region. The color (red-orange-yellow-green-blue-purple) represents the direction of electrical activation in the RA during typical (counterclockwise) atrial flutter. Each flutter wave seen on ECG represents a single electrical activation of this entire circuit. Graphic 89570 Version 1.0 https://www.uptodate.com/contents/overview-of-atrial-flutter/print 16/22 7/5/23, 10:22 AM Overview of atrial flutter - UpToDate ECG of counterclockwise typical atrial flutter Sawtooth-like oscillations of baseline between flutter waves, best seen in the inferior leads. Negative flutter waves in II, III, aVF, V6. Positive flutter waves in V1. ECG: electrocardiogram. Graphic 89571 Version 2.0 https://www.uptodate.com/contents/overview-of-atrial-flutter/print 17/22 7/5/23, 10:22 AM Overview of atrial flutter - UpToDate ECG of clockwise typical atrial flutter Sawtooth-like oscillations of baseline between flutter waves, best seen in inferior leads. Positive flutter waves in II, III, aVF, V6. Negative flutter waves in V1. ECG: electrocardiogram. Graphic 89576 Version 2.0 https://www.uptodate.com/contents/overview-of-atrial-flutter/print 18/22 7/5/23, 10:22 AM Overview of atrial flutter - UpToDate ECG of atypical atrial flutter Note the lack of classic sawtooth flutter waves in the inferior leads II, III, and aVF. ECG: electrocardiogram. Graphic 89577 Version 4.0 https://www.uptodate.com/contents/overview-of-atrial-flutter/print 19/22 7/5/23, 10:22 AM Overview of atrial flutter - UpToDate Revised (2018) Vaughan Williams classification of antiarrhythmic drugs abridged table Class 0 (HCN channel blockers) Ivabradine Class I (voltage-gated Na+ channel blockers) Class Ia (intermediate dissociation): Quinidine, ajmaline, disopyramide, procainamide Class Ib (rapid dissociation): Lidocaine, mexilitine Class Ic (slow dissociation): Propafenone, flecainide Class Id (late current): Ranolazine Class II (autonomic inhibitors and activators) Class IIa (beta blockers): Nonselective: carvedilol, propranolol, nadolol Selective: atenolol, bisoprolol, betaxolol, celiprolol, esmolol, metoprolol Class IIb (nonselective beta agonists): Isoproterenol Class IIc (muscarinic M2 receptor inhibitors): Atropine, anisodamine, hyoscine, scopolamine Class IId (muscarinic M2 receptor activators): Carbachol, pilocarpine, methacholine, digoxin Class IIe (adenosine A1 receptor activators): Adenosine Class III (K+ channel blockers and openers) Class IIIa (voltage dependent K+ channel blockers): Ambasilide, amiodarone, dronedarone, dofetilide, ibutilide, sotalol, vernakalant Class IIIb (metabolically dependent K+ channel openers): https://www.uptodate.com/contents/overview-of-atrial-flutter/print 20/22 7/5/23, 10:22 AM Overview of atrial flutter - UpToDate Nicorandil, pinacidil Class IV (Ca++ handling modulators) Class IVa (surface membrane Ca++ channel blockers): Bepridil, diltiazem, verapamil Class IVb (intracellular Ca++ channel blockers): Flecainide, propafenone Class V (mechanosensitive channel blockers): No approved medications Class VI (gap junction channel blockers) No approved medications Class VII (upstream target modulators) Angiotensin converting enzyme inhibitors Angiotensin receptor blockers Omega-3 fatty acids Statins HCN: hyperpolarization-activated cyclic nucleotide-gated; Na: sodium; K: potassium; Ca: calcium. Graphic 120433 Version 3.0 https://www.uptodate.com/contents/overview-of-atrial-flutter/print 21/22 7/5/23, 10:22 AM Overview of atrial flutter - UpToDate Contributor Disclosures Robert Phang, MD, FACC, FHRS No relevant financial relationship(s) with ineligible companies to disclose. Jordan M Prutkin, MD, MHS, FHRS No relevant financial relationship(s) with ineligible companies to disclose. Peter J Zimetbaum, MD Consultant/Advisory Boards: Abbott Medical [Lead extraction]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/overview-of-atrial-flutter/print 22/22

7/5/23, 10:22 AM Restoration of sinus rhythm in atrial flutter - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Restoration of sinus rhythm in atrial flutter : Jordan M Prutkin, MD, MHS, FHRS : Bradley P Knight, MD, FACC : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Mar 24, 2023. INTRODUCTION Atrial flutter is a supraventricular arrhythmia that can cause bothersome symptoms and promote atrial thrombus formation with the potential for systemic embolization. Restoration of sinus rhythm improves symptoms and decreases the risk of embolization if recurrence does not occur. (See "Overview of atrial flutter", section on 'Clinical manifestations' and "Embolic risk and the role of anticoagulation in atrial flutter", section on 'Embolic risk'.) Issues related to the indications and therapeutic options for the restoration of sinus rhythm in atrial flutter will be reviewed here. Causes of atrial flutter, rate control therapy, the maintenance of sinus rhythm after cardioversion, and the role of anticoagulation in atrial flutter are discussed separately. (See "Control of ventricular rate in atrial flutter" and "Atrial flutter: Maintenance of sinus rhythm" and "Embolic risk and the role of anticoagulation in atrial flutter".) RATIONALE Atrial flutter is a relatively common supraventricular arrhythmia that is characterized by rapid, regular atrial depolarizations at a characteristic rate of approximately 300 beats/min. (See "ECG tutorial: Atrial and atrioventricular nodal (supraventricular) arrhythmias", section on 'Atrial fibrillation and atrial flutter' and "Overview of atrial flutter".) In the absence of rate slowing drugs or atrioventricular (AV) nodal disease, most commonly, every other beat is conducted through the AV node so that the ventricular rate is usually around 150 beats per minute. Because of the rapid rate, the patient may present with symptoms of https://www.uptodate.com/contents/restoration-of-sinus-rhythm-in-atrial-flutter/print 1/17 7/5/23, 10:22 AM Restoration of sinus rhythm in atrial flutter - UpToDate palpitations, chest pain, dyspnea, fatigue, dizziness, and rarely hemodynamic shock, similar to patients with atrial fibrillation (AF) with a rapid ventricular response. (See "Hemodynamic consequences of atrial fibrillation and cardioversion to sinus rhythm", section on 'Adverse hemodynamics in AF'.) In addition to improving symptoms, the restoration of sinus rhythm prevents the potential for the development of tachycardia-mediated cardiomyopathy and somewhat reduces the risk of systemic embolization. (See "Arrhythmia-induced cardiomyopathy", section on 'Atrial fibrillation and atrial flutter' and "Embolic risk and the role of anticoagulation in atrial flutter", section on 'Embolic risk'.) Atrial flutter is often an electrically unstable rhythm, meaning that it frequently degenerates into the more disorganized atrial fibrillation (AF) or reverts to sinus rhythm within hours or days, though it can also be chronic. Spontaneous reversion to a sinus mechanism may occur after predisposing problems are improved, such as decompensated heart failure (HF) or the sequelae of cardiac surgery. In patients who do not spontaneously convert to sinus rhythm, rate slowing with drugs may be considered a therapeutic option. The ventricular rate is frequently difficult to control, however, as most medications are ineffective for rate slowing and for many patients it is not worth attempting as a long-term alternative to rhythm control. Rate control may be appropriate for patients who are reluctant to undergo cardioversion or who have no or minimal symptoms. (See "Control of ventricular rate in atrial flutter".) For those patients in whom a decision has been made to restore sinus rhythm, most can be cardioverted successfully without complication. Factors that predict spontaneous reversion to sinus rhythm or a successful cardioversion are similar to those for AF, and include a left atrial size less than 4.5 to 5 cm, little or no heart failure or left ventricular dysfunction, no underlying reversible cause such as hyperthyroidism, myocardial infarction, or pulmonary embolism, and atrial flutter of recent onset. (See "Atrial fibrillation: Cardioversion", section on 'Reasons not to perform cardioversion'.) INDICATIONS Most patients with atrial flutter who do not undergo spontaneous conversion to sinus rhythm should undergo cardioversion. The following are indications for urgent cardioversion: Patients with atrial flutter who have a rapid ventricular rate and significant hemodynamic compromise (hypotension or heart failure) should undergo urgent cardioversion. In https://www.uptodate.com/contents/restoration-of-sinus-rhythm-in-atrial-flutter/print 2/17 7/5/23, 10:22 AM Restoration of sinus rhythm in atrial flutter - UpToDate patients with atrial flutter and hemodynamic compromise, but with a controlled ventricular rate (eg, 100 beats/min), explanations for hemodynamic instability other than the atrial flutter should be sought. Restoration of sinus rhythm in these patients may not necessarily improve the clinical status. Most patients with atrial flutter who are identified as having an accessory pathway with ventricular preexcitation should undergo immediate cardioversion. (See "Wolff-Parkinson- White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis", section on 'Atrial flutter'.) For patients with minimal symptoms or signs attributable to atrial flutter, conversion to sinus rhythm may be deferred in anticipation of either spontaneous conversion or radiofrequency catheter ablation. (See 'Radiofrequency catheter ablation' below.) Among those patients who are not urgently cardioverted and who do not spontaneously revert to sinus rhythm, elective restoration of sinus rhythm is favored to decrease the risk of tachycardia-mediated cardiomyopathy. (See 'Rationale' above.) This is in contrast to atrial fibrillation (AF), in which tolerance of permanent AF may be more likely chosen since rate control is usually possible. (See "Management of atrial fibrillation: Rhythm control versus rate control" and "Control of ventricular rate in atrial flutter", section on 'Summary and recommendations'.) Circumstances in which it is reasonable to avoid cardioversion in patients with new onset atrial flutter include: Patients who are completely asymptomatic, particularly those who are elderly with multiple comorbidities or poor overall prognosis, where the risks of undergoing cardioversion and/or pharmacologic rhythm control may outweigh the benefits of restoring sinus rhythm. Patients who have a bleeding risk and cannot be anticoagulated during the peri- cardioversion and post-cardioversion periods. METHOD OF CARDIOVERSION For most patients in whom a decision is made to restore sinus rhythm urgently, we prefer electrical to pharmacologic cardioversion. Radiofrequency catheter ablation is an option for stable patients who can wait until this procedure can be performed. Electrical Cardioversion Electrical cardioversion, also called direct current (DC) cardioversion, is a routine procedure in the management of patients with cardiac arrhythmias and is the https://www.uptodate.com/contents/restoration-of-sinus-rhythm-in-atrial-flutter/print 3/17 7/5/23, 10:22 AM Restoration of sinus rhythm in atrial flutter - UpToDate preferred means for the immediate restoration of sinus rhythm. With appropriate patient selection and technique, DC cardioversion is rapid and safe. The success rate of 96 to 97 percent is higher than for any antiarrhythmic drug [1,2]. (See 'Pharmacologic cardioversion' below.) Electrical cardioversion should be performed by physicians experienced in the procedure. The patient should be fasting to allow for safe use of sedation, serum electrolytes should be normal, and drug levels, such as digoxin, should be within the therapeutic range. Cardioversion techniques are discussed in detail separately. (See "Basic principles and technique of external electrical cardioversion and defibrillation".) It is expected that normal sinus rhythm will resume once the atrial flutter terminates. Sometimes, atrial fibrillation, ectopic atrial rhythm, or a significant bradycardia may result. The approach to each of these is discussed separately. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation" and "Temporary cardiac pacing".) Pharmacologic enhancement of direct current cardioversion We use pharmacologic enhancement in selected patients. While the success of DC cardioversion is high for atrial flutter, antiarrhythmic drugs may be initiated prior to electrical cardioversion to increase the likelihood of successful cardioversion and long-term maintenance of sinus rhythm [3]. (See "Atrial fibrillation: Cardioversion", section on 'Preprocedural antiarrhythmic drugs'.) The decision to pretreat is often made by a physician experienced with the care of patients with one or more risk factors for cardioversion failure. (See "Atrial fibrillation: Cardioversion", section on 'Reasons not to perform cardioversion'.) The antiarrhythmic drug may restore sinus rhythm prior to DC cardioversion in some cases or may help prevent recurrent episodes of atrial flutter early after cardioversion. In addition, for patients in whom long-term antiarrhythmic therapy will be used, early initiation (prior to DC cardioversion) may allow for an evaluation of tolerability of one or more drugs. For those patients in whom a decision has been made to attempt the long- term maintenance of sinus rhythm with antiarrhythmic drug therapy, it is reasonable to preferentially select a drug for cardioversion that can also be used for long-term maintenance. Based on these considerations, we use pharmacologic enhancement in selected patients, such as those in whom ablation will not be performed. Pharmacologic cardioversion A number of antiarrhythmic drugs may be used to terminate atrial flutter and restore sinus rhythm. However, antiarrhythmic drugs are less effective than DC cardioversion and carry some degree of proarrhythmic risk. Thus, pharmacologic cardioversion is generally reserved for selected clinical scenarios. The most common reason for selecting pharmacologic cardioversion is that moderate or deep sedation is either unavailable or is expected to be poorly tolerated (for example, as in patients with hypotension). https://www.uptodate.com/contents/restoration-of-sinus-rhythm-in-atrial-flutter/print 4/17 7/5/23, 10:22 AM Restoration of sinus rhythm in atrial flutter - UpToDate Most of the available data on the efficacy of antiarrhythmic drugs for the restoration of sinus rhythm are from patients with atrial fibrillation (AF). The drugs that are effective in converting AF to sinus rhythm may also be effective in converting atrial flutter. These include flecainide, dofetilide, propafenone, ibutilide, and amiodarone. Ibutilide and dofetilide have been better studied than the other drugs discussed below. (See "Atrial fibrillation: Cardioversion", section on 'Pharmacologic cardioversion'.) Ibutilide Ibutilide, approved by the United States Food and Drug Administration for intravenous use, converts atrial flutter to sinus rhythm in approximately 60 percent of patients (compared to a 0 to 2 percent response to placebo) with a mean time to conversion of 30 minutes [4-6]. Ibutilide is more effective than procainamide for reversion of atrial flutter (64 to 76 versus 0 to 14 percent) [7,8], and is also more effective than sotalol (70 versus 19 percent) ( figure 1) [9] and amiodarone (87 versus 29 percent) [10]. (See "Therapeutic use of ibutilide".) The most serious concern with ibutilide is QT interval prolongation that can lead to torsades de pointes [4-6]. The potential for torsades de pointes is increased in patients with severe heart failure or those who are being treated with another drug that prolongs the QT interval. On the other hand, the risk of proarrhythmia does not appear to be increased when ibutilide is given with amiodarone [11]. Because of the risk of torsades de pointes, patients treated with ibutilide should be observed with continuous electrocardiogram (ECG) monitoring for at least four hours after the infusion. (See "Therapeutic use of ibutilide", section on 'Proarrhythmia'.) The addition of intravenous magnesium, in doses of 4 to 10 grams, can enhance the cardioverting effect of ibutilide and may reduce the risk of torsades de pointes as well [12,13]. Dofetilide Oral dofetilide is effective for conversion of atrial flutter and the conversion rate appears to be higher than in AF. As an example, the SAFIRE-D study randomly assigned 325 patients with AF (n = 277) or atrial flutter (n = 48) to 125, 250, and 500 g of dofetilide twice daily [14]. At a dose of 500 g, the conversion rates for AF and atrial flutter were 22 and 67 percent, respectively, compared to 1.2 percent for placebo. Conversion to sinus rhythm occurred in 70 percent within 24 hours, while 91 percent converted within 36 hours. Dofetilide has the disadvantage of requiring the patient to be hospitalized for the first six doses, as it can cause torsade de pointes and sudden death [15,16]. Intravenous dofetilide, which is not available in the United States, also appears to be effective for conversion of atrial flutter. In one study of 16 patients, 54 percent reverted to https://www.uptodate.com/contents/restoration-of-sinus-rhythm-in-atrial-flutter/print 5/17 7/5/23, 10:22 AM Restoration of sinus rhythm in atrial flutter - UpToDate sinus rhythm after dofetilide administration while in another series of 17 patients the rate of reversion was 64 percent, compared with 0 percent for placebo [17,18]. Intravenous dofetilide is more effective than intravenous amiodarone. In a randomized trial that included 31 patients with atrial flutter, the reversion rate with dofetilide was 75 percent versus 0 and 10 percent for amiodarone and placebo, respectively [19]. The following drugs are less commonly used or not recommended in this setting: Amiodarone Intravenous (IV) amiodarone is sometimes used for atrial flutter conversion, but data are limited. A small study of nine patients with atrial flutter demonstrated no patients converting with IV amiodarone [19]. Another study of 21 patients showed a success rate of 29 percent with IV amiodarone compared to 87 percent for ibutilide [10]. Class IA antiarrhythmic drugs The class IA antiarrhythmic drugs (quinidine, procainamide, and disopyramide) slow the rate of contraction of the atria but also may have a significant vagolytic effect which increases atrioventricular (AV) nodal conduction. These combined actions can result in 1:1 conduction at very rapid ventricular rates ( waveform 1). For this reason, we do not recommend their use unless patients are pretreated with a drug(s) that blocks AV nodal conduction such as beta or calcium channel blockers. Class IC antiarrhythmic drugs The class IC antiarrhythmic drugs propafenone and flecainide are less efficacious than other agents. Although they do not accelerate AV conduction, they can slow the atrial flutter rate, often to a greater extent than the class IA drugs. Slowing of the atrial flutter rate alone (eg, to 200 or 250 beats/min) can lead to 1:1 AV conduction. We do not recommend their use unless patients are pretreated with a drug(s) that blocks AV nodal conduction such as beta or calcium channel blockers. Rate control drugs Digoxin, nondihydropyridine calcium channel blockers [20-22], and beta blockers can all be effective in the control of the ventricular rate during atrial flutter. Although the hemodynamic improvement associated with a normalized ventricular rate may indirectly facilitate reversion to sinus rhythm, these drugs should be considered for the purpose of rate control, not for restoring sinus rhythm. (See "Control of ventricular rate in atrial flutter".) Vernakalant Intravenous vernakalant is approved by the European Commission for the rapid conversion of recent-onset atrial fibrillation ( 7 days duration for patients not undergoing surgery and 3 days duration for postcardiac surgery patients) to sinus rhythm. Based on one study in which the drug converted only 1 of 14 patients with atrial https://www.uptodate.com/contents/restoration-of-sinus-rhythm-in-atrial-flutter/print 6/17 7/5/23, 10:22 AM Restoration of sinus rhythm in atrial flutter - UpToDate flutter, we do not recommend its use [23]. (See "Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs", section on 'Class III'.) Radiofrequency catheter ablation Radiofrequency catheter ablation (RFA) can be performed while a stable patient is in atrial flutter. In this setting, sinus rhythm is restored during the procedure. The use of RFA to interrupt the reentrant circuit supporting atrial flutter in order to permanently maintain normal sinus rhythm is discussed elsewhere [24,25]. (See "Atrial flutter: Maintenance of sinus rhythm".) Atrial overdrive pacing Atrial overdrive pacing may be used for cardioversion in selected patients with flutter, though it is rarely performed because of the high success rate of direct current cardioversion and/or ablation. In atrial flutter, if the atrium is paced approximately 10 percent faster than the atrial flutter rate for 15 to 30 seconds, the rate of the tachycardia increases to match that of the faster pacing rate; that is, it is entrained [26-28]. When the pacing is discontinued, one of several results may ensue: The original atrial flutter may return. The atrial flutter may cease with restoration of normal sinus rhythm ( waveform 2). The patient may convert to AF. The atrial flutter may change, possibly at a faster rate [29]. Atrial pacing can be useful in selected patients, including the following [26-28,30-32]: After cardiac surgery, since atrial pacing wires are often left in place during the early postoperative period. In patients with a pacemaker or implantable cardioverter-defibrillator where rapid pacing may be available through the device. Very rarely, a temporary pacemaker may be used: In patients who have recurrent atrial flutter due to an acute stress such as a myocardial infarction or respiratory failure; this represents a setting in which one would like to avoid repeated DC shocks and a temporary transvenous pacemaker can be used. In patients who have digitalis toxicity, a condition in which DC cardioversion may be particularly dangerous. https://www.uptodate.com/contents/restoration-of-sinus-rhythm-in-atrial-flutter/print 7/17 7/5/23, 10:22 AM Restoration of sinus rhythm in atrial flutter - UpToDate In patients in whom anesthesia is a risk and pharmacologic cardioversion is not desired or unavailable [26-28,33,34]. The success rate of rapid atrial pacing may be increased by the concurrent intravenous administration of procainamide or ibutilide [35-37]. ANTICOAGULATION We agree with recommendations from the American Heart Association/American College of Cardiology/Heart Rhythm Society guideline on atrial fibrillation, which recommend that consideration be given to managing anticoagulation during cardioversion of atrial flutter in a manner similar to that for atrial fibrillation [38-41]. (See "Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation" and "Embolic risk and the role of anticoagulation in atrial flutter", section on 'Cardioversion'.) MAINTENANCE OF SINUS RHYTHM After conversion to sinus rhythm, an attempt should be made to address all correctable causes of atrial flutter (eg, thyrotoxicosis or obesity). (See "Overview of atrial flutter", section on 'Etiology and risk factors'.) In addition to radiofrequency catheter ablation (see 'Radiofrequency catheter ablation' above), pharmacologic therapy can be used to maintain sinus rhythm. This issue is discussed in detail elsewhere. (See "Atrial flutter: Maintenance of sinus rhythm", section on 'Pharmacologic therapy'.) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Atrial fibrillation" and "Society guideline links: Arrhythmias in adults".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and Beyond the Basics. th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given https://www.uptodate.com/contents/restoration-of-sinus-rhythm-in-atrial-flutter/print 8/17 7/5/23, 10:22 AM Restoration of sinus rhythm in atrial flutter - UpToDate condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on patient info and the keyword(s) of interest.) Basics topics (see "Patient education: Atrial flutter (The Basics)") SUMMARY AND RECOMMENDATIONS Hemodynamically unstable patient For atrial flutter patients who have a rapid ventricular rate and evidence of hemodynamic instability or severe symptoms including myocardial ischemia, hypotension, angina, heart failure, or evidence of ventricular preexcitation, we recommend urgent electrical cardioversion rather than any other approach (Grade 1A). (See 'Indications' above and 'Electrical Cardioversion' above.) Stable patient For stable patients with atrial flutter, we suggest elective electrical cardioversion rather than pharmacologic cardioversion or atrial pacing in patients without atrial leads (Grade 2A). Patients who may reasonably prefer other approaches such as an attempt at pharmacologic conversion (or at rate control) include those who prefer not to undergo electrical cardioversion or those for whom moderate or deep sedation will be poorly tolerated or not available. Radiofrequency catheter ablation, if performed in a timely manner, is a reasonable alternative to electrical cardioversion. (See 'Indications' above and 'Electrical Cardioversion' above.) Available data do not support the recommendation of a specific antiarrhythmic drug if pharmacologic conversion will be attempted. Options include ibutilide, amiodarone, flecainide, propafenone, or dofetilide. We prefer ibutilide in situations where we desire acute pharmacologic cardioversion of atrial flutter. (See 'Pharmacologic cardioversion' above.) Indications for overdrive pacing For patients with atrial pacing wires in place (either as part of a permanent pacemaker, implantable-cardioverter defibrillator, or temporary https://www.uptodate.com/contents/restoration-of-sinus-rhythm-in-atrial-flutter/print 9/17 7/5/23, 10:22 AM Restoration of sinus rhythm in atrial flutter - UpToDate pacing wires after cardiac surgery), we suggest rapid atrial pacing rather than electrical cardioversion (Grade 2C). (See 'Atrial overdrive pacing' above.) As rapid atrial pacing can cause atrial flutter to degenerate into atrial fibrillation (AF), the physician should be prepared for the management of AF. Anticoagulation Anticoagulation during cardioversion of atrial flutter should be managed in a manner similar to that for atrial fibrillation. (See "Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation" and "Embolic risk and the role of anticoagulation in atrial flutter", section on 'Cardioversion'.) Method of rhythm control In addition to radiofrequency catheter ablation, pharmacologic therapy can be used to maintain sinus rhythm. (See "Atrial flutter: Maintenance of sinus rhythm", section on 'RF catheter ablation' and "Atrial flutter: Maintenance of sinus rhythm", section on 'Pharmacologic therapy'.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Gallagher MM, Guo XH, Poloniecki JD, et al. Initial energy setting, outcome and efficiency in direct current cardioversion of atrial fibrillation and flutter. J Am Coll Cardiol 2001; 38:1498. 2. Van Gelder IC, Crijns HJ, Van Gilst WH, et al. Prediction of uneventful cardioversion and maintenance of sinus rhythm from direct-current electrical cardioversion of chronic atrial fibrillation and flutter. Am J Cardiol 1991; 68:41. 3. Naccarelli GV, Dell'Orfano JT, Wolbrette DL, et al. Cost-effective management of acute atrial fibrillation: role of rate control, spontaneous conversion, medical and direct current cardioversion, transesophageal echocardiography, and antiembolic therapy. Am J Cardiol 2000; 85:36D. 4. Stambler BS, Wood MA, Ellenbogen KA, et al. Efficacy and safety of repeated intravenous doses of ibutilide for rapid conversion of atrial flutter or fibrillation. Ibutilide Repeat Dose Study Investigators. Circulation 1996; 94:1613. 5. Ellenbogen KA, Stambler BS, Wood MA, et al. Efficacy of intravenous ibutilide for rapid termination of atrial fibrillation and atrial flutter: a dose-response study. J Am Coll Cardiol 1996; 28:130. 6. Abi-Mansour P, Carberry PA, McCowan RJ, et al. Conversion efficacy and safety of repeated doses of ibutilide in patients with atrial flutter and atrial fibrillation. Study Investigators. Am Heart J 1998; 136:632. https://www.uptodate.com/contents/restoration-of-sinus-rhythm-in-atrial-flutter/print 10/17 7/5/23, 10:22 AM Restoration of sinus rhythm in atrial flutter - UpToDate 7. Stambler BS, Wood MA, Ellenbogen KA. Antiarrhythmic actions of intravenous ibutilide compared with procainamide during human atrial flutter and fibrillation: electrophysiological determinants of enhanced conversion efficacy. Circulation 1997; 96:4298. 8. Volgman AS, Carberry PA, Stambler B, et al. Conversion efficacy and safety of intravenous ibutilide compared with intravenous procainamide in patients with atrial flutter or fibrillation. J Am Coll Cardiol 1998; 31:1414. 9. Vos MA, Golitsyn SR, Stangl K, et al. Superiority of ibutilide (a new class III agent) over DL- sotalol in converting atrial flutter and atrial fibrillation. The Ibutilide/Sotalol Comparator Study Group. Heart 1998; 79:568. 10. Kafkas NV, Patsilinakos SP, Mertzanos GA, et al. Conversion efficacy of intravenous ibutilide compared with intravenous amiodarone in patients with recent-onset atrial fibrillation and atrial flutter. Int J Cardiol 2007; 118:321. 11. Glatter K, Yang Y, Chatterjee K, et al. Chemical cardioversion of atrial fibrillation or flutter with ibutilide in patients receiving amiodarone therapy. Circulation 2001; 103:253. 12. Patsilinakos S, Christou A, Kafkas N, et al. Effect of high doses of magnesium on converting ibutilide to a safe and more effective agent. Am J Cardiol 2010; 106:673. 13. Tercius AJ, Kluger J, Coleman CI, White CM. Intravenous magnesium sulfate enhances the ability of intravenous ibutilide to successfully convert atrial fibrillation or flutter. Pacing Clin Electrophysiol 2007; 30:1331. 14. Singh S, Zoble RG, Yellen L, et al. Efficacy and safety of oral dofetilide in converting to and maintaining sinus rhythm in patients with chronic atrial fibrillation or atrial flutter: the symptomatic atrial fibrillation investigative research on dofetilide (SAFIRE-D) study. Circulation 2000; 102:2385. 15. Mounsey JP, DiMarco JP. Cardiovascular drugs. Dofetilide. Circulation 2000; 102:2665. 16. Abraham JM, Saliba WI, Vekstein C, et al. Safety of oral dofetilide for rhythm control of atrial fibrillation and atrial flutter. Circ Arrhythm Electrophysiol 2015; 8:772. 17. Falk RH, Pollak A, Singh SN, Friedrich T. Intravenous dofetilide, a class III antiarrhythmic agent, for the termination of sustained atrial fibrillation or flutter. Intravenous Dofetilide Investigators. J Am Coll Cardiol 1997; 29:385. 18. N rgaard BL, Wachtell K, Christensen PD, et al. Efficacy and safety of intravenously administered dofetilide in acute termination of atrial fibrillation and flutter: a multicenter, randomized, double-blind, placebo-controlled trial. Danish Dofetilide in Atrial Fibrillation and Flutter Study Group. Am Heart J 1999; 137:1062. https://www.uptodate.com/contents/restoration-of-sinus-rhythm-in-atrial-flutter/print 11/17 7/5/23, 10:22 AM Restoration of sinus rhythm in atrial flutter - UpToDate 19. Bianconi L, Castro A, Dinelli M, et al. Comparison of intravenously administered dofetilide versus amiodarone in the acute termination of atrial fibrillation and flutter. A multicentre, randomized, double-blind, placebo-controlled study. Eur Heart J 2000; 21:1265. 20. Schamroth L, Krikler DM, Garrett C. Immediate effects of intravenous verapamil in cardiac arrhythmias. Br Med J 1972; 1:660. 21. Hagemeijer F. Verapamil in the management of supraventricular tachyarrhythmias occurring after a recent myocardial infarction. Circulation 1978; 57:751. 22. Wolfson S, Herman MV, Sullivan JM, Gorlin R. Conversion of atrial fibrillation and flutter by propranolol. Br Heart J 1967; 29:305. 23. Pratt CM, Roy D, Torp-Pedersen C, et al. Usefulness of vernakalant hydrochloride injection for rapid conversion of atrial fibrillation. Am J Cardiol 2010; 106:1277. 24. Saoudi N, Atallah G, Kirkorian G, Touboul P. Catheter ablation of the atrial myocardium in human type I atrial flutter. Circulation 1990; 81:762. 25. Da Costa A, Th venin J, Roche F, et al. Results from the Loire-Ard che-Dr me-Is re-Puy-de- D me (LADIP) trial on atrial flutter, a multicentric prospective randomized study comparing amiodarone and radiofrequency ablation after the first episode of symptomatic atrial flutter. Circulation 2006; 114:1676. 26. Waldo AL, MacLean WA, Karp RB, et al. Entrainment and interruption of atrial flutter with atrial pacing: studies in man following open heart surgery. Circulation 1977; 56:737. 27. Waldo AL, Carlson MD, Biblo LA, Henthorn RW. The role of transient entrainment in atrial flu tter. In: Atrial Arrhythmias: Current Concepts and Management, Tourboul P, Waldo AL (Eds), Mosby Year Book, St Louis 1990. p.210. 28. Greenberg ML, Kelly TA, Lerman BB, DiMarco JP. Atrial pacing for conversion of atrial flutter. Am J Cardiol 1986; 58:95. 29. Cheng J, Scheinman MM. Acceleration of typical atrial flutter due to double-wave reentry induced by programmed electrical stimulation. Circulation 1998; 97:1589. 30. Peters RW, Shorofsky SR, Pelini M, et al. Overdrive atrial pacing for conversion of atrial flutter: comparison of postoperative with nonpostoperative patients. Am Heart J 1999; 137:100. 31. Das G, Anand KM, Ankineedu K, et al. Atrial pacing for cardioversion of atrial flutter in digitalized patients. Am J Cardiol 1978; 41:308. 32. Orlando J, Cassidy J, Aronow WS. High reversion of atrial flutter to sinus rhythm after atrial pacing in patients with pulmonary disease. Chest 1977; 71:580. https://www.uptodate.com/contents/restoration-of-sinus-rhythm-in-atrial-flutter/print 12/17 7/5/23, 10:22 AM Restoration of sinus rhythm in atrial flutter - UpToDate 33. Resnekov L. Cardiac arrhythmias. 6. Present status of electroversion in the management of cardiac dysrhythmias. Circulation 1973; 47:1356. 34. Mann DL, Maisel AS, Atwood JE, et al. Absence of cardioversion-induced ventricular arrhythmias in patients with therapeutic digoxin levels. J Am Coll Cardiol 1985; 5:882. 35. Cheng J, Glatter K, Yang Y, et al. Electrophysiological response of the right atrium to ibutilide during typical atrial flutter. Circulation 2002; 106:814. 36. Olshansky B, Okumura K, Hess PG, et al. Use of procainamide with rapid atrial pacing for successful conversion of atrial flutter to sinus rhythm. J Am Coll Cardiol 1988; 11:359. 37. Stambler BS, Wood MA, Ellenbogen KA. Comparative efficacy of intravenous ibutilide versus procainamide for enhancing termination of atrial flutter by atrial overdrive pacing. Am J Cardiol 1996; 77:960. 38. You JJ, Singer DE, Howard PA, et al. Antithrombotic therapy for atrial fibrillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e531S. 39. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation 2014; 130:2071. 40. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation 2014; 130:e199. 41. Writing Group Members, January CT, Wann LS, et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Heart Rhythm 2019; 16:e66. Topic 1069 Version 35.0 https://www.uptodate.com/contents/restoration-of-sinus-rhythm-in-atrial-flutter/print 13/17 7/5/23, 10:22 AM Restoration of sinus rhythm in atrial flutter - UpToDate GRAPHICS Ibutilide is more effective than sotalol for acute reversion of atrial tachyarrhythmias Among 281 patients with atrial fibrillation or atrial flutter randomized to intravenous ibutilide or intravenous sotalol, both doses of ibutilide were more effective than sotalol for reverting atrial flutter. Among the patients with atrial fibrillation, only the higher dose of ibutilide was significantly more effective than sotalol for restoring sinus rhythm. p <0.05 compared with sotalol. p <0.05 compared with 1 mg ibutilide. Data from: Vos MA, Golitsyn SR, Stangl K, et al. for the Ibutilide/Sotalol Comparator Study Group, Heart 1998; 79:568. Graphic 51703 Version 3.0 https://www.uptodate.com/contents/restoration-of-sinus-rhythm-in-atrial-flutter/print 14/17 7/5/23, 10:22 AM Restoration of sinus rhythm in atrial flutter - UpToDate Type I atrial flutter The 1:1 AV conduction was induced by quinidine which both slowed the flutter wave and, via its vagolytic effect, enhanced conduction through the AV node. Courtesy of Morton Arnsdorf, MD. Graphic 55441 Version 3.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/restoration-of-sinus-rhythm-in-atrial-flutter/print 15/17 7/5/23, 10:22 AM Restoration of sinus rhythm in atrial flutter - UpToDate Entrainment in typical atrial flutter with right atrial pacing with the rate of recording by the ECG machine being slowed by one-half The spontaneous rhythm, in which the flutter waves are not clearly apparent, is shown in the left side of panel A. The right atrium is then paced at just under 400 beats/min; entrainment is achieved at the asterisk when there is a sudden change in atrial morphology as the flutter rate matched the pacing rate. Cessation of pacing led to conversion to sinus rhythm (panel B). Courtesy of Morton Arnsdorf, MD. Graphic 56947 Version 3.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/restoration-of-sinus-rhythm-in-atrial-flutter/print 16/17 7/5/23, 10:22 AM Restoration of sinus rhythm in atrial flutter - UpToDate Contributor Disclosures Jordan M Prutkin, MD, MHS, FHRS No relevant financial relationship(s) with ineligible companies to disclose. Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/restoration-of-sinus-rhythm-in-atrial-flutter/print 17/17

7/5/23, 10:24 AM Focal atrial tachycardia - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Focal atrial tachycardia : Peter Kistler, MBBS, FRACP, PhD : Samuel L vy, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: May 30, 2023. INTRODUCTION Atrial tachycardia (AT) is a regular atrial rhythm at a constant rate of >100 beats per minute originating outside of the sinus node ( waveform 1) [1]. Focal ATs (also referred to as atrial ectopic tachycardias) arise from a single site within the left or right atrium, in contrast to macroreentrant atrial arrhythmias (eg, atrial flutter) and atrial fibrillation, which involve multiple sites or larger circuits. In the past, focal ATs were considered to be due predominantly to enhanced automaticity. Thus, they were often referred to as automatic ATs. However, the more inclusive term focal AT is preferred, as this encompasses automatic, triggered, and microreentrant etiologies that cannot be distinguished easily on the surface electrocardiogram. Focal ATs are usually paroxysmal and self-limited, although in some patients, focal AT may be present nearly continuously (ie, incessant AT). Incessant AT is important as it may be associated with left ventricular dysfunction [2]. (See "Arrhythmia-induced cardiomyopathy", section on 'Atrial tachycardia'.) The characteristics and management of the common, repetitive forms of focal AT are discussed here. Macroreentrant atrial arrhythmias (eg, atrial flutter), atrial fibrillation, and other forms of supraventricular tachycardia are discussed in detail separately. (See "Overview of atrial flutter" and "Atrial fibrillation: Overview and management of new-onset atrial fibrillation" and "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation".) https://www.uptodate.com/contents/focal-atrial-tachycardia/print 1/26 7/5/23, 10:24 AM Focal atrial tachycardia - UpToDate BACKGROUND Definition In 2001, the Joint Expert Group from the Working Group of Arrhythmias of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology (now called the Heart Rhythm Society) classified regular ATs according to electrophysiologic mechanisms and anatomy [1]. The Joint Expert Group defined focal AT as "being characterized by atrial activation starting rhythmically at a small area (focus) from where it spreads centrifugally." This definition indicates that the arrhythmia arises from an area that is smaller than would be required for classical macroreentry, which conventionally is considered to be a circuit greater than 2 cm in diameter. Incidence Focal AT is relatively uncommon, accounting for between 5 and 15 percent of arrhythmias in adults undergoing study for paroxysmal supraventricular tachycardia [3]. Males and females seem to be equally affected. MECHANISMS AND ETIOLOGY Electrophysiologic mechanisms The focal activity responsible for AT can be produced by three distinct electrophysiologic mechanisms [3-6]: Enhanced automaticity Enhanced automaticity refers to an acceleration of a normal automatic pacemaker by an increase in the slope of phase four depolarization ( figure 1), shortening of the refractory period, a decrease in the threshold for excitation, or some combination of these mechanisms. (See "Enhanced cardiac automaticity".) Triggered activity Triggered activity is the result of electrophysiologic phenomena called afterdepolarizations. Afterdepolarizations are focal electrical events that result in repeat depolarization of a single cell or small area prior to full repolarization. Early afterdepolarizations occur during the plateau phase of the action potential, while delayed afterdepolarizations occur during phase four. Microreentry Microreentry requires a small circuit, defined as <2 cm to distinguish from macroreentry, in which conduction is sufficiently slow that the tissue can recover its excitability and be re-excited by the time the wave of depolarization returns. Such slow conduction classically occurs at discrete regions of fibrosis such as following ablation or surgery or anatomic sites of change in fiber orientation. The hypothesis that cellular uncoupling is required for the development of focal atrial tachycardias is supported by the following observations: https://www.uptodate.com/contents/focal-atrial-tachycardia/print 2/26 7/5/23, 10:24 AM Focal atrial tachycardia - UpToDate Low-amplitude fractionated electrograms are commonly found in the focal areas in which these atrial arrhythmias arise [7,8]. Focal arrhythmogenesis often occurs in regions of discontinuity in atrial architecture [8]. Sites of origin Focal ATs do not occur randomly throughout the atria, but rather cluster at predefined anatomic locations [9]. These locations are characterized by alterations in myocardial fiber orientation or sites of automatic tissue. In a series of 186 patients with clinically documented paroxysmal or incessant AT, 63 percent of ATs arose in the right atrium (RA) and 37 percent in the left atrium (LA) ( figure 2) [10]. The distribution of sites of origin among the right atrial tachycardias was: Tricuspid annulus (35 percent) ( waveform 1) Crista terminalis (34 percent) ( waveform 2) Coronary sinus ostium (17 percent) Perinodal tissues (9 percent) RA appendage (4 percent) Left atrial tachycardias were predominantly located around the pulmonary veins (67 percent) ( waveform 3). Less common sites of origin include the mitral annulus (17 percent), coronary sinus body (6 percent), left intraatrial septum (6 percent), and the LA appendage (4 percent) [10,11]. The non-coronary cusp is an unusual site for atrial tachycardia, which should be considered for apparent paraseptal tachycardias [12]. Associated conditions Focal AT may occur in patients with organic heart disease in response to atrial stretch due to elevated atrial pressure in conditions such as hypertension and cardiomyopathy. In addition to chronic heart disease, AT can also be associated with acute events such as a myocardial infarction, pulmonary decompensation, infection, excessive alcohol ingestion, hypokalemia, hypoxia, stimulants, cocaine ingestion, and theophylline [13]. More commonly AT occurs in the absence of heart disease and generally has a benign prognosis [14]. Incessant AT resulting in cardiomyopathy The term "incessant" is applied to an AT when the AT is present for at least 90 percent of the time a patient is monitored [15]. Incessant AT is often found in otherwise normal young individuals, including children, although it may occur in patients with organic heart disease [16-19]. The rate tends to be faster during the day than at night, and the rate may increase with exercise or pregnancy [20]. Incessant focal AT may be responsible for tachycardia-mediated cardiomyopathy, which refers to left ventricular (LV) chamber dilatation and systolic dysfunction in a patient with persistent tachyarrhythmias [18,21,22]. Focal ATs originating in the atrial appendages and pulmonary veins https://www.uptodate.com/contents/focal-atrial-tachycardia/print 3/26 7/5/23, 10:24 AM Focal atrial tachycardia - UpToDate are more frequently associated with cardiomyopathy [23]. (See "Arrhythmia-induced cardiomyopathy".) Post-atrial fibrillation ablation The incidence of atrial tachycardia appears to be higher among patients who have undergone catheter ablation for atrial fibrillation (AF) [24]. Catheter ablation of persistent AF may involve an extensive biatrial ablation strategy that combines linear ablation and the targeting of complex fractionated activity beyond pulmonary vein isolation. In a multicenter international randomized study, catheter ablation for persistent AF that involved targeting complex fractionated activity or linear ablation was not associated with an increase in freedom from AF compared with pulmonary vein isolation alone [25]. This study may translate to a more conservative approach to atrial substrate modification with a consequent reduction in post ablation atrial tachycardia. ATs post-AF ablation are often incessant, associated with rapid ventricular rates, and respond poorly to pharmacologic measures. Although they may be seen as a positive sign in the longer-term restoration of sinus rhythm, post-AF ablation AT poses specific challenges often requiring repeat catheter ablation procedures. (See "Atrial fibrillation: Catheter ablation", section on 'Efficacy'.) Medications A 2020 scientific statement from the American Heart Association details drugs associated with AT [26]. Digitalis toxicity In patients taking digitalis, toxicity should be suspected if a new AT develops, particularly if 2:1 or higher grade atrioventricular block is present. Digitalis should be discontinued in this case, and anti-digitalis antibodies should be considered if hemodynamic compromise is present or other dangerous arrhythmias accompany the tachycardia. (See "Digitalis (cardiac glycoside) poisoning".) CLINICAL FEATURES Most patients with focal AT report palpitations. Palpitations can manifest in different ways. The abrupt onset of a rapid fluttering sensation in the chest or neck is most consistent with a tachyarrhythmia such as focal AT. The symptom burden is typically higher in focal compared with reentrant supraventricular tachycardia. (See "Evaluation of palpitations in adults".) Patients with focal AT can rarely present with syncope, predominantly if the ventricular heart rate exceeds 200 beats/minute. Syncope, however, is more frequently seen with a ventricular tachyarrhythmia such as ventricular tachycardia than with focal AT. (See "Syncope in adults: Epidemiology, pathogenesis, and etiologies", section on 'Cardiac arrhythmias'.) https://www.uptodate.com/contents/focal-atrial-tachycardia/print 4/26 7/5/23, 10:24 AM Focal atrial tachycardia - UpToDate Patients with other underlying cardiac comorbidities (eg, heart failure, angina) can present with symptoms associated with worsening of their underlying disease (eg, dyspnea, chest pain). DIAGNOSIS The diagnosis of focal AT is based primarily on electrocardiographic (ECG) findings demonstrating an atrial arrhythmia of >100 beats per minute originating from outside the sinus node [6]. The tachycardia is generally sudden in onset and offset and frequently demonstrates a change in P-wave morphology. Focal AT is suggested by bursts of atrial activity with an isoelectric interval between P waves with confirmation of focal as opposed to macroreentry dependent on the findings at EP study. (See 'Electrophysiologic study and catheter ablation' below.) Electrocardiographic features P waves The atrial rate during focal AT is generally between 110 and 250 beats per minute. Infants, children and young adults often have faster rates. The P-wave morphology can appear normal or abnormal, depending upon the site of origin of the tachycardia. If the focus is from the superior portion of the crista terminalis, the P wave may be similar in appearance to the sinus P wave. Usually, there is a subtle difference in P waves from sinus rhythm to AT, so comparison with an ECG with known sinus P waves is recommended whenever possible. ECG leads V1 and lead II are the most useful in assessing P-wave morphology. Observation over several minutes with multiple ECGs is invaluable in distinguishing focal AT from sinus tachycardia. Although focal ATs are regular, the rate may accelerate or "warm up" in the first few beats of the tachycardia and decelerate in the last few beats. An abrupt onset or termination (eg, over three to four beats) favors a focal AT. Sinus tachycardia requires 30 seconds to several minutes to speed up or slow down. In occasional patients, no P waves appear on the surface ECG, which may suggest atrioventricular nodal reentrant tachycardia (AVNRT) [27] as the responsible mechanism. However, this may occur with focal AT if the atrial and ventricular complexes are closely associated such that the P wave is buried in the QRS complex. Atrioventricular relationship In focal AT, AV conduction is usually 1:1. The PR interval is often in the normal range, producing a long R-P interval, which can help to distinguish focal AT from other forms of supraventricular tachycardia (SVT). AT is unlikely if a P wave is present at https://www.uptodate.com/contents/focal-atrial-tachycardia/print 5/26 7/5/23, 10:24 AM Focal atrial tachycardia - UpToDate tachycardia termination. (See "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'RP relationship'.) Mobitz type 1 and 2 conduction may also be seen depending on the rate of the atrial tachycardia and the conducting properties of the AV node. The appearance of "grouped beating" as seen in Mobitz type 1 conduction (Wenckebach) favors focal atrial tachycardia as the responsible mechanism for SVT. QRS morphology The QRS morphology is usually the same as in sinus rhythm, although aberrant conduction may occur at higher ventricular rates. Localization of AT focus Algorithms which attempt to predict the origin of the atrial tachycardia focus have been proposed [6,10,28]. A P-wave algorithm was developed to predict the site of AT origin to guide mapping and ablation at the time of electrophysiology study. A study of 126 patients undergoing electrophysiology study for focal AT served as the basis for an algorithm that was able to predict the arrhythmogenic focus in 93 percent of ATs ( algorithm 1) [10]. The algorithm begins with an evaluation of the P wave in lead V1 [10]: If the P wave in V1 is negative or biphasic with an initially positive/terminally negative deflection, the AT focus is likely in the right atrium ( waveform 1 and waveform 2). If the P wave in V1 is biphasic with an initial negative/terminally positive deflection, the AT focus is likely paraseptal and may require transseptal puncture or mapping of the noncoronary cusp. If the P wave in V1 is positive, the AT focus is likely in the left atrium ( waveform 3) with the exception of the crista terminalis. With close inspection of the P wave in other leads, likely sites of origin could be predicted, including those in the coronary sinus, crista terminalis, left atrial appendage, right atrial appendage, interatrial septum, or pulmonary veins. This algorithm was later simplified and updated with equivalent accuracy [29]. The revised algorithm included the following changes: focal AT arising from the coronary sinus os, right septum, perinodal, left septum, noncoronary cusp, and superior mitral annulus regions were grouped together as paraseptal AT. The term "paraseptal" was defined as anatomic sites in close proximity to either side of the interatrial septum with a similar-appearing P wave. Coronary sinus body was removed from the revised algorithm. The presence of an isoelectric versus https://www.uptodate.com/contents/focal-atrial-tachycardia/print 6/26 7/5/23, 10:24 AM Focal atrial tachycardia - UpToDate negative P wave in lead I was used to discriminate between left pulmonary vein/left atrial appendage AT and right pulmonary vein AT. Electrophysiologic study and catheter ablation The electrophysiologic evaluation of ATs is complex and the characteristics of the arrhythmia depend upon the mechanism [3,4]. The studies are best performed initially under light sedation as automatic ATs may be more difficult to induce under deeper sedation or general anesthesia. Other ATs are inducible by premature stimulation, and less sensitive to the effects of anesthesia. The findings on electrophysiologic study vary depending upon the mechanism of AT: Automatic ATs cannot be initiated, entrained, or terminated by electrophysiologic stimulation ( waveform 4). They may be initiated with isoproterenol or adrenaline. Microreentrant ATs can be initiated, terminated, and entrained by programmed stimulation. The ability to identify the focus responsible for AT has improved with the development of invasive three-dimensional mapping systems. Once a focus has been identified, treatment with catheter ablation can be performed during the same setting. The development of high density multi-electrode mapping catheters can assist in the localization of focal AT. (See 'Chronic or maintenance therapy' below.) DIFFERENTIAL DIAGNOSIS Focal AT originating from the crista terminalis may be difficult to distinguish from inappropriate sinus node tachycardia, as the P wave will be similar. Focal AT more often occurs in bursts of atrial activity with rapid onset/offset compared with a more gradual acceleration and slowing seen with IAST. Additionally, IAST more often has a postural component with tachycardia on standing, an excessive heart rate response to exertion, and is responsive to ivabradine [30]. (See "Sinus tachycardia: Evaluation and management", section on 'Inappropriate sinus tachycardia'.) TREATMENT The management of focal AT is divided into acute treatment and chronic suppressive, or prophylactic, therapy. There are few data to guide treatment strategies. Our approach is consistent with that presented in the 2019 European Society of Cardiology guidelines for the management of supraventricular arrhythmias [31]. https://www.uptodate.com/contents/focal-atrial-tachycardia/print 7/26 7/5/23, 10:24 AM Focal atrial tachycardia - UpToDate Acute treatment The acute management of a patient with an AT is guided by the ventricular rate, symptoms, and the hemodynamic stability of the patient. (See "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'Assessing the patient for hemodynamic stability' and "Overview of the acute management of tachyarrhythmias", section on 'Atrial tachycardia'.) There have been no randomized trials to assess the efficacy of the acute pharmacologic management of AT. For the acute management of patients with AT with a rapid ventricular response, we suggest the following approach, which is based upon small case series and retrospective studies, but is in general agreement with professional society guidelines [6,31]: Efforts should be made to identify and treat any precipitating factors (see 'Associated conditions' above). In particular, patients who present with hypokalemia should have potassium repleted. Efforts can be made to terminate focal AT by having the patient perform vagal maneuvers or by administering intravenous adenosine ( algorithm 2) [31]. However, vagal maneuvers and adenosine are generally less effective for termination of AT than for atrioventricular (AV) nodal dependent supraventricular tachycardias (SVT). Intravenous adenosine is an important diagnostic tool in patients with SVT as generally AV nodal dependent tachycardias will terminate provided sufficient dosing and administration of adenosine. In most forms of AT, adenosine may unmask persisting rapid atrial activity in the presence of transient AV slowing. (See "Vagal maneuvers" and "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'Intravenous adenosine'.) Intravenous beta blockers (eg, metoprolol or esmolol) or nondihydropyridine calcium channel blockers (eg, diltiazem or verapamil) may be given to the hemodynamically stable patient. These drugs should not be used in decompensated heart failure. They slow the ventricular response and may terminate the arrhythmia. In patients with a borderline blood pressure, cautious use of these medications (initially at low doses) may paradoxically improve blood pressure due to improved cardiac output at lower heart rates. Metoprolol can be given as a 2.5 to 5 mg IV bolus over two to five minutes; if there is no response, an additional bolus may be administered every 10 minutes to a total dose of 15 mg. Diltiazem can be given 20 mg IV bolus over two minutes; this may be repeated after 15 minutes if there is an inadequate response. https://www.uptodate.com/contents/focal-atrial-tachycardia/print 8/26 7/5/23, 10:24 AM Focal atrial tachycardia - UpToDate Verapamil can be given 5 to 10 mg IV bolus over two minutes; if no response, an additional 10 mg IV bolus may be administered 15 to 30 minutes following the initial dose. In patients who are intolerant of, or are likely to be intolerant of, beta blockers and nondihydropyridine calcium channel blockers, we suggest intravenous amiodarone, which can provide acute rate control, may terminate the arrhythmia, and results in less hypotension than beta blockers, diltiazem, and verapamil. In appropriately selected patients, class IC (eg, flecainide) or class III (eg, sotalol) antiarrhythmic drugs can also be used. However, because of the unique risk profiles of each of these agents, decisions regarding the use of antiarrhythmic drugs, other than amiodarone, should be made with the assistance of a cardiologist experienced in arrhythmia management. In particular, class IC drugs are contraindicated in the setting of structural heart disease. In patients without structural heart disease, sotalol or flecainide is preferable to amiodarone as they are less toxic long-term therapies. For patients with hemodynamically unstable AT with a rapid ventricular response who do not respond to medical therapy and do not have a reversible precipitating cause, we suggest an attempt at electrical cardioversion. However, ATs may be particularly resistant to cardioversion for two reasons. First, many ATs are caused by enhanced automaticity, and electrical cardioversion is ineffective for such arrhythmias. Secondly, ATs are often precipitated by significant underlying illnesses that both limit the efficacy of cardioversion and increase the likelihood of early arrhythmia recurrence. (See 'Electrophysiologic mechanisms' above and 'Associated conditions' above.) Hemodynamically unstable patients with persistent AT despite treatment with rate- controlling medications and efforts at electrical cardioversion should have an attempt at chemical cardioversion using amiodarone. Chronic or maintenance therapy Chronic therapy of repetitive focal AT is designed to prevent arrhythmia recurrence and to control the ventricular rate if the arrhythmia recurs. Patients with relatively rare and brief arrhythmias and few or no symptoms do not require maintenance therapy. In the absence of coexisting atrial fibrillation/flutter, atrial tachycardia carries a low risk of systemic embolization and chronic oral anticoagulation is not necessary. The published literature addressing chronic suppressive treatment of AT includes only observational studies of small numbers of patients [32]. Some of these studies included patients with atrial fibrillation and atrial flutter, which have different mechanisms and may respond differently to therapy. With these limitations in mind, we suggest the following approach for https://www.uptodate.com/contents/focal-atrial-tachycardia/print 9/26 7/5/23, 10:24 AM Focal atrial tachycardia - UpToDate chronic treatment of patients with frequent or symptomatic AT, which is in general agreement with professional society guidelines [6,31]: Since focal AT may be short in duration and resolve spontaneously, we suggest initial therapy with oral beta blockers or nondihydropyridine calcium channel blockers (ie, diltiazem or verapamil). Patients who do not respond to one of these agents may have successful suppression with another. Patients with recurrent or refractory symptomatic AT despite therapy with beta blockers, diltiazem, or verapamil, or patients who would potentially require long-term pharmacologic therapy are candidates for catheter ablation. The threshold for considering catheter ablation is lower for younger patients, incessant tachycardia, and in patients with tachycardia-mediated cardiomyopathy. (See 'Incessant AT resulting in cardiomyopathy' above.) More aggressive antiarrhythmic drugs may be considered for patients who fail beta blockers, diltiazem, and verapamil who do not want or are not good candidates for ablation therapy. Class IC (eg, flecainide, propafenone) antiarrhythmic drugs can be used in appropriately selected patients in the absence of structural or ischemic heart disease. However, because of the unique risk profiles of each of these agents, decisions regarding the use of antiarrhythmic drugs should be made with the assistance of a cardiologist experienced in arrhythmia management. In patients with significant comorbidities and structural heart disease, amiodarone is frequently the preferred agent. Patients with recurrent symptomatic AT in whom all other therapeutic options have been unsuccessful (including catheter ablation) may also be considered for pacemaker implantation and should preferably include biventricular or his bundle pacing followed by AV nodal ablation. This typically provides symptomatic relief although generally leaves the patient pacemaker dependent. Catheter ablation With the advent of 3D mapping systems and high density multipolar mapping systems, radiofrequency ablation offers a potential cure in patients with recurrent atrial tachycardia [33]. In a large single-center series, mapping and ablation was performed in 303 of 345 (90 percent) patients for focal AT. Radiofrequency ablation (RFA) was not pursued in the remainder due to close proximity to the AV node, multiple changing morphologies or insufficient ectopy/tachycardia to allow the detailed mapping required to identify the responsible atrial focus. Success off medication was achieved in 272 of 303 (90 percent) patients [2]. https://www.uptodate.com/contents/focal-atrial-tachycardia/print 10/26 7/5/23, 10:24 AM Focal atrial tachycardia - UpToDate Multiple ectopic atrial foci and the presence of structural cardiac disease are predictors of recurrence after an initially successful ablation [21]. Mapping and ablating atrial tachycardia is technically more challenging than other forms of paroxysmal SVT [34]. Atrial tachycardia can originate from any site in the right or left atrium, and even from the proximal pulmonary veins or superior vena cava. Identification of a tachycardia's origin as left versus right atrial may be difficult ( figure 2) but can usually be successfully predicted using the surface ECG ( algorithm 1). Localizing the origin of atrial tachycardia is discussed in detail elsewhere. (See 'Localization of AT focus' above and "Invasive diagnostic cardiac electrophysiology studies", section on 'Mapping and ablation'.) Anticoagulation Atrial tachycardia carries a low risk of systemic embolization in the absence of co-existing atrial fibrillation/flutter, and chronic oral anticoagulation is not necessary. Treatment of incessant AT As described above, patients with incessant AT may present with a cardiomyopathy. Even patients with normal left ventricular systolic function on initial presentation are at risk of developing a cardiomyopathy following extended periods of tachycardia. This LV systolic dysfunction typically reverses weeks to months following the restoration of sinus rhythm. As such, aggressive efforts should be made to restore normal sinus rhythm in an attempt to prevent or reverse LV systolic dysfunction. (See 'Incessant AT resulting in cardiomyopathy' above and "Arrhythmia-induced cardiomyopathy".) While there have been occasional reports of the successful treatment of incessant AT using beta blockers and Class IC antiarrhythmic drugs (ie, flecainide), pharmacologic therapy is generally ineffective in incessant AT [6,35-37]. For this reason, if medical therapy with rate-controlling medications and antiarrhythmic drugs is unsuccessful, patients with AT and concomitant LV systolic dysfunction should undergo catheter ablation ( waveform 2) [6]. Only 10 to 15 percent of patients will have recurrence of AT following catheter ablation. (See 'Catheter ablation' above.) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Supraventricular arrhythmias".) SUMMARY AND RECOMMENDATIONS https://www.uptodate.com/contents/focal-atrial-tachycardia/print 11/26 7/5/23, 10:24 AM Focal atrial tachycardia - UpToDate Definition Atrial tachycardia (AT) is a regular atrial rhythm at a constant rate of >100 beats per minute, usually paroxysmal and self-limited, which originates outside of the sinus node. Focal AT accounts for between 5 and 15 percent of paroxysmal supraventricular tachycardia in adults. (See 'Background' above.) Sites of origin The majority of ATs originate in the right atrium along the crista terminalis and tricuspid annulus. Left AT predominantly originates near the pulmonary veins. (See 'Sites of origin' above.) Symptoms Most patients with focal AT report palpitations. Rarely, patients may present with syncope or exacerbation of an underlying cardiac condition (eg, angina). (See 'Clinical features' above.) ECG features The P-wave morphology can appear normal or abnormal, depending upon the site of origin of the tachycardia. Usually, there is a subtle difference in P waves from sinus rhythm to AT, so comparison with an ECG with known sinus P waves is advised, whenever possible. (See 'Electrocardiographic features' above.) Acute treatment The acute treatment of patients with AT depends upon the presence of symptoms and the patient s hemodynamic status: For symptomatic patients Hemodynamically unstable Patients who are hemodynamically unstable are not candidates for medical therapy with intravenous beta blocker or nondihydropyridine calcium channel blocker because these treatments are likely to exacerbate hypotension. For such patients, we proceed with an attempt at electrical cardioversion, however this may be unsuccessful in patients with automatic AT. Hemodynamically unstable patients with persistent AT despite treatment with rate- controlling medications and efforts at electrical cardioversion should have an attempted chemical cardioversion using intravenous amiodarone. (See 'Acute treatment' above.) Hemodynamically stable For a hemodynamically stable patient with symptomatic AT, we suggest acute treatment with an oral or intravenous beta blocker or nondihydropyridine calcium channel blocker (ie, diltiazem or verapamil) rather than an antiarrhythmic drug (Grade 2C). Such treatment may slow the ventricular response and/or terminate the arrhythmia. Intravenous amiodarone is an acceptable alternative that may be preferred in a patient with borderline hypotension with structural heart disease. (See 'Acute treatment' above.) https://www.uptodate.com/contents/focal-atrial-tachycardia/print 12/26 7/5/23, 10:24 AM Focal atrial tachycardia - UpToDate For asymptomatic patients For an asymptomatic hemodynamically stable patient with AT, we suggest initial observation rather than acute treatment with a beta blocker or nondihydropyridine calcium channel blocker (ie, diltiazem or verapamil) (Grade 2C). (See 'Acute treatment' above.) Chronic therapy Chronic therapy of repetitive focal AT is designed to prevent arrhythmia recurrence and to control the ventricular rate if the arrhythmia recurs. For rare or brief episodes Patients with relatively rare or brief AT episodes with few or no symptoms can receive treatment as needed for acute episodes of AT but do not require chronic suppressive therapy. (See 'Chronic or maintenance therapy' above.) For frequent symptomatic episodes Initial therapy For patients with frequent, symptomatic AT, we suggest chronic management with an oral beta blocker or nondihydropyridine calcium channel blocker (ie, diltiazem or verapamil) as the initial treatment rather than an antiarrhythmic drug or catheter ablation (Grade 2C). (See 'Chronic or maintenance therapy' above.) For recurrent or refractory episodes Patients with frequent, symptomatic AT who have failed initial medical therapy or require long-term medical therapy are candidates for catheter ablation. (See 'Chronic or maintenance therapy' above.) For incessant AT For few or no symptoms For patients with incessant AT with preserved left ventricular function and few or no symptoms, an initial trial of rate-controlling medications or antiarrhythmic medications may be reasonable. The efficacy of this approach should be reassessed within two weeks and, if unsuccessful, the patient should be referred for catheter ablation. (See 'Treatment of incessant AT' above.) For cardiomyopathy related to incessant AT For patients with cardiomyopathy felt to be related to incessant AT, we recommend aggressive attempts to restore a normal ventricular heart rate rather than rate control alone (Grade 1B). This can be accomplished in most patients by catheter ablation of the AT focus. In the unusual likelihood that catheter ablation is unsuccessful, pacemaker implantation, preferably including biventricular or his bundle pacing followed by atrioventricular nodal ablation, typically provides symptomatic relief. (See 'Catheter ablation' above and "Arrhythmia-induced cardiomyopathy", section on 'Treatment'.) https://www.uptodate.com/contents/focal-atrial-tachycardia/print 13/26 7/5/23, 10:24 AM Focal atrial tachycardia - UpToDate Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Saoudi N, Cos o F, Waldo A, et al. A classification of atrial flutter and regular atrial tachycardia according to electrophysiological mechanisms and anatomical bases; a Statement from a Joint Expert Group from The Working Group of Arrhythmias of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Eur Heart J 2001; 22:1162. 2. Medi C, Kalman JM, Haqqani H, et al. Tachycardia-mediated cardiomyopathy secondary to focal atrial tachycardia: long-term outcome after catheter ablation. J Am Coll Cardiol 2009; 53:1791. 3. Chen SA, Chiang CE, Yang CJ, et al. Sustained atrial tachycardia in adult patients. Electrophysiological characteristics, pharmacological response, possible mechanisms, and effects of radiofrequency ablation. Circulation 1994; 90:1262. 4. Roberts-Thomson KC, Kistler PM, Kalman JM. Atrial tachycardia: mechanisms, diagnosis, and management. Curr Probl Cardiol 2005; 30:529. 5. Roberts-Thomson KC, Kistler PM, Kalman JM. Focal atrial tachycardia I: clinical features, diagnosis, mechanisms, and anatomic location. Pacing Clin Electrophysiol 2006; 29:643. 6. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation 2016; 133:e506. 7. Higa S, Tai CT, Lin YJ, et al. Focal atrial tachycardia: new insight from noncontact mapping and catheter ablation. Circulation 2004; 109:84. 8. De Groot NM, Schalij MJ. Fragmented, long-duration, low-amplitude electrograms characterize the origin of focal atrial tachycardia. J Cardiovasc Electrophysiol 2006; 17:1086. 9. Kistler PM, Sanders P, Hussin A, et al. Focal atrial tachycardia arising from the mitral annulus: electrocardiographic and electrophysiologic characterization. J Am Coll Cardiol 2003; 41:2212. 10. Kistler PM, Roberts-Thomson KC, Haqqani HM, et al. P-wave morphology in focal atrial tachycardia: development of an algorithm to predict the anatomic site of origin. J Am Coll Cardiol 2006; 48:1010. 11. Wong MC, Kalman JM, Ling LH, et al. Left septal atrial tachycardias: electrocardiographic and electrophysiologic characterization of a paraseptal focus. J Cardiovasc Electrophysiol 2013; https://www.uptodate.com/contents/focal-atrial-tachycardia/print 14/26 7/5/23, 10:24 AM Focal atrial tachycardia - UpToDate 24:413. 12. Ouyang F, Ma J, Ho SY, et al. Focal atrial tachycardia originating from the non-coronary aortic sinus: electrophysiological characteristics and catheter ablation. J Am Coll Cardiol 2006; 48:122. 13. Akhtar, M. Supraventricular tachycardias. Electrophysiologic mechanisms, diagnosis and ph armacologic therapy. In: Tachycardias: Mechanisms, Diagnosis, Treatment, Josephson, ME, Wellens, H (Eds), Lea & Febiger, Philadelphia 1984. p.137. 14. Levine HD, Smith C Jr. Repetitive paroxysmal tachycardia in adults. Cardiology 1970; 55:2. 15. Sung RJ. Incessant supraventricular tachycardia. Pacing Clin Electrophysiol 1983; 6:1306. 16. Gillette PC, Smith RT, Garson A Jr, et al. Chronic supraventricular tachycardia. A curable cause of congestive cardiomyopathy. JAMA 1985; 253:391. 17. Gillette PC, Wampler DG, Garson A Jr, et al. Treatment of atrial automatic tachycardia by ablation procedures. J Am Coll Cardiol 1985; 6:405. 18. Packer DL, Bardy GH, Worley SJ, et al. Tachycardia-induced cardiomyopathy: a reversible form of left ventricular dysfunction. Am J Cardiol 1986; 57:563. 19. Bertil Olsson S, Blomstr m P, Sabel KG, William-Olsson G. Incessant ectopic atrial tachycardia: successful surgical treatment with regression of dilated cardiomyopathy picture. Am J Cardiol 1984; 53:1465. 20. Doig JC, McComb JM, Reid DS. Incessant atrial tachycardia accelerated by pregnancy. Br Heart J 1992; 67:266. 21. Chen SA, Tai CT, Chiang CE, et al. Focal atrial tachycardia: reanalysis of the clinical and electrophysiologic characteristics and prediction of successful radiofrequency ablation. J Cardiovasc Electrophysiol 1998; 9:355. 22. Koike K, Hesslein PS, Finlay CD, et al. Atrial automatic tachycardia in children. Am J Cardiol 1988; 61:1127. 23. Kistler PM, Sanders P, Fynn SP, et al. Electrophysiological and electrocardiographic characteristics of focal atrial tachycardia originating from the pulmonary veins: acute and long-term outcomes of radiofrequency ablation. Circulation 2003; 108:1968. 24. O'Neill MD, Wright M, Knecht S, et al. Long-term follow-up of persistent atrial fibrillation ablation using termination as a procedural endpoint. Eur Heart J 2009; 30:1105. 25. Verma A, Jiang CY, Betts TR, et al. Approaches to catheter ablation for persistent atrial fibrillation. N Engl J Med 2015; 372:1812. 26. Tisdale JE, Chung MK, Campbell KB, et al. Drug-Induced Arrhythmias: A Scientific Statement From the American Heart Association. Circulation 2020; 142:e214. https://www.uptodate.com/contents/focal-atrial-tachycardia/print 15/26 7/5/23, 10:24 AM Focal atrial tachycardia - UpToDate 27. Zipes DP, Gaum WE, Genetos BC, et al. Atrial tachycardia without P waves masquerading as an A-V junctional tachycardia. Circulation 1977; 55:253. 28. Qian ZY, Hou XF, Xu DJ, et al. An algorithm to predict the site of origin of focal atrial tachycardia. Pacing Clin Electrophysiol 2011; 34:414. 29. Kistler PM, Chieng D, Tonchev IR, et al. P-Wave Morphology in Focal Atrial Tachycardia: An Updated Algorithm to Predict Site of Origin. JACC Clin Electrophysiol 2021; 7:1547. 30. Cappato R, Castelvecchio S, Ricci C, et al. Clinical efficacy of ivabradine in patients with inappropriate sinus tachycardia: a prospective, randomized, placebo-controlled, double- blind, crossover evaluation. J Am Coll Cardiol 2012; 60:1323. 31. Brugada J, Katritsis DG, Arbelo E, et al. 2019 ESC Guidelines for the management of patients

require chronic suppressive therapy. (See 'Chronic or maintenance therapy' above.) For frequent symptomatic episodes Initial therapy For patients with frequent, symptomatic AT, we suggest chronic management with an oral beta blocker or nondihydropyridine calcium channel blocker (ie, diltiazem or verapamil) as the initial treatment rather than an antiarrhythmic drug or catheter ablation (Grade 2C). (See 'Chronic or maintenance therapy' above.) For recurrent or refractory episodes Patients with frequent, symptomatic AT who have failed initial medical therapy or require long-term medical therapy are candidates for catheter ablation. (See 'Chronic or maintenance therapy' above.) For incessant AT For few or no symptoms For patients with incessant AT with preserved left ventricular function and few or no symptoms, an initial trial of rate-controlling medications or antiarrhythmic medications may be reasonable. The efficacy of this approach should be reassessed within two weeks and, if unsuccessful, the patient should be referred for catheter ablation. (See 'Treatment of incessant AT' above.) For cardiomyopathy related to incessant AT For patients with cardiomyopathy felt to be related to incessant AT, we recommend aggressive attempts to restore a normal ventricular heart rate rather than rate control alone (Grade 1B). This can be accomplished in most patients by catheter ablation of the AT focus. In the unusual likelihood that catheter ablation is unsuccessful, pacemaker implantation, preferably including biventricular or his bundle pacing followed by atrioventricular nodal ablation, typically provides symptomatic relief. (See 'Catheter ablation' above and "Arrhythmia-induced cardiomyopathy", section on 'Treatment'.) https://www.uptodate.com/contents/focal-atrial-tachycardia/print 13/26 7/5/23, 10:24 AM Focal atrial tachycardia - UpToDate Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Saoudi N, Cos o F, Waldo A, et al. A classification of atrial flutter and regular atrial tachycardia according to electrophysiological mechanisms and anatomical bases; a Statement from a Joint Expert Group from The Working Group of Arrhythmias of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Eur Heart J 2001; 22:1162. 2. Medi C, Kalman JM, Haqqani H, et al. Tachycardia-mediated cardiomyopathy secondary to focal atrial tachycardia: long-term outcome after catheter ablation. J Am Coll Cardiol 2009; 53:1791. 3. Chen SA, Chiang CE, Yang CJ, et al. Sustained atrial tachycardia in adult patients. Electrophysiological characteristics, pharmacological response, possible mechanisms, and effects of radiofrequency ablation. Circulation 1994; 90:1262. 4. Roberts-Thomson KC, Kistler PM, Kalman JM. Atrial tachycardia: mechanisms, diagnosis, and management. Curr Probl Cardiol 2005; 30:529. 5. Roberts-Thomson KC, Kistler PM, Kalman JM. Focal atrial tachycardia I: clinical features, diagnosis, mechanisms, and anatomic location. Pacing Clin Electrophysiol 2006; 29:643. 6. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation 2016; 133:e506. 7. Higa S, Tai CT, Lin YJ, et al. Focal atrial tachycardia: new insight from noncontact mapping and catheter ablation. Circulation 2004; 109:84. 8. De Groot NM, Schalij MJ. Fragmented, long-duration, low-amplitude electrograms characterize the origin of focal atrial tachycardia. J Cardiovasc Electrophysiol 2006; 17:1086. 9. Kistler PM, Sanders P, Hussin A, et al. Focal atrial tachycardia arising from the mitral annulus: electrocardiographic and electrophysiologic characterization. J Am Coll Cardiol 2003; 41:2212. 10. Kistler PM, Roberts-Thomson KC, Haqqani HM, et al. P-wave morphology in focal atrial tachycardia: development of an algorithm to predict the anatomic site of origin. J Am Coll Cardiol 2006; 48:1010. 11. Wong MC, Kalman JM, Ling LH, et al. Left septal atrial tachycardias: electrocardiographic and electrophysiologic characterization of a paraseptal focus. J Cardiovasc Electrophysiol 2013; https://www.uptodate.com/contents/focal-atrial-tachycardia/print 14/26 7/5/23, 10:24 AM Focal atrial tachycardia - UpToDate 24:413. 12. Ouyang F, Ma J, Ho SY, et al. Focal atrial tachycardia originating from the non-coronary aortic sinus: electrophysiological characteristics and catheter ablation. J Am Coll Cardiol 2006; 48:122. 13. Akhtar, M. Supraventricular tachycardias. Electrophysiologic mechanisms, diagnosis and ph armacologic therapy. In: Tachycardias: Mechanisms, Diagnosis, Treatment, Josephson, ME, Wellens, H (Eds), Lea & Febiger, Philadelphia 1984. p.137. 14. Levine HD, Smith C Jr. Repetitive paroxysmal tachycardia in adults. Cardiology 1970; 55:2. 15. Sung RJ. Incessant supraventricular tachycardia. Pacing Clin Electrophysiol 1983; 6:1306. 16. Gillette PC, Smith RT, Garson A Jr, et al. Chronic supraventricular tachycardia. A curable cause of congestive cardiomyopathy. JAMA 1985; 253:391. 17. Gillette PC, Wampler DG, Garson A Jr, et al. Treatment of atrial automatic tachycardia by ablation procedures. J Am Coll Cardiol 1985; 6:405. 18. Packer DL, Bardy GH, Worley SJ, et al. Tachycardia-induced cardiomyopathy: a reversible form of left ventricular dysfunction. Am J Cardiol 1986; 57:563. 19. Bertil Olsson S, Blomstr m P, Sabel KG, William-Olsson G. Incessant ectopic atrial tachycardia: successful surgical treatment with regression of dilated cardiomyopathy picture. Am J Cardiol 1984; 53:1465. 20. Doig JC, McComb JM, Reid DS. Incessant atrial tachycardia accelerated by pregnancy. Br Heart J 1992; 67:266. 21. Chen SA, Tai CT, Chiang CE, et al. Focal atrial tachycardia: reanalysis of the clinical and electrophysiologic characteristics and prediction of successful radiofrequency ablation. J Cardiovasc Electrophysiol 1998; 9:355. 22. Koike K, Hesslein PS, Finlay CD, et al. Atrial automatic tachycardia in children. Am J Cardiol 1988; 61:1127. 23. Kistler PM, Sanders P, Fynn SP, et al. Electrophysiological and electrocardiographic characteristics of focal atrial tachycardia originating from the pulmonary veins: acute and long-term outcomes of radiofrequency ablation. Circulation 2003; 108:1968. 24. O'Neill MD, Wright M, Knecht S, et al. Long-term follow-up of persistent atrial fibrillation ablation using termination as a procedural endpoint. Eur Heart J 2009; 30:1105. 25. Verma A, Jiang CY, Betts TR, et al. Approaches to catheter ablation for persistent atrial fibrillation. N Engl J Med 2015; 372:1812. 26. Tisdale JE, Chung MK, Campbell KB, et al. Drug-Induced Arrhythmias: A Scientific Statement From the American Heart Association. Circulation 2020; 142:e214. https://www.uptodate.com/contents/focal-atrial-tachycardia/print 15/26 7/5/23, 10:24 AM Focal atrial tachycardia - UpToDate 27. Zipes DP, Gaum WE, Genetos BC, et al. Atrial tachycardia without P waves masquerading as an A-V junctional tachycardia. Circulation 1977; 55:253. 28. Qian ZY, Hou XF, Xu DJ, et al. An algorithm to predict the site of origin of focal atrial tachycardia. Pacing Clin Electrophysiol 2011; 34:414. 29. Kistler PM, Chieng D, Tonchev IR, et al. P-Wave Morphology in Focal Atrial Tachycardia: An Updated Algorithm to Predict Site of Origin. JACC Clin Electrophysiol 2021; 7:1547. 30. Cappato R, Castelvecchio S, Ricci C, et al. Clinical efficacy of ivabradine in patients with inappropriate sinus tachycardia: a prospective, randomized, placebo-controlled, double- blind, crossover evaluation. J Am Coll Cardiol 2012; 60:1323. 31. Brugada J, Katritsis DG, Arbelo E, et al. 2019 ESC Guidelines for the management of patients with supraventricular tachycardiaThe Task Force for the management of patients with supraventricular tachycardia of the European Society of Cardiology (ESC). Eur Heart J 2020; 41:655. 32. Kang KT, Etheridge SP, Kantoch MJ, et al. Current management of focal atrial tachycardia in children: a multicenter experience. Circ Arrhythm Electrophysiol 2014; 7:664. 33. Chieng D, Lahiri A, Sugumar H, et al. Multipolar mapping with the high-density grid catheter compared with conventional point-by-point mapping to guide catheter ablation for focal arrhythmias. J Cardiovasc Electrophysiol 2020; 31:2288. 34. Lesh MD. Radiofrequency catheter ablation of atrial tachycardia and flutter. In: Cardiac Elect rophysiology: From Cell to Bedside, 2nd ed, Zipes DP, Jalife J (Eds), WB Saunders, Philadelphi a 1995. p.1461. 35. Iwai S, Markowitz SM, Stein KM, et al. Response to adenosine differentiates focal from macroreentrant atrial tachycardia: validation using three-dimensional electroanatomic mapping. Circulation 2002; 106:2793. 36. Berns E, Rinkenberger RL, Jeang MK, et al. Efficacy and safety of flecainide acetate for atrial tachycardia or fibrillation. Am J Cardiol 1987; 59:1337. 37. Brugada P, Abdollah H, Wellens HJ. Suppression of incessant supraventricular tachycardia by intravenous and oral encainide. J Am Coll Cardiol 1984; 4:1255. Topic 900 Version 36.0 https://www.uptodate.com/contents/focal-atrial-tachycardia/print 16/26 7/5/23, 10:24 AM Focal atrial tachycardia - UpToDate GRAPHICS Electrocardiogram showing an ectopic atrial tachycardia originating from the tricuspid annulus Electrocardiographic tracing showing a narrow complex tachycardia with uniform P waves consistent with an ectopic atrial tachycardia originating from the tricuspid annulus. Prior to the final QRS complex, there is spontaneous return to normal sinus rhythm with P wave of a different morphology. Courtesy of Peter Kistler, MBBS, FRACP, PhD. Graphic 74611 Version 10.0 https://www.uptodate.com/contents/focal-atrial-tachycardia/print 17/26 7/5/23, 10:24 AM Focal atrial tachycardia - UpToDate Relationship between fast sodium-mediated myocardial action potential and surface electrocardiogram Each phase of the myocardial action potential (numbers, upper panel) corresponds to a deflection or interval on the surface ECG (lower panel). Phase 4, the resting membrane potential, is responsible for the TQ segment; this segment has a prominent role in the ECG manifestations of ischemia during exercise testing. ECG: electrocardiogram. Graphic 64133 Version 4.0 https://www.uptodate.com/contents/focal-atrial-tachycardia/print 18/26 7/5/23, 10:24 AM Focal atrial tachycardia - UpToDate A schematic representation of the anatomic distribution of focal atrial tachycardias The atrioventricular valvular annuli have been removed. %: percent; CS: coronary sinus; CT: crista terminalis; LA: left atrium; LAA: left atrial appendage; MA: mitral annulus; PV: pulmonary vein; RA: right atrium; RAA: right atrial appendage; TA: tricuspid annulus. Reproduced with permission from: Kistler, PM, Roberts-Thomson, KC, Haqqani, HM, et al. P- wave morphology in focal atrial tachycardia: development of an algorithm to predict the anatomic site of origin. J Am Coll Cardiol 2006; 48:1010. Copyright 2006 Elsevier. Graphic 62431 Version 1.0 https://www.uptodate.com/contents/focal-atrial-tachycardia/print 19/26 7/5/23, 10:24 AM Focal atrial tachycardia - UpToDate Electrocardiogram (ECG) showing atrial tachycardia originating from the crista terminalis. Electrocardiographic tracing showing a narrow complex tachycardia with uniform P waves consistent with atrial tachycardia originating from the crista terminalis. Following the third beat there is spontaneous return to normal sinus rhythm with uniform P waves of a different morphology. Courtesy of Dr. Peter M Kistler. Graphic 50523 Version 7.0 https://www.uptodate.com/contents/focal-atrial-tachycardia/print 20/26 7/5/23, 10:24 AM Focal atrial tachycardia - UpToDate Electrocardiogram (ECG) showing atrial tachycardia originating from the left superior pulmonary vein. Electrocardiographic tracing showing a narrow complex tachycardia with uniform P waves consistent with atrial tachycardia originating from the left superior pulmonary vein. The initial QRS complex shows a normal sinus beat, followed by the development of atrial tachycardia. Courtesy of Dr. Peter Kistler. Graphic 57390 Version 3.0 https://www.uptodate.com/contents/focal-atrial-tachycardia/print 21/26 7/5/23, 10:24 AM Focal atrial tachycardia - UpToDate P-wave algorithm to predict anatomic origin of atrial tachycardia A P-wave algorithm constructed on the basis of findings from 130 atrial tachycardias correctly localized the focus in 93%. The algorithm begins with assessment of the P-wave morphology in lead V1 on the surface electrocardiogram, then utilizes other leads as needed. Neg: negative P-wave morphology; Pos: positive P-wave morphology; Iso: isoelectric P-wave morphology; CT: crista terminalis; CS: coronary sinus ostium; LS: left superior pulmonary vein; SMA: superior mitral annulus; TA: tricuspid annulus; RAA: right atrial appendage; LPV: left inferior pulmonary vein; LAA: left atrial appendage; RPV: right inferior pulmonary vein. Reproduced with permission from: Kistler PM, Roberts-Thomson KC, Haqqani HM, et al. P-wave morphology in focal atrial tachycardia: development of an algorithm to predict the anatomic site of origin. J Am Coll Cardiol 2006; 48:1010. Copyright 2006 Elsevier. Graphic 53718 Version 6.0 https://www.uptodate.com/contents/focal-atrial-tachycardia/print 22/26 7/5/23, 10:24 AM Focal atrial tachycardia - UpToDate Electrophysiology study (EPS) tracing showing atrial tachycardia onset and termination From top to bottom, surface ECG leads I, II, III, and VI and intracardiac recordings in the high right atrium (2 leads) and His bundle, obtained during electrophysiologic study performed in a 79-year-old with an incessant atrial tachycardia with a rate of 130 beats per minute. This figure shows that a tachychycardia similar to the spontaneous tachycardia could be induced using programmed electrical stimulation with one stimulus (St) and terminated with one stimulus, which favors a reentrant mechanism. This tachycardia was successfully ablated by detecting the earliest atrial activation in reference to the onset or the P wave on the surface ECG. Note during the tachycardia that the QRS complexes are preceded (lead II) by a P wave with a configuration different of that of the sinus P wave (last beat). Graphic 90888 Version 1.0 https://www.uptodate.com/contents/focal-atrial-tachycardia/print 23/26 7/5/23, 10:24 AM Focal atrial tachycardia - UpToDate Approach to adenosine dosing in stable adults with suspected supraventricular tachyarrhythmia This figure summarizes the initial dosing, administration, and need for repeat dosing of adenosine in a hemo stable adult with suspected AV node-dependent SVT. Adenosine can be used as a diagnostic aid to identify th rhythm or as a therapy to terminate SVTs that rely on AV node conduction. AV node-dependent SVTs include A reentrant tachycardia (AVNRT) and AV reentrant (or reciprocating) tachycardia (AVRT). The management of su node-dependent SVT in hemodynamically stable adults commonly starts with a trial of 1 or more vagal mane proceeding to adenosine therapy. If the patient has hemodynamically unstable SVT, cardioversion is indicate UpToDate content for details on management of SVTs. https://www.uptodate.com/contents/focal-atrial-tachycardia/print 24/26 7/5/23, 10:24 AM Focal atrial tachycardia - UpToDate AV: atrioventricular; SVT: supraventricular tachycardia; IV: intravenous; ACC: American College of Cardiology; American Heart Association; HRS: Heart Rhythm Society; ECG: electrocardiogram. Lower adenosine doses are indicated in certain clinical settings. If central venous administration is perform adenosine dose is 3 mg; if needed (SVT persists and there is no AV block), the dose may be increased to 6 mg mg for subsequent doses. For heart transplant recipients, the initial adenosine dose is 1 mg; if needed (SVT p there is no AV block), the dose may be increased to 2 mg and then 3 mg for subsequent doses. An 18 mg dose is more likely to be required to produce AV block in patients with a body weight >70 kg, par [1] those weighing >110 kg. When a third dose is indicated, an alternative approach is to administer 12 mg (in mg) as described in the 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients with Supraventr Tachycardia. [2] SVT termination in response to adenosine includes SVT termination closely followed by SVT recurrence. Refer to UpToDate content on treatment of SVT for dosing of second-line AV nodal blockers. If the SVT pers second-line AV nodal blocker therapy, electrical cardioversion is performed, as discussed in UpToDate conten treatment of SVT. SVTs that are not AV node dependent include atrial flutter, atrial fibrillation, and atrial tachycardia. When AV is induced by adenosine, the ECG may reveal atrial activity diagnostic of these rhythms. References: 1. Prabhu S, Mackin V, McLellan AJA, et al. Determining the optimal dose of adenosine for unmasking dormant pulmonary vein co following atrial brillation ablation: Electrophysiological and hemodynamic assessment. DORMANT-AF study. J Cardiovasc Electr 28:13. 2. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Hea Society. Circulation 2016; 133:e506. Graphic 141417 Version 3.0 https://www.uptodate.com/contents/focal-atrial-tachycardia/print 25/26 7/5/23, 10:24 AM Focal atrial tachycardia - UpToDate Contributor Disclosures Peter Kistler, MBBS, FRACP, PhD Consultant/Advisory Boards: Biosense Webster [Advanced mapping technologies in arrhythmias]. Speaker's Bureau: Biosense Webster [Atrial fibrillation]; St Jude Medical/Abbott [Atrial fibrillation]. All of the relevant financial relationships listed have been mitigated. Samuel L vy, MD No relevant financial relationship(s) with ineligible companies to disclose. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/focal-atrial-tachycardia/print 26/26

7/5/23, 10:24 AM Intraatrial reentrant tachycardia - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Intraatrial reentrant tachycardia : Munther K Homoud, MD : Samuel L vy, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Oct 18, 2021. INTRODUCTION Atrial tachycardias have traditionally been characterized as automatic, triggered, or reentrant. However, the European Society of Cardiology and the North American Society of Pacing and Electrophysiology in 2001 proposed a classification that takes into consideration both anatomic features and electrophysiologic mechanisms [1]. Atrial tachycardia is the overriding term that includes two major categories: Focal atrial tachycardia due to an automatic, triggered, or microreentrant mechanism. Macroreentrant atrial tachycardia, including typical atrial flutter and other well- characterized macroreentrant circuits in the right and left atrium. Intraatrial reentrant tachycardia (IART) falls into the latter group. Furthermore, the joint American College of Cardiology/American Heart Association/Heart Rhythm Society 2015 guidelines further defined macroreentrant atrial tachycardias that do not involve the tricuspid valve isthmus as "atypical or non-cavo-tricuspid isthmus-dependent atrial flutter" [2]. These macroreentrant supraventricular tachycardias often involve the left atrium, particularly after atrial fibrillation (AF) ablation or Maze surgery for AF. They may involve any atrium where a scar, surgical or catheter-induced, may have taken place. This topic will discuss the mechanisms, clinical manifestations, and treatment of IART. Discussions of other specific atrial arrhythmias are presented separately. (See "Focal atrial tachycardia" and "Sinoatrial nodal reentrant tachycardia (SANRT)" and "Overview of atrial flutter".) https://www.uptodate.com/contents/intraatrial-reentrant-tachycardia/print 1/24 7/5/23, 10:24 AM Intraatrial reentrant tachycardia - UpToDate DEFINITION, PREVALENCE, AND MECHANISMS Intraatrial reentrant tachycardia (IART) refers to any macroreentrant atrial tachycardia that does not utilize the cavotricuspid isthmus ( figure 1) as a critical pathway for the reentry to perpetuate. IART generally occurs in one of three settings: post-surgical repair of congenital heart disease (incidence of 16 to 50 percent post Fontan procedure, 15 to 48 percent post Mustard or Senning procedures, 12 to 34 percent post Tetralogy of Fallot repair), post-surgical scar (incisional tachycardia), or post catheter based or surgical management of atrial fibrillation (AF) [3,4]. With the increase in AF ablation, an increase in IART is arising due to the surgical maze and catheter based procedures in the left atrium. IART has also been reported in the absence of surgical or catheter intervention [5]. Reentry refers to a circuit in which previously excited tissue is re-excited, producing an extra beat or a sustained rhythm. Sinoatrial (SA) nodal reentrant tachycardia and IART (also called reentrant atrial tachycardia) are the two major types of paroxysmal reentrant supraventricular tachycardias in which the reentrant circuit does not involve the atrioventricular (AV) node or accessory pathways ( figure 2). (See "Sinoatrial nodal reentrant tachycardia (SANRT)".) Reentry pathways are usually defined by the following characteristics: Two discrete but connected pathways. Slow conduction in one of the pathways and unidirectional block in the other pathway. Block in the pathway with unidirectional block following a premature beat, with conduction through the slower pathway allowing the pathway with unidirectional block to recover conduction and conduct the impulse back to the first pathway, hence initiating reentry. Block may be anatomical (accessory bypass tract, slow or fast AVN pathway), functional (ischemia, electrolyte imbalance or anti arrhythmic agents), or both. IART has a different activation sequence of atrial depolarization, leading to a P wave morphology that differs from that of normal sinus rhythm. In comparison, SA nodal reentrant tachycardia has an activation sequence similar to that of normal sinus rhythm so that the P waves on the surface ECG appear to be normal. Only the abrupt onset and termination of this arrhythmia distinguish it clinically from sinus tachycardia. (See 'Electrophysiological features' below and "Sinoatrial nodal reentrant tachycardia (SANRT)".) IART was responsible for approximately 6 percent of atrial tachycardias in patients referred for electrophysiologic studies to an active electrophysiologic group [6]. Organic heart disease is https://www.uptodate.com/contents/intraatrial-reentrant-tachycardia/print 2/24 7/5/23, 10:24 AM Intraatrial reentrant tachycardia - UpToDate common in adults with this arrhythmia. In children, intraatrial tachycardia is often associated with surgery that involves the atrium, such as the repair of an atrial septal defect or correction of transposition [7], but may occur with any repair that includes an atrial scar. IART may be quite detrimental because of the elevated heart rate and the frequent loss of normal AV synchrony. It has been suggested that there is an increased rate of right and atrial thrombosis with IART. The other group of patients in whom IART is seen is individuals who have undergone catheter or surgical ablation for AF. The incidence varies between 2.9 percent following pulmonary vein isolation (PVI) and 31 percent following circumferential ablation associated with creation of linear lesions [8,9]. Within this group of patients, reentrant tachycardia either exists as a macro- or microreentrant tachycardia. Microreentrant tachycardias are usually seen at sites of pulmonary vein reconnection following PVI for AF. Gaps in linear lesions formed for ablation of persistent or long-standing persistent AF promote the emergence of reentrant atrial tachyarrhythmias. These arrhythmias are often less well tolerated than the AF that prompted the ablation in the first place. They are often seen around the mitral valve (peri-mitral), in the atrium roof, or, less commonly, the septum. The cavotricuspid isthmus is not uncommonly involved. Studies have shown no added advantage to the creation of these lesions [10]. Society guidelines dissuade creation of these lines, confining them only to cases where IARTs are encountered [11]. Focal IARTs are eliminated by isolating the reconnected pulmonary vein. IART most often begins with an premature atrial complex (PAC; also referred to a premature atrial beat, premature supraventricular complex, or premature supraventricular beat) that tends to occur quite early [6,12-14]. The initiating beat may arise in either atrium, and an intraatrial conduction delay is necessary for the induction and maintenance of the arrhythmia. Ventricular premature beats very rarely initiate intraatrial reentrant tachycardia, and, if they do, it is usually due to rapid retrograde conduction through an accessory bypass tract, which results in the early prematurity usually required to initiate reentry [6]. CLINICAL MANIFESTATIONS The clinical manifestations and significance of intraatrial reentrant tachycardia (IART) are variable, depending upon the hemodynamic effects of the increase in heart rate and the heart rate achieved. Some patients are asymptomatic, while others have symptoms that range from palpitations and lightheadedness to, in rare cases, syncope. If a patient is examined during an episode of arrhythmia, they will have a regular heart rate greater than 100 beats per minute. Most episodes of IART do not precipitate hemodynamic compromise or limiting symptoms. However, higher ventricular rates associated with IART in a patient with underlying advanced https://www.uptodate.com/contents/intraatrial-reentrant-tachycardia/print 3/24 7/5/23, 10:24 AM Intraatrial reentrant tachycardia - UpToDate cardiac or pulmonary disease can sometimes exacerbate their disease, leading to signs and symptoms of angina, heart failure, or worsening systemic oxygenation. In the face of persistently elevated ventricular rates (eg, for weeks to months), particularly if baseline ventricular dysfunction exists, heart failure (tachycardia-mediated cardiomyopathy) may ensue. The atrial rates tend to be slower than the atrial rates in isthmus dependent atrial flutter, allowing 1:1 conduction from the atria to the ventricles and, subsequently, more potentially detrimental hemodynamic effects [15]. (See "Arrhythmia-induced cardiomyopathy".) DIAGNOSIS The diagnosis of intraatrial reentrant tachycardia (IART) should be considered in the presence of a regular but rapid pulse and heartbeat on physical examination. The diagnosis cannot be confirmed, however, without an electrocardiogram or, in most cases, invasive electrophysiologic studies. The suspicion for IART rests on the patient's history combined with the electrocardiogram. A patient with a cardiac surgical history, particularly for correction of a congenital heart defect, presenting with what looks like atrial flutter should be considered to suffer from IART. Like other reentrant tachycardias, the onset is sudden, and vagal maneuvers may help slow the ventricular rate but will not change the atrial rate. Electrocardiographic findings During an arrhythmic episode, the electrocardiographic (ECG) findings in IART are similar to those of most other regular supraventricular tachycardias (SVT), with evidence of atrial activity (P waves) associated with ventricular activity (QRS complexes) in a 1:1 fashion. In the appropriate clinical setting (eg, prior cardiac surgery, prior ablation, etc), the surface ECG can be highly suggestive of IART. However, the surface ECG alone cannot reliably distinguish between IART and other types of SVT, most notably focal atrial tachycardia. (See 'Electrophysiological features' below and 'Differential diagnosis' below.) As noted above, P wave morphology in IART is different from that in normal subjects due to a difference in the activation sequence of atrial depolarization. The sequence depends upon the reentrant circuit ( figure 1) which, in turn, may involve an anatomical obstacle or result from functional changes in refractoriness. (See 'Definition, prevalence, and mechanisms' above.) Clinically, the P wave morphology in aVL and V1 are useful clues in identifying the site of origin of the arrhythmia. A positive P wave in V1 and a negative P wave in aVL suggest a left atrial origin ( waveform 1), while a negative P wave in V1 and a positive P wave in aVL suggests a right atrial origin. These changes reflect the vectorial sequence. The left atrium is posterior and https://www.uptodate.com/contents/intraatrial-reentrant-tachycardia/print 4/24 7/5/23, 10:24 AM Intraatrial reentrant tachycardia - UpToDate to the left, so the sequence of the activation for an impulse arising in the left atrium usually is anterior towards V1 (leading to a positive P wave) and rightward away from aVL (leading to a negative P wave); the sequence is reversed with a right atrial origin. Both reentrant and automatic atrial tachycardias will show these morphologies. However, the electrocardiogram can be misleading in non-isthmus dependent macro reentrant tachycardias, particularly after catheter ablation for atrial fibrillation where the index of suspicion is always high that the atrial tachyarrhythmia is left sided [16]. Counterclockwise isthmus dependent atrial flutter characteristically displays upright flutter waves in V1 and negative flutter waves in leads II, III, and aVF. If the isthmus dependent flutter is clockwise, leads II, III, and aVF will display upright flutter waves. V1 will remain upright as well. Any departure from this pattern, particularly in the appropriate setting (postsurgical procedure, catheter, or surgical ablation) should lead one to suspect a nonisthmus dependent IART. Left sided IART can display similar electrocardiographic findings. (See "Electrocardiographic and electrophysiologic features of atrial flutter".) Electrophysiological features Clinically, it is important to distinguish intraatrial reentrant tachycardia (IART) from other supraventricular tachycardias (SVT), particularly focal atrial tachycardia. Since the surface electrocardiogram alone is not reliable in distinguishing IART from other types of SVT, invasive electrophysiologic studies (EPS) are employed to help make this distinction. Since macroreentrant atrial arrhythmias, including IART, are reentrant, they can be entrained during EPS with manifest and concealed fusion, and upon cessation of atrial pacing, the post pacing interval should be within 30 milliseconds of the tachycardia cycle length. The use of newer mapping techniques such as electroanatomic mapping further helps to make this distinction where focal mechanisms display centrifugal activation patterns, reentry displays an "early meets late", and the entire cycle length of the tachycardia can be mapped to the chamber containing the tachycardia. (See "Invasive diagnostic cardiac electrophysiology studies".) The behavior of reentrant and triggered activity atrial rhythms may be quite similar ( table 1), and intracardiac recordings are usually necessary to make the diagnosis with certainty. The following criteria have been used to help identify the type of arrhythmia: Atrial tachycardia has conventionally been called reentry when the arrhythmia is abrupt in onset and termination and can be started or stopped by spontaneous or programmed premature beats. However, triggered activity can show the same features [17]. A response to adenosine has been thought to be quite specific for atrial tachycardias due to cyclic AMP-mediated triggered activity and to enhanced automaticity. In several small cohort studies, adenosine was ineffective in terminating IART [18-20]. Although some https://www.uptodate.com/contents/intraatrial-reentrant-tachycardia/print 5/24 7/5/23, 10:24 AM Intraatrial reentrant tachycardia - UpToDate studies have provided conflicting data [17,21,22], the criteria used to define macroreentry did not exclude triggered activity as the cause of the arrhythmia [19]. In comparison to the atrial abnormalities, conduction through the AV node, the specialized infranodal conduction system (His bundle, fascicles and bundle branches, terminal Purkinje fibers), and the ventricles is not directly impaired in intraatrial reentrant tachycardia. Thus, the QRS pattern and duration should not be abnormal unless the rapid rate causes some type of functional conduction disturbance. Dual-loop figure-8 intraatrial reentry has been described that electrocardiographically mimics atrial flutter [23]. All such patients had undergone surgery for ostium secundum atrial septal defect (ASD) closure. The arrhythmias were quite resistant to antiarrhythmic therapy, and ablation of both loops may be required. This mechanism should be kept in mind in patients with corrected secundum ASD surgery. Differential diagnosis The differential diagnosis for intraatrial reentrant tachycardia (IART) is similar to that for other narrow QRS complex tachycardias (assuming there is normal AV conduction without bundle branch block) and includes: Atrial flutter Atrioventricular reciprocating tachycardia Focal atrial tachycardia Sinoatrial nodal reentrant tachycardia Sinus tachycardia, including inappropriate sinus tachycardia Atrioventricular nodal reentrant tachycardia A more in-depth discussion of the differential diagnosis of narrow QRS complex tachycardias is presented separately. TREATMENT While intraatrial reentrant tachycardia (IART) can be transient and asymptomatic, persistent and/or symptomatic IART requires treatment to relieve symptoms and to prevent long-term sequelae such as tachycardia-mediated cardiomyopathy. (See "Arrhythmia-induced cardiomyopathy".) Efforts to acutely terminate IART should begin with vagal maneuvers. If vagal maneuvers are unsuccessful, intravenous adenosine or verapamil can be administered. Catheter ablation of https://www.uptodate.com/contents/intraatrial-reentrant-tachycardia/print 6/24 7/5/23, 10:24 AM Intraatrial reentrant tachycardia - UpToDate IART is generally the treatment of choice for chronic management of this arrhythmia, given its efficacy combined with the relatively poor efficacy of pharmacologic therapy. Acute termination Autonomic maneuvers The autonomic innervation of the atria is less than that of the specialized myocardial areas which comprise the sinoatrial and atrioventricular nodes. Thus, vagal stimulation has a variable and often negligible effect on reentrant intraatrial rhythms. However, it has been estimated that this arrhythmia can be terminated by carotid sinus massage in approximately one-fourth of cases, particularly those arising in the right atrium [6]. As such, for the acute termination of symptomatic IART, we suggest carotid sinus massage or another vagal maneuver as the initial therapy. (See "Vagal maneuvers".) IV adenosine and verapamil Although there is controversy as to the specificity and efficacy of calcium channel blockers, both verapamil and adenosine have been reported to be effective in 30 to 50 percent or more of cases [17,18,21,24]. For symptomatic IART that is persistent in spite of vagal maneuvers, we suggest using adenosine via intravenous push for acute termination of the arrhythmia. (See "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'Intravenous adenosine'.) If adenosine is unsuccessful and symptomatic IART persists, we then use intravenous verapamil. We typically give a 5 to 10 mg IV bolus over two minutes; if no response, an additional 10 mg IV bolus may be administered 15 to 30 minutes following the initial dose. Chronic therapy Few studies have been published regarding chronic pharmacologic therapy in IART, which appears limited in many cases by lack of efficacy and drug toxicity [15]. Catheter ablation, however, has relatively high success rates for the acute termination of IART and for the long-term prevention of recurrences. Catheter ablation For IART that is symptomatic or persistent, thereby requiring long-term preventive therapy, we suggest catheter ablation as initial therapy rather than treatment with an antiarrhythmic agent. This is particularly true in younger patients who might be subject to the long-term side effect of years or decades of antiarrhythmic therapy. Catheter ablation of macroreentrant atrial arrhythmias, including IART, has become the preferred treatment modality, with rates of acute success in terminating IART exceeding 80 percent in several cohort studies [25-28]. However, ablation does require specialized expertise and background knowledge of the predisposing factors. Electroanatomic mapping (EAD) and irrigated tipped catheters have further improved the outcomes after these ablations [28-31]. https://www.uptodate.com/contents/intraatrial-reentrant-tachycardia/print 7/24 7/5/23, 10:24 AM Intraatrial reentrant tachycardia - UpToDate Excitable gaps are critical for all reentrant arrhythmias. An excitable gap allows a reentrant arrhythmia to be entrained, and if entrainment is achieved with concealed conduction, the critical pathway is identified. This feature is used therapeutically when overdrive atrial pacing is employed to terminate these arrhythmias. This was employed in the management of IART complicating surgically corrected transposition of the great arteries. The problem was that if it fails or if overdrive pacing accelerates the heart rate, it may lead to hemodynamic compromise and, in turn, death [32]. Since an excitable gap is usually present in IART, a PAC or atrial pacing can usually cause a beat to be inserted in the reentrant pathway, thereby terminating the arrhythmia [25,26]. Radiofrequency catheter ablation is extremely effective in patients with recurrent arrhythmias and has largely replaced chronic pacemaker therapy or surgery ( waveform 2A-C) [6,25-27]. Intraatrial reentrant tachycardia is common after surgery for congenital heart disease. Radiofrequency ablation is successful, but the recurrence rate is high [33-37]. The reentrant circuit for intraatrial reentrant tachycardia often involves the tricuspid valve isthmus following the Mustard/Senning procedure and in other types of repaired congenital heart disease [37]. The circuits in patients after the Fontan procedures differ, with the lateral right atrial wall being the more common area for successful radiofrequency ablation [37]. Ablation or pacing for typical atrial flutter may give rise to macroreentrant tachycardias arising in the right atrium, with such arrhythmias occurring more frequently as the use of ablation and devices becomes more common. The term "lower loop reentry" has been used to describe counterclockwise reentry around the inferior vena cava where the anterior portion of the reentrant circuit is the IVC-tricuspid valve isthmus and the posterior arm is the low posterior right atrial wall across the crista terminalis, making it a variant of typical atrial flutter in which the superior pivot point is lower [38]. At other times, circuits may involve the free wall of the right atrium. The ECG usually shows negative atrial deflections in the inferior leads [39]. EAD has proven useful in ablating right macro-reentrant tachycardias including IART, particularly when the mid-diastolically activated isthmus can be identified [40]. (See "Invasive diagnostic cardiac electrophysiology studies", section on 'Mapping and ablation'.) Pharmacologic therapy Available pharmacologic options for the prevention of IART include calcium channel blockers, sodium channel blockers, beta blockers, and amiodarone, all of which have been tried with some success at preventing IART recurrences. However, many patients with IART have structural heart disease, which limits the choice of available antiarrhythmic agents. If IART cannot be prevented, rate control can be attempted with non-dihydropyridine calcium channel blockers or beta adrenergic blockers. https://www.uptodate.com/contents/intraatrial-reentrant-tachycardia/print 8/24 7/5/23, 10:24 AM Intraatrial reentrant tachycardia - UpToDate For chronic therapy of IART when ablation is not an option or has been unsuccessful in preventing recurrent IART, we suggest verapamil as first-line therapy rather than a beta blocker or antiarrhythmic agent. This suggestion is based on the efficacy of verapamil in the acute termination of IART in addition to it generally being well-tolerated [24]. Beta blockers are also effective in some cases but have a larger spectrum of side effects. The use of calcium channel modulators, particularly class IC antiarrhythmic drugs ( table 2) such as flecainide and propafenone, is limited by major toxicities and proarrhythmic actions, especially in patients with coronary artery disease. Permanent pacemaker insertion In rare circumstances, such as when IART persists following an unsuccessful ablation and standard pharmacologic therapy, insertion of a permanent pacemaker may be considered. Pacemaker insertion allows for the more aggressive use of rate controlling medications, especially in patients with sinus node dysfunction. (See "Sinus node dysfunction: Treatment".) Pacemakers with anti-tachycardia features have been used to successfully terminate IART but have been associated with sudden death [41]. Our approach to treatment Based on the available evidence, we take the following approach to treatment: For the acute termination of symptomatic IART, we suggest carotid sinus massage or another vagal maneuver as the initial therapy. For symptomatic IART that is persistent in spite of vagal maneuvers, we suggest using adenosine via intravenous push rather than verapamil for acute termination of the arrhythmia. If adenosine is unsuccessful and symptomatic IART persists, we then use intravenous verapamil. For IART that is symptomatic or persistent, thereby requiring long-term preventive therapy, we suggest catheter ablation as initial therapy rather than treatment with an antiarrhythmic agent. For chronic therapy of IART when ablation is not an option or has been unsuccessful in preventing recurrent IART, we suggest verapamil as first-line therapy rather than a beta blocker or antiarrhythmic agent. If verapamil is unsuccessful or not tolerated, beta blockers or antiarrhythmic agents can be used. SOCIETY GUIDELINE LINKS https://www.uptodate.com/contents/intraatrial-reentrant-tachycardia/print 9/24 7/5/23, 10:24 AM Intraatrial reentrant tachycardia - UpToDate Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Supraventricular arrhythmias".) SUMMARY AND RECOMMENDATIONS Intraatrial reentrant tachycardia (IART) refers to any macroreentrant atrial tachycardia that does not utilize the cavotricuspid isthmus ( figure 1) as a critical pathway for the reentry to perpetuate. IART generally occurs in one of three settings: post-surgical repair of congenital heart disease, post-surgical scar (incisional tachycardia), or post-catheter-based or surgical management of atrial fibrillation, although it has also been reported in the absence of surgical or catheter intervention. (See 'Definition, prevalence, and mechanisms' above.) IART, which is responsible for approximately 6 percent of atrial tachycardias in patients referred for electrophysiologic studies, has a different activation sequence of atrial depolarization, leading to a P wave morphology that differs from that of normal sinus rhythm. IART most often begins with a PAC and is perpetuated via a reentry circuit. (See 'Definition, prevalence, and mechanisms' above.) The clinical manifestations and significance of IART are variable, depending upon the hemodynamic effects of the increase in heart rate and the heart rate achieved. Some patients are asymptomatic, while others have symptoms that range from palpitations and lightheadedness to, in rare cases, syncope. (See 'Clinical manifestations' above.) During an arrhythmic episode, the electrocardiographic (ECG) findings in IART are similar to those of most other regular supraventricular tachycardias (SVT), with evidence of atrial activity (P waves) associated with ventricular activity (QRS complexes) in a 1:1 fashion. In the appropriate clinical setting (eg, prior cardiac surgery, prior ablation, etc), the surface ECG can be highly suggestive of IART. However, the surface ECG alone cannot reliably distinguish between IART and other types of SVT, most notably focal atrial tachycardia. Because the surface electrocardiogram alone is not reliable in distinguishing IART from other types of SVT, invasive electrophysiological studies (EPS) are employed to help make this distinction. (See 'Electrocardiographic findings' above and 'Electrophysiological features' above.) The differential diagnosis for intraatrial reentrant tachycardia (IART) is similar to that for other narrow QRS complex tachycardias (assuming there is normal AV conduction without bundle branch block). (See 'Differential diagnosis' above.) https://www.uptodate.com/contents/intraatrial-reentrant-tachycardia/print 10/24 7/5/23, 10:24 AM Intraatrial reentrant tachycardia - UpToDate While intraatrial reentrant tachycardia (IART) can be transient and asymptomatic, persistent and/or symptomatic IART requires treatment to relieve symptoms and to prevent long-term sequelae such as tachycardia-mediated cardiomyopathy. For the acute termination of symptomatic IART, we suggest carotid sinus massage or another vagal maneuver as the initial therapy (Grade 2C). (See 'Autonomic maneuvers' above and "Vagal maneuvers".) For symptomatic IART that is persistent in spite of vagal maneuvers, we suggest using adenosine via intravenous push rather than verapamil for acute termination of the arrhythmia (Grade 2C). If adenosine is unsuccessful and symptomatic IART persists, we then use intravenous verapamil. (See 'IV adenosine and verapamil' above.) For IART that is symptomatic or persistent, thereby requiring long-term preventive therapy, we suggest catheter ablation as initial therapy rather than treatment with an antiarrhythmic agent (Grade 2C). (See 'Catheter ablation' above.) For chronic therapy of IART when ablation is not an option or has been unsuccessful in preventing recurrent IART, we suggest verapamil as first-line therapy rather than a beta blocker or antiarrhythmic agent (Grade 2C). If verapamil is unsuccessful or not tolerated, beta blockers or antiarrhythmic agents can be used. (See 'Pharmacologic therapy' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Saoudi N, Cos o F, Waldo A, et al. A classification of atrial flutter and regular atrial tachycardia according to electrophysiological mechanisms and anatomical bases; a Statement from a Joint Expert Group from The Working Group of Arrhythmias of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Eur Heart J 2001; 22:1162. 2. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Heart Rhythm 2016; 13:e136. 3. Kirsh JA, Walsh EP, Triedman JK. Prevalence of and risk factors for atrial fibrillation and intra- atrial reentrant tachycardia among patients with congenital heart disease. Am J Cardiol 2002; 90:338. https://www.uptodate.com/contents/intraatrial-reentrant-tachycardia/print 11/24 7/5/23, 10:24 AM Intraatrial reentrant tachycardia - UpToDate 4. Chae S, Oral H, Good E, et al. Atrial tachycardia after circumferential pulmonary vein ablation of atrial fibrillation: mechanistic insights, results of catheter ablation, and risk factors for recurrence. J Am Coll Cardiol 2007; 50:1781. 5. Fiala M, Chovanc k J, Neuwirth R, et al. Atrial macroreentry tachycardia in patients without obvious structural heart disease or previous cardiac surgical or catheter intervention: characterization of arrhythmogenic substrates, reentry circuits, and results of catheter ablation. J Cardiovasc Electrophysiol 2007; 18:824. 6. Josephson ME. Supraventricular Tachycardias. In: Clinical Cardiac Electrophysiology: Techniq ues and Interpretations, 4th, Lippincott, Williams, and Wilkins, Philadelphia 2008. 7. Gillette PC. Supraventricular arrhythmias in children. J Am Coll Cardiol 1985; 5:122B. 8. Gerstenfeld EP, Callans DJ, Dixit S, et al. Mechanisms of organized left atrial tachycardias occurring after pulmonary vein isolation. Circulation 2004; 110:1351. 9. Deisenhofer I, Estner H, Zrenner B, et al. Left atrial tachycardia after circumferential pulmonary vein ablation for atrial fibrillation: incidence, electrophysiological characteristics, and results of radiofrequency ablation. Europace 2006; 8:573. 10. Verma A, Jiang CY, Betts TR, et al. Approaches to catheter ablation for persistent atrial fibrillation. N Engl J Med 2015; 372:1812. 11. Calkins H, Hindricks G, Cappato R, et al. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Heart Rhythm 2017; 14:e275. 12. Wu D, Amat-y-leon F, Denes P, et al. Demonstration of sustained sinus and atrial re-entry as a mechanism of paroxysmal supraventricular tachycardia. Circulation 1975; 51:234. 13. Josephson ME. Paroxysmal supraventricular tachycardia: an electrophysiologic approach. Am J Cardiol 1978; 41:1123. 14. Akhtar M. Supraventricular tachycardias. Electrophysiologic mechanisms, diagnosis and pha rmacologic therapy. In: Tachycardias: Mechanisms, Diagnosis, Treatment, Josephson ME, We llens HJJ (Eds), Lea & Febiger, Philadelphia 1984. p.137. 15. Garson A Jr, Bink-Boelkens M, Hesslein PS, et al. Atrial flutter in the young: a collaborative study of 380 cases. J Am Coll Cardiol 1985; 6:871. 16. Medi C, Kalman JM. Prediction of the atrial flutter circuit location from the surface electrocardiogram. Europace 2008; 10:786. 17. Chen SA, Chiang CE, Yang CJ, et al. Sustained atrial tachycardia in adult patients. Electrophysiological characteristics, pharmacological response, possible mechanisms, and effects of radiofrequency ablation. Circulation 1994; 90:1262. https://www.uptodate.com/contents/intraatrial-reentrant-tachycardia/print 12/24 7/5/23, 10:24 AM Intraatrial reentrant tachycardia - UpToDate 18. Engelstein ED, Lippman N, Stein KM, Lerman BB. Mechanism-specific effects of adenosine on atrial tachycardia. Circulation 1994; 89:2645. 19. Iwai S, Markowitz SM, Stein KM, et al. Response to adenosine differentiates focal from macroreentrant atrial tachycardia: validation using three-dimensional electroanatomic mapping. Circulation 2002; 106:2793. 20. Markowitz SM, Nemirovksy D, Stein KM, et al. Adenosine-insensitive focal atrial tachycardia: evidence for de novo micro-re-entry in the human atrium. J Am Coll Cardiol 2007; 49:1324. 21. Kall JG, Kopp D, Olshansky B, et al. Adenosine-sensitive atrial tachycardia. Pacing Clin Electrophysiol 1995; 18:300. 22. Glatter KA, Cheng J, Dorostkar P, et al. Electrophysiologic effects of adenosine in patients with supraventricular tachycardia. Circulation 1999; 99:1034. 23. Shah D, Ja s P, Takahashi A, et al. Dual-loop intra-atrial reentry in humans. Circulation 2000; 101:631. 24. Garratt C, Linker N, Griffith M, et al. Comparison of adenosine and verapamil for termination of paroxysmal junctional tachycardia. Am J Cardiol 1989; 64:1310. 25. Kay GN, Chong F, Epstein AE, et al. Radiofrequency ablation for treatment of primary atrial tachycardias. J Am Coll Cardiol 1993; 21:901. 26. Lesh MD, Van Hare GF, Epstein LM, et al. Radiofrequency catheter ablation of atrial arrhythmias. Results and mechanisms. Circulation 1994; 89:1074. 27. Baker BM, Lindsay BD, Bromberg BI, et al. Catheter ablation of clinical intraatrial reentrant tachycardias resulting from previous atrial surgery: localizing and transecting the critical isthmus. J Am Coll Cardiol 1996; 28:411. 28. Delacretaz E, Ganz LI, Soejima K, et al. Multi atrial maco-re-entry circuits in adults with repaired congenital heart disease: entrainment mapping combined with three-dimensional electroanatomic mapping. J Am Coll Cardiol 2001; 37:1665. 29. Ja s P, Shah DC, Ha ssaguerre M, et al. Prospective randomized comparison of irrigated-tip versus conventional-tip catheters for ablation of common flutter. Circulation 2000; 101:772. 30. Triedman JK, Alexander ME, Berul CI, et al. Electroanatomic mapping of entrained and exit zones in patients with repaired congenital heart disease and intra-atrial reentrant tachycardia. Circulation 2001; 103:2060. 31. Triedman JK, Alexander ME, Love BA, et al. Influence of patient factors and ablative technologies on outcomes of radiofrequency ablation of intra-atrial re-entrant tachycardia in patients with congenital heart disease. J Am Coll Cardiol 2002; 39:1827. https://www.uptodate.com/contents/intraatrial-reentrant-tachycardia/print 13/24 7/5/23, 10:24 AM Intraatrial reentrant tachycardia - UpToDate 32. Stephenson EA, Casavant D, Tuzi J, et al. Efficacy of atrial antitachycardia pacing using the Medtronic AT500 pacemaker in patients with congenital heart disease. Am J Cardiol 2003; 92:871. 33. Triedman JK, Saul JP, Weindling SN, Walsh EP. Radiofrequency ablation of intra-atrial reentrant tachycardia after surgical palliation of congenital heart disease. Circulation 1995; 91:707. 34. Van Hare GF, Lesh MD, Ross BA, et al. Mapping and radiofrequency ablation of intraatrial reentrant tachycardia after the Senning or Mustard procedure for transposition ofthe great arteries. Am J Cardiol 1996; 77:985. 35. Triedman JK, Bergau DM, Saul JP, et al. Efficacy of radiofrequency ablation for control of intraatrial reentrant tachycardia in patients with congenital heart disease. J Am Coll Cardiol 1997; 30:1032. 36. Dorostkar PC, Cheng J, Scheinman MM. Electroanatomical mapping and ablation of the substrate supporting intraatrial reentrant tachycardia after palliation for complex congenital heart disease. Pacing Clin Electrophysiol 1998; 21:1810. 37. Collins KK, Love BA, Walsh EP, et al. Location of acutely successful radiofrequency catheter ablation of intraatrial reentrant tachycardia in patients with congenital heart disease. Am J Cardiol 2000; 86:969. 38. Cheng J, Cabeen WR Jr, Scheinman MM. Right atrial flutter due to lower loop reentry: mechanism and anatomic substrates. Circulation 1999; 99:1700. 39. Kall JG, Rubenstein DS, Kopp DE, et al. Atypical atrial flutter originating in the right atrial free wall. Circulation 2000; 101:270. 40. DePonti, R, Verlato, et al. Treatment of macro-re-entrant atrial tachycardia based on electroanatomic mapping: Identification and ablation of the mid-diastolic isthmus. Europace 2007; 9:499. 41. Rhodes LA, Walsh EP, Gamble WJ, et al. Benefits and potential risks of atrial antitachycardia pacing after repair of congenital heart disease. Pacing Clin Electrophysiol 1995; 18:1005. Topic 937 Version 28.0 https://www.uptodate.com/contents/intraatrial-reentrant-tachycardia/print 14/24 7/5/23, 10:24 AM Intraatrial reentrant tachycardia - UpToDate GRAPHICS Reentrant circuit of typical atrial flutter within the right atrium Schematic representation of reentrant circuit (red arrow) of typical (type 1) atrial flutter. The reentrant impulse rotates in a counterclockwise direction around the tricuspid annulus. The crista terminalis (CT) and eustacian ridge (ER) serve as lines of block, preventing the impulse from short-circuiting the annulus. Ablation is performed in the isthmus between the IVC and TA, which is an obligatory part of the circuit. SVC: superior vena cava; CS: coronary sinus; IVC: inferior vena cava; FO: foramen ovale Graphic 52904 Version 5.0 https://www.uptodate.com/contents/intraatrial-reentrant-tachycardia/print 15/24 7/5/23, 10:24 AM Intraatrial reentrant tachycardia - UpToDate Sites of reentry in supraventricular tachyarrhythmias Reentry may occur around a fixed anatomic obstacle or may be functional, developing in the absence of an anatomic obstacle and resulting from the intrinsic heterogeneity of electrophysiologic properties of the myocardial tissue. Reentrant circuits leading to a supraventricular tachyarrhythmia may develop in various parts of the heart: within and around the sinoatrial node (sinus node reentry); within the atrial myocardium (atrial tachycardia, atrial flutter, or atrial fibrillation); within the atrioventricular (AV) node due to the presence of a slow and fast pathway (atrioventricular nodal reentrant tachycardia); or involving the AV node and an accessory pathway (AP) (atrioventricular reentrant tachycardia). LAF: left anterior fascicle; LPF: left posterior fascicle. Graphic 82249 Version 4.0 https://www.uptodate.com/contents/intraatrial-reentrant-tachycardia/print 16/24 7/5/23, 10:24 AM Intraatrial reentrant tachycardia - UpToDate Electrocardiogram in atrial tachycardia suggesting left atrial origin of the arrhythmia

2017; 14:e275. 12. Wu D, Amat-y-leon F, Denes P, et al. Demonstration of sustained sinus and atrial re-entry as a mechanism of paroxysmal supraventricular tachycardia. Circulation 1975; 51:234. 13. Josephson ME. Paroxysmal supraventricular tachycardia: an electrophysiologic approach. Am J Cardiol 1978; 41:1123. 14. Akhtar M. Supraventricular tachycardias. Electrophysiologic mechanisms, diagnosis and pha rmacologic therapy. In: Tachycardias: Mechanisms, Diagnosis, Treatment, Josephson ME, We llens HJJ (Eds), Lea & Febiger, Philadelphia 1984. p.137. 15. Garson A Jr, Bink-Boelkens M, Hesslein PS, et al. Atrial flutter in the young: a collaborative study of 380 cases. J Am Coll Cardiol 1985; 6:871. 16. Medi C, Kalman JM. Prediction of the atrial flutter circuit location from the surface electrocardiogram. Europace 2008; 10:786. 17. Chen SA, Chiang CE, Yang CJ, et al. Sustained atrial tachycardia in adult patients. Electrophysiological characteristics, pharmacological response, possible mechanisms, and effects of radiofrequency ablation. Circulation 1994; 90:1262. https://www.uptodate.com/contents/intraatrial-reentrant-tachycardia/print 12/24 7/5/23, 10:24 AM Intraatrial reentrant tachycardia - UpToDate 18. Engelstein ED, Lippman N, Stein KM, Lerman BB. Mechanism-specific effects of adenosine on atrial tachycardia. Circulation 1994; 89:2645. 19. Iwai S, Markowitz SM, Stein KM, et al. Response to adenosine differentiates focal from macroreentrant atrial tachycardia: validation using three-dimensional electroanatomic mapping. Circulation 2002; 106:2793. 20. Markowitz SM, Nemirovksy D, Stein KM, et al. Adenosine-insensitive focal atrial tachycardia: evidence for de novo micro-re-entry in the human atrium. J Am Coll Cardiol 2007; 49:1324. 21. Kall JG, Kopp D, Olshansky B, et al. Adenosine-sensitive atrial tachycardia. Pacing Clin Electrophysiol 1995; 18:300. 22. Glatter KA, Cheng J, Dorostkar P, et al. Electrophysiologic effects of adenosine in patients with supraventricular tachycardia. Circulation 1999; 99:1034. 23. Shah D, Ja s P, Takahashi A, et al. Dual-loop intra-atrial reentry in humans. Circulation 2000; 101:631. 24. Garratt C, Linker N, Griffith M, et al. Comparison of adenosine and verapamil for termination of paroxysmal junctional tachycardia. Am J Cardiol 1989; 64:1310. 25. Kay GN, Chong F, Epstein AE, et al. Radiofrequency ablation for treatment of primary atrial tachycardias. J Am Coll Cardiol 1993; 21:901. 26. Lesh MD, Van Hare GF, Epstein LM, et al. Radiofrequency catheter ablation of atrial arrhythmias. Results and mechanisms. Circulation 1994; 89:1074. 27. Baker BM, Lindsay BD, Bromberg BI, et al. Catheter ablation of clinical intraatrial reentrant tachycardias resulting from previous atrial surgery: localizing and transecting the critical isthmus. J Am Coll Cardiol 1996; 28:411. 28. Delacretaz E, Ganz LI, Soejima K, et al. Multi atrial maco-re-entry circuits in adults with repaired congenital heart disease: entrainment mapping combined with three-dimensional electroanatomic mapping. J Am Coll Cardiol 2001; 37:1665. 29. Ja s P, Shah DC, Ha ssaguerre M, et al. Prospective randomized comparison of irrigated-tip versus conventional-tip catheters for ablation of common flutter. Circulation 2000; 101:772. 30. Triedman JK, Alexander ME, Berul CI, et al. Electroanatomic mapping of entrained and exit zones in patients with repaired congenital heart disease and intra-atrial reentrant tachycardia. Circulation 2001; 103:2060. 31. Triedman JK, Alexander ME, Love BA, et al. Influence of patient factors and ablative technologies on outcomes of radiofrequency ablation of intra-atrial re-entrant tachycardia in patients with congenital heart disease. J Am Coll Cardiol 2002; 39:1827. https://www.uptodate.com/contents/intraatrial-reentrant-tachycardia/print 13/24 7/5/23, 10:24 AM Intraatrial reentrant tachycardia - UpToDate 32. Stephenson EA, Casavant D, Tuzi J, et al. Efficacy of atrial antitachycardia pacing using the Medtronic AT500 pacemaker in patients with congenital heart disease. Am J Cardiol 2003; 92:871. 33. Triedman JK, Saul JP, Weindling SN, Walsh EP. Radiofrequency ablation of intra-atrial reentrant tachycardia after surgical palliation of congenital heart disease. Circulation 1995; 91:707. 34. Van Hare GF, Lesh MD, Ross BA, et al. Mapping and radiofrequency ablation of intraatrial reentrant tachycardia after the Senning or Mustard procedure for transposition ofthe great arteries. Am J Cardiol 1996; 77:985. 35. Triedman JK, Bergau DM, Saul JP, et al. Efficacy of radiofrequency ablation for control of intraatrial reentrant tachycardia in patients with congenital heart disease. J Am Coll Cardiol 1997; 30:1032. 36. Dorostkar PC, Cheng J, Scheinman MM. Electroanatomical mapping and ablation of the substrate supporting intraatrial reentrant tachycardia after palliation for complex congenital heart disease. Pacing Clin Electrophysiol 1998; 21:1810. 37. Collins KK, Love BA, Walsh EP, et al. Location of acutely successful radiofrequency catheter ablation of intraatrial reentrant tachycardia in patients with congenital heart disease. Am J Cardiol 2000; 86:969. 38. Cheng J, Cabeen WR Jr, Scheinman MM. Right atrial flutter due to lower loop reentry: mechanism and anatomic substrates. Circulation 1999; 99:1700. 39. Kall JG, Rubenstein DS, Kopp DE, et al. Atypical atrial flutter originating in the right atrial free wall. Circulation 2000; 101:270. 40. DePonti, R, Verlato, et al. Treatment of macro-re-entrant atrial tachycardia based on electroanatomic mapping: Identification and ablation of the mid-diastolic isthmus. Europace 2007; 9:499. 41. Rhodes LA, Walsh EP, Gamble WJ, et al. Benefits and potential risks of atrial antitachycardia pacing after repair of congenital heart disease. Pacing Clin Electrophysiol 1995; 18:1005. Topic 937 Version 28.0 https://www.uptodate.com/contents/intraatrial-reentrant-tachycardia/print 14/24 7/5/23, 10:24 AM Intraatrial reentrant tachycardia - UpToDate GRAPHICS Reentrant circuit of typical atrial flutter within the right atrium Schematic representation of reentrant circuit (red arrow) of typical (type 1) atrial flutter. The reentrant impulse rotates in a counterclockwise direction around the tricuspid annulus. The crista terminalis (CT) and eustacian ridge (ER) serve as lines of block, preventing the impulse from short-circuiting the annulus. Ablation is performed in the isthmus between the IVC and TA, which is an obligatory part of the circuit. SVC: superior vena cava; CS: coronary sinus; IVC: inferior vena cava; FO: foramen ovale Graphic 52904 Version 5.0 https://www.uptodate.com/contents/intraatrial-reentrant-tachycardia/print 15/24 7/5/23, 10:24 AM Intraatrial reentrant tachycardia - UpToDate Sites of reentry in supraventricular tachyarrhythmias Reentry may occur around a fixed anatomic obstacle or may be functional, developing in the absence of an anatomic obstacle and resulting from the intrinsic heterogeneity of electrophysiologic properties of the myocardial tissue. Reentrant circuits leading to a supraventricular tachyarrhythmia may develop in various parts of the heart: within and around the sinoatrial node (sinus node reentry); within the atrial myocardium (atrial tachycardia, atrial flutter, or atrial fibrillation); within the atrioventricular (AV) node due to the presence of a slow and fast pathway (atrioventricular nodal reentrant tachycardia); or involving the AV node and an accessory pathway (AP) (atrioventricular reentrant tachycardia). LAF: left anterior fascicle; LPF: left posterior fascicle. Graphic 82249 Version 4.0 https://www.uptodate.com/contents/intraatrial-reentrant-tachycardia/print 16/24 7/5/23, 10:24 AM Intraatrial reentrant tachycardia - UpToDate Electrocardiogram in atrial tachycardia suggesting left atrial origin of the arrhythmia Leads aVL and V1 show a regular narrow QRS complex tachycardia with P waves present before each QRS complex. The P waves are abnormal when compared with those during sinus rhythm occurring after the tachycardia breaks (arrow). The P wave morphology - negative in aVL, positive in V1 - suggests a left atrial origin. Graphic 73578 Version 4.0 https://www.uptodate.com/contents/intraatrial-reentrant-tachycardia/print 17/24 7/5/23, 10:24 AM Intraatrial reentrant tachycardia - UpToDate Electrophysiologic characteristics of the different types of supraventricular tachycardia (SVT) Characteristic Reentrant Triggered Automatic Initiation by extrastimuli and/or continuous pacing Yes Yes No Initiation by continuous pacing depends upon the rate No Yes No and number of stimuli Termination by extrastimuli Yes No No Termination by continuous pacing (overdrive) Yes Yes No Overdrive suppression of tachycardia No No Yes Overdrive enhancement of tachycardia Yes Yes No Entrainment possible Yes No No First P wave identical to P waves in arrhythmia No Sometimes Yes Warm-up or acceleration of pacemaker after onset No Sometimes Yes Graphic 53347 Version 2.0 https://www.uptodate.com/contents/intraatrial-reentrant-tachycardia/print 18/24 7/5/23, 10:24 AM Intraatrial reentrant tachycardia - UpToDate Electrophysiology study (EPS) tracing during mapping of atrial tachycardia Shown are three surface electrocardiogram (ECG) leads (I, aVF, V1) and intracardiac recordings from the high posterior right atrium (HRA); posterior left atrium (USER1 and USER 3); proximal, mid, and distal coronary sinuses (CS9-10, CS5-6, CS1-2); and right ventricular apex (RVA). The patient had an incessant atrial tachycardia and dilated cardiomyopathy (left ventricular ejection fraction 9 percent) referred for cardiac transplant evaluation. The P wave (*) falls at the end of the T wave in the surface ECG; its onset is difficult to discern. However, the intracardiac electrograms demonstrate obvious atrial (A) and ventricular (V) activity. Activation mapping involves positioning the mapping catheters in the right (HRA) and left atria (USER) to record earliest electrical activity during the tachycardia. The left atrial catheter records earlier electrical activity (arrow) than the right atrial catheter, but the timing with respect to the surface P wave is obscured because of the T wave of the preceding QRS complex. Graphic 58120 Version 7.0 https://www.uptodate.com/contents/intraatrial-reentrant-tachycardia/print 19/24 7/5/23, 10:24 AM Intraatrial reentrant tachycardia - UpToDate Electrophysiologic (EP) study tracing showng a ventricular premature beat (VPB) during mapping of an atrial tachycardia Three surface ECG leads (I, aVF, V1) and intracardiac recordings from the high posterior right atrium (HRA); posterior left atrium (USER1 and USER 3); proximal, mid, and distal coronary sinus (CS9-10, CS5-6, CS1-2); and right ventricular apex (RVA) in a patient with atrial tachycardia. A ventricular premature beat (VPB) introduced from the right ventricular outflow tract has no effect on the underlying atrial tachycardia, but the onset of the P wave (P) in the surface ECG recordings can be seen more clearly as it is no longer superimposed on the T wave. The atrial electrogram (A) recorded from the right atrial catheter precedes the surface P wave by 30 msec, but the signal from the left atrial catheter (USER1) precedes the surface P wave by 50 msec (arrow). V: ventricular electrogram. Graphic 50219 Version 3.0 https://www.uptodate.com/contents/intraatrial-reentrant-tachycardia/print 20/24 7/5/23, 10:24 AM Intraatrial reentrant tachycardia - UpToDate Electrophysiology (EP) study tracing obtained during radiofrequency catheter ablation of atrial tachycardia Three surface ECG leads (I, aVF, V1) and intracardiac recordings from the high posterior right atrium (HRA); posterior left atrium (USER1 and USER 3); proximal, mid, and distal coronary sinus (CS9-10, CS5-6, CS1-2); and right ventricular apex (RVA) in a patient with atrial tachycardia. Radiofrequency energy application at the left atrial site of earliest atrial activation (USER1) causes initial rate acceleration, consistent with heating of an automatic focus; this is followed by abrupt termination (*) of the atrial tachycardia, resulting in a junctional rhythm. The patient had no further tachycardia during follow-up and left ventricular function returned to normal within four months of the ablation procedure, confirming that the cardiomyopathy was tachycardia induced. Graphic 82052 Version 3.0 https://www.uptodate.com/contents/intraatrial-reentrant-tachycardia/print 21/24 7/5/23, 10:24 AM Intraatrial reentrant tachycardia - UpToDate Revised (2018) Vaughan Williams classification of antiarrhythmic drugs abridged table Class 0 (HCN channel blockers) Ivabradine Class I (voltage-gated Na+ channel blockers) Class Ia (intermediate dissociation): Quinidine, ajmaline, disopyramide, procainamide Class Ib (rapid dissociation): Lidocaine, mexilitine Class Ic (slow dissociation): Propafenone, flecainide Class Id (late current): Ranolazine Class II (autonomic inhibitors and activators) Class IIa (beta blockers): Nonselective: carvedilol, propranolol, nadolol Selective: atenolol, bisoprolol, betaxolol, celiprolol, esmolol, metoprolol Class IIb (nonselective beta agonists): Isoproterenol Class IIc (muscarinic M2 receptor inhibitors): Atropine, anisodamine, hyoscine, scopolamine Class IId (muscarinic M2 receptor activators): Carbachol, pilocarpine, methacholine, digoxin Class IIe (adenosine A1 receptor activators): Adenosine Class III (K+ channel blockers and openers) Class IIIa (voltage dependent K+ channel blockers): Ambasilide, amiodarone, dronedarone, dofetilide, ibutilide, sotalol, vernakalant Class IIIb (metabolically dependent K+ channel openers): https://www.uptodate.com/contents/intraatrial-reentrant-tachycardia/print 22/24 7/5/23, 10:24 AM Intraatrial reentrant tachycardia - UpToDate Nicorandil, pinacidil Class IV (Ca++ handling modulators) Class IVa (surface membrane Ca++ channel blockers): Bepridil, diltiazem, verapamil Class IVb (intracellular Ca++ channel blockers): Flecainide, propafenone Class V (mechanosensitive channel blockers): No approved medications Class VI (gap junction channel blockers) No approved medications Class VII (upstream target modulators) Angiotensin converting enzyme inhibitors Angiotensin receptor blockers Omega-3 fatty acids Statins HCN: hyperpolarization-activated cyclic nucleotide-gated; Na: sodium; K: potassium; Ca: calcium. Graphic 120433 Version 3.0 https://www.uptodate.com/contents/intraatrial-reentrant-tachycardia/print 23/24 7/5/23, 10:24 AM Intraatrial reentrant tachycardia - UpToDate Contributor Disclosures Munther K Homoud, MD Speaker's Bureau: Abbott [Live heart dissection]. All of the relevant financial relationships listed have been mitigated. Samuel L vy, MD No relevant financial relationship(s) with ineligible companies to disclose. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. 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7/5/23, 10:25 AM Multifocal atrial tachycardia - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Multifocal atrial tachycardia : Alfred Buxton, MD : Hugh Calkins, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Feb 21, 2022. INTRODUCTION Multifocal atrial tachycardia (MAT) is an arrhythmia that can be seen in a variety of clinical disorders [1]. In addition to a heart rate greater than 100 beats per minute (bpm), the characteristic electrocardiographic (ECG) feature is variability in P-wave morphology. Although this abnormality had been noted for many years during some types of atrial tachycardia, the term MAT became commonplace terminology in the late 1960s [2]. Patients with multiple P-wave morphologies but a normal heart rate (60 to 100 bpm) are considered to have a wandering atrial pacemaker, since the heart rate does not meet criteria for a tachycardia. (See 'Terminology' below.) This topic will review the definition, pathogenesis, etiology, and treatment of MAT in adults. Other tachycardias of atrial origin, as well as the discussion of this arrhythmia in children, are reviewed separately. (See "Focal atrial tachycardia" and "Atrial tachyarrhythmias in children" and "Atrioventricular nodal reentrant tachycardia" and "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway" and "Atrial fibrillation: Overview and management of new-onset atrial fibrillation".) DEFINITION, PATHOGENESIS, AND PREVALENCE As with any tachycardia, the heart rate in MAT exceeds 100 bpm. To distinguish MAT from other tachyarrhythmias of atrial origin, there should be organized atrial activity yielding P waves with three or more different morphologies. (See 'Clinical manifestations and diagnosis' below.) https://www.uptodate.com/contents/multifocal-atrial-tachycardia/print 1/20 7/5/23, 10:25 AM Multifocal atrial tachycardia - UpToDate Terminology A number of authors have used the term "chaotic" to describe MAT [3-5]. However, chaos in modern usage in nonlinear dynamics and mathematics implies there is order in what appear to be random events [6]. A more accurate term for this arrhythmia is probably "multiform" as there is no proof that the arrhythmia is actually multifocal, although multifocal remains the commonly used term [1]. The tachycardic threshold for multifocal atrial tachycardia (MAT) has traditionally been set at 100 bpm, but a review of 60 patients with multifocal atrial arrhythmias found a stronger association between the incidence of COPD exacerbations and the diagnosis of MAT if a threshold of 90 bpm was used [7]. The definition of MAT also requires the presence of at least three distinct P-wave morphologies. Some patients have similar ECG findings with multiple P-wave morphologies but do not meet criteria for tachycardia. The arrhythmia is called a multifocal atrial rhythm or wandering atrial pacemaker if the rate is between 60 and 100 bpm. A distinction has been made between the two based on the clinical picture, with a wandering atrial pacemaker usually occurring in the asymptomatic or less ill individual [1]. Mechanisms The changing morphology of the P waves and the variable PR interval suggests that the atrial pacemaker activity arises from different atrial locations. However, the variable PR interval is probably more likely a result of the variable atrial rate. Alternatively, a single focus with different exit pathways or abnormalities in intraatrial conduction could produce the identical ECG findings. There have only been a few invasive electrophysiologic investigations of MAT, but one study did show abnormal intraatrial, atrionodal, and atrioventricular (AV) nodal conduction in many individuals with MAT [5]. One case report demonstrated origin of multiform premature atrial complex (PACs; also referred to a premature atrial beat, premature supraventricular complex, or premature supraventricular beat) from adjacent areas in the right pulmonary veins [8]. However, this patient did not have the typical setting in which MAT is seen. Automaticity refers to normal, accelerated normal, or abnormal pacemaker activity. Triggered activity, on the other hand, results from a normal stimulus giving rise to afterdepolarization, which, if threshold is attained, can result in regenerative action potentials (resulting in tachycardia) in any cardiac tissue. Reentry refers to a circuit in which previously excited tissue is re-excited, producing an extra beat or a sustained rhythm. The occasional responsiveness of MAT to verapamil suggests intracellular calcium overload causing afterdepolarizations leading to triggered activity as the underlying mechanism [9,10]. It is thought that MAT results from right atrial hypertension and distension, either from secondary pulmonary hypertension from advanced COPD or left ventricular dysfunction caused https://www.uptodate.com/contents/multifocal-atrial-tachycardia/print 2/20 7/5/23, 10:25 AM Multifocal atrial tachycardia - UpToDate by comorbid processes such as coronary heart disease, systemic hypertension, or aortic stenosis [11,12]. However, although frequently associated with exacerbations of pulmonary disease, MAT may occur in other circumstances, so atrial distension may not be a universal mechanism. Associated arrhythmias MAT (and wandering atrial pacemaker) is commonly accompanied by PACs and can itself be considered a prolonged sequence of PACs [1]. The majority of episodes of MAT are self-limited and nonsustained. MAT may be associated with or precede atrial fibrillation [2,13]. In one report of 31 patients, for example, 55 percent developed atrial fibrillation or flutter [14]. Prevalence MAT is an uncommon but not rare arrhythmia. It has been estimated to occur in 0.05 to 0.32 percent of ECGs in general hospitals and in 0.37 percent of hospitalized patients [1,2]. The average age is approximately 70 years. These older adults are generally quite ill, with an in-hospital mortality rate of 40 to 60 percent due to pulmonary, cardiac, and other serious diseases. ASSOCIATED CLINICAL CONDITIONS Pulmonary disease MAT is associated with significant lung disease in roughly 60 percent of cases [1,15]. Furthermore, this arrhythmia has been identified in up to 20 percent of patients hospitalized for acute respiratory failure [16]. COPD is the most common pulmonary disorder associated with MAT, but this arrhythmia can also occur with pneumonia and pulmonary embolism. Hypoxia, hypercapnia, acidosis, autonomic imbalance, right atrial enlargement, and therapy with aminophylline, theophylline, or isoproterenol all may contribute to the enhanced ectopic atrial activity [2,9,17] (see "Arrhythmias in COPD"). MAT has also been identified in patients with coronavirus disease 2019 (COVID-19) [18]. In this setting, the presence of MAT was reported to not be associated with increased mortality [18]. (See "COVID-19: Arrhythmias and conduction system disease".) Cardiac disease MAT can occur in the presence of coronary, valvular, hypertensive and other types of heart disease, particularly when associated with heart failure and/or underlying lung disease. Affected patients tend to have elevated pulmonary capillary wedge and pulmonary end- diastolic pressures as well as a low-normal cardiac index [2,13]. Interactions between cardiac and pulmonary disease In advanced cases of cardiac and pulmonary disease, MAT may be part of a complicated pathophysiologic complex in which several conditions (eg, pulmonary hypertension, elevated left ventricular filling pressures, and https://www.uptodate.com/contents/multifocal-atrial-tachycardia/print 3/20 7/5/23, 10:25 AM Multifocal atrial tachycardia - UpToDate MAT) contribute to the progression and persistence of each other [12,19,20]. Illustrations of these relationships include: Severe pulmonary arterial hypertension has been associated with and may cause LV diastolic dysfunction [19,20]. (See "Pulmonary hypertension due to left heart disease (group 2 pulmonary hypertension) in adults" and "Heart failure with preserved ejection fraction: Clinical manifestations and diagnosis" and "Treatment and prognosis of pulmonary arterial hypertension in adults (group 1)".) Theoretically, the rapid heart rate associated with MAT decreases diastolic filling time and can result in increased LV diastolic pressure, which in turn increases pulmonary artery pressure that encourages MAT [12]. However, the vast majority of episodes of MAT are brief and not associated with symptoms or recognizable hemodynamic compromise. (See "Heart failure with preserved ejection fraction: Clinical manifestations and diagnosis".) Prolonged episodes of tachycardia can cause a cardiomyopathy. (See "Arrhythmia-induced cardiomyopathy".) Miscellaneous MAT is also associated with a number of other disorders: Hypokalemia MAT has been associated with hypokalemia, most often induced by diuretic use [1-3]. Hypokalemia may predispose to MAT by increasing the rate of phase 4 depolarization ( figure 1) in atrial tissues. (See "Clinical manifestations and treatment of hypokalemia in adults", section on 'Cardiac arrhythmias and ECG abnormalities'.) Hypomagnesemia The administration of magnesium can suppress MAT in hypomagnesemic and, at times, in apparently normomagnesemic patients [21]. (See "Hypomagnesemia: Clinical manifestations of magnesium depletion".) Drugs As noted above, isoproterenol, aminophylline, and theophylline can induce or exacerbate MAT, particularly in the presence of pulmonary disease [2,9,17]. By comparison, digitalis is generally not considered to be a cause of MAT, although some reports suggest that such an association may exist [2,3,13,14,22,23]. Chronic renal failure Approximately 15 percent of patients with MAT have chronic renal failure [3,22]. It is unclear, however, if this represents a cause-and-effect relationship. Other MAT also can occur in sepsis and after recent surgery, particularly if the patient has pulmonary compromise and/or heart failure [1,2]. https://www.uptodate.com/contents/multifocal-atrial-tachycardia/print 4/20 7/5/23, 10:25 AM Multifocal atrial tachycardia - UpToDate MAT in children and young adults The association of MAT with serious illness is generally less in children than in adults. Information on multifocal (or chaotic) atrial tachycardia in children is presented separately. (See "Atrial tachyarrhythmias in children", section on 'Chaotic atrial tachycardia'.) CLINICAL MANIFESTATIONS AND DIAGNOSIS Clinical manifestations In most cases, the clinical manifestations of MAT differ from those of other tachyarrhythmias in that symptoms predominantly relate to the underlying precipitating illness rather than the arrhythmia [15]. Patients have an irregular heart rate greater than 100 bpm. The arrhythmia is usually recognized only by ECG monitoring, as the majority of patients are acutely ill and on continuous ECG monitoring. Patients rarely present with symptoms such as palpitations. Presyncope or syncope is generally not associated with this arrhythmia. Given that the majority of patients with MAT are concurrently affected by advanced or decompensated pulmonary disease, many patients have typical symptoms related to the underlying lung disease (eg, shortness of breath, wheezing, productive cough, etc) or acute metabolic derangements. Most episodes of MAT do not precipitate hemodynamic compromise or limiting symptoms [15]. However, higher heart rates associated with MAT can sometimes worsen systemic oxygenation in patients with advanced pulmonary disease. Additionally, in patients with coexistent advanced cardiac disease, namely those with severe multivessel obstructive coronary artery disease or decompensated heart failure, the faster heart rates associated with MAT can exacerbate heart disease, leading to signs and symptoms of cardiac decompensation (eg, angina, dyspnea, orthopnea). Symptomatic decompensation of underlying cardiac or pulmonary disease is an indication for pharmacologic therapy aimed specifically at the tachycardia rather than therapy to control the underlying disease process. (See 'Pharmacologic therapy' below.) Diagnosis The diagnosis of MAT can be suspected from the presence of an irregular rapid pulse and heartbeat on physical examination, usually in a patient with underlying, often poorly controlled, cardiac or pulmonary disease. The diagnosis cannot be confirmed, however, without an ECG. A diagnosis of MAT requires the following be present on the ECG ( waveform 1) [1,2]: Discrete P waves with at least three different morphologies (including the normal sinus P wave). An atrial rate greater than 100 bpm, which is the classic definition of MAT [2]. However, based upon data from a series of patients with chronic obstructive pulmonary disease https://www.uptodate.com/contents/multifocal-atrial-tachycardia/print 5/20 7/5/23, 10:25 AM Multifocal atrial tachycardia - UpToDate (COPD), a threshold of 90 bpm has been proposed [7]. P waves that return to the baseline and thus are separated by isoelectric intervals. P-P intervals, P-R duration, and R-R intervals that vary. It should be recognized that the primary abnormality is the variability in P-P intervals. The variation in P-R intervals follows because of the physiologic response of the AV node to changing atrial rate. The variation in R-R intervals follows as a physiologic consequence of the variation in the P-P and P-R intervals. Differential diagnosis The differential diagnosis for MAT is similar to that of other narrow QRS complex tachycardias with an irregular rhythm (assuming there is normal AV conduction without bundle branch block) and includes: Sinus tachycardia with frequent PACs or ventricular premature beats (VPBs) Atrial tachycardias (including atrial flutter) with variable AV conduction Atrial fibrillation MAT can usually be differentiated from both atrial flutter with variable AV conduction and sinus tachycardia with APBs/VPBs by the regular P-P interval seen in both atrial flutter and sinus tachycardia, which is not present in MAT. (See "Electrocardiographic and electrophysiologic features of atrial flutter", section on 'Electrocardiographic features'.) MAT, with its organized atrial activity resulting in P waves on surface ECG, can be readily distinguished from atrial fibrillation, which lacks any discernible P waves. However, MAT can and does degenerate into atrial fibrillation in some patients. (See "The electrocardiogram in atrial fibrillation".) A more in-depth discussion of the differential diagnosis of narrow QRS complex tachycardias is presented separately. (See "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation".) TREATMENT Most episodes of MAT do not precipitate hemodynamic compromise or symptoms. Thus, therapy in patients with MAT should be aimed at the inciting underlying disease [15,24,25]. Amelioration of MAT generally parallels improvement in severe pulmonary or cardiac disease or sepsis. Not infrequently, medication used for the treatment of pulmonary disease, such as theophylline, induces or exacerbates MAT [2,9,17]. In many cases, MAT is precipitated by poor oxygenation and/or acid-base disturbances. https://www.uptodate.com/contents/multifocal-atrial-tachycardia/print 6/20 7/5/23, 10:25 AM Multifocal atrial tachycardia - UpToDate In addition to treatment for the underlying pathologic condition associated with MAT, specific therapies for the tachycardia are sometimes used (usually only if the arrhythmia is so frequent or sustained as to compromise oxygenation or cause hemodynamic compromise). In patients with electrolyte disturbances, maintaining magnesium and potassium levels in the normal range is important. Pharmacologic therapy to slow the ventricular heart rate, using either verapamil or a beta blocker, is administered for patients with signs or symptoms felt to be related to their tachycardia. While rate control therapy is often very effective, there is no role for electrical cardioversion or antiarrhythmic drug therapy in patients with MAT. Magnesium and potassium repletion Patients with MAT and associated hypokalemia or hypomagnesemia should undergo electrolyte repletion prior to the initiation of additional medical therapy for MAT [24]. Hypomagnesemia appears to promote the development of some atrial and ventricular arrhythmias. The administration of magnesium has been reported to suppress MAT in the hypomagnesemic patient and, at times, in patients with normal plasma magnesium levels [21,26]. As an example, one study randomized 14 patients with chronic obstructive pulmonary disease and MAT to magnesium therapy (2 grams over five minutes and 10 grams over five hours) or placebo [26]. At five hours, patients treated with magnesium had a slowing of heart rate from 130 to 99 bpm, while there was no change in the placebo group. Sinus rhythm was present at the end of the infusion in seven of nine patients treated with magnesium versus one of five receiving placebo. (See "Hypomagnesemia: Clinical manifestations of magnesium depletion".) Mild hypomagnesemia (serum magnesium 1.4 to 1.7 mg/dL) can be treated with 240 mg of elemental magnesium orally twice per day as magnesium oxide (400 mg twice daily) or a delayed release magnesium chloride preparation. Dose-dependent diarrhea occurs frequently. More significant hypomagnesemia (serum magnesium <1.4 mg/dL) can be treated with 1 gram (8 mEq) of magnesium sulfate given intravenously over 15 minutes, followed by a continuous infusion of 3 to 6 grams (24 to 48 mEq) over 24 hours, OR as repeated intermittent infusions, each consisting of 1 gram over one hour, for a total of 3 to 6 grams over 12 hours. Because magnesium distributes gradually to tissues, early serum levels can appear artificially high, and repletion may require several days of treatment. The dose should be reduced by approximately 50 percent with even mild renal insufficiency. Response to the initial dose may give an indication of whether the MAT will be responsive to magnesium therapy. (Conversion relationships: 1 mmol = 2 mEq = 24 mg of elemental magnesium.) Potassium repletion in the hypokalemic patient may also control MAT, with or without magnesium supplementation [21,27]. In an observational study of eight patients, the combined https://www.uptodate.com/contents/multifocal-atrial-tachycardia/print 7/20 7/5/23, 10:25 AM Multifocal atrial tachycardia - UpToDate use of magnesium and potassium was associated with conversion to sinus rhythm in seven [21]. Potassium depletion can be treated with potassium chloride given either orally (20 to 60 mEq per day in divided doses if >40 mEq) or intravenously (generally up to 10 mEq per hour, but occasionally at an initial rate of as much as 40 mEq per hour with severe hypokalemia with continuous echocardiogram monitoring). The patient's serum potassium should be carefully monitored to avoid hyperkalemia. Over the long-term, the cause of potassium loss should also be treated, (eg, the administration of a potassium-sparing diuretic to patients treated with loop or thiazide diuretics). (See "Clinical manifestations and treatment of hypokalemia in adults".) Pharmacologic therapy The use of antiarrhythmic drugs in the treatment of MAT has generally been disappointing [1,24]. Additionally, administration of antiarrhythmic agents to acutely ill patients with renal and/or hepatic dysfunction increases the risk of toxic reactions to these agents. There is, however, evidence of benefit with agents to control the ventricular heart rate, namely verapamil and beta blockers. Medical therapy for MAT is indicated only if MAT causes a sustained rapid ventricular response that causes or worsens myocardial ischemia, heart failure, peripheral perfusion, or oxygenation [15,28]. For patients with symptomatic MAT requiring ventricular rate control, we recommend therapy with verapamil or a beta blocker ( table 1). Nondihydropyridine calcium channel blockers While both diltiazem and verapamil can be effective agents for slowing AV nodal conduction and controlling ventricular heart rates, verapamil has been most commonly used in MAT, and the response in some cases suggests that triggered activity may initiate the arrhythmia. (See 'Mechanisms' above.) Verapamil decreases the ventricular rate by reducing the degree of atrial ectopy and/or by limiting the transmission of beats through the AV node [1,29-32]. In an analysis of pooled data, verapamil lowered the ventricular rate by an average of 31 bpm, but only 43 percent of patients reverted to a sinus rhythm [1]. Furthermore, MAT may recur if verapamil is discontinued. The following regimen, given with continuous ECG and blood pressure monitoring, has been suggested for intravenous verapamil ( table 1) [10]. A 5 to 10 mg IV bolus over two minutes; if no response, an additional 10 mg IV bolus may be administered 15 to 30 minutes following the initial dose. A lower initial dose (eg, 2.5 mg IV) may be chosen in patients who are older or who have multiple comorbidities, in whom there are concerns about potential hypotension or other side effects. If MAT reverts to sinus rhythm, oral verapamil is given at an initial dose of 80 mg every six hours and subsequently titrated as blood pressure and heart rate allow (total daily dose range 120 to 480 mg). https://www.uptodate.com/contents/multifocal-atrial-tachycardia/print 8/20 7/5/23, 10:25 AM Multifocal atrial tachycardia - UpToDate Beta blockers Beta blockers can suppress ectopic foci and decrease transmission through the AV node, thereby slowing the ventricular response. Their use in MAT has been limited because of the risk in patients with underlying heart failure or chronic obstructive pulmonary disease, particularly when bronchospasm is part of the picture. However, several studies showing a benefit have been performed, particularly with the relatively cardioselective agent metoprolol [33-35]. Esmolol and acebutolol have also been used in small numbers of patients [36-38]. The pooled data from the metoprolol studies revealed an average decrease in ventricular rate of 51 bpm, with 79 percent of patients reverting to sinus rhythm [1]. Side effects were few, but long-term therapy is required in approximately one-quarter of patients [35]. We use the following protocol for intravenous (IV) metoprolol ( table 1) [34]. Metoprolol 2.5 to 5 mg IV bolus over two to five minutes; if no response, an additional 2.5 to 5 mg IV bolus may be administered every 10 minutes to a total dose of 15 mg. In patients who are unable to receive oral medications, subsequent doses of IV metoprolol can be administered every 4 to 6 hours with the patient in a monitored setting. An advantage of metoprolol is the ease of switching to an oral preparation (typically long-acting metoprolol at a dose of 50 mg once daily or short-acting metoprolol 25 mg twice daily, with titration as needed based on heart rate and blood pressure). Beta blockers should generally not be given to patients with acute decompensated heart failure, severe reactive pulmonary disease, hypotension, drug hypersensitivity, and a history or ECG showing greater than first-degree heart block, bifascicular block, or serious sinus node dysfunction (unless a pacemaker is implanted). Precautions with verapamil and beta blockers Verapamil and beta blockers should not be given to patients with sinus node dysfunction or preexisting second- or third-degree block unless a temporary or permanent pacemaker has been implanted. Verapamil should be administered cautiously in patients with preexisting heart failure or hypotension as it has both negative inotropic and peripheral vasodilator activity, potentially leading to a reduction in blood pressure or even significant hypotension [29,32]. Beta blockers should also be administered cautiously in patients with acutely decompensated heart failure. Verapamil and beta blockers should either be avoided or used at lower doses and with caution in patients already treated with a beta blocker, verapamil or another calcium channel blocker, or digoxin. (See "Major side effects of beta blockers" and "Major side effects and safety of calcium channel blockers".) Which to use first: Calcium channel blocker or beta blocker? The decision to use a nondihydropyridine calcium channel blocker or a beta blocker is most often determined by the presence or absence of acute decompensated heart failure with reduced left ventricular ejection https://www.uptodate.com/contents/multifocal-atrial-tachycardia/print 9/20 7/5/23, 10:25 AM Multifocal atrial tachycardia - UpToDate fraction and severe bronchospasm. We prefer metoprolol before verapamil in patients without these complications. In a randomized, double-blind study of 13 patients, the incidence of benefit was 89 percent with metoprolol versus 44 percent with verapamil [28]. (See "Treatment and prognosis of heart failure with preserved ejection fraction", section on 'Secondary therapies' and "Primary pharmacologic therapy for heart failure with reduced ejection fraction", section on 'Beta blocker'.) By contrast, we prefer to begin with verapamil (or diltiazem) in patients with severe bronchospasm. Beta blockers may be used cautiously in some patients with heart failure, but active bronchospasm is a contraindication. (See "Primary pharmacologic therapy for heart failure with reduced ejection fraction", section on 'Beta blocker'.) In either case, repletion of electrolyte deficiencies (hypomagnesemia and hypokalemia) should occur simultaneously. (See 'Magnesium and potassium repletion' above.) Antiarrhythmic drugs For patients with symptomatic MAT that remains inadequately rate- controlled following treatment of the underlying disorder and initiation of rate controlling therapy, we do not use an antiarrhythmic drug. This is based on extensive literature showing a general lack of efficacy of standard antiarrhythmic drugs in treating MAT [24]. Ineffective drugs include quinidine, procainamide, lidocaine, and phenytoin, among others [1]. Digitalis also appears to have little benefit [2,13]. Ibutilide has been used successfully to treat MAT in one older adult, but more experience with this drug is need [39]. Additionally, ibutilide should never be used in the presence of known or suspected hypokalemia or hypomagnesemia. (See "Therapeutic use of ibutilide".) DC cardioversion DC cardioversion has not proven effective in converting MAT into a sinus rhythm [13,24,40]. As such, we do not perform cardioversion for patients with symptomatic MAT that remains inadequately rate-controlled. Radiofrequency ablation Ablation of the AV node and the use of a permanent ventricular pacemaker is an option for patients with ongoing symptomatic MAT who do not respond to, or cannot tolerate, pharmacologic therapy. This procedure should rarely be required, because the vast majority of MAT episodes are brief and because the arrhythmia resolves with correction of the underlying abnormality [15]. To re-emphasize this, AV junction ablation resulting in creation of complete heart block necessitating permanent pacemaker implantation should not be performed for the purpose of making the ECG appear more normal. It should only be performed in order to improve cardiopulmonary function after proving that the arrhythmia is actually the cause of hemodynamic compromise. https://www.uptodate.com/contents/multifocal-atrial-tachycardia/print 10/20 7/5/23, 10:25 AM Multifocal atrial tachycardia - UpToDate Since most of the manifestations associated with MAT are due to the rapid ventricular rate, an alternative approach for rate control is radiofrequency modification of the AV junction, similar to the approach taken for rate control in atrial fibrillation. Ablation to cure MAT is rarely indicated and not likely to be effective given the underlying diffuse atrial abnormalities. Early data concerning radiofrequency modification of the AV node were encouraging, but modification of AV transmission without producing complete heart block is unreliable and rarely long-lasting. AV node modification with ablation was evaluated in one study of 13 patients with chronic obstructive lung disease and medically refractory MAT who underwent AV junctional modification [41]. This procedure resulted in adequate control of the ventricular response rate in 84 percent of patients, and the rate was reduced from an average of 145 to 89 bpm. One patient developed complete heart block, and one patient had recurrent symptomatic MAT, requiring a second procedure. After a six-month follow-up, all patients with successful modification had an improved quality of life, a reduction in symptoms, and an increase in left ventricular ejection fraction. (See "Atrial fibrillation: Atrioventricular node ablation".) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Supraventricular arrhythmias".) SUMMARY AND RECOMMENDATIONS Multifocal atrial tachycardia (MAT) is an arrhythmia that can be seen in a variety of clinical disorders in adults, children, and infants. In addition to a heart rate >100 beats per minute (bpm), the characteristic electrocardiographic (ECG) feature in MAT is variability in P-wave morphology, with three or more distinct P-wave morphologies. (See 'Introduction' above.) Some patients have similar ECG findings with multiple P-wave morphologies but do not meet criteria for tachycardia. The arrhythmia is called a multifocal atrial rhythm or wandering atrial pacemaker if the rate is between 60 and 100 bpm. (See 'Terminology' above.) MAT is associated with significant lung disease in roughly 60 percent of cases and is identified in up to 20 percent of patients hospitalized for acute respiratory failure. MAT can also occur in the presence of coronary, valvular, hypertensive and other types of heart https://www.uptodate.com/contents/multifocal-atrial-tachycardia/print 11/20 7/5/23, 10:25 AM Multifocal atrial tachycardia - UpToDate disease, particularly when associated with heart failure and/or underlying lung disease. (See 'Associated clinical conditions' above.) In most cases, the clinical manifestations of MAT differ from those of other tachyarrhythmias in that symptoms predominantly relate to the underlying precipitating illness rather than the arrhythmia. Patients have an irregular heart rate greater than 100 bpm, usually identified only during the physical exam by the health care provider, and they rarely present with symptoms of palpitations, presyncope, or syncope as the sole manifestation of MAT. (See 'Clinical manifestations and diagnosis' above.) The diagnosis of MAT can be suspected from the presence of an irregular rapid pulse and heartbeat on physical examination; however, the diagnosis cannot be confirmed without an ECG. A diagnosis of MAT requires the following be present on the ECG ( waveform 1) (see 'Clinical manifestations and diagnosis' above): Discrete P waves with at least three different morphologies (including the normal sinus P wave) An atrial rate greater than 100 bpm P waves which are separated by isoelectric intervals P-P intervals, P-R duration, and R-R intervals which vary Most episodes of MAT do not precipitate hemodynamic compromise or limiting symptoms. Thus, therapy in patients with MAT should be aimed at the inciting underlying disease. (See 'Treatment' above.) Patients with MAT and associated hypokalemia or hypomagnesemia should undergo electrolyte repletion prior to the initiation of additional medical therapy for MAT. (See 'Magnesium and potassium repletion' above.) Medical therapy for MAT is indicated only if MAT causes a sustained rapid ventricular response that causes or worsens myocardial ischemia, heart failure, peripheral perfusion, or oxygenation. Options for medical therapy for patients with symptomatic MAT requiring ventricular rate control include nondihydropyridine calcium channel blockers and beta blockers. For patients without heart failure or bronchospasm, we suggest initial therapy with a beta blocker, usually metoprolol, before calcium channel blockers (Grade 2C). Conversely, for patients with severe bronchospasm, we suggest initial therapy with a nondihydropyridine calcium channel blocker, usually verapamil, rather than a beta blocker (Grade 2C). Beta blockers may be used cautiously in some patients with heart failure. (See 'Pharmacologic therapy' above.) https://www.uptodate.com/contents/multifocal-atrial-tachycardia/print 12/20 7/5/23, 10:25 AM Multifocal atrial tachycardia - UpToDate Extensive literature has shown a lack of efficacy of numerous standard antiarrhythmic drugs (including quinidine, procainamide, lidocaine, phenytoin, and digoxin) as well as electrical cardioversion in treating MAT. (See 'Antiarrhythmic drugs' above and 'DC cardioversion' above.) Ablation of the atrioventricular (AV) node and the use of a permanent ventricular pacemaker is rarely indicated, and should be reserved for patients with ongoing symptomatic MAT who do not respond to or cannot tolerate pharmacologic therapy. (See 'Radiofrequency ablation' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Kastor JA. Multifocal atrial tachycardia. N Engl J Med 1990; 322:1713. 2. Shine KI, Kastor JA, Yurchak PM. Multifocal atrial tachycardia. Clinical and electrocardiographic features in 32 patients. N Engl J Med 1968; 279:344. 3. Berlinerblau R, Feder W. Chaotic atrial rhythm. J Electrocardiol 1972; 5:135. 4. Bisset GS 3rd, Seigel SF, Gaum WE, Kaplan S. Chaotic atrial tachycardia in childhood. Am Heart J 1981; 101:268. 5. Gavrilescu, S, Luca, C . Chaotic atrial rhythm: Studies with His bundle electrography. Eur J Cardiol 1974; 2:153. 6. Glass L, Mackey MC. From Clocks to Chaos: The Rhythms of Life, Princeton University Press, Princeton, NJ 1988. 7. Kothari SA, Apiyasawat S, Asad N, Spodick DH. Evidence supporting a new rate threshold for multifocal atrial tachycardia. Clin Cardiol 2005; 28:561. 8. Yokoshiki H, Mitsuyama H, Watanabe M, Tsutsui H. Swallowing-induced multifocal atrial tachycardia originating from right pulmonary veins. J Electrocardiol 2011; 44:395.e1. 9. Marchlinski FE, Miller JM. Atrial arrhythmias exacerbated by theophylline. Response to verapamil and evidence for triggered activity in man. Chest 1985; 88:931. https://www.uptodate.com/contents/multifocal-atrial-tachycardia/print 13/20 7/5/23, 10:25 AM Multifocal atrial tachycardia - UpToDate 10. Levine JH, Michael JR, Guarnieri T. Treatment of multifocal atrial tachycardia with verapamil. N Engl J Med 1985; 312:21. 11. Santos-Ocampo CD, Sadaniantz A, Elion JL, et al. Echocardiographic assessment of the cardiac anatomy in patients with multifocal atrial tachycardia: a comparison with atrial fibrillation. Am J Med Sci 1994; 307:264. 12. Engel TR, Radhagopalan S. Treatment of multifocal atrial tachycardia by treatment of pulmonary insufficiency: or is it vice versa? Chest 2000; 117:7. 13. Wang K, Goldfarb BL, Gobel FL, Richman HG. Multifocal atrial tachycardia. Arch Intern Med 1977; 137:161. 14. Lipson MJ, Naimi S. Multifocal atrial tachycardia (chaotic atrial tachycardia). Clinical associations and significance. Circulation 1970; 42:397. 15. Goudis CA, Konstantinidis AK, Ntalas IV, Korantzopoulos P. Electrocardiographic abnormalities and cardiac arrhythmias in chronic obstructive pulmonary disease. Int J Cardiol 2015; 199:264. 16. Hudson LD, Kurt TL, Petty TL, Genton E. Arrhythmias associated with acute respiratory failure in patients with chronic airway obstruction. Chest 1973; 63:661. 17. Levine JH, Michael JR, Guarnieri T. Multifocal atrial tachycardia: a toxic effect of theophylline. Lancet 1985; 1:12. 18. Antwi-Amoabeng D, Beutler BD, Singh S, et al. Association between electrocardiographic features and mortality in COVID-19 patients. Ann Noninvasive Electrocardiol 2021; 26:e12833. 19. Tutar E, Kaya A, G le S, et al. Echocardiographic evaluation of left ventricular diastolic function in chronic cor pulmonale. Am J Cardiol 1999; 83:1414. 20. Moustapha A, Kaushik V, Diaz S, et al. Echocardiographic evaluation of left-ventricular diastolic function in patients with chronic pulmonary hypertension. Cardiology 2001; 95:96. 21. Iseri LT, Fairshter RD, Hardemann JL, Brodsky MA. Magnesium and potassium therapy in multifocal atrial tachycardia. Am Heart J 1985; 110:789. 22. Phillips J, Spano J, Burch G. Chaotic atrial mechanism. Am Heart J 1969; 78:171. 23. Chung EK. Appraisal of multifocal atrial tachycardia. Br Heart J 1971; 33:500. 24. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation 2016; 133:e506. https://www.uptodate.com/contents/multifocal-atrial-tachycardia/print 14/20 7/5/23, 10:25 AM Multifocal atrial tachycardia - UpToDate 25. Brugada J, Katritsis DG, Arbelo E, et al. 2019 ESC Guidelines for the management of patients with supraventricular tachycardiaThe Task Force for the management of patients with supraventricular tachycardia of the European Society of Cardiology (ESC). Eur Heart J 2020; 41:655. 26. McCord JK, Borzak S, Davis T, Gheorghiade M. Usefulness of intravenous magnesium for multifocal atrial tachycardia in patients with chronic obstructive pulmonary disease. Am J Cardiol 1998; 81:91. 27. Strickberger SA, Miller CB, Levine JH. Multifocal atrial tachycardia from electrolyte imbalance. Am Heart J 1988; 115:680. 28. Parrillo, JE . Treating multifocal atrial tachycardia (MAT) in a critical care unit: New data regarding verapamil and metoprolol. Update Crit Care Med 1987; 2:1, 3. 29. Schettini B, Katz S, Zeldis SM. Verapamil in tachycardia therapy. Chest 1986; 89:616. 30. Mukerji V, Alpert MA, Diaz-Arias M, Sanfelippo JF. Termination and suppression of multifocal atrial tachycardia with verapamil. South Med J 1987; 80:269. 31. Salerno DM, Anderson B, Sharkey PJ, Iber C. Intravenous verapamil for treatment of multifocal atrial tachycardia with and without calcium pretreatment. Ann Intern Med 1987; 107:623. 32. Hazard PB, Burnett CR. Verapamil in multifocal atrial tachycardia. Hemodynamic and respiratory changes. Chest 1987; 91:68. 33. Hanau, SP, Solar, et al. Metoprolol in the treatment of multifocal atrial tachycardia. Cardiovasc Rev Rep 1984; 5:1182. 34. Arsura EL, Solar M, Lefkin AS, et al. Metoprolol in the treatment of multifocal atrial tachycardia. Crit Care Med 1987; 15:591. 35. Hazard PB, Burnett CR. Treatment of multifocal atrial tachycardia with metoprolol. Crit Care Med 1987; 15:20. 36. Byrd RC, Sung RJ, Marks J, Parmley WW. Safety and efficacy of esmolol (ASL-8052: an ultrashort-acting beta-adrenergic blocking agent) for control of ventricular rate in

P-P intervals, P-R duration, and R-R intervals which vary Most episodes of MAT do not precipitate hemodynamic compromise or limiting symptoms. Thus, therapy in patients with MAT should be aimed at the inciting underlying disease. (See 'Treatment' above.) Patients with MAT and associated hypokalemia or hypomagnesemia should undergo electrolyte repletion prior to the initiation of additional medical therapy for MAT. (See 'Magnesium and potassium repletion' above.) Medical therapy for MAT is indicated only if MAT causes a sustained rapid ventricular response that causes or worsens myocardial ischemia, heart failure, peripheral perfusion, or oxygenation. Options for medical therapy for patients with symptomatic MAT requiring ventricular rate control include nondihydropyridine calcium channel blockers and beta blockers. For patients without heart failure or bronchospasm, we suggest initial therapy with a beta blocker, usually metoprolol, before calcium channel blockers (Grade 2C). Conversely, for patients with severe bronchospasm, we suggest initial therapy with a nondihydropyridine calcium channel blocker, usually verapamil, rather than a beta blocker (Grade 2C). Beta blockers may be used cautiously in some patients with heart failure. (See 'Pharmacologic therapy' above.) https://www.uptodate.com/contents/multifocal-atrial-tachycardia/print 12/20 7/5/23, 10:25 AM Multifocal atrial tachycardia - UpToDate Extensive literature has shown a lack of efficacy of numerous standard antiarrhythmic drugs (including quinidine, procainamide, lidocaine, phenytoin, and digoxin) as well as electrical cardioversion in treating MAT. (See 'Antiarrhythmic drugs' above and 'DC cardioversion' above.) Ablation of the atrioventricular (AV) node and the use of a permanent ventricular pacemaker is rarely indicated, and should be reserved for patients with ongoing symptomatic MAT who do not respond to or cannot tolerate pharmacologic therapy. (See 'Radiofrequency ablation' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Kastor JA. Multifocal atrial tachycardia. N Engl J Med 1990; 322:1713. 2. Shine KI, Kastor JA, Yurchak PM. Multifocal atrial tachycardia. Clinical and electrocardiographic features in 32 patients. N Engl J Med 1968; 279:344. 3. Berlinerblau R, Feder W. Chaotic atrial rhythm. J Electrocardiol 1972; 5:135. 4. Bisset GS 3rd, Seigel SF, Gaum WE, Kaplan S. Chaotic atrial tachycardia in childhood. Am Heart J 1981; 101:268. 5. Gavrilescu, S, Luca, C . Chaotic atrial rhythm: Studies with His bundle electrography. Eur J Cardiol 1974; 2:153. 6. Glass L, Mackey MC. From Clocks to Chaos: The Rhythms of Life, Princeton University Press, Princeton, NJ 1988. 7. Kothari SA, Apiyasawat S, Asad N, Spodick DH. Evidence supporting a new rate threshold for multifocal atrial tachycardia. Clin Cardiol 2005; 28:561. 8. Yokoshiki H, Mitsuyama H, Watanabe M, Tsutsui H. Swallowing-induced multifocal atrial tachycardia originating from right pulmonary veins. J Electrocardiol 2011; 44:395.e1. 9. Marchlinski FE, Miller JM. Atrial arrhythmias exacerbated by theophylline. Response to verapamil and evidence for triggered activity in man. Chest 1985; 88:931. https://www.uptodate.com/contents/multifocal-atrial-tachycardia/print 13/20 7/5/23, 10:25 AM Multifocal atrial tachycardia - UpToDate 10. Levine JH, Michael JR, Guarnieri T. Treatment of multifocal atrial tachycardia with verapamil. N Engl J Med 1985; 312:21. 11. Santos-Ocampo CD, Sadaniantz A, Elion JL, et al. Echocardiographic assessment of the cardiac anatomy in patients with multifocal atrial tachycardia: a comparison with atrial fibrillation. Am J Med Sci 1994; 307:264. 12. Engel TR, Radhagopalan S. Treatment of multifocal atrial tachycardia by treatment of pulmonary insufficiency: or is it vice versa? Chest 2000; 117:7. 13. Wang K, Goldfarb BL, Gobel FL, Richman HG. Multifocal atrial tachycardia. Arch Intern Med 1977; 137:161. 14. Lipson MJ, Naimi S. Multifocal atrial tachycardia (chaotic atrial tachycardia). Clinical associations and significance. Circulation 1970; 42:397. 15. Goudis CA, Konstantinidis AK, Ntalas IV, Korantzopoulos P. Electrocardiographic abnormalities and cardiac arrhythmias in chronic obstructive pulmonary disease. Int J Cardiol 2015; 199:264. 16. Hudson LD, Kurt TL, Petty TL, Genton E. Arrhythmias associated with acute respiratory failure in patients with chronic airway obstruction. Chest 1973; 63:661. 17. Levine JH, Michael JR, Guarnieri T. Multifocal atrial tachycardia: a toxic effect of theophylline. Lancet 1985; 1:12. 18. Antwi-Amoabeng D, Beutler BD, Singh S, et al. Association between electrocardiographic features and mortality in COVID-19 patients. Ann Noninvasive Electrocardiol 2021; 26:e12833. 19. Tutar E, Kaya A, G le S, et al. Echocardiographic evaluation of left ventricular diastolic function in chronic cor pulmonale. Am J Cardiol 1999; 83:1414. 20. Moustapha A, Kaushik V, Diaz S, et al. Echocardiographic evaluation of left-ventricular diastolic function in patients with chronic pulmonary hypertension. Cardiology 2001; 95:96. 21. Iseri LT, Fairshter RD, Hardemann JL, Brodsky MA. Magnesium and potassium therapy in multifocal atrial tachycardia. Am Heart J 1985; 110:789. 22. Phillips J, Spano J, Burch G. Chaotic atrial mechanism. Am Heart J 1969; 78:171. 23. Chung EK. Appraisal of multifocal atrial tachycardia. Br Heart J 1971; 33:500. 24. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation 2016; 133:e506. https://www.uptodate.com/contents/multifocal-atrial-tachycardia/print 14/20 7/5/23, 10:25 AM Multifocal atrial tachycardia - UpToDate 25. Brugada J, Katritsis DG, Arbelo E, et al. 2019 ESC Guidelines for the management of patients with supraventricular tachycardiaThe Task Force for the management of patients with supraventricular tachycardia of the European Society of Cardiology (ESC). Eur Heart J 2020; 41:655. 26. McCord JK, Borzak S, Davis T, Gheorghiade M. Usefulness of intravenous magnesium for multifocal atrial tachycardia in patients with chronic obstructive pulmonary disease. Am J Cardiol 1998; 81:91. 27. Strickberger SA, Miller CB, Levine JH. Multifocal atrial tachycardia from electrolyte imbalance. Am Heart J 1988; 115:680. 28. Parrillo, JE . Treating multifocal atrial tachycardia (MAT) in a critical care unit: New data regarding verapamil and metoprolol. Update Crit Care Med 1987; 2:1, 3. 29. Schettini B, Katz S, Zeldis SM. Verapamil in tachycardia therapy. Chest 1986; 89:616. 30. Mukerji V, Alpert MA, Diaz-Arias M, Sanfelippo JF. Termination and suppression of multifocal atrial tachycardia with verapamil. South Med J 1987; 80:269. 31. Salerno DM, Anderson B, Sharkey PJ, Iber C. Intravenous verapamil for treatment of multifocal atrial tachycardia with and without calcium pretreatment. Ann Intern Med 1987; 107:623. 32. Hazard PB, Burnett CR. Verapamil in multifocal atrial tachycardia. Hemodynamic and respiratory changes. Chest 1987; 91:68. 33. Hanau, SP, Solar, et al. Metoprolol in the treatment of multifocal atrial tachycardia. Cardiovasc Rev Rep 1984; 5:1182. 34. Arsura EL, Solar M, Lefkin AS, et al. Metoprolol in the treatment of multifocal atrial tachycardia. Crit Care Med 1987; 15:591. 35. Hazard PB, Burnett CR. Treatment of multifocal atrial tachycardia with metoprolol. Crit Care Med 1987; 15:20. 36. Byrd RC, Sung RJ, Marks J, Parmley WW. Safety and efficacy of esmolol (ASL-8052: an ultrashort-acting beta-adrenergic blocking agent) for control of ventricular rate in supraventricular tachycardias. J Am Coll Cardiol 1984; 3:394. 37. Aronow WS, Van Camp S, Turbow M, et al. Acebutolol in supraventricular arrhythmias. Clin Pharmacol Ther 1979; 25:149. 38. Williams DO, Tatelbaum R, Most AS. Effective treatment of supraventricular arrhythmias with acebutolol. Am J Cardiol 1979; 44:521. 39. Pierce WJ, McGroary K. Multifocal atrial tachycardia and Ibutilide. Am J Geriatr Cardiol 2001; 10:193. https://www.uptodate.com/contents/multifocal-atrial-tachycardia/print 15/20 7/5/23, 10:25 AM Multifocal atrial tachycardia - UpToDate 40. Kones RJ, Phillips JH, Hersh J. Mechanism and management of chaotic atrial mechanism. Cardiology 1974; 59:92. 41. Ueng KC, Lee SH, Wu DJ, et al. Radiofrequency catheter modification of atrioventricular junction in patients with COPD and medically refractory multifocal atrial tachycardia. Chest 2000; 117:52. Topic 901 Version 28.0 https://www.uptodate.com/contents/multifocal-atrial-tachycardia/print 16/20 7/5/23, 10:25 AM Multifocal atrial tachycardia - UpToDate GRAPHICS Relationship between fast sodium-mediated myocardial action potential and surface electrocardiogram Each phase of the myocardial action potential (numbers, upper panel) corresponds to a deflection or interval on the surface ECG (lower panel). Phase 4, the resting membrane potential, is responsible for the TQ segment; this segment has a prominent role in the ECG manifestations of ischemia during exercise testing. ECG: electrocardiogram. Graphic 64133 Version 4.0 https://www.uptodate.com/contents/multifocal-atrial-tachycardia/print 17/20 7/5/23, 10:25 AM Multifocal atrial tachycardia - UpToDate Electrocardiogram single-lead multifocal atrial tachycardia Clinical features: Elderly patients Decompensation of pulmonary disease Postoperative Arrhythmia usually does not cause severe hemodynamic compromise High mortality ECG features: P waves have 3 forms Atrial rate is usually 100 to 200 bpm Atrial rate is irregular PR interval varies Isoelectric baseline between P waves May progress to atrial fibrillation ECG: electrocardiogram; bpm: beats per minute. Courtesy of Alfred Buxton, MD. Graphic 127222 Version 1.0 https://www.uptodate.com/contents/multifocal-atrial-tachycardia/print 18/20 7/5/23, 10:25 AM Multifocal atrial tachycardia - UpToDate Pharmacologic agents for acute heart rate control in patients with multifocal atrial tachycardia and chronic obstructive pulmonary disease Initial Subsequent Maintenance Drug Onset Side effects dose doses dose Verapamil* 5 to 10 mg IV over 2 1 to 2 minutes 10 mg IV bolus over 2 120 to 480 mg daily Hypotension, heart block, heart failure minutes minutes given 15 to 30 minutes after initial dose Metoprolol 2.5 to 5 mg IV over 2 5 minutes 2.5 to 5 mg IV over 2 to 5 Long-acting: Hypotension, heart block, bradycardia, 50 mg orally to 5 minutes minutes at 10- minute intervals up to heart failure, bronchoconstriction once daily Short-acting: a maximum of 15 mg IV 25 mg orally twice daily MAT: multifocal atrial tachycardia; COPD: chronic obstructive pulmonary disease. For all patients with COPD and MAT and a rapid ventricular response, correction of hypoxemia, acidosis, and other metabolic disturbances is recommended. Theophylline can increase the ventricular response, so dosing should be regulated to keep the serum level in the range of 8 to 12 mg/mL; discontinuation of the medication should be considered. Verapamil is preferred over metoprolol for heart rate control of MAT in patients with COPD due to concerns about exacerbating bronchoconstriction. Representative of the type of selective beta-1 blockers that could be used, but similar drugs could be given in appropriate doses. Verapamil and beta blockers should not be given to patients with sinus node dysfunction or preexisting second- or third-degree block unless a temporary or permanent pacemaker has been implanted. Verapamil and beta blockers should be administered cautiously in patients with decompensated heart failure or hypotension to avoid worsening these conditions. Graphic 83358 Version 8.0 https://www.uptodate.com/contents/multifocal-atrial-tachycardia/print 19/20 7/5/23, 10:25 AM Multifocal atrial tachycardia - UpToDate Contributor Disclosures Alfred Buxton, MD No relevant financial relationship(s) with ineligible companies to disclose. Hugh Calkins, MD Grant/Research/Clinical Trial Support: Adagio Medical [Atrial fibrillation]; Boston Scientific [ARVC]; Farapulse [Atrial fibrillation]; Medtronic [Atrial fibrillation]. Consultant/Advisory Boards: Abbott [Atrial fibrillation]; Atricure [Atrial fibrillation]; Biosense Webster [Catheter ablation]; Boston Scientific [ARVC and atrial fibrillation]; Medtronic [Atrial fibrillation]; Sanofi [Atrial fibrillation]. Other Financial Interest: Atricure [Lecture honoraria]; Biosense Webster [Lecture honoraria]; Boston Scientific [Lecture honoraria]; Medtronic [Lecture honoraria]. All of the relevant financial relationships listed have been mitigated. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/multifocal-atrial-tachycardia/print 20/20

7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Overview of the acute management of tachyarrhythmias : Jordan M Prutkin, MD, MHS, FHRS : James Hoekstra, MD, Hugh Calkins, MD : Todd F Dardas, MD, MS All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Feb 03, 2023. INTRODUCTION Tachyarrhythmias, defined as abnormal heart rhythms with a ventricular rate of 100 or more beats per minute, are frequently symptomatic and often result in patients seeking care at their provider's office or the emergency department. Signs and symptoms related to the tachyarrhythmia may include shock, hypotension, heart failure, shortness of breath, chest pain, acute myocardial infarction, palpitations, and/or decreased level of consciousness. An overview of the management of these various arrhythmias will be presented here. More complete reviews of the individual arrhythmias are discussed separately. INITIAL DIAGNOSTIC AND TREATMENT DECISIONS In patients who present with a symptomatic tachyarrhythmia, a 12-lead electrocardiogram (ECG) should be obtained while a brief initial assessment of the patient's overall clinical assessment is performed. If the patient is hemodynamically unstable, it may be preferable to obtain only a rhythm strip prior to urgent cardioversion and not wait for a 12-lead ECG. The information acquired from these initial assessments is crucial for subsequent management of the patient. Is the patient clinically (or hemodynamically) unstable? The most important clinical determination in a patient presenting with a tachyarrhythmia is whether or not the patient is experiencing signs and symptoms related to the rapid heart rate. These can include hypotension, shortness of breath, chest pain suggestive of coronary ischemia, shock, and/or decreased level of consciousness. https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 1/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate Determining whether a patient's symptoms are related to the tachycardia depends upon several factors, including age and the presence of underlying cardiac disease. Hemodynamically unstable and not sinus rhythm If a patient has clinically significant hemodynamic instability potentially due to the tachyarrhythmia, an attempt should be made as quickly as possible to determine whether the rhythm is sinus tachycardia ( algorithm 1). If the rhythm is not sinus tachycardia, or if there is any doubt that the rhythm is sinus tachycardia, urgent conversion to sinus rhythm is recommended. (See "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'Similar to sinus rhythm' and "Basic principles and technique of external electrical cardioversion and defibrillation" and "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'Assessment of hemodynamic stability'.) Hemodynamically stable If the patient is not experiencing hemodynamic instability, a nonemergent approach to the diagnosis of the patient's rhythm can be undertaken [1-3]. A close examination of the 12-lead ECG should permit the correct identification of the arrhythmia in 80 percent of cases [4]. (See 'Is the QRS complex narrow or wide? Regular or irregular?' below and "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'Evaluation' and "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'Evaluation of the electrocardiogram'.) Is the QRS complex narrow or wide? Regular or irregular? Treatment of any tachyarrhythmia depends on a variety of clinical factors. However, most treatment decisions are made based on the width, morphology, and regularity of the QRS complex ( algorithm 2). In most patients, the differentiation between narrow and wide QRS complex tachyarrhythmias requires only a surface ECG. Narrow QRS complex tachyarrhythmias have a QRS complex <120 milliseconds in duration Wide QRS complex tachyarrhythmias have a QRS complex 120 milliseconds in duration The various types of narrow and wide QRS complex tachyarrhythmias are discussed below. (See 'Narrow QRS complex tachyarrhythmias' below and 'Wide QRS complex tachyarrhythmias' below.) NARROW QRS COMPLEX TACHYARRHYTHMIAS Discussion of the treatment of narrow QRS complex tachycardias will be divided into those with a regular ventricular response and those with an irregular ventricular response ( algorithm 3 and algorithm 1). https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 2/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate Regular narrow QRS complex tachyarrhythmias The regular narrow QRS complex tachycardias include ( algorithm 2) [3]: Sinus tachycardia (see "Sinus tachycardia: Evaluation and management") Inappropriate sinus tachycardia (see "Sinus tachycardia: Evaluation and management", section on 'Inappropriate sinus tachycardia') Sinoatrial nodal reentrant tachycardia (SANRT) (see "Sinoatrial nodal reentrant tachycardia (SANRT)") Atrioventricular nodal reentrant tachycardia (AVNRT) (see "Atrioventricular nodal reentrant tachycardia") Atrioventricular reentrant (or reciprocating) tachycardia (AVRT) (see "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway") Atrial tachycardia (AT) (see "Focal atrial tachycardia") Atrial flutter (see "Overview of atrial flutter") Intraatrial reentrant tachycardia (IART) (see "Intraatrial reentrant tachycardia") Junctional ectopic tachycardia Nonparoxysmal junctional tachycardia Because the vast majority of regular narrow QRS complex tachycardias are due to sinus tachycardia, AVNRT, AVRT, AT, and atrial flutter, these conditions will be presented here. Discussions regarding the treatment of the other less common types of regular narrow QRS complex tachycardias are presented separately. (See "Sinus tachycardia: Evaluation and management", section on 'Inappropriate sinus tachycardia' and "Sinoatrial nodal reentrant tachycardia (SANRT)", section on 'Treatment' and "Intraatrial reentrant tachycardia", section on 'Treatment' and "Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome", section on 'Permanent junctional reciprocating tachycardia'.) Sinus tachycardia The most common tachycardia is sinus tachycardia. If it is certain that the patient's rhythm is sinus tachycardia and clinically significant cardiac symptoms are present, management should be focused on the underlying disorder and on treating any contributing cause of the rapid heart rate (eg, coronary ischemia, pulmonary embolism, respiratory or cardiac failure, hypovolemia, anemia, hyperthyroidism, fever, pain, or anxiety). This may include volume replacement or diuresis, antibiotics, anti-pyretics, oxygen, pain control, or other treatments as appropriate. In patients with sinus tachycardia and certain forms of heart disease, such as coronary disease or aortic stenosis, treatment may need to be directed at the heart rate itself. In such cases, cautious use of an intravenous beta blocker is appropriate. (See "Sinus tachycardia: Evaluation and management" and "Acute myocardial infarction: Role of beta blocker therapy" and "Medical management of symptomatic aortic stenosis".) https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 3/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate Atrioventricular nodal reentrant tachycardia (AVNRT) Patients with AVNRT associated with hemodynamic compromise or severe symptoms due to the tachycardia (eg, angina, hypotension, or heart failure) require rapid termination of the arrhythmia. (See "Atrioventricular nodal reentrant tachycardia", section on 'Initial management'.) For patients with AVNRT who are hemodynamically unstable related to their arrhythmia, we recommend immediate DC cardioversion. Consideration for using vagal maneuvers (Valsalva maneuver or carotid sinus massage) is also reasonable if it does not delay cardioversion. (See "Vagal maneuvers".) For patients with AVNRT associated with severe symptoms due to the tachycardia (eg, angina, hypotension, heart failure, or mental status changes) in whom intravenous access is available, we suggest an initial attempt at termination with adenosine ( algorithm 4) rather than cardioversion. If adenosine cannot be administered or is ineffective, patients should undergo immediate DC cardioversion. For patients with AVNRT that is not associated with severe symptoms or hemodynamic collapse, including patients without symptoms, we suggest the following sequential approach to acute termination: Vagal maneuvers (see "Vagal maneuvers") IV adenosine ( algorithm 4) IV non-dihydropyridine calcium channel blocker or an IV beta blocker Atrioventricular reentrant tachycardia (AVRT) Patients with any arrhythmia (ie, orthodromic AVRT, antidromic AVRT, atrial fibrillation/flutter) involving an accessory pathway should have a prompt initial assessment of hemodynamic status. AVRT may result in either a narrow QRS complex tachycardia or a wide QRS complex tachycardia depending on the direction of conduction across the accessory pathway and also the presence of aberrant conduction. (See 'Antidromic AVRT' below and "Treatment of arrhythmias associated with the Wolff-Parkinson- White syndrome", section on 'Acute treatment of symptomatic arrhythmias'.) For patients with AVRT who are hemodynamically unstable related to their arrhythmia, we recommend immediate DC cardioversion. Consideration for using vagal maneuvers is reasonable if it does not delay cardioversion. (See "Vagal maneuvers".) For patients with acute symptomatic orthodromic AVRT (usually narrow QRS complex in the absence of an underlying conduction delay) who are hemodynamically stable, our approach is as follows ( table 1): https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 4/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate We recommend initial treatment with one or more vagal maneuvers rather than pharmacologic therapy. (See "Vagal maneuvers".) If vagal maneuvers are ineffective, pharmacologic therapy with an AV nodal blocking agent (ie, adenosine, verapamil, beta blockers) should be instituted. We suggest intravenous adenosine ( algorithm 4) rather than intravenous verapamil as the initial choice based on its high efficacy and short half-life. If adenosine is ineffective, we proceed with intravenous verapamil as the second-line agent. If orthodromic AVRT persists, intravenous procainamide and beta blockers approved for intravenous administration (propranolol, metoprolol, and esmolol) are additional therapeutic options. Amiodarone may also be considered. Because most patients with acute symptomatic antidromic AVRT have a wide QRS complex, the approach to this arrhythmia is discussed below. (See 'Antidromic AVRT' below.) Atrial tachycardia Focal atrial tachycardias (AT), usually paroxysmal and self-limited, arise from a single site or area of microreentry or enhanced automaticity outside of the sinus node. (See "Focal atrial tachycardia", section on 'Acute treatment'.) For patients with AT who are felt to be hemodynamically unstable related to their arrhythmia, we recommend immediate DC cardioversion. For a hemodynamically stable patient with symptomatic AT, we suggest acute treatment with an oral or intravenous beta blocker or non-dihydropyridine calcium channel blocker (ie, diltiazem or verapamil). Such treatment may slow the ventricular response and/or terminate the arrhythmia. Intravenous amiodarone is an acceptable alternative that may be preferred in a patient with borderline hypotension as amiodarone may slow the rate or convert the rhythm back to normal sinus. Atrial flutter Atrial flutter usually presents as a regular narrow complex tachycardia, though it occasionally may have an irregular ventricular response. Atrial flutter should always be considered high on the differential diagnosis when a patient presents with a regular narrow complex tachycardia with a ventricular response of approximately 150 beats per minute. As with atrial fibrillation, the early steps in the management of a patient with new onset atrial flutter involve an assessment of the need for cardioversion, ventricular rate slowing therapy, and antithrombotic therapy. Our initial approach to the management of patients with atrial flutter is the same as our approach for atrial fibrillation. (See 'Atrial fibrillation' below.) Irregular narrow QRS complex tachyarrhythmias The irregular narrow QRS complex tachycardias include ( algorithm 2): https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 5/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate Atrial fibrillation (AF) (see "Atrial fibrillation: Overview and management of new-onset atrial fibrillation") Atrial flutter with variable conduction (see "Overview of atrial flutter") Focal atrial tachycardia with variable conduction (see "Focal atrial tachycardia") Multifocal atrial tachycardia (MAT) (see "Multifocal atrial tachycardia") Atrial fibrillation Most patients with new onset (ie, first detected or diagnosed) AF with a rapid rate present with symptoms related to the arrhythmia. Except for embolization, the symptoms associated with new onset AF are primarily due to a rapid and/or irregular ventricular response. The early steps in the management of a patient with new onset rapid AF involve an assessment of the need for cardioversion, ventricular rate slowing therapy, and antithrombotic therapy. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation".) Urgent or emergent cardioversion should be considered for patients with active ischemia, significant hypotension, severe heart failure, or the presence of a preexcitation syndrome associated with rapid conduction using the accessory pathway. (See 'Atrioventricular reentrant tachycardia (AVRT)' above.) For all patients who do not require urgent or emergent cardioversion, we recommend rate control to improve symptoms and to reduce the risk of tachycardia-mediated cardiomyopathy. We believe a goal of less than 110 beats per minute is reasonable for an asymptomatic patient with a normal ejection fraction. Beta blockers and non- dihydropyridine calcium channel blockers are preferred as first-line agents in most patients, and digoxin should only rarely be used. Intravenous preparations are preferred to oral preparations when rapid control of rate is necessary. For patients with AF less than 48 hours in duration in whom cardioversion is planned, the use of antithrombotic therapy pre-cardioversion to reduce the risk of embolization can be considered. For patients with AF longer than 48 hours in duration (or of unknown duration), we recommend four weeks of therapeutic oral anticoagulation prior to cardioversion, as opposed to immediate cardioversion. Transesophageal echocardiography-based (TEE) screening for the presence of atrial thrombi is recommended if cardioversion is desired earlier than four weeks. Anticoagulation must be continued for a minimum of four weeks after cardioversion. Whether long-term anticoagulation is indicated depends on assessment of the patient's thromboembolic risk profile. (See "Atrial fibrillation in adults: Selection of candidates for anticoagulation".) https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 6/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate Atrial flutter As with atrial fibrillation, the early steps in the management of a patient with new onset atrial flutter involve an assessment of the need for cardioversion, ventricular rate slowing therapy, and antithrombotic therapy. Our initial approach to the management of patients with atrial flutter is the same as our approach for atrial fibrillation. (See 'Atrial fibrillation' above.) Multifocal atrial tachycardia Multifocal atrial tachycardia (MAT) is an arrhythmia with organized atrial activity yielding P waves with three or more different morphologies. MAT is commonly associated with significant underlying pulmonary or cardiac illness. (See "Multifocal atrial tachycardia", section on 'Treatment'.) Most episodes of MAT do not precipitate hemodynamic compromise or limiting symptoms. Thus, therapy in patients with MAT should be aimed at the inciting underlying disease. Patients with MAT and associated hypokalemia or hypomagnesemia should undergo electrolyte repletion prior to the initiation of additional medical therapy for MAT. Medical therapy for MAT is indicated only if MAT causes a sustained rapid ventricular response that causes or worsens myocardial ischemia, heart failure, peripheral perfusion, or oxygenation. Options for medical therapy for patients with symptomatic MAT requiring ventricular rate control include non-dihydropyridine calcium channel blockers and beta blockers. For patients without heart failure or bronchospasm, we suggest initial therapy with a beta blocker, usually metoprolol, before calcium channel blockers. Conversely, for patients with severe bronchospasm, we suggest initial therapy with a non-dihydropyridine calcium channel blocker, usually verapamil, rather than a beta blocker. Beta blockers may be used cautiously in patients with stable heart failure. Rate control therapy is typically unsuccessful, however, without treating the underlying disorder. WIDE QRS COMPLEX TACHYARRHYTHMIAS Discussion of the treatment of wide QRS complex tachycardias, similar to narrow QRS complex tachycardias, can be divided into those with a regular or irregular ventricular rate. Regular wide QRS complex tachyarrhythmias The regular wide QRS complex tachycardias include ( algorithm 2): Monomorphic ventricular tachycardia (VT). (See "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis" and "Ventricular tachycardia in the absence of apparent structural heart disease".) https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 7/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate Supraventricular tachycardia with aberrant conduction, underlying conduction delay, conduction over an accessory pathway (eg, AVNRT with right bundle branch block), or a paced ventricular response. Supraventricular tachycardia in a patient on certain antiarrhythmic medications or with significant electrolyte abnormalities. Antidromic AVRT. The most concerning potential cause of a wide QRS complex tachycardia is VT, and, in the majority of patients, the arrhythmia should be assumed to be VT until proven otherwise. Immediate assessment of patient stability takes precedence over any further diagnostic evaluation. (See "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'Summary and recommendations'.) A patient who is unresponsive or pulseless should be treated according to standard advance cardiac life support (ACLS) algorithms ( algorithm 5). In a patient who is unstable but conscious, we recommend immediate synchronized cardioversion with appropriate sedation when possible. In a stable patient, a focused diagnostic evaluation may proceed to determine the etiology of the arrhythmia and guide specific therapy. Ventricular tachycardia In stable patients with known or presumed VT, we recommend the following approach (see "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'Summary and recommendations'): We recommend synchronized external cardioversion, following appropriate sedation, as the initial therapy for most patients with stable VT. If the patient has an implantable cardioverter-defibrillator, it may be possible to terminate the arrhythmia by antitachycardia pacing prior to an attempted cardioversion. In patients with refractory or recurrent wide complex tachycardia (WCT), we suggest an intravenous class I or III antiarrhythmic drug ( table 2), such as amiodarone, lidocaine, or procainamide. In selected patients known to have one of the syndromes of VT in the setting of a structurally normal heart, we suggest calcium channel blockers or beta blockers be used for arrhythmia termination or suppression. However, the decision to use these drugs in this https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 8/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate setting should be made in consultation with a cardiologist experienced in arrhythmia management. Supraventricular tachycardia with aberrant conduction The narrow complex supraventricular tachycardia (SVT) rhythms may present with a wide complex in the setting of aberrant conduction or conduction over an accessory pathway (not including AVRT). In stable patients with a WCT that is known to be an SVT, initial management is similar to that of an SVT with a narrow QRS complex. A continuous rhythm strip should be obtained during any intervention that is intended to slow or terminate the arrhythmia. (See 'Regular narrow QRS complex tachyarrhythmias' above.) For AVNRT or AVRT, or an SVT in which the specific arrhythmia is unknown, we suggest the following sequence of interventions in order to terminate the arrhythmia or to slow ventricular response and facilitate diagnosis in stable patients: Vagotonic maneuvers (eg, valsalva or carotid sinus pressure) Intravenous adenosine ( algorithm 4) Intravenous calcium channel blockers or beta blockers Cardioversion in selected persistent cases, or if the patient is unstable Supraventricular tachycardia with a pacemaker Regular wide QRS complex tachycardias in patients with a pacemaker may be due to tracking of one of the typical supraventricular tachycardias (eg, sinus tachycardia, atrial flutter, etc) or may be due to endless loop tachycardia (ELT, also referred to as pacemaker-mediated tachycardia [PMT]). (See "Unexpected rhythms with normally functioning dual-chamber pacing systems", section on 'Pacemaker-mediated tachycardia'.) In patients with tracking of a native supraventricular tachyarrhythmia, the pacemaker usually should automatically mode switch to a non-tracking mode. If it does not, placing a magnet on the pacemaker will lead to asynchronous pacing at a fixed and lower rate, and the pacemaker settings can be adjusted to prevent rapid pacing. If the rhythm is due to ELT, retrograde conduction from the ventricle to the atrium is sensed by the pacemaker and serves as a trigger to pace the ventricle, which again conducts back to the atrium and perpetuates the tachycardia. Placing a magnet on the pacemaker leads to asynchronous pacing and will stop the tachycardia. Most pacemakers have algorithms to prevent or treat ELT, but pacemaker settings can usually be reprogrammed if they are ineffective. https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 9/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate Antidromic AVRT For patients with acute symptomatic antidromic AVRT (regular and wide QRS complex) who are hemodynamically stable, our approach is as follows (see "Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome", section on 'Antidromic AVRT'): We treat with intravenous procainamide in an effort to terminate the tachycardia or, if the tachycardia persists, slow the ventricular response. This is because it is often difficult to correctly determine that the rhythm is due to antidromic AVRT and not ventricular tachycardia. If the rhythm is definitely known to be antidromic AVRT, then adenosine ( algorithm 4), verapamil, or IV beta blockers may be considered, but monitoring should be continued to ensure that there is not a rapid ventricular rate if atrial fibrillation (AF) subsequently develops after SVT termination. Irregular wide QRS complex tachyarrhythmias The irregular wide QRS complex tachycardias include ( algorithm 2): Polymorphic VT, including torsades de pointes. (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes".) Irregular narrow complex tachycardias with aberrant conduction, antegrade conduction over an accessory pathway (eg, preexcited AF), or underlying conduction delay (eg, AF with right bundle branch block). Ventricular fibrillation. Polymorphic ventricular tachycardia Polymorphic (or polymorphous) ventricular tachycardia (VT) is defined as an unstable rhythm with a continuously varying QRS complex morphology in any recorded electrocardiographic (ECG) lead. Polymorphic VT is generally a rapid and hemodynamically unstable rhythm, and urgent defibrillation is usually necessary. In addition to immediate defibrillation, further therapy is intended to treat underlying disorders and to prevent recurrences. The specific approach depends upon whether or not the QT interval on the baseline ECG is prolonged. Polymorphic VT that occurs in the setting of QT prolongation in sinus rhythm is considered as a distinct arrhythmia, called torsades de pointes. (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes".) Prompt defibrillation is indicated in patients with hemodynamically unstable torsades de pointes. In the conscious patient with recurrent episodes of torsades de pointes: https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 10/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate Intravenous magnesium sulfate (initial dose of 1 to 2 grams IV over 15 minutes, may be followed by an infusion) is first-line therapy, as it is highly effective for both treatment and prevention of recurrence of long QT-related ventricular ectopic beats that trigger torsades de pointes. The benefit is seen even in patients with normal serum magnesium concentrations at baseline. Temporary transvenous overdrive pacing (atrial or ventricular) at about 100 beats per minute is generally reserved for patients who do not respond to intravenous magnesium. In those with congenital long QT syndrome, beta blockers may be used to reduce the frequency of premature ventricular contractions and shorten the QT interval. For patients with polymorphic VT triggered by pauses or bradycardia, isoproterenol (initial dose 0.05 to 0.1 mcg/kg per minute in children and 2 mcg/minute in adults, then titrated to achieve a heart rate of 100 beats per minute) can be used as a temporizing measure to achieve a heart rate of 100 beats per minute prior to pacing. For patients with polymorphic VT and a normal baseline QT interval, the most likely cause is myocardial ischemia. Treatments may include: Prompt defibrillation in the hemodynamically unstable patient. Beta-blockers if blood pressure tolerates. Metoprolol 5 mg intravenously every five minutes, to a total of 15 mg, may be given. IV amiodarone may prevent a recurrent episode. Urgent coronary angiography and possible revascularization. Short-term mechanical circulatory support. Magnesium is less likely to be effective for polymorphic VT if the baseline QT interval is normal. If the polymorphic VT is due to catecholaminergic polymorphic ventricular tachycardia (CPVT), beta blockers should be used. If it is due to Brugada syndrome, isoproterenol should be initiated. (See "Catecholaminergic polymorphic ventricular tachycardia", section on 'Acute management' and "Brugada syndrome or pattern: Management and approach to screening of relatives".) https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 11/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate Preexcited atrial fibrillation For patients with acute symptomatic preexcited AF who are hemodynamically stable, our approach is as follows: We suggest initial medical therapy with rhythm control versus rate control. While there is no clear first-line medication for rhythm control, options include ibutilide and procainamide. (See "Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome", section on 'Atrial fibrillation with preexcitation'.) For all patients with preexcited AF, we recommend not using standard AV nodal blocking medications (ie, beta blockers, non-dihydropyridine calcium channel blockers [verapamil and diltiazem], digoxin, adenosine). Blocking the AV node may result in increased conduction of atrial impulses to the ventricle by way of the accessory pathway, increasing the ventricular rate and potentially resulting in hemodynamic instability and development of ventricular fibrillation. While preexcited AF conducts down a bypass pathway, in contrast to AVRT, the rhythm is irregularly irregular and wide complex. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Atrial fibrillation" and "Society guideline links: Arrhythmias in adults" and "Society guideline links: Ventricular arrhythmias" and "Society guideline links: Basic and advanced cardiac life support in adults" and "Society guideline links: Supraventricular arrhythmias".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 12/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Tachycardia (The Basics)" and "Patient education: Ventricular tachycardia (The Basics)" and "Patient education: Supraventricular tachycardia (SVT) (The Basics)") SUMMARY AND RECOMMENDATIONS Initial diagnostic and treatment decisions In patients who present with a symptomatic tachyarrhythmia, a 12-lead ECG should be obtained while a brief initial assessment of the patient's overall clinical assessment is performed. If the patient is hemodynamically unstable, it may be preferable to obtain only a rhythm strip prior to urgent cardioversion and not wait for a 12-lead ECG. The information acquired from these initial assessments is crucial for subsequent management of the patient (see 'Initial diagnostic and treatment decisions' above): Narrow QRS complex tachycardias If the QRS complex is narrow ( algorithm 2), the approach to acute management is based on whether the patient is stable ( algorithm 3) or unstable ( algorithm 1). (See 'Narrow QRS complex tachyarrhythmias' above.) Wide QRS complex tachycardias If the QRS complex is wide ( algorithm 2), the approach to acute management is based on whether the patient is stable or unstable; pulseless patients should be treated according to the adult cardiac life support algorithm ( algorithm 5). (See 'Wide QRS complex tachyarrhythmias' above.) ACKNOWLEDGMENTS The UpToDate editorial staff acknowledges Philip Podrid, MD, FACC, and Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 13/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate 1. Link MS. Clinical practice. Evaluation and initial treatment of supraventricular tachycardia. N Engl J Med 2012; 367:1438. 2. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2016; 67:e27. 3. Brugada J, Katritsis DG, Arbelo E, et al. 2019 ESC Guidelines for the management of patients with supraventricular tachycardiaThe Task Force for the management of patients with supraventricular tachycardia of the European Society of Cardiology (ESC). Eur Heart J 2020; 41:655. 4. Kalbfleisch SJ, el-Atassi R, Calkins H, et al. Differentiation of paroxysmal narrow QRS complex tachycardias using the 12-lead electrocardiogram. J Am Coll Cardiol 1993; 21:85. Topic 936 Version 43.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 14/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate GRAPHICS Algorithm for the evaluation of narrow QRS complex tachycardias in unstable patients IV: intravenous. Graphic 109811 Version 2.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 15/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate Algorithm for the initial ECG review and differential diagnosis of tachycardia ECG: electrocardiogram; AVNRT: atrioventricular nodal reentrant tachycardia; AVRT: atrioventricular reciprocating (bypass-tract mediated) tachycardia; AT: atrial tachycardia; SANRT: sinoatrial nodal reentrant tachycardia; AF: atrial fibrillation; AV: atrioventricular; VT: ventricular tachycardia; SVT: supraventricular tachycardia; WPW: Wolff-Parkinson-White. A narrow QRS complex is <120 milliseconds in duration, whereas a wide QRS complex is 120 milliseconds duration. Refer to UpToDate topic reviews for additional details on specific ECG findings and management of individu arrhythmias. Monomorphic VT accounts for 80% of wide QRS complex tachycardias; refer to UpToDate topic on diagnosi wide QRS complex tachycardias for additional information on discriminating VT from SVT. Graphic 117571 Version 3.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 16/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate Algorithm for the evaluation of narrow QRS complex tachycardias in stable pati AVNRT: atrioventricular nodal reentrant tachycardia; AVRT: atrioventricular reentrant tachycardia (due to an a electrocardiogram; SANRT: sinoatrial nodal reentrant tachycardia. Graphic 76920 Version 3.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 17/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate Approach to adenosine dosing in stable adults with suspected supraventricular tachyarrhythmia This figure summarizes the initial dosing, administration, and need for repeat dosing of adenosine in a hemo stable adult with suspected AV node-dependent SVT. Adenosine can be used as a diagnostic aid to identify th rhythm or as a therapy to terminate SVTs that rely on AV node conduction. AV node-dependent SVTs include A reentrant tachycardia (AVNRT) and AV reentrant (or reciprocating) tachycardia (AVRT). The management of su node-dependent SVT in hemodynamically stable adults commonly starts with a trial of 1 or more vagal mane proceeding to adenosine therapy. If the patient has hemodynamically unstable SVT, cardioversion is indicate UpToDate content for details on management of SVTs. https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 18/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate AV: atrioventricular; SVT: supraventricular tachycardia; IV: intravenous; ACC: American College of Cardiology; American Heart Association; HRS: Heart Rhythm Society; ECG: electrocardiogram. Lower adenosine doses are indicated in certain clinical settings. If central venous administration is perform adenosine dose is 3 mg; if needed (SVT persists and there is no AV block), the dose may be increased to 6 mg mg for subsequent doses. For heart transplant recipients, the initial adenosine dose is 1 mg; if needed (SVT p there is no AV block), the dose may be increased to 2 mg and then 3 mg for subsequent doses. An 18 mg dose is more likely to be required to produce AV block in patients with a body weight >70 kg, par [1] those weighing >110 kg. When a third dose is indicated, an alternative approach is to administer 12 mg (in mg) as described in the 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients with Supraventr Tachycardia. [2] SVT termination in response to adenosine includes SVT termination closely followed by SVT recurrence. Refer to UpToDate content on treatment of SVT for dosing of second-line AV nodal blockers. If the SVT pers second-line AV nodal blocker therapy, electrical cardioversion is performed, as discussed in UpToDate conten treatment of SVT. SVTs that are not AV node dependent include atrial flutter, atrial fibrillation, and atrial tachycardia. When AV is induced by adenosine, the ECG may reveal atrial activity diagnostic of these rhythms. References: 1. Prabhu S, Mackin V, McLellan AJA, et al. Determining the optimal dose of adenosine for unmasking dormant pulmonary vein co following atrial brillation ablation: Electrophysiological and hemodynamic assessment. DORMANT-AF study. J Cardiovasc Electr 28:13. 2. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Hea Society. Circulation 2016; 133:e506. Graphic 141417 Version 3.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 19/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate Medical therapy of arrhythmias associated with Wolff-Parkinson-White syndrome Arrhythmia Treatment options Contraindicated therapies Orthodromic AV reentrant tachycardia Acute termination* Unstable patients: Synchronized cardioversion Stable patients: First line: Vagal maneuvers Second line: IV adenosine Third line: IV verapamil OR IV diltiazem Other therapies: IV procainamide OR IV beta blocker; synchronized cardioversion if other therapies are ineffective or not feasible Chronic prevention First line: Catheter ablation of the accessory pathway Second line: Oral flecainide or

crucial for subsequent management of the patient (see 'Initial diagnostic and treatment decisions' above): Narrow QRS complex tachycardias If the QRS complex is narrow ( algorithm 2), the approach to acute management is based on whether the patient is stable ( algorithm 3) or unstable ( algorithm 1). (See 'Narrow QRS complex tachyarrhythmias' above.) Wide QRS complex tachycardias If the QRS complex is wide ( algorithm 2), the approach to acute management is based on whether the patient is stable or unstable; pulseless patients should be treated according to the adult cardiac life support algorithm ( algorithm 5). (See 'Wide QRS complex tachyarrhythmias' above.) ACKNOWLEDGMENTS The UpToDate editorial staff acknowledges Philip Podrid, MD, FACC, and Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 13/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate 1. Link MS. Clinical practice. Evaluation and initial treatment of supraventricular tachycardia. N Engl J Med 2012; 367:1438. 2. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2016; 67:e27. 3. Brugada J, Katritsis DG, Arbelo E, et al. 2019 ESC Guidelines for the management of patients with supraventricular tachycardiaThe Task Force for the management of patients with supraventricular tachycardia of the European Society of Cardiology (ESC). Eur Heart J 2020; 41:655. 4. Kalbfleisch SJ, el-Atassi R, Calkins H, et al. Differentiation of paroxysmal narrow QRS complex tachycardias using the 12-lead electrocardiogram. J Am Coll Cardiol 1993; 21:85. Topic 936 Version 43.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 14/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate GRAPHICS Algorithm for the evaluation of narrow QRS complex tachycardias in unstable patients IV: intravenous. Graphic 109811 Version 2.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 15/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate Algorithm for the initial ECG review and differential diagnosis of tachycardia ECG: electrocardiogram; AVNRT: atrioventricular nodal reentrant tachycardia; AVRT: atrioventricular reciprocating (bypass-tract mediated) tachycardia; AT: atrial tachycardia; SANRT: sinoatrial nodal reentrant tachycardia; AF: atrial fibrillation; AV: atrioventricular; VT: ventricular tachycardia; SVT: supraventricular tachycardia; WPW: Wolff-Parkinson-White. A narrow QRS complex is <120 milliseconds in duration, whereas a wide QRS complex is 120 milliseconds duration. Refer to UpToDate topic reviews for additional details on specific ECG findings and management of individu arrhythmias. Monomorphic VT accounts for 80% of wide QRS complex tachycardias; refer to UpToDate topic on diagnosi wide QRS complex tachycardias for additional information on discriminating VT from SVT. Graphic 117571 Version 3.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 16/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate Algorithm for the evaluation of narrow QRS complex tachycardias in stable pati AVNRT: atrioventricular nodal reentrant tachycardia; AVRT: atrioventricular reentrant tachycardia (due to an a electrocardiogram; SANRT: sinoatrial nodal reentrant tachycardia. Graphic 76920 Version 3.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 17/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate Approach to adenosine dosing in stable adults with suspected supraventricular tachyarrhythmia This figure summarizes the initial dosing, administration, and need for repeat dosing of adenosine in a hemo stable adult with suspected AV node-dependent SVT. Adenosine can be used as a diagnostic aid to identify th rhythm or as a therapy to terminate SVTs that rely on AV node conduction. AV node-dependent SVTs include A reentrant tachycardia (AVNRT) and AV reentrant (or reciprocating) tachycardia (AVRT). The management of su node-dependent SVT in hemodynamically stable adults commonly starts with a trial of 1 or more vagal mane proceeding to adenosine therapy. If the patient has hemodynamically unstable SVT, cardioversion is indicate UpToDate content for details on management of SVTs. https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 18/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate AV: atrioventricular; SVT: supraventricular tachycardia; IV: intravenous; ACC: American College of Cardiology; American Heart Association; HRS: Heart Rhythm Society; ECG: electrocardiogram. Lower adenosine doses are indicated in certain clinical settings. If central venous administration is perform adenosine dose is 3 mg; if needed (SVT persists and there is no AV block), the dose may be increased to 6 mg mg for subsequent doses. For heart transplant recipients, the initial adenosine dose is 1 mg; if needed (SVT p there is no AV block), the dose may be increased to 2 mg and then 3 mg for subsequent doses. An 18 mg dose is more likely to be required to produce AV block in patients with a body weight >70 kg, par [1] those weighing >110 kg. When a third dose is indicated, an alternative approach is to administer 12 mg (in mg) as described in the 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients with Supraventr Tachycardia. [2] SVT termination in response to adenosine includes SVT termination closely followed by SVT recurrence. Refer to UpToDate content on treatment of SVT for dosing of second-line AV nodal blockers. If the SVT pers second-line AV nodal blocker therapy, electrical cardioversion is performed, as discussed in UpToDate conten treatment of SVT. SVTs that are not AV node dependent include atrial flutter, atrial fibrillation, and atrial tachycardia. When AV is induced by adenosine, the ECG may reveal atrial activity diagnostic of these rhythms. References: 1. Prabhu S, Mackin V, McLellan AJA, et al. Determining the optimal dose of adenosine for unmasking dormant pulmonary vein co following atrial brillation ablation: Electrophysiological and hemodynamic assessment. DORMANT-AF study. J Cardiovasc Electr 28:13. 2. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Hea Society. Circulation 2016; 133:e506. Graphic 141417 Version 3.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 19/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate Medical therapy of arrhythmias associated with Wolff-Parkinson-White syndrome Arrhythmia Treatment options Contraindicated therapies Orthodromic AV reentrant tachycardia Acute termination* Unstable patients: Synchronized cardioversion Stable patients: First line: Vagal maneuvers Second line: IV adenosine Third line: IV verapamil OR IV diltiazem Other therapies: IV procainamide OR IV beta blocker; synchronized cardioversion if other therapies are ineffective or not feasible Chronic prevention First line: Catheter ablation of the accessory pathway Second line: Oral flecainide or propafenone in the absence of structural or ischemic heart disease Third line: Oral IA antiarrhythmic agent OR oral amiodarone Antidromic AV reentrant tachycardia Acute termination* Unstable patients: Adenosine, verapamil, diltiazem, Synchronized cardioversion beta blockers, digoxin should all be avoided if NOT certain of diagnosis Stable patients (if CERTAIN of the diagnosis): Same progression of therapies as acute termination of orthodromic AVRT Stable patients (if NOT certain of the diagnosis): IV procainamide, synchronized cardioversion if procainamide is ineffective or not available https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 20/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate Chronic prevention First line: Catheter ablation of the accessory pathway Digoxin Beta blockers Second line: Oral flecainide or propafenone in the absence of Verapamil, diltiazem structural or ischemic heart disease Other therapies: Oral IA antiarrhythmic agent OR oral amiodarone Pre-excited atrial fibrillation Acute termination* Unstable patients: Amiodarone Synchronized cardioversion Stable patients: Digoxin Beta blockers First line: IV ibutilide or IV procainamide Adenosine Other therapies: IC antiarrhythmic agent or dofetilide; synchronized cardioversion if other therapies are ineffective or not available Verapamil, diltiazem Chronic prevention First line: Catheter ablation or the accessory pathway Oral digoxin Second line: Oral flecainide or propafenone in the absence of structural or ischemic heart disease Third line: Oral IA antiarrhythmic agent OR oral amiodarone AVRT: atrioventricular reciprocating tachycardia; IV: intravenous; class IC: flecainide, propafenone; class IA: quinidine, procainamide, disopyramide. Cardioversion is indicated if hemodynamically unstable or drugs are ineffective. Ablation of the accessory pathway is generally preferred to cure the arrhythmia. Procainamide is the intravenous drug of choice for acute termination of suspected antidromic AVRT. If the tachycardia is definitely known to be antidromic AVRT, and it has been verified that the AV node (rather than a second accessory pathway) is acting as the retrograde limb of the circuit, one could consider treatment with an agent such as adenosine similar to therapy for orthodromic AVRT, https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 21/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate but it is rare to have all of the necessary data in the acute setting to justify use of AV nodal blocking agents. Graphic 62762 Version 7.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 22/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate Adult cardiac arrest algorithm https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 23/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 24/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate Reprinted with permission. Highlights of the 2020 American Heart Association Guidelines for CPR and ECC. Copyright 2020 American Association, Inc. Graphic 129983 Version 9.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 25/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate Revised (2018) Vaughan Williams classification of antiarrhythmic drugs abridged table Class 0 (HCN channel blockers) Ivabradine Class I (voltage-gated Na+ channel blockers) Class Ia (intermediate dissociation): Quinidine, ajmaline, disopyramide, procainamide Class Ib (rapid dissociation): Lidocaine, mexilitine Class Ic (slow dissociation): Propafenone, flecainide Class Id (late current): Ranolazine Class II (autonomic inhibitors and activators) Class IIa (beta blockers): Nonselective: carvedilol, propranolol, nadolol Selective: atenolol, bisoprolol, betaxolol, celiprolol, esmolol, metoprolol Class IIb (nonselective beta agonists): Isoproterenol Class IIc (muscarinic M2 receptor inhibitors): Atropine, anisodamine, hyoscine, scopolamine Class IId (muscarinic M2 receptor activators): Carbachol, pilocarpine, methacholine, digoxin Class IIe (adenosine A1 receptor activators): Adenosine Class III (K+ channel blockers and openers) Class IIIa (voltage dependent K+ channel blockers): Ambasilide, amiodarone, dronedarone, dofetilide, ibutilide, sotalol, vernakalant Class IIIb (metabolically dependent K+ channel openers): https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 26/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate Nicorandil, pinacidil Class IV (Ca++ handling modulators) Class IVa (surface membrane Ca++ channel blockers): Bepridil, diltiazem, verapamil Class IVb (intracellular Ca++ channel blockers): Flecainide, propafenone Class V (mechanosensitive channel blockers): No approved medications Class VI (gap junction channel blockers) No approved medications Class VII (upstream target modulators) Angiotensin converting enzyme inhibitors Angiotensin receptor blockers Omega-3 fatty acids Statins HCN: hyperpolarization-activated cyclic nucleotide-gated; Na: sodium; K: potassium; Ca: calcium. Graphic 120433 Version 3.0 https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 27/28 7/5/23, 10:25 AM Overview of the acute management of tachyarrhythmias - UpToDate Contributor Disclosures Jordan M Prutkin, MD, MHS, FHRS No relevant financial relationship(s) with ineligible companies to disclose. James Hoekstra, MD No relevant financial relationship(s) with ineligible companies to disclose. Hugh Calkins, MD Grant/Research/Clinical Trial Support: Adagio Medical [Atrial fibrillation]; Boston Scientific [ARVC]; Farapulse [Atrial fibrillation]; Medtronic [Atrial fibrillation]. Consultant/Advisory Boards: Abbott [Atrial fibrillation]; Atricure [Atrial fibrillation]; Biosense Webster [Catheter ablation]; Boston Scientific [ARVC and atrial fibrillation]; Medtronic [Atrial fibrillation]; Sanofi [Atrial fibrillation]. Other Financial Interest: Atricure [Lecture honoraria]; Biosense Webster [Lecture honoraria]; Boston Scientific [Lecture honoraria]; Medtronic [Lecture honoraria]. All of the relevant financial relationships listed have been mitigated. Todd F Dardas, MD, MS No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/overview-of-the-acute-management-of-tachyarrhythmias/print 28/28

7/5/23, 10:33 AM Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances : Mark S Link, MD, Antonio Pelliccia, MD : Peter J Zimetbaum, MD, Ary L Goldberger, MD : Todd F Dardas, MD, MS All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Dec 12, 2022. INTRODUCTION As with the population in general, apparent electrocardiographic (ECG) abnormalities, including conduction disturbances and arrhythmias, are often documented in athletes. ECG findings in athletes may be benign, physiologic consequences of cardiovascular adaptation to regular exercise training or may be the expression of pathologic conditions. Therefore, there is a need for appropriate knowledge of what is normal and physiologic versus nonphysiologic and abnormal in an athlete's ECG. These abnormalities can impact eligibility for participation and lead to a costly and sometimes invasive work-up, even when they are not associated with significant symptoms or impaired athletic performance. Rarely are arrhythmias fatal; however, sudden cardiac death (SCD) resulting from a malignant ventricular tachyarrhythmia is a devastating event, particularly in young and apparently healthy persons. Thus, appropriate assessment of ECG anomalies in athletes is of major importance. The two primary and interrelated goals when evaluating athletes for apparent ECG abnormalities are: To document the presence of ECG abnormalities that may be due to underlying structural heart disease that place the athlete at risk for SCD. To evaluate the importance of an arrhythmia in assessing the athlete's eligibility for competition. https://www.uptodate.com/contents/athletes-with-arrhythmias-electrocardiographic-abnormalities-and-conduction-disturbances/print 1/27 7/5/23, 10:33 AM Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances - UpToDate This topic will discuss ECG abnormalities, including conduction disturbances and their importance in athletes. The clinical manifestations, diagnostic evaluation, and treatment of athletes with arrhythmias, along with the discussion of returning to athletic participation, are discussed separately. (See "Athletes: Overview of sudden cardiac death risk and sport participation" and "Athletes with arrhythmias: Clinical manifestations and diagnostic evaluation" and "Athletes with arrhythmias: Treatment and returning to athletic participation".) The approach to pre-participation evaluation and screening of athletes is also discussed separately. (See "Screening to prevent sudden cardiac death in competitive athletes" and "Sports participation in children and adolescents: The preparticipation physical evaluation".) PREVALENCE A broad range of ECG abnormalities can be seen in trained athletes ( table 1) [1-3]. The type of sport appears to impact the resulting changes, with endurance athletes more likely to have ECG abnormalities than non-endurance athletes [3]. The type of abnormality and whether the abnormality is related or unrelated to training impacts the decision regarding further evaluation and participation in athletics [1]. In one report of 1005 athletes who were evaluated with ECG and echocardiography, the ECG was found to be abnormal in 14 percent, while echocardiographic abnormalities were found in 5 percent [2]. Apparently abnormal ECG patterns were associated with a larger left ventricular (LV) end-diastolic dimension and wall thickness and were more common in: Males Younger athletes Endurance athletes (eg, cycling, rowing, cross-country skiing) These findings would suggest a causative role of exercise in physiologic LV remodeling [3]. Notably, the vast majority of the ECG abnormalities were composed of increased R/S wave voltages, suggestive of LV hypertrophy (LVH). Other major abnormalities such as repolarization abnormalities and primarily negative T waves were relatively rare (3 percent) and unrelated to cardiac dimensions. The negative T waves should raise suspicion for underlying structural cardiac diseases, and these ECG abnormalities may have clinical or pathologic implications [4]. Subsequent reports have confirmed that a large proportion of the ECG changes in athletes are likely a consequence of the physiologic cardiac remodeling and characterized by a benign clinical significance. Thus, the proportion of abnormal ECG patterns with clinical relevance has substantially decreased. As an example, the proportion of abnormal ECG patterns was found to https://www.uptodate.com/contents/athletes-with-arrhythmias-electrocardiographic-abnormalities-and-conduction-disturbances/print 2/27 7/5/23, 10:33 AM Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances - UpToDate be about 5 percent in a large population of White athletes [5], but up to 16 percent in Afro- Caribbean and Black athletes [6]. CLINICAL APPROACH TO READING THE ECG IN ATHLETES A clinical approach to the ECG reading (ie, distinguishing the few ECGs that may be the expression of an underlying pathologic condition from the majority of ECG changes that are simply a consequence of the athletic conditioning) was suggested in 2010 [7] and subsequently refined in 2017 by an international group [7-9]. For practical purposes, ECG changes in athletes can be classified into two groups ( figure 1): one related to whether the ECG abnormality is likely a result of chronic training (normal ECG changes in athletes); the other related to whether the ECG finding occurs independently of training and thus may be expression of a pathologic condition (borderline or abnormal ECG changes in athletes) [7]. Common ECG abnormalities ("normal" in athletes) are frequent and are not associated with an increased risk of underlying cardiac disease and incidence of adverse events during exercise ( table 1). These include, among others, sinus bradycardia, sinus arrhythmia, ectopic atrial rhythm, junctional rhythm, first degree atrioventricular (AV) block, incomplete right bundle branch block (RBBB), isolated voltage meeting standard criteria for LVH or right ventricular hypertrophy (RVH), and early repolarization. Athletes with these ECG abnormalities do not require additional evaluation and can continue to participate safely in athletics. In contrast, uncommon ECG abnormalities are unrelated to training and often occur secondary to an underlying pathologic disease process (eg, hypertrophic cardiomyopathy, arrhythmogenic RV cardiomyopathy, Wolff-Parkinson-White syndrome, long QT syndrome, and other ion channelopathies) ( table 1). These abnormalities are associated with an increased risk of SCD. Persons with uncommon ECG abnormalities should undergo additional cardiovascular testing and evaluation for clinically important cardiac pathology. However, there is a potential overlap between training-related versus training-unrelated ECG changes. In addition, in some athletes, the distinction between an athlete's heart and a pathologic condition is difficult, and gray areas will exist. As a result, the international criteria also include a third category of borderline ECG changes, comprehensive of left or right axis deviation, left or right atrial enlargement, and complete RBBB. The presence of a single, borderline abnormality is likely unrelated to structural cardiac abnormalities, while the combination of two or more of these borderline changes https://www.uptodate.com/contents/athletes-with-arrhythmias-electrocardiographic-abnormalities-and-conduction-disturbances/print 3/27 7/5/23, 10:33 AM Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances - UpToDate increases the probability of finding an underlying structural cardiac abnormality and requiring additional investigations. NORMAL ECG FINDINGS There are multiple ECG findings in athletes that represent normal (physiologic) variants. In asymptomatic persons with no family history of inherited cardiac disease or SCD, no further evaluation is required, and patients are not restricted from activity [9]. These include: Increased QRS voltage meeting standard criteria for LVH or RVH found in isolation (ie, without other ECG abnormalities). Incomplete right bundle branch block. Early repolarization variants/ST-segment elevation. (See "Early repolarization".) ST-segment elevation followed by terminal T-wave inversion in leads V1 to V4 in Afro- Caribbean and Black athletes. T-wave inversion in leads V1 to V3 in children <16 years of age. Sinus bradycardia. (See "Sinus bradycardia".) Sinus arrhythmia. (See "Normal sinus rhythm and sinus arrhythmia", section on 'Sinus arrhythmia'.) Ectopic atrial rhythm. (See "ECG tutorial: Atrial and atrioventricular nodal (supraventricular) arrhythmias", section on 'Ectopic atrial rhythm'.) Junctional rhythm. (See "ECG tutorial: Atrial and atrioventricular nodal (supraventricular) arrhythmias", section on 'Junctional ectopic rhythm'.) First degree AV conduction delay (block). (See "First-degree atrioventricular block".) Second degree AV block: Mobitz type I (Wenckebach). (See "Second-degree atrioventricular block: Mobitz type I (Wenckebach block)".) BORDERLINE ECG FINDINGS Borderline ECG findings may represent pathology or innocent ECG alterations. If one of the borderline ECG findings is present alone in an asymptomatic person with no family history of https://www.uptodate.com/contents/athletes-with-arrhythmias-electrocardiographic-abnormalities-and-conduction-disturbances/print 4/27 7/5/23, 10:33 AM Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances - UpToDate inherited cardiac disease or SCD, no further evaluation is required, and the patient is not restricted from activity. In contrast, if two or more of the borderline ECG findings are present, further evaluation is required. Right/left axis deviation and right/left atrial enlargement Axis deviation and atrial abnormality (the latter as defined by ECG voltage criteria) are not uncommonly seen in both athletes and non-athletes. Among a cohort of over 2500 athletes and nearly 10,000 non-athletes, axis deviation or findings consistent with atrial enlargement were seen in 5.5 and 4.4 percent of persons, respectively [10]. Among 579 patients with identified ECG abnormalities who underwent follow-up testing with echocardiography, none of the 579 persons had an identified major structural or functional cardiac abnormality. These observations suggested that right axis deviation and right atrial enlargement occurring in isolation or in association with other electrical markers of "athlete's heart" are probably normal variants, whereas left axis deviation and left atrial enlargement may reflect a relative increase in LV dimensions in some athletes (but not pathologic conditions). Complete right bundle branch block Complete right bundle branch block (RBBB) ( waveform 1) is not uncommon among athletes and nonathletic young individuals and generally is not a sign of underlying structural heart disease [11]. Complete RBBB is detected in approximately 1 percent of the general population and large data sets in young adult athletes reveal a prevalence of 0.5 to 2.5 percent. In a study of 510 United States collegiate athletes, RBBB was reported in 13 (2.5 percent) athletes. The athletes with complete RBBB exhibited larger RV dimensions and a lower RV ejection fraction, but preserved fractional area change. None of the athletes with complete or incomplete RBBB had pathological structural cardiac disease, suggesting that this particular ECG pattern may be an adaptation to exercise that manifests as only an electrical change in the absence of any RV morphological change [11]. (See "Right bundle branch block" and "Athletes with arrhythmias: Treatment and returning to athletic participation", section on 'Bundle branch block'.) ABNORMAL ECG FINDINGS Abnormal ECG findings are significantly more likely to represent pathology rather than a normal response to training. As such, patients with an abnormal ECG finding should undergo further evaluation to search for cardiac pathology. T-wave inversion T-wave inversion of at least 1 mm in two or more contiguous leads is generally abnormal and should prompt additional evaluation. In contrast, however, ST-segment elevation followed by terminal T-wave inversion in leads V1 to V4 in Afro-Caribbean and Black https://www.uptodate.com/contents/athletes-with-arrhythmias-electrocardiographic-abnormalities-and-conduction-disturbances/print 5/27 7/5/23, 10:33 AM Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances - UpToDate athletes, as well as T-wave inversion in leads V1 to V3 in children <16 years of age, is considered normal ECG findings. T-wave inversion is more commonly seen in patients with structural heart disease, notably hypertrophic cardiomyopathy and arrhythmogenic RV cardiomyopathy (ARVC), among others. In HCM, T-wave inversion is usually prevalent in inferolateral leads and is associated with other abnormalities (eg, ST-segment depression, Q waves, left axis deviation, or left atrial enlargement). In one study of 100 healthy athletes who were age- and sex-matched with 100 patients with ARVC, those with ARVC were significantly more likely to have T-wave inversion extending beyond lead V3, inferior T-wave inversions, often associated with premature ventricular beats, and/or lower LVH voltage scores [12]. Moreover, ARVC patients do not usually present with ST-segment elevation preceding the inverted T-wave, in contrast to normal young subjects [9]. The finding of T-wave inversion on the ECG should prompt additional evaluation, usually beginning with echocardiography. Serial imaging may be required if the initial imaging evaluation is unrevealing but the ECG findings persist. (See "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation", section on 'Electrocardiography' and "Arrhythmogenic right ventricular cardiomyopathy: Diagnostic evaluation and diagnosis", section on 'Electrocardiography' and 'Normal ECG findings' above.) ST-segment depression ST-segment depression can be seen in a variety of cardiomyopathic conditions, and is not considered a normal response to exercise training. This finding on the ECG should prompt additional evaluation. Echocardiography is the minimum evaluation for athletes with ST-segment depression to investigate for underlying cardiomyopathy. Cardiovascular magnetic resonance (CMR) imaging should be considered based on the echocardiographic findings and/or level of clinical suspicion. Pathologic Q waves Contemporary practice considers pathologic Q waves present if the Q/R ratio 0.25 or a duration 40 milliseconds (again in two or more contiguous leads). Q waves can be seen in a variety of cardiomyopathic conditions as well as in the setting of an accessory pathway. The presence of possibly pathologic Q waves should prompt close scrutiny of the ECG for other evidence of an accessory pathway, along with echocardiography to evaluate for cardiomyopathy. (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis", section on 'Electrocardiographic findings'.) Left bundle branch block In contrast to right bundle branch block (RBBB), left bundle branch block (LBBB) ( waveform 2) is rarely seen (in athletes or nonathletes) and often reflects underlying structural heart disease, mandating careful investigation for underlying cardiac https://www.uptodate.com/contents/athletes-with-arrhythmias-electrocardiographic-abnormalities-and-conduction-disturbances/print 6/27 7/5/23, 10:33 AM Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances - UpToDate abnormality. LBBB is generally not associated with symptoms but when identified should prompt further evaluation. Athletes with complete LBBB require a thorough investigation for myocardial disease, typically beginning with echocardiography. CMR imaging should be considered based on the echocardiographic findings and/or level of clinical suspicion. (See "Left bundle branch block" and "Athletes with arrhythmias: Treatment and returning to athletic participation", section on 'Bundle branch block'.) QRS duration 140 milliseconds While the exact implications in athletes are uncertain, a prominent intraventricular conduction delay ( 140 milliseconds) that does not meet criteria for LBBB or RBBB has been associated with increased risk of death or cardiomyopathy in general populations [13]. In asymptomatic athletes with profound non-specific intraventricular conduction delay, an echocardiogram is recommended to evaluate for myocardial disease. Other testing may be indicated depending on echocardiographic findings and/or clinical suspicion. Epsilon wave An epsilon wave is defined as a distinct low-amplitude signal (appearing as small positive deflections or notches) localized between the end of the QRS complex and onset of the T wave in leads V1 to V3. Epsilon waves are among the more subtle ECG abnormalities, and, not surprisingly, subject to high interobserver variability [14]. The presence of epsilon waves is a highly specific ECG marker and represents one of the diagnostic criteria for arrhythmogenic RV cardiomyopathy. However, epsilon waves are typically a manifestation of more advanced disease and unlikely to be an isolated ECG finding, especially in young asymptomatic athletes. Ventricular preexcitation Patients with Wolff-Parkinson-White (WPW) pattern manifest ventricular preexcitation on the surface ECG ( table 1). When this pattern is associated with documented tachycardia or symptoms referable to tachycardia, the patient is said to have the WPW syndrome. (See 'Supraventricular tachyarrhythmias' below and "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis".) The WPW pattern occurs in approximately 1/1000 to 4/1000 athletes. The presence of an accessory pathway can predispose an athlete to sudden death because rapid conduction of atrial fibrillation (AF) across the accessory pathway can result in ventricular fibrillation (VF). SCD due to VF in patients with WPW is a risk but is quite rare (<1 percent of the WPW patients). This complication appears to be confined to patients with AF or atrial flutter and rapid conduction to the ventricles over a bypass tract, which has a particularly short functional refractory period [15- 17]. The optimal approach to asymptomatic athletes with a WPW ECG pattern who have no history of palpitations or tachycardia and no evidence of structural heart disease is uncertain, but Pediatric https://www.uptodate.com/contents/athletes-with-arrhythmias-electrocardiographic-abnormalities-and-conduction-disturbances/print 7/27 7/5/23, 10:33 AM Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances - UpToDate Society Guidelines recommend that symptomatic athletes with WPW pattern should be investigated for the presence of a low- or high-risk accessory pathway. Noninvasive risk stratification begins with an exercise stress test in which abrupt, complete loss of preexcitation as the heart rate increases suggests a low-risk accessory pathway. However, as a practical matter, this determination may be difficult at high heart rates due to shortening PR intervals; therefore, if noninvasive testing cannot confirm a low-risk pathway or is inconclusive, electrophysiology testing should be considered to determine the shortest preexcited RR interval during AF. If the shortest preexcited RR interval is 250 ms (240 bpm) and when multiple pathways exist, then the accessory pathway is deemed to be at high risk, and prophylactic treatment (typically catheter ablation) is advised. Ablation of the accessory pathway is recommended in competitive and recreational athletes with preexcitation and documented arrhythmias. (See "Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome", section on 'Treatment to prevent recurrent arrhythmias' and "Athletes with arrhythmias: Treatment and returning to athletic participation", section on 'Wolff-Parkinson- White syndrome'.) Long QT syndrome Overall, the average QTc in healthy persons after puberty is 420 20 milliseconds, while during infancy the average QTc is 400 20 milliseconds. The calculation of the QT interval in athletes has limitations due to sinus arrhythmia, slightly widened QRS complexes, and T-U complexes. To properly perform a manual QT measurement, it is critical to identify the end of the T wave since the onset of the QRS is typically seen easily. Leads II and V5 usually provide the best delineation of the T wave. Corrections for heart rates are usually made with the Bazett formula, although it may be inaccurate at heart rates 40 beats per minute and >120 beats per minute [18]. Consensus statements on ECG interpretation in athletes have recommended that male athletes with a QTc >470 milliseconds and female athletes with a QTc >480 milliseconds undergo further evaluation for long QT syndrome (LQTS) to better balance false-positive and false-negative findings [1,9]. Recording QTc intervals beyond the normal cutoff values should raise the suspicion of either acquired or congenital LQTS. The most frequent cause is congenital LQTS, a potentially lethal ventricular arrhythmia syndrome with the hallmark ECG feature of QT prolongation. Symptoms, if present, include arrhythmic syncope, seizures, or aborted cardiac arrest/sudden death stemming from torsades de pointes and VF. Athletes with an occasional finding of a QTc interval above the normal limits should have repeated ECG evaluations. Indeed, personal symptoms, family history, the scoring systems, the QTc changes during exercise, and recovery and genetic testing are needed to clarify the https://www.uptodate.com/contents/athletes-with-arrhythmias-electrocardiographic-abnormalities-and-conduction-disturbances/print 8/27 7/5/23, 10:33 AM Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances - UpToDate diagnosis. Since the risk of cardiac events during sports activities is largely gene specific, genetic testing and cascade screening of family members should be performed following a clinical diagnosis of LQTS. Individuals with LQT1 are at highest risk during stressful exercise. (See "Congenital long QT syndrome: Epidemiology and clinical manifestations".) Brugada pattern and syndrome Clinical concern for this syndrome is based primarily on the presence of the so-called type 1 Brugada pattern, which is defined as coved-type ST-segment elevation 2 mm followed by a negative T wave in 1 of the right precordial leads positioned in the fourth, third, or second intercostal space, noted either spontaneously or following provocation by a sodium ion channel blocker ( waveform 3). Confirmation of proper precordial lead placement is paramount, as high placement of the V1 and V2 electrodes in the second and/or third intercostal spaces (rather than the fourth intercostal space) can accentuate a type 1 Brugada ECG pattern and result in a false diagnosis. Patients with typical ECG features who are asymptomatic and have no other clinical criteria are said to have Brugada pattern, whereas patients with typical ECG features who have experienced SCD or a sustained ventricular tachyarrhythmia, or who have one or more of the other associated clinical criteria, are said to have Brugada syndrome. (See "Brugada syndrome: Epidemiology and pathogenesis", section on 'Brugada pattern versus Brugada syndrome'.) Although Brugada syndrome is associated with an increased risk of SCD, such events in patients with the Brugada pattern type 1 are typically not related to exercise, and Brugada syndrome has not been noted as a cause of SCD in athletes [19-21]. The type 1 Brugada ECG pattern is not a recognized variant of athlete's heart and should raise the possibility of a sodium ion channelopathy. Patients with a type 1 ECG pattern should be referred to a cardiac electrophysiologist for further evaluation, regardless of symptoms. There is general agreement that type 2 Brugada pattern should not be considered diagnostic for the pathologic variant, and should not prompt any testing, unless in the presence of the disease in the family or suspicious symptoms (ie, syncope). (See "Brugada syndrome: Clinical presentation, diagnosis, and evaluation" and "Athletes: Overview of sudden cardiac death risk and sport participation", section on 'Brugada syndrome'.) Profound sinus bradycardia Well-conditioned athletes, particularly endurance athletes, frequently exhibit some degree of sinus bradycardia with PR interval prolongation and even Mobitz type I (Wenckebach) second-degree AV block due to physiologically enhanced cardiac vagal tone. This is more likely when the patient is at rest or asleep. However, profound sinus bradycardia <30 beats per minute and/or PR prolongation >400 milliseconds are unusual in athletes and may be a marker of underlying cardiac disease. https://www.uptodate.com/contents/athletes-with-arrhythmias-electrocardiographic-abnormalities-and-conduction-disturbances/print 9/27 7/5/23, 10:33 AM Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances - UpToDate In most athletes, a formal or informal exercise test documenting an appropriate response of HR and PR interval with exercise is satisfactory. However, if there are concerns of an inadequate chronotropic response to exercise, additional testing (eg, echocardiogram, ambulatory ECG monitoring) should be pursued. Advanced AV block Second degree AV block: Mobitz type II Mobitz type II second degree atrioventricular (AV) block ( waveform 4) is usually due to disease in the His-Purkinje system. Mobitz type II AV block is identified by consistent unchanging PR intervals (which are usually normal in duration but may be prolonged) followed by the block of one or more P waves that fail to conduct to the ventricles. Mobitz type II second degree AV block is by nature unstable and requires prompt evaluation. (See "Second-degree atrioventricular block: Mobitz type II" and "Athletes with arrhythmias: Treatment and returning to athletic participation", section on 'Second degree AV block: Mobitz type II'.) Acquired third degree (complete) AV block Patients with third degree (complete) AV block will have evidence of atrial (P waves) and ventricular (QRS complexes) activity that are independent of each other on the surface ECG. When acquired and in the AV node, complete AV block ( waveform 5) escape rhythms are often junctional with a narrow QRS complex. By contrast, the escape rhythm is ventricular with a wide QRS complex when complete AV block is due to structural disease of the His-Purkinje system ( waveform 6). Regardless of the etiology, third degree (complete) AV block requires prompt evaluation. (See "Third-degree (complete) atrioventricular block" and "Athletes with arrhythmias: Treatment and returning to athletic participation", section on 'Third degree (complete) AV block'.) Congenital third degree (complete) AV block Congenital complete AV block is due to disease in the AV node, often occurring in the absence of other structural cardiac abnormalities. Most patients have a narrow complex and junctional escape rhythm. These patients will also require cardiac evaluation. (See "Congenital third-degree (complete) atrioventricular block".) Evaluation of athletes with advanced AV block In athletes with evidence of advanced AV block (either Mobitz type II second degree AV block or third degree [complete] AV block), further evaluation typically includes an echocardiogram, ambulatory ECG monitoring, and an exercise ECG test. Based on these results, laboratory testing and CMR imaging may be considered. Referral to a heart rhythm specialist is essential. Atrial fibrillation and atrial flutter AF, which may be present intermittently or persistently, is the most common arrhythmia in clinical practice, increasing in incidence with age, including older athletes. Among younger athletes, AF is relatively rare, with an incidence of approximately https://www.uptodate.com/contents/athletes-with-arrhythmias-electrocardiographic-abnormalities-and-conduction-disturbances/print 10/27 7/5/23, 10:33 AM Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances - UpToDate 3 in 1000 athletes in one study [22]. Atrial flutter is uncommon in athletes. AF and atrial flutter are rarely life-threatening and usually lead to symptoms like palpitations, shortness of breath, chest pressure, dizziness, neck pounding, or syncope from rapid heart rates. In young athletes, AF may occur in the absence of any structural heart disease or other provoking condition and is termed "lone AF." However, in older athletes, hypertension and coronary artery disease are common underlying conditions. Moreover, AF or flutter can be associated with other conditions that can lead to SCD, including WPW, Brugada syndrome, myocarditis, congenital heart disease, and any form of cardiomyopathy. When AF or flutter is found, a comprehensive clinical evaluation is advised, including echocardiogram to assess for structural heart disease. Anticoagulation is considered based on standard guidelines (CHA DS - 2 2 VASc score). Subsequent investigation should be directed as needed based on the clinical findings. (See "Athletes with arrhythmias: Treatment and returning to athletic participation", section on 'Atrial fibrillation' and "Overview of atrial flutter" and "Athletes with arrhythmias: Treatment and returning to athletic participation", section on 'Atrial flutter' and "Atrial fibrillation: Overview and management of new-onset atrial fibrillation", section on 'Evaluation'.) Supraventricular tachyarrhythmias AV nodal reentrant tachycardia (AVNRT) is a common arrhythmia in young people and is often associated with symptoms resulting from a rapid heart rate. (See "Atrioventricular nodal reentrant tachycardia" and "Athletes with arrhythmias: Treatment and returning to athletic participation", section on 'Atrioventricular nodal reentrant tachycardia'.) AV reentrant tachycardia (AVRT) occurs in patients with manifest WPW syndrome or a concealed (ie, not seen on 12-lead ECG) bypass tract. This arrhythmia may have a narrow QRS complex when ventricular activation is via the normal AV node-His Purkinje system (orthodromic AVRT) or, less commonly, a wide QRS complex when ventricular activation is via the accessory pathway (antidromic AVRT). It should be noted, however, that a wide complex tachycardia with an orthodromic AVRT may also be observed if there is aberrant conduction. (See "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway" and "Athletes with arrhythmias: Treatment and returning to athletic participation", section on 'Wolff-Parkinson-White syndrome'.) Atrial tachycardia may be due to an automatic focus or reentry; these arrhythmias are not commonly seen in athletes ( table 1). (See "Athletes with arrhythmias: Treatment and returning to athletic participation", section on 'Atrial tachycardia'.) Detection on ECG (or suspicion from history) of supraventricular tachyarrhythmias should prompt evaluation, including an echocardiogram, ambulatory ECG monitor, and exercise https://www.uptodate.com/contents/athletes-with-arrhythmias-electrocardiographic-abnormalities-and-conduction-disturbances/print 11/27 7/5/23, 10:33 AM Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances - UpToDate treadmill test, and referral to a heart rhythm specialist is generally indicated for consideration of electrophysiology study and ablation. Individuals with proven supraventricular tachycardia without preexcitation should be educated on how to perform vagal maneuvers (such as carotid sinus massage or, preferably, Valsalva maneuver) to facilitate termination of the arrhythmia. Ventricular premature beats Ventricular premature beats (VPBs) are common in athletes of all age groups and occur in those with or without structural heart disease. VPBs may be idiopathic or secondary to the cardiomyopathies, ion channelopathies, or other diseases such as myocarditis, myocardial infarction, or sarcoidosis. The presence of two or more VPBs in a 10- second ECG tracing is considered abnormal and warrants further investigation. Largely, their prognostic importance is based upon the possible association with underlying structural heart disease ( table 1). Exclusion of underlying cardiac disease is the first step in these individuals and should be performed with echocardiography. With regard to the ECG characteristics, the morphology of the VPBs is relevant, with those presenting with an RBBB or LBBB, wide QRS, and superior axis (originating from the left ventricle or RV free wall) and those exacerbating during effort having high index of suspicion for underlying cardiac disease. Additional features associated with higher probability of cardiac disease are the high frequency (>2000 VPBs in 24- hour ECG monitoring) and the complexity (couplets, or nonsustained ventricular tachycardia [VT] associated to VPBs) [9]. Athletes with VPBs who do not have structural heart disease do not appear to have an increased risk of cardiovascular events [23,24]. (See "Premature ventricular complexes: Clinical presentation and diagnostic evaluation" and "Athletes with arrhythmias: Treatment and returning to athletic participation", section on 'Ventricular premature beats'.) Ventricular tachycardia Monomorphic VT may be idiopathic (eg, RV outflow tract VT or left anterior fascicular [Belhassen-type]) or secondary to underlying cardiac disease. Most otherwise fit individuals who present with polymorphic VT have underlying structural heart disease. Further evaluation is essential for either of these presentations. The evaluation should include a thorough family history, an echocardiogram to evaluate for structural heart disease, ambulatory ECG monitoring, and an exercise ECG test. Depending on the results, further evaluation may be indicated, including CMR imaging to assess for arrhythmogenic RV cardiomyopathy or other cardiomyopathies, or genetic testing. All individuals with sustained monomorphic or polymorphic VT should be referred to a heart rhythm specialist. (See "Cardiac evaluation of the survivor of sudden cardiac arrest" and "Ventricular tachycardia in the absence of apparent structural heart disease" and "Athletes with arrhythmias: Treatment and returning to athletic participation", section on 'Ventricular arrhythmias'.) https://www.uptodate.com/contents/athletes-with-arrhythmias-electrocardiographic-abnormalities-and-conduction-disturbances/print 12/27 7/5/23, 10:33 AM Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances - UpToDate SUMMARY AND RECOMMENDATIONS Prevalence A broad range of ECG abnormalities can be seen in trained athletes, particularly increased QRS voltage and repolarization abnormalities ( table 1). (See 'Prevalence' above.) Clinical approach to reading the ECG in athletes For practical purposes, ECG changes in athletes can be classified into three main groups ( figure 1): one related to whether the ECG abnormality is likely to be a physiologic result of chronic training (normal ECG changes in athletes), one in which the ECG finding is borderline abnormal, and the third related to whether the ECG finding occurs independently of training and thus may be an expression of a pathologic condition (borderline or abnormal ECG changes in athletes). (See 'Clinical approach to reading the ECG in athletes' above.) Normal ECG findings Common ECG abnormalities ("normal" in athletes) are frequent and are not associated with an increased risk of underlying cardiac disease and incidence of adverse events during exercise. (See 'Normal ECG findings' above.) Borderline ECG findings Borderline ECG findings may represent pathologic or innocent ECG alterations. (See 'Borderline ECG findings' above.) Abnormal ECG findings Abnormal ECG findings are significantly more likely to represent pathology rather than a normal response to training. As such, patients with an abnormal ECG finding should undergo further evaluation to search for cardiac pathology. (See 'Abnormal ECG findings' above.) Sport participation The approaches to risk stratification and returning to participation/competition in athletes who have an abnormal ECGs or a cardiovascular disease are discussed in detail separately. (See "Athletes: Overview of sudden cardiac death risk and sport participation" and "Athletes with arrhythmias: Treatment and returning to athletic participation".) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Maron BJ, Levine BD, Washington RL, et al. Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 2: Preparticipation Screening for Cardiovascular Disease in Competitive Athletes: A Scientific Statement From https://www.uptodate.com/contents/athletes-with-arrhythmias-electrocardiographic-abnormalities-and-conduction-disturbances/print 13/27 7/5/23, 10:33 AM Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances - UpToDate the American Heart Association and American College of Cardiology. J Am Coll Cardiol 2015; 66:2356. 2. Pelliccia A, Maron BJ, Culasso F, et al. Clinical significance of abnormal electrocardiographic patterns in trained athletes. Circulation 2000; 102:278. 3. Brosnan M, La Gerche A, Kalman J, et al. Comparison of frequency of significant electrocardiographic abnormalities in endurance versus nonendurance athletes. Am J Cardiol 2014; 113:1567. 4. Serra-Grima R, Estorch M, Carri I, et al. Marked ventricular repolarization abnormalities in highly trained athletes' electrocardiograms: clinical and prognostic implications. J Am Coll Cardiol 2000; 36:1310. 5. Pelliccia A, Culasso F, Di Paolo FM, et al. Prevalence of abnormal electrocardiograms in a large, unselected population undergoing pre-participation cardiovascular screening. Eur Heart J 2007; 28:2006. 6. Sheikh N, Papadakis M, Ghani S, et al. Comparison of electrocardiographic criteria for the detection of cardiac abnormalities in elite black and white athletes. Circulation 2014; 129:1637. 7. Corrado D, Pelliccia A, Heidbuchel H, et al. Recommendations for interpretation of 12-lead electrocardiogram in the athlete. Eur Heart J 2010; 31:243. 8. Drezner JA, Ackerman MJ, Anderson J, et al. Electrocardiographic interpretation in athletes: the 'Seattle criteria'. Br J Sports Med 2013; 47:122. 9. Sharma S, Drezner JA, Baggish A, et al. International Recommendations for Electrocardiographic Interpretation in Athletes. J Am Coll Cardiol 2017; 69:1057. 10. Gati S, Sheikh N, Ghani S, et al. Should axis deviation or atrial enlargement be categorised as abnormal in young athletes? The athlete's electrocardiogram: time for re-appraisal of

Detection on ECG (or suspicion from history) of supraventricular tachyarrhythmias should prompt evaluation, including an echocardiogram, ambulatory ECG monitor, and exercise https://www.uptodate.com/contents/athletes-with-arrhythmias-electrocardiographic-abnormalities-and-conduction-disturbances/print 11/27 7/5/23, 10:33 AM Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances - UpToDate treadmill test, and referral to a heart rhythm specialist is generally indicated for consideration of electrophysiology study and ablation. Individuals with proven supraventricular tachycardia without preexcitation should be educated on how to perform vagal maneuvers (such as carotid sinus massage or, preferably, Valsalva maneuver) to facilitate termination of the arrhythmia. Ventricular premature beats Ventricular premature beats (VPBs) are common in athletes of all age groups and occur in those with or without structural heart disease. VPBs may be idiopathic or secondary to the cardiomyopathies, ion channelopathies, or other diseases such as myocarditis, myocardial infarction, or sarcoidosis. The presence of two or more VPBs in a 10- second ECG tracing is considered abnormal and warrants further investigation. Largely, their prognostic importance is based upon the possible association with underlying structural heart disease ( table 1). Exclusion of underlying cardiac disease is the first step in these individuals and should be performed with echocardiography. With regard to the ECG characteristics, the morphology of the VPBs is relevant, with those presenting with an RBBB or LBBB, wide QRS, and superior axis (originating from the left ventricle or RV free wall) and those exacerbating during effort having high index of suspicion for underlying cardiac disease. Additional features associated with higher probability of cardiac disease are the high frequency (>2000 VPBs in 24- hour ECG monitoring) and the complexity (couplets, or nonsustained ventricular tachycardia [VT] associated to VPBs) [9]. Athletes with VPBs who do not have structural heart disease do not appear to have an increased risk of cardiovascular events [23,24]. (See "Premature ventricular complexes: Clinical presentation and diagnostic evaluation" and "Athletes with arrhythmias: Treatment and returning to athletic participation", section on 'Ventricular premature beats'.) Ventricular tachycardia Monomorphic VT may be idiopathic (eg, RV outflow tract VT or left anterior fascicular [Belhassen-type]) or secondary to underlying cardiac disease. Most otherwise fit individuals who present with polymorphic VT have underlying structural heart disease. Further evaluation is essential for either of these presentations. The evaluation should include a thorough family history, an echocardiogram to evaluate for structural heart disease, ambulatory ECG monitoring, and an exercise ECG test. Depending on the results, further evaluation may be indicated, including CMR imaging to assess for arrhythmogenic RV cardiomyopathy or other cardiomyopathies, or genetic testing. All individuals with sustained monomorphic or polymorphic VT should be referred to a heart rhythm specialist. (See "Cardiac evaluation of the survivor of sudden cardiac arrest" and "Ventricular tachycardia in the absence of apparent structural heart disease" and "Athletes with arrhythmias: Treatment and returning to athletic participation", section on 'Ventricular arrhythmias'.) https://www.uptodate.com/contents/athletes-with-arrhythmias-electrocardiographic-abnormalities-and-conduction-disturbances/print 12/27 7/5/23, 10:33 AM Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances - UpToDate SUMMARY AND RECOMMENDATIONS Prevalence A broad range of ECG abnormalities can be seen in trained athletes, particularly increased QRS voltage and repolarization abnormalities ( table 1). (See 'Prevalence' above.) Clinical approach to reading the ECG in athletes For practical purposes, ECG changes in athletes can be classified into three main groups ( figure 1): one related to whether the ECG abnormality is likely to be a physiologic result of chronic training (normal ECG changes in athletes), one in which the ECG finding is borderline abnormal, and the third related to whether the ECG finding occurs independently of training and thus may be an expression of a pathologic condition (borderline or abnormal ECG changes in athletes). (See 'Clinical approach to reading the ECG in athletes' above.) Normal ECG findings Common ECG abnormalities ("normal" in athletes) are frequent and are not associated with an increased risk of underlying cardiac disease and incidence of adverse events during exercise. (See 'Normal ECG findings' above.) Borderline ECG findings Borderline ECG findings may represent pathologic or innocent ECG alterations. (See 'Borderline ECG findings' above.) Abnormal ECG findings Abnormal ECG findings are significantly more likely to represent pathology rather than a normal response to training. As such, patients with an abnormal ECG finding should undergo further evaluation to search for cardiac pathology. (See 'Abnormal ECG findings' above.) Sport participation The approaches to risk stratification and returning to participation/competition in athletes who have an abnormal ECGs or a cardiovascular disease are discussed in detail separately. (See "Athletes: Overview of sudden cardiac death risk and sport participation" and "Athletes with arrhythmias: Treatment and returning to athletic participation".) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Maron BJ, Levine BD, Washington RL, et al. Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 2: Preparticipation Screening for Cardiovascular Disease in Competitive Athletes: A Scientific Statement From https://www.uptodate.com/contents/athletes-with-arrhythmias-electrocardiographic-abnormalities-and-conduction-disturbances/print 13/27 7/5/23, 10:33 AM Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances - UpToDate the American Heart Association and American College of Cardiology. J Am Coll Cardiol 2015; 66:2356. 2. Pelliccia A, Maron BJ, Culasso F, et al. Clinical significance of abnormal electrocardiographic patterns in trained athletes. Circulation 2000; 102:278. 3. Brosnan M, La Gerche A, Kalman J, et al. Comparison of frequency of significant electrocardiographic abnormalities in endurance versus nonendurance athletes. Am J Cardiol 2014; 113:1567. 4. Serra-Grima R, Estorch M, Carri I, et al. Marked ventricular repolarization abnormalities in highly trained athletes' electrocardiograms: clinical and prognostic implications. J Am Coll Cardiol 2000; 36:1310. 5. Pelliccia A, Culasso F, Di Paolo FM, et al. Prevalence of abnormal electrocardiograms in a large, unselected population undergoing pre-participation cardiovascular screening. Eur Heart J 2007; 28:2006. 6. Sheikh N, Papadakis M, Ghani S, et al. Comparison of electrocardiographic criteria for the detection of cardiac abnormalities in elite black and white athletes. Circulation 2014; 129:1637. 7. Corrado D, Pelliccia A, Heidbuchel H, et al. Recommendations for interpretation of 12-lead electrocardiogram in the athlete. Eur Heart J 2010; 31:243. 8. Drezner JA, Ackerman MJ, Anderson J, et al. Electrocardiographic interpretation in athletes: the 'Seattle criteria'. Br J Sports Med 2013; 47:122. 9. Sharma S, Drezner JA, Baggish A, et al. International Recommendations for Electrocardiographic Interpretation in Athletes. J Am Coll Cardiol 2017; 69:1057. 10. Gati S, Sheikh N, Ghani S, et al. Should axis deviation or atrial enlargement be categorised as abnormal in young athletes? The athlete's electrocardiogram: time for re-appraisal of markers of pathology. Eur Heart J 2013; 34:3641. 11. Kim JH, Noseworthy PA, McCarty D, et al. Significance of electrocardiographic right bundle branch block in trained athletes. Am J Cardiol 2011; 107:1083. 12. Brosnan MJ, te Riele ASJM, Bosman LP, et al. Electrocardiographic features differentiating arrhythmogenic right ventricular cardiomyopathy from an athlete's heart. J Am Coll Cardiol EP 2018; 4:1613. 13. Aro AL, Anttonen O, Tikkanen JT, et al. Intraventricular conduction delay in a standard 12- lead electrocardiogram as a predictor of mortality in the general population. Circ Arrhythm Electrophysiol 2011; 4:704. https://www.uptodate.com/contents/athletes-with-arrhythmias-electrocardiographic-abnormalities-and-conduction-disturbances/print 14/27 7/5/23, 10:33 AM Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances - UpToDate 14. Platonov PG, Calkins H, Hauer RN, et al. High interobserver variability in the assessment of epsilon waves: Implications for diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia. Heart Rhythm 2016; 13:208. 15. Munger TM, Packer DL, Hammill SC, et al. A population study of the natural history of Wolff- Parkinson-White syndrome in Olmsted County, Minnesota, 1953-1989. Circulation 1993; 87:866. 16. Furlanello F, Bertoldi A, Bettini R, et al. Life-threatening tachyarrhythmias in athletes. Pacing Clin Electrophysiol 1992; 15:1403. 17. Klein GJ, Yee R, Sharma AD. Longitudinal electrophysiologic assessment of asymptomatic patients with the Wolff-Parkinson-White electrocardiographic pattern. N Engl J Med 1989; 320:1229. 18. Indik JH, Pearson EC, Fried K, Woosley RL. Bazett and Fridericia QT correction formulas interfere with measurement of drug-induced changes in QT interval. Heart Rhythm 2006; 3:1003. 19. Corrado D, Basso C, Schiavon M, Thiene G. Screening for hypertrophic cardiomyopathy in young athletes. N Engl J Med 1998; 339:364. 20. Maron BJ, Ackerman MJ, Nishimura RA, et al. Task Force 4: HCM and other cardiomyopathies, mitral valve prolapse, myocarditis, and Marfan syndrome. J Am Coll Cardiol 2005; 45:1340. 21. Corrado D, Basso C, Buja G, et al. Right bundle branch block, right precordial st-segment elevation, and sudden death in young people. Circulation 2001; 103:710. 22. Boraita A, Santos-Lozano A, Heras ME, et al. Incidence of Atrial Fibrillation in Elite Athletes. JAMA Cardiol 2018; 3:1200. 23. Biffi A, Pelliccia A, Verdile L, et al. Long-term clinical significance of frequent and complex ventricular tachyarrhythmias in trained athletes. J Am Coll Cardiol 2002; 40:446. 24. Biffi A, Maron BJ, Verdile L, et al. Impact of physical deconditioning on ventricular tachyarrhythmias in trained athletes. J Am Coll Cardiol 2004; 44:1053. Topic 991 Version 25.0 https://www.uptodate.com/contents/athletes-with-arrhythmias-electrocardiographic-abnormalities-and-conduction-disturbances/print 15/27 7/5/23, 10:33 AM Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances - UpToDate GRAPHICS Seattle criteria classifying the normal and abnormal electrocardiogram findings in athletes Normal ECG findings in athletes 1. Sinus bradycardia ( 30 bpm) 2. Sinus arrhythmia 3. Ectopic atrial rhythm 4. Junctional escape rhythm 5. 1 AV block (PR interval >200 ms) 6. Mobitz Type I (Wenckebach) 2 AV block 7. Incomplete RBBB 8. Isolated QRS voltage criteria for LVH Except: QRS voltage criteria for LVH occurring with any non-voltage criteria for LVH such as left atrial enlargement, left axis deviation, ST segment depression, T-wave inversion, or pathological Q waves 9. Early repolarization (ST elevation, J-point elevation, J-waves, or terminal QRS slurring) 10. Convex ("domed") ST segment elevation combined with T-wave inversion in leads V1 V4 in black/African athletes These common training-related ECG alterations are physiological adaptations to regular exercise, considered normal variants in athletes and do not require further evaluation in asymptomatic athletes Abnormal ECG findings in athletes Abnormal ECG Definition finding T-wave inversion >1 mm in depth in two or more leads V2 V6, II and aVF, or I and aVL (excludes III, aVR and V1) 0.5 mm in depth in two or more leads ST segment depression Pathologic Q >3 mm in depth or >40 ms in duration in two or more leads (except for III and waves aVR) QRS 120 ms, predominantly negative QRS complex in lead V1 (QS or rS), and upright monophasic R wave in leads I and V6 Complete left bundle branch block https://www.uptodate.com/contents/athletes-with-arrhythmias-electrocardiographic-abnormalities-and-conduction-disturbances/print 16/27 7/5/23, 10:33 AM Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances - UpToDate Any QRS duration 140 ms Intraventricular conduction delay Left axis deviation 30 to 90 Left atrial enlargement Prolonged P wave duration of >120 ms in leads I or II with negative portion of the P wave 1 mm in depth and 40 ms in duration in lead V1 Right ventricular hypertrophy R V1+S V5 >10.5 mm AND right axis deviation >120 pattern Ventricular pre- PR interval <120 ms with a delta wave (slurred upstroke in the QRS complex) and excitation wide QRS (>120 ms) QTc 470 ms (male) Long QT interval* QTc 480 ms (female) QTc 500 ms (marked QT prolongation) Short QT interval* QTc 320 ms Brugada-like ECG High take-off and downsloping ST segment elevation followed by a negative T wave in 2 leads in V1 V3 pattern <30 bpm or sinus pauses 3 s Profound sinus bradycardia Atrial tachyarrhythmias Supraventricular tachycardia, atrial fibrillation, atrial flutter 2 PVCs per 10 s tracing Premature ventricular contractions Ventricular arrhythmias Couplets, triplets, and non-sustained ventricular tachycardia ECG: electrocardiogram; bpm: beats per minute; AV: atrioventricular; RBBB: right bundle branch block; LVH: left ventricular hypertrophy; PVC: premature ventricular contraction; ms: milliseconds. The QT interval corrected for heart rate is ideally measured with heart rates of 60 to 90 bpm. Consider repeating the ECG after mild aerobic activity for borderline or abnormal QTc values with a heart rate <50 bpm. From: Drezner JA, Ackerman MJ, Anderson J, et al. Electrocardiographic interpretation in athletes: The "Seattle Criteria". Br J Sports Med 2013; 47:123. Reproduced with permission from BMJ Publishing Group Ltd. Copyright 2013. Graphic 102509 Version 3.0 https://www.uptodate.com/contents/athletes-with-arrhythmias-electrocardiographic-abnormalities-and-conduction-disturbances/print 17/27 7/5/23, 10:33 AM Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances - UpToDate Algorithm showing international consensus standards ECG interpretation in athletes and need for subsequent evaluation ECG: electrocardiogram; LVH: left ventricular hypertrophy; RVH: right ventricular hypertrophy; RBBB: right bundle branch block; AV: atrioventricular; LBBB: left bundle branch block; bpm: beats per minute; PVC: premature ventricular contraction; SCD: sudden cardiac death. Reproduced with permission from: Drezner JA, Sharma S, Baggish A, et al. International criteria for electrocardiographic interpretation in athletes. Br J Sports Med 2017; 51:704. Copyright 2017 BMJ Publishing Group Ltd. Graphic 115355 Version 1.0 https://www.uptodate.com/contents/athletes-with-arrhythmias-electrocardiographic-abnormalities-and-conduction-disturbances/print 18/27 7/5/23, 10:33 AM Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances - UpToDate Electrocardiogram (ECG) showing common right bundle branch block (RBBB) Electrocardiogram showing characteristic changes in the precordial leads in complete RBBB. The asynchronous activation of the two ventricles increases the QRS duration (0.13 seconds). The terminal forces are rightward and anterior due to the delayed activation of the right ventricle, resulting in an rsR' pattern in the anterior-posterior lead V1 and a wide negative S wave in the left-right lead V6 (and, not shown, in lead I). Courtesy of Ary Goldberger, MD. Graphic 64393 Version 7.0 Normal ECG https://www.uptodate.com/contents/athletes-with-arrhythmias-electrocardiographic-abnormalities-and-conduction-disturbances/print 19/27 7/5/23, 10:33 AM Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances - UpToDate Normal electrocardiogram showing normal sinus rhythm at a rate of 75 beats/minute, a PR interval of 0.14 seconds, a QRS interval of 0.10 seconds, and a QRS axis of approximately 75 . Courtesy of Ary Goldberger, MD. Graphic 76183 Version 4.0 https://www.uptodate.com/contents/athletes-with-arrhythmias-electrocardiographic-abnormalities-and-conduction-disturbances/print 20/27 7/5/23, 10:33 AM Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances - UpToDate 12-lead electrocardiogram (ECG) showing typical left bundle branch block Electrocardiogram in typical complete left bundle branch block. The asynchronous activation of the 2 ventricles increases the QRS duration (0.16 seconds in this example). The abnormal initial vector results in loss of "normal" septal forces as manifested by absence of q waves in leads I, aVL, and V6. The late activation of the left ventricle prolongs the dominant leftward progression of the middle and terminal forces, leading to a positive and widened R wave in the lateral leads. Both the ST segment and T wave vectors are opposite in direction from the QRS, a "secondary" repolarization abnormality. Courtesy of Ary Goldberger, MD. Graphic 61594 Version 9.0 Normal ECG https://www.uptodate.com/contents/athletes-with-arrhythmias-electrocardiographic-abnormalities-and-conduction-disturbances/print 21/27 7/5/23, 10:33 AM Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances - UpToDate Normal electrocardiogram showing normal sinus rhythm at a rate of 75 beats/minute, a PR interval of 0.14 seconds, a QRS interval of 0.10 seconds, and a QRS axis of approximately 75 . Courtesy of Ary Goldberger, MD. Graphic 76183 Version 4.0 https://www.uptodate.com/contents/athletes-with-arrhythmias-electrocardiographic-abnormalities-and-conduction-disturbances/print 22/27 7/5/23, 10:33 AM Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances - UpToDate 12-lead electrocardiogram (ECG) from a patient with the Brugada syndrome shows downsloping ST elevation ST segment elevation and T wave inversion in the right precordial leads V1 and V2 (arrows); the QRS is normal. The widened S wave in the left lateral leads (V5 and V6) that is characteristic of right bundle branch block is absent. Courtesy of Rory Childers, MD, University of Chicago. Graphic 64510 Version 10.0 https://www.uptodate.com/contents/athletes-with-arrhythmias-electrocardiographic-abnormalities-and-conduction-disturbances/print 23/27 7/5/23, 10:33 AM Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances - UpToDate Electrocardiographic and electrophysiologic features of Mobitz type II second-degree atrioventricular block The PR and RR intervals are constant, but the third atrial beat (A) is not conducted (arrow). His bundle electrocardiography (HBE) shows constant AH (85 msec) and HV (95 msec) intervals and normal AH but no HV conduction in the nonconducted beat. The last finding indicates that the block is distal to the His bundle, in contrast with the more proximal location of Mobitz type I atrioventricular block. Adapted from: Josephson ME, Clinical Cardiac Electrophysiology: Techniques and nd Interpretations, 2 ed, Lea & Febiger, Philadelphia 1993. Graphic 79539 Version 7.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/athletes-with-arrhythmias-electrocardiographic-abnormalities-and-conduction-disturbances/print 24/27 7/5/23, 10:33 AM Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances - UpToDate Single-lead electrocardiogram (ECG) showing sinus rhythm with third degree (complete) AV block Sinus rhythm with third degree (complete) heart block. There is independent atrial (as shown by the P waves) and ventricular activity, with respective rates of 83 and 43 beats per minute. The wide QRS complexes may represent a junctional escape rhythm with underlying bundle branch block or an idioventricular pacemaker. Courtesy of Ary Goldberger, MD. Graphic 72863 Version 6.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/athletes-with-arrhythmias-electrocardiographic-abnormalities-and-conduction-disturbances/print 25/27 7/5/23, 10:33 AM Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances - UpToDate Third degree (complete) atrioventricular block with wide QRS escape rhythm The P waves are completely dissociated from the QRS complexes and the PR intervals are variable. The atrial or PP rate (75 beats per minute) is faster than the ventricular or RR rate (30 beats per minute), establishing complete atrioventricular blockade as the etiology. The QRS complexes are wide indicating that the escape rhythm is ventricular. Graphic 51446 Version 5.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/athletes-with-arrhythmias-electrocardiographic-abnormalities-and-conduction-disturbances/print 26/27 7/5/23, 10:33 AM Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances - UpToDate Contributor Disclosures Mark S Link, MD No relevant financial relationship(s) with ineligible companies to disclose. Antonio Pelliccia, MD No relevant financial relationship(s) with ineligible companies to disclose. Peter J Zimetbaum, MD Consultant/Advisory Boards: Abbott Medical [Lead extraction]. All of the relevant financial relationships listed have been mitigated. Ary L Goldberger, MD Other Financial Interest: Elsevier book royalties [Clinical electrocardiography]. All of the relevant financial relationships listed have been mitigated. Todd F Dardas, MD, MS No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/athletes-with-arrhythmias-electrocardiographic-abnormalities-and-conduction-disturbances/print 27/27

7/5/23, 10:34 AM Chronic bifascicular blocks - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Chronic bifascicular blocks : William H Sauer, MD : N A Mark Estes, III, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Dec 06, 2022. INTRODUCTION Bifascicular block, a pattern seen on the surface electrocardiogram (ECG), results when normal physiologic activation in the His-Purkinje system is interrupted. The normal sequence of activation is altered dramatically in patients with bifascicular block, with a resultant characteristic appearance on the ECG that varies depending upon the exact fascicles which are blocked. Interruptions in conduction may result in right bundle branch block (RBBB), left anterior fascicular block (LAFB), or left posterior fascicular block (LPFB), with bifascicular block resulting when two of these three are identified from the ECG. A 2009 American Heart Association/American College of Cardiology Foundation/Heart Rhythm Society (AHA/ACCF/HRS) scientific statement on the standardization and interpretation of the electrocardiogram recommends against using the term bifascicular block (and also trifascicular block) since these patterns do not have unique anatomic and pathologic substrates [1]. However, these terms are still widely entrenched in clinical practice and scientific literature, meriting their discussion here. The anatomy, clinical manifestations, differential diagnosis, prognostic implications, and treatment of bifascicular block (RBBB with either LAFB or LPFB) will be reviewed here. Though technically a type of bifascicular block, complete LBBB is discussed separately, as are conduction system abnormalities involving only a single fascicle. (See "Left bundle branch block" and "Right bundle branch block" and "Left anterior fascicular block" and "Left posterior fascicular block" and "Left septal fascicular block".) https://www.uptodate.com/contents/chronic-bifascicular-blocks/print 1/19 7/5/23, 10:34 AM Chronic bifascicular blocks - UpToDate DEFINITIONS Bifascicular block The term bifascicular block most commonly refers to conduction disturbances below the atrioventricular (AV) node in which the right bundle branch and one of the two fascicles (anterior or posterior) of the left bundle branch are involved. Although this definition is most commonly used, left bundle branch block (LBBB) is also a type of bifascicular block since LBBB, as noted, implies block in both fascicles [2,3]. Trifascicular block The term trifascicular block is most commonly used to describe bifascicular block associated with prolongation of the PR interval (ie, first degree AV block). However, this description, though commonly used in clinical practice, is inaccurate as the conduction delay resulting in the PR interval prolongation does not usually occur in a fascicle, but in the AV node. True trifascicular block would involve block of the right bundle branch and both fascicles of the left bundle branch; this manifests as third degree (complete) heart block and is referred to as such. Sinus rhythm with alternating left/right bundle branch block or right bundle branch block (RBBB) with alternating fascicular blocks on a beat-to-beat basis is a very rare manifestation of trifascicular block, usually heralding complete AV block. (See "Third-degree (complete) atrioventricular block".) ANATOMY AND BLOOD SUPPLY Anatomy The bundle of His divides at the juncture of the fibrous and muscular boundaries of the intraventricular septum into the left and right bundle branches ( figure 1). The right bundle branch is a long, thin, discrete structure that courses down the right side of interventricular septum near the endocardium in its upper third, deeper in the muscular portion of the septum in the middle third, and then again near the endocardium in its lower third. The right bundle branch does not divide throughout most of its course, but begins to ramify as it approaches the base of the right anterior papillary muscle with fascicles going to the septal and free walls of the right ventricle. The main left bundle branch penetrates the membranous portion of the interventricular septum under the aortic ring and then divides into several fairly discrete branches. The components of the left bundle branch are ( figure 1) [4-8]: A pre-divisional segment An anterior fascicle that crosses the left ventricular outflow tract and terminates in the Purkinje system of the anterolateral wall of the left ventricle https://www.uptodate.com/contents/chronic-bifascicular-blocks/print 2/19 7/5/23, 10:34 AM Chronic bifascicular blocks - UpToDate A posterior fascicle that fans out extensively inferiorly and posteriorly into Purkinje fibers In some hearts, a median fascicle to the interventricular septum Blood supply The blood supply to the fascicles is complex and somewhat variable between patients: The right bundle branch receives most of its blood supply from septal branches of the left anterior descending coronary artery, particularly in its initial course. In most patients, it also receives some collateral supply from either the right or circumflex coronary systems depending upon the dominance of the coronary system ( figure 2). The left anterior fascicle (and median fascicle, when present) is supplied either by septal branches of the left anterior descending artery or by the atrioventricular (AV) nodal artery ( figure 2). The proximal part of the left posterior fascicle is supplied by the artery to the AV node and, at times, by septal branches of the left anterior descending artery. The distal portion has a dual blood supply from both anterior and posterior septal perforating arteries. As is true for the right bundle branch, the left fascicles may receive some collateral flow from the right and circumflex coronary systems. ETIOLOGY The right bundle branch is vulnerable to stretch and trauma for two-thirds of its course when it is near the subendocardial surface ( figure 1). Additionally, conduction in both the right and left bundle branches can be compromised by both structural and functional factors (eg, chronic ventricular pressure or volume overload, myocardial ischemia, myocarditis, etc). A more extensive discussion of the etiologies of conduction disturbances in the right and left bundles is presented elsewhere. (See "Right bundle branch block", section on 'Etiology' and "Left bundle branch block", section on 'Etiology'.) CLINICAL PRESENTATION, DIAGNOSIS, AND EVALUATION ECG findings Bifascicular block may present with one of three potential appearances on the surface electrocardiogram (ECG): Right bundle branch block (RBBB) and left anterior fascicular block (LAFB) ( waveform 1) RBBB and left posterior fascicular block (LPFB) ( waveform 2) LAFB and LPFB (ie, left bundle branch block [LBBB]) ( waveform 3) https://www.uptodate.com/contents/chronic-bifascicular-blocks/print 3/19 7/5/23, 10:34 AM Chronic bifascicular blocks - UpToDate Detailed descriptions of the ECG findings associated with RBBB, LAFB, LPFB, and LBBB are presented separately. (See "Right bundle branch block", section on 'ECG findings and diagnosis' and "Left anterior fascicular block", section on 'Electrocardiographic findings' and "Left posterior fascicular block", section on 'Electrocardiographic findings' and "Left bundle branch block", section on 'ECG findings and diagnosis'.) Asymptomatic patients In nearly all instances, the clinical presentation of bifascicular block is asymptomatic and fairly benign, as bifascicular block in and of itself does not produce symptoms, and there are no specific signs of bifascicular block during physical examination. As such, bifascicular block is identified when patients are undergoing an ECG for another indication. For asymptomatic patients with bifascicular block, no further diagnostic evaluation or therapy is required. However, patients should be carefully screened for symptoms and signs suggesting occult cardiac disease, as concomitant structural heart disease is frequently present. If underlying cardiac disease is suspected, additional diagnostic testing and therapy would proceed accordingly. Symptomatic patients For patients who present with presyncope or syncope and are noted to have bifascicular block on ECG, additional monitoring and evaluation are required, as such patients may have intermittent complete heart block that results in hemodynamic instability leading to their symptoms of presyncope or syncope. In those patients with syncope or presyncope who have suspected advanced conduction disease, we perform continuous ECG monitoring for 24 to 48 hours, usually in an inpatient setting, to monitor for high-grade AV block that would require a permanent pacemaker [3]. Additionally, cardiac imaging with echocardiography is indicated, as this presentation could be the initial manifestation of structural heart disease [3]. In our opinion, patients presenting with unexplained syncope and bifascicular block should be evaluated immediately as possible progression to heart block is unknown at initial presentation. In those patients with a structurally normal heart and unexplained syncope with bifascicular block, an electrophysiologic study (EPS) could identify occult infranodal conduction disease and prompt permanent pacemaker implantation [2,9]. Patients with an abnormal EPS (HV >70 msec or His-Purkinje AV block with pacing or pharmacologic challenge) would generally benefit from permanent pacemaker implantation. In those patients with unexplained syncope and no obvious etiology, long-term monitoring with an insertable cardiac monitor (also sometimes referred to as an implantable cardiac monitor or an implantable loop recorder) is indicated. (See "Ambulatory ECG monitoring".) https://www.uptodate.com/contents/chronic-bifascicular-blocks/print 4/19 7/5/23, 10:34 AM Chronic bifascicular blocks - UpToDate Limited data suggest that tilt table testing is not helpful in patients with bifascicular block with unexplained syncope, and as such we do not recommend tilt table testing in this population. In a study comparing such patients with control subjects with bifascicular block and no syncope, no difference in the incidence of a positive tilt table test (28 versus 32 percent) was observed, suggesting that test specificity in this population is poor [10]. DIFFERENTIAL DIAGNOSIS While bifascicular block has one of two fairly characteristic appearances on electrocardiogram (ECG), there are other conditions in which the ECG may have a similar appearance that need to be excluded prior to confirming the diagnosis of bifascicular block. Ventricular tachycardia and accelerated idioventricular rhythm If the dominant ventricular rhythm originates from a pacemaker in the ventricle, the QRS will be widened and can have the appearance of bifascicular block. However, both ventricular tachycardia (heart rate greater than 100 beats per minute) ( waveform 4) and accelerated idioventricular rhythm (heart rate between 60 and 100 beats per minute) ( waveform 5) are associated with atrioventricular (AV) dissociation, which should distinguish the rhythm from a supraventricular rhythm with bifascicular block. (See "Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation" and "ECG tutorial: Ventricular arrhythmias", section on 'Accelerated idioventricular rhythm'.) Ventricular pacing Ventricular pacing from the right ventricle typically results in a QRS complex resembling that seen with LBBB on the surface ECG. Biventricular pacing, in theory, could also result in the appearance of bifascicular block. In nearly all patients, however, the presence of pacemaker spikes preceding the QRS complex differentiates a paced complex from bifascicular block. Ventricular pre-excitation (Wolff-Parkinson-White syndrome) In some patients with manifest accessory pathways, the pre-excitation pattern can mimic bifascicular block. In Wolff- Parkinson-White (WPW) syndrome, however, the PR interval is typically short, which is generally not the case with bifascicular block. NATURAL HISTORY AND PROGNOSIS Progression of chronic bifascicular block and bifascicular block with a prolonged PR interval to complete heart block appears to be infrequent among asymptomatic patients [11,12]. In one https://www.uptodate.com/contents/chronic-bifascicular-blocks/print 5/19 7/5/23, 10:34 AM Chronic bifascicular blocks - UpToDate study of 554 patients with bifascicular or trifascicular block who were followed for an average of 42 months, only 1 percent per year progressed to complete heart block [11]. Among patients with syncope or other symptoms at baseline, the likelihood of progression to symptomatic high-grade heart block appears high. In a study of 249 patients with bifascicular block (of which 41 percent were left bundle branch block [LBBB]), 57 patients required a permanent pacemaker for "significant atrioventricular (AV) block" over a median follow-up of 4.5 years (5 percent per year) [13]. Otherwise unexplained syncope in the presence of bifascicular block is an indication for a permanent pacemaker [2,14]. However, because unexplained syncope can be due to nonarrhythmic causes, it is possible for those with a pacemaker to continue to experience syncope, and thus an accurate diagnosis is desirable [15]. Despite the expectation for prevention of syncope with pacing, patients who receive a pacemaker with fascicular block do not have a different mortality rate compared with those without pacers [16]. This is likely due to competing causes of cardiac death independent of heart block progression. The significance and treatment of bifascicular or trifascicular block appearing during acute myocardial infarction is considered separately. (See "Conduction abnormalities after myocardial infarction".) TREATMENT Management of patients with chronic bifascicular block begins by looking for and correcting reversible causes of impaired conduction such as myocardial ischemia and drugs that may slow conduction or prolong the refractory period of fascicular tissue. (See "Etiology of atrioventricular block".) If no reversible causes are present, management involves the avoidance of medications that impair atrioventricular (AV) nodal conduction (when possible). Consideration of additional treatment with a permanent pacemaker depends on the presence or absence of symptoms: For patients with bifascicular block and no apparent symptoms, no specific treatment is required. For patients with bifascicular block and symptoms of syncope or presyncope of suspected cardiac etiology (specifically due to suspected intermittent complete heart block with bradyarrhythmia), we suggest permanent pacemaker implantation. Our approach is consistent with the guideline recommendations of various professional societies for patients with unexplained syncope in the setting of chronic bifascicular block if https://www.uptodate.com/contents/chronic-bifascicular-blocks/print 6/19 7/5/23, 10:34 AM Chronic bifascicular blocks - UpToDate other likely causes of syncope have been excluded [9,14]. (See 'Natural history and prognosis' above.) A randomized trial of permanent pacing versus implantable loop recorder monitoring in patients with bifascicular block and syncope demonstrated a significant reduction in a composite endpoint of cardiovascular death, syncope, bradycardia, and device-related complications with empiric pacing [17]. Interestingly, syncope was still observed in 29 percent of patients who received a pacemaker, indicating a vasodepressor etiology in many of these patients. This clinical trial adds to the clinical evidence supporting the pacing recommendation. A number of neuromuscular diseases are associated with conduction abnormalities. These include myotonic muscular dystrophy, Kearns-Sayre syndrome, Erb dystrophy (limb-girdle), and peroneal muscular atrophy. These patients represent a special class and are treated more aggressively with pacemakers due to the potential for unpredictably rapid progression of conduction disease. (See "Inherited syndromes associated with cardiac disease" and "Permanent cardiac pacing: Overview of devices and indications", section on 'Neuromuscular diseases'.) Detailed reviews of the indications for permanent pacemaker placement and of the modes of cardiac pacing are presented separately. (See "Permanent cardiac pacing: Overview of devices and indications", section on 'Acquired AV block' and "Modes of cardiac pacing: Nomenclature and selection".) SUMMARY AND RECOMMENDATIONS Bifascicular block, a pattern seen on the surface electrocardiogram (ECG), results when normal electrical activity in the His-Purkinje system is interrupted. Interruptions in conduction may result in right bundle branch block (RBBB), left anterior fascicular block (LAFB), or left posterior fascicular block (LPFB), with bifascicular block resulting when two of these three are identified on the ECG. Bifascicular block most commonly refers to conduction disturbances involving the right bundle branch and one of the two fascicles (anterior or posterior) of the left bundle branch. (See 'Introduction' above.) In nearly all instances, the clinical presentation of bifascicular block is asymptomatic and fairly benign, as bifascicular block in and of itself does not produce symptoms, and there are no specific signs of bifascicular block during physical examination. As such, bifascicular block is identified when patients are undergoing an ECG for another indication. For asymptomatic patients with bifascicular block, no further diagnostic evaluation or therapy is required, although patients should be screened carefully for symptoms and signs suggesting occult cardiac disease. (See 'Asymptomatic patients' above.) https://www.uptodate.com/contents/chronic-bifascicular-blocks/print 7/19 7/5/23, 10:34 AM Chronic bifascicular blocks - UpToDate For patients who present with presyncope or syncope and are noted to have bifascicular block on ECG, additional monitoring and evaluation are required, as intermittent complete heart block may result in hemodynamic instability leading to their symptoms. In such patients, we perform continuous ECG monitoring for 24 to 48 hours, usually in an inpatient setting, to monitor for high-grade atrioventricular (AV) block. We also perform echocardiography to assess for underlying structural heart disease. (See 'Symptomatic patients' above.) Progression of chronic bifascicular block and bifascicular block with a prolonged PR interval to complete heart block is infrequent, with an annual rate of approximately 1 percent in asymptomatic patients and up to 5 percent in symptomatic patients. (See 'Natural history and prognosis' above.) Management of patients with chronic bifascicular block begins by looking for and correcting reversible causes of impaired conduction such as myocardial ischemia and drugs that may slow conduction or prolong the refractory period of fascicular tissue. If no reversible causes are present, treatment involves the avoidance of medications that impair AV nodal conduction (when possible) and evaluation for permanent pacemaker placement. (See 'Treatment' above and "Permanent cardiac pacing: Overview of devices and indications", section on 'Acquired AV block'.) For patients with bifascicular block and no apparent symptoms, no specific treatment is required. For patients with bifascicular block and symptoms of syncope or presyncope of suspected cardiac etiology (specifically due to suspected intermittent complete heart block with bradyarrhythmia), we suggest permanent pacemaker implantation (Grade 2C). Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Surawicz B, Childers R, Deal BJ, et al. AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part III: intraventricular conduction disturbances: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society: endorsed by the International Society for Computerized Electrocardiology. Circulation 2009; 119:e235. https://www.uptodate.com/contents/chronic-bifascicular-blocks/print 8/19 7/5/23, 10:34 AM Chronic bifascicular blocks - UpToDate 2. Brignole M, Moya A, de Lange FJ, et al. 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J 2018; 39:1883. 3. Kusumoto FM, Schoenfeld MH, Barrett C, et al. 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2019; 74:e51. 4. Tawara S. Das Reizleitungssystem des S uegetierherzens. Gustav Fischer, Jena 1906. 5. Rosenbaum M, Elizari MV, Lazzari JO. The Hemiblocks. Tampa Tracings, Tampa 1970. 6. Uhley HN. Some controversy regarding the peripheral distribution of the conduction system. Am J Cardiol 1972; 30:919. 7. Hecht HH, Kossmann CE, Childers RW, et al. Atrioventricular and intraventricular conduction. Revised nomenclature and concepts. Am J Cardiol 1973; 31:232. 8. Demoulin JC, Kulbertus HE. Histopathological examination of concept of left hemiblock. Br Heart J 1972; 34:807. 9. Brignole M, Auricchio A, Baron-Esquivias G, et al. 2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: the Task Force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Eur Heart J 2013; 34:2281. 10. Englund A, Fredrikson M, Rosenqvist M. Head-up tilt test. A nonspecific method of evaluating patients with bifascicular block. Circulation 1997; 95:951. 11. McAnulty JH, Rahimtoola SH, Murphy E, et al. Natural history of "high-risk" bundle-branch block: final report of a prospective study. N Engl J Med 1982; 307:137. 12. Schneider JF, Thomas HE, Kreger BE, et al. Newly acquired right bundle-branch block: The Framingham Study. Ann Intern Med 1980; 92:37. 13. Mart -Almor J, Cladellas M, Baz n V, et al. [Novel predictors of progression of atrioventricular block in patients with chronic bifascicular block]. Rev Esp Cardiol 2010; 63:400. 14. Shen WK, Sheldon RS, Benditt DG, et al. 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, and the Heart Rhythm Society. J Am Coll Cardiol 2017. 15. Kalscheur MM, Donateo P, Wenzke KE, et al. Long-Term Outcome of Patients with Bifascicular Block and Unexplained Syncope Following Cardiac Pacing. Pacing Clin Electrophysiol 2016; 39:1126. https://www.uptodate.com/contents/chronic-bifascicular-blocks/print 9/19 7/5/23, 10:34 AM Chronic bifascicular blocks - UpToDate 16. Moulki N, Kealhofer JV, Benditt DG, et al. Association of cardiac implantable electronic devices with survival in bifascicular block and prolonged PR interval on electrocardiogram. J Interv Card Electrophysiol 2018; 52:335. 17. Sheldon R, Talajic M, Tang A, et al. Randomized Pragmatic Trial of Pacemaker Versus Implantable Cardiac Monitor in Syncope and Bifascicular Block. JACC Clin Electrophysiol 2022; 8:239. Topic 1063 Version 26.0 https://www.uptodate.com/contents/chronic-bifascicular-blocks/print 10/19 7/5/23, 10:34 AM Chronic bifascicular blocks - UpToDate GRAPHICS Normal conduction system Schematic representation of the normal intraventricular conduction system (His- Purkinje system). The Bundle of His divides into the left bundle branch and right bundle branch. The left bundle branch divides into anterior, posterior, and, in some cases, median fascicles. AV: atrioventricular; RA: right atrium; LA: left atrium; RV: right ventricle; LV: left ventricle. Graphic 63340 Version 6.0 https://www.uptodate.com/contents/chronic-bifascicular-blocks/print 11/19 7/5/23, 10:34 AM Chronic bifascicular blocks - UpToDate Coronary artery anatomy Graphic 70956 Version 2.0 https://www.uptodate.com/contents/chronic-bifascicular-blocks/print 12/19 7/5/23, 10:34 AM Chronic bifascicular blocks - UpToDate 12-lead electrocardiogram (ECG) showing bifascicular block with right bundle branch block and left anterior fascicular block The 12-lead ECG from a patient with a history of an anteroseptal myocardial infarction (Q waves seen in lead V1-V3) shows bifascicular block with RBBB and LAFB. A typical RBBB is seen with a QRS duration of 0.16 seconds and an rSR' configuration in lead V1 and a deep S wave in V6. The QRS complexes in leads II, III, and avF are negative, with a rS morphology, diagnostic of a pathologic left axis deviation, known as LAFB. ECG: electrocardiogram; RBBB: right bundle branch block; LAFB: left anterior fascicular block. Reproduced with permission by Samuel Levy, MD. Graphic 69886 Version 4.0 https://www.uptodate.com/contents/chronic-bifascicular-blocks/print 13/19 7/5/23, 10:34 AM Chronic bifascicular blocks - UpToDate ECG bifascicular block RBBB and LPFB The 12-lead ECG from a patient with bifascicular block with RBBB and LPFB. ECG: electrocardiogram; RBBB: right bundle branch block; LPFB: left posterior fascicular block. Reproduced with permission from: Nathanson LA, McClennen S, Safran C, Goldberger AL. ECG Wave-Maven: Self-Assessment Program f Clinicians. Available at: http://ecg.bidmc.harvard.edu (Accessed on January 11, 2017). Graphic 111524 Version 2.0 https://www.uptodate.com/contents/chronic-bifascicular-blocks/print 14/19 7/5/23, 10:34 AM Chronic bifascicular blocks - UpToDate 12-lead electrocardiogram (ECG) showing typical left bundle branch block Electrocardiogram in typical complete left bundle branch block. The asynchronous activation of the 2 ventricles increases the QRS duration (0.16 seconds in this example). The abnormal initial vector results in loss of "normal" septal forces as manifested by absence of q waves in leads I, aVL, and V6. The late activation of the left ventricle prolongs the dominant leftward progression of the middle and terminal forces, leading to a positive and widened R wave in the lateral leads. Both the ST segment and T wave vectors are opposite in direction from the QRS, a "secondary" repolarization abnormality. Courtesy of Ary Goldberger, MD. Graphic 61594 Version 9.0 Normal ECG https://www.uptodate.com/contents/chronic-bifascicular-blocks/print 15/19 7/5/23, 10:34 AM Chronic bifascicular blocks - UpToDate Normal electrocardiogram showing normal sinus rhythm at a rate of 75 beats/minute, a PR interval of 0.14 seconds, a QRS interval of 0.10 seconds, and a QRS axis of approximately 75 . Courtesy of Ary Goldberger, MD. Graphic 76183 Version 4.0 https://www.uptodate.com/contents/chronic-bifascicular-blocks/print 16/19 7/5/23, 10:34 AM Chronic bifascicular blocks - UpToDate Single lead electrocardiogram (ECG) showing monomorphic ventricular tachycardia Three or more successive ventricular beats are defined as ventricular tachycardia (VT). This VT is monomorphic since all of the QRS complexes have an identical appearance. Although the P waves are not distinct, they can be seen altering the QRS complex and ST-T waves in an irregular fashion, indicating the absence of a relationship between the P waves and the QRS complexes (ie, AV dissociation is present). AV: atrioventricular. Graphic 63176 Version 7.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/chronic-bifascicular-blocks/print 17/19 7/5/23, 10:34 AM Chronic bifascicular blocks - UpToDate ECG 12-lead accelerated idioventricular rhythm 12-lead ECG showing idioventricular rhythm with AV dissociation and wide QRS complexes occurring at a rate faster than the sinus rate but slower than 100 bpm (hence not meeting the criteria for ventricular tachycardia). ECG: electrocardiogram. Graphic 118943 Version 2.0 https://www.uptodate.com/contents/chronic-bifascicular-blocks/print 18/19 7/5/23, 10:34 AM Chronic bifascicular blocks - UpToDate Contributor Disclosures William H Sauer, MD Grant/Research/Clinical Trial Support: Biosense-Webster [Catheter ablation]; Boston Scientific [Catheter ablation]. All of the relevant financial relationships listed have been mitigated. N A Mark Estes, III, MD Consultant/Advisory Boards: Boston Scientific [Arrhythmias]; Medtronic [Arrhythmias]. All of the relevant financial relationships listed have been mitigated. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/chronic-bifascicular-blocks/print 19/19

7/5/23, 10:34 AM Conduction abnormalities after myocardial infarction - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Conduction abnormalities after myocardial infarction : Peter J Zimetbaum, MD, Joseph E Marine, MD, FACC, FHRS : Bradley P Knight, MD, FACC, Bernard J Gersh, MB, ChB, DPhil, FRCP, MACC, James Hoekstra, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Sep 23, 2021. INTRODUCTION Electrical conduction abnormalities are well-recognized complications of acute myocardial infarction (MI). They may be caused by either autonomic imbalance or ischemia/infarction involving the conduction system. The most common arrhythmic consequence is bradycardia, which may or may not be symptomatic. Complete heart block with a slow escape rhythm is a potentially life-threatening event in this setting if not detected and treated promptly. In addition, it is important to recognize which bradyarrhythmias are transient and which are likely to progress to irreversible and symptomatic high-degree atrioventricular (AV) block. The major conduction abnormalities associated with acute MI will be reviewed here. Supraventricular arrhythmias, including sinus bradycardia, are discussed separately. (See "Supraventricular arrhythmias after myocardial infarction" and "Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features".) ANATOMY AND ELECTROPHYSIOLOGY Anatomy The sinoatrial (SA) node is located high (superiorly) in the right atrium at the junction of the crista terminalis (a thick band of atrial muscle at the border of the atrial appendage) and the superior vena cava. The SA node is located beneath the epicardial surface of the crista terminalis; there is a layer of atrial muscle between the SA node and the endocardium so that it does not occupy the entire thickness of the atrial myocardium. Human https://www.uptodate.com/contents/conduction-abnormalities-after-myocardial-infarction/print 1/34 7/5/23, 10:34 AM Conduction abnormalities after myocardial infarction - UpToDate histologic studies have demonstrated that the SA node has a crescent-like shape with an average length of 13.5 mm [1]. Following atrial activation, the impulse reaches the AV node. This structure generates a slow calcium-mediated action potential ( figure 1). Thus, there is a delay in impulse transmission through this structure. After leaving the AV node, the bundle of His divides at the juncture of the fibrous and muscular boundaries of the interventricular septum into the right and left bundle branches ( figure 2). The right bundle branch courses down the right side of interventricular septum near the endocardium in its upper third, deeper in the muscular portion of the septum in the middle third, and then again near the endocardium in its lower third. The right bundle does not branch throughout most of its course, but it begins to ramify as it approaches the base of the right anterior papillary muscle, with fascicles going to the septal and free wall of the right ventricle (RV). The apical free wall at the base of the right anterior papillary muscle is the earliest site of RV activation. The left bundle branch penetrates the membranous portion of the interventricular septum under the aortic ring. Shortly thereafter, it divides into several discrete branches [2-5]: An anterior fascicle that crosses the left ventricular (LV) outflow tract and terminates in the Purkinje system of the anterolateral wall of the LV. A posterior fascicle that fans out extensively inferiorly and posteriorly. In about 65 percent of hearts, a separate fascicle to the interventricular septum. In all patients there is early septal activation, either by a discrete septal branch or septal extensions of the posterior fascicle. It should also be noted that evidence suggests that certain fibers in the His bundle are predestined to form the left bundle branch. Blood supply In order to fully understand the relationship between MI and dysrhythmia, it is helpful to review the vascular supply of the different components of the conduction system ( figure 3) [6]: SA node Supplied by the right coronary artery (RCA) in 60 percent of patients; by the left circumflex artery (LCX) in 40 percent. AV node Supplied by the RCA in 90 percent (AV nodal branch); by the LCX in 10 percent of patients. https://www.uptodate.com/contents/conduction-abnormalities-after-myocardial-infarction/print 2/34 7/5/23, 10:34 AM Conduction abnormalities after myocardial infarction - UpToDate His bundle Supplied by the RCA (AV nodal branch) with a minor contribution from the septal perforators of the left anterior descending artery (LAD). Main or proximal left bundle branch The LAD provides most of the blood supply for the left bundle branch, particularly for the initial portion. There may be some collateral flow from the RCA and LCX systems. To the extent that the His bundle has predestined fibers to the left bundle, His bundle blood supply is also important. Left posterior fascicle The proximal portion of the left posterior fascicle is supplied by the AV nodal artery and, at times, by septal branches from the LAD. The distal portion has a dual blood supply from both anterior and posterior septal perforating arteries. Left anterior fascicle The left anterior and mid-septal fascicles are supplied by septal perforators of the LAD and, in about one-half of subjects, by the AV nodal artery. Right bundle branch The right bundle branch receives most of its blood supply from septal perforators from the LAD coronary artery, particularly in its initial course. It also receives some collateral supply from either the RCA or LCX coronary systems, depending upon the dominance of the coronary system. Electrophysiology While it may appear that the electrical signals from the SA node to the atrial periphery can exit randomly, there appear to be preferential pathways of conduction from the sinus pacemaker cells to the atrium [7]. Whether these are functional or anatomical exit paths remains unclear. The conduction velocity within the SA node is very slow compared with non-nodal atrial tissue. This is a result of poor electrical coupling arising from the relative paucity of gap junctions in the center of the SA node compared with the periphery [8]. With atrial activation, the electrical impulse reaches the AV node. This structure generates a slow calcium-mediated action potential ( figure 1). Thus, there is a delay in impulse transmission through this structure. Once the action potential traverses the AV node, it activates the proximal portion of the bundle of His, a specialized conducting tissue that generates a fast action potential. The bundle of His divides into the main left and right bundle branches, which consist of bundles of Purkinje cells covered by a dense sheath of connective tissue. Purkinje cells are specialized to conduct rapidly at 1 to 3 m/second, as phase 0 is dependent on the rapid inward sodium current ( figure 4), resulting in nearly synchronous depolarization of the terminal His Purkinje system and the adjacent ventricular myocardium. https://www.uptodate.com/contents/conduction-abnormalities-after-myocardial-infarction/print 3/34 7/5/23, 10:34 AM Conduction abnormalities after myocardial infarction - UpToDate TYPES OF CONDUCTION ABNORMALITIES Conduction abnormalities are manifest on the surface electrocardiogram (ECG) and are broadly categorized as follows: Left bundle branch block (LBBB). (See "Left bundle branch block", section on 'ECG findings and diagnosis' and "Electrocardiographic diagnosis of myocardial infarction in the presence of bundle branch block or a paced rhythm".) Left anterior, left posterior, or left septal (median) fascicular block. (See "Left anterior fascicular block" and "Left posterior fascicular block" and "Left septal fascicular block".) Right bundle branch block (RBBB). (See "Right bundle branch block", section on 'ECG findings and diagnosis'.) First degree AV block. (See "First-degree atrioventricular block", section on 'Definition'.) Second degree AV block. (See "Second-degree atrioventricular block: Mobitz type I (Wenckebach block)", section on 'ECG findings and diagnostic maneuvers' and "Second- degree atrioventricular block: Mobitz type II", section on 'ECG findings'.) High grade (ie, two or more consecutive blocked P waves) AV block. (See "Third-degree (complete) atrioventricular block" and "Second-degree atrioventricular block: Mobitz type II".) Third degree (complete) AV block. (See "Third-degree (complete) atrioventricular block", section on 'Electrocardiographic findings'.) INCIDENCE In the era of primary percutaneous coronary intervention (PCI), the rates of post-MI conduction abnormalities are decreasing, with rates between 1 and 3 percent reported in most studies. Additionally, new BBB complicating acute MI is uncommon in the reperfusion era (0.73 and 0.15 percent of patients developed RBBB and LBBB, respectively, in the first 60 minutes after presentation in one large study) [9]. Determining the incidence and prognostic significance of new conduction abnormalities associated with acute MI is difficult for several reasons: https://www.uptodate.com/contents/conduction-abnormalities-after-myocardial-infarction/print 4/34 7/5/23, 10:34 AM Conduction abnormalities after myocardial infarction - UpToDate Data are most commonly generated from retrospective reviews, sub-analyses of clinical trial data, or administrative databases. The incidence of conduction system disease depends on the cohort studied. For example, older patients are more likely to have underlying conduction system disease at baseline. Additionally, patients treated with prompt reperfusion with PCI have a lower incidence of conduction abnormalities compared with those who received thrombolytic reperfusion therapy, who in turn have lower rates of conduction abnormalities when compared with older studies in the era prior to reperfusion. It is frequently difficult to distinguish between ECG conduction abnormalities that are chronic (pre-existing) and those that are new abnormalities associated with the infarction. The National Registry of Myocardial Infarction 2 (NRMI-2) in the United States evaluated the incidence of bundle branch block in 297,832 patients admitted to a hospital with an acute MI between 1994 and 1997: 6.7 percent of patients had an LBBB and 6.2 percent had an RBBB on the initial ECG [10]. A similar rate of LBBB (9 percent) was noted in a prospective analysis of over 88,000 patients in Sweden [11]. Because both of these series only assessed the presence of BBB on the initial ECG, these data provide no information on the incidence of new conduction disease in acute MI. The largest experience with high degree AV block in the fibrinolytic era comes from a review of almost 76,000 patients with ST-elevation MI (STEMI) enrolled in four large randomized trials, in which the overall incidence was 6.9 percent (9.8 percent with inferior MI and 3.2 percent with anterior MI) [12]. In the primary PCI era, most studies have shown continued decreases in the rate of high-degree AV block, ranging from 1 to 3 percent of patients, with higher rates seen in patients with STEMI compared with non-ST elevation MI (NSTEMI) [13-19]. (See 'Conduction disturbances based on infarct location' below.) In a study of 418,396 United States patients with acute MI (32.5 percent STEMI with 77 percent receiving PCI, 67.5 percent NSTEMI with 37 percent receiving PCI) between 2010 and 2014 who were enrolled in the National Inpatient Sample database, high-degree AV block was seen in 2.4 percent of patients with STEMI compared with 0.6 percent of patients with NSTEMI [19]. Of the 1745 patients who developed high-degree AV block, a higher proportion of patients with NSTEMI (30 percent) underwent permanent pacemaker implantation than those with STEMI (10.6 percent). High-degree AV block was associated with elevated risk of in-hospital mortality in both NSTEMI (17 versus 3.8 percent, p<0.001) and STEMI (18 versus 8.2 percent) patients. https://www.uptodate.com/contents/conduction-abnormalities-after-myocardial-infarction/print 5/34 7/5/23, 10:34 AM Conduction abnormalities after myocardial infarction - UpToDate The Global Registry of Acute Coronary Events (GRACE) registry enrolled 59,229 patients with acute coronary syndromes (37 percent with STEMI, 33 percent with NSTEMI) at 126 hospitals in 14 countries [17]. Mobitz type II second degree AV block or third degree AV block occurred in 2.9 percent of patients (5 percent of STEMI patients, 1.9 percent of NSTEMI patients). When AV block was present, it more commonly occurred at presentation (54 percent versus 46 percent later in the hospitalization). The right coronary artery was the culprit vessel in 65 percent of patients with AV block. Temporal analysis showed a declining incidence of AV block between 1999 and 2007 (-0.2 percent per year). Conduction disturbances can occur after a "controlled" MI, as occurs with a septal (alcohol) ablation procedure for hypertrophic cardiomyopathy. This issue is discussed elsewhere. (See "Hypertrophic cardiomyopathy: Management of patients with outflow tract obstruction", section on 'Septal reduction therapy'.) CONDUCTION DISTURBANCES BASED ON INFARCT LOCATION The management and prognosis of patients with bradyarrhythmias or conduction abnormalities after an MI depends in part upon the location of the infarct. Often the anatomic location of the infarct can be gleaned from the ECG. In other cases, echocardiography or coronary arteriography supplies this information. (See 'Anatomy and electrophysiology' above and 'Management of conduction abnormalities' below.) For example, the management and prognosis of high degree AV block differs depending on infarct location: High (second or third) degree AV block associated with inferior wall MI is located proximal to the His bundle (ie, AV node) in 90 percent of patients [6,20]. For this reason, complete heart block usually results in only a modest and usually transient bradycardia with junctional or escape rhythm rates above 40 beats per minute. It is not uncommon, however, for the junctional escape pacemaker rate to exceed 60 beats per minute. The QRS is usually narrow in this setting. High degree AV block associated with anterior MI is more often located distal to the AV node [6]. It is usually symptomatic and has been associated with a high mortality rate due in large part to greater loss of functioning myocardium. The contemporary mortality may be lower due to improvements in reperfusion therapy and in the management of congestive heart failure and cardiogenic shock, but the risk remains substantial. https://www.uptodate.com/contents/conduction-abnormalities-after-myocardial-infarction/print 6/34 7/5/23, 10:34 AM Conduction abnormalities after myocardial infarction - UpToDate Inferior MI Conduction disturbance in inferior MI may occur upon presentation or after hours or days. Sinus bradycardia, Mobitz type I (Wenckebach), and complete heart block (CHB) are commonly seen, since the SA node, AV node, and His bundle are primarily supplied by the right coronary artery (RCA) [20]. (See 'Anatomy and electrophysiology' above.) Sinus bradycardia is the most common arrhythmia associated with inferior MI. It is present in up to 40 percent of patients in the first two hours, decreasing to 20 percent by the end of the first day. It is usually attributable to increased vagal tone or increased sensitivity to vagal tone in the first 24 hours after infarction. Transient sinus node dysfunction occurring later may be due to sinus node or atrial ischemia. First degree AV block (characterized by prolongation of the PR interval, >200 ms) can arise in the AV node, the bundle of His, or the bundle branches (see "First-degree atrioventricular block"). First degree AV block at the level of the AV node is common after occlusion of the coronary artery (right or circumflex) which gives rise to the AV nodal artery. RCA occlusion can lead to first degree AV block via ischemia of the AV node, by enhanced acetylcholine release from the inferoposterior myocardium, or possibly by making the AV node hypersensitive to the action of acetylcholine. First degree AV block due to occlusion of the RCA with involvement of the AV node is usually transient, generally resolving in five to seven days and requiring no specific therapy. Occlusion of the left circumflex artery, which may present as an inferior MI on the ECG, may affect the AV node directly in the 10 percent of individuals in whom it supplies the AV node. Inferior MI is typically associated with the more benign second degree AV block of the Wenckebach type (Mobitz type I) ( waveform 1A-B); Mobitz type II block is uncommon in this setting, generally occurring with anterior MI ( waveform 2). The mechanism is similar to that described above for first degree AV block. Mobitz type I block is usually transient, resolving in most cases within five days. (See "Second-degree atrioventricular block: Mobitz type I (Wenckebach block)".) Somewhat more than one-half of cases of high degree AV block in acute MI are present on admission and somewhat less than one-half develop later in the hospitalization [14]. Complete AV block (CHB) with inferior MI generally results from an AV nodal lesion. It is associated with a narrow QRS complex, and develops in a progressive fashion from first to second to third degree block. It often results in an asymptomatic bradycardia (40 to 60 beats per minute) and is usually transient, resolving within five to seven days. In the https://www.uptodate.com/contents/conduction-abnormalities-after-myocardial-infarction/print 7/34 7/5/23, 10:34 AM Conduction abnormalities after myocardial infarction - UpToDate substudy from the TRACE trial described above, the incidence of CHB was significantly higher among patients with an inferior MI than among those with an anterior MI (9.4 versus 2.5 percent) [21]. In the primary percutaneous coronary intervention (PCI) era, one study showed that high degree AV block occurred in 5.9 percent of patients with right coronary artery occlusion and in 1.5 percent of patients with other infarct-related arteries [14]. Another study from a large United States registry showed a rate of CHB of 3.8 percent of patients with inferior STEMI and 0.9 percent of patients with anterior STEMI [16]. Occasionally, RCA occlusion with inferior MI produces persistent complete AV block. This latter finding suggests concurrent involvement of the left coronary system, resulting in poor collateral flow. In one large United States registry, 11.5 percent of patients with inferior STEMI received a permanent pacemaker prior to discharge [16]. Anterior MI Conduction disturbances occurring with anteroseptal MI are less frequent but more serious, and the degree of arrhythmic complications is usually directly related to the extent of infarction. First degree AV block Prolongation of the PR interval due to slowed AV nodal conduction rarely occurs in anterior MI, since the AV node is usually supplied by the right or circumflex coronary artery, as opposed to the left anterior descending coronary artery, which is the cause of anterior infarctions in most cases. High (second or third) degree AV block Second degree AV block with anterior MI is usually at the level of the His bundle or below and is usually a Mobitz type II block. The clinical course may be unpredictable, with CHB developing with little warning. (See "Second-degree atrioventricular block: Mobitz type II".) CHB with anterior MI generally occurs abruptly in the first 24 hours. It can develop without warning or may be preceded by the development of right bundle branch block with either a left anterior fascicular block or left posterior fascicular block, or by alternating bundle branch block (bifascicular or trifascicular block) ( waveform 3) [22]. The escape rhythm usually has a wide QRS duration and is unstable, and the event is associated with a high mortality from both arrhythmias and pump failure. Heart block in this setting is thought to result from extensive necrosis that involves the bundle branches traveling within the septum [22]. Less commonly, anterior MI produces first degree AV block below the level of the AV node, a situation that should be suspected if first degree AV block occurs in the presence of a widened QRS complex. https://www.uptodate.com/contents/conduction-abnormalities-after-myocardial-infarction/print 8/34 7/5/23, 10:34 AM Conduction abnormalities after myocardial infarction - UpToDate MANAGEMENT OF CONDUCTION ABNORMALITIES The initial management of the patient with post-MI conduction abnormalities depends on the location of the MI and the presence and severity of hemodynamic instability ( algorithm 1). Second degree AV block, high grade AV block, or third degree (complete) AV block in the setting of an anterior MI is unlikely to recover following revascularization; these rhythms are by nature unstable rhythms and more likely to cause, or to be associated with, hemodynamic instability. Patients with newly developed bundle branch block (BBB), or alternating BBB, are also at increased risk of developing hemodynamic instability. Second degree AV block, high grade AV block, or third degree (complete) AV block in the setting of an inferior MI may respond to treatment with atropine and/or aminophylline, when the block occurs at the level of the AV node. Following revascularization, conduction abnormalities in the setting of an inferior MI are more likely to resolve and not require permanent pacing. Patients with first degree AV block or isolated BBB rarely develop hemodynamic instability related to their heart rhythm. If hemodynamic instability arises in these settings, a search for other causes is typically warranted. Hemodynamically unstable patients with Mobitz type II second degree AV block, high grade AV block, or third degree (complete) AV block require immediate pharmacologic therapy and, in many instances, should also receive temporary pacing to increase heart rate and cardiac output. Once the patient is hemodynamically stable, assessment and treatment for any potentially reversible causes (in addition to myocardial ischemia) should occur, followed by a period of continuous ECG rhythm monitoring. Patients whose advanced AV block does not resolve following revascularization and treatment of any other reversible etiologies should undergo placement of a permanent pacemaker [23]. Our approach is in agreement with published professional society guidelines, which discuss the role of temporary cardiac pacing during the peri-infarction period, as well as indications for implantation of a permanent cardiac pacemaker [23,24]. Management of patients with AV block Patients with anterior MI The location of the MI is important in determining the approach to therapy for conduction abnormalities. New conduction abnormalities in the setting of an anterior MI are typically indicative of extensive ischemia/infarction involving the infranodal conduction system and are unlikely to improve with atropine or resolve following https://www.uptodate.com/contents/conduction-abnormalities-after-myocardial-infarction/print 9/34 7/5/23, 10:34 AM Conduction abnormalities after myocardial infarction - UpToDate revascularization. As such, we proceed directly to temporary cardiac pacing in such patients, with a plan for permanent cardiac pacing if conduction is not restored after the first few days of recovery. Unstable inferior MI patients Patients with inferior MI and second degree AV block, high grade AV block, or third degree (complete) AV block who are hemodynamically unstable should be urgently treated ( algorithm 1) with atropine and, if hemodynamic instability persists, temporary cardiac pacing (either with transcutaneous or, if immediately available, transvenous pacing). In general, beta agonists (eg, dopamine, epinephrine, dobutamine, etc) should be avoided in hypotensive patients with acute MI and AV block due to the potential for worsening ischemia. For patients with high grade AV block associated with inferior MI, aminophylline may improve AV conduction and symptoms. Additionally, in the setting of an acute myocardial ischemia, patients should undergo prompt revascularization; following revascularization, most conduction abnormalities will improve or resolve and will not require permanent pacing. (See "Advanced cardiac life support (ACLS) in adults", section on 'Bradycardia'.) Approach to managing unstable patients with AV block The most important clinical determination in a patient presenting with AV block is whether or not the patient is hemodynamically unstable due to the resulting bradycardia and reduced cardiac output ( algorithm 1). Signs and symptoms of hemodynamic instability include hypotension, altered mental status, signs of shock, ongoing ischemic chest pain, and evidence of acute pulmonary edema. In general, such patients should be treated according to the Advanced Cardiac Life Support protocol for patients with symptomatic bradycardia ( algorithm 2), with the exception of avoiding beta agonists (eg, dopamine, epinephrine, dobutamine, etc) in patients with ongoing ischemia due to the potential for worsening ischemia [25]: Atropine should be promptly administered if intravenous (IV) access is available, but treatment with atropine should not delay treatment with transcutaneous pacing. The initial dose of atropine is 0.5 mg IV. This dose may be repeated every three to five minutes to a total dose of 3 mg, but should not delay the initiation of temporary cardiac pacing for patients who remain hemodynamically unstable. A favorable response to atropine also suggests that AV block is due to abnormal conduction in the AV node. Atropine is not likely to be effective for patients with an escape rhythm at or below the bundle of His, since the more distal conducting system is not as sensitive to vagal activity. Caution should be used with administering atropine in the setting of active ischemia and BBB or Mobitz Type 2 AV block because of potential for precipitating ventricular arrhythmia or worsening degree of AV block [23]. https://www.uptodate.com/contents/conduction-abnormalities-after-myocardial-infarction/print 10/34 7/5/23, 10:34 AM Conduction abnormalities after myocardial infarction - UpToDate If refractory hypotension occurs after correction of bradycardia with atropine in the setting of an inferior MI, volume depletion or concurrent RV infarction should be suspected. This can be confirmed by right-sided ECG leads or bedside echocardiography. Volume infusion is the treatment of choice in this setting. (See "Right ventricular myocardial infarction".) For patients with second or third degree AV block associated with symptoms or hemodynamic compromise in the setting of acute inferior MI that persist following atropine, we suggest intravenous aminophylline to improve AV conduction, increase ventricular rate, and improve symptoms [23]. Several small case series (eight patients or fewer) have shown prompt reversal of AV block in this clinical setting without adverse effects [26]. The typical dose is 250 mg IV or 6 mg/kg IV in 100 to 200 mL of IV fluid over 20 to 30 minutes. Preparations should continue for temporary cardiac pacing in the event that symptoms worsen or do not improve following aminophylline administration. Temporary cardiac pacing should be provided for patients with acute MI and persistent unstable bradycardia. In the absence of central venous access, the most immediate way to provide temporary cardiac pacing is via transcutaneous pacing. Transcutaneous pacing is uncomfortable for the patient and may have variable efficacy depending on how well the impulses are transmitted to the myocardium; as such, transcutaneous pacing should be viewed as a temporizing measure until temporary transvenous pacing can be provided. Patients should be monitored by arterial palpation, plethysmography, or intra-arterial monitoring to ascertain that transcutaneous pacing produces a pulse pressure. (See 'Temporary pacing' below and "Temporary cardiac pacing".) Once a hemodynamically unstable patient has been stabilized, the approach to further management is similar to patients who were initially stable. Temporary pacing Our recommendations regarding temporary pacing are in general agreement with those in the 2013 American College of Cardiology Federation/American Heart Association (ACCF/AHA) guideline for the management of patients with ST-elevation MI and in the 2018 American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) guideline on the evaluation and management of patients with bradycardia and cardiac conduction delay [23,24]. When temporary pacing is required, we recommend transvenous pacing. We do not favor the use of external/transcutaneous cardiac pacing, except in emergency circumstances, because of the associated physical discomfort and difficulty in ascertaining consistent myocardial capture. If transcutaneous pacing is utilized, it should be used as a temporary bridge to transvenous pacing, while the transvenous pacemaker placement is being arranged. It should be used with https://www.uptodate.com/contents/conduction-abnormalities-after-myocardial-infarction/print 11/34 7/5/23, 10:34 AM Conduction abnormalities after myocardial infarction - UpToDate appropriate procedural sedation and monitoring for production of a pulse pressure. Placement of transcutaneous pacing pads is also reasonable when observing a patient at risk for development of AV block while a decision regarding temporary transvenous pacing is being made. (See "Temporary cardiac pacing".) The following points should be considered in deciding whether to place a temporary pacemaker ( algorithm 1): In patients with inferior MI, third degree (complete) AV block may be transient and hemodynamically tolerated. We do not routinely insert a pacemaker for third degree (complete) AV block if the escape rhythm has a narrow QRS and an adequate ventricular rate with stable blood pressure and peripheral perfusion, because this junctional rhythm is usually stable. However, careful monitoring is mandatory and we have a low threshold for pacing should deterioration occur. Bradycardia may occur in patients with RV infarction. Hemodynamic status may deteriorate in such patients, since the ischemic RV has a relatively fixed stroke volume and is therefore dependent upon heart rate. Patients with RV infarction associated with second or third degree (complete) AV block often benefit hemodynamically from temporary AV sequential pacing. (See "Right ventricular myocardial infarction".) New BBB is associated with substantial short-term mortality, particularly in the setting of an anterior MI (>30 percent at 30 days) [9]. However, the incidence of progressive conduction disease (ie, second and third degree AV block) is not known, and therefore the potential benefit of prophylactic temporary pacing in this setting is unclear. Temporary transvenous pacing is rarely needed for isolated BBB in the setting of acute MI and efforts should be focused on reperfusion and medical therapy. (See 'Management of patients with BBB' below.) For patients who will require temporary pacing for more than 48 hours and are hemodynamically stable for transport to the electrophysiology lab, we generally place an active fixation permanent pacing lead in the RV and externalize the pin for use in an external resterilized permanent pacemaker generator or conventional temporary pacing box. This form of temporary pacing has been shown to be far more stable and better tolerated by patients than conventional temporary pacing wires [27]. Stable inferior MI patients Second degree AV block, high grade AV block, or third degree (complete) AV block Patients with inferior MI and second degree AV block, high grade AV block, or third https://www.uptodate.com/contents/conduction-abnormalities-after-myocardial-infarction/print 12/34 7/5/23, 10:34 AM Conduction abnormalities after myocardial infarction - UpToDate degree (complete) AV block who are hemodynamically stable generally do not require urgent therapy with atropine or temporary cardiac pacing. However, many ventricular escape rhythms are unreliable and potentially unstable, so patients should be continuously monitored with transcutaneous pacing pads in place in the event of clinical deterioration ( algorithm 1). Additionally, in the setting of an acute myocardial ischemia, patients should undergo prompt revascularization; following revascularization, most conduction abnormalities will improve or resolve and will not require permanent pacing. Following revascularization, if second degree AV block, high grade AV block, or third degree (complete) AV block persists, patients should remain on continuous ECG monitoring and should be evaluated for any additional potentially reversible causes of AV block (eg, increased vagal tone, hypothyroidism, hyperkalemia, and drugs that depress conduction). Patients with AV block felt to be medication-induced should be observed while the offending agent or agents are withdrawn; such patients may have improvement or resolution of AV block following removal of the medication with or without administration of reversal agents. Patients with AV block in the setting of hyperkalemia should receive therapy to reduce serum potassium levels. If AV block subsequently resolves, a permanent pacemaker is not usually needed. (See "Treatment and prevention of hyperkalemia in adults" and "Treatment of primary hypothyroidism in adults".) In general, a waiting period of several days should be employed to determine potential reversibility of AV block, particularly in patients with acute inferior MI [23]. If no reversible causes are present, definitive treatment of Mobitz type II second degree AV block, high grade AV block, or third degree (complete) AV block involves permanent pacemaker placement in most patients ( algorithm 1) [23,28]. Dual-chamber (ie, AV) pacing to maintain AV synchrony is preferred (rather than single chamber RV pacing) in most patients due to the favorable hemodynamic benefits of AV synchrony [23]. Some trials suggest that biventricular cardiac pacing (ie, cardiac resynchronization) is superior to standard dual chamber pacing in patients with heart block and depressed LV systolic function [29,30]. Implantable cardioverter-defibrillators, specifically cardiac resynchronization therapy devices (CRT-Ds), should be considered in patients with AV block and significant LV dysfunction that is likely to be permanent and irreversible despite medical therapy and revascularization. (See "Permanent cardiac pacing: Overview of devices and indications", section on 'Acquired AV block' and "Modes of cardiac pacing: Nomenclature and selection".) First degree AV block and Mobitz type I second degree AV block Patients with first degree AV block or Mobitz type I second degree AV block who are hemodynamically stable and https://www.uptodate.com/contents/conduction-abnormalities-after-myocardial-infarction/print 13/34 7/5/23, 10:34 AM Conduction abnormalities after myocardial infarction - UpToDate asymptomatic do not require any specific therapy, other than avoidance of AV nodal-blocking agents. We agree with the professional society guidelines which do not recommend a pacemaker for most cases of first degree AV block or Mobitz type I second degree AV block [23,28]. Management of patients with BBB Patients with isolated left BBB (LBBB) or right BBB (RBBB) (complete or incomplete) are generally asymptomatic related to their conduction disorder and do not require placement of a pacemaker (temporary or permanent) or any other specific therapy. The one exception to this is for patients with alternating RBBB and LBBB, or RBBB with alternating left anterior fascicular block and left posterior fascicular block, as these indicate a higher likelihood of significant conduction system disease which may progress to unstable AV block. In cases of alternating BBB in the setting of acute MI, we insert a temporary transvenous pacemaker and pursue prompt revascularization. If alternating BBB persists or progresses following revascularization, patients typically receive a permanent pacemaker. Transient second or third degree AV block associated with new persistent BBB after MI is rarely encountered in the primary percutaneous coronary intervention era. Based on small studies in the 1970s showing high mortality in these patients, older versions of pacemaker guidelines recommended routine permanent pacemaker implantation [31]. However, this recommendation has not been adopted in the most recent American or European guidelines [23,28]. Invasive electrophysiology studies looking for severe His-Purkinje conduction disease and/or follow-up event monitoring to guide therapy may be helpful in this rarely-encountered clinical scenario. PROGNOSIS High degree AV block Advanced (second or third degree) AV block is associated with an increase in mortality in patients with an inferior or anterior MI [12-17,21,32]. The increase in mortality risk is seen largely within the first 30 days; among 30-day survivors, subsequent mortality does not appear to be consistently increased in reports of various AMI cohorts [12,13,18,21]. AV block following inferior MI Although high grade AV block in patients with an inferior MI is usually transient, it is associated with increased in-hospital mortality. Following primary PCI In one large United States registry in the PCI era, complete heart block (CHB) in the setting of inferior STEMI increased in-hospital mortality twofold [16]. A similar increase in mortality with inferior STEMI was seen in other studies in the PCI era [14,15]. https://www.uptodate.com/contents/conduction-abnormalities-after-myocardial-infarction/print 14/34 7/5/23, 10:34 AM Conduction abnormalities after myocardial infarction - UpToDate Following thrombolysis An increase in mortality with high degree AV block of about 15 percent at 30 days is seen in patients with an inferior MI treated with a thrombolytic agent [12,21,32-36]. AV block following anterior MI High degree AV block in patients with an anterior wall MI is associated with a greater increase in in-hospital and 30-day mortality than seen with an inferior wall infarction, probably due to more extensive myocardial involvement and a higher incidence of hemodynamic complications [12,32]. Following primary PCI In the United States National Inpatient Sample registry from the PCI era, CHB in the setting of anterior STEMI increased in-hospital mortality fourfold, versus only twofold in inferior STEMI patients [16]. A similar increase in mortality with CHB and anterior STEMI was seen in other studies in the PCI era [14,15,37]. In a study of 1295 STEMI patients undergoing PCI in Japan, complete AV block occurred in 1.7 percent of patients with anterior STEMI and 10.7 percent of those with nonanterior STEMI [37].

BBB' below.) For patients who will require temporary pacing for more than 48 hours and are hemodynamically stable for transport to the electrophysiology lab, we generally place an active fixation permanent pacing lead in the RV and externalize the pin for use in an external resterilized permanent pacemaker generator or conventional temporary pacing box. This form of temporary pacing has been shown to be far more stable and better tolerated by patients than conventional temporary pacing wires [27]. Stable inferior MI patients Second degree AV block, high grade AV block, or third degree (complete) AV block Patients with inferior MI and second degree AV block, high grade AV block, or third https://www.uptodate.com/contents/conduction-abnormalities-after-myocardial-infarction/print 12/34 7/5/23, 10:34 AM Conduction abnormalities after myocardial infarction - UpToDate degree (complete) AV block who are hemodynamically stable generally do not require urgent therapy with atropine or temporary cardiac pacing. However, many ventricular escape rhythms are unreliable and potentially unstable, so patients should be continuously monitored with transcutaneous pacing pads in place in the event of clinical deterioration ( algorithm 1). Additionally, in the setting of an acute myocardial ischemia, patients should undergo prompt revascularization; following revascularization, most conduction abnormalities will improve or resolve and will not require permanent pacing. Following revascularization, if second degree AV block, high grade AV block, or third degree (complete) AV block persists, patients should remain on continuous ECG monitoring and should be evaluated for any additional potentially reversible causes of AV block (eg, increased vagal tone, hypothyroidism, hyperkalemia, and drugs that depress conduction). Patients with AV block felt to be medication-induced should be observed while the offending agent or agents are withdrawn; such patients may have improvement or resolution of AV block following removal of the medication with or without administration of reversal agents. Patients with AV block in the setting of hyperkalemia should receive therapy to reduce serum potassium levels. If AV block subsequently resolves, a permanent pacemaker is not usually needed. (See "Treatment and prevention of hyperkalemia in adults" and "Treatment of primary hypothyroidism in adults".) In general, a waiting period of several days should be employed to determine potential reversibility of AV block, particularly in patients with acute inferior MI [23]. If no reversible causes are present, definitive treatment of Mobitz type II second degree AV block, high grade AV block, or third degree (complete) AV block involves permanent pacemaker placement in most patients ( algorithm 1) [23,28]. Dual-chamber (ie, AV) pacing to maintain AV synchrony is preferred (rather than single chamber RV pacing) in most patients due to the favorable hemodynamic benefits of AV synchrony [23]. Some trials suggest that biventricular cardiac pacing (ie, cardiac resynchronization) is superior to standard dual chamber pacing in patients with heart block and depressed LV systolic function [29,30]. Implantable cardioverter-defibrillators, specifically cardiac resynchronization therapy devices (CRT-Ds), should be considered in patients with AV block and significant LV dysfunction that is likely to be permanent and irreversible despite medical therapy and revascularization. (See "Permanent cardiac pacing: Overview of devices and indications", section on 'Acquired AV block' and "Modes of cardiac pacing: Nomenclature and selection".) First degree AV block and Mobitz type I second degree AV block Patients with first degree AV block or Mobitz type I second degree AV block who are hemodynamically stable and https://www.uptodate.com/contents/conduction-abnormalities-after-myocardial-infarction/print 13/34 7/5/23, 10:34 AM Conduction abnormalities after myocardial infarction - UpToDate asymptomatic do not require any specific therapy, other than avoidance of AV nodal-blocking agents. We agree with the professional society guidelines which do not recommend a pacemaker for most cases of first degree AV block or Mobitz type I second degree AV block [23,28]. Management of patients with BBB Patients with isolated left BBB (LBBB) or right BBB (RBBB) (complete or incomplete) are generally asymptomatic related to their conduction disorder and do not require placement of a pacemaker (temporary or permanent) or any other specific therapy. The one exception to this is for patients with alternating RBBB and LBBB, or RBBB with alternating left anterior fascicular block and left posterior fascicular block, as these indicate a higher likelihood of significant conduction system disease which may progress to unstable AV block. In cases of alternating BBB in the setting of acute MI, we insert a temporary transvenous pacemaker and pursue prompt revascularization. If alternating BBB persists or progresses following revascularization, patients typically receive a permanent pacemaker. Transient second or third degree AV block associated with new persistent BBB after MI is rarely encountered in the primary percutaneous coronary intervention era. Based on small studies in the 1970s showing high mortality in these patients, older versions of pacemaker guidelines recommended routine permanent pacemaker implantation [31]. However, this recommendation has not been adopted in the most recent American or European guidelines [23,28]. Invasive electrophysiology studies looking for severe His-Purkinje conduction disease and/or follow-up event monitoring to guide therapy may be helpful in this rarely-encountered clinical scenario. PROGNOSIS High degree AV block Advanced (second or third degree) AV block is associated with an increase in mortality in patients with an inferior or anterior MI [12-17,21,32]. The increase in mortality risk is seen largely within the first 30 days; among 30-day survivors, subsequent mortality does not appear to be consistently increased in reports of various AMI cohorts [12,13,18,21]. AV block following inferior MI Although high grade AV block in patients with an inferior MI is usually transient, it is associated with increased in-hospital mortality. Following primary PCI In one large United States registry in the PCI era, complete heart block (CHB) in the setting of inferior STEMI increased in-hospital mortality twofold [16]. A similar increase in mortality with inferior STEMI was seen in other studies in the PCI era [14,15]. https://www.uptodate.com/contents/conduction-abnormalities-after-myocardial-infarction/print 14/34 7/5/23, 10:34 AM Conduction abnormalities after myocardial infarction - UpToDate Following thrombolysis An increase in mortality with high degree AV block of about 15 percent at 30 days is seen in patients with an inferior MI treated with a thrombolytic agent [12,21,32-36]. AV block following anterior MI High degree AV block in patients with an anterior wall MI is associated with a greater increase in in-hospital and 30-day mortality than seen with an inferior wall infarction, probably due to more extensive myocardial involvement and a higher incidence of hemodynamic complications [12,32]. Following primary PCI In the United States National Inpatient Sample registry from the PCI era, CHB in the setting of anterior STEMI increased in-hospital mortality fourfold, versus only twofold in inferior STEMI patients [16]. A similar increase in mortality with CHB and anterior STEMI was seen in other studies in the PCI era [14,15,37]. In a study of 1295 STEMI patients undergoing PCI in Japan, complete AV block occurred in 1.7 percent of patients with anterior STEMI and 10.7 percent of those with nonanterior STEMI [37]. Multivariate analysis showed that CHB was associated with all-cause mortality (hazard ratio [HR] 3.01, 95% CI 1.33-6.09) and major adverse cardiac endpoints (HR 2.23, 95% CI 1.01- 4.38) in anterior STEMI patients. In contrast, CHB was not associated with adverse outcomes in patients with nonanterior STEMI. Following thrombolysis In a review of nearly 76,000 patients from four randomized trials of fibrinolytic therapy, 3.2 percent of patients with anterior MI developed AV block and had a significant increase in mortality at 30 days (41 versus 8 percent in those without AV block; odds ratio [OR] 3.0, 95% CI 2.2-4.1) [12]. Bundle branch block The presence of fascicular or BBB during an acute MI is associated with an increase in in-hospital and long-term mortality [9-11,22,38-47]. However, interpreting the prognostic significance of BBB is complicated for several reasons: In contrast to CHB, which is almost always a new finding due to the MI, BBB often precedes the MI. This finding most commonly reflects the prevalence of BBB among patients presenting with acute MI, not the incidence of new BBB due to the infarction, which is generally very low. In the HERO-2 trial, BBB was present on 5.1 percent of initial ECGs, but new BBB developed in only 0.9 percent of patients on a second ECG taken 60 minutes later [9]. The development of a new BBB post-MI is generally felt to be associated with increased mortality [48]. Chronic and new conduction abnormalities may both predict worse outcomes, but for different reasons. The former is due to more extensive underlying cardiac disease and the latter is due to the association with larger infarctions. https://www.uptodate.com/contents/conduction-abnormalities-after-myocardial-infarction/print 15/34 7/5/23, 10:34 AM Conduction abnormalities after myocardial infarction - UpToDate The following observations illustrate the range of findings among patients with BBB. These studies made the assessment of the presence or absence of BBB largely based on the initial ECG. Thus, it could not be determined whether the BBB was pre-existing or associated with the infarction unless there was resolution of the BBB. Following primary PCI Among patients undergoing primary PCI, the presence of BBB on the baseline ECG is associated with increased mortality [48-50]. In a review of 3053 patients in the Primary Angioplasty in Myocardial Infarction (PAMI) trials, LBBB was present in 1.6 percent and RBBB in 3.1 percent [43]. In-hospital mortality was 14.6, 7.4, and 2.8 percent in patients with LBBB, RBBB, and no BBB, respectively. Following thrombolysis In an analysis of 26,003 North American patients entered into the GUSTO-I trial of thrombolytic therapy, the in-hospital mortality was 18 versus 11 percent with and without a BBB [42]. Patients with a BBB were more likely to experience cardiogenic shock (19 versus 11 percent), AV block or asystole (30 versus 19 percent), and to require a pacemaker (18 versus 11 percent). Mortality was higher when the BBB was persistent (20 percent versus 12 and 8 percent in the 24 percent of patients who had partial or complete resolution of the BBB, respectively). In a meta-analysis of eight studies that included 105,861 acute MI patients (STEMI and non- STEMI), new LBBB was associated with higher mortality at 30 days (OR 2.10; 95% CI 1.27- 3.48) and at one year (OR 2.81; 95% CI 1.64-4.80) [46]. In a meta-analysis of 10 studies that included 63,103 patients (STEMI and non-STEMI), RBBB (new or old) was associated with higher in-hospital (OR 1.94; 95% CI 1.60-2.37) and long-term mortality (OR 1.49; 95% CI 1.37-1.62) [47]. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Non-ST-elevation acute coronary syndromes (non-ST-elevation myocardial infarction)" and "Society guideline links: ST- elevation myocardial infarction (STEMI)".) SUMMARY AND RECOMMENDATIONS Bradyarrhythmias and conduction disturbances are well-recognized complications of acute myocardial infarction (MI). They are caused by either autonomic imbalance or ischemia/necrosis of the conduction system. (See 'Introduction' above.) https://www.uptodate.com/contents/conduction-abnormalities-after-myocardial-infarction/print 16/34 7/5/23, 10:34 AM Conduction abnormalities after myocardial infarction - UpToDate Atrioventricular (AV) block with inferior MI generally results from ischemic and autonomic effects on the AV node. It is associated with a narrow QRS complex and develops in a progressive fashion from first to second to third degree block. It often results in an asymptomatic bradycardia (40 to 60 beats per min) and is usually transient, resolving within five to seven days. (See 'Inferior MI' above.) AV block with anterior MI generally occurs abruptly in the first 24 hours. It can develop without warning or may be preceded by the development of right bundle branch block (RBBB) with either a left anterior or posterior fascicular block pattern (bifascicular or trifascicular block). The escape rhythm usually has a wide QRS complex and is unstable, and the event is associated with a high mortality from both arrhythmias and pump failure. In-hospital and 30-day mortality are higher than seen with an inferior wall infarction. (See 'Anterior MI' above.) The initial management of the patient with post-MI conduction abnormalities depends on the presence and severity of any signs and symptoms of hemodynamic instability ( algorithm 1). Mobitz type II second degree AV block, high grade AV block, or third degree (complete) AV block are often unstable rhythms and more likely to cause, or to be associated with, hemodynamic instability. Patients with newly developed BBB, or alternating BBB, are also at increased risk of developing hemodynamic instability. Patients with Mobitz type I second degree AV block, first degree AV block, or isolated BBB rarely develop hemodynamic instability related to their heart rhythm. (See 'Management of conduction abnormalities' above.) Patients with acute MI and second degree AV block, high grade AV block, or third degree (complete) AV block who are hemodynamically unstable should be urgently treated with atropine (if block is suspected to be at the AV nodal level) and generally temporary cardiac pacing should be instituted (either with transcutaneous or, if immediately available, transvenous pacing). For patients with acute inferior MI who are unresponsive to atropine, we suggest IV aminophylline (Grade 2C). Temporary transvenous pacing is generally warranted in patients with acute MI in the following circumstances (see 'Temporary pacing' above): Complete (third degree) AV block. Alternating right and left bundle branch block (LBBB). Right BBB with alternating left anterior and posterior fascicular block. https://www.uptodate.com/contents/conduction-abnormalities-after-myocardial-infarction/print 17/34 7/5/23, 10:34 AM Conduction abnormalities after myocardial infarction - UpToDate Asystole. Symptomatic bradycardia of any etiology, including sinus bradycardia and Mobitz type I second degree AV block, if adverse hemodynamic effects are present and the bradyarrhythmia is not responsive to atropine. Mobitz type II second degree AV block. Bradycardia-induced tachyarrhythmias, such as torsades de pointes. In general, a waiting period of several days should be employed to determine potential reversibility of AV block, particularly in patients with acute inferior MI. If no reversible causes are present, definitive treatment of Mobitz type II second degree AV block, high grade AV block, or third degree (complete) AV block involves permanent pacemaker placement in most patients. (See 'Second degree AV block, high grade AV block, or third degree (complete) AV block' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges the late Mark E. Josephson, MD, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. S nchez-Quintana D, Cabrera JA, Farr J, et al. Sinus node revisited in the era of electroanatomical mapping and catheter ablation. Heart 2005; 91:189. 2. Rosenbaum M, Elizari MV, Lazzari JO. The Hemiblocks, Tampa Tracings, Tampa 1970. 3. Uhley HN. Some controversy regarding the peripheral distribution of the conduction system. Am J Cardiol 1972; 30:919. 4. Hecht HH, Kossmann CE, Childers RW, et al. Atrioventricular and intraventricular conduction. Revised nomenclature and concepts. Am J Cardiol 1973; 31:232. 5. Demoulin JC, Kulbertus HE. Histopathological examination of concept of left hemiblock. Br Heart J 1972; 34:807. 6. Zimetbaum PJ, Josephson ME. 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Primary angioplasty in acute myocardial infarction with right bundle branch block: should new onset right bundle branch block be added to future guidelines as an indication for reperfusion therapy? Eur Heart J 2012; 33:86. 50. Vivas D, P rez-Vizcayno MJ, Hern ndez-Antol n R, et al. Prognostic implications of bundle branch block in patients undergoing primary coronary angioplasty in the stent era. Am J Cardiol 2010; 105:1276. Topic 45 Version 29.0 https://www.uptodate.com/contents/conduction-abnormalities-after-myocardial-infarction/print 22/34 7/5/23, 10:34 AM Conduction abnormalities after myocardial infarction - UpToDate GRAPHICS Action potentials generated by different parts of conduction system The sinoatrial (SA) and atrioventricular (AV) nodes generate a slow action potential, mediated by calcium ions. In comparison, the tissues of the atria, ventricles, and the His-Purkinje system generate a fast action potential mediated by sodium ions. Sequential activation of these structures results in the characteristic waveforms visible on the surface electrocardiogram (ECG). The AV node and bundle of His are small structures; as a result, no electrical activity is recorded on the surface ECG during their activation. Graphic 61989 Version 4.0 https://www.uptodate.com/contents/conduction-abnormalities-after-myocardial-infarction/print 23/34 7/5/23, 10:34 AM Conduction abnormalities after myocardial infarction - UpToDate Normal conduction system Schematic representation of the normal intraventricular conduction system (His- Purkinje system). The Bundle of His divides into the left bundle branch and right bundle branch. The left bundle branch divides into anterior, posterior, and, in some cases, median fascicles. AV: atrioventricular; RA: right atrium; LA: left atrium; RV: right ventricle; LV: left ventricle. Graphic 63340 Version 6.0 https://www.uptodate.com/contents/conduction-abnormalities-after-myocardial-infarction/print 24/34 7/5/23, 10:34 AM Conduction abnormalities after myocardial infarction - UpToDate Coronary artery anatomy Graphic 70956 Version 2.0 https://www.uptodate.com/contents/conduction-abnormalities-after-myocardial-infarction/print 25/34 7/5/23, 10:34 AM Conduction abnormalities after myocardial infarction - UpToDate Relationship between fast sodium-mediated myocardial action potential and surface electrocardiogram Each phase of the myocardial action potential (numbers, upper panel) corresponds to a deflection or interval on the surface ECG (lower panel). Phase 4, the resting membrane potential, is responsible for the TQ segment; this segment has a prominent role in the ECG manifestations of ischemia during exercise testing. ECG: electrocardiogram. Graphic 64133 Version 4.0 https://www.uptodate.com/contents/conduction-abnormalities-after-myocardial-infarction/print 26/34 7/5/23, 10:34 AM Conduction abnormalities after myocardial infarction - UpToDate Electrocardiogram showing Mobitz type I (Wenckebach) atrioventricular block Single-lead electrocardiogram showing Mobitz type I (Wenckebach) second-degree atrioventricular block with 5:4 conduction. The characteristics of this arrhythmia include: a progressively increasing PR interval until a P wave is not conducted (arrow), a progressive decrease in the increment in the PR interval, a progressive decrease in the RR interval, and the RR interval that includes the dropped beat (0.96 sec) is less than twice the RR interval between conducted beats (0.53 to 0.57 sec). Courtesy of Morton Arnsdorf, MD. Graphic 73051 Version 6.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/conduction-abnormalities-after-myocardial-infarction/print 27/34 7/5/23, 10:34 AM Conduction abnormalities after myocardial infarction - UpToDate Electrocardiogram (ECG) showing concurrent Mobitz type I (Wenckebach) atrioventricular (AV) block and inferior myocardial infarction (MI) This rhythm strip shows a Mobitz type I (Wenckebach) atrioventricular block with 4:3 and 3:2 conduction and progressive prolongation of the PR intervals of conducted beats. The marked ST segment elevation suggests acute inferior wall ischemia or infarction that may be responsible for the arrhythmia. Courtesy of Ary Goldberger, MD. Graphic 62040 Version 3.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/conduction-abnormalities-after-myocardial-infarction/print 28/34 7/5/23, 10:34 AM Conduction abnormalities after myocardial infarction - UpToDate Electrocardiographic and electrophysiologic features of Mobitz type II second-degree atrioventricular block The PR and RR intervals are constant, but the third atrial beat (A) is not conducted (arrow). His bundle electrocardiography (HBE) shows constant AH (85 msec) and HV (95 msec) intervals and normal AH but no HV conduction in the nonconducted beat. The last finding indicates that the block is distal to the His bundle, in contrast with the more proximal location of Mobitz type I atrioventricular block. Adapted from: Josephson ME, Clinical Cardiac Electrophysiology: Techniques and nd Interpretations, 2 ed, Lea & Febiger, Philadelphia 1993. Graphic 79539 Version 7.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/conduction-abnormalities-after-myocardial-infarction/print 29/34 7/5/23, 10:34 AM Conduction abnormalities after myocardial infarction - UpToDate 12-lead electrocardiogram (ECG) showing bifascicular block with right bundle branch block and left anterior fascicular block The 12-lead ECG from a patient with a history of an anteroseptal myocardial infarction (Q waves seen in lead V1-V3) shows bifascicular block with RBBB and LAFB. A typical RBBB is seen with a QRS duration of 0.16 seconds and an rSR' configuration in lead V1 and a deep S wave in V6. The QRS complexes in leads II, III, and avF are negative, with a rS morphology, diagnostic of a pathologic left axis deviation, known as LAFB. ECG: electrocardiogram; RBBB: right bundle branch block; LAFB: left anterior fascicular block. Reproduced with permission by Samuel Levy, MD. Graphic 69886 Version 4.0 https://www.uptodate.com/contents/conduction-abnormalities-after-myocardial-infarction/print 30/34 7/5/23, 10:34 AM Conduction abnormalities after myocardial infarction - UpToDate Treatment of peri-myocardial infarction conduction abnormalities ECG: electrocardiogram; AV: atrioventricular; MI: myocardial infarction; PPM: permanent pacemaker. https://www.uptodate.com/contents/conduction-abnormalities-after-myocardial-infarction/print 31/34 7/5/23, 10:34 AM Conduction abnormalities after myocardial infarction - UpToDate Transcutaneous pacing is frequently the quickest way to provide temporary cardiac pacing, but is unreliable for extended periods of treatment and uncomfortable for the patient. While transcutaneous pacing may be initially successful in stabilizing the patient, central venous access should be established and transvenous pacing provided in the vast majority of patients requiring temporary cardiac pacing. The initial dose of atropine is 0.5 mg IV. This dose may be repeated every three to five minutes to a total dose of 3 mg. If the patient does not respond promptly and/or clinically deteriorates, proceed directly to temporary pacing. The typical aminophylline dose is 250 mg IV bolus. In patients with a prior heart transplant, a higher weight-based dose is preferred (6 mg/kg IV mixed in 100 to 200 mL of IV fluid adminstered over 20 to 30 minutes). Refer to UpToDate content on management of acute MI. In general, a waiting period of several days should be employed to determine potential reversibility of AV block, particularly in patients with acute inferior MI. If no reversible causes are present, definitive treatment involves PPM placement in most patients. Graphic 120722 Version 1.0 https://www.uptodate.com/contents/conduction-abnormalities-after-myocardial-infarction/print 32/34 7/5/23, 10:34 AM Conduction abnormalities after myocardial infarction - UpToDate Adult bradycardia algorithm 2020 update Reprinted with permission. ACLS Provider Manual. Copyright 2020 American Heart Association, Inc. Graphic 130748 Version 10.0 https://www.uptodate.com/contents/conduction-abnormalities-after-myocardial-infarction/print 33/34 7/5/23, 10:34 AM Conduction abnormalities after myocardial infarction - UpToDate Contributor Disclosures Peter J Zimetbaum, MD Consultant/Advisory Boards: Abbott Medical [Lead extraction]. All of the relevant financial relationships listed have been mitigated. Joseph E Marine, MD, FACC, FHRS No relevant financial relationship(s) with ineligible companies to disclose. Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Bernard J Gersh, MB, ChB, DPhil, FRCP, MACC Consultant/Advisory Boards: Bain Institute [CRO for trials involving Edwards percutaneous valve devices]; Cardiovascular Research Foundation [Data safety monitoring board (RELIEVE-HF Trial)]; Caristo Diagnostics Limited [Imaging and inflammation/atherosclerosis]; Philips Image Guided Therapy Corporation [Imaging]; Sirtex Med Limited [General consulting]; Thrombosis Research Institute [Data safety monitoring board (GARFIELD study)]. All of the relevant financial relationships listed have been mitigated. James Hoekstra, MD No relevant financial relationship(s) with ineligible companies to disclose. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/conduction-abnormalities-after-myocardial-infarction/print 34/34

7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Congenital third-degree (complete) atrioventricular block : William H Sauer, MD, Edward P Walsh, MD : Mark S Link, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: May 16, 2023. INTRODUCTION Atrioventricular (AV) block is defined as a delay or interruption in the transmission of an impulse from the atria to the ventricles due to an anatomical or functional impairment in the conduction system. The conduction disturbance can be transient or permanent, with conduction that is delayed, intermittent, or absent. Commonly used terminology includes: First-degree AV block Delayed conduction from the atrium to the ventricle (defined as a prolonged PR interval of >200 milliseconds) without interruption in atrial to ventricular conduction. Second-degree AV block Intermittent atrial conduction to the ventricle, often in a regular pattern (eg, 2:1, 3:2), or higher degrees of block, which are further classified into Mobitz type I (Wenckebach) and Mobitz type II second-degree AV block. Third-degree (complete) AV block No atrial impulses conduct to the ventricle. High-grade AV block Two or more consecutive blocked P waves. Atrioventricular block is considered to be "congenital" when it occurs spontaneously in a fetus or young child. Congenital complete heart block (CHB) was first described in 1901 by Morquio, who also noted the familial occurrence and the association with Stokes-Adams attacks and death [1]. The presence of fetal bradycardia (40 to 80 beats per minute) as a manifestation of CHB was first noted in 1921 and is the initial sign of this disorder in many cases [2]. https://www.uptodate.com/contents/congenital-third-degree-complete-atrioventricular-block/print 1/20 7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate The epidemiology, etiologies, clinical presentation, diagnosis, treatment, and prognosis associated with congenital CHB will be presented here. Discussions of noncongenital complete AV block are presented separately. (See "Etiology of atrioventricular block" and "Third-degree (complete) atrioventricular block".) EPIDEMIOLOGY The incidence of congenital CHB in the general population varies between 1 in 15,000 to 1 in 22,000 live-born infants [3,4]. Injury to fetal conduction tissues caused by transplacental exposure to maternal autoantibodies related to systemic lupus erythematosus or Sj gren's disease is responsible for 60 to 90 percent of cases of congenital CHB overall [5-7]. Among women with anti-Ro/SSA and/or anti-La/SSB antibodies, fetal/neonatal CHB occurs in approximately 2 percent of pregnancies [8,9]. However, once a woman has given birth to an infant with autoimmune CHB block, the recurrence rate in subsequent pregnancies rises to approximately 15 percent. (See "The anti-Ro/SSA and anti-La/SSB antigen-antibody systems".) As many as 40 percent of cases of congenital CHB do not present until later in childhood (mean age five to six years) [7]. Only rarely do these patients (5 percent) have proven autoimmune etiology [7]. ETIOLOGY The etiologies of congenital CHB include the following [10]: Autoimmune antibodies. Structural heart abnormalities due to congenital heart disease (eg, congenitally corrected transposition of the great arteries, endocardial cushion defects). Idiopathic familial congenital CHB. Complete heart block may also be seen in the fetus or young child as a consequence of myocarditis or mechanical trauma from surgical or transcatheter interventions; however, these acquired forms are not considered "congenital." Autoimmune congenital CHB Autoimmune heart block typically begins in utero, though clinical detection may occasionally be delayed until after birth or during early childhood [11]. In most cases, the block is third degree, with lower-grade block seen only occasionally. The mechanism is understood to involve damage to developing specialized conduction tissue from https://www.uptodate.com/contents/congenital-third-degree-complete-atrioventricular-block/print 2/20 7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate passive transplacental passage of maternal autoantibodies to Ro/SSA and/or La/SSB intracellular ribonuclear proteins [10]. The risk of CHB in an individual fetus does not correlate directly with the maternal autoantibody titer. Importantly, the majority of mothers who give birth to a child with autoimmune CHB have never had symptoms of connective tissue disease up to time of delivery despite their positive serology. Some affected newborns may present with a multisystem neonatal lupus syndrome that can include skin rash, hepatobiliary disease, and thrombocytopenia [12]. (See "Neonatal lupus: Epidemiology, pathogenesis, clinical manifestations, and diagnosis", section on 'Clinical manifestations'.) Congenital CHB related to congenital heart defects Certain forms of congenital heart disease are associated with developmental abnormalities of the AV conduction tissues [13]. L-looped transposition of the great arteries (L-TGA) In L-TGA (also called "congenitally corrected" transposition of the great arteries) ( figure 1), the compact AV node develops outside of Koch's triangle in an unusual anterior location near the base of the right atrial appendage. This displaced node is often feeble and can deteriorate over time so that complete heart block is seen in as many as 5 percent of these patients at birth, and in more than 25 percent by adulthood. (See "L-transposition of the great arteries (L-TGA): Anatomy, clinical features, and diagnosis".) Endocardial cushion defects Displacement of the AV node also occurs in patients with endocardial cushion defects (ie, primum atrial septal defects or complete AV canal defects) ( figure 2). These hearts do not have a proper triangle of Koch, and the compact node is consequently displaced in a posterior direction beneath the mouth of coronary sinus. Similar to L-TGA, AV nodal function can be suboptimal in endocardial cushion defects, with complete heart block at birth in some individuals, and a significant risk of surgically- induced block following repairs. (See "Clinical manifestations and diagnosis of atrioventricular (AV) canal defects".) Syndromes with simple atrial septal defects Congenitally impaired AV nodal function can also be observed in some simple cases of atrial septal defect among patients with Holt- Oram syndrome, an autosomal dominant disorder causing cardiac and upper-limb abnormalities that involves a mutation on the TBX5 gene [14]. (See "Isolated atrial septal defects (ASDs) in children: Classification, clinical features, and diagnosis", section on 'Genetic disorders'.) Idiopathic familial congenital CHB Non-immune CHB in patients with a structurally normal heart has also been described as an idiopathic disorder with a strong familial tendency. In a https://www.uptodate.com/contents/congenital-third-degree-complete-atrioventricular-block/print 3/20 7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate retrospective cohort of 141 children with AV block diagnosed in utero or up to age 15 years (51 percent female, 84 percent asymptomatic, 71 percent with complete AV block on presentation, with an additional 21 percent progressing from incomplete to complete AV block), 112 patients (79 percent) received permanent pacemakers, most prophylactically in asymptomatic patients (70 of 112 patients [63 percent]) [15]. Familial screening electrocardiograms (ECGs) were obtained from 130 parents of patients in the cohort and were compared with 130 matched healthy controls [16]. Parents of the children with AV block were significantly more likely to have conduction abnormalities compared with healthy controls, including complete or incomplete right bundle branch block (39 versus 2 percent), complete or incomplete left bundle branch block (15 versus 3 percent), and PR prolongation (19 versus 0 percent). Progressive AV block has also been reported in association with an extracardiac phenotype that includes a brachyfacial abnormality, finger deformity, and dental dysplasia [17]. Members of these two unrelated families shared a common mutation in the third exon of the gene encoding for connexin-45, a gap junction channel involved in electrical signal propagation in the sinoatrial (SA) node, AV node, and His-Purkinje system. PATHOPHYSIOLOGY Most cases of congenital CHB are immune-mediated and are characterized pathologically by fibrous tissue that either replaces the atrioventricular (AV) node and its surrounding tissue or by an interruption between the atrial myocardium and the AV node [18-26]. The net effect is that the block is usually at the level of the AV node [20,22,24,27,28], allowing junctional escape rhythms that can usually support the fetal and neonatal circulation, at least temporarily [12,29]. The primary injury is caused by the binding of anti-Ro/SSA and/or anti-La/SSB antibodies to the developing AV node and its surrounding tissue [9,18,30]. Both Ro/SSA and La/SSB antigens are abundant in fetal heart tissue between 18 and 24 weeks [30]. Apoptosis induces translocation of Ro/SSA and La/SSB to the surface of fetal cardiomyocytes; anti-Ro and anti-La antibodies then bind to the surface of the fetal cardiocytes and induce the release of tumor necrosis factor by macrophages, which then results in fibrosis [31]. In addition to inducing tissue damage, anti-Ro/SSA and/or anti-La/SSB antibodies inhibit calcium channel activation or the cardiac L- and T- type calcium channels themselves; L-type channels are crucial to action potential propagation and conduction in the AV node [32,33]. Congenital CHB in patients with congenital heart defects is directly related to abnormalities in the embryologic development of the specialized atrioventricular conduction tissues that lead to displacement and functional impairment of the AV node and/or His bundle. https://www.uptodate.com/contents/congenital-third-degree-complete-atrioventricular-block/print 4/20 7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate CLINICAL MANIFESTATIONS The manifestations of congenital CHB vary according to the age at presentation, underlying etiology, ventricular rate of the escape rhythm, and ventricular function. Patients with autoimmune congenital CHB tend to present earlier than those with CHB due to other causes [34]. In addition to atrioventricular conduction defects, in a small number of cases autoimmune CHB can be associated with sinoatrial node dysfunction as well as a more diffuse cardiomyopathy that can result in depressed ventricular function and endocardial fibroelastosis [7,9,18,35,36]. (See "Neonatal lupus: Epidemiology, pathogenesis, clinical manifestations, and diagnosis", section on 'Other cardiac abnormalities'.) Autoimmune heart block typically begins in utero, though clinical detection may occasionally be delayed until after birth or during early childhood. In most cases, the block is third degree, with lower-grade block seen only occasionally. The noncardiac manifestations of neonatal lupus resolve as maternal antibodies dissipate in the infant, but cardiac damage tends to be irreversible. In utero presentation Congenital heart block may present with fetal bradycardia between 18 and 28 weeks of gestation [7,11,12]. The clinical manifestations, diagnosis, and approach to management of intrauterine congenital CHB are discussed separately. (See "Neonatal lupus: Epidemiology, pathogenesis, clinical manifestations, and diagnosis" and "Fetal arrhythmias", section on 'Heart block'.) Neonatal presentation The primary finding in neonates with congenital CHB is a slow heart rate that is usually less than 100 beats per minute. Neonates with congenital CHB otherwise have few specific physical examination findings, although they may appear pale or diaphoretic related to the reduction in cardiac output. Other clinical clues in the neonate may include: Intermittent cannon waves in the neck Variable intensity of the first heart sound (see "Auscultation of heart sounds") Intermittent gallops and murmurs Signs of congestive heart failure (eg, crackles on lung examination, elevated jugular venous pulsations, peripheral edema, etc) As with cases presenting in utero, almost all presenting in the neonatal period (90 percent in one series) are due to maternal autoantibodies [7,37]. First- or second-degree AV block found in infants at birth can progress to CHB and should be followed carefully [35,38]. https://www.uptodate.com/contents/congenital-third-degree-complete-atrioventricular-block/print 5/20 7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate Presentation in later childhood Up to 40 percent of patients with congenital CHB present later in childhood. Reasons for the late presentation are speculative, but likely relate to an intermittent early course or a higher ventricular rate of the escape rhythm [39]. The primary finding in children with congenital CHB is a slow heart rate with or without bradycardia-related symptoms, including reduced exercise tolerance and presyncope or syncope (Stokes-Adams attacks) [7,40]. Sudden death has also rarely been described [29,41,42]. Although congenital CHB may be intermittent when first detected, it usually becomes persistent over time [7]. While congenital CHB diagnosed for the first time later in childhood may be congenital in origin, escaping notice because of a higher ventricular rate and the absence of symptoms, patients who present later in childhood likely have preserved AV conduction at birth and acquire progressive AV nodal disease thereafter [7]. In a single-center study of 102 patients with congenital CHB diagnosed over a 34-year period, the number of presentations later in childhood remained constant from 1980 to 1998 despite the introduction of fetal echocardiography and the wide availability of heart rate monitoring during pregnancy and labor, suggesting that AV conduction is preserved at birth and becomes abnormal at a later time in a subset of patients [7]. Maternal autoantibody exposure accounts for almost all cases presenting in utero or the neonatal period, but for only a few cases occurring at older ages (5 percent in one report) [7]. (See 'Epidemiology' above and "Neonatal lupus: Epidemiology, pathogenesis, clinical manifestations, and diagnosis".) DIAGNOSIS In nearly all cases, the diagnosis of complete heart block can be made by obtaining a surface ECG, ideally a full 12-lead ECG, though a single-lead rhythm strip is sometimes adequate if a full 12-lead ECG cannot be obtained. The diagnosis is usually suspected when a slow pulse is detected and heart block is confirmed by ECG or by ambulatory ECG monitoring [7,40,41]. DIFFERENTIAL DIAGNOSIS Complete heart block has a relatively unique appearance on the ECG, with evidence of atrial (P waves) and ventricular (QRS complexes) activity that are independent of each other, and an atrial rate faster than the ventricular rate. Rarely, complete AV block can occur in which the atrial rate is exactly twice the ventricular rate (eg, atrial rate of 80 beats per minute with a ventricular rate of 40 beats per minute), in which case the appearance on ECG could be similar to that of second- https://www.uptodate.com/contents/congenital-third-degree-complete-atrioventricular-block/print 6/20 7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate degree AV (ie, 2:1) block. However, any slight variation in the exact multiples should result in variations on the ECG that allow the distinction between third-degree (complete) AV block and second-degree AV block. In utero CHB must be differentiated from benign bradycardia caused by frequent blocked premature atrial complexes (also referred to a premature atrial beat, premature supraventricular complex, or premature supraventricular beat), which can be reliably distinguished on the basis of the fetal echocardiogram. TREATMENT In utero treatment The management options for congenital CHB in utero are limited, and treatment of the fetus with CHB is primarily expectant. Fortunately, the fetus will tolerate the slow escape rhythm in the majority of cases. If hydrops fetalis or other signs of fetal distress should develop, early delivery and emergency pacing may be needed. The approach to in utero treatment of fetal CHB is discussed in detail separately. (See "Neonatal lupus: Management and outcomes", section on 'In utero management' and "Fetal arrhythmias", section on 'Heart block'.) Postnatal treatment For neonates and children who present later with congenital CHB, the principal therapeutic decision involves the need for, and the potential timing of, permanent pacemaker insertion. For older children who are able to express themselves about symptoms, the presence or absence of symptoms will help guide the decision. Patients with an adequate ventricular heart rate and no symptoms can usually be followed with serial observation, while symptomatic patients (typically those with a slower ventricular heart rate) will require a permanent pacemaker [43]. Most patients (approximately 90 percent or greater) ultimately have a pacemaker inserted ( figure 3), regardless of when CHB developed (ie, in utero or following delivery) [7,41]. Our approach to pacemaker implantation is in general agreement with the professional society guidelines for management of bradycardia, which specifically address the population of patients with congenital CHB [43-45]. Pacemaker implantation was recommended (class I) or felt to be reasonable (class IIa) for patients with congenital CHB and the following characteristics: Symptomatic bradycardia or low cardiac output (class I). Wide QRS escape rhythm, complex ventricular ectopy, or ventricular dysfunction (class I). Asymptomatic adults with congenital CHB (class IIa). Infants with normal anatomy and a ventricular rate less than 55 beats per minute (class I). https://www.uptodate.com/contents/congenital-third-degree-complete-atrioventricular-block/print 7/20 7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate Infants with other structural congenital heart disease and a ventricular rate less than 70 beats per minute (class I). Children beyond the first year of life with an average heart rate less than 50 beats per minute, or abrupt pauses two to three times the basic R-R cycle length (class IIa). The type of pacemaker implanted is based primarily upon patient age/size, as well as the presence or absence of congenital heart defects. Implants for infants and very young children will usually require epicardial leads due to small caliber of the standard insertion veins used for transvenous devices, as well as the expectation for thoracic growth that may eventually place tension on transvenous leads [46]. Epicardial leads are also used in patients of any age with septal defects that allow intracardiac shunting and thus increase the risk of thromboembolic complications [47]. A transvenous dual-chamber pacemaker is preferred at most centers when there are no significant size constraints or other contraindications. When feasible, consideration should be given to techniques for ventricular lead placement that activate the native His bundle or left bundle branch [48]. (See "Modes of cardiac pacing: Nomenclature and selection".) PROGNOSIS CHB presenting in utero or the neonatal period, which is mostly due to maternal autoantibodies, is associated with a high early mortality [10,49-51]. The outcome for patients diagnosed as neonates is better than for those diagnosed in utero. Infants and young children with complete heart block who are asymptomatic usually remain so until later childhood, adolescence, or adulthood [3,52]. (See "Neonatal lupus: Management and outcomes".) Among 175 cases of congenital CHB diagnosed in the fetus, 29 (17 percent) died either in utero or within the first three months of life [7,12]. Survival appears to relate to gestational age at birth, with offspring born before 34 weeks having a higher mortality rate than those born later (52 versus 9 percent) [12]. Infants with first- or second-degree heart block at birth can progress to complete heart block [12,35,38]. (See 'Clinical manifestations' above.) In a single-center cohort of 33 patients who presented in the neonatal period, five had signs of heart failure, but none had hydrops fetalis [7]. None died within the first six months, but two died at 0.9 and 1.5 years of age. Prognosis is generally excellent among infants and those diagnosed later in childhood [10]. However, exercise limitation and even mortality in childhood are not negligible [40,53,54]. Children with a mean heart rate below 50 beats per minute and evidence of an unstable junctional escape rhythm may be at particular risk [37,40]. Even patients who have been https://www.uptodate.com/contents/congenital-third-degree-complete-atrioventricular-block/print 8/20 7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate asymptomatic throughout childhood are at increased risk of sudden death. In a review of 102 patients who were without symptoms through age 15, 27 (26 percent) had a subsequent syncopal episode, eight of which were fatal [41]. Those patients who do not experience symptoms or syncopal attacks may still suffer physiologic consequences of bradycardia. The ventricular rate tends to fall slowly with age [41]. To compensate for the slow heart rate, the heart enlarges to produce a higher stroke volume; in some cases, this can lead to voltage criteria for left ventricular enlargement and nonspecific ST-T wave changes [55] as well as to heart failure [56,57]. In general, the prognosis following pacemaker implantation is excellent [37,58,59]. However, a significant number of patients (5 to 11 percent) develop heart failure over the long-term, even if a pacemaker is inserted [56,57,60]. In a study of 149 patients followed for 10 years, 6 percent developed a dilated cardiomyopathy by 6.5 years of age; risk factors included anti-Ro/SSA or anti-La/SSB antibodies, increased heart size at initial evaluation, and the absence of improvement with a pacemaker [57]. Patients diagnosed prior to one month of age are more likely to have left ventricular systolic dysfunction both prior to permanent pacemaker implantation and over the long-term [37]. In another study of 114 subjects followed over a period of 40 years, 26 subjects (23 percent) reached the primary composite outcome of death, LV systolic dysfunction, heart failure, cardiomyopathy, or use of cardiac resynchronization therapy, with an incidence rate of 2.2 per 100 person-years [60]. The primary outcome occurred at a median of 3.1 years after diagnosis. While the development of heart failure in such patients may be a consequence of myocardial fibrosis associated with CHB [56], heart failure is also a well-recognized long-term consequence of right ventricular pacing with consequent ventricular asynchrony [61] (see "Modes of cardiac pacing: Nomenclature and selection", section on 'Modes to minimize ventricular pacing'). Patients with congenital heart block who develop ventricular dysfunction in the setting of chronic right ventricular pacing will usually benefit from upgrading to cardiac resynchronization with addition of a left ventricular pacing lead [62]. An alternative for this patient group is His bundle pacing as a method to mitigate detrimental effects of asynchronous right ventricular pacing [63]. (See "Cardiac resynchronization therapy in heart failure: Indications and choice of system".) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cardiac implantable https://www.uptodate.com/contents/congenital-third-degree-complete-atrioventricular-block/print 9/20 7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate electronic devices".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Heart block in adults (The Basics)" and "Patient education: Heart block in children (The Basics)") SUMMARY AND RECOMMENDATIONS Congenital third-degree (complete) heart block (CHB), a relatively rare disorder affecting between 1 in 15,000 to 1 in 22,000 live-born infants, may result from autoimmune antibodies, structural heart abnormalities due to congenital heart disease, or may be idiopathic. Autoimmune CHB due to maternal auto antibodies that cross the placenta is responsible for 60 to 90 percent of cases of congenital CHB overall. (See 'Epidemiology' above and 'Etiology' above.) The manifestations of congenital CHB vary according to the age at presentation, underlying etiology, ventricular rate of the escape rhythm, and ventricular function. The primary finding in neonates with congenital CHB is a slow heart rate that is usually less than 100 beats per minute. Neonates with congenital CHB otherwise have few specific physical examination findings, although they may appear pale or diaphoretic related to the reduction in cardiac output. (See 'Clinical manifestations' above.) In nearly all cases, the diagnosis of complete heart block can be made by obtaining a surface ECG. The diagnosis is usually suspected when a slow pulse is detected and heart https://www.uptodate.com/contents/congenital-third-degree-complete-atrioventricular-block/print 10/20 7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate block is confirmed by ECG or by ambulatory ECG monitoring. (See 'Diagnosis' above.) For neonates and children who present later with congenital CHB, the principal therapeutic decision involves the need for and the potential timing of permanent pacemaker insertion. For older children who are able to express themselves about symptoms, the presence or absence of symptoms will help guide the decision. Patients with an adequate ventricular heart rate and no symptoms can usually be followed with serial observation, while symptomatic patients (typically those with a slower ventricular heart rate) will require a permanent pacemaker. In general, the prognosis following pacemaker implantation is excellent. (See 'Treatment' above and 'Prognosis' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Morquio, L . Sur une maladie infantile et familiale characteris e par des modifications permanentes du pouls, des attaques syncopales et epileptiforme et la mort subite. Arch M d d'Enfants 1901; 4:467. 2. White, P, Eustis, R . Congenital heart block. Am J Dis Child 1921; 22:299. 3. Micha lsson M, Engle MA. Congenital complete heart block: an international study of the natural history. Cardiovasc Clin 1972; 4:85. 4. Brito-Zer n P, Izmirly PM, Ramos-Casals M, et al. The clinical spectrum of autoimmune congenital heart block. Nat Rev Rheumatol 2015; 11:301. 5. Johansen AS, Herlin T. [Neonatal lupus syndrome. Association with complete congenital atrioventricular block]. Ugeskr Laeger 1998; 160:2521. 6. Ross BA. Congenital complete atrioventricular block. Pediatr Clin North Am 1990; 37:69. 7. Jaeggi ET, Hamilton RM, Silverman ED, et al. Outcome of children with fetal, neonatal or childhood diagnosis of isolated congenital atrioventricular block. A single institution's experience of 30 years. J Am Coll Cardiol 2002; 39:130. 8. Brucato A, Frassi M, Franceschini F, et al. Risk of congenital complete heart block in newborns of mothers with anti-Ro/SSA antibodies detected by https://www.uptodate.com/contents/congenital-third-degree-complete-atrioventricular-block/print 11/20 7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate counterimmunoelectrophoresis: a prospective study of 100 women. Arthritis Rheum 2001; 44:1832. 9. Buyon JP, Kim MY, Copel JA, Friedman DM. Anti-Ro/SSA antibodies and congenital heart block: necessary but not sufficient. Arthritis Rheum 2001; 44:1723. 10. Brito-Zer n P, Izmirly PM, Ramos-Casals M, et al. Autoimmune congenital heart block: complex and unusual situations. Lupus 2016; 25:116. 11. Eliasson H, Sonesson SE, Sharland G, et al. Isolated atrioventricular block in the fetus: a retrospective, multinational, multicenter study of 175 patients. Circulation 2011; 124:1919. 12. Buyon JP, Hiebert R, Copel J, et al. Autoimmune-associated congenital heart block: demographics, mortality, morbidity and recurrence rates obtained from a national neonatal lupus registry. J Am Coll Cardiol 1998; 31:1658. 13. Anderson RH, Ho SY. The disposition of the conduction tissues in congenitally malformed hearts with reference to their embryological development. J Perinat Med 1991; 19 Suppl 1:201. 14. Mori AD, Bruneau BG. TBX5 mutations and congenital heart disease: Holt-Oram syndrome revealed. Curr Opin Cardiol 2004; 19:211. 15. Baruteau AE, Fouchard S, Behaghel A, et al. Characteristics and long-term outcome of non- immune isolated atrioventricular block diagnosed in utero or early childhood: a multicentre study. Eur Heart J 2012; 33:622. 16. Baruteau AE, Behaghel A, Fouchard S, et al. Parental electrocardiographic screening identifies a high degree of inheritance for congenital and childhood nonimmune isolated atrioventricular block. Circulation 2012; 126:1469. 17. Seki A, Ishikawa T, Daumy X, et al. Progressive Atrial Conduction Defects Associated With Bone Malformation Caused by a Connexin-45 Mutation. J Am Coll Cardiol 2017; 70:358. 18. Ho SY, Esscher E, Anderson RH, Micha lsson M. Anatomy of congenital complete heart block and relation to maternal anti-Ro antibodies. Am J Cardiol 1986; 58:291. 19. Anderson RH, Wenick AC, Losekoot TG, Becker AE. Congenitally complete heart block. Developmental aspects. Circulation 1977; 56:90. 20. NAKAMURA FF, NADAS AS. COMPLETE HEART BLOCK IN INFANTS AND CHILDREN. N Engl J Med 1964; 270:1261. 21. ROWE JC, WHITE PD. Complete heart block: a follow-up study. Ann Intern Med 1958; 49:260. 22. Rosen KM, Mehta A, Rahimtoola SH, Miller RA. Sites of congenital and surgical heart block as defined by His bundle electrocardiography. Circulation 1971; 44:833. https://www.uptodate.com/contents/congenital-third-degree-complete-atrioventricular-block/print 12/20 7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate 23. Feldt RH, DuShane JW, Titus JL. The atrioventricular conduction system in persistent common atrioventricular canal defect: correlations with electrocardiogram. Circulation 1970; 42:437. 24. Lev M, Silverman J, Fitzmaurice FM, et al. Lack of connection between the atria and the more peripheral conduction system in congenital atrioventricular block. Am J Cardiol 1971; 27:481. 25. Lev M, Cuadros H, Paul MH. Interruption of the atrioventricular bundle with congenital atrioventricular block. Circulation 1971; 43:703. 26. James TN, Spencer MS, Kloepfer JC. De Subitaneis Mortibus. XXI. Adult onset syncope. with comments on the nature of congenital heart block and the morphogenesis of the human atrioventricular septal junction. Circulation 1976; 54:1001. 27. Reid JM, Coleman EN, Doig W. Complete congenital heart block. Report of 35 cases. Br Heart J 1982; 48:236. 28. Nasrallah AT, Gillette PC, Mullins CE. Congenital and surgical atrioventricular block within the His bundle. Am J Cardiol 1975; 36:914. 29. Sholler GF, Walsh EP. Congenital complete heart block in patients without anatomic cardiac defects. Am Heart J 1989; 118:1193. 30. Alexander E, Buyon JP, Provost TT, Guarnieri T. Anti-Ro/SS-A antibodies in the pathophysiology of congenital heart block in neonatal lupus syndrome, an experimental model. In vitro electrophysiologic and immunocytochemical studies. Arthritis Rheum 1992; 35:176. 31. Miranda-Car s ME, Askanase AD, Clancy RM, et al. Anti-SSA/Ro and anti-SSB/La autoantibodies bind the surface of apoptotic fetal cardiocytes and promote secretion of TNF-alpha by macrophages. J Immunol 2000; 165:5345. 32. Garcia S, Nascimento JH, Bonfa E, et al. Cellular mechanism of the conduction abnormalities induced by serum from anti-Ro/SSA-positive patients in rabbit hearts. J Clin Invest 1994; 93:718. 33. Xiao GQ, Hu K, Boutjdir M. Direct inhibition of expressed cardiac l- and t-type calcium channels by igg from mothers whose children have congenital heart block. Circulation 2001; 103:1599. 34. Cruz RB, Viana VS, Nishioka SA, et al. Is isolated congenital heart block associated to neonatal lupus requiring pacemaker a distinct cardiac syndrome? Pacing Clin Electrophysiol 2004; 27:615. https://www.uptodate.com/contents/congenital-third-degree-complete-atrioventricular-block/print 13/20 7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate 35. Askanase AD, Friedman DM, Copel J, et al. Spectrum and progression of conduction abnormalities in infants born to mothers with anti-SSA/Ro-SSB/La antibodies. Lupus 2002; 11:145. 36. Nield LE, Silverman ED, Taylor GP, et al. Maternal anti-Ro and anti-La antibody-associated endocardial fibroelastosis. Circulation 2002; 105:843. 37. Eliasson H, Sonesson SE, Salomonsson S, et al. Outcome in young patients with isolated complete atrioventricular block and permanent pacemaker treatment: A nationwide study of 127 patients. Heart Rhythm 2015; 12:2278. 38. Waltuck J, Buyon JP. Autoantibody-associated congenital heart block: outcome in mothers and children. Ann Intern Med 1994; 120:544. 39. Pinsky WW, Gillette PC, Garson A Jr, McNamara DG. Diagnosis, management, and long-term results of patients with congenital complete atrioventricular block. Pediatrics 1982; 69:728. 40. Dewey RC, Capeless MA, Levy AM. Use of ambulatory electrocardiographic monitoring to identify high-risk patients with congenital complete heart block. N Engl J Med 1987; 316:835. 41. Micha lsson M, Jonzon A, Riesenfeld T. Isolated congenital complete atrioventricular block in adult life. A prospective study. Circulation 1995; 92:442. 42. Karpawich PP, Gillette PC, Garson A Jr, et al. Congenital complete atrioventricular block: clinical and electrophysiologic predictors of need for pacemaker insertion. Am J Cardiol 1981; 48:1098. 43. Kusumoto FM, Schoenfeld MH, Barrett C, et al. 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2019; 74:e51. 44. Epstein AE, DiMarco JP, Ellenbogen KA, et al. 2012 ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2013; 61:e6. 45. Writing Committee Members, Shah MJ, Silka MJ, et al. 2021 PACES Expert Consensus Statement on the Indications and Management of Cardiovascular Implantable Electronic Devices in Pediatric Patients. Heart Rhythm 2021; 18:1888. 46. Baruteau AE, Pass RH, Thambo JB, et al. Congenital and childhood atrioventricular blocks: pathophysiology and contemporary management. Eur J Pediatr 2016; 175:1235. https://www.uptodate.com/contents/congenital-third-degree-complete-atrioventricular-block/print 14/20 7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate 47. Khairy P, Landzberg MJ, Gatzoulis MA, et al. Transvenous pacing leads and systemic thromboemboli in patients with intracardiac shunts: a multicenter study. Circulation 2006; 113:2391. 48. Chubb H, Mah D, Dubin AM, Moore J. Conduction system pacing in pediatric and congenital heart disease. Front Physiol 2023; 14:1154629. 49. Izmirly PM, Saxena A, Kim MY, et al. Maternal and fetal factors associated with mortality and morbidity in a multi-racial/ethnic registry of anti-SSA/Ro-associated cardiac neonatal lupus. Circulation 2011; 124:1927. 50. Levesque K, Morel N, Maltret A, et al. Description of 214 cases of autoimmune congenital heart block: Results of the French neonatal lupus syndrome. Autoimmun Rev 2015; 14:1154. 51. Hernstadt H, Regan W, Bhatt H, et al. Cohort study of congenital complete heart block among preterm neonates: a single-center experience over a 15-year period. Eur J Pediatr 2022; 181:1047. 52. McHenry MM. Factors influencing longevity in adults with congenital complete heart block. Am J Cardiol 1972; 29:416. 53. Reybrouck T, Vanden Eynde B, Dumoulin M, Van der Hauwaert LG. Cardiorespiratory response to exercise in congenital complete atrioventricular block. Am J Cardiol 1989; 64:896. 54. Motonaga KS, Punn R, Axelrod DM, et al. Diminished exercise capacity and chronotropic incompetence in pediatric patients with congenital complete heart block and chronic right ventricular pacing. Heart Rhythm 2015; 12:560. 55. Kertesz NJ, Friedman RA, Colan SD, et al. Left ventricular mechanics and geometry in patients with congenital complete atrioventricular block. Circulation 1997; 96:3430. 56. Moak JP, Barron KS, Hougen TJ, et al. Congenital heart block: development of late-onset cardiomyopathy, a previously underappreciated sequela. J Am Coll Cardiol 2001; 37:238. 57. Udink ten Cate FE, Breur JM, Cohen MI, et al. Dilated cardiomyopathy in isolated congenital complete atrioventricular block: early and long-term risk in children. J Am Coll Cardiol 2001; 37:1129. 58. Pordon CM, Moodie DS. Adults with congenital complete heart block: 25-year follow-up. Cleve Clin J Med 1992; 59:587. 59. Groves AM, Allan LD, Rosenthal E. Outcome of isolated congenital complete heart block diagnosed in utero. Heart 1996; 75:190. 60. Weinreb SJ, Okunowo O, Griffis H, Vetter V. Incidence of morbidity and mortality in a cohort

22. Rosen KM, Mehta A, Rahimtoola SH, Miller RA. Sites of congenital and surgical heart block as defined by His bundle electrocardiography. Circulation 1971; 44:833. https://www.uptodate.com/contents/congenital-third-degree-complete-atrioventricular-block/print 12/20 7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate 23. Feldt RH, DuShane JW, Titus JL. The atrioventricular conduction system in persistent common atrioventricular canal defect: correlations with electrocardiogram. Circulation 1970; 42:437. 24. Lev M, Silverman J, Fitzmaurice FM, et al. Lack of connection between the atria and the more peripheral conduction system in congenital atrioventricular block. Am J Cardiol 1971; 27:481. 25. Lev M, Cuadros H, Paul MH. Interruption of the atrioventricular bundle with congenital atrioventricular block. Circulation 1971; 43:703. 26. James TN, Spencer MS, Kloepfer JC. De Subitaneis Mortibus. XXI. Adult onset syncope. with comments on the nature of congenital heart block and the morphogenesis of the human atrioventricular septal junction. Circulation 1976; 54:1001. 27. Reid JM, Coleman EN, Doig W. Complete congenital heart block. Report of 35 cases. Br Heart J 1982; 48:236. 28. Nasrallah AT, Gillette PC, Mullins CE. Congenital and surgical atrioventricular block within the His bundle. Am J Cardiol 1975; 36:914. 29. Sholler GF, Walsh EP. Congenital complete heart block in patients without anatomic cardiac defects. Am Heart J 1989; 118:1193. 30. Alexander E, Buyon JP, Provost TT, Guarnieri T. Anti-Ro/SS-A antibodies in the pathophysiology of congenital heart block in neonatal lupus syndrome, an experimental model. In vitro electrophysiologic and immunocytochemical studies. Arthritis Rheum 1992; 35:176. 31. Miranda-Car s ME, Askanase AD, Clancy RM, et al. Anti-SSA/Ro and anti-SSB/La autoantibodies bind the surface of apoptotic fetal cardiocytes and promote secretion of TNF-alpha by macrophages. J Immunol 2000; 165:5345. 32. Garcia S, Nascimento JH, Bonfa E, et al. Cellular mechanism of the conduction abnormalities induced by serum from anti-Ro/SSA-positive patients in rabbit hearts. J Clin Invest 1994; 93:718. 33. Xiao GQ, Hu K, Boutjdir M. Direct inhibition of expressed cardiac l- and t-type calcium channels by igg from mothers whose children have congenital heart block. Circulation 2001; 103:1599. 34. Cruz RB, Viana VS, Nishioka SA, et al. Is isolated congenital heart block associated to neonatal lupus requiring pacemaker a distinct cardiac syndrome? Pacing Clin Electrophysiol 2004; 27:615. https://www.uptodate.com/contents/congenital-third-degree-complete-atrioventricular-block/print 13/20 7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate 35. Askanase AD, Friedman DM, Copel J, et al. Spectrum and progression of conduction abnormalities in infants born to mothers with anti-SSA/Ro-SSB/La antibodies. Lupus 2002; 11:145. 36. Nield LE, Silverman ED, Taylor GP, et al. Maternal anti-Ro and anti-La antibody-associated endocardial fibroelastosis. Circulation 2002; 105:843. 37. Eliasson H, Sonesson SE, Salomonsson S, et al. Outcome in young patients with isolated complete atrioventricular block and permanent pacemaker treatment: A nationwide study of 127 patients. Heart Rhythm 2015; 12:2278. 38. Waltuck J, Buyon JP. Autoantibody-associated congenital heart block: outcome in mothers and children. Ann Intern Med 1994; 120:544. 39. Pinsky WW, Gillette PC, Garson A Jr, McNamara DG. Diagnosis, management, and long-term results of patients with congenital complete atrioventricular block. Pediatrics 1982; 69:728. 40. Dewey RC, Capeless MA, Levy AM. Use of ambulatory electrocardiographic monitoring to identify high-risk patients with congenital complete heart block. N Engl J Med 1987; 316:835. 41. Micha lsson M, Jonzon A, Riesenfeld T. Isolated congenital complete atrioventricular block in adult life. A prospective study. Circulation 1995; 92:442. 42. Karpawich PP, Gillette PC, Garson A Jr, et al. Congenital complete atrioventricular block: clinical and electrophysiologic predictors of need for pacemaker insertion. Am J Cardiol 1981; 48:1098. 43. Kusumoto FM, Schoenfeld MH, Barrett C, et al. 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2019; 74:e51. 44. Epstein AE, DiMarco JP, Ellenbogen KA, et al. 2012 ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2013; 61:e6. 45. Writing Committee Members, Shah MJ, Silka MJ, et al. 2021 PACES Expert Consensus Statement on the Indications and Management of Cardiovascular Implantable Electronic Devices in Pediatric Patients. Heart Rhythm 2021; 18:1888. 46. Baruteau AE, Pass RH, Thambo JB, et al. Congenital and childhood atrioventricular blocks: pathophysiology and contemporary management. Eur J Pediatr 2016; 175:1235. https://www.uptodate.com/contents/congenital-third-degree-complete-atrioventricular-block/print 14/20 7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate 47. Khairy P, Landzberg MJ, Gatzoulis MA, et al. Transvenous pacing leads and systemic thromboemboli in patients with intracardiac shunts: a multicenter study. Circulation 2006; 113:2391. 48. Chubb H, Mah D, Dubin AM, Moore J. Conduction system pacing in pediatric and congenital heart disease. Front Physiol 2023; 14:1154629. 49. Izmirly PM, Saxena A, Kim MY, et al. Maternal and fetal factors associated with mortality and morbidity in a multi-racial/ethnic registry of anti-SSA/Ro-associated cardiac neonatal lupus. Circulation 2011; 124:1927. 50. Levesque K, Morel N, Maltret A, et al. Description of 214 cases of autoimmune congenital heart block: Results of the French neonatal lupus syndrome. Autoimmun Rev 2015; 14:1154. 51. Hernstadt H, Regan W, Bhatt H, et al. Cohort study of congenital complete heart block among preterm neonates: a single-center experience over a 15-year period. Eur J Pediatr 2022; 181:1047. 52. McHenry MM. Factors influencing longevity in adults with congenital complete heart block. Am J Cardiol 1972; 29:416. 53. Reybrouck T, Vanden Eynde B, Dumoulin M, Van der Hauwaert LG. Cardiorespiratory response to exercise in congenital complete atrioventricular block. Am J Cardiol 1989; 64:896. 54. Motonaga KS, Punn R, Axelrod DM, et al. Diminished exercise capacity and chronotropic incompetence in pediatric patients with congenital complete heart block and chronic right ventricular pacing. Heart Rhythm 2015; 12:560. 55. Kertesz NJ, Friedman RA, Colan SD, et al. Left ventricular mechanics and geometry in patients with congenital complete atrioventricular block. Circulation 1997; 96:3430. 56. Moak JP, Barron KS, Hougen TJ, et al. Congenital heart block: development of late-onset cardiomyopathy, a previously underappreciated sequela. J Am Coll Cardiol 2001; 37:238. 57. Udink ten Cate FE, Breur JM, Cohen MI, et al. Dilated cardiomyopathy in isolated congenital complete atrioventricular block: early and long-term risk in children. J Am Coll Cardiol 2001; 37:1129. 58. Pordon CM, Moodie DS. Adults with congenital complete heart block: 25-year follow-up. Cleve Clin J Med 1992; 59:587. 59. Groves AM, Allan LD, Rosenthal E. Outcome of isolated congenital complete heart block diagnosed in utero. Heart 1996; 75:190. 60. Weinreb SJ, Okunowo O, Griffis H, Vetter V. Incidence of morbidity and mortality in a cohort of congenital complete heart block patients followed over 40 years. Heart Rhythm 2022; https://www.uptodate.com/contents/congenital-third-degree-complete-atrioventricular-block/print 15/20 7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate 19:1149. 61. Thambo JB, Bordachar P, Garrigue S, et al. Detrimental ventricular remodeling in patients with congenital complete heart block and chronic right ventricular apical pacing. Circulation 2004; 110:3766. 62. Chandler SF, Fynn-Thompson F, Mah DY. Role of cardiac pacing in congenital complete heart block. Expert Rev Cardiovasc Ther 2017; 15:853. 63. Dandamudi G, Simon J, Cano O, et al. Permanent His Bundle Pacing in Patients With Congenital Complete Heart Block: A Multicenter Experience. JACC Clin Electrophysiol 2021; 7:522. Topic 912 Version 35.0 https://www.uptodate.com/contents/congenital-third-degree-complete-atrioventricular-block/print 16/20 7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate GRAPHICS Anatomy of a normal heart and L-transposition of the great arteries RA: right atrium; RV: right ventricle; Ao: aorta; LV: left ventricle; LA: left atrium; PT: pulmonary trunk. Graphic 83845 Version 1.0 https://www.uptodate.com/contents/congenital-third-degree-complete-atrioventricular-block/print 17/20 7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate Different forms of atrioventricular canal defects Anatomic and physiologic similarities between the different forms of AVSDs are illustrated. Complete AVSDs have 1 annulus with large interatrial and interventricular communications. Intermediate defects (1 annulus, 2 orifices) are a subtype of complete AVSD. Complete AVSDs have physiology of VSDs and ASDs. In contrast, partial AVSDs have physiology of ASDs. Transitional defects are a form of complete AVSD in which a small, insignificant inlet VSD is present and, as a result, the physiology is more similar to that of a partial defect. Partial defects and the intermediate form of complete AVSD share a similar anatomic feature: A tongue of tissue divides the common AV valve into distinct right and left orifices. LA: left atrium; LPV: left pulmonary vein; LV: left ventricle; RA: right atrium; RPV: right pulmonary vein; RV: right ventricle; VSD: ventricular septal defect; ASD: atrial septal defect; AV: atrioventricular; AVSD: atrioventricular septal defect. Reproduced with permission from: Cetta F, Minich LL, Edwards WD, et al. Atrioventricular septal defects. In: Moss and Adams' Heart Disease in Infants, Children, and Adolescents Including the Fetus and Young Adult, 7th ed, Allen HD, Shaddy RE, Driscoll DJ, Feltes TF (Eds), Lippincott Williams & Wilkins, Philadelphia 2007. Copyright 2007 Lippincott Williams & Wilkins. www.lww.com. Graphic 86346 Version 9.0 https://www.uptodate.com/contents/congenital-third-degree-complete-atrioventricular-block/print 18/20 7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate Timing of pacemaker implantation according to age at diagnosis of congenital CHB In a study of 102 cases of congenital complete heart block (CHB), most patients ultimately had a pacemaker inserted, regardless of the time of onset of the syndrome. By 20 years of age, only 11 percent of neonatal and 12 percent of childhood cases had not required pacemaker implantation. Data from Jaeggi ET, Hamilton RM, Silverman ED, et al, J Am Coll Cardiol 2002; 39:130. Graphic 55309 Version 2.0 https://www.uptodate.com/contents/congenital-third-degree-complete-atrioventricular-block/print 19/20 7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate Contributor Disclosures William H Sauer, MD Grant/Research/Clinical Trial Support: Biosense-Webster [Catheter ablation]; Boston Scientific [Catheter ablation]. All of the relevant financial relationships listed have been mitigated. Edward P Walsh, MD No relevant financial relationship(s) with ineligible companies to disclose. Mark S Link, MD No relevant financial relationship(s) with ineligible companies to disclose. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/congenital-third-degree-complete-atrioventricular-block/print 20/20

7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. COVID-19: Arrhythmias and conduction system disease : Jordan M Prutkin, MD, MHS, FHRS : Bradley P Knight, MD, FACC : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Feb 07, 2023. INTRODUCTION Coronaviruses are important human and animal pathogens. At the end of 2019, a novel coronavirus was identified as the cause of a cluster of pneumonia cases in Wuhan, a city in the Hubei Province of China. It rapidly spread, resulting in a global pandemic. The disease is designated COVID-19, which stands for "coronavirus disease 2019" [1]. The virus that causes COVID-19 is designated "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2); previously, it was referred to as 2019-nCoV. Understanding of COVID-19 is evolving rapidly. Interim guidance has been issued by the World Health Organization and the United States Centers for Disease Control and Prevention [2,3]. Links to these and other related society guidelines are found elsewhere. (See "COVID-19: Epidemiology, virology, and prevention", section on 'Society guideline links' and "COVID-19: Clinical features", section on 'Society guideline links'.) This topic will discuss the epidemiology, prevalence, evaluation, diagnosis, and management of arrhythmias and conduction system disease in patients with COVID-19. Clinical presentation, diagnosis, and management of other cardiac presentations (eg, acute coronary syndrome, heart failure, etc) and noncardiac manifestations of COVID-19 are discussed in detail elsewhere: (See "COVID-19: Epidemiology, virology, and prevention".) (See "COVID-19: Clinical features".) (See "COVID-19: Diagnosis".) (See "COVID-19: Management in hospitalized adults".) (See "COVID-19: Management of the intubated adult".) https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 1/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate (See "COVID-19: Myocardial infarction and other coronary artery disease issues".) (See "COVID-19: Evaluation and management of cardiac disease in adults".) (See "COVID-19: Clinical manifestations and diagnosis in children".) (See "COVID-19: Infection prevention for persons with SARS-CoV-2 infection".) (See "COVID-19: Questions and answers".) Community-acquired coronaviruses, severe acute respiratory syndrome (SARS) coronavirus, and Middle East respiratory syndrome (MERS) coronavirus are discussed separately. (See "Coronaviruses" and "Severe acute respiratory syndrome (SARS)" and "Middle East respiratory syndrome coronavirus: Virology, pathogenesis, and epidemiology".) EPIDEMIOLOGY Patients with COVID-19 may be at increased risk of certain arrhythmias. Factors such as severity of illness and taking specific medications for COVID-19 treatment may increase the risk of developing an arrythmia. Incidence and prevalence The prevalence of arrhythmias and conduction system disease (and cardiovascular disease in general) in patients with COVID-19 varies from population to population [4]. The vast majority of patients presenting with a systemic illness consistent with COVID-19 will not have symptoms or signs of arrhythmias or conduction system disease. Patients may be tachycardic (with or without palpitations) in the setting of other illness-related symptoms (eg, fever, shortness of breath, pain, etc). The following observations have been reported from various cohorts: QTc prolongation Among 4250 patients with COVID-19 from a multicenter New York cohort, 260 (6.1 percent) had QTc >500 milliseconds at the time of admission [5]. However, in another study of 84 patients who received hydroxychloroquine and azithromycin, the baseline QTc was 435 milliseconds before taking these medications [6]. Atrial fibrillation In a large United States registry of nearly 31,000 patients hospitalized with COVID-19, 5.4 percent developed new-onset atrial fibrillation (AF) during their index hospitalization [7]. In a separate meta-analysis of 19 observational studies with 21,653 patients hospitalized with COVID-19, the prevalence of AF was 11 percent. AF was higher in patients with severe versus non-severe COVID-19 (19 versus 3 percent) [8]. Out-of-hospital cardiac arrest Two studies suggest an increase in the risk of out-of- hospital cardiac arrest during the pandemic. In a study from Italy, there was a nearly 60 percent increase in the rate of out-of-hospital cardiac arrest during the peak of the 2020 https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 2/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate COVID-19 pandemic (when compared with the same time frame from 2019) [9]. In a study from France, there was a 52 percent increase in the cumulative incidence of out-of-hospital cardiac arrest during a two-month period between February and April 2020 compared with 2019 [10]. These observations could be related to COVID-19 infections, stress related to the pandemic, or delays in seeking medical attention by those with cardiac symptoms. In-hospital cardiac arrest In a single-center United States study of 700 patients admitted with COVID-19 (11 percent in the intensive care unit), nine patients experienced cardiac arrest, although only one patient had a shockable rhythm of torsades de pointes (eight patients had PEA/asystole) [11]. In a separate cohort of 136 Chinese patients with severe pneumonia due to COVID-19, and who experienced in-hospital cardiac arrest and attempted resuscitation, most arrests were deemed respiratory in origin, and the initial rhythm was non-shockable in the vast majority of patients (asystole in 90 percent, pulseless electrical activity in 4 percent) [12]. Return of spontaneous circulation (13 percent), survival to 30 days (3 percent), and survival with intact neurologic function (1 percent) were extremely low in this critically ill cohort. Ventricular ectopy and tachycardia In 143 patients admitted to a single center, nonsustained VT occurred in 15.4 percent, premature ventricular contractions in 28.8 percent, ventricular fibrillation 1.4 percent, and sustained ventricular tachycardia occurred in 0.7 percent [13]. A more recent analysis from the COVID-19-Associated Hospitalization Surveillance Network of over 8600 hospitalizations for COVID-19 found that ventricular tachycardia occurred 0.9 percent of the time [14]. Bradyarrhythmias In 143 patients admitted to a single center, complete atrioventricular block occurred in 1.4 percent and sinus arrest in 0.7 percent [13]. Potential risk factors These may include the following: The presence of cardiovascular complications in the setting of COVID-19 infection, such as myocardial injury or myocardial ischemia. (See "COVID-19: Myocardial infarction and other coronary artery disease issues" and "COVID-19: Evaluation and management of cardiac disease in adults".) More severe infection and mechanical ventilation can predispose to AF and other atrial arrythmias [8,15]. The presence of hypoxia, shock (septic or cardiogenic), or evidence of widespread systemic inflammation can predispose to arrhythmia [16]. (See "COVID-19: Management of the intubated adult".) https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 3/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate The presence of electrolyte disturbances (eg, hypokalemia) may predispose to the development of arrhythmias. (See "Clinical manifestations and treatment of hypokalemia in adults", section on 'Cardiac arrhythmias and ECG abnormalities' and "Hypomagnesemia: Clinical manifestations of magnesium depletion", section on 'Cardiovascular'.) Therapies that prolong the QT interval may increase the risk of polymorphic VT. (See 'Patients with polymorphic ventricular tachycardia (torsades de pointes)' below.) Remdesivir may be a risk factor for bradycardia [17-20]. However, several large randomized trials of remdesivir did not report bradycardia as an adverse event [21-24]. (See "COVID-19: Management in hospitalized adults", section on 'Remdesivir'.) The presence of fever, which can unmask cardiac channelopathies such as Brugada syndrome and long QT syndrome in susceptible patients [25,26]. (See 'Brugada syndrome' below and "Brugada syndrome: Clinical presentation, diagnosis, and evaluation" and "Congenital long QT syndrome: Epidemiology and clinical manifestations".) Outcomes Mortality post-cardiac arrest Mortality after cardiac arrest is extremely high and may be even higher in the setting of COVID-19. A national registry study from France compared 30- day mortality rates for patients with and without COVID-19 who had out-of-hospital cardiac arrest and subsequent admission to an intensive care unit [27]. In this study, 127 patients with confirmed COVID-19 had a 100 percent 30-day mortality, compared with 96.5 percent of such patients without COVID-19. A separate study from a hospital in rural Georgia showed that 63 patients with COVID-19 who experienced an in-hospital cardiac arrest had a 100 percent in-hospital mortality [28]. The latter study did not have a COVID-19 negative control group. AF and mortality Studies are mixed as to whether AF and new-onset AF are associated with all-cause mortality among hospitalized patients with COVID-19 [7,29]; in such patients, AF has not been shown to be associated with adverse major cardiac events. In a large United States registry of nearly 31,000 patients hospitalized with COVID-19 from 120 institutions, 5.4 percent developed new-onset AF during their index hospitalization, and new-onset AF was associated with a higher rate of death (45.2 versus 11.9 percent) and major adverse cardiac events (23.8 versus 6.5 percent) [7]. However, after adjusting for patient comorbidities, new-onset AF was nonsignificantly associated with a higher risk of death (hazard ratio [HR] 1.10, 95% CI 0.99-1.23) and was not associated with major adverse cardiac events (HR 1.31 95% CI 1.14-1.50). https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 4/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate On the other hand, in a cohort of 9564 patients hospitalized with COVID-19 from New York with propensity score matching of 1238 pairs of patients with and without and AF, in- hospital mortality was higher in patients with AF: 54 versus 37 percent (relative risk [RR] 1.46, 95% CI 1.34-1.59) [29]. In a propensity-score-matched analysis of 500 patients, patients with new-onset AF had worse outcomes compared with those with a history of AF (55 versus 47 percent [RR 1.18, 95% CI 1.04-1.33]). A strength of this study was the use of propensity score matching, which better balanced the comorbidities in the AF cases and non-AF control groups, leading to more reliable mortality risk ratios. However, generalizability of this single-center study may be lower than that of the multicenter registry described above [7]. EVALUATION In most available reports, the specific cause of palpitations or type of arrhythmia have not been specified. Hypoxia and electrolyte abnormalities, both known to contribute to the development of acute arrhythmias, have been frequently reported in the acute phase of severe COVID-19 illness; therefore, the exact contribution of COVID-19 infection to the development of arrhythmias in asymptomatic, mildly ill, critically ill, and recovered patients is not known [30]. Cardiovascular testing ECG Most patients in whom COVID-19 is suspected and, in particular, patients with severe disease or in whom QT-prolonging medications will be used, should have a baseline electrocardiogram (ECG) performed at the time of entry into the health care system [31]. Ideally, this would be a 12-lead ECG, but a single- or multi-lead ECG from telemetry monitoring or multiple lead positions from a hand-held ECG device may be adequate in this situation to minimize staff exposure to the patient [32]. This will allow for documenting baseline QRS-T morphology should the patient develop signs/symptoms suggestive of myocardial injury or an acute coronary syndrome. Additionally, the baseline ECG allows for documentation of the QT (and corrected QTc) interval. Importantly, QTc will need to be monitored if QT-prolonging therapies are initiated to reduce the risk of acquired long QT syndrome. (See "Acquired long QT syndrome: Clinical manifestations, diagnosis, and management" and 'Patients receiving therapies that prolong the QT interval' below.) Continuous ECG monitoring In the absence of documented cardiac arrhythmias, suspected myocardial ischemia, or other standard indications, continuous ECG monitoring is not required. However, as part of infection control mechanisms for patients with established or suspected COVID-19 infection, many hospitals are utilizing continuous ECG monitoring (in conjunction with https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 5/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate automated blood pressure readings and oxygen saturation monitors) in lieu of standard vital sign checks by nursing staff. This practice reduces the number of clinical staff interacting with the patient, thereby reducing the risk to health care workers and preserving personal protective equipment. Transthoracic echocardiography While some patients may develop cardiac manifestations, including myocardial injury, an initial transthoracic echocardiogram is not necessary for all patients. Providers may consider using a point-of-care ultrasound for a focused exam. (See "COVID-19: Evaluation and management of cardiac disease in adults".) DIAGNOSIS OF ARRHYTHMIAS Arrhythmias are most commonly diagnosed from a combination of vital signs and review of the ECG, ideally a 12-lead ECG, but a rhythm strip can also be used. Tachycardias present with a pulse greater than 100 beats per minute, while most bradyarrhythmias present with a pulse less than 50 to 60 beats per minute. The most common arrhythmia overall in patients with COVID-19 is sinus tachycardia, but the most likely pathologic arrhythmias include atrial fibrillation, atrial flutter, and monomorphic or polymorphic VT. The differentiation between various tachycardias based on regularity (ie, regular or irregular) and QRS width (ie, narrow or wide QRS complex) requires only a surface ECG. (See "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation" and "Wide QRS complex tachycardias: Approach to the diagnosis".) Bradyarrhythmias, including sinus pauses or high-grade heart block with slow escape rhythms, have not typically been seen but can be identified using a surface ECG if present. (See "Sinus node dysfunction: Clinical manifestations, diagnosis, and evaluation" and "Second-degree atrioventricular block: Mobitz type II" and "Third-degree (complete) atrioventricular block".) The diagnosis of acquired long QT syndrome can be made in a patient with sufficient QT prolongation on the surface ECG in association with a medication or other clinical scenario (ie, hypokalemia or hypomagnesemia) known to cause QT prolongation. Ideally, the diagnosis is made following review of a full 12-lead ECG, but sometimes a single-lead rhythm strip is adequate if a full 12-lead ECG cannot be obtained. Acquired QT prolongation is typically reversible upon removal of the underlying etiology, such as discontinuation of an offending medication or correction of electrolyte derangements. (See 'Management' below.) https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 6/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate Overall, the average QTc in healthy persons after puberty is 420 20 milliseconds. In general, the 99th percentile QTc values are 470 milliseconds in postpubertal males and 480 milliseconds in postpubertal females [33]. A QTc >500 milliseconds is considered highly abnormal for both males and females. MANAGEMENT Patients with polymorphic ventricular tachycardia (torsades de pointes) All patients with torsades de pointes (TdP) should have an immediate assessment of the symptoms, vital signs, and level of consciousness to determine if they are hemodynamically stable or unstable. Unstable patients Patients with sustained TdP usually become hemodynamically unstable, severely symptomatic, or pulseless and should be treated according to standard resuscitation algorithms [34], including cardioversion/defibrillation ( algorithm 1 and algorithm 2 and algorithm 3). Initial treatment with antiarrhythmic medications, with the exception of intravenous (IV) magnesium, is not indicated for hemodynamically unstable or pulseless patients. A full discussion of the standard approaches to basic life support and advanced cardiac life support is presented separately. (See "Adult basic life support (BLS) for health care providers" and "Advanced cardiac life support (ACLS) in adults".) Stable patients Patients with TdP who are hemodynamically stable on presentation may remain stable or may become unstable rapidly and without warning. As such, therapy should be promptly provided to most patients. A stable patient is one who typically shows no evidence of hemodynamic compromise but may have frequent, repetitive bursts of TdP. This patient should have continuous monitoring and frequent reevaluations due to the potential for rapid deterioration as long as the TdP persists. (See "Acquired long QT syndrome: Clinical manifestations, diagnosis, and management", section on 'Initial management'.) Patients with other arrhythmias The management of other arrhythmias in the setting of COVID-19 infection is no different from the routine management of these conditions without COVID-19 infection. Please refer to the following topics for management: Atrial fibrillation and other supraventricular tachycardias: (See "Overview of the acute management of tachyarrhythmias".) (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation".) (See "Overview of atrial flutter".) (See "Atrioventricular nodal reentrant tachycardia".) (See "Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome".) https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 7/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate (See "Focal atrial tachycardia".) Monomorphic VT: (See "Wide QRS complex tachycardias: Approach to management".) (See "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis".) (See "Ventricular tachycardia in the absence of apparent structural heart disease".) Conduction system disease: (See "Sinus node dysfunction: Treatment".) (See "Third-degree (complete) atrioventricular block".) (See "Second-degree atrioventricular block: Mobitz type II".) (See "Temporary cardiac pacing".) Patients receiving therapies that prolong the QT interval Hydroxychloroquine and chloroquine are two medications that can cause acquired long QT syndrome (LQTS). (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes".) Neither hydroxychloroquine nor chloroquine are recommended for treatment of COVID-19; additionally, in June 2020, the US FDA revoked its emergency use authorization for these agents in patients with severe COVID-19, noting that the known and potential benefits no longer outweighed the known and potential risks [35]. However, patients may still be treated with chloroquine or hydroxychloroquine [6,36], which are structurally similar to quinidine and have QT-prolonging effects by blocking activation of the potassium channel IKr (hERG/Kv11.1) [30,37- 39]. Other medications with QT-prolonging effects may be tried for COVID-19 ( table 1). In addition, both chloroquine and hydroxychloroquine are metabolized by CYP3A4, so other medications that inhibit this cytochrome could raise plasma levels [37]. Monitoring for QT prolongation As in patients without COVID-19, among patients with COVID-19, the baseline QTc value should be obtained prior to administering any drugs with the potential to prolong the QT interval [40]. When patients are receiving any QT-prolonging medications, a dynamic discussion of the benefits and risks of these medications should be ongoing based on the baseline risk (including baseline QTc, electrolyte levels, etc), perceived or actual benefit of therapy, and development of significant QT prolongation or TdP. A systematic review of 14 studies showed that about 10 percent of patients developed a QTc interval 500 ms or change of >60 ms while taking hydroxychloroquine or chloroquine [41]. Data from various cohort studies of patients with COVID-19 treated with one or more QT prolonging drugs suggest https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 8/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate a modest increase in QTc (20 to 30 milliseconds) in most patients, although the response in an individual patient may be more profound [42-44]. Patients with COVID-19 who have a baseline QTc interval 500 milliseconds (with a QRS 120 milliseconds) are at increased risk for significant QT prolongation and polymorphic VT [45]. In such patients, as with any patient at risk for acquired LQTS, efforts should be made to correct any contributing electrolyte abnormalities (eg, hypocalcemia, hypokalemia, and/or hypomagnesemia), with a goal potassium of close to 5 mEq/L. Even in those with a normal QT interval, there should be a review and discontinuation of any QT-prolonging medications that may not be essential to the immediate care of the patient (eg, proton pump inhibitors, etc) ( table 1) [46]. The diagnosis and treatment of acquired long QT syndrome are discussed separately. (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes" and "Acquired long QT syndrome: Clinical manifestations, diagnosis, and management".) The following caveats and observations may be relevant to the ECG diagnosis of acquired LQTS during the COVID-19 pandemic: The best method to obtain the QT interval is with a 12-lead ECG, but to reduce exposure to staff, this may not always be feasible. A single-lead ECG may underestimate the QT interval, and there should be an attempt to use a multiple-lead telemetry system to monitor the QT interval. There is no clear guidance regarding the optimal approach to monitor outpatients with COVID-19 who are receiving QT-prolonging medications. Ambulatory ECG monitoring technologies, including the use of mobile or wearable technologies (eg, mobile cardiac outpatient telemetry), have been reported as reliable alternatives when the demand exceeds capacity for standard telemetry monitoring [47]. In one study of 100 patients during the COVID-19 pandemic, in which a single-lead ECG was recorded using a smartwatch in three different locations (left wrist, left ankle, left lateral chest wall), 94 percent of patients were able to obtain an accurate QT interval which correlated to the 12-lead ECG [48]. A specific protocol for medication-related QT prolongation monitoring in patients with COVID-19 is provided below: One protocol has been published from the Mayo Clinic, using the same QTc cutoffs as above [49]. If two to three hours after a dose of a QT-prolonging agent, the QTc increases to 500 milliseconds or if the change in QT interval is 60 milliseconds, there should be a https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 9/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate reevaluation of the risk of TdP versus benefit of the medication, and the following steps should be taken: Recognition that there is an increased risk of TdP. Discontinuation of all other QT-prolonging medications. Correction of all electrolyte abnormalities. Place the patient on continuous telemetry, with consideration of a wearable defibrillator or placement of external defibrillator patches. If TdP develops, then QT-prolonging medications should be stopped. Another protocol proposes an ECG at baseline and again at four hours after administration of QT-prolonging medication only if there is congenital or acquired long QT syndrome, patients are already taking other QT-prolonging medications, or patients have structural heart disease or bradycardia [37]. Another ECG can be completed one to three days later. For most others, an ECG or other QTc interval-monitoring method can be done 24 hours after starting the medication. If the QTc increases to 500 milliseconds, if the change in QT interval is 60 milliseconds, or if ventricular ectopy develops, this protocol recommends cardiology consultation. Brugada syndrome Because there is an increased risk of ventricular arrhythmias in the setting of fever in those with Brugada syndrome, aggressive fever reduction with acetaminophen is imperative. High-risk patients, such as those with a spontaneous type 1 pattern ECG and prior syncope, might consider going to an emergency department if they have fever that cannot be promptly lowered with acetaminophen [37]. (See "Brugada syndrome or pattern: Management and approach to screening of relatives", section on 'High-risk patients'.) IMPORTANT INFORMATION FOR PROVIDERS CARING FOR COVID-19 PATIENTS In addition to providing the best possible care for each patient, infection control to limit transmission is an essential component of care in patients with suspected or documented COVID-19 [30,50-54]. Inpatient care and consultation The approach to caring for hospitalized patients with documented or suspected COVID-19 differs slightly, with the intent to reduce exposure to (and spread of) COVID-19 to health care providers. In general, the number of persons interacting https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 10/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate directly with the patient and the time spent in the room should be minimized. Social distancing should be maintained, with both the patient and other members of the health care team. The following steps, when possible, will minimize exposure of personnel and limit the use of personal protective equipment (PPE): For stable new admissions, the patient should be seen in person by the attending physician and at most one house officer or advanced practitioner (when applicable). For stable patients on daily rounds, one person on the primary care team should enter the room to conduct the needed physical exam, with the rest of the team participating from outside the room via video chat or telephone. Routine arrhythmia consultations, particularly in stable patients with ECG evidence documenting a specific arrhythmia or conduction disorder, can be completed without entering the patient's room by reviewing the available records and ECG monitoring data. Consider placing all patients on telemetry with concerns of arrhythmias, thereby reducing the need for in-room vital signs. Utilize rooms with windows in the door to assist with monitoring patients from outside of the room. Patients can be contacted by telephone for routine matters without requiring entry into the room. Arrhythmia-related procedures In order to minimize the potential exposure of health care personnel to asymptomatic carriers of the virus, elective and nonurgent procedures in patients with symptomatic or asymptomatic infection should be postponed until a later date. A discussion of the reasoning behind the decision to postpone any procedure should be communicated to the patient and documented in the medical record. Conversely, urgent and semiurgent procedures should be performed when the perceived benefits of the procedure to the patient outweigh the risks of resource utilization and health care personnel exposure. Examples of the types of procedures in each category are as follows [30,50]: Urgent (substantial risk of decompensation, hospitalization, or death if the procedure is delayed): VT ablation for medically uncontrolled electrical storm in a hemodynamically compromised patient. Catheter ablation of incessant, hemodynamically significant, severely symptomatic tachycardia (supraventricular VT [SVT]/atrial fibrillation [AF]/atrial flutter) not responding to antiarrhythmic drugs, rate control, and/or cardioversion. https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 11/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate Catheter ablation for Wolff-Parkinson-White syndrome or preexcited AF with syncope or cardiac arrest. Lead revision for malfunction in a pacemaker-dependent patient or implantable cardioverter-defibrillator (ICD) patient receiving inappropriate therapy. Generator change in pacemaker-dependent patients who are at elective replacement indicator (ERI) or at device end of life. Pacemaker or ICD generator change with minimal battery remaining, depending on specific clinical situations. Secondary prevention ICD. Pacemaker implant for complete heart block, Mobitz II AV block, or high-grade AV block with symptoms or severe symptomatic sinus node dysfunction with long pauses. Lead/device extraction for infection, including patients not responding to antibiotics for endocarditis, bacteremia, or pocket infection. Cardiac resynchronization therapy in the setting of severe refractory heart failure in guideline-indicated patients. Cardioversion for highly symptomatic atrial arrhythmias or rapid ventricular rates not controlled with medications. Transesophageal echocardiogram for patients who need urgent cardioversion. Semiurgent (those procedures not deemed urgent but should be performed in a timely manner due to the clinical scenario): VT ablation for medically refractory recurrent VT. SVT ablation in patients with medically refractory SVT, resulting in emergency department visits. Cardiac implantable electrical device (CIED) generator replacement for ERI battery status that is not urgent. Primary prevention ICD in patients at particularly high risk of life-threating ventricular arrhythmia. Nonurgent (those procedures that may be delayed for weeks or months): https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 12/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate Premature ventricular complex ablation. SVT ablation. AF and atrial flutter ablation in stable patients without heart failure, not at significant risk of getting hospitalized by delaying the procedure, or at high risk for procedure-related complications due to comorbidities. Electrophysiology testing to evaluate stable tachyarrhythmias or bradycardia. Primary prevention ICD that is not semiurgent. Cardiac resynchronization therapy in stable patients. CIED upgrade. Pacemaker implant for sinus node dysfunction, Mobitz I AV block, other stable non-high- degree AV block, or tachy-brady syndrome in mildly symptomatic patients. Pacemaker or ICD generator replacements in patients with >6 weeks of battery remaining. Extraction of noninfected devices/leads unless device function is dependent on lead extraction and reimplant. Cardioversion for stable arrhythmias with well-tolerated symptoms. Left atrial appendage (LAA) closure in patients who can be on anticoagulation. Transesophageal echocardiogram for routine assessment of valves or LAA closure devices and cardioversions that can be done after appropriate period of anticoagulation. Implantable loop recorder implants. Tilt-table testing. Perioperative cardiac implantable electrical device management For patients with a CIED undergoing surgery or an endoscopic procedure, it is important to know if the patient is pacemaker dependent, if the patient has an ICD with therapies activated, and the likelihood of electromagnetic interference (EMI) during the procedure (eg, due to electrocautery, etc). In a patient with documented or suspected COVID-19 who is undergoing a procedure with a high likelihood of EMI that could result in pacemaker or ICD malfunction, application of a magnet may be used to suspend antitachyarrhythmia therapy in an ICD or to produce asynchronous pacing in a pacemaker [51]. This allows the patient to safely proceed with the necessary procedure without https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 13/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate reprogramming the CIED before and after the procedure, thereby reducing the risk to health care personnel and preserving PPE. The standard approach to CIED management, which includes in-person reprogramming of the CIED before and after the procedure, is discussed in detail elsewhere. (See "Perioperative management of patients with a pacemaker or implantable cardioverter-defibrillator".) Cardiac implantable electrical device interrogations For most patients, the majority of CIED follow-up device interrogations on modern-era devices can be done either in person or remotely. To maintain social distancing during the COVID-19 pandemic, we recommend remote CIED interrogations for the vast majority of stable patients [51]. Certain situations remain, however, in which an in-person CIED interrogation may be the preferred option, including [30,51]: Suspected CIED malfunction, including: Inappropriate pacemaker pacing or sensing noted on ECG or telemetry monitoring. Failure of ICD to deliver therapy during documented sustained ventricular tachyarrhythmia. Clinically actionable abnormality of CIED or suspicion of the device being at or near end of battery life, noted on remote monitoring, telemetry, or ambulatory monitoring. ICD shocks, presyncope, or syncope concerning for an arrhythmic event to perform programming changes. Untreated sustained ventricular arrhythmias in a patient with an ICD. Evaluation of symptoms suspicious for arrhythmia or abnormal device function in patients who are not enrolled in remote monitoring. Identified need for reprogramming of the CIED, or ICD patients whose device is delivering auditory or vibratory alerts. Assessment of AF in a patient with a stroke and no clear documentation of AF on ECG or telemetry monitoring. For CIED patients requiring urgent or emergent magnetic resonance imaging (MRI) scanning, consider performing a computed tomography scan instead if possible (to minimize the need for additional health care provider or device manufacturer representative contact); if not urgent, delay the MRI. https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 14/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate Patients in the emergency department (or other setting) where remote monitoring is not available. Remote monitoring should be used wherever possible, including the option of asking caregivers to bring the patient's home monitoring equipment to the hospital. After in-person CIED interrogation is performed, it is important to disinfect any parts of the programmer (eg, the programming wand and cord) that have been in contact with the patient. If available, disposable plastic wand coverings may be used to minimize contamination, and consideration should also be given to using a dedicated interrogation device in all settings with known or suspected COVID-19-positive patients. To reduce exposure of health care personnel to CIED patients, a doughnut magnet can be used as an alternative to a complete CIED interrogation or reprogramming [52]. When a hospitalized patient has a pacemaker that does not have remote monitoring capabilities, and proper function of the pacemaker is in question, temporary application of a doughnut magnet over the pacemaker is safe to quickly determine whether or not the pacemaker is capable of delivering pacing stimuli that can capture the heart. Magnet application will place the pacemaker in an asynchronous pacing mode. Depending on the manufacturer and programmed settings, this may include changes in the paced rate, which gives evidence of battery status (ie, elective replacement indicator) or whether there is pacemaker capture. In addition, demonstration of ventricular capture should provide basic reassurance that the pacemaker is functional and can avoid the need for a complete pacemaker interrogation. (See "Perioperative management of patients with a pacemaker or implantable cardioverter-defibrillator".) Patients requiring cardiopulmonary resuscitation (CPR) In general, basic life support and advanced cardiac life support for patients with COVID-19 should be administered in standard fashion, similar to patients without COVID-19, with the following exceptions ( algorithm 1 and algorithm 2) [30,53,55] (see "Adult basic life support (BLS) for health care providers" and "Adult basic life support (BLS) for health care providers", section on 'Resuscitation of patients with COVID-19'): Any personnel caring for a patient with suspected or confirmed COVID-19 should wear the appropriate PPE before entering the room: gown, gloves, eye protection, and a respirator (eg, an N95 respirator). If supply of respirators is limited, the United States Centers for Disease Control and Prevention acknowledges that facemasks are an acceptable alternative (in addition to contact precautions and eye protection), but respirators should be worn during aerosol-generating procedures, which includes intubation. The appropriate PPE should all be donned prior to interacting with the patient, even if this leads to a delay in the provision of resuscitative care [56,57]. https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 15/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate The number of people involved in the resuscitation should be kept to a minimum. This typically includes a team leader, anesthesiologist to manage the airway (if the patient is not already intubated), recorder/scribe, and persons to perform chest compressions, defibrillation, and administration of medications (often, these participants can rotate to allow for periods of rest after performing chest compressions). In COVID-19 patients who are not yet intubated at the time of cardiac arrest, early intubation should be performed by the provider most likely to achieve success on the first pass, utilizing all readily available technology (eg, video laryngoscopy) to optimize first-pass success. Chest compression can be stopped during intubation, and intubation (with a cuffed endotracheal tube) can be performed prior to the standard two minutes of chest compressions and early defibrillation as a means of controlling the potential spread of airborne droplets. If available, mechanical chest compression device may be used in place of manual

Pacemaker or ICD generator replacements in patients with >6 weeks of battery remaining. Extraction of noninfected devices/leads unless device function is dependent on lead extraction and reimplant. Cardioversion for stable arrhythmias with well-tolerated symptoms. Left atrial appendage (LAA) closure in patients who can be on anticoagulation. Transesophageal echocardiogram for routine assessment of valves or LAA closure devices and cardioversions that can be done after appropriate period of anticoagulation. Implantable loop recorder implants. Tilt-table testing. Perioperative cardiac implantable electrical device management For patients with a CIED undergoing surgery or an endoscopic procedure, it is important to know if the patient is pacemaker dependent, if the patient has an ICD with therapies activated, and the likelihood of electromagnetic interference (EMI) during the procedure (eg, due to electrocautery, etc). In a patient with documented or suspected COVID-19 who is undergoing a procedure with a high likelihood of EMI that could result in pacemaker or ICD malfunction, application of a magnet may be used to suspend antitachyarrhythmia therapy in an ICD or to produce asynchronous pacing in a pacemaker [51]. This allows the patient to safely proceed with the necessary procedure without https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 13/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate reprogramming the CIED before and after the procedure, thereby reducing the risk to health care personnel and preserving PPE. The standard approach to CIED management, which includes in-person reprogramming of the CIED before and after the procedure, is discussed in detail elsewhere. (See "Perioperative management of patients with a pacemaker or implantable cardioverter-defibrillator".) Cardiac implantable electrical device interrogations For most patients, the majority of CIED follow-up device interrogations on modern-era devices can be done either in person or remotely. To maintain social distancing during the COVID-19 pandemic, we recommend remote CIED interrogations for the vast majority of stable patients [51]. Certain situations remain, however, in which an in-person CIED interrogation may be the preferred option, including [30,51]: Suspected CIED malfunction, including: Inappropriate pacemaker pacing or sensing noted on ECG or telemetry monitoring. Failure of ICD to deliver therapy during documented sustained ventricular tachyarrhythmia. Clinically actionable abnormality of CIED or suspicion of the device being at or near end of battery life, noted on remote monitoring, telemetry, or ambulatory monitoring. ICD shocks, presyncope, or syncope concerning for an arrhythmic event to perform programming changes. Untreated sustained ventricular arrhythmias in a patient with an ICD. Evaluation of symptoms suspicious for arrhythmia or abnormal device function in patients who are not enrolled in remote monitoring. Identified need for reprogramming of the CIED, or ICD patients whose device is delivering auditory or vibratory alerts. Assessment of AF in a patient with a stroke and no clear documentation of AF on ECG or telemetry monitoring. For CIED patients requiring urgent or emergent magnetic resonance imaging (MRI) scanning, consider performing a computed tomography scan instead if possible (to minimize the need for additional health care provider or device manufacturer representative contact); if not urgent, delay the MRI. https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 14/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate Patients in the emergency department (or other setting) where remote monitoring is not available. Remote monitoring should be used wherever possible, including the option of asking caregivers to bring the patient's home monitoring equipment to the hospital. After in-person CIED interrogation is performed, it is important to disinfect any parts of the programmer (eg, the programming wand and cord) that have been in contact with the patient. If available, disposable plastic wand coverings may be used to minimize contamination, and consideration should also be given to using a dedicated interrogation device in all settings with known or suspected COVID-19-positive patients. To reduce exposure of health care personnel to CIED patients, a doughnut magnet can be used as an alternative to a complete CIED interrogation or reprogramming [52]. When a hospitalized patient has a pacemaker that does not have remote monitoring capabilities, and proper function of the pacemaker is in question, temporary application of a doughnut magnet over the pacemaker is safe to quickly determine whether or not the pacemaker is capable of delivering pacing stimuli that can capture the heart. Magnet application will place the pacemaker in an asynchronous pacing mode. Depending on the manufacturer and programmed settings, this may include changes in the paced rate, which gives evidence of battery status (ie, elective replacement indicator) or whether there is pacemaker capture. In addition, demonstration of ventricular capture should provide basic reassurance that the pacemaker is functional and can avoid the need for a complete pacemaker interrogation. (See "Perioperative management of patients with a pacemaker or implantable cardioverter-defibrillator".) Patients requiring cardiopulmonary resuscitation (CPR) In general, basic life support and advanced cardiac life support for patients with COVID-19 should be administered in standard fashion, similar to patients without COVID-19, with the following exceptions ( algorithm 1 and algorithm 2) [30,53,55] (see "Adult basic life support (BLS) for health care providers" and "Adult basic life support (BLS) for health care providers", section on 'Resuscitation of patients with COVID-19'): Any personnel caring for a patient with suspected or confirmed COVID-19 should wear the appropriate PPE before entering the room: gown, gloves, eye protection, and a respirator (eg, an N95 respirator). If supply of respirators is limited, the United States Centers for Disease Control and Prevention acknowledges that facemasks are an acceptable alternative (in addition to contact precautions and eye protection), but respirators should be worn during aerosol-generating procedures, which includes intubation. The appropriate PPE should all be donned prior to interacting with the patient, even if this leads to a delay in the provision of resuscitative care [56,57]. https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 15/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate The number of people involved in the resuscitation should be kept to a minimum. This typically includes a team leader, anesthesiologist to manage the airway (if the patient is not already intubated), recorder/scribe, and persons to perform chest compressions, defibrillation, and administration of medications (often, these participants can rotate to allow for periods of rest after performing chest compressions). In COVID-19 patients who are not yet intubated at the time of cardiac arrest, early intubation should be performed by the provider most likely to achieve success on the first pass, utilizing all readily available technology (eg, video laryngoscopy) to optimize first-pass success. Chest compression can be stopped during intubation, and intubation (with a cuffed endotracheal tube) can be performed prior to the standard two minutes of chest compressions and early defibrillation as a means of controlling the potential spread of airborne droplets. If available, mechanical chest compression device may be used in place of manual compressions for adults and adolescents who meet minimum height and weight requirements. For a critically ill patient who is already intubated and in the prone position at the time of arrest, CPR may be attempted with the patient prone by performing compressions of usual depth (ie, 5 to 6 cm) with the hands between the scapulae (over the T4-T7 vertebral bodies) [55,58]. Defibrillation may be performed with the pads in the anterior-posterior position. The patient should be turned to the supine position for resuscitation only if able to do so without equipment disconnections that may lead to aerosolization of viral particles [59]. For out-of-hospital resuscitation efforts, lay rescuers should perform chest compression- only CPR while wearing a face mask or cloth covering. When available, an automated external defibrillator should be applied and used according to the usual protocol. (See "Automated external defibrillators" and "Adult basic life support (BLS) for health care providers", section on 'Defibrillation'.) Initial treatment with antiarrhythmic medications, with the exception of IV magnesium, is not indicated for hemodynamically unstable or pulseless patients. A full discussion of the standard approaches to basic life support and advanced cardiac life support is presented separately. (See "Adult basic life support (BLS) for health care providers" and "Advanced cardiac life support (ACLS) in adults".) SOCIETY GUIDELINE LINKS https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 16/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: COVID-19 Index of guideline topics".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topic (see "Patient education: COVID-19 overview (The Basics)") Basics topic (see "Patient education: COVID-19 vaccines (The Basics)") SUMMARY AND RECOMMENDATIONS The vast majority of patients presenting with a systemic illness consistent with COVID-19 will not have symptoms or signs of arrhythmias or conduction system disease. However, patients in whom arrhythmias may be seen include patients with myocardial injury, myocardial ischemia, hypoxia, shock, electrolyte disturbances, or those receiving medications known to prolong the QT interval. (See 'Evaluation' above.) All patients in whom COVID-19 is suspected should have a baseline electrocardiogram (ECG) performed at the time of entry into the health care system. Ideally, this would be a 12-lead ECG, but a single-lead or multi-lead ECG from telemetry monitoring may be adequate in this situation to minimize staff exposure to the patient. Continuous ECG monitoring and echocardiography are not required in all patients but can be used in select situations. (See 'Cardiovascular testing' above.) https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 17/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate Patients with sustained torsades de pointes (TdP) usually become hemodynamically unstable, severely symptomatic, or pulseless and should be treated according to standard resuscitation algorithms, including cardioversion/defibrillation ( algorithm 1 and algorithm 2 and algorithm 3). Patients with TdP who are hemodynamically stable on presentation may remain stable or may become unstable rapidly and without warning. These patients should have continuous monitoring and frequent reevaluations due to the potential for rapid deterioration as long as TdP persists. (See 'Patients with polymorphic ventricular tachycardia (torsades de pointes)' above.) Patients receiving QT-prolonging medications should have a baseline QTc value obtained prior to administering the drugs. When patients are receiving any QT-prolonging medications, a dynamic discussion of the benefits and risks of these medications should be ongoing based on the baseline risk (including baseline QTc, electrolyte levels, etc), perceived or actual benefit of therapy, and development of significant QT prolongation or TdP. If the QTc subsequently increases to 500 milliseconds or if the change in QT interval is 60 milliseconds from the baseline ECG, electrolytes (notably potassium and magnesium) should be corrected to the normal range (if needed), and continuous inpatient ECG telemetry should be maintained, with additional management changes that may include dose adjustment or medication withdrawal. (See 'Patients receiving therapies that prolong the QT interval' above.) The approach to caring for hospitalized patients with documented or suspected COVID-19 differs slightly, with the intent to reduce exposure to (and spread of) COVID-19 to health care providers. In general, the number of persons interacting directly with the patient and the time spent in the room should be minimized. Social distancing should be maintained, with both the patient and other members of the health care team. (See 'Inpatient care and consultation' above and 'Arrhythmia-related procedures' above.) The approaches to cardiac implantable electrical device (CIED) interrogations and perioperative CIED management are summarized in the text. Strategies to avoid in-person device interrogations should be deployed. (See 'Cardiac implantable electrical device interrogations' above and 'Perioperative cardiac implantable electrical device management' above.) In general, basic life support and advanced cardiac life support for patients with COVID-19 should be administered in standard fashion as for patients without COVID-19. However, any personnel caring for a patient with suspected or confirmed COVID-19 should wear the appropriate personal protective equipment (including gown, gloves, eye protection, and a respirator or face mask) before entering the room, the number of people involved in the https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 18/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate resuscitation should be kept to a minimum, and early intubation should be performed for patients who are not yet intubated at the time of cardiac arrest. (See 'Patients requiring cardiopulmonary resuscitation (CPR)' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. World Health Organization. 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A need for prone position CPR guidance for intubated and non-intubated patients during the COVID-19 pandemic. Resuscitation 2020; 151:135. Topic 127551 Version 41.0 https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 23/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate GRAPHICS ACLS cardiac arrest algorithm for suspected or confirmed COVID-19 patients https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 24/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 25/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate PPE: personal protective equipment; CPR: cardiopulmonary resuscitation; IV: intravenous; IO: intraosseous. Refer to UpToDate topics on post-cardiac arrest management for additional information. Reproduced with permission. 10.1161/CIRCULATIONAHA.120.047463. Copyright 2020 American Heart Association, Inc. Graphic 127851 Version 9.0 https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 26/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate BLS healthcare provider acute cardiac arrest algorithm for suspected or confirm COVID-19 patients PPE: personal protective equipment; AED: automatic external defibrillator; CPR: cardiopulmonary resuscitatio advanced life support. Reproduced with permission. 10.1161/CIRCULATIONAHA.120.047463. Copyright 2020 American Heart Association, Inc. https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 27/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate Graphic 127846 Version 9.0 https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 28/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate Adult cardiac arrest algorithm https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 29/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 30/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate Reprinted with permission. Highlights of the 2020 American Heart Association Guidelines for CPR and ECC. Copyright 2020 American Association, Inc. Graphic 129983 Version 9.0 https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 31/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate Some reported causes and potentiators of the long QT syndrome Congenital Jervell and Lange-Nielsen syndrome (including "channelopathies") Romano-Ward syndrome Idiopathic Acquired Metabolic disorders Other factors Androgen deprivation therapy Hypokalemia Myocardial GnRH agonist/antagonist therapy ischemia or Hypomagnesemia Bilateral surgical orchiectomy infarction, Hypocalcemia Diuretic therapy via electrolyte disorders especially with Starvation particularly hypokalemia and hypomagnesemia prominent T-wave Anorexia nervosa Herbs inversions Liquid protein diets Cinchona (contains quinine), iboga Intracranial Hypothyroidism (ibogaine), licorice extract in overuse via disease electrolyte disturbances Bradyarrhythmias HIV infection Sinus node Hypothermia dysfunction Toxic exposure: AV block: Second or Organophosphate third degree insecticides Medications* High risk Adagrasib Cisaparide Lenvatinib Selpercatinib (restricted Ajmaline Levoketoconazole Sertindole availability) Amiodarone Methadone Sotalol Delamanid Arsenic trioxide Mobocertinib Terfenadine Disopyramide Astemizole Papavirine Vandetanib Dofetilide (intracoronary) Bedaquline Vernakalant Dronedarone Procainamide Bepridil Ziprasidone Haloperidol (IV) Quinidine Chlorpromazine Ibutilide Quinine Ivosidenib Moderate risk Amisulpride (oral) Droperidol Inotuzumab ozogamacin Propafenone Azithromycin Encorafenib Propofol Isoflurane Capecitabine Entrectinib Quetiapine Carbetocin Erythromycin Ribociclib https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 32/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate Certinib Escitalopram Levofloxacin Risperidone (systemic) Chloroquine Etelcalcetide Saquinavir Lofexidine Citalopram Fexinidazole Sevoflurane Meglumine Clarithromycin Flecainide Sparfloxacin antimoniate Clofazimine Floxuridine Sunitinib Midostaurin Clomipramine Fluconazole Tegafur Moxifloxacin Clozapine Fluorouracil Terbutaline Nilotinib (systemic) Crizotinib Thioridazine Olanzapine Flupentixol Dabrafenib Toremifene Ondansetrol (IV > Gabobenate Dasatinib Vemurafenib oral) dimeglumine Deslurane Voriconazole Osimertinib Gemifloxacin Domperidone Oxytocin Gilteritinib Doxepin Pazopanib Halofantrine Doxifluridine Pentamidine Haloperidol (oral) Pilsicainide Imipramine Pimozide Piperaquine Probucol Low risk Albuterol Fingolimod Mequitazine Ranolazine (due to bradycardia) Alfuzosin Fluoxetine Methotrimeprazine Relugolix Amisulpride (IV) Fluphenazine Metoclopramide (rare reports) Rilpivirine Amitriptyline Formoterol Metronidazole Romidepsin Anagrelide Foscarnet (systemic) Roxithromycin Apomorphine Fostemsavir Mifepristone Salmeterol Arformoterol Gadofosveset Mirtazapine Sertraline Artemether- Glasdegib Mizolastine lumefantrine Siponimod Goserelin Nelfinavir Asenapine Solifenacin Granisetron Norfloxacin Atomoxetine Sorafenib Hydroxychloroquine Nortriptyline Benperidol (rare reports) Sulpiride Ofloxacin (systemic) Bilastine Hydroxyzine Tacrolimus Olodaterol (systemic) Bosutinib Iloperidone Osilodrostat Tamoxifen Bromperidol Indacaterol Oxaliplatin Telavancin Buprenorphine Itraconazole Ozanimod Telithromycin Buserelin Ketoconazole (systemic) Pacritinib Teneligliptin Ciprofloxacin (Systemic) Lacidipine Paliperidone Tetrabenazine Cocaine (Topical) Lapatinib Panobinostat Trazodone Degarelix Lefamulin Pasireotide Triclabendazole https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 33/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate Desipramine Leuprolide Pefloxacin Triptorelin Deutetrabenazine Leuprolide- Periciazine Tropisetron norethindrone Dexmedetomidine** Pimavanserin Vardenafil Levalbuterol Dolasetron Pipamperone Vilanterol Levomethadone Donepezil Pitolisant Vinflunine Lithium Efavirenz Ponesimod Voclosporin Loperamide in Eliglustat Primaquine Vorinostat overdose Eribulin Promazine Zuclopenthixol Lopinavir Ezogabine Radotinib Macimorelin Mefloquine This is not a complete list of all corrected QT interval (QTc)-prolonging drugs and does not include drugs with either a minor degree or isolated association(s) with QTc prolongation that appear to be safe in most patients but may need to be avoided in patients with congenital long QT syndrome depending upon clinical circumstances. A more complete list of such drugs is available at the CredibleMeds website. For clinical use and precautions related to medications and drug interactions, refer to the UpToDate topic review of acquired long QT syndrome discussion of medications and the Lexicomp drug interactions tool. AV: atrioventricular; IV: intravenous; QTc: rate-corrected QT interval on the electrocardiogram. Classifications provided by Lexicomp according to US Food & Drug Administration guidance: Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythic Potential for Non-Antiarrhythmic Drugs Questions and Answers; Guidance for Industry US Food and Drug Administration, June 2017 (revision 2) available at: https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM [1,2] 073161.pdf with additional data from CredibleMeds QT drugs list . The use of other classification criteria may lead to some agents being classified differently by other sources. Not available in the United States. In contrast with other class III antiarrhythmic drugs, amiodarone is rarely associated with torsades de pointes; refer to accompanying text within UpToDate topic reviews of acquired long QT syndrome. Withdrawn from market in most countries due to adverse cardiovascular effects. IV amisulpride antiemetic use is associated with less QTc prolongation than the higher doses administered orally as an antipsychotic. Other cyclic antidepressants may also prolong the QT interval; refer to UpToDate clinical topic on cyclic antidepressant pharmacology, side effects, and separate UpToDate topic on tricyclic antidepressant poisoning. The "low risk" category includes drugs with limited evidence of clinically significant QTc prolongation or TdP risk; many of these drugs have label warnings regarding possible QTc effects or recommendations to avoid use or increase ECG monitoring when combined with other QTc prolonging drugs. https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 34/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate Rarely associated with significant QTc prolongation at usual doses for treatment of opioid use disorder, making buprenorphine a suitable alternative for patients with methadone-associated QTc prolongation. Refer to UpToDate clinical topic reviews. * The United States FDA labeling for the sublingual preparation of dexmedetomidine warns against use in patients at elevated risk for QTc prolongation. Both intravenous (ie, sedative) and sublingual formulations of dexmedetomidine have a low risk of QTc prolongation and have not been implicated in TdP. Over-the-counter; available without a prescription. Not associated with significant QTc prolongation in healthy persons. Refer to UpToDate clinical topic for potential adverse cardiovascular (CV) effects in patients with CV disease. Data from: 1. Lexicomp Online. Copyright 1978-2023 Lexicomp, Inc. All Rights Reserved. 2. CredibleMeds QT drugs list website sponsored by Science Foundation of the University of Arizona. Available at http://crediblemeds.org/. Graphic 57431 Version 142.0 https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 35/36 7/5/23, 10:34 AM COVID-19: Arrhythmias and conduction system disease - UpToDate Contributor Disclosures Jordan M Prutkin, MD, MHS, FHRS No relevant financial relationship(s) with ineligible companies to disclose. Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/covid-19-arrhythmias-and-conduction-system-disease/print 36/36

7/5/23, 10:35 AM Etiology of atrioventricular block - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Etiology of atrioventricular block : William H Sauer, MD : Mark S Link, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Dec 06, 2022. INTRODUCTION Atrioventricular (AV) block is defined as a delay or interruption in the transmission of an impulse from the atria to the ventricles due to an anatomical or functional impairment in the conduction system. The conduction disturbance can be transient or permanent, with conduction that is delayed, intermittent, or absent. Commonly used terminology includes: First-degree AV block Delayed conduction from the atrium to the ventricle (defined as a prolonged PR interval of >200 milliseconds) without interruption in atrial to ventricular conduction. Second-degree AV block Intermittent atrial conduction to the ventricle, often in a regular pattern (eg, 2:1, 3:2, or other pattern), which are further classified into Mobitz type I (Wenckebach) and Mobitz type II second degree AV block. Third-degree (complete AV) block No atrial impulses conduct to the ventricle. High-grade AV block Intermittent atrial conduction to the ventricle with two or more consecutive blocked P waves but without complete AV block. AV block has a variety of causes ( table 1). The various etiologies of AV block will be reviewed here. The management of the specific types of AV block is discussed separately. (See "First- degree atrioventricular block" and "Second-degree atrioventricular block: Mobitz type I (Wenckebach block)" and "Second-degree atrioventricular block: Mobitz type II" and "Third- degree (complete) atrioventricular block".) https://www.uptodate.com/contents/etiology-of-atrioventricular-block/print 1/15 7/5/23, 10:35 AM Etiology of atrioventricular block - UpToDate PHYSIOLOGIC AV BLOCK AV block can result from physiologic slowing of cardiac conduction in response to increased parasympathetic nervous system output. Enhanced vagal tone due to athletic training, sleep, pain, carotid sinus massage, or carotid sinus hypersensitivity syndrome can result in slowing of the sinus rate and/or the development of AV conduction disturbances. In general, enhanced vagal tone leads to lower degrees of AV block (ie, first degree or Mobitz type I second degree); higher degree AV block that occurs in the setting of enhanced vagal tone could suggest other pathologic contributions to AV conduction disturbance. (See "Sinus node dysfunction: Epidemiology, etiology, and natural history" and "Carotid sinus hypersensitivity and carotid sinus syndrome".) PATHOPHYSIOLOGIC AV BLOCK Fibrosis and sclerosis of the conduction system, which appears idiopathic, accounts for about one-half of cases of AV block. Conduction system fibrosis and sclerosis may be induced by several different conditions that often cannot be distinguished clinically [1]. Additionally, some degree of fibrosis and sclerosis occurs as part of the normal aging process, with the prevalence increasing progressively with age with approximately a 2:1 male:female predominance. Among a prospective cohort of more than half a million United Kingdom residents, the prevalence of conduction system disease (which included all levels of AV block, as well as bundle branch blocks) was approximately 11 per 10,000 persons under age 55 and increased to between 55 per 10,000 persons 65 years of age [2]. Idiopathic Apparently idiopathic progressive cardiac conduction defects are the most common cause of AV block, occurring in approximately 50 percent of cases. Idiopathic AV conduction abnormalities are characterized by progressive impairment of the conduction system which occurs gradually over decades: Lenegre disease The term Lenegre disease has been traditionally used to describe a progressive, fibrotic, sclerodegenerative affliction of the conduction system in younger (age <60 years) individuals. Lenegre disease is frequently associated with slow progression to complete heart block and may be hereditary. (See 'Familial disease' below.) Lev disease The term Lev disease has been used to refer to "sclerosis of the left side of the cardiac skeleton" in older patients (age >70 years old), such as that associated with calcific involvement of the aortic and mitral rings [3-5]. Lev disease is caused by fibrosis or https://www.uptodate.com/contents/etiology-of-atrioventricular-block/print 2/15 7/5/23, 10:35 AM Etiology of atrioventricular block - UpToDate calcification extending from any of the fibrous structures adjacent to the conduction system into the conduction system [4,5]. Depending upon the anatomic location of the areas of fibrosis and sclerosis, various conduction abnormalities can result: Fibrosis of the superior and basal aspect of the muscular septum is a common cause of right bundle branch block (RBBB) with left anterior fascicular block in the older adult. Involvement of the mitral ring or the central fibrous body, for example, may be the most common cause of complete heart block with a narrow QRS complex in the older adult. Aortic valve calcification, on the other hand, can invade the bundle of His, the right and/or left bundle branch as well as the left anterior fascicle. Thus, the QRS complex may be prolonged. Associated with other cardiac disease Ischemic heart disease Ischemic heart disease accounts for about 40 percent of cases of AV block [1]. Conduction can be disturbed with either chronic ischemic heart disease or during an acute myocardial infarction (MI) [6-10]. Up to 20 percent of patients with an acute MI develop some degree of AV block, with the likelihood and severity related to the area and extent of ischemia/infarction [8-10]. While restoration of perfusion in the setting of acute MI frequently leads to improved conduction, coronary revascularization in stable patients with AV block rarely if ever improves AV conduction. Intraventricular conduction disturbances (IVCDs), including bundle and fascicular blocks, also occur in 10 to 20 percent of cases of acute MI [11-17]. Left bundle branch block (LBBB) and RBBB with left anterior fascicle block are most common. (See "Conduction abnormalities after myocardial infarction".) Cardiomyopathies and myocarditis AV block can be seen in patients with cardiomyopathies, including hypertrophic obstructive cardiomyopathy and infiltrative processes such as amyloidosis and sarcoidosis, and in patients with myocarditis due to a variety of causes including rheumatic fever, Lyme disease, diphtheria, viruses, systemic lupus erythematosus, toxoplasmosis, bacterial endocarditis, and syphilis [4,5,18-29]. Patients with COVID-19-associated myocarditis have been observed to have varying degrees of AV block [30,31]. The development of AV block in myocarditis is often a poor prognostic sign. (See "Clinical manifestations and diagnosis of myocarditis in adults" and "Lyme carditis", section on 'Atrioventricular conduction abnormalities'.) https://www.uptodate.com/contents/etiology-of-atrioventricular-block/print 3/15 7/5/23, 10:35 AM Etiology of atrioventricular block - UpToDate Congenital heart disease AV block of varying degrees can be associated with a variety of congenital heart defects that result in structural abnormalities (eg, congenitally corrected transposition of the great arteries, large primum atrial septal defects, and large AV septal defects [AV canal defects]). Additionally, complete heart block may be an isolated lesion (ie, with no associated structural heart disease), most commonly associated with neonatal lupus, which results from transplacental passage of anti-Ro/SSA or anti-La/SSB antibodies from the mother. (See "Atrial arrhythmias (including AV block) in congenital heart disease", section on 'Congenital AV block' and "Congenital third-degree (complete) atrioventricular block" and "Neonatal lupus: Epidemiology, pathogenesis, clinical manifestations, and diagnosis".) Familial disease Familial AV block, characterized by a progression in the degree of AV block in association with a variable apparent site of block, may be transmitted as an autosomal dominant trait. One form of AV conduction block has been mapped to a genetic locus at chromosome 19q13 and the other to chromosome 3p21, where the cardiac sodium channel, SCN5A, is encoded [32]. Several SCN5A mutations have been associated with AV conduction block [33-39]. Some patients with hereditary AV block are identified in childhood due to the presents of bundle branch disease (ie, RBBB, LBBB, left anterior fascicular block [LAFB], or left posterior fascicular block [LPFB]), while others present in middle-age and have been called hereditary Lenegre disease [33,34,36,40]. In the latter setting, it has been proposed that haploinsufficiency combined with aging leads to a progressive decline in conduction [41]. (See 'Idiopathic' above.) Different SCN5A mutations are associated with other cardiac abnormalities including congenital long QT syndrome, the Brugada syndrome, familial sinus node dysfunction, and familial dilated cardiomyopathy with conduction defects and susceptibility to atrial fibrillation. (See "Congenital long QT syndrome: Pathophysiology and genetics" and "Sinus node dysfunction: Epidemiology, etiology, and natural history" and "Genetics of dilated cardiomyopathy" and "Brugada syndrome: Epidemiology and pathogenesis", section on 'SCN5A'.) Other genetic forms of familial AV block have been described, including a form of progressive cardiac conduction system disease mapped to a locus on chromosome 19q13 and a form associated with congenital heart disease for which a point mutation has been identified in the cardiac transcription factor CSX/NKX2-5 [40,42-47]. (See 'Associated with other cardiac disease' above.) Miscellaneous causes AV block can also occur in a variety of other disorders: Hyperkalemia, usually when the plasma potassium concentration is above 6.3 meq/L [48- 50]. (See "Clinical manifestations of hyperkalemia in adults", section on 'Conduction https://www.uptodate.com/contents/etiology-of-atrioventricular-block/print 4/15 7/5/23, 10:35 AM Etiology of atrioventricular block - UpToDate abnormalities and arrhythmias'.) Additive effects of hyperkalemia and AV blocking agents are discussed below. (See 'Medications' below.) Hyperthyroidism and hypothyroidism, myxedema, and thyrotoxic periodic paralysis [4,5,51]. (See "Cardiovascular effects of hypothyroidism", section on 'Rhythm disturbances' and "Thyrotoxic periodic paralysis", section on 'Clinical features'.) Hereditary neuromuscular heredodegenerative disease such as myotonic dystrophy, Kearns-Sayre syndrome, and Erb's dystrophy [52-54]. (See "Inherited syndromes associated with cardiac disease".) Cardiac tumors, cysts, myocardial bridging, and trauma [3-5,55-57]. (See "Cardiac tumors" and "Myocardial bridging of the coronary arteries", section on 'Clinical relevance'.) Rheumatologic disorders including dermatomyositis [3-5]. (See "Clinical manifestations of dermatomyositis and polymyositis in adults", section on 'Cardiac involvement'.) IATROGENIC AV BLOCK Iatrogenic AV block, which can result from either medications or invasive procedures, is common. As with physiologic AV block, iatrogenic AV block can occur in isolation, but can also exacerbate underlying pathophysiologic AV block. Medications A variety of drugs can impair AV conduction, resulting in AV block. The common medications which can result in AV block include: Beta blockers Non-dihydropyridine calcium channel blockers (especially verapamil and to a lesser extent diltiazem) Digoxin Adenosine Antiarrhythmic medications, commonly amiodarone but also drugs that modulate the sodium channel (eg, quinidine, procainamide, disopyramide, etc) Most patients with AV block who are taking drugs that can impair conduction probably have some degree of underlying conduction system disease, although toxicity may result from medication overdose (either intentional or as a result of decreased clearance in the setting of renal or hepatic dysfunction). The association between medications altering AV conduction and https://www.uptodate.com/contents/etiology-of-atrioventricular-block/print 5/15 7/5/23, 10:35 AM Etiology of atrioventricular block - UpToDate underlying conduction system disease was suggested by a study of 169 patients with second or third degree AV block not related to acute MI, digitalis toxicity, or vasovagal syncope [58]. Of these, 92 (54 percent) were receiving beta blockers and/or verapamil or diltiazem. Drug discontinuation resulted in resolution of AV block in 32 of 79 cases; however, AV block later recurred in the absence of therapy in 18 of these patients. In patients receiving one or more AV blockers, a syndrome involving bradycardia (sinus arrest), renal failure, AV block, shock, and hyperkalemia (BRASH), has been described. In patients with BRASH, the severity of bradycardia (caused by sinus arrest and/or AV block) may be greater than generally caused by either the dose/level of AV blocker or level of hyperkalemia alone. This syndrome is discussed further separately. (See "Sinoatrial nodal pause, arrest, and exit block", section on 'Etiology'.) A 2020 scientific statement from the American Heart Association details drugs associated with AV block [59]. Cardiac procedures AV conduction abnormalities may result from a variety of invasive cardiac procedures. Open heart surgery AV block may occur following replacement of either the aortic or mitral valve, closure of a ventricular septal defect, or other surgical procedures [5,60-65]. In many instances, this is a transient phenomenon related to periprocedural edema which resolves in the hours to days following surgery and can be managed with temporary pacing. However, surgery may result in a permanent conduction abnormality requiring a permanent pacemaker. Transcatheter aortic valve implantation (TAVI) Between 2 and 8 percent of patients who undergo percutaneous TAVI develop AV block following the procedure. Pre-existing disturbances of cardiac conduction (particularly right bundle branch block), a narrow left ventricular outflow tract, and the severity of mitral annular calcification appear to be predictors of this complication. There may also be a higher rate of heart block observed with self-expanding implanted aortic valves compared with balloon expandable versions [66,67]. (See "Transcatheter aortic valve implantation: Complications", section on 'High degree heart block'.) Catheter ablation for arrhythmias AV block is a potential complication of catheter ablation of reentrant arrhythmias when the reentrant pathway lies within or near the AV node. As an example, catheter ablation for AV nodal reentrant tachycardia typically involves areas of the atrium very close to the AV node, with a resulting 1.4 percent risk of heart https://www.uptodate.com/contents/etiology-of-atrioventricular-block/print 6/15 7/5/23, 10:35 AM Etiology of atrioventricular block - UpToDate block following this procedure [68]. (See "Overview of catheter ablation of cardiac arrhythmias", section on 'Complications'.) Transcatheter closure of VSD A variety of devices have been used to percutaneously close muscular ventricular septal defects (VSDs), both congenital and those that occur after myocardial infarction. The Amplatzer ventricular septal defect occluder, for example, completely occluded 28 of 30 VSDs in one report [69]. One patient with complete left bundle branch block after the procedure progressed to complete heart block at one year. The presumed mechanism is that the right ventricular retention disk overlaps the ventricular conduction system as it passes above or anterosuperiorly to the defect. (See "Management and prognosis of congenital ventricular septal defect in adults", section on 'Arrhythmias and AV block'.) Alcohol (ethanol) septal ablation Percutaneous transluminal alcohol (ethanol) septal ablation is an invasive septal reduction therapy for patients with hypertrophic cardiomyopathy and significant left ventricular outflow tract obstruction. This intervention consists of infarction and thinning of the proximal interventricular septum via infusion of alcohol into the first septal perforating branch of the left anterior descending coronary artery through an angioplasty catheter. Complete heart block is seen in approximately 8 to 10 percent of patients after this procedure. (See "Hypertrophic cardiomyopathy: Management of patients with outflow tract obstruction", section on 'Septal reduction therapy'.) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Heart block in adults (The Basics)") https://www.uptodate.com/contents/etiology-of-atrioventricular-block/print 7/15 7/5/23, 10:35 AM Etiology of atrioventricular block - UpToDate SUMMARY AND RECOMMENDATIONS Atrioventricular (AV) block is defined as a delay or interruption in the transmission of an impulse from the atria to the ventricles due to an anatomical or functional impairment in the conduction system. The conduction disturbance can be transient or permanent, and it can have many causes ( table 1). (See 'Introduction' above.) Fibrosis and sclerosis of the conduction system accounts for about 50 percent of cases of AV block and may be induced by several different conditions that often cannot be distinguished clinically. When fibrosis and sclerosis of the conduction system are present, they are frequently progressive and may ultimately progress to complete heart block. (See 'Idiopathic' above.) Ischemic disease accounts for about 40 percent of cases of AV block. Conduction can be disturbed with either chronic ischemic heart disease or during an acute myocardial infarction. AV block can be seen in patients with cardiomyopathies and in the setting of congenital heart disease. (See 'Associated with other cardiac disease' above.) Familial AV block, characterized by a progression in the degree of AV block in association with a variable apparent site of block, may be transmitted as an autosomal dominant trait. (See 'Familial disease' above and "Congenital third-degree (complete) atrioventricular block", section on 'Etiology'.) A variety of drugs, including beta blockers, non-dihydropyridine calcium channel blockers (especially verapamil and to a lesser extent diltiazem), digitalis, adenosine, and antiarrhythmic medications, can impair AV conduction, occasionally resulting in AV block. In most cases, the resulting AV block is at least partially reversible following withdrawal of the offending medication(s). (See 'Medications' above.) A variety of procedures performed on the heart may result in AV block, including most commonly open heart surgery, but also following transcatheter aortic valve implantation, catheter ablation of arrhythmias, transcatheter closure of a ventricular septal defect, and alcohol septal ablation. (See 'Cardiac procedures' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Leonard Ganz, MD, FHRS, FACC, who contributed to earlier versions of this topic review. https://www.uptodate.com/contents/etiology-of-atrioventricular-block/print 8/15 7/5/23, 10:35 AM Etiology of atrioventricular block - UpToDate Use of UpToDate is subject to the Terms of Use. REFERENCES 1. ZOOB M, SMITH KS. THE AETIOLOGY OF COMPLETE HEART-BLOCK. Br Med J 1963; 2:1149. 2. Khurshid S, Choi SH, Weng LC, et al. Frequency of Cardiac Rhythm Abnormalities in a Half Million Adults. Circ Arrhythm Electrophysiol 2018; 11:e006273. 3. LENEGRE J. ETIOLOGY AND PATHOLOGY OF BILATERAL BUNDLE BRANCH BLOCK IN RELATION TO COMPLETE HEART BLOCK. Prog Cardiovasc Dis 1964; 6:409. 4. LEV M. ANATOMIC BASIS FOR ATRIOVENTRICULAR BLOCK. Am J Med 1964; 37:742. 5. LEV M. THE PATHOLOGY OF COMPLETE ATRIOVENTRICULAR BLOCK. Prog Cardiovasc Dis 1964; 6:317. 6. Begg FR, Magovern GJ, Cushing WJ, et al. Selective cine coronary arteriography in patients with complete heart block. J Thorac Cardiovasc Surg 1969; 57:9. 7. Simon AB, Zloto AE. Atrioventricular block: natural history after permanent ventricular pacing. Am J Cardiol 1978; 41:500. 8. LEVINE SA, MILLER H, PENTON GB. Some clinical features of complete heart block. Circulation 1956; 13:801. 9. HEJTMANCIK MR, HERRMANN GR, SHIELDS AH, WRIGHT JC. A clinical study of complete heart block. Am Heart J 1956; 52:369. 10. ROWE JC, WHITE PD. Complete heart block: a follow-up study. Ann Intern Med 1958; 49:260. 11. Killip T 3rd, Kimball JT. Treatment of myocardial infarction in a coronary care unit. A two year experience with 250 patients. Am J Cardiol 1967; 20:457. 12. Godman MJ, Lassers BW, Julian DG. Complete bundle-branch block complicating acute myocardial infarction. N Engl J Med 1970; 282:237. 13. Sugiura T, Iwasaka T, Hasegawa T, et al. Factors associated with persistent and transient fascicular blocks in anterior wall acute myocardial infarction. Am J Cardiol 1989; 63:784. 14. Mullins CB, Atkins JM. Prognoses and management of venticular conduction blocks in acute myocardial infarction. Mod Concepts Cardiovasc Dis 1976; 45:129. 15. Hindman MC, Wagner GS, JaRo M, et al. The clinical significance of bundle branch block complicating acute myocardial infarction. 1. Clinical characteristics, hospital mortality, and one-year follow-up. Circulation 1978; 58:679. 16. Scheinman MM, Gonzalez RP. Fascicular block and acute myocardial infarction. JAMA 1980; 244:2646. https://www.uptodate.com/contents/etiology-of-atrioventricular-block/print 9/15 7/5/23, 10:35 AM Etiology of atrioventricular block - UpToDate 17. Dubois C, Pi rard LA, Smeets JP, et al. Short- and long-term prognostic importance of complete bundle-branch block complicating acute myocardial infarction. Clin Cardiol 1988; 11:292. 18. Harris A, Davies M, Redwood D, et al. Aetiology of chronic heart block. A clinico-pathological correlation in 65 cases. Br Heart J 1969; 31:206. 19. Bernstein, M . Auriculoventricular dissociation following scarlet fever: Report of a case. Am Heart J 1938; 16:582. 20. Rantz, LA, Spink, et al. Abnormalities in the electrocardiogram following hemolytic streptococcus sore throat. Arch Intern Med 1946; 77:66. 21. Lev M, Bharati S, Hoffman FG, Leight L. The conduction system in rheumatoid arthritis with complete atrioventricular block. Am Heart J 1975; 90:78. 22. CLARK NS. Complete heart block in children; report of three cases possibly attributable to measles. Arch Dis Child 1948; 23:156. 23. Rosenberg, DH . Electrocardiographic changes in epidemic parotitis (mumps). Proc Soc Exp Biol Med 1945; 58:9. 24. ENGLE MA. Recovery from complete heart block in diphtheria. Pediatrics 1949; 3:222. 25. Menon TB, Rao CK. Tuberculosis of the Myocardium Causing Complete Heart Block. Am J Pathol 1945; 21:1193. 26. SHEE JC. STOKES-ADAMS ATTACKS DUE TO TOXOPLASMA MYOCARDITIS. Br Heart J 1964; 26:151. 27. Lim CH, Toh CC, Chia BL, Low LP. Stokes-Adams attacks due to acute nonspecific myocarditis. Am Heart J 1975; 90:172. 28. Wray R, Iveson M. Complete heart block and systemic lupus erythematosus. Br Heart J 1975; 37:982. 29. Kleid JJ, Kim ES, Brand B, et al. Heart block complicating acute bacterial endocarditis. Chest 1972; 61:301. 30. Kir D, Mohan C, Sancassani R. Heart Brake: An Unusual Cardiac Manifestation of COVID-19. JACC Case Rep 2020; 2:1252. 31. Sardana M, Scheinman MM, Moss JD. Atrioventricular block after COVID-19: What is the mechanism, site of block, and treatment? Heart Rhythm 2021; 18:489. 32. Schott JJ, Alshinawi C, Kyndt F, et al. Cardiac conduction defects associate with mutations in SCN5A. Nat Genet 1999; 23:20. 33. Tan HL, Bink-Boelkens MT, Bezzina CR, et al. A sodium-channel mutation causes isolated https://www.uptodate.com/contents/etiology-of-atrioventricular-block/print 10/15 7/5/23, 10:35 AM Etiology of atrioventricular block - UpToDate cardiac conduction disease. Nature 2001; 409:1043. 34. Wang DW, Viswanathan PC, Balser JR, et al. Clinical, genetic, and biophysical characterization of SCN5A mutations associated with atrioventricular conduction block. Circulation 2002; 105:341. 35. Herfst LJ, Potet F, Bezzina CR, et al. Na+ channel mutation leading to loss of function and non-progressive cardiac conduction defects. J Mol Cell Cardiol 2003; 35:549. 36. Probst V, Kyndt F, Potet F, et al. Haploinsufficiency in combination with aging causes SCN5A- linked hereditary Len gre disease. J Am Coll Cardiol 2003; 41:643. 37. McNair WP, Ku L, Taylor MR, et al. SCN5A mutation associated with dilated cardiomyopathy, conduction disorder, and arrhythmia. Circulation 2004; 110:2163. 38. Olson TM, Michels VV, Ballew JD, et al. Sodium channel mutations and susceptibility to heart failure and atrial fibrillation. JAMA 2005; 293:447. 39. Makiyama T, Akao M, Tsuji K, et al. High risk for bradyarrhythmic complications in patients with Brugada syndrome caused by SCN5A gene mutations. J Am Coll Cardiol 2005; 46:2100. 40. https://www.ncbi.nlm.nih.gov/gtr/conditions/C1879286/ (Accessed on January 04, 2017). 41. Royer A, van Veen TA, Le Bouter S, et al. Mouse model of SCN5A-linked hereditary Len gre's disease: age-related conduction slowing and myocardial fibrosis. Circulation 2005; 111:1738. 42. Brink PA, Ferreira A, Moolman JC, et al. Gene for progressive familial heart block type I maps to chromosome 19q13. Circulation 1995; 91:1633. 43. Schott JJ, Benson DW, Basson CT, et al. Congenital heart disease caused by mutations in the transcription factor NKX2-5. Science 1998; 281:108. 44. Ikeda Y, Hiroi Y, Hosoda T, et al. Novel point mutation in the cardiac transcription factor CSX/NKX2.5 associated with congenital heart disease. Circ J 2002; 66:561. 45. Jay PY, Harris BS, Maguire CT, et al. Nkx2-5 mutation causes anatomic hypoplasia of the cardiac conduction system. J Clin Invest 2004; 113:1130. 46. Pashmforoush M, Lu JT, Chen H, et al. Nkx2-5 pathways and congenital heart disease; loss of ventricular myocyte lineage specification leads to progressive cardiomyopathy and complete heart block. Cell 2004; 117:373. 47. Gray B, Behr ER. New Insights Into the Genetic Basis of Inherited Arrhythmia Syndromes. Circ Cardiovasc Genet 2016; 9:569. 48. Arnsdorf MF, Schreiner E, Gambetta M, et al. Electrophysiological changes in the canine atrium and ventricle during progressive hyperkalaemia: electrocardiographical correlates and the in vivo validation of in vitro predictions. Cardiovasc Res 1977; 11:409. https://www.uptodate.com/contents/etiology-of-atrioventricular-block/print 11/15 7/5/23, 10:35 AM Etiology of atrioventricular block - UpToDate 49. Surawicz B. Relationship between electrocardiogram and electrolytes. Am Heart J 1967; 73:814. 50. Fisch C. Relation of electrolyte disturbances to cardiac arrhythmias. Circulation 1973; 47:408. 51. Hsu YJ, Lin YF, Chau T, et al. Electrocardiographic manifestations in patients with thyrotoxic periodic paralysis. Am J Med Sci 2003; 326:128. 52. Roberts NK, Perloff JK, Kark RA. Cardiac conduction in the Kearns-Sayre syndrome (a neuromuscular disorder associated with progressive external ophthalmoplegia and pigmentary retinopathy). Report of 2 cases and review of 17 published cases. Am J Cardiol 1979; 44:1396. 53. Sanyal SK, Johnson WW. Cardiac conduction abnormalities in children with Duchenne's progressive muscular dystrophy: electrocardiographic features and morphologic correlates. Circulation 1982; 66:853. 54. Komajda M, Frank R, Vedel J, et al. Intracardiac conduction defects in dystrophia myotonica. Electrophysiological study of 12 cases. Br Heart J 1980; 43:315. 55. James TN, Carson DJ, Marshall TK. De subitaneis mortibus. I. Fibroma compressing His bundle. Circulation 1973; 48:428. 56. den Dulk K, Brugada P, Braat S, et al. Myocardial bridging as a cause of paroxysmal atrioventricular block. J Am Coll Cardiol 1983; 1:965. 57. Rosen KM, Heller R, Ehsani A, Rahimtoola SH. Localization of site of traumatic heart block with His bundle recordings: electrophysiologic observations regarding the nature of "split" H potentials. Am J Cardiol 1972; 30:412. 58. Zeltser D, Justo D, Halkin A, et al. Drug-induced atrioventricular block: prognosis after discontinuation of the culprit drug. J Am Coll Cardiol 2004; 44:105. 59. Tisdale JE, Chung MK, Campbell KB, et al. Drug-Induced Arrhythmias: A Scientific Statement From the American Heart Association. Circulation 2020; 142:e214. 60. Sanoudos G, Reed GE. Late heart block in aortic valve replacement. J Cardiovasc Surg (Torino) 1974; 15:475. 61. Rosen KM, Mehta A, Rahimtoola SH, Miller RA. Sites of congenital and surgical heart block as defined by His bundle electrocardiography. Circulation 1971; 44:833. 62. Furman S, Young D. Cardiac pacing in children and adolescents. Am J Cardiol 1977; 39:550. 63. Hofschire PJ, Nicoloff DM, Moller JH. Postoperative complete heart block in 64 children treated with and without cardiac pacing. Am J Cardiol 1977; 39:559. https://www.uptodate.com/contents/etiology-of-atrioventricular-block/print 12/15 7/5/23, 10:35 AM Etiology of atrioventricular block - UpToDate 64. Berdajs D, Schurr UP, Wagner A, et al. Incidence and pathophysiology of atrioventricular block following mitral valve replacement and ring annuloplasty. Eur J Cardiothorac Surg 2008; 34:55. 65. Murray LE, Smith AH, Flack EC, et al. Genotypic and phenotypic predictors of complete heart block and recovery of conduction after surgical repair of congenital heart disease. Heart Rhythm 2017; 14:402. 66. Roten L, Wenaweser P, Delacr taz E, et al. Incidence and predictors of atrioventricular conduction impairment after transcatheter aortic valve implantation. Am J Cardiol 2010; 106:1473. 67. El-Sabawi B, Welle GA, Cha YM, et al. Temporal Incidence and Predictors of High-Grade Atrioventricular Block After Transcatheter Aortic Valve Replacement. J Am Heart Assoc 2021; 10:e020033. 68. Kesek M, Lindmark D, Rashid A, Jensen SM. Increased risk of late pacemaker implantation after ablation for atrioventricular nodal reentry tachycardia: A 10-year follow-up of a nationwide cohort. Heart Rhythm 2019; 16:1182. 69. Thanopoulos BD, Rigby ML. Outcome of transcatheter closure of muscular ventricular septal defects with the Amplatzer ventricular septal defect occluder. Heart 2005; 91:513. Topic 907 Version 30.0 https://www.uptodate.com/contents/etiology-of-atrioventricular-block/print 13/15 7/5/23, 10:35 AM Etiology of atrioventricular block - UpToDate GRAPHICS Major causes of atrioventricular (AV) block Physiologic and pathophysiologic Increased vagal tone Progressive cardiac conduction system disease With fibrosis and/or sclerosis (Lenegre disease) With calcification (Lev disease) Ischemic heart disease, including acute myocardial infarction Cardiomyopathy Infiltrative processes (eg, sarcoidosis, amyloidosis, hemochromatosis, malignancy, etc) Other non-ischemic cardiomyopathies (eg, idiopathic, infectious, etc) Infections (eg, viral myocarditis, Lyme carditis) Congenital AV block Related to structural congenital heart disease As part of neonatal lupus syndrome Other Hyperkalemia, severe hypo- or hyperthyroidism, trauma, degenerative neuromuscular diseases Iatrogenic Drugs Beta blockers, calcium channel blockers, digoxin, adenosine, antiarrhythmic drugs Cardiac surgery Post valvular surgery, post surgical correction of congenital heart disease Transcatheter aortic valve implantation Catheter ablation of arrhythmias Transcatheter closure of VSD Alcohol septal ablation for HCM VSD: ventricular septal defect; HCM: hypertrophic cardiomyopathy. Graphic 62885 Version 6.0 https://www.uptodate.com/contents/etiology-of-atrioventricular-block/print 14/15 7/5/23, 10:35 AM Etiology of atrioventricular block - UpToDate Contributor Disclosures William H Sauer, MD Grant/Research/Clinical Trial Support: Biosense-Webster [Catheter ablation]; Boston Scientific [Catheter ablation]. All of the relevant financial relationships listed have been mitigated. Mark S Link, MD No relevant financial relationship(s) with ineligible companies to disclose. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. 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7/5/23, 10:35 AM First-degree atrioventricular block - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. First-degree atrioventricular block : William H Sauer, MD : Mark S Link, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Oct 14, 2022. INTRODUCTION Atrioventricular (AV) block is defined as a delay or interruption in the transmission of an impulse from the atria to the ventricles due to an anatomic or functional impairment in the conduction system. The conduction disturbance can be transient or permanent, with conduction that is delayed, intermittent, or absent. Commonly used terminology includes: First-degree AV block Delayed conduction from the atrium to the ventricle (defined as a prolonged PR interval of >200 ms) without interruption in atrial to ventricular conduction. Second-degree AV block Intermittent atrial conduction to the ventricle, often in a regular pattern (eg, 2:1, 3:2), or higher degrees of block, which are further classified into Mobitz type I (Wenckebach) and Mobitz type II second-degree AV block. Third-degree (complete AV) block No atrial impulses conduct to the ventricle. High-grade AV block Intermittent atrial conduction to the ventricle with two or more consecutive blocked P waves but without complete AV block. The clinical presentation, evaluation, and management of first-degree AV block will be reviewed here. The etiology of AV block in general, and the management of other specific types of AV block, are discussed separately. (See "Etiology of atrioventricular block" and "Second-degree atrioventricular block: Mobitz type I (Wenckebach block)" and "Second-degree atrioventricular block: Mobitz type II" and "Third-degree (complete) atrioventricular block" and "Congenital third- degree (complete) atrioventricular block".) https://www.uptodate.com/contents/first-degree-atrioventricular-block/print 1/15 7/5/23, 10:35 AM First-degree atrioventricular block - UpToDate DEFINITION The PR interval, which measures conduction between the atria and the ventricles, includes atrial depolarization (the P wave) and subsequent conduction through the AV node, His bundle, bundle branches and fascicles, and terminal Purkinje fibers ( figure 1). The normal PR interval is considered to be between 120 and 200 ms (0.12 to 0.20 s) and tends to shorten with increases in heart rate due in part to rate-related shortening of action potentials. However, some apparently healthy persons have longer PR intervals, with PR intervals as long as 280 ms having been reported in 1.6 percent of healthy aviators [1]. (See "ECG tutorial: Basic principles of ECG analysis", section on 'PR interval'.) First-degree AV block, defined as a prolonged PR interval (>200 ms at resting heart rates), is not a true block but is rather delayed or slowed AV conduction. Because of this, it is more appropriate to use the term "prolonged AV conduction" rather than AV block. The conduction delay is most frequently in the AV node but may also be in the His-Purkinje system. ETIOLOGY Patients who have a slow resting heart rate, such as highly conditioned endurance athletes, may have evidence of first-degree AV block simply due to increased vagal tone and a lower resting heart rate [2]. However, prolongation of the PR interval often represents underlying cardiac pathology. A partial list of pathologic causes of first-degree AV block include the following: Underlying structural abnormalities of the node. An increase in vagal tone that causes a reduction in the rate of impulse conduction. Drugs that impair or slow nodal conduction including digoxin, beta blockers, and non- dihydropyridine calcium channel blocking agents. Myocardial infarction When seen in the setting of an anterior wall myocardial infarction, this finding usually indicates bundle and fascicular block. In comparison, an inferior wall myocardial infarction is more likely to be associated with delay in the AV node since the AV node and inferior wall are usually supplied by the right coronary artery. Infiltrative and dilated cardiomyopathies (eg, sarcoidosis). Certain muscular dystrophies. Myocarditis (eg, Lyme, viral). https://www.uptodate.com/contents/first-degree-atrioventricular-block/print 2/15 7/5/23, 10:35 AM First-degree atrioventricular block - UpToDate Lev disease and Lenegre disease. (See "Etiology of atrioventricular block", section on 'Idiopathic'.) LEVEL OF CONDUCTION DELAY First-degree AV block, or prolonged AV conduction, can occur at a variety of levels within the heart. Clinically, because first-degree AV block is most often asymptomatic and diagnosed by electrocardiogram (ECG), there is usually little clinical significance to the level of conduction delay. However, the presence of additional evidence of conduction abnormalities (eg, bundle branch block) may be an indicator of more widespread conduction disease. The levels of conduction delay associated with first-degree AV block, and potential related etiologies, includes the following: The AV node is the most common site of conduction delay in first-degree block. Conduction through the AV node is approximated quite well by the atrial-His (AH) time determined by His bundle ECG. The normal AH time is 60 to 125 ms. Over 90 percent of patients with a PR interval greater than 300 ms have slowed AV nodal conduction [3]. Among the causes of first-degree AV block with a prolonged AH interval are increased vagal tone, calcium channel blockers (which block the inward calcium current responsible for depolarization), digoxin (acting via its vagotonic action), and beta-blockers. PR interval prolongation associated with a narrow or wide P wave but a narrow QRS complex strongly implicates the AV node as the site of the conduction delay. (See "Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs", section on 'Action potential in slow response tissues'.) Atrium Myocardial disease involving the atria, such as endocardial cushion defects and Ebstein's anomaly of the tricuspid valve. AV node Increased vagal tone, calcium channel blockers (which block the inward calcium current responsible for depolarization), digoxin (acting via its vagotonic action), and beta- blockers. Bundle of His Rare, but drugs that block the sodium channels (eg, quinidine, procainamide, and disopyramide) can slow conduction in the bundle of His. Infra-Hisian conduction system (ie, bundle branches, fascicles, Purkinje system) Rare, but if conduction is equally slowed in the right and left conducting systems, there will be prolongations in the His-ventricular (HV) time and therefore in the PR interval; most https://www.uptodate.com/contents/first-degree-atrioventricular-block/print 3/15 7/5/23, 10:35 AM First-degree atrioventricular block - UpToDate commonly due to drugs that block the sodium channels (eg, quinidine, procainamide, and disopyramide). CLINICAL PRESENTATION The clinical presentation of first-degree AV block is almost universally benign and only very rarely are symptoms felt to be directly related to first-degree AV block. There are no signs or symptoms that are either sensitive or specific that are related to first-degree AV block, and first- degree AV block cannot be detected from history or physical examination alone. When marked first-degree AV block results in atrial contraction immediately following the preceding ventricular contraction, this may result in signs and symptoms similar to "pacemaker syndrome" and sometimes referred to as "pseudopacemaker syndrome." [4-6]. (See "Modes of cardiac pacing: Nomenclature and selection", section on 'Pacemaker syndrome'.) DIAGNOSIS AND EVALUATION The diagnosis of first-degree AV block is typically confirmed using ECG evidence from either a single-lead telemetry strip or a 12-lead ECG. The evaluation of all patients with first-degree AV block identified by ECG includes a thorough history, including medications and recent changes in medications, along with bloodwork (which includes serum electrolytes and thyroid-stimulating hormone [TSH]). All patients with suspected first-degree AV block should be questioned about any history of heart disease, both congenital and acquired, as well as any recent cardiac procedures or medications that could predispose to AV conduction abnormalities. There is an overlap of cardiac conduction disturbances and other cardiac diseases including infiltrative cardiomyopathies, cardiomyopathies associated with muscular dystrophy, and other dilated cardiomyopathies. Therefore, newly recognized first-degree AV block should include an assessment of patient symptoms and exam findings to exclude these rare but serious conditions. (See "Etiology of atrioventricular block".) Patients without known or suspected cardiac or systemic disease should be questioned about their level of athletic activities and fitness, as increased vagal tone in a well-conditioned athlete is a relatively common cause of sinus bradycardia and first-degree AV block. Patients without known cardiac disease should also provide a full list of medications and be questioned about any recent changes in dosing, with particular attention paid to drugs that alter AV nodal conduction (ie, beta blockers, non-dihydropyridine calcium channel blockers, digoxin, select antiarrhythmic https://www.uptodate.com/contents/first-degree-atrioventricular-block/print 4/15 7/5/23, 10:35 AM First-degree atrioventricular block - UpToDate drugs). Such patients should be questioned about other systemic diseases associated with heart block (eg, amyloidosis, sarcoidosis). Patients who live in an area with endemic Lyme disease should be questioned about any recent outdoor exposure to ticks or known tick bites. (See 'Etiology' above.) The diagnosis of first-degree AV block can only be made from an ECG in a patient whose PR interval exceeds 200 ms (or >210 ms at slow heart rates). Rarely, first-degree AV block may be seen during an invasive electrophysiology study (EPS) being performed for other indications, but in such instances the surface ECG should provide the diagnosis without the need for invasive EPS. For patients with isolated first-degree AV block, there is rarely if ever a need to determine the precise level of conduction abnormality which has resulted in first-degree AV block. However, the presence of a wide QRS complex in conjunction with prolongation of the PR interval implies that there is a significant possibility that the conduction delay is below the AV node. There are several clinical approaches to determining the site of first-degree AV block, including surface ECG hints, noninvasive evaluation in response to atropine or vagal maneuvers, and invasive EPS. Recognizing the site of AV block is clinically important because it can determine the potential need for permanent pacing, especially in a patient with syncope or other symptoms that may be due to higher levels of block not previously captured on ECG monitoring. Surface ECG The ECG is usually of limited value in indicating the site of first-degree AV block, but there may be some helpful clues. A PR interval duration of 300 ms or greater with a normal QRS complex is most often due to delay in the AV node ( waveform 1), while a PR interval of 200 to 300 ms is less specific. First-degree AV block coupled with a wide QRS complex can be due to infranodal disease ( waveform 2) [7-10]. (See 'Level of conduction delay' above.) Vagal maneuvers Increased vagal tone slows conduction in the AV node but has little effect on the infranodal conduction system. Vagal maneuvers (eg, Valsalva maneuver, carotid sinus massage, etc) tend to slow conduction in the AV node. However, this effect may be obscured because of concurrent slowing of the sinus rate, which allows more time for both the AV node and infranodal conduction systems to recover excitability and to conduct more normally. (See "Vagal maneuvers".) Atropine, a vagolytic drug, can have a variable effect on first-degree AV block depending on the level of the block. The direct vagolytic effect of atropine will enhance AV node https://www.uptodate.com/contents/first-degree-atrioventricular-block/print 5/15 7/5/23, 10:35 AM First-degree atrioventricular block - UpToDate conduction and shorten the PR interval in patients whose block is at the level of the AV node. However, atropine also increases heart rate by accelerating sinoatrial nodal output; this accelerated heart rate can encroach on the refractory period and exacerbate the AV conduction delay in persons with infranodal conduction delays. Invasive EPS Conduction through the AV node is approximated quite well by the atrial-His (AH) time determined by His bundle ECG as part of invasive electrophysiology studies (EPS). The normal AH time is 60 to 125 ms. Over 90 percent of patients with a PR interval greater than 300 ms have slowed AV nodal conduction [3]. Atrial pacing, during EPS or by means of a previously implanted pacemaker, can worsen first-degree block in patients with AV nodal conduction delay and, less commonly, infranodal conduction delay. The most common EPS finding in patients with first-degree AV block is prolongation of the AH interval. MANAGEMENT Asymptomatic patients with first-degree AV block do not require any specific therapy. A general principle in considering the use of pacemakers for AV block of any severity is whether symptoms will be relieved and/or survival prolonged. We agree with the professional society guidelines which do not recommend a pacemaker for most cases of first-degree AV block [11,12]. Prior to considering placement of a permanent pacemaker, any reversible causes of AV block (ie, ischemia, prior administration of AV nodal blocking medications) should be identified and treated (ischemia) or withdrawn (offending medications). Patients with first-degree AV block and symptoms consistent with the loss of AV synchrony, a situation referred to as "pseudopacemaker syndrome," are potential candidates for a pacemaker [11,12]. Pacemaker syndrome describes the uncomfortable awareness of one's heart beat due to atrial contraction against a closed mitral valve or when atrial contraction occurs shortly after ventricular systole with incomplete atrial filling that can occur with single-chamber ventricular pacing. Pseudopacemaker syndrome refers to a similar constellation of symptoms that can occur with first-degree AV block and other heart rhythms that have AV dissociation. There has been a case described where pseudopacemaker syndrome was effectively treated with modification of the slow pathway [5]; however, this is an extremely uncommon indication for catheter ablation. Likewise, implantation of a permanent pacemaker strictly for pseudopacemaker syndrome from first-degree AV block is exceedingly rare. Other situations in which a pacemaker may be considered include [12]: First-degree AV block with concurrent neuromuscular disease or Lamin A/C associated cardiomyopathy (eg, myotonic muscular dystrophy, Kearns-Sayre syndrome, Erb dystrophy https://www.uptodate.com/contents/first-degree-atrioventricular-block/print 6/15 7/5/23, 10:35 AM First-degree atrioventricular block - UpToDate [limb-girdle], and peroneal muscular atrophy) due to the unpredictable risk of progressive AV conduction disturbances. Patients with a wide QRS complex in conjunction with prolongation of the PR interval, which implies a significant possibility of conduction delay below the AV node. Given the unpredictability of progression to second- and third- degree heart block, we consider His bundle ECG and the use of a permanent pacemaker in patients with marked prolongation of the HV interval (>70 ms). PROGNOSIS The prognosis related to first-degree AV block remains uncertain, with mixed results reported from a variety of population-based studies. Several studies of first-degree AV block have suggested a benign prognosis, while other cohort studies have suggested an adverse prognosis related to PR prolongation [13-20]. In a 2016 meta-analysis that included 14 studies and over 400,000 patients, first-degree AV block was associated with a higher risk of mortality (risk ratio [RR] 1.2, 95% CI 1.0-1.5) as well as heart failure or left ventricular dysfunction (RR 1.4, 95% CI 1.2- 1.7) and atrial fibrillation (RR 1.5, 95% CI 1.2-1.7) but was not associated with a higher risk of cardiovascular mortality, coronary heart disease, myocardial infarction, or stroke [21]. As examples of the individual studies performed in different populations: In a prospective cohort of 10,785 Finnish persons aged 30 to 59 years who received a baseline 12-lead ECG and were followed for an average of 30 years, a baseline PR interval >200 ms was present in 222 people (2.1 percent) [18]. Compared with those with a PR interval <200 ms, individuals with first-degree AV block had no significant differences in mortality or cardiovascular morbidity. In a prospective community-based study of 7575 individuals from the Framingham Heart Study (only 2 percent with prior myocardial infarction or heart failure), a baseline PR interval 200 ms was present in 124 people (1.6 percent) [15]. Compared with those with a PR interval <200 ms, individuals with first-degree AV block were significantly more likely to develop atrial fibrillation (adjusted hazard ratio [HR] 2.1, 95% CI 1.4-3.1) or to need a permanent pacemaker (adjusted HR 2.9, 95% CI 1.8-4.6), and had a higher all-cause mortality (adjusted HR 1.4, 95% CI 1.1-1.9). In a prospective study of 938 patients with stable coronary heart disease (history of myocardial infarction, greater than 50 percent coronary stenosis by angiography, exercise- induced ischemia on stress testing, or prior revascularization) from the Heart and Soul https://www.uptodate.com/contents/first-degree-atrioventricular-block/print 7/15 7/5/23, 10:35 AM First-degree atrioventricular block - UpToDate Study, a baseline PR interval 220 ms was present in 87 people (9.3 percent) [17]. Compared with those with normal AV conduction (PR interval <220 ms), persons with first- degree AV block had a higher risk of hospitalization for heart failure (adjusted HR 2.3, 95% CI 1.5-3.7), cardiovascular mortality (adjusted HR 2.3, 95% CI 1.3-4.2), and all-cause mortality (adjusted HR 1.6, 95% CI 1.1-2.2). As such, the presence of first-degree AV block in healthy persons portends an uncertain prognosis, although there appears to be an increase in some cardiovascular risks but not others. Meanwhile, in those with underlying coronary heart disease, there appears to be a higher risk of morbidity and mortality. In nearly all patients, however, there is rarely if ever a need to provide permanent pacing for isolated first-degree AV block. (See 'Management' above.) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Bradycardia (The Basics)" and "Patient education: Heart block in adults (The Basics)") SUMMARY AND RECOMMENDATIONS Definition First-degree atrioventricular (AV) block, defined as a prolonged PR interval (>200 ms at resting heart rates), is not a true block but is rather delayed or slowed AV conduction. Because of this, it is more appropriate to use the term "prolonged AV conduction" rather than AV block. The conduction delay is most frequently in the AV node but may also be in the His-Purkinje system. (See 'Definition' above.) https://www.uptodate.com/contents/first-degree-atrioventricular-block/print 8/15 7/5/23, 10:35 AM First-degree atrioventricular block - UpToDate Etiology A variety of conditions can result in first-degree AV block, but it is most commonly seen in cases of increased vagal tone (eg, highly conditioned endurance athletes) or as a result of medications that slow AV node conduction (eg, digoxin, beta blockers, and non-dihydropyridine calcium channel blockers). (See 'Etiology' above.) Clinical presentation The clinical presentation of first-degree AV block is almost universally benign, and only very rarely are symptoms felt to be directly related to first- degree AV block. There are no signs or symptoms that are sensitive or specific for first- degree AV block, and this condition cannot be detected from history or physical examination alone. Diagnosis The diagnosis of first-degree AV block is typically confirmed using ECG evidence from either a single-lead telemetry strip or a 12-lead ECG. (See 'Clinical presentation' above.) Management Asymptomatic patients with first-degree AV block do not require any specific therapy. The rare patient with first-degree AV block and symptoms consistent with the loss of atrioventricular synchrony, a situation sometimes referred to as "pseudopacemaker syndrome," is a potential candidate for a pacemaker. Other situations in which a pacemaker may be considered for first-degree AV block due to unpredictable progression of conduction disease include patients with concurrent neuromuscular disease and patients with a wide QRS complex with suspected conduction delay below the AV node. (See 'Management' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Leonard Ganz, MD, FHRS, FACC, who contributed to earlier versions of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Graybiel, A, McFarland, et al. Analysis of the electrocardiogram obtained from 1000 young healthy aviators. Am Heart J 1944; 27:524. 2. Viitasalo MT, Kala R, Eisalo A. Ambulatory electrocardiographic recording in endurance athletes. Br Heart J 1982; 47:213. https://www.uptodate.com/contents/first-degree-atrioventricular-block/print 9/15 7/5/23, 10:35 AM First-degree atrioventricular block - UpToDate 3. Josephson ME. Clinical Cardiac Electrophysiology: Techniques and Interpretations, 2d ed, Le a & Febiger, Philadelphia 1993. 4. Barold SS. Indications for permanent cardiac pacing in first-degree AV block: class I, II, or III? Pacing Clin Electrophysiol 1996; 19:747. 5. Lader JM, Park D, Aizer A, et al. Slow pathway modification for treatment of pseudo- pacemaker syndrome due to first-degree atrioventricular block with dual atrioventricular nodal physiology. HeartRhythm Case Rep 2018; 4:98. 6. Shah R, Kumar V. Subvalvular His bundle pacing for pseudo-pacemaker syndrome and mitral regurgitation. HeartRhythm Case Rep 2018; 4:425. 7. Ranganathan N, Dhurandhar R, Phillips JH, Wigle ED. His Bundle electrogram in bundle- branch block. Circulation 1972; 45:282. 8. Rosen KM, Rahimtoola SH, Chuquimia R, et al. Electrophysiological significance of first degree atrioventricular block with intraventricular conduction disturbance. Circulation 1971; 43:491. 9. Scheinman MM, Peters RW, Modin G, et al. Prognostic value of infranodal conduction time in patients with chronic bundle branch block. Circulation 1977; 56:240. 10. Scheinman M, Brenman B. Clinical and anatomic implications of intraventricular conduction blocks in acute myocardial infarction. Circulation 1972; 46:753. 11. Brignole M, Auricchio A, Baron-Esquivias G, et al. 2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: the Task Force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Eur Heart J 2013; 34:2281. 12. Kusumoto FM, Schoenfeld MH, Barrett C, et al. 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2019; 74:e51. 13. PACKARD JM, GRAETTINGER JS, GRAYBIEL A. Analysis of the electrocardiograms obtained from 1000 young healthy aviators; ten year follow-up. Circulation 1954; 10:384. 14. Erikssen J, Otterstad JE. Natural course of a prolonged PR interval and the relation between PR and incidence of coronary heart disease. A 7-year follow-up study of 1832 apparently healthy men aged 40-59 years. Clin Cardiol 1984; 7:6. 15. Cheng S, Keyes MJ, Larson MG, et al. Long-term outcomes in individuals with prolonged PR interval or first-degree atrioventricular block. JAMA 2009; 301:2571. https://www.uptodate.com/contents/first-degree-atrioventricular-block/print 10/15 7/5/23, 10:35 AM First-degree atrioventricular block - UpToDate 16. Magnani JW, Wang N, Nelson KP, et al. Electrocardiographic PR interval and adverse outcomes in older adults: the Health, Aging, and Body Composition study. Circ Arrhythm Electrophysiol 2013; 6:84. 17. Crisel RK, Farzaneh-Far R, Na B, Whooley MA. First-degree atrioventricular block is associated with heart failure and death in persons with stable coronary artery disease: data from the Heart and Soul Study. Eur Heart J 2011; 32:1875. 18. Aro AL, Anttonen O, Kerola T, et al. Prognostic significance of prolonged PR interval in the general population. Eur Heart J 2014; 35:123. 19. Holmqvist F, Hellkamp AS, Lee KL, et al. Adverse effects of first-degree AV-block in patients with sinus node dysfunction: data from the mode selection trial. Pacing Clin Electrophysiol 2014; 37:1111. 20. Higuchi S, Minami Y, Shoda M, et al. Prognostic Implication of First-Degree Atrioventricular Block in Patients With Hypertrophic Cardiomyopathy. J Am Heart Assoc 2020; 9:e015064. 21. Kwok CS, Rashid M, Beynon R, et al. Prolonged PR interval, first-degree heart block and adverse cardiovascular outcomes: a systematic review and meta-analysis. Heart 2016; 102:672. Topic 913 Version 35.0 https://www.uptodate.com/contents/first-degree-atrioventricular-block/print 11/15 7/5/23, 10:35 AM First-degree atrioventricular block - UpToDate GRAPHICS Generation of the normal electrocardiogram Relation between cardiac depolarization, ventricular repolarization, and the appearance of the normal electrocardiogram, including the P wave, QRS complex, ST segment, and T wave. The PR interval can be prolonged by disease from the atria to the Purkinje fibers (steps 2 to 4). The SA node is not seen on the surface ECG due to its small mass; its activity is inferred from the P wave, which reflects atrial activation. SA: sinoatrial; AV: atrioventricular; ECG: electrocardiogram. Data from Arnsdorf MA in: Electrophysiology of the Heart. Electrocardiography II: Applied Theory, Part 1, American Physiological Society, Bethesda 1978. Graphic 76390 Version 5.0 https://www.uptodate.com/contents/first-degree-atrioventricular-block/print 12/15 7/5/23, 10:35 AM First-degree atrioventricular block - UpToDate Single-lead electrocardiogram (ECG) showing first degree atrioventricular (AV) block I Electrocardiogram of lead II showing normal sinus rhythm, first degree atrioventricular block with a prolonged PR interval of 0.30 seconds, and a QRS complex of normal duration. The tall P waves and P wave duration of approximately 0.12 seconds suggest concurrent right atrial enlargement. Courtesy of Morton Arnsdorf, MD. Graphic 67882 Version 5.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/first-degree-atrioventricular-block/print 13/15 7/5/23, 10:35 AM First-degree atrioventricular block - UpToDate First degree AV block II Electrocardiogram of lead II showing normal sinus rhythm, first degree atrioventricular block with a markedly prolonged PR interval of approximately 0.40 seconds, and a widened QRS complex (0.16 seconds) due to concurrent left bundle branch block. Courtesy of Morton Arnsdorf, MD. Graphic 75567 Version 3.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/first-degree-atrioventricular-block/print 14/15 7/5/23, 10:35 AM First-degree atrioventricular block - UpToDate Contributor Disclosures William H Sauer, MD Grant/Research/Clinical Trial Support: Biosense-Webster [Catheter ablation]; Boston Scientific [Catheter ablation]. All of the relevant financial relationships listed have been mitigated. Mark S Link, MD No relevant financial relationship(s) with ineligible companies to disclose. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/first-degree-atrioventricular-block/print 15/15

7/5/23, 10:35 AM Left anterior fascicular block - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Left anterior fascicular block : William H Sauer, MD : Ary L Goldberger, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Aug 15, 2022. INTRODUCTION Left anterior fascicular block (LAFB), a pattern (formerly called left anterior hemiblock) seen on the surface electrocardiogram (ECG), results when normal electrical activity in the His-Purkinje system is delayed or interrupted ( figure 1). The normal sequence of activation is altered in LAFB, with a resultant characteristic appearance on the ECG, associated with marked left axis deviation ( waveform 1). The anatomy, clinical manifestations, differential diagnosis, prognostic implications, and treatment of LAFB will be reviewed here. Additional details regarding the ECG manifestations of LAFB are discussed separately. (See "ECG tutorial: Intraventricular block", section on 'Left anterior fascicular block'.) In the discussion that follows, it is assumed that the reader understands the general concepts of cardiac vectors, asynchronous activation of the ventricles (delayed as in fascicular or bundle branch block, or early as in pre-excitation), and the effects that asynchrony has on the duration, morphology, and amplitude of the QRS complex. (See "ECG tutorial: Physiology of the conduction system" and "General principles of asynchronous activation and preexcitation".) ANATOMY AND ELECTROPHYSIOLOGY Anatomy The bundle of His divides at the juncture of the fibrous and muscular boundaries of the interventricular septum into the right and left bundle branches. The main left bundle branch penetrates the membranous portion of the interventricular septum under the aortic ring and https://www.uptodate.com/contents/left-anterior-fascicular-block/print 1/14 7/5/23, 10:35 AM Left anterior fascicular block - UpToDate then divides into several fairly discrete branches ( figure 1) [1]. There is a large amount of individual variability in the size and distribution of the left fascicles [2]. However, in most individuals, there are two main fascicles: The left anterior fascicle that crosses the left ventricular outflow tract and terminates in the Purkinje system of the anterolateral wall of the left ventricle. The left posterior fascicle that fans out extensively inferiorly and posteriorly into Purkinje fibers. In up to 65 percent of hearts, a left median (also called medial or septal) fascicle to the interventricular septum. This is found in nearly 65 percent of people and can arise from the common left bundle or from the anterior, posterior, or both fascicles. Support for the trifascicular nature of the left bundle comes from the observation in animals and humans that depolarization of the left ventricle begins in three areas corresponding to the terminal portions of the anterior, posterior, and septal fascicles [3,4]. In the normal heart, the three fascicles of the left bundle are simultaneously depolarized. Further evidence of simultaneous activation of the fascicles can be found with routine electroanatomic mapping of a structurally normal heart. (See "Invasive diagnostic cardiac electrophysiology studies", section on 'Mapping and ablation'.) Blood supply The left anterior and median fascicles are supplied either by septal branches of the left anterior descending (LAD) artery or by the atrioventricular nodal artery ( figure 2). The proximal part of the left posterior fascicle is supplied by the artery to the AV node and, at times, by septal branches of the LAD artery. The distal portion has a dual blood supply from both anterior and posterior septal perforating arteries. EPIDEMIOLOGY Estimates of the prevalence of LAFB in the general adult population range from 1 to 2.5 percent [5,6]. The incidence of LAFB increases with age and ranges from 0.2 percent in younger adults to 8.0 percent in patients older than 90 years of age [6,7]. ETIOLOGY The left anterior fascicle is often a discrete ramus that crosses the left ventricular outflow tract and can be damaged by high flow, high pressure, and turbulence as occurs with aortic valvular disease, hypertension, and cardiomyopathies. LAFB can also occur in coronary heart disease, https://www.uptodate.com/contents/left-anterior-fascicular-block/print 2/14 7/5/23, 10:35 AM Left anterior fascicular block - UpToDate Chagas disease, infiltrative and inflammatory diseases, congenital heart diseases (including tricuspid atresia, endocardial cushion defects, single ventricle, spontaneous and surgical closure of a ventricular septal defect, and other disorders), and as part of primary sclerodegenerative processes ("Len gre's and Lev's syndromes"), associated with fibrosis, and sometimes calcification of the proximal conduction system. Aortic valve surgery not uncommonly causes LAFB [8]. LAFB occurs in over 70 percent of patients with obstructive sleep apnea [9]. LAFB has been associated with significant disease in the left anterior descending (LAD) coronary artery and rarely has been induced by ischemia during exercise testing [10]. LAFB that develops during an acute inferior wall myocardial infarction may be an indicator of LAD lesions, multivessel coronary artery disease, and impaired left ventricular systolic function, and occurs more frequently in a left-dominant or balanced coronary artery system [11,12]. ELECTROCARDIOGRAPHIC FINDINGS Left anterior and posterior fascicular blocks mainly affect the direction but not the duration of the QRS complex because the conduction disturbance primarily involves the early phases of activation. (See "Left posterior fascicular block".) Definition The ECG features ( waveform 1) of isolated LAFB include [13]: Frontal plane axis between -45 and -90 (ie, marked left axis deviation) qR pattern in lead aVL QRS duration less than 120 milliseconds R-peak time in lead aVL of 45 milliseconds or more (this criterion is not used as much as other three in a clinical setting, because it is difficult to assess on standard ECGs at usual gain) These above criteria do not apply to patients with congenital heart disease in whom left axis deviation is present in infancy. ECG activation patterns The left anterior fascicle normally initiates activation in the upper part of the septum, the anterolateral left ventricular free wall, and the left anterior papillary muscle. The initial anterior paraseptal activation is absent in LAFB, while the remaining activation fronts caused by the posterior and median fascicles are normal. The net effect is a late leftward and superior vector and includes: S waves in the inferior leads, resulting in an rS pattern in II, III, and aVF. https://www.uptodate.com/contents/left-anterior-fascicular-block/print 3/14 7/5/23, 10:35 AM Left anterior fascicular block - UpToDate R waves in the leftward leads, resulting in a qR or R (depending upon the initial right or left orientation) pattern in leads I, aVL, V5, and V6. Because of the left axis deviation, the QRS complex in aVR and aVL ends in an R wave. There may also be a persistent terminal S wave in leads V5 and V6 due to the delayed activation of the high lateral wall that is normally activated by the left anterior fascicle. The S waves disappear if the precordial electrograms are recorded two interspaces higher. The terminal vectors are more superior and also to the left and posterior. The very last terminal components may be directed slightly to the right or left. There is, however, a spectrum of LAFB that probably begins in the range of what is defined as having no axis deviation, through left axis deviation (-30 to -44 ) to marked left axis deviation (-45 to -90 ) [14]. QRS duration and T waves The QRS duration in LAFB is often less than 100 milliseconds, although the World Health Organization/International Society and Federation of Cardiology Task Force allows up to 120 milliseconds or 20 milliseconds above the previous baseline [15]. The T waves are often normal, but the T wave vector may be directed anteriorly and downward. LAFB may cause the S waves to disappear in leads I, aVL, and rarely in V5 and V6, thereby obscuring the diagnosis of right bundle branch block (RBBB). At times, the ECG pattern more resembles left bundle branch block (LBBB) than RBBB, which is one of the causes of RBBB simulating LBBB. (See "Right bundle branch block".) DIFFERENTIAL DIAGNOSIS The ECG in LAFB can mimic the findings seen in a number of other conditions. These include: Previous myocardial infarction Prior myocardial infarction (MI), with resulting Q waves, may appear similar to LAFB on an ECG. (See "ECG tutorial: Myocardial ischemia and infarction", section on 'Prior Q wave myocardial infarction'.) An anteroseptal or even lateral MI may be suspected because of the QS pattern in V1 and V2 and the qR pattern in aVL. The Q waves in the precordial leads (eg, V1 and V2) are due to the inferior orientation of the initial vector. They may disappear in the precordial leads if the ECG leads are positioned one interspace lower. Small r waves in the inferior leads with the superior axis deviation may be confused with an inferior wall MI, particularly since approximately one-third of patients with an inferior infarct can reestablish small r waves in the inferior leads. There are a number of findings that help distinguish an inferior MI from LAFB. https://www.uptodate.com/contents/left-anterior-fascicular-block/print 4/14 7/5/23, 10:35 AM Left anterior fascicular block - UpToDate Persistent ST-T abnormalities suggest a prior inferior MI, while most patients with LAFB have normal T waves. Inferior MI is usually associated with Q waves. Vectorcardiography may be helpful in this setting since the vector loop in the frontal plane is counterclockwise with LAFB versus clockwise with an inferior infarct. (See "ECG tutorial: Electrical components of the ECG", section on 'Electrical fields'.) Left ventricular hypertrophy The orientation of the midtemporal vector in LAFB may mimic left ventricular hypertrophy (LVH) in leads I and aVL and, conversely, may conceal signs of LVH in the left precordial leads. Debate continues to exist about whether LAFB alone may cause relatively tall R waves in I and aVL in the absence of LVH [16]. In general, LVH does not shift the axis more leftward than -30 . However, LVH and LAFB may coexist. Clues to concomitant LVH with a QRS axis of -45 or more leftward include evidence of left atrial abnormality, prominent precordial voltage, ST-T changes consistent with LV overload (formerly called the "strain" pattern), and possibly a QRS duration of 120 milliseconds or more. (See "Left ventricular hypertrophy: Clinical findings and ECG diagnosis".) Pre-excitation Pre-excitation can occasionally produce left axis deviation. The presence of pre-excitation is indicated by a short PR interval, a delta wave, and a widened QRS complex. This pattern often has Q waves in leads II, III, and aVF and not infrequently is misdiagnosed as an inferior wall MI. (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis", section on 'Electrocardiographic findings'.) Pulmonary disease Severe chronic pulmonary disease (emphysematous type) may at times produce marked left axis deviation (approximately -90 ). Findings suggestive of emphysema include a negative P wave in aVL, slow R wave progression reflecting right ventricular dilation, and downward displacement of the diaphragm. In addition, S waves may be present in leads I, II, and III. Miscellaneous A number of conditions may alter the appearance of the ECG and present diagnostic problems, including an anatomically horizontal heart, hypertrophic cardiomyopathy, straight back syndrome [17], and some types of congenital heart disease including corrected transposition, tricuspid atresia, single ventricle, endocardial cushion malformations, and Ebstein's disease. If the S wave in standard lead II is deeper than in lead III, the diagnosis of LAFB is unlikely. Not infrequently, other diagnostic approaches, such as echocardiography, radionuclide myocardial perfusion imaging, and, with suspected pre-excitation, electrophysiologic studies, are required to clarify these issues. https://www.uptodate.com/contents/left-anterior-fascicular-block/print 5/14 7/5/23, 10:35 AM Left anterior fascicular block - UpToDate EVALUATION, TREATMENT, AND FOLLOW-UP Patients with isolated LAFB are generally asymptomatic and do not require further diagnostic evaluation for LAFB or placement of a pacemaker or any other specific therapy. Therapy should be considered only in patients with persistent bifascicular or trifascicular block or in certain other disorders (eg, neuromuscular disorders, Anderson-Fabry disease, etc). (See "Chronic bifascicular blocks".) A number of neuromuscular diseases are associated with fascicular block. These include myotonic muscular dystrophy, Kearns-Sayre syndrome, Erb s dystrophy (limb-girdle), and a peroneal muscular atrophy. These patients represent a special class and are treated more aggressively with pacemakers due to the potential for unpredictably rapid progression of conduction disease [18]. (See "Inherited syndromes associated with cardiac disease" and "Permanent cardiac pacing: Overview of devices and indications", section on 'Neuromuscular diseases'.) Patients with isolated findings of LAFB on the surface ECG do not require any specific follow-up aside from routine care. Any symptoms consistent with the development of cardiac disease (eg, coronary heart disease, heart failure [HF], atrial fibrillation [AF], etc) should immediately be evaluated. However, because LAFB is associated with a greater risk for subsequent development of AF and HF, patients should be aware of symptoms attributable to these conditions, and clinicians should consider further cardiac evaluation if there is any concerning history. (See 'Prognosis' below.) PROGNOSIS Atrial fibrillation and heart failure LAFB may be associated with heart failure (HF) and AF; however, this association may not be causal but instead due to a shared pathogenesis [19,20]. In the Cardiovascular Health Study, among 1614 persons without cardiovascular disease, 39 patients had isolated LAFB diagnosed by systematic study criteria [20]. Over 16 years of follow-up, those with LAFB had a higher risk of HF than those without LAFB (3.5 versus 1.6 per 100-person years; hazard ratio [HR] 2.4, 95% CI 1.4-4.1). Persons with LAFB also had a higher risk of AF (3.4 versus 1.8 per 100-person years; HR 1.9, 95% CI 1.1-3.2). In a separate analysis from the same study cohort including those with cardiovascular disease, LAFB was associated with a twofold increased risk of developing AF even after https://www.uptodate.com/contents/left-anterior-fascicular-block/print 6/14 7/5/23, 10:35 AM Left anterior fascicular block - UpToDate accounting for other ECG indices (eg, QTc and atrial premature complexes [HR 2.1, 95% CI 1.1-3.9]) [19]. Mortality Evidence regarding the association between LAFB and mortality is mixed [20- 22]. In the Cardiovascular Health Study described above, participants with LAFB had a somewhat increased risk of death over a median follow-up of 16 years (6.2 versus 4.5 per 100 person-years; HR 1.6, 95% CI 1.1-2.3) [20]. However, in a separate study of 358,000 primary care patients with a similar duration of follow-up, LAFB was not associated with increased mortality [21]. The latter study relied on electronic medical records (EMRs) compared with directly-read ECGs with standardized criteria to define LAFB; this may have led to misclassification of LAFB and a bias towards a null association with mortality [22]. Progressive conduction system disease In the EMR study of 358,000 primary care patients, LAFB was associated with an increased risk of third-degree heart block (HR 1.6, 95% CI 1.25-2.05) and pacemaker placement but not with right bundle branch block (RBBB; ie, development of bifascicular block) [21]. SUMMARY AND RECOMMENDATIONS Definition Left anterior fascicular block (LAFB), a pattern seen on the surface electrocardiogram (ECG), results when normal electrical activity in the His-Purkinje system is delayed or interrupted ( figure 1). The normal sequence of activation is altered in LAFB, with a resultant characteristic appearance on the ECG associated with marked left axis deviation ( waveform 1). (See 'Introduction' above.) Epidemiology Estimates of the prevalence of LAFB in the general adult population range from 1 to 2.5 percent. However, the incidence of LAFB increases with age and ranges from 0.2 percent in younger adults to 8.0 percent in patients older than 90 years of age. (See 'Epidemiology' above.) Electrocardiographic (ECG) findings Isolated LAFB has the following features ( waveform 1) on an ECG (see 'Definition' above): Frontal plane axis between -45 and -90 degrees (ie, marked left axis deviation) qR pattern in lead aVL QRS duration less than 120 milliseconds https://www.uptodate.com/contents/left-anterior-fascicular-block/print 7/14 7/5/23, 10:35 AM Left anterior fascicular block - UpToDate R-peak time in lead aVL of 45 milliseconds or more (this criteria is not used as much as other three in a clinical setting, because it is difficult to assess on standard ECGs at usual gain) Clinical implications Patients with isolated LAFB are generally asymptomatic and do not require further diagnostic evaluation for LAFB or placement of a pacemaker or any other specific therapy. Therapy should be considered only in patients with persistent bifascicular or trifascicular block patterns or in certain neuromuscular disorders. (See 'Evaluation, treatment, and follow-up' above.) Any symptoms consistent with the development of cardiac disease (eg, coronary heart disease, heart failure [HF], atrial fibrillation [AF], etc) should immediately be evaluated. (See 'Evaluation, treatment, and follow-up' above.) Prognosis In longitudinal studies with 16 years of follow-up, LAFB appears to be associated with AF, HF, and progressive conduction system disease (ie, third-degree atrioventricular block and pacemaker placement). An association with mortality is uncertain. (See 'Prognosis' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Elizari MV, Acunzo RS, Ferreiro M. Hemiblocks revisited. Circulation 2007; 115:1154. 2. Demoulin JC, Kulbertus HE. Histopathological examination of concept of left hemiblock. Br Heart J 1972; 34:807. 3. Myerburg RJ, Nilsson K, Gelband H. Physiology of canine intraventricular conduction and endocardial excitation. Circ Res 1972; 30:217. 4. Durrer D, van Dam RT, Freud GE, et al. Total excitation of the isolated human heart. Circulation 1970; 41:899. 5. Corne RA, Beamish RE, Rollwagen RL. Significance of left anterior hemiblock. Br Heart J 1978; 40:552. 6. Haataja P, Nikus K, K h nen M, et al. Prevalence of ventricular conduction blocks in the resting electrocardiogram in a general population: the Health 2000 Survey. Int J Cardiol 2013; 167:1953. 7. Kelley GP, Stellingworth MA, Broyles S, Glancy DL. Electrocardiographic findings in 888 patients > or =90 years of age. Am J Cardiol 2006; 98:1512. https://www.uptodate.com/contents/left-anterior-fascicular-block/print 8/14 7/5/23, 10:35 AM Left anterior fascicular block - UpToDate 8. Habicht JM, Scherr P, Zerkowski HR, Hoffmann A. Late conduction defects following aortic valve replacement. J Heart Valve Dis 2000; 9:629. 9. Khalil MM, Rifaie OA. Electrocardiographic changes in obstructive sleep apnoea syndrome. Respir Med 1998; 92:25. 10. Chandrashekhar Y, Kalita HC, Anand IS. Left anterior fascicular block: an ischaemic response during treadmill testing. 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Am J Cardiol 1975; 35:809. 15. Willems JL, Robles de Medina EO, Bernard R, et al. Criteria for intraventricular conduction disturbances and pre-excitation. World Health Organizational/International Society and Federation for Cardiology Task Force Ad Hoc. J Am Coll Cardiol 1985; 5:1261. 16. Ravi S, Rukshin V, Lancaster G, et al. Diagnosis of left ventricular hypertrophy in the presence of left anterior fascicular block: a reexamination of the 2009 AHA/ACCF/HRS guidelines. Ann Noninvasive Electrocardiol 2013; 18:21. 17. Wright CD. Straight Back Syndrome. Thorac Surg Clin 2017; 27:133. 18. Kusumoto FM, Schoenfeld MH, Barrett C, et al. 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2019; 74:e51. 19. Nguyen KT, Vittinghoff E, Dewland TA, et al. Electrocardiographic Predictors of Incident Atrial Fibrillation. Am J Cardiol 2016; 118:714. 20. Mandyam MC, Soliman EZ, Heckbert SR, et al. Long-term outcomes of left anterior fascicular block in the absence of overt cardiovascular disease. JAMA 2013; 309:1587. https://www.uptodate.com/contents/left-anterior-fascicular-block/print 9/14 7/5/23, 10:35 AM Left anterior fascicular block - UpToDate 21. Nyholm BC, Ghouse J, Lee CJ, et al. Fascicular heart blocks and risk of adverse cardiovascular outcomes: Results from a large primary care population. Heart Rhythm 2022; 19:252. 22. Cortigiani L, Bigi R, Gigli G, et al. Prognostic implications of intraventricular conduction defects in patients undergoing stress echocardiography for suspected coronary artery disease. Am J Med 2003; 115:12. Topic 2106 Version 26.0 https://www.uptodate.com/contents/left-anterior-fascicular-block/print 10/14 7/5/23, 10:35 AM Left anterior fascicular block - UpToDate GRAPHICS Normal conduction system Schematic representation of the normal intraventricular conduction system (His- Purkinje system). The Bundle of His divides into the left bundle branch and right bundle branch. The left bundle branch divides into anterior, posterior, and, in some cases, median fascicles. AV: atrioventricular; RA: right atrium; LA: left atrium; RV: right ventricle; LV: left ventricle. Graphic 63340 Version 6.0 https://www.uptodate.com/contents/left-anterior-fascicular-block/print 11/14 7/5/23, 10:35 AM Left anterior fascicular block - UpToDate Left anterior fascicular block Electrocardiogram showing left anterior fascicular (hemi-)block. Sinus rhythm is present with marked left axis deviation (about 50 degrees), with normal QRS duration. Note the qR complex in aVL and the rS morphologies in II, III, and aVF. Left atrial abnormality is also noted. Courtesy of Zachary D. Goldberger, MD. Graphic 138935 Version 1.0 https://www.uptodate.com/contents/left-anterior-fascicular-block/print 12/14 7/5/23, 10:35 AM Left anterior fascicular block - UpToDate Coronary artery anatomy Graphic 70956 Version 2.0 https://www.uptodate.com/contents/left-anterior-fascicular-block/print 13/14 7/5/23, 10:35 AM Left anterior fascicular block - UpToDate Contributor Disclosures William H Sauer, MD Grant/Research/Clinical Trial Support: Biosense-Webster [Catheter ablation]; Boston Scientific [Catheter ablation]. All of the relevant financial relationships listed have been mitigated. Ary L Goldberger, MD Other Financial Interest: Elsevier book royalties [Clinical electrocardiography]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/left-anterior-fascicular-block/print 14/14

7/5/23, 10:35 AM Left bundle branch block - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Left bundle branch block : William H Sauer, MD : Mark S Link, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Apr 18, 2022. INTRODUCTION Left bundle branch block (LBBB), a pattern seen on the surface electrocardiogram (ECG), results when normal electrical activity in the His-Purkinje system is interrupted ( figure 1). The normal sequence of activation is altered dramatically in LBBB, with a resultant characteristic appearance on the ECG ( waveform 1). LBBB most often occurs in patients with underlying heart disease and may be associated with progressive conducting system disease. However, LBBB can also be seen in asymptomatic patients with a structurally normal heart. The presence of LBBB complicates the diagnosis of myocardial ischemia/infarction and interferes with the interpretation of exercise testing. In patients with significant LV dysfunction, LBBB results in left ventricular dyssynchrony and may contribute to heart failure (HF). The anatomy, clinical manifestations, differential diagnosis, prognostic implications, and treatment of LBBB will be reviewed here. Additional details regarding the ECG manifestations of LBBB are discussed separately. (See "ECG tutorial: Intraventricular block", section on 'Left bundle branch block'.) ANATOMY AND ELECTROPHYSIOLOGY Anatomy The bundle of His divides at the juncture of the fibrous and muscular boundaries of the interventricular septum into the right and left bundle branches. The main left bundle branch penetrates the membranous portion of the interventricular septum under the aortic ring and https://www.uptodate.com/contents/left-bundle-branch-block/print 1/26 7/5/23, 10:35 AM Left bundle branch block - UpToDate then divides into several fairly discrete branches. The components of the left bundle branch are ( figure 1) [1-5]: A predivisional segment. An anterior fascicle that crosses the left ventricular outflow tract and terminates in the Purkinje system of the anterolateral wall of the left ventricle. A posterior fascicle that fans out extensively inferiorly and posteriorly into Purkinje fibers. In some hearts, a median fascicle to the interventricular septum. Blood supply The left anterior descending artery provides the primary blood supply for the left bundle branch, particularly for the initial portion ( figure 2). As is true for the right bundle branch, there may be some collateral flow from the right and circumflex coronary systems. Electrophysiology The main left bundle and its fascicles consist of Purkinje fibers that transmit impulses at a rate of 1 to 3 m/sec resulting in virtual simultaneous depolarization of the terminal His Purkinje system and the adjacent ventricular myocardium. Pathological studies in LBBB have suggested that the block may be proximal (particularly in diffuse myocardial disease), distal, or a combination of both [6]. The precise anatomical location of block is an important aspect for left bundle branch (LBB) pacing [7]. LBB pacing has been shown to reverse LBBB through stimulation distal to the site of block [8]. Electrophysiologic studies have revealed multiple and complicated patterns of myocardial activation, the heterogeneity of which depends upon the function or dysfunction of the distal specialized conduction system [9]. Changes in myocardial activation only affect the left ventricle in LBBB; thus, changes in the morphologic features of local electrograms can be recorded in the left, but not the right, ventricle [10]. An LV activation pattern study in patients with chronic HF and LBBB on ECG was studied in seven patients with an LV ejection fraction of less than 35 percent [11]. Three patients had preserved activation of the left bundle despite LBBB on the ECG. Four had conduction block. The remainder had homogeneous depolarization propagation within the LV. These findings suggest that there are variable patterns of LV endocardial activation, which may be important in cardiac resynchronization therapy. (See "Cardiac resynchronization therapy in heart failure: Indications and choice of system", section on 'Rationale for CRT'.) EPIDEMIOLOGY https://www.uptodate.com/contents/left-bundle-branch-block/print 2/26 7/5/23, 10:35 AM Left bundle branch block - UpToDate The prevalence of LBBB increases with age, occurring in less than 1 percent of the general population, with estimates ranging from 0.2 to 1.1 percent [12-17]. LBBB occurs infrequently in young healthy subjects [18-21]. As an example, a study of 237,000 airmen under age 30 found only 125 cases of LBBB, representing a prevalence of 0.05 percent [20]. Ninety percent of these subjects had no apparent structural heart disease, and an isolated LBBB in young males was generally benign. The increase in LBBB prevalence with age was illustrated in a prospective study of 855 Swedish males in the general population who were 50 years of age and followed for 30 years [18]. The prevalence of LBBB was 0.4 percent at age 50, 2.3 percent by age 75, and 5.7 percent by age 80. In this otherwise healthy population, there was no significant association with risk factors for or the presence of ischemic heart disease, myocardial infarction or cardiovascular deaths, suggesting that LBBB is more commonly a marker of a slowly progressive degenerative disease of the conduction system. Among 66,450 participants in the Women's Health Initiative trial, 714 had LBBB at study entry, representing a prevalence of 1.1 percent [15]. In contrast to the Swedish study, other studies have suggested an association between the new onset of LBBB and underlying advanced and/or advancing heart disease, particularly in older adults. This is illustrated in the following examples: Among 5209 persons from the Framingham Heart Study followed for 18 years, 55 subjects developed LBBB at a mean age of 62 years [22]. Patients who developed LBBB had significantly higher rates of antecedent hypertension, cardiomegaly, and coronary heart disease. Coincident with or subsequent to the onset of the LBBB, 48 percent developed clinically apparent coronary disease or HF for the first time. Over the period of follow-up, only 11 percent of those who developed LBBB remained free of cardiovascular disease compared to 50 percent in an age-matched control group without LBBB. Among 110,000 Irish subjects who underwent screening for cardiovascular disease, 112 were found to have LBBB [23]. At a mean follow-up of 9.5 years, patients with LBBB demonstrated a significantly increased prevalence of cardiovascular disease (21 versus 11 percent in patients without LBBB). The incidence of underlying cardiovascular disease is lower in younger subjects with LBBB [18,20]. However, because of the association of LBBB with the subsequent development of cardiovascular disease, even in otherwise asymptomatic patients, careful evaluation and follow- up are indicated. When LBBB is present, patients should be evaluated for hypertension, coronary disease, and other disorders that have been associated with LBBB (eg, myocarditis, valvular heart disease, cardiomyopathies) [6,24,25]. (See 'Evaluation' below.) https://www.uptodate.com/contents/left-bundle-branch-block/print 3/26 7/5/23, 10:35 AM Left bundle branch block - UpToDate ETIOLOGY Similar to the right bundle branch, conduction in the left bundle branch can be compromised by both structural and functional factors. Structural heart disease Excepting cases of acute anterior MI, LBBB is not generally the result of a single clinical entity but rather results from slowly progressive degenerative disease involving the conduction system. As such, numerous chronic conditions which contribute to myocardial fibrosis (eg, hypertension, coronary artery disease, cardiomyopathies) can contribute to the development of LBBB. LBBB may result following an acute myocardial insult such as myocardial ischemia, myocardial infarction, endocarditis with abscess formation, or myocarditis and in such circumstances is usually associated with a worse prognosis. (See 'Prognosis' below and "Conduction abnormalities after myocardial infarction" and "Complications and outcome of infective endocarditis", section on 'Perivalvular abscess' and "Clinical manifestations and diagnosis of myocarditis in adults", section on 'Electrocardiogram'.) LBBB may also develop following certain cardiac surgeries (eg, septal myectomy) or procedures (eg, transcatheter aortic valve implantation). (See "Transcatheter aortic valve implantation: Complications", section on 'High degree heart block' and "Hypertrophic cardiomyopathy: Management of patients with outflow tract obstruction", section on 'Septal reduction therapy'.) Functional LBBB LBBB may be functional, as a result of a long preceding R-R interval following by a short cycle ("rate-related bundle branch block"). Functional LBBB may be sustained if, after the initial aberration, the impulse traveling down the right bundle branch reenters the left bundle branch rendering it again refractory, and this pattern repeats for several cycles. Ventricular tachycardia may mimic LBBB, as in repetitive monomorphic ventricular tachycardia originating from the right ventricular outflow tract or in bundle branch reentrant ventricular tachycardia (see "Ventricular tachycardia in the absence of apparent structural heart disease" and "Bundle branch reentrant ventricular tachycardia"). Hyperkalemia can depress conduction in the His-Purkinje system and rarely causes LBBB [26,27]. (See "ECG tutorial: Miscellaneous diagnoses", section on 'Hyperkalemia'.) ECG FINDINGS AND DIAGNOSIS https://www.uptodate.com/contents/left-bundle-branch-block/print 4/26 7/5/23, 10:35 AM Left bundle branch block - UpToDate The abnormalities in conduction and activation of the myocardium in persons with LBBB result in two major changes: loss of normal early septal forces, and the development of large and prolonged QRS complexes in the leftward leads (I, avL, and V6). A task force from the American Heart Association, the American College of Cardiology, and the Heart Rhythm Society has defined the electrocardiographic features of LBBB. These criteria incorporate the activation forces described above and include [28]: QRS duration greater than or equal to 120 ms in adults, greater than 100 ms in children 4 to 16 years of age, and greater than 90 ms in children less than four years of age. Broad notched or slurred R wave in leads I, aVL, V5, and V6 and an occasional RS pattern in V5 and V6 attributed to displaced transition of QRS complex. Absent q waves in leads I, V5, and V6, but in the lead aVL, a narrow q wave may be present in the absence of myocardial pathology. R peak time greater than 60 ms in leads V5 and V6 but normal in leads V1, V2, and V3, when small initial r waves can be discerned in the above leads. ST and T waves usually opposite in direction to QRS complex. Sometimes positive T wave in leads with upright QRS complexes may be normal ("positive QRS-T" concordance). However, depressed ST segments and/or negative T waves in leads with negative QRS ("negative QRS-T" concordance) are generally abnormal, and may be a sign of underlying ischemia. The appearance of LBBB may change the mean QRS axis in the frontal plane to the right, to the left, or to a superior, in some cases in a rate-dependent manner. IMPACT OF LBBB ON THE ABILITY TO DIAGNOSE OTHER CONDITIONS The electrocardiographic changes in LBBB can cause diagnostic problems in a variety of clinical conditions: Ventricular hypertrophy The diagnosis of left ventricular hypertrophy (LVH) can only be established by echocardiography in the setting of LBBB since the two disorders produce similar ECG changes: https://www.uptodate.com/contents/left-bundle-branch-block/print 5/26 7/5/23, 10:35 AM Left bundle branch block - UpToDate The unmasking of left ventricular forces in LBBB (due to lack of counteracting right ventricular forces) results in increased QRS voltage in the leads used for the voltage criteria for LVH. The ST-T vectors in both LVH and LBBB are directed opposite to the QRS vector. The diagnostic issues are different in right ventricular hypertrophy (RVH). This disorder may cause the leftward directed initial vector characteristic of LBBB to shift to the right, resulting in "pseudonormalization" of the initial vector and the reappearance of q waves in I, aVL, and V6. Echocardiography can be used to determine RVH and ventricular function in this setting. (See "ECG tutorial: Chamber enlargement and hypertrophy".) Myocardial ischemia LBBB masks the ability to identify ischemia during exercise because of the associated ST and T wave abnormalities; as a result, exercise perfusion imaging or echocardiography is usually preferred when such patients are evaluated for CHD. It has been suggested that ST segment changes of 0.5 mm from baseline in leads II and AVF are predictive of ischemia in the setting of left bundle branch block [29]. However, this observation does not change the recommendation to use other exercise modalities. (See "Selecting the optimal cardiac stress test".) Acute myocardial infarction LBBB complicates and often prevents the electrocardiographic diagnosis of acute myocardial infarction. This important issue is discussed elsewhere. (See "Electrocardiographic diagnosis of myocardial infarction in the presence of bundle branch block or a paced rhythm".) DIFFERENTIAL DIAGNOSIS While LBBB has a fairly characteristic appearance on ECG, there are other conditions in which the ECG may have a similar appearance that need to be excluded prior to the diagnosis of LBBB, including other causes of prominent T wave inversions ( table 1). Incomplete LBBB Incomplete LBBB is characterized by a QRS duration of 0.10 to 0.12 sec, a diminutive or absent q in I and V6 that is frequently replaced by a slurred initial upstroke (pseudo-delta wave), a QRS morphology reminiscent of complete LBBB, a delayed intrinsicoid deflection (time from beginning of QRS to its maximal amplitude in V6), and usually increased voltage. Canine studies suggest that incomplete LBBB may be a form of left septal (median) fascicular block [30]. https://www.uptodate.com/contents/left-bundle-branch-block/print 6/26 7/5/23, 10:35 AM Left bundle branch block - UpToDate Ventricular tachycardia and accelerated idioventricular rhythm If the dominant ventricular rhythm originates from a pacemaker in the ventricle, the QRS will be widened and can have the appearance of a LBBB. However, both ventricular tachycardia (heart rate greater than 100 beats per minute) ( waveform 2) and accelerated idioventricular rhythm (heart rate between 60 and 100 beats per minute) ( waveform 3) are associated with atrioventricular (AV) dissociation, which should distinguish the rhythm from a supraventricular rhythm with aberrant conduction seen with LBBB. (See "Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation" and "ECG tutorial: Ventricular arrhythmias", section on 'Accelerated idioventricular rhythm'.) Ventricular pacing Ventricular pacing from the right ventricle typically results in a QRS complex resembling that seen with LBBB on the surface ECG. In nearly all patients, however, the presence of pacemaker spikes preceding the QRS complex differentiates a paced complex from LBBB. Ventricular preexcitation (Wolff-Parkinson-White syndrome) In some patients with manifest right-sided accessory pathways, the preexcitation pattern can mimic LBBB. In Wolff- Parkinson-White syndrome, however, the PR interval is typically short, which is generally not the case with LBBB. PROGNOSIS The prognosis in patients with LBBB is related largely to the type and severity of any concurrent underlying heart disease and to the possible presence of other conduction disturbances [17]. As an example, patients who also have type II second degree atrioventricular (AV) block or multi- fascicular block generally have more significant myocardial disease and a guarded prognosis. (See "Second-degree atrioventricular block: Mobitz type II" and "Chronic bifascicular blocks".) Asymptomatic patients LBBB appears to have a minimal effect on outcomes in younger, apparently healthy subjects, while LBBB in older individuals has been associated with an increase in mortality. Two large cohorts of younger asymptomatic persons have reported no increase in mortality in subjects with LBBB [20,23], while three other cohorts have reported increases in sudden cardiac death and overall mortality among those with LBBB [15,16,31-33]. In the cohort of 237,000 healthy young males discussed above, the presence of LBBB was not associated with cardiovascular disease or an increase in mortality [20]. Similarly, in a cohort of 110,000 subjects discussed above, the development of LBBB was associated with a higher incidence of subsequent cardiovascular disease without any https://www.uptodate.com/contents/left-bundle-branch-block/print 7/26 7/5/23, 10:35 AM Left bundle branch block - UpToDate increase in subsequent mortality [23]. In contrast, among 53,377 females without cardiovascular disease at baseline (excluding those with RBBB) who participated in the Women's Health Initiative trial, there was a significantly greater risk of death from coronary heart disease (adjusted hazard ratio [HR] 2.17, 95% CI 1.37-3.43) and a trend toward higher death from any cause (adjusted HR 1.18, 95% CI 0.90-1.55) among females with LBBB compared with no BBB [15]. In a study evaluating 202,268 subjects >40 years of age in a primary care population in Copenhagen, the presence of LBBB was associated with increased risk of myocardial infarction, HF, and pacemaker requirement in both males and females over a mean follow up of 7.8 years. In addition, LBBB was associated with an increased risk of cardiovascular death in males but not females (HR 1.80, 95% CI 1.38-2.35) [33]. Among 8527 participants in the NHANES study (87 percent White Americans, 53 percent female, 16 percent with coronary heart disease at baseline), cardiovascular mortality was significantly higher in those with LBBB at baseline (adjusted HR 2.4 compared with those without BBB, 95% CI 1.3-4.7) [16]. Similarly, in a Swedish primary prevention study that followed 7392 middle-aged males for 28 years, a higher mortality rate was demonstrated among the 46 males (0.6 percent) with LBBB [31]. Compared with males without bundle branch block, those with LBBB had significant increases in progression to high-degree AV block (adjusted HR 12.9, 95% CI 4.1 to 40.2) and all-cause mortality (adjusted HR 1.9, 95% CI 1.2 to 3.0) that was primarily due to out-of-hospital sudden death. The findings in the Swedish cohort are consistent with those seen in a cohort of 3983 asymptomatic Canadian males, 29 (0.7 percent) of whom developed LBBB during 30 years of follow-up [32]. The presence of LBBB was associated with a higher mortality and a 10-fold increase in sudden death. Patients with coronary heart disease LBBB is an independent predictor of all-cause mortality in patients with known or suspected coronary heart disease (CHD). This has been illustrated in several studies: In a review of 7073 adults referred for nuclear exercise testing, 2 percent of the subjects had LBBB [34]. After a mean follow-up of nearly seven years, those with LBBB had a greater mortality than those without LBBB (24 versus 11 percent; adjusted HR 1.5, 95% CI 1.1 to 2.0). In a post-hoc analysis of the 15,609 subjects with known CHD enrolled in the Coronary Artery Surgery Study (CASS), the presence of LBBB was associated with a more than fivefold https://www.uptodate.com/contents/left-bundle-branch-block/print 8/26 7/5/23, 10:35 AM Left bundle branch block - UpToDate increase in mortality after two years of follow-up [35]. In the Heart Outcomes Prevention Evaluation (HOPE) cohort of 9541 patients with cardiovascular disease or diabetes in the absence of HF, the presence of LBBB was associated with a significantly higher risk for major cardiovascular events, cardiovascular death, HF, sudden death, and all-cause mortality [36]. Among 12,354 females with cardiovascular disease (excluding those with RBBB) who participated in the Women's Health Initiative trial, there was a significantly greater risk of death from coronary heart disease (adjusted HR 2.92, 95% CI 2.08-4.08) and death from any cause (adjusted HR 1.43, 95% CI 1.11-1.83) among females with LBBB compared with no BBB [15]. In addition, individuals with type II diabetes mellitus and LBBB have more severe and extensive CHD and advanced left ventricular dysfunction as compared with diabetics without LBBB and in individuals with isolated LBBB [37]. Patients with acute myocardial infarction The presence of LBBB is associated with higher short-term and long-term mortality following an acute myocardial infarction (MI). In addition, the presence of LBBB in a patient presenting with chest discomfort can delay or complicate the diagnosis of acute myocardial infarction (MI). Both of these situations are discussed in greater detail elsewhere. (See "Electrocardiographic diagnosis of myocardial infarction in the presence of bundle branch block or a paced rhythm" and "Overview of the acute management of ST- elevation myocardial infarction" and "Conduction abnormalities after myocardial infarction", section on 'Bundle branch block'.) Patients with heart failure or cardiomyopathy Even in the absence of associated structural heart disease, LBBB is associated with dyssynchronous left ventricular activation, which reduces the efficiency of left ventricular contraction. The magnitude of the effect on left ventricular dyssynchrony was illustrated in a report in which 18 patients with isolated LBBB were compared with 10 normal controls [38]. Isolated LBBB was associated with dyssynchronous contraction and a significantly lower left ventricular ejection fraction than the controls (54 versus 62 percent, respectively). The adverse effect of ventricular dyssynchrony due to LBBB is more pronounced in the presence of HF, possibly even serving as a primary cause of HF [39]. Several studies have reported that LBBB is an independent risk factor for mortality in patients with HF and is associated with increased all-cause mortality and sudden death at one year [39-41]. Other studies, however, have not shown an association with LBBB and mortality over longer periods of follow-up [42,43]. https://www.uptodate.com/contents/left-bundle-branch-block/print 9/26 7/5/23, 10:35 AM Left bundle branch block - UpToDate The development of a new LBBB during treatment for dilated cardiomyopathy may be a poor prognostic sign. Among a single-center cohort of 608 patients with dilated cardiomyopathy followed for a median of 122 months, 189 patients (31 percent) had LBBB at baseline diagnosis while 47 patients (11 percent) developed a new LBBB during follow-up [43]. While there was no significant increase in mortality related to baseline LBBB status, total mortality was markedly higher among patients with new LBBB compared with patients without new LBBB (49 versus 25 percent; adjusted HR 3.2; 95% CI 1.9-5.3). Worse outcomes in heart-failure patients with LBBB may be expected due to dyssynchronous left ventricular activation [44,45]. This observation provides the rationale for the use of cardiac resynchronization therapy with biventricular pacing in patients with HF who have an intraventricular conduction delay, primarily due to LBBB. Worse outcomes, including mortality and likelihood of implantable cardioverter-defibrillator placement, have also been suggested in patients with LBBB and mildly reduced left ventricular ejection fraction (LVEF; 36 to 50 percent) who are not typically candidates for cardiac resynchronization therapy [46]. (See "Cardiac resynchronization therapy in heart failure: Indications and choice of system" and "Cardiac resynchronization therapy in heart failure: Indications and choice of system", section on 'Rationale for CRT'.) Exercise-induced LBBB Exercise-induced LBBB occurs transiently in approximately 0.5 percent of patients undergoing an exercise stress test. The prognostic value of exercise-induced LBBB was long debated. However, exercise-induced LBBB appears to be predictive of higher rates of mortality and cardiac events. In one study of 17,277 exercise stress tests, during which 70 episodes of exercise-induced LBBB occurred, death from any cause and major cardiac events were significantly more common in the group with exercise-induced LBBB [47]. (See "Exercise ECG testing: Performing the test and interpreting the ECG results", section on 'Bundle branch block'.) Painful LBBB syndrome Chest discomfort associated with the development of new LBBB in the absence of myocardial ischemia can rarely present as "painful LBBB syndrome." Clinically, painful LBBB syndrome has most commonly been reported as a "new" LBBB associated with otherwise unexplained chest pain [48]. The working hypothesis is that some patients are sensitive to the dyssynchronous ventricular contraction. This rare condition has been successfully treated with His bundle pacing and cardiac resynchronization therapy [49-51]. Patients undergoing noncardiac surgery In patients undergoing noncardiac surgery, the presence of a LBBB is not associated with an increase in postoperative cardiac complications but is associated with a nonsignificant increase in perioperative mortality as a result of non- https://www.uptodate.com/contents/left-bundle-branch-block/print 10/26 7/5/23, 10:35 AM Left bundle branch block - UpToDate cardiovascular complications [52]. (See "Evaluation of cardiac risk prior to noncardiac surgery", section on 'Initial evaluation'.) EVALUATION When LBBB is present, patients should be evaluated for hypertension, coronary disease, HF, and other disorders that have been associated with LBBB (eg, myocarditis, valvular heart disease, cardiomyopathies). In most patients, this can be accomplished with a careful history and physical examination. An assessment of LVEF, usually with echocardiography, is typically warranted [53,54]. Focused additional testing (ie, stress testing with imaging) may be indicated for a subset of patients directed by findings from the history, exam, or other data [54]. (See "Heart failure: Clinical manifestations and diagnosis in adults" and "Stress testing in patients with left bundle branch block or a paced ventricular rhythm".) TREATMENT For asymptomatic patients with an isolated LBBB and no other evidence of cardiac disease, no specific therapy is required. However, permanent pacemaker insertion is indicated for patients who develop symptomatic conduction system disturbances, such as third degree or Mobitz type II second degree AV block, which is not associated with a reversible or transient condition. Patients with LBBB and syncope felt to be cardiac in nature may also be considered for treatment with a permanent pacemaker [54]. In addition, patients with LBBB and HF with reduced LVEF are generally candidates for treatment with cardiac resynchronization therapy [53,55]. These are discussed in more detail separately. (See "Permanent cardiac pacing: Overview of devices and indications" and "Third-degree (complete) atrioventricular block" and "Second- degree atrioventricular block: Mobitz type II" and "Cardiac resynchronization therapy in heart failure: Indications and choice of system".) On rare occasions, insertion of a temporary pacemaker may be indicated for patients with LBBB. A temporary pacemaker may be considered for a patient undergoing right heart catheterization because of the potential for transient complete heart block associated with catheter manipulation. Temporary pacing is also indicated for a LBBB in association with an acute myocardial infarction, particularly when a first degree AV block is also present. The management of patients with a LBBB who have a myocardial infarction and those undergoing surgery is discussed elsewhere. (See "Temporary cardiac pacing" and "Conduction abnormalities after myocardial infarction".) https://www.uptodate.com/contents/left-bundle-branch-block/print 11/26 7/5/23, 10:35 AM Left bundle branch block - UpToDate SUMMARY AND RECOMMENDATIONS Definition Left bundle branch block (LBBB) results when normal electrical activity in the His-Purkinje system is interrupted, thereby altering the normal sequence of activation, resulting in the characteristic ECG appearance of a widened QRS complex and changes in the directional vectors of the R and S waves ( waveform 1). (See 'Introduction' above and 'ECG findings and diagnosis' above.) Anatomy The bundle of His divides at the juncture of the fibrous and muscular boundaries of the interventricular septum into the right and left bundle branches ( figure 1). The left bundle branch penetrates the membranous portion of the interventricular septum under the aortic ring and then divides into several fairly discrete branches, receiving most of its blood supply from the left anterior descending coronary artery ( figure 2). (See 'Anatomy and electrophysiology' above.) Prevalence The prevalence of LBBB, which appears to increase with age, has been estimated between 0.2 to 1.1 percent of the general population. (See 'Epidemiology' above.) Causes Various clinical conditions are associated with the development of LBBB, although LBBB most commonly results not from a single clinical entity but rather from slowly progressive degenerative disease involving the conduction system. LBBB may result following an acute myocardial insult such as myocardial ischemia, myocardial infarction, or myocarditis. In addition, LBBB may be functional as a result of a long preceding R-R interval following by a short cycle ("rate-related bundle branch block"). (See 'Etiology' above.) ECG features The ECG features of the QRS complex which define LBBB in adults include QRS duration greater than or equal to 120 ms; broad notched or slurred R wave in leads I, aVL, V5, and V6 and an occasional RS pattern in V5 and V6; absent q waves in leads I, V5, and V6; R peak time greater than 60 ms in leads V5 and V6 but normal in leads V1, V2, and V3; and ST and T waves usually opposite in direction to QRS complex ( waveform 1). (See 'ECG findings and diagnosis' above.) Impact on diagnosis of other conditions LBBB interferes with the correct ECG-based diagnoses of ventricular hypertrophy, myocardial ischemia, and acute myocardial infarction. (See 'Impact of LBBB on the ability to diagnose other conditions' above.) In patients with chest discomfort and LBBB, the diagnosis of acute myocardial ischemia or infarction may be delayed due to the challenges of interpreting the ECG changes. (See https://www.uptodate.com/contents/left-bundle-branch-block/print 12/26 7/5/23, 10:35 AM Left bundle branch block - UpToDate 'Patients with acute myocardial infarction' above.) Differential diagnosis Ventricular rhythms and ventricular pacing, conditions in which the QRS complex has a similar morphology to LBBB, need to be excluded prior to making the diagnosis of LBBB. (See 'Differential diagnosis' above.) Prognosis The prognosis in patients with LBBB is related largely to the type and severity of any concurrent underlying heart disease and to the possible presence of other conduction disturbances: Effect of age Among asymptomatic patients, LBBB appears to have minimal effect on outcomes in younger, apparently healthy subjects, while LBBB in older individuals has been associated with an increase in mortality. (See 'Asymptomatic patients' above.) With coronary artery disease LBBB is an independent predictor of all-cause mortality in patients with known or suspected coronary heart disease. The presence of LBBB is associated with higher short-term and long-term mortality following a myocardial infarction. (See 'Patients with coronary heart disease' above and 'Patients with acute myocardial infarction' above and "Overview of the acute management of ST-elevation myocardial infarction" and "Conduction abnormalities after myocardial infarction", section on 'Bundle branch block'.) With heart failure LBBB is an independent risk factor for mortality in patients with heart failure and is associated with increased all-cause mortality and sudden death at one year. (See 'Patients with heart failure or cardiomyopathy' above.) Evaluation for concurrent conditions When LBBB is present, patients should be evaluated for hypertension, coronary disease, and other disorders that have been associated with LBBB (eg, myocarditis, valvular heart disease, cardiomyopathies). In most patients, this can be accomplished with a careful history and physical examination. (See 'Evaluation' above.) Management If asymptomatic For asymptomatic patients with an isolated LBBB and no other evidence of cardiac disease, no specific therapy is required. If develop symptomatic AV block Permanent pacemaker insertion is indicated for patients with LBBB who develop symptomatic conduction system disturbances, such as third degree or type II second degree AV block, which is not associated with a reversible https://www.uptodate.com/contents/left-bundle-branch-block/print 13/26 7/5/23, 10:35 AM Left bundle branch block - UpToDate or transient condition. (See 'Treatment' above and "Permanent cardiac pacing: Overview of devices and indications".) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Tawara S. Das Reizleitungssystem des S uegetierherzens. Gustav Fischer, Jena 1906. 2. Rosenbaum M, Elizari MV, Lazzari JO. The Hemiblocks. Tampa Tracings, Tampa 1970. 3. Uhley HN. Some controversy regarding the peripheral distribution of the conduction system. Am J Cardiol 1972; 30:919. 4. Hecht HH, Kossmann CE, Childers RW, et al. Atrioventricular and intraventricular conduction. Revised nomenclature and concepts. Am J Cardiol 1973; 31:232. 5. Demoulin JC, Kulbertus HE. Histopathological examination of concept of left hemiblock. Br Heart J 1972; 34:807. 6. Davies MJ, Anderson RH, Becker AE. The Conduction System of the Heart, Butterworth, Lond on 1983. 7. Cabrera J , Porta-S nchez A, Tung R, S nchez-Quintana D. Tracking Down the Anatomy of the Left Bundle Branch to Optimize Left Bundle Branch Pacing. JACC Case Rep 2020; 2:750. 8. Su L, Wang S, Wu S, et al. Long-Term Safety and Feasibility of Left Bundle Branch Pacing in a Large Single-Center Study. Circ Arrhythm Electrophysiol 2021; 14:e009261. 9. Josephson ME. Clinical Cardiac Electrophysiology: Techniques and Interpretations, 2nd ed, L ea & Febiger, Philadelphia 1993. 10. Sarter BH, Hook BG, Callans DJ, Marchlinski FE. Effect of bundle branch block on local electrogram morphologic features: implications for arrhythmia diagnosis by stored electrogram analysis. Am Heart J 1996; 131:947. 11. Fung JW, Yu CM, Yip G, et al. Variable left ventricular activation pattern in patients with heart failure and left bundle branch block. Heart 2004; 90:17. 12. Siegman-Igra Y, Yahini JH, Goldbourt U, Neufeld HN. Intraventricular conduction disturbances: a review of prevalence, etiology, and progression for ten years within a stable https://www.uptodate.com/contents/left-bundle-branch-block/print 14/26 7/5/23, 10:35 AM Left bundle branch block - UpToDate population of Israeli adult males. Am Heart J 1978; 96:669. 13. OSTRANDER LD Jr, BRANDT RL, KJELSBERG MO, EPSTEIN FH. ELECTROCARDIOGRAPHIC FINDINGS AMONG THE ADULT POPULATION OF A TOTAL NATURAL COMMUNITY, TECUMSEH, MICHIGAN. Circulation 1965; 31:888. 14. HISS RG, LAMB LE. Electrocardiographic findings in 122,043 individuals. Circulation 1962; 25:947. 15. Zhang ZM, Rautaharju PM, Soliman EZ, et al. Mortality risk associated with bundle branch blocks and related repolarization abnormalities (from the Women's Health Initiative [WHI]). Am J Cardiol 2012; 110:1489. 16. Badheka AO, Singh V, Patel NJ, et al. QRS duration on electrocardiography and cardiovascular mortality (from the National Health and Nutrition Examination Survey-III). Am J Cardiol 2013; 112:671. 17. Tan NY, Witt CM, Oh JK, Cha YM. Left Bundle Branch Block: Current and Future Perspectives. Circ Arrhythm Electrophysiol 2020; 13:e008239. 18. Eriksson P, Hansson PO, Eriksson H, Dellborg M. Bundle-branch block in a general male population: the study of men born 1913. Circulation 1998; 98:2494. 19. Imanishi R, Seto S, Ichimaru S, et al. Prognostic significance of incident complete left bundle branch block observed over a 40-year period. Am J Cardiol 2006; 98:644. 20. Rotman M, Triebwasser JH. A clinical and follow-up study of right and left bundle branch block. Circulation 1975; 51:477. 21. LAMB LE, KABLE KD, AVERILL KH. Electrocardiographic findings in 67,375 asymptomatic subjects. V. Left bundle branch block. Am J Cardiol 1960; 6:130. 22. Schneider JF, Thomas HE Jr, Kreger BE, et al. Newly acquired left bundle-branch block: the Framingham study. Ann Intern Med 1979; 90:303. 23. Fahy GJ, Pinski SL, Miller DP, et al. Natural history of isolated bundle branch block. Am J Cardiol 1996; 77:1185. 24. Pryor R, Blount SG Jr. The clinical significance of true left axis deviation. Left intraventricular blocks. Am Heart J 1966; 72:391. 25. LEV M. ANATOMIC BASIS FOR ATRIOVENTRICULAR BLOCK. Am J Med 1964; 37:742. 26. Ohmae M, Rabkin SW. Hyperkalemia-induced bundle branch block and complete heart block. Clin Cardiol 1981; 4:43. 27. Bashour T, Hsu I, Gorfinkel HJ, et al. Atrioventricular and intraventricular conduction in hyperkalemia. Am J Cardiol 1975; 35:199. https://www.uptodate.com/contents/left-bundle-branch-block/print 15/26 7/5/23, 10:35 AM Left bundle branch block - UpToDate 28. Surawicz B, Childers R, Deal BJ, et al. AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part III: intraventricular conduction disturbances: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society. Endorsed by the International Society for Computerized Electrocardiology. J Am Coll Cardiol 2009; 53:976. 29. Ibrahim NS, Abboud G, Selvester RS, et al. Detecting exercise-induced ischemia in left bundle branch block using the electrocardiogram. Am J Cardiol 1998; 82:832. 30. Dabrowska B, Ruka M, Walczak E. The electrocardiographic diagnosis of left septal fascicular block. Eur J Cardiol 1978; 6:347. 31. Eriksson P, Wilhelmsen L, Rosengren A. Bundle-branch block in middle-aged men: risk of complications and death over 28 years. The Primary Prevention Study in G teborg, Sweden. Eur Heart J 2005; 26:2300. 32. Rabkin SW, Mathewson FA, Tate RB. Natural history of left bundle-branch block. Br Heart J 1980; 43:164. 33. Rasmussen PV, Skov MW, Ghouse J, et al. Clinical implications of electrocardiographic bundle branch block in primary care. Heart 2019; 105:1160.

of any concurrent underlying heart disease and to the possible presence of other conduction disturbances: Effect of age Among asymptomatic patients, LBBB appears to have minimal effect on outcomes in younger, apparently healthy subjects, while LBBB in older individuals has been associated with an increase in mortality. (See 'Asymptomatic patients' above.) With coronary artery disease LBBB is an independent predictor of all-cause mortality in patients with known or suspected coronary heart disease. The presence of LBBB is associated with higher short-term and long-term mortality following a myocardial infarction. (See 'Patients with coronary heart disease' above and 'Patients with acute myocardial infarction' above and "Overview of the acute management of ST-elevation myocardial infarction" and "Conduction abnormalities after myocardial infarction", section on 'Bundle branch block'.) With heart failure LBBB is an independent risk factor for mortality in patients with heart failure and is associated with increased all-cause mortality and sudden death at one year. (See 'Patients with heart failure or cardiomyopathy' above.) Evaluation for concurrent conditions When LBBB is present, patients should be evaluated for hypertension, coronary disease, and other disorders that have been associated with LBBB (eg, myocarditis, valvular heart disease, cardiomyopathies). In most patients, this can be accomplished with a careful history and physical examination. (See 'Evaluation' above.) Management If asymptomatic For asymptomatic patients with an isolated LBBB and no other evidence of cardiac disease, no specific therapy is required. If develop symptomatic AV block Permanent pacemaker insertion is indicated for patients with LBBB who develop symptomatic conduction system disturbances, such as third degree or type II second degree AV block, which is not associated with a reversible https://www.uptodate.com/contents/left-bundle-branch-block/print 13/26 7/5/23, 10:35 AM Left bundle branch block - UpToDate or transient condition. (See 'Treatment' above and "Permanent cardiac pacing: Overview of devices and indications".) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Tawara S. Das Reizleitungssystem des S uegetierherzens. Gustav Fischer, Jena 1906. 2. Rosenbaum M, Elizari MV, Lazzari JO. The Hemiblocks. Tampa Tracings, Tampa 1970. 3. Uhley HN. Some controversy regarding the peripheral distribution of the conduction system. Am J Cardiol 1972; 30:919. 4. Hecht HH, Kossmann CE, Childers RW, et al. Atrioventricular and intraventricular conduction. Revised nomenclature and concepts. Am J Cardiol 1973; 31:232. 5. Demoulin JC, Kulbertus HE. Histopathological examination of concept of left hemiblock. Br Heart J 1972; 34:807. 6. Davies MJ, Anderson RH, Becker AE. The Conduction System of the Heart, Butterworth, Lond on 1983. 7. Cabrera J , Porta-S nchez A, Tung R, S nchez-Quintana D. Tracking Down the Anatomy of the Left Bundle Branch to Optimize Left Bundle Branch Pacing. JACC Case Rep 2020; 2:750. 8. Su L, Wang S, Wu S, et al. Long-Term Safety and Feasibility of Left Bundle Branch Pacing in a Large Single-Center Study. Circ Arrhythm Electrophysiol 2021; 14:e009261. 9. Josephson ME. Clinical Cardiac Electrophysiology: Techniques and Interpretations, 2nd ed, L ea & Febiger, Philadelphia 1993. 10. Sarter BH, Hook BG, Callans DJ, Marchlinski FE. Effect of bundle branch block on local electrogram morphologic features: implications for arrhythmia diagnosis by stored electrogram analysis. Am Heart J 1996; 131:947. 11. Fung JW, Yu CM, Yip G, et al. Variable left ventricular activation pattern in patients with heart failure and left bundle branch block. Heart 2004; 90:17. 12. Siegman-Igra Y, Yahini JH, Goldbourt U, Neufeld HN. Intraventricular conduction disturbances: a review of prevalence, etiology, and progression for ten years within a stable https://www.uptodate.com/contents/left-bundle-branch-block/print 14/26 7/5/23, 10:35 AM Left bundle branch block - UpToDate population of Israeli adult males. Am Heart J 1978; 96:669. 13. OSTRANDER LD Jr, BRANDT RL, KJELSBERG MO, EPSTEIN FH. ELECTROCARDIOGRAPHIC FINDINGS AMONG THE ADULT POPULATION OF A TOTAL NATURAL COMMUNITY, TECUMSEH, MICHIGAN. Circulation 1965; 31:888. 14. HISS RG, LAMB LE. Electrocardiographic findings in 122,043 individuals. Circulation 1962; 25:947. 15. Zhang ZM, Rautaharju PM, Soliman EZ, et al. Mortality risk associated with bundle branch blocks and related repolarization abnormalities (from the Women's Health Initiative [WHI]). Am J Cardiol 2012; 110:1489. 16. Badheka AO, Singh V, Patel NJ, et al. QRS duration on electrocardiography and cardiovascular mortality (from the National Health and Nutrition Examination Survey-III). Am J Cardiol 2013; 112:671. 17. Tan NY, Witt CM, Oh JK, Cha YM. Left Bundle Branch Block: Current and Future Perspectives. Circ Arrhythm Electrophysiol 2020; 13:e008239. 18. Eriksson P, Hansson PO, Eriksson H, Dellborg M. Bundle-branch block in a general male population: the study of men born 1913. Circulation 1998; 98:2494. 19. Imanishi R, Seto S, Ichimaru S, et al. Prognostic significance of incident complete left bundle branch block observed over a 40-year period. Am J Cardiol 2006; 98:644. 20. Rotman M, Triebwasser JH. A clinical and follow-up study of right and left bundle branch block. Circulation 1975; 51:477. 21. LAMB LE, KABLE KD, AVERILL KH. Electrocardiographic findings in 67,375 asymptomatic subjects. V. Left bundle branch block. Am J Cardiol 1960; 6:130. 22. Schneider JF, Thomas HE Jr, Kreger BE, et al. Newly acquired left bundle-branch block: the Framingham study. Ann Intern Med 1979; 90:303. 23. Fahy GJ, Pinski SL, Miller DP, et al. Natural history of isolated bundle branch block. Am J Cardiol 1996; 77:1185. 24. Pryor R, Blount SG Jr. The clinical significance of true left axis deviation. Left intraventricular blocks. Am Heart J 1966; 72:391. 25. LEV M. ANATOMIC BASIS FOR ATRIOVENTRICULAR BLOCK. Am J Med 1964; 37:742. 26. Ohmae M, Rabkin SW. Hyperkalemia-induced bundle branch block and complete heart block. Clin Cardiol 1981; 4:43. 27. Bashour T, Hsu I, Gorfinkel HJ, et al. Atrioventricular and intraventricular conduction in hyperkalemia. Am J Cardiol 1975; 35:199. https://www.uptodate.com/contents/left-bundle-branch-block/print 15/26 7/5/23, 10:35 AM Left bundle branch block - UpToDate 28. Surawicz B, Childers R, Deal BJ, et al. AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part III: intraventricular conduction disturbances: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society. Endorsed by the International Society for Computerized Electrocardiology. J Am Coll Cardiol 2009; 53:976. 29. Ibrahim NS, Abboud G, Selvester RS, et al. Detecting exercise-induced ischemia in left bundle branch block using the electrocardiogram. Am J Cardiol 1998; 82:832. 30. Dabrowska B, Ruka M, Walczak E. The electrocardiographic diagnosis of left septal fascicular block. Eur J Cardiol 1978; 6:347. 31. Eriksson P, Wilhelmsen L, Rosengren A. Bundle-branch block in middle-aged men: risk of complications and death over 28 years. The Primary Prevention Study in G teborg, Sweden. Eur Heart J 2005; 26:2300. 32. Rabkin SW, Mathewson FA, Tate RB. Natural history of left bundle-branch block. Br Heart J 1980; 43:164. 33. Rasmussen PV, Skov MW, Ghouse J, et al. Clinical implications of electrocardiographic bundle branch block in primary care. Heart 2019; 105:1160. 34. Hesse B, Diaz LA, Snader CE, et al. Complete bundle branch block as an independent predictor of all-cause mortality: report of 7,073 patients referred for nuclear exercise testing. Am J Med 2001; 110:253. 35. Freedman RA, Alderman EL, Sheffield LT, et al. Bundle branch block in patients with chronic coronary artery disease: angiographic correlates and prognostic significance. J Am Coll Cardiol 1987; 10:73. 36. Sumner G, Salehian O, Yi Q, et al. The prognostic significance of bundle branch block in high-risk chronic stable vascular disease patients: a report from the HOPE trial. J Cardiovasc Electrophysiol 2009; 20:781. 37. Ozeke O, Aras D, Deveci B, et al. Comparison of presence and extent of coronary narrowing in patients with left bundle branch block without diabetes mellitus to patients with and without left bundle branch block but with diabetes mellitus. Am J Cardiol 2006; 97:857. 38. Grines CL, Bashore TM, Boudoulas H, et al. Functional abnormalities in isolated left bundle branch block. The effect of interventricular asynchrony. Circulation 1989; 79:845. 39. Huvelle E, Fay R, Alla F, et al. Left bundle branch block and mortality in patients with acute heart failure syndrome: a substudy of the EFICA cohort. Eur J Heart Fail 2010; 12:156. https://www.uptodate.com/contents/left-bundle-branch-block/print 16/26 7/5/23, 10:35 AM Left bundle branch block - UpToDate 40. Baldasseroni S, Opasich C, Gorini M, et al. Left bundle-branch block is associated with increased 1-year sudden and total mortality rate in 5517 outpatients with congestive heart failure: a report from the Italian network on congestive heart failure. Am Heart J 2002; 143:398. 41. McCullough PA, Hassan SA, Pallekonda V, et al. Bundle branch block patterns, age, renal dysfunction, and heart failure mortality. Int J Cardiol 2005; 102:303. 42. Barsheshet A, Goldenberg I, Garty M, et al. Relation of bundle branch block to long-term (four-year) mortality in hospitalized patients with systolic heart failure. Am J Cardiol 2011; 107:540. 43. Aleksova A, Carriere C, Zecchin M, et al. New-onset left bundle branch block independently predicts long-term mortality in patients with idiopathic dilated cardiomyopathy: data from the Trieste Heart Muscle Disease Registry. Europace 2014; 16:1450. 44. Auricchio A, Fantoni C, Regoli F, et al. Characterization of left ventricular activation in patients with heart failure and left bundle-branch block. Circulation 2004; 109:1133. 45. Das MK, Cheriparambil K, Bedi A, et al. Prolonged QRS duration (QRS >/=170 ms) and left axis deviation in the presence of left bundle branch block: A marker of poor left ventricular systolic function? Am Heart J 2001; 142:756. 46. Witt CM, Wu G, Yang D, et al. Outcomes With Left Bundle Branch Block and Mildly to Moderately Reduced Left Ventricular Function. JACC Heart Fail 2016; 4:897. 47. Grady TA, Chiu AC, Snader CE, et al. Prognostic significance of exercise-induced left bundle- branch block. JAMA 1998; 279:153. 48. Shvilkin A, Ellis ER, Gervino EV, et al. Painful left bundle branch block syndrome: Clinical and electrocardiographic features and further directions for evaluation and treatment. Heart Rhythm 2016; 13:226. 49. Prystowsky EN, Padanilam BJ. Cardiac resynchronization therapy reverses severe dyspnea associated with acceleration-dependent left bundle branch block in a patient with structurally normal heart. J Cardiovasc Electrophysiol 2019; 30:517. 50. Suryanarayana PG, Frankel DS, Marchlinski FE, Schaller RD. Painful left bundle branch block [corrected] syndrome treated successfully with permanent His bundle pacing. HeartRhythm Case Rep 2018; 4:439. 51. Viles-Gonzalez JF, Mahata I, Anter E, d'Avila A. Painful left bundle branch block syndrome treated with his bundle pacing. J Electrocardiol 2018; 51:1019. 52. Dorman T, Breslow MJ, Pronovost PJ, et al. Bundle-branch block as a risk factor in noncardiac surgery. Arch Intern Med 2000; 160:1149. https://www.uptodate.com/contents/left-bundle-branch-block/print 17/26 7/5/23, 10:35 AM Left bundle branch block - UpToDate 53. Moss AJ, Hall WJ, Cannom DS, et al. Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med 2009; 361:1329. 54. Kusumoto FM, Schoenfeld MH, Barrett C, et al. 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2019; 74:e51. 55. Tang AS, Wells GA, Talajic M, et al. Cardiac-resynchronization therapy for mild-to-moderate heart failure. N Engl J Med 2010; 363:2385. Topic 914 Version 36.0 https://www.uptodate.com/contents/left-bundle-branch-block/print 18/26 7/5/23, 10:35 AM Left bundle branch block - UpToDate GRAPHICS Normal conduction system Schematic representation of the normal intraventricular conduction system (His- Purkinje system). The Bundle of His divides into the left bundle branch and right bundle branch. The left bundle branch divides into anterior, posterior, and, in some cases, median fascicles. AV: atrioventricular; RA: right atrium; LA: left atrium; RV: right ventricle; LV: left ventricle. Graphic 63340 Version 6.0 https://www.uptodate.com/contents/left-bundle-branch-block/print 19/26 7/5/23, 10:35 AM Left bundle branch block - UpToDate 12-lead electrocardiogram (ECG) showing typical left bundle branch block Electrocardiogram in typical complete left bundle branch block. The asynchronous activation of the 2 ventricles increases the QRS duration (0.16 seconds in this example). The abnormal initial vector results in loss of "normal" septal forces as manifested by absence of q waves in leads I, aVL, and V6. The late activation of the left ventricle prolongs the dominant leftward progression of the middle and terminal forces, leading to a positive and widened R wave in the lateral leads. Both the ST segment and T wave vectors are opposite in direction from the QRS, a "secondary" repolarization abnormality. Courtesy of Ary Goldberger, MD. Graphic 61594 Version 9.0 Normal ECG https://www.uptodate.com/contents/left-bundle-branch-block/print 20/26 7/5/23, 10:35 AM Left bundle branch block - UpToDate Normal electrocardiogram showing normal sinus rhythm at a rate of 75 beats/minute, a PR interval of 0.14 seconds, a QRS interval of 0.10 seconds, and a QRS axis of approximately 75 . Courtesy of Ary Goldberger, MD. Graphic 76183 Version 4.0 https://www.uptodate.com/contents/left-bundle-branch-block/print 21/26 7/5/23, 10:35 AM Left bundle branch block - UpToDate Coronary artery anatomy Graphic 70956 Version 2.0 https://www.uptodate.com/contents/left-bundle-branch-block/print 22/26 7/5/23, 10:35 AM Left bundle branch block - UpToDate Selected causes of prominent T wave inversions Primary T wave inversions Normal variant Juvenile T wave pattern "Early repolarization" variant (sometimes associated with T wave inversions) Myocardial ischemia or infarction (including takotsubo syndrome) Left or right ventricular overload syndromes (formerly called "strain" patterns) Cerebrovascular injury (T waves may be massively inverted) "Memory T waves" (eg, with intermittent left bundle branch block, intermittent ventricular pacing, or intermittent Wolff-Parkinson-White pre-excitation) Post-tachycardia T wave pattern Apical hypertrophic cardiomyopathy (Yamaguchi's syndrome) Other myocardial/pericardial diseases - dilated and restrictive cardiomyopathies, arrhythmogenic right ventricular cardiomyopathy (dysplasia), pericarditis, myocardial tumor, etc. Idiopathic global T wave inversions Secondary T wave inversions Left bundle branch block Right bundle branch block Wolff-Parkinson-White patterns and variants Ventricular beats (paced, premature or escape) Graphic 63807 Version 1.0 https://www.uptodate.com/contents/left-bundle-branch-block/print 23/26 7/5/23, 10:35 AM Left bundle branch block - UpToDate Single lead electrocardiogram (ECG) showing monomorphic ventricular tachycardia Three or more successive ventricular beats are defined as ventricular tachycardia (VT). This VT is monomorphic since all of the QRS complexes have an identical appearance. Although the P waves are not distinct, they can be seen altering the QRS complex and ST-T waves in an irregular fashion, indicating the absence of a relationship between the P waves and the QRS complexes (ie, AV dissociation is present). AV: atrioventricular. Graphic 63176 Version 7.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/left-bundle-branch-block/print 24/26 7/5/23, 10:35 AM Left bundle branch block - UpToDate ECG 12-lead accelerated idioventricular rhythm 12-lead ECG showing idioventricular rhythm with AV dissociation and wide QRS complexes occurring at a rate faster than the sinus rate but slower than 100 bpm (hence not meeting the criteria for ventricular tachycardia). ECG: electrocardiogram. Graphic 118943 Version 2.0 https://www.uptodate.com/contents/left-bundle-branch-block/print 25/26 7/5/23, 10:35 AM Left bundle branch block - UpToDate Contributor Disclosures William H Sauer, MD Grant/Research/Clinical Trial Support: Biosense-Webster [Catheter ablation]; Boston Scientific [Catheter ablation]. All of the relevant financial relationships listed have been mitigated. Mark S Link, MD No relevant financial relationship(s) with ineligible companies to disclose. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/left-bundle-branch-block/print 26/26

7/5/23, 10:36 AM Left posterior fascicular block - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Left posterior fascicular block : William H Sauer, MD : Ary L Goldberger, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Dec 06, 2022. INTRODUCTION Left posterior fascicular block (LPFB), a pattern (formerly called left posterior hemiblock) seen on the surface electrocardiogram (ECG), results when normal electrical activity in the His-Purkinje system is delayed or interrupted ( figure 1). The normal sequence of activation is altered in LPFB, with a resultant characteristic appearance on the ECG, associated with marked right axis deviation ( waveform 1). The anatomy, clinical manifestations, differential diagnosis, prognostic implications, and treatment of LPFB will be reviewed here. Additional details regarding the ECG manifestations of LPFB are discussed separately. (See "ECG tutorial: Intraventricular block", section on 'Left anterior fascicular block'.) In the discussion that follows, it is assumed that the reader understands the general concepts of cardiac vectors, asynchronous activation of the ventricles (delayed as in fascicular or bundle branch block, or early as in pre-excitation), and the effects that asynchrony has on the duration, morphology, and amplitude of the QRS complex. (See "ECG tutorial: Physiology of the conduction system" and "General principles of asynchronous activation and preexcitation".) ANATOMY AND ELECTROPHYSIOLOGY Anatomy The bundle of His divides at the juncture of the fibrous and muscular boundaries of the interventricular septum into the right and left bundle branches. The main left bundle branch penetrates the membranous portion of the interventricular septum under the aortic ring and https://www.uptodate.com/contents/left-posterior-fascicular-block/print 1/13 7/5/23, 10:36 AM Left posterior fascicular block - UpToDate then divides into several fairly discrete branches ( figure 1) [1]. There is a large amount of individual variability in the size and distribution of the left fascicles [2]. However, in most patients, there are two main fascicles: The left anterior fascicle that crosses the left ventricular outflow tract and terminates in the Purkinje system of the anterolateral wall of the left ventricle. The left posterior fascicle that fans out extensively inferiorly and posteriorly into Purkinje fibers. A left median (also called medial or septal) fascicle to the interventricular septum is found in nearly 65 percent of people and can arise from the common left bundle or from the anterior, posterior, or both fascicles. Support for the trifascicular nature of the left bundle comes from the observation in animals and humans that depolarization of the left ventricle begins in three areas corresponding to the terminal portions of the anterior, posterior, and septal fascicles [3,4]. In the normal heart, the three fascicles of the left bundle are simultaneously depolarized. Further evidence of simultaneous activation of the fascicles can be found with routine electroanatomic mapping of a structurally normal heart. (See "Invasive diagnostic cardiac electrophysiology studies", section on 'Mapping and ablation'.) Blood supply The proximal part of the left posterior fascicle is supplied by the artery to the atrioventricular (AV) node and, at times, by septal branches of the left anterior descending (LAD) artery ( figure 2). The distal portion has a dual blood supply from both anterior and posterior septal perforating arteries. The left anterior and median fascicles are supplied either by septal branches of the LAD or by the AV nodal artery. EPIDEMIOLOGY Isolated LPFB is a rare finding, particularly among otherwise healthy persons, with estimates of its prevalence ranging from 0.1 to 0.6 percent [5,6]. In a cohort study involving 358,958 primary care patients, 0.8 percent presented with isolated LPFB [7]. Among a cohort of 6416 people participating in a Finnish public health study, only eight persons (0.12 percent) were identified with isolated LPFB [5]. In a study of 2254 patients with heart failure, only 14 (0.6 percent) had isolated LPFB [8]. https://www.uptodate.com/contents/left-posterior-fascicular-block/print 2/13 7/5/23, 10:36 AM Left posterior fascicular block - UpToDate Among a cohort of 2160 patients with acute myocardial infarction, the prevalence of LPFB was 0.4 percent [9]. In a cohort of 888 older adult subjects (age 90 years), there were only three with isolated LPFB [6]. LPFB is most often seen in association with right bundle branch block, as one of the manifestations of "bifascicular block." This is discussed in detail separately. (See "Chronic bifascicular blocks".) ETIOLOGY The left posterior fascicle branch is the first branch of the left bundle and is large in its initial course. It then fans extensively throughout the posterior and inferior left ventricle. The left posterior fascicle is exposed to lower pressures and less turbulence than the left anterior fascicle; it also has a dual blood supply. These characteristics probably explain why isolated LPFB is an uncommon finding. (See 'Epidemiology' above.) Isolated LPFB can, however, be seen in the setting of extensive arteriosclerotic cardiovascular disease, as an association with inferior myocardial infarction and extensive coronary disease has been suggested [10]. LPFB can also occur with cardiomyopathies, including those that result from hypertension and Chagas disease, myocarditis, hyperkalemia, acute cor pulmonale, and chronic degenerative and fibrotic processes of the conducting system. Transient LPFB is quite rare but also suggests extensive coronary artery disease [11]. ELECTROCARDIOGRAPHIC FINDINGS Left posterior and anterior fascicular blocks mainly affect the direction but not the duration of the QRS complex because the conduction disturbance primarily involves the early phases of activation. (See "Left anterior fascicular block".) Definition The ECG features ( waveform 1) of isolated LPFB include [12]: Frontal plane axis between 90 and 180 in adults rS pattern in leads I and aVL qR pattern in leads III and aVF QRS duration less than 120 milliseconds https://www.uptodate.com/contents/left-posterior-fascicular-block/print 3/13 7/5/23, 10:36 AM Left posterior fascicular block - UpToDate ECG activation patterns The left posterior fascicle normally initiates activation of the lower part of the septum, the inferolateral wall, and the posteromedial papillary muscle. The ECG criteria for LPFB (also called left posterior hemiblock) are depicted on the ECG ( waveform 1). The changes that are seen reflect alterations in the different phases of activation. Early activation Early activation by the normally conducting anterior and septal fascicles causes the initial vector to be directed to the left, anteriorly, and superiorly producing initial small r waves in leads I, V1, and V6. Mid-temporal and terminal activation The mid-temporal and terminal vectors in LPFB are directed to the right, posteriorly, and inferiorly due to delayed depolarization of the areas normally activated by the left posterior fascicle. This leads to the characteristic rightward axis of +90 to +180 [13]. As a result, there is a qR morphology in leads II, III, and aVF and an rS morphology in leads I and aVL. QRS duration and T waves The QRS duration usually does not exceed 100 milliseconds, although the World Health Organization/International Society and Federation of Cardiology (WHO/ISFC) Task Force allows up to 120 milliseconds, or 20 milliseconds above the previous baseline [13]. The T waves are often normal, but the T wave vector may be directed posteriorly and upward. DIFFERENTIAL DIAGNOSIS By contrast to left anterior fascicular block, LPFB is very rare as an isolated finding. The ECG in LPFB can mimic the findings seen in a number of other conditions. These include: Right ventricular hypertrophy The ECG criteria for LPFB apply only in the absence of other causes for a rightward axis, such as right ventricular hypertrophy (RVH) due to valvular heart disease or lung disease with cor pulmonale. Right axis deviation (axis >+90 to 100 ) is often present with RVH. The RV forces become predominant in patients with RVH (especially due to a pressure load as with pulmonic outflow obstruction or severe pulmonary hypertension), producing tall R waves in the right precordial leads (V1 and V2) and deep S waves in the left precordial leads (V5 and V6). There also may be associated right atrial overload and ST segment and T wave abnormalities in the right precordial leads. Old myocardial infarction Prior myocardial infarction (MI), with resulting Q waves, may appear similar to LPFB on an ECG. (See "ECG tutorial: Myocardial ischemia and infarction", section on 'Prior Q wave myocardial infarction'.) https://www.uptodate.com/contents/left-posterior-fascicular-block/print 4/13 7/5/23, 10:36 AM Left posterior fascicular block - UpToDate A high lateral or anterolateral MI can mimic LPFB. With an infarct, however, the initial r wave in leads 1 and aVL is absent, and only a Q wave is seen. The small q waves in the inferior leads in LPFB may cause confusion with an inferior wall MI. The presence of right bundle branch block (RBBB) might suggest right axis deviation because of the deep terminal S wave in leads 1, aVL and V5, and V6. However, these S waves reflect delayed RV activation, not left ventricular forces. An additional potential source of confusion is that RBBB can occur in association with LPFB ( table 1). Pre-excitation Pre-excitation can occasionally produce right axis deviation. The presence of pre-excitation is indicated by a short PR interval, a delta wave, and a widened QRS complex. This pattern often has Q waves in leads II, III, and aVF and not infrequently is misdiagnosed as an inferior wall MI. (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis", section on 'Electrocardiographic findings'.) Miscellaneous Isolated LPFB is a diagnosis of clinical exclusion, requiring that other more common causes of rightward QRS axis be ruled out. Once RVH, prior MI, and pre-excitation have been excluded, other conditions to exclude include misplacement of the ECG leads, typically with limb lead reversal, or the presence of a normal ECG variation (especially in younger adults). EVALUATION, TREATMENT, AND FOLLOW-UP Patients with isolated LPFB are generally asymptomatic and do not require further diagnostic evaluation for LPFB or placement of a pacemaker or any other specific therapy. Therapy should be considered only in patients with persistent bifascicular or trifascicular block or in certain other disorders (eg, neuromuscular disorders, Anderson-Fabry disease, etc). (See "Chronic bifascicular blocks".) A number of neuromuscular diseases are associated with fascicular block. These include myotonic muscular dystrophy, Kearns-Sayre syndrome, Erb's dystrophy (limb-girdle), and a peroneal muscular atrophy. These patients represent a special class and are treated more aggressively with pacemakers due to the potential for unpredictably rapid progression of conduction disease [14]. (See "Inherited syndromes associated with cardiac disease" and "Permanent cardiac pacing: Overview of devices and indications", section on 'Neuromuscular diseases'.) https://www.uptodate.com/contents/left-posterior-fascicular-block/print 5/13 7/5/23, 10:36 AM Left posterior fascicular block - UpToDate Patients with isolated findings of LPFB on the surface ECG do not require any specific follow-up aside from routine care. Any symptoms consistent with the development of cardiac disease (eg, coronary heart disease, heart failure, atrial fibrillation, etc) should immediately be evaluated. PROGNOSIS Isolated LPFB is very rare and thus, unlike left anterior fascicular block, left bundle branch block, and right bundle branch block, there are limited studies evaluating this ECG pattern with subsequent atrial fibrillation or other cardiovascular morbidity risk. In the above cited cohort study evaluating ECGs in 358,958 primary care patients, there was an observed increase in mortality among patients with isolated LPFB compared with those without any fascicular block over a 10-year follow-up period (hazard ratio 2.09, 95% CI 1.87-2.32) [7]. SUMMARY AND RECOMMENDATIONS Left posterior fascicular block (LPFB), a pattern seen on the surface electrocardiogram (ECG), results when normal electrical activity in the His-Purkinje system is delayed or interrupted ( figure 1). The normal sequence of activation is altered in LPFB, with a resultant characteristic appearance on the ECG associated with marked right axis deviation ( waveform 1). (See 'Introduction' above.) Isolated LPFB is a rare finding, particularly among otherwise healthy persons, with estimates of its prevalence ranging from 0.1 to 0.6 percent. (See 'Epidemiology' above.) Isolated LPFB has the following features on an ECG (see 'Definition' above): Frontal plane axis between 90 and 180 in adults (in the absence of other factors known to cause a rightward QRS axis) rS pattern in leads I and aVL qR pattern in leads III and aVF QRS duration less than 120 milliseconds Patients with isolated LPFB are generally asymptomatic and do not require further diagnostic evaluation for LPFB or placement of a pacemaker or any other specific therapy. Therapy should be considered only in patients with persistent bifascicular or trifascicular block or in certain neuromuscular disorders. (See 'Evaluation, treatment, and follow-up' above.) https://www.uptodate.com/contents/left-posterior-fascicular-block/print 6/13 7/5/23, 10:36 AM Left posterior fascicular block - UpToDate Patients with isolated findings of LPFB on the surface ECG do not require any specific follow-up aside from routine care. Any symptoms consistent with the development of cardiac disease (eg, coronary heart disease, heart failure, atrial fibrillation, etc) should immediately be evaluated. (See 'Evaluation, treatment, and follow-up' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Elizari MV, Acunzo RS, Ferreiro M. Hemiblocks revisited. Circulation 2007; 115:1154. 2. Demoulin JC, Kulbertus HE. Histopathological examination of concept of left hemiblock. Br Heart J 1972; 34:807. 3. Myerburg RJ, Nilsson K, Gelband H. Physiology of canine intraventricular conduction and endocardial excitation. Circ Res 1972; 30:217. 4. Durrer D, van Dam RT, Freud GE, et al. Total excitation of the isolated human heart. Circulation 1970; 41:899. 5. Haataja P, Nikus K, K h nen M, et al. Prevalence of ventricular conduction blocks in the resting electrocardiogram in a general population: the Health 2000 Survey. Int J Cardiol 2013; 167:1953. 6. Kelley GP, Stellingworth MA, Broyles S, Glancy DL. Electrocardiographic findings in 888 patients > or =90 years of age. Am J Cardiol 2006; 98:1512. 7. Nyholm BC, Ghouse J, Lee CJ, et al. Fascicular heart blocks and risk of adverse cardiovascular outcomes: Results from a large primary care population. Heart Rhythm 2022; 19:252. 8. Cinca J, Mendez A, Puig T, et al. Differential clinical characteristics and prognosis of intraventricular conduction defects in patients with chronic heart failure. Eur J Heart Fail 2013; 15:877. 9. Lewin RF, Sclarovsky S, Strasberg B, et al. Right axis deviation in acute myocardial infarction. Clinical significance, hospital evolution, and long-term follow-up. Chest 1984; 85:489. 10. Godat FJ, Gertsch M. Isolated left posterior fascicular block: a reliable marker for inferior myocardial infarction and associated severe coronary artery disease. Clin Cardiol 1993; 16:220. 11. Madias JE, Knez P. Transient left posterior hemiblock during myocardial ischemia-eliciting exercise treadmill testing: a report of a case and a critical analysis of the literature. J Electrocardiol 1999; 32:57. https://www.uptodate.com/contents/left-posterior-fascicular-block/print 7/13 7/5/23, 10:36 AM Left posterior fascicular block - UpToDate 12. Surawicz B, Childers R, Deal BJ, et al. AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part III: intraventricular conduction disturbances: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society. Endorsed by the International Society for Computerized Electrocardiology. J Am Coll Cardiol 2009; 53:976. 13. Willems JL, Robles de Medina EO, Bernard R, et al. Criteria for intraventricular conduction disturbances and pre-excitation. World Health Organizational/International Society and Federation for Cardiology Task Force Ad Hoc. J Am Coll Cardiol 1985; 5:1261. 14. Kusumoto FM, Schoenfeld MH, Barrett C, et al. 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2019; 74:e51. Topic 2107 Version 24.0 https://www.uptodate.com/contents/left-posterior-fascicular-block/print 8/13 7/5/23, 10:36 AM Left posterior fascicular block - UpToDate GRAPHICS Normal conduction system Schematic representation of the normal intraventricular conduction system (His- Purkinje system). The Bundle of His divides into the left bundle branch and right bundle branch. The left bundle branch divides into anterior, posterior, and, in some cases, median fascicles. AV: atrioventricular; RA: right atrium; LA: left atrium; RV: right ventricle; LV: left ventricle. Graphic 63340 Version 6.0 https://www.uptodate.com/contents/left-posterior-fascicular-block/print 9/13 7/5/23, 10:36 AM Left posterior fascicular block - UpToDate ECG left posterior fascicular block Sinus rhythm at about 95 beats per minute. QRS duration is normal. Note the marked right axis deviation consistent with left posterior fascicular block. As part of this pattern, rS pattern is present in lead aVL along with qR pattern in leads III and aVF. ECG: electrocardiogram. Graphic 116957 Version 1.0 https://www.uptodate.com/contents/left-posterior-fascicular-block/print 10/13 7/5/23, 10:36 AM Left posterior fascicular block - UpToDate Coronary artery anatomy Graphic 70956 Version 2.0 https://www.uptodate.com/contents/left-posterior-fascicular-block/print 11/13 7/5/23, 10:36 AM Left posterior fascicular block - UpToDate Major causes of right axis deviation Artifactual Left-right arm electrode reversal (look for negative P and negative QRS in lead I) Normal variant Right ventricular overload Acute pulmonary embolus or other causes of acute cor pulmonale Chronic Chronic thromboembolic pulmonary hypertension (CTEPH) syndrome Chronic obstructive lung disease Any cause of right ventricular hypertrophy Lateral wall myocardial infarction Dextrocardia, as with situs inversus Left posterior fascicular block - must exclude other causes listed above Graphic 71386 Version 3.0 https://www.uptodate.com/contents/left-posterior-fascicular-block/print 12/13 7/5/23, 10:36 AM Left posterior fascicular block - UpToDate Contributor Disclosures William H Sauer, MD Grant/Research/Clinical Trial Support: Biosense-Webster [Catheter ablation]; Boston Scientific [Catheter ablation]. All of the relevant financial relationships listed have been mitigated. Ary L Goldberger, MD Other Financial Interest: Elsevier book royalties [Clinical electrocardiography]. All of the relevant financial relationships listed have been mitigated. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/left-posterior-fascicular-block/print 13/13

7/5/23, 10:36 AM Left septal fascicular block - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Left septal fascicular block : William H Sauer, MD : Ary L Goldberger, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Jun 08, 2022. INTRODUCTION Left septal fascicular block (LSFB; also called left middle or left median fascicular block) results when one of the earliest phases of normal electrical activity in the His-Purkinje system is delayed or interrupted ( figure 1). Since the normal sequence of activation is altered in LSFB, it may be associated with alteration in the electrocardiogram (ECG). This form of block is one of the causes of a "counterclockwise rotation" pattern (early R wave transition) in the precordial leads and is quite variable, sometimes associated with a loss, not a gain, of anterior forces ( waveform 1). This variability has contributed to some of the controversies and unresolved issues regarding LSFB. (See 'Electrocardiographic findings' below.) The anatomy, clinical manifestations, differential diagnosis, prognostic implications, and treatment of LSFB will be reviewed here. In the discussion that follows, it is assumed that the reader understands the general concepts of cardiac vectors, asynchronous activation of the ventricles (delayed as in fascicular or bundle branch block or early as in preexcitation), and the effects that asynchrony has on the duration, morphology, and amplitude of the QRS complex. (See "ECG tutorial: Physiology of the conduction system" and "General principles of asynchronous activation and preexcitation".) ANATOMY AND ELECTROPHYSIOLOGY Anatomy The bundle of His divides at the juncture of the fibrous and muscular boundaries of the interventricular septum into the right and left bundle branches. The main left bundle branch https://www.uptodate.com/contents/left-septal-fascicular-block/print 1/11 7/5/23, 10:36 AM Left septal fascicular block - UpToDate penetrates the membranous portion of the interventricular septum under the aortic ring and then divides into several fairly discrete branches ( figure 1) [1]. There is a large amount of individual variability in the size and distribution of the left fascicles [2]. However, in most patients, there are two main fascicles: The left anterior fascicle that crosses the left ventricular outflow tract and terminates in the Purkinje system of the anterolateral wall of the left ventricle. The left posterior fascicle that fans out extensively inferiorly and posteriorly into Purkinje fibers. In up to 65 percent of hearts, a left septal fascicle (also called left middle or left median fascicle) to the interventricular septum. This has been reported in nearly 65 percent of people and can arise from the common left bundle or from the anterior, posterior, or both fascicles. The anatomy of the septal fascicle, when found, is more variable than the other fascicles, with a large number of interconnections [2,3]. Support for the trifascicular nature of the left bundle comes from the observation in animals and humans that depolarization of the left ventricle begins in three areas corresponding to the terminal portions of the anterior, posterior, and septal fascicles [4,5]. In the normal heart, the three fascicles of the left bundle are simultaneously depolarized. Further evidence of simultaneous activation of the fascicles can be found with routine electroanatomic mapping of a structurally normal heart. (See "Invasive diagnostic cardiac electrophysiology studies", section on 'Mapping and ablation'.) Blood supply The left anterior and septal fascicles are supplied either by septal branches of the left anterior descending (LAD) artery or by the atrioventricular (AV) nodal artery ( figure 2). The proximal part of the left posterior fascicle is supplied by the artery to the AV node and, at times, by septal branches of the LAD artery. The distal portion has a dual blood supply from both anterior and posterior septal perforating arteries. EPIDEMIOLOGY ECG findings consistent with isolated LSFB are an extremely rare finding, particularly among otherwise healthy persons. There are only a few reported estimates of isolated LSFB. In a review of some 26,000 ECGs, criteria for LSFB were found in approximately 0.5 percent, a prevalence similar to left posterior fascicular block (between 0.1 and 0.6 percent) but less than left anterior fascicular block (between 1 and 2.5 percent) [6]. https://www.uptodate.com/contents/left-septal-fascicular-block/print 2/11 7/5/23, 10:36 AM Left septal fascicular block - UpToDate ETIOLOGY A variety of underlying disorders may be responsible for LSFB, including ischemic or hypertensive heart disease, hypertrophic cardiomyopathy, and diabetes mellitus. LSFB can be induced by ischemia, fibrosis, or sclerodegenerative changes, which are generally associated with alterations in the other fascicles [2,7-10]. In addition, patients with no known structural heart disease can have transient LSFB with premature atrial ectopy [11]. Patients with prior catheter ablation of fascicular arrhythmias may also have LSFB as a consequence of the ablative treatment. ELECTROCARDIOGRAPHIC FINDINGS Similar but even more subtly than left anterior and posterior fascicular blocks, LSFB mainly affects the direction, but not the duration, of the QRS complex because the conduction disturbance primarily involves the early phases of activation ( waveform 1). The major clinical implication of LSFB is that the ECG mimics the changes induced by a septal or posterior myocardial infarction. (See "Left anterior fascicular block" and "Left posterior fascicular block".) Definition A task force from the American Heart Association, the American College of Cardiology, and the Heart Rhythm Society has defined the ECG features of left anterior and posterior fascicular blocks. This document acknowledges the lack of universally accepted criteria for LSFB, and therefore this condition was not electrocardiographically defined by this group [12]. In a separate consensus report, LSFB was specifically addressed with recognition of a lack of true universal ECG criteria [13]. There are several proposed ECG criteria including the loss of a septal q wave with an R pattern in leads V5 and V6 and the presence of an RS pattern in V1 to V2 indicating a gain in prominent anterior forces. However, because there are other conditions that can result in these ECG patterns, the consensus document is in agreement with the aforementioned task force conclusions. ECG activation patterns Myocardial activation may be affected in two ways by a conduction disturbance in the left septal fascicle: apparent loss or gain of anterior forces. In fact, the demonstration of these changes was one of the early observations suggesting the existence of a left septal fascicle. The ECG pattern seen with LSFB is probably determined by the differences in the sites of insertion of the septal, anterior, and posterior fascicles: Apparent gain of anterior forces with early precordial transition/counterclockwise rotation (CCWR) In marked contrast, prominent R waves are seen in the right precordial leads when LSFB leads to a gain of anterior forces [8,14]. These changes are similar to those that https://www.uptodate.com/contents/left-septal-fascicular-block/print 3/11 7/5/23, 10:36 AM Left septal fascicular block - UpToDate occur in true posterior (dorsal) myocardial infarction. The prominence of the R waves may be increased when LSFB occurs in association with right bundle branch block. The relationship between shift of the transitional zone on the standard 12-lead ECG and anatomic rotation of the heart in one plane was studied by cardiac computed tomography (CT) [15]. The left-sided angle between the interventricular septum and horizontal axis of the body (the septal angle) was determined on the cardiac CT. The mechanism of CCWR could be attributed to the septal angle in approximately two-thirds of the cases, but the remainder was thought to be due to LSFB. In one description of transient LSFB occurring during proximal occlusion of the left anterior descending artery, an acute gain of anterior forces was observed along with preservation of septal q waves [16]. Apparent loss of anterior forces Functional or hyperkalemia-induced dysfunction in the left septal fascicle can lead to the loss of anterior forces, resulting in the transient development of q waves in leads V1 and V2, which normally have a positive initial deflection due to septal depolarization [17,18]. Similar changes occur with permanent LSFB and are indistinguishable from septal fibrosis or infarction. EVALUATION, TREATMENT, AND FOLLOW-UP Patients with an ECG raising consideration of isolated LSFB are generally asymptomatic and do not require further diagnostic evaluation or placement of a pacemaker or any other specific therapy. Therapy should be considered only in patients with persistent bifascicular or trifascicular block or in certain neuromuscular disorders. (See "Chronic bifascicular blocks".) Any symptoms consistent with the development of cardiac disease (eg, coronary heart disease, heart failure, atrial fibrillation, etc) should immediately be evaluated. PROGNOSIS Similar to isolated left posterior fascicular block, isolated LSFB is very rare. Thus, unlike left anterior fascicular block, left bundle branch block, and right bundle branch block, there are no studies evaluating this ECG pattern with subsequent atrial fibrillation or other cardiovascular morbidity risk. SUMMARY AND RECOMMENDATIONS https://www.uptodate.com/contents/left-septal-fascicular-block/print 4/11 7/5/23, 10:36 AM Left septal fascicular block - UpToDate Left septal fascicular block (LSFB; also called left middle or left median fascicular block), a pattern seen on the surface electrocardiogram (ECG), results when normal electrical activity in the His-Purkinje system is delayed or interrupted ( figure 1). The normal sequence of activation is altered in LSFB, with a frequent counterclockwise rotation and a resultant appearance on the ECG that is variable, sometimes manifesting with a gain of anterior forces, but at other times with an apparent loss of anterior forces. (See 'Introduction' above.) Among experts and professional societies, there is an acknowledgment of the lack of universally accepted criteria for LSFB. Proposed ECG criteria include the loss of a septal q wave with an R pattern in lead V5 and V6 and presence of an RS pattern in V1 to V2 indicating a gain in anterior forces. However, there are other conditions that can result in these nonspecific ECG patterns. (See 'Electrocardiographic findings' above.) Isolated LSFB is an extremely rare finding, particularly among otherwise healthy persons. Criteria for LSFB have been reported only in approximately 0.5 percent of the general population. (See 'Epidemiology' above.) Patients with an ECG raising consideration of isolated LSFB are generally asymptomatic and do not require further diagnostic evaluation or placement of a pacemaker or other specific therapy. Any symptoms consistent with the development of cardiac disease (eg, coronary heart disease, heart failure, atrial fibrillation, etc) should immediately be evaluated. (See 'Evaluation, treatment, and follow-up' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Elizari MV, Acunzo RS, Ferreiro M. Hemiblocks revisited. Circulation 2007; 115:1154. 2. Demoulin JC, Kulbertus HE. Histopathological examination of concept of left hemiblock. Br Heart J 1972; 34:807. 3. Massing GK, James TN. Anatomical configuration of the His bundle and bundle branches in the human heart. Circulation 1976; 53:609. 4. Myerburg RJ, Nilsson K, Gelband H. Physiology of canine intraventricular conduction and endocardial excitation. Circ Res 1972; 30:217. 5. Durrer D, van Dam RT, Freud GE, et al. Total excitation of the isolated human heart. Circulation 1970; 41:899. 6. MacAlpin RN. In search of left septal fascicular block. Am Heart J 2002; 144:948. https://www.uptodate.com/contents/left-septal-fascicular-block/print 5/11 7/5/23, 10:36 AM Left septal fascicular block - UpToDate 7. Uhley HN. Some controversy regarding the peripheral distribution of the conduction system. Am J Cardiol 1972; 30:919. 8. Nakaya Y, Hiasa Y, Murayama Y, et al. Prominent anterior QRS force as a manifestation of left septal fascicular block. J Electrocardiol 1978; 11:39. 9. P rez-Riera AR, Barbosa-Barros R, Daminello-Raimundo R, et al. Transient left septal fascicular block and left anterior fascicular block as a consequence of proximal subocclusion of the left anterior descending coronary artery. Ann Noninvasive Electrocardiol 2019; 24:e12546. 10. Ibarrola M, Chiale PA, P rez-Riera AR, Baranchuk A. Phase 4 left septal fascicular block. Heart Rhythm 2014; 11:1655. 11. Acunzo RS, Konopka IV, Sanch z RA, et al. Right bundle branch block and middle septal fiber block with or without left anterior fascicular block manifested as aberrant conduction in apparent healthy individuals: Electro-vectorcardiographic characterization. J Electrocardiol 2013; 46:167. 12. Surawicz B, Childers R, Deal BJ, et al. AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part III: intraventricular conduction disturbances: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society. Endorsed by the International Society for Computerized Electrocardiology. J Am Coll Cardiol 2009; 53:976. 13. Bay s de Luna A, Riera AP, Baranchuk A, et al. Electrocardiographic manifestation of the middle fibers/septal fascicle block: a consensus report. J Electrocardiol 2012; 45:454. 14. DePadua FI, Pereirnha A, Lopes MG. Conduction defects. In: Comprehensive Electrocardiogr aphy: Theory and Practice in Health and Disease, MacFarlane P, Veitch Lawrie TD (Eds), Perg amon Press, New York 1989. p.459. 15. Tahara Y, Mizuno H, Ono A, Ishikawa K. Evaluation of the electrocardiographic transitional zone by cardiac computed tomography. J Electrocardiol 1991; 24:239. 16. Andreou AY. Transitory R wave growth in the midst of ST-segment elevation myocardial infarction: A case of left septal fascicular block with atypical electrocardiographic presentation. J Electrocardiol 2022; 72:39. 17. Gambetta M, Childers RW. Rate-dependent right precordial Q waves: "septal focal block". Am J Cardiol 1973; 32:196. 18. Arnsdorf MF. Electrocardiogram in Hyperkalemia: electrocardiographic pattern of anteroseptal myocardial infarction mimicked by hyperkalemia-induced disturbance of impulse conduction. Arch Intern Med 1976; 136:1161. https://www.uptodate.com/contents/left-septal-fascicular-block/print 6/11 7/5/23, 10:36 AM Left septal fascicular block - UpToDate Topic 2111 Version 26.0 https://www.uptodate.com/contents/left-septal-fascicular-block/print 7/11 7/5/23, 10:36 AM Left septal fascicular block - UpToDate GRAPHICS Normal conduction system Schematic representation of the normal intraventricular conduction system (His- Purkinje system). The Bundle of His divides into the left bundle branch and right bundle branch. The left bundle branch divides into anterior, posterior, and, in some cases, median fascicles. AV: atrioventricular; RA: right atrium; LA: left atrium; RV: right ventricle; LV: left ventricle. Graphic 63340 Version 6.0 https://www.uptodate.com/contents/left-septal-fascicular-block/print 8/11 7/5/23, 10:36 AM Left septal fascicular block - UpToDate Surface 12-lead ECG showing left septal fascicular block (LSFB) Surface 12-lead ECG depicting second-degree atrioventricular block and phase 4 or bradycardia-dependent L ECG: electrocardiogram; LSFB: left septal fascicular block. Original gure modi ed for this publication. From: Ibarrola M, Chiale PM, P rez-Riera AR, Baranchuk A. Phase 4 left septal fascicular b the permission of Elsevier Inc. All rights reserved. Graphic 118370 Version 2.0 https://www.uptodate.com/contents/left-septal-fascicular-block/print 9/11 7/5/23, 10:36 AM Left septal fascicular block - UpToDate Coronary artery anatomy Graphic 70956 Version 2.0 https://www.uptodate.com/contents/left-septal-fascicular-block/print 10/11 7/5/23, 10:36 AM Left septal fascicular block - UpToDate Contributor Disclosures William H Sauer, MD Grant/Research/Clinical Trial Support: Biosense-Webster [Catheter ablation]; Boston Scientific [Catheter ablation]. All of the relevant financial relationships listed have been mitigated. Ary L Goldberger, MD Other Financial Interest: Elsevier book royalties [Clinical electrocardiography]. All of the relevant financial relationships listed have been mitigated. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/left-septal-fascicular-block/print 11/11

7/5/23, 10:36 AM Right bundle branch block - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Right bundle branch block : William H Sauer, MD : Mark S Link, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Apr 29, 2022. INTRODUCTION Right bundle branch block (RBBB), a pattern seen on the surface electrocardiogram (ECG), results when normal electrical activity in the His-Purkinje system is interrupted ( figure 1). The normal sequence of activation is altered dramatically in RBBB, with a resultant characteristic appearance on the ECG manifest by a widened QRS complex and changes in the directional vectors of the R and S waves ( waveform 1). (See 'ECG findings and diagnosis' below.) The anatomy, clinical manifestations, differential diagnosis, prognostic implications, and treatment of RBBB will be reviewed here. Additional details regarding the ECG manifestations of RBBB are discussed separately. (See "ECG tutorial: Intraventricular block", section on 'Right bundle branch block'.) ANATOMY AND ELECTROPHYSIOLOGY Anatomy The bundle of His divides at the juncture of the fibrous and muscular boundaries of the intraventricular septum into the left and right bundle branches ( figure 1). The right bundle branch is a long, thin, discrete structure that consists of fast response Purkinje fibers. The right bundle branch courses down the right side of interventricular septum near the endocardium in its upper third, deeper in the muscular portion of the septum in the middle third, and then again near the endocardium in its lower third. The right bundle branch does not divide throughout most of its course, but begins to ramify as it approaches the base of the right anterior papillary muscle with fascicles going to the septal and free walls of the right ventricle. https://www.uptodate.com/contents/right-bundle-branch-block/print 1/27 7/5/23, 10:36 AM Right bundle branch block - UpToDate Blood supply The right bundle branch receives most of its blood supply from septal branches of the left anterior descending coronary artery, particularly in its initial course. In most patients, it also receives some collateral supply from either the right or circumflex coronary systems depending upon the dominance of the coronary system ( figure 2). Electrophysiology The right bundle branch consists of a bundle of Purkinje cells covered by a dense sheath of connective tissue. Purkinje cells are specialized to conduct rapidly at 1 to 3 m/sec, as phase 0 is dependent on the rapid inward sodium current ( figure 3). Initial activation occurs near the apex of the right ventricular endocardium, subsequently spreading to the septum and the free wall of the right ventricle, then moving much more slowly through the myocardial cells. (See "Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs".) Intraoperative studies in humans have shown that RBBB can occur at three discrete levels [1,2]: The proximal right bundle, which is the most common site of RBBB. The distal right bundle, which is unusual unless there has been transection of the moderator band during surgery. The terminal right bundle, which may be produced by ventriculotomy or transatrial resection. In addition, RBBB may be induced by disease in the His bundle, resulting in activation that is asynchronous from that in the rest of the infranodal conducting system, possibly resulting in a bundle branch or fascicular block [3-5]. EPIDEMIOLOGY The prevalence of RBBB increases with age. In one prospective study of 855 males followed for 30 years, the prevalence was 0.8 percent in subjects at age 50 and 11.3 percent by age 80 ( figure 4) [6]. There was no significant association with risk factors for, or the presence of, ischemic heart disease, myocardial infarction, or cardiovascular deaths, suggesting that RBBB is usually a marker of a slowly progressive degenerative disease that also affects the myocardium. Similar observations apply to left bundle branch block [6]. (See "Left bundle branch block".) RBBB can rarely occur in an otherwise normal heart, with a prevalence estimated between 0.2 and 2.3 percent, as illustrated by the following observations [7-11]: In a study of 237,000 airmen under age 30; there were 394 cases of complete RBBB, representing a prevalence of 0.2 percent [8]. https://www.uptodate.com/contents/right-bundle-branch-block/print 2/27 7/5/23, 10:36 AM Right bundle branch block - UpToDate Among 66,450 participants in the Women's Health Initiative trial, 832 had RBBB at study entry, representing a prevalence of 1.3 percent [9]. Among 8527 participants in the NHANES study (mean age 61 years, 87 percent were White Americans, 53 percent female, 16 percent with coronary heart disease at baseline), RBBB was present at baseline in 192 people (2.3 percent) [10]. Incomplete RBBB (QRS duration between 100 and 119 ms) can also be seen in apparently healthy persons, and in contrast to complete RBBB, it appears to be less common with advancing age. In a study of 43,401 Swiss military conscripts (mean age 19.1 years), incomplete RBBB was the most common ECG abnormality, seen in 13.5 percent of the cohort, while among 18,441 participants (mean age 50.1 years) in the Copenhagen City Heart Study, 3.4 percent had an incomplete RBBB [12,13]. ETIOLOGY The right bundle branch is vulnerable to stretch and trauma for two-thirds of its course when it is near the subendocardial surface ( figure 1). Conduction in the right bundle can be compromised by both structural and functional factors. Structural heart disease Cardiac conditions that can cause RBBB include the following: Chronically increased right ventricular pressure, as in cor pulmonale, which may also be associated with electrocardiographic findings of right ventricular hypertrophy ( waveform 2). (See "Pulmonary hypertension due to lung disease and/or hypoxemia (group 3 pulmonary hypertension): Epidemiology, pathogenesis, and diagnostic evaluation in adults", section on 'Diagnosis'.) A sudden increase in right ventricular pressure with stretch, as in pulmonary embolism. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Electrocardiography'.) Myocardial ischemia, infarction, or inflammation (as in myocarditis). (See "Conduction abnormalities after myocardial infarction" and "Clinical manifestations and diagnosis of myocarditis in adults", section on 'Electrocardiogram'.) Other less common causes of RBBB include hypertension, cardiomyopathies, and congenital heart disease. RBBB can also result from idiopathic progressive cardiac conduction disease (also called Lenegre's disease or Lev's disease) [8,14,15]. (See "Etiology of atrioventricular block", section on 'Idiopathic'.) https://www.uptodate.com/contents/right-bundle-branch-block/print 3/27 7/5/23, 10:36 AM Right bundle branch block - UpToDate Iatrogenic RBBB RBBB can also be caused by procedures and interventions: Right heart catheter insertion results in transient RBBB in approximately 5 percent of cases. In this setting, RBBB is related to minor catheter trauma to the conduction system, which is usually transient and relieved by removal of the catheter. (See "Pulmonary artery catheterization: Indications, contraindications, and complications in adults", section on 'Insertion'.) Nonsurgical septal reduction therapy with ethanol ablation, used in patients with hypertrophic cardiomyopathy and left ventricular outflow tract obstruction, results in RBBB in approximately 50 percent of cases. (See "Hypertrophic cardiomyopathy: Management of patients with outflow tract obstruction", section on 'Septal reduction therapy'.) Functional RBBB RBBB may be functional, as a result of a long preceding R-R interval following by a short cycle ("rate-related bundle branch block"). Functional RBBB may be sustained if, after the initial aberration, the impulse down the left bundle reenters the right bundle branch rendering it again refractory, and this pattern repeats for several cycles. Ventricular tachycardia may mimic RBBB, as in idiopathic left ventricular tachycardia with RBBB morphology and left axis deviation (Belhassen type) or in bundle branch reentrant ventricular tachycardia. (See "Ventricular tachycardia in the absence of apparent structural heart disease" and "Bundle branch reentrant ventricular tachycardia".) Hyperkalemia can depress conduction in the His-Purkinje system and rarely causes RBBB [16,17]. (See "ECG tutorial: Miscellaneous diagnoses", section on 'Hyperkalemia'.) Pseudo RBBB pattern Some patients with uncommon primary ventricular arrhythmia syndromes (ie, Brugada syndrome, arrhythmogenic right ventricular cardiomyopathy) have ECG patterns similar to RBBB. However, these patients have distinct types of right ventricular myocardial disease that produce an ECG pattern similar to RBBB and should not be considered to have true RBBB. (See 'Differential diagnosis' below and "Brugada syndrome: Clinical presentation, diagnosis, and evaluation" and "Arrhythmogenic right ventricular cardiomyopathy: Diagnostic evaluation and diagnosis".) ECG FINDINGS AND DIAGNOSIS To best understand the electrocardiographic (ECG) findings in RBBB, one should have a basic understanding of the vectors involved in electrocardiography as well as the basic conventions of https://www.uptodate.com/contents/right-bundle-branch-block/print 4/27 7/5/23, 10:36 AM Right bundle branch block - UpToDate nomenclature used in electrocardiography. This information is presented elsewhere. (See "ECG tutorial: Intraventricular block", section on 'Right bundle branch block'.) Most of the ECG findings with RBBB are related to the QRS complex. However, some accompanying changes may also be seen in the ST segment and T wave. QRS complex A task force from the American Heart Association, the American College of Cardiology, and the Heart Rhythm Society has defined the electrocardiographic features of RBBB [18]. These criteria incorporate the activation forces described above and include: QRS duration greater than or equal to 120 ms in adults. Rsr', rsR', or rSR' in leads V1 or V2. The R' or r' deflection is usually wider than the initial R wave. In a minority of patients, a wide and often notched R-wave pattern may be seen in lead V1 and/or V2. S wave of greater duration than R wave or greater than 40 ms in leads I and V6 in adults. Normal R peak time in leads V5 and V6 but greater than 50 ms in lead V1 (associated with the R' wave). The QRS morphology in patients with RBBB will vary depending on the position on the heart within the thorax as well as with other cardiac conditions that alter conduction (eg, prior anterior myocardial infarction). ST segment and T waves Accompanying ST-segment and T-wave changes are due to an altered sequence of repolarization. The ST-segment change is usually small, but, when present, it is discordant (ie, has an axis in the opposite direction) to the terminal mean QRS spatial vector. The T wave also tends to be discordant to the terminal conduction disturbance, resulting in inverted T waves in the right precordial leads (where there is a terminal R' wave) and upright T waves in the left precordial leads (where there is a terminal S wave). Other diagnostic considerations There are several other diagnostic considerations in the ECG interpretation of RBBB: RBBB does not interfere with the diagnosis of coexistent myocardial infarction on the basis of the usual Q- and R-wave criteria, since the vectorial forces of the initial 30 to 40 ms are essentially normal [19]. Increased right ventricular pressures may cause the initial vector to swing superiorly and posteriorly, which may produce Q waves in the inferior and right precordial leads. This can occasionally simulate the changes seen with inferior and anterior myocardial infarction. https://www.uptodate.com/contents/right-bundle-branch-block/print 5/27 7/5/23, 10:36 AM Right bundle branch block - UpToDate There is a low sensitivity in the voltage criteria for left ventricular enlargement due to the late anterior forces and due to the reduction of amplitude of the S wave in the right precordial leads [20,21]. DIFFERENTIAL DIAGNOSIS While RBBB has a fairly characteristic appearance on ECG, there are other conditions in which the ECG may have a similar appearance that need to be excluded prior to the diagnosis of RBBB. Incomplete RBBB Delay in the right bundle conduction ranges from trivial to severe, producing a similar spectrum displacement and duration of the rightward terminal conduction disturbance. RBBB is arbitrarily said to be "complete" when the QRS duration is 120 ms or more, and "incomplete" when it is between 100 and 119 ms. A RBBB pattern with a QRS duration less than 100 ms may be a normal variant, presumably reflecting a slight delay in the terminal posterobasal forces in some individuals. Ventricular tachycardia and accelerated idioventricular rhythm If the dominant ventricular rhythm originates from a pacemaker in the ventricle, the QRS will be widened and can have the appearance of a RBBB. However, both ventricular tachycardia (heart rate greater than 100 beats per minute) ( waveform 3) and accelerated idioventricular rhythm (heart rate between 60 and 100 beats per minute) ( waveform 4) are associated with atrioventricular (AV) dissociation, which should distinguish the rhythm from a supraventricular rhythm with aberrant conduction seen with RBBB. (See "Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation" and "ECG tutorial: Ventricular arrhythmias", section on 'Accelerated idioventricular rhythm'.) Ventricular pacing Ventricular pacing from the right ventricular apex typically results in a QRS complex resembling that seen with left bundle branch block (LBBB) on the surface ECG. However, the QRS complex resulting from biventricular pacing is more complicated and may sometimes give the appearance of a RBBB ( waveform 5). When a paced QRS complex has a RBBB morphology in the absence of an LV lead, the possibility of RV lead perforation or inadvertent LV lead placement must be considered. In nearly all patients, however, the presence of pacemaker spikes preceding the QRS complex differentiates a paced complex from a RBBB. Brugada syndrome The Brugada syndrome is associated with particular ECG changes and an increased risk of sudden death. The ECG pattern of Brugada syndrome occurs in less than 0.2 percent of individuals overall but in as many as 3 to 24 percent of those presenting with idiopathic ventricular fibrillation. (See "Brugada syndrome: Clinical presentation, diagnosis, and evaluation".) https://www.uptodate.com/contents/right-bundle-branch-block/print 6/27 7/5/23, 10:36 AM Right bundle branch block - UpToDate The ECG in Brugada syndrome consists of a pseudo-RBBB pattern and ST-segment elevation in leads V1 to V3 ( waveform 6) [22-24]. The ST-segment elevation usually slopes downward, and the T wave is inverted. The widened S wave in left lateral leads that is characteristic of typical RBBB is absent in most patients with Brugada syndrome. This observation suggests that there is a high takeoff of the ST segment in the right precordium (ie, a "J" wave) rather than a true RBBB [23]. In some patients, the ST-segment abnormalities are transient but can be exposed by a sodium channel blocker, such as flecainide, ajmaline, or procainamide [25,26]. PROGNOSIS The prognosis in patients with RBBB is related largely to the presence, type, and severity of underlying heart disease or associated conduction abnormalities: In patients with known or suspected cardiovascular disease (CVD), RBBB is an independent predictor of all-cause mortality. Several large cohort studies have shown an increase in mortality among patients with CVD and complete RBBB [9,27-29]. As an example, among 12,346 females with CVD (excluding those with LBBB) who participated in the Women's Health Initiative trial, there was a significantly greater risk of death from coronary heart disease (adjusted hazard ratio [HR] 1.62, 95% CI 1.08-2.43) but not overall mortality (adjusted HR 1.10, 95% CI 0.84-1.44) among females with RBBB compared with no BBB [9]. The presence of RBBB after a myocardial infarction is also associated with an increase in mortality. (See "Conduction abnormalities after myocardial infarction", section on 'Bundle branch block'.) The presence of a RBBB in the setting of an acute myocardial infarction is associated with a significant increase in mortality, even when thrombolytic therapy has been administered. This issue is discussed separately. (See "Conduction abnormalities after myocardial infarction".) In patients with heart failure (HF), there is an association between RBBB and higher mortality compared with those without a bundle branch block. In one study of 1888 patients with a recent HF hospitalization, RBBB was associated with worse long-term outcomes over a follow-up of four years [30]. This was also seen in 2907 consecutive patients admitted to an intensive care unit with decompensated HF [31]. Patients who also have type II second-degree atrioventricular (AV) block or multi-fascicular block generally have more significant myocardial disease and a guarded prognosis. (See https://www.uptodate.com/contents/right-bundle-branch-block/print 7/27 7/5/23, 10:36 AM Right bundle branch block - UpToDate "Second-degree atrioventricular block: Mobitz type II" and "Chronic bifascicular blocks".) Long-term outcomes are generally excellent in patients with RBBB and without apparent heart disease, although some reports have suggested an increase in all-cause and cardiac mortality in persons with a RBBB [8,11,32-39]. In a primary prevention study from Sweden in which 7392 middle-aged males were followed for 28 years, males with RBBB had a nonsignificant increase in progression to high-degree AV block and no increase in myocardial infarction (MI) or coronary or all-cause mortality compared with males without bundle branch block [32]. Similarly, among 53,197 females free of CVD (excluding those with LBBB) upon entry into the Women's Health Initiative trial, there was no significant increase in either death from coronary heart disease (adjusted HR 1.31, 95% CI 0.77-2.23) or death from any cause (adjusted HR 0.89, 95% CI 0.67-1.19) [9]. In contrast, among 18,441 participants in the Copenhagen City Heart Study without a prior MI, HF, or LBBB who were followed for over 20 years, persons with RBBB had significantly greater all-cause and cardiovascular mortality compared with those without RBBB (adjusted HR 1.31, 95% CI 1.11-1.54 for all-cause mortality and 1.87, 95% CI 1.48-2.36 for cardiovascular mortality, respectively) [13]. Similarly, among 8527 participants in the NHANES study (87 percent White Americans, 53 percent female, 16 percent with coronary heart disease at baseline), cardiovascular mortality was significantly higher in those with RBBB at baseline (adjusted HR 1.9 compared with those without BBB, 95% CI 1.2-3.0) [10]. A study evaluated 22,806 patients without known cardiovascular disease undergoing exercise stress testing. In that study, RBBB was associated with increased risk of all-cause mortality after adjusting for clinical risk factors [39]. There was also an association between RBBB and presence of hypertension and decreased exercise capacity. In a 2015 systematic review and meta-analysis, which included six cohorts free of known CVD (1019 patients with RBBB and 95,079 without RBBB), RBBB with associated with greater all-cause mortality (HR 1.17, 95% CI 1.03-1.33), although there was a moderate amount of heterogeneity identified between the studies [40]. In the largest single study evaluating 202,268 subjects >40 years of age in a primary care population in Copenhagen, the presence of RBBB was associated with increased risk of pacemaker requirement in both males and females over a mean follow up of 7.8 years. In addition, RBBB was associated with an increased risk of HF in both males and females. In this study, RBBB was associated with cardiovascular mortality in males but not females (HR 1.22, 95% CI 1.07-1.39) [11]. https://www.uptodate.com/contents/right-bundle-branch-block/print 8/27 7/5/23, 10:36 AM Right bundle branch block - UpToDate EVALUATION AND TREATMENT Patients with isolated chronic RBBB (complete or incomplete) are generally asymptomatic and do not require further diagnostic evaluation for RBBB or placement of a pacemaker or any other specific therapy. However, a pacemaker may be needed if syncope occurs, particularly if other conduction disturbances are present, such as third-degree or type II second-degree AV block. In a patient with a new RBBB, a careful history should be taken focused on potential causes of RV stretch/strain (eg, pulmonary hypertension, obstructive sleep apnea, pulmonary embolism); if there is suspicion of pulmonary disease potentially impacting the RV, an echocardiogram should be obtained for further evaluation. CRT is indicated in selected patients with RBBB and HF, although the evidence for such therapy is more limited than that for patients with LBBB and HF [41-43]. (See "Cardiac resynchronization therapy in heart failure: Indications and choice of system" and "Cardiac resynchronization therapy in heart failure: Indications and choice of system", section on 'Rationale for CRT'.) Patients with pre-existing left bundle branch block who require right heart catheter placement are at risk for complete heart block if RBBB develops. Although the risk is low and complete heart block is usually transient, catheter insertion should not be undertaken in patients with LBBB without the ability to institute immediate transcutaneous or transvenous cardiac pacing. (See "Pulmonary artery catheterization: Indications, contraindications, and complications in adults", section on 'Insertion'.) SUMMARY AND RECOMMENDATIONS Anatomy and electrophysiology Right bundle branch block (RBBB) results when normal electrical activity in the His-Purkinje system is interrupted, thereby altering the normal sequence of activation, resulting in the characteristic ECG appearance of a widened QRS complex and changes in the directional vectors of the R and S waves ( waveform 1). (See 'Anatomy and electrophysiology' above and 'ECG findings and diagnosis' above.) The bundle of His divides at the juncture of the fibrous and muscular boundaries of the intraventricular septum into the left and right bundle branches ( figure 1). The right bundle branch is a long, thin, discrete structure that courses down the right side of interventricular septum, receiving most of its blood supply from the left anterior descending coronary artery, although in most patients, it also receives some collateral supply from either the right or circumflex coronary systems. (See 'Anatomy and electrophysiology' above.) https://www.uptodate.com/contents/right-bundle-branch-block/print 9/27 7/5/23, 10:36 AM Right bundle branch block - UpToDate Epidemiology The prevalence of RBBB, which appears to increase with age, has been estimated between 0.2 to 0.8 percent of the general population. (See 'Epidemiology' above.) Causes Various clinical conditions are associated with the development of RBBB or other electrocardiographic findings similar to RBBB (see 'Etiology' above): RBBB is associated with several types of structural heart disease including cor pulmonale, pulmonary embolism, myocardial ischemia/infarction, myocarditis, hypertension, and congenital heart disease. (See 'Structural heart disease' above.) RBBB can develop iatrogenically in patients undergoing right heart catheterization or ethanol ablation of the basal ventricular septum. (See 'Iatrogenic RBBB' above.) Diagnostic features The electrocardiographic features of the QRS complex which define RBBB in adults include QRS duration greater than or equal to 120 ms, rsr', rsR', or rSR' in leads V1 or V2, S wave of greater duration than R wave or greater than 40 ms in leads I and V6, and normal R peak time in leads V5 and V6 but greater than 50 ms in lead V1. Accompanying ST-segment and T-wave changes are due to an altered sequence of repolarization. (See 'ECG findings and diagnosis' above.) Differential diagnosis Ventricular rhythms, ventricular pacing, and the Brugada syndrome, conditions in which the QRS complex has a similar morphology to RBBB, need to be excluded prior to making the diagnosis of RBBB. (See 'Differential diagnosis' above.) Impact on diagnosis of myocardial infarction The presence of RBBB does not interfere with the diagnosis of coexistent myocardial infarction on the basis of the usual Q- and R- wave criteria, since the vectorial forces of the initial 30 to 40 ms are essentially normal. (See 'Other diagnostic considerations' above.) Prognosis The prognosis in patients with RBBB is related largely to the type and severity of any concurrent underlying heart disease and to the possible presence of other conduction disturbances. Long-term outcomes are generally excellent in patients without apparent heart disease, while those with RBBB in the setting of underlying cardiac disease generally have worse outcomes than those without bundle branch block. (See 'Prognosis' above.) Management For asymptomatic patients with an isolated RBBB (complete or incomplete) and no other evidence of cardiac disease, no further diagnostic evaluation or specific therapy is required. However, permanent pacemaker insertion is indicated for patients with RBBB who develop symptomatic conduction system disturbances, such as third-degree or https://www.uptodate.com/contents/right-bundle-branch-block/print 10/27 7/5/23, 10:36 AM Right bundle branch block - UpToDate type II second-degree AV block that is not associated with a reversible or transient condition. (See 'Evaluation and treatment' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Horowitz LN, Alexander JA, Edmunds LH Jr. Postoperative right bundle branch block: identification of three levels of block. Circulation 1980; 62:319. 2. Josephson, ME. Clinical Cardiac Electrophysiology: Techniques and Interpretations, 2nd, Lea & Febiger, Philadelphia 1993. 3. Watt TB Jr, Pruitt RD. Focal lesions in the canine bundle of His. 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Curr Opin Cardiol 2002; 17:19. 25. Krishnan SC, Josephson ME. ST segment elevation induced by class IC antiarrhythmic agents: underlying electrophysiologic mechanisms and insights into drug-induced proarrhythmia. J Cardiovasc Electrophysiol 1998; 9:1167. 26. Brugada R, Brugada J, Antzelevitch C, et al. Sodium channel blockers identify risk for sudden death in patients with ST-segment elevation and right bundle branch block but structurally normal hearts. Circulation 2000; 101:510. 27. Hesse B, Diaz LA, Snader CE, et al. Complete bundle branch block as an independent predictor of all-cause mortality: report of 7,073 patients referred for nuclear exercise testing. Am J Med 2001; 110:253. 28. Freedman RA, Alderman EL, Sheffield LT, et al. Bundle branch block in patients with chronic coronary artery disease: angiographic correlates and prognostic significance. J Am Coll Cardiol 1987; 10:73. 29. Sumner G, Salehian O, Yi Q, et al. The prognostic significance of bundle branch block in high-risk chronic stable vascular disease patients: a report from the HOPE trial. J Cardiovasc Electrophysiol 2009; 20:781. 30. Barsheshet A, Goldenberg I, Garty M, et al. Relation of bundle branch block to long-term (four-year) mortality in hospitalized patients with systolic heart failure. Am J Cardiol 2011; 107:540. 31. McCullough PA, Hassan SA, Pallekonda V, et al. Bundle branch block patterns, age, renal dysfunction, and heart failure mortality. Int J Cardiol 2005; 102:303. 32. Eriksson P, Wilhelmsen L, Rosengren A. Bundle-branch block in middle-aged men: risk of complications and death over 28 years. The Primary Prevention Study in G teborg, Sweden. Eur Heart J 2005; 26:2300. 33. Taniguchi M, Nakano H, Kuwahara K, et al. Prognostic and clinical significance of newly acquired complete right bundle branch block in Japan Airline pilots. Intern Med 2003; 42:21. https://www.uptodate.com/contents/right-bundle-branch-block/print 13/27 7/5/23, 10:36 AM Right bundle branch block - UpToDate 34. Kim JH, Noseworthy PA, McCarty D, et al. Significance of electrocardiographic right bundle branch block in trained athletes. Am J Cardiol 2011; 107:1083. 35. Thrainsdottir IS, Hardarson T, Thorgeirsson G, et al. The epidemiology of right bundle branch block and its association with cardiovascular morbidity the Reykjavik Study. Eur Heart J 1993; 14:1590. 36. Fahy GJ, Pinski SL, Miller DP, et al. Natural history of isolated bundle branch block. Am J Cardiol 1996; 77:1185. 37. Miller WL, Hodge DO, Hammill SC. Association of uncomplicated electrocardiographic conduction blocks with subsequent cardiac morbidity in a community-based population (Olmsted County, Minnesota). Am J Cardiol 2008; 101:102. 38. Aro AL, Anttonen O, Tikkanen JT, et al. Intraventricular conduction delay in a standard 12- lead electrocardiogram as a predictor of mortality in the general population. Circ Arrhythm Electrophysiol 2011; 4:704. 39. Gaba P, Pedrotty D, DeSimone CV, et al. Mortality in Patients With Right Bundle-Branch Block in the Absence of Cardiovascular Disease. J Am Heart Assoc 2020; 9:e017430. 40. Xiong Y, Wang L, Liu W, et al. The Prognostic Significance of Right Bundle Branch Block: A Meta-analysis of Prospective Cohort Studies. Clin Cardiol 2015; 38:604. 41. Bilchick KC, Kamath S, DiMarco JP, Stukenborg GJ. Bundle-branch block morphology and other predictors of outcome after cardiac resynchronization therapy in Medicare patients. Circulation 2010; 122:2022. 42. Rickard J, Kumbhani DJ, Gorodeski EZ, et al. Cardiac resynchronization therapy in non-left bundle branch block morphologies. Pacing Clin Electrophysiol 2010; 33:590. 43. Egoavil CA, Ho RT, Greenspon AJ, Pavri BB. Cardiac resynchronization therapy in patients with right bundle branch block: analysis of pooled data from the MIRACLE and Contak CD trials. Heart Rhythm 2005; 2:611. Topic 915 Version 35.0 https://www.uptodate.com/contents/right-bundle-branch-block/print 14/27 7/5/23, 10:36 AM Right bundle branch block - UpToDate GRAPHICS Normal conduction system Schematic representation of the normal intraventricular conduction system (His- Purkinje system). The Bundle of His divides into the left bundle branch and right bundle branch. The left bundle branch divides into anterior, posterior, and, in some cases, median fascicles. AV: atrioventricular; RA: right atrium; LA: left atrium; RV: right ventricle; LV: left ventricle. Graphic 63340 Version 6.0 https://www.uptodate.com/contents/right-bundle-branch-block/print 15/27 7/5/23, 10:36 AM Right bundle branch block - UpToDate Electrocardiogram (ECG) showing common right bundle branch block (RBBB) Electrocardiogram showing characteristic changes in the precordial leads in complete RBBB. The asynchronous activation of the two ventricles increases the QRS duration (0.13 seconds). The terminal forces are rightward and anterior due to the delayed activation of the right ventricle, resulting in an rsR' pattern in the anterior-posterior lead V1 and a wide negative S wave in the left-right lead V6 (and, not shown, in lead I). Courtesy of Ary Goldberger, MD. Graphic 64393 Version 7.0 Normal ECG https://www.uptodate.com/contents/right-bundle-branch-block/print 16/27 7/5/23, 10:36 AM Right bundle branch block - UpToDate Normal electrocardiogram showing normal sinus rhythm at a rate of 75 beats/minute, a PR interval of 0.14 seconds, a QRS interval of 0.10 seconds, and a QRS axis of approximately 75 . Courtesy of Ary Goldberger, MD. Graphic 76183 Version 4.0 https://www.uptodate.com/contents/right-bundle-branch-block/print 17/27 7/5/23, 10:36 AM Right bundle branch block - UpToDate Coronary artery anatomy Graphic 70956 Version 2.0 https://www.uptodate.com/contents/right-bundle-branch-block/print 18/27 7/5/23, 10:36 AM Right bundle branch block - UpToDate Relationship between fast sodium-mediated myocardial action potential and surface electrocardiogram Each phase of the myocardial action potential (numbers, upper panel) corresponds to a deflection or interval on the surface ECG (lower panel). Phase 4, the resting membrane potential, is responsible for the TQ segment; this segment has a prominent role in the ECG manifestations of ischemia during exercise testing. ECG: electrocardiogram. Graphic 64133 Version 4.0 https://www.uptodate.com/contents/right-bundle-branch-block/print 19/27 7/5/23, 10:36 AM Right bundle branch block - UpToDate Incidence of bundle branch block increases with age In men, the cumulative incidence of right (RBBB), left (LBBB), or any bundle branch block (BBB) increases with age (upper panel). The lower panel shows the survival curve for 67-year-old men followed up for 13 years; there is no significant difference in survival between those with and without BBB. Data from Eriksson P, Hansson D, Eriksson H, et al, Circulation 1998; 98: 2494. Graphic 70445 Version 2.0 https://www.uptodate.com/contents/right-bundle-branch-block/print 20/27 7/5/23, 10:36 AM Right bundle branch block - UpToDate Electrocardiogram showing right ventricular hypertrophy Right ventricular hypertrophy due, in this case, to idiopathic pulmonary arterial hypertension. The characteristic features include marked right axis deviation (+210 which is equal to -150 ), tall R wave in V1 (as part of a qR complex), delayed precordial transition zone with prominent S waves in leads V5 and V6, inverted T waves and ST depression in V1 to V3 consistent with right ventricular "strain," and peaked P waves in lead II consistent with concomitant right atrial enlargement. Courtesy of Ary Goldberger, MD. Graphic 67622 Version 5.0 Normal ECG https://www.uptodate.com/contents/right-bundle-branch-block/print 21/27 7/5/23, 10:36 AM Right bundle branch block - UpToDate Normal electrocardiogram showing normal sinus rhythm at a rate of 75 beats/minute, a PR interval of 0.14 seconds, a QRS interval of 0.10 seconds, and a QRS axis of approximately 75 . Courtesy of Ary Goldberger, MD. Graphic 76183 Version 4.0

agents: underlying electrophysiologic mechanisms and insights into drug-induced proarrhythmia. J Cardiovasc Electrophysiol 1998; 9:1167. 26. Brugada R, Brugada J, Antzelevitch C, et al. Sodium channel blockers identify risk for sudden death in patients with ST-segment elevation and right bundle branch block but structurally normal hearts. Circulation 2000; 101:510. 27. Hesse B, Diaz LA, Snader CE, et al. Complete bundle branch block as an independent predictor of all-cause mortality: report of 7,073 patients referred for nuclear exercise testing. Am J Med 2001; 110:253. 28. Freedman RA, Alderman EL, Sheffield LT, et al. Bundle branch block in patients with chronic coronary artery disease: angiographic correlates and prognostic significance. J Am Coll Cardiol 1987; 10:73. 29. Sumner G, Salehian O, Yi Q, et al. The prognostic significance of bundle branch block in high-risk chronic stable vascular disease patients: a report from the HOPE trial. J Cardiovasc Electrophysiol 2009; 20:781. 30. Barsheshet A, Goldenberg I, Garty M, et al. Relation of bundle branch block to long-term (four-year) mortality in hospitalized patients with systolic heart failure. Am J Cardiol 2011; 107:540. 31. McCullough PA, Hassan SA, Pallekonda V, et al. Bundle branch block patterns, age, renal dysfunction, and heart failure mortality. Int J Cardiol 2005; 102:303. 32. Eriksson P, Wilhelmsen L, Rosengren A. Bundle-branch block in middle-aged men: risk of complications and death over 28 years. The Primary Prevention Study in G teborg, Sweden. Eur Heart J 2005; 26:2300. 33. Taniguchi M, Nakano H, Kuwahara K, et al. Prognostic and clinical significance of newly acquired complete right bundle branch block in Japan Airline pilots. Intern Med 2003; 42:21. https://www.uptodate.com/contents/right-bundle-branch-block/print 13/27 7/5/23, 10:36 AM Right bundle branch block - UpToDate 34. Kim JH, Noseworthy PA, McCarty D, et al. Significance of electrocardiographic right bundle branch block in trained athletes. Am J Cardiol 2011; 107:1083. 35. Thrainsdottir IS, Hardarson T, Thorgeirsson G, et al. The epidemiology of right bundle branch block and its association with cardiovascular morbidity the Reykjavik Study. Eur Heart J 1993; 14:1590. 36. Fahy GJ, Pinski SL, Miller DP, et al. Natural history of isolated bundle branch block. Am J Cardiol 1996; 77:1185. 37. Miller WL, Hodge DO, Hammill SC. Association of uncomplicated electrocardiographic conduction blocks with subsequent cardiac morbidity in a community-based population (Olmsted County, Minnesota). Am J Cardiol 2008; 101:102. 38. Aro AL, Anttonen O, Tikkanen JT, et al. Intraventricular conduction delay in a standard 12- lead electrocardiogram as a predictor of mortality in the general population. Circ Arrhythm Electrophysiol 2011; 4:704. 39. Gaba P, Pedrotty D, DeSimone CV, et al. Mortality in Patients With Right Bundle-Branch Block in the Absence of Cardiovascular Disease. J Am Heart Assoc 2020; 9:e017430. 40. Xiong Y, Wang L, Liu W, et al. The Prognostic Significance of Right Bundle Branch Block: A Meta-analysis of Prospective Cohort Studies. Clin Cardiol 2015; 38:604. 41. Bilchick KC, Kamath S, DiMarco JP, Stukenborg GJ. Bundle-branch block morphology and other predictors of outcome after cardiac resynchronization therapy in Medicare patients. Circulation 2010; 122:2022. 42. Rickard J, Kumbhani DJ, Gorodeski EZ, et al. Cardiac resynchronization therapy in non-left bundle branch block morphologies. Pacing Clin Electrophysiol 2010; 33:590. 43. Egoavil CA, Ho RT, Greenspon AJ, Pavri BB. Cardiac resynchronization therapy in patients with right bundle branch block: analysis of pooled data from the MIRACLE and Contak CD trials. Heart Rhythm 2005; 2:611. Topic 915 Version 35.0 https://www.uptodate.com/contents/right-bundle-branch-block/print 14/27 7/5/23, 10:36 AM Right bundle branch block - UpToDate GRAPHICS Normal conduction system Schematic representation of the normal intraventricular conduction system (His- Purkinje system). The Bundle of His divides into the left bundle branch and right bundle branch. The left bundle branch divides into anterior, posterior, and, in some cases, median fascicles. AV: atrioventricular; RA: right atrium; LA: left atrium; RV: right ventricle; LV: left ventricle. Graphic 63340 Version 6.0 https://www.uptodate.com/contents/right-bundle-branch-block/print 15/27 7/5/23, 10:36 AM Right bundle branch block - UpToDate Electrocardiogram (ECG) showing common right bundle branch block (RBBB) Electrocardiogram showing characteristic changes in the precordial leads in complete RBBB. The asynchronous activation of the two ventricles increases the QRS duration (0.13 seconds). The terminal forces are rightward and anterior due to the delayed activation of the right ventricle, resulting in an rsR' pattern in the anterior-posterior lead V1 and a wide negative S wave in the left-right lead V6 (and, not shown, in lead I). Courtesy of Ary Goldberger, MD. Graphic 64393 Version 7.0 Normal ECG https://www.uptodate.com/contents/right-bundle-branch-block/print 16/27 7/5/23, 10:36 AM Right bundle branch block - UpToDate Normal electrocardiogram showing normal sinus rhythm at a rate of 75 beats/minute, a PR interval of 0.14 seconds, a QRS interval of 0.10 seconds, and a QRS axis of approximately 75 . Courtesy of Ary Goldberger, MD. Graphic 76183 Version 4.0 https://www.uptodate.com/contents/right-bundle-branch-block/print 17/27 7/5/23, 10:36 AM Right bundle branch block - UpToDate Coronary artery anatomy Graphic 70956 Version 2.0 https://www.uptodate.com/contents/right-bundle-branch-block/print 18/27 7/5/23, 10:36 AM Right bundle branch block - UpToDate Relationship between fast sodium-mediated myocardial action potential and surface electrocardiogram Each phase of the myocardial action potential (numbers, upper panel) corresponds to a deflection or interval on the surface ECG (lower panel). Phase 4, the resting membrane potential, is responsible for the TQ segment; this segment has a prominent role in the ECG manifestations of ischemia during exercise testing. ECG: electrocardiogram. Graphic 64133 Version 4.0 https://www.uptodate.com/contents/right-bundle-branch-block/print 19/27 7/5/23, 10:36 AM Right bundle branch block - UpToDate Incidence of bundle branch block increases with age In men, the cumulative incidence of right (RBBB), left (LBBB), or any bundle branch block (BBB) increases with age (upper panel). The lower panel shows the survival curve for 67-year-old men followed up for 13 years; there is no significant difference in survival between those with and without BBB. Data from Eriksson P, Hansson D, Eriksson H, et al, Circulation 1998; 98: 2494. Graphic 70445 Version 2.0 https://www.uptodate.com/contents/right-bundle-branch-block/print 20/27 7/5/23, 10:36 AM Right bundle branch block - UpToDate Electrocardiogram showing right ventricular hypertrophy Right ventricular hypertrophy due, in this case, to idiopathic pulmonary arterial hypertension. The characteristic features include marked right axis deviation (+210 which is equal to -150 ), tall R wave in V1 (as part of a qR complex), delayed precordial transition zone with prominent S waves in leads V5 and V6, inverted T waves and ST depression in V1 to V3 consistent with right ventricular "strain," and peaked P waves in lead II consistent with concomitant right atrial enlargement. Courtesy of Ary Goldberger, MD. Graphic 67622 Version 5.0 Normal ECG https://www.uptodate.com/contents/right-bundle-branch-block/print 21/27 7/5/23, 10:36 AM Right bundle branch block - UpToDate Normal electrocardiogram showing normal sinus rhythm at a rate of 75 beats/minute, a PR interval of 0.14 seconds, a QRS interval of 0.10 seconds, and a QRS axis of approximately 75 . Courtesy of Ary Goldberger, MD. Graphic 76183 Version 4.0 https://www.uptodate.com/contents/right-bundle-branch-block/print 22/27 7/5/23, 10:36 AM Right bundle branch block - UpToDate Single lead electrocardiogram (ECG) showing monomorphic ventricular tachycardia Three or more successive ventricular beats are defined as ventricular tachycardia (VT). This VT is monomorphic since all of the QRS complexes have an identical appearance. Although the P waves are not distinct, they can be seen altering the QRS complex and ST-T waves in an irregular fashion, indicating the absence of a relationship between the P waves and the QRS complexes (ie, AV dissociation is present). AV: atrioventricular. Graphic 63176 Version 7.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/right-bundle-branch-block/print 23/27 7/5/23, 10:36 AM Right bundle branch block - UpToDate ECG 12-lead accelerated idioventricular rhythm 12-lead ECG showing idioventricular rhythm with AV dissociation and wide QRS complexes occurring at a rate faster than the sinus rate but slower than 100 bpm (hence not meeting the criteria for ventricular tachycardia). ECG: electrocardiogram. Graphic 118943 Version 2.0 https://www.uptodate.com/contents/right-bundle-branch-block/print 24/27 7/5/23, 10:36 AM Right bundle branch block - UpToDate Single lead electrocardiogram (ECG) showing biventricular pacing Courtesy of Dr. Jordan Prutkin. Graphic 64812 Version 4.0 https://www.uptodate.com/contents/right-bundle-branch-block/print 25/27 7/5/23, 10:36 AM Right bundle branch block - UpToDate 12-lead electrocardiogram (ECG) from a patient with the Brugada syndrome shows downsloping ST elevation ST segment elevation and T wave inversion in the right precordial leads V1 and V2 (arrows); the QRS is normal. The widened S wave in the left lateral leads (V5 and V6) that is characteristic of right bundle branch block is absent. Courtesy of Rory Childers, MD, University of Chicago. Graphic 64510 Version 10.0 https://www.uptodate.com/contents/right-bundle-branch-block/print 26/27 7/5/23, 10:36 AM Right bundle branch block - UpToDate Contributor Disclosures William H Sauer, MD Grant/Research/Clinical Trial Support: Biosense-Webster [Catheter ablation]; Boston Scientific [Catheter ablation]. All of the relevant financial relationships listed have been mitigated. Mark S Link, MD No relevant financial relationship(s) with ineligible companies to disclose. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/right-bundle-branch-block/print 27/27

7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Second-degree atrioventricular block: Mobitz type I (Wenckebach block) : William H Sauer, MD : Mark S Link, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Dec 06, 2022. INTRODUCTION Atrioventricular (AV) block is defined as a delay or interruption in the transmission of an impulse from the atria to the ventricles due to an anatomic or functional impairment in the conduction system. The conduction disturbance can be transient or permanent, with conduction that is delayed, intermittent, or absent. Commonly used terminology includes: First-degree AV block Delayed conduction from the atrium to the ventricle (defined as a prolonged PR interval of >200 ms) without interruption in atrial to ventricular conduction. Second-degree AV block Intermittent atrial conduction to the ventricle, often in a regular pattern (eg, 2:1, 3:2), or higher degrees of block, which are further classified into Mobitz type I (Wenckebach) and Mobitz type II second-degree AV block. Third-degree (complete AV) block No atrial impulses conduct to the ventricle. High-grade AV block Intermittent atrial conduction to the ventricle with two or more consecutive blocked P waves but without complete AV block. The clinical presentation, evaluation, and management of Mobitz type I second-degree AV block will be reviewed here. The etiology of AV block in general, and the management of other specific types of AV block, are discussed separately. (See "Etiology of atrioventricular block" and "First- degree atrioventricular block" and "Second-degree atrioventricular block: Mobitz type II" and https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 1/31 7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate "Third-degree (complete) atrioventricular block" and "Congenital third-degree (complete) atrioventricular block".) DEFINITIONS In second-degree AV block, some atrial impulses fail to reach the ventricles. Wenckebach described progressive delay between atrial and ventricular contraction and the eventual failure of a P wave to reach the ventricles [1]. Mobitz subsequently divided second-degree AV block into two subtypes, as determined by the findings on the electrocardiogram (ECG) [2]: Mobitz type I second-degree AV block ( waveform 1), in which progressive PR interval prolongation precedes a nonconducted P wave. The first P wave after block conducts to the ventricle with a shorter PR interval compared with the last P wave before block. Mobitz type II second-degree AV block ( waveform 2), in which the PR interval remains unchanged prior to a P wave that fails to conduct to the ventricle. High-grade AV block, in which two or more consecutive P waves are nonconducted. In contrast to third-degree or complete heart block ( waveform 3), however, some P waves continue to be conducted to the ventricle. Mobitz type I and Mobitz type II second-degree AV block cannot be differentiated from the ECG when 2:1 AV block is present. In this situation, every other P wave is nonconducted, and there is no opportunity to observe for possible PR prolongation that is characteristic of Mobitz type I second-degree AV block. (See 'ECG findings and diagnostic maneuvers' below.) ETIOLOGY Mobitz type I second-degree AV block can occur in normal subjects and athletes without underlying cardiac pathology. The potential etiologies of Mobitz type I second-degree AV block also include reversible (both pathologic and iatrogenic) and idiopathic causes that are similar to other degrees of AV block ( table 1). Common potentially reversible causes include: Pathologic Myocardial ischemia (acute or chronic) involving the conduction system, cardiomyopathy (eg, amyloidosis, sarcoidosis), myocarditis (eg, Lyme disease), endocarditis with abscess formation, hyperkalemia, and hypervagotonia. Iatrogenic Medication-related (AV nodal blocking medications), post-cardiac surgery, post-catheter ablation, post-transcatheter aortic valve implantation. https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 2/31 7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate In persons who are not highly conditioned athletes in whom no specific reversible cause is identified, the block is often felt to be related to idiopathic progressive cardiac conduction disease with myocardial fibrosis and/or sclerosis that affects the conduction system. (See "Etiology of atrioventricular block".) Normal subjects and athletes Mobitz type I second-degree AV block can occur in individuals who have high vagal tone, such as younger persons or highly conditioned athletes at rest [3-9]. The prognosis is excellent in these settings, as progressive block does not appear to occur [4,6- 8]. Progression to third-degree (complete) AV block has been reported in infants (occurring in 7 of 16 in one study) [10]. Sinus bradycardia and AV conduction abnormalities are often observed in well-trained endurance athletes. As an example, Mobitz type I second-degree AV block has been described in 2 to 10 percent of long-distance runners [9]. These findings may be related to increased parasympathetic activity associated with training (with a disappearance following detraining or after vagolytic or sympathetic maneuvers) or intrinsic AV nodal mechanisms [8,11]. Underlying heart disease Mobitz type I second-degree AV block can occur in patients with intrinsic AV nodal disease, myocarditis (including Chagas disease), acute inferior myocardial infarction or ischemia ( waveform 4), and cardiac surgery. In the majority of patients (approximately 90 percent), the right coronary artery supplies blood to the AV node. Thus, Mobitz type I second-degree AV block (due to ischemia of the AV node) can occur as a complication of an inferior myocardial infarction. The finding of Mobitz type I second-degree AV block in a patient with an inferior myocardial infarction is associated with increased mortality, presumably due to larger infarct size. (See "Conduction abnormalities after myocardial infarction".) Mobitz type I second-degree AV block, typically transient, has been described in approximately 3 percent of patients after mitral valve surgery and has been reported in patients with repaired tetralogy of Fallot and after repair of ventricular septal defects [12]. Mobitz type I second-degree AV block, can be induced by a Valsalva maneuver in patients with Chagas disease who do not have overt cardiac involvement. This may indicate early vagal dysfunction or involvement of the AV node [13]. (See "Chronic Chagas cardiomyopathy: Clinical manifestations and diagnosis".) PATHOPHYSIOLOGY https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 3/31 7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate Mobitz type I second-degree AV block usually occurs within the AV node, but may also reflect a delay elsewhere in the conduction system ( figure 1). Mobitz type I second-degree AV block can be observed in antegrade AV conduction, retrograde ventriculoatrial (VA) conduction across the AV node, or as part of exit block with ectopic and parasystolic pacemakers. Regardless of the site involved, what follows is a sequence in which there is a gradually increasing PR interval, usually a gradually decreasing R-R interval, and eventually a nonconducted P wave ( waveform 1). The following factors are required for this sequence to occur: A constant input The constant input is usually the SA nodal pacemaker that gives rise to atrial depolarization. An area of increasing conduction delay and a nonconducted P wave The PR interval is shortest in the first conducted P wave in the cycle and increases with each ensuing P wave. However, the largest absolute increase in delay occurs following the first P wave, a lesser increase in delay occurs following the second P wave, and so forth. The impulse eventually conducts very slowly and block occurs, resulting in a nonconducted P wave (no associated QRS complex). If the pause between the last conducted P wave and the first apparent QRS complex of the next cycle is very long, it may in fact be a junctional escape rather than a conducted P wave. Almost invariably, the second PR interval of the new cycle will be shorter than that of the last conducted P wave that preceded the block. An output with a decreasing interval The output, in this case the QRS-QRS interval (more commonly called the R-R interval), usually decreases with each conducted P wave of the cycle. The shortening R-R interval results from the decreasing increment in delay of AV nodal conduction (eg, the PR interval of beat 1 in a cycle increases by 0.05 seconds [from 0.18 to 0.23], the PR interval of next beat increases by 0.03 seconds [from 0.23 to 0.26], etc). Grouped beating The classic Wenckebach pattern occurs usually with ratios of 3:2, 4:3, or 5:4. This gives rise to a clustering of beats with decreasing R-R intervals that tends to repeat, although mixed ratios do occur fairly frequently. Conduction ratios of over 7:6 usually show an atypical pattern rather than the classic pattern. Pause shorter than two input cycles The R-R interval involving the nonconducted P wave is less than the summed R-R interval of any two previous cycles. This also results from the incremental conduction delay as the P wave that is not conducted is closer to the preceding QRS than any other in the cycle. https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 4/31 7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate Once conduction ratios exceed 6:5 or 7:6, the progressive increment in PR interval becomes unpredictable and the PR interval remains prolonged but constant. The most common explanation is that the sinus rate changes which, in turn, influences the PR interval through hemodynamic and autonomic effects. The PR interval is still longest in the conducted P wave before, and shortest after, the block ( waveform 5). The site of the Mobitz type I second-degree AV block is in the AV node in the vast majority of cases, with the remaining cases involving the His bundle, bundle branches, or fascicles. ECG The ECG cannot pinpoint with certainty the site of the Mobitz type I second-degree AV block [14,15]. (See 'ECG findings and diagnostic maneuvers' below.) His bundle ECG His bundle ECG, as part of an invasive electrophysiologic (EP) study, can easily confirm the site of the Mobitz type I second-degree AV block. (See 'Electrophysiology study' below.) CLINICAL PRESENTATION AND EVALUATION The clinical presentation of Mobitz type I second-degree AV block is typically fairly benign, as uncomplicated Mobitz type I second-degree AV block only rarely produces symptoms. Additionally, in contrast to Mobitz type II second-degree AV block, which can frequently progress to third-degree (complete) AV block, Mobitz type I second-degree AV block most often involves the AV node and rarely progresses to complete heart block. The evaluation of all patients with suspected Mobitz type I second-degree AV block includes a thorough history, including medications and recent changes in medications, along with a 12-lead ECG and bloodwork (which includes serum electrolytes and thyroid-stimulating hormone [TSH]). Clinical history All patients with suspected Mobitz type I second-degree AV block should be questioned about any history of heart disease, both congenital and acquired, as well as any recent cardiac procedures or medications that could predispose to AV conduction abnormalities. Patients without known cardiac disease should be questioned about other systemic diseases associated with heart block (eg, amyloidosis, sarcoidosis). Patients who live in an area with endemic Lyme disease should be questioned about any recent outdoor exposure to ticks or known tick bites. (See 'Etiology' above.) Patients with suspected Mobitz type I second-degree AV block that occurs in the setting of acute myocardial ischemia or infarction should undergo concurrent diagnosis and treatment for both conditions. (See "Conduction abnormalities after myocardial infarction", section on 'Management of conduction abnormalities'.) https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 5/31 7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate Patients without known or suspected cardiac or systemic disease should be questioned about their level of athletic activities and fitness. Such patients should also provide a full list of medications and be questioned about any recent changes in dosing, with particular attention paid to drugs that alter AV nodal conduction (ie, beta blockers, non-dihydropyridine calcium channel blockers, digoxin, select antiarrhythmic drugs). Signs and symptoms Most patients with Mobitz type I second-degree AV block are asymptomatic. Mobitz type I second-degree AV block that occurs in the setting of acute myocardial ischemia or myocarditis may result in clinical deterioration if the resulting ventricular rate is inadequate to maintain cardiac output. Additionally, even in otherwise healthy patients, if the sinus rate is slow and there are fewer conducted beats (2:1 or 3:2 block), there may be a significant reduction in cardiac output resulting in symptoms of hypoperfusion (including fatigue, lightheadedness, syncope, presyncope, or angina) or heart failure. Patients with Mobitz type I second-degree AV block often present with bradycardia but may have a normal sinus rhythm rate. Additionally, other than the presence of an irregular pulse, there are few specific physical examination findings. Patients may appear pale or diaphoretic if they have bradycardia with a resultant reduction in cardiac output. Patients with underlying heart failure that is exacerbated by the development of heart block may have crackles on lung examination, elevated jugular venous pulsations, and/or peripheral edema. ECG findings and diagnostic maneuvers Mobitz type I second-degree AV block is identified by progressive prolongation of the PR interval for several heart beats, followed by a nonconducted P wave ( waveform 1). Mobitz type I second-degree AV block is distinguished from other types of AV block as follows: Patients with first-degree AV block have a PR interval that is prolonged (>200 ms) but constant, and each P wave is followed by a QRS interval ( waveform 6). Patients with Mobitz type II second-degree AV block have a consistent unchanging PR intervals prior to a P wave that suddenly fails to conduct to the ventricles ( waveform 2). For patients with second-degree AV block with a ratio of atrial to ventricular conduction that is not 2:1, Mobitz type I and Mobitz type II second-degree AV block are easily distinguished. However, for patients with 2:1 atrial to ventricular conduction, the distinction between Mobitz type I and Mobitz type II second-degree AV block cannot be made from the surface ECG. Patients with third-degree (complete) AV block will have evidence of atrial (P waves) and ventricular (QRS complexes) activity that are independent of each other on the surface ECG https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 6/31 7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate ( waveform 3). In rare instances, the atrial rate may be exactly twice the ventricular rate, resulting in apparent 2:1 AV block that can mimic second-degree AV block. If 2:1 AV block is seen on the surface ECG, certain ECG features may aid in differentiating Mobitz type I from Mobitz type II second-degree AV block. Additionally, because of the varying effects of vagal tone on sinus node, AV node, and His-Purkinje system properties, vagal maneuvers can identify the site of a conduction abnormality in patients with second-degree AV block. If the PR interval of a conducted beat is very long (>300 ms) or the QRS complex is narrow, the level of block is more likely to be in the AV node, and the rhythm is most likely Mobitz type I second-degree AV block. If atropine is administered (typically 0.25 to 0.5 mg IV) and there is enhanced AV nodal conduction resulting in less frequent nonconducted P waves (ie, change from a 2:1 cycle to a 3:2 cycle), this confirms Mobitz type I second-degree AV block. A lack of response to atropine is consistent with but not diagnostic for Mobitz type II second-degree AV block. Carotid sinus massage, which increases vagal tone, would be expected to worsen Mobitz type I second-degree AV block by slowing AV nodal conduction. An increased conduction defect (ie, higher-grade block) following carotid sinus massage, which increases vagal tone, implies that the AV node is the site of the abnormality and is consistent with Mobitz type I second-degree AV block. Apparent improvement in AV conduction with the slowing of the sinus node rate (eg, restoration of 1:1 conduction) following carotid sinus massage suggests that the conduction abnormality is below the level of the AV node, consistent with Mobitz type II second-degree AV block. (See "Vagal maneuvers", section on 'Carotid sinus massage'.) Electrophysiology study Electrophysiology study (EPS) is not usually performed in patients with Mobitz type I second-degree AV block. EPS is indicated in those patients with syncope or presyncope and 2:1 AV block when the etiology of 2:1 block cannot be discerned with noninvasive maneuvers. When EPS is performed in such patients, there is typically a progressively longer A-H interval and a stable H-V interval until the final beat of the series in which there is an atrial electrogram with no subsequent His or ventricular electrogram. Less commonly, Mobitz type I second-degree AV block is observed in the His-Purkinje system (HPS) [16]. In this instance, there will usually be two His potentials (H and H') due to the slowing of conduction, with the H-H' interval prolonging before the H' and subsequent QRS complex are absent with block. https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 7/31 7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate DIAGNOSIS In nearly all cases, the diagnosis of Mobitz type I second-degree AV block can be made in a patient with an irregular pulse or suggestive symptoms (eg, fatigue, dyspnea, presyncope, and/or syncope) by obtaining a surface ECG. For patients with 2:1 AV block in whom the distinction between Mobitz type I and Mobitz type II second-degree AV block cannot be made using the surface ECG alone, a long rhythm strip should be obtained or a previous ECG examined to try to find evidence of PR prolongation with nonconducted P waves in a pattern other than 2:1 (eg, 3:2, 4:3, etc). Additionally, carotid sinus massage may be performed, or intravenous atropine administered, to help distinguish the level of AV block. If the diagnosis remains uncertain following these measures, invasive electrophysiology studies can definitively diagnose the type of AV block and accurately identify the level of the block. MANAGEMENT The management of Mobitz type I second-degree AV block depends on the presence and severity of any signs and symptoms related to the patient's rate and rhythm ( algorithm 1). Symptomatic patients should be treated with ventricular pacing (and, if hemodynamically unstable, atropine) and undergo treatment of any associated potentially reversible causes (eg, myocardial ischemia). In rare cases, cardioneural ablation can be considered for symptomatic patients with enhanced vagal tone [17]. Conversely, asymptomatic patients with Mobitz type I second-degree AV block do not require any specific therapy. Prior to initiating treatment for Mobitz type I second-degree AV block, reversible causes of slowed conduction such a myocardial ischemia, increased vagal tone, and medications should be excluded. (See "Etiology of atrioventricular block".) Initial management The initial management of patients with Mobitz type I second-degree AV block depends on the presence or absence of symptoms and the hemodynamic status of the patient ( algorithm 1). Symptomatic and hemodynamically unstable Patients with Mobitz type I second-degree AV block who are symptomatic and hemodynamically unstable should be urgently treated with atropine and temporary cardiac pacing if not responsive to atropine (either with transcutaneous or, if immediately available, transvenous pacing) ( algorithm 1). https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 8/31 7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate Signs and symptoms of hemodynamic instability include hypotension, altered mental status, signs of shock, ongoing ischemic chest pain, and evidence of acute pulmonary edema. Dopamine may be administered in hypotensive patients, while dobutamine is an option for patients with heart failure symptoms. This approach is similar to the patient who presents with unstable Mobitz type II second-degree AV block or unstable third-degree (complete) AV block ( algorithm 2) [18]. (See "Second-degree atrioventricular block: Mobitz type II", section on 'Unstable patients' and "Third-degree (complete) atrioventricular block", section on 'Unstable patients'.) Atropine should be promptly administered if intravenous (IV) access is available, but treatment with atropine should not delay treatment with transcutaneous pacing or a chronotropic agent. The initial dose of atropine is 0.5 mg IV. This dose may be repeated every three to five minutes to a total dose of 3 mg. A favorable response to atropine also suggests that AV block is due to abnormal conduction in the AV node since the more distal conducting system is not as sensitive to vagal activity. Temporary cardiac pacing should be provided. In the absence of central venous access, the most immediate way to provide temporary cardiac pacing is via transcutaneous pacing. Transcutaneous pacing is uncomfortable for the patient and may have variable efficacy depending on how well the impulses are transmitted to the myocardium; as such, transcutaneous pacing should be viewed as a temporizing measure until temporary transvenous pacing can be provided. (See "Temporary cardiac pacing".) Symptomatic and hemodynamically stable Patients with Mobitz type I second-degree AV block who are symptomatic and hemodynamically stable do not require urgent therapy with atropine or temporary cardiac pacing ( algorithm 1). However, patients should be continuously monitored with transcutaneous pacing pads in place ( figure 2) in the event of clinical deterioration. While stable patients are being monitored, reversible causes of Mobitz type I second-degree AV block such as myocardial ischemia, myocarditis, increased vagal tone, hypothyroidism, and drugs that depress conduction should be excluded in patients prior to implantation of a permanent pacemaker. Patients with Mobitz type I second-degree AV block in the setting of an acute myocardial infarction should be treated with temporary pacing and revascularization; following revascularization, most conduction abnormalities will improve or resolve and will not require permanent pacing. (See "Conduction abnormalities after myocardial infarction".) https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 9/31 7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate Patients with Mobitz type I second-degree AV block felt to be medication-induced should be observed while the offending agent or agents are withdrawn; such patients will often have improvement or resolution of AV block following removal of the medication. Asymptomatic patients Patients with Mobitz type I second-degree AV block who are asymptomatic do not require any initial treatment ( algorithm 1). Similar to symptomatic but hemodynamically stable patients, patients with asymptomatic Mobitz type I second-degree AV block should be evaluated for potentially reversible causes. If Mobitz type I second-degree AV block is identified in the hospital setting, patients should be monitored during their hospitalization to ensure stability of the rate and rhythm while undergoing evaluation for potentially reversible causes. Once a patient is defined as being truly asymptomatic and is not considered to be at risk for progression to higher levels of block, continuous monitoring is no longer indicated. Asymptomatic Mobitz type I block itself should not be considered as a reason for hospital admission and should not interfere with other noncardiac treatments in the hospitalized patient. If Mobitz type I second-degree AV block is identified in an ambulatory setting, patients should be evaluated for potentially reversible causes and seen for ambulatory follow-up within two to four weeks for a repeat ECG and symptom assessment. Most asymptomatic patients with Mobitz type I second-degree AV block do not require invasive electrophysiology studies (EPS). However, in patients who have otherwise unexplained syncope or presyncope in whom AV block may be the etiology (and therefore potentially symptomatic AV block), EPS may be considered. (See 'Electrophysiology study' above.) In asymptomatic patients who have undergone invasive EPS to determine the level of block within the AV node, the decision regarding a pacemaker is based on the level of block: For patients whose AV block is identified at the supra-His level (ie, within the AV node), we do not place a permanent pacemaker. For patients whose AV block is identified as infranodal, implantation of a permanent pacemaker can be considered based on the potential mortality benefit in asymptomatic patients whose block is identified as infranodal as well as a greater likelihood of progressive AV block and morbidity in patients with infranodal block. (See 'Subsequent management' below and "Permanent cardiac pacing: Overview of devices and indications", section on 'Acquired AV block'.) Subsequent management For the rare patient with Mobitz type I second-degree AV block and symptomatic bradycardia that is not due to a reversible etiology, we recommend https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 10/31 7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate implantation of a permanent pacemaker ( algorithm 1). For patients with Mobitz type I second-degree AV block and symptomatic bradycardia who require a pacemaker, we implant a dual chamber DDD pacemaker whenever possible in an effort to maintain physiologic AV synchrony ( algorithm 3). This approach in symptomatic patients is in agreement with the recommendations of professional society guidelines regarding device-based therapy for arrhythmias [19,20]. (See "Permanent cardiac pacing: Overview of devices and indications", section on 'Acquired AV block'.) For the large majority of patients with Mobitz type I second-degree AV block and asymptomatic bradycardia, we suggest not implanting a permanent pacemaker [20]. This is particularly true in younger patients and those patients in whom the AV block is felt to be supra-Hisian in nature (ie, within the AV node). These patients should have regular follow-up, including a surface ECG, every 6 to 12 months with questioning focused on the interval development of symptoms (eg, fatigue, dyspnea, presyncope, syncope) which could be attributable to the AV block. For patients with Mobitz type I second-degree AV block who remain asymptomatic, there has been disagreement among clinicians and professional societies regarding optimal management, with the ESC guidelines suggesting pacemaker placement and the ACC/AHA/HRS guidelines recommending against pacemaker placement. There are no randomized trial data to guide this decision. Observational data, with many limitations, provide some support for the use of a permanent pacemaker in such patients: Among a cohort of 86 asymptomatic patients with Mobitz type I second-degree AV block seen at a single institution in England from 1968 to 1993 (mean age 69 years, 65 percent male), 39 (45 percent) received a pacemaker for prophylactic purposes [21]. Despite the absence of symptoms, five-year survival was significantly higher among the group who received a pacemaker (87 versus 54 percent in the unpaced group). All mortality occurred in those greater than 45 years of age. Among a cohort of 299 patients with Mobitz type I second-degree AV block seen at a single Veterans Affairs Medical Center in the US from 1992 to 2010 (mean age 75 years, 99 percent male), the majority (175 patients) remained asymptomatic, while 124 patients (41 percent) received a pacemaker for symptomatic bradycardia or progression to higher- grade AV block [22]. During an average follow-up of 3.3 years, 190 patients (64 percent) died. Despite having greater cardiac comorbidity (eg, heart failure, coronary heart disease reduced left ventricular ejection fraction), patients who received a pacemaker had a 46 percent reduction in total mortality compared with those without a pacemaker (hazard ratio 0.54, 95% CI 0.35-0.83). This study, however, was a single-center study in an older- adult, predominantly male population with a high mortality rate. https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 11/31 7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate Our authors and editors feel that these data are insufficient to recommend pacemaker placement in patients with Mobitz type I second-degree AV block at the supra-His level (ie, within the AV node) which is not demonstrated to be infranodal by EP evaluation. INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Bradycardia (The Basics)" and "Patient education: Heart block in adults (The Basics)") SUMMARY AND RECOMMENDATIONS Definitions Atrioventricular (AV) block is defined as a delay or interruption in the transmission of an impulse from the atria to the ventricles due to an anatomic or functional impairment in the conduction system. In second-degree AV block, some atrial impulses fail to reach the ventricles. In Mobitz type I second-degree AV block ( waveform 1), there is progressive PR interval prolongation for several beats preceding a nonconducted P wave, whereas in Mobitz type II second-degree AV block ( waveform 2), the PR interval remains unchanged prior to a P wave that suddenly fails to conduct to the ventricles. (See 'Introduction' above and 'Definitions' above.) Etiology Mobitz type I second-degree AV block can occur in normal subjects and athletes without underlying cardiac pathology. The potential etiologies of Mobitz type I second- degree AV block also include reversible (both pathologic and iatrogenic) and idiopathic causes that are similar to other degrees of AV block ( table 1). Common potentially https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 12/31 7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate reversible causes include certain medications, myocardial ischemia, myocarditis, and cardiomyopathies. (See 'Etiology' above.) Clinical history All patients with suspected Mobitz type I second-degree AV block should be questioned about any history of heart disease, both congenital and acquired, as well as any recent cardiac procedures or medications that could predispose to AV conduction abnormalities. (See 'Clinical history' above.) Clinical presentation Most patients with Mobitz type I second-degree AV block are asymptomatic. Mobitz type I second-degree AV block that occurs in the setting of acute myocardial ischemia or myocarditis may result in clinical deterioration if the resulting ventricular rate is inadequate to maintain cardiac output. Additionally, even in otherwise healthy patients, if the sinus rate is slow and there are fewer conducted beats (2:1 or 3:2 block), there may be a significant reduction in cardiac output resulting in symptoms of hypoperfusion (including fatigue, lightheadedness, syncope, presyncope, or angina) or heart failure. (See 'Signs and symptoms' above.) ECG findings and diagnostic maneuvers Mobitz type I second-degree AV block is identified by progressive prolongation of the PR interval for several heart beats, followed by a nonconducted P wave ( waveform 1). If 2:1 AV block is seen on the surface ECG, certain ECG features (eg, PR interval >300 ms, narrow QRS complexes, etc) may aid in differentiating Mobitz type I from Mobitz type II second-degree AV block. Additionally, because of the varying effects of vagal tone on sinus node, AV node, and His-Purkinje system properties, vagal maneuvers can identify the site of a conduction abnormality in patients with second-degree AV block. (See 'ECG findings and diagnostic maneuvers' above and 'Diagnosis' above.) Initial management The initial management of patients with Mobitz type I second- degree AV block ( algorithm 1) depends on the presence or absence of symptoms and the hemodynamic status of the patient. (See 'Initial management' above.) Symptomatic patients Hemodynamically unstable Patients who are symptomatic and hemodynamically unstable should be urgently treated with atropine (0.5 mg intravenously, which may be repeated every three to five minutes to a total dose of 3 mg) and temporary cardiac pacing if not responsive to atropine (either with transcutaneous or, if immediately available, transvenous pacing). (See 'Symptomatic and hemodynamically unstable' above.) https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 13/31 7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate Hemodynamically stable Patients who are symptomatic and hemodynamically stable do not require urgent therapy with atropine or temporary cardiac pacing. However, patients should be continuously monitored with transcutaneous pacing pads in place ( figure 2) in the event of clinical deterioration. (See 'Symptomatic and hemodynamically stable' above.) Asymptomatic patients Patients who are asymptomatic do not require any initial treatment. Reversible causes of slowed conduction such as myocardial ischemia, increased vagal tone, and medications should be excluded. If no reversible causes are present, and the patient is asymptomatic, no specific therapy is required. (See 'Asymptomatic patients' above.) Subsequent management ( algorithm 1) (See 'Subsequent management' above.) Symptomatic patients For the rare patient with Mobitz type I second-degree AV block and symptomatic bradycardia that is not due to a reversible etiology, we recommend implantation of a permanent pacemaker (Grade 1A). We implant a dual chamber DDD pacemaker whenever possible in an effort to maintain physiologic AV synchrony. Asymptomatic patients For the large majority of patients with Mobitz type I second- degree AV block and asymptomatic bradycardia, we suggest not implanting a permanent pacemaker (Grade 2B). This is particularly true in younger patients and those patients in whom the AV block is felt to be supra-Hisian in nature (ie, within the AV node). These patients should have regularly follow-up, including a surface ECG, every 6 to 12 months. ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Wenckebach, KF . Zur Analyse der unregelm ssigen Pulses. Ztschr klin Med 1899; 36:181. 2. Mobitz, W . ber die unvollst ndige St rung der Erregungs berleitung zwischen Vorhof und Kammer des menschlichen Herzens. Z Gesamte Exp Med 1924; 41:180. https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 14/31 7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate 3. JOHNSON RL, AVERILL KH, LAMB LE. Electrocardiographic findings in 67,375 asymptomatic subjects. VII. Atrioventricular block. Am J Cardiol 1960; 6:153. 4. Brodsky M, Wu D, Denes P, et al. Arrhythmias documented by 24 hour continuous electrocardiographic monitoring in 50 male medical students without apparent heart disease. Am J Cardiol 1977; 39:390. 5. Dickinson DF, Scott O. Ambulatory electrocardiographic monitoring in 100 healthy teenage boys. Br Heart J 1984; 51:179. 6. Meytes I, Kaplinsky E, Yahini JH, et al. Wenckebach A-V block: a frequent feature following heavy physical training. Am Heart J 1975; 90:426. 7. Viitasalo MT, Kala R, Eisalo A. Ambulatory electrocardiographic recording in endurance athletes. Br Heart J 1982; 47:213. 8. Zeppilli P, Fenici R, Sassara M, et al. Wenckebach second-degree A-V block in top-ranking athletes: an old problem revisited. Am Heart J 1980; 100:281. 9. Zehender M, Meinertz T, Keul J, Just H. ECG variants and cardiac arrhythmias in athletes: clinical relevance and prognostic importance. Am Heart J 1990; 119:1378. 10. Young D, Eisenberg R, Fish B, Fisher JD. Wenckebach atrioventricular block (Mobitz type I) in children and adolescents. Am J Cardiol 1977; 40:393. 11. Stein R, Medeiros CM, Rosito GA, et al. Intrinsic sinus and atrioventricular node electrophysiologic adaptations in endurance athletes. J Am Coll Cardiol 2002; 39:1033. 12. Meimoun P, Zeghdi R, D'Attelis N, et al. Frequency, predictors, and consequences of

variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Bradycardia (The Basics)" and "Patient education: Heart block in adults (The Basics)") SUMMARY AND RECOMMENDATIONS Definitions Atrioventricular (AV) block is defined as a delay or interruption in the transmission of an impulse from the atria to the ventricles due to an anatomic or functional impairment in the conduction system. In second-degree AV block, some atrial impulses fail to reach the ventricles. In Mobitz type I second-degree AV block ( waveform 1), there is progressive PR interval prolongation for several beats preceding a nonconducted P wave, whereas in Mobitz type II second-degree AV block ( waveform 2), the PR interval remains unchanged prior to a P wave that suddenly fails to conduct to the ventricles. (See 'Introduction' above and 'Definitions' above.) Etiology Mobitz type I second-degree AV block can occur in normal subjects and athletes without underlying cardiac pathology. The potential etiologies of Mobitz type I second- degree AV block also include reversible (both pathologic and iatrogenic) and idiopathic causes that are similar to other degrees of AV block ( table 1). Common potentially https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 12/31 7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate reversible causes include certain medications, myocardial ischemia, myocarditis, and cardiomyopathies. (See 'Etiology' above.) Clinical history All patients with suspected Mobitz type I second-degree AV block should be questioned about any history of heart disease, both congenital and acquired, as well as any recent cardiac procedures or medications that could predispose to AV conduction abnormalities. (See 'Clinical history' above.) Clinical presentation Most patients with Mobitz type I second-degree AV block are asymptomatic. Mobitz type I second-degree AV block that occurs in the setting of acute myocardial ischemia or myocarditis may result in clinical deterioration if the resulting ventricular rate is inadequate to maintain cardiac output. Additionally, even in otherwise healthy patients, if the sinus rate is slow and there are fewer conducted beats (2:1 or 3:2 block), there may be a significant reduction in cardiac output resulting in symptoms of hypoperfusion (including fatigue, lightheadedness, syncope, presyncope, or angina) or heart failure. (See 'Signs and symptoms' above.) ECG findings and diagnostic maneuvers Mobitz type I second-degree AV block is identified by progressive prolongation of the PR interval for several heart beats, followed by a nonconducted P wave ( waveform 1). If 2:1 AV block is seen on the surface ECG, certain ECG features (eg, PR interval >300 ms, narrow QRS complexes, etc) may aid in differentiating Mobitz type I from Mobitz type II second-degree AV block. Additionally, because of the varying effects of vagal tone on sinus node, AV node, and His-Purkinje system properties, vagal maneuvers can identify the site of a conduction abnormality in patients with second-degree AV block. (See 'ECG findings and diagnostic maneuvers' above and 'Diagnosis' above.) Initial management The initial management of patients with Mobitz type I second- degree AV block ( algorithm 1) depends on the presence or absence of symptoms and the hemodynamic status of the patient. (See 'Initial management' above.) Symptomatic patients Hemodynamically unstable Patients who are symptomatic and hemodynamically unstable should be urgently treated with atropine (0.5 mg intravenously, which may be repeated every three to five minutes to a total dose of 3 mg) and temporary cardiac pacing if not responsive to atropine (either with transcutaneous or, if immediately available, transvenous pacing). (See 'Symptomatic and hemodynamically unstable' above.) https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 13/31 7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate Hemodynamically stable Patients who are symptomatic and hemodynamically stable do not require urgent therapy with atropine or temporary cardiac pacing. However, patients should be continuously monitored with transcutaneous pacing pads in place ( figure 2) in the event of clinical deterioration. (See 'Symptomatic and hemodynamically stable' above.) Asymptomatic patients Patients who are asymptomatic do not require any initial treatment. Reversible causes of slowed conduction such as myocardial ischemia, increased vagal tone, and medications should be excluded. If no reversible causes are present, and the patient is asymptomatic, no specific therapy is required. (See 'Asymptomatic patients' above.) Subsequent management ( algorithm 1) (See 'Subsequent management' above.) Symptomatic patients For the rare patient with Mobitz type I second-degree AV block and symptomatic bradycardia that is not due to a reversible etiology, we recommend implantation of a permanent pacemaker (Grade 1A). We implant a dual chamber DDD pacemaker whenever possible in an effort to maintain physiologic AV synchrony. Asymptomatic patients For the large majority of patients with Mobitz type I second- degree AV block and asymptomatic bradycardia, we suggest not implanting a permanent pacemaker (Grade 2B). This is particularly true in younger patients and those patients in whom the AV block is felt to be supra-Hisian in nature (ie, within the AV node). These patients should have regularly follow-up, including a surface ECG, every 6 to 12 months. ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Wenckebach, KF . Zur Analyse der unregelm ssigen Pulses. Ztschr klin Med 1899; 36:181. 2. Mobitz, W . ber die unvollst ndige St rung der Erregungs berleitung zwischen Vorhof und Kammer des menschlichen Herzens. Z Gesamte Exp Med 1924; 41:180. https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 14/31 7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate 3. JOHNSON RL, AVERILL KH, LAMB LE. Electrocardiographic findings in 67,375 asymptomatic subjects. VII. Atrioventricular block. Am J Cardiol 1960; 6:153. 4. Brodsky M, Wu D, Denes P, et al. Arrhythmias documented by 24 hour continuous electrocardiographic monitoring in 50 male medical students without apparent heart disease. Am J Cardiol 1977; 39:390. 5. Dickinson DF, Scott O. Ambulatory electrocardiographic monitoring in 100 healthy teenage boys. Br Heart J 1984; 51:179. 6. Meytes I, Kaplinsky E, Yahini JH, et al. Wenckebach A-V block: a frequent feature following heavy physical training. Am Heart J 1975; 90:426. 7. Viitasalo MT, Kala R, Eisalo A. Ambulatory electrocardiographic recording in endurance athletes. Br Heart J 1982; 47:213. 8. Zeppilli P, Fenici R, Sassara M, et al. Wenckebach second-degree A-V block in top-ranking athletes: an old problem revisited. Am Heart J 1980; 100:281. 9. Zehender M, Meinertz T, Keul J, Just H. ECG variants and cardiac arrhythmias in athletes: clinical relevance and prognostic importance. Am Heart J 1990; 119:1378. 10. Young D, Eisenberg R, Fish B, Fisher JD. Wenckebach atrioventricular block (Mobitz type I) in children and adolescents. Am J Cardiol 1977; 40:393. 11. Stein R, Medeiros CM, Rosito GA, et al. Intrinsic sinus and atrioventricular node electrophysiologic adaptations in endurance athletes. J Am Coll Cardiol 2002; 39:1033. 12. Meimoun P, Zeghdi R, D'Attelis N, et al. Frequency, predictors, and consequences of atrioventricular block after mitral valve repair. Am J Cardiol 2002; 89:1062. 13. Oliveira E, Ribeiro AL, Assis Silva F, et al. The Valsalva maneuver in Chagas disease patients without cardiopathy. Int J Cardiol 2002; 82:49. 14. Friedman HS, Gomes JA, Haft JI. An analysis of Wenckebach periodicity. J Electrocardiol 1975; 8:307. 15. Denes P, Levy L, Pick A, Rosen KM. The incidence of typical and atypical A-V Wenckebach periodicity. Am Heart J 1975; 89:26. 16. Callans DJ. Josephson's Clinical Cardiac Electrophysiology: Techniques and Interpretations, 6 th ed, Wolters Kluwer, Philadelphia 2020. 17. Aksu T, Gopinathannair R, Bozyel S, et al. Cardioneuroablation for Treatment of Atrioventricular Block. Circ Arrhythm Electrophysiol 2021; 14:e010018. 18. Link MS, Berkow LC, Kudenchuk PJ, et al. Part 7: Adult Advanced Cardiovascular Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015; 132:S444. https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 15/31 7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate 19. Brignole M, Auricchio A, Baron-Esquivias G, et al. 2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: the Task Force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Eur Heart J 2013; 34:2281. 20. Kusumoto FM, Schoenfeld MH, Barrett C, et al. 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2019; 74:e51. 21. Shaw DB, Gowers JI, Kekwick CA, et al. Is Mobitz type I atrioventricular block benign in adults? Heart 2004; 90:169. 22. Coumbe AG, Naksuk N, Newell MC, et al. Long-term follow-up of older patients with Mobitz type I second degree atrioventricular block. Heart 2013; 99:334. Topic 909 Version 38.0 https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 16/31 7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate GRAPHICS Electrocardiogram showing Mobitz type I (Wenckebach) atrioventricular block Single-lead electrocardiogram showing Mobitz type I (Wenckebach) second-degree atrioventricular block with 5:4 conduction. The characteristics of this arrhythmia include: a progressively increasing PR interval until a P wave is not conducted (arrow), a progressive decrease in the increment in the PR interval, a progressive decrease in the RR interval, and the RR interval that includes the dropped beat (0.96 sec) is less than twice the RR interval between conducted beats (0.53 to 0.57 sec). Courtesy of Morton Arnsdorf, MD. Graphic 73051 Version 6.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 17/31 7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate Single lead electrocardiogram (ECG) showing Mobitz type II second degree atrioventricular (AV) block The third and sixth P waves are not conducted through the AV node (there is no associated QRS complex). The PR interval is constant prior to and after the non-conducted beats. Graphic 58649 Version 4.0 Sinus rhythm The normal P wave in sinus rhythm is slightly notched since activation of the right atrium precedes that of the left atrium. The P wave is upright in a positive direction in leads I and II. A P wave with a uniform morphology precedes each QRS complex. The rate is between 60 and 100 beats per minute and the cycle length is uniform between sequential P waves and QRS complexes. In addition, the P wave morphology and PR intervals are identical from beat to beat. Graphic 69872 Version 2.0 https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 18/31 7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate Single-lead electrocardiogram (ECG) showing sinus rhythm with third degree (complete) AV block Sinus rhythm with third degree (complete) heart block. There is independent atrial (as shown by the P waves) and ventricular activity, with respective rates of 83 and 43 beats per minute. The wide QRS complexes may represent a junctional escape rhythm with underlying bundle branch block or an idioventricular pacemaker. Courtesy of Ary Goldberger, MD. Graphic 72863 Version 6.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 19/31 7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate Major causes of atrioventricular (AV) block Physiologic and pathophysiologic Increased vagal tone Progressive cardiac conduction system disease With fibrosis and/or sclerosis (Lenegre disease) With calcification (Lev disease) Ischemic heart disease, including acute myocardial infarction Cardiomyopathy Infiltrative processes (eg, sarcoidosis, amyloidosis, hemochromatosis, malignancy, etc) Other non-ischemic cardiomyopathies (eg, idiopathic, infectious, etc) Infections (eg, viral myocarditis, Lyme carditis) Congenital AV block Related to structural congenital heart disease As part of neonatal lupus syndrome Other Hyperkalemia, severe hypo- or hyperthyroidism, trauma, degenerative neuromuscular diseases Iatrogenic Drugs Beta blockers, calcium channel blockers, digoxin, adenosine, antiarrhythmic drugs Cardiac surgery Post valvular surgery, post surgical correction of congenital heart disease Transcatheter aortic valve implantation Catheter ablation of arrhythmias Transcatheter closure of VSD Alcohol septal ablation for HCM VSD: ventricular septal defect; HCM: hypertrophic cardiomyopathy. Graphic 62885 Version 6.0 https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 20/31 7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate Electrocardiogram (ECG) showing concurrent Mobitz type I (Wenckebach) atrioventricular (AV) block and inferior myocardial infarction (MI) This rhythm strip shows a Mobitz type I (Wenckebach) atrioventricular block with 4:3 and 3:2 conduction and progressive prolongation of the PR intervals of conducted beats. The marked ST segment elevation suggests acute inferior wall ischemia or infarction that may be responsible for the arrhythmia. Courtesy of Ary Goldberger, MD. Graphic 62040 Version 3.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 21/31 7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate Normal conduction system Schematic representation of the normal intraventricular conduction system (His- Purkinje system). The Bundle of His divides into the left bundle branch and right bundle branch. The left bundle branch divides into anterior, posterior, and, in some cases, median fascicles. AV: atrioventricular; RA: right atrium; LA: left atrium; RV: right ventricle; LV: left ventricle. Graphic 63340 Version 6.0 https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 22/31 7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate Electrocardiogram (ECG) showing atypical Mobitz type I (Wenckebach) atrioventricular (AV) block Single lead electrocardiogram (ECG) strip showing an atypical Mobitz type I (Wenckebach) AV block with 18:17 ratio. The last three cycles of the group, the skipped beat (with the P wave lost in the T wave; arrow), and the first three cycles of the next group are shown. The last three cycles had a PR interval of 0.36 sec while the first three cycles showed PR intervals of 0.23, 0.32 and 0.34 sec with a decreasing R-R interval. This demonstrates the importance of comparing the PR interval of the last beat before the dropped QRS to the PR interval of the first and second beats of the new cycle. The PR interval is the longest in the beat before the dropped beat, shortest in the first beat of the cycle, and increases in the second beat. Courtesy of Morton Arnsdorf, MD. Graphic 78766 Version 3.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 23/31 7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate Single-lead electrocardiogram (ECG) showing first degree atrioventricular (AV) block I Electrocardiogram of lead II showing normal sinus rhythm, first degree atrioventricular block with a prolonged PR interval of 0.30 seconds, and a QRS complex of normal duration. The tall P waves and P wave duration of approximately 0.12 seconds suggest concurrent right atrial enlargement. Courtesy of Morton Arnsdorf, MD. Graphic 67882 Version 5.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 24/31 7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate Algorithm management Mobitz I second degree AV block in adults AV: atrioventricular; ECG: electrocardiogram; CHB: complete heart block; BP: blood pressure; HF: heart failure; IV: intravenous; PPM: permanent pacemaker. The initial dose of atropine is 0.5 mg IV. This dose may be repeated every three to five minutes to a total dose of 3 mg. https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 25/31 7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate While transcutaneous pacing may be initially successful in stabilizing the patient, it may not be consistently reliable. Central venous access should be considered in the event that urgent transvenous pacing is required. Dopamine IV infusion typically begins at a dose of 3 mcg/kg/minute and can be titrated up to 20 mcg/kg/minute if needed for heart rate and blood pressure augmentation. Dobutamine IV infusion typically begins at a dose of 5 mcg/kg/minute and can be titrated up to 20 mcg/kg/minute if needed for heart rate and blood pressure augmentation. Graphic 109617 Version 1.0 https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 26/31 7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate Adult bradycardia algorithm 2020 update Reprinted with permission. ACLS Provider Manual. Copyright 2020 American Heart Association, Inc. Graphic 130748 Version 10.0 https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 27/31 7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate Options for hands-free pacemaker/defibrillator pad positioning Positioning options for hands-free pacemaker/defibrillator pads showing anterior/lateral positioning (left) and anterior/posterior positioning (right). Graphic 103268 Version 2.0 https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 28/31 7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate Selection of pacemaker systems for patients with atrioventricular block Decisions are illustrated by diamonds. Shaded boxes indicate type of pacemaker. AV: atrioventricular. Reproduced with permission from: Epstein AE, DiMarco JP, Ellenbogen KA, et al. ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2008; 51(21):e1-e62. Illustration used with permission of Elsevier Inc. All rights reserved. Copyright 2008 Elsevier Inc. https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 29/31 7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate Graphic 71370 Version 4.0 https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 30/31 7/5/23, 10:36 AM Second-degree atrioventricular block: Mobitz type I (Wenckebach block) - UpToDate Contributor Disclosures William H Sauer, MD Grant/Research/Clinical Trial Support: Biosense-Webster [Catheter ablation]; Boston Scientific [Catheter ablation]. All of the relevant financial relationships listed have been mitigated. Mark S Link, MD No relevant financial relationship(s) with ineligible companies to disclose. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-i-wenckebach-block/print 31/31

7/5/23, 10:37 AM Second-degree atrioventricular block: Mobitz type II - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Second-degree atrioventricular block: Mobitz type II : William H Sauer, MD : Mark S Link, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Apr 06, 2023. INTRODUCTION Atrioventricular (AV) block is defined as a delay or interruption in the transmission of an impulse from the atria to the ventricles due to an anatomic or functional impairment in the conduction system. The conduction disturbance can be transient or permanent, with conduction that is delayed, intermittent, or absent. Commonly used terminology includes: First-degree AV block Delayed conduction from the atrium to the ventricle (defined as a prolonged PR interval of >200 milliseconds) without interruption in atrial to ventricular conduction. Second-degree AV block Intermittent atrial conduction to the ventricle, often in a regular pattern (eg, 2:1, 3:2), or higher degrees of block, which are further classified into Mobitz type I (Wenckebach) and Mobitz type II second-degree AV block. Third-degree (complete) AV block No atrial impulses conduct to the ventricle. High-grade AV block Two or more consecutive blocked P waves. The clinical presentation, evaluation, and management of Mobitz type II second-degree AV block will be reviewed here. The etiology of AV block in general, and the management of other specific types of AV block, are discussed separately. (See "Etiology of atrioventricular block" and "First- degree atrioventricular block" and "Second-degree atrioventricular block: Mobitz type I (Wenckebach block)" and "Third-degree (complete) atrioventricular block" and "Congenital third- degree (complete) atrioventricular block".) https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-ii/print 1/25 7/5/23, 10:37 AM Second-degree atrioventricular block: Mobitz type II - UpToDate DEFINITION In second-degree AV block, some atrial impulses fail to reach the ventricles. Wenckebach described progressive delay between atrial and ventricular contraction and the eventual failure of a P wave to conduct to the ventricles [1]. Mobitz subsequently divided second-degree AV block into two subtypes, as determined by the findings on the electrocardiogram (ECG) [2]: Mobitz type I second-degree AV block ( waveform 1), in which progressive PR interval prolongation precedes a nonconducted P wave. The first P wave after block conducts to the ventricle with a shorter PR interval compared with the last P wave before block. Mobitz type II second-degree AV block ( waveform 2), in which the PR interval remains unchanged prior to a P wave that fails to conduct to the ventricles. High-grade AV block, in which two or more consecutive P waves are nonconducted. In contrast to third degree (complete) AV block ( waveform 3), however, some P waves continue to be conducted to the ventricle. Mobitz type I and Mobitz type II second-degree AV block cannot be differentiated from the ECG when 2:1 AV block is present. In this situation, every other P wave is nonconducted and there is no opportunity to observe for the constant PR interval that is characteristic of Mobitz type II second-degree AV block. (See 'ECG findings' below.) ETIOLOGY The potential etiologies of Mobitz type II second-degree AV block include reversible and irreversible conditions (pathologic, iatrogenic, and idiopathic) that are similar to other degrees of AV block ( table 1). Common causes include: Pathologic Myocardial ischemia (acute or chronic) involving the conduction system, cardiomyopathy (eg, amyloidosis, sarcoidosis), myocarditis (eg, Lyme disease), endocarditis with abscess formation, hyperkalemia, and hypervagotonia. Iatrogenic Medication-related (AV nodal blocking medications), post-cardiac surgery, post-catheter ablation, post-transcatheter aortic valve implantation. Mobitz type II second-degree AV block is rarely seen in patients without underlying heart disease. When identifiable, the reversible causes most commonly associated with Mobitz type II second-degree AV block are myocardial infarction with ischemia of the AV node and medications https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-ii/print 2/25 7/5/23, 10:37 AM Second-degree atrioventricular block: Mobitz type II - UpToDate that alter conduction through the AV node (eg, digoxin, beta blockers, calcium channel blockers). When no specific reversible cause is identified, the block is often felt to be related to idiopathic progressive cardiac conduction disease with myocardial fibrosis and/or sclerosis that affects the conduction system. (See "Cardiac arrhythmias due to digoxin toxicity" and "Etiology of atrioventricular block".) PATHOPHYSIOLOGY Mobitz type II second-degree AV block almost always results from conduction system disease below the level of the AV node ( figure 1), occurring in the bundle of His in approximately 20 percent of cases and in the bundle branches in the remainder [3]. Patients with bundle branch involvement also have axis shifts and QRS widening depending upon the location of the block. In addition, at least two-thirds of patients with this disorder also have bifascicular or even trifascicular disease [4,5]. (See "Basic approach to delayed intraventricular conduction", section on 'Bifascicular and trifascicular block' and "Chronic bifascicular blocks".) CLINICAL PRESENTATION AND EVALUATION The clinical presentation of Mobitz type II second-degree AV block is variable depending upon the underlying sinus rhythm heart rate, the frequency of nonconducted P waves, and the presence of comorbid conditions. The evaluation of all patients with suspected Mobitz type II second-degree AV block includes a thorough history, including medications and recent changes in medications, along with a 12-lead ECG and bloodwork (which includes serum electrolytes and thyroid-stimulating hormone [TSH]). Etiology and reversible causes All patients with suspected Mobitz type II second-degree AV block should be questioned about any history of heart disease, both congenital and acquired, as well as any recent cardiac procedures or medications that could predispose to AV conduction abnormalities. Patients without known cardiac disease should be questioned about other systemic diseases associated with heart block (eg, amyloidosis, sarcoidosis). Patients who live in an area with endemic Lyme disease should be questioned about any recent outdoor exposure to ticks or known tick bites. (See 'Etiology' above.) Patients with suspected Mobitz type II second-degree AV block that occurs in the setting of acute myocardial ischemia or infarction should undergo concurrent diagnosis and treatment for both conditions. (See "Conduction abnormalities after myocardial infarction", section on 'Management of conduction abnormalities'.) https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-ii/print 3/25 7/5/23, 10:37 AM Second-degree atrioventricular block: Mobitz type II - UpToDate Patients should provide a full list of medications and be questioned about any recent changes in dosing, with particular attention paid to drugs that alter AV nodal conduction (ie, beta blockers, nondihydropyridine calcium channel blockers, digoxin, select antiarrhythmic drugs). In patients under 60 years of age who present with otherwise unexplained heart block, previously undetected cardiac sarcoidosis has been identified in up to 25 to 35 percent of patients [6,7]. Such patients with otherwise unexplained complete heart block should be evaluated for cardiac sarcoidosis [8]. (See "Clinical manifestations and diagnosis of cardiac sarcoidosis".) Signs and symptoms Most patients with Mobitz type II second-degree AV block will present with some degree of symptoms, though the severity of the symptoms can be quite variable. Symptoms may include: Fatigue Dyspnea Chest pain Presyncope or syncope Sudden cardiac arrest Mobitz type II second-degree AV block with only infrequent nonconducted P waves in a patient with a normal sinus heart rate (ie, 60 to 100 beats per minute) may produce few or no symptoms. However, if the patient has sinus bradycardia at baseline, or there are more frequent nonconducted beats, there may be a significant reduction in cardiac output resulting in symptoms of hypoperfusion or heart failure. The failure of one or more P waves to conduct to the ventricles can lead to fatigue, lightheadedness, presyncope, or syncope (called Stokes-Adams attacks) since the lower intrinsic cardiac pacemakers are slower than junctional pacemakers ( waveform 4) [9-12]. Patients with Mobitz type II second-degree AV block often present with bradycardia but may have a normal sinus rhythm rate. Additionally, other than the presence of an irregular pulse, there are few specific physical examination findings. Patients may appear pale or diaphoretic if they have bradycardia with a resultant reduction in cardiac output. Patients with underlying heart failure that is exacerbated by the development of heart block may have crackles on lung examination, elevated jugular venous pulsations, and/or peripheral edema. ECG findings Mobitz type II second-degree AV block is identified by consistent unchanging PR intervals (which are usually normal in duration but may be prolonged) followed by the block of one or more P waves that fail to conduct to the ventricles ( waveform 5). https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-ii/print 4/25 7/5/23, 10:37 AM Second-degree atrioventricular block: Mobitz type II - UpToDate Mobitz type II second-degree AV block is distinguished from other types of AV block as follows: Patients with first degree AV block have a PR interval that is prolonged (>200 milliseconds) but constant, and each P wave is followed by a QRS interval ( waveform 6). Patients with Mobitz type I second-degree AV block have progressive prolongation of the PR interval for several heart beats, followed by a nonconducted P wave ( waveform 1). For patients with second-degree AV block with a ratio of atrial to ventricular conduction that is not 2:1, Mobitz type I and Mobitz type II second-degree AV block are easily distinguished. However, for patients with 2:1 atrial to ventricular conduction, the distinction between Mobitz type I and Mobitz type II second-degree AV block cannot be made from the surface ECG. (See "Second-degree atrioventricular block: Mobitz type I (Wenckebach block)", section on 'ECG findings and diagnostic maneuvers'.) Patients with third degree (complete) AV block will have evidence of atrial (P waves) and ventricular (QRS complexes) activity that are independent of each other on the surface ECG ( waveform 3). In rare instances, the atrial rate may be exactly twice the ventricular rate, resulting in 2:1 AV block which can mimic second-degree AV block. An increase in heart rate due to exercise, atropine, or atrial pacing can worsen Mobitz type II second-degree AV block. Conversely, vagal maneuvers may slow the sinus rate, allow more time for excitability to recover in or below the bundle of His, thereby facilitating conduction across the AV node and improving Mobitz type II second-degree AV block. (See "Second-degree atrioventricular block: Mobitz type I (Wenckebach block)", section on 'ECG findings and diagnostic maneuvers'.) Electrophysiology study Electrophysiology studies (EPS) performed for an evaluation of a suspected arrhythmia or when there is a question about the level of block leading to bradycardia can reveal intracardiac evidence of infra-Hisian block. In addition, an EPS may identify patients with Mobitz type II second-degree AV block who are at increased risk of progression to third degree (complete) heart block. However, since nearly all patients without a readily identifiable reversible cause are candidates for a permanent pacemaker, EPS is of limited value and not usually performed [13]. There is a 2017 case report that describes the successful treatment of second-degree AV block with catheter ablation of a ventricular nodal pathway manifesting as concealed and manifest junctional beats. In this very rare circumstance where concealed junctional extrasystoles are suspected, an EPS and possible ablation may be considered [14]. (See "Invasive diagnostic cardiac electrophysiology studies".) His bundle electrocardiography, performed as part of an invasive EPS, shows that the nonconducted A wave (P wave on surface ECG) is followed by a His deflection, and not https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-ii/print 5/25 7/5/23, 10:37 AM Second-degree atrioventricular block: Mobitz type II - UpToDate infrequently, a split His potential due to slowed intra-Hisian conduction ( waveform 5). Rarely, proximal His block does not demonstrate a His potential with the nonconducted A wave (P wave on the surface ECG), falsely suggesting that the block is in the AV node [3,15,16]. DIAGNOSIS In nearly all cases, the diagnosis of Mobitz type II second-degree AV block can be made in a patient with an irregular pulse or suggestive symptoms (eg, fatigue, dyspnea, presyncope, and/or syncope) by obtaining a surface ECG. (See 'ECG findings' above.) For patients with 2:1 AV block in whom the distinction between Mobitz type I and Mobitz type II second-degree AV block cannot be made using the surface ECG alone, a long rhythm strip should be obtained or a previous ECG examined to try to find evidence of constant PR intervals preceding a nonconducted P wave, as well as to identify nonconducted P waves in a pattern other than 2:1 (eg, 3:2, 4:3, etc) that would suggest Mobitz type I second-degree AV block. Additionally, carotid sinus massage may be performed, or intravenous atropine administered in those patients where carotid sinus massage may be unwanted because of concern for vascular disease, to help distinguish the level of AV block. If the diagnosis remains uncertain following these measures, invasive electrophysiology studies can definitively diagnose the type of AV block and accurately identify the level of the block. MANAGEMENT Initial management The initial management of the patient with Mobitz type II second- degree AV block depends on the presence and severity of any signs and symptoms related to the ventricular rate ( algorithm 1). Unstable patients require immediate pharmacologic therapy and, in most instances, should also receive temporary pacing to increase heart rate and cardiac output. Unstable patients Patients with Mobitz type II second-degree AV block who are hemodynamically unstable should be urgently treated with a beta-adrenergic agonist (eg, isoproterenol, dopamine, dobutamine, or epinephrine) if myocardial ischemia is unlikely [13] and, in most instances, with temporary cardiac pacing (either with transcutaneous or, if immediately available, transvenous pacing). Atropine is generally avoided in patients with Mobitz type II second-degree AV block, as the block is generally infranodal. Rarely, atropine or other agents can worsen infranodal block by increasing sinus rate without improving conduction. https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-ii/print 6/25 7/5/23, 10:37 AM Second-degree atrioventricular block: Mobitz type II - UpToDate Signs and symptoms of hemodynamic instability include hypotension, altered mental status, signs of shock, ongoing ischemic chest pain, and evidence of acute pulmonary edema. Dopamine may be administered in hypotensive patients, while dobutamine is an option for patients with heart failure symptoms. This approach is similar to the patient who presents with unstable third degree (complete) AV block. (See "Advanced cardiac life support (ACLS) in adults", section on 'Bradycardia' and "Third-degree (complete) atrioventricular block", section on 'Unstable patients'.) Stable patients Patients with Mobitz type II second-degree AV block who are hemodynamically stable do not require urgent therapy with atropine or temporary cardiac pacing. However, Mobitz type II second-degree AV block is by nature unstable and frequently progresses to third degree (complete) AV block, so patients should be continuously monitored with transcutaneous pacing pads in place in the event of clinical deterioration. In addition, most stable patients continue to have symptoms related to the bradycardia and will require identification and treatment of any reversible causes or permanent therapy with an implantable pacemaker. Further management Once unstable patients have been stabilized, and while stable patients are being monitored, reversible causes of Mobitz type II second-degree AV block such as myocardial ischemia, increased vagal tone, hypothyroidism, hyperkalemia, and drugs that depress conduction should be addressed prior to determining whether implantation of a permanent pacemaker is required ( algorithm 2). Patients with Mobitz type II second-degree AV block in the setting of an acute myocardial infarction should be treated with temporary pacing and revascularization; following revascularization, most conduction abnormalities will improve or resolve and will not require permanent pacing. (See "Conduction abnormalities after myocardial infarction", section on 'Summary and recommendations'.) Patients with Mobitz type II second-degree AV block felt to be medication-induced should be observed while the offending agent or agents are withdrawn; such patients will often have improvement or resolution of AV block following removal of the medication. Patients with Mobitz type II second-degree AV block in the setting of hyperkalemia should receive therapy to reduce serum potassium levels; similarly, patients with hypothyroidism should receive thyroid replacement therapy. If Mobitz type II second-degree AV block subsequently resolves, a permanent pacemaker is not usually needed. (See "Treatment and prevention of hyperkalemia in adults" and "Treatment of primary hypothyroidism in adults".) https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-ii/print 7/25 7/5/23, 10:37 AM Second-degree atrioventricular block: Mobitz type II - UpToDate Patients with Lyme carditis and associated heart block frequently do not require permanent cardiac pacing. Mobitz type II second-degree AV block typically improves to lesser degrees of AV block within one week, and more minor conduction disturbances usually resolve within six weeks. As such, while these patients may initially require temporary cardiac pacing, permanent cardiac pacing should be reserved for patients with persistent high grade AV block following an adequate course of therapy for Lyme disease. (See "Lyme carditis".) If no reversible causes are present, definitive treatment of Mobitz type II second-degree AV block involves permanent pacemaker placement in most patients [13,17]. Dual-chamber (ie, atrioventricular) pacing to maintain AV synchrony is preferred (rather than single chamber right ventricular pacing) in most patients due to the favorable hemodynamic benefits of AV synchrony ( algorithm 3). Unlike asymptomatic patients with Mobitz type I second-degree AV block who do not require any specific therapy, patients with Mobitz type II second-degree AV block have a high likelihood of progressing to symptomatic Mobitz type II second-degree AV block or complete heart block and should be considered candidates for pacemaker insertion on initial presentation [13,18,19]. (See "Permanent cardiac pacing: Overview of devices and indications", section on 'Acquired AV block' and "Modes of cardiac pacing: Nomenclature and selection".) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Arrhythmias in adults" and "Society guideline links: Cardiac implantable electronic devices".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-ii/print 8/25 7/5/23, 10:37 AM Second-degree atrioventricular block: Mobitz type II - UpToDate Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Bradycardia (The Basics)" and "Patient education: Heart block in adults (The Basics)") SUMMARY AND RECOMMENDATIONS Definition Atrioventricular (AV) block is defined as a delay or interruption in the transmission of an impulse from the atria to the ventricles due to an anatomic or functional impairment in the conduction system. In second-degree AV block, some atrial impulses fail to reach the ventricles. In Mobitz type I second-degree AV block, there is progressive PR interval prolongation for several beats preceding a nonconducted P wave. (See 'Introduction' above and 'Definition' above.) In Mobitz type II second-degree AV block, the PR interval remains unchanged prior to a P wave that suddenly fails to conduct to the ventricles ( waveform 5). (See 'ECG findings' above.) Etiology The potential etiologies of Mobitz type II second-degree AV block include reversible and irreversible conditions (pathologic, iatrogenic, and idiopathic) that are similar to other degrees of AV block ( table 1). Common potentially reversible causes include myocardial ischemia and medications. (See 'Etiology' above.) All patients with suspected Mobitz type II second-degree AV block should be questioned about any history of heart disease, both congenital and acquired, as well as any recent cardiac procedures or medications that could predispose to AV conduction abnormalities. (See 'Etiology and reversible causes' above.) Clinical presentation Most patients with Mobitz type II second-degree AV block will present with some degree of symptoms, though the severity of the symptoms can be quite variable. Symptoms may include fatigue, dyspnea, chest pain, presyncope, syncope, or sudden cardiac arrest. (See 'Signs and symptoms' above.) Management The management of patients with Mobitz type II second-degree AV block depends on the presence or absence of symptoms, the hemodynamic status of the patient, https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-ii/print 9/25 7/5/23, 10:37 AM Second-degree atrioventricular block: Mobitz type II - UpToDate the response to initial therapy, and the identification of any potentially reversible causes ( algorithm 1). (See 'Management' above.) Patients with Mobitz type II second-degree AV block who are hemodynamically unstable should be urgently treated with a beta-adrenergic agent and temporary cardiac pacing (either with transcutaneous or, if immediately available, transvenous pacing). (See 'Unstable patients' above.) Patients with Mobitz type II second-degree AV block who are hemodynamically stable do not require urgent therapy with atropine or temporary cardiac pacing. However, Mobitz type II second-degree AV block is by nature unstable and frequently progresses to third degree (complete) AV block, so patients should be continuously monitored with transcutaneous pacing pads in place in the event of clinical deterioration. (See 'Stable patients' above.) Address reversible causes Reversible causes of Mobitz type II second-degree AV block such as myocardial ischemia, increased vagal tone, hypothyroidism, hyperkalemia, and drugs that depress conduction should be addressed prior to determining whether permanent pacemaker implantation is required ( algorithm 2). If irreversible For patients with Mobitz type II second-degree AV block who do not have a reversible etiology, we recommend implantation of a permanent pacemaker (Grade 1A). We implant a dual chamber DDD pacemaker whenever possible in an effort to maintain physiologic AV synchrony. ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Wenckebach, KF . Zur Analyse der unregelm ssigen Pulses. Ztschr klin Med 1899; 36:181. 2. Mobitz, W . ber die unvollst ndige St rung der Erregungs berleitung zwischen Vorhof und Kammer des menschlichen Herzens. Z Gesamte Exp Med 1924; 41:180. https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-ii/print 10/25 7/5/23, 10:37 AM Second-degree atrioventricular block: Mobitz type II - UpToDate 3. Narula OS. Conduction disorders in the AV transmission system. In: Cardiac Arrhythmias, Dr eifus L, Likoff W (Eds), Grune and Stratton, New York 1973. p.259. 4. Peuch P. The value in intracardiac recordings. In: Cardiac Arrhythmias, Krikler D, Gododwin J F (Eds), Saunders, Philadelphia 1975. p.81. 5. Puech P, Wainwright RJ. Clinical electrophysiology of atrioventricular block. Cardiol Clin 1983; 1:209. 6. Takaya Y, Kusano KF, Nakamura K, Ito H. Outcomes in patients with high-degree atrioventricular block as the initial manifestation of cardiac sarcoidosis. Am J Cardiol 2015; 115:505. 7. Nery PB, Beanlands RS, Nair GM, et al. Atrioventricular block as the initial manifestation of cardiac sarcoidosis in middle-aged adults. J Cardiovasc Electrophysiol 2014; 25:875. 8. Birnie DH, Sauer WH, Bogun F, et al. HRS expert consensus statement on the diagnosis and management of arrhythmias associated with cardiac sarcoidosis. Heart Rhythm 2014; 11:1305. 9. Rosen KM, Dhingra RC, Loeb HS, Rahimtoola SH. Chronic heart block in adults. Clinical and electrophysiological observations. Arch Intern Med 1973; 131:663. 10. Gupta PK, Lichstein E, Chadda KD. Chronic His bundle block. Clinical, electrocardiographic, electrophysiological, and follow-up studies on 16 patients. Br Heart J 1976; 38:1343. 11. Narula OS, Narula JT. Junctional pacemakers in man. Response to overdrive suppression with and without parasympathetic blockade. Circulation 1978; 57:880. 12. Amat-y-Leon F, Dhingra R, Denes P, et al. The clinical spectrum of chronic His bundle block. Chest 1976; 70:747. 13. Kusumoto FM, Schoenfeld MH, Barrett C, et al. 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2019; 74:e51. 14. Tuohy S, Saliba W, Pai M, Tchou P. Catheter ablation as a treatment of atrioventricular block. Heart Rhythm 2018; 15:90. 15. Langendorf R, Cohen H, Gozo EG Jr. Observations on second degree atrioventricular block, including new criteria for the differential diagnosis between type I and type II block. Am J Cardiol 1972; 29:111. 16. Goodfriend MA, Barold SS. Tachycardia-dependent and bradycardia-dependent Mobitz type II atrioventricular block within the bundle of His. Am J Cardiol 1974; 33:908. https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-ii/print 11/25 7/5/23, 10:37 AM Second-degree atrioventricular block: Mobitz type II - UpToDate 17. Brignole M, Auricchio A, Baron-Esquivias G, et al. 2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: the Task Force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Eur Heart J 2013; 34:2281. 18. Dhingra RC, Palileo E, Strasberg B, et al. Significance of the HV interval in 517 patients with chronic bifascicular block. Circulation 1981; 64:1265. 19. Strasberg B, Amat-Y-Leon F, Dhingra RC, et al. Natural history of chronic second-degree atrioventricular nodal block. Circulation 1981; 63:1043. Topic 910 Version 37.0 https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-ii/print 12/25 7/5/23, 10:37 AM Second-degree atrioventricular block: Mobitz type II - UpToDate GRAPHICS Electrocardiogram showing Mobitz type I (Wenckebach) atrioventricular block Single-lead electrocardiogram showing Mobitz type I (Wenckebach) second-degree atrioventricular block with 5:4 conduction. The characteristics of this arrhythmia include: a progressively increasing PR interval until a P wave is not conducted (arrow), a progressive decrease in the increment in the PR interval, a progressive decrease in the RR interval, and the RR interval that includes the dropped beat (0.96 sec) is less than twice the RR interval between conducted beats (0.53 to 0.57 sec). Courtesy of Morton Arnsdorf, MD. Graphic 73051 Version 6.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-ii/print 13/25 7/5/23, 10:37 AM Second-degree atrioventricular block: Mobitz type II - UpToDate Single lead electrocardiogram (ECG) showing Mobitz type II second degree atrioventricular (AV) block The third and sixth P waves are not conducted through the AV node (there is no associated QRS complex). The PR interval is constant prior to and after the non-conducted beats. Graphic 58649 Version 4.0 Sinus rhythm The normal P wave in sinus rhythm is slightly notched since activation of the right atrium precedes that of the left atrium. The P wave is upright in a positive direction in leads I and II. A P wave with a uniform morphology precedes each QRS complex. The rate is between 60 and 100 beats per minute and the cycle length is uniform between sequential P waves and QRS complexes. In addition, the P wave morphology and PR intervals are identical from beat to beat. Graphic 69872 Version 2.0 https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-ii/print 14/25 7/5/23, 10:37 AM Second-degree atrioventricular block: Mobitz type II - UpToDate Single-lead electrocardiogram (ECG) showing sinus rhythm with third degree (complete) AV block Sinus rhythm with third degree (complete) heart block. There is independent atrial (as shown by the P waves) and ventricular activity, with respective rates of 83 and 43 beats per minute. The wide QRS complexes may represent a junctional escape rhythm with underlying bundle branch block or an idioventricular pacemaker. Courtesy of Ary Goldberger, MD. Graphic 72863 Version 6.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-ii/print 15/25 7/5/23, 10:37 AM Second-degree atrioventricular block: Mobitz type II - UpToDate Major causes of atrioventricular (AV) block Physiologic and pathophysiologic Increased vagal tone Progressive cardiac conduction system disease With fibrosis and/or sclerosis (Lenegre disease) With calcification (Lev disease) Ischemic heart disease, including acute myocardial infarction Cardiomyopathy Infiltrative processes (eg, sarcoidosis, amyloidosis, hemochromatosis, malignancy, etc) Other non-ischemic cardiomyopathies (eg, idiopathic, infectious, etc) Infections (eg, viral myocarditis, Lyme carditis) Congenital AV block Related to structural congenital heart disease As part of neonatal lupus syndrome Other Hyperkalemia, severe hypo- or hyperthyroidism, trauma, degenerative neuromuscular diseases Iatrogenic Drugs Beta blockers, calcium channel blockers, digoxin, adenosine, antiarrhythmic drugs Cardiac surgery Post valvular surgery, post surgical correction of congenital heart disease Transcatheter aortic valve implantation Catheter ablation of arrhythmias Transcatheter closure of VSD Alcohol septal ablation for HCM VSD: ventricular septal defect; HCM: hypertrophic cardiomyopathy. Graphic 62885 Version 6.0 https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-ii/print 16/25 7/5/23, 10:37 AM Second-degree atrioventricular block: Mobitz type II - UpToDate Normal conduction system Schematic representation of the normal intraventricular conduction system (His- Purkinje system). The Bundle of His divides into the left bundle branch and right bundle branch. The left bundle branch divides into anterior, posterior, and, in some cases, median fascicles. AV: atrioventricular; RA: right atrium; LA: left atrium; RV: right ventricle; LV: left ventricle. Graphic 63340 Version 6.0 https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-ii/print 17/25 7/5/23, 10:37 AM Second-degree atrioventricular block: Mobitz type II - UpToDate Electrocardiogram (ECG) showing complete heart block in a patient with syncopal episodes who previously had shown Mobitz II type AV block The first two beats are paced. After the pacemaker is turned off, a normally conducted beat followed with a PR interval of 0.19 sec and a LBBB morphology. The next eight P waves fail to conduct and no lower pacemaker appears to assume control of the ventricles. Restarting the artificial pacemaker led to the QRS complex at the end of the rhythm strip. LBBB: left bundle branch block. Courtesy of Morton Arnsdorf, MD. Graphic 64261 Version 4.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-ii/print 18/25 7/5/23, 10:37 AM Second-degree atrioventricular block: Mobitz type II - UpToDate Electrocardiographic and electrophysiologic features of Mobitz type II second-degree atrioventricular block The PR and RR intervals are constant, but the third atrial beat (A) is not conducted (arrow). His bundle electrocardiography (HBE) shows constant AH (85 msec) and HV (95 msec) intervals and normal AH but no HV conduction in the nonconducted beat. The last finding indicates that the block is distal to the His bundle, in contrast with the more proximal location of Mobitz type I atrioventricular block. Adapted from: Josephson ME, Clinical Cardiac Electrophysiology: Techniques and nd Interpretations, 2 ed, Lea & Febiger, Philadelphia 1993. Graphic 79539 Version 7.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-ii/print 19/25 7/5/23, 10:37 AM Second-degree atrioventricular block: Mobitz type II - UpToDate Single-lead electrocardiogram (ECG) showing first degree atrioventricular (AV) block I Electrocardiogram of lead II showing normal sinus rhythm, first degree atrioventricular block with a prolonged PR interval of 0.30 seconds, and a QRS complex of normal duration. The tall P waves and P wave duration of approximately 0.12 seconds suggest concurrent right atrial enlargement. Courtesy of Morton Arnsdorf, MD. Graphic 67882 Version 5.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-ii/print 20/25 7/5/23, 10:37 AM Second-degree atrioventricular block: Mobitz type II - UpToDate Overview of acute management of Mobitz type II second-degree AV block This algorithm discusses the acute management of Mobitz type II second-degree AV block. Refer to UpToDate content on subsequent management of this condition. AV: atrioventricular. Hemodynamic instability is identified by signs and symptoms of inadequate tissue perfusion, which include hypotension, lightheadedness, altered mental status, poor peripheral perfusion, and other signs of shock. Temporary cardiac pacing is performed with transcutaneous or transvenous pacing. Transcutaneous pacing may be initiated while access for transvenous pacing is obtained. Beta adrenergic agents which may be used in this setting include isoproterenol, dopamine, dobutamine, and epinephrine. Refer to UpToDate content regarding use of these chronotropic agents. Atropine is generally avoided in patients with Mobitz type II second-degree block as it is unlikely to be beneficial and may worsen infranodal block by increasing sinus rate without improving conduction. Graphic 140931 Version 1.0 https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-ii/print 21/25 7/5/23, 10:37 AM Second-degree atrioventricular block: Mobitz type II - UpToDate Mobitz type II second-degree AV block: Identifying candidates for permanent pacemaker placement This algorithm is an aid to identifying which patients with Mobitz type II second-degree AV block require a permanent pacemaker. Patients with persistent Mobitz type II second-degree AV block are at high risk for progressing to symptomatic Mobitz type II second- degree AV block or complete heart block and therefore are candidates for permanent pacemaker placement. Dual-chamber (AV) pacing is generally preferred to maintain AV synchrony. For additional details, refer to UpToDate content on management of Mobitz type II second-degree AV block. AV: atrioventricular. The time course for response to treatment of reversible causes varies depending upon the specific cause of AV conduction delay and other clinical factors. Graphic 140930 Version 1.0 https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-ii/print 22/25 7/5/23, 10:37 AM Second-degree atrioventricular block: Mobitz type II - UpToDate Selection of pacemaker systems for patients with atrioventricular block Decisions are illustrated by diamonds. Shaded boxes indicate type of pacemaker. AV: atrioventricular. Reproduced with permission from: Epstein AE, DiMarco JP, Ellenbogen KA, et al. ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy

idioventricular pacemaker. Courtesy of Ary Goldberger, MD. Graphic 72863 Version 6.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-ii/print 15/25 7/5/23, 10:37 AM Second-degree atrioventricular block: Mobitz type II - UpToDate Major causes of atrioventricular (AV) block Physiologic and pathophysiologic Increased vagal tone Progressive cardiac conduction system disease With fibrosis and/or sclerosis (Lenegre disease) With calcification (Lev disease) Ischemic heart disease, including acute myocardial infarction Cardiomyopathy Infiltrative processes (eg, sarcoidosis, amyloidosis, hemochromatosis, malignancy, etc) Other non-ischemic cardiomyopathies (eg, idiopathic, infectious, etc) Infections (eg, viral myocarditis, Lyme carditis) Congenital AV block Related to structural congenital heart disease As part of neonatal lupus syndrome Other Hyperkalemia, severe hypo- or hyperthyroidism, trauma, degenerative neuromuscular diseases Iatrogenic Drugs Beta blockers, calcium channel blockers, digoxin, adenosine, antiarrhythmic drugs Cardiac surgery Post valvular surgery, post surgical correction of congenital heart disease Transcatheter aortic valve implantation Catheter ablation of arrhythmias Transcatheter closure of VSD Alcohol septal ablation for HCM VSD: ventricular septal defect; HCM: hypertrophic cardiomyopathy. Graphic 62885 Version 6.0 https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-ii/print 16/25 7/5/23, 10:37 AM Second-degree atrioventricular block: Mobitz type II - UpToDate Normal conduction system Schematic representation of the normal intraventricular conduction system (His- Purkinje system). The Bundle of His divides into the left bundle branch and right bundle branch. The left bundle branch divides into anterior, posterior, and, in some cases, median fascicles. AV: atrioventricular; RA: right atrium; LA: left atrium; RV: right ventricle; LV: left ventricle. Graphic 63340 Version 6.0 https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-ii/print 17/25 7/5/23, 10:37 AM Second-degree atrioventricular block: Mobitz type II - UpToDate Electrocardiogram (ECG) showing complete heart block in a patient with syncopal episodes who previously had shown Mobitz II type AV block The first two beats are paced. After the pacemaker is turned off, a normally conducted beat followed with a PR interval of 0.19 sec and a LBBB morphology. The next eight P waves fail to conduct and no lower pacemaker appears to assume control of the ventricles. Restarting the artificial pacemaker led to the QRS complex at the end of the rhythm strip. LBBB: left bundle branch block. Courtesy of Morton Arnsdorf, MD. Graphic 64261 Version 4.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-ii/print 18/25 7/5/23, 10:37 AM Second-degree atrioventricular block: Mobitz type II - UpToDate Electrocardiographic and electrophysiologic features of Mobitz type II second-degree atrioventricular block The PR and RR intervals are constant, but the third atrial beat (A) is not conducted (arrow). His bundle electrocardiography (HBE) shows constant AH (85 msec) and HV (95 msec) intervals and normal AH but no HV conduction in the nonconducted beat. The last finding indicates that the block is distal to the His bundle, in contrast with the more proximal location of Mobitz type I atrioventricular block. Adapted from: Josephson ME, Clinical Cardiac Electrophysiology: Techniques and nd Interpretations, 2 ed, Lea & Febiger, Philadelphia 1993. Graphic 79539 Version 7.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-ii/print 19/25 7/5/23, 10:37 AM Second-degree atrioventricular block: Mobitz type II - UpToDate Single-lead electrocardiogram (ECG) showing first degree atrioventricular (AV) block I Electrocardiogram of lead II showing normal sinus rhythm, first degree atrioventricular block with a prolonged PR interval of 0.30 seconds, and a QRS complex of normal duration. The tall P waves and P wave duration of approximately 0.12 seconds suggest concurrent right atrial enlargement. Courtesy of Morton Arnsdorf, MD. Graphic 67882 Version 5.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-ii/print 20/25 7/5/23, 10:37 AM Second-degree atrioventricular block: Mobitz type II - UpToDate Overview of acute management of Mobitz type II second-degree AV block This algorithm discusses the acute management of Mobitz type II second-degree AV block. Refer to UpToDate content on subsequent management of this condition. AV: atrioventricular. Hemodynamic instability is identified by signs and symptoms of inadequate tissue perfusion, which include hypotension, lightheadedness, altered mental status, poor peripheral perfusion, and other signs of shock. Temporary cardiac pacing is performed with transcutaneous or transvenous pacing. Transcutaneous pacing may be initiated while access for transvenous pacing is obtained. Beta adrenergic agents which may be used in this setting include isoproterenol, dopamine, dobutamine, and epinephrine. Refer to UpToDate content regarding use of these chronotropic agents. Atropine is generally avoided in patients with Mobitz type II second-degree block as it is unlikely to be beneficial and may worsen infranodal block by increasing sinus rate without improving conduction. Graphic 140931 Version 1.0 https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-ii/print 21/25 7/5/23, 10:37 AM Second-degree atrioventricular block: Mobitz type II - UpToDate Mobitz type II second-degree AV block: Identifying candidates for permanent pacemaker placement This algorithm is an aid to identifying which patients with Mobitz type II second-degree AV block require a permanent pacemaker. Patients with persistent Mobitz type II second-degree AV block are at high risk for progressing to symptomatic Mobitz type II second- degree AV block or complete heart block and therefore are candidates for permanent pacemaker placement. Dual-chamber (AV) pacing is generally preferred to maintain AV synchrony. For additional details, refer to UpToDate content on management of Mobitz type II second-degree AV block. AV: atrioventricular. The time course for response to treatment of reversible causes varies depending upon the specific cause of AV conduction delay and other clinical factors. Graphic 140930 Version 1.0 https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-ii/print 22/25 7/5/23, 10:37 AM Second-degree atrioventricular block: Mobitz type II - UpToDate Selection of pacemaker systems for patients with atrioventricular block Decisions are illustrated by diamonds. Shaded boxes indicate type of pacemaker. AV: atrioventricular. Reproduced with permission from: Epstein AE, DiMarco JP, Ellenbogen KA, et al. ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2008; 51(21):e1-e62. Illustration used with permission of Elsevier Inc. All rights reserved. Copyright 2008 Elsevier Inc. https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-ii/print 23/25 7/5/23, 10:37 AM Second-degree atrioventricular block: Mobitz type II - UpToDate Graphic 71370 Version 4.0 https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-ii/print 24/25 7/5/23, 10:37 AM Second-degree atrioventricular block: Mobitz type II - UpToDate Contributor Disclosures William H Sauer, MD Grant/Research/Clinical Trial Support: Biosense-Webster [Catheter ablation]; Boston Scientific [Catheter ablation]. All of the relevant financial relationships listed have been mitigated. Mark S Link, MD No relevant financial relationship(s) with ineligible companies to disclose. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/second-degree-atrioventricular-block-mobitz-type-ii/print 25/25

7/5/23, 10:37 AM Third-degree (complete) atrioventricular block - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Third-degree (complete) atrioventricular block : William H Sauer, MD : Mark S Link, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Oct 13, 2022. INTRODUCTION Atrioventricular (AV) block is defined as a delay or interruption in the transmission of an impulse from the atria to the ventricles due to an anatomical or functional impairment in the conduction system. The conduction disturbance can be transient or permanent, with conduction that is delayed, intermittent, or absent. Commonly used terminology includes: First-degree AV block Slowed conduction without missed beats. Second-degree AV block Missed beats, often in a regular pattern (eg, 2:1, 3:2), or higher degrees of block, which is further classified into Mobitz type I (Wenckebach) and Mobitz II AV block. Third-degree (complete AV) block No atrial impulses reach the ventricle. High-grade AV block Intermittent atrial conduction to the ventricle with two or more consecutive blocked P waves but without complete AV block. The clinical presentation, evaluation, and management of acquired third-degree (complete) AV block will be discussed here. Congenital third-degree (complete) heart block, the etiology of AV block in general, and the management of other specific types of AV block are discussed separately. (See "Etiology of atrioventricular block" and "Congenital third-degree (complete) atrioventricular block" and "First-degree atrioventricular block" and "Second-degree atrioventricular block: Mobitz type I (Wenckebach block)" and "Second-degree atrioventricular block: Mobitz type II".) https://www.uptodate.com/contents/third-degree-complete-atrioventricular-block/print 1/18 7/5/23, 10:37 AM Third-degree (complete) atrioventricular block - UpToDate ETIOLOGY The potential etiologies of third-degree (complete) AV block are similar to lesser degrees of AV block and include reversible causes (both pathologic and iatrogenic) as well as idiopathic causes ( table 1). Common potentially reversible causes include: Pathologic Myocardial ischemia (acute or chronic) involving the conduction system, cardiomyopathy (eg, amyloidosis, sarcoidosis), myocarditis (eg, Lyme disease or COVID-19), endocarditis with abscess formation, hyperkalemia, profound hypothyroidism (myxedema), and hypervagotonia. Iatrogenic Medication-related (AV nodal blocking medications), post-cardiac surgery, post-catheter ablation, post-transcatheter aortic valve implantation. Other pathologic causes may be progressive or irreversible (eg, infiltrative malignancies, neuromuscular diseases). However, in half of more of the cases, no specific reversible causes are identified, and the block is felt to be related to idiopathic progressive cardiac conduction disease with myocardial fibrosis and/or sclerosis that affects the conduction system. A more extensive discussion of the etiology of AV block is presented separately. Congenital complete heart block is generally irreversible. (See "Etiology of atrioventricular block".) CLINICAL PRESENTATION AND EVALUATION The clinical presentation of third-degree (complete) AV block is variable depending upon the rate of the underlying escape rhythm and the presence of comorbid conditions. The evaluation of all patients with suspected third-degree (complete) AV block includes a thorough history, including medications and recent changes in medications, along with a 12-lead electrocardiogram (ECG) and bloodwork (which includes serum electrolytes and thyroid-stimulating hormone [TSH]). Clinical history All patients with suspected third-degree (complete) AV block should be questioned about any history of heart disease, both congenital and acquired, as well as any recent cardiac procedures that could predispose to AV conduction abnormalities. Patients without known cardiac disease should be questioned about other systemic diseases associated with heart block (eg, amyloidosis, sarcoidosis). Patients who live in an area with endemic Lyme disease should be questioned about any recent outdoor exposure to ticks or known tick bites. Congenital heart block can be associated with maternal lupus. (See 'Etiology' above and "Congenital third-degree (complete) atrioventricular block".) https://www.uptodate.com/contents/third-degree-complete-atrioventricular-block/print 2/18 7/5/23, 10:37 AM Third-degree (complete) atrioventricular block - UpToDate Patients with suspected third-degree (complete) AV block that occurs in the setting of acute myocardial ischemia or infarction should undergo concurrent diagnosis and treatment for both conditions. (See "Conduction abnormalities after myocardial infarction", section on 'Management of conduction abnormalities'.) Patients should provide a full list of medications and be questioned about any recent changes in dosing, with particular attention paid to drugs that alter AV nodal conduction (ie, beta blockers, non-dihydropyridine calcium channel blockers, digoxin, select antiarrhythmic drugs). In patients under 60 years of age who present with otherwise unexplained heart block, previously undetected cardiac sarcoidosis has been identified in up to 25 to 35 percent of patients [1,2]. Such patients with otherwise unexplained complete heart block should be evaluated for cardiac sarcoidosis [3]. (See "Clinical manifestations and diagnosis of cardiac sarcoidosis".) Signs and symptoms Nearly all patients with third-degree (complete) AV block will present with some degree of symptoms, though the severity of the symptoms can be quite variable. Symptoms may include: Fatigue Dyspnea Chest pain Presyncope or syncope Sudden cardiac arrest Most patients will present with some level of fatigue and/or dyspnea. These symptoms result from the reduced cardiac output associated with the slower ventricular rate (40 beats per minute or less) of most escape rhythms. Infrequently, patients with a faster escape rhythm (50 to 60 beats per minutes) may have minimal or no symptoms. Conversely, patients with a slower escape rhythm (30 beats per minute or less) are more likely to present with syncope. The absence of any escape rhythm may rarely lead to sudden cardiac death. The new onset of bradycardia associated with third-degree (complete) AV block may also exacerbate comorbid conditions. Patients with underlying coronary heart disease or heart failure may present with abrupt worsening of their typical angina or heart failure symptoms. Very few patients will be entirely asymptomatic with third-degree (complete) AV block. The complete absence of symptoms is likely to be seen only in relatively young, otherwise healthy patients with a high junctional escape rhythm and a ventricular heart rate greater than 40 beats per minute. https://www.uptodate.com/contents/third-degree-complete-atrioventricular-block/print 3/18 7/5/23, 10:37 AM Third-degree (complete) atrioventricular block - UpToDate Patients with third-degree (complete) AV block present with bradycardia but otherwise have few specific physical examination findings. Patients may appear pale or diaphoretic related to the abrupt reduction in cardiac output. Patients with underlying heart failure that is exacerbated by the development of heart block may have crackles on lung examination, elevated jugular venous pulsations, and/or peripheral edema. Electrocardiographic findings Patients with third-degree (complete) AV block will have evidence of atrial (P waves) and ventricular (QRS complexes) activity which are independent of each other on the surface electrocardiogram (ECG) ( waveform 1). In nearly all cases, the atrial rate will be faster than the ventricular escape rate, and there will be no association between the P waves and QRS complexes. As a general rule, the more distal the level of block and the resulting escape rhythm, the slower the ventricular rate will be. Junctional rhythms tend to have a ventricular rate between 40 and 60 beats per minute, while ventricular escape rhythms typically have rates of 40 beats per minute or less and often are unstable. Escape rhythms occur when a pacemaker other than the sinus node has sufficient time to depolarize, attain threshold, and produce a depolarization. In third-degree (complete) AV block, the escape rhythm that controls the ventricles can occur at any level below that of the conduction block and the morphology of the QRS complex can help to determine the location where this is occurring [4-6]. If third-degree AV block occurs within the AV node, about two-thirds of the escape rhythms have a narrow QRS complex (ie, a junctional or AV nodal rhythm) ( waveform 1) [7-9]. Block at the level of the bundle of His is also typically associated with a narrow QRS complex. Patients with infrahisian block have a subjunctional escape rhythm with a wide QRS complex ( waveform 2). If the escape rhythm has a normal QRS duration of less than 120 msec, the block occurs with almost equal frequency in the AV node and the bundle of His [7]. In comparison, involvement of these sites is infrequent with a prolonged QRS; the block in this setting is in the fascicles or bundle branches in over 80 percent of cases [7]. Patients in whom the development of third-degree (complete) AV block exacerbates underlying coronary heart disease may have ECG changes consistent with myocardial ischemia (eg, ST segment and T wave changes). Differential diagnosis of ECG findings Third-degree (complete) AV block has a relatively unique appearance on the ECG, with evidence of atrial (P waves) and ventricular (QRS https://www.uptodate.com/contents/third-degree-complete-atrioventricular-block/print 4/18 7/5/23, 10:37 AM Third-degree (complete) atrioventricular block - UpToDate complexes) activity which are independent of each other and an atrial rate faster than the ventricular rate. Rarely, complete AV block can occur in which the atrial rate is exactly twice the ventricular rate (eg, atrial rate of 80 beats per minute with a ventricular rate of 40 beats per minute), in which case the appearance on ECG could be similar to that of second-degree AV (ie, 2:1) block. However, any slight variation in the exact multiples should result in variations on the ECG that allow the distinction between third-degree (complete) AV block and second-degree AV block. Electrophysiology study With a very few select exceptions, electrophysiologic studies (EPS) are not necessary in patients with complete AV block [10,11]. Among patients with complete AV block, EPS may be indicated when symptoms are not present, the site of block is not apparent, or the block is potentially reversible. (See "Lyme carditis", section on 'Atrioventricular conduction abnormalities'.) DIAGNOSIS In nearly all cases, the diagnosis of third-degree (complete) AV block can be made in a patient with suggestive symptoms (eg, fatigue, dyspnea, presyncope, and/or syncope) by obtaining a surface electrocardiogram (ECG), ideally a full 12-lead ECG but sometime a single-lead rhythm strip is adequate if a full 12-lead ECG cannot be obtained. For the rare patient with a nondiagnostic surface ECG, invasive electrophysiology studies can definitively diagnose third- degree (complete) AV block and accurately identify the level of the block. MANAGEMENT The initial management of the patient with third-degree (complete) AV block depends on the presence and severity of any signs and symptoms related to the ventricular escape rhythm ( algorithm 1). Unstable patients require immediate pharmacologic therapy and, in most instances, should also receive temporary pacing to increase heart rate and cardiac output. Once the patient is hemodynamically stable, assessment and treatment for any potentially reversible causes should occur, followed by placement of a permanent pacemaker for patients without an identifiable reversible etiology [11]. Unstable patients Patients with third-degree (complete) AV block who are hemodynamically unstable should be urgently treated ( algorithm 1) with atropine, beta-adrenergic agonists, and/or temporary cardiac pacing (either with transcutaneous or, if immediately available, https://www.uptodate.com/contents/third-degree-complete-atrioventricular-block/print 5/18 7/5/23, 10:37 AM Third-degree (complete) atrioventricular block - UpToDate transvenous pacing). Beta-adrenergic agonists may be helpful, particularly in patients with block at the AV node. (See "Advanced cardiac life support (ACLS) in adults", section on 'Bradycardia'.) The most important clinical determination in a patient presenting with a third-degree (complete) AV block is whether or not the patient is hemodynamically unstable due to the resulting bradycardia and reduced cardiac output. Signs and symptoms of hemodynamic instability include hypotension, altered mental status, signs of shock, ongoing ischemic chest pain, and evidence of acute pulmonary edema. Such patients should be treated according to the Advanced Cardiac Life Support protocol for patients with symptomatic bradycardia ( algorithm 2) [12]: Atropine should be promptly administered if intravenous (IV) access is available, but treatment with atropine should not delay treatment with transcutaneous pacing or a chronotropic agent. The initial dose of atropine is 1 mg IV. This dose may be repeated every three to five minutes to a total dose of 3 mg. A favorable response to atropine also suggests that AV block is due to abnormal conduction in the AV node. Atropine is not likely to be effective for patients with an escape rhythm at or below the bundle of His since the more distal conducting system is not as sensitive to vagal activity. Atropine is contraindicated in patients with closed angle glaucoma, pyloric stenosis, myasthenia gravis, urinary retention/bladder obstruction, and other conditions. Temporary cardiac pacing should be provided. In the absence of central venous access, the most immediate way to provide temporary cardiac pacing is via transcutaneous pacing. Transcutaneous pacing is uncomfortable for the patient and may have variable efficacy depending on how well the impulses are transmitted to the myocardium; as such, transcutaneous pacing should be viewed as a temporizing measure until temporary transvenous pacing can be provided. (See "Temporary cardiac pacing".) In patients with hypotension associated with third-degree (complete) AV block, we administer dopamine via IV infusion, beginning at a dose of 5 mcg/kg/minute and titrating up to 20 mcg/kg/minute if needed for heart rate and blood pressure augmentation [13]. Our contributors do not use epinephrine in this setting but others do ( algorithm 2). Isoproterenol can also be used, with an initial infusion of 1 to 5 mcg/min, which is titrated to as high as 20 mcg/min based upon heart rate response. In patients with heart failure with reduced ejection fraction (HFrEF) associated with third- degree (complete) AV block, we administer dobutamine via IV infusion, beginning at a dose of 2 to 5 mcg/kg/minute and titrating as needed until an optimal clinical and hemodynamic response is achieved. The usual maintenance dose of dobutamine is 2 to 10 mcg/kg/min (maximum 20 mcg/kg/min). https://www.uptodate.com/contents/third-degree-complete-atrioventricular-block/print 6/18 7/5/23, 10:37 AM Third-degree (complete) atrioventricular block - UpToDate Once a hemodynamically unstable patient has been stabilized, the approach to further management is the same as for patients who were initially stable. (See 'Stable patients' below.) Stable patients Patients with third-degree (complete) AV block who are hemodynamically stable do not require urgent therapy with atropine or temporary cardiac pacing. However, many ventricular escape rhythms are unreliable and potentially unstable, so patients should be continuously monitored with transcutaneous pacing pads in place in the event of clinical deterioration ( algorithm 1). In addition, most stable patients continue to have symptoms related to the bradycardia and will require identification and treatment of any reversible causes or permanent therapy with an implantable pacemaker. While stable patients are being monitored, evaluation and treatment should proceed as follows: Reversible causes of third-degree (complete) AV block such as myocardial ischemia, increased vagal tone, hypothyroidism, hyperkalemia, and drugs that depress conduction, should be excluded in patients prior to implantation of a permanent pacemaker. Patients with third-degree (complete) AV block in the setting of an acute myocardial infarction should be treated with temporary pacing and revascularization; following revascularization, most conduction abnormalities will improve or resolve and will not require permanent pacing. (See "Conduction abnormalities after myocardial infarction", section on 'Summary and recommendations'.) Patients with third-degree (complete) AV block felt to be medication-induced should be observed while the offending agent or agents are withdrawn; such patients will often have improvement or resolution of AV block following removal of the medication. If the medication is deemed necessary, permanent pacing is indicated. Patients with third-degree (complete) AV block in the setting of hyperkalemia should receive therapy to reduce serum potassium levels; similarly, patients with hypothyroidism should receive thyroid replacement therapy. If third-degree (complete) AV block subsequently resolves, a permanent pacemaker is not usually needed. (See "Treatment and prevention of hyperkalemia in adults" and "Treatment of primary hypothyroidism in adults".) Patients with Lyme carditis and associated heart block frequently do not require permanent cardiac pacing. Third-degree (complete) AV block typically improves to lesser degrees of AV block within one week, and more minor conduction disturbances usually resolve within six weeks. As such, while these patients may initially require temporary cardiac pacing, permanent cardiac pacing should be reserved for patients with https://www.uptodate.com/contents/third-degree-complete-atrioventricular-block/print 7/18 7/5/23, 10:37 AM Third-degree (complete) atrioventricular block - UpToDate persistent third-degree (complete) AV block following an adequate course of therapy for Lyme disease. (See "Lyme carditis".) Patients who develop complete heart block after TAVR generally require permanent pacemakers, and should initially be treated with temporary transvenous pacing. Guidelines for patients with less severe conduction abnormalities after TAVR have been developed [14]. (See "Transcatheter aortic valve implantation: Complications".) Transient vagally mediated heart block, often seen on hospital telemetry during sleep, generally does not require specific intervention. Pacing is controversial in vagally mediated syncope, particularly in younger patients. If no reversible causes are present, definitive treatment of third-degree (complete) AV block generally involves permanent pacemaker placement [10,11]. Dual-chamber (ie, atrioventricular) to maintain AV synchrony is preferred (rather than single chamber right ventricular pacing) in most patients due to the favorable hemodynamic benefits of AV synchrony [11]. Some trials suggest that biventricular cardiac pacing (ie, cardiac resynchronization) is superior to standard dual chamber pacing in patients with heart block [15,16]. Implantable cardioverter-defibrillators, specifically cardiac resynchronization therapy devices (CRT-Ds), should be considered in patients with complete AV block and significant left ventricle dysfunction. Conducting system pacing (His- bundle or left-bundle pacing) has emerged as an alternative to CRT pacing [17,18]. Leadless pacing may be appropriate in selected patients. (See "Permanent cardiac pacing: Overview of devices and indications" and "Modes of cardiac pacing: Nomenclature and selection".) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Arrhythmias in adults" and "Society guideline links: Cardiac implantable electronic devices".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading https://www.uptodate.com/contents/third-degree-complete-atrioventricular-block/print 8/18 7/5/23, 10:37 AM Third-degree (complete) atrioventricular block - UpToDate level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Bradycardia (The Basics)" and "Patient education: Heart block in adults (The Basics)") SUMMARY AND RECOMMENDATIONS Definition and etiology In third-degree (complete) atrioventricular (AV) block, no atrial impulses reach the ventricle. Third-degree (complete) AV block can occur in the AV node or in the infranodal specialized conduction system. The potential etiologies of third-degree (complete) AV block include reversible causes (both pathologic and iatrogenic) as well as idiopathic causes. Common potentially reversible causes include myocardial ischemia, medications, and cardiac procedures. (See 'Introduction' above and 'Etiology' above and "Etiology of atrioventricular block".) Clinical presentation The clinical presentation of third-degree (complete) AV block varies depending upon the rate of the underlying escape rhythm and the presence of comorbid conditions. Nearly all patients with third-degree (complete) AV block will present with some degree of symptoms, though the severity of the symptoms can be quite variable. Most patients will present with some level of fatigue and/or dyspnea, and very few patients will be entirely asymptomatic. (See 'Signs and symptoms' above.) ECG findings Patients with third-degree (complete) AV block will have evidence of atrial (P waves) and ventricular (QRS complexes) activity which are independent of each other on the surface ECG. In complete heart block, the escape rhythm can occur at any level below that of the conduction block, and the morphology of the QRS complex can help to determine the location at which this is occurring. If third-degree AV block occurs within the AV node or the bundle of His, the escape rhythm tends to have a narrow QRS complex, whereas AV block occurring below the bundle of His (ie, infrahisian block) results in a subjunctional escape rhythm with a wide QRS complex. (See 'Electrocardiographic findings' above.) Diagnosis In nearly all cases, the diagnosis of third-degree (complete) AV block can be made in a patient with suggestive symptoms (eg, fatigue, dyspnea, presyncope, and/or https://www.uptodate.com/contents/third-degree-complete-atrioventricular-block/print 9/18 7/5/23, 10:37 AM Third-degree (complete) atrioventricular block - UpToDate syncope) by obtaining a surface ECG, ideally a full 12-lead ECG but sometime a single-lead rhythm strip is adequate if a full 12-lead ECG cannot be obtained. (See 'Diagnosis' above.) Initial management Initial treatment of the patient with third-degree (complete) AV block depends on the presence and severity of any signs and symptoms related to the ventricular escape rhythm ( algorithm 1). (See 'Management' above.) Hemodynamically unstable Unstable patients require immediate pharmacologic therapy and, in most instances, temporary pacing to increase heart rate and cardiac output. Atropine (initial dose 1 mg intravenously [IV]) should be promptly administered if IV access is available, but treatment with atropine should not delay treatment with transcutaneous pacing or a chronotropic agent. Temporary cardiac pacing should be provided. In the absence of central venous access, the most immediate way to provide temporary cardiac pacing is via transcutaneous pacing (see 'Unstable patients' above and "Temporary cardiac pacing"). Beta-adrenergic agonists may also be helpful in some patients with complete heart block. Hemodynamically stable Patients with third-degree (complete) AV block who are initially hemodynamically stable do not require urgent therapy with atropine or temporary cardiac pacing. However, many ventricular escape rhythms are unreliable and potentially unstable, so patients should be continuously monitored with transcutaneous pacing pads in place in the event of clinical deterioration. (See 'Stable patients' above.) Subsequent management Once the patient is hemodynamically stable, reversible causes of third-degree (complete) AV block such as myocardial ischemia, increased vagal tone, hypothyroidism, hyperkalemia, and drugs that depress conduction, should be excluded in patients prior to implantation of a permanent pacemaker. (See 'Stable patients' above.) Once reversible causes of heart block have been excluded, permanent pacing is generally indicated. (See 'Stable patients' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Leonard Ganz, MD, FHRS, FACC, who contributed to earlier versions of this topic review. Use of UpToDate is subject to the Terms of Use. https://www.uptodate.com/contents/third-degree-complete-atrioventricular-block/print 10/18 7/5/23, 10:37 AM Third-degree (complete) atrioventricular block - UpToDate REFERENCES 1. Takaya Y, Kusano KF, Nakamura K, Ito H. Outcomes in patients with high-degree atrioventricular block as the initial manifestation of cardiac sarcoidosis. Am J Cardiol 2015; 115:505. 2. Nery PB, Beanlands RS, Nair GM, et al. Atrioventricular block as the initial manifestation of cardiac sarcoidosis in middle-aged adults. J Cardiovasc Electrophysiol 2014; 25:875. 3. Birnie DH, Sauer WH, Bogun F, et al. HRS expert consensus statement on the diagnosis and management of arrhythmias associated with cardiac sarcoidosis. Heart Rhythm 2014; 11:1305. 4. Narula OS, Javier RP, Samet P, Maramba LC. Significance of His and left bundle recordings from the left heart in man. Circulation 1970; 42:385. 5. Narula OS, Scherlag BJ, Javier RP, et al. Analysis of the A-V conduction defect in complete heart block utilizing His bundle electrograms. Circulation 1970; 41:437. 6. Guimond C, Puech P. Intra-His bundle blocks (102 cases). Eur J Cardiol 1976; 4:481. 7. Peuch P, Grolleau R, Guimond C. Incidence of different types of A-V block and their localizati on by His bundle recordings. In: The Conduction System of the Heart, Wellens HJJ, Lie KI, Jan se MJ (Eds), Stenfert Kroese, Leiden 1976. p.467. 8. Narula OS. Current concepts of atrioventricular block. In: His Bundle Electrocardiography an d Clinical Electrophysiology, Narula OS (Ed), Davis, Philadelphia 1975. p.139. 9. Rosen KM, Dhingra RC, Loeb HS, Rahimtoola SH. Chronic heart block in adults. Clinical and electrophysiological observations. Arch Intern Med 1973; 131:663. 10. Brignole M, Auricchio A, Baron-Esquivias G, et al. 2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: the Task Force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Eur Heart J 2013; 34:2281. 11. Kusumoto FM, Schoenfeld MH, Barrett C, et al. 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2019; 74:e51. 12. Panchal AR, Bartos JA, Caba as JG, et al. Part 3: Adult Basic and Advanced Life Support: 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2020; 142:S366. https://www.uptodate.com/contents/third-degree-complete-atrioventricular-block/print 11/18 7/5/23, 10:37 AM Third-degree (complete) atrioventricular block - UpToDate 13. Kusumoto FM, Schoenfeld MH, Barrett C, et al. 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation 2019; 140:e382. 14. Rod s-Cabau J, Ellenbogen KA, Krahn AD, et al. Management of Conduction Disturbances Associated With Transcatheter Aortic Valve Replacement: JACC Scientific Expert Panel. J Am Coll Cardiol 2019; 74:1086. 15. Yu CM, Chan JY, Zhang Q, et al. Biventricular pacing in patients with bradycardia and normal ejection fraction. N Engl J Med 2009; 361:2123. 16. Curtis AB, Worley SJ, Adamson PB, et al. Biventricular pacing for atrioventricular block and systolic dysfunction. N Engl J Med 2013; 368:1585. 17. Upadhyay GA, Vijayaraman P, Nayak HM, et al. On-treatment comparison between corrective His bundle pacing and biventricular pacing for cardiac resynchronization: A secondary analysis of the His-SYNC Pilot Trial. Heart Rhythm 2019; 16:1797. 18. Sharma PS, Vijayaraman P, Ellenbogen KA. Permanent His bundle pacing: shaping the future of physiological ventricular pacing. Nat Rev Cardiol 2020; 17:22. Topic 911 Version 39.0 https://www.uptodate.com/contents/third-degree-complete-atrioventricular-block/print 12/18 7/5/23, 10:37 AM Third-degree (complete) atrioventricular block - UpToDate GRAPHICS Major causes of atrioventricular (AV) block Physiologic and pathophysiologic Increased vagal tone Progressive cardiac conduction system disease With fibrosis and/or sclerosis (Lenegre disease) With calcification (Lev disease) Ischemic heart disease, including acute myocardial infarction Cardiomyopathy Infiltrative processes (eg, sarcoidosis, amyloidosis, hemochromatosis, malignancy, etc) Other non-ischemic cardiomyopathies (eg, idiopathic, infectious, etc) Infections (eg, viral myocarditis, Lyme carditis) Congenital AV block Related to structural congenital heart disease As part of neonatal lupus syndrome Other Hyperkalemia, severe hypo- or hyperthyroidism, trauma, degenerative neuromuscular diseases Iatrogenic Drugs Beta blockers, calcium channel blockers, digoxin, adenosine, antiarrhythmic drugs Cardiac surgery Post valvular surgery, post surgical correction of congenital heart disease Transcatheter aortic valve implantation Catheter ablation of arrhythmias Transcatheter closure of VSD Alcohol septal ablation for HCM VSD: ventricular septal defect; HCM: hypertrophic cardiomyopathy. Graphic 62885 Version 6.0 https://www.uptodate.com/contents/third-degree-complete-atrioventricular-block/print 13/18 7/5/23, 10:37 AM Third-degree (complete) atrioventricular block - UpToDate Third degree (complete) atrioventricular block with narrow QRS escape rhythm The P waves are completely dissociated from the QRS complexes. The QRS complexes are narrow, indicating a junctional escape rhythm. The atrial and ventricular rates are stable; the former is faster than the latter. Graphic 65545 Version 5.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/third-degree-complete-atrioventricular-block/print 14/18 7/5/23, 10:37 AM Third-degree (complete) atrioventricular block - UpToDate Third degree (complete) atrioventricular block with wide QRS escape rhythm The P waves are completely dissociated from the QRS complexes and the PR intervals are variable. The atrial or PP rate (75 beats per minute) is faster than the ventricular or RR rate (30 beats per minute), establishing complete atrioventricular blockade as the etiology. The QRS complexes are wide indicating that the escape rhythm is ventricular. Graphic 51446 Version 5.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/third-degree-complete-atrioventricular-block/print 15/18 7/5/23, 10:37 AM Third-degree (complete) atrioventricular block - UpToDate Algorithm showing the treatment approach to the patient with complete heart block ECG: electrocardiogram; CHB: complete heart block; BP: blood pressure; HF: heart failure; IV: intravenous; PPM: permanent pacemaker. The initial dose of atropine is 1 mg IV. This dose may be repeated every 3 to 5 minutes to a total dose of 3 mg. While transcutaneous pacing may be initially successful in stabilizing the patient, it may not be consistently reliable. Central venous access should be considered in the event that urgent transvenous pacing is required. Dopamine IV infusion typically begins at a dose of 5 mcg/kg/minute and is titrated as needed to achieve an optimal clinical and hemodynamic response (maximum dose of 20 mcg/kg/minute). Dobutamine IV infusion typically begins at a dose of 2 to 5 mcg/kg/minute and is titrated as needed to achieve an optimal clinical and hemodynamic response. The usual maintenance dose of dobutamine is 2 to 10 mcg/kg/minute (maximum dose of 20 mcg/kg/minute). Graphic 103365 Version 7.0 https://www.uptodate.com/contents/third-degree-complete-atrioventricular-block/print 16/18 7/5/23, 10:37 AM Third-degree (complete) atrioventricular block - UpToDate Adult bradycardia algorithm 2020 update Reprinted with permission. ACLS Provider Manual. Copyright 2020 American Heart Association, Inc. Graphic 130748 Version 10.0 https://www.uptodate.com/contents/third-degree-complete-atrioventricular-block/print 17/18 7/5/23, 10:37 AM Third-degree (complete) atrioventricular block - UpToDate Contributor Disclosures William H Sauer, MD Grant/Research/Clinical Trial Support: Biosense-Webster [Catheter ablation]; Boston Scientific [Catheter ablation]. All of the relevant financial relationships listed have been mitigated. Mark S Link, MD No relevant financial relationship(s) with ineligible companies to disclose. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/third-degree-complete-atrioventricular-block/print 18/18

7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Electrocardiographic and electrophysiologic features of atrial flutter : Jordan M Prutkin, MD, MHS, FHRS : Peter J Zimetbaum, MD, Ary L Goldberger, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Mar 31, 2023. INTRODUCTION Atrial flutter (AFL) is an abnormal cardiac rhythm characterized by rapid, regular atrial depolarizations at a typical atrial rate of 250 to 350 beats per minute. There is frequently 2:1 conduction across the atrioventricular (AV) node, meaning that every other atrial depolarization reaches the ventricles. As a result, the ventricular rate is usually one-half the AFL rate in the absence of AV node dysfunction. AFL is classified as typical or atypical based on whether the flutter circuit traverses the cavotricuspid isthmus in the right atrium [1]. Other topic reviews discuss the clinical aspects of AFL. (See "Overview of atrial flutter" and "Restoration of sinus rhythm in atrial flutter" and "Control of ventricular rate in atrial flutter" and "Atrial flutter: Maintenance of sinus rhythm" and "Embolic risk and the role of anticoagulation in atrial flutter" and "Atrial fibrillation and flutter after cardiac surgery".) CLASSIFICATION The first classification scheme in 1970 defined atrial flutter (AFL) as "common" or "atypical," depending on whether the flutter wave had a negative sawtooth pattern in the inferior leads [2]. A few years later, the terms types I and II were created to describe flutter [1]. Type I AFL was classified as a macroreentrant atrial tachycardia while type II AFL was considered unclassified because the mechanisms were not fully understood. https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 1/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate A 2001 working group from Europe and North America tried to reconcile new data from electrophysiology studies and activation mapping [3]. Flutter was defined as a regular tachycardia 240 beats/min with no isoelectric baseline between atrial deflections. Typical and reversal typical flutter were characterized, as described below, and all other flutters were atypical. An American College of Cardiology, American Heart Association, and Heart Rhythm Society guideline on the management of supraventricular tachycardia reaffirmed the classification of AFL into cavo-tricuspid-isthmus (CTI)-dependent ("typical") versus non-CTI dependent ("atypical") [4] and this is the methodology currently used. Typical AFL is a macroreentrant atrial tachycardia, with the inferior border of the circuit traversing the isthmus of tissue between the inferior vena cava and tricuspid annulus as a necessary component. AFL involving this cavotricuspid isthmus is referred to as "typical" or "isthmus-dependent" flutter. In the most common form of CTI-dependent flutter, the reentrant circuit rotates around the tricuspid annulus in a counterclockwise direction when the heart is viewed in a left anterior oblique projection, traversing up the septum and down the lateral wall. This is the arrhythmia associated with the classic electrocardiogram finding of sawtooth flutter waves in the inferior leads. (See 'Electrocardiographic features' below.) Less often, the reentrant circuit rotates in the opposite direction. This arrhythmia is called "clockwise" or "reverse" typical flutter. Atypical AFL is an intraatrial reentrant tachycardia or AFL that does not involve the CTI. It may be a lesion macroreentrant tachycardia, upper loop flutter, intra-isthmus reentry, non-atriotomy- related right atrial flutter, left atrial macroreentry, post-Maze or atrial fibrillation ablation left atrial flutters, or mitral annular flutter [5]. It is frequently seen in those who have had prior cardiac surgery, prior intracardiac ablation, congenital heart disease, or cardiomyopathy but may also be idiopathic. Atypical flutter may be in the right or left atrium and usually revolves around a prior incisional or idiopathic scar, ablation lesion set, or other fixed anatomic barriers. If there has been an incomplete ablation line from a prior procedure, this can increase the chances of an atypical flutter. Many patients with congenital heart disease, especially with more complex disease or surgical repairs, will present with atypical flutter, known as intraatrial reentrant tachycardia [6]. Some patients with idiopathic atrial fibrosis will also present with scar- based atypical flutters. ELECTROPHYSIOLOGIC FEATURES https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 2/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Electrophysiologic studies, using entrainment mapping and electroanatomic mapping, have been used to define the atrial flutter (AFL) circuit in the electrophysiology laboratory and at surgery [7-11]. The principal electrophysiologic features of AFL are: Reentry Excitable gap Transient entrainment and termination by rapid atrial pacing Electrophysiologically, AFL is a reentrant arrhythmia in that it excites an area of the atrium and then travels sufficiently slowly in a pathway that is long enough such that the initially excited area recovers its excitability and is reactivated [7-9,12-15]. Either a single premature extrastimulus or rapid atrial pacing can initiate AFL and, because there is an excitable gap, terminate the arrhythmia [13-15]. The excitable gap is the portion of a reentrant circuit that has recovered its excitability and can again be depolarized, allowing for entrainment with overdrive pacing during AFL [13,14,16]. (See "Reentry and the development of cardiac arrhythmias", section on 'Definition and characteristics'.) Typical AFL commonly starts after a transitional rhythm of variable duration, usually atrial fibrillation [17,18]. It has been postulated that a fundamental feature that determines whether an atrial arrhythmia becomes sustained typical AFL or atrial fibrillation is the development of a line of functional refractoriness or block between the vena cavae [18]. In spontaneous typical AFL, the critical line of functional block between the vena cavae may be created by transient atrial fibrillation. This line of block results in unidirectional block and stable AFL follows. According to this theory, if the line of functional block is not created, atrial fibrillation persists or the rhythm reverts back to sinus. Another view, based in part on a small electrophysiologic study of 10 patients, emphasizes the anatomic barriers as well as the properties of conduction and refractoriness during atrial fibrillation to explain the usual pattern observed with typical AFL [19]. In the electrophysiology laboratory, premature electrical stimulation may function in a manner similar to the transitional atrial fibrillation in forming the critical functional line of block between the vena cavae [18]. An additional determinant of whether the transitional atrial tachyarrhythmia becomes AFL or atrial fibrillation may be the cycle length of the flutter [18]. If the cycle length is critically short, it will create fibrillatory conduction and atrial fibrillation. Lastly, the electrical properties of the isthmus may also be a factor in the tendency for AFL to disorganize into atrial fibrillation in some patients [20]. https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 3/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Similar to what has been reported in atrial fibrillation, AFL results in electrical remodeling of the atrial myocardium, perhaps accounting for the observation that untreated AFL can eventually lead to atrial fibrillation [21]. In contrast to the normal situation in which the atrial refractory period shortens with an increase in rate and prolongs when the rate decreases, the refractory period fails to lengthen appropriately at slow rates (eg, with return to sinus rhythm) in patients with AFL present for a mean of 8.5 months (range 1 to 32 months) [22]. This abnormality persists for at least 30 minutes after cardioversion to sinus rhythm; the duration of AFL has no significant impact upon the magnitude of these electrophysiologic changes. Those with a history of AFL, but not fibrillation, have significant changes in the electrophysiologic properties of the right atrium, even when they are in normal sinus rhythm. The right atrium is more likely to be enlarged, have lower voltage suggesting scar, longer P wave duration, and slowed conduction velocity most prominent in the lower right atrium, and sinus node dysfunction [23]. The duration of AFL does impact the time course of electrical remodeling recovery after arrhythmia termination. As an example, one study of 25 patients with paroxysmal or chronic flutter (average duration 17 months) found that, in those with paroxysmal AFL, the refractory period shortened after a 5- to 10-minute period of flutter and reversed within five minutes of restoration of sinus rhythm; atrial fibrillation developed in some patients when the refractory period was at its nadir [24]. In patients with chronic AFL, the atrial refractory period increased during the first three weeks after resumption of sinus rhythm. Typical flutters A large macroreentrant circuit in the right atrium is involved in typical AFL. If one begins the cycle at the end of the negative deflection of the F wave in lead II, the impulse at that point exists in the low right atrial septum between the inferior vena cava (IVC) and the tricuspid valve. In counterclockwise typical flutter, the impulse then travels anteriorly through the region of the low septum, ascends superiorly and anteriorly up the septal and posterior walls of the right atrium, and returns or descends over the anterior and lateral free wall ( figure 1) [25]. This circuit is then completed through the region between the tricuspid valve and IVC (counterclockwise reentry). A reverse direction of rotation (clockwise reentry, ascending the anterior wall, and descending the posterior and septal walls) is seen in reverse typical AFL [3,25]. The crista terminalis (and its continuation as the eustachian ridge) and IVC often form the posterior barrier, while the tricuspid annulus constitutes the anterior barrier of the circuit ( figure 1) [11,26]. This has potential clinical implications, since this region can be a target for ablation therapy in patients with refractory AFL [26,27]. (See "Atrial flutter: Maintenance of sinus rhythm", section on 'RF catheter ablation'.) https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 4/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate The presence of slow conduction in the cavotricuspid isthmus has been confirmed by noncontact mapping [28]. The cavotricuspid isthmus is a part of the circuit most vulnerable to interval-dependent conduction delay [16] and termination of AFL with ibutilide, propafenone, or amiodarone is due in part to failure of impulse conduction through this tissue [22]. (See "Overview of catheter ablation of cardiac arrhythmias", section on 'Noncontact mapping'.) The typical AFL circuit has been thought to run anterior to the superior vena cava (SVC) in most patients [29]. However, a study of 15 patients with typical flutter using noncontact and entrainment mapping showed that the posterior wall was a part of the circuit in seven patients [30]. In a study of 50 patients using entrainment mapping, between one-quarter to one-third did not use the atrial roof anterior to the SVC as part of the circuit [31]. These studies imply that the crista terminalis is not always a fixed barrier to conduction and the circuit can be posterior to the SVC. Partial isthmus atrial flutter is a type of typical flutter where a wavefront goes between the IVC and coronary sinus ostium after conducting through the posterior cavo-tricuspid-isthmus (CTI). This wavefront then conducts around the CS ostium and up the septum, but also goes retrograde back into the anterior CTI. For this circuit to occur, there must either be a pectinate muscle that breaks the CTI into an anterior and posterior portion [32] or rapid conduction through the eustachian ridge [26]. Intra-isthmus reentry is usually seen in those with prior CTI ablation [33]. The circuit is contained entirely within the CTI and may be in the septal, medial, or anterior portions, with areas of long fractionated potentials the best target for ablation [33]. The circuit for lower loop reentry circles around the IVC, on the septal side usually between the IVC and coronary sinus ostium [34]. It exits out on the low lateral wall, with wavefront one conducting up the lateral wall and wavefront two going through the CTI, anterior to the coronary sinus ostium, and up the septal wall in a manner similar to counterclockwise typical flutter. The two wave fronts collide somewhere in the lateral right atrium or septum, but the dominant circuit still encircles the IVC. Lower loop reentry frequently morphs into counterclockwise AFL and may be associated with an atrial myopathy [5]. Atypical right atrial flutters Lesion macroreentrant tachycardia An atriotomy scar or suture line can act as an obstacle to conduction and create reentry. There may also be atrial septal defect patches that can lead to an atypical flutter circuit. In addition, scar from congenital heart disease lesions such as after an atrial level switch surgery (Mustard or Senning repairs) for transposition of the great arteries or https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 5/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate after a Fontan repair may lead to atypical flutters. (See "Management of complications in patients with Fontan circulation", section on 'Arrhythmias'.) Atriotomy scar-related atypical flutters are the most common of this type, where the scar is vertical along the lateral right atrium. The anterior right atrial wall may have ascending or descending activation depending on whether the circuit is clockwise or counterclockwise, while the septum may have more variable conduction [3]. The circuit wraps around the incision, with the upper turnaround point between the scar and SVC and the lower turnaround point between the scar and IVC. Alternatively, one of the turnaround points may be through an area of conduction within the scar. As is true for all flutters, entrainment and activation mapping are helpful for defining the circuit. The atriotomy region will have double potentials and low voltage to denote its location. During flutter, the double potentials are more widely spaced in the center of the scar and usually become one single fractionated electrogram at the turnaround points. Typical flutter may be seen after ablation of this atypical flutter, if a prior cavotricuspid isthmus ablation has not previously been completed. Nonatriotomy-related right atrial flutter For unexplained reasons, some patients will have areas of low voltage in the right atrium. This may lead to a scar similar to an atriotomy lesion, even though there has been no cardiac incision. This leads to a flutter wrapping around the scar, though may also be a figure-8 reentry if there is conduction through the low voltage area [32]. Ablation from the lower border of the scar to the IVC frequently terminates the arrhythmia. Upper loop reentry This circuit crosses through a conduction gap in the crista terminalis in the upper right atrium, which is where the successful site of ablation can be [35]. It can be clockwise or counterclockwise, with activation going up or down the anterior right atrial free wall. At least one patient also demonstrated successful ablation in the region between the fossa ovalis and IVC [32], indicating that this tachycardia circuit may not be as clearly defined as previously thought. Atypical left atrial flutters Post-Maze or atrial fibrillation ablation left atrial flutters These tachycardias are most frequently due to incomplete ablation lines from either a transvenous catheter ablation or a surgical Maze procedure. They may also be related to left atrial fibrosis seen in those with a history of atrial arrhythmias. They are usually seen in the anterior wall, through the roof, or on the septum. Mapping can often be difficult due to low voltages. (See "Atrial fibrillation: Surgical ablation", section on 'Maze procedure'.) https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 6/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Mitral annular flutter wraps around the mitral valve clockwise or counterclockwise [36,37]. Entrainment from a catheter in the coronary sinus will frequently demonstrate concealed entrainment on all poles for mitral annular flutter, but not for other left atrial flutters. It can be difficult to terminate and often needs ablation within the coronary sinus or vein of Marshall to achieve a line of block [38]. Even in the presence of apparent complete block, there may still be recurrence of mitral flutter as there may only be significant conduction slowing rather than block [39]. Left atrial macroreentry Less commonly, atypical flutters can occur in those with no prior ablation or surgery in the left atrium. They may be located on the anterior or posterior wall and are bounded by an anatomic obstacle like the mitral annulus [40]. They may be a single circuit or double loop and are associated with low voltage signals with areas of fractionated signals [41]. Atrioventricular node and the ventricular response The electrophysiologic events in AFL can be viewed as an input (the F waves) and an output (QRS complexes) that is processed through a regulator or black box (the atrioventricular [AV] node). The electrophysiologic characteristics of the AV node, which is a "slow response" tissue in comparison to the atria, primarily determine the ventricular response. (See "The electrocardiogram in atrial fibrillation".) As noted below (see 'Electrophysiologic features' above), the ventricular response in AFL is generally one-half the atrial input, resulting in a ventricular rate of about 150 beats/min. 3:1 and 4:1 input/output ratios are also relatively common, leading to ventricular rates of about 100 and 75 beats/min, respectively. Thus, AFL should be considered whenever the electrocardiogram shows a heart rate of 150, 100, and 75 beats/min. Rarely, the input/output ratio is 1:1, resulting in a ventricular response of nearly 300 beats/min. This may occur in states characterized by marked catecholamine excess and in the presence of AV bypass tracts with preexcitation ( waveform 1). A 1:1 response is more commonly seen when the atrial rate is slowed and AV nodal conduction is enhanced, leading to ventricular rates of 220 to 250 beats/min. This combination can be induced by class IA or IC antiarrhythmic drugs ( table 1) due to: Slowing of the conduction velocity in the reentrant circuit and therefore the flutter rate by inhibition of sodium channels. Increasing AV nodal conduction by their vagolytic effects. These characteristics have implications for management. (See "Control of ventricular rate in atrial flutter".) https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 7/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Partial or complete block in the AV node or in the specialized infranodal conduction system (His bundle, bundle branches and fascicles, and terminal Purkinje fibers) may lead to escape or accelerated rhythms from within the AV node or below to assume control of the ventricles. The ventricular rate in this setting may be normal, faster, or slower than is normal for these lower pacemakers. The diagnosis of complete heart block may be missed if F waves are not carefully matched with R waves or when the lower escape rate approaches an arithmetic divisor of the flutter rate. As is true for atrial fibrillation, there may be a Wenckebach type of exit block around such an escape site, resulting in group beating. ELECTROCARDIOGRAPHIC FEATURES The electrocardiographic features of typical atrial flutter (AFL) in the presence of normal atrioventricular (AV) nodal conduction are ( waveform 2): P waves are absent. For counterclockwise typical AFL, biphasic "sawtooth" flutter waves (F waves) are present at a rate of about 300 beats/min, with the range being 240 to 340 beats/min [1]. The F waves are fairly regular on the surface electrocardiogram with constant amplitude, duration, morphology, and reproducibility throughout the cardiac cycles. There can be very subtle variability, however, as spectral analysis has detected an underlying periodic pattern modulated by an interplay between the autonomic nervous system, respiratory system, and ventricular rate [42]. The F waves usually do not have an isoelectric interval between them (ie, the F waves blend into one another) unless the rate of the AFL is slow. In counterclockwise typical AFL, the F waves have an axis of around 90 and are prominently negative in the inferior leads (II, III, aVF). The F waves often have an initial slowly downsloping segment followed by a sharp negative deflection, then a sharp positive deflection that may have a positive overshoot leading into the next downward deflection ( waveform 2). With 2:1 flutter, there is commonly a negative deflection superimposed on the ST segment, giving the appearance of ST depression related to myocardial ischemia. In clockwise typical AFL (reverse typical AFL), the F waves are usually positive in the inferior leads due to an opposite direction of atrial activation, but there is significant https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 8/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate heterogeneity in the F wave morphology [3]. The F wave may even have a sine wave pattern. The deflection in V1 is often broad and negative ( waveform 3) (panel B). The ventricular response (R-R intervals) is usually one-half the rate of the atrial input (ie, 2:1 AV nodal conduction with a ventricular response of about 150 beats/min). This finding is sufficiently common and the diagnosis of AFL should be considered whenever the ventricular rate is about 150 beats/min. AV block greater than 2:1 in the absence of drugs that slow the ventricular response suggests AV nodal disease and the possibility of associated sinus node disease, which may be part of the tachy-brady syndrome. A 1:1 AV response suggests accessory bypass tracts, sympathetic excess, parasympathetic withdrawal, or class IC antiarrhythmic agents. Even ratios of input to output (eg, 2:1, 4:1) are more common than odd numbers (eg, 3:1, 5:1). Odd ratios and shifting ratios (eg, alteration of 2:1 with 4:1) probably reflect bilevel block in the AV node. The QRS complex is narrow unless there is functional aberration, preexisting bundle branch or fascicular block, preexcitation, or ventricular pacing. The electrocardiographic features of atypical AFL are: P waves are absent. F waves are regular, but in contrast to typical AFL, there may be an isoelectric appearance between F waves if there is an area of significantly slowed conduction. There is no clear F wave morphology to identify the location consistently, as atypical flutters are often associated with atrial scar that can alter conduction velocity and direction. That said, some patterns described below may be seen. Lower loop reentry typically has negative F waves in the inferior leads ( waveform 4). Upper loop reentry has positive F waves in the inferior leads and negative, flat, or barely positive F waves in lead I [43]. Intra-isthmus reentry will appear like typical counterclockwise AFL. If there is a negative F wave in V1, the flutter is usually in the right atrium ( waveform 5). Left atrial flutters have variable morphologies, but may have a positive F wave in V1 or may be isoelectric ( waveform 6) [5]. It is often positive in the inferior leads, but not always ( waveform 7). https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 9/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Counterclockwise mitral annular flutter is positive in V1-6 and the inferior leads and negative in aVL [44]. Clockwise mitral annular flutter is positive in the right precordial leads but usually negative and then positive in the lateral precordial leads ( waveform 8). It is negative in the inferior leads and positive in I and aVL. Morphology of the QRS complex Activation through the AV node and infranodal conduction system is normal in AFL, so the QRS complex is narrow unless: A preexisting conduction defect is present. Functional block occurs in a portion of the infranodal conduction system, leading to a bundle branch or fascicular block. The refractory period of the bundle branches and fascicles is determined by the preceding cycle length. A long preceding cycle lengthens the refractory period in these structures, so a premature beat is more likely to be functionally blocked after a long cycle, known as Ashman's phenomenon. Preexcitation through an AV bypass tract is present. Ventricular pacing is present. Pitfalls The electrocardiographic criteria listed above are usually sufficient to make the proper diagnosis; there are, however, potential pitfalls: One of the F waves may be obscured by the QRS complex or the ST-T wave ( waveform 9) in patients with 2:1 AV nodal conduction. In this setting, AFL may be misdiagnosed as a sinus tachycardia or a paroxysmal supraventricular tachycardia with downsloping ST depression. In clockwise, typical flutter, the F waves may be positive, and if every other F wave is obscured, it may be mistaken for a long RP tachycardia such as sinus tachycardia, ectopic atrial tachycardia, atypical AV nodal reentrant tachycardia, or AV reciprocating tachycardia. The atrial electrical potential may be small and the F waves may be difficult to see in the standard leads. Sometimes it may be necessary to increase the gain of the electrocardiogram to see the F waves more clearly (ie, 20 mm/mV). Atrial fibrillation, especially with coarse fibrillatory waves in lead V1, is often misdiagnosed as AFL [45]. Examination of a rhythm strip will often show that the atrial fibrillatory rate and morphology change over a period of time. We discourage using the term AFL-fibrillation, since the rhythm more closely resembles atrial fibrillation in its response to drugs that slow AV nodal conduction and in the higher energy requirement for direct current cardioversion. https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 10/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Sometimes the negative F wave merges with the beginning or end of the QRS complex, suggesting a pathologic Q wave in the first case and a conduction delay in the second. Likewise, the F wave may appear to cause pathologic ST-segment depression. The F wave morphology may appear atypical in those with congenital heart disease, atrial fibrosis, following cardiac surgery, or after left atrial ablation for atrial fibrillation even though the rhythm is typical flutter [46,47]. Prior extensive ablation in the left atrium may alter the morphology of F waves in typical AFL, due to reductions in left atrial potentials and changes in the atrial activation sequence. This was illustrated in a series of 15 patients who had undergone circumferential left atrial ablation for the treatment of atrial fibrillation and later developed typical AFL (12 counterclockwise, 3 clockwise) [47]. In 9 of 15 cases, the F waves were upright in the inferior leads, including 7 of 12 of typical counterclockwise flutter. Electrocardiography and telemetry artifacts caused by tremor [48] or electromagnetic interference [49,50] may suggest the occurrence of AFL, but this pseudo-atrial flutter will be revealed when the tremor or interference ceases. DIFFERENTIAL DIAGNOSIS The differential diagnosis of atrial flutter (AFL) includes a number of supraventricular tachyarrhythmias. (See "Focal atrial tachycardia" and "Intraatrial reentrant tachycardia" and "Sinoatrial nodal reentrant tachycardia (SANRT)" and "Cardiac arrhythmias due to digoxin toxicity" and "Multifocal atrial tachycardia" and "Atrioventricular nodal reentrant tachycardia" and "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'Types of narrow QRS complex tachycardia'.) As noted above, obscured atrial activity or F waves that resemble normal or inverted P waves may suggest sinus tachycardia, paroxysmal supraventricular tachycardia, or atrial fibrillation. There are four major ways to help establish the correct diagnosis: An earlier electrocardiogram, if available, may allow comparison of the F or presumed P wave with the previous P wave morphology. Scrutiny of the ST-segment and T waves may show a bump or irregularity caused by a second flutter wave. Decreasing atrioventricular (AV) nodal conduction physiologically with a vagotonic maneuver (such as the Valsalva maneuver or carotid sinus massage) or with a rapidly https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 11/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate acting drug (such as adenosine, verapamil, or esmolol) will increase the AV nodal block and reveal the atrial F waves ( waveform 9). Recording from an atrial catheter, atrial pacing wire, or an esophageal electrode will also demonstrate the regular atrial activity ( waveform 10). Even with these maneuvers, ectopic atrial tachycardia and other supraventricular tachycardias with 2:1 block may remain in the differential diagnosis. Furthermore, two types of arrhythmia can occur in the same patient, as a supraventricular tachycardia can initiate AFL or atrial fibrillation. An example of this difficulty occurs when AFL has a slow ventricular response that overlaps with the rate seen in other supraventricular tachycardias. If, for example, the patient is taking digitalis for flutter, then an atrial tachycardia with a 2:1 AV response that reflects a high degree of digitalis toxicity must be excluded. Treatment of these two disorders is clearly different, and atrial morphology may be of little help in identifying the underlying arrhythmia. In this setting, establishment of the correct diagnosis may depend upon the clinical history, plasma digoxin levels, and the response following cessation of digoxin therapy. As noted above, complete heart block may be difficult to recognize in the presence of AFL. The presence of F waves and a regular rate of the lower pacemaker may lead to the appearance of an uncomplicated AFL. MANAGEMENT The control of ventricular rate and the approach to anticoagulant therapy for patient with atrial flutter is discussed elsewhere. (See "Overview of atrial flutter" and "Embolic risk and the role of anticoagulation in atrial flutter".) Cardioversion in patients with atrial flutter is discussed separately. (See "Restoration of sinus rhythm in atrial flutter".) The approach to the maintenance of sinus rhythm and the impact of electrophysiologic type is discussed separately. (See "Atrial flutter: Maintenance of sinus rhythm" and "Atrial flutter: Maintenance of sinus rhythm", section on 'RF catheter ablation'.) SUMMARY https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 12/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Atrial flutter (AFL) is a supraventricular tachycardia with regular flutter waves and usually an absent isoelectric interval. The rhythm is due to macroreentry, has an excitable gap, and can be transiently entrained and terminated by rapid atrial pacing. Electrocardiographic characteristics include: Biphasic, sawtooth F waves, best seen in the inferior electrocardiogram leads (II, III, aVF), at about 300 beats/min are the classic finding for typical, counterclockwise AFL. The ventricular response is a multiple of the atrial rate, though most frequently is 2:1 with a ventricular rate of 150 beats/min. Flutter waves may sometimes be obscured in the QRS complex in 2:1 conduction. Typical AFL most frequently rotates counterclockwise posterior to the tricuspid valve and uses the critical region of the cavotricuspid isthmus within the circuit. Clockwise, typical AFL uses the same circuit, but rotates in the opposite direction. Atypical AFL is any flutter that does not involve the cavotricuspid isthmus. The flutter wave morphology does not have a characteristic pattern to localize the flutter circuit. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Wells JL Jr, MacLean WA, James TN, Waldo AL. Characterization of atrial flutter. Studies in man after open heart surgery using fixed atrial electrodes. Circulation 1979; 60:665. 2. Puech P, Latour H, Grolleau R. [Flutter and his limits]. Arch Mal Coeur Vaiss 1970; 63:116. 3. Saoudi N, Cos o F, Waldo A, et al. A classification of atrial flutter and regular atrial tachycardia according to electrophysiological mechanisms and anatomical bases; a Statement from a Joint Expert Group from The Working Group of Arrhythmias of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Eur Heart J 2001; 22:1162. 4. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2016; 67:e27. 5. Bun SS, Latcu DG, Marchlinski F, Saoudi N. Atrial flutter: more than just one of a kind. Eur Heart J 2015; 36:2356. https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 13/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate 6. Khairy P, Aboulhosn J, Gurvitz MZ, et al. Arrhythmia burden in adults with surgically repaired tetralogy of Fallot: a multi-institutional study. Circulation 2010; 122:868. 7. Peuch P, Gallay P, Grolleau R. Mechanism of atrial flutter in humans. In: Atrial Arrhythmias: C urrent Concepts and Management, Tourboul P, Waldo AL (Eds), Mosby Year Book, St Louis 1 990. p.190. 8. Klein GJ, Guiraudon GM, Sharma AD, Milstein S. Demonstration of macroreentry and feasibility of operative therapy in the common type of atrial flutter. Am J Cardiol 1986; 57:587. 9. Cosio FG, Arribas F, Barbero JM, et al. Validation of double-spike electrograms as markers of conduction delay or block in atrial flutter. Am J Cardiol 1988; 61:775. 10. Tai CT, Chen SA, Chiang CE, et al. Characterization of low right atrial isthmus as the slow conduction zone and pharmacological target in typical atrial flutter. Circulation 1997; 96:2601. 11. Kalman JM, Olgin JE, Saxon LA, et al. Activation and entrainment mapping defines the tricuspid annulus as the anterior barrier in typical atrial flutter. Circulation 1996; 94:398. 12. Disertori M, Inama G, Vergara G, et al. Evidence of a reentry circuit in the common type of atrial flutter in man. Circulation 1983; 67:434. 13. Waldo AL, MacLean WA, Karp RB, et al. Entrainment and interruption of atrial flutter with atrial pacing: studies in man following open heart surgery. Circulation 1977; 56:737. 14. Watson RM, Josephson ME. Atrial flutter. I. Electrophysiologic substrates and modes of initiation and termination. Am J Cardiol 1980; 45:732. 15. Inoue H, Matsuo H, Takayanagi K, Murao S. Clinical and experimental studies of the effects of atrial extrastimulation and rapid pacing on atrial flutter cycle. Evidence of macro-reentry with an excitable gap. Am J Cardiol 1981; 48:623. 16. Callans DJ, Schwartzman D, Gottlieb CD, et al. Characterization of the excitable gap in human type I atrial flutter. J Am Coll Cardiol 1997; 30:1793. 17. Waldo AL, Cooper TB. Spontaneous onset of type I atrial flutter in patients. J Am Coll Cardiol 1996; 28:707. 18. Waldo AL. Mechanisms of atrial flutter and atrial fibrillation: distinct entities or two sides of a coin? Cardiovasc Res 2002; 54:217. 19. Roithinger FX, Karch MR, Steiner PR, et al. Relationship between atrial fibrillation and typical atrial flutter in humans: activation sequence changes during spontaneous conversion. Circulation 1997; 96:3484. https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 14/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate 20. Narayan SM, Bode F, Karasik PL, Franz MR. Alternans of atrial action potentials during atrial flutter as a precursor to atrial fibrillation. Circulation 2002; 106:1968. 21. Morton JB, Byrne MJ, Power JM, et al. Electrical remodeling of the atrium in an anatomic model of atrial flutter: relationship between substrate and triggers for conversion to atrial fibrillation. Circulation 2002; 105:258. 22. Franz MR, Karasik PL, Li C, et al. Electrical remodeling of the human atrium: similar effects in patients with chronic atrial fibrillation and atrial flutter. J Am Coll Cardiol 1997; 30:1785. 23. Stiles MK, Wong CX, John B, et al. Characterization of atrial remodeling studied remote from episodes of typical atrial flutter. Am J Cardiol 2010; 106:528. 24. Sparks PB, Jayaprakash S, Vohra JK, Kalman JM. Electrical remodeling of the atria associated with paroxysmal and chronic atrial flutter. Circulation 2000; 102:1807. 25. Kalman JM, Olgin JE, Saxon LA, et al. Electrocardiographic and electrophysiologic characterization of atypical atrial flutter in man: use of activation and entrainment mapping and implications for catheter ablation. J Cardiovasc Electrophysiol 1997; 8:121. 26. Nakagawa H, Lazzara R, Khastgir T, et al. Role of the tricuspid annulus and the eustachian valve/ridge on atrial flutter. Relevance to catheter ablation of the septal isthmus and a new technique for rapid identification of ablation success. Circulation 1996; 94:407. 27. Cosio FG, L pez-Gil M, Goicolea A, et al. Radiofrequency ablation of the inferior vena cava-

levels, and the response following cessation of digoxin therapy. As noted above, complete heart block may be difficult to recognize in the presence of AFL. The presence of F waves and a regular rate of the lower pacemaker may lead to the appearance of an uncomplicated AFL. MANAGEMENT The control of ventricular rate and the approach to anticoagulant therapy for patient with atrial flutter is discussed elsewhere. (See "Overview of atrial flutter" and "Embolic risk and the role of anticoagulation in atrial flutter".) Cardioversion in patients with atrial flutter is discussed separately. (See "Restoration of sinus rhythm in atrial flutter".) The approach to the maintenance of sinus rhythm and the impact of electrophysiologic type is discussed separately. (See "Atrial flutter: Maintenance of sinus rhythm" and "Atrial flutter: Maintenance of sinus rhythm", section on 'RF catheter ablation'.) SUMMARY https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 12/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Atrial flutter (AFL) is a supraventricular tachycardia with regular flutter waves and usually an absent isoelectric interval. The rhythm is due to macroreentry, has an excitable gap, and can be transiently entrained and terminated by rapid atrial pacing. Electrocardiographic characteristics include: Biphasic, sawtooth F waves, best seen in the inferior electrocardiogram leads (II, III, aVF), at about 300 beats/min are the classic finding for typical, counterclockwise AFL. The ventricular response is a multiple of the atrial rate, though most frequently is 2:1 with a ventricular rate of 150 beats/min. Flutter waves may sometimes be obscured in the QRS complex in 2:1 conduction. Typical AFL most frequently rotates counterclockwise posterior to the tricuspid valve and uses the critical region of the cavotricuspid isthmus within the circuit. Clockwise, typical AFL uses the same circuit, but rotates in the opposite direction. Atypical AFL is any flutter that does not involve the cavotricuspid isthmus. The flutter wave morphology does not have a characteristic pattern to localize the flutter circuit. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Wells JL Jr, MacLean WA, James TN, Waldo AL. Characterization of atrial flutter. Studies in man after open heart surgery using fixed atrial electrodes. Circulation 1979; 60:665. 2. Puech P, Latour H, Grolleau R. [Flutter and his limits]. Arch Mal Coeur Vaiss 1970; 63:116. 3. Saoudi N, Cos o F, Waldo A, et al. A classification of atrial flutter and regular atrial tachycardia according to electrophysiological mechanisms and anatomical bases; a Statement from a Joint Expert Group from The Working Group of Arrhythmias of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Eur Heart J 2001; 22:1162. 4. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2016; 67:e27. 5. Bun SS, Latcu DG, Marchlinski F, Saoudi N. Atrial flutter: more than just one of a kind. Eur Heart J 2015; 36:2356. https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 13/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate 6. Khairy P, Aboulhosn J, Gurvitz MZ, et al. Arrhythmia burden in adults with surgically repaired tetralogy of Fallot: a multi-institutional study. Circulation 2010; 122:868. 7. Peuch P, Gallay P, Grolleau R. Mechanism of atrial flutter in humans. In: Atrial Arrhythmias: C urrent Concepts and Management, Tourboul P, Waldo AL (Eds), Mosby Year Book, St Louis 1 990. p.190. 8. Klein GJ, Guiraudon GM, Sharma AD, Milstein S. Demonstration of macroreentry and feasibility of operative therapy in the common type of atrial flutter. Am J Cardiol 1986; 57:587. 9. Cosio FG, Arribas F, Barbero JM, et al. Validation of double-spike electrograms as markers of conduction delay or block in atrial flutter. Am J Cardiol 1988; 61:775. 10. Tai CT, Chen SA, Chiang CE, et al. Characterization of low right atrial isthmus as the slow conduction zone and pharmacological target in typical atrial flutter. Circulation 1997; 96:2601. 11. Kalman JM, Olgin JE, Saxon LA, et al. Activation and entrainment mapping defines the tricuspid annulus as the anterior barrier in typical atrial flutter. Circulation 1996; 94:398. 12. Disertori M, Inama G, Vergara G, et al. Evidence of a reentry circuit in the common type of atrial flutter in man. Circulation 1983; 67:434. 13. Waldo AL, MacLean WA, Karp RB, et al. Entrainment and interruption of atrial flutter with atrial pacing: studies in man following open heart surgery. Circulation 1977; 56:737. 14. Watson RM, Josephson ME. Atrial flutter. I. Electrophysiologic substrates and modes of initiation and termination. Am J Cardiol 1980; 45:732. 15. Inoue H, Matsuo H, Takayanagi K, Murao S. Clinical and experimental studies of the effects of atrial extrastimulation and rapid pacing on atrial flutter cycle. Evidence of macro-reentry with an excitable gap. Am J Cardiol 1981; 48:623. 16. Callans DJ, Schwartzman D, Gottlieb CD, et al. Characterization of the excitable gap in human type I atrial flutter. J Am Coll Cardiol 1997; 30:1793. 17. Waldo AL, Cooper TB. Spontaneous onset of type I atrial flutter in patients. J Am Coll Cardiol 1996; 28:707. 18. Waldo AL. Mechanisms of atrial flutter and atrial fibrillation: distinct entities or two sides of a coin? Cardiovasc Res 2002; 54:217. 19. Roithinger FX, Karch MR, Steiner PR, et al. Relationship between atrial fibrillation and typical atrial flutter in humans: activation sequence changes during spontaneous conversion. Circulation 1997; 96:3484. https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 14/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate 20. Narayan SM, Bode F, Karasik PL, Franz MR. Alternans of atrial action potentials during atrial flutter as a precursor to atrial fibrillation. Circulation 2002; 106:1968. 21. Morton JB, Byrne MJ, Power JM, et al. Electrical remodeling of the atrium in an anatomic model of atrial flutter: relationship between substrate and triggers for conversion to atrial fibrillation. Circulation 2002; 105:258. 22. Franz MR, Karasik PL, Li C, et al. Electrical remodeling of the human atrium: similar effects in patients with chronic atrial fibrillation and atrial flutter. J Am Coll Cardiol 1997; 30:1785. 23. Stiles MK, Wong CX, John B, et al. Characterization of atrial remodeling studied remote from episodes of typical atrial flutter. Am J Cardiol 2010; 106:528. 24. Sparks PB, Jayaprakash S, Vohra JK, Kalman JM. Electrical remodeling of the atria associated with paroxysmal and chronic atrial flutter. Circulation 2000; 102:1807. 25. Kalman JM, Olgin JE, Saxon LA, et al. Electrocardiographic and electrophysiologic characterization of atypical atrial flutter in man: use of activation and entrainment mapping and implications for catheter ablation. J Cardiovasc Electrophysiol 1997; 8:121. 26. Nakagawa H, Lazzara R, Khastgir T, et al. Role of the tricuspid annulus and the eustachian valve/ridge on atrial flutter. Relevance to catheter ablation of the septal isthmus and a new technique for rapid identification of ablation success. Circulation 1996; 94:407. 27. Cosio FG, L pez-Gil M, Goicolea A, et al. Radiofrequency ablation of the inferior vena cava- tricuspid valve isthmus in common atrial flutter. Am J Cardiol 1993; 71:705. 28. Schilling RJ, Peters NS, Goldberger J, et al. Characterization of the anatomy and conduction velocities of the human right atrial flutter circuit determined by noncontact mapping. J Am Coll Cardiol 2001; 38:385. 29. Shah DC, Ja s P, Ha ssaguerre M, et al. Three-dimensional mapping of the common atrial flutter circuit in the right atrium. Circulation 1997; 96:3904. 30. Dixit S, Lavi N, Robinson M, et al. Noncontact electroanatomic mapping to characterize typical atrial flutter: participation of right atrial posterior wall in the reentrant circuit. J Cardiovasc Electrophysiol 2011; 22:422. 31. Maury P, Duparc A, Hebrard A, et al. Prevalence of typical atrial flutter with reentry circuit posterior to the superior vena cava: use of entrainment at the atrial roof. Europace 2008; 10:190. 32. Yang Y, Cheng J, Bochoeyer A, et al. Atypical right atrial flutter patterns. Circulation 2001; 103:3092. 33. Yang Y, Varma N, Badhwar N, et al. Prospective observations in the clinical and electrophysiological characteristics of intra-isthmus reentry. J Cardiovasc Electrophysiol https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 15/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate 2010; 21:1099. 34. Cheng J, Cabeen WR Jr, Scheinman MM. Right atrial flutter due to lower loop reentry: mechanism and anatomic substrates. Circulation 1999; 99:1700. 35. Tai CT, Huang JL, Lin YK, et al. Noncontact three-dimensional mapping and ablation of upper loop re-entry originating in the right atrium. J Am Coll Cardiol 2002; 40:746. 36. Wasmer K, M nnig G, Bittner A, et al. Incidence, characteristics, and outcome of left atrial tachycardias after circumferential antral ablation of atrial fibrillation. Heart Rhythm 2012; 9:1660. 37. Chae S, Oral H, Good E, et al. Atrial tachycardia after circumferential pulmonary vein ablation of atrial fibrillation: mechanistic insights, results of catheter ablation, and risk factors for recurrence. J Am Coll Cardiol 2007; 50:1781. 38. Bai R, Di Biase L, Mohanty P, et al. Ablation of perimitral flutter following catheter ablation of atrial fibrillation: impact on outcomes from a randomized study (PROPOSE). J Cardiovasc Electrophysiol 2012; 23:137. 39. Miyazaki S, Shah AJ, Hocini M, et al. Recurrent spontaneous clinical perimitral atrial tachycardia in the context of atrial fibrillation ablation. Heart Rhythm 2015; 12:104. 40. Zhang J, Tang C, Zhang Y, et al. Electroanatomic characterization and ablation outcome of nonlesion related left atrial macroreentrant tachycardia in patients without obvious structural heart disease. J Cardiovasc Electrophysiol 2013; 24:53. 41. Fukamizu S, Sakurada H, Hayashi T, et al. Macroreentrant atrial tachycardia in patients without previous atrial surgery or catheter ablation: clinical and electrophysiological characteristics of scar-related left atrial anterior wall reentry. J Cardiovasc Electrophysiol 2013; 24:404. 42. Stambler BS, Ellenbogen KA. Elucidating the mechanisms of atrial flutter cycle length variability using power spectral analysis techniques. Circulation 1996; 94:2515. 43. Yuniadi Y, Tai CT, Lee KT, et al. A new electrocardiographic algorithm to differentiate upper loop re-entry from reverse typical atrial flutter. J Am Coll Cardiol 2005; 46:524. 44. Gerstenfeld EP, Dixit S, Bala R, et al. Surface electrocardiogram characteristics of atrial tachycardias occurring after pulmonary vein isolation. Heart Rhythm 2007; 4:1136. 45. Knight BP, Michaud GF, Strickberger SA, Morady F. Electrocardiographic differentiation of atrial flutter from atrial fibrillation by physicians. J Electrocardiol 1999; 32:315. 46. Khairy P, Stevenson WG. Catheter ablation in tetralogy of Fallot. Heart Rhythm 2009; 6:1069. 47. Chugh A, Latchamsetty R, Oral H, et al. Characteristics of cavotricuspid isthmus-dependent atrial flutter after left atrial ablation of atrial fibrillation. Circulation 2006; 113:609. https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 16/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate 48. Baranchuk A, Kang J. Pseudo-atrial flutter: Parkinson tremor. Cardiol J 2009; 16:373. 49. Chakravarthy M, Mattur K, Raghavan R, et al. Artifactual 'atrial flutter' caused by a continuous passive motion device after total knee replacement. Anaesth Intensive Care 2009; 37:1038. 50. Hoffmayer KS, Goldschlager N. Pseudoatrial flutter. J Electrocardiol 2008; 41:201. Topic 1061 Version 26.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 17/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate GRAPHICS Reentrant circuit of typical atrial flutter within the right atrium Schematic representation of reentrant circuit (red arrow) of typical (type 1) atrial flutter. The reentrant impulse rotates in a counterclockwise direction around the tricuspid annulus. The crista terminalis (CT) and eustacian ridge (ER) serve as lines of block, preventing the impulse from short-circuiting the annulus. Ablation is performed in the isthmus between the IVC and TA, which is an obligatory part of the circuit. SVC: superior vena cava; CS: coronary sinus; IVC: inferior vena cava; FO: foramen ovale Graphic 52904 Version 5.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 18/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate 12-lead electrocardiogram showing atrial flutter in preexcitation syndrome Atrial flutter is generated within the right atrium and the atrial impulses in this case are conducted to the ventricle by an accessory pathway. There is 1:1 conduction with a ventricular rate of 300 beats/min. The QRS complexes are widened or aberrant and have a bundle branch block morphology and a left axis deviation, suggesting the presence of an atriofascicular (Mahaim) accessory pathway. Courtesy of Morton Arnsdorf, MD. Graphic 78602 Version 4.0 Normal ECG https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 19/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Normal electrocardiogram showing normal sinus rhythm at a rate of 75 beats/minute, a PR interval of 0.14 seconds, a QRS interval of 0.10 seconds, and a QRS axis of approximately 75 . Courtesy of Ary Goldberger, MD. Graphic 76183 Version 4.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 20/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Revised (2018) Vaughan Williams classification of antiarrhythmic drugs abridged table Class 0 (HCN channel blockers) Ivabradine Class I (voltage-gated Na+ channel blockers) Class Ia (intermediate dissociation): Quinidine, ajmaline, disopyramide, procainamide Class Ib (rapid dissociation): Lidocaine, mexilitine Class Ic (slow dissociation): Propafenone, flecainide Class Id (late current): Ranolazine Class II (autonomic inhibitors and activators) Class IIa (beta blockers): Nonselective: carvedilol, propranolol, nadolol Selective: atenolol, bisoprolol, betaxolol, celiprolol, esmolol, metoprolol Class IIb (nonselective beta agonists): Isoproterenol Class IIc (muscarinic M2 receptor inhibitors): Atropine, anisodamine, hyoscine, scopolamine Class IId (muscarinic M2 receptor activators): Carbachol, pilocarpine, methacholine, digoxin Class IIe (adenosine A1 receptor activators): Adenosine Class III (K+ channel blockers and openers) Class IIIa (voltage dependent K+ channel blockers): Ambasilide, amiodarone, dronedarone, dofetilide, ibutilide, sotalol, vernakalant Class IIIb (metabolically dependent K+ channel openers): https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 21/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Nicorandil, pinacidil Class IV (Ca++ handling modulators) Class IVa (surface membrane Ca++ channel blockers): Bepridil, diltiazem, verapamil Class IVb (intracellular Ca++ channel blockers): Flecainide, propafenone Class V (mechanosensitive channel blockers): No approved medications Class VI (gap junction channel blockers) No approved medications Class VII (upstream target modulators) Angiotensin converting enzyme inhibitors Angiotensin receptor blockers Omega-3 fatty acids Statins HCN: hyperpolarization-activated cyclic nucleotide-gated; Na: sodium; K: potassium; Ca: calcium. Graphic 120433 Version 3.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 22/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Typical atrial flutter Electrocardiogram in type I counterclockwise typical atrial flutter. The biphasic flutter (F) waves are prominently negative (lead II) in counterclockwise typical flutter. The patient is on a beta-blocker which explains the predominant 4:1 conduction pattern. Graphic 74395 Version 4.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 23/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Reverse typical atrial flutter Electrocardiogram in type I clockwise typical atrial flutter. The flutter waves are positive in the inferior leads (II, III, aVF), with a more sinusoidal appearance and a broad negative F wave in V1. Graphic 81563 Version 3.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 24/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Electrocardiogram in lower loop reentry flutter Arrows point to flutter waves, which are positive in V1 and subtle but negative in the inferior leads. Graphic 106118 Version 1.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 25/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Electrocardiogram from a patient with an atriotomy-related right atrial flutter a mitral valve repair On electrophysiology study, the circuit was found to be wrapping around the atriotomy scar. The arrows poin flutter waves, which are negative in the inferior leads. Graphic 106119 Version 1.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 26/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Electrocardiogram of an atypical left atrial flutter occurring through a scar on t anterior septum in a patient with a prior atrial fibrillation ablation The arrows show the flutters waves, which are positive in V1. Graphic 106120 Version 1.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 27/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Electrocardiogram of an atypical roof dependent left atrial flutter after an atria fibrillation ablation The arrows show positive flutter waves in V1 indicative of a left atrial focus. Flutter waves are isoelectric in th leads. Graphic 106121 Version 2.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 28/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Electrocardiogram of a patient with clockwise mitral annular flutter The arrows show the flutter waves, which are low amplitude and negative in the inferior leads. They are posit 3, but become negative and then positive in V4-6. Graphic 106122 Version 1.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 29/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Atrial flutter at a rate of 250 beats/minute with 2:1 AV conduction in the presence of left bundle branch block Although every other flutter wave can be seen at the end of the T wave in the first part of the tracing (arrows), a sinus mechanism cannot be excluded. The flutter waves become clearly apparent after carotid sinus massage is applied to slow conduction through the AV node, thereby increasing the degree of AV block. AV: atrioventricular Courtesy of Morton Arnsdorf, MD. Graphic 76876 Version 3.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 30/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Atrial flutter RA recording Atrial flutter which is inapparent in lead I (upper panel); suggested by prominent negativity in lead II (arrows, middle panel), which could also represent biphasic T waves; and documented by right atrial recording, which shows prominent negative deflections (arrows, lower panel). Courtesy of Morton Arnsdorf, MD. Graphic 54591 Version 2.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 31/32 7/5/23, 10:39 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Contributor Disclosures Jordan M Prutkin, MD, MHS, FHRS No relevant financial relationship(s) with ineligible companies to disclose. Peter J Zimetbaum, MD Consultant/Advisory Boards: Abbott Medical [Lead extraction]. All of the relevant financial relationships listed have been mitigated. Ary L Goldberger, MD Other Financial Interest: Elsevier book royalties [Clinical electrocardiography]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 32/32

7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Mechanisms of atrial fibrillation : Brian Olshansky, MD, Rishi Arora, MD : Bradley P Knight, MD, FACC, Hugh Calkins, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: May 16, 2022. INTRODUCTION Atrial fibrillation (AF) is a most common cardiac arrhythmia. The chance of developing AF is tied closely to age, with AF rare before the age of 50 years [1]. In addition to age, there are many types of cardiac and medical conditions that are also closely linked to AF. These include hypertension, coronary artery disease, heart failure, valvular heart disease, obesity [2], and sleep-apnea syndrome. It is well established that high levels of alcohol [3] can increase the probability of developing AF, and that hyperthyroidism can cause AF. Evidence for caffeine and energy drinks, while suspected, is questionable [4]. Furthermore, while exercise can be protective against atrial fibrillation, endurance athletics may be a cause for atrial fibrillation [5]. It is also well established that AF is more common in individuals who have a first-degree relative who developed AF at a young age. There is also a variety of acute conditions that can initiate AF such as cardiac surgery, pulmonary embolus, and inflammatory lung conditions. (See "Epidemiology, risk factors, and prevention of atrial fibrillation".) The precise mechanisms by which age and the other conditions listed above increase the propensity for development of AF are understood poorly ( figure 1). However, these conditions may impact the triggers for AF, which commonly arise in the pulmonary veins or the substrate for maintenance of AF, which broadly relates to atrial size and the extent of fibrosis. Some of the factors that may play a role in the mechanisms of AF include autonomic tone, inflammation, atrial pressure and wall stress, and genetics. (See "Epidemiology, risk factors, and prevention of atrial fibrillation", section on 'Other factors'.) https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 1/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate This topic will provide a broad overview of the current understanding of the mechanisms of AF. This discussion will provide a relatively simplistic approach to a complex topic. The reader will be referred to a rapidly growing literature on this topic, including some comprehensive reviews [6]. DEFINITIONS The following terms are defined to help the reader s understanding of the material below: Trigger a rapidly firing focus often arising in the pulmonary veins that can initiate atrial fibrillation (AF). Triggered activity One of three mechanisms of cardiac arrhythmias (including automaticity and reentry). Triggered activity refers to additional depolarizations, which occur during or immediately following a cardiac depolarization and may cause a sustained cardiac arrhythmia. Substrate Mechanical and anatomic structure of the atria in which AF can occur. Substrate remodeling Changes in the mechanical and anatomic macro, micro, and ultrastructure of the atrial substrate that result from the development of AF and increase the propensity for the development and maintenance of AF over time. Electrical remodeling Changes in the atrial electrical properties (refractoriness and conduction) that result from the development of AF and increase the propensity for the development and maintenance of AF over time. Dispersion of refractoriness A range of differences in the refractory period properties throughout the atrial tissue. Spatial heterogeneity of refractoriness Dispersion of refractoriness manifest as variability in refractoriness throughout the atrial anatomy. Complex fractionated electrograms Local electrograms obtained from areas of the atrium that are rapid, of low amplitude, and have multiple components. Reentry/reentrant mechanism One of three mechanisms of cardiac arrhythmias (including automaticity and triggered activity). Reentry is the most common mechanism of cardiac arrhythmias and refers to the presence of one or more electrical circuit(s) in which electrical activation proceeds in a circular fashion to complete a self-sustaining circuit. https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 2/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate Atrial anisotropy Conduction properties related to directionality of conduction through atrial tissue. BASIC ATRIAL ELECTROPHYSIOLOGY The electrophysiologic properties of normal and fibrillating atria have been studied extensively [7]. A basic understanding of these properties is necessary to understand the pathologic processes that play a role in initiating and perpetuating atrial fibrillation (AF). In the aggregate, these electrophysiologic properties permit the development of very complex patterns of conduction and an extremely rapid atrial rate as seen in AF. The atrial myocardium consists of so-called "fast-response" tissues that depend on the rapidly activating sodium current for phase 0 of the action potential. (See "Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs".) Normal atrial myocardium has the following properties [7-9]: A short action-potential duration. Cellular reactivation can occur rapidly due to the short refractory period (in contrast to Purkinje fibers and ventricular muscle). Very rapid electrical conduction can occur. The refractory period shortens with increasing rate. In the aggregate, these electrophysiologic properties permit the development of very complex patterns of conduction and an extremely rapid atrial rate as seen in AF. CLINICAL FACTORS ASSOCIATED WITH AF The following are common clinical conditions associated with atrial fibrillation (AF) in developed countries, and the percent of AF cases in which they are found (see "Epidemiology, risk factors, and prevention of atrial fibrillation", section on 'Chronic disease associations') [6]: Hypertension (60 to 80 percent). Cardiovascular disease, including cardiomyopathy, valvular and coronary artery disease (25 to 30 percent). New York Heart Association class II to IV heart failure (30 percent). https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 3/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate Diabetes (20 percent). Age. Each of the first three is associated with left atrial dilatation, which is important in the development of a substrate for AF and also may increase the probability of electrical firing from the pulmonary veins. (See 'Mechanisms of atrial fibrillation: triggers and substrates' below.) The following section will discuss the link between these conditions and AF. MECHANISMS OF ATRIAL FIBRILLATION: TRIGGERS AND SUBSTRATES Atrial fibrillation (AF) may present as a paroxysmal (self-terminating AF within seven days), a persistent (one that lasts greater than seven days), or a long-standing persistent AF (continuous AF for 12 months or greater). The term permanent AF should be used when both the patient and physicians agree to not pursue strategies to restore or maintain sinus rhythm. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation", section on 'Classification and terminology'.) This wide range of clinical presentations is likely due to an interaction between a trigger and the substrate ( figure 1). AF is initiated by rapid firing (or triggers) from the pulmonary veins (PV). Early in the course of AF the atrium is relatively healthy and as a result sinus rhythm is spontaneously restored. As the substrate remodels further over time, AF no longer terminates spontaneously and becomes persistent. With more extensive remodeling of the atrium, it becomes increasingly difficult to maintain sinus rhythm and the patient and physician may agree no longer to attempt to maintain sinus rhythm, with the AF thereby being considered permanent [10]. Triggers of AF It has been known for many years that a single focus firing rapidly in the atria can be a trigger for fibrillatory conduction throughout the atria [11]. It is now well established that the most common site of the rapid atrial firing that triggers AF is the PVs. Catheter ablation of AF depends in large part on the electrical isolation of the PVs from the remainder of the atrium. Electrophysiologic evaluation of the PVs has identified myocardial tissue that can lead to repetitive firing or even the presence of episodic reentrant activation in the veins [6]. Additionally, stretch can increase the propensity for rapid firing from the PVs as a result of stretch sensitive ion channels. [12]. It has been speculated that the mechanism of atrial stretch may help explain the association between AF and mitral regurgitation as well as various types of heart failure. https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 4/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate Role of premature atrial complex and other arrhythmia triggers AF is initiated (triggered) predominantly by rapid firing from PVs. Much less commonly, AF can be triggered by non-PV sites of rapid firing (such as tissue near the PV including the Vein of Marshall, the superior vena cava, or coronary sinus) or by other types of supraventricular arrhythmias including atrioventricular nodal reentrant tachycardia (AVNRT), orthodromic AV reciprocating tachycardia, and atrial flutter [6,13-23]. In some patients, successful elimination of AF with catheter ablation requires both isolation of the PVs, as well as elimination of these non-PV triggers. (See "Atrial fibrillation: Catheter ablation" and "Atrial fibrillation: Surgical ablation".) Role of atrial flutter and supraventricular tachycardias Atrial tachycardia, atrial flutter, and other supraventricular tachycardias can initiate AF in predisposed patients. The interaction between these arrhythmias and AF is not well understood, but atrial flutter and AF commonly coexist. In some instances, elimination of atrial flutter will diminish and/or eliminate episodes of AF. Nevertheless, elimination of the right atrial reentry circuit responsible for typical flutter frequently does not eliminate the predisposition to AF that is predominately a left-atrial problem in a large number of patients. Many studies have demonstrated that patients who undergo catheter ablation of typical atrial flutter have a very high probability of developing AF over the ensuing five years. This is true regardless of whether AF had been observed prior to development of typical atrial flutter. This has clinical implications when it comes to ablation, but also has implications for anticoagulation strategies and patient follow-up. Nevertheless, for most patients, it makes sense to try to eliminate the organized supraventricular tachycardia, especially if right-sided by ablation before considering PV isolation and/or other more extensive ablation procedures to eliminate AF, as the AF may be reduced or eliminated by eliminating the other tachycardia first. Role of the autonomic nervous system The autonomic nervous system plays an important role in the development and maintenance of AF [24-26]. Clinical studies using heart rate variability analysis in patients with AF suggest that fluctuation in autonomic tone may be a major determinant of AF in patients with focal ectopy originating from the PVs [27]. Studies have also demonstrated a change in heart rate variability after PV ablation [28], further suggesting that PV triggers may be at least partially modulated by autonomic activity. Another study showed that the occurrence of paroxysmal AF greatly depends on variations of the autonomic tone, with a primary increase in adrenergic tone followed by an abrupt shift toward vagal predominance [29]. Anatomic studies of the autonomic innervation of the atria also indicate that the PVs and posterior left atrium (PLA) have a unique autonomic profile with a rich innervation from sympathetic and parasympathetic nerves [30-35]. The autonomic nervous system may also be https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 5/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate playing a role in the genesis of AF in diseased hearts [30,36,37]. Studies suggest that the parasympathetic and sympathetic nervous system may also be playing a role in creation of AF substrate in the setting of heart failure [36,37]. Both the sympathetic and parasympathetic nervous systems have been implicated in the genesis [30,38,39] and maintenance of AF: Sympathetic effects Early studies suggested that exercise-induced AF may be sympathetically driven [30,40]. PV ectopic foci appear to be at least partially modulated by autonomic signaling, with sympathetic stimulation with isoproterenol frequently utilized to elicit these triggers in patients undergoing ablation for AF [41]. Parasympathetic (vagal) effects The parasympathetic nervous system may contribute to AF in young patients with no structural heart disease [42]. Animal studies show that vagal stimulation contributes to the genesis of AF by nonuniform shortening of atrial effective refractory periods, thereby setting up substrate for reentry. Vagal stimulation can also lead to the emergence of focal triggers in the atrium [43-45]. Bezold-Jarisch-like "vagal" reflexes can be elicited during radiofrequency ablation and occur in and around the PVs. It has been suggested that elimination of these vagal reflexes during ablation may improve efficacy of AF ablation procedures [46]. Vagal responsiveness also appears to decrease following ablation in the left atrium [47]. In some series, adding ganglionated plexi (GP) ablation to PV isolation appears to increase ablation success for AF [12]. Data suggest that areas in the atrium demonstrating complex fractionated atrial electrograms (CFAE) may represent a suitable target site for ablation; although several studies have reported that ablation at these sites may increase the efficacy of PV isolation procedures [48,49], enthusiasm for this approach has fallen over time. One possible explanation for the improvement in ablation success reported in these trials is that several CFAE sites anatomically overlie fat pads containing GPs [18,50]. As indicated above, autonomic denervation performed by GP ablation is thought to improve efficacy of AF ablation. (See "Atrial fibrillation: Catheter ablation" and "Catheter ablation for the treatment of atrial fibrillation: https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 6/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate Technical considerations for non-electrophysiologists", section on 'Ablation techniques and targets'.) In a study of 40 patients with paroxysmal AF scheduled to undergo catheter ablation, individuals were randomly assigned to noninvasive transcutaneous low-level stimulation of the tragus (the anterior protuberance of the ear where the auricular branch of the vagus nerve is accessible) or to sham stimulation for one hour. Compared with control, low-level stimulation suppressed AF as measured by the decreased duration of atrial pacing-induced AF and an increased AF cycle length [51]. Maintenance of atrial fibrillation In patients with persistent AF, the prevailing understanding of the mechanism is that, once triggered, the arrhythmia is maintained (sustained) by one or more abnormalities in the atrial tissue. This process may explain why the failure rate of PV isolation is as high as 40 to 60 percent at one year: The trigger(s) may have been treated but not the abnormalities that sustain AF once triggered (initiated). The role of localized sources (electrical rotors and focal impulses) in the initiation and maintenance of AF was explored in the CONFIRM trial of 92 patients undergoing ablation procedures for paroxysmal or persistent (72 percent) AF [52]. Consecutive patients were prospectively treated (not randomly assigned) in a 1:2 case-cohort design with either conventional ablation at sources identified within the atria followed by conventional ablation or conventional ablation alone. Localized sources were identified in 97 percent of cases (70 percent rotors and 30 percent focal impulses) with sustained AF, each with an average of 2.1 sources. During a median of 273 days, patients treated with treatment of both sources and conventional ablation had a significantly higher freedom from AF (82.4 versus 44.9 percent). Similar information was reported, indicating that driver domains, located in specific areas of the atria, act as unstable re-entry circuits that perpetuate atrial fibrillation in patients who have persistent AF [53,54]. Murine cell cultures show a differential ion channel gene expression associated with atrial tissue remodeling (ie, decreased SCN5A, CACN1C, KCND3, and GJA1; and increased KCNJ2) [55]. Fibrillatory complexity, increased in late compared with early stage cultures, was associated with a decrease in rotor tip meandering and increase in wavefront curvature. Rotors are not the only explanation. In a study using high-density, simultaneous, biatrial, epicardial mapping of persistent and longstanding persistent AF in patients undergoing open heart surgery, several non-reentrant drivers were present in both atria in 11 or 12 patients with two to four foci per patient; foci were seen in both atria but generally in the lateral left atrial free wall, and likely acted as drivers. Reentry was not found to be the mechanism [56]. https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 7/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate Likely, the substrate to maintain AF is a combination of reentrant activity and focal triggers. In a study of biatrial epicardial mapping of AF in sheep, wave propagation patterns were passing wave (69 percent occurrence, 68.6 percent of total time), point source (20.4, 13.1 percent), wave collision (4, 2.8 percent), reentrant wave (0.7, 6.3 percent), half-rotation (2.9, 4.4 percent), wave splitting (2.7, 4.3 percent), conduction block (0.05, 0.03 percent) and figure of eight reentry (0.05, 0.05 percent) [57]. Periods of repetitive activity were detected in the left and right atria. The following sections describe factors that might contribute to the maintenance of AF. Atrial remodeling Atrial remodeling involves the concept that there are structural changes, such as fibrosis, or electrical changes, such as refractory-period dispersion or conduction display, in the atria that can predispose to the development and maintenance of AF. In some instances, structural and electrical changes occur simultaneously. These processes can facilitate or create electrical reentrant circuits or triggers that can lead to AF [13,58]. It is also well established that the presence of AF results in remodeling of the atrium over time [7]. This explains the well-established concept that AF begets AF ( figure 2). Thus, the longer a patient has been in continuous AF, the less likely it is to terminate spontaneously, and harder it is to restore and maintain sinus rhythm [59]. Electrical remodeling Paroxysmal AF commonly precedes chronic AF. It has been suggested even after only a few minutes, AF induces transient changes in atrial electrophysiology that promote its perpetuation [14]. This might occur through a tachycardiomyopathy or through "electrical remodeling" of the atria by AF, leading to a progressive decrease in atrial refractoriness [14,15]. Electrical remodeling results from the high rate of electrical activation, which stimulates the AF-induced changes in refractoriness [60]. Tachycardia-induced changes in refractoriness are spatially nonuniform and there is increased variability both within and among various atrial regions [61]. It is possible that the change in atrial refractory period observed after an episode of AF predisposes to the spontaneous recurrence of AF in the days following cardioversion. In addition to the shortening of the refractory period, chronic, rapid, atrial pacing-induced AF results in other changes within the atria, including an increase in the expression and distribution of connexin 43 and heterogeneity in the distribution of connexin 40, both of which are intercellular gap junction proteins ("gap junctional remodeling") [16,17]; cellular remodeling is due to apoptotic death of myocytes with myolysis, which may not be entirely reversible [18]; the induction of sinus node dysfunction, demonstrated by prolonged corrected sinus node recovery time, reduced maximal heart rate in response to isoproterenol, and lower intrinsic heart rate after administration of atropine and propranolol [19]; and an increase in P wave duration and intraatrial conduction time. https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 8/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate A clinical study evaluated the hypothesis of electrical remodeling by the use of atrial pacing- induced AF in patients with a history of supraventricular tachycardia [20]. AF significantly shortened the right-atrial effective refractory period after only a few minutes, and temporal recovery of the refractory period occurred over about eight minutes. Upon termination of AF, there was an increased propensity for the induction of another episode of AF that decreased with increasing time after the initial AF reversion. The second also tends to last longer than the first. The time to recurrence was also evaluated in a review of 61 patients who had daily electrocardiogram (ECG) recordings using transtelephonic monitoring: 57 percent had recurrent AF during the first month after cardioversion, with a peak incidence during the first five days [21]. Among patients with recurrence, there was a positive correlation between the duration of the shortest coupling interval of premature atrial complex (PAC; also referred to a premature atrial beat, premature supraventricular complex, or premature supraventricular beat) after cardioversion, which correlates with the refractory period and the timing of recurrence ( figure 3). (See "Atrial fibrillation: Cardioversion".) In contrast to the normal situation in which the atrial refractory period shortens with an increase in rate (as in AF) and prolongs when the rate decreases, the refractory period fails to lengthen appropriately at slow rates (eg, with return to sinus rhythm) in patients with acute or chronic AF. The duration of AF has no significant impact upon the extent of these electrophysiologic changes [22]. Atrial electrical remodeling is reversed gradually after the restoration of sinus rhythm [23,62]. This may be one of the explanations for the early or immediate return of AF after cardioversion. In one study of 25 patients, the atrial refractory period increased and the adaptation of atrial refractoriness to rate was normal by four weeks after cardioversion [23]. In another report of 38 patients, the atrial refractory period increased by one week, with some variation in different regions of the atrium [62]. This observation has important clinical implications. The mechanism for electrical remodeling and shortening of the atrial refractory period is not entirely clear; a possible explanation is ion-channel remodeling, with a decrease in the protein content of the L-type calcium channel [63]. Support for this comes from an animal study in which verapamil, an L-type calcium antagonist, prevented electric remodeling of short-duration AF (one day or less) and hastened complete recovery, without affecting inducibility of AF [64]. Similar findings have been noted in humans as verapamil, but not procainamide, prevented remodeling when given prior to the electrophysiologic induction of AF [65]. Oral diltiazem is also effective in some patients [66], while beta blockers had no effect on electrical remodeling in an animal model [60]. https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 9/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate In comparison, cytosolic calcium overload, induced by hypercalcemia or digoxin, which increases the intracellular concentration of calcium by activating the sodium-calcium exchanger, enhances electrical remodeling [64,67,68]. The effect of digoxin, which is not due to its vagotonic activity, is associated with an increase in the inducibility and duration of AF [68]. Calcium leak from the sarcoplasmic reticulum may trigger and maintain AF. It is known that protein kinase A (PKA) hyperphosphorylation of the cardiac ryanodine receptor (RyR2), resulting in dissociation of the channel-stabilizing subunit calstabin2, causes sarcoplasmic reticulum (SR) calcium leak in failing hearts. This phenomenon seems to be involved in triggering ventricular arrhythmias. Using similar logic, these proteins were investigated in atrial tissues from both dogs and humans with AF [69]. Atrial tissue in those with AF showed a significant increase in PKA phosphorylation of RyR2 and a decrease in calstabin2 binding to the channel. Channels isolated from dogs with AF had an increased open probability under conditions simulating diastole compared with channels from control hearts, suggesting that these AF channels could predispose to a diastolic SR calcium leak. The conclusion was that SR calcium leak due to RyR2 PKA hyperphosphorylation may play a role in the initiation and/or maintenance of AF. Other studies also suggest that RyR2 receptor-mediated calcium leak drives progressive development of an atrial fibrillation substrate in a transgenic mouse model [70,71]. The effects of calcium overload are quite complex. It is likely that triggers and substrates initiate short episodes of AF that then lead to calcium overload and over a period of minutes there is activation of the I current that increases I , decreases I , increases I , and decreases CaL K1 Na KACh I . This can affect the action-potential duration and allow for more reentry to occur. As reentry TO occurs, the substrate changes and there is remodeling through calcium handling abnormalities as well as mRNA transcription [59], and ultimately perhaps with protein decrease, changes in connexons, including, Cx40, that can affect conduction. The calcium-handling abnormalities can also lead to hypocontractility and atrial dilatation, thereby affecting even more the possibility of developing AF [59]. Both animal and human studies suggest that angiotensin II is involved in electrical and atrial myocardial remodeling [72,73] (see "Pathophysiology of heart failure: Neurohumoral adaptations", section on 'Renin-angiotensin system'). In an animal model, inhibition of angiotensin II with captopril or candesartan prevented shortening of the atrial effective refractory period and atrial electrical remodeling during rapid atrial pacing [72], while atrial tissue obtained during open heart surgery from patients with AF revealed downregulation of AT1 receptor proteins and upregulation of AT2 receptor [73]. The potential clinical importance of these changes is illustrated by the observations that angiotensin converting enzyme (ACE) https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 10/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate inhibitors reduce the incidence of AF in patients with left ventricular dysfunction after myocardial infarction [74] and in patients with chronic left ventricular dysfunction due to ischemic heart disease [75]. (See "Angiotensin converting enzyme inhibitors and receptor blockers in acute myocardial infarction: Clinical trials".) Another possible contributor to electrical remodeling and shortening of the atrial refractory period is atrial ischemia, which activates the sodium/hydrogen exchanger. The intravenous administration of HOE 642, a selective inhibitor of this sodium proton pump, to dogs undergoing rapid atrial pacing resulted in the lengthening of atrial refractoriness after one hour, while control dogs showed effective refractory-period shortening greater than 10 percent [76]. Role of fibrosis The development of AF invokes atrial remodeling processes that involve electrophysiological and structural alterations that serve to maintain, promote, and propagate AF. In addition to electrophysiological alterations, such as shortening of the atrial action potential, increased dispersion of refractoriness, and conduction velocity shortening, morphological changes consist of fibrosis, hypertrophy, necrotic and apoptotic cell loss, and dilation [77]. Of these, fibrosis is considered especially important in the creation of AF substrate, especially in the setting of chronic atrial dilatation caused by heart failure. A canine model of heart failure has demonstrated a progressive increase in AF inducibility with increasing fibrosis [78]. An increase in conduction heterogeneity noted in this model is thought to play a major role in the creation of reentrant circuits in the dilated atria. Patients with AF also display increased atrial fibrous tissue content, along with increased expression of collagen I and III [79], as well as up-regulation of MMP-2 protein, and down-regulation of the tissue inhibitor of metalloproteinase, TIMP-1 [79]. Expression of the active form of MMP-9 and of monocyte chemoattractant protein-1, an inflammatory mediator, is increased in AF patients [80]. The left atrial free wall around the PV area presents particularly strong interstitial fibrotic changes [81-83]. Although the underlying molecular mechanisms that lead to the development of atrial fibrosis are complex, work suggests that the TGF- pathway may be an important contributor to the development of fibrosis (especially in the setting of increasing atrial stretch/dilatation resulting from congestive heart failure) [84-86]. Role of inflammation and oxidative stress Emerging evidence suggests a significant role of inflammation in the pathogenesis of AF [87]. Evidence includes elevated serum levels of inflammatory biomarkers in patients with AF, the expression of inflammatory markers in atrial tissue from AF patients, and beneficial effects of antiinflammatory drugs in the setting of experimental AF [88]. Inflammation is suggested to be linked to various pathological processes, https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 11/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate such as oxidative stress, apoptosis, and fibrosis that promote the creation and perpetuation of AF substrate. Several of the downstream effects of inflammation in the heart are thought to be mediated by oxidative stress [89]. Indeed, studies in patients with AF demonstrate increased generation of reactive oxygen species (ROS) in the fibrillating atrium compared with normal atria [90,91]. Several major enzymatic sources of ROS have been implicated in AF. Of these, NAPDH oxidase (specifically its NOX2 isoform) has been shown to be elevated in humans with AF in a variety of studies [92,93]. Other sources of ROS implicated in AF include uncoupled nitric oxide synthase [94] and xanthine oxidase [95]. In addition to the increase in ROS noted in tissue from patients with AF, experimental evidence suggests that ROS may be implicated not only in promoting AF but also in maintaining atrial arrhythmia. The administration of antioxidants such as vitamin C or statins (which are known to have pleiotropic antioxidant effects) decreased AF inducibility in canine models of tachypacing-induced AF [96,97]. Antioxidants such as vitamin C and n-acetylcysteine have been administered to patients undergoing cardiac surgery and have been shown to decrease postoperative AF [98,99]. These early results are encouraging and warrant further investigation of inflammation and oxidative stress as viable therapeutic targets in patients with AF. Reentrant mechanism Maps of AF in animals and humans suggest that this arrhythmia is caused by multiple wandering wavelets ( figure 4), and these may be due to heterogeneity of atrial refractoriness and conduction. In addition, the response of atrial activity to adenosine infusion suggests a reentrant rather than a focal mechanism [100]. Adenosine increases the inward potassium rectifier current, which shortens refractory periods and would accelerate reentrant circuits. In contrast, this effect would slow an automatic or triggered focus. In a series of 33 patients with AF undergoing electrophysiology study, adenosine increased the dominant frequencies, supporting reentrant rather than focal sources for the perpetuation of AF. It has been suggested that at least four to six independent wavelets are required to maintain AF [101]. These wavelets rarely reenter themselves but can re-excite portions of the myocardium recently activated by another wavefront, a process called random reentry [7,102-104]. As a result, there are multiple wavefronts of activation that may collide with each other, extinguishing themselves or creating new wavelets and wavefronts, thereby perpetuating the arrhythmia ( figure 5). The reentrant circuits are therefore unstable; some disappear, while others reform. These circuits have variable but short cycle lengths, resulting in multiple circuits to which atrial tissue cannot respond in a 1:1 fashion. As a result, functional block, slow conduction, and multiple wave fronts develop [104]. https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 12/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate Patients with AF may have increased dispersion of refractoriness. This correlates with enhanced inducibility of AF and spontaneous episodes [105] likely related to unstable reentry circuits. Some patients have site-specific dispersion of atrial refractoriness and intraatrial conduction delays resulting from nonuniform atrial anisotropy [106]. This appears to be a common property of normal atrial tissue, but there are further conduction delays to and within area surrounding the AV node in patients with induced AF, suggesting an important role for the low right atrium in the genesis of AF. Abnormalities in restitution as well as the spatial distribution of such abnormalities can be related to the persistence of AF. In one study, monophasic action potential recordings were evaluated in patients with AF [107]. The action potential duration was plotted as a function of the preceding diastolic interval, and the slope of the action potential duration versus the diastolic interval (the restitution curve) was determined. If the slope was greater than one, oscillations occurred that may cause localized conduction delay or block resulting in a wave break giving rise to atrial fibrillation. These different patterns of conduction are reflected in the morphology of electrograms recorded with mapping during induced AF. Single potentials were indicative of rapid uniform conduction, short double potentials indicated collision, long double potentials were indicative of conduction block, while fragmented potentials were markers for pivoting points or slow conduction ( figure 6) [108,109]. Sites of fragmented potentials or complex fractionated atrial electrograms are potential targets for radiofrequency ablation to terminate AF as they may represent critical areas from which AF originates and perpetuates. (See "Atrial fibrillation: Catheter ablation".) This phenomenon has been termed microreentry to distinguish it from classic reentry in which the same reentrant pathway is repetitively traversed. The impulse may circulate around a central line of functional block, so-called leading circle reentry; this type of reentry tends not to be stable but rather to drift through the atria until it is extinguished. The perpetuation of AF may also depend importantly upon macroreentry around natural orifices and structures in the atrium, which provides a rationale and anatomic landmarks for ablative treatment. The collision of wavefronts cancels many atrial depolarizations that might otherwise reach the AV node, resulting in a slower heart rate than might otherwise have occurred ( figure 7A-B). Although multiple wandering wavelets probably account for the majority of AF, one study reported nine patients in whom a single, rapidly firing focus was identified with electrophysiologic mapping [110]. Organized and rapid atrial activity with a centrifugal and consistent pattern of atrial activation resulted from this focus, but it fired irregularly with striking https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 13/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate and abrupt changes in atrial cycle lengths. In most of the patients, the focus was near the ostia of great vessels and was amenable to radiofrequency ablation ( figure 8 and figure 9). Small reentrant sources, called rotors, may drive or maintain AF in some cases. These rotors result in a hierarchical distribution of frequencies throughout the atria that may be identified with spectral analysis of intracardiac recordings. Ablation of such sites has terminated paroxysmal AF, suggesting that they may play an important role [111], but it is not clear that the rotors are responsible for AF or are fixed in most instances. AF may be chaotic and have wavelets and rotors that are secondary rather than the predominant cause of AF [112]. However, antral pulmonary venous reentrant and focal drivers may be responsible for AF [54]. The complexity of such drivers increase with prolonged AF. These sites are often localized near the PV orifices in patients with paroxysmal AF, and are more often localized to the left or right atria in patients with chronic AF [100]. The fibrillating atrium cannot be captured by pacing when the atrial electrograms are disorganized. This observation supports the presence of microreentry, since there is no excitable gap (or it is very small) to permit capture. However, when type I ( figure 9) AF (which has organized atrial electrograms) is induced by rapid atrial pacing, the fibrillating atrium can be captured with rapid atrial pacing, suggesting the presence of an excitable gap [113]. ROLE OF THE ATRIOVENTRICULAR NODE The atrioventricular (AV) node regulates the number of atrial impulses that reach the ventricle. The ventricular rate in atrial fibrillation (AF) is typically irregularly irregular, with a ventricular rate that may be slow, moderate, or rapid depending on the capacity of the AV node to conduct impulses. The rate of AV nodal conduction is dependent upon multiple factors, including electrical properties of the node and the influence of the autonomic nervous system [114]. In addition, the use drugs such as digoxin, calcium channel blockers, or beta blockers may influence AV nodal function. There also may be a circadian rhythm for both AV nodal refractoriness and concealed conduction, accounting for the circadian variation in ventricular response rate [115]. AV nodal tissue consists of so-called "slow response" fibers, which depend on a mixed

experimental evidence suggests that ROS may be implicated not only in promoting AF but also in maintaining atrial arrhythmia. The administration of antioxidants such as vitamin C or statins (which are known to have pleiotropic antioxidant effects) decreased AF inducibility in canine models of tachypacing-induced AF [96,97]. Antioxidants such as vitamin C and n-acetylcysteine have been administered to patients undergoing cardiac surgery and have been shown to decrease postoperative AF [98,99]. These early results are encouraging and warrant further investigation of inflammation and oxidative stress as viable therapeutic targets in patients with AF. Reentrant mechanism Maps of AF in animals and humans suggest that this arrhythmia is caused by multiple wandering wavelets ( figure 4), and these may be due to heterogeneity of atrial refractoriness and conduction. In addition, the response of atrial activity to adenosine infusion suggests a reentrant rather than a focal mechanism [100]. Adenosine increases the inward potassium rectifier current, which shortens refractory periods and would accelerate reentrant circuits. In contrast, this effect would slow an automatic or triggered focus. In a series of 33 patients with AF undergoing electrophysiology study, adenosine increased the dominant frequencies, supporting reentrant rather than focal sources for the perpetuation of AF. It has been suggested that at least four to six independent wavelets are required to maintain AF [101]. These wavelets rarely reenter themselves but can re-excite portions of the myocardium recently activated by another wavefront, a process called random reentry [7,102-104]. As a result, there are multiple wavefronts of activation that may collide with each other, extinguishing themselves or creating new wavelets and wavefronts, thereby perpetuating the arrhythmia ( figure 5). The reentrant circuits are therefore unstable; some disappear, while others reform. These circuits have variable but short cycle lengths, resulting in multiple circuits to which atrial tissue cannot respond in a 1:1 fashion. As a result, functional block, slow conduction, and multiple wave fronts develop [104]. https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 12/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate Patients with AF may have increased dispersion of refractoriness. This correlates with enhanced inducibility of AF and spontaneous episodes [105] likely related to unstable reentry circuits. Some patients have site-specific dispersion of atrial refractoriness and intraatrial conduction delays resulting from nonuniform atrial anisotropy [106]. This appears to be a common property of normal atrial tissue, but there are further conduction delays to and within area surrounding the AV node in patients with induced AF, suggesting an important role for the low right atrium in the genesis of AF. Abnormalities in restitution as well as the spatial distribution of such abnormalities can be related to the persistence of AF. In one study, monophasic action potential recordings were evaluated in patients with AF [107]. The action potential duration was plotted as a function of the preceding diastolic interval, and the slope of the action potential duration versus the diastolic interval (the restitution curve) was determined. If the slope was greater than one, oscillations occurred that may cause localized conduction delay or block resulting in a wave break giving rise to atrial fibrillation. These different patterns of conduction are reflected in the morphology of electrograms recorded with mapping during induced AF. Single potentials were indicative of rapid uniform conduction, short double potentials indicated collision, long double potentials were indicative of conduction block, while fragmented potentials were markers for pivoting points or slow conduction ( figure 6) [108,109]. Sites of fragmented potentials or complex fractionated atrial electrograms are potential targets for radiofrequency ablation to terminate AF as they may represent critical areas from which AF originates and perpetuates. (See "Atrial fibrillation: Catheter ablation".) This phenomenon has been termed microreentry to distinguish it from classic reentry in which the same reentrant pathway is repetitively traversed. The impulse may circulate around a central line of functional block, so-called leading circle reentry; this type of reentry tends not to be stable but rather to drift through the atria until it is extinguished. The perpetuation of AF may also depend importantly upon macroreentry around natural orifices and structures in the atrium, which provides a rationale and anatomic landmarks for ablative treatment. The collision of wavefronts cancels many atrial depolarizations that might otherwise reach the AV node, resulting in a slower heart rate than might otherwise have occurred ( figure 7A-B). Although multiple wandering wavelets probably account for the majority of AF, one study reported nine patients in whom a single, rapidly firing focus was identified with electrophysiologic mapping [110]. Organized and rapid atrial activity with a centrifugal and consistent pattern of atrial activation resulted from this focus, but it fired irregularly with striking https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 13/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate and abrupt changes in atrial cycle lengths. In most of the patients, the focus was near the ostia of great vessels and was amenable to radiofrequency ablation ( figure 8 and figure 9). Small reentrant sources, called rotors, may drive or maintain AF in some cases. These rotors result in a hierarchical distribution of frequencies throughout the atria that may be identified with spectral analysis of intracardiac recordings. Ablation of such sites has terminated paroxysmal AF, suggesting that they may play an important role [111], but it is not clear that the rotors are responsible for AF or are fixed in most instances. AF may be chaotic and have wavelets and rotors that are secondary rather than the predominant cause of AF [112]. However, antral pulmonary venous reentrant and focal drivers may be responsible for AF [54]. The complexity of such drivers increase with prolonged AF. These sites are often localized near the PV orifices in patients with paroxysmal AF, and are more often localized to the left or right atria in patients with chronic AF [100]. The fibrillating atrium cannot be captured by pacing when the atrial electrograms are disorganized. This observation supports the presence of microreentry, since there is no excitable gap (or it is very small) to permit capture. However, when type I ( figure 9) AF (which has organized atrial electrograms) is induced by rapid atrial pacing, the fibrillating atrium can be captured with rapid atrial pacing, suggesting the presence of an excitable gap [113]. ROLE OF THE ATRIOVENTRICULAR NODE The atrioventricular (AV) node regulates the number of atrial impulses that reach the ventricle. The ventricular rate in atrial fibrillation (AF) is typically irregularly irregular, with a ventricular rate that may be slow, moderate, or rapid depending on the capacity of the AV node to conduct impulses. The rate of AV nodal conduction is dependent upon multiple factors, including electrical properties of the node and the influence of the autonomic nervous system [114]. In addition, the use drugs such as digoxin, calcium channel blockers, or beta blockers may influence AV nodal function. There also may be a circadian rhythm for both AV nodal refractoriness and concealed conduction, accounting for the circadian variation in ventricular response rate [115]. AV nodal tissue consists of so-called "slow response" fibers, which depend on a mixed calcium/sodium current. This current is often called the inward calcium current, since in a normal physiologic environment, the ions are almost exclusively calcium. The mixed current uses a kinetically slow channel and is responsible for phase 0 depolarization. (See "Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs".) https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 14/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate These characteristics lead to properties that are quite different from "fast-response" tissue in the atria, which as noted above, depend on an inward sodium current that uses a kinetically fast channel for phase 0 depolarization [8,116]: Partial and complete reactivation returns only 100 ms or more after return to the diastolic potential (versus 10 to 50 ms in the atria). The refractory period changes little as a function of rate. Conduction velocity is relatively slow, ranging from 0.01 to 0.1 m/s. Unlike tissue generating a fast action potential that has an all-or-none response (ie, the velocity of impulse conduction is similar at all stimulation rates until block occurs), tissue that generates a slow action potential exhibits a graded or decremental response, in which the velocity of impulse conduction slows as the stimulation rate increases. As noted above, the ventricular rate usually ranges 90 and 170 beats/min. Ventricular rates below 60 beats/min are seen with AV nodal disease, drugs that affect conduction, and high vagal tone as can occur in a well-conditioned athlete. Ventricular rates above 200 beats/min suggest catecholamine excess, parasympathetic withdrawal, or the existence of an accessory bypass tract as occurs in the preexcitation syndrome. The QRS complexes are widened in the last setting and must be distinguished from a rate-related or underlying bundle branch block. In the classical view, the AV node is bombarded by impulses from the fibrillating atria. Some impulses traverse the AV node and reach the specialized infranodal conduction system and then the ventricles. However, most atrial impulses penetrate the AV node from varying distances and then are extinguished when they encounter the refractoriness of an earlier wavefront; this phenomenon of concealed conduction in turn creates a refractory wave that affects succeeding impulses. The failure of the refractory period to shorten with increasing rate (as occurs in the atria) further decreases the likelihood of an impulse traversing the AV node. Anatomically distinct AV nodal inputs, called the slow and fast pathways, are involved in the ventricular response to AF. The importance of these pathways has been demonstrated in radiofrequency ablation studies in which ablation reduced the number of beats that successfully reached the infranodal conduction system and the ventricles [117-120]. (See "Atrioventricular nodal reentrant tachycardia".) In addition to its intrinsic properties, the AV node is richly supplied and affected by both components of the autonomic nervous system. AV conduction is enhanced and refractoriness https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 15/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate reduced by the sympathetic fibers, and conduction reduced and refractoriness prolonged by the parasympathetic fibers. The net effect of the electrophysiologic properties of the AV node is that the rate of conduction into the specialized infranodal conduction system is (fortunately) much slower than the rate of the fibrillating atria. In some cases, the high degree of refractoriness in the AV node with AF results in high-grade or third-degree block. In this setting, the pacemaker that controls the ventricles is below the AV node. (See "The electrocardiogram in atrial fibrillation".) In patients with the preexcitation syndrome, the AV node is bypassed by "fast-response" tracts, which activate and reactivate much faster than the AV node and are therefore capable of rapid conduction. The development of AF in such a patient can result in very rapid transmission of atrial impulses to the ventricles [120] and can rarely cause ventricular fibrillation [15]. (See "The electrocardiogram in atrial fibrillation".) It is also important to recognize that the presence of an accessory pathway can increase the propensity for development of AF. In patients with AF who have Wolff-Parkinson-White (WPW) syndrome, catheter ablation of the accessory pathway is indicated to lower the sudden death risk but also to decrease the probability of recurrent AF. Unexpected ventricular rates The ventricular response to AF characteristically is irregularly irregular although it may appear regular in the presence of complete AV block. The usual ventricular rate in AF is between 90 and 170 beats per minute in the absence of AV node disease, drugs that affect conduction, or enhanced vagal inputs. Ventricular rates that are clearly outside this range suggest some concurrent problem: A ventricular rate below 60 beats per minute, in the absence of AV nodal blocking agents, suggests AV nodal disease that may be associated with the sinus node dysfunction. (See "Sinus node dysfunction: Epidemiology, etiology, and natural history".) A ventricular rate above 170 beats per minute suggests thyrotoxicosis, catecholamine excess, parasympathetic withdrawal, or the existence of an accessory bypass tract in the preexcitation syndrome. (See "Epidemiology, risk factors, and prevention of atrial fibrillation".) SPECIFIC CLINICAL SITUATIONS Late recurrent AF after catheter ablation The etiology of late recurrent atrial fibrillation (AF) following pulmonary vein isolation (PVI) has been debated. In some cases, triggering foci outside of the PVs may initiate AF [121-124]. Alternatively, persistence of the substrate for https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 16/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate maintaining AF (abnormal electrical properties of the atria themselves) may be more important than the triggering foci, especially in chronic AF. However, there is increasing evidence that when AF does recur late after PVI, it often represents incomplete electrical isolation of the PVs, either due to resumption of conduction across the ablation scar or to residual conduction in PVs that were not successfully ablated. Most [125-128], but not all [129], studies of the former mechanism support the hypothesis that resumption of PV-left atrial (LA) conduction is associated with an increased risk of recurrent AF. However, recurrent conduction across ablated lesions is more common than clinically evident recurrent AF [127,130]. Pre-existing LA scarring may predispose patients to late recurrence. In a series of 700 consecutive patients undergoing first-time PVI, scarring was detected in 6 percent [131]. These patients had a much higher rate of recurrence than those without scarring (57 versus 19 percent). Possible causes of scarring include atrial remodeling and inflammation. The patients with scarring had significant elevations in serum C-reactive protein (CRP) compared to those without scarring (5.9 versus 0.31 mg/L). This is consistent with other studies showing a relationship between serum CRP and AF [132]. (See "Epidemiology, risk factors, and prevention of atrial fibrillation", section on 'Inflammation and infection'.) After cardiac surgery AF occurs frequently (approximately one of four patients) after cardiac surgery. Nonuniform atrial conduction is greatest on days two and three in this setting, and the longest atrial conduction time is greatest on day three after open heart surgery; these abnormalities coincide with the time of greatest risk for AF [133]. The degree of atrial inflammation after surgery in dogs was associated with a proportional increase in the inhomogeneity of atrial conduction and in the duration of AF; antiinflammatory therapy decreased the inhomogeneity [134]. Nevertheless, the mechanism of AF in the postoperative period is likely multifactorial. It is important to note that in most of the patients, especially those without a prior history of AF, that the AF is self-limited, and antiarrhythmic drug therapy can usually be stopped two to three months following surgery when the inflammation has subsided. (See "Atrial fibrillation and flutter after cardiac surgery".) Hyperthyroidism It is well established that hyperthyroidism can increase susceptibility to development of AF. As a consequence, all patients with new onset AF should have some measure of thyroid function tested. Successful treatment of the hyperthyroidism often results in elimination of the AF. https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 17/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate Obesity Obesity has been associated with AF and it is possible that both are related mechanistically [135]. In a sheep model, weight gain was associated with increased left atrial volume, fibrosis, inflammatory infiltrates, and lipidosis. There was reduced conduction velocity in atrial tissue and increased inducible and spontaneous AF with obesity. Atrial endothelin-A and -B receptors, endothelin-1, atrial interstitial and cytoplasmic transforming growth factor beta1, and platelet-derived growth factor were higher with obesity. In a clinical study of 110 patients undergoing AF ablation versus 20 reference patients without AF, pericardial fat volumes were associated with AF, its chronicity, and its symptom burden. Pericardial fat predicted AF recurrence post-ablation [136]. Associations persisted after adjusting for body weight but body mass index was not associated with these outcomes in multivariate-adjusted models. In another report [137], weight management with subsequent weight loss was associated with improved AF symptom burden scores, symptom severity scores, number of episodes, and cumulative duration of AF. This preliminary information does not yet prove that obesity causes AF by any specific mechanism. In a study of atrial sheep myocytes, acute, short-term incubation in free fatty acids resulted in no differences in passive or active properties of isolated left atrial myocytes but stearic acid reduced membrane capacitance and abbreviated the action potential duration, likely due to a reduction of the L-type calcium and of the transient outward potassium currents [138]. GENETICS OF AF Over the last decade, a preponderance of evidence suggests a large genetic contribution to atrial fibrillation (AF) [139,140]. Having a family member with AF is associated with a 40 percent increased risk for the arrhythmia [141]. Initially, traditional genetic techniques such as linkage analysis led to the discovery of rare, monogenic causes of AF. The first such study identified a genetic locus for AF using a series of related families with early onset AF [142]. A later study identified the first gene for familial AF [143]. Using a large Chinese kindred with autosomal dominant AF, they found a gain-of-function mutation in KCNQ1 (the gene encoding the subunit of the potassium channel current, I ). Since then, several additional gain-of-function variants Ks have been identified in KCNQ1 [144,145]. In addition to KCNQ1, mutations have been identified in other potassium channels genes, including KCNA5 [146], KCND3 [147], and KCNJ2 [148], and accessory subunits KCNE1 [149], KCNE2 [150], KCNE3 [151], and KCNE5 [152,153]. The majority of these functionally validated, AF-associated potassium channel variants have a gain-of-function channel, with an expected shortening of the atrial action potential duration and atrial refractory period. Variation in sodium channel subunits has also been identified as an important factor in the development of familial AF, with AF-causing variants observed in both the https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 18/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate major cardiac sodium channel alpha subunit SCN5A [154] and its associated beta subunits [155,156]. Several variants have also been identified in genes that do not directly alter the atrial action potential, but instead would be expected to cause AF through alternative mechanisms, eg, somatic mutations in GJA5, which encodes the gap junctional protein; connexin 40, a frameshift mutation that resulted in early truncation of NPPA [157], which encodes for the precursor for atrial natriuretic peptide; and genetic variation in several developmentally related cardiac transcription factors, ie, NKX2.5, PITX2, GATA4, GATA5, and GATA6 [156,158,159]. Genome-wide association studies (GWAS) have been used to identify genetic loci associated with AF. GWAS rely on the unbiased comparison of common single-nucleotide polymorphisms (SNPs) throughout the genome, with SNPs occurring with different frequency in individuals with a disease versus controls being used to localize disease-related genetic loci. The first GWAS performed for AF identified a region on chromosome 4q25, which was associated with AF in those of European and Asian descent [160]. Subsequently, these findings were broadly replicated in individuals of European, Asian, and African descent [161,162]. Genetic variants on chromosome 4q25 that are most significantly associated with AF reside about 150 kilobases upstream of the nearest gene PITX2. PITX2 encodes the paired-like homeodomain transcription factor 2, which helps determine cardiac laterality, suppresses the default expression of a sinoatrial nodal gene programme in the left atrium, and encodes the pulmonary venous myocardium [163]. In addition, PITX2 is associated with formation of the pulmonary veins. These findings are particularly interesting in light of the fact that AF triggers frequently arise in the pulmonary veins. In addition to the role of PITX2 in development, studies demonstrate a role for the PitX2c transcript in expression of gene-encoding ion channels, calcium cycling proteins, and gap junctions; these direct electrophysiological influences likely lead to formation of substrate for triggered activity as well as reentry [164]. Related analysis identified the same genomic region as being associated with an increased risk of cardioembolic stroke [156,165] and a prolonged PR interval [166]. To date, GWAS have identified 14 genomic regions of susceptibility for AF, with 17 independent signals at these loci [167]. These include the ZFHX3 gene that encodes a zinc finger homeobox transcription factor [168], the KCNN3 gene that encodes the SK3 potassium channel [169], and the PRRX1 gene that encodes a member of the paired-related homeobox gene family [168]. Whole exome and genome sequencing has been increasingly used to identify rare variants associated with AF [156]. For example, Oleson et al reported a much higher prevalence of rare variants in genes associated with AF (KCNQ1, KCNH2, SCN5A, KCNA5, KCND3, KCNE1, 2, 5, KCNJ2, SCN1-3B, NPPA, and GJA5) in early onset, lone AF patients than in the background population [170]. This approach is beginning to identify rare candidate variants in genes not previously linked to other types of https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 19/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate Mendelian disease and thus may offer new insights into AF pathogenesis and disease pathways that could ultimately provide novel therapeutic targets for this common condition. A 2018 meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than 500,000 individuals, sought to identify AF-associated genes at the GWAS loci by performing RNA sequencing and expression quantitative trait locus analyses in 101 left atrial samples (which is the most relevant tissue for AF) [171]. A transcriptome-wide analysis was also performed; this analysis identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci-implicated genes enriched within cardiac developmental, electrophysiological, contractile, and structural pathways. SUMMARY The precise mechanisms by which age and other risk factors such as hypertension, coronary artery or valvular heart disease, or heart failure increase the propensity for development of atrial fibrillation (AF) are poorly understood ( figure 1). These conditions may affect the triggers of or the substrate for the maintenance of AF. (See 'Introduction' above.) These mechanisms are complex and involve a dynamic interplay between the triggers and substrate abnormalities. It is likely that short-lived episodes are due to specific triggers, including autonomic perturbations, focal discharges, specific reentry circuits in the pulmonary veins (PVs), and effects of stretch, whereas inflammation, dilatation, fibrosis, repolarization abnormalities, and conduction disturbances allow for perpetuation of episodes of AF. (See 'Mechanisms of atrial fibrillation: triggers and substrates' above.) AF is most often initiated (triggered) by rapid firing from the PV. (See 'Triggers of AF' above.) Paroxysmal AF commonly precedes chronic AF. This suggests that, in addition to other predisposing factors, AF may play a role in its own natural history. (See 'Electrical remodeling' above.) The autonomic nervous system likely influences the initiation and perpetuation of AF. (See 'Role of the autonomic nervous system' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 20/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate 1. Wasmer K, Eckardt L, Breithardt G. Predisposing factors for atrial fibrillation in the elderly. J Geriatr Cardiol 2017; 14:179. 2. Goudis CA, Korantzopoulos P, Ntalas IV, et al. Obesity and atrial fibrillation: A comprehensive review of the pathophysiological mechanisms and links. 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JAMA 2013; 310:2050. https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 30/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate 138. O'Connell RP, Musa H, Gomez MS, et al. Free Fatty Acid Effects on the Atrial Myocardium: Membrane Ionic Currents Are Remodeled by the Disruption of T-Tubular Architecture. PLoS One 2015; 10:e0133052. 139. Ellinor PT, Yoerger DM, Ruskin JN, MacRae CA. Familial aggregation in lone atrial fibrillation. Hum Genet 2005; 118:179. 140. Darbar D, Herron KJ, Ballew JD, et al. Familial atrial fibrillation is a genetically heterogeneous disorder. J Am Coll Cardiol 2003; 41:2185. 141. Lubitz SA, Yin X, Fontes JD, et al. Association between familial atrial fibrillation and risk of new-onset atrial fibrillation. JAMA 2010; 304:2263. 142. Brugada R, Tapscott T, Czernuszewicz GZ, et al. Identification of a genetic locus for familial atrial fibrillation. N Engl J Med 1997; 336:905. 143. Chen YH, Xu SJ, Bendahhou S, et al. KCNQ1 gain-of-function mutation in familial atrial fibrillation. Science 2003; 299:251. 144. Hasegawa K, Ohno S, Ashihara T, et al. A novel KCNQ1 missense mutation identified in a patient with juvenile-onset atrial fibrillation causes constitutively open IKs channels. Heart Rhythm 2014; 11:67. 145. Bartos DC, Duchatelet S, Burgess DE, et al. R231C mutation in KCNQ1 causes long QT syndrome type 1 and familial atrial fibrillation. Heart Rhythm 2011; 8:48. 146. Christophersen IE, Olesen MS, Liang B, et al. Genetic variation in KCNA5: impact on the atrial-specific potassium current IKur in patients with lone atrial fibrillation. Eur Heart J 2013; 34:1517. 147. Olesen MS, Refsgaard L, Holst AG, et al. A novel KCND3 gain-of-function mutation associated with early-onset of persistent lone atrial fibrillation. Cardiovasc Res 2013; 98:488. 148. Deo M, Ruan Y, Pandit SV, et al. KCNJ2 mutation in short QT syndrome 3 results in atrial fibrillation and ventricular proarrhythmia. Proc Natl Acad Sci U S A 2013; 110:4291. 149. Olesen MS, Bentzen BH, Nielsen JB, et al. Mutations in the potassium channel subunit KCNE1 are associated with early-onset familial atrial fibrillation. BMC Med Genet 2012; 13:24. 150. Yang Y, Xia M, Jin Q, et al. Identification of a KCNE2 gain-of-function mutation in patients with familial atrial fibrillation. Am J Hum Genet 2004; 75:899. 151. Lundby A, Ravn LS, Svendsen JH, et al. KCNE3 mutation V17M identified in a patient with lone atrial fibrillation. Cell Physiol Biochem 2008; 21:47. 152. Ravn LS, Aizawa Y, Pollevick GD, et al. Gain of function in IKs secondary to a mutation in KCNE5 associated with atrial fibrillation. Heart Rhythm 2008; 5:427. https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 31/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate 153. Enriquez A, Antzelevitch C, Bismah V, Baranchuk A. Atrial fibrillation in inherited cardiac channelopathies: From mechanisms to management. Heart Rhythm 2016; 13:1878. 154. Darbar D, Kannankeril PJ, Donahue BS, et al. Cardiac sodium channel (SCN5A) variants associated with atrial fibrillation. Circulation 2008; 117:1927. 155. Olesen MS, Holst AG, Svendsen JH, et al. SCN1Bb R214Q found in 3 patients: 1 with Brugada syndrome and 2 with lone atrial fibrillation. Heart Rhythm 2012; 9:770. 156. Tucker NR, Ellinor PT. Emerging directions in the genetics of atrial fibrillation. Circ Res 2014; 114:1469. 157. Hodgson-Zingman DM, Karst ML, Zingman LV, et al. Atrial natriuretic peptide frameshift mutation in familial atrial fibrillation. N Engl J Med 2008; 359:158. 158. Huang RT, Xue S, Xu YJ, et al. A novel NKX2.5 loss-of-function mutation responsible for familial atrial fibrillation. Int J Mol Med 2013; 31:1119. 159. Zhou YM, Zheng PX, Yang YQ, et al. A novel PITX2c loss of function mutation underlies lone atrial fibrillation. Int J Mol Med 2013; 32:827. 160. Gudbjartsson DF, Arnar DO, Helgadottir A, et al. Variants conferring risk of atrial fibrillation on chromosome 4q25. Nature 2007; 448:353. 161. K b S, Darbar D, van Noord C, et al. Large scale replication and meta-analysis of variants on chromosome 4q25 associated with atrial fibrillation. Eur Heart J 2009; 30:813. 162. Delaney JT, Jeff JM, Brown NJ, et al. Characterization of genome-wide association-identified variants for atrial fibrillation in African Americans. PLoS One 2012; 7:e32338. 163. Bapat A, Anderson CD, Ellinor PT, Lubitz SA. Genomic basis of atrial fibrillation. Heart 2018; 104:201. 164. Gutierrez A, Chung MK. Genomics of Atrial Fibrillation. Curr Cardiol Rep 2016; 18:55. 165. Shi L, Li C, Wang C, et al. Assessment of association of rs2200733 on chromosome 4q25 with atrial fibrillation and ischemic stroke in a Chinese Han population. Hum Genet 2009; 126:843. 166. Kolek MJ, Parvez B, Muhammad R, et al. A common variant on chromosome 4q25 is associated with prolonged PR interval in subjects with and without atrial fibrillation. Am J Cardiol 2014; 113:309. 167. Tucker NR, Clauss S, Ellinor PT. Common variation in atrial fibrillation: navigating the path from genetic association to mechanism. Cardiovasc Res 2016; 109:493. 168. Ellinor PT, Lunetta KL, Albert CM, et al. Meta-analysis identifies six new susceptibility loci for atrial fibrillation. Nat Genet 2012; 44:670. https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 32/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate 169. Ellinor PT, Lunetta KL, Glazer NL, et al. Common variants in KCNN3 are associated with lone atrial fibrillation. Nat Genet 2010; 42:240. 170. Olesen MS, Andreasen L, Jabbari J, et al. Very early-onset lone atrial fibrillation patients have a high prevalence of rare variants in genes previously associated with atrial fibrillation. Heart Rhythm 2014; 11:246. 171. Roselli C, Chaffin MD, Weng LC, et al. Multi-ethnic genome-wide association study for atrial fibrillation. Nat Genet 2018; 50:1225. Topic 16402 Version 27.0 https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 33/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate GRAPHICS AF mechanisms Overview of mechanisms of AF. Four different positive-feedback loops are proposed as 2 the main driving forces for the atrial remodeling process. Enhanced Ca + loading during AF is believed to underlie most of the cellular proarrhythmic mechanisms (trigger loop). The main process in the electrical loop is an altered contribution of ion channels to the 2 action potential configuration that protects atrial myocytes against excessive Ca + loading. Abbreviation of the action potential facilitates re-entry and thereby promotes AF. In the structural loop, chronic atrial stretch activates numerous signaling cascades that produce alterations of the extracellular matrix and conduction disturbances, also facilitating re-entrant mechanisms. The main changes of the contractile properties of the heart are loss of atrial contractility which increases atrial compliance and the development of a ventricular tachycardiomyopathy, both of which increase stretch in the atrial wall. The circular positive-feedback enhancement of these pathophysiological changes explains the general tendency of AF to become more stable with time. It should be noted that the different loops are interconnected by mechanisms that are part of more than one loop. For example, increased Ca + loading enhances trigger activity 2 (trigger loop) and also results in a change in the ion channel population and activity (electrical loop). Re-entrant mechanisms are promoted by both shortening of refractoriness (electrical loop) as well as by conduction disturbances resulting from https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 34/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate tissue fibrosis (structural loop). Like in a system of meshing gear wheels, one loop will drive the other, leading to progression of the arrhythmia. However, the proposed system of gear wheels does not start to move spontaneously. Structural heart diseases, arrhythmias, aging, or inherited diseases are required to initiate movement of one or more of these wheels. When the pathophysiological alterations eventually reach a certain threshold, AF will ensue. Ulrich Schotten, Sander Verheule, Paulus Kirchhof, and Andreas Goette. Pathophysiological Mechanisms of Atrial Fibrillation: A Translational Appraisal. Physiol Rev January 2011 91:265-325 [PRV1/2011]. Reproduced with permission. Copyright 2011 The American Physiological Society. Graphic 63675 Version 5.0 https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 35/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate AF remodeling 2+ Mechanisms underlying ATR. Rapid atrial rates increase potentially cytotoxic Ca loading. Autoprotective I changes (I reductions occur via rapidly developing functional Ca,L inactivation) and more slowly developing changes in gene and protein Ca,L expression. Decreased I shortens refractoriness and reduces the wavelength (WL), which allows for smaller and 2+ reduces Ca loading but decreases APD. Diminished APD Ca,L more atrial reentry circuits, thus making AF unlikely to terminate. Atrial tachycardia also increases inward-rectifier currents such as I APD and promotes AF. and I , which further reduces K1 K,ACh,c RP: refractory period; WL: wavelength. Reproduced with permission from: Nattel S, Burstein B, Dobrev D. Atrial Remodeling and Atrial Fibrillation: Mechanisms and Implications. Circ Arrhythm Electrophysiol 2008; 1:62. Copyright 2008 Lippincott Williams & Wilkins. Graphic 51670 Version 8.0 https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 36/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate Signal averaged electrocardiogram predicts atrial fibrillation after coronary artery bypass graft (CABG) surgery The incidence of atrial fibrillation (AF) after coronary artery bypass graft surgery is directly related to the duration of the P wave on a signal averaged ECG. Data from Zaman AG, Archbold RA, Helft G, et al. Circulation 2000; 101:1403. Graphic 60431 Version 4.0 https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 37/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate Atrial activation in atrial fibrillation Spread of activation through right (upper half) and left (lower half) atria during stable atrial fibrillation. These activation maps show propagation of impulse through the atria, as visualized by color isochrones of 10 milliseconds (ms). White arrows indicate general direction of wavelets. Asterisks represent sites of impulse fragmentation and development of new wavelets. Redrawn from Allissie MA, Lammers WJEP, Bonke FIM, et al. In: Cardiac Arrhythmias, Grane &Stratton, Orlando, 1985, p. 265. Graphic 59310 Version 2.0 https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 38/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate Two types of reentry in atrial fibrillation The isochronal activation maps demonstrate two types of reentry in atrial fibrillation. Map A shows random reentry with three simultaneous wavefronts (black arrows) activating most of the recording area. Map B also shows three simultaneous wavefronts, but they are coming from different directions than those in map A. Maps C and D show two consecutive cycles of complete reentry. The wave of activation (black arrow) spreads clockwise in a circular fashion around a line of unexcited tissue. Reproduced with permission from Holm M, Johansson R, Brandt J, et al. Eur Heart J 1997; 18:290. Graphic 73931 Version 2.0 https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 39/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate Atrial electogram morphology in atrial fibrillation The morphology of unipolar electrograms recorded during atrial fibrillation reflect different patterns of conduction, as demonstrated by the isochrone maps. Black arrows indicate the direction of activation. Single potentials are indicative of rapid uniform conduction. Short doubles result from collision of the wavefronts along a line of collision (map A). Long doubles are due to conduction block (Map B). Fragmented electrograms refect multiple discrete deflections that may result from impulse conduction around a pivotal point (map C) or from slow or delayed conduction (map D). Reproduced with permission from Konings KTS, Smeets JLRM, Penn OC, et al. Circulation 1997; 95:1231. Graphic 52152 Version 2.0 https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 40/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate Schema of normal impulse conduction in the heart The sinoatrial node (SAN) generates an action potential that is conducted through the right and left atria, resulting in atrial contraction. The impulse is then conducted through the atrioventricular node (AVN), activating the ventricular myocardium, resulting in contraction of the right and left ventricle. SVC: superior vena cava; IVC: inferior vena cava; PV: pulmonary veins; LAA: left atrial appendage; RAA: right atrial appendage. Graphic 57781 Version 2.0 https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 41/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate Electrical activity in atrial fibrillation During atrial fibrillation there are multiple reentrant circuits within the right and left atrium, resulting in nonuniform activitation of the atrial myocardium. These circuits, which produce multiple wavelets, often occur around the normal structures of the atrial including the orifices of the superior (SVC) and inferior (IVC) vena cavae, the orifice of the pulmonary veins (PVs), and the right (RAA) and left (LAA) atrial appendages. Graphic 58689 Version 1.0 https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 42/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate Noncontact endocardial activation map of focal atrial fibrillation The noncontact endocardial activation map of the half-open left atrium shows that the initial depolarization from an ectopic focus spreads centrifugally from the ostium of the right upper pulmonary vein (RUP), indicated by the white-blue color. LUP: left upper pulmonary vein. Reproduced with permission from Schneider MA, Ndrepepa G, Zrenner B, et al. Noncontact mapping-guided catheter ablation of atrial brillation associated with left atrial ectopy. J Cardiovascular Electrophysiol 2000; 11:475. Copyright 2000 Futura Publishing Company, Inc. Graphic 55997 Version 2.0 https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 43/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate Activation patterns in atrial fibrillation Isochronal activation maps obtained from the right atrial free wall during atrial fibrillation show four distinct patterns of myocardial activation, indicated by black arrows. Activation from a localizable site which spreads in all directions away from the site is termed focal atrial activation (upper left). Type I activation is a single broad wavefront that propagates without conduction delay (upper right). Type II activation is a single wavefront that is associated with conduction slowing or block, or with two wavefronts (lower left). Type III activation results from the presence of three or more wave fronts associated with areas of slow and blocked conduction (lower right). Reproduced with permission from Holm M, Johansson R, Brandt J, et al. Eur Heart J 1997; 18:290. Graphic 66498 Version 2.0 https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 44/45 7/5/23, 10:40 AM Mechanisms of atrial fibrillation - UpToDate Contributor Disclosures Brian Olshansky, MD Other Financial Interest: AstraZeneca [Member of the DSMB for the DIALYZE trial]; Medtelligence [Cardiovascular disease]. All of the relevant financial relationships listed have been mitigated. Rishi Arora, MD No relevant financial relationship(s) with ineligible companies to disclose. Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Hugh Calkins, MD Grant/Research/Clinical Trial Support: Adagio Medical [Atrial fibrillation]; Boston Scientific [ARVC]; Farapulse [Atrial fibrillation]; Medtronic [Atrial fibrillation]. Consultant/Advisory Boards: Abbott [Atrial fibrillation]; Atricure [Atrial fibrillation]; Biosense Webster [Catheter ablation]; Boston Scientific [ARVC and atrial fibrillation]; Medtronic [Atrial fibrillation]; Sanofi [Atrial fibrillation]. Other Financial Interest: Atricure [Lecture honoraria]; Biosense Webster [Lecture honoraria]; Boston Scientific [Lecture honoraria]; Medtronic [Lecture honoraria]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 45/45

7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation : Bradley P Knight, MD, FACC : Ary L Goldberger, MD, James Hoekstra, MD : Todd F Dardas, MD, MS All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: May 19, 2023. INTRODUCTION Tachyarrhythmias, defined as abnormal heart rhythms with a ventricular rate of 100 or more beats per minute (bpm), can result from a variety of pathologies and are frequently symptomatic. Signs and symptoms related to the tachyarrhythmia most commonly include palpitations or chest discomfort, but may also include shock, hypotension, heart failure (HF), shortness of breath, and/or decreased level of consciousness. Symptoms can sometimes be more subtle and may include fatigue, lightheadedness, or exercise intolerance. Some patients are truly asymptomatic; this may be more common in nonparoxysmal (incessant) tachycardias. This topic will provide a broad overview of the different causes of narrow QRS complex tachycardia and an approach to their evaluation and diagnosis. An overview of the acute management of tachyarrhythmias, along with detailed discussions of specific narrow complex tachycardias (eg, atrioventricular [AV] nodal reentrant tachycardia [AVNRT], AV reentrant (or reciprocating) tachycardia [AVRT], and atrial tachycardia [AT]) and a broad discussion of wide complex tachycardias, are presented separately. (See "Overview of the acute management of tachyarrhythmias" and "Atrioventricular nodal reentrant tachycardia" and "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway" and "Focal atrial tachycardia" and "Wide QRS complex tachycardias: Approach to the diagnosis" and "Wide QRS complex tachycardias: Approach to management".) https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 1/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate DEFINITIONS Tachycardias, with a ventricular heart rate exceeding 100 bpm, are broadly categorized based upon the width of the QRS complex on the electrocardiogram (ECG) [1]. A narrow QRS complex (<120 ms) reflects rapid activation of the ventricles via the normal His-Purkinje system, which in turn suggests that the arrhythmia originates above or within the His bundle (ie, a supraventricular tachycardia). The mechanism of tachycardia may be in the sinus node, the atria, the AV node, the His bundle, or some combination of these sites. A widened QRS ( 120 ms) occurs when ventricular activation is abnormally slow. The most common reason that a QRS is widened is because the arrhythmia originates below the His bundle in the bundle branches, Purkinje fibers, or ventricular myocardium (eg, ventricular tachycardia). Alternatively, a supraventricular arrhythmia can produce a widened QRS if there are either preexisting or rate-related abnormalities within the His-Purkinje system (eg, supraventricular tachycardia with aberrancy), or if conduction occurs over an accessory pathway. Thus, wide QRS complex tachycardias may be either supraventricular or ventricular in origin. (See "Wide QRS complex tachycardias: Approach to the diagnosis".) TYPES OF NARROW QRS COMPLEX TACHYCARDIA Differential diagnosis of narrow QRS complex tachycardias Narrow QRS complex tachycardias can be divided into those that require only atrial tissue for their initiation and maintenance, and those that require the AV junction ( table 1) [2]. The narrow QRS complex tachycardias include: Sinus tachycardia (ST) (see "Sinus tachycardia: Evaluation and management") AV nodal reentrant tachycardia (AVNRT) (see "Atrioventricular nodal reentrant tachycardia") AV reentrant (or reciprocating) tachycardia (AVRT) (see "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway") Atrial tachycardia (AT, also known as ectopic atrial tachycardia [EAT]) (see "Focal atrial tachycardia") Inappropriate ST (see "Sinus tachycardia: Evaluation and management", section on 'Inappropriate sinus tachycardia') Sinoatrial nodal reentrant tachycardia (SANRT) (see "Sinoatrial nodal reentrant tachycardia (SANRT)") https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 2/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Intraatrial reentrant tachycardia (IART) (see "Intraatrial reentrant tachycardia") Junctional ectopic tachycardia Nonparoxysmal junctional tachycardia Atrial fibrillation (AF) (see "Atrial fibrillation: Overview and management of new-onset atrial fibrillation") Atrial flutter (see "Overview of atrial flutter") Multifocal AT (MAT) (see "Multifocal atrial tachycardia") Paroxysmal and incessant SVT The term "paroxysmal supraventricular tachycardias (PSVT)" defines a subset of narrow QRS complex tachycardias that are intermittent, start and stop abruptly, and have a regular ventricular response. This term is usually reserved for tachycardias that are sustained (>30 seconds). The term "incessant SVT" is used to describe an SVT that is unlikely to spontaneously terminate. AF, atrial flutter, and MAT have an irregular ventricular response and distinct clinical characteristics; these rhythms are not considered PSVTs and are described elsewhere. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation" and "Overview of atrial flutter" and "Multifocal atrial tachycardia".) Features of paroxysmal SVTs The prevalence of PSVT is similar in males and females (although it is slightly higher in males) and increases progressively with age. Among a prospective cohort of more than half a million United Kingdom residents, the prevalence of PSVT was approximately 29 per 10,000 persons under age 55 and increased to between 53 (females) and 74 (males) per 10,000 persons 65 years of age [3]. PSVTs are often due to reentry, although the mechanisms of reentry vary ( figure 1) [1,4]. The major causes of symptomatic PSVTs that are sustained and require therapy are AVNRT, which accounts for approximately 60 percent of cases; AVRT, which accounts for approximately 30 percent of cases; and, in about 10 percent of cases, an AT or SANRT [5,6]. Junctional ectopic tachycardia and nonparoxysmal junctional tachycardia are rare in adults but can represent a larger portion of PSVTs in children. Brief runs of PSVT captured on Holter monitoring or other recording devices are usually due to AT. AVNRT is characterized by two pathways within the AV node or perinodal atrial tissue. (See "Atrioventricular nodal reentrant tachycardia".) AVRT is characterized by an extranodal accessory pathway connecting the atrium and ventricle. The ECG shows delta waves during sinus rhythm if there is antegrade conduction via the accessory pathway, leading to a diagnosis of Wolff-Parkinson-White syndrome (WPW). The delta waves are lost during an episode of orthodromic AVRT, the most common tachyarrhythmia in patients with WPW. Most patients with AVRT, https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 3/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate however, have a concealed accessory pathway and do not have ventricular preexcitation during sinus rhythm. (See "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway" and "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis".) AT is the least common form of PSVT in patients with sustained PSVT. Most ATs in patients without prior surgery or ablation are due to a focal mechanism and can arise from anywhere in the atria, such as the crista terminalis, left atrial appendage, or near the tricuspid or mitral annulus, or can arise from a large vein such as the coronary sinus or a pulmonary vein. ATs in patients with atrial scar can be due to macroreentry. The reentrant circuit does not involve the AV node or an accessory pathway. AT can be paroxysmal or, at times, incessant. AT with 1:1 (or fixed 2:1, 3:1, etc) conduction into the ventricles is a regular tachycardia, but if there is variable conduction, the tachycardia can be irregular. (See "Sinoatrial nodal reentrant tachycardia (SANRT)" and "Intraatrial reentrant tachycardia".) Permanent junctional reciprocating tachycardia (PJRT) is a syndrome of nearly incessant, relatively slow PSVT in a patient who can, at times, present with a tachycardia-induced cardiomyopathy and HF. The SVT mechanism in most patients with PJRT is AVRT due to a slowly conducting concealed accessory pathway, and the term PJRT is often used interchangeably with incessant, slow AVRT. However, a patient with PJRT can also have nearly incessant atypical AVNRT or AT. (See "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway", section on 'Permanent junctional reciprocating tachycardia' and "Focal atrial tachycardia".) PATHOGENESIS Reentry is the most common cause of narrow QRS complex tachycardia. Increased automaticity and triggered activity occur less frequently [7]. Mechanisms of reentry Reviewed briefly, reentry requires two distinct electrical conduction pathways or tissues with different electrophysiologic properties that are linked proximally and distally, forming an anatomic or functional circuit ( figure 2) [1,4]. The reentrant circuit may become repetitively activated, producing a sustained reentrant tachycardia. The type of arrhythmia that ensues with narrow QRS tachycardias is determined by the characteristics and location of the reentrant circuit ( figure 1). The mechanisms of reentry are discussed in detail elsewhere. (See "Reentry and the development of cardiac arrhythmias".) https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 4/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Automaticity and triggered activity Other mechanisms of narrow QRS complex tachycardia include: Enhanced normal automaticity (as in sinus tachycardia) Abnormal automaticity (resulting in an ectopic atrial or junctional tachycardia) "Triggered activity," which may underlie some arrhythmias due to digitalis intoxication (such as atrial tachycardia with or without AV block or arrhythmias in the setting of acute ischemia or infarction) These mechanisms are considered in detail in topics dealing with the specific arrhythmias. (See "Focal atrial tachycardia", section on 'Mechanisms and etiology' and "Cardiac arrhythmias due to digoxin toxicity".) CLINICAL MANIFESTATIONS The response to a rapid heart rate can be quite variable depending on how fast the heart is beating, resultant blood pressure and tissue perfusion, underlying comorbidities, and the sensitivity of the individual patient to the symptoms. Patients with a narrow QRS complex tachycardia can present with a variety of symptoms, including: Palpitations Syncope or presyncope Lightheadedness or dizziness Diaphoresis Chest pain Shortness of breath Most commonly, patients with a narrow QRS complex tachycardia present with palpitations, the sensation of a rapid or irregular heart beat felt in the anterior chest or neck. Usually the symptoms are abrupt in onset, although this may vary depending on the specific arrhythmia. Palpitations may be associated with diaphoresis, lightheadedness, or dizziness. Patients with a narrow QRS complex tachycardia may also report shortness of breath or chest discomfort. While shortness of breath or chest discomfort can occur in any patient, those with underlying cardiac comorbidities (eg, coronary heart disease, cardiomyopathy or valvular heart disease with or without HF) are more likely to present in this fashion, particularly at higher heart rates (>150 bpm). https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 5/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Syncope is a rare presentation for persons presenting with a narrow QRS complex tachycardia, since in most instances the heart rate is not so rapid as to impair ventricular function and cardiac output. However, a narrow QRS complex tachycardia with a very rapid ventricular rate (>250 bpm, as might be seen in persons with AF or atrial flutter and an accessory pathway) may result in diminished cardiac output and syncope. (See 'Atrial rate' below.) The physical examination in a patient with narrow QRS complex tachycardia reveals a rapid pulse which may be regular or irregular depending on the underlying cardiac rhythm. Cardiac auscultation also reveals a rapid heartbeat. While other physical examination findings may be present in situations where the tachycardia has led to or exacerbated another condition (eg, hypotension following syncope, lung congestion in a patient with HF), there are no other specific physical examination findings which are universally seen in patients with a narrow complex tachycardia. DIAGNOSIS The diagnosis of a narrow QRS complex tachycardia is usually suspected in a patient with palpitations when a pulse greater than 100 bpm is present on physical examination. The differentiation between narrow and wide QRS complex tachycardia requires only a surface ECG, which shows a heart rate greater than 100 bpm along with narrow QRS complexes that are less than 120 ms in duration. A variety of arrhythmias result in the ECG appearance of a narrow QRS complex tachycardia. (See 'Types of narrow QRS complex tachycardia' above.) Once a narrow QRS complex tachycardia has been identified, further scrutiny of the ECG is required to identify the specific arrhythmia in a particular patient, as diagnostic evaluation and therapy will differ depending on the underlying arrhythmia. (See 'Evaluation' below.) Invasive electrophysiology testing is not required to broadly make the diagnosis of a narrow QRS complex tachycardia, but on rare occasions it is needed to diagnose (and potentially treat with catheter ablation) the specific arrhythmia. (See 'Electrophysiologic testing' below.) EVALUATION Evaluation of a patient with a narrow QRS complex tachycardia involves two primary components: Assessment of the patient for symptoms and signs of hemodynamic stability (or instability) Assessment of the patient's ECG for clues to the type of tachycardia present https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 6/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Often these steps are performed nearly simultaneously in an acute care setting, as the provider can be assessing the patient at the same time that the ECG is being obtained. Assessing the patient for hemodynamic stability The most important clinical determination to make when a narrow QRS tachycardia is noted is whether the patient is experiencing signs and symptoms related to the rapid heart rate. These can include hypotension, shortness of breath, chest pain suggestive of coronary ischemia, shock, and/or decreased level of consciousness ( algorithm 1 and algorithm 2). Determining whether a patient's symptoms are related to the tachycardia depends upon several factors, including age and the presence of underlying cardiac disease. As an example, PSVT with a heart rate of 200 bpm may be tolerated by an otherwise healthy young adult with no or few symptoms (eg, palpitations). On the other hand, AF at a rate of 120 bpm may precipitate angina in an older adult patient with significant coronary heart disease. Hemodynamically unstable and not sinus rhythm If a patient has clinically significant hemodynamic instability potentially due to a narrow QRS complex tachycardia ( algorithm 1), an attempt should be made as quickly as possible to determine whether the rhythm is sinus tachycardia (ST). If the rhythm is not sinus tachycardia, or if there is any doubt that the rhythm is sinus tachycardia, urgent conversion to sinus rhythm is recommended. (See 'Similar to sinus rhythm' below and "Overview of the acute management of tachyarrhythmias" and "Basic principles and technique of external electrical cardioversion and defibrillation".) Hemodynamically unstable and sinus rhythm If it is certain that the patient's rhythm is ST and clinically significant cardiac symptoms are present ( algorithm 2), management should be focused on the underlying cardiac disorder and on treating any contributing cause of the rapid heart rate (such as coronary ischemia, respiratory or cardiac failure, cardiac tamponade, hypovolemia, anemia, fever, pain, or anxiety). In patients with ST and certain forms of heart disease, such as coronary disease or aortic stenosis, treatment may need to be directed at the heart rate itself. In such cases, cautious use of an intravenous beta blocker is appropriate (eg, metoprolol 5 mg intravenously every two minutes until the heart rate is controlled, to a total of 15 mg, followed by an oral regimen). (See "Sinus tachycardia: Evaluation and management" and "Acute myocardial infarction: Role of beta blocker therapy" and "Medical management of symptomatic aortic stenosis".) Hemodynamically stable If the patient is not experiencing hemodynamic instability, a nonemergent approach to the diagnosis of the patient's rhythm can be undertaken ( algorithm 2) [1]. A close examination of the 12-lead ECG should permit the correct https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 7/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate identification of the arrhythmia in 80 percent of cases [8]. In some patients, increasing the ECG paper speed (from the standard 25 mm/sec to 50 mm/sec) can improve the likelihood of a correct diagnosis, or simple vagal blocking maneuvers may slow the ventricular rate to better elucidate the underlying rhythm [9]. (See 'ECG identification of atrial activity' below and 'ECG characterization of atrial activity' below.) Assessing the ECG for regularity of the rhythm Following the determination of hemodynamic stability, the next step in the assessment of a narrow QRS complex tachycardia is to determine if the rhythm appears to be regular or irregular ( algorithm 2). While the majority of narrow QRS complex tachycardias are associated with a regular ventricular rate (with AF being the most notable exception), underlying conduction system disease and certain drug toxicities (ie, digoxin) can lead to irregular appearing rhythms due to intermittent block of conduction between the atria and the ventricles. Examples of regular and irregular rhythms include: Regular Sinus tachycardia, AV nodal reentrant tachycardia, AV reciprocating tachycardia, atrial flutter (usually), atrial tachycardia (AT). Irregular AF, multifocal AT. If the rhythm is irregular, the ECG should be scrutinized for discrete atrial activity and for any evidence of a pattern to the irregularity. If the rhythm is irregularly irregular (that is, no pattern can be detected), the arrhythmia will almost always be either: AF, where no discernible discrete P waves ( waveform 1 and waveform 2) can be identified. (See "The electrocardiogram in atrial fibrillation".) Multifocal AT, in which discrete P waves of several morphologies ( waveform 3) are present. (See "Multifocal atrial tachycardia".) If the rhythm is irregular but has some periods of regularity, other arrhythmias (Mobitz I second- degree AV block) and/or drug toxicity (ie, digoxin toxicity) should be considered. (See "Second- degree atrioventricular block: Mobitz type I (Wenckebach block)" and "Cardiac arrhythmias due to digoxin toxicity".) ECG identification of atrial activity Characterization of atrial activity is essential to the diagnosis of narrow complex tachycardias ( algorithm 2). However, the first step in this process, the identification of P waves, can be difficult. https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 8/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Methods to aid in identifying P waves In ideal circumstances, P waves can be easily seen on the surface ECG. However, due to the rapid rate of the tachycardia, P waves are often superimposed on other parts of the surface ECG. In cases where P waves cannot be clearly identified, the Valsalva maneuver, carotid sinus massage, or the administration of intravenous adenosine may help to clarify the diagnosis [10]. These maneuvers may also terminate the arrhythmia in some cases (especially if the rhythm is AV nodal reentrant tachycardia AVNRT or AV reentrant tachycardia [AVRT]). (See 'Possible outcomes following vagal maneuvers or adenosine administration' below.) Valsalva maneuver The Valsalva maneuver induces a temporary slowing of SA nodal activity and AV nodal conduction by stimulating baroreceptors in the aorta, which triggers a reflex increase in vagus nerve activity and sympathetic withdrawal. Patients must be cooperative enough to comply with instructions and must be continually monitored on a cardiac monitor in order for this maneuver to be successful. The process of performing and interpreting the hemodynamic responses to the Valsalva maneuver is discussed in detail elsewhere. (See "Vagal maneuvers", section on 'Valsalva maneuver'.) The Valsalva maneuver is generally safe and well-tolerated, though it does require some effort on the patient's part to perform. While the Valsalva maneuver may not be as effective as adenosine in slowing the AV nodal conduction rate, it can often be accomplished while preparing for an adenosine challenge, especially in patients not eligible for carotid sinus massage. Additionally, the Valsalva maneuver may terminate some narrow complex tachycardias, although data regarding the effectiveness of the maneuver are inconclusive. In a 2013 Cochrane Review of three randomized trials (316 patients) that compared the Valsalva maneuver with other vagal maneuvers, there was insufficient evidence to support or refute the effectiveness of the Valsalva maneuver [11]. However, given the general safety of the maneuver, its lack of expense, and its occasional effectiveness, we ask patients to perform the Valsalva maneuver prior to using other vagal maneuvers or medications. Carotid sinus massage Carotid sinus massage induces a temporary slowing of SA nodal activity and AV nodal conduction. External pressure on the carotid bulb stimulates baroreceptors in the carotid sinus, which triggers a reflex increase in vagus nerve activity and sympathetic withdrawal. The process of performing carotid sinus massage is discussed in detail elsewhere. (See "Vagal maneuvers", section on 'Carotid sinus massage'.) Carotid sinus massage is generally safe and well tolerated, but potential complications include profound hypotension and bradycardia (including transient loss of consciousness), transient ischemic attack or stroke, and arrhythmias. Due to these potential complications, carotid sinus https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 9/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate massage should be performed with simultaneous ECG and blood pressure monitoring. (See "Vagal maneuvers", section on 'Complications'.) Intravenous adenosine Adenosine interacts with A1 receptors on the surface of cardiac cells, activating potassium channels and causing an increase in potassium conductance (IK). Adenosine also indirectly reduces calcium influx (ICa) into cells by antagonizing catecholamine- stimulated adenylate cyclase. The resulting effects include a slowing of the sinus rate and an increase in the AV nodal conduction delay, similar to the effects seen with the Valsalva maneuver and carotid sinus massage [1]. Adenosine is used for the intravenous management of paroxysmal narrow QRS complex tachycardias in which the AV node is involved. However, like the Valsalva maneuver and carotid sinus massage, adenosine can have both diagnostic and therapeutic effects, terminating some AV node dependent arrhythmias and producing transient AV nodal block that can clarify diagnoses such as atrial flutter or AT. Adenosine is cleared from the circulation extremely rapidly, with a half-life of less than five seconds, which reduces the likelihood of serious untoward effects [4]. Administration and side effects For intravenous adenosine administration ( algorithm 3), the patient should be supine and should have ECG and blood pressure monitoring. It is valuable to perform a 12-lead rhythm strip during administration of adenosine, as there are often clues at the time of termination as to the mechanism of the PSVT. The drug is administered by rapid intravenous injection over one to two seconds at a peripheral site, followed by a normal saline flush. The rapid administration of both the drug and the saline flush is most easily accomplished through a three-way stopcock. Adenosine is typically given in increasing doses until the rhythm terminates or AV block occurs. The initial dose is 6 mg. If the initial dose is not effective, a subsequent dose of 12 mg can be given. If there is no effect from the second dose, we give another 12 mg dose or an 18 mg dose. If a central intravenous access site is used, the initial dose should not exceed 3 mg [4,10]. The effects of adenosine are blocked by methylxanthines such as theophylline and caffeine and potentiated by dipyridamole. Heart transplant recipients exhibit a supersensitive response to adenosine [12]. The most common side effects of adenosine are facial flushing (18 percent), shortness of breath, palpitations, chest pain, and lightheadedness. Patients should be warned regarding these symptoms before adenosine administration. Transient asystole is a rare complication. In patients with an accessory pathway capable of antegrade (atrium to ventricle, antidromic reentrant tachycardia) conduction, AF can degenerate into ventricular fibrillation with adenosine https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 10/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate administration. As a result, caution should be used when giving adenosine if an accessory pathway with antegrade conduction is a possible mechanism, and emergency resuscitation equipment should be available. (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis", section on 'Atrial fibrillation'.) Possible outcomes following vagal maneuvers or adenosine administration Following the Valsalva maneuver, carotid sinus massage, or the intravenous administration of adenosine to patients with a narrow QRS complex tachycardia, one of four possible results may be seen: The slowing of SA nodal activity can cause a temporary decrease in the atrial rate (in patients with sinus tachycardia). The slowing of AV nodal conduction can lead to AV nodal block, which may "unmask" atrial electrical activity (ie, reveal P waves or flutter waves) by decreasing the number of QRS complexes that obscure the electrical baseline ( waveform 4). In some cases, no response is obtained. Usually the lack of any response would suggest inadequate performance of the vagal maneuver or inadequate dosing of the adenosine (either insufficient dose or administration which was too slow such that the adenosine was metabolized prior to arrival in the heart). The transient slowing of AV nodal conduction can terminate some narrow QRS complex arrhythmias by interrupting a reentry circuit that requires AV nodal conduction (especially AVNRT and AVRT). A continuous ECG tracing should be recorded during these maneuvers, because the response may aid in the diagnosis [7]: Termination of the tachycardia with a P wave after the last QRS complex is most common in AVRT or AVNRT and is rarely seen with AT. Termination of the tachycardia with a QRS complex can be seen with AVRT, AVNRT, or AT. If the tachycardia continues despite successful induction of at least some degree of AV nodal blockade, the rhythm is almost certainly AT or atrial flutter; AVRT is excluded, and AVNRT is very unlikely. If the use of carotid sinus massage and/or adenosine does not terminate the tachycardia or permit a diagnosis for the tachycardia that was terminated, further evaluation begins with characterization of the atrial activity (P waves) on the ECG. (See 'ECG characterization of atrial activity' below.) https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 11/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate ECG characterization of atrial activity Identification and characterization of atrial activity (ie, the P wave) is central to the diagnosis of narrow QRS complex tachycardias ( algorithm 2). The evaluation of atrial activity includes assessment of four features: The atrial rate The P wave morphology (ie, identical to normal sinus rhythm, retrograde, or abnormal) (see 'P wave morphology' below) The position of the P wave in relation to the preceding and following QRS complexes (ie, the RP relationship) [8] (see 'RP relationship' below) The relationship between atrial and ventricular rates (1:1 or otherwise) It is uncommon that any one of these features can identify the mechanism of an arrhythmia. In combination, however, these features (particularly the P wave morphology and RP relationship) often provide a probable diagnosis. Atrial rate There is substantial overlap between the atrial rates of most narrow QRS complex tachycardias. Thus, this feature in isolation is rarely diagnostic. The exception is with very fast atrial rates (eg >250 bpm), which are generally associated with one of two diagnoses: atrial flutter or AT. Atrial flutter has several unique features that often make it easily distinguishable from other narrow QRS complex tachycardias, including the following: The atrial rate is typically 250 to 350 bpm. Classically, the atrial rate is close to 300 bpm with 2:1 AV conduction, resulting in a ventricular rate of 150 bpm. The P waves typically exhibit a classic "sawtooth" pattern without an isoelectric baseline; these complexes are referred to as flutter waves or "F" waves ( waveform 5). If this pattern is not evident initially, vagal stimulation and intravenous adenosine can reduce the ventricular rate and make the "F" waves more evident ( waveform 4). Atypical reentrant circuits (often seen post-operatively or post-ablation) and the influence of antiarrhythmic drugs can alter these classic findings, resulting in atypical flutter waves ( waveform 6). The electrocardiographic and electrophysiologic features of atrial flutter are discussed in detail separately. (See "Electrocardiographic and electrophysiologic features of atrial flutter".) P wave morphology The P wave morphology provides insight into the site of origin of atrial activity, and therefore the mechanism of the tachycardia. The P wave should be evaluated in as many leads as possible, ideally all 12 leads of a surface ECG, although in some situations a single-lead ECG strip may be all that is available for review. https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 12/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate The P wave morphology can be classified into one of three general categories: Similar to sinus rhythm Retrograde Abnormal Similar to sinus rhythm The most reliable way to determine if the P wave in a narrow complex tachycardia is consistent with an origin from the sinus node is to compare the P wave during the tachycardia to that from the same patient during sinus rhythm. Although sinus P wave morphology can vary slightly with changes in heart rates, the P wave during the tachycardia should be nearly identical to that seen on the baseline ECG in all 12 leads. If a baseline ECG is not available, characteristics of the P wave can still suggest origin from the region of the sinus node. A sinus P wave is usually upright in leads I, aVL, and the inferior leads II, III, and aVF, and negative in lead aVR. These features indicate that atrial activity is proceeding in a right-to-left and superior-to-inferior direction. (See "ECG tutorial: Basic principles of ECG analysis", section on 'P wave'.) At atrial rates greater than approximately 140 bpm or in the presence of first degree AV block, the P wave tends to merge into the preceding T or U wave, making P wave identification difficult ( waveform 7). In such cases, slowing of the ventricular response using the Valsalva maneuver, carotid sinus massage, or adenosine may allow for better analysis of the P waves. If P wave morphology is consistent with origination from the sinus node, the differential diagnosis of the tachycardia includes: ST(see "Sinus tachycardia: Evaluation and management", section on 'Definition and ECG features') Inappropriate ST (IST) (see "Sinus tachycardia: Evaluation and management", section on 'Inappropriate sinus tachycardia') Sinoatrial nodal reentrant tachycardia (SANRT) ( waveform 8) (see "Sinoatrial nodal reentrant tachycardia (SANRT)") AT, usually originating near the sinus node (see "Focal atrial tachycardia", section on 'Electrocardiographic features') P wave morphology alone is not sufficient to distinguish these arrhythmias from one another. In persons with a P wave morphology that is consistent with origination from the sinus node, additional ECG features that assist in the diagnosis include: Atrial rate In ST and IST, the rate typically ranges from 100 to 180 bpm. Faster atrial rates suggest an AT. https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 13/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Onset/offset pattern ST and IST have smooth, gradual changes in rate. Both SANRT and AT have an abrupt onset and offset, although the rate in AT can vary significantly with autonomic tone. Relationship between atrial and ventricular activity In ST and IST, there is usually a 1:1 relationship between atrial and ventricular activity. The response to vagal maneuvers or adenosine With ST or IST, there is a gradual slowing of the atrial and ventricular rates, followed by a gradual resumption of the previous rate. In contrast, SNRT can terminate abruptly with these maneuvers. Abnormal P waves Any P wave that does not have the characteristics of a sinus P wave is considered an abnormal P wave. Abnormal P waves that are due to retrograde conduction from the ventricle to the atrium are a specific subset of abnormal P waves. (See 'Retrograde P waves' below.) Abnormal P waves that are not retrograde are most consistent with AT, although some patients with AVRT have abnormal P waves. Retrograde P waves P waves that are due to retrograde conduction from the ventricle to the atrium are a specific subset of abnormal P waves. These P waves have a characteristic morphology and suggest certain diagnoses, specifically: AVNRT AVRT Junctional ectopic tachycardia Nonparoxysmal junctional tachycardia The most common retrograde P wave morphology is associated with atrial activation that originates from the AV node and proceeds in an inferior-to-superior direction. Thus, the defining trait of a retrograde P wave is that it is negative in the inferior leads II, III, and aVF. Due to the central location of the AV node, atrial activation proceeds simultaneously leftward and rightward, so the P wave morphology in leads I, aVL, and aVR varies among patients, but it is often relatively narrow. In addition, because the AV node is posteriorly located, the activation is usually posterior-to-anterior, producing a narrow but positive P wave in lead V1. Retrograde P waves due to conduction via an accessory pathway can have a variety of morphologies, depending upon the site of the pathway. However, they are still usually negative in the inferior leads. (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis".) https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 14/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Because retrograde P waves are often associated with a short RP interval, they can blend with the terminal portion of the QRS. If a baseline ECG during sinus rhythm is available for comparison, a pseudo S wave in the inferior leads or a pseudo R' in V1 that is not present during sinus rhythm is often a retrograde P wave ( figure 3) [7,8,13]. (See 'RP relationship' below.) RP relationship In patients with a retrograde P wave, the temporal relationship between the P wave and the R wave divides narrow complex tachycardias into two categories: short RP and long RP tachycardias. The RP interval is defined as the interval from the onset of the QRS to the onset of the P wave. Short RP tachycardias tend to be paroxysmal, while long RP tachycardias can be paroxysmal or incessant. Short RP tachycardias If the RP interval is less than one-half of the RR interval, the tachycardia is considered a short RP tachycardia. The differential diagnosis of a short RP tachycardia is generated by considering the P wave morphology. Abnormal P wave The combination of abnormal P waves and a short RP interval is most often seen in the setting of an AT with AV nodal conduction delay. (See 'Abnormal P waves' above.) Retrograde P wave The combination of retrograde P waves and a short RP interval is typical of the "common" form of AVNRT and of AVRT utilizing an accessory pathway. (See 'Retrograde P waves' above.) In the "common" form of AVNRT (which accounts for 90 percent of AVNRT) [14], reentry occurs in the AV node and perinodal tissues. Antegrade conduction occurs down the slow pathway and retrograde conduction up the fast pathway ( figure 4 and figure 5). This slow-fast pattern gives rise to retrograde P waves that may be inapparent if obscured by the QRS complex ( figure 3). (See "Atrioventricular nodal reentrant tachycardia".)

Atypical reentrant circuits (often seen post-operatively or post-ablation) and the influence of antiarrhythmic drugs can alter these classic findings, resulting in atypical flutter waves ( waveform 6). The electrocardiographic and electrophysiologic features of atrial flutter are discussed in detail separately. (See "Electrocardiographic and electrophysiologic features of atrial flutter".) P wave morphology The P wave morphology provides insight into the site of origin of atrial activity, and therefore the mechanism of the tachycardia. The P wave should be evaluated in as many leads as possible, ideally all 12 leads of a surface ECG, although in some situations a single-lead ECG strip may be all that is available for review. https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 12/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate The P wave morphology can be classified into one of three general categories: Similar to sinus rhythm Retrograde Abnormal Similar to sinus rhythm The most reliable way to determine if the P wave in a narrow complex tachycardia is consistent with an origin from the sinus node is to compare the P wave during the tachycardia to that from the same patient during sinus rhythm. Although sinus P wave morphology can vary slightly with changes in heart rates, the P wave during the tachycardia should be nearly identical to that seen on the baseline ECG in all 12 leads. If a baseline ECG is not available, characteristics of the P wave can still suggest origin from the region of the sinus node. A sinus P wave is usually upright in leads I, aVL, and the inferior leads II, III, and aVF, and negative in lead aVR. These features indicate that atrial activity is proceeding in a right-to-left and superior-to-inferior direction. (See "ECG tutorial: Basic principles of ECG analysis", section on 'P wave'.) At atrial rates greater than approximately 140 bpm or in the presence of first degree AV block, the P wave tends to merge into the preceding T or U wave, making P wave identification difficult ( waveform 7). In such cases, slowing of the ventricular response using the Valsalva maneuver, carotid sinus massage, or adenosine may allow for better analysis of the P waves. If P wave morphology is consistent with origination from the sinus node, the differential diagnosis of the tachycardia includes: ST(see "Sinus tachycardia: Evaluation and management", section on 'Definition and ECG features') Inappropriate ST (IST) (see "Sinus tachycardia: Evaluation and management", section on 'Inappropriate sinus tachycardia') Sinoatrial nodal reentrant tachycardia (SANRT) ( waveform 8) (see "Sinoatrial nodal reentrant tachycardia (SANRT)") AT, usually originating near the sinus node (see "Focal atrial tachycardia", section on 'Electrocardiographic features') P wave morphology alone is not sufficient to distinguish these arrhythmias from one another. In persons with a P wave morphology that is consistent with origination from the sinus node, additional ECG features that assist in the diagnosis include: Atrial rate In ST and IST, the rate typically ranges from 100 to 180 bpm. Faster atrial rates suggest an AT. https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 13/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Onset/offset pattern ST and IST have smooth, gradual changes in rate. Both SANRT and AT have an abrupt onset and offset, although the rate in AT can vary significantly with autonomic tone. Relationship between atrial and ventricular activity In ST and IST, there is usually a 1:1 relationship between atrial and ventricular activity. The response to vagal maneuvers or adenosine With ST or IST, there is a gradual slowing of the atrial and ventricular rates, followed by a gradual resumption of the previous rate. In contrast, SNRT can terminate abruptly with these maneuvers. Abnormal P waves Any P wave that does not have the characteristics of a sinus P wave is considered an abnormal P wave. Abnormal P waves that are due to retrograde conduction from the ventricle to the atrium are a specific subset of abnormal P waves. (See 'Retrograde P waves' below.) Abnormal P waves that are not retrograde are most consistent with AT, although some patients with AVRT have abnormal P waves. Retrograde P waves P waves that are due to retrograde conduction from the ventricle to the atrium are a specific subset of abnormal P waves. These P waves have a characteristic morphology and suggest certain diagnoses, specifically: AVNRT AVRT Junctional ectopic tachycardia Nonparoxysmal junctional tachycardia The most common retrograde P wave morphology is associated with atrial activation that originates from the AV node and proceeds in an inferior-to-superior direction. Thus, the defining trait of a retrograde P wave is that it is negative in the inferior leads II, III, and aVF. Due to the central location of the AV node, atrial activation proceeds simultaneously leftward and rightward, so the P wave morphology in leads I, aVL, and aVR varies among patients, but it is often relatively narrow. In addition, because the AV node is posteriorly located, the activation is usually posterior-to-anterior, producing a narrow but positive P wave in lead V1. Retrograde P waves due to conduction via an accessory pathway can have a variety of morphologies, depending upon the site of the pathway. However, they are still usually negative in the inferior leads. (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis".) https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 14/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Because retrograde P waves are often associated with a short RP interval, they can blend with the terminal portion of the QRS. If a baseline ECG during sinus rhythm is available for comparison, a pseudo S wave in the inferior leads or a pseudo R' in V1 that is not present during sinus rhythm is often a retrograde P wave ( figure 3) [7,8,13]. (See 'RP relationship' below.) RP relationship In patients with a retrograde P wave, the temporal relationship between the P wave and the R wave divides narrow complex tachycardias into two categories: short RP and long RP tachycardias. The RP interval is defined as the interval from the onset of the QRS to the onset of the P wave. Short RP tachycardias tend to be paroxysmal, while long RP tachycardias can be paroxysmal or incessant. Short RP tachycardias If the RP interval is less than one-half of the RR interval, the tachycardia is considered a short RP tachycardia. The differential diagnosis of a short RP tachycardia is generated by considering the P wave morphology. Abnormal P wave The combination of abnormal P waves and a short RP interval is most often seen in the setting of an AT with AV nodal conduction delay. (See 'Abnormal P waves' above.) Retrograde P wave The combination of retrograde P waves and a short RP interval is typical of the "common" form of AVNRT and of AVRT utilizing an accessory pathway. (See 'Retrograde P waves' above.) In the "common" form of AVNRT (which accounts for 90 percent of AVNRT) [14], reentry occurs in the AV node and perinodal tissues. Antegrade conduction occurs down the slow pathway and retrograde conduction up the fast pathway ( figure 4 and figure 5). This slow-fast pattern gives rise to retrograde P waves that may be inapparent if obscured by the QRS complex ( figure 3). (See "Atrioventricular nodal reentrant tachycardia".) AVRT utilizing an accessory pathway can be either orthodromic or antidromic. Orthodromic AVRT is more common, and in this form of the arrhythmia, antegrade conduction occurs through the AV node, producing a narrow QRS complex, and retrograde conduction to the atrium occurs over an AV bypass tract ( figure 6). (See "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway".) In contrast, during antidromic AVRT, antegrade conduction occurs through the AV bypass tract and retrograde conduction occurs through the AV node or a second accessory pathway. This pattern of activation results in a wide QRS complex (thus, antidromic AVRT is not a narrow QRS complex tachycardia). (See "Wide QRS complex tachycardias: Approach to the diagnosis".) https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 15/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Long RP tachycardias If the RP interval is more than one-half of the RR interval, the tachycardia is considered a long RP tachycardia. As with short RP tachycardias, the differential diagnosis is generated by combining the PR relationship with the P wave morphology. Retrograde P waves The combination of retrograde P waves and a long RP interval is usually caused by either "atypical" AVNRT or by AVRT with a slowly conducting accessory pathway (also known as permanent junctional reciprocating tachycardia [PJRT]); this combination can also be seen in AT with a focus that is close to the AV node [7]. P waves are inverted in the inferior leads as the atria are depolarized from bottom to top. (See 'Retrograde P waves' above.) Abnormal P wave morphology The combination of abnormal P wave morphology and a long RP interval usually suggests some form of AT. However, this pattern can also occur in the atypical or uncommon form of AVNRT and in AVRT with a slowly conducting accessory pathway [7]. (See 'Abnormal P waves' above.) The atypical form of AVNRT, which accounts for 10 percent of AVNRT [14], is characterized by antegrade conduction down a fast pathway and retrograde conduction through a slow pathway. As a result, the P wave occurs very late in the cardiac cycle (positioning it near to the next QRS complex) ( figure 7). (See "Atrioventricular nodal reentrant tachycardia".) In AVRT with a slowly conducting accessory pathway, antegrade conduction probably occurs through the AV node, and retrograde conduction through a slowly conducting accessory pathway [1,13]. Because of slow conduction through the retrograde limb of the circuit, the retrograde P wave occurs late in the cardiac cycle. (See "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway".) Undetectable P waves If atrial activity is not evident despite the use of carotid sinus massage and/or adenosine to "unmask" atrial activity, the most common rhythm is AVNRT [7]. Other possible rhythms are AF, AVRT, and junctional tachycardia. Although AF is typically an irregularly irregular rhythm, when the ventricular rate is very rapid, it may appear to be more regular. Vagal maneuvers produce a transient decrease in the ventricular rate with AF, which may make the irregularity more evident. Junctional tachycardia is an arrhythmia arising from a discrete focus within the AV node or His bundle. In children, junctional tachycardia, also known as junctional ectopic tachycardia (JET), is usually associated with significant underlying heart disease. In adults, this rhythm, generally called nonparoxysmal junctional tachycardia (NPJT), is seen with acute myocardial infarction, https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 16/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate digitalis toxicity, and myocarditis. (See "Supraventricular arrhythmias after myocardial infarction".) Atrial activity during junctional tachycardia is variable. Retrograde atrial activation may occur, with a P wave that either follows each QRS complex or is concealed in the QRS complex. If retrograde conduction does not occur, independent atrial activity may be seen, with complete AV dissociation that must be distinguished from AV dissociation due to complete heart block (in complete heart block, the atrial rate exceeds the ventricular rate). Electrophysiologic testing In some cases, narrow QRS complex tachycardias cannot be discriminated from each other using noninvasive testing. An electrophysiologic study (EPS) can provide a definitive diagnosis but is only used when a definitive diagnosis will influence therapy. [13]. For some arrhythmias, EPS with ablation can also be curative. For these reasons, invasive EP testing to define the mechanism of SVT is rarely carried out as a standalone diagnostic procedure, but rather as a "prelude" to ablation. Diagnostic EP may be indicated to determine the mechanism of the arrhythmia in the following patients with a narrow QRS complex tachycardia: Those with severe symptoms such as syncope or presyncope in association with the arrhythmia, particularly if the resting ECG manifests the pattern of preexcitation with a delta wave ( waveform 9) or a short PR interval without a delta wave. Those with underlying organic heart disease who develop angina or acute HF during their arrhythmia, even if the rate is relatively slow. EPS and catheter ablation are discussed in greater detail elsewhere. (See "Invasive diagnostic cardiac electrophysiology studies" and "Overview of catheter ablation of cardiac arrhythmias", section on 'Introduction'.) Other cardiac testing In addition to close scrutiny of the available ECG data, patients with narrow QRS complex tachycardia should generally have a baseline echocardiogram to assess for any evidence of significant underlying structural heart disease [15]. In some patients, additional cardiac testing may be required to identify or characterize an arrhythmia; its use depends upon the particular arrhythmia and symptoms but may include one or more of the following tests: Ambulatory ECG monitoring (for patients without a definitive ECG-based diagnosis of their arrhythmia). Exercise stress testing (for patients with exercise-associated arrhythmias). https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 17/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Stress testing (exercise or pharmacologic) for underlying myocardial ischemia (for those with symptoms of angina and risk factors for coronary artery disease). SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Atrial fibrillation" and "Society guideline links: Arrhythmias in adults" and "Society guideline links: Supraventricular arrhythmias".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topic (see "Patient education: Supraventricular tachycardia (SVT) (The Basics)") SUMMARY AND RECOMMENDATIONS Definitions Tachycardias, defined as abnormal heart rhythms with a ventricular rate of 100 or more beats per minute (bpm), can present with either a narrow or wide QRS complex. A narrow QRS complex (<120 ms) reflects rapid activation of the ventricles via the normal His-Purkinje system, which in turn suggests that the arrhythmia originates above or within the His bundle (ie, a supraventricular tachycardia). The site of origin may be in the sinus node, the atria, the atrioventricular (AV) node, the His bundle, or some combination of these sites. (See 'Introduction' above and 'Definitions' above.) https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 18/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Clinical manifestations Most commonly, patients with a narrow QRS complex tachycardia present with palpitations, usually abrupt in onset. Other presenting symptoms may include syncope or presyncope, lightheadedness, dizziness, diaphoresis, chest pain, or shortness of breath. (See 'Clinical manifestations' above.) Diagnosis The diagnosis of a narrow QRS complex tachycardia requires only a surface ECG that shows a heart rate greater than 100 bpm along with narrow QRS complexes that are less than 120 ms in duration. (See 'Diagnosis' above.) Types of narrow QRS complex tachycardia The differential diagnosis of narrow QRS complex tachycardias is broad ( table 1), including atrial fibrillation (AF), atrial flutter, sinus tachycardia (ST), and a variety of paroxysmal supraventricular tachycardias. (See 'Types of narrow QRS complex tachycardia' above.) Evaluation Evaluation of a patient with a narrow QRS complex tachycardia involves two primary components: assessment of the patient for symptoms and signs of hemodynamic stability (or instability), and assessment of the patient's ECG for clues to the type of tachycardia present. (See 'Evaluation' above.) Unstable patients If a patient has clinically significant hemodynamic instability and the rhythm is not ST, or if there is any doubt that the rhythm is sinus tachycardia, urgent conversion to sinus rhythm is recommended ( algorithm 1). If it is certain that the patient's rhythm is ST, and clinically significant cardiac symptoms are present, management should be focused on the underlying cardiac disorder and on treating any contributing cause of the rapid heart rate (such as myocardial ischemia due to coronary heart disease, respiratory or cardiac failure, hypovolemia, anemia, fever, pain, or anxiety). Stable patients If the patient is not experiencing hemodynamic instability, a nonemergency approach to the diagnosis of the patient's rhythm can be undertaken ( algorithm 2). Approach to identifying the type of SVT Following the determination of hemodynamic stability, the next steps in the assessment of a narrow QRS complex tachycardia include: Determine if the rhythm appears to be regular or irregular. (See 'Assessing the ECG for regularity of the rhythm' above.) https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 19/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Determine the atrial activity by identifying and characterizing the atrial rate, P-wave morphology, RP relationship, and AV relationship. (See 'Atrial rate' above and 'P wave morphology' above and 'RP relationship' above.) Role of electrophysiologic testing In some cases, narrow QRS complex tachycardias cannot be discriminated from each other using noninvasive testing. An electrophysiologic study (EPS) can provide a definitive diagnosis but is only used when a definitive diagnosis will influence therapy. (See 'Electrophysiologic testing' above.) Other cardiac testing In some patients, additional cardiac testing may be required to identify or characterize an arrhythmia; its use depends upon the particular arrhythmia and symptoms. (See 'Other cardiac testing' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Ganz LI, Friedman PL. Supraventricular tachycardia. N Engl J Med 1995; 332:162. 2. Katritsis DG, Josephson ME. Differential diagnosis of regular, narrow-QRS tachycardias. Heart Rhythm 2015; 12:1667. 3. Khurshid S, Choi SH, Weng LC, et al. Frequency of Cardiac Rhythm Abnormalities in a Half Million Adults. Circ Arrhythm Electrophysiol 2018; 11:e006273. 4. Ferguson JD, DiMarco JP. Contemporary management of paroxysmal supraventricular tachycardia. Circulation 2003; 107:1096. 5. Trohman RG. Supraventricular tachycardia: implications for the intensivist. Crit Care Med 2000; 28:N129. 6. Knight BP, Ebinger M, Oral H, et al. Diagnostic value of tachycardia features and pacing maneuvers during paroxysmal supraventricular tachycardia. J Am Coll Cardiol 2000; 36:574. 7. Blomstr m-Lundqvist C, Scheinman MM, Aliot EM, et al. ACC/AHA/ESC guidelines for the management of patients with supraventricular arrhythmias executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Supraventricular Arrhythmias). Circulation 2003; 108:1871. 8. Kalbfleisch SJ, el-Atassi R, Calkins H, et al. Differentiation of paroxysmal narrow QRS complex tachycardias using the 12-lead electrocardiogram. J Am Coll Cardiol 1993; 21:85. https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 20/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate 9. Accardi AJ, Miller R, Holmes JF. Enhanced diagnosis of narrow complex tachycardias with increased electrocardiograph speed. J Emerg Med 2002; 22:123. 10. Link MS. Clinical practice. Evaluation and initial treatment of supraventricular tachycardia. N Engl J Med 2012; 367:1438. 11. Smith GD, Dyson K, Taylor D, et al. Effectiveness of the Valsalva Manoeuvre for reversion of supraventricular tachycardia. Cochrane Database Syst Rev 2013; :CD009502. 12. Ellenbogen KA, Thames MD, DiMarco JP, et al. Electrophysiological effects of adenosine in the transplanted human heart. Evidence of supersensitivity. Circulation 1990; 81:821. 13. Chauhan VS, Krahn AD, Klein GJ, et al. Supraventricular tachycardia. Med Clin North Am 2001; 85:193. 14. Akhtar M, Jazayeri MR, Sra J, et al. Atrioventricular nodal reentry. Clinical, electrophysiological, and therapeutic considerations. Circulation 1993; 88:282. 15. Brugada J, Katritsis DG, Arbelo E, et al. 2019 ESC Guidelines for the management of patients with supraventricular tachycardiaThe Task Force for the management of patients with supraventricular tachycardia of the European Society of Cardiology (ESC). Eur Heart J 2020; 41:655. Topic 943 Version 36.0 https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 21/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate GRAPHICS Classification of narrow QRS complex tachycardias by structures required for initiation and maintenance Atrial tissue only AV junction Sinus tachycardia AV nodal reentrant tachycardia (AVNRT) Inappropriate sinus tachycardia Atrioventricular reentrant tachycardia (AVRT) Sinoatrial nodal reentrant tachycardia (SANRT) Junctional tachycardia Intraatrial reentrant tachycardia (IART) Junctional ectopic tachycardia in children Atrial tachycardia Nonparoxysmal junctional tachycardia in adults Multifocal atrial tachycardia Atrial fibrillation Atrial flutter Graphic 58019 Version 2.0 https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 22/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Sites of reentry in supraventricular tachyarrhythmias Reentry may occur around a fixed anatomic obstacle or may be functional, developing in the absence of an anatomic obstacle and resulting from the intrinsic heterogeneity of electrophysiologic properties of the myocardial tissue. Reentrant circuits leading to a supraventricular tachyarrhythmia may develop in various parts of the heart: within and around the sinoatrial node (sinus node reentry); within the atrial myocardium (atrial tachycardia, atrial flutter, or atrial fibrillation); within the atrioventricular (AV) node due to the presence of a slow and fast pathway (atrioventricular nodal reentrant tachycardia); or involving the AV node and an accessory pathway (AP) (atrioventricular reentrant tachycardia). LAF: left anterior fascicle; LPF: left posterior fascicle. Graphic 82249 Version 4.0 https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 23/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Mechanisms of reentry in cardiac arrhythmias Schematic representation of possible reentrant circuits. The thick black arrow represents the circulating impulse; thin black lines represent advancing wavefronts in completely refractory tissue; speckled areas are partially refractory tissue; white areas are fully excitable tissue. A is the original model of circus movement around a fixed obstacle. There is a fully excitable gap, and the length and location of the circuit are fixed. B represents circus movement around 2 fixed anatomic obstacles. A fully excitable gap is present. C represents rapidly conducting bundles forming closed loops that serve as preferential circuits through which the impulse may travel. D is the leading circle type of reentry which does not require an anatomic obstacle. Instead, the impulse propagates around a functionally refractory core and among neighboring fibers that have different electrophysiologic properties. Since the refractoriness of the core is variable, the circuit size changes but will be the smallest possible circuit that can continue to propagate an impulse. Functional circuits tend to be small, rapid, and unstable. E represents reentry around a fixed anatomic obstacle, but a fully excitable gap is absent. F demonstrates an area of slowed conduction (hatched lines) between anatomic boundaries, while in G all areas of slowed conduction neighbor an anatomic obstacle. H represents anisotropic reentry. There are differences in the conduction of a single impulse in various fibers as a result of differences in their orientation. https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 24/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Courtesy of Philip J Podrid, MD, FACC. Graphic 52134 Version 5.0 https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 25/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Algorithm for the evaluation of narrow QRS complex tachycardias in unstable patients IV: intravenous. Graphic 109811 Version 2.0 https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 26/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Algorithm for the evaluation of narrow QRS complex tachycardias in stable pati AVNRT: atrioventricular nodal reentrant tachycardia; AVRT: atrioventricular reentrant tachycardia (due to an a electrocardiogram; SANRT: sinoatrial nodal reentrant tachycardia. Graphic 76920 Version 3.0 https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 27/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Single-lead electrocardiogram (ECG) showing atrial fibrillation Lead V1 showing coarse AF with moderate ventricular response. The two characteristic findings in AF are present: the very rapid atrial fibrillatory waves (f waves), which are variable in appearance; and the irregularly irregular ventricular response as the R-R interval between beats is unpredictable. Coarse AF may appear similar to atrial flutter. However, the variable height and duration of the f waves differentiate them from atrial flutter (F) waves, which are identical in appearance and occur at a constant rate of about 250 to 350 beats/min. AF: atrial fibrillation. Courtesy of Ary Goldberger, MD. Graphic 73958 Version 6.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 28/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Single-lead electrocardiogram (ECG) showing atrial fibrillation with minimally apparent atrial activity F waves are not apparent in this lead, as the only finding suggestive of AF is the irregularly irrregular ventricular response. AF: atrial fibrillation. Courtesy of Morton Arnsdorf, MD. Graphic 53988 Version 4.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 29/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Electrocardiogram single-lead multifocal atrial tachycardia Clinical features: Elderly patients Decompensation of pulmonary disease Postoperative Arrhythmia usually does not cause severe hemodynamic compromise High mortality ECG features: P waves have 3 forms Atrial rate is usually 100 to 200 bpm Atrial rate is irregular PR interval varies Isoelectric baseline between P waves May progress to atrial fibrillation ECG: electrocardiogram; bpm: beats per minute. Courtesy of Alfred Buxton, MD. Graphic 127222 Version 1.0 https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 30/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Approach to adenosine dosing in stable adults with suspected supraventricular tachyarrhythmia This figure summarizes the initial dosing, administration, and need for repeat dosing of adenosine in a hemo stable adult with suspected AV node-dependent SVT. Adenosine can be used as a diagnostic aid to identify th rhythm or as a therapy to terminate SVTs that rely on AV node conduction. AV node-dependent SVTs include A reentrant tachycardia (AVNRT) and AV reentrant (or reciprocating) tachycardia (AVRT). The management of su node-dependent SVT in hemodynamically stable adults commonly starts with a trial of 1 or more vagal mane proceeding to adenosine therapy. If the patient has hemodynamically unstable SVT, cardioversion is indicate UpToDate content for details on management of SVTs. https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 31/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate AV: atrioventricular; SVT: supraventricular tachycardia; IV: intravenous; ACC: American College of Cardiology; American Heart Association; HRS: Heart Rhythm Society; ECG: electrocardiogram. Lower adenosine doses are indicated in certain clinical settings. If central venous administration is perform adenosine dose is 3 mg; if needed (SVT persists and there is no AV block), the dose may be increased to 6 mg mg for subsequent doses. For heart transplant recipients, the initial adenosine dose is 1 mg; if needed (SVT p there is no AV block), the dose may be increased to 2 mg and then 3 mg for subsequent doses. An 18 mg dose is more likely to be required to produce AV block in patients with a body weight >70 kg, par [1] those weighing >110 kg. When a third dose is indicated, an alternative approach is to administer 12 mg (in mg) as described in the 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients with Supraventr Tachycardia. [2] SVT termination in response to adenosine includes SVT termination closely followed by SVT recurrence. Refer to UpToDate content on treatment of SVT for dosing of second-line AV nodal blockers. If the SVT pers second-line AV nodal blocker therapy, electrical cardioversion is performed, as discussed in UpToDate conten treatment of SVT. SVTs that are not AV node dependent include atrial flutter, atrial fibrillation, and atrial tachycardia. When AV is induced by adenosine, the ECG may reveal atrial activity diagnostic of these rhythms. References: 1. Prabhu S, Mackin V, McLellan AJA, et al. Determining the optimal dose of adenosine for unmasking dormant pulmonary vein co following atrial brillation ablation: Electrophysiological and hemodynamic assessment. DORMANT-AF study. J Cardiovasc Electr 28:13. 2. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Hea Society. Circulation 2016; 133:e506. Graphic 141417 Version 3.0 https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 32/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Atrial flutter at a rate of 250 beats/minute with 2:1 AV conduction in the presence of left bundle branch block Although every other flutter wave can be seen at the end of the T wave in the first part of the tracing (arrows), a sinus mechanism cannot be excluded. The flutter waves become clearly apparent after carotid sinus massage is applied to slow conduction through the AV node, thereby increasing the degree of AV block. AV: atrioventricular Courtesy of Morton Arnsdorf, MD. Graphic 76876 Version 3.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 33/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Single-lead electrocardiogram showing atrial flutter The atrial rate in this tracing of atrial waves is 300 beats per minute, and the flutter waves, which are "saw toothed," are uniform in morphology, amplitude, and cycle length. Impulse conduction to the ventricles is dependent upon the electrophysiologic characteristics of the atrioventricular node. Most commonly, every other atrial impulse is conducted and there is 2:1 block. However, when conduction through the atrioventricular node is impaired as a result of underlying disease, drugs, or increased vagal tone, there may be higher degrees of block, which may be variable, resulting in a regularly irregular ventricular rate. Graphic 82303 Version 6.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 34/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Electrocardiogram in atypical atrial flutter There are three findings that distinguish this arrhythmia from typical atrial flutter: the flutter rate is faster at 375 beats/minute; there is no isoelectric interval between the flutter waves; and there is more apparent positivity in leads II, III, and avF. The high degree of AV block is due to digoxin and some underlying AV nodal disease. Courtesy of Morton Arnsdorf, MD. Graphic 68846 Version 3.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 35/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Electrocardiogram (ECG) showing sinus tachycardia at a rate of 150 beats/min Note the difficulty in separating the P waves from the T waves in the standard leads. The P waves are most evident in lead V1 (arrow) where the terminal negativity suggests left atrial enlargement. Courtesy of Morton Arnsdorf, MD. Graphic 78938 Version 3.0 https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 36/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Single-lead electrocardiogram (ECG) showing sinoatrial (SA) nodal reentrant tachycardia Electrocardiogram showing SA nodal reentrant tachycardia. The first three beats are normal sinus beats at a rate of about 107 beats/min; the fourth beat is an atrial premature beat that is followed by a return to sinus rhythm. The eighth beat (arrow) represents the sudden onset of SA nodal reentrant tachycardia at a rate of about 145 beats/min. Since the P waves are similar to the sinus beats, the diagnosis is suggested only by the abrupt onset of the tachycardia. Courtesy of Morton F Arnsdorf, MD. Graphic 76364 Version 5.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 37/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Typical atrioventricular nodal reentrant tachycardia The first two complexes are normal sinus beats with a normal P wave followed by a QRS complex. The third complex, an atrial premature beat (APB), has a prolonged PR interval; it initiates a common or typical atrioventricular nodal reentrant tachycardia (AVNRT) in which antegrade conduction to the ventricle is via the slow pathway and

proceeding to adenosine therapy. If the patient has hemodynamically unstable SVT, cardioversion is indicate UpToDate content for details on management of SVTs. https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 31/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate AV: atrioventricular; SVT: supraventricular tachycardia; IV: intravenous; ACC: American College of Cardiology; American Heart Association; HRS: Heart Rhythm Society; ECG: electrocardiogram. Lower adenosine doses are indicated in certain clinical settings. If central venous administration is perform adenosine dose is 3 mg; if needed (SVT persists and there is no AV block), the dose may be increased to 6 mg mg for subsequent doses. For heart transplant recipients, the initial adenosine dose is 1 mg; if needed (SVT p there is no AV block), the dose may be increased to 2 mg and then 3 mg for subsequent doses. An 18 mg dose is more likely to be required to produce AV block in patients with a body weight >70 kg, par [1] those weighing >110 kg. When a third dose is indicated, an alternative approach is to administer 12 mg (in mg) as described in the 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients with Supraventr Tachycardia. [2] SVT termination in response to adenosine includes SVT termination closely followed by SVT recurrence. Refer to UpToDate content on treatment of SVT for dosing of second-line AV nodal blockers. If the SVT pers second-line AV nodal blocker therapy, electrical cardioversion is performed, as discussed in UpToDate conten treatment of SVT. SVTs that are not AV node dependent include atrial flutter, atrial fibrillation, and atrial tachycardia. When AV is induced by adenosine, the ECG may reveal atrial activity diagnostic of these rhythms. References: 1. Prabhu S, Mackin V, McLellan AJA, et al. Determining the optimal dose of adenosine for unmasking dormant pulmonary vein co following atrial brillation ablation: Electrophysiological and hemodynamic assessment. DORMANT-AF study. J Cardiovasc Electr 28:13. 2. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Hea Society. Circulation 2016; 133:e506. Graphic 141417 Version 3.0 https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 32/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Atrial flutter at a rate of 250 beats/minute with 2:1 AV conduction in the presence of left bundle branch block Although every other flutter wave can be seen at the end of the T wave in the first part of the tracing (arrows), a sinus mechanism cannot be excluded. The flutter waves become clearly apparent after carotid sinus massage is applied to slow conduction through the AV node, thereby increasing the degree of AV block. AV: atrioventricular Courtesy of Morton Arnsdorf, MD. Graphic 76876 Version 3.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 33/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Single-lead electrocardiogram showing atrial flutter The atrial rate in this tracing of atrial waves is 300 beats per minute, and the flutter waves, which are "saw toothed," are uniform in morphology, amplitude, and cycle length. Impulse conduction to the ventricles is dependent upon the electrophysiologic characteristics of the atrioventricular node. Most commonly, every other atrial impulse is conducted and there is 2:1 block. However, when conduction through the atrioventricular node is impaired as a result of underlying disease, drugs, or increased vagal tone, there may be higher degrees of block, which may be variable, resulting in a regularly irregular ventricular rate. Graphic 82303 Version 6.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 34/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Electrocardiogram in atypical atrial flutter There are three findings that distinguish this arrhythmia from typical atrial flutter: the flutter rate is faster at 375 beats/minute; there is no isoelectric interval between the flutter waves; and there is more apparent positivity in leads II, III, and avF. The high degree of AV block is due to digoxin and some underlying AV nodal disease. Courtesy of Morton Arnsdorf, MD. Graphic 68846 Version 3.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 35/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Electrocardiogram (ECG) showing sinus tachycardia at a rate of 150 beats/min Note the difficulty in separating the P waves from the T waves in the standard leads. The P waves are most evident in lead V1 (arrow) where the terminal negativity suggests left atrial enlargement. Courtesy of Morton Arnsdorf, MD. Graphic 78938 Version 3.0 https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 36/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Single-lead electrocardiogram (ECG) showing sinoatrial (SA) nodal reentrant tachycardia Electrocardiogram showing SA nodal reentrant tachycardia. The first three beats are normal sinus beats at a rate of about 107 beats/min; the fourth beat is an atrial premature beat that is followed by a return to sinus rhythm. The eighth beat (arrow) represents the sudden onset of SA nodal reentrant tachycardia at a rate of about 145 beats/min. Since the P waves are similar to the sinus beats, the diagnosis is suggested only by the abrupt onset of the tachycardia. Courtesy of Morton F Arnsdorf, MD. Graphic 76364 Version 5.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 37/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Typical atrioventricular nodal reentrant tachycardia The first two complexes are normal sinus beats with a normal P wave followed by a QRS complex. The third complex, an atrial premature beat (APB), has a prolonged PR interval; it initiates a common or typical atrioventricular nodal reentrant tachycardia (AVNRT) in which antegrade conduction to the ventricle is via the slow pathway and retrograde atrial activation is by the fast pathway. Although no distinct P wave is seen, the QRS complex has a small terminal deflection, known as a pseudo r', which is the P wave superimposed upon the terminal portion of the QRS complex. Graphic 54290 Version 3.0 https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 38/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Slow-fast form of atrioventricular nodal reentrant tachycardia (AVNRT) Representation of dual pathway physiology involving the atrioventricular (AV) node and perinodal atrial tissue in the common form of AVNRT. Left panel: A normal sinus beat (A ) is conducted through the fast pathway (F) to the final common pathway (fcp) in the AV node and into the Bundle of His. The conduction through the slow pathway (S) runs into the refractory period of the impulse through the fast pathway and is extinguished. 1 Middle panel: A critically timed atrial premature beat (A ) finds the fast pathway refractory in the antegrade direction but is able to conduct antegrade through the slow pathway, which has a shorter refractory period. If excitability in the fast pathway has recovered by 2 the time the impulse reaches the fcp, there may be retrograde activation of the fast pathway. Right panel: The retrograde impulse throws off an echo to the atrium (A*), and, if the slow pathway has recovered its excitability, the impulse reenters the slow pathway and produces ventricular depolarization (V*). If the mechanism persists, a repetitive circuit is established that creates a sustained reentrant tachycardia. The sequence of antegrade (S) and retrograde (F) conduction is called the slow-fast form of AVNRT. Graphic 79760 Version 6.0 https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 39/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Generation of ECG in common form of atrioventricular nodal reentrant tachycardia (AVNRT) Ladder diagram of the common (slow-fast) form of AVNRT showing transmission of the impulse in atrial, atrioventricular (AV) nodal, and ventricular tissue and the resultant ECG. The first two cycles show the normal sinus beat (A ) conducting through the fast pathway (F) to the ventricle (V ) with the impulse blocked in the slow pathway. The premature atrial beat (A on ladder diagram, P on ECG) is timed critically; it finds the fast pathway refractory but is able to conduct through slow pathway, resulting in a long PR interval, and a ventricular depolarization (V ). It is also able to reenter and conduct 1 1 2 2 retrogradely up the now recovered fast pathway, resulting in an inverted P wave (A*) that is buried in the QRS complex. This atrial echo beat (A*) then reenters the now recovered slow pathway, which conducts anterogradely and results in ventricular depolarization (V*). The cycle repeats, and AV nodal reentry is established. ECG: electrocardiogram. Graphic 50122 Version 6.0 https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 40/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Orthodromic atrioventricular reentrant tachycardia (AVRT) in the setting of an accessory AV pathway The rhythm strip shows a sinus (S) beat that has a short PR interval and a wide QRS complex as a result of a delta wave (d). Panel A shows an atrial premature beat (APB,*) that is blocked in the accessory pathway (AP), which has a long refractory period but is conducted antegradely through the atrioventricular node (N) and the His-Purkinje system, resulting in a normal PR interval and a narrow and normal QRS complex, as seen on the rhythm strip. After normal myocardial activation, the impulse is conducted retrogradely along the AP, activating the atrium in a retrograde fashion (panel B), which results in a negative P wave. If this activation sequence repeats itself (panel C), an orthodromic atrioventricular reentrant (or reciprocating) tachycardia (AVRT) is established. Graphic 71302 Version 7.0 https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 41/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Uncommon fast-slow variant of atrioventricular nodal reentrant tachycardia (AVNRT) Diagrammatic representation in the circuit (left panel) and the ladder diagram (right panel) of the uncommon form of AVNRT (fast-slow variant). Antegrade conduction is through the fast (F) pathway and retrograde conduction is through the slow (S) pathway. Because of slow retrograde activation of the atrium, the P wave occurs after the QRS complex with a long RP interval and relatively short PR interval before the next QRS complex. ECG: electrocardiogram. Graphic 56806 Version 4.0 https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 42/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate ECG in Wolff-Parkinson-White The 12-lead ECG shows the typical features of Wolff-Parkinson-White; the PR interval is short (*) and the QRS duration prolonged as a result of a delta wave (arrow), indicating ventricular preexcitation. Courtesy of Martin Burke, DO. Graphic 67181 Version 3.0 Normal ECG https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 43/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Normal electrocardiogram showing normal sinus rhythm at a rate of 75 beats/minute, a PR interval of 0.14 seconds, a QRS interval of 0.10 seconds, and a QRS axis of approximately 75 . Courtesy of Ary Goldberger, MD. Graphic 76183 Version 4.0 https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 44/45 7/5/23, 10:40 AM Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation - UpToDate Contributor Disclosures Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Ary L Goldberger, MD Other Financial Interest: Elsevier book royalties [Clinical electrocardiography]. All of the relevant financial relationships listed have been mitigated. James Hoekstra, MD No relevant financial relationship(s) with ineligible companies to disclose. Todd F Dardas, MD, MS No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/narrow-qrs-complex-tachycardias-clinical-manifestations-diagnosis-and-evaluation/print 45/45

7/5/23, 10:40 AM Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation : Alfred Buxton, MD : N A Mark Estes, III, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Feb 06, 2023. INTRODUCTION Sustained monomorphic ventricular tachycardia (SMVT) is defined by the following characteristics: A regular (<50 msec beat-to-beat cycle length variation) wide QRS complex ( 120 milliseconds) tachycardia at a rate greater than 100 beats per minute The consecutive beats have a uniform and stable QRS morphology The arrhythmia lasts 30 seconds or causes hemodynamic collapse in <30 seconds In patients with coronary heart disease (CHD) or other structural heart disease, a wide QRS complex tachycardia (WCT) should be considered to be ventricular tachycardia until proven otherwise. (See "Wide QRS complex tachycardias: Approach to the diagnosis".) This topic will focus on the clinical presentation, diagnosis, and evaluation of SMVT. The approach to treatment of SMVT, the approach to patients with monomorphic VT and no apparent heart disease, and the management of non-sustained VT are discussed separately. (See "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis" and "Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features" and "Nonsustained ventricular tachycardia: Clinical manifestations, evaluation, and management" and "Ventricular tachycardia in the absence of apparent structural heart disease".) https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-clinical-manifestations-diagnosis-and-evaluation/print 1/22 7/5/23, 10:40 AM Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation - UpToDate EPIDEMIOLOGY AND RISK FACTORS Cardiovascular disease (CVD) is common in the general population, affecting the majority of adults past the age of 60 years. In 2012 and 2013, CVD was estimated to result in 17.3 million deaths worldwide on an annual basis [1,2]. Many patients who die from CVD experience unexpected sudden cardiac death (SCD), with more than 50 percent of SCD episodes occurring as a first event in persons thought to be at low risk [3]. Along with ventricular fibrillation, SMVT is responsible for nearly all of the arrhythmic SCD, although ventricular arrhythmias are fairly uncommon in the general population populations. Among a prospective cohort of more than half a million United Kingdom residents, the prevalence of ventricular arrhythmias (which included ventricular premature beats, as well as ventricular tachycardia [VT] and ventricular fibrillation [VF]) was approximately 12 per 10,000 persons under age 55 and increased to between 20 (females) and 59 (males) per 10,000 persons 65 years of age [4]. These data are most likely weight toward VPBs rather than VT or VF in this cross-sectional community population. (See "Overview of sudden cardiac arrest and sudden cardiac death" and "Overview of established risk factors for cardiovascular disease".) SMVT may be idiopathic but occurs most frequently in patients with underlying heart disease of various types including: Coronary heart disease (CHD), especially with prior myocardial infarction Dilated cardiomyopathy Infiltrative cardiomyopathy Chagas heart disease Complex congenital heart disease Cardiac sarcoidosis Arrhythmogenic right ventricular cardiomyopathy Left ventricular noncompaction CHD is responsible for the majority of cases of SMVT. Approximately 70 percent of the cases of SCD in the United States are due to CHD, resulting in hundreds of thousands of deaths. However, SCD can result from VT that occurs in the absence of known heart disease. Monomorphic VT occurring in the absence of apparent structural heart disease is discussed in detail separately. (See "Ventricular tachycardia in the absence of apparent structural heart disease".) Drugs Flecainide and encainide have been associated with ventricular proarrhythmia in patients with prior infarct. By extension, propafenone is usually not recommended in this setting. Antiarrhythmic drugs in general can lead to more frequent (and at times incessant, albeit slower) SMVT. Inotropes, sympathomimetic agents, and other stimulants have been https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-clinical-manifestations-diagnosis-and-evaluation/print 2/22 7/5/23, 10:40 AM Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation - UpToDate associated with SMVT. A number of other agents have been implicated in SMVT but at very low frequencies. A 2020 scientific statement from the American Heart Association details drugs associated with SMVT [5]. CLINICAL MANIFESTATIONS AND ECG FINDINGS The history, physical examination, and 12-lead electrocardiogram (ECG) during SMVT and in sinus rhythm can all provide information to help confirm the diagnosis of SMVT. Because time may not allow for extensive questioning or examination, identifying a history of coronary heart disease (CHD) or other structural heart disease is the most important piece of historical information, along with obtaining an accurate list of medications and potential intoxicants (eg, flecainide, digoxin, etc) to identify any potential triggers for SMVT. (See "Wide QRS complex tachycardias: Approach to the diagnosis".) History and associated symptoms The clinical presentation of SMVT is highly variable, ranging from sudden cardiac arrest to mild symptoms. Although most patients with SMVT experience symptoms, in the occasional patient, symptoms may be minimal. Most patients with SMVT will have a history of underlying structural heart disease (eg, CHD, heart failure, hypertrophic cardiomyopathy, congenital heart disease, etc), although SMVT can also be seen in patients without known structural heart disease. Although SMVT is most commonly related to the development of reentrant circuits that follow healing of a prior myocardial infarction (MI), patients with prior MI may also develop SMVT due to non-reentrant mechanisms. (See "Ventricular tachycardia in the absence of apparent structural heart disease".) In the most severe instances, when SMVT significantly impairs cardiac output and results in immediate hemodynamic collapse, patients may briefly experience the onset of symptoms prior to the abrupt loss of consciousness and sudden cardiac arrest. Patients with faster ventricular rates, underlying heart disease, and decompensated heart failure with reduced left ventricular systolic function are more likely to develop hemodynamic instability. In such cases, prompt defibrillation and resuscitation to restore a perfusing heart rhythm is required. (See "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis", section on 'Unstable patients'.) For patients without immediate sudden cardiac arrest, the type and intensity of symptoms will vary depending upon the rate and duration of SMVT along with the presence or absence of significant comorbid conditions. Patients with SMVT typically present with one or more of the following symptoms: Shortness of breath/dyspnea https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-clinical-manifestations-diagnosis-and-evaluation/print 3/22 7/5/23, 10:40 AM Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation - UpToDate Chest discomfort Palpitations Syncope or presyncope General malaise Most commonly, symptomatic patients will report chest discomfort and/or shortness of breath. Palpitations are less common during VT in persons with significant ventricular dysfunction because the heart does not contract with enough vigor to cause palpitations. If the associated rate of SMVT is rapid enough to result in hemodynamic compromise, patients may experience presyncope or even syncope and further deterioration into cardiac arrest. On occasion, patients may experience syncope at the onset of SMVT and then recover consciousness while remaining in VT. The patient's medication list should be reviewed carefully, with special attention for rate- controlling drugs and antiarrhythmic drugs, to assess potential proarrhythmic effects and to guide therapy. QT-prolonging drugs, however, typically cause torsades de pointes (ie, polymorphic VT). (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes".) Physical examination Few physical examination findings in patients with SMVT are unique and specific. By definition, patients will have a pulse exceeding 100 beats per minute during the episode. In addition, if the physical examination is performed while SMVT persists, this can reveal evidence of atrioventricular (AV) dissociation, although it is not always easy to detect [6]. During AV dissociation, the normal coordination of atrial and ventricular contraction is lost, which may produce characteristic physical examination findings including (see "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'AV dissociation'): Marked fluctuations in the blood pressure because of the variability in the degree of left atrial contribution to left ventricular filling, stroke volume, and cardiac output. Variability in the occurrence and intensity of heart sounds, especially S1, which is heard more frequently when the rate of the tachycardia is slower. Cannon "A" waves Cannon A waves are intermittent and irregular jugular venous pulsations of greater amplitude than normal waves. They reflect simultaneous atrial and ventricular activation, resulting in contraction of the right atrium against a closed tricuspid valve. Prominent A waves can also be seen during some SVTs. Such prominent waves result from simultaneous atrial and ventricular contraction occurring with every beat. (See "Examination of the jugular venous pulse".) Electrocardiogram In patients with sudden cardiac arrest or hemodynamically unstable SMVT, often the only ECG available is a single-lead assessment from the telemetry monitor or defibrillator showing a wide QRS complex tachycardia (WCT); in such instances, a full 12-lead ECG https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-clinical-manifestations-diagnosis-and-evaluation/print 4/22 7/5/23, 10:40 AM Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation - UpToDate is not typically obtained until the patient has been stabilized. However, for patients with suspected SMVT who are hemodynamically stable, a 12-lead ECG should be performed as this provides the maximal ECG information for making an accurate diagnosis and determining a possible etiology and may help to direct future therapy. If available, a previous ECG when the patient was in normal sinus rhythm is very helpful for comparison. For example, if a patient with underlying bundle branch block develops wide QRS complex tachycardia with a bundle branch block pattern opposite to the baseline bundle branch block (ie, a left bundle branch block pattern in a patient with right bundle branch block during NSR), the tachycardia is very likely to be VT, not SVT with aberrant conduction. SMVT typically generates a WCT, usually with a QRS width >0.12 seconds ( waveform 1). WCT occurring in patients with prior MI is almost always SMVT. In rare instances, SMVT may present as a relatively narrow complex tachycardia ( algorithm 1). Such an arrhythmia may be incorrectly diagnosed and treated as a supraventricular tachycardia [7]. Although uncommon, a QRS complex that is narrower during tachycardia than during sinus rhythm (usually in patients with chronic bundle branch block or intraventricular conduction delay during sinus rhythm) is diagnostic of SMVT. (See "Ventricular tachycardia in the absence of apparent structural heart disease", section on 'Idiopathic left ventricular tachycardia'.) A detailed discussion of the ECG characteristics of SMVT is found elsewhere (see "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'Evaluation of the electrocardiogram'). Summarized briefly: The ECG hallmark for the diagnosis of SMVT is a wide complex tachycardia with the obvious presence of AV dissociation ( waveform 2). If not obvious, AV dissociation is suggested by the presence of fusion complexes (which reflect a supraventricular impulse coming from above the AV node fusing with an impulse generated in the ventricle) or sinus capture complexes (which reflect an impulse coming from above the AV node that depolarizes the ventricles when they are no longer refractory but before the next VT-generated complex). The occurrence of persistent or intermittent retrograde block is virtually diagnostic of SMVT. However, up to 40 percent of patients have intact ventriculoatrial (VA) conduction during SMVT, and AV dissociation is not seen ( waveform 3) [8]. VA conduction may occur in a 1:1 pattern or with second-degree VA block (eg, 2:1 or 3:1). Variability in the ST and T waves may be present, reflecting superimposed P waves as well as changes in ventricular repolarization. The tachycardia rate is usually constant but may warm up at start and may exhibit some subtle variability. https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-clinical-manifestations-diagnosis-and-evaluation/print 5/22 7/5/23, 10:40 AM Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation - UpToDate While concordance, or the presence of monophasic QRS complexes with the same polarity in leads V1 through V6, has been reported to have a specificity of greater than 90 percent for VT, positive concordance can also be present in preexcited tachyarrhythmias, specifically antidromic reciprocating tachycardia, which occur less frequently than VT [9]. Negative concordance is rarely seen but is consistent with VT. The specific QRS morphology, particularly when a shift in QRS axis occurs during WCT, may be helpful. Given the number of exceptions and the need to establish the correct diagnosis, ECG criteria may only be suggestive of SMVT. Confirmation sometimes requires other means, such as intracardiac ECGs from an implantable cardioverter-defibrillator (ICD) or pacemaker or invasive electrophysiologic testing. If a patient with sustained tachycardia has an ICD or pacemaker, interrogation and review of intracardiac electrograms are often diagnostic. DIAGNOSIS The diagnosis of SMVT should be suspected in a patient who presents with either sudden cardiac arrest, syncope, or sustained palpitations, particularly in a patient with a known history of structural heart disease. The diagnosis of SMVT is typically confirmed following review of an ECG, acquired during the arrhythmia, showing a wide QRS complex tachycardia with the presence of AV dissociation (manifest as an atrial rate slower than the ventricular rate). Frequently, however, it is not possible to identify P waves and the atrial rate amongst the wide QRS complexes, so other evidence of AV dissociation (ie, fusion and capture beats) is helpful in confirming the diagnosis of VT. Additional ECG features (eg, QRS axis, concordance, QRS morphology, etc) can provide additional supportive evidence for a diagnosis of VT versus supraventricular tachycardia ( table 1). (See "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'Evaluation of the electrocardiogram'.) DIFFERENTIAL DIAGNOSIS The differential diagnosis for a wide QRS complex tachycardia (WCT) includes SMVT, supraventricular tachycardia with aberrant conduction (either preexistent or rate-related), supraventricular tachycardia with preexcitation, and tachycardia with ventricular pacing ( algorithm 1). Differentiating SMVT from other causes of WCT may be difficult, particularly if a high-quality 12-lead ECG is not available during the time of the arrhythmia. The presence of a https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-clinical-manifestations-diagnosis-and-evaluation/print 6/22 7/5/23, 10:40 AM Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation - UpToDate WCT in a patient with prior myocardial infarction (MI) or other structural heart disease probably represents SMVT. By contrast, a WCT in a patient without coronary heart disease (CHD) or structural heart disease more likely represents supraventricular tachycardia. Bundle branch reentry Bundle branch reentrant tachycardia (BBRT) should always be considered in patients presenting with SMVT in the setting of nonischemic cardiomyopathy because it is eminently curable by catheter ablation. While the most common ECG appearance is that of a left bundle branch block with left axis pattern, rarely, it may have a right bundle branch block pattern. BBRT has rarely been reported in persons without apparent structural heart disease or persons with coronary disease. These patients usually display an IVCD on the standard ECG, usually a left bundle branch block type pattern. Supraventricular tachycardia A patient with an underlying bundle branch block, or someone that is dependent on a ventricular pacemaker, who then develops tachycardia will, by definition, have a WCT. Review of a baseline ECG showing bundle branch block or ventricular paced rhythm with a similar QRS morphology to that seen during WCT suggests a higher likelihood of supraventricular tachycardia with aberrancy, but does not exclude ventricular tachycardia. In patients who present with symptomatic WCT, where time may be limited, a history of prior MI or other structural heart disease (or absence thereof) is the most important piece of historical information helping the clinician to distinguish supraventricular tachycardia from SMVT. While the absence of CHD or other structural heart disease does not exclude SMVT, supraventricular tachycardia is much more likely in patients without CHD or structural heart disease. (See 'History and associated symptoms' above and "Wide QRS complex tachycardias: Approach to the diagnosis".) Electrocardiogram artifact ECG artifact, particularly when observed on a rhythm strip, can be misdiagnosed as VT ( waveform 4). Artifact is highly probable, and a true WCT excluded, if narrow-complex beats can be identified regularly "marching" through the rhythm strip, particularly if there is a one-to-one association between P waves and QRS complexes. (See "Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations", section on 'Artifact mimicking ventricular tachycardia'.) ADDITIONAL DIAGNOSTIC EVALUATION Following acute treatment for SMVT, reversible causes of arrhythmia should be sought. These include myocardial ischemia and adverse drug effects. Neither anemia nor electrolyte disturbances cause SMVT, hypotension, and heart failure, which may, with the appropriate https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-clinical-manifestations-diagnosis-and-evaluation/print 7/22 7/5/23, 10:40 AM Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation - UpToDate substrate, facilitate the induction of SMVT or contribute to its persistence but are rarely the primary cause for the arrhythmia. Thereafter, a thorough diagnostic evaluation to exclude associated structural heart disease is warranted. Even young, otherwise healthy patients need a thorough evaluation to exclude entities such as undiagnosed cardiomyopathy, anomalous origin of a coronary artery, hypertrophic cardiomyopathy, or arrhythmogenic right ventricular cardiomyopathy. (See "Congenital and pediatric coronary artery abnormalities" and "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death" and "Arrhythmogenic right ventricular cardiomyopathy: Anatomy, histology, and clinical manifestations".) The diagnostic evaluation to establish the presence and type of heart disease generally includes various invasive and noninvasive techniques, depending in part upon the clinical history and presentation. Cardiac imaging (with echocardiography and preferably cardiac magnetic resonance [CMR] imaging) and continuous ECG monitoring (for 24 hours or longer while hospitalized) should be performed in all patients. Invasive electrophysiology studies (EPS) can frequently be helpful but are not routinely performed in most patients, unless catheter ablation is being considered or there is persistent diagnostic uncertainty. Signal-averaged ECG (SAECG) is rarely helpful in evaluating patients with SMVT. In patients presenting with SMVT without known structural heart disease, stress testing can be helpful as a screen for coronary heart disease (CHD), and may help elicit VT in patients with idiopathic VT, arrhythmogenic right ventricular cardiomyopathy, or other unusual structural abnormalities. In patients with SMVT and history of prior myocardial infarction [MI], revascularization is rarely adequate as monotherapy to prevent recurrent VT, as SMVT is usually due to a reentrant circuit emanating from a prior infarct scar. CPVT is classically triggered by exertion, but condition is usually associated with frequent PVCs and PMVT on stress testing, not SMVT. Cardiac imaging All patients with SMVT should undergo cardiac imaging to evaluate for structural heart disease [10-12]. Echocardiography has long been the preferred method for evaluation of structural heart disease because of its widespread availability, accuracy in diagnosing a variety of structural cardiac defects (myocardial, valvular, congenital), safety to the patients, and relatively low expense. However, CMR imaging generally provides superior image quality and also allows for tissue characterization, making it an important imaging option for certain diagnoses (eg, arrhythmogenic right ventricular cardiomyopathy, cardiac sarcoidosis, other infiltrative cardiomyopathies, etc) and for patients with poor quality or nondiagnostic echocardiographic images [13-15]. In addition, if ablation is contemplated, CMR findings (areas of delayed gadolinium enhancement) may help guide ablation. (See "Tests to evaluate left ventricular systolic function" and "Arrhythmogenic right ventricular cardiomyopathy: Diagnostic evaluation and diagnosis", section on 'Cardiovascular magnetic resonance'.) https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-clinical-manifestations-diagnosis-and-evaluation/print 8/22 7/5/23, 10:40 AM Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation - UpToDate Continuous ECG monitoring Following acute treatment for SMVT, hospitalized patients should have continuous ECG monitoring while any potential reversible causes are identified and corrected. Typically the duration of continuous ECG monitoring should be at least 24 hours following the last episode of SMVT, but additional monitoring may be useful if patients have reversible causes that have not been fully remedied (eg, ongoing myocardial ischemia, heart failure, hypokalemia, etc). Since SMVT generally occurs infrequently and sporadically, we do not routinely perform outpatient ambulatory ECG monitoring [16,17]. However, in patients with syncope suspected of having SMVT, but in whom the diagnosis has not been, extended ambulatory ECG monitoring with an event (loop) monitor, extended Holter monitor, or insertable cardiac monitor (also sometimes referred to as an implantable cardiac monitor or implantable loop recorder) can successfully aid in establishing the diagnosis [18-20]. (See "Ambulatory ECG monitoring".) Signal-averaged electrocardiogram We do not routinely perform a signal-averaged ECG (SAECG) for diagnostic purposes in patients with documented SMVT. The rationale for not routinely obtaining a SAECG is that, while the SAECG often demonstrates late potentials (low amplitude oscillations occurring after the QRS complex) in patients with SMVT and ischemic heart disease, the presence of late potentials provides only indirect data that are suggestive, but not diagnostic, of SMVT [21-23]. Although the SAECG has a prognostic role for predicting the risk of SMVT in patients with ischemic heart disease, it has a limited role in the evaluation of patients who have already experienced SMVT and is rarely used in current cardiology practice [24-26]. (See "Signal-averaged electrocardiogram: Overview of technical aspects and clinical applications".) The rare patients in whom the SAECG can aid in the diagnosis of underlying heart disease include patients with suspected arrhythmogenic right ventricular cardiomyopathy, in whom the SAECG findings are part of the diagnostic criteria for the disorder, as well as patients with suspected Brugada syndrome. The diagnostic approaches to these conditions are discussed in detail separately. (See "Brugada syndrome: Clinical presentation, diagnosis, and evaluation", section on 'Diagnostic evaluation' and "Arrhythmogenic right ventricular cardiomyopathy: Diagnostic evaluation and diagnosis", section on 'Diagnostic evaluation'.) Exercise testing Exercise stress testing, or pharmacologic stress testing if the patient cannot exercise, is an important component of the diagnostic approach in patients presenting with SMVT and suspected myocardial ischemia. For patients with SMVT and evidence of an acute coronary syndrome, stress testing is typically deferred in favor of prompt coronary angiography (with or without https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-clinical-manifestations-diagnosis-and-evaluation/print 9/22 7/5/23, 10:40 AM Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation - UpToDate revascularization as indicated). (See "Overview of the acute management of ST-elevation myocardial infarction" and "Overview of the acute management of non-ST-elevation acute coronary syndromes".) For patients with SMVT in whom CHD is a possible contributing factor to SMVT (eg, patients with numerous risk factors for atherosclerotic cardiovascular disease, patients with cardiac imaging findings suggesting CHD, etc), we proceed with stress testing primarily for prognostic purposes. The choice of the optimal stress test should be based upon the patient's ability to exercise, the ability to interpret the patient's baseline ECG, and the pre- test probability of CHD [27]. (See "Selecting the optimal cardiac stress test".) In patients in whom significant myocardial ischemia is identified, the decision to proceed with revascularization should primarily be based on the presence or absence of symptoms attributable to the ischemia. However, treatment of myocardial ischemia does not eliminate the risk of recurrent SMVT, particularly in patients with prior MI and the presence of myocardial scar. Electrophysiologic studies EPS is the most definitive means of establishing the diagnosis of SMVT [28]. (See "Invasive diagnostic cardiac electrophysiology studies".) There are a number of potential uses for EPS in the evaluation of patients with SMVT: To establish the diagnosis of SMVT when the diagnosis is uncertain. To establish the mechanism of the SMVT. When combined with mapping, the location of the arrhythmogenic focus can be identified, which is useful in cases where ablation is being considered. (See "Invasive diagnostic cardiac electrophysiology studies", section on 'Mapping and ablation'.) Prior to catheter ablation of SMVT, EPS should be performed to assess whether the clinical VT is inducible and also to assess the extensiveness of scar tissue. When BBRT is suspected, EPS can confirm the diagnosis, and ablation is highly effective. While EPS can be helpful in the diagnosis of VT, it is not without limitations: Patients with a prior MI and a history of SMVT almost always (90+ percent) have inducible SMVT with EPS. However, in some studies of patients with ischemic heart disease, up to 5 percent of patients with clinically documented SMVT are not inducible; thus, noninducibility does not exclude this diagnosis [28,29]. The clinically occurring morphology of SMVT is frequently not the same as the morphology of the induced VT during EPS and may have consequences for eventual catheter ablation. https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-clinical-manifestations-diagnosis-and-evaluation/print 10/22 7/5/23, 10:40 AM Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation - UpToDate This is in part related to the limited number of induction attempts during routine diagnostic studies. INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials: "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching for "patient info" and the keyword[s] of interest.) Basics topics (see "Patient education: Ventricular tachycardia (The Basics)") SUMMARY AND RECOMMENDATIONS Background Sustained monomorphic ventricular tachycardia (SMVT) is a potentially life- threatening arrhythmia which requires urgent attention and evaluation. Clinical manifestations Patients with structural heart disease, especially coronary artery disease and a prior myocardial infarction, who present with a wide QRS complex tachycardia (WCT) should be presumed to have VT. All available telemetry recordings and surface electrocardiograms (ECGs), including prior ECGs, should be reviewed for clues to the diagnosis of VT which include (see 'Electrocardiogram' above and "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'Evaluation of the electrocardiogram'): Atrioventricular (AV) dissociation with P waves appearing independently of the QRS complexes. If not obvious, AV dissociation is suggested by the presence of fusion or captured complexes. Variability of ST and T waves from superimposed P waves or from changes in repolarization. https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-clinical-manifestations-diagnosis-and-evaluation/print 11/22 7/5/23, 10:40 AM Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation - UpToDate QRS axis shift from baseline ECG axis. Morphology of QRS complex, especially in leads V1-V6. Differential diagnosis The differential diagnosis of SMVT includes supraventricular tachycardia with aberrant conduction (preexisting or rate-related), supraventricular tachycardia with preexcitation, supraventricular tachycardia in a pacemaker dependent patient, and ECG artifact ( waveform 4). (See 'Differential diagnosis' above.) Cardiac imaging Echocardiography should be performed to evaluate for structural heart disease. If the echocardiographic evaluation is inconclusive, cardiac computed tomography (CT) or magnetic resonance imaging (MRI) should be performed. (See 'Cardiac imaging' above.) Exercise testing All patients should be evaluated for ischemic heart disease. We typically proceed with exercise stress testing (or pharmacologic stress testing if the patient is unable to exercise) with or without cardiac imaging, as clinically appropriate, and coronary angiography when indicated. (See 'Exercise testing' above.) Electrophysiologic studies Invasive electrophysiologic studies can provide a more definitive diagnosis in instances where the diagnosis of ventricular tachycardia (VT) remains uncertain, or in cases where catheter ablation is being considered. However, if the diagnosis of VT is certain, and therapy with an implantable cardiac defibrillator (ICD) placement is planned, electrophysiologic studies are unlikely to affect further management and are not recommended unless catheter ablation is also being planned. (See 'Electrophysiologic studies' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Philip J. Podrid, MD, FACC and Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age- sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015; 385:117. https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-clinical-manifestations-diagnosis-and-evaluation/print 12/22 7/5/23, 10:40 AM Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation - UpToDate 2. Roth GA, Huffman MD, Moran AE, et al. Global and regional patterns in cardiovascular mortality from 1990 to 2013. Circulation 2015; 132:1667. 3. Myerburg RJ. Sudden cardiac death: exploring the limits of our knowledge. J Cardiovasc Electrophysiol 2001; 12:369. 4. Khurshid S, Choi SH, Weng LC, et al. Frequency of Cardiac Rhythm Abnormalities in a Half Million Adults. Circ Arrhythm Electrophysiol 2018; 11:e006273. 5. Tisdale JE, Chung MK, Campbell KB, et al. Drug-Induced Arrhythmias: A Scientific Statement From the American Heart Association. Circulation 2020; 142:e214. 6. Gupta AK, Thakur RK. Wide QRS complex tachycardias. Med Clin North Am 2001; 85:245. 7. Hayes JJ, Stewart RB, Green HL, Bardy GH. Narrow QRS ventricular tachycardia. Ann Intern Med 1991; 114:460. 8. Militianu A, Salacata A, Meissner MD, et al. Ventriculoatrial conduction capability and prevalence of 1:1 retrograde conduction during inducible sustained monomorphic ventricular tachycardia in 305 implantable cardioverter defibrillator recipients. Pacing Clin Electrophysiol 1997; 20:2378. 9. Miller JM, Das MK. Differential diagnosis of wide complex tachycardia. In: Cardiac electrophy siology: from cell to bedside, 4th, Zipes DP, Jalife J (Eds), Saunders, 2004. p.751. 10. European Heart Rhythm Association, Heart Rhythm Society, Zipes DP, et al. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death). J Am Coll Cardiol 2006; 48:e247. 11. American College of Cardiology Foundation Appropriate Use Criteria Task Force, American Society of Echocardiography, American Heart Association, et al. ACCF/ASE/AHA/ASNC/HFSA/HRS/SCAI/SCCM/SCCT/SCMR 2011 Appropriate Use Criteria for Echocardiography. A Report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, American Society of Echocardiography, American Heart Association, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Critical Care Medicine, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Resonance Endorsed by the American College of Chest Physicians. J Am Coll Cardiol 2011; 57:1126. https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-clinical-manifestations-diagnosis-and-evaluation/print 13/22 7/5/23, 10:40 AM Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation - UpToDate 12. Priori SG, Blomstr m-Lundqvist C, Mazzanti A, et al. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Eur Heart J 2015; 36:2793. 13. Ki s P, Bootsma M, Bax J, et al. Arrhythmogenic right ventricular dysplasia/cardiomyopathy: screening, diagnosis, and treatment. Heart Rhythm 2006; 3:225. 14. Marcus F, Towbin JA, Zareba W, et al. Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C): a multidisciplinary study: design and protocol. Circulation 2003; 107:2975. 15. Marcus FI, McKenna WJ, Sherrill D, et al. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the Task Force Criteria. Eur Heart J 2010; 31:806. 16. Bay s de Luna A, Coumel P, Leclercq JF. Ambulatory sudden cardiac death: mechanisms of production of fatal arrhythmia on the basis of data from 157 cases. Am Heart J 1989; 117:151. 17. Gradman AH, Batsford WP, Rieur EC, et al. Ambulatory electrocardiographic correlates of ventricular inducibility during programmed electrical stimulation. J Am Coll Cardiol 1985; 5:1087. 18. Linzer M, Pritchett EL, Pontinen M, et al. Incremental diagnostic yield of loop electrocardiographic recorders in unexplained syncope. Am J Cardiol 1990; 66:214. 19. Krahn AD, Klein GJ, Yee R, et al. Use of an extended monitoring strategy in patients with problematic syncope. Reveal Investigators. Circulation 1999; 99:406. 20. Kadish AH, Buxton AE, Kennedy HL, et al. ACC/AHA clinical competence statement on electrocardiography and ambulatory electrocardiography. A report of the ACC/AHA/ACP- ASIM Task Force on Clinical Competence (ACC/AHA Committee to Develop a Clinical Competence Statement on Electrocardiography and Ambulatory Electrocardiography). J Am Coll Cardiol 2001; 38:2091. 21. Denniss AR, Richards DA, Cody DV, et al. Prognostic significance of ventricular tachycardia and fibrillation induced at programmed stimulation and delayed potentials detected on the signal-averaged electrocardiograms of survivors of acute myocardial infarction. Circulation 1986; 74:731. 22. Vaitkus PT, Kindwall KE, Marchlinski FE, et al. Differences in electrophysiological substrate in patients with coronary artery disease and cardiac arrest or ventricular tachycardia. Insights https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-clinical-manifestations-diagnosis-and-evaluation/print 14/22 7/5/23, 10:40 AM

Morphology of QRS complex, especially in leads V1-V6. Differential diagnosis The differential diagnosis of SMVT includes supraventricular tachycardia with aberrant conduction (preexisting or rate-related), supraventricular tachycardia with preexcitation, supraventricular tachycardia in a pacemaker dependent patient, and ECG artifact ( waveform 4). (See 'Differential diagnosis' above.) Cardiac imaging Echocardiography should be performed to evaluate for structural heart disease. If the echocardiographic evaluation is inconclusive, cardiac computed tomography (CT) or magnetic resonance imaging (MRI) should be performed. (See 'Cardiac imaging' above.) Exercise testing All patients should be evaluated for ischemic heart disease. We typically proceed with exercise stress testing (or pharmacologic stress testing if the patient is unable to exercise) with or without cardiac imaging, as clinically appropriate, and coronary angiography when indicated. (See 'Exercise testing' above.) Electrophysiologic studies Invasive electrophysiologic studies can provide a more definitive diagnosis in instances where the diagnosis of ventricular tachycardia (VT) remains uncertain, or in cases where catheter ablation is being considered. However, if the diagnosis of VT is certain, and therapy with an implantable cardiac defibrillator (ICD) placement is planned, electrophysiologic studies are unlikely to affect further management and are not recommended unless catheter ablation is also being planned. (See 'Electrophysiologic studies' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Philip J. Podrid, MD, FACC and Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age- sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015; 385:117. https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-clinical-manifestations-diagnosis-and-evaluation/print 12/22 7/5/23, 10:40 AM Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation - UpToDate 2. Roth GA, Huffman MD, Moran AE, et al. Global and regional patterns in cardiovascular mortality from 1990 to 2013. Circulation 2015; 132:1667. 3. Myerburg RJ. Sudden cardiac death: exploring the limits of our knowledge. J Cardiovasc Electrophysiol 2001; 12:369. 4. Khurshid S, Choi SH, Weng LC, et al. Frequency of Cardiac Rhythm Abnormalities in a Half Million Adults. Circ Arrhythm Electrophysiol 2018; 11:e006273. 5. Tisdale JE, Chung MK, Campbell KB, et al. Drug-Induced Arrhythmias: A Scientific Statement From the American Heart Association. Circulation 2020; 142:e214. 6. Gupta AK, Thakur RK. Wide QRS complex tachycardias. Med Clin North Am 2001; 85:245. 7. Hayes JJ, Stewart RB, Green HL, Bardy GH. Narrow QRS ventricular tachycardia. Ann Intern Med 1991; 114:460. 8. Militianu A, Salacata A, Meissner MD, et al. Ventriculoatrial conduction capability and prevalence of 1:1 retrograde conduction during inducible sustained monomorphic ventricular tachycardia in 305 implantable cardioverter defibrillator recipients. Pacing Clin Electrophysiol 1997; 20:2378. 9. Miller JM, Das MK. Differential diagnosis of wide complex tachycardia. In: Cardiac electrophy siology: from cell to bedside, 4th, Zipes DP, Jalife J (Eds), Saunders, 2004. p.751. 10. European Heart Rhythm Association, Heart Rhythm Society, Zipes DP, et al. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death). J Am Coll Cardiol 2006; 48:e247. 11. American College of Cardiology Foundation Appropriate Use Criteria Task Force, American Society of Echocardiography, American Heart Association, et al. ACCF/ASE/AHA/ASNC/HFSA/HRS/SCAI/SCCM/SCCT/SCMR 2011 Appropriate Use Criteria for Echocardiography. A Report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, American Society of Echocardiography, American Heart Association, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Critical Care Medicine, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Resonance Endorsed by the American College of Chest Physicians. J Am Coll Cardiol 2011; 57:1126. https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-clinical-manifestations-diagnosis-and-evaluation/print 13/22 7/5/23, 10:40 AM Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation - UpToDate 12. Priori SG, Blomstr m-Lundqvist C, Mazzanti A, et al. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Eur Heart J 2015; 36:2793. 13. Ki s P, Bootsma M, Bax J, et al. Arrhythmogenic right ventricular dysplasia/cardiomyopathy: screening, diagnosis, and treatment. Heart Rhythm 2006; 3:225. 14. Marcus F, Towbin JA, Zareba W, et al. Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C): a multidisciplinary study: design and protocol. Circulation 2003; 107:2975. 15. Marcus FI, McKenna WJ, Sherrill D, et al. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the Task Force Criteria. Eur Heart J 2010; 31:806. 16. Bay s de Luna A, Coumel P, Leclercq JF. Ambulatory sudden cardiac death: mechanisms of production of fatal arrhythmia on the basis of data from 157 cases. Am Heart J 1989; 117:151. 17. Gradman AH, Batsford WP, Rieur EC, et al. Ambulatory electrocardiographic correlates of ventricular inducibility during programmed electrical stimulation. J Am Coll Cardiol 1985; 5:1087. 18. Linzer M, Pritchett EL, Pontinen M, et al. Incremental diagnostic yield of loop electrocardiographic recorders in unexplained syncope. Am J Cardiol 1990; 66:214. 19. Krahn AD, Klein GJ, Yee R, et al. Use of an extended monitoring strategy in patients with problematic syncope. Reveal Investigators. Circulation 1999; 99:406. 20. Kadish AH, Buxton AE, Kennedy HL, et al. ACC/AHA clinical competence statement on electrocardiography and ambulatory electrocardiography. A report of the ACC/AHA/ACP- ASIM Task Force on Clinical Competence (ACC/AHA Committee to Develop a Clinical Competence Statement on Electrocardiography and Ambulatory Electrocardiography). J Am Coll Cardiol 2001; 38:2091. 21. Denniss AR, Richards DA, Cody DV, et al. Prognostic significance of ventricular tachycardia and fibrillation induced at programmed stimulation and delayed potentials detected on the signal-averaged electrocardiograms of survivors of acute myocardial infarction. Circulation 1986; 74:731. 22. Vaitkus PT, Kindwall KE, Marchlinski FE, et al. Differences in electrophysiological substrate in patients with coronary artery disease and cardiac arrest or ventricular tachycardia. Insights https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-clinical-manifestations-diagnosis-and-evaluation/print 14/22 7/5/23, 10:40 AM Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation - UpToDate from endocardial mapping and signal-averaged electrocardiography. Circulation 1991; 84:672. 23. Martinez-Rubio A, Shenasa M, Borggrefe M, et al. Electrophysiologic variables characterizing the induction of ventricular tachycardia versus ventricular fibrillation after myocardial infarction: relation between ventricular late potentials and coupling intervals for the induction of sustained ventricular tachyarrhythmias. J Am Coll Cardiol 1993; 21:1624. 24. Ommen SR, Hammill SC, Bailey KR. Failure of signal-averaged electrocardiography with use of time-domain variables to predict inducible ventricular tachycardia in patients with conduction defects. Mayo Clin Proc 1995; 70:132. 25. Steinberg JS, Prystowsky E, Freedman RA, et al. Use of the signal-averaged electrocardiogram for predicting inducible ventricular tachycardia in patients with unexplained syncope: relation to clinical variables in a multivariate analysis. J Am Coll Cardiol 1994; 23:99. 26. Cain, ME, Anderson, et al. Signal-averaged electrocardiography. ACC Expert Consensus Document. J Am Coll Cardiol 1996; 27:238. 27. Hendel RC, Berman DS, Di Carli MF, et al. ACCF/ASNC/ACR/AHA/ASE/SCCT/SCMR/SNM 2009 Appropriate Use Criteria for Cardiac Radionuclide Imaging: A Report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the American Society of Nuclear Cardiology, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the Society of Cardiovascular Computed Tomography, the Society for Cardiovascular Magnetic Resonance, and the Society of Nuclear Medicine. J Am Coll Cardiol 2009; 53:2201. 28. Volgman AS, Zheutlin TA, Mattioni TA, et al. Reproducibility of programmed electrical stimulation responses in patients with ventricular tachycardia or fibrillation associated with coronary artery disease. Am J Cardiol 1992; 70:758. 29. Bhandari AK, Hong R, Kulick D, et al. Day to day reproducibility of electrically inducible ventricular arrhythmias in survivors of acute myocardial infarction. J Am Coll Cardiol 1990; 15:1075. Topic 1029 Version 35.0 https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-clinical-manifestations-diagnosis-and-evaluation/print 15/22 7/5/23, 10:40 AM Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation - UpToDate GRAPHICS ECG of sustained monomorphic ventricular tachycardia Shown are the six precordial electrocardiogram (ECG) leads (V1-V6). The QRS complex is wide and bizarre and the rhythm is ventricular tachycardia (VT). The sixth (+) and seventh (*) QRS complexes show a change in morphology, resembling a normal QRS complex; these represent fusion beats, with partial (+) or complete (*) normalization of the QRS complex. The seventh QRS complex (*) is preceded by a distinct P wave, which is probably conducted, capturing the ventricle for one beat, but not terminating the VT; this is also known as a Dressler beat. Reproduced with permission by Samuel Levy, MD. Graphic 69201 Version 3.0 https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-clinical-manifestations-diagnosis-and-evaluation/print 16/22 7/5/23, 10:40 AM Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation - UpToDate Algorithm for the initial ECG review and differential diagnosis of tachycardia ECG: electrocardiogram; AVNRT: atrioventricular nodal reentrant tachycardia; AVRT: atrioventricular reciprocating (bypass-tract mediated) tachycardia; AT: atrial tachycardia; SANRT: sinoatrial nodal reentrant tachycardia; AF: atrial fibrillation; AV: atrioventricular; VT: ventricular tachycardia; SVT: supraventricular tachycardia; WPW: Wolff-Parkinson-White. A narrow QRS complex is <120 milliseconds in duration, whereas a wide QRS complex is 120 milliseconds duration. Refer to UpToDate topic reviews for additional details on specific ECG findings and management of individu arrhythmias. Monomorphic VT accounts for 80% of wide QRS complex tachycardias; refer to UpToDate topic on diagnosi wide QRS complex tachycardias for additional information on discriminating VT from SVT. Graphic 117571 Version 3.0 https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-clinical-manifestations-diagnosis-and-evaluation/print 17/22 7/5/23, 10:40 AM Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation - UpToDate Atrioventricular dissociation Independent activation of the atria and ventricles results in no fixed relationship between the P waves (arrows) and the QRS complexes; the PR intervals are variable in a random fashion. Graphic 52123 Version 2.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-clinical-manifestations-diagnosis-and-evaluation/print 18/22 7/5/23, 10:40 AM Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation - UpToDate 12-lead ECG sustained monomorphic VT The electrocardiogram (ECG) hallmark for the diagnosis of sustained monomorphic ventricular tachycardia (S is a wide complex tachycardia with the obvious presence of atrioventricular (AV) dissociation. AV dissociation suggested by the presence of fusion complexes (which reflect a supraventricular impulse coming from above AV node fusing with an impulse generated in the ventricle) or captured complexes (which reflect an impulse coming from above the AV node that depolarizes the ventricles when they are no longer refractory but befor next ventricle-generated complex). Beats 12, 17, and 22 on this ECG likely represent capture beats. Graphic 111254 Version 1.0 https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-clinical-manifestations-diagnosis-and-evaluation/print 19/22 7/5/23, 10:40 AM Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation - UpToDate ECG features of ventricular tachycardia QRS width >120 milliseconds Shift in QRS axis, particularly to a "northwest" axis (between 90 and 180 degrees) AV dissociation (including the presence of fusion complexes and/or capture beats) Negative concordance in leads V1 to V6 RS >100 milliseconds in any of leads V1 to V6 Morphology: VT with RBBB-like morphology in V1: R/S <1 in V6 VT with LBBB-like morphology in V1: Any Q wave in V6 ECG: electrocardiogram; AV: atrioventricular; VT: ventricular tachycardia; RBBB: right bundle branch block; LBBB: left bundle branch block. Graphic 111307 Version 2.0 https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-clinical-manifestations-diagnosis-and-evaluation/print 20/22 7/5/23, 10:40 AM Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation - UpToDate Ventricular tachycardia artifact Courtesy of Alfred Buxton, MD. Graphic 140806 Version 1.0 https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-clinical-manifestations-diagnosis-and-evaluation/print 21/22 7/5/23, 10:40 AM Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation - UpToDate Contributor Disclosures Alfred Buxton, MD No relevant financial relationship(s) with ineligible companies to disclose. N A Mark Estes, III, MD Consultant/Advisory Boards: Boston Scientific [Arrhythmias]; Medtronic [Arrhythmias]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/sustained-monomorphic-ventricular-tachycardia-clinical-manifestations-diagnosis-and-evaluation/print 22/22

7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. The electrocardiogram in atrial fibrillation : Brian Olshansky, MD, Zachary D Goldberger, MD, FACC, FHRS, Steven M Pogwizd, MD : Bradley P Knight, MD, FACC : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Sep 10, 2021. INTRODUCTION Atrial fibrillation (AF) can cause significant symptoms; impair functional status, hemodynamics, and quality of life; and increase the risk of stroke and death. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation".) Diagnosis of AF has important implications for acute and long-term management. A missed diagnosis of AF may result in a failure to appropriately anticoagulate for stroke prophylaxis or effectively treat symptoms due to AF, while overdiagnosis of AF may lead to inappropriate testing and therapy including unwarranted anticoagulation with associated risk of major bleeding. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation".) This topic will review the electrocardiographic (ECG) features of AF. The mechanisms of AF are presented separately. (See "Mechanisms of atrial fibrillation".) DIAGNOSIS OF ATRIAL FIBRILLATION AF is diagnosed by interpretation of the 12-lead ECG. In most patients, a single 12-lead ECG, recorded while the patient is in AF, is sufficient to secure the diagnosis. Examination of prior ECGs may be helpful, but prior diagnosis (or misdiagnosis) of AF should not influence interpretation of a current ECG. In some patients, AF is detected on ECG recordings from cardiac telemetry, ambulatory ECG monitor (eg, Holter monitor or loop recorder), or cardiac implantable electronic device (permanent pacemaker [PPM] or implantable cardioverter-defibrillator [ICD]). (See "Ambulatory ECG monitoring" and "Permanent cardiac pacing: Overview of devices and https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 1/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate indications" and "Implantable cardioverter-defibrillators: Overview of indications, components, and functions".) Our approach While the ECG diagnosis of AF with typical features can be straightforward in patients with characteristic features of AF (see 'Key features of atrial fibrillation' below), misdiagnosis of AF is common, as there are a significant number of AF mimics that should be excluded. (See 'Differential diagnosis' below.) The following is our approach to ECG identification of the cause of an irregularly irregular ventricular rhythm (or regular rhythm with fibrillatory or absent P waves) ( algorithm 1): Exclude artifact If artifact may be present, examine all 12 leads and examine atrial activity in the leads with the least amount of artifact-related oscillations ( waveform 1 and waveform 2). If atrial activity cannot be adequately assessed, address the cause of the artifact to the extent possible and repeat the ECG. (See 'Differential diagnosis' below.) Identify atrial activity Examine all 12 leads of the ECG closely for the presence of atrial activity, particularly the inferior leads and lead V1. Focus on areas with longer R-R intervals that display longer periods of isoelectric baseline. Increase amplitude, if needed If no atrial activity is detected or the morphology of atrial activity is not well visualized, use ECG amplification (either digital magnification or an increase in gain for the entire ECG signal) ( waveform 3). Examine atrial activity The morphology, frequency, and timing of atrial activity in relationship to QRS complexes should be assessed. Exclude AF mimics. (See 'Differential diagnosis' below.) If AF mimics are excluded, and there are fibrillatory waves or no P waves (despite ECG amplification), AF is diagnosed. Common and uncommon ECG characteristics of AF are described below. (See 'Key features of atrial fibrillation' below.) Key features of atrial fibrillation Common findings The following findings are commonly seen with AF: Atrial activity (see 'Atrial activity' below): Lack of discrete P waves ( waveform 4). https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 2/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Rapid, low-amplitude fibrillatory (or f) waves vary continuously in amplitude, morphology, and rate. The rate may be between 350 to 600 beats per minute (bpm) or unmeasurable. If present, f waves usually are best seen in the inferior leads and in V1. The f waves may be identified between QRS complexes and are sometimes visible superimposed on the ST segment and T waves. Ventricular activity (see 'Ventricular activation' below): The ventricular rhythm is described as "irregularly irregular," meaning lacking a repetitive, predictable pattern. (See 'General features' below.) The ventricular rate (especially in absence of atrioventricular [AV] nodal blocking drugs or intrinsic conduction disease) is usually 90 to 170 bpm, with higher rates seen in younger individuals (see 'General features' below). Based on the ventricular rate, AF is often characterized as having "slow" (<60 bpm), "moderate" (60 to 100 bpm), or "rapid" (>100 bpm) ventricular response ( waveform 5). The QRS complexes are narrow unless conduction through the His-Purkinje system is abnormal due to preexisting right or left bundle branch ( waveform 6), fascicular block, functional (rate-related) aberration, or ventricular preexcitation with anterograde conduction via an AV accessory pathway. (See 'With aberrant conduction' below and 'With Wolff-Parkinson-White syndrome' below.) Uncommon findings The following findings are less commonly identified in patients with AF: A regular (rather than an irregularly irregular) ventricular rhythm: Regular ventricular escape complexes in patients with complete or high-grade AV block are referred to as "regularization of AF." Complete or high-grade AV block may be caused by conduction system disease, AV node ablation, or drugs (including digoxin toxicity). (See "Etiology of atrioventricular block" and "Atrial fibrillation: Atrioventricular node ablation" and "Third-degree (complete) atrioventricular block" and "Cardiac arrhythmias due to digoxin toxicity", section on 'Digoxin-induced arrhythmias'.) Junctional escape Most commonly, the escape pacemaker is located in the AV junction above the bifurcation of the bundle branches, leading to a QRS complex that has the same morphology as if it had conducted from the atria through the AV node ( waveform 7). This pacemaker generally has a characteristic rate of approximately 60 bpm, unless it is accelerated or depressed due to pathology, ischemia, or drugs (eg, digoxin). https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 3/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Ventricular escape With less commonly seen ventricular (subjunctional or fascicular) escape rhythms, the QRS is wide and, unless accelerated, the ventricular rate is generally 30 to 50 bpm ( waveform 7). Ventricular pacing produces a regular paced ventricular rhythm with wide QRS. (See "Permanent cardiac pacing: Overview of devices and indications" and "Modes of cardiac pacing: Nomenclature and selection".) The ventricular rhythm is typically regular when there is ventricular tachycardia in the presence of AF. With very fast rates of AV conduction, the ventricular rate may appear regular. If there is conversion between AF and atrial flutter with a fixed ratio of conduction, the ventricular rate will be regular during periods of atrial flutter. Variable (rather than consistent) QRS morphology may result from varying combinations of AV conduction and native or paced ventricular beats ( waveform 8). In these unusual cases, there may be AV conduction and fusion beats (hybrid complexes produced by coincident AV conduction and ventricular or paced beats) or pseudofusion beats (QRS complexes with morphology of AV conducted beats but with superimposed pacemaker stimuli). An example is the occurrence of AF with rapid ventricular response in concert with a "competing" tachycardia (eg, ventricular tachycardia) ( waveform 9). (See "ECG tutorial: Miscellaneous diagnoses", section on 'Fusion and capture beats' and "ECG tutorial: Pacemakers", section on 'Ventricular pacing only'.) Differential diagnosis When there are no recognizable atrial deflections in any ECG lead, turning up the gain on the ECG may enable identification of f or P waves and thus help distinguish fine AF from sinus rhythm with irregularity (due to ectopy or sinus arrhythmia) ( waveform 3). AF can be confused with a number of other supraventricular arrhythmias that exhibit atrial activity (ie, sinus P waves, ectopic P waves, or flutter waves). "Coarse" AF (large-amplitude f waves, especially in lead V1) should be distinguished from atrial flutter and multifocal atrial tachycardia, as discussed below. Specific AF mimics can be subdivided based on the type of atrial activity present. One or more of the following types of rhythms may be present: Artifact Artifact from tremor, shivering, or loose lead connection superimposed on sinus rhythm (or any other non-AF rhythm) can mimic AF ( waveform 1 and waveform 2). https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 4/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial flutter Atrial flutter is characterized by flutter waves on the isoelectric baseline between longer R-R intervals and on the ST segments and/or T waves, usually best seen in inferior leads or V1 ( waveform 10). Both typical and atypical atrial flutter can mimic AF. In atrial flutter, atrial rates are generally 250 to 350 bpm (but are sometimes as low as 190 to 200 bpm). While atrial flutter with a constant degree of AV block (2:1, 3:1, 4:1) typically results in regular rhythms, atrial flutter with variable AV conduction is irregular. Some patients with AF also have episodes of atrial flutter. (See "Overview of atrial flutter", section on 'Electrocardiogram'.) We avoid use of the term "atrial fibrillation/flutter," which is commonly used when the precise type of atrial activity is unclear. The term is inaccurate and may impact care as there are differences in the short- and long-term management for AF and atrial flutter. When it is difficult to distinguish these conditions, we use alternate language such as "The atrial activity is unclear and coarse, but the likely diagnosis is AF. However, atrial flutter with variable conduction cannot be excluded." Some patients have both of these conditions. If an ECG catches a transition between AF and atrial flutter, this transition should be noted and not labeled as "atrial fibrillation/flutter." The presence of sinus P waves (upright in II, inverted in aVR, and biphasic in V1) suggests an underlying sinus rhythm. Sinus arrhythmia If all P waves are sinus, variation in PP (by >0.16 seconds) with a relatively constant PR suggests sinus arrhythmia ( waveform 11). There is progressive increase and decrease in the P-P interval (See "ECG tutorial: Rhythms and arrhythmias of the sinus node", section on 'Sinus arrhythmia' and "Normal sinus rhythm and sinus arrhythmia", section on 'Sinus arrhythmia'.) Sinus arrhythmia with competing junctional escape rhythm If there is variation in PP and there is one or more QRS complex without a preceding P wave or preceded by a shorter than normal PR interval, consider sinus arrhythmia with a competing junctional escape rhythm (also known as isorhythmic AV dissociation) ( waveform 12). This occurs when the sinus rate intermittently drops below that of the junctional escape rhythm. The inconsistent P-QRS relationship is more challenging for the standard AF algorithms of ECG machines, and the rhythm is often misinterpreted as AF. (See "ECG tutorial: Rhythms and arrhythmias of the sinus node", section on 'Types' and "ECG tutorial: Atrial and atrioventricular nodal (supraventricular) arrhythmias", section on 'Junctional escape beats'.) https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 5/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Sinus rhythm with second-degree AV block Sinus rhythm with second-degree AV block can result in an irregular rhythm with occasional dropped beats (nonconducted P waves) which may (Mobitz I) or may not (Mobitz II) be preceded by progressive PR prolongation ( waveform 13). (See "Second-degree atrioventricular block: Mobitz type I (Wenckebach block)" and "Second-degree atrioventricular block: Mobitz type II" and "ECG tutorial: Atrioventricular block".) Sinus rhythm with premature ventricular complexes (PVCs) Sinus rhythm with PVCs can result in an irregular rhythm that may be mistaken as AF when P wave amplitude is diminished or in the setting of artifact. One morphology of nonsinus P waves (along with sinus P waves): Sinus rhythm with premature atrial complexes (PACs) The combination of sinus rhythm and PACs results in an irregular rhythm that can resemble AF, especially when the P waves of sinus beats and/or PACs are superimposed on the ST segment or T waves of preceding beats . To distinguish this rhythm from AF, magnification of digitized ECG tracings may facilitate recognition of sinus and ectopic P waves and demonstrate a consistent one-to-one relationship between P waves and QRS complexes ( waveform 3). (See "ECG tutorial: Atrial and atrioventricular nodal (supraventricular) arrhythmias", section on 'Premature atrial complex'.) Runs of nonsinus P waves A shift in atrial activation arising from the sinus node to that from an ectopic atrial site (or vice versa) can lead to a sudden change in P wave morphology and, often, some irregularity that could mimic AF. Ectopic atrial rhythm Atrial rate is 100; generally, 30 to 60 bpm ( waveform 14). (See "ECG tutorial: Atrial and atrioventricular nodal (supraventricular) arrhythmias", section on 'Ectopic atrial rhythm'.) Focal atrial tachycardia Atrial tachycardia (AT) is characterized by atrial rates in the 140 to 180 bpm range ( waveform 15). In the presence of AV block, the ventricular response can be irregular and mimic AF. While AT with block has been commonly described with digoxin toxicity, it can occur in the absence of digoxin. (See "Cardiac arrhythmias due to digoxin toxicity", section on 'Digoxin-induced arrhythmias'.) Three or more P wave morphologies: Wandering atrial pacemaker or multifocal atrial rhythm is an irregular rhythm that is also characterized by P waves of at least three morphologies and is characterized by https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 6/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate ventricular rates <100 bpm ( waveform 16). (See "ECG tutorial: Atrial and atrioventricular nodal (supraventricular) arrhythmias" and "ECG tutorial: Atrial and atrioventricular nodal (supraventricular) arrhythmias", section on 'Wandering atrial pacemaker'.) Multifocal atrial tachycardia (MAT) MAT is a rapid irregularly irregular rhythm (ventricular rate 100 bpm) characterized by P waves of at least three different morphologies and with a one-to-one correspondence of P waves to QRS complexes ( waveform 17). (See "ECG tutorial: Atrial and atrioventricular nodal (supraventricular) arrhythmias", section on 'Multifocal atrial tachycardia' and "Multifocal atrial tachycardia", section on 'Clinical manifestations and diagnosis'.) Ventricular tachycardia AF with aberrant conduction may include consecutive runs of aberrantly conducted beats with wide QRS complexes, which may appear similar to ventricular tachycardia. The ventricular rate with AF is generally irregular. (See 'With aberrant conduction' below.) EXPLANATION OF ECG FEATURES Atrial activity In AF, there is no regular or organized atrial activity ( waveform 4). Numerous apparent microreentrant circuits within the atria may generate multiple waves of impulses that compete with or extinguish each other in what is termed "fibrillatory conduction." The sinus node is suppressed and cannot activate the atrium. Mechanisms causing this abnormal pattern of atrial electrical activity are discussed elsewhere. (See "Mechanisms of atrial fibrillation".) Rapid, irregular, and variable fibrillatory (f) waves may be coarse (amplitude 1 mm) or fine (<1 mm) and may not be identified. Some studies have found that fine AF is associated with older age, but age ranges for coarse and fine AF overlap widely [1,2]. The amplitude of f waves does not correlate with left atrial size [1,3]. The differential diagnosis for AF is discussed above. (See 'Differential diagnosis' above.) Ventricular activation General features In AF, the ventricular response rate is dependent on properties of the AV conduction system. As rapid and irregular atrial impulses bombard the AV node, some impulses occur in such rapid succession that they are blocked due to the refractoriness of the AV node, resulting in irregular impulse conduction through the AV node to the ventricular myocardium via https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 7/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate the His-Purkinje system. High frequency of atrial stimuli reaching the AV node does not lead to high frequency of AV conduction, as frequent impulses may cause "concealed" depolarization (ie, not evident on the surface ECG) impairing AV conduction. The large number of atrial impulses arriving at the AV node compete with each other, interfering with their penetration into and through the node, leaving this tissue variably refractory. While the ventricular rate in adults with AF is usually 90 to 170 bpm, in young, untreated individuals, rates are 160 to 200 bpm, reflecting the maximal rate at which the AV node can conduct (as determined by its refractory period in lieu of concealed conduction). Increases in the ventricular response rate to over 200 bpm may occur if the refractory period of the AV node is shortened, as with an increase in circulating catecholamines (eg, sympathetic stimulation or pheochromocytoma, hyperthyroidism, or conduction down a manifest accessory pathway). A decrease in the ventricular response rate occurs when the refractory period of the AV node is increased (eg, with aging, conduction system disease, drugs, or enhanced vagal tone) or AV conduction otherwise slows. With aberrant conduction A common cause for QRS widening during AF is aberrant conduction, which is a rate-related change in conduction. Most aberrancy is tachycardia- dependent, although bradycardia-dependent aberrancy does occur [4]. The aberrant conduction in AF involves a rate-related (tachycardia-induced) change in conduction, typically a functional bundle branch block; right bundle branch block (RBBB) is more common than left bundle branch block (LBBB), as the RBBB has a longer refractory period than the LBBB. An important property of the conducting system and myocardium is that refractoriness is longer at slow rates and shorter at faster rates. The refractoriness of the conducting system varies on a beat-by-beat basis and is related to the coupling interval of the preceding beat. As such, a long coupling interval leads to prolongation of bundle branch refractoriness (typically R>L), and if the next beat comes in early (ie, a long-short cycle), the refractoriness of the RBBB leads to a RBBB configuration and QRS widening that resembles a premature ventricular complex (PVC). This pattern of long-short cycle typically leads to RBBB morphology (known as Ashman phenomenon [5]) and can occur during sinus rhythm with appropriately timed premature atrial complexes (PACs) ( waveform 18) as well as during AF ( waveform 19). Aberrancy with LBBB morphology is less common but can occur. The QRS of aberrant beats typically exhibits an upstroke similar to those of other native supraventricular beats in leads other than V1 to V2, while PVCs typically exhibit markedly different morphology from supraventricular beats in multiple leads, as shown for sinus rhythm ( waveform 18). The approach to evaluating wide QRS complex tachycardia to distinguish supraventricular tachycardia from ventricular tachycardia is discussed separately. (See "Wide QRS complex tachycardias: Approach to the diagnosis".) https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 8/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate During AF, Ashman phenomenon is associated with frequent isolated wide-complex aberrantly conducted beats. However, aberrantly conducted beats can also occur in couplets or longer nonsustained runs that can resemble ventricular tachycardia ( waveform 19). In these situations, there is no longer a long-short cycle but rather short-short cycles of rapid AF. In this case, the functional RBBB and activation down the LBBB is followed by partial penetration up the right bundle, leading to RBBB of the subsequent beat. This represents "concealed conduction" up the right bundle (ie, not evident on the surface ECG, which solely reflects atrial and ventricular activity). This can continue for a number of consecutive beats until functional BBB resolves either despite continued short cycle length or when the cycle length lengthens. As such, AF with aberrant conduction can resemble ventricular tachycardia, and it is critical to distinguish between ventricular tachycardia and sustained aberrancy . (See 'Differential diagnosis' above.) With Wolff-Parkinson-White syndrome When AF is associated with ventricular preexcitation due to anterograde conduction down an accessory pathway in patients with Wolff- Parkinson-White syndrome (WPW), the ventricular response rate may be very rapid and may exceed 280 to 300 bpm ( waveform 20), since impulse activation bypasses the AV node. Preexcited AF is facilitated when the refractory period of the accessory pathway is very short. Accessory pathway tissue differs from that of the AV node. Specifically, the accessory pathway does not exhibit postrepolarization refractoriness but rather conducts rapidly as the tissue is dependent on sodium (rather than calcium) channel activity. Conduction down the accessory pathway typically results in a slurred QRS upstroke (ie, "delta" wave), and the QRS morphology depends on the location of the pathway and its insertion into the ventricular myocardium. The QRS complex is usually wide, with rapid activation down the accessory pathway into ventricular muscle, often in concert with some conduction down the AV node and His-Purkinje system. The more conduction proceeds through the accessory pathway, the wider and more slurred the QRS complex. (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis", section on 'Electrocardiographic findings'.) A distinguishing feature of AF with preexcitation is the relationship between heart rate and QRS duration; the faster the rate, the wider the QRS. At times, it can resemble ventricular tachycardia (based on its appearance and, often, the presence of precordial concordance). While the rhythm is irregularly irregular, variations may be difficult to measure at extremely fast rates. The clinical significance of AF with rapid ventricular response in patients with WPW is discussed separately. (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis", section on 'Ventricular fibrillation and sudden death'.) ROLE OF COMPUTER TECHNOLOGY https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 9/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Computer interpretation Each ECG computer interpretation should be overread by a trained clinician as an essential requirement for patient care and safety. Automatic computer interpretation of the ECG is common practice, with over 100 million automatic ECG interpretations yearly. Limited data are available on the accuracy of automatic computer interpretation for AF, but an estimated 10 to 30 percent of the computer ECG interpretations may misdiagnose AF, and such misdiagnosis may be frequently missed by clinicians [6,7]. Such misdiagnosis can lead to inappropriate interventions and therapies. The methodological approaches that computers utilize to determine whether or not AF is present are not well clarified. Insufficient overreading may be a growing problem as formal ECG interpretation becomes less of a focus in many training programs. Wearable consumer devices While ambulatory ECG monitoring (Holter, event, or patch- based monitors, and implantable loop recorders) is a commonly employed clinical method to detect occult AF (see "Ambulatory ECG monitoring"), there has been growing use of wearable consumer devices such as smart watches and other devices that can connect to smart phones [8,9] to monitor heart rate and rhythm [10,11]. While these widely used electronic devices have potential capabilities for detecting AF, and algorithms are improving, they are subject to limitations. Generally, the methodology (often proprietary) monitors the irregularity in ventricular response rates but does not monitor the presence and type of atrial activation. Also, some devices may require a threshold episode duration (eg, 30 seconds) to detect an arrhythmia. These limitations are likely to limit the sensitivity and specificity of these devices in detecting and diagnosing AF. Thus, all patients with suspected AF require clinician review of recordings on clinically approved ECG equipment, as described above . (See 'Our approach' above.) SUMMARY AND RECOMMENDATIONS Atrial fibrillation (AF) is diagnosed by interpretation of the 12-lead electrocardiogram (ECG). AF should be considered in patients with an irregularly irregular ventricular rhythm (or regular rhythm with fibrillatory or absent P waves). (See 'Diagnosis of atrial fibrillation' above and 'Differential diagnosis' above.) In some patients, AF is detected on ECG recordings from cardiac telemetry, ambulatory ECG monitor (eg, Holter monitor or loop recorder), or cardiac implantable electronic device (permanent pacemaker [PPM] or implantable cardioverter-defibrillator [ICD]). (See "Ambulatory ECG monitoring" and "Permanent cardiac pacing: Overview of devices and indications" and "Implantable cardioverter-defibrillators: Overview of indications, components, and functions".) https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 10/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Our approach to diagnosis of AF involves exclusion of artifact, ECG amplification (if no atrial activity is detected or the morphology of atrial activity is not well-visualized), and exclusion of AF mimics ( algorithm 1). (See 'Our approach' above and 'Differential diagnosis' above.) Common features of AF include lack of discrete P waves, presence of fibrillatory (f) waves, and irregularly irregular ventricular rhythm. QRS complexes are narrow unless there is a right or left bundle branch block, fascicular block, functional (rate-related) aberration, or antegrade conduction via an AV accessory pathway. (See 'Common findings' above.) ECG features that are uncommonly associated with AF include a regular ventricular rhythm and variable QRS morphology. (See 'Uncommon findings' above.) The differential diagnosis of AF includes artifact, atrial flutter, sinus rhythm (with sinus arrhythmia, second-degree AV block, or premature atrial complexes [PACs]), ectopic atrial rhythm, multifocal atrial tachycardia (MAT), wandering atrial pacemaker, focal atrial tachycardia with block, sinus rhythm with competing junctional rhythm, and ventricular tachycardia. (See 'Differential diagnosis' above.) Each ECG computer interpretation should be overread by a trained clinician as an essential requirement for patient care and safety. Limited data on the accuracy of automatic computer interpretation for AF suggest that 10 to 30 percent of the computer ECG interpretations may misdiagnose AF. (See 'Computer interpretation' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Pourafkari L, Baghbani-Oskouei A, Aslanabadi N, et al. Fine versus coarse atrial fibrillation in rheumatic mitral stenosis: The impact of aging and the clinical significance. Ann Noninvasive Electrocardiol 2018; 23:e12540. 2. Yilmaz MB, Guray Y, Guray U, et al. Fine vs. coarse atrial fibrillation: which one is more risky? Cardiology 2007; 107:193. 3. Li YH, Hwang JJ, Tseng YZ, et al. Clinical significance of fibrillatory wave amplitude. A clue to left atrial appendage function in nonrheumatic atrial fibrillation. Chest 1995; 108:359. 4. Fisch C, Miles WM. Deceleration-dependent left bundle branch block: a spectrum of bundle branch conduction delay. Circulation 1982; 65:1029. https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 11/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate 5. GOUAUX JL, ASHMAN R. Auricular fibrillation with aberration simulating ventricular paroxysmal tachycardia. Am Heart J 1947; 34:366. 6. Bogun F, Anh D, Kalahasty G, et al. Misdiagnosis of atrial fibrillation and its clinical consequences. Am J Med 2004; 117:636. 7. Lindow T, Kron J, Thulesius H, et al. Erroneous computer-based interpretations of atrial fibrillation and atrial flutter in a Swedish primary health care setting. Scand J Prim Health Care 2019; 37:426. 8. https://www.forbes.com/sites/paullamkin/2018/02/22/smartwatch-popularity-booms-with-fi tness-trackers-on-the-slide/#6ebca2b97d96 (Accessed on April 15, 2021). 9. http://www.pewresearch.org/fact-tank/2017/01/12/evolution-of-technology (Accessed on Ap ril 15, 2021). 10. Perez MV, Mahaffey KW, Hedlin H, et al. Large-Scale Assessment of a Smartwatch to Identify Atrial Fibrillation. N Engl J Med 2019; 381:1909. 11. D rr M, Nohturfft V, Brasier N, et al. The WATCH AF Trial: SmartWATCHes for Detection of Atrial Fibrillation. JACC Clin Electrophysiol 2019; 5:199. Topic 1014 Version 27.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 12/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate GRAPHICS Approach to diagnosis of an irregularly irregular supraventricular rhythm* This graphic describes an approach to distinguishing atrial fibrillation (identified with a thick border) from other causes of an irregularly irregular supraventricular rhythm. While atrial fibrillation is the rhythm most commonly described as irregularly irregular, mimics of atrial fibrillation should be excluded when an irregularly irregular rhythm is identified. Of note, atrial fibrillation uncommonly occurs with a regular ventricular rhythm, as described in UpToDate content on the electrocardiogram in atrial fibrillation. ECG: electrocardiogram; AV: atrioventricular; PVCs: premature ventricular complexes; PACs: premature atrial complexes. Refer to UpToDate content on distinguishing supraventricular from ventricular rhythms. https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 13/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate If no atrial activity is detected or the morphology of atrial activity is unclear, use ECG amplification (digital magnification or increase in gain for the entire ECG signal). The ventricular rhythm associated with Mobitz I or II second-degree AV block is not irregularly irregular since there is a pattern to the variation in ventricular rate, but this pattern may not be immediately recognized. Graphic 132103 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 14/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Normal sinus rhythm with artifact Normal sinus rhythm with artifact: 12-lead ECG showing sinus rhythm (best seen in lead V1) along with baseline artifact that resembles AF (most evident in leads II, III, and aVF). The best way to avoid misinterpretation of this AF mimic is to carefully review all leads of the 12-lead tracing, noting any leads with evidence of regular P waves, a consistent PR interval, and a one-to-one correspondence of P waves to QRS complexes (in this case, lead V1 along with the occasional concurrent P waves in lead II demonstrates sinus rhythm). ECG: electrocardiogram; AF: atrial fibrillation. Graphic 132168 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 15/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Normal sinus rhythm with tremor Normal sinus rhythm with tremor: Lead V1 and lead II rhythm strips show sinus rhythm, evident from typical sinus P waves in leads V1 and lead II, with superimposed 3 to 5 Hz oscillations consistent with tremor activity. Graphic 132169 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 16/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Value of increasing ECG gain with possible AF Value of increasing ECG gain with possible AF. (A) Lead V1 and lead II rhythm strips show an irregularly irregular rhythm. At first glance, the rhythm looks li with moderate ventricular response. (B) However, when the gain is increased twofold, it is now apparent that there are P waves preceding each QR th (*). Some P waves (eg, the 1 , 2 5 , 10 , 11 , 12 , and 13 P waves appear to be nonsinus, suggesting frequent atrial premature complex st nd th th th th th rd , 6 , 7 , 8 , 9 , and 14 ) appear to be sinus P waves, while the 3 , 4 th th th th th In this case, magnification of the ECG tracing facilitates recognition of a common AF mimic that could be associated with a preliminary ECG machine interpretation of AF. ECG: electrocardiogram; AF: atrial fibrillation. Graphic 132167 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 17/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate ECG atrial fibrillation Atrial fibrillation. 12-lead ECG shows an irregularly irregular rhythm. Discrete P waves are not seen, and there is fibrillatory atrial activity, best seen in lead V1. The average heart rate is 102 bpm, with a normal axis, QRS duration, and QTc interval, and with nonspecific ST-T changes. ECG: electrocardiogram; bpm: beats per minute. Graphic 132160 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 18/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial fibrillation with a slow, moderate, and rapid ventricular response Atrial fibrillation with a slow (A), moderate (B), and rapid (C) ventricular response. Lead V1 and lead II rhythm strips show irregularly irregular rhythms without discrete P waves and with fibrillatory atrial activity. Graphic 132159 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 19/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial fibrillation with left bundle branch block Atrial fibrillation with LBBB. Rhythm strip shows an irregularly irregular rhythm. Discrete P waves are not seen, and there is fibrillatory atrial activity. The QRS duration is approximately 120 ms, and a complete LBBB is seen with a QS complex in lead V1. LBBB: left bundle branch block. Graphic 132162 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 20/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial fibrillation with complete heart block AF with complete heart block. Lead V1 and lead II rhythm strips show AF with complete heart block with a na complex junctional escape rhythm (A) or with a wide complex ventricular escape rhythm (B). AF: atrial fibrillation. Graphic 132164 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 21/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial fibrillation with fully paced QRS complexes Atrial fibrillation with fully paced QRS complexes (beats 1 ,5, 6, 7, 8). Native ventricular conduction is present (beats 2, 3, 4), and there are complexes (beats 9, 10) where the pacer stimulus occurs while the native complex is being conducted, resulting in a complex that has the same morphology as the native QRS complex (pacemaker pseudofusion). Graphic 132165 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 22/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial fibrillation with ventricular tachycardia AF with ventricular tachycardia. Lead V1 and lead II rhythm strips show AF with rapid ventricular response and the onset of monomorphic ventricular tachycardia at approximately 170 bpm. AF: atrial fibrillation; bpm: beats per minute. Graphic 132166 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 23/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial flutter Atrial flutter. (A) Lead V1 and lead II ECG tracings show AFL with a moderate ventricular response and variable AV conduct with flutter waves discernable in lead II. They are uniform, and occur at a rate of 300/min. Inferiorly directed flutter waves that are positive in V1 are suggestive of typical (cavotricuspid isthmus-dependent), countercloc AFL. (B) Lead V1 and lead II ECG tracings show AFL with moderate ventricular response and variable AV conductio with flutter waves in lead II at a rate of 272 bpm, consistent with typical AFL. ECG: electrocardiogram; AFL: atrial flutter; AV: atrioventricular; bpm: beats per minute. Graphic 132170 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 24/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Sinus rhythm with sinus arrhythmia Sinus rhythm with sinus arrhythmia. Lead V1 and lead II rhythm strips show an irregular rhythm with a ventricular rate that gradually increases, and with each QRS preceded by a sinus P wave, indicating sinus rhythm with sinus arrhythmia. This can mimic AF, especially if the P wave amplitude is low. AF: atrial fibrillation. Graphic 132171 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 25/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate ECG: Sinus arrhythmia and a junctional escape rhythm Sinus arrhythmia and a junctional escape rhythm. Lead V1 and lead II rhythm strips show an irregular

ECG: electrocardiogram; AV: atrioventricular; PVCs: premature ventricular complexes; PACs: premature atrial complexes. Refer to UpToDate content on distinguishing supraventricular from ventricular rhythms. https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 13/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate If no atrial activity is detected or the morphology of atrial activity is unclear, use ECG amplification (digital magnification or increase in gain for the entire ECG signal). The ventricular rhythm associated with Mobitz I or II second-degree AV block is not irregularly irregular since there is a pattern to the variation in ventricular rate, but this pattern may not be immediately recognized. Graphic 132103 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 14/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Normal sinus rhythm with artifact Normal sinus rhythm with artifact: 12-lead ECG showing sinus rhythm (best seen in lead V1) along with baseline artifact that resembles AF (most evident in leads II, III, and aVF). The best way to avoid misinterpretation of this AF mimic is to carefully review all leads of the 12-lead tracing, noting any leads with evidence of regular P waves, a consistent PR interval, and a one-to-one correspondence of P waves to QRS complexes (in this case, lead V1 along with the occasional concurrent P waves in lead II demonstrates sinus rhythm). ECG: electrocardiogram; AF: atrial fibrillation. Graphic 132168 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 15/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Normal sinus rhythm with tremor Normal sinus rhythm with tremor: Lead V1 and lead II rhythm strips show sinus rhythm, evident from typical sinus P waves in leads V1 and lead II, with superimposed 3 to 5 Hz oscillations consistent with tremor activity. Graphic 132169 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 16/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Value of increasing ECG gain with possible AF Value of increasing ECG gain with possible AF. (A) Lead V1 and lead II rhythm strips show an irregularly irregular rhythm. At first glance, the rhythm looks li with moderate ventricular response. (B) However, when the gain is increased twofold, it is now apparent that there are P waves preceding each QR th (*). Some P waves (eg, the 1 , 2 5 , 10 , 11 , 12 , and 13 P waves appear to be nonsinus, suggesting frequent atrial premature complex st nd th th th th th rd , 6 , 7 , 8 , 9 , and 14 ) appear to be sinus P waves, while the 3 , 4 th th th th th In this case, magnification of the ECG tracing facilitates recognition of a common AF mimic that could be associated with a preliminary ECG machine interpretation of AF. ECG: electrocardiogram; AF: atrial fibrillation. Graphic 132167 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 17/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate ECG atrial fibrillation Atrial fibrillation. 12-lead ECG shows an irregularly irregular rhythm. Discrete P waves are not seen, and there is fibrillatory atrial activity, best seen in lead V1. The average heart rate is 102 bpm, with a normal axis, QRS duration, and QTc interval, and with nonspecific ST-T changes. ECG: electrocardiogram; bpm: beats per minute. Graphic 132160 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 18/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial fibrillation with a slow, moderate, and rapid ventricular response Atrial fibrillation with a slow (A), moderate (B), and rapid (C) ventricular response. Lead V1 and lead II rhythm strips show irregularly irregular rhythms without discrete P waves and with fibrillatory atrial activity. Graphic 132159 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 19/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial fibrillation with left bundle branch block Atrial fibrillation with LBBB. Rhythm strip shows an irregularly irregular rhythm. Discrete P waves are not seen, and there is fibrillatory atrial activity. The QRS duration is approximately 120 ms, and a complete LBBB is seen with a QS complex in lead V1. LBBB: left bundle branch block. Graphic 132162 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 20/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial fibrillation with complete heart block AF with complete heart block. Lead V1 and lead II rhythm strips show AF with complete heart block with a na complex junctional escape rhythm (A) or with a wide complex ventricular escape rhythm (B). AF: atrial fibrillation. Graphic 132164 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 21/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial fibrillation with fully paced QRS complexes Atrial fibrillation with fully paced QRS complexes (beats 1 ,5, 6, 7, 8). Native ventricular conduction is present (beats 2, 3, 4), and there are complexes (beats 9, 10) where the pacer stimulus occurs while the native complex is being conducted, resulting in a complex that has the same morphology as the native QRS complex (pacemaker pseudofusion). Graphic 132165 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 22/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial fibrillation with ventricular tachycardia AF with ventricular tachycardia. Lead V1 and lead II rhythm strips show AF with rapid ventricular response and the onset of monomorphic ventricular tachycardia at approximately 170 bpm. AF: atrial fibrillation; bpm: beats per minute. Graphic 132166 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 23/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial flutter Atrial flutter. (A) Lead V1 and lead II ECG tracings show AFL with a moderate ventricular response and variable AV conduct with flutter waves discernable in lead II. They are uniform, and occur at a rate of 300/min. Inferiorly directed flutter waves that are positive in V1 are suggestive of typical (cavotricuspid isthmus-dependent), countercloc AFL. (B) Lead V1 and lead II ECG tracings show AFL with moderate ventricular response and variable AV conductio with flutter waves in lead II at a rate of 272 bpm, consistent with typical AFL. ECG: electrocardiogram; AFL: atrial flutter; AV: atrioventricular; bpm: beats per minute. Graphic 132170 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 24/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Sinus rhythm with sinus arrhythmia Sinus rhythm with sinus arrhythmia. Lead V1 and lead II rhythm strips show an irregular rhythm with a ventricular rate that gradually increases, and with each QRS preceded by a sinus P wave, indicating sinus rhythm with sinus arrhythmia. This can mimic AF, especially if the P wave amplitude is low. AF: atrial fibrillation. Graphic 132171 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 25/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate ECG: Sinus arrhythmia and a junctional escape rhythm Sinus arrhythmia and a junctional escape rhythm. Lead V1 and lead II rhythm strips show an irregular rhythm that initiates with sinus rhythm with sinus arrhythmia and a gradual slowing of heart rate. When the heart rate slows below a rate of approximately 35 bpm, a junctional escape beat appears followed by an atrial premature complex (note the different P wave morphology in lead V1 compared with initial sinus beats). The variation in rate and the presence of some QRS complexes not preceded by a P wave contribute to this rhythm being incorrectly labeled as atrial fibrillation by a preliminary ECG machine interpretation. ECG: electrocardiogram; bpm: beats per minute. Graphic 132172 Version 3.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 26/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Normal sinus rhythm with Mobitz I second-degree AV block Normal sinus rhythm with Mobitz I second-degree AV block. Lead V1 and lead II rhythm strips show a regularly irregular rhythm with group beat. There are distinct P waves before each QRS as well as during the relative pauses. The P-P interval is constant, consistent with a sinus rhythm at a rate of 80 bpm. There is progressive prolongation of the PR interval followed by a dropped beat (nonconducted sinus P wave), reflective of Mobitz I second-degree AV block. AV: atrioventricular; bpm: beats per minute. Graphic 132173 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 27/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Normal sinus rhythm with an ectopic atrial rhythm Normal sinus rhythm with an ectopic atrial rhythm. Lead V1 and lead II rhythm strips show a somewhat irregular narrow QRS complex rhythm that starts off (first 3 beats) with sinus P waves, which then shift to a different (nonsinus) focus, evident by the change in P wave morphology in subsequent beats. Graphic 132174 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 28/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial tachycardia with block Atrial tachycardia with block. Lead V1 and lead II rhythm strips show regular atrial activity at a rate of 160 bpm with variable AV block, consistent with atrial tachycardia with AV block. bpm: beats per minute; AV: atrioventricular. Graphic 132175 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 29/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Wandering atrial pacemaker Wandering atrial pacemaker. Lead V1 and lead II rhythm strips show an irregularly irregular rhythm. On close examination there are more than 3 different P wave morphologies preceding each QRS complex. As the rate is <100 beats per minute, the rhythm is wandering atrial pacemaker (rather than multifocal atrial tachycardia). Graphic 132176 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 30/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Multifocal atrial tachycardia Multifocal atrial tachycardia. Lead V1 and lead II rhythm strips show an irregularly irregular narrow QRS complex rhythm that, on first glance, looks like AF with rapid ventricular response. On closer examination, there are P waves preceding each QRS complex, and, overall, there are more than 3 different P wave morphologies, consistent with the diagnosis of multifocal atrial tachycardia. AF: atrial fibrillation. Graphic 132177 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 31/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Sinus rhythm with frequent PACs with aberrant conduction Sinus rhythm with frequent PACs with aberrant conduction. st rd th th th th (A) Lead V1 and lead II rhythm strips show sinus rhythm with the 1 , 3 , 5 , 7 , 9 , and 11 beats preced t by normal sinus P waves. The 2 nd th th th th th th , 4 , 6 , 8 , 10 , and 12 beats are all PACs. However, while the 4 , 10 th nd th th th and 12 beats conduct normally, the 2 aberrant conduction with a RBBB morphology evident in lead V1. In lead II, the aberrantly conducted PACs ha similar appearance to normally conducted PACs except for a deep terminal S wave and some QRS widening d to the rate-related RBBB. , 6 , 8 , and 12 beats conduct with a wide QRS complex due to rd (B) Lead V1 and lead II rhythm strips show sinus rhythm with a PAC with aberrant conduction (3 beat) and w an interpolated PVC (8 beat). th PACs: premature atrial complexes; RBBB: right bundle branch block; PVC: premature ventricular complex. Graphic 132178 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 32/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate AF with aberrant conduction and concealed conduction AF with aberrant conduction and concealed conduction. Lead V1 and lead II rhythm strips show AF with th rapid ventricular response. Note that the 5 and 6 QRS complexes, as well as the 18 and the 20 to th th th th the 30 QRS complexes, are wide with a right bundle branch pattern apparent in lead V1, while the QRS complexes for these beats in lead II are similar to native AF beats. These are all aberrantly conducted beats. th While the initial or isolated aberrant beats (5 , 18 , and 20 ) occur after a relative long-short interval th th th st th (Ashman phenomenon), the subsequent beats (6 and 21 to 30 ) occur with a short-short sequence but are aberrant due to concealed conduction. For more detail, refer to UpToDate content on the electrocardiogram in atrial fibrillation. AF: Atrial fibrillation. Graphic 132179 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 33/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate AF with Wolff-Parkinson-White syndrome AF with Wolff-Parkinson-White syndrome. 12-lead ECG showing AF with preexcitation. There is an irregular, wide-complex tachycardia, with many QRS complexes showing a slurred upstroke (delta wave). At times, the ventricular rate can be as high as 300 bpm. AF: atrial fibrillation; ECG: electrocardiogram; bpm: beats per minute. Reproduced with permission from: Nathanson LA, McClennen S, Safran C, Goldberger AL. ECG Wave-Maven: Self-Assessment Program for Students and Clinicians. Copyright 2021 Beth Israel Deaconess Medical Center. Available at: http://ecg.bidmc.harvard.edu (Accessed on August 2, 2021). Graphic 132180 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 34/35 7/5/23, 10:40 AM The electrocardiogram in atrial fibrillation - UpToDate Contributor Disclosures Brian Olshansky, MD Other Financial Interest: AstraZeneca [Member of the DSMB for the DIALYZE trial]; Medtelligence [Cardiovascular disease]. All of the relevant financial relationships listed have been mitigated. Zachary D Goldberger, MD, FACC, FHRS Other Financial Interest: Elsevier [Book royalties from Goldberger s Clinical Electrocardiography]. All of the relevant financial relationships listed have been mitigated. Steven M Pogwizd, MD No relevant financial relationship(s) with ineligible companies to disclose. Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 35/35

7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to management - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Wide QRS complex tachycardias: Approach to management : Peter J Zimetbaum, MD : Ary L Goldberger, MD, James Hoekstra, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Jul 11, 2022. INTRODUCTION Tachycardias are broadly categorized based upon the width of the QRS complex on the electrocardiogram (ECG). A narrow QRS complex (<120 milliseconds) reflects rapid activation of the ventricles via the normal His-Purkinje system, which in turn suggests that the arrhythmia originates above or within the atrioventricular (AV) node (ie, a supraventricular tachycardia [SVT]). A widened QRS ( 120 milliseconds) occurs when ventricular activation is abnormally slow for one of the following reasons (see "Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations", section on 'Differential diagnosis of WCT'): The arrhythmia originates outside of the normal conduction system (ie, ventricular tachycardia [VT]) Abnormalities within the His-Purkinje system (ie, SVT with aberrancy) Pre-excitation with an SVT conducting antegrade over an accessory pathway, resulting in direct activation of the ventricular myocardium A wide complex tachycardia (WCT) represents a unique clinical challenge for two reasons: Diagnosing the arrhythmia is difficult Although most WCTs are due to VT, the differential diagnosis includes a variety of SVTs ( algorithm 1). Diagnostic algorithms to differentiate these two etiologies are complex and imperfect. https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-management/print 1/22 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to management - UpToDate Urgent therapy is often required Patients may be unstable at the onset of the arrhythmia or deteriorate rapidly at any time, particularly if the WCT is VT [1-4]. The management of patients with a wide QRS complex tachycardia will be discussed here. The clinical manifestations, diagnosis, and initial evaluation of patients with a wide QRS complex tachycardia, as well as discussion of narrow QRS complex tachycardias, is presented separately. (See "Wide QRS complex tachycardias: Approach to the diagnosis" and "Overview of the acute management of tachyarrhythmias" and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy" and "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation".) MANAGEMENT The acute management of a patient with WCT depends on the hemodynamic stability of the patient [5]. Urgent or emergency management is required in unstable patients, with management taking precedence over further diagnostic workup until the patient has been stabilized. Following initial management and stabilization of the patient, chronic management of the patient with WCT will be directed by the etiology of the WCT (supraventricular versus ventricular). Initial management All patients with a WCT should have a brief immediate assessment of the symptoms, vital signs, and level of consciousness to determine if they are hemodynamic stable or unstable. While the assessment of hemodynamic status is being performed by a clinician, other members of the health care team should: Administer supplemental oxygen Establish intravenous access Send blood for appropriate initial studies (see "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'Ancillary testing') Attach the patient to a continuous cardiac monitor Obtain a 12-lead ECG Differentiation between a hemodynamically stable versus unstable patient is as follows (see "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'Assessment of hemodynamic stability'): An unstable patient will have evidence of hemodynamic compromise, such as hypotension, altered mental status, chest pain, or heart failure, but generally remains awake with a https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-management/print 2/22 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to management - UpToDate discernible pulse. Patients who become unresponsive or pulseless are considered to have a cardiac arrest and are treated according to standard resuscitation algorithms. A stable patient shows no evidence of hemodynamic compromise despite a sustained rapid heart rate, but should have continuous monitoring and frequent reevaluations due to the potential for rapid deterioration as long as the WCT persists. Patients who are initially stable may rapidly become unstable, particularly in the setting of extremely rapid heart rates (greater than 200 beats per minute) or significant underlying cardiac comorbidities. Unstable patients Hemodynamic compromise may occur with any WCT, regardless of the etiology, but is more likely in patients with ventricular tachycardia (VT). Patients who are felt to be hemodynamically unstable require prompt treatment with electrical cardioversion/defibrillation to prevent further clinical deterioration or sudden cardiac arrest (SCA). Patients with WCT who are hemodynamically unstable and pulseless, or who become pulseless during the course of evaluation and treatment, should be managed according to standard advance cardiac life support (ACLS) resuscitation algorithms, with immediate high-energy countershock and cardiopulmonary resuscitation (CPR) ( algorithm 2). Patients should initially be treated with a synchronized (if possible) 120 to 200 joule shock from a biphasic defibrillator or a 360 joule shock from a monophasic defibrillator; if synchronization is not possible, then an unsynchronized countershock should be delivered, typically at higher energy doses [6]. (See "Advanced cardiac life support (ACLS) in adults" and "Adult basic life support (BLS) for health care providers" and "Supportive data for advanced cardiac life support in adults with sudden cardiac arrest".) For patients with WCT who are hemodynamically unstable, but still responsive with a discernible blood pressure and pulse, we recommend urgent cardioversion (with procedural sedation when feasible). The selection of energy level and the choice between synchronized and unsynchronized shocks depends on the clinical situation ( algorithm 3): If the QRS complex and T wave can be distinguished, an attempt at emergent synchronized cardioversion can be performed. Initial cardioversion is performed with a synchronized shock of 100 joules using either a biphasic or monophasic defibrillator, with upward titration of the energy if additional shocks are needed [6]. If the QRS complex and T wave cannot be distinguished accurately, a synchronized shock is not possible. Patients should initially be treated with an unsynchronized 120 to https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-management/print 3/22 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to management - UpToDate 200 joule shock from a biphasic defibrillator or a 360 joule shock from a monophasic defibrillator [6]. Intravenous analgesics or sedatives should be cautiously administered if the blood pressure will tolerate their use. However, the use of such agents must be balanced against the risks of further hemodynamic deterioration, and therapy should not be unnecessarily delayed if the ability to administer conscious sedation is not readily available. Stable patients with uncertain WCT etiology In a patient with WCT who is hemodynamically stable, additional time may be spent attempting to determine the diagnosis. If the initial diagnosis of WCT was made from a single-lead rhythm strip, a full 12-lead ECG should be obtained during the WCT and methodically reviewed as this may provide additional clues to the etiology. In addition, a trial of vagal maneuvers and/or pharmacologic intervention can provide both diagnostic information and, on occasion, prove therapeutic if there is resolution of the WCT. (See "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'Evaluation of the electrocardiogram'.) For hemodynamically stable patients with WCT which is regular and monomorphic in whom the etiology of the WCT remains uncertain, we suggest the following approach ( algorithm 3): Perform vagal maneuvers (Valsalva, carotid sinus massage, etc) Introducing transient block at the AV node can serve as a diagnostic/therapeutic challenge. Most supraventricular tachycardias (SVTs) are AV node dependent (eg, atrioventricular nodal reentrant tachycardia, atrioventricular reentrant tachycardia [AVRT]), so transient AV nodal block will terminate most SVTs. Atrial flutter and atrial tachycardia may be "unmasked" by transient AVN block. Vagal maneuvers should have no significant effect on VT. (See "Vagal maneuvers".) Administer adenosine Intravenous adenosine has essentially the same effect as vagal maneuvers on SVT and atrial flutter/tachycardia. Some idiopathic VTs (eg, right ventricular outflow tract [RVOT] VT) may terminate with adenosine. Resuscitation equipment should be immediately available as rarely adenosine will precipitate hemodynamic collapse. The initial dose of adenosine is 6 mg; if this has no effect, 12 mg can be administered. Avoidance of other pharmacologic agents Intravenous beta blockers, calcium channel blockers, and digoxin are not typically used, due to the potential for hemodynamic deterioration (often the result of hypotension) in patients with a previously stable WCT. https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-management/print 4/22 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to management - UpToDate Further treatment is directed by the response to vagal maneuvers and/or adenosine, specifically targeting VT or the relevant SVT. If the WCT persists and the etiology remains uncertain, we proceed as though the WCT is VT and treat accordingly. (See 'Stable patients with known WCT etiology' below.) While any ECG analysis and diagnostic/therapeutic maneuvers are being performed, close observation and continuous ECG monitoring are paramount, as patients with WCT who appear stable initially may experience a rapid deterioration of their clinical status with little or no warning. Vagal maneuvers In patients with WCT of uncertain etiology, the response to vagal maneuvers may provide insight to the mechanism responsible for the arrhythmia. We perform one or more vagal maneuvers in all patients with WCT who are hemodynamically stable, often while preparing for pharmaceutical therapy or cardioversion. However, these interventions are associated with some risk, primarily the potential for hemodynamic deterioration in a borderline unstable patient, and as such should only be performed by experienced individuals in an environment capable of dealing with potential sequelae. Vagal maneuvers increase parasympathetic input to the heart, which slows the rate of sinus node impulse formation and slows AV node conduction velocity while simultaneously lengthening the refractory period. The Valsalva maneuver and carotid sinus massage, two of the most commonly performed vagal maneuvers which enhance vagal tone and therefore depresses sinus and AV nodal activity, can be easily and quickly done at the bedside. (See "Vagal maneuvers".) Examples of how various arrhythmias respond to vagal stimulation include (see "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'Possible outcomes following vagal maneuvers or adenosine administration'): Sinus tachycardia will gradually slow during the maneuver and then accelerate upon completion of the maneuver. During atrial tachycardia or atrial flutter, the ventricular response will transiently slow (due to increased AV nodal blockade). The arrhythmia itself, which occurs within the atria, is usually unaffected. A paroxysmal SVT (either atrioventricular nodal reentrant tachycardia [AVNRT] or AVRT) will frequently terminate because of the dependence on the AV node. VT is generally unaffected by vagal maneuvers, although these maneuvers may slow or block retrograde conduction. In some cases, this response exposes AV dissociation by https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-management/print 5/22 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to management - UpToDate altering the sinus rate (or PP intervals). Rarely, VT terminates in response to carotid sinus pressure. Pharmacologic interventions In patients with WCT of uncertain etiology, the response to the administration of certain drugs can provide diagnostic information, which in certain circumstances may also provide a therapeutic benefit (eg, adenosine which may terminate some SVTs) [5]. However, some drugs used for the diagnosis or treatment of SVT (eg, verapamil, adenosine, or beta blockers) can cause severe hemodynamic deterioration (often the result of hypotension) in patients with a previously stable VT, potentially resulting in ventricular fibrillation (VF) and cardiac arrest [1-3]. Thus, other than adenosine, these medications are generally reserved for the treatment of patients in whom the diagnosis of SVT is already known; they are rarely used for diagnostic purposes for a WCT. (See 'Supraventricular tachycardia' below.) Adenosine slows conduction time through the AV node. Arrhythmias that are dependent upon the AV node (eg, AVNRT, AVRT) will frequently be terminated following adenosine administration. Adenosine will usually not terminate other non-AV node dependent arrhythmias; a subgroup of atrial tachycardias may be adenosine sensitive. In addition, some idiopathic VTs (specifically RV outflow tract VT) may terminate with adenosine. If the tachycardia does not terminate, the ventricular response following adenosine administration is often helpful in distinguishing the etiology of the WCT. Not infrequently, adenosine will promote the conversion of SVT to atrial fibrillation (AF). If the patient has underlying Wolff-Parkinson-White (WPW) syndrome, this may lead to extremely rapid ventricular rates, and potentially deterioration to VF. Thus, an external defibrillator should always be available. (See "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'Possible outcomes following vagal maneuvers or adenosine administration'.) If there is no change in the ventricular rate and rhythm, the WCT is likely VT. One exception would be if the adenosine was not properly administered (ie, rapid intravenous push followed by saline flush) and, because of its short half-life and metabolism by red blood cells, did not reach the heart. If the ventricular activity temporarily slows or ceases (for 5 to 10 seconds), the remaining atrial activity is typically easily seen on the ECG and can be analyzed to determine the etiology of WCT. A second dose of 12 mg of adenosine, although appropriate for the treatment of known SVT, is probably not appropriate for WCT that is not known to be SVT. Adenosine is administered via rapid intravenous push, followed immediately by 10 mL saline flush. Common side effects include facial flushing, shortness of breath, palpitations, chest pain, https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-management/print 6/22 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to management - UpToDate and lightheadedness. (See "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'Administration and side effects'.) Stable patients with known WCT etiology In a patient with WCT who is hemodynamically stable, therapy may be targeted to the specific arrhythmia (VT or SVT) when identifiable from the available data. (See "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'ECG initial impressions'.) VT should be suspected in patients with clearly identified AV dissociation, patients with QRS concordance and a right superior axis (or axis shift of greater than 40 degrees from baseline), and in patients with known structural heart disease. VT is typically regular, though slight variation of the RR interval may be seen. SVT should be suspected in young patients with structurally normal hearts in whom none of the historical (eg, family history of sudden cardiac death), physical, or ECG criteria supporting VT are present, or in patients with a history of SVT with a similar presentation. The RR interval in SVT is generally very regular. Significant irregularity in a WCT is most often seen in patients with AF and aberrant conduction, though polymorphic VT is also irregular. Patients with AF should have similar QRS morphologies for every beat, while the QRS morphology varies in polymorphic VT. An important exception is pre-excited AF in patients with WPW syndrome, in which the QRS morphology is variable in width and morphology. (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis", section on 'Atrial fibrillation'.) Ventricular tachycardia Once the WCT has been established as VT, therapy should be promptly provided. Patients with VT who are hemodynamically stable may remain stable or may become unstable rapidly and without warning. The choice of initial treatments for hemodynamically stable VT includes electrical or pharmacologic cardioversion. Some of our experts proceed directly to electrical cardioversion, while others prefer to begin with an intravenous antiarrhythmic agent and reserve cardioversion for refractory patients or for those who become unstable. If electrical cardioversion with appropriate procedural sedation is the chosen approach, intravenous analgesics or sedatives should be cautiously administered if the blood pressure will tolerate their use. If the QRS complex and T wave can be distinguished, an attempt at emergent synchronized cardioversion can be performed with a synchronized shock of 100 joules using either a biphasic or monophasic defibrillator. If the QRS complex and T wave cannot be distinguished accurately, and a synchronized shock is not possible, https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-management/print 7/22 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to management - UpToDate we administer an unsynchronized 120 to 200 joule shock from a biphasic defibrillator or a 360 joule shock from a monophasic defibrillator. If pharmacologic cardioversion is the chosen approach, we administer intravenous amiodarone (150 mg IV over 10 minutes, followed by 1 mg/minute for the next six hours) or procainamide (20 to 50 mg per minute until arrhythmia terminates or a maximum dose of 17 mg/kg is administered). Often administration of these drugs may result in hypotension, which may hasten the need for electrical cardioversion. (See 'Recurrent or refractory WCT' below.) Any associated conditions should be treated, including cardiac ischemia, heart failure, electrolyte abnormalities, or drug toxicities. For patients with one of the known syndromes of VT in structurally normal hearts, calcium channel blockers or beta blockers may be used, particularly if the patient has been successfully treated in the past with such medications. These drugs can be used either to terminate the arrhythmia, or after cardioversion to suppress recurrences. (See "Ventricular tachycardia in the absence of apparent structural heart disease".) Given the risk for hemodynamic deterioration at any time, an external defibrillator should be immediately available at all times prior to and during the administration of any antiarrhythmic drugs. Supraventricular tachycardia Once the WCT has been definitively established as SVT, therapy directed at the SVT may be given. In such cases, management is similar to an SVT with a normal QRS duration [5]. The ECG recording when the tachycardia slows or terminates can provide valuable information for diagnosing the specific type of SVT. Thus, in a stable patient, a continuous rhythm strip, preferably a 12-lead rhythm strip, should be recorded during any intervention intended to terminate the arrhythmia or slow the ventricular response. For patients with known SVT, we suggest the following approach: If the SVT is likely to be AVNRT or AVRT, or if the specific SVT diagnosis is uncertain, the following treatments are recommended: Vagal maneuvers We recommend Valsalva maneuver or carotid sinus pressure (if no carotid bruits are present) as the initial intervention, given the ease with which this can be rapidly performed at the bedside. Adenosine For patients with persistent SVT following vagal maneuvers, adenosine is highly effective in terminating many SVTs (eg, AVNRT, AVRT), and for others (eg, AF, https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-management/print 8/22 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to management - UpToDate atrial flutter), adenosine may facilitate the diagnosis by slowing the ventricular response to allow clearer assessment of atrial activity [7]. The usual initial dose is 6 mg, which can be followed by a maximal single dose of 12 mg if not successful. The drug is administered by rapid intravenous injection over one to two seconds at a peripheral site, followed by a normal saline flush, most easily accomplished through a three-way stopcock. Repeated dosing beyond the 12 mg bolus is not usually effective. If a central intravenous access site is used, the initial dose should not exceed 3 mg and may be as little as 1 mg. Not infrequently, adenosine will promote the conversion of SVT to AF. If the patient has underlying WPW syndrome, this may lead to extremely rapid ventricular rates, and potentially deterioration to VF. Thus, an external defibrillator should always be available. (See "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'Administration and side effects'.) Calcium channel blockers or beta blockers If SVT persists after vagal maneuvers and adenosine administration, the choice of initial pharmacologic therapies includes non-dihydropyridine calcium channel blockers and beta blockers. We generally start with intravenous verapamil (5 to 10 mg IV bolus over two minutes; if no response, an additional 10 mg IV bolus may be administered 15 to 30 minutes following the initial dose) or diltiazem (15 to 20 mg IV), although a beta blocker (eg, metoprolol 2.5 to 5 mg IV bolus over two to five minutes; if no response, additional 2.5 to 5 mg IV boluses may be given to a total dose of 15 mg over 15 minutes) may be given. These medications can terminate AVNRT or AVRT, as well as some atrial tachycardias. If the specific SVT diagnosis remains unknown, these drugs may slow the ventricular response and facilitate diagnosis. Cardioversion Electrical cardioversion is rarely necessary in patients with a stable SVT. However, if WCT persist after the above interventions, synchronized cardioversion is usually effective in restoring sinus rhythm. Following appropriate procedural sedation, an initial synchronized shock of 100 to 200 joules (monophasic) or 50 to 100 joules (biphasic) is administered. If the arrhythmia is known to be atrial fibrillation, atrial flutter, or an atrial tachycardia, management options include rate control and cardioversion (ie, rhythm control). Decisions regarding which strategy is appropriate in a given patient are addressed separately. (See "Overview of atrial flutter" and "Atrial fibrillation: Overview and management of new-onset atrial fibrillation".) After the WCT is terminated or controlled, the further management of an SVT depends upon which SVT is present. (See "Atrioventricular nodal reentrant tachycardia" and "Atrioventricular https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-management/print 9/22 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to management - UpToDate reentrant tachycardia (AVRT) associated with an accessory pathway".) Patients with a pacemaker Patients with a permanent pacemaker are subject to the same array of WCTs as patients without a pacemaker. Rarely, however, WCT can result from a pacemaker tracking an underlying atrial arrhythmia or be due to pacemaker-mediated tachycardia. Most patients with WCT involving a pacemaker will be hemodynamically stable, unless the resulting tachycardia exacerbated underlying comorbidities (eg, angina, heart failure, etc). If the WCT is thought to be directly related to the function of the pacemaker, the appropriate therapy is the placement of a magnet over the pacemaker. The magnet will disable all pacemaker sensing, thereby terminating the ability of the pacemaker to track atrial impulses. With the magnet, the pacemaker will function in an asynchronous, fixed-rate mode (ie, VOO or DOO). In this situation, there will be pacemaker stimuli that do not sense the P wave or QRS complex and will occur with a fixed rate (ie, the lower rate limit of the pacemaker). If WCT is due to pacemaker-mediated tachycardia (PMT) or "pseudo PMT" (non-reentrant repetitive VA synchrony), transient magnet application will terminate the WCT, and the underlying rhythm (with pacing, if appropriate) will ensue when the magnet is removed. If the WCT is due to inappropriate tracking of atrial fibrillation or atrial flutter, the WCT will likely resume once the magnet is removed. Patients with pacemakers may also be subject to WCTs that do not involve the pacemaker, like other patients. In stable patients, the pacemaker programmer can be used to telemeter the intracardiac electrograms from the pacemaker leads. Examination of these electrograms may yield the diagnosis, as in the electrophysiology laboratory. Patients with an ICD Patients with an implantable cardioverter-defibrillator (ICD) represent a specific high-risk population in whom WCT is far more likely to represent VT. Patients who underwent ICD implantation for secondary prevention have previously experienced a sustained ventricular tachyarrhythmia or sudden cardiac death, while those who received an ICD for primary prevention were felt to be at increased risk of sustained ventricular tachyarrhythmia. In either case, WCT in patients with an ICD should be treated as VT until proven otherwise. When no ICD therapy has been delivered, and the device cannot be immediately interrogated (due either to lack of equipment or personnel, or patient instability), the initial management should proceed as if no ICD were present. The presence of an ICD has a number of unique implications for patients with a WCT. Although the ICD should be programmed to delivery therapies (either antitachycardia pacing or shocks) for a WCT, such therapies are usually delivered within the first minutes of the arrhythmia. https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-management/print 10/22 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to management - UpToDate In a patient with a persistent or recurrent WCT, the ICD may not always provide definitive management if the device has reached the limit of programmed therapies. Patients with a WCT which persists following multiple ICD therapies most likely have either VT storm with an underlying trigger (eg, ischemia, hypokalemia) or an SVT with aberrant conduction which recurs or persists in spite of the ICD therapies. (See "Electrical storm and incessant ventricular tachycardia".) Patients with and ICD and WCT will not receive therapy from the ICD if the WCT rate is lower than the programmed rate for ICD therapy. Patients with an ICD who receive multiple shocks but do not have a tachycardia most likely have device malfunction, usually related to lead malfunction. In these patients, magnet application can temporarily suspend tachycardia therapy and prevent further inappropriate shocks. Magnet application is also appropriate in patients receiving shocks for narrow complex tachyarrhythmias (SVT, AF, atrial flutter, sinus tachycardia). (See "Cardiac implantable electronic devices: Long-term complications".) All modern ICDs also have the capacity to function as a pacemaker. Patients with a single lead ICD (typically an endovascular lead in the right ventricle) cannot sense and track atrial arrhythmias and, as such, are not subject to WCT associated with the device. Conversely, patients with both an atrial and a ventricular lead have the capacity to sense and track atrial arrhythmias and therefore can potentially develop WCT associated with the pacemaker. However, given the risk of WCT representing VT in a patient with an ICD, pacemaker-associated WCT should be considered only after exclusion of other WCT etiologies and following ICD interrogation. Magnet application does not force asynchronous pacing in ICDs and will therefore not terminate PMT in patients with ICDs. As in pacemaker patients, telemetered intracardiac recordings may be helpful diagnostically. (See 'Patients with a pacemaker' above.) Recurrent or refractory WCT If the WCT recurs or persists following initial attempts at vagal maneuvers, diagnostic pharmacologic interventions, and electrical cardioversion, suppression of the arrhythmia by pharmacologic means should be attempted and further evaluation should focus upon the presence of arrhythmia triggers (eg, ischemia, electrolyte abnormalities, and drug toxicity). Amiodarone is generally the most effective agent for treatment of recurrent or refractory WCT, particularly VT [6]. Cardioversion or defibrillation should be repeated as necessary in patients who are hemodynamically unstable. (See "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis".) For patients with recurrent VT or WCT of uncertain etiology, we suggest the following: https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-management/print 11/22 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to management - UpToDate Amiodarone is administered in most settings, due to its efficacy in the suppression of both atrial and ventricular arrhythmias. The initial dose is 150 mg IV over 10 minutes followed by an infusion of 1 mg/minute for six hours, then 0.5 mg/minute for an additional 18 hours or longer. Repeat amiodarone boluses can be administered if necessary. Procainamide is an alternative to amiodarone that also suppresses both SVTs and VT. The initial dose is 15 to 18 mg/kg administered as slow infusion over 25 to 30 minutes, followed by 1 to 4 mg/minute by continuous infusion. In addition, because of its ability to suppress conduction over a bypass tract, procainamide is recommended if antidromic AVRT or an SVT conducting over a bypass tract is suspected. For pre-excited atrial fibrillation or atrial flutter, intravenous procainamide or ibutilide is recommended; amiodarone and AV nodal blocking agents are not recommended. (See "Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome".) For patients with a known SVT that recurs or persists, intravenous verapamil, diltiazem, or beta blockers may be used. Multiple recurrences of WCT should raise concern about cardiac ischemia, hypokalemia, digitalis toxicity, and polymorphic VT with or without QT prolongation, all of which have specific appropriate therapy. (See "Overview of the acute management of ST-elevation myocardial infarction" and "Overview of the acute management of non-ST-elevation acute coronary syndromes" and "Cardiac arrhythmias due to digoxin toxicity" and "Clinical manifestations and treatment of hypokalemia in adults", section on 'Treatment' and "Acquired long QT syndrome: Clinical manifestations, diagnosis, and management".) Chronic therapy Chronic therapy for patients with WCT will be driven by the underlying etiology of the WCT. Patients with VT should generally undergo implantation of an ICD. Following ICD implantation, those patients with recurrent symptomatic VT, or those who have received multiple ICD therapies, may require adjunctive antiarrhythmic therapy in an effort to suppress recurrent VT. In some cases, radiofrequency catheter ablation may be an option to reduce the frequency of VT. An important exception is idiopathic VT, which is treated with ablation or pharmacologic therapy, not with ICD. (See "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis", section on 'Chronic therapy' and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy", section on 'Other treatment options'.) https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-management/print 12/22 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to management - UpToDate The approach to patients with WCT due to an SVT will vary significantly depending upon the etiology of the SVT. Patients with AVNRT or AVRT associated with a concealed accessory pathway may require no therapy, may be able to self-terminate arrhythmias using vagal maneuvers, may be candidates for pharmacologic suppressive therapy, or may be effectively cured with catheter ablation. (See "Atrioventricular nodal reentrant tachycardia", section on 'Preventive therapy' and "Treatment of arrhythmias associated with the Wolff- Parkinson-White syndrome", section on 'Treatment to prevent recurrent arrhythmias'.) Patients with AVRT associated with a manifest accessory pathway or pre-excited atrial fibrillation or atrial flutter (ie, patients with arrhythmias related to WPW) should undergo electrophysiology testing and catheter ablation of accessory pathway due to the small risk of sudden cardiac death in patients with symptomatic WPW syndrome. (See "Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome", section on 'Treatment to prevent recurrent arrhythmias'.) The approach to a patient with atrial fibrillation may include ventricular rate control, restoration of sinus rhythm, or catheter ablation. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation".) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Arrhythmias in adults" and "Society guideline links: Ventricular arrhythmias" and "Society guideline links: Cardiac implantable electronic devices" and "Society guideline links: Supraventricular arrhythmias".) SUMMARY AND RECOMMENDATIONS The acute management of a patient with wide QRS complex tachycardia (WCT) depends on the hemodynamic stability of the patient. Urgent or emergency management is required in unstable patients, with management taking precedence over further diagnostic workup until the patient has been stabilized. Following initial management and stabilization of the patient, chronic management of the patient with WCT will be directed by the etiology of the WCT (supraventricular versus ventricular). (See 'Management' above.) https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-management/print 13/22 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to management - UpToDate All patients with a WCT should have a brief immediate assessment of the symptoms, vital signs, and level of consciousness to determine if they are hemodynamic stable or unstable. An unstable patient will have evidence of hemodynamic compromise, such as hypotension, altered mental status, chest pain, or heart failure, whereas a stable patient shows none of these despite a sustained rapid heart rate. (See 'Initial management' above.) While the assessment of hemodynamic status is being performed by a clinician, other members of the health care team should administer supplemental oxygen, establish intravenous access, send blood for appropriate initial studies, attach the patient to a continuous cardiac monitor, and obtain a 12-lead electrocardiogram (ECG). (See 'Initial management' above and "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'Ancillary testing'.) Patients with WCT who are hemodynamically unstable and pulseless, or who become pulseless during the course of evaluation and treatment, should be managed according to standard advance cardiac life support (ACLS) resuscitation algorithms, with immediate high-energy defibrillation and cardiopulmonary resuscitation (CPR) ( algorithm 2). Patients should initially be treated with a synchronized (if possible) 120 to 200 joule shock from a biphasic defibrillator or a 360 joule shock from a monophasic defibrillator. An unsynchronized shock should be delivered if synchronization is not possible [6]. (See 'Unstable patients' above and "Advanced cardiac life support (ACLS) in adults" and "Adult basic life support (BLS) for health care providers".) For patients with WCT who are hemodynamically unstable, but still responsive with a discernible blood pressure and pulse, we recommend urgent cardioversion (with procedural sedation when feasible) (Grade 1A). (See 'Unstable patients' above.) If the QRS complex and T wave can be distinguished, an attempt at emergency synchronized cardioversion can be performed with a synchronized shock of 100 joules using either a biphasic or monophasic defibrillator. If the QRS complex and T wave cannot be distinguished accurately, and a synchronized shock is not possible, we administer an unsynchronized 120 to 200 joule shock from a biphasic defibrillator or a 360 joule shock from a monophasic defibrillator. For hemodynamically stable patients with WCT which is regular and monomorphic in whom the etiology of the WCT remains uncertain, we suggest vagal maneuvers (ie, Valsalva, carotid sinus massage) followed by intravenous adenosine if no response to the vagal maneuvers (Grade 2C). Further treatment is directed by the response to vagal maneuvers and/or adenosine, specifically targeting ventricular tachycardia (VT) or the https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-management/print 14/22 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to management - UpToDate relevant supraventricular tachycardia (SVT). If the WCT persists and the etiology remains uncertain, we proceed as though the WCT is VT and treat accordingly. (See 'Stable patients with uncertain WCT etiology' above.) For patients who are hemodynamically stable and known to have VT, some of our experts proceed directly to electrical cardioversion, while others prefer to begin with an intravenous antiarrhythmic agent and reserve cardioversion for refractory patients or for those who become unstable. (See 'Ventricular tachycardia' above.) For patients who are hemodynamically stable and known to have SVT, we suggest the following approach (Grade 2C) (see 'Supraventricular tachycardia' above): If the SVT is likely to be atrioventricular nodal reentrant tachycardia (AVNRT) or atrioventricular reciprocating tachycardia (AVRT), we perform vagal maneuvers, followed by adenosine, followed by intravenous verapamil or diltiazem, and, in

toxicity, and polymorphic VT with or without QT prolongation, all of which have specific appropriate therapy. (See "Overview of the acute management of ST-elevation myocardial infarction" and "Overview of the acute management of non-ST-elevation acute coronary syndromes" and "Cardiac arrhythmias due to digoxin toxicity" and "Clinical manifestations and treatment of hypokalemia in adults", section on 'Treatment' and "Acquired long QT syndrome: Clinical manifestations, diagnosis, and management".) Chronic therapy Chronic therapy for patients with WCT will be driven by the underlying etiology of the WCT. Patients with VT should generally undergo implantation of an ICD. Following ICD implantation, those patients with recurrent symptomatic VT, or those who have received multiple ICD therapies, may require adjunctive antiarrhythmic therapy in an effort to suppress recurrent VT. In some cases, radiofrequency catheter ablation may be an option to reduce the frequency of VT. An important exception is idiopathic VT, which is treated with ablation or pharmacologic therapy, not with ICD. (See "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis", section on 'Chronic therapy' and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy", section on 'Other treatment options'.) https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-management/print 12/22 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to management - UpToDate The approach to patients with WCT due to an SVT will vary significantly depending upon the etiology of the SVT. Patients with AVNRT or AVRT associated with a concealed accessory pathway may require no therapy, may be able to self-terminate arrhythmias using vagal maneuvers, may be candidates for pharmacologic suppressive therapy, or may be effectively cured with catheter ablation. (See "Atrioventricular nodal reentrant tachycardia", section on 'Preventive therapy' and "Treatment of arrhythmias associated with the Wolff- Parkinson-White syndrome", section on 'Treatment to prevent recurrent arrhythmias'.) Patients with AVRT associated with a manifest accessory pathway or pre-excited atrial fibrillation or atrial flutter (ie, patients with arrhythmias related to WPW) should undergo electrophysiology testing and catheter ablation of accessory pathway due to the small risk of sudden cardiac death in patients with symptomatic WPW syndrome. (See "Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome", section on 'Treatment to prevent recurrent arrhythmias'.) The approach to a patient with atrial fibrillation may include ventricular rate control, restoration of sinus rhythm, or catheter ablation. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation".) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Arrhythmias in adults" and "Society guideline links: Ventricular arrhythmias" and "Society guideline links: Cardiac implantable electronic devices" and "Society guideline links: Supraventricular arrhythmias".) SUMMARY AND RECOMMENDATIONS The acute management of a patient with wide QRS complex tachycardia (WCT) depends on the hemodynamic stability of the patient. Urgent or emergency management is required in unstable patients, with management taking precedence over further diagnostic workup until the patient has been stabilized. Following initial management and stabilization of the patient, chronic management of the patient with WCT will be directed by the etiology of the WCT (supraventricular versus ventricular). (See 'Management' above.) https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-management/print 13/22 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to management - UpToDate All patients with a WCT should have a brief immediate assessment of the symptoms, vital signs, and level of consciousness to determine if they are hemodynamic stable or unstable. An unstable patient will have evidence of hemodynamic compromise, such as hypotension, altered mental status, chest pain, or heart failure, whereas a stable patient shows none of these despite a sustained rapid heart rate. (See 'Initial management' above.) While the assessment of hemodynamic status is being performed by a clinician, other members of the health care team should administer supplemental oxygen, establish intravenous access, send blood for appropriate initial studies, attach the patient to a continuous cardiac monitor, and obtain a 12-lead electrocardiogram (ECG). (See 'Initial management' above and "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'Ancillary testing'.) Patients with WCT who are hemodynamically unstable and pulseless, or who become pulseless during the course of evaluation and treatment, should be managed according to standard advance cardiac life support (ACLS) resuscitation algorithms, with immediate high-energy defibrillation and cardiopulmonary resuscitation (CPR) ( algorithm 2). Patients should initially be treated with a synchronized (if possible) 120 to 200 joule shock from a biphasic defibrillator or a 360 joule shock from a monophasic defibrillator. An unsynchronized shock should be delivered if synchronization is not possible [6]. (See 'Unstable patients' above and "Advanced cardiac life support (ACLS) in adults" and "Adult basic life support (BLS) for health care providers".) For patients with WCT who are hemodynamically unstable, but still responsive with a discernible blood pressure and pulse, we recommend urgent cardioversion (with procedural sedation when feasible) (Grade 1A). (See 'Unstable patients' above.) If the QRS complex and T wave can be distinguished, an attempt at emergency synchronized cardioversion can be performed with a synchronized shock of 100 joules using either a biphasic or monophasic defibrillator. If the QRS complex and T wave cannot be distinguished accurately, and a synchronized shock is not possible, we administer an unsynchronized 120 to 200 joule shock from a biphasic defibrillator or a 360 joule shock from a monophasic defibrillator. For hemodynamically stable patients with WCT which is regular and monomorphic in whom the etiology of the WCT remains uncertain, we suggest vagal maneuvers (ie, Valsalva, carotid sinus massage) followed by intravenous adenosine if no response to the vagal maneuvers (Grade 2C). Further treatment is directed by the response to vagal maneuvers and/or adenosine, specifically targeting ventricular tachycardia (VT) or the https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-management/print 14/22 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to management - UpToDate relevant supraventricular tachycardia (SVT). If the WCT persists and the etiology remains uncertain, we proceed as though the WCT is VT and treat accordingly. (See 'Stable patients with uncertain WCT etiology' above.) For patients who are hemodynamically stable and known to have VT, some of our experts proceed directly to electrical cardioversion, while others prefer to begin with an intravenous antiarrhythmic agent and reserve cardioversion for refractory patients or for those who become unstable. (See 'Ventricular tachycardia' above.) For patients who are hemodynamically stable and known to have SVT, we suggest the following approach (Grade 2C) (see 'Supraventricular tachycardia' above): If the SVT is likely to be atrioventricular nodal reentrant tachycardia (AVNRT) or atrioventricular reciprocating tachycardia (AVRT), we perform vagal maneuvers, followed by adenosine, followed by intravenous verapamil or diltiazem, and, in refractory cases, electrical cardioversion. If the SVT terminates after any of the interventions, the subsequent interventions are not performed acutely. If the arrhythmia is known to be atrial fibrillation (AF), atrial flutter, or an atrial tachycardia, management options include rate control and cardioversion (ie, rhythm control). (See "Overview of atrial flutter" and "Atrial fibrillation: Overview and management of new-onset atrial fibrillation".) If the WCT is thought to be directly related to the function of pacemaker, the appropriate therapy is the placement of a magnet over the pacemaker. (See 'Patients with a pacemaker' above.) Chronic therapy for patients with WCT will be driven by the underlying etiology of the WCT, with patients having VT generally considered for implantable cardioverter-defibrillator (ICD) implantation, while therapy for patients with SVT will need to be tailored to the underlying arrhythmia. (See 'Chronic therapy' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-management/print 15/22 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to management - UpToDate REFERENCES 1. Buxton AE, Marchlinski FE, Doherty JU, et al. Hazards of intravenous verapamil for sustained ventricular tachycardia. Am J Cardiol 1987; 59:1107. 2. Stewart RB, Bardy GH, Greene HL. Wide complex tachycardia: misdiagnosis and outcome after emergent therapy. Ann Intern Med 1986; 104:766. 3. Dancy M, Camm AJ, Ward D. Misdiagnosis of chronic recurrent ventricular tachycardia. Lancet 1985; 2:320. 4. Akhtar M, Shenasa M, Jazayeri M, et al. Wide QRS complex tachycardia. Reappraisal of a common clinical problem. Ann Intern Med 1988; 109:905. 5. Brugada J, Katritsis DG, Arbelo E, et al. 2019 ESC Guidelines for the management of patients with supraventricular tachycardiaThe Task Force for the management of patients with supraventricular tachycardia of the European Society of Cardiology (ESC). Eur Heart J 2020; 41:655. 6. Link MS, Atkins DL, Passman RS, et al. Part 6: electrical therapies: automated external defibrillators, defibrillation, cardioversion, and pacing: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010; 122:S706. 7. Gupta AK, Thakur RK. Wide QRS complex tachycardias. Med Clin North Am 2001; 85:245. Topic 101641 Version 31.0 https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-management/print 16/22 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to management - UpToDate GRAPHICS Algorithm for the initial ECG review and differential diagnosis of tachycardia ECG: electrocardiogram; AVNRT: atrioventricular nodal reentrant tachycardia; AVRT: atrioventricular reciprocating (bypass-tract mediated) tachycardia; AT: atrial tachycardia; SANRT: sinoatrial nodal reentrant tachycardia; AF: atrial fibrillation; AV: atrioventricular; VT: ventricular tachycardia; SVT: supraventricular tachycardia; WPW: Wolff-Parkinson-White. A narrow QRS complex is <120 milliseconds in duration, whereas a wide QRS complex is 120 milliseconds duration. Refer to UpToDate topic reviews for additional details on specific ECG findings and management of individu arrhythmias. Monomorphic VT accounts for 80% of wide QRS complex tachycardias; refer to UpToDate topic on diagnosi wide QRS complex tachycardias for additional information on discriminating VT from SVT. Graphic 117571 Version 3.0 https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-management/print 17/22 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to management - UpToDate Adult cardiac arrest algorithm https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-management/print 18/22 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to management - UpToDate https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-management/print 19/22 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to management - UpToDate Reprinted with permission. Highlights of the 2020 American Heart Association Guidelines for CPR and ECC. Copyright 2020 American Association, Inc. Graphic 129983 Version 9.0 https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-management/print 20/22 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to management - UpToDate Adult tachycardia with a pulse algorithm 2020 update Reprinted with permission. ACLS Provider Manual. Copyright 2020 American Heart Association, Inc. Graphic 130747 Version 10.0 https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-management/print 21/22 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to management - UpToDate Contributor Disclosures Peter J Zimetbaum, MD Consultant/Advisory Boards: Abbott Medical [Lead extraction]. All of the relevant financial relationships listed have been mitigated. Ary L Goldberger, MD Other Financial Interest: Elsevier book royalties [Clinical electrocardiography]. All of the relevant financial relationships listed have been mitigated. James Hoekstra, MD No relevant financial relationship(s) with ineligible companies to disclose. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-management/print 22/22

7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Wide QRS complex tachycardias: Approach to the diagnosis : Peter J Zimetbaum, MD : Ary L Goldberger, MD, James Hoekstra, MD, N A Mark Estes, III, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Jun 13, 2022. INTRODUCTION Tachycardias are broadly categorized ( algorithm 1) based upon the width of the QRS complex on the electrocardiogram (ECG). A narrow QRS complex (<120 milliseconds) reflects rapid activation of the ventricles via the normal His-Purkinje system, which in turn suggests that the arrhythmia originates above or within the atrioventricular (AV) node (ie, a supraventricular tachycardia [SVT]). A widened QRS complex ( 120 milliseconds) occurs when ventricular activation is abnormally slow for one of the following reasons (see "Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations", section on 'Differential diagnosis of WCT'): The arrhythmia originates outside of the normal conduction system and below the AV node (ie, ventricular tachycardia [VT]) Abnormalities within the His-Purkinje system (ie, SVT with aberrancy) Pre-excitation with an SVT conducting antegrade over an accessory pathway, resulting in direct activation of the ventricular myocardium A wide QRS complex tachycardia (WCT) represents a unique clinical challenge for two reasons: Diagnosing the arrhythmia is difficult Although most WCTs are due to VT, the differential diagnosis includes a variety of SVTs. Diagnostic algorithms to differentiate these two https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 1/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate etiologies are complex and imperfect. (See "Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations", section on 'Differential diagnosis of WCT' and 'Diagnosis' below.) Urgent therapy is often required Patients may be unstable at the onset of the arrhythmia or deteriorate rapidly at any time, particularly if the WCT is VT or SVT at an extremely rapid rate (eg, >200 beats per minute). The initial evaluation and approach to diagnosis of patients with a WCT will be discussed here. The causes, epidemiology, clinical manifestations, and management of WCTs, as well as discussion of narrow QRS complex tachycardias, are presented separately. (See "Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations" and "Wide QRS complex tachycardias: Approach to management" and "Overview of the acute management of tachyarrhythmias" and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy" and "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation".) INITIAL APPROACH The first priority when evaluating a patient with a WCT is an assessment of patient stability. Unstable patients (ie, pulseless patients in cardiac arrest or patients who are hemodynamically unstable) should be treated immediately, before an extensive diagnostic evaluation. (See 'Assessment of hemodynamic stability' below and "Wide QRS complex tachycardias: Approach to management", section on 'Unstable patients'.) Stable patients (ie, patients with no or minimal symptoms and who are hemodynamically stable) will most often have already had an ECG showing the presence of a WCT. In a stable patient, the ECG should be thoroughly and systematically reviewed in an effort to determine the etiology of the WCT. (See 'Evaluation of the electrocardiogram' below.) Assessment of hemodynamic stability Immediate assessment of the patient's symptoms, vital signs, and the level of consciousness are of primary importance. In the discussions that follow, patients are categorized as follows: Unstable An unstable patient with WCT has evidence of hemodynamic compromise, such as hypotension, altered mental status, chest pain, or HF, but generally remains awake with a discernible pulse. In this setting, emergency synchronized cardioversion (after intravenous sedation, whenever possible) is the treatment of choice regardless of the https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 2/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate mechanism of the arrhythmia. (See "Wide QRS complex tachycardias: Approach to management", section on 'Unstable patients'.) Patients who become unresponsive or pulseless are considered to have a cardiac arrest and are treated according to standard resuscitation algorithms. (See "Advanced cardiac life support (ACLS) in adults" and "Adult basic life support (BLS) for health care providers".) Stable A stable patient with WCT shows no evidence of hemodynamic compromise despite a sustained rapid heart rate. Such patients should have continuous monitoring (if hospitalized) and frequent reevaluations (in either the inpatient or outpatient setting) due to the potential for rapid deterioration as long as the WCT persists. The presence of hemodynamic stability should not be regarded as diagnostic of SVT [1,2]. Misdiagnosis of VT as SVT based upon hemodynamic stability is a common error that can lead to inappropriate and potentially dangerous therapy [1,3]. (See "Wide QRS complex tachycardias: Approach to management", section on 'Pharmacologic interventions'.) Immediate cardioversion in unstable patients Hemodynamic compromise may occur with any WCT, regardless of the etiology, but is more likely in patients with ventricular tachycardia (VT). Patients who are felt to be hemodynamically unstable require prompt treatment with electrical cardioversion/defibrillation to prevent further clinical deterioration or sudden cardiac arrest (SCA). The approach to treatment in these patients is discussed in detail separately. (See "Wide QRS complex tachycardias: Approach to management", section on 'Unstable patients'.) Initial evaluation in stable patients In a stable patient, a focused clinical evaluation should include the following: History (see 'History' below) Physical examination (see 'Physical examination' below and "Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations", section on 'Physical examination findings') Laboratory testing (see 'Ancillary testing' below) Diagnostic maneuvers in selected patients The primary goals of the initial evaluation of a stable patient with WCT are to determine the etiology of the WCT (through evaluation of the ECG) and to elucidate any underlying conditions related to the event (eg, heart failure, myocardial ischemia, drug reaction, or electrolyte abnormalities). (See 'Evaluation of the electrocardiogram' below.) Among patients with WCT, VT is much more common than supraventricular tachycardia (SVT) with aberrant conduction. In addition, inadvertently treating VT as though it were SVT could https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 3/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate precipitate hemodynamic collapse and/or cardiac arrest, while "mistreating" SVT as though it were VT will rarely cause a clinically significant adverse effect. Thus, if there is any uncertainty of the diagnosis, it is generally preferable to be conservative and presume VT in the case of WCT. The approach to treatment of WCT is discussed in detail separately. (See "Wide QRS complex tachycardias: Approach to management".) History When evaluating the stable patient with a WCT, the following historical features may help determine the likely etiology and/or guide therapy: History of heart disease The presence of structural heart disease, especially coronary heart disease and/or a previous myocardial infarction (MI), strongly suggests VT as an etiology [1,4]. It is also important to establish whether a cardiac arrhythmia has occurred in the past and, if so, whether the patient is aware of the etiology. (See "Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations", section on 'Epidemiology'.) Presence of an implantable cardioverter-defibrillator (ICD) The presence of an ICD implies a known increased risk of VTs and suggests strongly (but does not prove) that the WCT is VT. (See "Implantable cardioverter-defibrillators: Overview of indications, components, and functions".) Presence of a pacemaker The patient should be asked about the presence of pacemaker, which raises the possibility of a device-associated WCT. (See "Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations", section on 'Supraventricular tachycardia'.) Atrial arrhythmias In a patient known to have persistent atrial fibrillation (AF), a regular WCT is likely VT, as aberrant conduction during AF would create an irregular rhythm. An exception is when AF "organizes" into atrial flutter; this can occur spontaneously but occurs much more commonly in the setting of antiarrhythmic drugs (especially class IC agents, amiodarone, or dronedarone). Age For patients over the age of 35 years presenting to an emergency department, a WCT is likely to be VT (positive predictive value 85 percent in one series) [5]. SVT is more likely in younger patients (positive predictive value 70 percent). However, VT must be considered in younger patients, particularly those with a family history of ventricular arrhythmias or premature sudden cardiac death. Symptoms Symptoms are not useful in determining the diagnosis, but they may be important as an indicator of the severity of hemodynamic compromise. Symptoms are https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 4/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate primarily due to the elevated heart rate, associated heart disease, and the presence of left ventricular dysfunction [1,4]. Some patients with a WCT have no or relatively minor symptoms (palpitations, lightheadedness, diaphoresis), while others have severe manifestations including chest pain or angina, syncope, shock, seizures, and cardiac arrest. Medications Many medications have proarrhythmic effects, either directly by prolonging the QT interval or indirectly via alterations in electrolyte levels, and obtaining a medication history is among the first priorities in the evaluation of a patient with a WCT. The most common drug- induced WCT is a form of polymorphic VT called torsades de pointes (TdP). This arrhythmia is associated with QT interval prolongation when the patient is in sinus rhythm. Many medications (eg, antiarrhythmic drugs, anti-infective drugs, psychotropic drugs, etc) are known to prolong the QT interval ( table 1) and are associated with a risk of polymorphic VT. An internet resource with updated lists of specific drugs that cause TdP is available at the Credible Meds website. (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes".) Class IC antiarrhythmic drugs can sometimes organize AF into a relatively slow atrial flutter, which may conduct 1:1 with a very wide QRS complex, mimicking VT. Physical examination As with the history, the initial physical examination should search for evidence of underlying cardiovascular disease, which can impact the likelihood that the WCT is VT. Findings suggestive of cardiovascular disease include: Signs of acute or chronic HF (eg, hypoxia, lung crackles, etc). (See "Treatment of acute decompensated heart failure: General considerations" and "Heart failure: Clinical manifestations and diagnosis in adults".) A healed sternal incision as evidence of previous cardiothoracic surgery. The sequelae of peripheral artery disease or stroke (eg, surgical scars consistent with vascular surgery, residual neurologic deficits, etc). A pacemaker or ICD. These devices are usually palpable and are in the left or, less commonly, right pectoral area below the clavicle; rarely, ICDs are found in the anterior abdominal wall. ECG initial impressions Once a WCT has been identified on the ECG, prompt diagnosis and management is important. Unstable patients should be presumed to have VT and treated as such. While the Brugada criteria are the most widely known and applied criteria for distinguishing VT from SVT, time and/or technical limitations may not allow for immediate review https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 5/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate of the ECG in such detail, particularly in a symptomatic or borderline unstable patient. (See 'Brugada criteria' below.) The absence of the historical or ECG features of VT does not confirm a diagnosis of SVT. The diagnosis of SVT should be considered primarily in young patients, whose hearts are structurally normal, in whom none of the historical (eg, family history of sudden cardiac death), physical, or ECG criteria supporting VT are present, or in patients with a history of SVT with a similar presentation. When the diagnosis of a WCT remains uncertain, we recommend that the patient be treated as if the rhythm is VT until definitively proven otherwise. Our approach emphasizes immediate ECG review for key high-yield features in parallel with a brief history that can guide the management of most patients with a WCT. Is the rhythm regular or irregular? VT and most SVTs are generally regular, though slight variation of the RR interval can be seen in VT. An irregular WCT usually represents AF with aberrant conduction, although polymorphic VT should also be considered. (See 'Basic features' below.) What is the QRS axis ( figure 1)? Extreme right axis deviation (ie, a right superior axis [axis from -90 to 180 degrees]) strongly favors VT, as does any axis shift of greater than 40 degrees when compared with baseline or concordance of the QRS complexes. (See 'Basic features' below and 'Concordance' below.) Is there AV dissociation? If AV dissociation can be quickly identified, an atrial rate slower than the ventricular rate, along with any fusion or capture beats, strongly suggests VT. (See 'AV dissociation' below.) Is there a history of heart disease or arrhythmias? A quick history focusing on structural heart disease, particularly coronary heart disease and/or prior MI as well as any known arrhythmias or cardiac implantable electronic devices (eg, pacemaker or ICD), can aid in identifying the most likely etiology of WCT. The WCT is far more likely to be VT in patients over 35 years of age with known coronary heart disease or prior MI and in those with an ICD. (See 'History' above.) Ancillary testing A number of additional tests may provide further insight to the mechanism of the tachycardia and the presence of associated conditions. Laboratory testing Initial laboratory testing in all patients with a WCT should include electrolytes and cardiac troponin, with additional testing for elevated serum drug levels in patients taking certain medications. https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 6/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate The plasma potassium and magnesium concentrations should be measured as part of the initial evaluation since hypokalemia and hypomagnesemia both predispose to the development of VT. Hyperkalemia can cause a wide QRS complex rhythm with the loss of a detectable P wave, although this usually is a supraventricular rhythm with a slow rate (so-called "sinoventricular rhythm"). (See "Causes and evaluation of hyperkalemia in adults" and "ECG tutorial: Miscellaneous diagnoses", section on 'Hyperkalemia'.) Cardiac troponin testing should be performed in patients with WCT when the patient is having ongoing chest pain or hemodynamic instability. Cardiac troponin can be elevated in the setting of myocardial ischemia (as the result of myocardial oxygen supply and demand mismatch) or MI (as a possible cause of the arrhythmia). Elevated cardiac troponin is associated with an increased risk of adverse outcomes and may guide hospital admission decisions, cardiac testing, and/or anti-ischemic therapy. (See "Troponin testing: Clinical use".) In patients taking digoxin, quinidine, or procainamide, plasma concentrations of these drugs (and, in the case of procainamide, the metabolite N-acetylprocainamide) should be measured to assist in evaluating possible toxicity. (See "Major side effects of class I antiarrhythmic drugs", section on 'Procainamide'.) Chest radiograph A chest radiograph can provide evidence suggestive of structural heart disease, such as cardiomegaly, or evidence of HF with pulmonary congestion. In general, a chest radiograph should be ordered when there is concern for HF or a thoracic or pulmonary process, or to assess for underlying structural heart disease when the patient is unable to provide a history. Early diagnostic/therapeutic interventions In patients with a WCT who are hemodynamically stable, certain vagal maneuvers (eg, carotid sinus massage) or the administration of certain intravenous medications (eg, adenosine, beta blockers, verapamil) may be both helpful for establishing the diagnosis and potentially therapeutic, although they do carry a risk of hemodynamic deterioration and should only be performed in closely monitored settings by experienced clinicians. These potential interventions are discussed in detail separately. (See "Wide QRS complex tachycardias: Approach to management", section on 'Vagal maneuvers'.) EVALUATION OF THE ELECTROCARDIOGRAM In most patients, a probable diagnosis (ventricular tachycardia [VT] or supraventricular tachycardia [SVT]) may be made by closely reviewing the ECG, although definitive diagnosis is https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 7/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate not always possible. For optimal ECG analysis, both a 12-lead ECG and a rhythm strip should be obtained. However, if there are any questions regarding the patient's stability, detailed ECG evaluation should be deferred in favor of urgent therapy. (See "Wide QRS complex tachycardias: Approach to management", section on 'Unstable patients'.) Basic features As with the interpretation of any ECG, the standard initial approach includes an assessment of rate, regularity, axis, QRS duration, and QRS morphology. If available, comparison with a baseline ECG tracing in sinus rhythm (or atrial fibrillation [AF]) can be very helpful. Helpful clues on a baseline ECG may include fascicular and/or bundle branch block, signs of prior infarction, or ventricular pre-excitation. Patients with aberrant conduction at baseline will virtually always have aberrant conduction during SVT. A QRS complex during WCT identical to that during SR usually implies SVT, though an unusual form of VT called bundle branch reentrant VT may be possible. If the patient is known to have persistent AF at baseline, a regular WCT usually implies VT. Rate The rate of the WCT is of limited use in distinguishing VT from SVT. When the rate is approximately 150 beats per minute, atrial flutter with 2:1 AV block and with aberrant conduction should be considered, although this diagnosis should not be accepted without other supporting evidence. Regularity VT is generally regular. Slight variation in the RR intervals is sometimes seen and suggests VT as opposed to most SVTs, which are characterized by uniformity of the RR intervals. When the onset of the arrhythmia is available for analysis, a period of some irregularity and acceleration ("warm-up phenomenon") suggests VT. More marked irregularity of RR intervals occurs in polymorphic VT and in AF with aberrant conduction. Morphology For distinguishing between VT and SVT, there are no universal morphologic criteria that would allow for the distinction. However, when describing WCTs, the QRS morphology in lead V1 is the key. If the complex is primarily negative in lead V1, the WCT is said to be left bundle branch block (LBBB)-like. If the QRS is primarily positive in lead V1, the WCT is said to be right bundle branch block (RBBB)-like. (See 'QRS morphology' below.) Axis The QRS axis in the frontal plane can be useful in distinguishing SVT from VT. The presence of one or more of the following is highly suggestive of VT: right superior axis, shift in axis >40 degrees from a prior baseline, and a specific QRS axis in association with other QRS morphologies. (See "Basic principles of electrocardiographic interpretation", section on 'QRS axis'.) A right superior axis (axis from -90 to 180 degrees) ( figure 1), sometimes called an extreme axis deviation, indeterminate axis, or "northwest" axis, is rare in SVT and https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 8/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate strongly suggests VT. There are two exceptions to this rule. The first is an antidromic AV reentrant tachycardia (AVRT) seen with ventricular pre-excitation. In this situation, there is direct activation of the ventricular myocardium, bypassing the normal His-Purkinje system, and the QRS complex may have an indeterminate axis. The second is a biventricular pacemaker in which the axis is often indeterminate with an initial Q wave in lead I. Compared with the axis during sinus rhythm (when an old ECG is available for review), an axis shift during the WCT of more than 40 degrees suggests VT [6]. In a patient with an RBBB-like WCT, a QRS axis to the left of -30 degrees suggests VT. (See 'QRS morphology' below.) In a patient with an LBBB-like WCT, a QRS axis to the right of +90 degrees suggests VT [7]. (See 'QRS morphology' below.) QRS duration By definition, the QRS duration is at least 120 milliseconds in a WCT. In general, a wider QRS favors VT. In an RBBB-like WCT, a QRS duration >140 milliseconds suggests VT; while in an LBBB-like WCT, a QRS duration >160 milliseconds suggests VT [7]. (See 'QRS morphology' below.) In an analysis of several studies, a QRS duration >160 milliseconds was a strong predictor of VT (likelihood ratio >20:1) [8]. However, a QRS duration >160 milliseconds is not helpful in some settings, including SVT with an AV accessory pathway; the presence of drugs capable of slowing intraventricular conduction, such as class I antiarrhythmic drugs; and in association with hyperkalemia [7,9,10]. A very wide QRS complex may also be seen with a dilated cardiomyopathy in which diffuse fibrosis may produce a marked slowing of impulse conduction through the ventricular myocardium. (See 'VT versus AVRT' below and 'Medications' above.) A QRS duration <140 milliseconds does not exclude VT since VT originating from the septum or within the His-Purkinje system (as opposed to the myocardium) may be associated with a relatively narrow QRS complex. (See "Ventricular tachycardia in the absence of apparent structural heart disease", section on 'Idiopathic left ventricular tachycardia'.) Concordance Concordance is present when the QRS complexes in all six precordial leads (V1 through V6) are monophasic with the same polarity. When present, concordance is frequently associated with VT but by itself is not diagnostic for VT ( waveform 1). If any of the six leads have a biphasic QRS (qR or RS complexes), concordance is not present. https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 9/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate Negative concordance (ie, V1 through V6 entirely negative with deep, monophasic QS complexes) is strongly suggestive of VT but is not definitive. Rarely, SVT with LBBB aberrancy will demonstrate negative concordance, but there is almost always some evidence of an R wave in the lateral precordial leads ( waveform 2). Positive concordance (ie, V1 through V6 entirely positive with tall, monophasic R waves) is most often due to VT but can also occur in the relatively rare case of antidromic AVRT with a left posterior accessory pathway ( waveform 3) [7]. (See "Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome".) While the presence of concordance strongly suggests VT (>90 percent specificity), its absence is not helpful diagnostically (approximately 20 percent sensitivity) [11]. AV dissociation When identified on the ECG, the presence of AV dissociation largely establishes VT as the diagnosis. AV dissociation is characterized by atrial activity that is independent of ventricular activity, usually with the ventricular rate exceeding the atrial rate (except in the instance of a "double tachycardia" with, for example, concurrent atrial flutter and VT) ( waveform 4). Though not always present, fusion beats and capture beats are readily recognized indicators of AV dissociation. In a WCT with AV dissociation, an atrial rate slower than the ventricular rate strongly suggests VT. An atrial rate that is faster than the ventricular rate is seen with some SVTs, such as atrial flutter or an atrial tachycardia with 2:1 AV conduction associated with blocked atrial impulses (due to refractoriness of the AV node). In these settings, however, there is a consistent relationship between the P waves and the QRS complexes, so there is not true AV dissociation. While AV dissociation largely establishes the diagnosis, its absence is not as helpful for two reasons: AV dissociation may be present but not obvious on the ECG. In some cases of VT, the ventricular impulses conduct backward through the AV node and capture the atrium (referred to as 1:1 retrograde conduction), so in fact, there is AV association rather than AV dissociation [12]. This may be seen more commonly when the rate of VT is slower. VT with retrograde Wenckebach conduction, or with 2:1 ventriculoatrial (VA) conduction, technically does not exhibit AV dissociation, though the ventricular rate exceeds the atrial rate. In all cases in which there is retrograde VA conduction, the P waves will be inverted in the inferior leads. Dissociated P waves P waves are said to be dissociated if they are not consistently coupled to the QRS complexes, as evidenced by the following: https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 10/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate PP and RR intervals are different PR intervals are variable There is no association between P and QRS complexes The presence of a P wave with one or more, but not all, QRS complexes During a WCT, P waves are often difficult to identify. If P waves are not evident on the surface ECG, direct recordings of atrial activity (eg, via an implanted pacemaker or implantable cardioverter-defibrillator, or via an esophageal electrode or temporary pacing catheter or epicardial pacing wires after heart surgery) can reveal AV dissociation [13]. Fusion and capture beats Fusion and/or capture beats, when identified on the surface ECG in a patient with WCT, are diagnostic for VT. Fusion beats occur when one impulse originating from the ventricle and a second supraventricular impulse simultaneously activate the ventricular myocardium. The resulting QRS complex has a morphology intermediate between that of a sinus beat and a purely ventricular complex ( waveform 5). Intermittent fusion beats during a WCT are diagnostic of AV dissociation and therefore of VT. Capture beats, or Dressler beats, are QRS complexes during a WCT that are identical to the sinus QRS complex ( waveform 5). The term "capture beat" implies that the normal conduction system has momentarily "captured" control of ventricular activation from the VT focus. Fusion beats and capture beats are more commonly seen when the tachycardia rate is slower. QRS morphology A definitive diagnosis of VT or SVT cannot be made based upon QRS morphology alone. Further ECG evaluation involves assessment of the morphology of the QRS complex. (See 'Diagnosis' below.) Analysis of QRS morphology is based upon an understanding of the relationships between the sites of tachycardia origin, ventricular activation patterns, and the resulting morphologies of the QRS complex in the 12 standard ECG leads. Subtle, non-rate-related fluctuations or variations in QRS and ST-T wave configuration suggest VT and may reflect variations in the VT reentrant circuit within the myocardium as well as a subtle difference in the activation sequence of the myocardium reflecting activation that bypasses the normal conduction system. AV dissociation can cause variability in the ST segment and T wave morphology. By contrast, SVT, because it follows a fixed conduction pathway to and through the ventricular myocardium, is characterized by uniformity of QRS and ST-T shape unless the rate changes. https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 11/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate DIAGNOSIS Most patients with WCT will have some, but not all, of the ECG features favoring ventricular tachycardia (VT). There is no single criterion or combination of criteria that provides complete diagnostic accuracy in evaluating a WCT . It is typically necessary, therefore, to integrate multiple ECG findings into a diagnostic strategy. Of the several strategies that have been proposed, the Brugada criteria are the most widely known and reflect the initial approach that we generally use [8,14,15]. (See 'Brugada criteria' below.) However, because the diagnosis of a WCT cannot always be made with complete certainty even when using multiple ECG criteria, an unknown or uncertain rhythm should be presumed to be VT in the absence of contrary evidence [16]. VT is far more common than supraventricular tachycardia (SVT), by a factor of four in unselected populations and by as much as 10-fold in patients with prior myocardial infarction. Additionally, presuming VT guards against inappropriate and potentially dangerous therapies directed at an SVT, which can precipitate hemodynamic deterioration in patients with VT, and treatment of SVT as if it were VT is safe and frequently effective in restoring sinus rhythm. (See "Wide QRS complex tachycardias: Approach to management", section on 'Management'.) An algorithmic approach to the diagnosis of a WCT will be reviewed here, with emphasis on the distinction between VT and SVT. The approach to a narrow QRS complex tachycardia is discussed separately. (See "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation".) Brugada criteria The Brugada criteria, the most commonly used ECG algorithm to differentiate VT from SVT, are a stepwise approach in which four criteria for VT are sequentially assessed ( algorithm 2) [14]. If any of the four criteria are satisfied, the diagnosis of VT is made, and if none are fulfilled, an SVT is diagnosed. An exception is an antidromic AV reentrant tachycardia (AVRT) in Wolff-Parkinson-White syndrome. The steps are as follows: Leads V1-V6 are inspected to detect an RS complex (ie, a biphasic QRS complex with both positive R and negative S wave components). If there are no RS complexes, concordance is present, and the diagnosis of VT can be made ( waveform 2). (See 'Concordance' above.) If an RS complex is present, measure the interval between the onset of the R wave and the nadir of the S wave (RS interval). If the longest RS interval in any lead is >100 milliseconds and the R wave is wider than the S wave, the diagnosis of VT can be made. This reflects that https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 12/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate with VT, the entire QRS complex is wide and abnormal (even the initial R wave portion), while aberration is due to a terminal delay resulting in a wider terminal portion of the QRS complex (ie, S wave). This criterion, however, may be limited in the presence of an underlying diffuse cardiomyopathy, as in this situation, even initial ventricular activation may be slow and abnormal. If the longest RS interval is <100 milliseconds, the presence or absence of AV dissociation is assessed. If AV dissociation is seen, the diagnosis of VT is made. (See 'AV dissociation' above.) If AV dissociation cannot clearly be demonstrated, the QRS morphology criteria for V1- positive and V1-negative wide QRS complex tachycardias are considered. QRS morphology criteria consistent with VT must be present in leads V1 or V2 and in lead V6 to diagnose VT. If either the V1-V2 or the V6 criteria are not consistent with VT, an SVT is assumed. (See 'QRS morphology' above.) Alternative approaches Several alternative approaches have been proposed in the literature, although none are as commonly used as the Brugada criteria. These approaches are generally best performed in consultation with an electrophysiologist with expertise in the diagnosis of WCT. An alternative algorithm (Vereckei approach) uses a stepwise approach similar to the Brugada criteria but includes different ECG features ( algorithm 3) [15]. Two unique features of this algorithm include: An initial R wave in aVR (diagnostic of VT). Vi:Vt ratio. Vi and Vt are the magnitude of voltage change in the initial and terminal 40 milliseconds of a QRS, respectively. Vi and Vt should be measured from the same biphasic or multiphasic QRS complex. A Vi:Vt ratio 1 is diagnostic of VT. One study of 51 patients with WCT induced during electrophysiology study showed equivalent sensitivity for diagnosis between the Vereckei and Brugada approaches (89 versus 90 percent), but the Vereckei approach yielded significantly fewer incorrect diagnoses following the first step (2 versus 27 percent) and was slightly faster to perform (9.1 versus 9.9 seconds) [17]. An additional algorithm (limb leads algorithm) diagnoses VT in the presence of at least one of the following criteria: https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 13/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate Monophasic R wave in lead aVR Predominantly negative QRS complex in leads I, II, III Opposing QRS complex in the limb leads (concordant monophasic QRS complex in all inferior leads [II, III, aVF] and concordant monophasic QRS complex in two or three of the remaining limb leads [I, aVR, aVL] with opposite polarity of the inferior leads) Among a series of 528 wide QRS complex tachycardias (397 VT, 131 SVT), the limb leads algorithm had similar overall accuracy compared to other algorithms (88 percent versus 85 percent with Brugada criteria and 88 percent with Vereckei approach); in general, the limb leads algorithm had lower sensitivity but higher specificity for diagnosing VT [18]. A Bayesian approach utilizes likelihood ratios (LR) for six ECG criteria [8]. Patients are presumed to start with a "prior odds ratio" of 4.0 (4:1) in favor of VT. As each criterion is evaluated sequentially, the associated LR is multiplied by the prior odds ratio to calculate the new probability of VT. The final odds ratio (posterior probability) is considered consistent with VT if the value is 1.0 and SVT if the value is <1.0. Intravenous adenosine may be administered as both a diagnostic and potentially therapeutic agent. (See "Wide QRS complex tachycardias: Approach to management", section on 'Pharmacologic interventions'.) VT versus AVRT Differentiation between VT and antidromic AVRT is particularly difficult. Because there is direct myocardial activation (since ventricular activation begins outside of the normal conduction system) in both VT and antidromic AVRT, many of the standard criteria are not able to discriminate antidromic AVRT from VT. The clinical significance of this problem is often limited, however, because pre-excitation is an uncommon cause of WCT (6 percent in one series), particularly if other clinical factors (eg, age, underlying heart disease) suggest VT [11]. For cases in which pre-excitation is thought to be likely (such as a young patient without structural heart disease, or a patient with a known accessory pathway), a separate algorithm was developed that consists of the following three steps ( algorithm 4) [14]: The predominant polarity of the QRS complex in leads V4 through V6 is defined either as positive or negative. If predominantly negative, the diagnosis of VT can be made. If the polarity of the QRS complex is predominantly positive in V4 through V6, the ECG should be examined for the presence of a qR complex in one or more of the precordial leads V2 through V6. If a qR complex can be identified, VT can be diagnosed. https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 14/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate If a qR wave in leads V2 through V6 is absent, the AV relationship is then evaluated (AV dissociation). If a 1:1 AV relationship is not present and there are more QRS complexes present than P waves, VT can be diagnosed. When any of these criteria are met, VT is likely. However, if the ECG does not display any of the three morphologic characteristics diagnostic of VT in this algorithm, the diagnosis of antidromic AVRT must be considered. Importantly, the QRS complex morphology and ST-T waves are uniform with AVRT as every impulse to the ventricle is conducted through the same accessory pathway. Algorithm performance Algorithms often perform well in initial reports. However, such studies include selected populations and experienced ECG analysts. In its initial description, the reported sensitivity and specificity of the Brugada criteria were 98.7 and 96.5 percent, respectively [14]. However, in two subsequent reports in which a total of nine clinicians (two cardiologists, two emergency department clinicians, and five internists) used these criteria in interpreting a total of 168 WCTs that had been diagnosed with electrophysiologic testing, the sensitivity ranged from 79 to 92 percent and specificity ranged from 43 to 70 percent [19,20]. In a comparison of the Brugada criteria and the Bayesian approach, the two approaches performed similarly, with sensitivities of 92 and 97 percent and specificities of 44 and 56 percent, respectively [20]. In the initial description of the alternative algorithm (Vereckei approach), it was significantly more accurate than the Brugada criteria [15]. Further study is necessary to confirm both the overall accuracy of this approach and its superiority to the Brugada criteria. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions

tachycardia (AVRT) in Wolff-Parkinson-White syndrome. The steps are as follows: Leads V1-V6 are inspected to detect an RS complex (ie, a biphasic QRS complex with both positive R and negative S wave components). If there are no RS complexes, concordance is present, and the diagnosis of VT can be made ( waveform 2). (See 'Concordance' above.) If an RS complex is present, measure the interval between the onset of the R wave and the nadir of the S wave (RS interval). If the longest RS interval in any lead is >100 milliseconds and the R wave is wider than the S wave, the diagnosis of VT can be made. This reflects that https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 12/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate with VT, the entire QRS complex is wide and abnormal (even the initial R wave portion), while aberration is due to a terminal delay resulting in a wider terminal portion of the QRS complex (ie, S wave). This criterion, however, may be limited in the presence of an underlying diffuse cardiomyopathy, as in this situation, even initial ventricular activation may be slow and abnormal. If the longest RS interval is <100 milliseconds, the presence or absence of AV dissociation is assessed. If AV dissociation is seen, the diagnosis of VT is made. (See 'AV dissociation' above.) If AV dissociation cannot clearly be demonstrated, the QRS morphology criteria for V1- positive and V1-negative wide QRS complex tachycardias are considered. QRS morphology criteria consistent with VT must be present in leads V1 or V2 and in lead V6 to diagnose VT. If either the V1-V2 or the V6 criteria are not consistent with VT, an SVT is assumed. (See 'QRS morphology' above.) Alternative approaches Several alternative approaches have been proposed in the literature, although none are as commonly used as the Brugada criteria. These approaches are generally best performed in consultation with an electrophysiologist with expertise in the diagnosis of WCT. An alternative algorithm (Vereckei approach) uses a stepwise approach similar to the Brugada criteria but includes different ECG features ( algorithm 3) [15]. Two unique features of this algorithm include: An initial R wave in aVR (diagnostic of VT). Vi:Vt ratio. Vi and Vt are the magnitude of voltage change in the initial and terminal 40 milliseconds of a QRS, respectively. Vi and Vt should be measured from the same biphasic or multiphasic QRS complex. A Vi:Vt ratio 1 is diagnostic of VT. One study of 51 patients with WCT induced during electrophysiology study showed equivalent sensitivity for diagnosis between the Vereckei and Brugada approaches (89 versus 90 percent), but the Vereckei approach yielded significantly fewer incorrect diagnoses following the first step (2 versus 27 percent) and was slightly faster to perform (9.1 versus 9.9 seconds) [17]. An additional algorithm (limb leads algorithm) diagnoses VT in the presence of at least one of the following criteria: https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 13/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate Monophasic R wave in lead aVR Predominantly negative QRS complex in leads I, II, III Opposing QRS complex in the limb leads (concordant monophasic QRS complex in all inferior leads [II, III, aVF] and concordant monophasic QRS complex in two or three of the remaining limb leads [I, aVR, aVL] with opposite polarity of the inferior leads) Among a series of 528 wide QRS complex tachycardias (397 VT, 131 SVT), the limb leads algorithm had similar overall accuracy compared to other algorithms (88 percent versus 85 percent with Brugada criteria and 88 percent with Vereckei approach); in general, the limb leads algorithm had lower sensitivity but higher specificity for diagnosing VT [18]. A Bayesian approach utilizes likelihood ratios (LR) for six ECG criteria [8]. Patients are presumed to start with a "prior odds ratio" of 4.0 (4:1) in favor of VT. As each criterion is evaluated sequentially, the associated LR is multiplied by the prior odds ratio to calculate the new probability of VT. The final odds ratio (posterior probability) is considered consistent with VT if the value is 1.0 and SVT if the value is <1.0. Intravenous adenosine may be administered as both a diagnostic and potentially therapeutic agent. (See "Wide QRS complex tachycardias: Approach to management", section on 'Pharmacologic interventions'.) VT versus AVRT Differentiation between VT and antidromic AVRT is particularly difficult. Because there is direct myocardial activation (since ventricular activation begins outside of the normal conduction system) in both VT and antidromic AVRT, many of the standard criteria are not able to discriminate antidromic AVRT from VT. The clinical significance of this problem is often limited, however, because pre-excitation is an uncommon cause of WCT (6 percent in one series), particularly if other clinical factors (eg, age, underlying heart disease) suggest VT [11]. For cases in which pre-excitation is thought to be likely (such as a young patient without structural heart disease, or a patient with a known accessory pathway), a separate algorithm was developed that consists of the following three steps ( algorithm 4) [14]: The predominant polarity of the QRS complex in leads V4 through V6 is defined either as positive or negative. If predominantly negative, the diagnosis of VT can be made. If the polarity of the QRS complex is predominantly positive in V4 through V6, the ECG should be examined for the presence of a qR complex in one or more of the precordial leads V2 through V6. If a qR complex can be identified, VT can be diagnosed. https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 14/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate If a qR wave in leads V2 through V6 is absent, the AV relationship is then evaluated (AV dissociation). If a 1:1 AV relationship is not present and there are more QRS complexes present than P waves, VT can be diagnosed. When any of these criteria are met, VT is likely. However, if the ECG does not display any of the three morphologic characteristics diagnostic of VT in this algorithm, the diagnosis of antidromic AVRT must be considered. Importantly, the QRS complex morphology and ST-T waves are uniform with AVRT as every impulse to the ventricle is conducted through the same accessory pathway. Algorithm performance Algorithms often perform well in initial reports. However, such studies include selected populations and experienced ECG analysts. In its initial description, the reported sensitivity and specificity of the Brugada criteria were 98.7 and 96.5 percent, respectively [14]. However, in two subsequent reports in which a total of nine clinicians (two cardiologists, two emergency department clinicians, and five internists) used these criteria in interpreting a total of 168 WCTs that had been diagnosed with electrophysiologic testing, the sensitivity ranged from 79 to 92 percent and specificity ranged from 43 to 70 percent [19,20]. In a comparison of the Brugada criteria and the Bayesian approach, the two approaches performed similarly, with sensitivities of 92 and 97 percent and specificities of 44 and 56 percent, respectively [20]. In the initial description of the alternative algorithm (Vereckei approach), it was significantly more accurate than the Brugada criteria [15]. Further study is necessary to confirm both the overall accuracy of this approach and its superiority to the Brugada criteria. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Arrhythmias in adults" and "Society guideline links: Ventricular arrhythmias" and "Society guideline links: Supraventricular arrhythmias".) INFORMATION FOR PATIENTS https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 15/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Ventricular tachycardia (The Basics)") SUMMARY AND RECOMMENDATIONS The first priority when evaluating a patient with a wide QRS complex tachycardia (WCT) is an immediate assessment of patient stability, including the patient's symptoms, vital signs, and the level of consciousness. An unstable patient will have evidence of hemodynamic compromise, such as hypotension, altered mental status, chest pain, or heart failure. A patient who is unresponsive or pulseless should be treated according to standard advanced cardiac life support (ACLS) algorithms ( algorithm 5). (See 'Assessment of hemodynamic stability' above and "Advanced cardiac life support (ACLS) in adults".) For a patient who is unstable, with evidence of hemodynamic compromise but who remains conscious, emergency synchronized cardioversion (after intravenous sedation, whenever possible) is the treatment of choice regardless of the mechanism of the arrhythmia. (See 'Assessment of hemodynamic stability' above and "Wide QRS complex tachycardias: Approach to management", section on 'Unstable patients'.) In a stable patient, or following cardioversion to stabilize an unstable patient, our initial approach includes the following: A succinct history and physical examination, focusing on the presence of structural heart disease, especially coronary heart disease and/or a previous myocardial infarction, as well as the history of any arrhythmias and the presence of a https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 16/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate pacemaker or implantable cardioverter-defibrillator. (See 'History' above and 'Physical examination' above.) Review of the patient s medications for drugs that may be proarrhythmic (by prolonging the QT interval or promoting electrolyte disturbances). (See 'Medications' above.) Initial review of the ECG, with a focus on whether the rhythm is regular or irregular, the width of the QRS complex, the presence or absence of AV dissociation, and any preexisting arrhythmias. (See 'ECG initial impressions' above.) Ancillary testing including serum electrolyte levels, cardiac troponin, and a chest radiograph in all patients. (See 'Ancillary testing' above.) In most patients with WCT, a probable diagnosis (ventricular tachycardia [VT] or supraventricular tachycardia [SVT]) may be made by closely reviewing the ECG, although definitive diagnosis is not always possible and may be time consuming. The standard initial approach to ECG interpretation includes an assessment of rate, regularity, axis, QRS duration, and QRS morphology. (See 'Evaluation of the electrocardiogram' above.) Most patients with WCT will have some, but not all, of the ECG features favoring VT. There is no single criterion or combination of criteria that provides complete diagnostic accuracy in evaluating a WCT, even when employing an algorithmic approach to the diagnosis of a WCT. (See 'Diagnosis' above.) We prefer using the Brugada algorithm to evaluate for VT versus SVT in patients with WCT when the diagnosis is uncertain and when patient hemodynamic stability allows. ECG features consistent with VT include concordance ( waveform 2), AV dissociation, fusion/capture beats, and specific QRS morphologies. The absence of the historical or ECG features of VT does not confirm a diagnosis of SVT. The diagnosis of SVT should be considered primarily in young patients, whose hearts are structurally normal, in whom none of the historical (eg, family history of sudden cardiac death), physical, or ECG criteria supporting VT are present, or in patients with a history of SVT with a similar presentation. When the diagnosis of a WCT is uncertain despite a careful initial evaluation, the patient should be treated as if the rhythm is VT. (See "Wide QRS complex tachycardias: Approach to management".) https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 17/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Philip Podrid, MD, and Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Akhtar M, Shenasa M, Jazayeri M, et al. Wide QRS complex tachycardia. Reappraisal of a common clinical problem. Ann Intern Med 1988; 109:905. 2. Morady F, Baerman JM, DiCarlo LA Jr, et al. A prevalent misconception regarding wide- complex tachycardias. JAMA 1985; 254:2790. 3. Dancy M, Camm AJ, Ward D. Misdiagnosis of chronic recurrent ventricular tachycardia. Lancet 1985; 2:320. 4. Tchou P, Young P, Mahmud R, et al. Useful clinical criteria for the diagnosis of ventricular tachycardia. Am J Med 1988; 84:53. 5. Baerman JM, Morady F, DiCarlo LA Jr, de Buitleir M. Differentiation of ventricular tachycardia from supraventricular tachycardia with aberration: value of the clinical history. Ann Emerg Med 1987; 16:40. 6. Griffith MJ, de Belder MA, Linker NJ, et al. Multivariate analysis to simplify the differential diagnosis of broad complex tachycardia. Br Heart J 1991; 66:166. 7. Wellens HJ. Electrophysiology: Ventricular tachycardia: diagnosis of broad QRS complex tachycardia. Heart 2001; 86:579. 8. Lau EW, Pathamanathan RK, Ng GA, et al. The Bayesian approach improves the electrocardiographic diagnosis of broad complex tachycardia. Pacing Clin Electrophysiol 2000; 23:1519. 9. Crijns HJ, van Gelder IC, Lie KI. Supraventricular tachycardia mimicking ventricular tachycardia during flecainide treatment. Am J Cardiol 1988; 62:1303. 10. Murdock CJ, Kyles AE, Yeung-Lai-Wah JA, et al. Atrial flutter in patients treated for atrial fibrillation with propafenone. Am J Cardiol 1990; 66:755. 11. Miller JM, Das MK. Differential diagnosis of narrow and wide complex tachycardias. In: Cardi ac Electrophysiology From Cell to Bedside, 7th, Zipes DP, Jalife J, Stevenson WG (Eds), W.B. Sa unders, Philadelphia 2018. https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 18/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate 12. Militianu A, Salacata A, Meissner MD, et al. Ventriculoatrial conduction capability and prevalence of 1:1 retrograde conduction during inducible sustained monomorphic ventricular tachycardia in 305 implantable cardioverter defibrillator recipients. Pacing Clin Electrophysiol 1997; 20:2378. 13. Haley JH, Reeder GS. Images in cardiovascular Medicine. Wide-complex tachycardia. Circulation 2000; 102:E52. 14. Brugada P, Brugada J, Mont L, et al. A new approach to the differential diagnosis of a regular tachycardia with a wide QRS complex. Circulation 1991; 83:1649. 15. Vereckei A, Duray G, Sz n si G, et al. Application of a new algorithm in the differential diagnosis of wide QRS complex tachycardia. Eur Heart J 2007; 28:589. 16. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2018; 72:e91. 17. Kaiser E, Darrieux FC, Barbosa SA, et al. Differential diagnosis of wide QRS tachycardias: comparison of two electrocardiographic algorithms. Europace 2015; 17:1422. 18. Chen Q, Xu J, Gianni C, et al. Simple electrocardiographic criteria for rapid identification of wide QRS complex tachycardia: The new limb lead algorithm. Heart Rhythm 2020; 17:431. 19. Isenhour JL, Craig S, Gibbs M, et al. Wide-complex tachycardia: continued evaluation of diagnostic criteria. Acad Emerg Med 2000; 7:769. 20. Lau EW, Ng GA. Comparison of the performance of three diagnostic algorithms for regular broad complex tachycardia in practical application. Pacing Clin Electrophysiol 2002; 25:822. Topic 920 Version 45.0 https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 19/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate GRAPHICS Algorithm for the initial ECG review and differential diagnosis of tachycardia ECG: electrocardiogram; AVNRT: atrioventricular nodal reentrant tachycardia; AVRT: atrioventricular reciprocating (bypass-tract mediated) tachycardia; AT: atrial tachycardia; SANRT: sinoatrial nodal reentrant tachycardia; AF: atrial fibrillation; AV: atrioventricular; VT: ventricular tachycardia; SVT: supraventricular tachycardia; WPW: Wolff-Parkinson-White. A narrow QRS complex is <120 milliseconds in duration, whereas a wide QRS complex is 120 milliseconds duration. Refer to UpToDate topic reviews for additional details on specific ECG findings and management of individu arrhythmias. Monomorphic VT accounts for 80% of wide QRS complex tachycardias; refer to UpToDate topic on diagnosi wide QRS complex tachycardias for additional information on discriminating VT from SVT. Graphic 117571 Version 3.0 https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 20/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate Some reported causes and potentiators of the long QT syndrome Congenital Jervell and Lange-Nielsen syndrome (including "channelopathies") Romano-Ward syndrome Idiopathic Acquired Metabolic disorders Other factors Androgen deprivation therapy Hypokalemia Myocardial GnRH agonist/antagonist therapy ischemia or infarction, Hypomagnesemia Bilateral surgical orchiectomy Hypocalcemia Diuretic therapy via electrolyte disorders especially with Starvation particularly hypokalemia and hypomagnesemia prominent T-wave inversions Anorexia nervosa Herbs Liquid protein diets Cinchona (contains quinine), iboga (ibogaine), licorice extract in overuse via electrolyte disturbances Intracranial disease Hypothyroidism Bradyarrhythmias HIV infection Sinus node dysfunction Hypothermia Toxic exposure: Organophosphate insecticides AV block: Second or third degree Medications* High risk Adagrasib Cisaparide Lenvatinib Selpercatinib (restricted availability) Ajmaline Levoketoconazole Sertindole Amiodarone Methadone Sotalol Delamanid Arsenic trioxide Mobocertinib Terfenadine Disopyramide Astemizole Papavirine Vandetanib Dofetilide (intracoronary) Bedaquline Vernakalant Dronedarone Procainamide Bepridil Ziprasidone Haloperidol (IV) Quinidine Chlorpromazine Ibutilide Quinine Ivosidenib Moderate risk Amisulpride (oral) Droperidol Inotuzumab ozogamacin Propafenone Azithromycin Encorafenib Propofol Isoflurane Capecitabine Entrectinib Quetiapine Carbetocin Erythromycin Ribociclib https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 21/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate Certinib Escitalopram Levofloxacin Risperidone (systemic) Chloroquine Etelcalcetide Saquinavir Lofexidine Citalopram Fexinidazole Sevoflurane Meglumine Clarithromycin Flecainide Sparfloxacin antimoniate Clofazimine Floxuridine Sunitinib Midostaurin Clomipramine Fluconazole Tegafur Moxifloxacin Clozapine Fluorouracil Terbutaline Nilotinib (systemic) Crizotinib Thioridazine Olanzapine Flupentixol Dabrafenib Toremifene Ondansetrol (IV > Gabobenate dimeglumine Dasatinib Vemurafenib oral) Deslurane Voriconazole Osimertinib Gemifloxacin Domperidone Oxytocin Gilteritinib Doxepin Pazopanib Halofantrine Doxifluridine Pentamidine Haloperidol (oral) Pilsicainide Imipramine Pimozide Piperaquine Probucol Low risk Albuterol Fingolimod Mequitazine Ranolazine (due to bradycardia) Alfuzosin Fluoxetine Methotrimeprazine Relugolix Amisulpride (IV) Fluphenazine Metoclopramide (rare reports) Rilpivirine Amitriptyline Formoterol Metronidazole (systemic) Romidepsin Anagrelide Foscarnet Roxithromycin Apomorphine Fostemsavir Mifepristone Salmeterol Arformoterol Gadofosveset Mirtazapine Sertraline Artemether- Glasdegib Mizolastine lumefantrine Siponimod Goserelin Nelfinavir Asenapine Solifenacin Granisetron Norfloxacin Atomoxetine Sorafenib Hydroxychloroquine Nortriptyline Benperidol (rare reports) Sulpiride Ofloxacin (systemic) Bilastine Hydroxyzine Tacrolimus Olodaterol (systemic) Bosutinib Iloperidone Osilodrostat Tamoxifen Bromperidol Indacaterol Oxaliplatin Telavancin Buprenorphine Itraconazole Ozanimod Telithromycin Buserelin Ketoconazole (systemic) Pacritinib Teneligliptin Ciprofloxacin (Systemic) Lacidipine Paliperidone Tetrabenazine Cocaine (Topical) Lapatinib Panobinostat Trazodone Degarelix Lefamulin Pasireotide Triclabendazole https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 22/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate Desipramine Leuprolide Pefloxacin Triptorelin Deutetrabenazine Leuprolide- Periciazine Tropisetron norethindrone Dexmedetomidine** Pimavanserin Vardenafil Levalbuterol Dolasetron Pipamperone Vilanterol Levomethadone Donepezil Pitolisant Vinflunine Lithium Efavirenz Ponesimod Voclosporin Loperamide overdose in Eliglustat Primaquine Vorinostat Eribulin Promazine Zuclopenthixol Lopinavir Ezogabine Radotinib Macimorelin Mefloquine This is not a complete list of all corrected QT interval (QTc)-prolonging drugs and does not include drugs with either a minor degree or isolated association(s) with QTc prolongation that appear to be safe in most patients but may need to be avoided in patients with congenital long QT syndrome depending upon clinical circumstances. A more complete list of such drugs is available at the CredibleMeds website. For clinical use and precautions related to medications and drug interactions, refer to the UpToDate topic review of acquired long QT syndrome discussion of medications and the Lexicomp drug interactions tool. AV: atrioventricular; IV: intravenous; QTc: rate-corrected QT interval on the electrocardiogram. Classifications provided by Lexicomp according to US Food & Drug Administration guidance: Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythic Potential for Non-Antiarrhythmic Drugs Questions and Answers; Guidance for Industry US Food and Drug Administration, June 2017 (revision 2) available at: https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM 073161.pdf with additional data from CredibleMeds QT drugs list criteria may lead to some agents being classified differently by other sources. [1,2] . The use of other classification Not available in the United States. In contrast with other class III antiarrhythmic drugs, amiodarone is rarely associated with torsades de pointes; refer to accompanying text within UpToDate topic reviews of acquired long QT syndrome. Withdrawn from market in most countries due to adverse cardiovascular effects. IV amisulpride antiemetic use is associated with less QTc prolongation than the higher doses administered orally as an antipsychotic. Other cyclic antidepressants may also prolong the QT interval; refer to UpToDate clinical topic on cyclic antidepressant pharmacology, side effects, and separate UpToDate topic on tricyclic antidepressant poisoning. The "low risk" category includes drugs with limited evidence of clinically significant QTc prolongation or TdP risk; many of these drugs have label warnings regarding possible QTc effects or recommendations to avoid use or increase ECG monitoring when combined with other QTc prolonging drugs. https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 23/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate Rarely associated with significant QTc prolongation at usual doses for treatment of opioid use disorder, making buprenorphine a suitable alternative for patients with methadone-associated QTc prolongation. Refer to UpToDate clinical topic reviews. * The United States FDA labeling for the sublingual preparation of dexmedetomidine warns against use in patients at elevated risk for QTc prolongation. Both intravenous (ie, sedative) and sublingual formulations of dexmedetomidine have a low risk of QTc prolongation and have not been implicated in TdP. Over-the-counter; available without a prescription. Not associated with significant QTc prolongation in healthy persons. Refer to UpToDate clinical topic for potential adverse cardiovascular (CV) effects in patients with CV disease. Data from: 1. Lexicomp Online. Copyright 1978-2023 Lexicomp, Inc. All Rights Reserved. 2. CredibleMeds QT drugs list website sponsored by Science Foundation of the University of Arizona. Available at http://crediblemeds.org/. Graphic 57431 Version 142.0 https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 24/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate Calculation of frontal plane axis If the QRS complex is positive in leads I and II, it falls between -30 and 90 and is normal, as indicated by the yellow area. If the QRS complex is negative in I and positive in aVF, there is right axis deviation. If the QRS complex is positive in I and negative in II, there is left axis deviation. If the QRS complex is negative in I and aVF, there is extreme axis deviation. Graphic 85682 Version 1.0 https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 25/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate Ventricular tachycardia An example of concordance/absence of rS complex and initial R wave in AVR. Courtesy of Leonard Ganz, MD. Graphic 129901 Version 1.0 https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 26/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate Wide complex tachycardia with wide concordance Extreme tachycardia with wide complex. Courtesy of Leonard Ganz, MD. Graphic 129926 Version 2.0 https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 27/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate Ventricular tachycardia with positive concordance Monophasic R waves are noted in all the precordial leads; this is positive concordance. Dissociated P waves a evident in the lead II rhythm strip and in lead aVR. Thick arrow shows artifact. Arrowheads show P waves, marching out at approximately 54 beats per minute. P waves are less evident on the left side of the lead II rh strip. Courtesy of Leonard Ganz, MD. Graphic 129857 Version 1.0 https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 28/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate Atrioventricular dissociation Independent activation of the atria and ventricles results in no fixed relationship between the P waves (arrows) and the QRS complexes; the PR intervals are variable in a random fashion. Graphic 52123 Version 2.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 29/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate Fusion beats The rhythm strip in a patient with sustained ventricular tachycardia shows a fusion beat and a capture beat. The fusion beat occurs when a supraventricular impulse (following the first P wave) causes ventricular activation, which fuses with the complex originating in the ventricle, producing a hybrid complex. The complex following the second P wave has the appearance of a normal QRS complex and is known as a capture beat. Graphic 72600 Version 4.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 30/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate Brugada algorithm for the diagnosis of ventricular tachycardia or supraventricular tachycardia in a patient with wide QRS complex tachycardia Brugada algorithm for distinguishing VT from SVT. VT: ventricular tachycardia; SVT: supraventricular tachycardia. Adapted from: Brugada P, Brugada J, Mont L, et al. A new approach to the di erential diagnosis of a regular tachycardia with a wide QRS complex. Circulation 1991; 83:1649. Graphic 73159 Version 4.0 https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 31/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate Vereckei algorithm for the diagnosis of ventricular tachycardia (VT) or supraventricular tachycardia (SVT) in a patient with wide QRS complex tachycardia Vereckei algorithm for the diagnosis of wide complex tachycardias. In step 4, V represents the magnitude of voltage change in the initial 40 milliseconds of the QRS complex, while V represents the i t magnitude of voltage change in the terminal 40 milliseconds of the QRS complex. The initial V and terminal V voltages should be i t measured from the same biphasic or multiphasic QRS complex. A-V: atrio-ventricular; BBB: bundle branch block; FB: fascicular block; SVT: supraventricular tachycardia; VT: ventricular tachycardia. Reproduced with permission from: Vereckei A, Duray G, Szenasi G, et al. Application of a new algorithm in the di erential diagnosis of wide QRS complex tachycardia. https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 32/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate Eur Heart J 2007; 28:589. Copyright 2007 Oxford University Press. Graphic 79624 Version 6.0 https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 33/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate Algorithm for the diagnosis of wide QRS tachycardia in the setting of ventricular pre- excitation Algorithm for distinguishing VT from SVT in the setting of pre- excitation syndrome. VT: ventricular tachycardia; AV: atrioventricular; SVT: supraventricular tachycardia; ECG: electrocardiography; EP: electrophysiologic. Graphic 59336 Version 8.0 https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 34/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate Adult cardiac arrest algorithm https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 35/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 36/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate Reprinted with permission. Highlights of the 2020 American Heart Association Guidelines for CPR and ECC. Copyright 2020 American Association, Inc. Graphic 129983 Version 9.0 https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 37/38 7/5/23, 10:41 AM Wide QRS complex tachycardias: Approach to the diagnosis - UpToDate Contributor Disclosures Peter J Zimetbaum, MD Consultant/Advisory Boards: Abbott Medical [Lead extraction]. All of the relevant financial relationships listed have been mitigated. Ary L Goldberger, MD Other Financial Interest: Elsevier book royalties [Clinical electrocardiography]. All of the relevant financial relationships listed have been mitigated. James Hoekstra, MD No relevant financial relationship(s) with ineligible companies to disclose. N A Mark Estes, III, MD Consultant/Advisory Boards: Boston Scientific [Arrhythmias]; Medtronic [Arrhythmias]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-approach-to-the-diagnosis/print 38/38

7/5/23, 10:41 AM Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations : Peter J Zimetbaum, MD : Ary L Goldberger, MD, James Hoekstra, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Nov 11, 2022. INTRODUCTION Tachycardias are broadly categorized ( algorithm 1) based upon the width of the QRS complex on the electrocardiogram (ECG). A narrow QRS complex (<120 milliseconds) reflects rapid activation of the ventricles via the normal His-Purkinje system ( figure 1), which in turn suggests that the arrhythmia originates above or within the atrioventricular (AV) node (ie, a supraventricular tachycardia [SVT]). A widened QRS complex ( 120 milliseconds) occurs when ventricular activation is abnormally slow for one of the following reasons (see 'Differential diagnosis of WCT' below): The arrhythmia originates outside of the normal conduction system and below the AV node (ie, ventricular tachycardia [VT]) Abnormalities within the His-Purkinje system (ie, SVT with aberrancy) Pre-excitation with an SVT conducting antegrade over an accessory pathway, resulting in direct activation of the ventricular myocardium A wide QRS complex tachycardia (WCT) represents a unique clinical challenge for three reasons: Diagnosing the arrhythmia is difficult Although most WCTs are due to VT, the differential diagnosis includes a variety of SVTs. Diagnostic algorithms to differentiate these two https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-causes-epidemiology-and-clinical-manifestations/print 1/27 7/5/23, 10:41 AM Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations - UpToDate etiologies are complex and imperfect. (See 'Differential diagnosis of WCT' below and "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'Diagnosis'.) Urgent therapy is often required Patients may be unstable at the onset of the arrhythmia or deteriorate rapidly at any time, particularly if the WCT is VT or SVT at an extremely rapid rate (eg, >200 beats per minute). Misdiagnosis of SVT when the true diagnosis is VT can lead to inappropriate therapy, which can precipitate hemodynamic collapse and cardiac arrest. The causes, epidemiology, and clinical manifestations of patients with a WCT will be discussed here. The initial evaluation, diagnosis, and management of wide QRS complex tachycardias, as well as discussion of narrow QRS complex tachycardias, are presented separately. (See "Wide QRS complex tachycardias: Approach to the diagnosis" and "Wide QRS complex tachycardias: Approach to management" and "Overview of the acute management of tachyarrhythmias" and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy" and "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation".) EPIDEMIOLOGY Ventricular tachycardia (VT) is the most common cause of WCT, particularly in patients with a history of cardiac disease. In a series of unselected patients, VT accounted for up to 80 percent of cases of WCT [1,2]. Among patients with structural heart disease (eg, those with a prior myocardial infarction), the likelihood of a WCT being VT exceeds 90 percent [2]. Supraventricular tachycardia (SVT) results in WCT much less frequently than VT. Among patients with WCT due to SVT, aberrant conduction is the most common reason for a widened QRS (21 percent of cases in one series) [1]. However, an aberrantly conducted SVT is still much less common than VT as the cause of WCT. Antidromic AV reentrant tachycardia (AVRT) is a relatively uncommon cause of WCT (6 percent of cases in one series) [1]. CLINICAL MANIFESTATIONS Symptoms Patients with WCT are rarely asymptomatic, although the type and intensity of symptoms will vary depending upon the rate of the WCT, the presence or absence of significant comorbid conditions, and whether the WCT is ventricular tachycardia (VT) or supraventricular tachycardia (SVT). Patients with WCT typically present with one or more of the following symptoms: https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-causes-epidemiology-and-clinical-manifestations/print 2/27 7/5/23, 10:41 AM Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations - UpToDate Palpitations Chest pain Shortness of breath Syncope or presyncope Sudden cardiac arrest Physical examination findings Few physical examination findings in patients with a WCT are unique to WCT. Common findings may include: Tachycardia By definition, patients will have a pulse exceeding 100 beats per minute related to the tachycardia. Hypotension Patients may be hypotensive, particularly those with underlying cardiac disease who are unable to tolerate tachycardia, which may result in alterations in consciousness. Hypoxia and lung crackles Patients in whom pulmonary congestion and heart failure result from the WCT may have hypoxia and crackles on lung examination. Often these patients will have underlying heart disease. Evidence of AV dissociation AV dissociation, which is present in up to 75 percent of patients with VT, is not always easy to detect [3-5]. During AV dissociation, the normal coordination of atrial and ventricular contraction is lost, which may produce characteristic physical findings. The presence of AV dissociation strongly suggests VT, although its absence is less helpful. Although AV dissociation is typically diagnosed on the ECG, characteristic physical examination findings include (see "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'AV dissociation'): Marked fluctuations in the blood pressure because of the variability in the degree of left atrial contribution to left ventricular filling, stroke volume, and cardiac output. Variability in the occurrence and intensity of heart sounds (especially S1; "cacophony of heart sounds"), which are heard more frequently when the rate of the tachycardia is slower. Cannon "A" waves Cannon A waves are intermittent and irregular jugular venous pulsations of greater amplitude than normal waves. They reflect simultaneous atrial and ventricular activation, resulting in contraction of the right atrium against a closed tricuspid valve. Prominent A waves can also be seen during some SVTs, but they are https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-causes-epidemiology-and-clinical-manifestations/print 3/27 7/5/23, 10:42 AM Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations - UpToDate usually regular, not irregular. Such prominent waves result from simultaneous atrial and ventricular contraction occurring with every beat. Classically, this is seen in AV nodal reentrant tachycardia (AVNRT) and has been called the "frog" sign. (See "Examination of the jugular venous pulse".) DIFFERENTIAL DIAGNOSIS OF WCT WCTs most often result from ventricular tachycardia (VT). Other less common causes include supraventricular tachycardia (SVT) with aberrant conduction, SVT with pre-excitation, SVT with ventricular pacing, and some types of artifact mimicking WCT ( table 1). Ventricular tachycardia VT usually originates within the ventricular myocardium, outside of the normal conduction system, resulting in direct myocardial activation. Compared with a normally conducted supraventricular beat (which activates the ventricular myocardium via the normal AV node-His-Purkinje system), ventricular activation during VT is slower and proceeds in a different sequence. Thus, the QRS complex is wide and abnormal ( waveform 1). As there may be slight changes of the activation sequence during the VT, reflecting the abnormal pathway of impulse conduction, there may be subtle changes in QRS complex morphology or in the ST-T waves. VT may have one of three typical patterns: Monomorphic Having a uniform and a fairly stable QRS morphology during an episode Polymorphic Having a continuously varying QRS complex morphology and/or axis during an episode Bidirectional Every other beat has a different axis as it travels alternately down different conduction pathways The features of each form of VT are discussed separately. (See "Sustained monomorphic ventricular tachycardia: Clinical manifestations, diagnosis, and evaluation" and "Catecholaminergic polymorphic ventricular tachycardia" and "Congenital long QT syndrome: Epidemiology and clinical manifestations".) Supraventricular tachycardia When an SVT conducts to the ventricles via the normal AV node and His-Purkinje system, the activation wavefront spreads quickly through the ventricles, and the QRS is usually narrow. In addition, the pathway of conduction to the ventricles is fixed and the same for each impulse, accounting for the uniformity of the QRS complexes and ST-T waves. However, SVT can also produce a widened QRS by a number of mechanisms, including aberrant conduction, pre-excitation, and the activation of ventricular pacing. https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-causes-epidemiology-and-clinical-manifestations/print 4/27 7/5/23, 10:42 AM Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations - UpToDate Aberrant conduction The conduction of a supraventricular impulse can be delayed or blocked in the bundle branches or in the distal Purkinje system, resulting in a wide, abnormal QRS. This phenomenon is referred to as aberrancy. (See "Basic approach to delayed intraventricular conduction".) Aberrant conduction may either be present at baseline or under certain conditions, such as faster heart rates. In patients with a left bundle branch block (LBBB), right bundle branch block, or a nonspecific intraventricular conduction delay on their baseline ECG, any SVT will have a widened QRS. Thus, if time allows, review of a baseline ECG can be helpful in differentiating VT from SVT with aberrancy. The presence of a conduction abnormality on the baseline ECG does not prove that the tachycardia is SVT with aberrancy, but the more similar the QRS during the WCT is to the QRS during sinus rhythm, the more likely it is that the WCT is an SVT with aberrancy. In patients with aberrancy at baseline who manifest a WCT in which the QRS complex is narrower than the baseline QRS, the WCT is likely VT originating near the ventricular septum, with early engagement of the specialized conducting system. This scenario is extremely unusual. In patients with a narrow QRS complex at baseline which widens at faster heart rates, conduction is normal during sinus rhythm but aberrant during the tachycardia. The most common reason for this is rate-related aberration (functional bundle branch block), in which rapidly generated impulses reach the conducting fibers before they have fully recovered from the previous impulse. Such a delay in recovery may also be the result of underlying disease of the His-Purkinje system, hyperkalemia, or the actions of antiarrhythmic drugs, particularly the class IC agents (eg, flecainide, propafenone). The class I antiarrhythmic drugs ( table 2) can cause significant slowing of conduction during SVT and also VT. These drugs, especially class IC agents, slow conduction and have a property of "use-dependency" (a progressive decrease in impulse conduction velocity and wider QRS complex duration at faster heart rates). As a result, these drugs can cause rate- related aberration and a wide QRS complex during any SVT. However, they can also cause VT with a very wide, bizarre QRS, which may be incessant [6,7]. (See "Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs".) Pre-excitation syndrome In the pre-excitation syndromes, AV conduction can occur over the normal conduction system and also via an accessory AV pathway ( figure 2A-C). These two pathways create the anatomic substrate for a reentrant circuit (macroreentrant circuit), https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-causes-epidemiology-and-clinical-manifestations/print 5/27 7/5/23, 10:42 AM Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations - UpToDate facilitating the development of a circus movement or reentrant tachycardia known as AV reentrant tachycardia (AVRT). (See "ECG tutorial: Preexcitation syndromes" and "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway", section on 'Narrow complex AVRT' and "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway", section on 'Wide complex AVRT'.) AVRT, which occurs both in patients with manifest pre-excitation (Wolff-Parkinson-White [WPW] syndrome) or concealed accessory pathways, can present with a narrow or a wide QRS complex: If antegrade conduction occurs over an accessory pathway and retrograde conduction occurs over the AV node or a second accessory pathway, the QRS complex will be wide with an unusual morphology. This is known as an antidromic AVRT ( figure 3 and waveform 2). Antidromic AVRT is difficult to differentiate from VT because ventricular activation starts outside the normal intraventricular conduction system in both types of tachycardia (ie, there is direct myocardial activation). (See "Wide QRS complex tachycardias: Approach to the diagnosis", section on 'VT versus AVRT'.) If antegrade conduction to the ventricles occurs over the AV node and retrograde conduction is over the accessory pathway, the QRS complex will be narrow (unless there is aberrant conduction at baseline with a wide QRS complex). This narrow complex AVRT is known as an orthodromic AVRT ( figure 4 and waveform 3). Orthodromic AVRT can also occur with rate-related aberrancy, creating a WCT. In addition, patients with a manifest accessory pathway (ie, WPW syndrome) may develop a different SVT (eg, atrial tachycardia, atrial fibrillation [AF], or atrial flutter). In such cases, the atrial impulses may use the accessory pathway to conduct to the ventricles, and the QRS could be either narrow or wide, depending upon whether ventricular activation occurs over the normal conduction system, the accessory pathway, or both ( waveform 4). (See "Wolff-Parkinson- White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis", section on 'Arrhythmias associated with WPW'.) Pacemakers When the ventricles are activated by a pacing device, the QRS complex is generally wide: Most transvenous ventricular pacemakers pace the right ventricle, causing a wide QRS complex of the LBBB type. Typically, the surface ECG shows a broad R wave in lead I, indicating conduction from right to left. (See "Overview of pacemakers in heart failure".) Pacemakers used in cardiac resynchronization therapy (CRT) usually pace both ventricles. Although CRT generates a QRS complex that is narrower than the patient's baseline (a https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-causes-epidemiology-and-clinical-manifestations/print 6/27 7/5/23, 10:42 AM Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations - UpToDate chronically widened QRS is one of the components of the indication for CRT), it is still usually longer than 120 milliseconds. The surface ECG usually shows a Q wave or QS complex in lead I, indicating activation from left to right, and there is usually a RBBB pattern in lead V . (See "Cardiac resynchronization therapy in heart failure: Indications and 1 choice of system".) Recognizing that a QRS complex is due to ventricular pacing can be challenging, particularly during a tachycardia. In addition to characteristic QRS morphology, a pacing "spike" or stimulus artifact can often be identified. The stimulus artifact is a narrow electrical signal too rapid to represent myocardial depolarization. Among patients with a pacemaker or an implantable cardioverter-defibrillator, further possibilities need to be considered in addition to the usual differential diagnosis of a WCT. These include: In the presence of sinus tachycardia or some SVTs (eg, an atrial tachycardia, AF, or atrial flutter), the device may "track" the atrial impulse and pace the ventricle at the rapid rate, resulting in a WCT. (See "Modes of cardiac pacing: Nomenclature and selection", section on 'Mode switching'.) A WCT can result if ventricular paced beats are conducted retrograde (backward) through the AV node to the atrium, resulting in an atrial signal, which the pacemaker senses and tracks with another ventricular stimulus. This ventricular paced beat is also conducted retrograde, and the cycle repeats indefinitely, a process termed pacemaker-mediated tachycardia (PMT) or endless loop tachycardia. PMT usually occurs at the upper rate limit. A different mechanism of pacemaker-associated tachycardia, non-reentrant repetitive ventriculoatrial synchrony, also creates a wide complex rhythm, but usually at the lower rate limit or sensor-mediated rate rather than at the upper rate limit. These and other arrhythmias associated with pacemakers are discussed in detail separately. (See "Unexpected rhythms with normally functioning dual-chamber pacing systems", section on 'Pacemaker-mediated tachycardia'.) Artifact mimicking ventricular tachycardia ECG artifact, particularly when observed on a single-lead rhythm strip, may be misdiagnosed as VT ( waveform 5) [8]. The presence of narrow-complex beats that can be seen to "march" through the supposed WCT at a fixed rate strongly supports the diagnosis of artifact. SOCIETY GUIDELINE LINKS https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-causes-epidemiology-and-clinical-manifestations/print 7/27 7/5/23, 10:42 AM Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations - UpToDate Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Arrhythmias in adults" and "Society guideline links: Ventricular arrhythmias" and "Society guideline links: Supraventricular arrhythmias".) SUMMARY AND RECOMMENDATIONS Background A wide QRS complex tachycardia (WCT) represents a unique clinical challenge for two reasons: Diagnosis of the arrhythmia is frequently difficult, and urgent therapy is often required. (See 'Introduction' above.) Epidemiology Ventricular tachycardia (VT) is the most common cause of WCT, particularly in patients with a history of cardiac disease, while supraventricular tachycardia (SVT) results in WCT (due to aberrant conduction, pre-excitation, or ventricular pacing) much less frequently. WCT is identified as VT in up to 80 percent of unselected patients and more than 90 percent of patients with known structural heart disease. (See 'Epidemiology' above and 'Differential diagnosis of WCT' above.) Clinical manifestations Patients with WCT are rarely asymptomatic, although the type and intensity of symptoms will vary depending upon the rate of the WCT, the presence or absence of significant comorbid conditions, and whether the WCT is VT or SVT. Patients with WCT typically present with one or more of the following: palpitations, chest pain, shortness of breath, syncope/presyncope, or sudden cardiac arrest. (See 'Clinical manifestations' above.) Differential diagnosis The differential diagnosis of WCTs includes (see 'Differential diagnosis of WCT' above): VT, including monomorphic VT, polymorphic VT, and bidirectional VT SVT with aberrant conduction SVT with conduction over an accessory pathway Paced ventricular rhythms ECG artifact ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-causes-epidemiology-and-clinical-manifestations/print 8/27 7/5/23, 10:42 AM Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations - UpToDate Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Miller JM, Das MK. Differential diagnosis of narrow and wide complex tachycardias. In: Cardi ac Electrophysiology From Cell to Bedside, 7th, Zipes DP, Jalife J, Stevenson WG (Eds), W.B. Sa unders, Philadelphia 2018. 2. Vereckei A. Current algorithms for the diagnosis of wide QRS complex tachycardias. Curr Cardiol Rev 2014; 10:262. 3. Gupta AK, Thakur RK. Wide QRS complex tachycardias. Med Clin North Am 2001; 85:245. 4. Tchou P, Young P, Mahmud R, et al. Useful clinical criteria for the diagnosis of ventricular tachycardia. Am J Med 1988; 84:53. 5. Wellens HJ, B r FW, Lie KI. The value of the electrocardiogram in the differential diagnosis of a tachycardia with a widened QRS complex. Am J Med 1978; 64:27. 6. Ranger S, Talajic M, Lemery R, et al. Kinetics of use-dependent ventricular conduction slowing by antiarrhythmic drugs in humans. Circulation 1991; 83:1987. 7. Ranger S, Talajic M, Lemery R, et al. Amplification of flecainide-induced ventricular conduction slowing by exercise. A potentially significant clinical consequence of use- dependent sodium channel blockade. Circulation 1989; 79:1000. 8. Knight BP, Pelosi F, Michaud GF, et al. Physician interpretation of electrocardiographic artifact that mimics ventricular tachycardia. Am J Med 2001; 110:335. Topic 116601 Version 16.0 https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-causes-epidemiology-and-clinical-manifestations/print 9/27 7/5/23, 10:42 AM Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations - UpToDate GRAPHICS Algorithm for the initial ECG review and differential diagnosis of tachycardia ECG: electrocardiogram; AVNRT: atrioventricular nodal reentrant tachycardia; AVRT: atrioventricular reciprocating (bypass-tract mediated) tachycardia; AT: atrial tachycardia; SANRT: sinoatrial nodal reentrant tachycardia; AF: atrial fibrillation; AV: atrioventricular; VT: ventricular tachycardia; SVT: supraventricular tachycardia; WPW: Wolff-Parkinson-White. A narrow QRS complex is <120 milliseconds in duration, whereas a wide QRS complex is 120 milliseconds duration. Refer to UpToDate topic reviews for additional details on specific ECG findings and management of individu arrhythmias. Monomorphic VT accounts for 80% of wide QRS complex tachycardias; refer to UpToDate topic on diagnosi wide QRS complex tachycardias for additional information on discriminating VT from SVT. Graphic 117571 Version 3.0 https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-causes-epidemiology-and-clinical-manifestations/print 10/27 7/5/23, 10:42 AM Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations - UpToDate Normal conduction system Schematic representation of the normal intraventricular conduction system (His- Purkinje system). The Bundle of His divides into the left bundle branch and right bundle branch. The left bundle branch divides into anterior, posterior, and, in some cases, median fascicles. AV: atrioventricular; RA: right atrium; LA: left atrium; RV: right ventricle; LV: left ventricle. Graphic 63340 Version 6.0 https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-causes-epidemiology-and-clinical-manifestations/print 11/27 7/5/23, 10:42 AM Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations - UpToDate Causes of a wide QRS complex tachycardia Ventricular tachycardia (VT) Any type of supraventricular tachycardia (SVT) with a preexistent bundle branch block or a rate-related (functional) bundle branch block Sinus tachycardia Atrial tachycardia Atrial flutter Atrioventricular nodal reentrant tachycardia Atrioventricular reentrant tachycardia (orthodromic) Any SVT which occurs in a patient receiving an antiarrhythmic drug, primarily class IA or IC, or in a patient with severe hyperkalemia Any SVT with antegrade conduction via an accessory pathway (Wolff-Parkinson-White syndrome) Sinus tachycardia Atrial tachycardia Atrial flutter Atrioventricular reentrant tachycardia (antidromic) Electronic pacemaker in certain specific settings Graphic 51512 Version 2.0 https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-causes-epidemiology-and-clinical-manifestations/print 12/27 7/5/23, 10:42 AM Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations - UpToDate 12-lead electrocardiogram (ECG) recorded in a patient with repetitive monomorphic ventricular tachycardia (RMVT) arising from the left ventricular outflow tract (LVOT) This electrocardiogram (ECG) illustrates repetitive monomorphic ventricular tachycardia (RMVT) with a right bundle, inferior axis morphology signifying its left ventricular site of origin. This VT was localized to the area of the aorto-mitral continuity in the left ventricular outflow tract (LVOT). Graphic 81690 Version 3.0 https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-causes-epidemiology-and-clinical-manifestations/print 13/27 7/5/23, 10:42 AM Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations - UpToDate Revised (2018) Vaughan Williams classification of antiarrhythmic drugs abridged table Class 0 (HCN channel blockers) Ivabradine Class I (voltage-gated Na+ channel blockers) Class Ia (intermediate dissociation): Quinidine, ajmaline, disopyramide, procainamide Class Ib (rapid dissociation): Lidocaine, mexilitine Class Ic (slow dissociation): Propafenone, flecainide Class Id (late current): Ranolazine Class II (autonomic inhibitors and activators) Class IIa (beta blockers): Nonselective: carvedilol, propranolol, nadolol Selective: atenolol, bisoprolol, betaxolol, celiprolol, esmolol, metoprolol Class IIb (nonselective beta agonists): Isoproterenol Class IIc (muscarinic M2 receptor inhibitors): Atropine, anisodamine, hyoscine, scopolamine Class IId (muscarinic M2 receptor activators): Carbachol, pilocarpine, methacholine, digoxin Class IIe (adenosine A1 receptor activators): Adenosine Class III (K+ channel blockers and openers) Class IIIa (voltage dependent K+ channel blockers): Ambasilide, amiodarone, dronedarone, dofetilide, ibutilide, sotalol, vernakalant Class IIIb (metabolically dependent K+ channel openers): https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-causes-epidemiology-and-clinical-manifestations/print 14/27 7/5/23, 10:42 AM Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations - UpToDate Nicorandil, pinacidil Class IV (Ca++ handling modulators) Class IVa (surface membrane Ca++ channel blockers): Bepridil, diltiazem, verapamil Class IVb (intracellular Ca++ channel blockers): Flecainide, propafenone Class V (mechanosensitive channel blockers): No approved medications Class VI (gap junction channel blockers) No approved medications Class VII (upstream target modulators) Angiotensin converting enzyme inhibitors Angiotensin receptor blockers Omega-3 fatty acids Statins HCN: hyperpolarization-activated cyclic nucleotide-gated; Na: sodium; K: potassium; Ca: calcium. Graphic 120433 Version 3.0 https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-causes-epidemiology-and-clinical-manifestations/print 15/27 7/5/23, 10:42 AM Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations - UpToDate AV conduction with a concealed accessory pathway Schematic representation of AV conduction. The normal pacemaker is in the sinoatrial (SA) node at the junction of the superior vena cava and the right atrium. The SA node activates the right and left atria (shown in green). In the absence of an accessory pathway (AP) or, as in this case, if the AP is concealed, ventricular activation results from the impulse traversing the AV node, the specialized infranodal conducting system (His bundle, bundle branches, and fascicular branches, shown in red), thereby activating the ventricular myocardium (shown in yellow). The ECG shows a normal PR interval and a narrow QRS complex. The inset on the right shows the timing of SA node (SAN), right (RA) and left atrial (LA), His bundle (H), and the beginning of normal ventricular activation (V ). All of ventricular activation (shown in yellow) is due to normal AV nodal and infranodal conduction. N AV: atrioventricular; ECG: electrocardiogram. Graphic 73740 Version 5.0 https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-causes-epidemiology-and-clinical-manifestations/print 16/27 7/5/23, 10:42 AM Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations - UpToDate AV conduction through an overt accessory pathway Compared with normal conduction in the preceding diagram, the accessory pathway (AP) is now overt. As a result, ventricular activation results from both early activation (pre-excitation) of the free wall of the left ventricle (shown in blue) and from normal activation (shown in yellow). The degree of unopposed pre-excitation depends upon the time required to conduct through the right and left atria, the AP, and the ventricular myocardium as compared with conduction through the normal pathways. The inset on the right shows the ECG timing of these events. The net effect is a QRS complex that is a fusion of ventricular pre-excitation (blue) and normal excitation (yellow). Early activation throughout the AP (V ) P occurs at about the same time as His bundle depolarization (H). This leads to a shorter PR interval, a small delta wave (arrow), and some prolongation of the QRS duration. AV: atrioventricular. Graphic 53773 Version 6.0 https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-causes-epidemiology-and-clinical-manifestations/print 17/27 7/5/23, 10:42 AM Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations - UpToDate Conduction through an accessory pathway with AV nodal delay Compared with conduction through an AP with normal AV node conduction, delayed conduction through the AV node allows more of the ventricular myocardium to be activated by pre-excitation (shown in blue). The inset on the right shows the ECG timing of these events. The atrial to His interval is increased due to the AV nodal delay (RA to H); His activation is so delayed that it follows activation caused by the AP (V ). The PR interval is short due to the pre- excitation, the delta wave (arrow) is more pronounced due to the greater and unopposed early forces (blue), and the QRS duration is P prolonged due to the later than normal ventricular activation caused by the AV nodal delay (yellow). AV: atrioventricular; ECG: electrocardiogram. Graphic 62454 Version 6.0 https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-causes-epidemiology-and-clinical-manifestations/print 18/27 7/5/23, 10:42 AM Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations - UpToDate Antidromic atrioventricular reentrant tachycardia (AVRT) in the setting of an accessory AV pathway The rhythm strip shows a sinus (S) beat that has a short PR interval and a wide QRS complex as a result of a delta wave (d). Panel A shows the activation sequence with an atrial premature beat (APB,*). The impulse reaches the atrioventricular node (N) before it has repolarized and hence is blocked in this structure. However, the accessory pathway (AP), which has a short refractory period, is able to conduct the impulse antegradely, resulting in an APB with a widened QRS morphology similar to the sinus beat. As seen in panel B, following myocardial activation, the impulse is conducted retrogradely along the His-Purkinje system and AV node, resulting in retrograde atrial activation, seen on the rhythm strip as an inverted P wave. If this activation sequence repeats itself (panel C), a wide QRS complex antidromic atrioventricular reentrant (or reciprocating) tachycardia (AVRT) is established. Graphic 50433 Version 4.0 https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-causes-epidemiology-and-clinical-manifestations/print 19/27 7/5/23, 10:42 AM Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations - UpToDate 12-lead electrocardiogram (ECG) showing antidromic atrioventricular reentrant tachycardia (AVRT) in a patient with an accessory AV pathway The 12-lead ECG of a patient with Wolff-Parkinson-White shows a regular tachycardia. The QRS complexes are widened and are identical to the QRS complexes seen in sinus rhythm; the antegrade conduction to the ventricle is via the accessory pathway and retrograde conduction is via the normal His- atrioventricular node pathway. This is, therefore, an antidromic atrioventricular reentrant tachycardia (AVRT). Courtesy of Martin Burke, DO. Graphic 54484 Version 20.0 ECG in Wolff-Parkinson-White https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-causes-epidemiology-and-clinical-manifestations/print 20/27 7/5/23, 10:42 AM Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations - UpToDate The 12-lead ECG shows the typical features of Wolff-Parkinson-White; the PR interval is short (*) and the QRS duration prolonged as a result of a delta wave (arrow), indicating ventricular preexcitation. Courtesy of Martin Burke, DO. Graphic 67181 Version 3.0 https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-causes-epidemiology-and-clinical-manifestations/print 21/27 7/5/23, 10:42 AM Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations - UpToDate Orthodromic atrioventricular reentrant tachycardia (AVRT) in the setting of an accessory AV pathway The rhythm strip shows a sinus (S) beat that has a short PR interval and a wide QRS complex as a result of a delta wave (d). Panel A shows an atrial premature beat (APB,*) that is blocked in the accessory pathway (AP), which has a long refractory period but is conducted antegradely through the atrioventricular node (N) and the His-Purkinje system, resulting in a normal PR interval and a narrow and normal QRS complex, as seen on the rhythm strip. After normal myocardial activation, the impulse is conducted retrogradely along the AP, activating the atrium in a retrograde fashion (panel B), which results in a negative P wave. If this activation sequence repeats itself (panel C), an orthodromic atrioventricular reentrant (or reciprocating) tachycardia (AVRT) is established. Graphic 71302 Version 7.0 https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-causes-epidemiology-and-clinical-manifestations/print 22/27 7/5/23, 10:42 AM Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations - UpToDate 12-lead electrocardiogram (ECG) showing orthodromic atrioventricular reentrant tachycardia (AVRT) in a patient with an accessory AV pathway The 12-lead ECG from a patient with Wolff-Parkinson-White shows a regular tachycardia. However, in contrast to the QRS pattern during sinus rhythm, the QRS complexes are narrow, without evidence of a delta wave or pre-excitation; this is due to the fact that antegrade ventricular activation occurs via the normal atrioventricular node-His Purkinje pathway, while retrograde atrial activation is via the accessory pathway. Therefore, this is called an orthodromic atrioventricular reentrant tachycardia (OAVRT). Courtesy of Martin Burke, DO. Graphic 68804 Version 5.0 ECG in Wolff-Parkinson-White https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-causes-epidemiology-and-clinical-manifestations/print 23/27 7/5/23, 10:42 AM Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations - UpToDate The 12-lead ECG shows the typical features of Wolff-Parkinson-White; the PR interval is short (*) and the QRS duration prolonged as a result of a delta wave (arrow), indicating ventricular preexcitation. Courtesy of Martin Burke, DO. Graphic 67181 Version 3.0 https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-causes-epidemiology-and-clinical-manifestations/print 24/27 7/5/23, 10:42 AM Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations - UpToDate ECG pre-excited atrial fibrillation 12-lead ECG showing atrial fibrillation in a patient with antegrade conduction through both the AV node and accessory pathway. The occasional narrow QRS complexes reflect conduction through the AV node, while the QRS complexes, with instantaneous rates close to 300 beats per minute, are due to antegrade conduction via accessory pathway (probably postero-septal based on the QRS morphology). AV: atrioventricular; ECG: electrocardiogram. Reproduced with permission from: Nathanson LA, McClennen S, Safran C, Goldberger AL. ECG Wave-Maven: Self-Assessment Program f Students and Clinicians. http://ecg.bidmc.harvard.edu. Graphic 117553 Version 1.0 https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-causes-epidemiology-and-clinical-manifestations/print 25/27 7/5/23, 10:42 AM Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations - UpToDate Tremor artifact This dramatic example of tremor artifact demonstrates complexes that simulate a run of ventricular tachycardia. However, QRS complexes (arrows) can clearly be seen marching through the rhythm strip. Graphic 62575 Version 3.0 https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-causes-epidemiology-and-clinical-manifestations/print 26/27 7/5/23, 10:42 AM Wide QRS complex tachycardias: Causes, epidemiology, and clinical manifestations - UpToDate Contributor Disclosures Peter J Zimetbaum, MD Consultant/Advisory Boards: Abbott Medical [Lead extraction]. All of the relevant financial relationships listed have been mitigated. Ary L Goldberger, MD Other Financial Interest: Elsevier book royalties [Clinical electrocardiography]. All of the relevant financial relationships listed have been mitigated. James Hoekstra, MD No relevant financial relationship(s) with ineligible companies to disclose. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/wide-qrs-complex-tachycardias-causes-epidemiology-and-clinical-manifestations/print 27/27

7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome : Bradley P Knight, MD, FACC : Peter J Zimetbaum, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Dec 06, 2021. INTRODUCTION Conduction from the atria to the ventricles normally occurs via the atrioventricular (AV) node/His-Purkinje system. Patients with a preexcitation syndrome have an additional or alternative pathway, known as an accessory pathway, which directly connects the atria and ventricle and bypasses the AV node. AV conduction through an accessory pathway (most commonly a direct AV connection) results in the earlier activation of the ventricles than if the impulse had traveled through the AV node; hence the term preexcitation. Accessory pathway is a generic term which may indicate either a "tract" which bypasses the AV node but inserts into the specialized conduction system (eg, the bundle of His, right or left bundles, or one of the fascicles), or a "connection" which bypasses the AV node and terminates directly within the myocardium. Other names that may be used include anomalous AV pathway, connection, or tract; accessory AV bypass pathway, connection, or tract; or simply AV bypass, tract, or pathway. (See "General principles of asynchronous activation and preexcitation".) At other times, the specific sites of origin and termination are used. Examples include accessory AV connection, atrio-Hisian pathway or connection, or atriofascicular pathway or connection ( table 1). Preexcitation through an AV bypass tract, the bundle of Kent, during sinus rhythm produces the electrocardiographic (ECG) pattern described by Wolff, Parkinson, and White in 1930 [1]. The terms preexcitation and Wolff-Parkinson-White (WPW) pattern are often used interchangeably. https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 1/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate The ECG pattern of WPW should be differentiated from the "WPW syndrome," since patients with the latter have both the ECG pattern of preexcitation and paroxysmal tachyarrhythmias [2]. (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis".) This topic will review the anatomy and electrophysiologic properties of the accessory pathways. These accessory pathways are clinically important because they can serve as one limb of a reentrant circuit during AV reentrant tachycardia, either orthodromic and antidromic, or can allow for frequent rapid conduction to the ventricles during atrial fibrillation leading to ventricular fibrillation and cardiac arrest. The related issue of asynchronous activation, the arrhythmias associated with WPW, and the pharmacologic and nonpharmacologic treatments of patients with this syndrome are discussed separately. A detailed discussion of electrophysiologic mapping techniques is found elsewhere. (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis" and "Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome" and "Invasive diagnostic cardiac electrophysiology studies", section on 'Mapping and ablation'.) ANATOMIC CONSIDERATIONS There are several types of accessory pathways ( table 1 and figure 1) [3,4]: The classic accessory pathway is the AV bypass tract or bundle of Kent in patients with Wolff-Parkinson-White pattern. This pathway directly connects atrial and ventricular myocardium, bypassing the AV node/His-Purkinje system. James fibers, atrionodal tracts, connect the atrium to the distal or compact AV node. (See "Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction".) Atrio-Hisian tracts connect the atrium to His bundle. Various types of Hisian-fascicular tracts, also known as Mahaim fibers, connect the atrium (atriofascicular pathways), AV node (nodofascicular pathways) or His bundle (fasciculoventricular) to distal Purkinje fibers or ventricular myocardium. (See "Atriofascicular ("Mahaim") pathway tachycardia".) The gross anatomy of AV accessory pathways should be considered in two planes that run transversely at the level of and parallel to the AV groove and longitudinally perpendicular to the AV groove [5]. https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 2/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate Transverse plane In the transverse plane, bypass tracts can cross the AV groove anywhere except between the left and right fibrous trigones where the atrial myocardium is not in direct juxtaposition with ventricular myocardium. The remainder of the transverse plane can then be divided into quadrants consisting of the left free wall, posteroseptal, right free wall, and anteroseptal spaces ( figure 2) [5,6]. The distribution of accessory pathways within these regions is not homogeneous [7,8]: 46 to 60 percent of accessory pathways are found within the left free wall space 25 percent are within the posteroseptal space 13 to 21 percent of pathways are within the right free wall space 2 percent are within the anteroseptal space The left and right free wall spaces can be subdivided into anterior, anterolateral, lateral, posterolateral, and posterior zones. Distinctive 12-lead ECG patterns of fully preexcited QRS morphology have been validated during surgical mapping and ablation of accessory pathways within each of these subdivisions [9-13] Detailed knowledge of accessory pathway location within the free wall regions is of critical importance to the interventional electrophysiologist performing catheter ablation procedures [14]. Longitudinal plane Accessory pathway anatomy in the longitudinal plane can be most easily understood by studying a longitudinal section of the left free wall region ( figure 3). AV accessory pathways exist only between the annulus fibrosus and the epicardial reflection off the atrial and ventricular walls, confined within the AV groove subepicardial fat of the right and left free walls, the anteroseptal space, and the posteroseptal space. Accessory pathways insert directly into the atrial and basal ventricular myocardium, although they may course through the AV groove at a variable depth from subepicardial to subendocardial [5]. There are also vascular structures located in these regions. These include the circumflex coronary artery and coronary sinus in the left free wall space; the coronary sinus, middle cardiac vein, and posterior descending artery in the posteroseptal space; and the right coronary artery in the anteroseptal and right free wall spaces. AV accessory pathways may run in an oblique course rather than perpendicular to the transverse plane of the AV groove. As a result, the fibers may have an atrial insertion point that is transversely several centimeters removed from the point of ventricular attachment [15]. Finally, bypass tracts may occasionally exist as broad bands of tissue rather than discrete hair- like structures [5]. Associated structural cardiac abnormalities Accessory pathways are associated with structural heart abnormalities. Patients with hypertrophic cardiomyopathy appear to have a https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 3/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate higher incidence of accessory pathways than the normal population. (See "Hypertrophic cardiomyopathy in adults: Supraventricular tachycardias including atrial fibrillation".) In one study, familial hypertrophic cardiomyopathy with Wolff-Parkinson-White syndrome was mapped to a locus on chromosome 7q3 [16]. Patients with Ebstein anomaly can have right sided accessory pathways associated with the abnormal tricuspid valve and often have multiple accessory pathways. (See "Clinical manifestations and diagnosis of Ebstein anomaly".) There is an association with a dilated cardiomyopathy and ventricular preexcitation that can have a genetic basis. In addition, there are patients with a dilated cardiomyopathy felt to be caused by the ventricular dyssynchrony introduced by the ventricular preexcitation. This can resolve after ablation of the accessory pathway analogous to the improvements in ventricular function seen after cardiac resynchronization pacing therapy in patients with left bundle branch block and ventricular dysfunction [17,18]. Posteroseptal accessory pathways may involve more than just the atrial and ventricular musculature, and include the musculature surrounding the coronary sinus [19]. In a study of 480 patients with posteroseptal or left posterior accessory pathways, 171 were found to involve the coronary sinus musculature [20]. The delta wave was negative in lead II in 70 percent of these patients. A coronary sinus diverticulum was found in 21 percent of these patients at this tertiary referral center, but in only 2 percent of the patients who had not had a prior ablation attempt. For this reason, it is important to perform venography of the proximal coronary sinus during an ablation procedure in a patient with a posteroseptal accessory pathway when elimination of the pathway proves to be difficult. ELECTROPHYSIOLOGY OF PREEXCITATION The normal temporal and spatial sequence of atrial and ventricular activation is altered in the Wolff-Parkinson-White (WPW) type of preexcitation because conduction between the atria and ventricles involves both an accessory pathway and the normal AV node-His Purkinje system. The vast majority of accessory pathways generate a fast action potential due to the rapid inward sodium current, similar to normal His-Purkinje tissue and atrial and ventricular myocardium (see "Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs"). As a result, they have constant antegrade and retrograde conduction at all rates until the refractory period is reached, at which time conduction is completely blocked (nondecremental conduction). In contrast, the AV node, which depends on the slow inward calcium current for generation and propagation of its action potential, exhibits decremental conduction in which the conduction https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 4/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate time of the impulse propagating through the AV node increases as the cycle length shortens (heart rate increased) [21]. Thus, AV conduction is more rapid through the accessory pathway than through the AV node, a difference that is increased at fast heart rates. This difference has potentially great clinical importance. The progressive prolongation of AV nodal conduction time at faster atrial rates has a protective role, limiting the ventricular response to rapid atrial rates in atrial fibrillation or atrial flutter. This decreasing speed of conduction until some but not all beats are transmitted through the AV nodal tissue is called decremental conduction. Accessory pathways are dependent on the rapid inward sodium current for depolarization and characteristically do not demonstrate decremental conduction. As a result, arrhythmias that utilize accessory pathways can conduct frequently and rapidly, leading to very fast ventricular rates during atrial fibrillation that may degenerate into ventricular fibrillation. (See "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway".) Mahaim fibers may have somewhat different properties in that they may show slow and decremental anterograde conduction, proximal AV nodal-like electrophysiologic properties and distal bundle branch-like properties, conduction block in response to adenosine, and heat- induced automaticity during radiofrequency catheter ablation. Spontaneous automaticity may arise in Mahaim fibers, particularly during ablation procedures of the atrial insertion, and this may trigger antidromic circus movement tachycardias [22]. Accessory pathways that directly connect the atrium to the ventricle can occasionally show slow and decremental conduction in the retrograde direction. When these slowly conducting pathways serve as the retrograde limb during orthodromic AV reentrant tachycardia, the RP interval is usually longer than the PR interval. These accessory pathways can lead to the permanent form of junctional reciprocating tachycardia and are usually located in the posteroseptal space [23]. (See "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway", section on 'Permanent junctional reciprocating tachycardia'.) Rarely, accessory pathways that directly connect the atrium to the ventricle can also show decremental conduction in the antegrade direction. In these patients, preexcitation is not evident during sinus rhythm because conduction over the AV node is faster than over the accessory pathway, but the pathway can serve as the antegrade limb during antidromic AV reentrant tachycardia and give rise to a wide QRS tachycardia. These pathways are also usually in the posteroseptal location [24]. Ventricular activation Since an AV accessory pathway usually bypasses and conducts faster than the AV node, the onset of ventricular activation is earlier than expected if depolarization https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 5/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate occurred via the AV node. Since the accessory pathway usually exhibits nondecremental conduction, early activation remains constant at all heart rates. Preexcited intraventricular conduction in WPW spreads from the insertion point of the AV bypass tract in the ventricular myocardium via direct muscle fiber-to-muscle fiber conduction. This process is inherently slower than ventricular depolarization resulting from rapid His-Purkinje system conduction. Thus, the net effect is earlier initial excitation of the ventricles (via the accessory pathway) but slower activation of the ventricular myocardium than occurs normally. The net effect is that the QRS complex consists of fusion between early ventricular activation caused by preexcitation with the later ventricular activation resulting from transmission through the AV node and the infranodal conduction system to the ventricles. The initial part of ventricular activation is slowed and the upstroke of the QRS complex is slurred because of slow muscle fiber-to-muscle fiber conduction; this is termed a delta wave ( figure 4A-B). The sooner conduction occurs over the accessory pathway in relation to the AV node, the greater the amount of myocardium depolarized via the accessory pathway, resulting in a more prominent or wider delta wave, and increasing prolongation of the QRS complex ( figure 5). Minimal preexcitation in WPW Preexcitation and delta waves may not be apparent in sinus rhythm in patients with WPW who have a left-lateral bypass tract as the antegrade route for conduction; in this setting, the time for the atrial impulse to travel from the sinus node to reach the atrial insertion of the accessory pathway is longer than the time to reach the AV node. The presence of a septal Q wave in lead V6 of the surface ECG is useful to exclude minimal preexcitation with a high degree of reliability [25]. When there is uncertainty regarding the presence of ventricular preexcitation, vagal maneuvers can be performed or intravenous adenosine can be administered to cause transient AV nodal blockade. The P wave signal-averaged ECG may also be of help in identifying a concealed left-sided accessory pathway. In one series, such a bypass tract was associated with a more prolonged filtered P wave duration (132 versus 119 milliseconds in controls or patients with an AV nodal reentrant tachycardia) [26]. In addition, delta waves are not seen with non-WPW forms of preexcitation, such as Mahaim or James fibers, since these pathways terminate in the conducting system or in the ventricular myocardium close to the conducting system. Most Mahaim tachycardias, for example, are due to atriofascicular pathways. (See "Atriofascicular ("Mahaim") pathway tachycardia".) PR interval Since the impulse bypasses the AV node, the preexcited PR interval is often shorter than what would be considered normal; however, it may not be abnormally short in the https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 6/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate absolute sense [27]. The degree of PR interval shortening and the amount of QRS interval widening depend upon several factors: The balance between the antegrade conduction time and refractory period of the accessory pathway and those of the normal AV node/His-Purkinje system; the conduction properties of both are variably influenced by the autonomic nervous system. The atrial insertion point of the AV bypass tract. The site of atrial impulse origin. Interatrial conduction time. Atrial refractoriness. Because of these factors, preexcitation may be less apparent during sinus tachycardia when AV node conduction time is short due to elevated sympathetic tone and decreased vagal tone. In addition, as mentioned above, an AV bypass tract that crosses the AV groove in the left lateral region may result in inapparent preexcitation and minimal PR interval shortening in sinus rhythm because of the greater interatrial distance required for impulse propagation from the sinus node to the left atrial insertion of the bypass tract. Intermittent preexcitation Intermittent preexcitation should be distinguished from day-to- day variability in preexcitation which results from changes in AV nodal conduction in relation to those of the accessory pathway usually due to changes in autonomic tone. True intermittent preexcitation is characterized by abrupt loss of the delta wave, normalization of the QRS duration, and an increase in the PR interval during a continuous ECG recording in the absence of any significant change in heart rate. This finding is generally a reliable sign that the AV bypass tract has a relatively long antegrade refractory period and is not capable of frequent impulse conduction, thus placing the patient at low risk for ventricular arrhythmias [27]. Preexcitation alternans In preexcitation alternans, a QRS complex manifesting a delta wave alternates with a normal QRS complex. This is also a marker for an accessory pathway with a relatively long antegrade refractory period. Concertina effect The amount of fusion of the QRS complex varies with the electrophysiologic properties of the accessory pathway, which are influenced by sympathetic and parasympathetic tone and their effect on the AV node. As a result, the appearance and width of the QRS complex depends upon the balance between preexcitation and normal excitation via the AV node. If AV nodal conduction is fast, the amount of myocardium activated via the accessory pathway is less, and hence there is a longer PR interval, less prominent delta https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 7/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate wave, and narrower QRS complex. If AV nodal conduction is slow, more myocardium is activated via the accessory pathway, resulting in a shorter PR interval, more prominent delta wave, and wider QRS complex. Changing degrees of AV nodal conduction and hence fusion in some patients may cause the QRS duration and the PR interval to periodically wax and wane, resulting in an appearance referred to as the "concertina effect" of preexcitation ( waveform 1 and waveform 2). In this phenomenon, PR intervals and QRS complex durations show a cyclic pattern, eg, preexcitation becomes progressively more prominent over a number of QRS complex cycles followed by a gradual diminution in the degree of preexcitation over several QRS cycles despite a fairly constant heart rate [28,29]. Accessory pathways exhibiting decremental conduction Approximately 10 percent of patients have accessory pathways in which conduction slows at faster rates of stimulation (decremental conduction), similar to the situation with the AV node. As noted above, the progressive prolongation of AV nodal conduction time at faster atrial rates has a protective role, limiting the ventricular response to rapid atrial rates in atrial fibrillation or atrial flutter. Accessory pathways which display decremental conduction in one direction may exhibit varied electrophysiologic properties in the other. As an example, one study examined the characteristics of the accessory pathway in 74 patients with decremental accessory pathways [30]. Among 64 patients with retrograde decremental conduction, anterograde conduction was not present in 64 percent, was intermittent in 8 percent, and was nondecremental in 28 percent. Five patients had anterograde but not retrograde conduction, and five had conduction in both directions. Another study examined 384 symptomatic patients with a single accessory pathway and found that retrograde decremental conduction over the accessory pathway was present in the posteroseptal (17 percent) and left free wall (3 percent), but absent in the other locations. Anterograde decremental conduction was only seen in the right free wall location (12 percent) [24]. Concealed accessory pathways Although AV accessory pathways usually conduct antegradely and retrogradely, some AV bypass tracts are capable of propagating impulses in only one direction [8,12,14,29-31]. Bypass tracts that conduct only in an antegrade direction are uncommon. They often cross the right AV groove, and frequently possess decremental conduction properties [8,27,31-33]. Bypass tracts that conduct only in the retrograde direction occur more frequently with an incidence reported as high as 16 percent [34]. Because they do not preexcite the ventricles, the surface ECG during sinus rhythm appears normal and therefore these pathways are called https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 8/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate "concealed." Some concealed pathways may be able to conduct anterograde, but have such long refractory periods that they do not conduct during sinus rhythm and are concealed. Preexcitation can sometimes be seen in patients with this type of a concealed accessory pathway after a long sinus pause, such as immediately after termination of AV reciprocating tachycardia. Most concealed AV bypass tracts exhibit nondecremental conduction and, because they serve as conduit for retrograde ventriculoatrial conduction, they are associated with reentrant arrhythmias [34,35]. Concealed accessory pathways that have decremental properties are usually located in the posteroseptal region. However, these pathways also occur in nonseptal locations with an incidence as high as 25 percent in one series [36]. (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis", section on 'Prevalence of concealed accessory pathways'.) RELATIONSHIP BETWEEN ACCESSORY PATHWAY SITE AND THE ELECTROCARDIOGRAPHIC PATTERN Many articles have attempted to correlate the site of the accessory pathway with the ECG pattern [13,37-41]. However, the ECG appearance of activation depends upon the extent of preexcitation and fusion; as a result, the same pathway may not always produce the identical ECG pattern. Furthermore, as many as 13 percent of individuals with preexcitation have more than one accessory pathway. (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis", section on 'Accessory pathway location'.) The surface ECG does, however, provide important clues for the cardiologist to direct invasive mapping. It also serves as a guide for the electrophysiologist to anticipate the morbidity of the particular procedural approach required to treat a particular accessory pathway (eg, ablation of pathways near the AV node and bundle of His has a higher inherent risk of inducing AV block and requiring a permanent pacemaker). This information related to pathway location is helpful when counseling patients about the risks of ablation. The optimal time to use the surface ECG to estimate the location of the accessory pathway is in the electrophysiology laboratory during atrial pacing at a rate that results in maximal preexcitation. Localizing the accessory AV connection site based upon the ECG A useful approach to map the location of the common form of accessory pathway, the accessory AV connection (AAVC), combines the algorithms of Milstein ( figure 2 and algorithm 1) and Arruda ( figure 2 and algorithm 2) [13,39,41,42]. The Milstein approach accurately localizes the AAVC to general regions along the AV rings; the Arruda approach is more precise, as has been confirmed by https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 9/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate endocardial mapping, and is helpful in further discriminating the septal areas of the AV rings. Distinctly classifying the posteroseptal/midseptal/anteroseptal areas also helps the clinician prepare the patient for different treatment options, including radiofrequency ablation, medical therapy, or monitoring. (See "Treatment of arrhythmias associated with the Wolff-Parkinson- White syndrome".) Vector of the delta wave The first step is to assess the vector of the delta wave: Is the delta wave vector directed away from or isoelectric to the leftward leads I, aVL, or V6? In other words, is the delta wave a Q wave or isoelectric in I, aVL, or V6? If yes and a left bundle branch block (LBBB)-type pattern is also present, (QRS 0.09 sec in lead I with an rS pattern in V1 or V2), a right anteroseptal pathway is suggested ( waveform 3). This connection initiates a generally rightward activation of the right ventricle (RV) in one of the leftward leads (leading to negative delta waves in aVL and/or V6). The asynchronous activation of the right and then the left ventricle (LV) produces the LBBB-like ECG pattern. The QRS axis is greater than +30 which helps distinguish the right anteroseptal from a right lateral pathway. If yes and a LBBB-type configuration is not present, a left lateral pathway is suggested ( waveform 4 and waveform 5). Preexcitation begins in the lateral portion of the left ventricle; as a result, initial activation is to the right as reflected by a negative delta wave in one or more of the leftward leads (ECG 2 shows isoelectric to negative polarity in I and aVL while ECG 3 shows a negative delta wave in aVL). The pattern may then resemble an atypical right bundle branch block, because preexcitation begins in the left ventricle. If the delta waves in leads I, aVL and V6 are other than a Q wave or isoelectric, examine the vector first in the frontal plane and then in the horizontal plane. Specifically, see if the delta wave vector in the frontal plane forms a Q wave or is isoelectric in two of leads II, III, or aVF. If yes, examine the horizontal plane. If there is an Rs or RS in V1, V2, or V3, a posteroseptal pathway is suggested ( waveform 6A-D). Preexcitation therefore begins in the posterior portion of the septum and sweeps anteriorly, giving the initial positive R complex in the anterior precordial leads. Further discrimination is discussed in the legends to the ECGs. If yes, and the pattern is other than an Rs or RS in V1, V2, or V3, a right lateral pathway is suggested ( waveform 7). Preexcitation begins in the lateral portion of the right ventricle, which is anatomically anterior and to the right; as a result, activation is posteriorly and to the left. A LBBB-type pattern results because the RV is activated before the LV. The axis is https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 10/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate less than +30 (ECG 5 has a negative delta wave in III and is isoelectric in aVF), which distinguishes the right lateral from the anteroseptal pathway. If the pattern in leads II, III or aVF is not a Q or isoelectric delta wave, then: A left bundle branch type of pattern (QRS equal to or greater than 90 msec in I and rS in V1 or V2) with a QRS axis of more than +30 suggests a right anteroseptal pathway ( waveform 3). A left bundle branch type of pattern (QRS equal to or greater than 90 msec in I and rS in V1 or V2) with an axis that is +30 or less suggests a right lateral pathway ( waveform 7). An Rs or RS in V1 or V2, but a pattern not that of a left bundle branch type as defined above, suggests a left lateral pathway ( waveform 4 and waveform 5). If other than an Rs or RS, the pathway may be difficult to localize and probably represents a left anterior lateral pathway ( waveform 8). Another algorithm is based upon a stepwise discriminant analysis of 18 variables in patients who had undergone successful catheter ablation [13]: Right-sided pathways were distinguished from left-sided pathways by the QRS transition in V1 to V3. Anterior-posterior, septal, and lateral pathways were localized by an analysis of delta wave and QRS polarities. The algorithm was quite successful in identifying right- and left-sided accessory pathways, right free wall from right septal, right anterolateral from posterolateral, and anteroseptal from other right septal pathways ( waveform 9). Left anterolateral pathways were also distinguished from left posterior pathways, and right posterolateral pathways were distinguished from left posteroseptal pathways. The reader who wishes to pursue the ECG patterns further should consult the sophisticated and complex scheme based upon delta wave polarity, which has been described in detail elsewhere [9]. Mahaim fibers may be suggested by a narrow QRS with an rS pattern in lead III. During tachycardia, these individuals usually have a LBBB-like QRS complex with left axis deviation [43]. A more detailed discussion for the specialist is available elsewhere [44]. SUMMARY https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 11/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate Patients with a preexcitation syndrome have an additional or alternative pathway, known as an accessory pathway, which directly connects the atria and ventricle and bypasses the atrioventricular (AV) node. During sinus rhythm, AV conduction through an accessory pathway (most commonly a direct AV connection) results in the earlier activation of the ventricles than if the impulse had traveled through the AV node, resulting in ventricular preexcitation. (See 'Introduction' above.) Some accessory pathways are associated with structural heart abnormalities. (See 'Anatomic considerations' above.) The classic accessory pathway is the AV bypass tract in patients with the Wolff-Parkinson- White (WPW) pattern. This pathway directly connects atrial and ventricular myocardium, bypassing the AV node/His-Purkinje system. (See 'Anatomic considerations' above.) Delta waves may not be apparent in sinus rhythm in patients with WPW who have a left- lateral bypass tract as the antegrade route for conduction. (See 'Minimal preexcitation in WPW' above.) Although AV accessory pathways usually conduct antegrade and retrograde, some AV bypass tracts are capable of propagating impulses in only one direction. (See 'Concealed accessory pathways' above.) The electrocardiographic (ECG) appearance of activation depends upon the extent of preexcitation and fusion; as a result, the same pathway may not always produce the identical ECG pattern. (See 'Relationship between accessory pathway site and the electrocardiographic pattern' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Wolff, L, Parkinson, et al. Bundle branch block with a short P-R interval in healthy young people prone to paroxysmal tachycardia. Am Heart J 1930; 5:685. 2. Definition of terms related to cardiac rhythm. Am Heart J 1978; 95:796. 3. Waller BF. Clinicopathological correlations of the human cardiac conduction system. In: Card iac Electrophysiology, Zipes DP, Jalife J (Eds), WB Saunders, Philadelphia 1990. p.249. 4. Anderson RH, Becker AE, Brechenmacher C, et al. Ventricular preexcitation. A proposed nomenclature for its substrates. Eur J Cardiol 1975; 3:27. https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 12/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 5. Ferguson TB, Cox JL. Surgical treatment for the Wolff-Parkinson-White syndrome: the endoc ardial approach. In: Cardiac Electrophysiology, Zipes DP, Jalife J (Eds), WB Saunders, Philadel phia 1990. p.897. 6. Cox JL, Gallagher JJ, Cain ME. Experience with 118 consecutive patients undergoing operation for the Wolff-Parkinson-White syndrome. J Thorac Cardiovasc Surg 1985; 90:490. 7. Cain ME, Cox JL. Surgical treatment of supraventricular arrhythmias. In: Management of car diac arrhythmias: the nonpharmacologic approach, Platia E (Ed), JB Lippincott, Philadelphia 1987. p.304. 8. Gallagher JJ, Sealy WC, Kasell J. Intraoperative mapping studies in the Wolff-Parkinson-White syndrome. Pacing Clin Electrophysiol 1979; 2:523. 9. Gallagher JJ, Pritchett EL, Sealy WC, et al. The preexcitation syndromes. Prog Cardiovasc Dis 1978; 20:285. 10. Reddy GV, Schamroth L. The localization of bypass tracts in the Wolff-Parkinson-White syndrome from the surface electrocardiogram. Am Heart J 1987; 113:984. 11. Fananapazir L, German LD, Gallagher JJ, et al. Importance of preexcited QRS morphology during induced atrial fibrillation to the diagnosis and localization of multiple accessory pathways. Circulation 1990; 81:578. 12. Lindsay BD, Crossen KJ, Cain ME. Concordance of distinguishing electrocardiographic features during sinus rhythm with the location of accessory pathways in the Wolff- Parkinson-White syndrome. Am J Cardiol 1987; 59:1093. 13. Milstein S, Sharma AD, Guiraudon GM, Klein GJ. An algorithm for the electrocardiographic localization of accessory pathways in the Wolff-Parkinson-White syndrome. Pacing Clin Electrophysiol 1987; 10:555. 14. Cain ME, Luke RA, Lindsay BD. Diagnosis and localization of accessory pathways. Pacing Clin Electrophysiol 1992; 15:801. 15. Otomo K, Gonzalez MD, Beckman KJ, et al. Reversing the direction of paced ventricular and atrial wavefronts reveals an oblique course in accessory AV pathways and improves localization for catheter ablation. Circulation 2001; 104:550. 16. MacRae CA, Ghaisas N, Kass S, et al. Familial Hypertrophic cardiomyopathy with Wolff- Parkinson-White syndrome maps to a locus on chromosome 7q3. J Clin Invest 1995; 96:1216. 17. Dai CC, Guo BJ, Li WX, et al. Dyssynchronous ventricular contraction in Wolff-Parkinson- White syndrome: a risk factor for the development of dilated cardiomyopathy. Eur J Pediatr 2013; 172:1491. https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 13/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 18. Chiu SN, Chang CW, Lu CW, Wu MH. Restored cardiac function after successful resynchronization by right anterior and anteroseptal accessory pathway ablation in Wolff- Parkinson-White syndrome associated dilated cardiomyopathy. Int J Cardiol 2013; 163:e19. 19. Chauvin M, Shah DC, Ha ssaguerre M, et al. The anatomic basis of connections between the coronary sinus musculature and the left atrium in humans. Circulation 2000; 101:647. 20. Sun Y, Arruda M, Otomo K, et al. Coronary sinus-ventricular accessory connections producing posteroseptal and left posterior accessory pathways: incidence and electrophysiological identification. Circulation 2002; 106:1362. 21. Prystowsky EN, Page RL. Electrophysiology and autonomic influences of the human atrioven tricular node. In: Electrophysiology of the Sinoatrial and Atrioventricular Nodes, Mazgalev T, Dreifus L, Michelson EL (Eds). 22. Sternick EB, Timmermans C, Sosa E, et al. The electrocardiogram during sinus rhythm and tachycardia in patients with Mahaim fibers: the importance of an "rS" pattern in lead III. J Am Coll Cardiol 2004; 44:1626. 23. Gaita F, Haissaguerre M, Giustetto C, et al. Catheter ablation of permanent junctional reciprocating tachycardia with radiofrequency current. J Am Coll Cardiol 1995; 25:648. 24. de Chillou C, Rodriguez LM, Schl pfer J, et al. Clinical characteristics and electrophysiologic properties of atrioventricular accessory pathways: importance of the accessory pathway location. J Am Coll Cardiol 1992; 20:666. 25. Bogun F, Kalusche D, Li YG, et al. Septal Q waves in surface electrocardiographic lead V6 exclude minimal ventricular preexcitation. Am J Cardiol 1999; 84:101. 26. Yoshida T, Ikeda H, Hiraki T, et al. Detection of concealed left sided accessory atrioventricular pathway by P wave signal averaged electrocardiogram. J Am Coll Cardiol 1999; 33:55. 27. Josephson ME. Preexcitation Syndromes. In: Clinical Cardiac Electrophysiology, Lea & Febige r, Philadelphia 1993. p.311. 28. German LD, Gallagher JJ. Functional properties of accessory atrioventricular pathways in Wolff-Parkinson-White syndrome. Clinical implications. Am J Med 1984; 76:1079. 29. Nalos, PC, Deng, et al. Intermittent preexcitation: Clinical recognition and management. Pract Cardiol 1985; 11:49. 30. Chen SA, Tai CT, Chiang CE, et al. Electrophysiologic characteristics, electropharmacologic responses and radiofrequency ablation in patients with decremental accessory pathway. J Am Coll Cardiol 1996; 28:732.

SUMMARY https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 11/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate Patients with a preexcitation syndrome have an additional or alternative pathway, known as an accessory pathway, which directly connects the atria and ventricle and bypasses the atrioventricular (AV) node. During sinus rhythm, AV conduction through an accessory pathway (most commonly a direct AV connection) results in the earlier activation of the ventricles than if the impulse had traveled through the AV node, resulting in ventricular preexcitation. (See 'Introduction' above.) Some accessory pathways are associated with structural heart abnormalities. (See 'Anatomic considerations' above.) The classic accessory pathway is the AV bypass tract in patients with the Wolff-Parkinson- White (WPW) pattern. This pathway directly connects atrial and ventricular myocardium, bypassing the AV node/His-Purkinje system. (See 'Anatomic considerations' above.) Delta waves may not be apparent in sinus rhythm in patients with WPW who have a left- lateral bypass tract as the antegrade route for conduction. (See 'Minimal preexcitation in WPW' above.) Although AV accessory pathways usually conduct antegrade and retrograde, some AV bypass tracts are capable of propagating impulses in only one direction. (See 'Concealed accessory pathways' above.) The electrocardiographic (ECG) appearance of activation depends upon the extent of preexcitation and fusion; as a result, the same pathway may not always produce the identical ECG pattern. (See 'Relationship between accessory pathway site and the electrocardiographic pattern' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Wolff, L, Parkinson, et al. Bundle branch block with a short P-R interval in healthy young people prone to paroxysmal tachycardia. Am Heart J 1930; 5:685. 2. Definition of terms related to cardiac rhythm. Am Heart J 1978; 95:796. 3. Waller BF. Clinicopathological correlations of the human cardiac conduction system. In: Card iac Electrophysiology, Zipes DP, Jalife J (Eds), WB Saunders, Philadelphia 1990. p.249. 4. Anderson RH, Becker AE, Brechenmacher C, et al. Ventricular preexcitation. A proposed nomenclature for its substrates. Eur J Cardiol 1975; 3:27. https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 12/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 5. Ferguson TB, Cox JL. Surgical treatment for the Wolff-Parkinson-White syndrome: the endoc ardial approach. In: Cardiac Electrophysiology, Zipes DP, Jalife J (Eds), WB Saunders, Philadel phia 1990. p.897. 6. Cox JL, Gallagher JJ, Cain ME. Experience with 118 consecutive patients undergoing operation for the Wolff-Parkinson-White syndrome. J Thorac Cardiovasc Surg 1985; 90:490. 7. Cain ME, Cox JL. Surgical treatment of supraventricular arrhythmias. In: Management of car diac arrhythmias: the nonpharmacologic approach, Platia E (Ed), JB Lippincott, Philadelphia 1987. p.304. 8. Gallagher JJ, Sealy WC, Kasell J. Intraoperative mapping studies in the Wolff-Parkinson-White syndrome. Pacing Clin Electrophysiol 1979; 2:523. 9. Gallagher JJ, Pritchett EL, Sealy WC, et al. The preexcitation syndromes. Prog Cardiovasc Dis 1978; 20:285. 10. Reddy GV, Schamroth L. The localization of bypass tracts in the Wolff-Parkinson-White syndrome from the surface electrocardiogram. Am Heart J 1987; 113:984. 11. Fananapazir L, German LD, Gallagher JJ, et al. Importance of preexcited QRS morphology during induced atrial fibrillation to the diagnosis and localization of multiple accessory pathways. Circulation 1990; 81:578. 12. Lindsay BD, Crossen KJ, Cain ME. Concordance of distinguishing electrocardiographic features during sinus rhythm with the location of accessory pathways in the Wolff- Parkinson-White syndrome. Am J Cardiol 1987; 59:1093. 13. Milstein S, Sharma AD, Guiraudon GM, Klein GJ. An algorithm for the electrocardiographic localization of accessory pathways in the Wolff-Parkinson-White syndrome. Pacing Clin Electrophysiol 1987; 10:555. 14. Cain ME, Luke RA, Lindsay BD. Diagnosis and localization of accessory pathways. Pacing Clin Electrophysiol 1992; 15:801. 15. Otomo K, Gonzalez MD, Beckman KJ, et al. Reversing the direction of paced ventricular and atrial wavefronts reveals an oblique course in accessory AV pathways and improves localization for catheter ablation. Circulation 2001; 104:550. 16. MacRae CA, Ghaisas N, Kass S, et al. Familial Hypertrophic cardiomyopathy with Wolff- Parkinson-White syndrome maps to a locus on chromosome 7q3. J Clin Invest 1995; 96:1216. 17. Dai CC, Guo BJ, Li WX, et al. Dyssynchronous ventricular contraction in Wolff-Parkinson- White syndrome: a risk factor for the development of dilated cardiomyopathy. Eur J Pediatr 2013; 172:1491. https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 13/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 18. Chiu SN, Chang CW, Lu CW, Wu MH. Restored cardiac function after successful resynchronization by right anterior and anteroseptal accessory pathway ablation in Wolff- Parkinson-White syndrome associated dilated cardiomyopathy. Int J Cardiol 2013; 163:e19. 19. Chauvin M, Shah DC, Ha ssaguerre M, et al. The anatomic basis of connections between the coronary sinus musculature and the left atrium in humans. Circulation 2000; 101:647. 20. Sun Y, Arruda M, Otomo K, et al. Coronary sinus-ventricular accessory connections producing posteroseptal and left posterior accessory pathways: incidence and electrophysiological identification. Circulation 2002; 106:1362. 21. Prystowsky EN, Page RL. Electrophysiology and autonomic influences of the human atrioven tricular node. In: Electrophysiology of the Sinoatrial and Atrioventricular Nodes, Mazgalev T, Dreifus L, Michelson EL (Eds). 22. Sternick EB, Timmermans C, Sosa E, et al. The electrocardiogram during sinus rhythm and tachycardia in patients with Mahaim fibers: the importance of an "rS" pattern in lead III. J Am Coll Cardiol 2004; 44:1626. 23. Gaita F, Haissaguerre M, Giustetto C, et al. Catheter ablation of permanent junctional reciprocating tachycardia with radiofrequency current. J Am Coll Cardiol 1995; 25:648. 24. de Chillou C, Rodriguez LM, Schl pfer J, et al. Clinical characteristics and electrophysiologic properties of atrioventricular accessory pathways: importance of the accessory pathway location. J Am Coll Cardiol 1992; 20:666. 25. Bogun F, Kalusche D, Li YG, et al. Septal Q waves in surface electrocardiographic lead V6 exclude minimal ventricular preexcitation. Am J Cardiol 1999; 84:101. 26. Yoshida T, Ikeda H, Hiraki T, et al. Detection of concealed left sided accessory atrioventricular pathway by P wave signal averaged electrocardiogram. J Am Coll Cardiol 1999; 33:55. 27. Josephson ME. Preexcitation Syndromes. In: Clinical Cardiac Electrophysiology, Lea & Febige r, Philadelphia 1993. p.311. 28. German LD, Gallagher JJ. Functional properties of accessory atrioventricular pathways in Wolff-Parkinson-White syndrome. Clinical implications. Am J Med 1984; 76:1079. 29. Nalos, PC, Deng, et al. Intermittent preexcitation: Clinical recognition and management. Pract Cardiol 1985; 11:49. 30. Chen SA, Tai CT, Chiang CE, et al. Electrophysiologic characteristics, electropharmacologic responses and radiofrequency ablation in patients with decremental accessory pathway. J Am Coll Cardiol 1996; 28:732. https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 14/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 31. Murdock CJ, Leitch JW, Teo WS, et al. Characteristics of accessory pathways exhibiting decremental conduction. Am J Cardiol 1991; 67:506. 32. Tchou P, Lehmann MH, Jazayeri M, Akhtar M. Atriofascicular connection or a nodoventricular Mahaim fiber? Electrophysiologic elucidation of the pathway and associated reentrant circuit. Circulation 1988; 77:837. 33. Gillette PC, Garson A Jr, Cooley DA, McNamara DG. Prolonged and decremental antegrade conduction properties in right anterior accessory connections: Wide QRS antidromic tachycardia of left bundle branch block pattern without Wolff-Parkinson-White configuration in sinus rhythm. Am Heart J 1982; 103:66. 34. Ross DL, Uther JB. Diagnosis of concealed accessory pathways in supraventricular tachycardia. Pacing Clin Electrophysiol 1984; 7:1069. 35. Gillette PC. Concealed anomalous cardiac conduction pathways: a frequent cause of supraventricular tachycardia. Am J Cardiol 1977; 40:848. 36. Meiltz A, Weber R, Halimi F, et al. Permanent form of junctional reciprocating tachycardia in adults: peculiar features and results of radiofrequency catheter ablation. Europace 2006; 8:21. 37. Fitzpatrick AP, Gonzales RP, Lesh MD, et al. New algorithm for the localization of accessory atrioventricular connections using a baseline electrocardiogram. J Am Coll Cardiol 1994; 23:107. 38. Gallagher JJ, Sealy WC, Kasell J, Wallace AG. Multiple accessory pathways in patients with the pre-excitation syndrome. Circulation 1976; 54:571. 39. Arruda, M, Wang, et al. ECG algorithm for predicting sites of successful radiofrequency ablation of accessory pathways (abstract). Pacing Clin Electrophysiol 1993; 16(Pt 2):865. 40. Epstein AE, Kirklin JK, Holman WL, et al. Intermediate septal accessory pathways: electrocardiographic characteristics, electrophysiologic observations and their surgical implications. J Am Coll Cardiol 1991; 17:1570. 41. Arruda MS, McClelland JH, Wang X, et al. Development and validation of an ECG algorithm for identifying accessory pathway ablation site in Wolff-Parkinson-White syndrome. J Cardiovasc Electrophysiol 1998; 9:2. 42. Moss JD, Gerstenfeld EP, Deo R, et al. ECG criteria for accurate localization of left anterolateral and posterolateral accessory pathways. Pacing Clin Electrophysiol 2012; 35:1444. 43. Sternick EB, Sosa EA, Timmermans C, et al. Automaticity in Mahaim fibers. J Cardiovasc Electrophysiol 2004; 15:738. https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 15/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 44. Sternick EB, Gerken LM. The 12-lead ECG in patients with Mahaim fibers. Ann Noninvasive Electrocardiol 2006; 11:63. Topic 953 Version 28.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 16/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate GRAPHICS Terminology and anatomic connections of preexcitation pathways Old Proposed or commonly used Anatomic connections terminology terminology Kent bundle* Accessory AV connection or AV bypass Atrium to ventricle tract James fiber Atrionodal bypass tract Atrium to low AV node Atriofascicular bypass tract Atrium to bundle of His Mahaim fiber Atriofascicular bypass tract Atrium to bundle branch Nodofascicular bypass tract AV node to bundle branch Nodoventricular bypass tract AV node to ventricular tissue Fasciculoventricular bypass tract Bundle branch to ventricular tissue AV: atrioventricular. These bypass tracts result in delta waves and the Wolff-Parkinson-White syndrome. These bypass tracts result in the Lown-Ganong-Levine syndrome and enhanced AV nodal conduction. Graphic 53343 Version 6.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 17/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate Types of accessory pathways Diagram of 4 types of abnormal conduction pathways: classic accessory atrioventricular pathway (red), atriofascicular pathway (green), fasciculoventricular pathway (light blue), and nodoventricular pathway (dark blue). The atrioventricular node and His-Purkinje system are represented in yellow. Atrioventricular, atriofascicular, and nodoventricular pathways are capable of supporting atrioventricular reciprocating tachycardias. In contrast, an isolated fasciculoventricular pathway can cause subtle preexcitation but does not support clinical tachycardia. Graphic 138850 Version 1.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 18/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate Schematic showing anatomic locations of accessory pathways as they cross the AV junction The atrioventricular (AV) valve plane of the heart is viewed from the cardiac apex. The tricuspid valve is on the left in this figure and the mitral valve on the right; the coronary sinus, which provides the venous drainage of the heart, passes posterior to the mitral valve and empties into the right atrium above the tricuspid valve. All AV bypass tracts cross the AV valve plane; their locations are named with respect to this orientation (eg, an anteroseptal bypass tract crosses the AV valve plane from atrium to ventricle in the region marked "anteroseptal" in the figure, at approximately 10 to 11 o'clock with respect to the mitral valve ring). Reproduced with permission from: Cosio FG, Anderson RH, Becker A, et al. Living anatomy of the atrioventricular junctions. A guide to electrophysiological Statement from the Cardiac Nomenclature Study Group, Working Group of Arrythmias, European Society of Cardiology, and the Task Force on Cardiac Nomenclature from NASPE. North American Society of Pacing and Electrophysiology. Eur Heart J 1999; 20:1068. Copyright 1999 European Society of Cardiology. Graphic 77941 Version 3.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 19/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate Schematic showing anatomic locations of accessory pathways in the left ventricular (LV) free wall Longitudinal cross section of the free wall of the left ventricle at the level of the atrioventricular (AV) groove. The accessory pathways are present in the AV groove fat pad at variable depths in relation to the mitral annulus and the epicardium overlying the AV groove. Graphic 76316 Version 2.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 20/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate AV conduction with a concealed accessory pathway Schematic representation of AV conduction. The normal pacemaker is in the sinoatrial (SA) node at the junction of the superior vena cava and the right atrium. The SA node activates the right and left atria (shown in green). In the absence of an accessory pathway (AP) or, as in this case, if the AP is concealed, ventricular activation results from the impulse traversing the AV node, the specialized infranodal conducting system (His bundle, bundle branches, and fascicular branches, shown in red), thereby activating the ventricular myocardium (shown in yellow). The ECG shows a normal PR interval and a narrow QRS complex. The inset on the right shows the timing of SA node (SAN), right (RA) and left atrial (LA), His bundle (H), and the beginning of normal ventricular activation (V ). All of ventricular activation (shown in yellow) is due to normal AV nodal and infranodal conduction. N AV: atrioventricular; ECG: electrocardiogram. Graphic 73740 Version 5.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 21/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate AV conduction through an overt accessory pathway Compared with normal conduction in the preceding diagram, the accessory pathway (AP) is now overt. As a result, ventricular activation results from both early activation (pre-excitation) of the free wall of the left ventricle (shown in blue) and from normal activation (shown in yellow). The degree of unopposed pre-excitation depends upon the time required to conduct through the right and left atria, the AP, and the ventricular myocardium as compared with conduction through the normal pathways. The inset on the right shows the ECG timing of these events. The net effect is a QRS complex that is a fusion of ventricular pre-excitation (blue) and normal excitation (yellow). Early activation throughout the AP (V ) P occurs at about the same time as His bundle depolarization (H). This leads to a shorter PR interval, a small delta wave (arrow), and some prolongation of the QRS duration. AV: atrioventricular. Graphic 53773 Version 6.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 22/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate Conduction through an accessory pathway with AV nodal delay Compared with conduction through an AP with normal AV node conduction, delayed conduction through the AV node allows more of the ventricular myocardium to be activated by pre-excitation (shown in blue). The inset on the right shows the ECG timing of these events. The atrial to His interval is increased due to the AV nodal delay (RA to H); His activation is so delayed that it follows activation caused by the AP (V ). The PR interval is short due to the pre- excitation, the delta wave (arrow) is more pronounced due to the greater and unopposed early forces (blue), and the QRS duration is P prolonged due to the later than normal ventricular activation caused by the AV nodal delay (yellow). AV: atrioventricular; ECG: electrocardiogram. Graphic 62454 Version 6.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 23/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 12-lead electrocardiogram (ECG) showing concertina effect in Wolff-Parkinson-White syndrome The 12-lead ECG and rhythm strip during sinus rhythm show a short PR interval and QRS complex which is aberrated and has a delta wave. After the fifth complex on the rhythm strip, there is a sinus pause after which the QRS compex is still aberrated but the PR interval is somewhat longer. Subsequently, the PR interval becomes progressively shorter. This variability in the PR interval during sinus rhythm is known as the "concertina effect." Graphic 53508 Version 6.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 24/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate Single-lead electrocardiogram (ECG) strip showing concertina effect in Wolff-Parkinson-White syndrome Single channel rhythm strip from a patient with the Wolff-Parkinson- White syndrome shows progressive shortening of the PR interval with the development of a widened QRS complex due to a delta wave. The P wave appears to merge with the QRS complex (arrows). The last two QRS complexes again show a normal PR interval and a narrow QRS complex. Graphic 65293 Version 3.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 25/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate Algorithm (Milstein) to localize accessory pathway in preexcitation syndrome Mapping algorithm for localization of accessory pathway in the preexcitation syndrome using the morphology of the delta wave on the electrocardiogram. LBBB: left bundle branch block; RAS: right anteroseptal; LL: left lateral; PS: posteroseptal; RL: right lateral. + QRS 90 msec in L1 and rS in V1 and V2. Reproduced with permission from Milstein S, Sharma AD, Guiraudon GM, et al. Pacing Clin Electrophysiol 1987; 10:555. Copyright 1987 Futura Publishing Company. Graphic 70648 Version 5.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 26/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate Algorithm (Arruda) to localize accessory pathway in preexcitation syndrome https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 27/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 28/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate Mapping algorithm for localization of accessory pathway in the preexcitation syndrome using the morphology of the delta wave on the electrocardiogram. R/S: R-S wave ratio; PPV: positive predictive value; LL: left lateral; LAL: left anterolateral; LP: left posterior; LPL: left posterolateral; CS/MCV: coronary sinus/middle cardiac vein; AS: right anteroseptal; MS: midseptal; LPS: left posteroseptal; RPS: right posteroseptal; RA: right anterior; RAP: right anterior paraseptal; RAL: right anterolateral; RL: right lateral; RP: right posterior; RPL: right posterolateral. Data from Arruda M, Wang X, McClelland J, et al, Pacing Clin Electrophysiol 1993; 16:865. Graphic 57692 Version 5.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 29/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 12-lead electrocardiogram (ECG) of a right anterior septal accessory AV pathway Electrocardiogram from a patient with Wolff-Parkinson-White syndrome during sinus tachycardia shows a maximally preexcited QRS complex which has a left bundle branch block pattern and is markedly positive in the inferior leads. The delta wave is isoelectric in leads aVL and V6. These features localize the accessory pathway to the right anterior septum. Graphic 50415 Version 4.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 30/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 12-lead electrocardiogram (ECG) of a left lateral accessory AV pathway Electrocardiogram in sinus rhythm from a patient with the Wolff-Parkinson- White syndrome shows a maximally preexcited QRS. The PR is short, the QRS has a right bundle branch block morphology, there is a prominent RS complex in V1, the QRS is negative, and the delta wave is isoelectric in leads I and aVL, localizing the accessory pathway to the left lateral annulus. Graphic 74370 Version 3.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 31/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 12-lead electrocardiogram (ECG) of a left lateral accessory AV pathway Electrocardiogram in sinus rhythm from a patient with Wolff-Parkinson- White syndrome shows a widened QRS complex which is not maximally preexcited. Although the delta wave and QRS are positive in lead I, the negative delta wave in lead aVL and the right bundle branch block morphology localize the accessory pathway to the left lateral mitral annulus. Graphic 50322 Version 3.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 32/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 12-lead electrocardiogram (ECG) of a right posteroseptal accessory AV pathway Electrocardiogram in sinus rhythm from a patient with Wolff-Parkinson-White syndrome shows a maximally preexcited QRS complex. There is early transition across the precordial leads, with R/S ratio of 1 occurring in lead V2. The delta waves are positive in the lateral leads I, aVL, and V6, and negative in leads III and aVF, localizing the pathway to the posteroseptal area. The positive delta wave in lead II and in the lateral leads localize the pathway to the right side. Graphic 69988 Version 3.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 33/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 12-lead electrocardiogram (ECG) of a right posteroseptal accessory AV pathway Electrocardiogram during rapid atrial pacing from a patient with Wolff- Parkinson-White syndrome. The QRS complex is maximally excited; the PR interval is short, and there is a left bundle branch morphology, left axis deviation, and early transition across the anterior precordial leads. The delta waves are positive in the lateral leads I, aVL, and V6 and negative in the inferior leads, localizing the pathway to the posteroseptal region. The negative delta wave in lead II places the pathway on the right, in the area between the coronary sinus os and middle cardiac vein. Graphic 57211 Version 3.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 34/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 12-lead electrocardiogram (ECG) of a right posteroseptal accessory AV pathway The 12 lead ECG during rapid atrial pacing shows QRS complexes that are maximally preexcited; the complexes have a pattern suggesting an AV accessory pathway located in the right posteroseptal area. At the time of ablation, the pathway was localized to the midseptal region. Graphic 59055 Version 3.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 35/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 12-lead electrocardiogram (ECG) of a left posteroseptal accessory AV pathway Electrocardiogram during right atrial pacing in a patient with Wolff- Parkinson-White syndrome shows a long stimulus to the P wave with a short PR interval, the appearance of both right and left bundle branch block morphologies, and a negative QRS morphology and delta wave in the inferior leads. This localizes the pathway to the posteroseptal area. The presence of a positive delta wave in lead I, RS ratio in lead V1 of approximately 1, and a negative delta wave in lead II places the pathway on the left side, inside the coronary sinus os or along the middle cardiac vein. This type of accessory pathway may be related to cardiac venous anomalies and aneurysms. Graphic 71868 Version 4.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 36/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 12-lead electrocardiogram (ECG) of a right lateral accessory AV pathway Electrocardiogram in sinus rhythm from a patient with Wolff-Parkinson-White syndrome shows classic preexcitation with a short PR interval, delta wave, and widened QRS complex with a left bundle branch block morphology. The delta wave is positive in the lateral leads 1, aVL, and V6, it is negative in lead III and isoelectric in lead aVF. The QRS axis of <30L distinguishes this pathway from an anteroseptal accessory AV pathway. Courtesy of Morton F Arnsdorf, MD. Graphic 77218 Version 3.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 37/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 12-lead electrocardiogram (ECG) of a left anterior lateral accessory pathway Electrocardiogram during atrial pacing in a patient with the Wolff- Parkinson-White syndrome shows QRS complexes that are maximally preexcited. The PR interval is short, there is a right bundle branch morphology, and the axis is rightward. The delta wave is positive in the lateral leads I, avL, and V6, localizing the pathway to the left anterior lateral region. Courtesy of Morton F Arnsdorf, MD. Graphic 69928 Version 3.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 38/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate 12-lead electrocardiogram (ECG) of a midseptal accessory AV pathway Electrocardiogram from a patient with Wolff-Parkinson-White syndrome. The ECG criteria for a midseptal pathway are intermediate between those for posteroseptal and anteroseptal connections within the triangle of Koch. These pathways have been difficult to predict from the surface ECG and have usually been grouped as septal pathways. The ECG shows positive delta waves in the lateral leads I, aVL, and V6, with early transition and a tall R wave in lead V2. The delta wave is positive in leads II and aVF and negative in lead III, and the QRS axis is <0 , localizing the pathway in the midseptum. Graphic 51236 Version 3.0 https://www.uptodate.com/contents/anatomy-pathophysiology-and-localization-of-accessory-pathways-in-the-preexcitation-syndrome/print 39/40 7/5/23, 10:45 AM Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome - UpToDate Contributor Disclosures Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Peter J Zimetbaum, MD Consultant/Advisory Boards: Abbott Medical [Lead extraction]. All of the relevant financial relationships listed have been mitigated. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. 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7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs : Jonathan C Makielski, MD, FACC, L Lee L Eckhardt, MD, FHRS : Samuel L vy, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Sep 29, 2021. INTRODUCTION The myocardial action potential refers to the "all or nothing" depolarization followed by repolarization of the cell membrane, which results from a complex interaction of voltage and time dependent ion channels and carriers in the cellular membrane. When abnormalities arise in the normal process of cardiac excitability, patients may develop tachyarrhythmias by a variety of mechanisms. This topic will review the normal cardiac excitation process and the generation of the myocardial action potential, along with mechanisms of arrhythmia and the classes of antiarrhythmic medications and their impact on cardiac excitability. The treatment of specific tachyarrhythmias is discussed elsewhere. (See "Overview of the acute management of tachyarrhythmias".) CARDIAC EXCITABILITY Cardiac excitability refers to the ease with which cardiac cells undergo a series of events characterized by sequential depolarization and repolarization, communication with adjacent cells, and propagation of the electrical activity. The normal heartbeat arises from an organized flow of ionic currents across the cell membrane, through the myoplasm and between cells and the extracellular space [1,2]. Excitable membranes containing specialized ion-specific channels, cell-to-cell connecting proteins, and intracellular components transmit the action potential and lead to excitation-contraction coupling. https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 1/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate Understanding cardiac electrophysiology requires knowing the types and regulation pathways of ion channels, electrogenic exchange transporters, gap junctions, and the proportional contribution of each mechanism. Abnormalities of these elements, both inherited and acquired, can lead to arrhythmia. Acquired abnormalities occurring in the setting of cardiac disease such as cardiomyopathy are called electrical remodeling. Inherited abnormalities arise from mutations in genes encoding the subunits and associated proteins of these channels, and have been associated with familial arrhythmic syndromes and sudden cardiac death. Examples include the congenital long QT syndrome (mainly sodium and potassium current), the Brugada syndrome (mainly sodium current), and congenital heart block (sodium current). (See "Congenital long QT syndrome: Pathophysiology and genetics" and "Brugada syndrome: Epidemiology and pathogenesis" and "Etiology of atrioventricular block", section on 'Familial disease'.) + + Cardiac ion channels and currents Ions (sodium [Na ], potassium [K ], chloride [Cl ], and 2+ calcium [Ca ]) flow through cardiac membrane channels with pores formed by proteins, with these ion channels encoded by specific genes [3]. The pore-forming protein is called the alpha subunit, which also contains the voltage-dependent sensors and gates. For many ion channels, one or more secondary regulatory subunit proteins are present (usually named beta, gamma, delta, and so on) in association with the alpha subunit, and many ion channel proteins have subunit isoforms adding to their complexity. The encoding genes, amino acid sequences, and structure-function relationships for many ion channels have been described and are now reasonably well understood ( figure 1) [4]. Ion channels are grouped and currents are named in one of three ways: by the ionic charge species to which the channel is permeant, the distinguishing kinetics, or pharmacology ( figure 1). For example, the voltage-dependent sodium current (I ) flows through the protein Na NaV1.5 encoded by the gene SCN5A and similarly for other ion channels. The dominant channel + 2+ types in heart cells are Na channels (I ), L-type and T-type Ca channels (I , I Ca-L Ca-T ), and Na + several K channels (I , I , I , I , I ). The sodium-potassium pump and the sodium-calcium K1 to1 to2 Kr Ks exchanger are not considered channels because they require energy to drive ions across the membrane against their gradients, however they do generate currents ( figure 1). Resting membrane potential The resting cardiac cell membrane potential is normally polarized between -80 and -95 mV, with the cell interior negative relative to the extracellular 2+ space. The resting membrane potential is determined by the balance of inward (Na and Ca ) + + and outward (K ) currents and the corresponding equilibrium potentials of these currents. In https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 2/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate turn, the equilibrium potential for a given ion is determined by the concentrations of that ion inside and outside the cell. Using these concentrations, the equilibrium potential is calculated by the Nernst equation. As an example, potassium ion concentrations are higher inside than outside the cell, and the potassium equilibrium potential is between -80 and -95 mV. When potassium channels open, potassium ions flow down their gradient as an outward current, carrying positive ions outside the cell and taking the cell toward more negative potentials. In the heart, the resting membrane potential is generated by the inward rectifier current (I ), K1 which is the predominant open channel at rest. Potassium current flowing through these channels continues until the interior negative potential is at the same magnitude as the equilibrium potential for potassium. Only small amounts of actual potassium flow are required to maintain this potential. The equilibrium potentials for sodium and calcium are positive (approximately +40 mV and approximately +80 mV, respectively) so that when these channels are open, they tend to depolarize the membrane. Voltage-sensitive sodium, calcium, and potassium channels play only a small role in the resting state since most of these channels are closed [5,6]. The Na-K-ATPase pump maintains the potassium and sodium gradients by pumping potassium into and sodium out of the cells. The Na-Ca exchanger uses the power of the Na gradient to pump Ca out of the cell. These and other pumps maintain the ion channel gradient that is important for both excitability and contraction. Action potential in fast response tissues Tissues that depend upon the opening of voltage- sensitive, kinetically rapid (opening in less than a millisecond) sodium channels to initiate depolarization are called fast response tissues [7]. Fast response tissues include the atria, the specialized infranodal conducting system (bundle of His, fascicles and bundle branches, and terminal Purkinje fibers), and the ventricles ( figure 2), while the sinoatrial (SA) and atrioventricular (AV) nodes represent slow response tissues. It is important to recognize that accessory AV pathways (ie, bypass tracts) associated with Wolff-Parkinson-White syndrome are derived from the atria and are thus also fast response tissues dependent upon sodium current for depolarization. (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis".) The following is a simplified description of the steps involved in the generation of an action potential in the heart ( figure 1 and figure 3 and movie 1) [8]. The particular shape and duration of the individual action potential varies for atria, nodal tissue, specialized conduction tissue, and the ventricles ( figure 4), depending upon differences in the density of ion channels in these tissues. The shape and duration of the action potentials also vary in the right and left ventricle, and transmurally across the wall of the heart [9], again depending upon differences in ion channel and current densities. https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 3/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate Phase 0 Rapid depolarization (phase 0) occurs when the resting cell is brought to threshold, leading sequentially to activation or opening of voltage-dependent sodium channels, rapid sodium entry into the cells down a favorable concentration gradient, and a cell interior positive potential that can approach +45 mV. The marked depolarization initiates voltage-dependent inactivation of the sodium channels. Calcium channels also open during depolarization, but the inward calcium flux is much slower. Phase 1 Phase 1 repolarization often inscribes a "notch" and is primarily caused by activation of the transient outward potassium currents (I ) combined with a corresponding to rapid decay of the sodium current. The degree of repolarization in phase 1 is dependent on the density of I and varies between cardiac chambers and regions within chambers. to Phase 2 Following initial repolarization in phase 1, phase 2 represents a plateau that lasts for hundreds of milliseconds and distinguishes the cardiac action potential from nerve and skeletal muscle action potentials, which are significantly shorter. Late inactivating depolarizing calcium and sodium currents are balanced by activating repolarizing potassium currents to maintain the plateau, which is often down-sloping as repolarizing currents begin to dominate. Phases 3 and 4 The final rapid repolarizing phase 3 is driven by the decay of the calcium current and progressive activation of repolarizing potassium currents (I , I Kr Ks ). Terminal repolarization toward the potassium equilibrium potential is dominated in phase 3 by I , K1 which then maintains the resting membrane potential (phase 4). During one cycle of depolarization and repolarization, the voltage-dependent channels cycle through three different kinetic or gating states: Resting. Open, as the channels open during phase 0 depolarization. Inactivated, which occurs at positive potentials (end of phase 0) and during sustained depolarization (as during the phase 2 plateau). During recovery in diastole, the channel returns to the resting state. The resting and inactivated states are different physiologically, even though the channel is effectively nonconducting in both settings. In the resting state, the channels can be opened positive to the threshold potential. In comparison, the inactivated channel cannot be activated until it cycles or "recovers" to the resting state. These different states are important clinically, since, for example, some antiarrhythmic drugs (such as the class I antiarrhythmic drugs) preferentially bind to open and inactivated sodium channels. https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 4/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate Action potential in slow response tissues The SA and AV nodes represent slow response tissues, which have different properties from the fast response tissues ( table 1). Phase 0 depolarization depends on an inward calcium (not sodium) current via L-type calcium channels [10]. These channels are selective for calcium, have a slower conduction velocity than the sodium channels, and take longer to reactivate. In some cases, as with tissue damage or changes in the extracellular milieu, fast response tissues can be converted to slow response tissues. In this setting, sodium channels become inactivated and depolarization is dependent upon the slow calcium channels. Impulse propagation When an action potential forms in a patch of membrane (the source), current flows from this patch to neighboring patches (the sink). Gap junctions are the low resistance structures that allow ions to flow from one cell to another and, if the current flow is sufficient, to cause sequential depolarization from cell to cell. The gap junctions are actually active, opening and closing in response to changes in pH, calcium, and, at times, voltage. In addition to ion flow and gap junction resistance, impulse propagation can also be affected by the orientation of fibers and of the collagen matrix in which the fibers reside. "Fast" tissues may conduct very slowly (declining from meters/second to millimeters/second) in a number of circumstances, resulting in prolongation of the QRS and QT intervals on the surface electrocardiogram (ECG). These include inactivation of sodium channels induced by hyperkalemia or ischemia-induced acidosis, direct damage to the cells, or the effect of drugs, particularly antiarrhythmic drugs. (See 'Action of antiarrhythmic drugs' below.) MECHANISMS OF TACHYARRHYTHMIA FORMATION While the term "arrhythmia" also includes bradyarrhythmias caused by a failure of impulse generation, this section will focus on the cellular and tissue mechanisms of tachyarrhythmias. Three distinct mechanisms underlie tachyarrhythmia induction: enhanced automaticity, reentry, and triggered activity ( figure 5). Enhanced automaticity Enhanced automaticity refers to abnormal phase 4 diastolic depolarization, and occurs when spontaneous depolarization develops during diastole ( figure 5). While this is a normal phenomenon in nodal cells, and with subsidiary pacemakers at slower rates in all myocardial cells, enhanced or abnormal automaticity may lead to tachyarrhythmia. A typical example is automatic (ie, focal) atrial tachycardia. Common automaticity stimulants include excess catecholamine or situations causing hypoxia, acidosis, or ischemic related metabolites. (See "Focal atrial tachycardia" and "Enhanced cardiac automaticity".) https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 5/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate Reentry Reentry is the most commonly encountered arrhythmia mechanism and refers to any arrhythmia dependent on an electrical circuit within the heart ( figure 5). Critical components for reentry include both of the following: The presence of fast and slow conduction with varying refractory/recovery periods A fixed or functional core about which the circuit moves Initiation of reentry requires a unidirectional block within the reentrant path, such that one arm of the circuit conducts the approaching electrical wave front and the blocks it in the other arm. Reentry can travel around a fixed or anatomical circuit such as myocardial scar, or a functional circuit such as an area of tissue that is depolarized or refractory and does not support conduction. A common example of a reentry-based arrhythmia is AV reciprocating tachycardia (AVRT) related to an accessory pathway (ie, bypass tract) as part of the Wolff-Parkinson-White syndrome. In AVRT, the fast conducting limb (for either antegrade or retrograde AVRT) is the accessory + pathway, which uses Na channels to support rapid conduction, while the slow conducting limb is the normal AV node. An example of fixed reentry arrhythmia is ventricular tachycardia with a fixed myocardial scar and variable conduction in the surrounding myocardium. Interventions to terminate reentrant arrhythmias differ from other mechanisms and are + 2+ generally geared to modify the critical components of the reentrant circuit. Blocking Na or Ca + channels can slow or block conduction, while blocking K channels prolongs the action potential and therefore increases refractoriness. Another approach is to improve functional properties such as ischemia in an area of functional block that can terminate the arrhythmia. Interventions that electrically interrupt the reentrant loop include delivering a small electrical impulse to depolarize or block a small part of the reentrant loop (ie, anti-tachycardia pacing), delivering a large electrical shock to depolarize most or all the reentrant loop (ie, cardioversion), or ablating tissue critical to the reentrant loop. (See "Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features".) Triggered activity Triggered activity refers to a depolarization that occurs after the initial depolarization wavefront and comes in two forms, either early or late. Secondary depolarizations that occur before the action potential has fully repolarized are early afterdepolarizations (EADs) ( figure 5). Those that occur after the action potential has fully repolarized are delayed afterdepolarizations (DADs) ( figure 5). Both EADs and DADs depend on the previous action potential to trigger them, hence an afterdepolarization is said to be a triggered arrhythmia. However, it is important to understand that DADs and EADs differ in mechanism. https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 6/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate EADs EADs are triggered during prolonged action potentials. A prolonged action 2+ potential allows a longer window for reopening of L-type Ca channels during phase 2 (or 2+ occasionally phase 3) of the action potential. L-type Ca current depolarizes the membrane 2+ before repolarization, triggering an afterdepolarization. Due to L-type Ca channel time and voltage dependence, EADs occur at slow stimulation rates or after a ventricular pause when action potential duration (phase 2) is prolonged and they are suppressed with faster heart rates. EADs are thought to initiate the polymorphic ventricular arrhythmias torsades de pointes (TdP) found in inherited and acquired long QT syndrome (LQTS), for example drug-induced LQTS. A point of distinction to be made here is that triggered activity can initiate TdP, but TdP may be a re-entrant mechanism at the organ level with a functional (spiral reentry) rather than fixed anatomical core. (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes".) 2+ DADs DADs, which result from intracellular Ca overload, are triggered after the action 2+ 2+ potential is fully repolarized. Under conditions of Ca overload, Ca taken back up by the sarcoplasmic reticulum is then transiently re-released into the cytoplasm. This in turn 2+ causes a transient rise in cytoplasmic Ca activating Ca -dependent depolarizing 2+ + 2+ + membrane current mostly through the Na -Ca exchanger. The exchange of three Na for 2+ one Ca produces a net inward and transient depolarization or a DAD. If the DAD reaches 2+ threshold voltage, it can initiate an action potential. Conditions which enhance cellular Ca loading, such as rapid heart rates, enhance DAD susceptibility. DADs may be important in myocardial ischemia, digoxin toxicity, and in some inherited arrhythmia syndromes such as catecholaminergic polymorphic ventricular tachycardia. (See "Cardiac arrhythmias due to digoxin toxicity", section on 'Mechanisms of cardiac toxicity' and "Catecholaminergic polymorphic ventricular tachycardia".) ACTION OF ANTIARRHYTHMIC DRUGS Classification of antiarrhythmic drugs The different antiarrhythmic drugs often have several effects on action potential generation and propagation and may also affect the autonomic nervous system. The classification of antiarrhythmic drugs according to the Harrison modification of the Vaughan Williams classification was originally based upon their effects on the action potential, but later modification and enhancements included the molecular targets such as specific ion channels and beta adrenergic receptors [8,11]. The most recent modification ( table 2 and table 3) adds additional classes and subclasses to the four traditional classes based on targets, some of which have clinically available drugs (eg, Class 0 pacemaker channel blocker ivabradine), and others that are experimental or theoretical targets (eg, Class VI gap https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 7/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate junction blockers) [11]. This scheme differs slightly from a classification endorsed by international societies [4]. Further modifications are to be expected. All these classification schemes assume that individual drugs have a predominant mechanism of action. This distinction remains useful, even though it does not account for the complicated electrophysiologic and autonomic interactions that are present, with some drugs having actions on more than one target. The modified Vaughan Williams classification has proven surprisingly useful even though it represents an oversimplification of the electrophysiologic events that occur. The classification appears to work because the multiple factors that influence cardiac excitability are sufficiently coordinated to produce predictable outcomes, rather than unpredictably complex behavior [12,13]. There is an electrophysiologic matrix or substrate of interacting active (ion channels) and passive (lipid bilayer of the cell membrane, myoplasm, and gap junctions) cellular properties that determine normal cardiac excitability. The normal substrate is altered by arrhythmogenic influences that affect one or more determinants of excitability. The ensuing proarrhythmic state can result in reentrant, automatic, or triggered arrhythmias. (See "Reentry and the development of cardiac arrhythmias" and "Enhanced cardiac automaticity".) The substrate that is deformed by arrhythmogenic factors interacts with antiarrhythmic drugs. Depending upon the substrate encountered, the resulting substrate may be antiarrhythmic, antifibrillatory, or proarrhythmic. Certain arrhythmogenic substrates are common, such as those induced by ischemia or infarction. In this setting, a certain effect of a drug becomes predominant and predictable, as with class I activity in ischemia, and a drug classification appears accurate. However, the major drug effect may be quite different if a different proarrhythmic substrate exists. Consider, for example, the differences in digitalis action in hypokalemia and hyperkalemia. Class 0 Drugs in the newly proposed Class 0 modulate the pacemaker channel HCN4, affecting the pacemaker current I [11]. The blocker ivabradine slows heart rate. f Class I The class I drugs act by modulating or blocking the sodium channels, thereby inhibiting phase 0 depolarization. They are all at least in part positively charged and presumably interact with specific amino acid residues in the internal pore of the sodium channel. Three different subgroups ( table 2 and table 3) have been identified because their mechanism or https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 8/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate duration of action is somewhat different due to variable rates of drug binding to and dissociation from the channel receptor [14]: The class Ic agents have the slowest binding and dissociation from the binding site. The class Ib agents have the most rapid binding and dissociation from the binding site. The class Ia agents are intermediate in terms of the speed of binding and dissociation from the binding site. During faster heart rates, less time exists for the drug to dissociate from the receptor, resulting in an increased number of blocked channels and enhanced blockade. These pharmacologic effects may cause a progressive decrease in impulse conduction velocity and a widening of the QRS complex. This property is known as "use-dependence" and is seen most frequently with the class Ic agents, less frequently with the class Ia drugs, and rarely with the class Ib agents [15]. Class Ia drugs (quinidine, procainamide, and disopyramide) depress phase 0 (sodium- dependent) depolarization, thereby slowing conduction. They also have moderate potassium channel blocking activity (which tends to slow the rate of repolarization and prolong action potential duration [APD]), and quinidine in particular also blocks potassium current I , which is useful for suppressing certain ventricular arrhythmias such as those To found in the Brugada syndrome. Class Ia agents also have anticholinergic activity and tend to depress myocardial contractility. At slower heart rates, when use-dependent blockade of the sodium current is not significant, potassium channel blockade may become predominant (reverse use-dependence), leading to prolongation of the APD and QT interval and increased automaticity. One difference between the drugs is that quinidine and procainamide generally decrease vascular resistance, whereas disopyramide increases vascular resistance. In addition, N- acetyl-procainamide (NAPA), a metabolite of procainamide, has little sodium current blocking activity, while retaining potassium current blocking activity. Thus, NAPA behaves like a class III drug. (See 'Class III' below.) The class Ib drugs (lidocaine and mexiletine) have less prominent sodium channel blocking activity at rest, but effectively block the sodium channel in depolarized tissues. They tend to bind in the inactivated state (which is induced by depolarization) and dissociate from the sodium channel more rapidly than other class I drugs. As a result, they are more effective with tachyarrhythmias than with slow arrhythmias. Class Ic drugs (flecainide and propafenone) primarily block open sodium channels and slow conduction. They dissociate slowly from the sodium channels during diastole, resulting in https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 9/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate increased effect at a more rapid rate (use-dependence). This characteristic is the basis for their antiarrhythmic efficacy, especially against supraventricular arrhythmias. Use- dependence may also contribute to the proarrhythmic activity of these drugs, especially in the diseased myocardium, resulting in incessant ventricular tachycardia. Flecainide and propafenone also have potassium channel blocking activity and can increase the APD in ventricular myocytes. Propafenone has significant beta blocking activity. Another recognized target for antiarrhythmic action is the late sodium current, which is enhanced in both acquired and inherited arrhythmias. When enhanced, it lengthens the APD and can create a substrate for arrhythmia by reentry and triggered activity (both early and delayed afterdepolarizations). Some class I drugs such as mexiletine and flecainide and class III drugs such as amiodarone preferentially block the late sodium current. The most selective late sodium current blocking drug is ranolazine, a drug approved for the treatment of chronic angina, but which may have antiarrhythmic activity [16]. This target has been proposed as a new sub-classification, Id [11]. Class II Class II drugs act by inhibiting sympathetic activity, primarily by causing beta blockade. They may also have a mild inhibitory effect on the sodium channels. Sympathetic stimulation has the following potential proarrhythmic actions [17]: An increase in automaticity due to enhancement of phase 4 spontaneous depolarization (see "Enhanced cardiac automaticity"). An increase in membrane excitability due to shortening in refractoriness (phases 2 and 3 of the action potential). An increase in the rate of impulse conduction through the myocardial membrane, resulting from acceleration of phase 0 upstroke velocity or the rate of membrane depolarization. An increase in delayed afterpotentials, especially when the cell is calcium loaded, such as in digoxin toxicity. By blocking catecholamine and sympathetically mediated actions, beta blockers slow the rate of discharge of the sinus and ectopic pacemakers, and increase the effective refractory period of the AV node. They also slow both antegrade and retrograde conduction in anomalous pathways [18]. Carvedilol is a beta-blocker with unique additional properties. In addition to beta- and alpha- adrenergic blockade, carvedilol can also block potassium (KCNH2, formerly HERG), calcium, and sodium currents and modestly prolong APD. However, when administered chronically, carvedilol https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 10/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate increases the number of these channels, which is probably a favorable effect in diseased hearts [19]. The most recent classification ( table 2 and table 3) expands the definition of class II to include "autonomic inhibitors and activators," with subclass IIa as beta adrenergic blockers such as those mentioned above, IIb as adrenergic activators such as isoproterenol, IIc as muscarinic inhibitors such as atropine, IId as muscarinic activators such as carbachol and digoxin, and IIe as adenosine receptor activators [11]. Adrenergic activators and muscarinic inhibitors augment, and muscarinic activators and adenosine activators decrease, heart rate by actions on the electrophysiology of the sinoatrial (SA) node and AV node. These additional classifications bring drugs that were previously outside the Vaughan Williams classification into the scheme. Class III The class III drugs (eg, amiodarone, dronedarone, ibutilide, dofetilide, sotalol, vernakalant) block the potassium channels to inhibit I , I , I , and I , thereby prolonging Kr Ks K1 KUR repolarization, the APD, and the refractory period. The relative potency of these drugs for specific potassium currents may account for atrial selectivity, for example I is only known to KUR be in the atria [19]. Blockage of ventricular potassium currents is manifested on the surface ECG by prolongation of the QT interval, providing the substrate for torsades de pointes, a polymorphic ventricular tachycardia. Amiodarone and dronedarone are exceptions with very little proarrhythmic activity, perhaps because of a balance of offsetting actions. Additionally, there are more atrial-specific agents such as vernakalant that block primarily I . KUR These drugs also have other antiarrhythmic effects: Sotalol has beta blocking activity. (See "Clinical uses of sotalol".) Amiodarone and dronedarone block sodium channels in depolarized tissues (a Class Ib effect) and also block calcium channels, potassium channels, and adrenergic receptors. Amiodarone also has thyroid effects that dronedarone, an amiodarone derivative without the iodine moiety, lacks. (See "Amiodarone: Clinical uses" and "Clinical uses of dronedarone" and "Amiodarone and thyroid dysfunction".) Ibutilide, which is available in intravenous form, is approved for the acute termination of atrial flutter and atrial fibrillation, and it prolongs the QT interval by enhancing the slow, delayed inward sodium current as well as blocking potassium channels during repolarization. (See "Therapeutic use of ibutilide".) Some of the class III agents, such as sotalol, dofetilide, and ibutilide, exhibit reverse use- dependent effects on repolarization [20]. This pharmacologic property is characterized by a dynamic increase in the repolarization time and the refractory period during slower heart rates. https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 11/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate Clinically, this property manifests as an increased QT interval at slower heart rates, which can increase the risk of torsades de pointes [20]. The new classification scheme ( table 2 and table 3) adds subclass IIIb and IIIc agents. + Subclass IIIb agents (metabolically dependent K channel openers, eg, pinacidil) may shorten the action potential but do not have antiarrhythmic activity [11]. Subclass IIIc agents (transmitter-dependent K-channel blockers, such as acetylcholine) activate potassium channels, but there are no clinically available drugs in this subclass. Class IV The class IV drugs are calcium channel blockers. Verapamil has a more pronounced inhibitory effect on the slow response SA and AV nodes than diltiazem. In comparison, the dihydropyridines, such as nifedipine, have little electrophysiologic effect on the heart. Verapamil and diltiazem can slow the sinus rate (usually in the presence of sinus node dysfunction or beta blockade), increase the refractoriness of and prolong conduction through the AV node, occasionally prolong the PR interval, and depress LV function. The newer classification scheme ( table 2 and table 3) calls this class "Ca handling modulators" and divides it into five subclassifications of targets, of which Class IVa is the classic Vaughan Williams surface channel blockers [11]. The additional classes IVb through IVe for the most part do not yet contain clinically available drugs, but this scheme does serve as a template for further research. An exception to this are the Class I drugs flecainide and propafenone, which qualify as class IVd ryanodine receptor blockers and are active against catecholaminergic polymorphic ventricular tachycardia. Additional proposed classes include Class V (mechanosensitive channel blockers) and Class VI (gap junction blockers), which have drugs under investigation. Class VII (upstream target modulators) includes angiotensin converting enzyme inhibitors and angiotensin receptor blockers that may have antiarrhythmic action by their effects on cardiac remodeling. A position paper on antiarrhythmic drugs produced by international societies provides additional detail [4]. SUMMARY AND RECOMMENDATIONS Antiarrhythmic drugs target ion channels and receptors in the heart, generally blocking or inhibiting function. (See 'Cardiac excitability' above.) Classification of antiarrhythmic drugs is generally done by their predominant action and target ( table 2 and table 3). Note that nearly all clinically used drugs act on multiple https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 12/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate targets. (See 'Classification of antiarrhythmic drugs' above.) The multiple electrophysiologic actions of antiarrhythmic drugs interacting with the variable underlying substrate present in each patient determine whether the clinical effect will be proarrhythmic or antiarrhythmic. (See 'Classification of antiarrhythmic drugs' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Arnsdorf MF. The cellular basis of cardiac arrhythmias. A matrical perspective. Ann N Y Acad Sci 1990; 601:263. 2. Fozzard HA, Arnsdor MF. Cardiac electrophysiology. In: The Heart and Cardiovascular Syste m, Fozzard HA, Haber E, Jennings A, et al (Eds), Raven Press, New York 1991. p.63. 3. Grant AO. Cardiac Ion Channels. Circ Arrythm Electrophysiol 2009; 2:185. 4. Dan GA, Martinez-Rubio A, Agewall S, et al. Antiarrhythmic drugs-clinical use and clinical decision making: a consensus document from the European Heart Rhythm Association (EHRA) and European Society of Cardiology (ESC) Working Group on Cardiovascular Pharmacology, endorsed by the Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS) and International Society of Cardiovascular Pharmacotherapy (ISCP). Europace 2018; 20:731. 5. Catterall WA. Structure and function of voltage-sensitive ion channels. Science 1988; 242:50. 6. St hmer W, Conti F, Suzuki H, et al. Structural parts involved in activation and inactivation of the sodium channel. Nature 1989; 339:597. 7. Fozzard HA, Danck DA. Sodium channels. In: The Heart and Cardiovascular System, Fozzard HA, Haber E, Jennings A, et al (Eds), Raven Press, New York 1991. p.1091. 8. The Sicilian gambit. A new approach to the classification of antiarrhythmic drugs based on their actions on arrhythmogenic mechanisms. Task Force of the Working Group on Arrhythmias of the European Society of Cardiology. Circulation 1991; 84:1831. 9. Liu DW, Gintant GA, Antzelevitch C. Ionic bases for electrophysiological distinctions among epicardial, midmyocardial, and endocardial myocytes from the free wall of the canine left ventricle. Circ Res 1993; 72:671. 10. Pelzer D, Pelzer S, McDonald TF. Calcium channels in heart. In: The Heart and Cardiovascular System,, Fozzard HA, Haber E, Jennings A, et al (Eds), Raven Press, New York1 991. p.1049. https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 13/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate 11. Lei M, Wu L, Terrar DA, Huang CL. Modernized Classification of Cardiac Antiarrhythmic Drugs. Circulation 2018; 138:1879. 12. Arnsdorf MF. Arnsdorf's paradox. J Cardiovasc Electrophysiol 1990; 1:42. 13. Arnsdorf MF. Cardiac excitability, the electrophysiologic matrix and electrically induced ventricular arrhythmias: order and reproducibility in seeming electrophysiologic chaos. J Am Coll Cardiol 1991; 17:139. 14. Snyders DJ, Hondeghem LM, Bennett PB. Mechanisms of drug-channel interaction. In: The H eart and Cardiovascular System, Fozzard HA, Haber E, Jennings A, et al (Eds), Raven Press, N ew York 1991. p.2165. 15. Hondeghem LM, Katzung BG. Antiarrhythmic agents: the modulated receptor mechanism of action of sodium and calcium channel-blocking drugs. Annu Rev Pharmacol Toxicol 1984; 24:387. 16. Antzelevitch C, Nesterenko V, Shryock JC, et al. The role of late I Na in development of cardiac arrhythmias. Handb Exp Pharmacol 2014; 221:137. 17. Podrid PJ, Fuchs T, Candinas R. Role of the sympathetic nervous system in the genesis of ventricular arrhythmia. Circulation 1990; 82:I103. 18. Frishman W, Silverman R. Clinical pharmacology of the new beta-adrenergic blocking drugs. Part 2. Physiologic and metabolic effects. Am Heart J 1979; 97:797. 19. Naccarelli GV, Lukas MA. Carvedilol's antiarrhythmic properties: therapeutic implications in patients with left ventricular dysfunction. Clin Cardiol 2005; 28:165. 20. Hondeghem LM, Snyders DJ. Class III antiarrhythmic agents have a lot of potential but a long way to go. Reduced effectiveness and dangers of reverse use dependence. Circulation 1990; 81:686. Topic 895 Version 30.0

dronedarone" and "Amiodarone and thyroid dysfunction".) Ibutilide, which is available in intravenous form, is approved for the acute termination of atrial flutter and atrial fibrillation, and it prolongs the QT interval by enhancing the slow, delayed inward sodium current as well as blocking potassium channels during repolarization. (See "Therapeutic use of ibutilide".) Some of the class III agents, such as sotalol, dofetilide, and ibutilide, exhibit reverse use- dependent effects on repolarization [20]. This pharmacologic property is characterized by a dynamic increase in the repolarization time and the refractory period during slower heart rates. https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 11/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate Clinically, this property manifests as an increased QT interval at slower heart rates, which can increase the risk of torsades de pointes [20]. The new classification scheme ( table 2 and table 3) adds subclass IIIb and IIIc agents. + Subclass IIIb agents (metabolically dependent K channel openers, eg, pinacidil) may shorten the action potential but do not have antiarrhythmic activity [11]. Subclass IIIc agents (transmitter-dependent K-channel blockers, such as acetylcholine) activate potassium channels, but there are no clinically available drugs in this subclass. Class IV The class IV drugs are calcium channel blockers. Verapamil has a more pronounced inhibitory effect on the slow response SA and AV nodes than diltiazem. In comparison, the dihydropyridines, such as nifedipine, have little electrophysiologic effect on the heart. Verapamil and diltiazem can slow the sinus rate (usually in the presence of sinus node dysfunction or beta blockade), increase the refractoriness of and prolong conduction through the AV node, occasionally prolong the PR interval, and depress LV function. The newer classification scheme ( table 2 and table 3) calls this class "Ca handling modulators" and divides it into five subclassifications of targets, of which Class IVa is the classic Vaughan Williams surface channel blockers [11]. The additional classes IVb through IVe for the most part do not yet contain clinically available drugs, but this scheme does serve as a template for further research. An exception to this are the Class I drugs flecainide and propafenone, which qualify as class IVd ryanodine receptor blockers and are active against catecholaminergic polymorphic ventricular tachycardia. Additional proposed classes include Class V (mechanosensitive channel blockers) and Class VI (gap junction blockers), which have drugs under investigation. Class VII (upstream target modulators) includes angiotensin converting enzyme inhibitors and angiotensin receptor blockers that may have antiarrhythmic action by their effects on cardiac remodeling. A position paper on antiarrhythmic drugs produced by international societies provides additional detail [4]. SUMMARY AND RECOMMENDATIONS Antiarrhythmic drugs target ion channels and receptors in the heart, generally blocking or inhibiting function. (See 'Cardiac excitability' above.) Classification of antiarrhythmic drugs is generally done by their predominant action and target ( table 2 and table 3). Note that nearly all clinically used drugs act on multiple https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 12/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate targets. (See 'Classification of antiarrhythmic drugs' above.) The multiple electrophysiologic actions of antiarrhythmic drugs interacting with the variable underlying substrate present in each patient determine whether the clinical effect will be proarrhythmic or antiarrhythmic. (See 'Classification of antiarrhythmic drugs' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Arnsdorf MF. The cellular basis of cardiac arrhythmias. A matrical perspective. Ann N Y Acad Sci 1990; 601:263. 2. Fozzard HA, Arnsdor MF. Cardiac electrophysiology. In: The Heart and Cardiovascular Syste m, Fozzard HA, Haber E, Jennings A, et al (Eds), Raven Press, New York 1991. p.63. 3. Grant AO. Cardiac Ion Channels. Circ Arrythm Electrophysiol 2009; 2:185. 4. Dan GA, Martinez-Rubio A, Agewall S, et al. Antiarrhythmic drugs-clinical use and clinical decision making: a consensus document from the European Heart Rhythm Association (EHRA) and European Society of Cardiology (ESC) Working Group on Cardiovascular Pharmacology, endorsed by the Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS) and International Society of Cardiovascular Pharmacotherapy (ISCP). Europace 2018; 20:731. 5. Catterall WA. Structure and function of voltage-sensitive ion channels. Science 1988; 242:50. 6. St hmer W, Conti F, Suzuki H, et al. Structural parts involved in activation and inactivation of the sodium channel. Nature 1989; 339:597. 7. Fozzard HA, Danck DA. Sodium channels. In: The Heart and Cardiovascular System, Fozzard HA, Haber E, Jennings A, et al (Eds), Raven Press, New York 1991. p.1091. 8. The Sicilian gambit. A new approach to the classification of antiarrhythmic drugs based on their actions on arrhythmogenic mechanisms. Task Force of the Working Group on Arrhythmias of the European Society of Cardiology. Circulation 1991; 84:1831. 9. Liu DW, Gintant GA, Antzelevitch C. Ionic bases for electrophysiological distinctions among epicardial, midmyocardial, and endocardial myocytes from the free wall of the canine left ventricle. Circ Res 1993; 72:671. 10. Pelzer D, Pelzer S, McDonald TF. Calcium channels in heart. In: The Heart and Cardiovascular System,, Fozzard HA, Haber E, Jennings A, et al (Eds), Raven Press, New York1 991. p.1049. https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 13/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate 11. Lei M, Wu L, Terrar DA, Huang CL. Modernized Classification of Cardiac Antiarrhythmic Drugs. Circulation 2018; 138:1879. 12. Arnsdorf MF. Arnsdorf's paradox. J Cardiovasc Electrophysiol 1990; 1:42. 13. Arnsdorf MF. Cardiac excitability, the electrophysiologic matrix and electrically induced ventricular arrhythmias: order and reproducibility in seeming electrophysiologic chaos. J Am Coll Cardiol 1991; 17:139. 14. Snyders DJ, Hondeghem LM, Bennett PB. Mechanisms of drug-channel interaction. In: The H eart and Cardiovascular System, Fozzard HA, Haber E, Jennings A, et al (Eds), Raven Press, N ew York 1991. p.2165. 15. Hondeghem LM, Katzung BG. Antiarrhythmic agents: the modulated receptor mechanism of action of sodium and calcium channel-blocking drugs. Annu Rev Pharmacol Toxicol 1984; 24:387. 16. Antzelevitch C, Nesterenko V, Shryock JC, et al. The role of late I Na in development of cardiac arrhythmias. Handb Exp Pharmacol 2014; 221:137. 17. Podrid PJ, Fuchs T, Candinas R. Role of the sympathetic nervous system in the genesis of ventricular arrhythmia. Circulation 1990; 82:I103. 18. Frishman W, Silverman R. Clinical pharmacology of the new beta-adrenergic blocking drugs. Part 2. Physiologic and metabolic effects. Am Heart J 1979; 97:797. 19. Naccarelli GV, Lukas MA. Carvedilol's antiarrhythmic properties: therapeutic implications in patients with left ventricular dysfunction. Clin Cardiol 2005; 28:165. 20. Hondeghem LM, Snyders DJ. Class III antiarrhythmic agents have a lot of potential but a long way to go. Reduced effectiveness and dangers of reverse use dependence. Circulation 1990; 81:686. Topic 895 Version 30.0 https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 14/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate GRAPHICS Action potential currents Major cardiac ion currents and channels responsible for a ventricular action potential are shown with their common name, abbreviation, and the gene and protein for the alpha subunit that forms the pore or transporter. The diagram on the left shows the time course of amplitude of each current during the action potential, but does not accurately reflect amplitudes relative to each of the other currents. This summary represents a ventricular myocyte, and lists only the major ion channels. The currents and their molecular nature vary within regions of the ventricles, and in atria, and other specialized cells such as nodal and Purkinje. Ion channels exist as part of multi-molecular complexes including beta subunits and other associated regulatory proteins which are also not shown. Courtesy of Jonathan C Makielski, MD, FACC. Graphic 70771 Version 4.0 https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 15/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate Normal conduction system Schematic representation of the normal intraventricular conduction system (His- Purkinje system). The Bundle of His divides into the left bundle branch and right bundle branch. The left bundle branch divides into anterior, posterior, and, in some cases, median fascicles. AV: atrioventricular; RA: right atrium; LA: left atrium; RV: right ventricle; LV: left ventricle. Graphic 63340 Version 6.0 https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 16/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate Myocardial action potential Representation of a ventricular action potential. There are 5 phases of the action potential beginning with phase 0, rapid depolarization by sodium influx. Phase 1 is a rapid repolarization via potassium efflux followed by phase 2 or the plateau phase. The plateau phase results from entry of calcium into the cell and potassium efflux. Phase 3 repolarization is dominated by potassium currents which polarize the cell and potassium inward rectifier maintains the resting potential or phase 4. See text for full description. Graphic 71390 Version 4.0 https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 17/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate Action potentials generated by different parts of conduction system The sinoatrial (SA) and atrioventricular (AV) nodes generate a slow action potential, mediated by calcium ions. In comparison, the tissues of the atria, ventricles, and the His-Purkinje system generate a fast action potential mediated by sodium ions. Sequential activation of these structures results in the characteristic waveforms visible on the surface electrocardiogram (ECG). The AV node and bundle of His are small structures; as a result, no electrical activity is recorded on the surface ECG during their activation. Graphic 61989 Version 4.0 https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 18/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate Fast versus slow response cardiac tissues Properties Fast response tissues Slow response tissues Atria, specialized infranodal SA and AV nodes, depolarized fast Location conducting system, ventricles, AV bypass tracts response tissues in which phase 0 depends upon calcium current Passive cellular properties Normal resting 80 to -95 mV 40 to -65 mV potential Active cellular properties Phase 0 current Sodium Primarily calcium Phase 0 channel kinetics Fast Slow activation; inactivation depends upon voltage and cell calcium concentration Peak overshoot +20 to +40 mV 5 to + 20 mV Action potential amplitude 90 to 135 mV 30 to 70 mV Properties dependent upon active and passive properties Threshold voltage 60 to -75 mV 40 to -60 mV Conduction 0.5 to 5 m/second 0.01 to 0.1 m/second velocity Conducive to reentry Only with inactivation of sodium channels with marked slowing of conduction velocity Present in normal tissue Yes Yes Automaticity Comparison of the major electrophysiologic characteristics of "fast" and "slow" response tissues. AV: atrioventricular; SA: sinoatrial. Graphic 71831 Version 3.0 https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 19/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate Mechanisms of tachyarrhythmias (A) Enhanced automaticity: nodal action potentials with normal automaticity (solid orange line) compared wit (dotted blue line) as would be seen with increased pacemaker current (I ) and/or decreased inward rectifier c enhanced automaticity arrhythmia, atrial tachycardia, is shown in the figure. f (B) Reentry: a schematic of a reentrant circuit with fast and slow conduction adjacent to a fixed core. An exam of ventricular tachycardia is shown below the figure. (C) Triggered activity, DADs: DADs with the first DAD (solid orange line) not reaching threshold to trigger an a subsequent DADs reaching threshold (dotted blue line). Bidirectional ventricular tachycardia from a catechola ventricular tachycardia patient is depicted and thought to initiate with DADs. https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 20/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate (D) Triggered activity, EADs: reverence action potentials (solid black line) with a prolonged action potential an a long interval, which sets up conditions for a single EAD (dotted blue line) or oscillatory EADs. Typical short-l torsade de pointes in a patient with drug-induced long QT syndrome. AP: action potential; DAD: delayed afterdepolarization; EAD: early afterdepolarization. Courtesy of Lee Eckhardt, MD. Graphic 120258 Version 2.0 https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 21/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate Revised (2018) Vaughan Williams classification of antiarrhythmic drugs Pharmacological Electrophysiological Examples of Class Subclass targets effects drugs HCN channel blockers 0 HCN channel- mediated Inhibition of I reducing SAN phase 4 pacemaker Ivabradine f pacemaker current (I ) block depolarization rate, thereby reducing heart f rate; possible decreased AVN and Purkinje cell automaticity; increase in RR intervals + Voltage-gated Na channel blockers https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 22/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate I Ia Nav1.5 open state; intermediate (Tau 1 to 10 seconds) dissociation kinetics; Reduction in peak I AP generation, and , Quinidine, ajmaline, Na (dV/dt) increased excitation with disopyramide max often concomitant K channel block threshold; slowing of AP conduction in atria, + ventricles, and specialized ventricular conduction pathways; concomitant I block increasing APD and ERP; K increase in QT intervals https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 23/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate Ib Nav1.5 open state; rapid dissociation (Tau 0.1 to 1 second); I Reduction in peak I AP generation and , Lidocaine, mexiletine Na (dV/dt) increased excitation with max ; window Na current threshold; slowing of AP conduction in atria, ventricles, and specialized ventricular conduction pathways; shortening of APD and ERP in normal ventricular and Purkinje myocytes; prolongation of ERP and postrepolarization refractoriness with reduced window current in ischemic, partially depolarized cells Relatively little electrocardiographic effect; slight QTc shortening Ic Nav1.5 inactivated state; slow dissociation (Tau >10 Reduction in peak I AP generation and (dV/dt) , Propafenone, flecainide Na with max seconds) increased excitation threshold; slowing of AP conduction in atria, ventricles, and specialized ventricular conduction pathways; reduced overall excitability; prolongation of APD at high heart rates; increase in QRS duration https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 24/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate + Id Nav1.5 late current Reduction in late Na Ranolazine current (I NaL AP recovery, ), affecting refractoriness, repolarization reserve, and QT interval Autonomic inhibitors and activators https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 25/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate II IIa Nonselective beta- and selective beta1- Inhibition of adrenergically induced Nonselective beta inhibitors: adrenergic receptor inhibitors G protein-mediated effects of increased carvedilol, propranolol, s adenylyl kinase activity and [cAMP] with effects i including slowed SAN nadolol Selective beta1- adrenergic receptor pacemaker rate caused by reduced I and I ; f CaL inhibitors: increased AVN conduction time and atenolol, bisoprolol, betaxolol, refractoriness, and decreased SAN pacing celiprolol, and triggered activity esmolol, metoprolol resulting from reduced ; and reduced RyR2- I CaL mediated SR Ca release and triggered activity; increase in RR and PR intervals 2+ https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 26/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 27/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate IIb Nonselective beta- adrenergic receptor Activation of adrenergically induced Isoproterenol activators G -protein effects of increasing adenylyl s kinase activity and [cAMP] (refer to entry i above); decrease in RR and PR intervals IIc Muscarinic M receptor inhibitors Inhibition of supraventricular (SAN, atrial, AVN) muscarinic M cholinergic receptors (refer to entry below); Atropine, anisodamine, hyoscine, scopolamine 2 2 decreased RR and PR intervals IId Muscarinic M Activation of Carbachol, 2 receptor activators supraventricular (SAN, atrial, AVN) muscarinic M cholinergic receptors channels, activates K ACh hyperpolarizing the SAN pilocarpine, methacholine, digoxin 2 and shortening APDs in atrial and AVN tissue, and reduces [cAMP] and therefore I i and SAN CaL I ; inhibitory effects on f adenylyl cyclase and cAMP activation, reducing its stimulatory effects on I , I , CaL Ks Cl , I and I in adrenergically activated ventricular ti tissue; increased RR and PR intervals https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 28/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate IIe Adenosine A receptor activators Activation of adenosine A receptors in Adenosine, ATP; aminophylline 1 1 supraventricular tissue (SAN, atrial, AVN) acts as an adenosine activates G protein- coupled inward receptor inhibitor + rectifying K channels and I hyperpolarizing the SAN current, KAdo and shortening APDs in atrial and AVN tissue, and reduces [cAMP] and therefore I i and SAN CaL I ; inhibitory effects on f adenylyl cyclase and cAMP activation, reducing its stimulatory effects on I and I in adrenergically activated ventricular tissue; increased RR and increased PR intervals , I , CaL Ks Cl , I ti + K channel blockers and openers III + + Voltage dependent K channel blockers IIIa Nonselective K channel blockers Block of multiple K channel targets resulting in prolonged atrial, Purkinje, and/or ventricular myocyte AP recovery, increased ERP, Ambasilide, amiodarone, dronedarone + and reduced repolarization reserve; prolonged QT intervals https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 29/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate Kv11.1 (HERG) Prolonged atrial, Dofetilide, channel-mediated rapid K current (I Purkinje, and ventricular myocyte AP recovery, ibutilide, sotalol + ) Kr blockers increased ERP, and reduced repolarization reserve; prolonged QT intervals Kv7.1 channel- Prolonged atrial, No clinically + mediated, slow K current (I Purkinje, and ventricular myocyte AP recovery, approved drugs in use ) blockers Ks increased ERP, and reduced repolarization reserve; prolonged QT intervals https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 30/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate Kv1.5 channel- mediated, ultrarapid Prolonged atrial AP recovery, increased ERP, Vernakalant + K current (I blockers ) and reduced repolarization reserve Kur Kv1.4 and Kv4.2 Prolonged atrial, Blocker under channel-mediated transient outward Purkinje, and ventricular myocyte AP recovery, regulatory review for the acute + K current (I ) increased ERP, and conversion of to1 blockers reduced repolarization reserve, particularly in subepicardial as atrial fibrillation: tedisamil opposed to subendocardial ventricular cardiomyocytes Metabolically + dependent K channel IIIb Kir6.2 (I ) openers Opening of ATP- Nicorandil, pinacidil KATP + sensitive K channels ), shortening AP (I KATP openers recovery, refractoriness, and repolarization reserve in all cardiomyocytes apart from SAN cells; shortened QT intervals Transmitter dependent K channel blockers IIIc GIRK1 and GIRK4 (I Inhibition of direct or G protein -subunit- mediated activation of , particularly in I Blocker under regulatory review for management of atrial i + ) blockers KACh KACh SAN, AVN, and atrial cells, prolonging APD fibrillation: BMS 914392 and ERP and decreasing repolarization reserve 2+ Ca handling modulators IV 2+ Surface IVa Nonselective surface Block of Ca current Bepridil 2+ membrane membrane Ca (I ), resulting in Ca 2+ Ca channel blockers channel blockers inhibition of SAN pacing, inhibition of AVN conduction, prolonged ERP, increased AP https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 31/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate recovery time, increased refractory period, diminished repolarization reserve, and suppression of intracellular Ca 2+ signaling; increased PR intervals 2+ Ca 1.2 and Ca 1.3 channel mediated L- Block of Ca current ), resulting in (I Phenylalkylamines (eg, verapamil), v v Ca 2+ type Ca current ) blockers (I inhibition of SAN pacing, inhibition of AVN benzothiazepines (eg, diltiazem) CaL conduction, prolonged ERP, increased AP recovery time, increased refractory period, diminished repolarization reserve, and suppression of intracellular Ca signaling; increased PR intervals 2+ Ca 3.1 channel mediated T-type Ca current (I blockers Inhibition of SAN pacing, prolonged His- Purkinje phase 4 repolarization, absent No clinically approved drugs in use v 2+ ) CaT from ventricular cells 2+ 2+ Intracellular Ca channel blockers IVb SR RyR2-Ca channel blockers Reduced SR Ca release: reduced 2+ cytosolic and SR [Ca ] Flecainide, propafenone 2+ 2+ IP R-Ca channel blockers 2+ Reduced atrial SR Ca release; reduced No clinically approved drugs in 3 2+ cytosolic and SR [Ca ] use 2+ Sarcoplasmic 2+ reticular Ca - ATPase IVc Sarcoplasmic 2+ Increased Ca -ATPase No clinically reticular Ca pump activators activity, increased SR 2+ [Ca ] approved drugs in use activators + 2+ Surface IVd Surface membrane Reduced Na Ca No clinically membrane ion exchange ion exchanger (eg, SLC8A) inhibitors exchange reduces depolarization approved drugs in use inhibitors associated with rises in 2+ subsarcolemmal [Ca ] https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 32/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate Phosphokinase and IVe Increased/decreased phosphorylation Includes CaMKII modulators: altered No clinically approved drugs in 2+ phosphorylase inhibitors levels of cytosolic Ca handling intracellular Ca signaling use 2+ proteins Mechanosensitive channel blockers 2+ V Transient receptor Intracellular Ca Blocker under potential channel (TRPC3/TRPC6) signaling investigation: N (p-amylcinnamoyl) blockers anthranilic acid Gap junction channel blockers VI Cx (Cx40, Cx43, Cx45) blockers Reduced cell-cell coupling and AP Blocker under investigation: propagation; Cx40: atria, AVN, ventricular conduction system; carbenoxolone Cx43: atria and ventricles, distal conduction system; Cx45: SAN, AVN, conducting bundles Upstream target modulators https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 33/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate VII Angiotensin- converting enzyme Electrophysiological and structural (fibrotic, Captopril, enalapril, delapril, inhibitors hypertrophic, or inflammatory) ramipril, quinapril perindopril, remodeling lisinopril, benazepril, imidapril, trandolapril, cilazapril Angiotensin receptor blockers Electrophysiological and structural (fibrotic, Losartan, candesartan, hypertrophic, or eprosartan, inflammatory) remodeling telmisartan, irbesartan, olmesartan, valsartan, saprisartan Omega-3 fatty acids Electrophysiological and Omega-3 fatty structural (fibrotic, hypertrophic, or inflammatory) remodeling acids: eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid Statins Electrophysiological and structural (fibrotic, hypertrophic, or Statins inflammatory) remodeling HCN: hyperpolarization-activated cyclic nucleotide-gated; SAN: sino-atrial node; AVN: atrioventricular node; AP: action potential; APD: action potential duration; ERP: effective refractory period; SQTS: short-QT syndrome; DAD: delayed afterdepolarization; EAD: early afterdepolarization; RyR2: ryanodine receptor 2; SR: sarcoplasmic reticulum; CaMKII: calcium/calmodulin kinase II. https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 34/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate From: Lei M, Wu L, Terrar DA, et al. Modernized classi cation of cardiac antiarrhythmic drugs. Circulation 2018; 138:1879. Available at: https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.118.035455 (Accessed on January 29, 2019). Reproduced under the terms of the Creative Commons Attribution License. Graphic 120226 Version 2.0 https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 35/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate Revised (2018) Vaughan Williams classification of antiarrhythmic drugs abridged table Class 0 (HCN channel blockers) Ivabradine Class I (voltage-gated Na+ channel blockers) Class Ia (intermediate dissociation): Quinidine, ajmaline, disopyramide, procainamide Class Ib (rapid dissociation): Lidocaine, mexilitine Class Ic (slow dissociation): Propafenone, flecainide Class Id (late current): Ranolazine Class II (autonomic inhibitors and activators) Class IIa (beta blockers): Nonselective: carvedilol, propranolol, nadolol Selective: atenolol, bisoprolol, betaxolol, celiprolol, esmolol, metoprolol Class IIb (nonselective beta agonists): Isoproterenol Class IIc (muscarinic M2 receptor inhibitors): Atropine, anisodamine, hyoscine, scopolamine Class IId (muscarinic M2 receptor activators): Carbachol, pilocarpine, methacholine, digoxin Class IIe (adenosine A1 receptor activators): Adenosine Class III (K+ channel blockers and openers) Class IIIa (voltage dependent K+ channel blockers): Ambasilide, amiodarone, dronedarone, dofetilide, ibutilide, sotalol, vernakalant Class IIIb (metabolically dependent K+ channel openers): https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 36/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate Nicorandil, pinacidil Class IV (Ca++ handling modulators) Class IVa (surface membrane Ca++ channel blockers): Bepridil, diltiazem, verapamil Class IVb (intracellular Ca++ channel blockers): Flecainide, propafenone Class V (mechanosensitive channel blockers): No approved medications Class VI (gap junction channel blockers) No approved medications Class VII (upstream target modulators) Angiotensin converting enzyme inhibitors Angiotensin receptor blockers Omega-3 fatty acids Statins HCN: hyperpolarization-activated cyclic nucleotide-gated; Na: sodium; K: potassium; Ca: calcium. Graphic 120433 Version 3.0 https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 37/38 7/5/23, 10:45 AM Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs - UpToDate Contributor Disclosures Jonathan C Makielski, MD, FACC No relevant financial relationship(s) with ineligible companies to disclose. L Lee L Eckhardt, MD, FHRS No relevant financial relationship(s) with ineligible companies to disclose. Samuel L vy, MD No relevant financial relationship(s) with ineligible companies to disclose. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/cardiac-excitability-mechanisms-of-arrhythmia-and-action-of-antiarrhythmic-drugs/print 38/38

7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Electrocardiographic and electrophysiologic features of atrial flutter : Jordan M Prutkin, MD, MHS, FHRS : Peter J Zimetbaum, MD, Ary L Goldberger, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Mar 31, 2023. INTRODUCTION Atrial flutter (AFL) is an abnormal cardiac rhythm characterized by rapid, regular atrial depolarizations at a typical atrial rate of 250 to 350 beats per minute. There is frequently 2:1 conduction across the atrioventricular (AV) node, meaning that every other atrial depolarization reaches the ventricles. As a result, the ventricular rate is usually one-half the AFL rate in the absence of AV node dysfunction. AFL is classified as typical or atypical based on whether the flutter circuit traverses the cavotricuspid isthmus in the right atrium [1]. Other topic reviews discuss the clinical aspects of AFL. (See "Overview of atrial flutter" and "Restoration of sinus rhythm in atrial flutter" and "Control of ventricular rate in atrial flutter" and "Atrial flutter: Maintenance of sinus rhythm" and "Embolic risk and the role of anticoagulation in atrial flutter" and "Atrial fibrillation and flutter after cardiac surgery".) CLASSIFICATION The first classification scheme in 1970 defined atrial flutter (AFL) as "common" or "atypical," depending on whether the flutter wave had a negative sawtooth pattern in the inferior leads [2]. A few years later, the terms types I and II were created to describe flutter [1]. Type I AFL was classified as a macroreentrant atrial tachycardia while type II AFL was considered unclassified because the mechanisms were not fully understood. https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 1/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate A 2001 working group from Europe and North America tried to reconcile new data from electrophysiology studies and activation mapping [3]. Flutter was defined as a regular tachycardia 240 beats/min with no isoelectric baseline between atrial deflections. Typical and reversal typical flutter were characterized, as described below, and all other flutters were atypical. An American College of Cardiology, American Heart Association, and Heart Rhythm Society guideline on the management of supraventricular tachycardia reaffirmed the classification of AFL into cavo-tricuspid-isthmus (CTI)-dependent ("typical") versus non-CTI dependent ("atypical") [4] and this is the methodology currently used. Typical AFL is a macroreentrant atrial tachycardia, with the inferior border of the circuit traversing the isthmus of tissue between the inferior vena cava and tricuspid annulus as a necessary component. AFL involving this cavotricuspid isthmus is referred to as "typical" or "isthmus-dependent" flutter. In the most common form of CTI-dependent flutter, the reentrant circuit rotates around the tricuspid annulus in a counterclockwise direction when the heart is viewed in a left anterior oblique projection, traversing up the septum and down the lateral wall. This is the arrhythmia associated with the classic electrocardiogram finding of sawtooth flutter waves in the inferior leads. (See 'Electrocardiographic features' below.) Less often, the reentrant circuit rotates in the opposite direction. This arrhythmia is called "clockwise" or "reverse" typical flutter. Atypical AFL is an intraatrial reentrant tachycardia or AFL that does not involve the CTI. It may be a lesion macroreentrant tachycardia, upper loop flutter, intra-isthmus reentry, non-atriotomy- related right atrial flutter, left atrial macroreentry, post-Maze or atrial fibrillation ablation left atrial flutters, or mitral annular flutter [5]. It is frequently seen in those who have had prior cardiac surgery, prior intracardiac ablation, congenital heart disease, or cardiomyopathy but may also be idiopathic. Atypical flutter may be in the right or left atrium and usually revolves around a prior incisional or idiopathic scar, ablation lesion set, or other fixed anatomic barriers. If there has been an incomplete ablation line from a prior procedure, this can increase the chances of an atypical flutter. Many patients with congenital heart disease, especially with more complex disease or surgical repairs, will present with atypical flutter, known as intraatrial reentrant tachycardia [6]. Some patients with idiopathic atrial fibrosis will also present with scar- based atypical flutters. ELECTROPHYSIOLOGIC FEATURES https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 2/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Electrophysiologic studies, using entrainment mapping and electroanatomic mapping, have been used to define the atrial flutter (AFL) circuit in the electrophysiology laboratory and at surgery [7-11]. The principal electrophysiologic features of AFL are: Reentry Excitable gap Transient entrainment and termination by rapid atrial pacing Electrophysiologically, AFL is a reentrant arrhythmia in that it excites an area of the atrium and then travels sufficiently slowly in a pathway that is long enough such that the initially excited area recovers its excitability and is reactivated [7-9,12-15]. Either a single premature extrastimulus or rapid atrial pacing can initiate AFL and, because there is an excitable gap, terminate the arrhythmia [13-15]. The excitable gap is the portion of a reentrant circuit that has recovered its excitability and can again be depolarized, allowing for entrainment with overdrive pacing during AFL [13,14,16]. (See "Reentry and the development of cardiac arrhythmias", section on 'Definition and characteristics'.) Typical AFL commonly starts after a transitional rhythm of variable duration, usually atrial fibrillation [17,18]. It has been postulated that a fundamental feature that determines whether an atrial arrhythmia becomes sustained typical AFL or atrial fibrillation is the development of a line of functional refractoriness or block between the vena cavae [18]. In spontaneous typical AFL, the critical line of functional block between the vena cavae may be created by transient atrial fibrillation. This line of block results in unidirectional block and stable AFL follows. According to this theory, if the line of functional block is not created, atrial fibrillation persists or the rhythm reverts back to sinus. Another view, based in part on a small electrophysiologic study of 10 patients, emphasizes the anatomic barriers as well as the properties of conduction and refractoriness during atrial fibrillation to explain the usual pattern observed with typical AFL [19]. In the electrophysiology laboratory, premature electrical stimulation may function in a manner similar to the transitional atrial fibrillation in forming the critical functional line of block between the vena cavae [18]. An additional determinant of whether the transitional atrial tachyarrhythmia becomes AFL or atrial fibrillation may be the cycle length of the flutter [18]. If the cycle length is critically short, it will create fibrillatory conduction and atrial fibrillation. Lastly, the electrical properties of the isthmus may also be a factor in the tendency for AFL to disorganize into atrial fibrillation in some patients [20]. https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 3/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Similar to what has been reported in atrial fibrillation, AFL results in electrical remodeling of the atrial myocardium, perhaps accounting for the observation that untreated AFL can eventually lead to atrial fibrillation [21]. In contrast to the normal situation in which the atrial refractory period shortens with an increase in rate and prolongs when the rate decreases, the refractory period fails to lengthen appropriately at slow rates (eg, with return to sinus rhythm) in patients with AFL present for a mean of 8.5 months (range 1 to 32 months) [22]. This abnormality persists for at least 30 minutes after cardioversion to sinus rhythm; the duration of AFL has no significant impact upon the magnitude of these electrophysiologic changes. Those with a history of AFL, but not fibrillation, have significant changes in the electrophysiologic properties of the right atrium, even when they are in normal sinus rhythm. The right atrium is more likely to be enlarged, have lower voltage suggesting scar, longer P wave duration, and slowed conduction velocity most prominent in the lower right atrium, and sinus node dysfunction [23]. The duration of AFL does impact the time course of electrical remodeling recovery after arrhythmia termination. As an example, one study of 25 patients with paroxysmal or chronic flutter (average duration 17 months) found that, in those with paroxysmal AFL, the refractory period shortened after a 5- to 10-minute period of flutter and reversed within five minutes of restoration of sinus rhythm; atrial fibrillation developed in some patients when the refractory period was at its nadir [24]. In patients with chronic AFL, the atrial refractory period increased during the first three weeks after resumption of sinus rhythm. Typical flutters A large macroreentrant circuit in the right atrium is involved in typical AFL. If one begins the cycle at the end of the negative deflection of the F wave in lead II, the impulse at that point exists in the low right atrial septum between the inferior vena cava (IVC) and the tricuspid valve. In counterclockwise typical flutter, the impulse then travels anteriorly through the region of the low septum, ascends superiorly and anteriorly up the septal and posterior walls of the right atrium, and returns or descends over the anterior and lateral free wall ( figure 1) [25]. This circuit is then completed through the region between the tricuspid valve and IVC (counterclockwise reentry). A reverse direction of rotation (clockwise reentry, ascending the anterior wall, and descending the posterior and septal walls) is seen in reverse typical AFL [3,25]. The crista terminalis (and its continuation as the eustachian ridge) and IVC often form the posterior barrier, while the tricuspid annulus constitutes the anterior barrier of the circuit ( figure 1) [11,26]. This has potential clinical implications, since this region can be a target for ablation therapy in patients with refractory AFL [26,27]. (See "Atrial flutter: Maintenance of sinus rhythm", section on 'RF catheter ablation'.) https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 4/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate The presence of slow conduction in the cavotricuspid isthmus has been confirmed by noncontact mapping [28]. The cavotricuspid isthmus is a part of the circuit most vulnerable to interval-dependent conduction delay [16] and termination of AFL with ibutilide, propafenone, or amiodarone is due in part to failure of impulse conduction through this tissue [22]. (See "Overview of catheter ablation of cardiac arrhythmias", section on 'Noncontact mapping'.) The typical AFL circuit has been thought to run anterior to the superior vena cava (SVC) in most patients [29]. However, a study of 15 patients with typical flutter using noncontact and entrainment mapping showed that the posterior wall was a part of the circuit in seven patients [30]. In a study of 50 patients using entrainment mapping, between one-quarter to one-third did not use the atrial roof anterior to the SVC as part of the circuit [31]. These studies imply that the crista terminalis is not always a fixed barrier to conduction and the circuit can be posterior to the SVC. Partial isthmus atrial flutter is a type of typical flutter where a wavefront goes between the IVC and coronary sinus ostium after conducting through the posterior cavo-tricuspid-isthmus (CTI). This wavefront then conducts around the CS ostium and up the septum, but also goes retrograde back into the anterior CTI. For this circuit to occur, there must either be a pectinate muscle that breaks the CTI into an anterior and posterior portion [32] or rapid conduction through the eustachian ridge [26]. Intra-isthmus reentry is usually seen in those with prior CTI ablation [33]. The circuit is contained entirely within the CTI and may be in the septal, medial, or anterior portions, with areas of long fractionated potentials the best target for ablation [33]. The circuit for lower loop reentry circles around the IVC, on the septal side usually between the IVC and coronary sinus ostium [34]. It exits out on the low lateral wall, with wavefront one conducting up the lateral wall and wavefront two going through the CTI, anterior to the coronary sinus ostium, and up the septal wall in a manner similar to counterclockwise typical flutter. The two wave fronts collide somewhere in the lateral right atrium or septum, but the dominant circuit still encircles the IVC. Lower loop reentry frequently morphs into counterclockwise AFL and may be associated with an atrial myopathy [5]. Atypical right atrial flutters Lesion macroreentrant tachycardia An atriotomy scar or suture line can act as an obstacle to conduction and create reentry. There may also be atrial septal defect patches that can lead to an atypical flutter circuit. In addition, scar from congenital heart disease lesions such as after an atrial level switch surgery (Mustard or Senning repairs) for transposition of the great arteries or https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 5/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate after a Fontan repair may lead to atypical flutters. (See "Management of complications in patients with Fontan circulation", section on 'Arrhythmias'.) Atriotomy scar-related atypical flutters are the most common of this type, where the scar is vertical along the lateral right atrium. The anterior right atrial wall may have ascending or descending activation depending on whether the circuit is clockwise or counterclockwise, while the septum may have more variable conduction [3]. The circuit wraps around the incision, with the upper turnaround point between the scar and SVC and the lower turnaround point between the scar and IVC. Alternatively, one of the turnaround points may be through an area of conduction within the scar. As is true for all flutters, entrainment and activation mapping are helpful for defining the circuit. The atriotomy region will have double potentials and low voltage to denote its location. During flutter, the double potentials are more widely spaced in the center of the scar and usually become one single fractionated electrogram at the turnaround points. Typical flutter may be seen after ablation of this atypical flutter, if a prior cavotricuspid isthmus ablation has not previously been completed. Nonatriotomy-related right atrial flutter For unexplained reasons, some patients will have areas of low voltage in the right atrium. This may lead to a scar similar to an atriotomy lesion, even though there has been no cardiac incision. This leads to a flutter wrapping around the scar, though may also be a figure-8 reentry if there is conduction through the low voltage area [32]. Ablation from the lower border of the scar to the IVC frequently terminates the arrhythmia. Upper loop reentry This circuit crosses through a conduction gap in the crista terminalis in the upper right atrium, which is where the successful site of ablation can be [35]. It can be clockwise or counterclockwise, with activation going up or down the anterior right atrial free wall. At least one patient also demonstrated successful ablation in the region between the fossa ovalis and IVC [32], indicating that this tachycardia circuit may not be as clearly defined as previously thought. Atypical left atrial flutters Post-Maze or atrial fibrillation ablation left atrial flutters These tachycardias are most frequently due to incomplete ablation lines from either a transvenous catheter ablation or a surgical Maze procedure. They may also be related to left atrial fibrosis seen in those with a history of atrial arrhythmias. They are usually seen in the anterior wall, through the roof, or on the septum. Mapping can often be difficult due to low voltages. (See "Atrial fibrillation: Surgical ablation", section on 'Maze procedure'.) https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 6/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Mitral annular flutter wraps around the mitral valve clockwise or counterclockwise [36,37]. Entrainment from a catheter in the coronary sinus will frequently demonstrate concealed entrainment on all poles for mitral annular flutter, but not for other left atrial flutters. It can be difficult to terminate and often needs ablation within the coronary sinus or vein of Marshall to achieve a line of block [38]. Even in the presence of apparent complete block, there may still be recurrence of mitral flutter as there may only be significant conduction slowing rather than block [39]. Left atrial macroreentry Less commonly, atypical flutters can occur in those with no prior ablation or surgery in the left atrium. They may be located on the anterior or posterior wall and are bounded by an anatomic obstacle like the mitral annulus [40]. They may be a single circuit or double loop and are associated with low voltage signals with areas of fractionated signals [41]. Atrioventricular node and the ventricular response The electrophysiologic events in AFL can be viewed as an input (the F waves) and an output (QRS complexes) that is processed through a regulator or black box (the atrioventricular [AV] node). The electrophysiologic characteristics of the AV node, which is a "slow response" tissue in comparison to the atria, primarily determine the ventricular response. (See "The electrocardiogram in atrial fibrillation".) As noted below (see 'Electrophysiologic features' above), the ventricular response in AFL is generally one-half the atrial input, resulting in a ventricular rate of about 150 beats/min. 3:1 and 4:1 input/output ratios are also relatively common, leading to ventricular rates of about 100 and 75 beats/min, respectively. Thus, AFL should be considered whenever the electrocardiogram shows a heart rate of 150, 100, and 75 beats/min. Rarely, the input/output ratio is 1:1, resulting in a ventricular response of nearly 300 beats/min. This may occur in states characterized by marked catecholamine excess and in the presence of AV bypass tracts with preexcitation ( waveform 1). A 1:1 response is more commonly seen when the atrial rate is slowed and AV nodal conduction is enhanced, leading to ventricular rates of 220 to 250 beats/min. This combination can be induced by class IA or IC antiarrhythmic drugs ( table 1) due to: Slowing of the conduction velocity in the reentrant circuit and therefore the flutter rate by inhibition of sodium channels. Increasing AV nodal conduction by their vagolytic effects. These characteristics have implications for management. (See "Control of ventricular rate in atrial flutter".) https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 7/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Partial or complete block in the AV node or in the specialized infranodal conduction system (His bundle, bundle branches and fascicles, and terminal Purkinje fibers) may lead to escape or accelerated rhythms from within the AV node or below to assume control of the ventricles. The ventricular rate in this setting may be normal, faster, or slower than is normal for these lower pacemakers. The diagnosis of complete heart block may be missed if F waves are not carefully matched with R waves or when the lower escape rate approaches an arithmetic divisor of the flutter rate. As is true for atrial fibrillation, there may be a Wenckebach type of exit block around such an escape site, resulting in group beating. ELECTROCARDIOGRAPHIC FEATURES The electrocardiographic features of typical atrial flutter (AFL) in the presence of normal atrioventricular (AV) nodal conduction are ( waveform 2): P waves are absent. For counterclockwise typical AFL, biphasic "sawtooth" flutter waves (F waves) are present at a rate of about 300 beats/min, with the range being 240 to 340 beats/min [1]. The F waves are fairly regular on the surface electrocardiogram with constant amplitude, duration, morphology, and reproducibility throughout the cardiac cycles. There can be very subtle variability, however, as spectral analysis has detected an underlying periodic pattern modulated by an interplay between the autonomic nervous system, respiratory system, and ventricular rate [42]. The F waves usually do not have an isoelectric interval between them (ie, the F waves blend into one another) unless the rate of the AFL is slow. In counterclockwise typical AFL, the F waves have an axis of around 90 and are prominently negative in the inferior leads (II, III, aVF). The F waves often have an initial slowly downsloping segment followed by a sharp negative deflection, then a sharp positive deflection that may have a positive overshoot leading into the next downward deflection ( waveform 2). With 2:1 flutter, there is commonly a negative deflection superimposed on the ST segment, giving the appearance of ST depression related to myocardial ischemia. In clockwise typical AFL (reverse typical AFL), the F waves are usually positive in the inferior leads due to an opposite direction of atrial activation, but there is significant https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 8/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate heterogeneity in the F wave morphology [3]. The F wave may even have a sine wave pattern. The deflection in V1 is often broad and negative ( waveform 3) (panel B). The ventricular response (R-R intervals) is usually one-half the rate of the atrial input (ie, 2:1 AV nodal conduction with a ventricular response of about 150 beats/min). This finding is sufficiently common and the diagnosis of AFL should be considered whenever the ventricular rate is about 150 beats/min. AV block greater than 2:1 in the absence of drugs that slow the ventricular response suggests AV nodal disease and the possibility of associated sinus node disease, which may be part of the tachy-brady syndrome. A 1:1 AV response suggests accessory bypass tracts, sympathetic excess, parasympathetic withdrawal, or class IC antiarrhythmic agents. Even ratios of input to output (eg, 2:1, 4:1) are more common than odd numbers (eg, 3:1, 5:1). Odd ratios and shifting ratios (eg, alteration of 2:1 with 4:1) probably reflect bilevel block in the AV node. The QRS complex is narrow unless there is functional aberration, preexisting bundle branch or fascicular block, preexcitation, or ventricular pacing. The electrocardiographic features of atypical AFL are: P waves are absent. F waves are regular, but in contrast to typical AFL, there may be an isoelectric appearance between F waves if there is an area of significantly slowed conduction. There is no clear F wave morphology to identify the location consistently, as atypical flutters are often associated with atrial scar that can alter conduction velocity and direction. That said, some patterns described below may be seen. Lower loop reentry typically has negative F waves in the inferior leads ( waveform 4). Upper loop reentry has positive F waves in the inferior leads and negative, flat, or barely positive F waves in lead I [43]. Intra-isthmus reentry will appear like typical counterclockwise AFL. If there is a negative F wave in V1, the flutter is usually in the right atrium ( waveform 5). Left atrial flutters have variable morphologies, but may have a positive F wave in V1 or may be isoelectric ( waveform 6) [5]. It is often positive in the inferior leads, but not always ( waveform 7). https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 9/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Counterclockwise mitral annular flutter is positive in V1-6 and the inferior leads and negative in aVL [44]. Clockwise mitral annular flutter is positive in the right precordial leads but usually negative and then positive in the lateral precordial leads ( waveform 8). It is negative in the inferior leads and positive in I and aVL. Morphology of the QRS complex Activation through the AV node and infranodal conduction system is normal in AFL, so the QRS complex is narrow unless: A preexisting conduction defect is present. Functional block occurs in a portion of the infranodal conduction system, leading to a bundle branch or fascicular block. The refractory period of the bundle branches and fascicles is determined by the preceding cycle length. A long preceding cycle lengthens the refractory period in these structures, so a premature beat is more likely to be functionally blocked after a long cycle, known as Ashman's phenomenon. Preexcitation through an AV bypass tract is present. Ventricular pacing is present. Pitfalls The electrocardiographic criteria listed above are usually sufficient to make the proper diagnosis; there are, however, potential pitfalls: One of the F waves may be obscured by the QRS complex or the ST-T wave ( waveform 9) in patients with 2:1 AV nodal conduction. In this setting, AFL may be misdiagnosed as a sinus tachycardia or a paroxysmal supraventricular tachycardia with downsloping ST depression. In clockwise, typical flutter, the F waves may be positive, and if every other F wave is obscured, it may be mistaken for a long RP tachycardia such as sinus tachycardia, ectopic atrial tachycardia, atypical AV nodal reentrant tachycardia, or AV reciprocating tachycardia. The atrial electrical potential may be small and the F waves may be difficult to see in the standard leads. Sometimes it may be necessary to increase the gain of the electrocardiogram to see the F waves more clearly (ie, 20 mm/mV). Atrial fibrillation, especially with coarse fibrillatory waves in lead V1, is often misdiagnosed as AFL [45]. Examination of a rhythm strip will often show that the atrial fibrillatory rate and morphology change over a period of time. We discourage using the term AFL-fibrillation, since the rhythm more closely resembles atrial fibrillation in its response to drugs that slow AV nodal conduction and in the higher energy requirement for direct current cardioversion. https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 10/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Sometimes the negative F wave merges with the beginning or end of the QRS complex, suggesting a pathologic Q wave in the first case and a conduction delay in the second. Likewise, the F wave may appear to cause pathologic ST-segment depression. The F wave morphology may appear atypical in those with congenital heart disease, atrial fibrosis, following cardiac surgery, or after left atrial ablation for atrial fibrillation even though the rhythm is typical flutter [46,47]. Prior extensive ablation in the left atrium may alter the morphology of F waves in typical AFL, due to reductions in left atrial potentials and changes in the atrial activation sequence. This was illustrated in a series of 15 patients who had undergone circumferential left atrial ablation for the treatment of atrial fibrillation and later developed typical AFL (12 counterclockwise, 3 clockwise) [47]. In 9 of 15 cases, the F waves were upright in the inferior leads, including 7 of 12 of typical counterclockwise flutter. Electrocardiography and telemetry artifacts caused by tremor [48] or electromagnetic interference [49,50] may suggest the occurrence of AFL, but this pseudo-atrial flutter will be revealed when the tremor or interference ceases. DIFFERENTIAL DIAGNOSIS The differential diagnosis of atrial flutter (AFL) includes a number of supraventricular tachyarrhythmias. (See "Focal atrial tachycardia" and "Intraatrial reentrant tachycardia" and "Sinoatrial nodal reentrant tachycardia (SANRT)" and "Cardiac arrhythmias due to digoxin toxicity" and "Multifocal atrial tachycardia" and "Atrioventricular nodal reentrant tachycardia" and "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation", section on 'Types of narrow QRS complex tachycardia'.) As noted above, obscured atrial activity or F waves that resemble normal or inverted P waves may suggest sinus tachycardia, paroxysmal supraventricular tachycardia, or atrial fibrillation. There are four major ways to help establish the correct diagnosis: An earlier electrocardiogram, if available, may allow comparison of the F or presumed P wave with the previous P wave morphology. Scrutiny of the ST-segment and T waves may show a bump or irregularity caused by a second flutter wave. Decreasing atrioventricular (AV) nodal conduction physiologically with a vagotonic maneuver (such as the Valsalva maneuver or carotid sinus massage) or with a rapidly https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 11/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate acting drug (such as adenosine, verapamil, or esmolol) will increase the AV nodal block and reveal the atrial F waves ( waveform 9). Recording from an atrial catheter, atrial pacing wire, or an esophageal electrode will also demonstrate the regular atrial activity ( waveform 10). Even with these maneuvers, ectopic atrial tachycardia and other supraventricular tachycardias with 2:1 block may remain in the differential diagnosis. Furthermore, two types of arrhythmia can occur in the same patient, as a supraventricular tachycardia can initiate AFL or atrial fibrillation. An example of this difficulty occurs when AFL has a slow ventricular response that overlaps with the rate seen in other supraventricular tachycardias. If, for example, the patient is taking digitalis for flutter, then an atrial tachycardia with a 2:1 AV response that reflects a high degree of digitalis toxicity must be excluded. Treatment of these two disorders is clearly different, and atrial morphology may be of little help in identifying the underlying arrhythmia. In this setting, establishment of the correct diagnosis may depend upon the clinical history, plasma digoxin levels, and the response following cessation of digoxin therapy. As noted above, complete heart block may be difficult to recognize in the presence of AFL. The presence of F waves and a regular rate of the lower pacemaker may lead to the appearance of an uncomplicated AFL. MANAGEMENT The control of ventricular rate and the approach to anticoagulant therapy for patient with atrial flutter is discussed elsewhere. (See "Overview of atrial flutter" and "Embolic risk and the role of anticoagulation in atrial flutter".) Cardioversion in patients with atrial flutter is discussed separately. (See "Restoration of sinus rhythm in atrial flutter".) The approach to the maintenance of sinus rhythm and the impact of electrophysiologic type is discussed separately. (See "Atrial flutter: Maintenance of sinus rhythm" and "Atrial flutter: Maintenance of sinus rhythm", section on 'RF catheter ablation'.) SUMMARY https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 12/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Atrial flutter (AFL) is a supraventricular tachycardia with regular flutter waves and usually an absent isoelectric interval. The rhythm is due to macroreentry, has an excitable gap, and can be transiently entrained and terminated by rapid atrial pacing. Electrocardiographic characteristics include: Biphasic, sawtooth F waves, best seen in the inferior electrocardiogram leads (II, III, aVF), at about 300 beats/min are the classic finding for typical, counterclockwise AFL. The ventricular response is a multiple of the atrial rate, though most frequently is 2:1 with a ventricular rate of 150 beats/min. Flutter waves may sometimes be obscured in the QRS complex in 2:1 conduction. Typical AFL most frequently rotates counterclockwise posterior to the tricuspid valve and uses the critical region of the cavotricuspid isthmus within the circuit. Clockwise, typical AFL uses the same circuit, but rotates in the opposite direction. Atypical AFL is any flutter that does not involve the cavotricuspid isthmus. The flutter wave morphology does not have a characteristic pattern to localize the flutter circuit. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Wells JL Jr, MacLean WA, James TN, Waldo AL. Characterization of atrial flutter. Studies in man after open heart surgery using fixed atrial electrodes. Circulation 1979; 60:665. 2. Puech P, Latour H, Grolleau R. [Flutter and his limits]. Arch Mal Coeur Vaiss 1970; 63:116. 3. Saoudi N, Cos o F, Waldo A, et al. A classification of atrial flutter and regular atrial tachycardia according to electrophysiological mechanisms and anatomical bases; a Statement from a Joint Expert Group from The Working Group of Arrhythmias of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Eur Heart J 2001; 22:1162. 4. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2016; 67:e27. 5. Bun SS, Latcu DG, Marchlinski F, Saoudi N. Atrial flutter: more than just one of a kind. Eur Heart J 2015; 36:2356. https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 13/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate 6. Khairy P, Aboulhosn J, Gurvitz MZ, et al. Arrhythmia burden in adults with surgically repaired tetralogy of Fallot: a multi-institutional study. Circulation 2010; 122:868. 7. Peuch P, Gallay P, Grolleau R. Mechanism of atrial flutter in humans. In: Atrial Arrhythmias: C urrent Concepts and Management, Tourboul P, Waldo AL (Eds), Mosby Year Book, St Louis 1 990. p.190. 8. Klein GJ, Guiraudon GM, Sharma AD, Milstein S. Demonstration of macroreentry and feasibility of operative therapy in the common type of atrial flutter. Am J Cardiol 1986; 57:587. 9. Cosio FG, Arribas F, Barbero JM, et al. Validation of double-spike electrograms as markers of conduction delay or block in atrial flutter. Am J Cardiol 1988; 61:775. 10. Tai CT, Chen SA, Chiang CE, et al. Characterization of low right atrial isthmus as the slow conduction zone and pharmacological target in typical atrial flutter. Circulation 1997; 96:2601. 11. Kalman JM, Olgin JE, Saxon LA, et al. Activation and entrainment mapping defines the tricuspid annulus as the anterior barrier in typical atrial flutter. Circulation 1996; 94:398. 12. Disertori M, Inama G, Vergara G, et al. Evidence of a reentry circuit in the common type of atrial flutter in man. Circulation 1983; 67:434. 13. Waldo AL, MacLean WA, Karp RB, et al. Entrainment and interruption of atrial flutter with atrial pacing: studies in man following open heart surgery. Circulation 1977; 56:737. 14. Watson RM, Josephson ME. Atrial flutter. I. Electrophysiologic substrates and modes of initiation and termination. Am J Cardiol 1980; 45:732. 15. Inoue H, Matsuo H, Takayanagi K, Murao S. Clinical and experimental studies of the effects of atrial extrastimulation and rapid pacing on atrial flutter cycle. Evidence of macro-reentry with an excitable gap. Am J Cardiol 1981; 48:623. 16. Callans DJ, Schwartzman D, Gottlieb CD, et al. Characterization of the excitable gap in human type I atrial flutter. J Am Coll Cardiol 1997; 30:1793. 17. Waldo AL, Cooper TB. Spontaneous onset of type I atrial flutter in patients. J Am Coll Cardiol 1996; 28:707. 18. Waldo AL. Mechanisms of atrial flutter and atrial fibrillation: distinct entities or two sides of a coin? Cardiovasc Res 2002; 54:217. 19. Roithinger FX, Karch MR, Steiner PR, et al. Relationship between atrial fibrillation and typical atrial flutter in humans: activation sequence changes during spontaneous conversion. Circulation 1997; 96:3484. https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 14/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate 20. Narayan SM, Bode F, Karasik PL, Franz MR. Alternans of atrial action potentials during atrial flutter as a precursor to atrial fibrillation. Circulation 2002; 106:1968. 21. Morton JB, Byrne MJ, Power JM, et al. Electrical remodeling of the atrium in an anatomic model of atrial flutter: relationship between substrate and triggers for conversion to atrial fibrillation. Circulation 2002; 105:258. 22. Franz MR, Karasik PL, Li C, et al. Electrical remodeling of the human atrium: similar effects in patients with chronic atrial fibrillation and atrial flutter. J Am Coll Cardiol 1997; 30:1785. 23. Stiles MK, Wong CX, John B, et al. Characterization of atrial remodeling studied remote from episodes of typical atrial flutter. Am J Cardiol 2010; 106:528. 24. Sparks PB, Jayaprakash S, Vohra JK, Kalman JM. Electrical remodeling of the atria associated with paroxysmal and chronic atrial flutter. Circulation 2000; 102:1807. 25. Kalman JM, Olgin JE, Saxon LA, et al. Electrocardiographic and electrophysiologic characterization of atypical atrial flutter in man: use of activation and entrainment mapping and implications for catheter ablation. J Cardiovasc Electrophysiol 1997; 8:121. 26. Nakagawa H, Lazzara R, Khastgir T, et al. Role of the tricuspid annulus and the eustachian valve/ridge on atrial flutter. Relevance to catheter ablation of the septal isthmus and a new technique for rapid identification of ablation success. Circulation 1996; 94:407. 27. Cosio FG, L pez-Gil M, Goicolea A, et al. Radiofrequency ablation of the inferior vena cava-

levels, and the response following cessation of digoxin therapy. As noted above, complete heart block may be difficult to recognize in the presence of AFL. The presence of F waves and a regular rate of the lower pacemaker may lead to the appearance of an uncomplicated AFL. MANAGEMENT The control of ventricular rate and the approach to anticoagulant therapy for patient with atrial flutter is discussed elsewhere. (See "Overview of atrial flutter" and "Embolic risk and the role of anticoagulation in atrial flutter".) Cardioversion in patients with atrial flutter is discussed separately. (See "Restoration of sinus rhythm in atrial flutter".) The approach to the maintenance of sinus rhythm and the impact of electrophysiologic type is discussed separately. (See "Atrial flutter: Maintenance of sinus rhythm" and "Atrial flutter: Maintenance of sinus rhythm", section on 'RF catheter ablation'.) SUMMARY https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 12/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Atrial flutter (AFL) is a supraventricular tachycardia with regular flutter waves and usually an absent isoelectric interval. The rhythm is due to macroreentry, has an excitable gap, and can be transiently entrained and terminated by rapid atrial pacing. Electrocardiographic characteristics include: Biphasic, sawtooth F waves, best seen in the inferior electrocardiogram leads (II, III, aVF), at about 300 beats/min are the classic finding for typical, counterclockwise AFL. The ventricular response is a multiple of the atrial rate, though most frequently is 2:1 with a ventricular rate of 150 beats/min. Flutter waves may sometimes be obscured in the QRS complex in 2:1 conduction. Typical AFL most frequently rotates counterclockwise posterior to the tricuspid valve and uses the critical region of the cavotricuspid isthmus within the circuit. Clockwise, typical AFL uses the same circuit, but rotates in the opposite direction. Atypical AFL is any flutter that does not involve the cavotricuspid isthmus. The flutter wave morphology does not have a characteristic pattern to localize the flutter circuit. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Wells JL Jr, MacLean WA, James TN, Waldo AL. Characterization of atrial flutter. Studies in man after open heart surgery using fixed atrial electrodes. Circulation 1979; 60:665. 2. Puech P, Latour H, Grolleau R. [Flutter and his limits]. Arch Mal Coeur Vaiss 1970; 63:116. 3. Saoudi N, Cos o F, Waldo A, et al. A classification of atrial flutter and regular atrial tachycardia according to electrophysiological mechanisms and anatomical bases; a Statement from a Joint Expert Group from The Working Group of Arrhythmias of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Eur Heart J 2001; 22:1162. 4. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2016; 67:e27. 5. Bun SS, Latcu DG, Marchlinski F, Saoudi N. Atrial flutter: more than just one of a kind. Eur Heart J 2015; 36:2356. https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 13/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate 6. Khairy P, Aboulhosn J, Gurvitz MZ, et al. Arrhythmia burden in adults with surgically repaired tetralogy of Fallot: a multi-institutional study. Circulation 2010; 122:868. 7. Peuch P, Gallay P, Grolleau R. Mechanism of atrial flutter in humans. In: Atrial Arrhythmias: C urrent Concepts and Management, Tourboul P, Waldo AL (Eds), Mosby Year Book, St Louis 1 990. p.190. 8. Klein GJ, Guiraudon GM, Sharma AD, Milstein S. Demonstration of macroreentry and feasibility of operative therapy in the common type of atrial flutter. Am J Cardiol 1986; 57:587. 9. Cosio FG, Arribas F, Barbero JM, et al. Validation of double-spike electrograms as markers of conduction delay or block in atrial flutter. Am J Cardiol 1988; 61:775. 10. Tai CT, Chen SA, Chiang CE, et al. Characterization of low right atrial isthmus as the slow conduction zone and pharmacological target in typical atrial flutter. Circulation 1997; 96:2601. 11. Kalman JM, Olgin JE, Saxon LA, et al. Activation and entrainment mapping defines the tricuspid annulus as the anterior barrier in typical atrial flutter. Circulation 1996; 94:398. 12. Disertori M, Inama G, Vergara G, et al. Evidence of a reentry circuit in the common type of atrial flutter in man. Circulation 1983; 67:434. 13. Waldo AL, MacLean WA, Karp RB, et al. Entrainment and interruption of atrial flutter with atrial pacing: studies in man following open heart surgery. Circulation 1977; 56:737. 14. Watson RM, Josephson ME. Atrial flutter. I. Electrophysiologic substrates and modes of initiation and termination. Am J Cardiol 1980; 45:732. 15. Inoue H, Matsuo H, Takayanagi K, Murao S. Clinical and experimental studies of the effects of atrial extrastimulation and rapid pacing on atrial flutter cycle. Evidence of macro-reentry with an excitable gap. Am J Cardiol 1981; 48:623. 16. Callans DJ, Schwartzman D, Gottlieb CD, et al. Characterization of the excitable gap in human type I atrial flutter. J Am Coll Cardiol 1997; 30:1793. 17. Waldo AL, Cooper TB. Spontaneous onset of type I atrial flutter in patients. J Am Coll Cardiol 1996; 28:707. 18. Waldo AL. Mechanisms of atrial flutter and atrial fibrillation: distinct entities or two sides of a coin? Cardiovasc Res 2002; 54:217. 19. Roithinger FX, Karch MR, Steiner PR, et al. Relationship between atrial fibrillation and typical atrial flutter in humans: activation sequence changes during spontaneous conversion. Circulation 1997; 96:3484. https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 14/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate 20. Narayan SM, Bode F, Karasik PL, Franz MR. Alternans of atrial action potentials during atrial flutter as a precursor to atrial fibrillation. Circulation 2002; 106:1968. 21. Morton JB, Byrne MJ, Power JM, et al. Electrical remodeling of the atrium in an anatomic model of atrial flutter: relationship between substrate and triggers for conversion to atrial fibrillation. Circulation 2002; 105:258. 22. Franz MR, Karasik PL, Li C, et al. Electrical remodeling of the human atrium: similar effects in patients with chronic atrial fibrillation and atrial flutter. J Am Coll Cardiol 1997; 30:1785. 23. Stiles MK, Wong CX, John B, et al. Characterization of atrial remodeling studied remote from episodes of typical atrial flutter. Am J Cardiol 2010; 106:528. 24. Sparks PB, Jayaprakash S, Vohra JK, Kalman JM. Electrical remodeling of the atria associated with paroxysmal and chronic atrial flutter. Circulation 2000; 102:1807. 25. Kalman JM, Olgin JE, Saxon LA, et al. Electrocardiographic and electrophysiologic characterization of atypical atrial flutter in man: use of activation and entrainment mapping and implications for catheter ablation. J Cardiovasc Electrophysiol 1997; 8:121. 26. Nakagawa H, Lazzara R, Khastgir T, et al. Role of the tricuspid annulus and the eustachian valve/ridge on atrial flutter. Relevance to catheter ablation of the septal isthmus and a new technique for rapid identification of ablation success. Circulation 1996; 94:407. 27. Cosio FG, L pez-Gil M, Goicolea A, et al. Radiofrequency ablation of the inferior vena cava- tricuspid valve isthmus in common atrial flutter. Am J Cardiol 1993; 71:705. 28. Schilling RJ, Peters NS, Goldberger J, et al. Characterization of the anatomy and conduction velocities of the human right atrial flutter circuit determined by noncontact mapping. J Am Coll Cardiol 2001; 38:385. 29. Shah DC, Ja s P, Ha ssaguerre M, et al. Three-dimensional mapping of the common atrial flutter circuit in the right atrium. Circulation 1997; 96:3904. 30. Dixit S, Lavi N, Robinson M, et al. Noncontact electroanatomic mapping to characterize typical atrial flutter: participation of right atrial posterior wall in the reentrant circuit. J Cardiovasc Electrophysiol 2011; 22:422. 31. Maury P, Duparc A, Hebrard A, et al. Prevalence of typical atrial flutter with reentry circuit posterior to the superior vena cava: use of entrainment at the atrial roof. Europace 2008; 10:190. 32. Yang Y, Cheng J, Bochoeyer A, et al. Atypical right atrial flutter patterns. Circulation 2001; 103:3092. 33. Yang Y, Varma N, Badhwar N, et al. Prospective observations in the clinical and electrophysiological characteristics of intra-isthmus reentry. J Cardiovasc Electrophysiol https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 15/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate 2010; 21:1099. 34. Cheng J, Cabeen WR Jr, Scheinman MM. Right atrial flutter due to lower loop reentry: mechanism and anatomic substrates. Circulation 1999; 99:1700. 35. Tai CT, Huang JL, Lin YK, et al. Noncontact three-dimensional mapping and ablation of upper loop re-entry originating in the right atrium. J Am Coll Cardiol 2002; 40:746. 36. Wasmer K, M nnig G, Bittner A, et al. Incidence, characteristics, and outcome of left atrial tachycardias after circumferential antral ablation of atrial fibrillation. Heart Rhythm 2012; 9:1660. 37. Chae S, Oral H, Good E, et al. Atrial tachycardia after circumferential pulmonary vein ablation of atrial fibrillation: mechanistic insights, results of catheter ablation, and risk factors for recurrence. J Am Coll Cardiol 2007; 50:1781. 38. Bai R, Di Biase L, Mohanty P, et al. Ablation of perimitral flutter following catheter ablation of atrial fibrillation: impact on outcomes from a randomized study (PROPOSE). J Cardiovasc Electrophysiol 2012; 23:137. 39. Miyazaki S, Shah AJ, Hocini M, et al. Recurrent spontaneous clinical perimitral atrial tachycardia in the context of atrial fibrillation ablation. Heart Rhythm 2015; 12:104. 40. Zhang J, Tang C, Zhang Y, et al. Electroanatomic characterization and ablation outcome of nonlesion related left atrial macroreentrant tachycardia in patients without obvious structural heart disease. J Cardiovasc Electrophysiol 2013; 24:53. 41. Fukamizu S, Sakurada H, Hayashi T, et al. Macroreentrant atrial tachycardia in patients without previous atrial surgery or catheter ablation: clinical and electrophysiological characteristics of scar-related left atrial anterior wall reentry. J Cardiovasc Electrophysiol 2013; 24:404. 42. Stambler BS, Ellenbogen KA. Elucidating the mechanisms of atrial flutter cycle length variability using power spectral analysis techniques. Circulation 1996; 94:2515. 43. Yuniadi Y, Tai CT, Lee KT, et al. A new electrocardiographic algorithm to differentiate upper loop re-entry from reverse typical atrial flutter. J Am Coll Cardiol 2005; 46:524. 44. Gerstenfeld EP, Dixit S, Bala R, et al. Surface electrocardiogram characteristics of atrial tachycardias occurring after pulmonary vein isolation. Heart Rhythm 2007; 4:1136. 45. Knight BP, Michaud GF, Strickberger SA, Morady F. Electrocardiographic differentiation of atrial flutter from atrial fibrillation by physicians. J Electrocardiol 1999; 32:315. 46. Khairy P, Stevenson WG. Catheter ablation in tetralogy of Fallot. Heart Rhythm 2009; 6:1069. 47. Chugh A, Latchamsetty R, Oral H, et al. Characteristics of cavotricuspid isthmus-dependent atrial flutter after left atrial ablation of atrial fibrillation. Circulation 2006; 113:609. https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 16/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate 48. Baranchuk A, Kang J. Pseudo-atrial flutter: Parkinson tremor. Cardiol J 2009; 16:373. 49. Chakravarthy M, Mattur K, Raghavan R, et al. Artifactual 'atrial flutter' caused by a continuous passive motion device after total knee replacement. Anaesth Intensive Care 2009; 37:1038. 50. Hoffmayer KS, Goldschlager N. Pseudoatrial flutter. J Electrocardiol 2008; 41:201. Topic 1061 Version 26.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 17/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate GRAPHICS Reentrant circuit of typical atrial flutter within the right atrium Schematic representation of reentrant circuit (red arrow) of typical (type 1) atrial flutter. The reentrant impulse rotates in a counterclockwise direction around the tricuspid annulus. The crista terminalis (CT) and eustacian ridge (ER) serve as lines of block, preventing the impulse from short-circuiting the annulus. Ablation is performed in the isthmus between the IVC and TA, which is an obligatory part of the circuit. SVC: superior vena cava; CS: coronary sinus; IVC: inferior vena cava; FO: foramen ovale Graphic 52904 Version 5.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 18/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate 12-lead electrocardiogram showing atrial flutter in preexcitation syndrome Atrial flutter is generated within the right atrium and the atrial impulses in this case are conducted to the ventricle by an accessory pathway. There is 1:1 conduction with a ventricular rate of 300 beats/min. The QRS complexes are widened or aberrant and have a bundle branch block morphology and a left axis deviation, suggesting the presence of an atriofascicular (Mahaim) accessory pathway. Courtesy of Morton Arnsdorf, MD. Graphic 78602 Version 4.0 Normal ECG https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 19/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Normal electrocardiogram showing normal sinus rhythm at a rate of 75 beats/minute, a PR interval of 0.14 seconds, a QRS interval of 0.10 seconds, and a QRS axis of approximately 75 . Courtesy of Ary Goldberger, MD. Graphic 76183 Version 4.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 20/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Revised (2018) Vaughan Williams classification of antiarrhythmic drugs abridged table Class 0 (HCN channel blockers) Ivabradine Class I (voltage-gated Na+ channel blockers) Class Ia (intermediate dissociation): Quinidine, ajmaline, disopyramide, procainamide Class Ib (rapid dissociation): Lidocaine, mexilitine Class Ic (slow dissociation): Propafenone, flecainide Class Id (late current): Ranolazine Class II (autonomic inhibitors and activators) Class IIa (beta blockers): Nonselective: carvedilol, propranolol, nadolol Selective: atenolol, bisoprolol, betaxolol, celiprolol, esmolol, metoprolol Class IIb (nonselective beta agonists): Isoproterenol Class IIc (muscarinic M2 receptor inhibitors): Atropine, anisodamine, hyoscine, scopolamine Class IId (muscarinic M2 receptor activators): Carbachol, pilocarpine, methacholine, digoxin Class IIe (adenosine A1 receptor activators): Adenosine Class III (K+ channel blockers and openers) Class IIIa (voltage dependent K+ channel blockers): Ambasilide, amiodarone, dronedarone, dofetilide, ibutilide, sotalol, vernakalant Class IIIb (metabolically dependent K+ channel openers): https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 21/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Nicorandil, pinacidil Class IV (Ca++ handling modulators) Class IVa (surface membrane Ca++ channel blockers): Bepridil, diltiazem, verapamil Class IVb (intracellular Ca++ channel blockers): Flecainide, propafenone Class V (mechanosensitive channel blockers): No approved medications Class VI (gap junction channel blockers) No approved medications Class VII (upstream target modulators) Angiotensin converting enzyme inhibitors Angiotensin receptor blockers Omega-3 fatty acids Statins HCN: hyperpolarization-activated cyclic nucleotide-gated; Na: sodium; K: potassium; Ca: calcium. Graphic 120433 Version 3.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 22/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Typical atrial flutter Electrocardiogram in type I counterclockwise typical atrial flutter. The biphasic flutter (F) waves are prominently negative (lead II) in counterclockwise typical flutter. The patient is on a beta-blocker which explains the predominant 4:1 conduction pattern. Graphic 74395 Version 4.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 23/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Reverse typical atrial flutter Electrocardiogram in type I clockwise typical atrial flutter. The flutter waves are positive in the inferior leads (II, III, aVF), with a more sinusoidal appearance and a broad negative F wave in V1. Graphic 81563 Version 3.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 24/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Electrocardiogram in lower loop reentry flutter Arrows point to flutter waves, which are positive in V1 and subtle but negative in the inferior leads. Graphic 106118 Version 1.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 25/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Electrocardiogram from a patient with an atriotomy-related right atrial flutter a mitral valve repair On electrophysiology study, the circuit was found to be wrapping around the atriotomy scar. The arrows poin flutter waves, which are negative in the inferior leads. Graphic 106119 Version 1.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 26/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Electrocardiogram of an atypical left atrial flutter occurring through a scar on t anterior septum in a patient with a prior atrial fibrillation ablation The arrows show the flutters waves, which are positive in V1. Graphic 106120 Version 1.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 27/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Electrocardiogram of an atypical roof dependent left atrial flutter after an atria fibrillation ablation The arrows show positive flutter waves in V1 indicative of a left atrial focus. Flutter waves are isoelectric in th leads. Graphic 106121 Version 2.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 28/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Electrocardiogram of a patient with clockwise mitral annular flutter The arrows show the flutter waves, which are low amplitude and negative in the inferior leads. They are posit 3, but become negative and then positive in V4-6. Graphic 106122 Version 1.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 29/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Atrial flutter at a rate of 250 beats/minute with 2:1 AV conduction in the presence of left bundle branch block Although every other flutter wave can be seen at the end of the T wave in the first part of the tracing (arrows), a sinus mechanism cannot be excluded. The flutter waves become clearly apparent after carotid sinus massage is applied to slow conduction through the AV node, thereby increasing the degree of AV block. AV: atrioventricular Courtesy of Morton Arnsdorf, MD. Graphic 76876 Version 3.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 30/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Atrial flutter RA recording Atrial flutter which is inapparent in lead I (upper panel); suggested by prominent negativity in lead II (arrows, middle panel), which could also represent biphasic T waves; and documented by right atrial recording, which shows prominent negative deflections (arrows, lower panel). Courtesy of Morton Arnsdorf, MD. Graphic 54591 Version 2.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 31/32 7/5/23, 10:46 AM Electrocardiographic and electrophysiologic features of atrial flutter - UpToDate Contributor Disclosures Jordan M Prutkin, MD, MHS, FHRS No relevant financial relationship(s) with ineligible companies to disclose. Peter J Zimetbaum, MD Consultant/Advisory Boards: Abbott Medical [Lead extraction]. All of the relevant financial relationships listed have been mitigated. Ary L Goldberger, MD Other Financial Interest: Elsevier book royalties [Clinical electrocardiography]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/electrocardiographic-and-electrophysiologic-features-of-atrial-flutter/print 32/32

7/5/23, 10:46 AM General principles of asynchronous activation and preexcitation - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. General principles of asynchronous activation and preexcitation : Bradley P Knight, MD, FACC : Peter J Zimetbaum, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Aug 25, 2021. INTRODUCTION Normal electrical activation of the right and left ventricles during the cardiac cycle follows a precisely defined pattern. After an impulse emerges from the atrioventricular (AV) node, it traverses the His bundle, and propagates down the bundle branches and the fascicles of the bundle branches to the terminal Purkinje fibers and ultimately the ventricular myocardium. Conduction abnormalities result in asynchronous electrical activation causing asynchronous mechanical activation of the ventricles. This problem can be induced by one of two mechanisms: delayed activation of an area of the ventricles or early activation (preexcitation) of an area of the ventricles. This topic will present an overview of asynchronous activation and preexcitation. The clinical manifestations of abnormal activation or preexcitation are discussed in detail separately. (See "Right bundle branch block" and "Left bundle branch block" and "Left anterior fascicular block" and "Left posterior fascicular block" and "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway".) DELAYED ACTIVATION Delayed activation causes asynchronous activation and may be a result of anatomic abnormalities or of physiologic properties of the cardiac tissues. Activation delay may occur https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 1/18 7/5/23, 10:46 AM General principles of asynchronous activation and preexcitation - UpToDate between the ventricles or portions of the ventricles (interventricular delay), within the terminal Purkinje fibers and/or ventricular myocardium (intraventricular delay) or between layers of the heart (intramural delay) [1]. Clinically, conduction delay causing ventricular electrical dyssynchrony is manifest as an abnormal QRS complex on the electrocardiogram (ECG). Specific ECG patterns that are clinically distinguished include right bundle branch block (RBBB), left bundle branch block (LBBB), a prolonged QRS complex without specific features of LBBB or RBBB (usually called "intraventricular conduction delay" or IVCD), left anterior hemiblock, and left posterior hemiblock. While all of these conduction patterns are sometimes referred to collectively as forms of intraventricular conduction delay, the precise location of the conduction disturbance cannot be reliably determined from the surface ECG. In the case of RBBB and LBBB, it is probably more accurate to refer to these entities as forms of "interventricular conduction delay." Interventricular conduction delay Delayed or blocked conduction in the bundles or their fascicles results in asynchronous activation and repolarization of the right and left ventricles. This, in turn, gives rise to characteristic ECG patterns. The classic examples of interventricular conduction delay are RBBB and LBBB. Fascicular block is not strictly an interventricular conduction delay, but results from a conduction disturbance in the left anterior or posterior fascicle. It is important to recognize that a bundle branch pattern on an ECG can be due to conduction delay rather than complete block, because delay in the other bundle branch can cause equal delay to the ventricles resulting in apparent resolution of the bundle branch block pattern. (See "Right bundle branch block" and "Left bundle branch block".) Intraventricular and intramural conduction delay Intraventricular conduction delay is a delay within the myocardium itself. This occurs commonly in cardiomyopathies, resulting in regional differences in the time to peak systolic contraction. Intramural or transmural delay is a delay in activation between the endocardium and myocardium, also commonly noted in cardiomyopathies. Both intraventricular and intramural conduction delays occur together with interventricular left bundle branch block. The term parietal block has been used to describe conduction delays in the terminal Purkinje conduction system. This phenomenon may result in a QRS duration in ECG leads V1 to V3 that significantly exceeds the QRS duration in leads V4 to V6 (right ventricular parietal block) or vice versa (left ventricular parietal block). Right ventricular parietal block is seen in some patients with arrhythmogenic right ventricular cardiomyopathy. Genesis of ECG pattern Two factors, magnitude and duration, determine the ECG changes seen with a given type of block. https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 2/18 7/5/23, 10:46 AM General principles of asynchronous activation and preexcitation - UpToDate Magnitude The magnitude (or amplitude) of the extracellular signal generated by the wavefront of unopposed dipoles can be affected by a number of factors. Examples include: A gain of force as with ventricular enlargement A loss of force as with myocardial infarction A change in cancellation due to asynchrony that can increase or decrease unopposed dipoles With regard to cancellation, the term "activation" is used to describe those unopposed boundaries that result in an electrocardiographically recorded potential. Many other wavefronts exist, however, and "cancel" each other. Normal synchronous ventricular depolarization results in a predictable sequence of opposed and unopposed wavefronts that result in the normal ECG [2,3]. Asynchronous activation generally reduces the amount of signal cancellation, resulting in a larger extracellularly recorded electrogram. With left bundle block, for example, left ventricular activation is delayed, occurring later than activation of the right bundle. As a result, the left ventricular signal is not partially canceled by that from the right ventricle, leading to an increase in amplitude of the QRS complex. This is the reason that standard voltage criteria for ventricular enlargement are invalid in bundle branch blocks. Duration Asynchronous activation can also affect the duration of the recorded potential. The time of initiation of activation is unchanged in this setting, but termination is delayed due to slower conduction to the blocked ventricle. The net effect is increased duration of the P wave or QRS complex, depending upon the site of disease. PREEXCITATION Ventricular preexcitation can occur when there is a premature ventricular complex/contraction (PVC; also referred to a premature ventricular beats or premature ventricular depolarizations) or when ventricular pacing occurs before the expected timing of ventricular activation through the atrioventricular (AV) node. Ventricular pacing causes asynchronous activation due to preexcitation of either ventricle. Right ventricular pacing preexcites the right ventricle and causes a pattern that has some of the electrocardiographic (ECG) features of left bundle branch block (LBBB); left ventricular pacing preexcites the left ventricle and has some of the ECG features of a right bundle branch block. Preexciting the ventricles with pacing is used in patients with congestive heart failure and ventricular mechanical dyssynchrony caused by an LBBB to resynchronize the ventricles and improve mechanical synchrony. (See "Cardiac resynchronization therapy in heart failure: System implantation and programming".) https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 3/18 7/5/23, 10:46 AM General principles of asynchronous activation and preexcitation - UpToDate Preexciting the right ventricle with right ventricular pacing can be used to intentionally induce mechanical dyssynchrony. This has been used to reduce the outflow tract gradient in patients with hypertrophic cardiomyopathy and an outflow tract obstruction. (See "Hypertrophic cardiomyopathy: Management of patients with outflow tract obstruction", section on 'Therapies of limited benefit'.) However, the term "ventricular preexcitation" is usually used to refer to preexcitation of the ventricle caused by AV conduction over an accessory pathway. The preexcitation syndromes are conditions in which atrial activation of the ventricles occurs earlier than would be expected if atrioventricular conduction occurred normally through the AV node. General anatomic considerations A number of conducting pathways have been described ( table 1). These include: Accessory atrioventricular connections, often called Kent bundles in the older literature, which directly connect the atria and ventricles [4-6]. These connections are typically located at one of the atrioventricular valves. (See "Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome".) James fibers, which connect the atria with the low AV node (atrionodal accessory pathway) or the bundle of His (atriofascicular accessory pathway) [7]. (See "Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction", section on 'Lown-Ganong- Levine pattern'.) So-called Mahaim fibers of several types that arise from the atrium and insert into a bundle branch (atriofascicular), arise from the AV node and insert into a bundle branch (nodofascicular), arise from the AV node and insert into ventricular tissue (nodoventricular accessory pathways). An accessory pathway can also arise from the His-bundle or one of the bundle branches and insert into ventricular tissue (fasciculoventricular accessory pathway) [8-11]. Terminology based upon anatomic connections is gradually replacing the venerable eponyms and some attempt has been made at standardization [8]. The European Study Group for Preexcitation suggests that the term "connection" should be used to describe pathways that insert into ventricular myocardium while "tracts" should be applied to pathways that insert into specialized conduction tissue [5]. However, the terms are often used interchangeably and tract is increasingly replacing connection ( table 1) [12]. Atrioventricular accessory pathways (connections) Ninety-five percent of atrioventricular accessory pathways conduct rapidly and have the characteristics of INa (sodium) dependent https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 4/18 7/5/23, 10:46 AM General principles of asynchronous activation and preexcitation - UpToDate phase 0 action potentials that occur in normal "fast response" myocardium. (See "Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs".) Five percent show decremental conduction, the mechanism of which is uncertain. Possible explanations include geometric factors, partial inactivation of the sodium channel, or perhaps dependence on a calcium channel. The fast response pathways often conduct rapidly, have short refractory periods, and can conduct frequently. This poses a particular problem during rapid supraventricular tachycardias such as atrial flutter, which may conduct 1:1, and atrial fibrillation, which may produce ventricular flutter and fibrillation. In preexcitation syndromes in which the accessory pathway inserts eccentrically, the resultant ventricular depolarization represents a fusion between ventricular activation initiated by the fast response, rapidly conducting bypass pathway and that initiated by the slow response, slowly conducting atrioventricular node. This is the pattern characteristic of patients with the Wolff- Parkinson-White syndrome. The principles of this fusion are illustrated in the figure ( figure 1A-C). The PR interval is shortened due to the preexcitation The eccentric ventricular activation results in a slurred upstroke of the QRS or delta wave The QRS duration is increased due to the asynchronous activation between the preexcited and normally excited portions of the ventricular myocardium How the ECG can be used to identify the location of the accessory pathway is discussed elsewhere. (See "Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome".) James fibers (intranodal or atrionodal bypass tract) Lown-Ganong-Levine syndrome The Lown-Ganong-Levine syndrome is characterized by palpitations in patients with an ECG that shows a short PR interval and a normal QRS duration [13]. For many years, this disorder was thought to be due to tracts that connected the atrium with the low AV node or the His bundle (via James fibers) [7]. (See "Lown-Ganong-Levine syndrome and enhanced atrioventricular nodal conduction".) The current concept, however, is that the short PR interval with a normal QRS pattern results, in most cases, from enhanced or accelerated AV nodal conduction and less often from an accessory pathway [12,14-16]. A short PR interval appears to be more frequent in patients with concealed accessory pathways, but has also been associated with dual pathway physiology and AV nodal reentrant tachycardia [15]. However, only patients with symptomatic tachyarrhythmias https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 5/18 7/5/23, 10:46 AM General principles of asynchronous activation and preexcitation - UpToDate are studied electrophysiologically. As a result, it is uncertain whether all individuals with a short PR interval and normal QRS complex have enhanced AV nodal conduction or accessory pathways near the AV node. Reentrant SVT A case of incessant supraventricular tachycardia (SVT), which continued despite AV block, has been reported [17]. An atrial tachycardia, AV nodal reentrant tachycardia, and an orthodromic tachycardia using a concealed accessory AV pathway were excluded as causes. The earliest retrograde atrial activation was at the posterolateral tricuspid annulus, and the tachycardia was eliminated by ablation at this site. These observations strongly suggest a concealed atrionodal pathway as the cause. Role of Mahaim fibers Mahaim pathways arise from the atria, AV node, fascicle, or one of the bundle branches and insert into fascicle or ventricular tissue. The precise characteristics of Mahaim fibers have been debated [10]. It was presumed that certain of these pathways, in which the AV node was normally traversed, could explain the situation in which the PR interval was normal but the QRS was widened (presumably due to eccentric activation of the ventricles) [18]. Some patients also had a prolonged PR interval with eccentric ventricular activation. This could be explained by slowed AV nodal conduction and anomalous connections at the level of or below the AV node. However, surgical and catheter ablation studies suggest that electrophysiologic characteristics attributed to nodoventricular Mahaim fibers are due to atriofascicular accessory connections with decremental conduction [19-24]. One report, for example, suggests the presence of an atrioventricular connection in the tricuspid ring [21]. This connection has slow and rate- dependent conduction, blocks with adenosine, has intrinsic automaticity, and links to a rapidly conducting insulated pathway that generates a "His-like" potential. Despite these observations, some experts still believe that nodofascicular tracts exist and are functional [12]. An orthodromic AVRT with atrioventricular dissociation has been presented as evidence for a nodoventricular type of Mahaim fiber [25]. Fasciculoventricular pathways can be demonstrated in 1 to 2 percent of adults who show ventricular preexcitation and are referred for electrophysiologic investigation [11,26]. These pathways can be thought of as a loss of insulation around the His-Purkinje system resulting in a direct connection to the local ventricular myocardium causing ventricular preexcitation. These pathways do not participate in reentrant rhythms and must be recognized during an EP study, mostly so that ablation is not attempted unnecessarily. Enhanced AV nodal conduction with a short AH interval is common, but normal AH interval lengthening may occur during incremental atrial pacing [11,26]. The administration of https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 6/18 7/5/23, 10:46 AM General principles of asynchronous activation and preexcitation - UpToDate adenosine may help to reveal the relationship between the fasciculoventricular pathway and its connection to the AV node and the infranodal conduction system. With AV nodal connections, a high degree of AV block or even complete AV block may occur with preexcited conducted beats. Familial Mahaim syndrome has been reported and suggests possible genetic transmission in some patients [27]. Classification of arrhythmias associated with accessory pathways The accessory pathways have two effects, which facilitate the development of certain supraventricular tachyarrhythmias: they can provide a pathway for reentry; and they can produce preexcitation, which results in a wide complex tachycardia. The atrioventricular reentrant tachycardias (AVRT) can utilize both the AV node and an accessory pathway in the reentrant circuit. (See "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway".) Orthodromic AVRT, the most common form, uses a circuit consisting of antegrade conduction through the AV node and retrograde conduction through the accessory pathway. In the absence of preexisting or functional bundle branch block, this produces a narrow QRS tachycardia in which the P wave follows the QRS complex ( figure 2). The less common, or antidromic, form of AVRT conducts antegrade through the accessory pathway and retrograde through the AV node, producing a wide QRS complex with a delta wave and a P wave that follows the QRS complex. This would be a reentrant form of a "preexcited tachycardia" that uses the AV node (see below) ( figure 3). The permanent form of junctional reciprocating tachycardia (PJRT) is a clinical syndrome of a nearly incessant supraventricular tachycardia. It is typically seen in young patients who can present with a tachycardia-mediated cardiomyopathy. The term PJRT is often used interchangeably with a nearly incessant AVRT using a slowly conducting concealed accessory pathway [28]. However, some patients with an atrial tachycardia or atypical AV nodal reentry can also present with a nearly incessant SVT. (See "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway", section on 'Permanent junctional reciprocating tachycardia'.) As discussed above, the so-called James and Mahaim fibers may also be involved in reentrant arrhythmias. Preexcited tachycardias Preexcited tachycardias, such as the WPW syndrome, are wide complex tachycardias that conduct antegrade over the accessory pathway. They are induced by supraventricular tachycardias, including atrial fibrillation, atrial flutter, and the family of atrial https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 7/18 7/5/23, 10:46 AM General principles of asynchronous activation and preexcitation - UpToDate tachycardias including the antidromic form of AVRT. (See "Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome" and "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway".) SUMMARY Delayed activation causes asynchronous electrical and mechanical activation and may be a result of anatomic abnormalities or of physiologic properties of the cardiac tissues. Clinically, conduction delay causing asynchronous ventricular activation is usually manifest as an abnormal QRS complex on the electrocardiogram (ECG). Specific ECG patterns that are clinically distinguished include right bundle branch block (RBBB), left bundle branch block (LBBB), a prolonged QRS complex without specific features of LBBB or RBBB (usually called "intraventricular conduction delay" or IVCD), left anterior hemiblock, and left posterior hemiblock. (See 'Delayed activation' above.) Two factors, magnitude and duration, determine the ECG changes seen with a given type of block. Normal synchronous ventricular depolarization results in a predictable sequence of opposed and unopposed wavefronts that results in the normal ECG. Asynchronous activation generally reduces the amount of signal cancellation, resulting in a larger extracellularly recorded electrogram. The time of initiation of activation is unchanged in the setting of asynchronous activation, but termination is delayed due to slower conduction to the blocked ventricle. The net effect is an increased duration of the QRS complex. (See 'Genesis of ECG pattern' above.) Ventricular preexcitation can occur when there is a PVC or when ventricular pacing occurs before the expected timing of ventricular activation through the atrioventricular (AV) node. However, the term "ventricular preexcitation" is usually used to refer to preexcitation of the ventricle caused by AV conduction over an accessory pathway. The preexcitation syndromes are conditions in which atrial activation of the ventricles occurs earlier than would be expected if atrioventricular conduction occurred normally through the AV node. (See 'Preexcitation' above.) A number of conducting pathways have been described, including those connecting the atria with the ventricles, the atria with the AV node, the atria with the His-Purkinje system, and the AV node with the ventricles ( table 1). (See 'General anatomic considerations' above.) The accessory pathways have two effects which facilitate the development of certain supraventricular tachyarrhythmias: they can provide a pathway for reentry, either https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 8/18 7/5/23, 10:46 AM General principles of asynchronous activation and preexcitation - UpToDate orthodromically or antidromically; and they can produce preexcitation, which, during tachycardia and anterograde conduction over the pathway, either as part of the circuit or as a bystander, results in a wide QRS complex tachycardia. (See 'Classification of arrhythmias associated with accessory pathways' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Auricchio A, Fantoni C, Regoli F, et al. Characterization of left ventricular activation in patients with heart failure and left bundle-branch block. Circulation 2004; 109:1133. 2. Durrer D, van Dam RT, Freud GE, et al. Total excitation of the isolated human heart. Circulation 1970; 41:899. 3. Van Dam RT, Janse MJ. Activation of the Heart. In: Comprehensive Electrocardiology: Theory and Practice in Health and Disease, MacFarlane P, Veitch Lawrie TD (Eds), Pergamon Press, New York 1980. p.101. 4. Kent, AF . Researches on the structure and function of the mammalian heart. J Physiol 1893; 14:233. 5. Anderson RH, Becker AE, Brechenmacher C, et al. Ventricular preexcitation. A proposed nomenclature for its substrates. Eur J Cardiol 1975; 3:27. 6. Boineau JP, Moore EN. Evidence for propagation of activation across an accessory atrioventricular connection in types A and B pre-excitation. Circulation 1970; 41:375. 7. JAMES TN. Morphology of the human atrioventricular node, with remarks pertinent to its electrophysiology. Am Heart J 1961; 62:756. 8. MAHAIM I. Kent's fibers and the A-V paraspecific conduction through the upper connections of the bundle of His-Tawara. Am Heart J 1947; 33:651. 9. Lev M, Fox SM 3rd, Bharati S, et al. Mahaim and James fibers as a basis for a unique variety of ventricular preexcitation. Am J Cardiol 1975; 36:880. 10. Klein GJ, Guiraudon G, Guiraudon C, Yee R. The nodoventricular Mahaim pathway: an endangered concept? Circulation 1994; 90:636. 11. Sternick EB, Gerken LM, Vrandecic MO, Wellens HJ. Fasciculoventricular pathways: clinical and electrophysiologic characteristics of a variant of preexcitation. J Cardiovasc Electrophysiol 2003; 14:1057. 12. Josephson ME. Clinical Cardiac Electrophysiology: Techniques and Interpretations, 2d ed, Le a & Febiger, Philadelphia 1993. https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 9/18 7/5/23, 10:46 AM General principles of asynchronous activation and preexcitation - UpToDate 13. LOWN B, GANONG WF, LEVINE SA. The syndrome of short P-R interval, normal QRS complex and paroxysmal rapid heart action. Circulation 1952; 5:693. 14. Denes P, Wu D, Amat-y-Leon F, et al. The determinants of atrioventricular nodal re-entrance with premature atrial stimulation in patients with dual A-V nodal pathways. Circulation 1977; 56:253. 15. Benditt DG, Pritchett LC, Smith WM, et al. Characteristics of atrioventricular conduction and the spectrum of arrhythmias in lown-ganong-levine syndrome. Circulation 1978; 57:454. 16. Bauernfeind RA, Swiryn S, Strasberg B, et al. Analysis of anterograde and retrograde fast pathway properties in patients with dual atrioventricular nodal pathways: observations regarding the pathophysiology of the Lown-Ganong-Levine syndrome. Am J Cardiol 1982; 49:283. 17. Zivin A, Morady F. Incessant tachycardia using a concealed atrionodal bypass tract. J Cardiovasc Electrophysiol 1998; 9:191. 18. Wellens HJJ. The preexcitation syndrome. In: Electrical Stimulation of the Heart, Wellens HJJ (Ed), University Park Press, Baltimore 1971. p.97. 19. Gillette PC, Garson A Jr, Cooley DA, McNamara DG. Prolonged and decremental antegrade conduction properties in right anterior accessory connections: Wide QRS antidromic tachycardia of left bundle branch block pattern without Wolff-Parkinson-White configuration in sinus rhythm. Am Heart J 1982; 103:66. 20. Klein GJ, Guiraudon GM, Kerr CR, et al. "Nodoventricular" accessory pathway: evidence for a distinct accessory atrioventricular pathway with atrioventricular node-like properties. J Am Coll Cardiol 1988; 11:1035. 21. McClelland JH, Wang X, Beckman KJ, et al. Radiofrequency catheter ablation of right atriofascicular (Mahaim) accessory pathways guided by accessory pathway activation potentials. Circulation 1994; 89:2655. 22. Cappato R, Schl ter M, Mont L, Kuck KH. Anatomic, electrical, and mechanical factors affecting bipolar endocardial electrograms. Impact on catheter ablation of manifest left free-wall accessory pathways. Circulation 1994; 90:884. 23. Grogin HR, Lee RJ, Kwasman M, et al. Radiofrequency catheter ablation of atriofascicular and nodoventricular Mahaim tracts. Circulation 1994; 90:272. 24. Li HG, Klein GJ, Thakur RK, Yee R. Radiofrequency ablation of decremental accessory pathways mimicking "nodoventricular" conduction. Am J Cardiol 1994; 74:829. 25. Mantovan R, Verlato R, Corrado D, et al. Orthodromic tachycardia with atrioventricular dissociation: evidence for a nodoventricular (Mahaim) fiber. Pacing Clin Electrophysiol 2000; https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 10/18 7/5/23, 10:46 AM General principles of asynchronous activation and preexcitation - UpToDate 23:276. 26. Gallagher JJ, Smith WM, Kasell JH, et al. Role of Mahaim fibers in cardiac arrhythmias in man. Circulation 1981; 64:176. 27. Ott P, Marcus FI. Familial Mahaim syndrome. Ann Noninvasive Electrocardiol 2001; 6:272. 28. Shih HT, Miles WM, Klein LS, et al. Multiple accessory pathways in the permanent form of junctional reciprocating tachycardia. Am J Cardiol 1994; 73:361. Topic 898 Version 20.0 https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 11/18 7/5/23, 10:46 AM General principles of asynchronous activation and preexcitation - UpToDate GRAPHICS Terminology and anatomic connections of preexcitation pathways Old terminology Proposed or commonly used terminology Anatomic connections Kent bundle* Accessory AV connection or AV bypass tract Atrium to ventricle James fiber Atrionodal bypass tract Atrium to low AV node Atriofascicular bypass tract Atrium to bundle of His Mahaim fiber Atriofascicular bypass tract Atrium to bundle branch Nodofascicular bypass tract AV node to bundle branch Nodoventricular bypass tract AV node to ventricular tissue Fasciculoventricular bypass tract Bundle branch to ventricular tissue AV: atrioventricular. These bypass tracts result in delta waves and the Wolff-Parkinson-White syndrome. These bypass tracts result in the Lown-Ganong-Levine syndrome and enhanced AV nodal conduction. Graphic 53343 Version 6.0 https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 12/18 7/5/23, 10:46 AM General principles of asynchronous activation and preexcitation - UpToDate AV conduction with a concealed accessory pathway Schematic representation of AV conduction. The normal pacemaker is in the sinoatrial (SA) node at the junction of the superior vena cava and the right atrium. The SA node activates the right and left atria (shown in green). In the absence of an accessory pathway (AP) or, as in this case, if the AP is concealed, ventricular activation results from the impulse traversing the AV node, the specialized infranodal conducting system (His bundle, bundle branches, and fascicular branches, shown in red), thereby activating the ventricular myocardium (shown in yellow). The ECG shows a normal PR interval and a narrow QRS complex. The inset on the right shows the timing of SA node (SAN), right (RA) and left atrial (LA), His bundle (H), and the beginning of normal ventricular activation (V ). All of ventricular activation (shown in yellow) is due to normal AV nodal and infranodal conduction. N AV: atrioventricular; ECG: electrocardiogram. Graphic 73740 Version 5.0 https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 13/18 7/5/23, 10:46 AM General principles of asynchronous activation and preexcitation - UpToDate AV conduction through an overt accessory pathway Compared with normal conduction in the preceding diagram, the accessory pathway (AP) is now overt. As a result, ventricular activation results from both early activation (pre-excitation) of the free wall of the left ventricle (shown in blue) and from normal activation (shown in yellow). The degree of unopposed pre-excitation depends upon the time required to conduct through the right and left atria, the AP, and the ventricular myocardium as compared with conduction through the normal pathways. The inset on the right shows the ECG timing of these events. The net effect is a QRS complex that is a fusion of ventricular pre-excitation (blue) and normal excitation (yellow). Early activation throughout the AP (V ) P occurs at about the same time as His bundle depolarization (H). This leads to a shorter PR interval, a small delta wave (arrow), and some prolongation of the QRS duration. AV: atrioventricular. Graphic 53773 Version 6.0 https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 14/18 7/5/23, 10:46 AM General principles of asynchronous activation and preexcitation - UpToDate Conduction through an accessory pathway with AV nodal delay Compared with conduction through an AP with normal AV node conduction, delayed conduction through the AV node allows more of the ventricular myocardium to be activated by pre-excitation (shown in blue). The inset on the right shows the ECG timing of these events. The atrial to His interval is increased due to the AV nodal delay (RA to H); His activation is so delayed that it follows activation caused by the AP (V ). The PR interval is short due to the pre- excitation, the delta wave (arrow) is more pronounced due to the greater and unopposed early forces (blue), and the QRS duration is prolonged due to the later than normal ventricular activation caused by the AV nodal delay (yellow). P AV: atrioventricular; ECG: electrocardiogram. Graphic 62454 Version 6.0 https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 15/18 7/5/23, 10:46 AM General principles of asynchronous activation and preexcitation - UpToDate Orthodromic atrioventricular reentrant tachycardia (AVRT) in the setting of an accessory AV pathway The rhythm strip shows a sinus (S) beat that has a short PR interval and a wide QRS complex as a result of a delta wave (d). Panel A shows an atrial premature beat (APB,*) that is blocked in the accessory pathway (AP), which has a long refractory period but is conducted antegradely through the atrioventricular node (N) and the His-Purkinje system, resulting in a normal PR interval and a narrow and normal QRS complex, as seen on the rhythm strip. After normal myocardial activation, the impulse is conducted retrogradely along the AP, activating the atrium in a retrograde fashion (panel B), which results in a negative P wave. If this activation sequence repeats itself (panel C), an orthodromic atrioventricular reentrant (or reciprocating) tachycardia (AVRT) is established. Graphic 71302 Version 7.0 https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 16/18 7/5/23, 10:46 AM General principles of asynchronous activation and preexcitation - UpToDate Antidromic atrioventricular reentrant tachycardia (AVRT) in the setting of an accessory AV pathway The rhythm strip shows a sinus (S) beat that has a short PR interval and a wide QRS complex as a result of a delta wave (d). Panel A shows the activation sequence with an atrial premature beat (APB,*). The impulse reaches the atrioventricular node (N) before it has repolarized and hence is blocked in this structure. However, the accessory pathway (AP), which has a short refractory period, is able to conduct the impulse antegradely, resulting in an APB with a widened QRS morphology similar to the sinus beat. As seen in panel B, following myocardial activation, the impulse is conducted retrogradely along the His-Purkinje system and AV node, resulting in retrograde atrial activation, seen on the rhythm strip as an inverted P wave. If this activation sequence repeats itself (panel C), a wide QRS complex antidromic atrioventricular reentrant (or reciprocating) tachycardia (AVRT) is established. Graphic 50433 Version 4.0 https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 17/18 7/5/23, 10:46 AM General principles of asynchronous activation and preexcitation - UpToDate Contributor Disclosures Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Peter J Zimetbaum, MD Consultant/Advisory Boards: Abbott Medical [Lead extraction]. All of the relevant financial relationships listed have been mitigated. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/general-principles-of-asynchronous-activation-and-preexcitation/print 18/18

7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Invasive diagnostic cardiac electrophysiology studies : Munther K Homoud, MD : Bradley P Knight, MD, FACC : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Aug 19, 2022. INTRODUCTION Invasive cardiac electrophysiology (EP) is a collection of clinical techniques for the investigation and treatment of cardiac rhythm disorders. These techniques permit a detailed analysis of the mechanism(s) underlying the cardiac arrhythmia, precise location of the site of origin, and, when applicable, definitive treatment via catheter-based ablation techniques. An overview of invasive cardiac EP studies will be presented here. Issues related to its use in the evaluation of specific arrhythmias are discussed separately. (See "Overview of catheter ablation of cardiac arrhythmias" and "Catheter ablation for the treatment of atrial fibrillation: Technical considerations for non-electrophysiologists" and "Atrial fibrillation: Catheter ablation".) INDICATIONS AND CONTRAINDICATIONS Indications Broadly speaking, the indications for invasive EP studies can be broken down to two categories: diagnosis and risk stratification [1]. EP studies suffer from limited sensitivity and specificity. The significance of the findings is often determined by the underlying cardiac disease and the patient's clinical presentation. Diagnosis EP studies can be helpful to diagnose the etiology of syncope, sudden cardiac death, wide complex tachyarrhythmia, and atrioventricular conduction delay or disease. Syncope In many cases of syncope, an EP study can serve as a useful diagnostic test. Specific scenarios are described below: https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 1/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate Syncope and ischemic or other structural heart disease The concurrent diagnosis of cardiac disease can be based on history, physical examination, electrocardiography, and/or echocardiography. The aim of an EP study for such patients would be to determine if sustained ventricular arrhythmias (or atrial tachyarrhythmias in the case of adults with congenital heart disease such as transposition of the great arteries with atrial switch) or bradyarrhythmias may be the underlying cause of heart disease [2-4]. If a patient with syncope undergoes an EP study and is induced into a clinically relevant and hemodynamically significant sustained ventricular tachycardia (VT) or ventricular fibrillation (VF), the implantation of an implantable cardioverter-defibrillator (ICD) is indicated. Syncope with suspected sinus node dysfunction Often, this is suspected based on inappropriate sinus bradycardia. The detection of a prolonged corrected sinus node recovery time may predict future recurrence of syncope [3]. Syncope in patients with bifascicular block This includes patients who have syncope with left bundle branch block, or right bundle branch block with a fascicular block when noninvasive evaluation has been unrevealing [3]. The causes of syncope in patients with bifascicular block can be multifactorial. An EP study can help delineate the cause, define the prognosis, and determine the therapy [5]. The induction of infra-Hisian block in patients with bifascicular block can predict future adverse cardiovascular events [6]. Syncope in patients who are employed in high-risk occupations (eg, airline pilots, school bus drivers, police officers) An EP study can be helpful when all other noninvasive diagnostic tools have failed to arrive at a cause for syncope. Syncope immediately following palpitations [3]. Unexplained syncope [7]. Other diagnostic indications Sudden cardiac death (SCD) with no established cause In this case, an EP study is considered a step in the diagnostic cascade recommended to try to establish a diagnosis [2,8]. Patients with wide complex tachyarrhythmias In patients in whom a diagnosis cannot be established by noninvasive means or who are suspected of harboring a life- threatening arrhythmia, an EP study can define the mechanism of the arrhythmia to help determine therapy and prognosis [9]. https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 2/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate Abnormal atrioventricular (AV) conduction An EP study in such patients can help determine the site of block when clinical and electrocardiographic information fail to help localize the site of block. Rare cases of AV conduction abnormalities may be due to concealed junctional beats that can only be demonstrated through an invasive EP study [4,10]. Patients with documented tachyarrhythmias who are undergoing catheter ablation These patients will automatically undergo a diagnostic EP study, usually directed at the putative tachyarrhythmia, before catheter ablation is performed. The purpose of this EP study is to define the diagnosis and localize the pathway responsible for the arrhythmia. In the pediatric population, the role of programmed electrical stimulation is limited and is not expected to confer value beyond what has already been collected noninvasively. While a diagnostic EP study is employed in conjunction with a preplanned catheter ablation for a documented arrhythmia, it is rarely used to risk stratify patients with nonsustained polymorphic ventricular arrhythmias or to define endocardial scar [11]. Risk stratification EP studies may be helpful to risk stratify in the following conditions. Selected patients with ischemic cardiomyopathy and nonsustained VT Among patients with an ischemic cardiomyopathy due to a prior myocardial infarction or revascularization and who have left ventricular ejection fraction (LVEF) <40 percent with nonsustained VT on ambulatory cardiac rhythm monitoring, the induction of sustained VT or VF constitutes a class I indication for the implantation of an ICD [12]. The MUSTT trial enrolled patients with recent myocardial infarction or revascularization, LVEF <40 percent, and asymptomatic nonsustained VT [13]. All patients underwent an EP study. Patients in whom sustained ventricular tachyarrhythmias were induced by programmed stimulation were randomly assigned to receive either antiarrhythmic therapy, including drugs and implantable defibrillators, as indicated by the results of EP testing, or no antiarrhythmic therapy. The patients who were assigned an ICD had a lower risk of sudden cardiac death. Asymptomatic second-degree AV block, if the site of block cannot be determined reliably AV conduction abnormalities below the level of the AV node may progress to complete AV block with catastrophic consequences [14]. The site of block in patients with Mobitz type II second degree AV block is infranodal (intra- or infra-Hisian), and this constitutes an indication for pacing even if the patient is asymptomatic. An EP study is indicated if the site of block cannot be determined reliably in an asymptomatic individual with second degree AV block. If the site is infranodal, pacing is indicated [4]. https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 3/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate Asymptomatic young (8 to 21 years) patients with electrocardiographic evidence of preexcitation Such patients may be at high risk of SCD due to atrial fibrillation progressing to VF. These patients are advised to undergo exercise stress testing. The clear and sudden loss of preexcitation with exercise stress testing predicts a favorable prognosis. If clear loss of preexcitation is not seen or the data are uninterpretable, invasive risk stratification via transesophageal pacing or EP studies is recommended [15]. Programmed electrical stimulation for risk stratification of a manifest accessory bypass tract is a class I indication in a symptomatic patient and a class IIa indication in an asymptomatic patient if the noninvasive measures described cannot be met [16]. (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis", section on 'Risk stratification of asymptomatic patients with WPW pattern'.) Cardiac sarcoidosis In patients with cardiac sarcoidosis and an LVEF >35 percent despite optimal medical therapy and immunosuppression, an EP study can be helpful. In such patients, programmed electrical stimulation can be considered to help risk stratify sudden cardiac death [12,17]. Arrhythmogenic right ventricular cardiomyopathy In patients who are asymptomatic, programmed electrical stimulation is occasionally used to help risk stratify them [12,18]. (See "Arrhythmogenic right ventricular cardiomyopathy: Diagnostic evaluation and diagnosis", section on 'Electrophysiologic testing and electroanatomic mapping'.) Tetralogy of Fallot EP studies are used for risk stratification of adults with tetralogy of Fallot with high-risk factors for sudden cardiac death, such as left ventricular systolic and diastolic dysfunction, QRS 180 milliseconds, extensive right ventricular scarring, pulmonary regurgitation or stenosis, and nonsustained VT (class IIa indication). EP studies should not be used as a screening test on patients with tetralogy of Fallot who do not have high-risk factors or in patients with repaired tetralogy of Fallot [2]. Adult patients with congenital heart disease of moderate to severe complexity who display high-risk features such as syncope and ventricular arrhythmias should undergo invasive EP studies to determine if they are at risk for sudden cardiac death and may benefit from an ICD (class IIa indication) [12]. Brugada syndrome The role of EP studies in Brugada syndrome is controversial. Patients with Brugada syndrome who have had a history of syncope or have survived sudden cardiac death are more likely to be inducible. However, the role of EP studies in predicting future events is controversial [8]. The implantation of an ICD may be considered in a patient with Brugada syndrome who is induced into VF. One study analyzed the role of clinical factors and programmed ventricular stimulation in determining the risk of https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 4/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate arrhythmic events in patients with Brugada syndrome. The investigators concluded that clinical factors such as syncope and spontaneous type 1 Brugada pattern and the induction of ventricular arrhythmias by programmed ventricular stimulation all portend a higher risk of events. The value of programmed ventricular stimulation was greater if ventricular arrhythmias were induced with single or double extrastimuli. A negative study did not predict arrhythmia-free survival [19]. Professional society guidelines allow the use of invasive programmed electrical stimulation with one to two premature ventricular extrastimuli for risk stratification of asymptomatic patients with class I Brugada pattern (class IIb) [12]. (See "Brugada syndrome or pattern: Management and approach to screening of relatives".) Contraindications Absolute contraindications to EP study include [20]: Unstable angina Bacteremia or septicemia Acute decompensated congestive heart failure not caused by the arrhythmia Major bleeding diathesis Acute lower extremity venous thrombosis if femoral vein cannulation is desired PREPROCEDURAL EVALUATION In all patients undergoing invasive EP study, the preprocedure evaluation includes a thorough history and physical examination and review of the available electrocardiograms (ECGs), both at baseline and, if available, during the tachycardia. The history should focus on the appropriateness of invasive EP study for the particular patient and screen for any potential contraindications to the procedure. Additional evaluation prior to the procedure in select patients may include: Event monitoring for up to four weeks in an effort to document the tachycardia. Event monitoring for longer periods is typically more useful than short-term (24 to 48 hours) Holter monitoring in documenting the tachycardia. (See "Ambulatory ECG monitoring".) Transthoracic echocardiography to assess for structural heart disease. Cardiac magnetic resonance imaging may also be considered for special situations (eg, suspicion of arrhythmogenic right ventricular cardiomyopathy, hypertrophic cardiomyopathy, etc). Exercise testing, if there is a history of exercise-induced arrhythmia. https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 5/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate Cardiac catheterization and coronary angiography, if indicated by the patient's clinical presentation and symptoms suggesting coronary heart disease. If the clinical presentation is prehospital cardiac arrest or ventricular tachycardia causing hemodynamic collapse, coronary angiography and an assessment of ventricular function (eg, echocardiography, ventriculography) should usually be obtained prior to invasive EP studies with programmed cardiac stimulation. In most patients, all atrioventricular (AV) nodal blocking agents, including beta blockers, calcium blockers, digoxin, and class I and III antiarrhythmic drugs ( table 1) are discontinued several days prior to the scheduled procedure. In general, beta blockers should be gradually tapered and discontinued, while other agents can be discontinued without tapering. Because radiation exposure is a necessary component of an invasive EP study, it is reasonable to obtain a pregnancy test on all women of childbearing capacity on the morning of the procedure. (See 'Fluoroscopy' below.) PREPARATION AND MONITORING Invasive EP studies are typically performed in a dedicated EP laboratory [20]. In addition to the electrophysiologist, several other staff members are required. Intravenous conscious sedation is typically used to ensure patient comfort, although in some situations (ie, prolonged catheter ablation procedures) general anesthesia can be used. Standard electrocardiogram (ECG) leads are applied to the patient, as well as "hands-off" defibrillation pads. Arterial pressure may be monitored invasively or noninvasively, depending upon the complexity of the procedure. Oxygen saturation, as well as in some cases end-tidal CO , is monitored. 2 The following are considered part of the routine preparation and monitoring involved in invasive EP studies: Patients should be fasting after midnight on the day of the procedure, except for oral medications with sips of water. Patients should hold their normal cardiovascular medications, particularly medications which affect atrioventricular (AV) node conduction (ie, beta blockers, dihydropyridine calcium channel blockers, and digoxin) and antiarrhythmic medications ( table 1). (See 'Preprocedural evaluation' above.) Standard cardiorespiratory monitoring should include blood pressure (noninvasively or via arterial monitoring), pulse, oxygen saturation, and cardiac telemetry. https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 6/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate Defibrillation pads should be placed on the patient prior to beginning the procedure ( figure 1). Intravenous access is required for administration of sedation and for management of any rhythm-related complications (ie, ventricular fibrillation, sinus bradycardia, etc). Supplemental oxygen, a suction device, and intubation equipment should be immediately available for management of respiratory complications (though supplemental oxygen should be removed prior to delivery of any electrical shocks). (See "Cardioversion for specific arrhythmias", section on 'Supplemental oxygen'.) A code cart with medications used in advanced cardiac life support should be immediately available in the event of life-threatening arrhythmias that do not respond to defibrillation. (See "Advanced cardiac life support (ACLS) in adults".) While many cardiologists are trained in the administration of procedural sedation, sedation may also be administered by an anesthesiologist who can immediately assist in the management of respiratory complications should any develop. (See "Procedural sedation in adults: General considerations, preparation, monitoring, and mitigating complications", section on 'Anticipating and mitigating Complications'.) FLUOROSCOPY Fluoroscopy is required for anatomic orientation throughout the EP study, including vascular access, catheter positioning, etc. Operators should make every effort to minimize radiation exposure to the patient as well as the procedural staff. (See "Radiation-related risks of imaging".) VASCULAR ACCESS AND ELECTRODE CATHETER PLACEMENT In nearly all EP studies, venous vascular access is required, often from multiple sites. The Seldinger technique is employed to place multiple venous accesses. The femoral approach is most common, but the subclavian, internal jugular, or brachial approach may be used, most often for placement of a catheter in the coronary sinus. Multipolar electrode catheters are positioned in the heart. Typical positions include: The right atrium (high right atrium [HRA]) Anterior tricuspid valve annulus to record the bundle of His The right ventricle (right ventricular apex [RVA]) https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 7/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate A catheter may be placed in the coronary sinus to record left atrial activation, particularly in studies of patients with supraventricular tachycardia (SVT). When mapping and ablation are performed, electrodes may be placed in the left heart. Left heart access may be obtained via either a transseptal or retrograde aortic approach. Intracardiac recordings and programmed electrical stimulation (PES) are performed via the electrode catheters. Typically, for evaluation of ventricular arrhythmias requiring LV mapping, a retrograde aortic approach is employed, while the transseptal approach is preferred for left-sided SVTs. Either approach may be used for patients with a suspected left-sided accessory pathway. When catheters are placed into left-sided cardiac chambers, systemic anticoagulation is required to prevent thromboembolic complications. Typically intravenous heparin is initiated at the time of the procedure and continued until the catheters are removed from the left-sided cardiac chambers. At the conclusion of the procedure, the access sheaths are pulled and hemostasis is achieved using manual or mechanical pressure or a vascular closure device. The patient is generally kept on bed rest for four to six more hours to ensure adequate hemostasis has been achieved. (See "Complications of diagnostic cardiac catheterization", section on 'Hemostasis at the access site' and "Percutaneous arterial access techniques for diagnostic or interventional procedures", section on 'Hemostasis at the access site'.) ELECTROCARDIOGRAPHIC AND ELECTROPHYSIOLOGIC RECORDINGS Baseline recordings Baseline recordings obtained during a typical invasive EP study include several surface electrocardiograms (ECGs) to time events from the body's surface and several intracardiac electrograms, all of which are recorded simultaneously. The intracardiac electrograms are generally displayed in the order of normal cardiac activation ( waveform 1). The first intracardiac tracing is a recording from the high right atrium (HRA) close to the sinus node. Pacing at this position allows evaluation of sinoatrial node function and atrioventricular (AV) conduction; the addition of premature atrial complex (also referred to a premature atrial beat, premature supraventricular complex, or premature supraventricular beat) or burst atrial pacing may result in the induction of supraventricular tachyarrhythmias. Sinus node function is determined by measuring the sinus node recovery time (SNRT), a reflection of the node's automaticity, and the sinoatrial conduction time (SACT), a reflection of peri-sinus node conduction properties. Great care must be exercised in interpreting the findings from EP studies due to limited sensitivity and specificity. https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 8/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate The next intracardiac tracing is the His bundle recording (HBE), obtained from a catheter positioned at the bundle of His (in the area of the tricuspid annulus). One to three recordings may be obtained from the coronary sinus (CS) in patients with supraventricular tachyarrhythmias or preexcitation. Since the coronary sinus runs in the mitral annulus, these recordings reflect left atrial activation. The next is a recording from a right ventricular apex (RVA) electrode catheter. The stability and reproducibility of the right ventricle apex position (during a given study as well as from one study to the next) makes it a useful site for adding premature stimuli during programmed ventricular stimulation. (See 'Programmed electrical stimulation' below.) Depending upon the particular study, other required recordings may include right bundle branch recording, left ventricular recording, transseptal left-atrial recording, and atrial and ventricular mapping catheter tracings for EP mapping and ablation. AH interval The AH interval is measured on the His bundle electrogram and represents the interval from the earliest rapid deflection of the atrial recording (activation of the lowest part of the right atrium) to the earliest onset of the His bundle deflection. This interval approximates AV nodal conduction. More precisely, however, it is the sum of conduction through the low right atrial inputs into the atrioventricular node, the atrioventricular node proper, and the proximal His bundle. The AH interval has a wide range in normal subjects (50 to 120 milliseconds) and is markedly influenced by the autonomic nervous system [21,22]. Short AH intervals may be seen in the following circumstances [23]: Increased sympathetic tone Enhanced AV nodal conduction, which may be due in some patients to steroid use or pregnancy Preferential left-atrial input into the atrioventricular node Long AH intervals are most commonly due to: Impaired or delayed AV node conduction from drugs such as digoxin, beta blockers, calcium channel blockers, and antiarrhythmic drugs, particularly amiodarone Increase parasympathetic (vagal) tone Intrinsic disease of the atrioventricular node https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 9/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate Artifactually prolonged AH intervals may result from an improperly positioned catheter and the incorrect identification of a right bundle branch potential as a His bundle potential. This situation needs to be distinguished from true AH prolongation. His bundle electrogram duration The His bundle electrogram duration reflects conduction through the short length of compact His bundle that penetrates the fibrous septum. This interval is normally short (15 to 25 milliseconds), with fractionation and prolongation or even splitting of the His bundle potential, seen with disturbances of His bundle conduction ( waveform 2) [24,25]. HV interval The HV interval is measured from the earliest onset of the His bundle deflection to the earliest registered surface or intracardiac ventricular activation anywhere. This measurement reflects conduction time through the distal His-Purkinje system. Unlike the AV node, the His-Purkinje system is far less influenced by the autonomic nervous system, and the range in normal subjects is narrow (35 to 55 milliseconds) [26]. A prolonged HV interval is consistent with diseased distal conduction in all fascicles [27]. In patients with symptoms suggesting a bradyarrhythmia, a prolonged HV interval (>55 milliseconds) warrants pacemaker therapy. In asymptomatic patients with an HV interval >100 milliseconds, a pacemaker is also indicated [28,29]. In asymptomatic patients with an HV interval >70 milliseconds, pacemakers are more controversial [27,28,30]. A validated short HV interval suggests one of two situations: Ventricular preexcitation via an AV bypass tract Ventricular origin for the beats, such as ventricular premature beats (VPBs) or an accelerated idioventricular rhythm that is isorhythmic with the sinus rhythm A spurious explanation for a short HV interval is the inadvertent recording of a right bundle branch potential rather than a His potential. VA conduction The assessment of ventriculoatrial (VA) conduction is also important in the EP study, particularly for patients with a supraventricular tachycardia (SVT). This is performed by ventricular extrastimulus and incremental ventricular pacing. Absence of VA conduction makes certain SVTs less likely (ie, atrioventricular reciprocating tachycardia and atrioventricular nodal reentrant tachycardia) and suggests an atrial tachycardia (AT), since AT is independent of retrograde VA conduction. Sinoatrial conduction time The usual method of calculating sinoatrial conduction time (SACT), which is a measure of sinus node function, is an indirect measure. This approach involves the placement of a catheter in the superior aspect of the right atrium approximating the main https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 10/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate intrinsic pacemaker site of the SA node. Progressively premature atrial extrastimuli are introduced by way of that catheter after every 8th to 10th beat of either a stable sinus rhythm (Strauss method) [31] or atrial pacing (Narula method) [32]. Due to the limitations of indirect methods in assessing the SACT, techniques for direct recording of the sinus electrogram (EGM) have been developed [33-38]. Endocardial recordings demonstrate diastolic phase 4 activity followed by a slow upstroke culminating in a rapid atrial EGM. The directly measured SACT was defined as the interval between the local EGM and the rapid atrial deflection. Normal SACT times generally range from 40 to 150 milliseconds, depending upon the laboratory [39,40]. Studies have shown a good correlation between indirect and direct methods of measuring SACT [35,37,38,41]. However, SACT is a relatively insensitive test for SA node dysfunction. Sinus node recovery time The sinus node recovery time (SNRT) is performed by placing a catheter near the SA node and pacing (overdrive suppression) for at least 30 seconds at a fixed cycle length starting slightly faster than the intrinsic sinus rate. This is repeated at progressively shorter cycle lengths. Pacing rates up to 200 beats per minute may be employed for improved sensitivity [42]. It is important to wait at least one minute between pacing sequences to allow full recovery of the SN. Confirmation that the escape beat is sinus by examining P-wave morphology and atrial activation sequence is essential to exclude a shift in pacemaker site [43]. The maximum SNRT is the longest pause from the last pacing stimulus to the first spontaneously occurring sinus beat at any paced cycle length. As the sinus cycle length (SCL) affects the SNRT, it is often normalized or corrected: The SNRT is normalized by dividing this value by the SCL. The corrected sinus node recovery time (CSNRT) is determined by subtracting the SCL from the SNRT ( waveform 3). A total recovery time (TRT) can also be calculated, which is the time required to return to the basal sinus rate. Normal values have generally been estimated as follows [43]: SNRT/SCL <150 percent CSNRT <550 milliseconds TRT less than five seconds https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 11/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate There are several limitations to the use of overdrive suppression in determining SN function, which include changes in autonomic tone due to the effects of pacing, changes in P-wave morphology or atrial activation suggesting a pacemaker shift, sinoatrial entrance block, and secondary pauses. PROGRAMMED ELECTRICAL STIMULATION After baseline measurements are recorded, pacing is performed via the intracardiac electrode catheters. Burst pacing at various fixed cycle lengths as well as programmed electrical stimulation (PES) is administered. With PES, a number of stimuli at a fixed cycle length are delivered (eg, eight beats at a rate of 100 beats per minute), followed by a premature beat. The coupling interval of the premature beat is progressively shortened until the refractory period of the tissue being paced is reached. Multiple premature stimuli can be introduced. The technique of PES is used to assess the atrioventricular (AV) conducting system and to induce supraventricular and ventricular arrhythmias. Premature beats can be introduced during a tachyarrhythmia to probe the mechanism of the tachycardia. Programmed atrial stimulation is usually from the high right atrium, although a second atrial site such as coronary sinus pacing is also employed in certain situations ( waveform 4A-B) [44,45]. One or sometimes two atrial extrastimuli with progressively shorter coupling intervals are delivered following a train of eight or more drive beats at several cycle lengths until atrial refractoriness is encountered [45,46]. Incremental atrial pacing in steps of 10 milliseconds is also performed until second degree AV block develops. Programmed atrial extrastimuli can be used to determine the effective refractory period of the His-Purkinje system (HPS), which should be <450 milliseconds. However, the response of refractory periods to pacing may reveal severe HPS disease. As the refractory period of the HPS should shorten with the cycle length, an increasing refractory period with shorter cycle lengths indicates abnormal HPS conduction [29]. MEDICATIONS USED FOR DIAGNOSTIC PURPOSES DURING EPS Administration of pharmacologic agents may be of help in certain settings. Selective blocking of antegrade atrioventricular (AV) nodal conduction with adenosine, for example, may unmask latent accessory pathway conduction. Atropine or isoproterenol may be used to facilitate the induction of AV nodal reentrant tachycardia (AVNRT) or AV reentrant tachycardia (AVRT) by enhancing ventriculoatrial (VA) conduction in patients with poorer AV nodal conduction https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 12/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate characteristics [47] or by widening the tachycardia zone or the section of the cardiac cycle during which extrastimuli cause the necessary block and the critical delay to initiate reentrant activation. Procainamide normally prolongs the HV interval by 10 to 20 percent [48]. Doubling of the HV interval, an HV interval >100 milliseconds, or the development of infra-Hisian block after administering procainamide represent poor HPS reserve and probably mandates permanent pacing ( waveform 5) [29,49]. Evaluation of His-Purkinje system (HPS) conduction can be limited by AV nodal conduction (ie, block in the AV node preventing evaluation of the HPS). In these instances, atropine is often used to shorten the refractory period of the AV node without affecting HPS conduction [50]. MAPPING AND ABLATION In many cases, catheter ablation immediately follows the diagnostic EP study. Cardiac mapping refers to careful movement of a mapping or ablation catheter in the area of interest, probing for the site at which radiofrequency ablation will be successful at curing the arrhythmia. Cardiac mapping during EP testing identifies the temporal and spatial distributions of electrical potentials generated by the myocardium during normal and abnormal rhythms. This process allows description of the spread of activation from its initiation to its completion within a region of interest and, in its usual application, is focused toward the identification of the site of origin or a critical site of conduction for an arrhythmia. Multiple techniques for mapping have been developed. (See "Overview of catheter ablation of cardiac arrhythmias", section on 'Mapping and localization of the arrhythmia'.) COMPLICATIONS OF INVASIVE CARDIAC ELECTROPHYSIOLOGY STUDIES Complications of invasive cardiac EP studies are rare, with reported complication rates of approximately 2 percent [51,52]. Serious complications of these procedures are generally related to the catheterization process itself, including vascular injury, tricuspid valve damage, pulmonary embolism, hemorrhage requiring transfusion therapy, cardiac chamber perforation resulting in pericardial tamponade, sepsis from catheterization site abscess, myocardial infarction, stroke, and death ( table 2). The induction of serious ventricular tachyarrhythmias occurs frequently during diagnostic EP testing. Such arrhythmias can usually be promptly terminated, either by overdrive pacing or https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 13/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate external defibrillation. However, if the arrhythmia is difficult to revert and is of long duration, there may be complications related to the prolonged hypotension and, rarely, sudden death. Complications with concomitant catheter ablation Catheter-based radiofrequency (RF) ablation procedures are typically much longer studies with more radiation exposure, administration of higher doses of sedative and analgesic agents, more frequent catheterization of the left heart, and more frequent change of catheters. The duration of some of the RF ablation procedures may raise morbidity from vascular complications, thromboembolic complications, cardiac chamber rupture, or radiation exposure including skin injuries and a possible increased risk for malignancy ( table 2). These issues are discussed in detail separately. (See "Overview of catheter ablation of cardiac arrhythmias", section on 'Complications'.) With the rapid expansion of clinical cardiac EP beginning in the 1990s, the complexity of the procedures performed in the EP laboratory has greatly increased, and, along with the increased complexity, the risks involved have increased. To meet the expanding demands and help provide patients and staff with the safest possible and most productive environment, guidelines concerning the staffing and qualifications of the EP laboratory personnel, as well as the design of the laboratory itself, have been issued [53]. SUMMARY AND RECOMMENDATIONS Background Invasive cardiac electrophysiology (EP) study permits a detailed analysis of the mechanism underlying the cardiac arrhythmia and precise location of the site of origin. (See 'Introduction' above and 'Indications and contraindications' above.) Preprocedural evaluation This occurs prior to catheter ablation and includes a history and physical examination along with an electrocardiogram (ideally during the arrhythmia) or strips from ambulatory monitoring that document the arrhythmia in every patient. Consideration of other testing prior to the ablation should be based on the patient's clinical presentation and symptoms but may include echocardiography, stress testing, cardiac magnetic resonance imaging, or coronary angiography to evaluate for underlying structural heart disease. (See 'Preprocedural evaluation' above.) Catheter placement and baseline recordings Multipolar electrode catheters are positioned in the heart. Typical positions include the right atrium (high right atrium) and right ventricle (right ventricular apex); a catheter is also positioned across the tricuspid annulus to record a potential from the bundle of His https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 14/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate (His). A catheter may be placed in the coronary sinus to record left-atrial activation, particularly in studies of patients with supraventricular tachycardia (SVT). These electrodes allow for the measurement of several intervals with diagnostic implications. (See 'Vascular access and electrode catheter placement' above.) Baseline recordings obtained during a typical invasive EP study include several surface electrocardiograms to time events from the body's surface and several intracardiac electrograms, all of which are recorded simultaneously. The intracardiac electrograms are generally displayed in the order of normal cardiac activation ( waveform 1). (See 'Electrocardiographic and electrophysiologic recordings' above.) Programmed electrical stimulation After baseline measurements are recorded, pacing is performed via the intracardiac electrode catheters. Burst pacing at various fixed cycle lengths as well as programmed electrical stimulation (PES) is administered. The technique of PES is used to assess the atrioventricular (AV) conducting system and to induce supraventricular and ventricular arrhythmias. Administration of pharmacologic agents may be of help in certain settings. (See 'Programmed electrical stimulation' above and 'Medications used for diagnostic purposes during EPS' above.) Mapping and ablation Cardiac mapping refers to careful movement of a mapping or ablation catheter in the area of interest, probing for the site at which radiofrequency ablation will be successful at curing the arrhythmia. Cardiac mapping during EP testing identifies the temporal and spatial distributions of electrical potentials generated by the myocardium during normal and abnormal rhythms. This process allows description of the spread of activation from its initiation to its completion within a region of interest. Multiple techniques for mapping have been developed. (See 'Mapping and ablation' above.) Complications These are rare but can be potentially life threatening ( table 2). (See 'Complications of invasive cardiac electrophysiology studies' above.) ACKNOWLEDGMENT The authors and UpToDate thank Dr. Philip Podrid, Dr. Leonard Ganz, Dr. Joseph Germano, Dr. Peter Zimetbaum, and Dr. Brian Olshansky who contributed to earlier versions of this content. Use of UpToDate is subject to the Terms of Use. REFERENCES https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 15/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate 1. Muresan L, Cismaru G, Martins RP, et al. Recommendations for the use of

activation. Procainamide normally prolongs the HV interval by 10 to 20 percent [48]. Doubling of the HV interval, an HV interval >100 milliseconds, or the development of infra-Hisian block after administering procainamide represent poor HPS reserve and probably mandates permanent pacing ( waveform 5) [29,49]. Evaluation of His-Purkinje system (HPS) conduction can be limited by AV nodal conduction (ie, block in the AV node preventing evaluation of the HPS). In these instances, atropine is often used to shorten the refractory period of the AV node without affecting HPS conduction [50]. MAPPING AND ABLATION In many cases, catheter ablation immediately follows the diagnostic EP study. Cardiac mapping refers to careful movement of a mapping or ablation catheter in the area of interest, probing for the site at which radiofrequency ablation will be successful at curing the arrhythmia. Cardiac mapping during EP testing identifies the temporal and spatial distributions of electrical potentials generated by the myocardium during normal and abnormal rhythms. This process allows description of the spread of activation from its initiation to its completion within a region of interest and, in its usual application, is focused toward the identification of the site of origin or a critical site of conduction for an arrhythmia. Multiple techniques for mapping have been developed. (See "Overview of catheter ablation of cardiac arrhythmias", section on 'Mapping and localization of the arrhythmia'.) COMPLICATIONS OF INVASIVE CARDIAC ELECTROPHYSIOLOGY STUDIES Complications of invasive cardiac EP studies are rare, with reported complication rates of approximately 2 percent [51,52]. Serious complications of these procedures are generally related to the catheterization process itself, including vascular injury, tricuspid valve damage, pulmonary embolism, hemorrhage requiring transfusion therapy, cardiac chamber perforation resulting in pericardial tamponade, sepsis from catheterization site abscess, myocardial infarction, stroke, and death ( table 2). The induction of serious ventricular tachyarrhythmias occurs frequently during diagnostic EP testing. Such arrhythmias can usually be promptly terminated, either by overdrive pacing or https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 13/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate external defibrillation. However, if the arrhythmia is difficult to revert and is of long duration, there may be complications related to the prolonged hypotension and, rarely, sudden death. Complications with concomitant catheter ablation Catheter-based radiofrequency (RF) ablation procedures are typically much longer studies with more radiation exposure, administration of higher doses of sedative and analgesic agents, more frequent catheterization of the left heart, and more frequent change of catheters. The duration of some of the RF ablation procedures may raise morbidity from vascular complications, thromboembolic complications, cardiac chamber rupture, or radiation exposure including skin injuries and a possible increased risk for malignancy ( table 2). These issues are discussed in detail separately. (See "Overview of catheter ablation of cardiac arrhythmias", section on 'Complications'.) With the rapid expansion of clinical cardiac EP beginning in the 1990s, the complexity of the procedures performed in the EP laboratory has greatly increased, and, along with the increased complexity, the risks involved have increased. To meet the expanding demands and help provide patients and staff with the safest possible and most productive environment, guidelines concerning the staffing and qualifications of the EP laboratory personnel, as well as the design of the laboratory itself, have been issued [53]. SUMMARY AND RECOMMENDATIONS Background Invasive cardiac electrophysiology (EP) study permits a detailed analysis of the mechanism underlying the cardiac arrhythmia and precise location of the site of origin. (See 'Introduction' above and 'Indications and contraindications' above.) Preprocedural evaluation This occurs prior to catheter ablation and includes a history and physical examination along with an electrocardiogram (ideally during the arrhythmia) or strips from ambulatory monitoring that document the arrhythmia in every patient. Consideration of other testing prior to the ablation should be based on the patient's clinical presentation and symptoms but may include echocardiography, stress testing, cardiac magnetic resonance imaging, or coronary angiography to evaluate for underlying structural heart disease. (See 'Preprocedural evaluation' above.) Catheter placement and baseline recordings Multipolar electrode catheters are positioned in the heart. Typical positions include the right atrium (high right atrium) and right ventricle (right ventricular apex); a catheter is also positioned across the tricuspid annulus to record a potential from the bundle of His https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 14/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate (His). A catheter may be placed in the coronary sinus to record left-atrial activation, particularly in studies of patients with supraventricular tachycardia (SVT). These electrodes allow for the measurement of several intervals with diagnostic implications. (See 'Vascular access and electrode catheter placement' above.) Baseline recordings obtained during a typical invasive EP study include several surface electrocardiograms to time events from the body's surface and several intracardiac electrograms, all of which are recorded simultaneously. The intracardiac electrograms are generally displayed in the order of normal cardiac activation ( waveform 1). (See 'Electrocardiographic and electrophysiologic recordings' above.) Programmed electrical stimulation After baseline measurements are recorded, pacing is performed via the intracardiac electrode catheters. Burst pacing at various fixed cycle lengths as well as programmed electrical stimulation (PES) is administered. The technique of PES is used to assess the atrioventricular (AV) conducting system and to induce supraventricular and ventricular arrhythmias. Administration of pharmacologic agents may be of help in certain settings. (See 'Programmed electrical stimulation' above and 'Medications used for diagnostic purposes during EPS' above.) Mapping and ablation Cardiac mapping refers to careful movement of a mapping or ablation catheter in the area of interest, probing for the site at which radiofrequency ablation will be successful at curing the arrhythmia. Cardiac mapping during EP testing identifies the temporal and spatial distributions of electrical potentials generated by the myocardium during normal and abnormal rhythms. This process allows description of the spread of activation from its initiation to its completion within a region of interest. Multiple techniques for mapping have been developed. (See 'Mapping and ablation' above.) Complications These are rare but can be potentially life threatening ( table 2). (See 'Complications of invasive cardiac electrophysiology studies' above.) ACKNOWLEDGMENT The authors and UpToDate thank Dr. Philip Podrid, Dr. Leonard Ganz, Dr. Joseph Germano, Dr. Peter Zimetbaum, and Dr. Brian Olshansky who contributed to earlier versions of this content. Use of UpToDate is subject to the Terms of Use. REFERENCES https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 15/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate 1. Muresan L, Cismaru G, Martins RP, et al. Recommendations for the use of electrophysiological study: Update 2018. Hellenic J Cardiol 2019; 60:82. 2. Khairy P, Van Hare GF, Balaji S, et al. PACES/HRS Expert Consensus Statement on the Recognition and Management of Arrhythmias in Adult Congenital Heart Disease: developed in partnership between the Pediatric and Congenital Electrophysiology Society (PACES) and the Heart Rhythm Society (HRS). 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Significance of block distal to the His bundle induced by atrial pacing in patients with chronic bifascicular block. Circulation 1979; 60:1455. 7. Krol RB, Morady F, Flaker GC, et al. Electrophysiologic testing in patients with unexplained syncope: clinical and noninvasive predictors of outcome. J Am Coll Cardiol 1987; 10:358. 8. Priori SG, Wilde AA, Horie M, et al. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm 2013; 10:1932. 9. Pedersen CT, Kay GN, Kalman J, et al. EHRA/HRS/APHRS expert consensus on ventricular arrhythmias. Heart Rhythm 2014; 11:e166. 10. Josephson MD. Chapter 4: Atrioventricular Conduction. In: Clinical Cardiac Electrophysiolog y: Techniques and Interpretations, 4, Lippincott Williams & Wilkins, Philadelphia 2008. p.107. 11. Crosson JE, Callans DJ, Bradley DJ, et al. PACES/HRS expert consensus statement on the evaluation and management of ventricular arrhythmias in the child with a structurally normal heart. Heart Rhythm 2014; 11:e55. https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 16/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate 12. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2018; 72:e91. 13. Buxton AE, Lee KL, Fisher JD, et al. A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Unsustained Tachycardia Trial Investigators. N Engl J Med 1999; 341:1882. 14. Zipes DP. Second-degree atrioventricular block. Circulation 1979; 60:465. 15. Pediatric and Congenital Electrophysiology Society (PACES), Heart Rhythm Society (HRS), American College of Cardiology Foundation (ACCF), et al. PACES/HRS expert consensus statement on the management of the asymptomatic young patient with a Wolff-Parkinson- White (WPW, ventricular preexcitation) electrocardiographic pattern: developed in partnership between the Pediatric and Congenital Electrophysiology Society (PACES) and the Heart Rhythm Society (HRS). Endorsed by the governing bodies of PACES, HRS, the American College of Cardiology Foundation (ACCF), the American Heart Association (AHA), the American Academy of Pediatrics (AAP), and the Canadian Heart Rhythm Society (CHRS). Heart Rhythm 2012; 9:1006. 16. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Heart Rhythm 2016; 13:e136. 17. Birnie DH, Sauer WH, Bogun F, et al. HRS expert consensus statement on the diagnosis and management of arrhythmias associated with cardiac sarcoidosis. Heart Rhythm 2014; 11:1305. 18. Saguner AM, Medeiros-Domingo A, Schwyzer MA, et al. Usefulness of inducible ventricular tachycardia to predict long-term adverse outcomes in arrhythmogenic right ventricular cardiomyopathy. Am J Cardiol 2013; 111:250. 19. Sroubek J, Probst V, Mazzanti A, et al. Programmed Ventricular Stimulation for Risk Stratification in the Brugada Syndrome: A Pooled Analysis. Circulation 2016; 133:622. 20. Zipes DP, Calkins H, Daubert JP, et al. 2015 ACC/AHA/HRS Advanced Training Statement on Clinical Cardiac Electrophysiology (A Revision of the ACC/AHA 2006 Update of the Clinical Competence Statement on Invasive Electrophysiology Studies, Catheter Ablation, and Cardioversion). J Am Coll Cardiol 2015; 66:2767. https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 17/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate 21. Narula OS, Cohen LS, Samet P, et al. Localization of A-V conduction defects in man by recording of the His bundle electrogram. Am J Cardiol 1970; 25:228. 22. Castellanos A Jr, Castillo CA, Agha AS. Symposium on Electophysiologic Correlates of Clinical Arrhythmias. 3. Contribution of His bundle recordings to the understanding of clinical arrhythmias. Am J Cardiol 1971; 28:499. 23. Benditt DG, Klein GJ, Kriett JM, et al. Enhanced atrioventricular nodal conduction in man: electrophysiologic effects of pharmacologic autonomic blockade. Circulation 1984; 69:1088. 24. Amat-y-Leon F, Dhingra R, Denes P, et al. The clinical spectrum of chronic His bundle block. Chest 1976; 70:747. 25. Bharati S, Lev M, Wu D, et al. Pathophysiologic correlations in two cases of split His bundle potentials. Circulation 1974; 49:615. 26. Kupersmith J, Krongrad E, Waldo AL. Conduction intervals and conduction velocity in the human cardiac conduction system. Studies during open-heart surgery. Circulation 1973; 47:776. 27. Dhingra RC, Palileo E, Strasberg B, et al. Significance of the HV interval in 517 patients with chronic bifascicular block. Circulation 1981; 64:1265. 28. Scheinman MM, Peters RW, Suav MJ, et al. Value of the H-Q interval in patients with bundle branch block and the role of prophylactic permanent pacing. Am J Cardiol 1982; 50:1316. 29. Josephson ME. Intraventricular Conduction Disturbances. In: Clinical Cardiac Electrophysiolo gy. Techniques and Interpretations, 3rd ed, Josephson ME (Ed), Lippincott, Philadelphia 200 2. p.110. 30. McAnulty JH, Rahimtoola SH, Murphy E, et al. Natural history of "high-risk" bundle-branch block: final report of a prospective study. N Engl J Med 1982; 307:137. 31. Strauss HC, Bigger JT, Saroff AL, Giardina EG. Electrophysiologic evaluation of sinus node function in patients with sinus node dysfunction. Circulation 1976; 53:763. 32. Narula OS, Shantha N, Vasquez M, et al. A new method for measurement of sinoatrial conduction time. Circulation 1978; 58:706. 33. Cramer M, Hariman RJ, Boxer R, Hoffman BF. Electrograms from the canine sinoatrial pacemaker recorded in vitro and in situ. Am J Cardiol 1978; 42:939. 34. Cramer M, Siegal M, Bigger JT Jr, Hoffman BF. Characteristics of extracellular potentials recorded from the sinoatrial pacemaker of the rabbit. Circ Res 1977; 41:292. 35. Gomes JA, Kang PS, El-Sherif N. The sinus node electrogram in patients with and without sick sinus syndrome: techniques and correlation between directly measured and indirectly estimated sinoatrial conduction time. Circulation 1982; 66:864. https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 18/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate 36. Hariman RJ, Krongrad E, Boxer RA, et al. Method for recording electrical activity of the sinoatrial node and automatic atrial foci during cardiac catheterization in human subjects. Am J Cardiol 1980; 45:775. 37. Reiffel JA, Bigger JT Jr. Current status of direct recordings of the sinus node electrogram in man. Pacing Clin Electrophysiol 1983; 6:1143. 38. Reiffel JA, Gang E, Gliklich J, et al. The human sinus node electrogram: a transvenous catheter technique and a comparison of directly measured and indirectly estimated sinoatrial conduction time in adults. Circulation 1980; 62:1324. 39. Dhingra RC, Wyndham C, Amat-Y-Leon, et al. Sinus nodal responses to atrial extrastimuli in patients without apparent sinus node disease. Am J Cardiol 1975; 36:445. 40. Strauss HC, Saroff AL, Bigger JT Jr, Giardina EG. Premature atrial stimulation as a key to the understanding of sinoatrial conduction in man. Presentation of data and critical review of the literature. Circulation 1973; 47:86. 41. Rakovec P, Jakopin J, Rode P, et al. Clinical comparison of indirectly and directly determined sinoatrial conduction time. Am Heart J 1981; 102:292. 42. Heddle, W, Dorveaux, et al. Use of rapid atrial pacing to assess sinus node function. Clin Prog Electrophysiol Pacing 1985; 3:299. 43. Josephson ME. Sinus Node Dysfunction. In: Clinical Cardiac Electrophysiology. Techniques an d Interpretations, 3rd ed, Josephson ME (Ed), Lippincott, Philadelphia 2002. p.68. 44. Wellens HJ, Brugada P, B r FW. Indications for use of intracardiac electrophysiologic studies for the diagnosis of site of origin and mechanism of tachycardias. Circulation 1987; 75:III110. 45. Brugada P, Farr J, Green M, et al. Observations in patients with supraventricular tachycardia having a P-R interval shorter than the R-P interval: differentiation between atrial tachycardia and reciprocating atrioventricular tachycardia using an accessory pathway with long conduction times. Am Heart J 1984; 107:556. 46. Denes P, Wu D, Amat-y-Leon F, et al. The determinants of atrioventricular nodal re-entrance with premature atrial stimulation in patients with dual A-V nodal pathways. Circulation 1977; 56:253. 47. Yu WC, Chen SA, Chiang CE, et al. Effects of isoproterenol in facilitating induction of slow- fast atrioventricular nodal reentrant tachycardia. Am J Cardiol 1996; 78:1299. 48. Josephson ME, Caracta AR, Ricciutti MA, et al. Electrophysiologic properties of procainamide in man. Am J Cardiol 1974; 33:596. https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 19/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate 49. Tonkin AM, Heddle WF, Tornos P. Intermittent atrioventricular block: procainamide administration as a provocative test. Aust N Z J Med 1978; 8:594. 50. Akhtar M, Damato AN, Caracta AR, et al. Electrophysiologic effects of atropine on atrioventricular conduction studied by His bundle electrogram. Am J Cardiol 1974; 33:333. 51. Dimarco JP, Garan H, Ruskin JN. Complications in patients undergoing cardiac electrophysiologic procedures. Ann Intern Med 1982; 97:490. 52. Horowitz LN, Kay HR, Kutalek SP, et al. Risks and complications of clinical cardiac electrophysiologic studies: a prospective analysis of 1,000 consecutive patients. J Am Coll Cardiol 1987; 9:1261. 53. Haines DE, Beheiry S, Akar JG, et al. Heart Rythm Society expert consensus statement on electrophysiology laboratory standards: process, protocols, equipment, personnel, and safety. Heart Rhythm 2014; 11:e9. Topic 980 Version 32.0 https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 20/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate GRAPHICS Revised (2018) Vaughan Williams classification of antiarrhythmic drugs abridged table Class 0 (HCN channel blockers) Ivabradine Class I (voltage-gated Na+ channel blockers) Class Ia (intermediate dissociation): Quinidine, ajmaline, disopyramide, procainamide Class Ib (rapid dissociation): Lidocaine, mexilitine Class Ic (slow dissociation): Propafenone, flecainide Class Id (late current): Ranolazine Class II (autonomic inhibitors and activators) Class IIa (beta blockers): Nonselective: carvedilol, propranolol, nadolol Selective: atenolol, bisoprolol, betaxolol, celiprolol, esmolol, metoprolol Class IIb (nonselective beta agonists): Isoproterenol Class IIc (muscarinic M2 receptor inhibitors): Atropine, anisodamine, hyoscine, scopolamine Class IId (muscarinic M2 receptor activators): Carbachol, pilocarpine, methacholine, digoxin Class IIe (adenosine A1 receptor activators): Adenosine Class III (K+ channel blockers and openers) Class IIIa (voltage dependent K+ channel blockers): https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 21/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate Ambasilide, amiodarone, dronedarone, dofetilide, ibutilide, sotalol, vernakalant Class IIIb (metabolically dependent K+ channel openers): Nicorandil, pinacidil Class IV (Ca++ handling modulators) Class IVa (surface membrane Ca++ channel blockers): Bepridil, diltiazem, verapamil Class IVb (intracellular Ca++ channel blockers): Flecainide, propafenone Class V (mechanosensitive channel blockers): No approved medications Class VI (gap junction channel blockers) No approved medications Class VII (upstream target modulators) Angiotensin converting enzyme inhibitors Angiotensin receptor blockers Omega-3 fatty acids Statins HCN: hyperpolarization-activated cyclic nucleotide-gated; Na: sodium; K: potassium; Ca: calcium. Graphic 120433 Version 3.0 https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 22/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate Options for hands-free pacemaker/defibrillator pad positioning Positioning options for hands-free pacemaker/defibrillator pads showing anterior/lateral positioning (left) and anterior/posterior positioning (right). Graphic 103268 Version 2.0 https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 23/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate Normal intracardiac electrograms obtained during invasive electrophysiologic study (EPS) The normal intracardiac electrograms, during sinus rhythm, obtained during an electrophysiologic study are shown. Three surface electrocardiogram (ECG) leads are monitored (I, aVF, and V1); intracardiac electrograms are obtained from the high right atrium (HRA); the proximal (p), mid (m), and distal (d) bundle of His (HBE); the p, m, and d coronary sinus (CS); and right ventricular apex (RVA). For an ablation procedure, an exploratory catheter (exp) is also used for more extensive mapping. The electrogram obtained includes those from the atrium (A), bundle of His (H), and ventricle (V). Graphic 64875 Version 4.0 https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 24/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate Electrophysiologic study (EPS) in advanced conduction disease showing intra-Hisian block The tracing, obtained during an electophysiologic study, records three surface electrocardiogram (ECG) leads (1, 2, and V1) and the bundle of His electrogram (HBE). The first two sinus beats (SB) are conducted normally from the atrium to the ventricle, but the HBE manifests a split bundle of His electrograms (H and H'). The proximal component (H) is present following a nonconducted P wave (P*), but the distal bundle of His (H') is not activated. The level of atrioventricular block is sharply defined as being intra-Hisian, indicating advanced conduction system disease. A: atrial electrogam; V: ventricular electrogram. Graphic 80538 Version 7.0 https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 25/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate Electrophysiology study (EPS) tracings used in the determination of the corrected sinus node recovery time (SNRT) This tracing is from a 76-year-old male with paroxysmal atrial fibrillation and recurrent near syncope associated with palpitations. Surface leads represented are I, II, III, V1, and V6. Intracardiac tracings shown are the high right atrium (HRA d), the proximal His bundle electrogram (HIS p), the mid His bundle electrogram (HIS m), the distal His bundle electrogram (HIS d), and the right ventricular apex (RVa d). High right atrial pacing at 400 milliseconds (150 beats per minute) is performed for 30 seconds. Upon termination of pacing, a sinus node recovery time of 2150 milliseconds is observed (arrow). The basal sinus cycle length was 1200 milliseconds, giving a corrected sinus node recovery time of 950 milliseconds, consistent with severe sinus node dysfunction. Note the significant secondary pause extending beyond the end of the tracing providing additional evidence of sinus node dysfunction. ms: milliseconds. Courtesy of Joseph J Germano, DO. Graphic 58763 Version 5.0 https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 26/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate Initiation and termination of an atrioventricular reentrant tachycardia captured during invasive electrophysiology studies (EPS) During atrial pacing (S1), a premature atrial beat (S2) is blocked antegradely in the accessory pathway and conducts through the atrioventricular node with a long delay (A2H2 interval), which allows for the recovery of the accessory pathway before retrograde conduction (panel A). The mechanism is an orthodromic atrioventricular reentrant tachycardia (AVRT) using a left- sided pathway, suggested by the atrial activation sequence; earliest retrograde atrial activation during the first echo beat of AVRT (Ae) is in the https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 27/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate mid coronary sinus (CSm). A single ventricular premature beat (VPB) terminates the AVRT (panel B). The VPB conducts to the left atrium but encounters the refractory period of the AV node and is blocked, interrupting conduction in the antegrade limb and terminating the arrhythmia. V: ventricular electrogram; A: atrial electrogram; NSR: normal sinus rhythm; d: distal; p: proximal. Graphic 81938 Version 7.0 https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 28/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate Electrophysiology study (EPS) tracing during mapping of atrial tachycardia Shown are three surface electrocardiogram (ECG) leads (I, aVF, V1) and intracardiac recordings from the high posterior right atrium (HRA); posterior left atrium (USER1 and USER 3); proximal, mid, and distal coronary sinuses (CS9-10, CS5-6, CS1-2); and right ventricular apex (RVA). The patient had an incessant atrial tachycardia and dilated cardiomyopathy (left ventricular ejection fraction 9 percent) referred for cardiac transplant evaluation. The P wave (*) falls at the end of the T wave in the surface ECG; its onset is difficult to discern. However, the intracardiac electrograms demonstrate obvious atrial (A) and ventricular (V) activity. Activation mapping involves positioning the mapping catheters in the right (HRA) and left atria (USER) to record earliest electrical activity during the tachycardia. The left atrial catheter records earlier electrical activity (arrow) than the right atrial catheter, but the timing with respect to the surface P wave is obscured because of the T wave of the preceding QRS complex. Graphic 58120 Version 7.0 https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 29/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate Electrophysiology study (EPS) tracing showing the effects of procainamide on an abnormal His-Purkinje conduction system These tracings were taken from a 58-year-old male with syncope. The baseline 12-lead electrocardiogram demonstrated sinus rhythm with prolonged atrioventricular (AV) conduction and a left bundle branch block with left axis deviation. Surface leads represented are I, II, III, and V1. Intracardiac tracings shown are the high right atrium (HRA), the distal His bundle electrogram (HIS d), the proximal His bundle electrogram (HIS 2), and the right ventricular apex (RVa). The left side of Panel A shows a baseline HV interval of 68 milliseconds. The right side of Panel A demonstrates prolongation of the HV interval to 100 milliseconds after the administration of procainamide indicating severe His-Purkinje conduction disease. Panel B (same lead schema) demonstrates high right atrial pacing at 400 milliseconds (150 beats per minute) with infra-Hisian block (arrow) after the administration of procainamide, confirming severe His-Purkinje disease. A: atrial depolarization; H: His bundle depolarization; msec: milliseconds; V: ventricular depolarization. Courtesy of Joseph J Germano, DO. Graphic 56786 Version 5.0 https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 30/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate Complications of invasive cardiac electrophysiology studies Associated with percutaneous catheterization of veins and arteries Pain Adverse drug reaction Infection/abscess at the catheterization site, sepsis Excessive bleeding, hematoma formation Thrombophlebitis Pulmonary thromboembolism Arterial damage, aortic dissection Systemic thromboembolism Transient ischemic attack/stroke Associated with intracardiac catheters and programmed cardiac stimulation Cardiac chamber or coronary sinus perforation Hemopericardium, cardiac tamponade Atrial fibrillation Ventricular tachycardia/ventricular fibrillation Myocardial infarction Right or left bundle branch block Associated with transcatheter ablation Complete heart block Thromboembolism Vascular access problems (bleeding, infection, hematoma, vascular injury) Cardiac trauma (myocardial perforation, tamponade, valvular damage) Coronary artery thrombosis/myocardial infarction Cardiac arrhythmias Pericarditis Pulmonary vein stenosis Phrenic nerve paralysis Radiation skin burns Possible late malignancy Atrioesophageal fistula https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 31/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate Death resulting from one of the above complications Graphic 63157 Version 4.0 https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 32/33 7/5/23, 10:46 AM Invasive diagnostic cardiac electrophysiology studies - UpToDate Contributor Disclosures Munther K Homoud, MD Speaker's Bureau: Abbott [Live heart dissection]. All of the relevant financial relationships listed have been mitigated. Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/invasive-diagnostic-cardiac-electrophysiology-studies/print 33/33

7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Mechanisms of atrial fibrillation : Brian Olshansky, MD, Rishi Arora, MD : Bradley P Knight, MD, FACC, Hugh Calkins, MD : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: May 16, 2022. INTRODUCTION Atrial fibrillation (AF) is a most common cardiac arrhythmia. The chance of developing AF is tied closely to age, with AF rare before the age of 50 years [1]. In addition to age, there are many types of cardiac and medical conditions that are also closely linked to AF. These include hypertension, coronary artery disease, heart failure, valvular heart disease, obesity [2], and sleep-apnea syndrome. It is well established that high levels of alcohol [3] can increase the probability of developing AF, and that hyperthyroidism can cause AF. Evidence for caffeine and energy drinks, while suspected, is questionable [4]. Furthermore, while exercise can be protective against atrial fibrillation, endurance athletics may be a cause for atrial fibrillation [5]. It is also well established that AF is more common in individuals who have a first-degree relative who developed AF at a young age. There is also a variety of acute conditions that can initiate AF such as cardiac surgery, pulmonary embolus, and inflammatory lung conditions. (See "Epidemiology, risk factors, and prevention of atrial fibrillation".) The precise mechanisms by which age and the other conditions listed above increase the propensity for development of AF are understood poorly ( figure 1). However, these conditions may impact the triggers for AF, which commonly arise in the pulmonary veins or the substrate for maintenance of AF, which broadly relates to atrial size and the extent of fibrosis. Some of the factors that may play a role in the mechanisms of AF include autonomic tone, inflammation, atrial pressure and wall stress, and genetics. (See "Epidemiology, risk factors, and prevention of atrial fibrillation", section on 'Other factors'.) https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 1/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate This topic will provide a broad overview of the current understanding of the mechanisms of AF. This discussion will provide a relatively simplistic approach to a complex topic. The reader will be referred to a rapidly growing literature on this topic, including some comprehensive reviews [6]. DEFINITIONS The following terms are defined to help the reader s understanding of the material below: Trigger a rapidly firing focus often arising in the pulmonary veins that can initiate atrial fibrillation (AF). Triggered activity One of three mechanisms of cardiac arrhythmias (including automaticity and reentry). Triggered activity refers to additional depolarizations, which occur during or immediately following a cardiac depolarization and may cause a sustained cardiac arrhythmia. Substrate Mechanical and anatomic structure of the atria in which AF can occur. Substrate remodeling Changes in the mechanical and anatomic macro, micro, and ultrastructure of the atrial substrate that result from the development of AF and increase the propensity for the development and maintenance of AF over time. Electrical remodeling Changes in the atrial electrical properties (refractoriness and conduction) that result from the development of AF and increase the propensity for the development and maintenance of AF over time. Dispersion of refractoriness A range of differences in the refractory period properties throughout the atrial tissue. Spatial heterogeneity of refractoriness Dispersion of refractoriness manifest as variability in refractoriness throughout the atrial anatomy. Complex fractionated electrograms Local electrograms obtained from areas of the atrium that are rapid, of low amplitude, and have multiple components. Reentry/reentrant mechanism One of three mechanisms of cardiac arrhythmias (including automaticity and triggered activity). Reentry is the most common mechanism of cardiac arrhythmias and refers to the presence of one or more electrical circuit(s) in which electrical activation proceeds in a circular fashion to complete a self-sustaining circuit. https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 2/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate Atrial anisotropy Conduction properties related to directionality of conduction through atrial tissue. BASIC ATRIAL ELECTROPHYSIOLOGY The electrophysiologic properties of normal and fibrillating atria have been studied extensively [7]. A basic understanding of these properties is necessary to understand the pathologic processes that play a role in initiating and perpetuating atrial fibrillation (AF). In the aggregate, these electrophysiologic properties permit the development of very complex patterns of conduction and an extremely rapid atrial rate as seen in AF. The atrial myocardium consists of so-called "fast-response" tissues that depend on the rapidly activating sodium current for phase 0 of the action potential. (See "Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs".) Normal atrial myocardium has the following properties [7-9]: A short action-potential duration. Cellular reactivation can occur rapidly due to the short refractory period (in contrast to Purkinje fibers and ventricular muscle). Very rapid electrical conduction can occur. The refractory period shortens with increasing rate. In the aggregate, these electrophysiologic properties permit the development of very complex patterns of conduction and an extremely rapid atrial rate as seen in AF. CLINICAL FACTORS ASSOCIATED WITH AF The following are common clinical conditions associated with atrial fibrillation (AF) in developed countries, and the percent of AF cases in which they are found (see "Epidemiology, risk factors, and prevention of atrial fibrillation", section on 'Chronic disease associations') [6]: Hypertension (60 to 80 percent). Cardiovascular disease, including cardiomyopathy, valvular and coronary artery disease (25 to 30 percent). New York Heart Association class II to IV heart failure (30 percent). https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 3/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate Diabetes (20 percent). Age. Each of the first three is associated with left atrial dilatation, which is important in the development of a substrate for AF and also may increase the probability of electrical firing from the pulmonary veins. (See 'Mechanisms of atrial fibrillation: triggers and substrates' below.) The following section will discuss the link between these conditions and AF. MECHANISMS OF ATRIAL FIBRILLATION: TRIGGERS AND SUBSTRATES Atrial fibrillation (AF) may present as a paroxysmal (self-terminating AF within seven days), a persistent (one that lasts greater than seven days), or a long-standing persistent AF (continuous AF for 12 months or greater). The term permanent AF should be used when both the patient and physicians agree to not pursue strategies to restore or maintain sinus rhythm. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation", section on 'Classification and terminology'.) This wide range of clinical presentations is likely due to an interaction between a trigger and the substrate ( figure 1). AF is initiated by rapid firing (or triggers) from the pulmonary veins (PV). Early in the course of AF the atrium is relatively healthy and as a result sinus rhythm is spontaneously restored. As the substrate remodels further over time, AF no longer terminates spontaneously and becomes persistent. With more extensive remodeling of the atrium, it becomes increasingly difficult to maintain sinus rhythm and the patient and physician may agree no longer to attempt to maintain sinus rhythm, with the AF thereby being considered permanent [10]. Triggers of AF It has been known for many years that a single focus firing rapidly in the atria can be a trigger for fibrillatory conduction throughout the atria [11]. It is now well established that the most common site of the rapid atrial firing that triggers AF is the PVs. Catheter ablation of AF depends in large part on the electrical isolation of the PVs from the remainder of the atrium. Electrophysiologic evaluation of the PVs has identified myocardial tissue that can lead to repetitive firing or even the presence of episodic reentrant activation in the veins [6]. Additionally, stretch can increase the propensity for rapid firing from the PVs as a result of stretch sensitive ion channels. [12]. It has been speculated that the mechanism of atrial stretch may help explain the association between AF and mitral regurgitation as well as various types of heart failure. https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 4/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate Role of premature atrial complex and other arrhythmia triggers AF is initiated (triggered) predominantly by rapid firing from PVs. Much less commonly, AF can be triggered by non-PV sites of rapid firing (such as tissue near the PV including the Vein of Marshall, the superior vena cava, or coronary sinus) or by other types of supraventricular arrhythmias including atrioventricular nodal reentrant tachycardia (AVNRT), orthodromic AV reciprocating tachycardia, and atrial flutter [6,13-23]. In some patients, successful elimination of AF with catheter ablation requires both isolation of the PVs, as well as elimination of these non-PV triggers. (See "Atrial fibrillation: Catheter ablation" and "Atrial fibrillation: Surgical ablation".) Role of atrial flutter and supraventricular tachycardias Atrial tachycardia, atrial flutter, and other supraventricular tachycardias can initiate AF in predisposed patients. The interaction between these arrhythmias and AF is not well understood, but atrial flutter and AF commonly coexist. In some instances, elimination of atrial flutter will diminish and/or eliminate episodes of AF. Nevertheless, elimination of the right atrial reentry circuit responsible for typical flutter frequently does not eliminate the predisposition to AF that is predominately a left-atrial problem in a large number of patients. Many studies have demonstrated that patients who undergo catheter ablation of typical atrial flutter have a very high probability of developing AF over the ensuing five years. This is true regardless of whether AF had been observed prior to development of typical atrial flutter. This has clinical implications when it comes to ablation, but also has implications for anticoagulation strategies and patient follow-up. Nevertheless, for most patients, it makes sense to try to eliminate the organized supraventricular tachycardia, especially if right-sided by ablation before considering PV isolation and/or other more extensive ablation procedures to eliminate AF, as the AF may be reduced or eliminated by eliminating the other tachycardia first. Role of the autonomic nervous system The autonomic nervous system plays an important role in the development and maintenance of AF [24-26]. Clinical studies using heart rate variability analysis in patients with AF suggest that fluctuation in autonomic tone may be a major determinant of AF in patients with focal ectopy originating from the PVs [27]. Studies have also demonstrated a change in heart rate variability after PV ablation [28], further suggesting that PV triggers may be at least partially modulated by autonomic activity. Another study showed that the occurrence of paroxysmal AF greatly depends on variations of the autonomic tone, with a primary increase in adrenergic tone followed by an abrupt shift toward vagal predominance [29]. Anatomic studies of the autonomic innervation of the atria also indicate that the PVs and posterior left atrium (PLA) have a unique autonomic profile with a rich innervation from sympathetic and parasympathetic nerves [30-35]. The autonomic nervous system may also be https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 5/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate playing a role in the genesis of AF in diseased hearts [30,36,37]. Studies suggest that the parasympathetic and sympathetic nervous system may also be playing a role in creation of AF substrate in the setting of heart failure [36,37]. Both the sympathetic and parasympathetic nervous systems have been implicated in the genesis [30,38,39] and maintenance of AF: Sympathetic effects Early studies suggested that exercise-induced AF may be sympathetically driven [30,40]. PV ectopic foci appear to be at least partially modulated by autonomic signaling, with sympathetic stimulation with isoproterenol frequently utilized to elicit these triggers in patients undergoing ablation for AF [41]. Parasympathetic (vagal) effects The parasympathetic nervous system may contribute to AF in young patients with no structural heart disease [42]. Animal studies show that vagal stimulation contributes to the genesis of AF by nonuniform shortening of atrial effective refractory periods, thereby setting up substrate for reentry. Vagal stimulation can also lead to the emergence of focal triggers in the atrium [43-45]. Bezold-Jarisch-like "vagal" reflexes can be elicited during radiofrequency ablation and occur in and around the PVs. It has been suggested that elimination of these vagal reflexes during ablation may improve efficacy of AF ablation procedures [46]. Vagal responsiveness also appears to decrease following ablation in the left atrium [47]. In some series, adding ganglionated plexi (GP) ablation to PV isolation appears to increase ablation success for AF [12]. Data suggest that areas in the atrium demonstrating complex fractionated atrial electrograms (CFAE) may represent a suitable target site for ablation; although several studies have reported that ablation at these sites may increase the efficacy of PV isolation procedures [48,49], enthusiasm for this approach has fallen over time. One possible explanation for the improvement in ablation success reported in these trials is that several CFAE sites anatomically overlie fat pads containing GPs [18,50]. As indicated above, autonomic denervation performed by GP ablation is thought to improve efficacy of AF ablation. (See "Atrial fibrillation: Catheter ablation" and "Catheter ablation for the treatment of atrial fibrillation: https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 6/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate Technical considerations for non-electrophysiologists", section on 'Ablation techniques and targets'.) In a study of 40 patients with paroxysmal AF scheduled to undergo catheter ablation, individuals were randomly assigned to noninvasive transcutaneous low-level stimulation of the tragus (the anterior protuberance of the ear where the auricular branch of the vagus nerve is accessible) or to sham stimulation for one hour. Compared with control, low-level stimulation suppressed AF as measured by the decreased duration of atrial pacing-induced AF and an increased AF cycle length [51]. Maintenance of atrial fibrillation In patients with persistent AF, the prevailing understanding of the mechanism is that, once triggered, the arrhythmia is maintained (sustained) by one or more abnormalities in the atrial tissue. This process may explain why the failure rate of PV isolation is as high as 40 to 60 percent at one year: The trigger(s) may have been treated but not the abnormalities that sustain AF once triggered (initiated). The role of localized sources (electrical rotors and focal impulses) in the initiation and maintenance of AF was explored in the CONFIRM trial of 92 patients undergoing ablation procedures for paroxysmal or persistent (72 percent) AF [52]. Consecutive patients were prospectively treated (not randomly assigned) in a 1:2 case-cohort design with either conventional ablation at sources identified within the atria followed by conventional ablation or conventional ablation alone. Localized sources were identified in 97 percent of cases (70 percent rotors and 30 percent focal impulses) with sustained AF, each with an average of 2.1 sources. During a median of 273 days, patients treated with treatment of both sources and conventional ablation had a significantly higher freedom from AF (82.4 versus 44.9 percent). Similar information was reported, indicating that driver domains, located in specific areas of the atria, act as unstable re-entry circuits that perpetuate atrial fibrillation in patients who have persistent AF [53,54]. Murine cell cultures show a differential ion channel gene expression associated with atrial tissue remodeling (ie, decreased SCN5A, CACN1C, KCND3, and GJA1; and increased KCNJ2) [55]. Fibrillatory complexity, increased in late compared with early stage cultures, was associated with a decrease in rotor tip meandering and increase in wavefront curvature. Rotors are not the only explanation. In a study using high-density, simultaneous, biatrial, epicardial mapping of persistent and longstanding persistent AF in patients undergoing open heart surgery, several non-reentrant drivers were present in both atria in 11 or 12 patients with two to four foci per patient; foci were seen in both atria but generally in the lateral left atrial free wall, and likely acted as drivers. Reentry was not found to be the mechanism [56]. https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 7/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate Likely, the substrate to maintain AF is a combination of reentrant activity and focal triggers. In a study of biatrial epicardial mapping of AF in sheep, wave propagation patterns were passing wave (69 percent occurrence, 68.6 percent of total time), point source (20.4, 13.1 percent), wave collision (4, 2.8 percent), reentrant wave (0.7, 6.3 percent), half-rotation (2.9, 4.4 percent), wave splitting (2.7, 4.3 percent), conduction block (0.05, 0.03 percent) and figure of eight reentry (0.05, 0.05 percent) [57]. Periods of repetitive activity were detected in the left and right atria. The following sections describe factors that might contribute to the maintenance of AF. Atrial remodeling Atrial remodeling involves the concept that there are structural changes, such as fibrosis, or electrical changes, such as refractory-period dispersion or conduction display, in the atria that can predispose to the development and maintenance of AF. In some instances, structural and electrical changes occur simultaneously. These processes can facilitate or create electrical reentrant circuits or triggers that can lead to AF [13,58]. It is also well established that the presence of AF results in remodeling of the atrium over time [7]. This explains the well-established concept that AF begets AF ( figure 2). Thus, the longer a patient has been in continuous AF, the less likely it is to terminate spontaneously, and harder it is to restore and maintain sinus rhythm [59]. Electrical remodeling Paroxysmal AF commonly precedes chronic AF. It has been suggested even after only a few minutes, AF induces transient changes in atrial electrophysiology that promote its perpetuation [14]. This might occur through a tachycardiomyopathy or through "electrical remodeling" of the atria by AF, leading to a progressive decrease in atrial refractoriness [14,15]. Electrical remodeling results from the high rate of electrical activation, which stimulates the AF-induced changes in refractoriness [60]. Tachycardia-induced changes in refractoriness are spatially nonuniform and there is increased variability both within and among various atrial regions [61]. It is possible that the change in atrial refractory period observed after an episode of AF predisposes to the spontaneous recurrence of AF in the days following cardioversion. In addition to the shortening of the refractory period, chronic, rapid, atrial pacing-induced AF results in other changes within the atria, including an increase in the expression and distribution of connexin 43 and heterogeneity in the distribution of connexin 40, both of which are intercellular gap junction proteins ("gap junctional remodeling") [16,17]; cellular remodeling is due to apoptotic death of myocytes with myolysis, which may not be entirely reversible [18]; the induction of sinus node dysfunction, demonstrated by prolonged corrected sinus node recovery time, reduced maximal heart rate in response to isoproterenol, and lower intrinsic heart rate after administration of atropine and propranolol [19]; and an increase in P wave duration and intraatrial conduction time. https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 8/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate A clinical study evaluated the hypothesis of electrical remodeling by the use of atrial pacing- induced AF in patients with a history of supraventricular tachycardia [20]. AF significantly shortened the right-atrial effective refractory period after only a few minutes, and temporal recovery of the refractory period occurred over about eight minutes. Upon termination of AF, there was an increased propensity for the induction of another episode of AF that decreased with increasing time after the initial AF reversion. The second also tends to last longer than the first. The time to recurrence was also evaluated in a review of 61 patients who had daily electrocardiogram (ECG) recordings using transtelephonic monitoring: 57 percent had recurrent AF during the first month after cardioversion, with a peak incidence during the first five days [21]. Among patients with recurrence, there was a positive correlation between the duration of the shortest coupling interval of premature atrial complex (PAC; also referred to a premature atrial beat, premature supraventricular complex, or premature supraventricular beat) after cardioversion, which correlates with the refractory period and the timing of recurrence ( figure 3). (See "Atrial fibrillation: Cardioversion".) In contrast to the normal situation in which the atrial refractory period shortens with an increase in rate (as in AF) and prolongs when the rate decreases, the refractory period fails to lengthen appropriately at slow rates (eg, with return to sinus rhythm) in patients with acute or chronic AF. The duration of AF has no significant impact upon the extent of these electrophysiologic changes [22]. Atrial electrical remodeling is reversed gradually after the restoration of sinus rhythm [23,62]. This may be one of the explanations for the early or immediate return of AF after cardioversion. In one study of 25 patients, the atrial refractory period increased and the adaptation of atrial refractoriness to rate was normal by four weeks after cardioversion [23]. In another report of 38 patients, the atrial refractory period increased by one week, with some variation in different regions of the atrium [62]. This observation has important clinical implications. The mechanism for electrical remodeling and shortening of the atrial refractory period is not entirely clear; a possible explanation is ion-channel remodeling, with a decrease in the protein content of the L-type calcium channel [63]. Support for this comes from an animal study in which verapamil, an L-type calcium antagonist, prevented electric remodeling of short-duration AF (one day or less) and hastened complete recovery, without affecting inducibility of AF [64]. Similar findings have been noted in humans as verapamil, but not procainamide, prevented remodeling when given prior to the electrophysiologic induction of AF [65]. Oral diltiazem is also effective in some patients [66], while beta blockers had no effect on electrical remodeling in an animal model [60]. https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 9/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate In comparison, cytosolic calcium overload, induced by hypercalcemia or digoxin, which increases the intracellular concentration of calcium by activating the sodium-calcium exchanger, enhances electrical remodeling [64,67,68]. The effect of digoxin, which is not due to its vagotonic activity, is associated with an increase in the inducibility and duration of AF [68]. Calcium leak from the sarcoplasmic reticulum may trigger and maintain AF. It is known that protein kinase A (PKA) hyperphosphorylation of the cardiac ryanodine receptor (RyR2), resulting in dissociation of the channel-stabilizing subunit calstabin2, causes sarcoplasmic reticulum (SR) calcium leak in failing hearts. This phenomenon seems to be involved in triggering ventricular arrhythmias. Using similar logic, these proteins were investigated in atrial tissues from both dogs and humans with AF [69]. Atrial tissue in those with AF showed a significant increase in PKA phosphorylation of RyR2 and a decrease in calstabin2 binding to the channel. Channels isolated from dogs with AF had an increased open probability under conditions simulating diastole compared with channels from control hearts, suggesting that these AF channels could predispose to a diastolic SR calcium leak. The conclusion was that SR calcium leak due to RyR2 PKA hyperphosphorylation may play a role in the initiation and/or maintenance of AF. Other studies also suggest that RyR2 receptor-mediated calcium leak drives progressive development of an atrial fibrillation substrate in a transgenic mouse model [70,71]. The effects of calcium overload are quite complex. It is likely that triggers and substrates initiate short episodes of AF that then lead to calcium overload and over a period of minutes there is activation of the I current that increases I , decreases I , increases I , and decreases CaL K1 Na KACh I . This can affect the action-potential duration and allow for more reentry to occur. As reentry TO occurs, the substrate changes and there is remodeling through calcium handling abnormalities as well as mRNA transcription [59], and ultimately perhaps with protein decrease, changes in connexons, including, Cx40, that can affect conduction. The calcium-handling abnormalities can also lead to hypocontractility and atrial dilatation, thereby affecting even more the possibility of developing AF [59]. Both animal and human studies suggest that angiotensin II is involved in electrical and atrial myocardial remodeling [72,73] (see "Pathophysiology of heart failure: Neurohumoral adaptations", section on 'Renin-angiotensin system'). In an animal model, inhibition of angiotensin II with captopril or candesartan prevented shortening of the atrial effective refractory period and atrial electrical remodeling during rapid atrial pacing [72], while atrial tissue obtained during open heart surgery from patients with AF revealed downregulation of AT1 receptor proteins and upregulation of AT2 receptor [73]. The potential clinical importance of these changes is illustrated by the observations that angiotensin converting enzyme (ACE) https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 10/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate inhibitors reduce the incidence of AF in patients with left ventricular dysfunction after myocardial infarction [74] and in patients with chronic left ventricular dysfunction due to ischemic heart disease [75]. (See "Angiotensin converting enzyme inhibitors and receptor blockers in acute myocardial infarction: Clinical trials".) Another possible contributor to electrical remodeling and shortening of the atrial refractory period is atrial ischemia, which activates the sodium/hydrogen exchanger. The intravenous administration of HOE 642, a selective inhibitor of this sodium proton pump, to dogs undergoing rapid atrial pacing resulted in the lengthening of atrial refractoriness after one hour, while control dogs showed effective refractory-period shortening greater than 10 percent [76]. Role of fibrosis The development of AF invokes atrial remodeling processes that involve electrophysiological and structural alterations that serve to maintain, promote, and propagate AF. In addition to electrophysiological alterations, such as shortening of the atrial action potential, increased dispersion of refractoriness, and conduction velocity shortening, morphological changes consist of fibrosis, hypertrophy, necrotic and apoptotic cell loss, and dilation [77]. Of these, fibrosis is considered especially important in the creation of AF substrate, especially in the setting of chronic atrial dilatation caused by heart failure. A canine model of heart failure has demonstrated a progressive increase in AF inducibility with increasing fibrosis [78]. An increase in conduction heterogeneity noted in this model is thought to play a major role in the creation of reentrant circuits in the dilated atria. Patients with AF also display increased atrial fibrous tissue content, along with increased expression of collagen I and III [79], as well as up-regulation of MMP-2 protein, and down-regulation of the tissue inhibitor of metalloproteinase, TIMP-1 [79]. Expression of the active form of MMP-9 and of monocyte chemoattractant protein-1, an inflammatory mediator, is increased in AF patients [80]. The left atrial free wall around the PV area presents particularly strong interstitial fibrotic changes [81-83]. Although the underlying molecular mechanisms that lead to the development of atrial fibrosis are complex, work suggests that the TGF- pathway may be an important contributor to the development of fibrosis (especially in the setting of increasing atrial stretch/dilatation resulting from congestive heart failure) [84-86]. Role of inflammation and oxidative stress Emerging evidence suggests a significant role of inflammation in the pathogenesis of AF [87]. Evidence includes elevated serum levels of inflammatory biomarkers in patients with AF, the expression of inflammatory markers in atrial tissue from AF patients, and beneficial effects of antiinflammatory drugs in the setting of experimental AF [88]. Inflammation is suggested to be linked to various pathological processes, https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 11/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate such as oxidative stress, apoptosis, and fibrosis that promote the creation and perpetuation of AF substrate. Several of the downstream effects of inflammation in the heart are thought to be mediated by oxidative stress [89]. Indeed, studies in patients with AF demonstrate increased generation of reactive oxygen species (ROS) in the fibrillating atrium compared with normal atria [90,91]. Several major enzymatic sources of ROS have been implicated in AF. Of these, NAPDH oxidase (specifically its NOX2 isoform) has been shown to be elevated in humans with AF in a variety of studies [92,93]. Other sources of ROS implicated in AF include uncoupled nitric oxide synthase [94] and xanthine oxidase [95]. In addition to the increase in ROS noted in tissue from patients with AF, experimental evidence suggests that ROS may be implicated not only in promoting AF but also in maintaining atrial arrhythmia. The administration of antioxidants such as vitamin C or statins (which are known to have pleiotropic antioxidant effects) decreased AF inducibility in canine models of tachypacing-induced AF [96,97]. Antioxidants such as vitamin C and n-acetylcysteine have been administered to patients undergoing cardiac surgery and have been shown to decrease postoperative AF [98,99]. These early results are encouraging and warrant further investigation of inflammation and oxidative stress as viable therapeutic targets in patients with AF. Reentrant mechanism Maps of AF in animals and humans suggest that this arrhythmia is caused by multiple wandering wavelets ( figure 4), and these may be due to heterogeneity of atrial refractoriness and conduction. In addition, the response of atrial activity to adenosine infusion suggests a reentrant rather than a focal mechanism [100]. Adenosine increases the inward potassium rectifier current, which shortens refractory periods and would accelerate reentrant circuits. In contrast, this effect would slow an automatic or triggered focus. In a series of 33 patients with AF undergoing electrophysiology study, adenosine increased the dominant frequencies, supporting reentrant rather than focal sources for the perpetuation of AF. It has been suggested that at least four to six independent wavelets are required to maintain AF [101]. These wavelets rarely reenter themselves but can re-excite portions of the myocardium recently activated by another wavefront, a process called random reentry [7,102-104]. As a result, there are multiple wavefronts of activation that may collide with each other, extinguishing themselves or creating new wavelets and wavefronts, thereby perpetuating the arrhythmia ( figure 5). The reentrant circuits are therefore unstable; some disappear, while others reform. These circuits have variable but short cycle lengths, resulting in multiple circuits to which atrial tissue cannot respond in a 1:1 fashion. As a result, functional block, slow conduction, and multiple wave fronts develop [104]. https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 12/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate Patients with AF may have increased dispersion of refractoriness. This correlates with enhanced inducibility of AF and spontaneous episodes [105] likely related to unstable reentry circuits. Some patients have site-specific dispersion of atrial refractoriness and intraatrial conduction delays resulting from nonuniform atrial anisotropy [106]. This appears to be a common property of normal atrial tissue, but there are further conduction delays to and within area surrounding the AV node in patients with induced AF, suggesting an important role for the low right atrium in the genesis of AF. Abnormalities in restitution as well as the spatial distribution of such abnormalities can be related to the persistence of AF. In one study, monophasic action potential recordings were evaluated in patients with AF [107]. The action potential duration was plotted as a function of the preceding diastolic interval, and the slope of the action potential duration versus the diastolic interval (the restitution curve) was determined. If the slope was greater than one, oscillations occurred that may cause localized conduction delay or block resulting in a wave break giving rise to atrial fibrillation. These different patterns of conduction are reflected in the morphology of electrograms recorded with mapping during induced AF. Single potentials were indicative of rapid uniform conduction, short double potentials indicated collision, long double potentials were indicative of conduction block, while fragmented potentials were markers for pivoting points or slow conduction ( figure 6) [108,109]. Sites of fragmented potentials or complex fractionated atrial electrograms are potential targets for radiofrequency ablation to terminate AF as they may represent critical areas from which AF originates and perpetuates. (See "Atrial fibrillation: Catheter ablation".) This phenomenon has been termed microreentry to distinguish it from classic reentry in which the same reentrant pathway is repetitively traversed. The impulse may circulate around a central line of functional block, so-called leading circle reentry; this type of reentry tends not to be stable but rather to drift through the atria until it is extinguished. The perpetuation of AF may also depend importantly upon macroreentry around natural orifices and structures in the atrium, which provides a rationale and anatomic landmarks for ablative treatment. The collision of wavefronts cancels many atrial depolarizations that might otherwise reach the AV node, resulting in a slower heart rate than might otherwise have occurred ( figure 7A-B). Although multiple wandering wavelets probably account for the majority of AF, one study reported nine patients in whom a single, rapidly firing focus was identified with electrophysiologic mapping [110]. Organized and rapid atrial activity with a centrifugal and consistent pattern of atrial activation resulted from this focus, but it fired irregularly with striking https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 13/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate and abrupt changes in atrial cycle lengths. In most of the patients, the focus was near the ostia of great vessels and was amenable to radiofrequency ablation ( figure 8 and figure 9). Small reentrant sources, called rotors, may drive or maintain AF in some cases. These rotors result in a hierarchical distribution of frequencies throughout the atria that may be identified with spectral analysis of intracardiac recordings. Ablation of such sites has terminated paroxysmal AF, suggesting that they may play an important role [111], but it is not clear that the rotors are responsible for AF or are fixed in most instances. AF may be chaotic and have wavelets and rotors that are secondary rather than the predominant cause of AF [112]. However, antral pulmonary venous reentrant and focal drivers may be responsible for AF [54]. The complexity of such drivers increase with prolonged AF. These sites are often localized near the PV orifices in patients with paroxysmal AF, and are more often localized to the left or right atria in patients with chronic AF [100]. The fibrillating atrium cannot be captured by pacing when the atrial electrograms are disorganized. This observation supports the presence of microreentry, since there is no excitable gap (or it is very small) to permit capture. However, when type I ( figure 9) AF (which has organized atrial electrograms) is induced by rapid atrial pacing, the fibrillating atrium can be captured with rapid atrial pacing, suggesting the presence of an excitable gap [113]. ROLE OF THE ATRIOVENTRICULAR NODE The atrioventricular (AV) node regulates the number of atrial impulses that reach the ventricle. The ventricular rate in atrial fibrillation (AF) is typically irregularly irregular, with a ventricular rate that may be slow, moderate, or rapid depending on the capacity of the AV node to conduct impulses. The rate of AV nodal conduction is dependent upon multiple factors, including electrical properties of the node and the influence of the autonomic nervous system [114]. In addition, the use drugs such as digoxin, calcium channel blockers, or beta blockers may influence AV nodal function. There also may be a circadian rhythm for both AV nodal refractoriness and concealed conduction, accounting for the circadian variation in ventricular response rate [115]. AV nodal tissue consists of so-called "slow response" fibers, which depend on a mixed

experimental evidence suggests that ROS may be implicated not only in promoting AF but also in maintaining atrial arrhythmia. The administration of antioxidants such as vitamin C or statins (which are known to have pleiotropic antioxidant effects) decreased AF inducibility in canine models of tachypacing-induced AF [96,97]. Antioxidants such as vitamin C and n-acetylcysteine have been administered to patients undergoing cardiac surgery and have been shown to decrease postoperative AF [98,99]. These early results are encouraging and warrant further investigation of inflammation and oxidative stress as viable therapeutic targets in patients with AF. Reentrant mechanism Maps of AF in animals and humans suggest that this arrhythmia is caused by multiple wandering wavelets ( figure 4), and these may be due to heterogeneity of atrial refractoriness and conduction. In addition, the response of atrial activity to adenosine infusion suggests a reentrant rather than a focal mechanism [100]. Adenosine increases the inward potassium rectifier current, which shortens refractory periods and would accelerate reentrant circuits. In contrast, this effect would slow an automatic or triggered focus. In a series of 33 patients with AF undergoing electrophysiology study, adenosine increased the dominant frequencies, supporting reentrant rather than focal sources for the perpetuation of AF. It has been suggested that at least four to six independent wavelets are required to maintain AF [101]. These wavelets rarely reenter themselves but can re-excite portions of the myocardium recently activated by another wavefront, a process called random reentry [7,102-104]. As a result, there are multiple wavefronts of activation that may collide with each other, extinguishing themselves or creating new wavelets and wavefronts, thereby perpetuating the arrhythmia ( figure 5). The reentrant circuits are therefore unstable; some disappear, while others reform. These circuits have variable but short cycle lengths, resulting in multiple circuits to which atrial tissue cannot respond in a 1:1 fashion. As a result, functional block, slow conduction, and multiple wave fronts develop [104]. https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 12/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate Patients with AF may have increased dispersion of refractoriness. This correlates with enhanced inducibility of AF and spontaneous episodes [105] likely related to unstable reentry circuits. Some patients have site-specific dispersion of atrial refractoriness and intraatrial conduction delays resulting from nonuniform atrial anisotropy [106]. This appears to be a common property of normal atrial tissue, but there are further conduction delays to and within area surrounding the AV node in patients with induced AF, suggesting an important role for the low right atrium in the genesis of AF. Abnormalities in restitution as well as the spatial distribution of such abnormalities can be related to the persistence of AF. In one study, monophasic action potential recordings were evaluated in patients with AF [107]. The action potential duration was plotted as a function of the preceding diastolic interval, and the slope of the action potential duration versus the diastolic interval (the restitution curve) was determined. If the slope was greater than one, oscillations occurred that may cause localized conduction delay or block resulting in a wave break giving rise to atrial fibrillation. These different patterns of conduction are reflected in the morphology of electrograms recorded with mapping during induced AF. Single potentials were indicative of rapid uniform conduction, short double potentials indicated collision, long double potentials were indicative of conduction block, while fragmented potentials were markers for pivoting points or slow conduction ( figure 6) [108,109]. Sites of fragmented potentials or complex fractionated atrial electrograms are potential targets for radiofrequency ablation to terminate AF as they may represent critical areas from which AF originates and perpetuates. (See "Atrial fibrillation: Catheter ablation".) This phenomenon has been termed microreentry to distinguish it from classic reentry in which the same reentrant pathway is repetitively traversed. The impulse may circulate around a central line of functional block, so-called leading circle reentry; this type of reentry tends not to be stable but rather to drift through the atria until it is extinguished. The perpetuation of AF may also depend importantly upon macroreentry around natural orifices and structures in the atrium, which provides a rationale and anatomic landmarks for ablative treatment. The collision of wavefronts cancels many atrial depolarizations that might otherwise reach the AV node, resulting in a slower heart rate than might otherwise have occurred ( figure 7A-B). Although multiple wandering wavelets probably account for the majority of AF, one study reported nine patients in whom a single, rapidly firing focus was identified with electrophysiologic mapping [110]. Organized and rapid atrial activity with a centrifugal and consistent pattern of atrial activation resulted from this focus, but it fired irregularly with striking https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 13/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate and abrupt changes in atrial cycle lengths. In most of the patients, the focus was near the ostia of great vessels and was amenable to radiofrequency ablation ( figure 8 and figure 9). Small reentrant sources, called rotors, may drive or maintain AF in some cases. These rotors result in a hierarchical distribution of frequencies throughout the atria that may be identified with spectral analysis of intracardiac recordings. Ablation of such sites has terminated paroxysmal AF, suggesting that they may play an important role [111], but it is not clear that the rotors are responsible for AF or are fixed in most instances. AF may be chaotic and have wavelets and rotors that are secondary rather than the predominant cause of AF [112]. However, antral pulmonary venous reentrant and focal drivers may be responsible for AF [54]. The complexity of such drivers increase with prolonged AF. These sites are often localized near the PV orifices in patients with paroxysmal AF, and are more often localized to the left or right atria in patients with chronic AF [100]. The fibrillating atrium cannot be captured by pacing when the atrial electrograms are disorganized. This observation supports the presence of microreentry, since there is no excitable gap (or it is very small) to permit capture. However, when type I ( figure 9) AF (which has organized atrial electrograms) is induced by rapid atrial pacing, the fibrillating atrium can be captured with rapid atrial pacing, suggesting the presence of an excitable gap [113]. ROLE OF THE ATRIOVENTRICULAR NODE The atrioventricular (AV) node regulates the number of atrial impulses that reach the ventricle. The ventricular rate in atrial fibrillation (AF) is typically irregularly irregular, with a ventricular rate that may be slow, moderate, or rapid depending on the capacity of the AV node to conduct impulses. The rate of AV nodal conduction is dependent upon multiple factors, including electrical properties of the node and the influence of the autonomic nervous system [114]. In addition, the use drugs such as digoxin, calcium channel blockers, or beta blockers may influence AV nodal function. There also may be a circadian rhythm for both AV nodal refractoriness and concealed conduction, accounting for the circadian variation in ventricular response rate [115]. AV nodal tissue consists of so-called "slow response" fibers, which depend on a mixed calcium/sodium current. This current is often called the inward calcium current, since in a normal physiologic environment, the ions are almost exclusively calcium. The mixed current uses a kinetically slow channel and is responsible for phase 0 depolarization. (See "Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs".) https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 14/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate These characteristics lead to properties that are quite different from "fast-response" tissue in the atria, which as noted above, depend on an inward sodium current that uses a kinetically fast channel for phase 0 depolarization [8,116]: Partial and complete reactivation returns only 100 ms or more after return to the diastolic potential (versus 10 to 50 ms in the atria). The refractory period changes little as a function of rate. Conduction velocity is relatively slow, ranging from 0.01 to 0.1 m/s. Unlike tissue generating a fast action potential that has an all-or-none response (ie, the velocity of impulse conduction is similar at all stimulation rates until block occurs), tissue that generates a slow action potential exhibits a graded or decremental response, in which the velocity of impulse conduction slows as the stimulation rate increases. As noted above, the ventricular rate usually ranges 90 and 170 beats/min. Ventricular rates below 60 beats/min are seen with AV nodal disease, drugs that affect conduction, and high vagal tone as can occur in a well-conditioned athlete. Ventricular rates above 200 beats/min suggest catecholamine excess, parasympathetic withdrawal, or the existence of an accessory bypass tract as occurs in the preexcitation syndrome. The QRS complexes are widened in the last setting and must be distinguished from a rate-related or underlying bundle branch block. In the classical view, the AV node is bombarded by impulses from the fibrillating atria. Some impulses traverse the AV node and reach the specialized infranodal conduction system and then the ventricles. However, most atrial impulses penetrate the AV node from varying distances and then are extinguished when they encounter the refractoriness of an earlier wavefront; this phenomenon of concealed conduction in turn creates a refractory wave that affects succeeding impulses. The failure of the refractory period to shorten with increasing rate (as occurs in the atria) further decreases the likelihood of an impulse traversing the AV node. Anatomically distinct AV nodal inputs, called the slow and fast pathways, are involved in the ventricular response to AF. The importance of these pathways has been demonstrated in radiofrequency ablation studies in which ablation reduced the number of beats that successfully reached the infranodal conduction system and the ventricles [117-120]. (See "Atrioventricular nodal reentrant tachycardia".) In addition to its intrinsic properties, the AV node is richly supplied and affected by both components of the autonomic nervous system. AV conduction is enhanced and refractoriness https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 15/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate reduced by the sympathetic fibers, and conduction reduced and refractoriness prolonged by the parasympathetic fibers. The net effect of the electrophysiologic properties of the AV node is that the rate of conduction into the specialized infranodal conduction system is (fortunately) much slower than the rate of the fibrillating atria. In some cases, the high degree of refractoriness in the AV node with AF results in high-grade or third-degree block. In this setting, the pacemaker that controls the ventricles is below the AV node. (See "The electrocardiogram in atrial fibrillation".) In patients with the preexcitation syndrome, the AV node is bypassed by "fast-response" tracts, which activate and reactivate much faster than the AV node and are therefore capable of rapid conduction. The development of AF in such a patient can result in very rapid transmission of atrial impulses to the ventricles [120] and can rarely cause ventricular fibrillation [15]. (See "The electrocardiogram in atrial fibrillation".) It is also important to recognize that the presence of an accessory pathway can increase the propensity for development of AF. In patients with AF who have Wolff-Parkinson-White (WPW) syndrome, catheter ablation of the accessory pathway is indicated to lower the sudden death risk but also to decrease the probability of recurrent AF. Unexpected ventricular rates The ventricular response to AF characteristically is irregularly irregular although it may appear regular in the presence of complete AV block. The usual ventricular rate in AF is between 90 and 170 beats per minute in the absence of AV node disease, drugs that affect conduction, or enhanced vagal inputs. Ventricular rates that are clearly outside this range suggest some concurrent problem: A ventricular rate below 60 beats per minute, in the absence of AV nodal blocking agents, suggests AV nodal disease that may be associated with the sinus node dysfunction. (See "Sinus node dysfunction: Epidemiology, etiology, and natural history".) A ventricular rate above 170 beats per minute suggests thyrotoxicosis, catecholamine excess, parasympathetic withdrawal, or the existence of an accessory bypass tract in the preexcitation syndrome. (See "Epidemiology, risk factors, and prevention of atrial fibrillation".) SPECIFIC CLINICAL SITUATIONS Late recurrent AF after catheter ablation The etiology of late recurrent atrial fibrillation (AF) following pulmonary vein isolation (PVI) has been debated. In some cases, triggering foci outside of the PVs may initiate AF [121-124]. Alternatively, persistence of the substrate for https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 16/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate maintaining AF (abnormal electrical properties of the atria themselves) may be more important than the triggering foci, especially in chronic AF. However, there is increasing evidence that when AF does recur late after PVI, it often represents incomplete electrical isolation of the PVs, either due to resumption of conduction across the ablation scar or to residual conduction in PVs that were not successfully ablated. Most [125-128], but not all [129], studies of the former mechanism support the hypothesis that resumption of PV-left atrial (LA) conduction is associated with an increased risk of recurrent AF. However, recurrent conduction across ablated lesions is more common than clinically evident recurrent AF [127,130]. Pre-existing LA scarring may predispose patients to late recurrence. In a series of 700 consecutive patients undergoing first-time PVI, scarring was detected in 6 percent [131]. These patients had a much higher rate of recurrence than those without scarring (57 versus 19 percent). Possible causes of scarring include atrial remodeling and inflammation. The patients with scarring had significant elevations in serum C-reactive protein (CRP) compared to those without scarring (5.9 versus 0.31 mg/L). This is consistent with other studies showing a relationship between serum CRP and AF [132]. (See "Epidemiology, risk factors, and prevention of atrial fibrillation", section on 'Inflammation and infection'.) After cardiac surgery AF occurs frequently (approximately one of four patients) after cardiac surgery. Nonuniform atrial conduction is greatest on days two and three in this setting, and the longest atrial conduction time is greatest on day three after open heart surgery; these abnormalities coincide with the time of greatest risk for AF [133]. The degree of atrial inflammation after surgery in dogs was associated with a proportional increase in the inhomogeneity of atrial conduction and in the duration of AF; antiinflammatory therapy decreased the inhomogeneity [134]. Nevertheless, the mechanism of AF in the postoperative period is likely multifactorial. It is important to note that in most of the patients, especially those without a prior history of AF, that the AF is self-limited, and antiarrhythmic drug therapy can usually be stopped two to three months following surgery when the inflammation has subsided. (See "Atrial fibrillation and flutter after cardiac surgery".) Hyperthyroidism It is well established that hyperthyroidism can increase susceptibility to development of AF. As a consequence, all patients with new onset AF should have some measure of thyroid function tested. Successful treatment of the hyperthyroidism often results in elimination of the AF. https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 17/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate Obesity Obesity has been associated with AF and it is possible that both are related mechanistically [135]. In a sheep model, weight gain was associated with increased left atrial volume, fibrosis, inflammatory infiltrates, and lipidosis. There was reduced conduction velocity in atrial tissue and increased inducible and spontaneous AF with obesity. Atrial endothelin-A and -B receptors, endothelin-1, atrial interstitial and cytoplasmic transforming growth factor beta1, and platelet-derived growth factor were higher with obesity. In a clinical study of 110 patients undergoing AF ablation versus 20 reference patients without AF, pericardial fat volumes were associated with AF, its chronicity, and its symptom burden. Pericardial fat predicted AF recurrence post-ablation [136]. Associations persisted after adjusting for body weight but body mass index was not associated with these outcomes in multivariate-adjusted models. In another report [137], weight management with subsequent weight loss was associated with improved AF symptom burden scores, symptom severity scores, number of episodes, and cumulative duration of AF. This preliminary information does not yet prove that obesity causes AF by any specific mechanism. In a study of atrial sheep myocytes, acute, short-term incubation in free fatty acids resulted in no differences in passive or active properties of isolated left atrial myocytes but stearic acid reduced membrane capacitance and abbreviated the action potential duration, likely due to a reduction of the L-type calcium and of the transient outward potassium currents [138]. GENETICS OF AF Over the last decade, a preponderance of evidence suggests a large genetic contribution to atrial fibrillation (AF) [139,140]. Having a family member with AF is associated with a 40 percent increased risk for the arrhythmia [141]. Initially, traditional genetic techniques such as linkage analysis led to the discovery of rare, monogenic causes of AF. The first such study identified a genetic locus for AF using a series of related families with early onset AF [142]. A later study identified the first gene for familial AF [143]. Using a large Chinese kindred with autosomal dominant AF, they found a gain-of-function mutation in KCNQ1 (the gene encoding the subunit of the potassium channel current, I ). Since then, several additional gain-of-function variants Ks have been identified in KCNQ1 [144,145]. In addition to KCNQ1, mutations have been identified in other potassium channels genes, including KCNA5 [146], KCND3 [147], and KCNJ2 [148], and accessory subunits KCNE1 [149], KCNE2 [150], KCNE3 [151], and KCNE5 [152,153]. The majority of these functionally validated, AF-associated potassium channel variants have a gain-of-function channel, with an expected shortening of the atrial action potential duration and atrial refractory period. Variation in sodium channel subunits has also been identified as an important factor in the development of familial AF, with AF-causing variants observed in both the https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 18/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate major cardiac sodium channel alpha subunit SCN5A [154] and its associated beta subunits [155,156]. Several variants have also been identified in genes that do not directly alter the atrial action potential, but instead would be expected to cause AF through alternative mechanisms, eg, somatic mutations in GJA5, which encodes the gap junctional protein; connexin 40, a frameshift mutation that resulted in early truncation of NPPA [157], which encodes for the precursor for atrial natriuretic peptide; and genetic variation in several developmentally related cardiac transcription factors, ie, NKX2.5, PITX2, GATA4, GATA5, and GATA6 [156,158,159]. Genome-wide association studies (GWAS) have been used to identify genetic loci associated with AF. GWAS rely on the unbiased comparison of common single-nucleotide polymorphisms (SNPs) throughout the genome, with SNPs occurring with different frequency in individuals with a disease versus controls being used to localize disease-related genetic loci. The first GWAS performed for AF identified a region on chromosome 4q25, which was associated with AF in those of European and Asian descent [160]. Subsequently, these findings were broadly replicated in individuals of European, Asian, and African descent [161,162]. Genetic variants on chromosome 4q25 that are most significantly associated with AF reside about 150 kilobases upstream of the nearest gene PITX2. PITX2 encodes the paired-like homeodomain transcription factor 2, which helps determine cardiac laterality, suppresses the default expression of a sinoatrial nodal gene programme in the left atrium, and encodes the pulmonary venous myocardium [163]. In addition, PITX2 is associated with formation of the pulmonary veins. These findings are particularly interesting in light of the fact that AF triggers frequently arise in the pulmonary veins. In addition to the role of PITX2 in development, studies demonstrate a role for the PitX2c transcript in expression of gene-encoding ion channels, calcium cycling proteins, and gap junctions; these direct electrophysiological influences likely lead to formation of substrate for triggered activity as well as reentry [164]. Related analysis identified the same genomic region as being associated with an increased risk of cardioembolic stroke [156,165] and a prolonged PR interval [166]. To date, GWAS have identified 14 genomic regions of susceptibility for AF, with 17 independent signals at these loci [167]. These include the ZFHX3 gene that encodes a zinc finger homeobox transcription factor [168], the KCNN3 gene that encodes the SK3 potassium channel [169], and the PRRX1 gene that encodes a member of the paired-related homeobox gene family [168]. Whole exome and genome sequencing has been increasingly used to identify rare variants associated with AF [156]. For example, Oleson et al reported a much higher prevalence of rare variants in genes associated with AF (KCNQ1, KCNH2, SCN5A, KCNA5, KCND3, KCNE1, 2, 5, KCNJ2, SCN1-3B, NPPA, and GJA5) in early onset, lone AF patients than in the background population [170]. This approach is beginning to identify rare candidate variants in genes not previously linked to other types of https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 19/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate Mendelian disease and thus may offer new insights into AF pathogenesis and disease pathways that could ultimately provide novel therapeutic targets for this common condition. A 2018 meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than 500,000 individuals, sought to identify AF-associated genes at the GWAS loci by performing RNA sequencing and expression quantitative trait locus analyses in 101 left atrial samples (which is the most relevant tissue for AF) [171]. A transcriptome-wide analysis was also performed; this analysis identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci-implicated genes enriched within cardiac developmental, electrophysiological, contractile, and structural pathways. SUMMARY The precise mechanisms by which age and other risk factors such as hypertension, coronary artery or valvular heart disease, or heart failure increase the propensity for development of atrial fibrillation (AF) are poorly understood ( figure 1). These conditions may affect the triggers of or the substrate for the maintenance of AF. (See 'Introduction' above.) These mechanisms are complex and involve a dynamic interplay between the triggers and substrate abnormalities. It is likely that short-lived episodes are due to specific triggers, including autonomic perturbations, focal discharges, specific reentry circuits in the pulmonary veins (PVs), and effects of stretch, whereas inflammation, dilatation, fibrosis, repolarization abnormalities, and conduction disturbances allow for perpetuation of episodes of AF. (See 'Mechanisms of atrial fibrillation: triggers and substrates' above.) AF is most often initiated (triggered) by rapid firing from the PV. (See 'Triggers of AF' above.) Paroxysmal AF commonly precedes chronic AF. This suggests that, in addition to other predisposing factors, AF may play a role in its own natural history. (See 'Electrical remodeling' above.) The autonomic nervous system likely influences the initiation and perpetuation of AF. (See 'Role of the autonomic nervous system' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 20/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate 1. Wasmer K, Eckardt L, Breithardt G. Predisposing factors for atrial fibrillation in the elderly. J Geriatr Cardiol 2017; 14:179. 2. Goudis CA, Korantzopoulos P, Ntalas IV, et al. Obesity and atrial fibrillation: A comprehensive review of the pathophysiological mechanisms and links. 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JAMA 2013; 310:2050. https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 30/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate 138. O'Connell RP, Musa H, Gomez MS, et al. Free Fatty Acid Effects on the Atrial Myocardium: Membrane Ionic Currents Are Remodeled by the Disruption of T-Tubular Architecture. PLoS One 2015; 10:e0133052. 139. Ellinor PT, Yoerger DM, Ruskin JN, MacRae CA. Familial aggregation in lone atrial fibrillation. Hum Genet 2005; 118:179. 140. Darbar D, Herron KJ, Ballew JD, et al. Familial atrial fibrillation is a genetically heterogeneous disorder. J Am Coll Cardiol 2003; 41:2185. 141. Lubitz SA, Yin X, Fontes JD, et al. Association between familial atrial fibrillation and risk of new-onset atrial fibrillation. JAMA 2010; 304:2263. 142. Brugada R, Tapscott T, Czernuszewicz GZ, et al. Identification of a genetic locus for familial atrial fibrillation. N Engl J Med 1997; 336:905. 143. Chen YH, Xu SJ, Bendahhou S, et al. KCNQ1 gain-of-function mutation in familial atrial fibrillation. Science 2003; 299:251. 144. Hasegawa K, Ohno S, Ashihara T, et al. A novel KCNQ1 missense mutation identified in a patient with juvenile-onset atrial fibrillation causes constitutively open IKs channels. Heart Rhythm 2014; 11:67. 145. Bartos DC, Duchatelet S, Burgess DE, et al. R231C mutation in KCNQ1 causes long QT syndrome type 1 and familial atrial fibrillation. Heart Rhythm 2011; 8:48. 146. Christophersen IE, Olesen MS, Liang B, et al. Genetic variation in KCNA5: impact on the atrial-specific potassium current IKur in patients with lone atrial fibrillation. Eur Heart J 2013; 34:1517. 147. Olesen MS, Refsgaard L, Holst AG, et al. A novel KCND3 gain-of-function mutation associated with early-onset of persistent lone atrial fibrillation. Cardiovasc Res 2013; 98:488. 148. Deo M, Ruan Y, Pandit SV, et al. KCNJ2 mutation in short QT syndrome 3 results in atrial fibrillation and ventricular proarrhythmia. Proc Natl Acad Sci U S A 2013; 110:4291. 149. Olesen MS, Bentzen BH, Nielsen JB, et al. Mutations in the potassium channel subunit KCNE1 are associated with early-onset familial atrial fibrillation. BMC Med Genet 2012; 13:24. 150. Yang Y, Xia M, Jin Q, et al. Identification of a KCNE2 gain-of-function mutation in patients with familial atrial fibrillation. Am J Hum Genet 2004; 75:899. 151. Lundby A, Ravn LS, Svendsen JH, et al. KCNE3 mutation V17M identified in a patient with lone atrial fibrillation. Cell Physiol Biochem 2008; 21:47. 152. Ravn LS, Aizawa Y, Pollevick GD, et al. Gain of function in IKs secondary to a mutation in KCNE5 associated with atrial fibrillation. Heart Rhythm 2008; 5:427. https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 31/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate 153. Enriquez A, Antzelevitch C, Bismah V, Baranchuk A. Atrial fibrillation in inherited cardiac channelopathies: From mechanisms to management. Heart Rhythm 2016; 13:1878. 154. Darbar D, Kannankeril PJ, Donahue BS, et al. Cardiac sodium channel (SCN5A) variants associated with atrial fibrillation. Circulation 2008; 117:1927. 155. Olesen MS, Holst AG, Svendsen JH, et al. SCN1Bb R214Q found in 3 patients: 1 with Brugada syndrome and 2 with lone atrial fibrillation. Heart Rhythm 2012; 9:770. 156. Tucker NR, Ellinor PT. Emerging directions in the genetics of atrial fibrillation. Circ Res 2014; 114:1469. 157. Hodgson-Zingman DM, Karst ML, Zingman LV, et al. Atrial natriuretic peptide frameshift mutation in familial atrial fibrillation. N Engl J Med 2008; 359:158. 158. Huang RT, Xue S, Xu YJ, et al. A novel NKX2.5 loss-of-function mutation responsible for familial atrial fibrillation. Int J Mol Med 2013; 31:1119. 159. Zhou YM, Zheng PX, Yang YQ, et al. A novel PITX2c loss of function mutation underlies lone atrial fibrillation. Int J Mol Med 2013; 32:827. 160. Gudbjartsson DF, Arnar DO, Helgadottir A, et al. Variants conferring risk of atrial fibrillation on chromosome 4q25. Nature 2007; 448:353. 161. K b S, Darbar D, van Noord C, et al. Large scale replication and meta-analysis of variants on chromosome 4q25 associated with atrial fibrillation. Eur Heart J 2009; 30:813. 162. Delaney JT, Jeff JM, Brown NJ, et al. Characterization of genome-wide association-identified variants for atrial fibrillation in African Americans. PLoS One 2012; 7:e32338. 163. Bapat A, Anderson CD, Ellinor PT, Lubitz SA. Genomic basis of atrial fibrillation. Heart 2018; 104:201. 164. Gutierrez A, Chung MK. Genomics of Atrial Fibrillation. Curr Cardiol Rep 2016; 18:55. 165. Shi L, Li C, Wang C, et al. Assessment of association of rs2200733 on chromosome 4q25 with atrial fibrillation and ischemic stroke in a Chinese Han population. Hum Genet 2009; 126:843. 166. Kolek MJ, Parvez B, Muhammad R, et al. A common variant on chromosome 4q25 is associated with prolonged PR interval in subjects with and without atrial fibrillation. Am J Cardiol 2014; 113:309. 167. Tucker NR, Clauss S, Ellinor PT. Common variation in atrial fibrillation: navigating the path from genetic association to mechanism. Cardiovasc Res 2016; 109:493. 168. Ellinor PT, Lunetta KL, Albert CM, et al. Meta-analysis identifies six new susceptibility loci for atrial fibrillation. Nat Genet 2012; 44:670. https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 32/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate 169. Ellinor PT, Lunetta KL, Glazer NL, et al. Common variants in KCNN3 are associated with lone atrial fibrillation. Nat Genet 2010; 42:240. 170. Olesen MS, Andreasen L, Jabbari J, et al. Very early-onset lone atrial fibrillation patients have a high prevalence of rare variants in genes previously associated with atrial fibrillation. Heart Rhythm 2014; 11:246. 171. Roselli C, Chaffin MD, Weng LC, et al. Multi-ethnic genome-wide association study for atrial fibrillation. Nat Genet 2018; 50:1225. Topic 16402 Version 27.0 https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 33/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate GRAPHICS AF mechanisms Overview of mechanisms of AF. Four different positive-feedback loops are proposed as 2 the main driving forces for the atrial remodeling process. Enhanced Ca + loading during AF is believed to underlie most of the cellular proarrhythmic mechanisms (trigger loop). The main process in the electrical loop is an altered contribution of ion channels to the 2 action potential configuration that protects atrial myocytes against excessive Ca + loading. Abbreviation of the action potential facilitates re-entry and thereby promotes AF. In the structural loop, chronic atrial stretch activates numerous signaling cascades that produce alterations of the extracellular matrix and conduction disturbances, also facilitating re-entrant mechanisms. The main changes of the contractile properties of the heart are loss of atrial contractility which increases atrial compliance and the development of a ventricular tachycardiomyopathy, both of which increase stretch in the atrial wall. The circular positive-feedback enhancement of these pathophysiological changes explains the general tendency of AF to become more stable with time. It should be noted that the different loops are interconnected by mechanisms that are part of more than one loop. For example, increased Ca + loading enhances trigger activity 2 (trigger loop) and also results in a change in the ion channel population and activity (electrical loop). Re-entrant mechanisms are promoted by both shortening of refractoriness (electrical loop) as well as by conduction disturbances resulting from https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 34/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate tissue fibrosis (structural loop). Like in a system of meshing gear wheels, one loop will drive the other, leading to progression of the arrhythmia. However, the proposed system of gear wheels does not start to move spontaneously. Structural heart diseases, arrhythmias, aging, or inherited diseases are required to initiate movement of one or more of these wheels. When the pathophysiological alterations eventually reach a certain threshold, AF will ensue. Ulrich Schotten, Sander Verheule, Paulus Kirchhof, and Andreas Goette. Pathophysiological Mechanisms of Atrial Fibrillation: A Translational Appraisal. Physiol Rev January 2011 91:265-325 [PRV1/2011]. Reproduced with permission. Copyright 2011 The American Physiological Society. Graphic 63675 Version 5.0 https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 35/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate AF remodeling 2+ Mechanisms underlying ATR. Rapid atrial rates increase potentially cytotoxic Ca loading. Autoprotective I changes (I reductions occur via rapidly developing functional Ca,L inactivation) and more slowly developing changes in gene and protein Ca,L expression. Decreased I shortens refractoriness and reduces the wavelength (WL), which allows for smaller and 2+ reduces Ca loading but decreases APD. Diminished APD Ca,L more atrial reentry circuits, thus making AF unlikely to terminate. Atrial tachycardia also increases inward-rectifier currents such as I APD and promotes AF. and I , which further reduces K1 K,ACh,c RP: refractory period; WL: wavelength. Reproduced with permission from: Nattel S, Burstein B, Dobrev D. Atrial Remodeling and Atrial Fibrillation: Mechanisms and Implications. Circ Arrhythm Electrophysiol 2008; 1:62. Copyright 2008 Lippincott Williams & Wilkins. Graphic 51670 Version 8.0 https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 36/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate Signal averaged electrocardiogram predicts atrial fibrillation after coronary artery bypass graft (CABG) surgery The incidence of atrial fibrillation (AF) after coronary artery bypass graft surgery is directly related to the duration of the P wave on a signal averaged ECG. Data from Zaman AG, Archbold RA, Helft G, et al. Circulation 2000; 101:1403. Graphic 60431 Version 4.0 https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 37/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate Atrial activation in atrial fibrillation Spread of activation through right (upper half) and left (lower half) atria during stable atrial fibrillation. These activation maps show propagation of impulse through the atria, as visualized by color isochrones of 10 milliseconds (ms). White arrows indicate general direction of wavelets. Asterisks represent sites of impulse fragmentation and development of new wavelets. Redrawn from Allissie MA, Lammers WJEP, Bonke FIM, et al. In: Cardiac Arrhythmias, Grane &Stratton, Orlando, 1985, p. 265. Graphic 59310 Version 2.0 https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 38/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate Two types of reentry in atrial fibrillation The isochronal activation maps demonstrate two types of reentry in atrial fibrillation. Map A shows random reentry with three simultaneous wavefronts (black arrows) activating most of the recording area. Map B also shows three simultaneous wavefronts, but they are coming from different directions than those in map A. Maps C and D show two consecutive cycles of complete reentry. The wave of activation (black arrow) spreads clockwise in a circular fashion around a line of unexcited tissue. Reproduced with permission from Holm M, Johansson R, Brandt J, et al. Eur Heart J 1997; 18:290. Graphic 73931 Version 2.0 https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 39/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate Atrial electogram morphology in atrial fibrillation The morphology of unipolar electrograms recorded during atrial fibrillation reflect different patterns of conduction, as demonstrated by the isochrone maps. Black arrows indicate the direction of activation. Single potentials are indicative of rapid uniform conduction. Short doubles result from collision of the wavefronts along a line of collision (map A). Long doubles are due to conduction block (Map B). Fragmented electrograms refect multiple discrete deflections that may result from impulse conduction around a pivotal point (map C) or from slow or delayed conduction (map D). Reproduced with permission from Konings KTS, Smeets JLRM, Penn OC, et al. Circulation 1997; 95:1231. Graphic 52152 Version 2.0 https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 40/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate Schema of normal impulse conduction in the heart The sinoatrial node (SAN) generates an action potential that is conducted through the right and left atria, resulting in atrial contraction. The impulse is then conducted through the atrioventricular node (AVN), activating the ventricular myocardium, resulting in contraction of the right and left ventricle. SVC: superior vena cava; IVC: inferior vena cava; PV: pulmonary veins; LAA: left atrial appendage; RAA: right atrial appendage. Graphic 57781 Version 2.0 https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 41/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate Electrical activity in atrial fibrillation During atrial fibrillation there are multiple reentrant circuits within the right and left atrium, resulting in nonuniform activitation of the atrial myocardium. These circuits, which produce multiple wavelets, often occur around the normal structures of the atrial including the orifices of the superior (SVC) and inferior (IVC) vena cavae, the orifice of the pulmonary veins (PVs), and the right (RAA) and left (LAA) atrial appendages. Graphic 58689 Version 1.0 https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 42/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate Noncontact endocardial activation map of focal atrial fibrillation The noncontact endocardial activation map of the half-open left atrium shows that the initial depolarization from an ectopic focus spreads centrifugally from the ostium of the right upper pulmonary vein (RUP), indicated by the white-blue color. LUP: left upper pulmonary vein. Reproduced with permission from Schneider MA, Ndrepepa G, Zrenner B, et al. Noncontact mapping-guided catheter ablation of atrial brillation associated with left atrial ectopy. J Cardiovascular Electrophysiol 2000; 11:475. Copyright 2000 Futura Publishing Company, Inc. Graphic 55997 Version 2.0 https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 43/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate Activation patterns in atrial fibrillation Isochronal activation maps obtained from the right atrial free wall during atrial fibrillation show four distinct patterns of myocardial activation, indicated by black arrows. Activation from a localizable site which spreads in all directions away from the site is termed focal atrial activation (upper left). Type I activation is a single broad wavefront that propagates without conduction delay (upper right). Type II activation is a single wavefront that is associated with conduction slowing or block, or with two wavefronts (lower left). Type III activation results from the presence of three or more wave fronts associated with areas of slow and blocked conduction (lower right). Reproduced with permission from Holm M, Johansson R, Brandt J, et al. Eur Heart J 1997; 18:290. Graphic 66498 Version 2.0 https://www.uptodate.com/contents/mechanisms-of-atrial-fibrillation/print 44/45 7/5/23, 10:46 AM Mechanisms of atrial fibrillation - UpToDate Contributor Disclosures Brian Olshansky, MD Other Financial Interest: AstraZeneca [Member of the DSMB for the DIALYZE trial]; Medtelligence [Cardiovascular disease]. All of the relevant financial relationships listed have been mitigated. Rishi Arora, MD No relevant financial relationship(s) with ineligible companies to disclose. Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Hugh Calkins, MD Grant/Research/Clinical Trial Support: Adagio Medical [Atrial fibrillation]; Boston Scientific [ARVC]; Farapulse [Atrial fibrillation]; Medtronic [Atrial fibrillation]. Consultant/Advisory Boards: Abbott [Atrial fibrillation]; Atricure [Atrial fibrillation]; Biosense Webster [Catheter ablation]; Boston Scientific [ARVC and atrial fibrillation]; Medtronic [Atrial fibrillation]; Sanofi [Atrial fibrillation]. Other Financial Interest: Atricure [Lecture honoraria]; Biosense Webster [Lecture honoraria]; Boston Scientific [Lecture honoraria]; Medtronic [Lecture honoraria]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. 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7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Reentry and the development of cardiac arrhythmias : Philip J Podrid, MD, FACC : Bernard J Gersh, MB, ChB, DPhil, FRCP, MACC : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Feb 03, 2023. INTRODUCTION Cardiac arrhythmias are generally produced by one of three mechanisms: enhanced automaticity, triggered activity, or reentry. Reentry, due to a circuit within the myocardium, occurs when a propagating impulse fails to die out after normal activation of the heart and persists as a result of continuous activity around the circuit to re-excite the heart after the refractory period has ended; it is the electrophysiologic mechanism responsible for the majority of clinically important arrhythmias. Included among these arrhythmias are atrial fibrillation (where there are multiple small circuits in the left and right atria), atrial flutter (where there is a single circuit in the right atrium), atrioventricular (AV) nodal reentry (where the circuit is in the AV node as a result of dual AV nodal pathways), AV reentry (which involves a bypass tract and the normal AV node His-Purkinje system), ventricular tachycardia (with a circuit in the ventricular myocardium after myocardial infarction [MI] with the presence of left ventricular scar or in the presence of a cardiomyopathy due to fibrosis or infiltration), and ventricular fibrillation. The first demonstration of reentry in its simplest form (ie, the ring model) probably occurred in 1906 following the application of a stimulus to tissue from a jellyfish which initiated rhythmic contraction [1]. However, reentry was first conceived as a mechanism for arrhythmias in 1913 when it was recognized that reentrant tachycardias arise from circular electrical pathways, often initiated by a blocked impulse [2]. It was subsequently realized that reentry tachycardias may also be due to other mechanisms, including functional or leading circle circuits and abnormal electrical circuits caused by diseased myocardium. https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 1/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate The definition and characteristics of the different reentry circuits responsible for the most clinically significant arrhythmias are presented here, along with the electrophysiologic properties of these arrhythmias. The clinical presentation and management of the individual arrhythmias are discussed separately. (See "Overview of atrial flutter" and "Atrioventricular nodal reentrant tachycardia" and "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway" and "Sustained monomorphic ventricular tachycardia in patients with structural heart disease: Treatment and prognosis" and "Atrial fibrillation: Overview and management of new-onset atrial fibrillation".) DEFINITION AND CHARACTERISTICS Reentrant tachycardia (variously named reentrant excitation, reciprocating tachycardia, circus movement, and reciprocal or echo beats) is defined as a continuous repetitive propagation of an excitatory wave traveling in a circular path (reentrant circuit), returning to its site of origin to reactivate that site [1]. The one event crucial to the development of a reentrant tachycardia is the failure of a group of fibers to activate during a depolarization wave. The initiation of a reentrant arrhythmia also requires the presence of myocardial tissue with the following electrophysiologic properties ( figure 1) [3-6]: Adjacent tissue or pathways must have different electrophysiologic properties (conduction and refractoriness) and be joined proximally and distally, forming a circuit. These circuits may be fixed or stationary or may move within the myocardial substrate (as occurs with spiral waves). Each involved pathway of the circuit must be capable of conducting an impulse in an antegrade and retrograde direction. Transient or permanent unidirectional block of one pathway must exist as a result of heterogeneity of electrophysiologic properties of the myocardium. This event usually results when one electrical pathway has either a prolonged refractory period or a prolonged repolarization time, producing a wave which only travels down the remaining pathway. Conduction velocity in the normal unblocked pathway must be slow enough relative to the refractoriness of the blocked pathway to allow recovery of the previously blocked pathway. The impulse can then be conducted through the previously blocked but recovered pathway in a retrograde direction. https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 2/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate Retrograde conduction in this previously blocked pathway must be slow enough to allow the normal pathway to recover, and again be capable of being excited. A sustained reentrant arrhythmia will occur if these conditions are present and maintained. In general, the onset and offset of the arrhythmia are abrupt. In contrast, when enhanced automaticity is the mechanism for the arrhythmia, there are often warm-up and cool-down phases (gradual increase and gradual decrease in the rate of the arrhythmia). Patients who develop reentrant arrhythmias usually have an anatomic or electrical (functional) abnormality, which could be caused by an accessory pathway, by an abnormal separation of adjacent fibers that may form two limbs of a reentrant circuit, or by juxtaposed fibers that possess different electrophysiologic characteristics, often resulting from abnormalities of the myocardium and Purkinje fibers as the result of a disease process. Susceptible patients with appropriate underlying abnormalities usually do not suffer from incessant tachycardia because the different electrophysiologic mechanisms required for the initiation and maintenance of a reentrant tachycardia are infrequently present at exactly the same time. However, changes in heart rate or autonomic tone, ischemia, electrolyte or pH abnormalities, or the occurrence of a premature beat (which results in transient changes in the electrophysiologic properties of the myocardium) may be sufficient to initiate a reentrant tachycardia. In fact, premature depolarizations frequently initiate these tachyarrhythmias when there are appropriate electrophysiologic conditions (ie, slow conduction and unidirectional block). They are associated with more rapid depolarization (as they are early or premature) that may block in one pathway (ie, unidirectional block), conduct through the second pathway, retrogradely enter the first pathway, and then reenter the second pathway. CRITERIA FOR DIAGNOSIS The initial criteria for the diagnosis of reentry proposed in the early 20th century are still valid, but are often difficult to prove [1]. As a result, the following twelve conditions in the electrophysiology laboratory were proposed to either prove or to identify the existence of a reentrant tachycardia [7]: Activation of the myocardium mapped in one direction around a continuous loop. Correlation of continuous electrical activity occurring when the tachycardia develops. Correlation of unidirectional block with initiation of reentry. Initiation and termination by premature stimulation. https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 3/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate Dependence of initiation of the arrhythmia on the site of pacing. Inverse relationship between the coupling interval of the initiating premature beat and the interval to the first tachycardia beat. Resetting of the tachycardia by a premature beat with an inverse relationship between the coupling interval of the premature beat and the cycle length of the first or return beat of the tachycardia. Fusion between a premature beat and the tachycardia beat followed by resetting. Transient entrainment (with external overdrive pacing, the ability to enter the reentrant circuit and "capture" the circuit, resulting in a tachycardia at the pacing rate and having fused or paced complexes). Abrupt termination by premature stimulation or the termination of entrainment. Dependence of initiation on a critical slowing of conduction in the circuit. Similarity with experimental models in which reentry is proven and is the only mechanism of tachycardia. The segment of the reentrant circuit that is, at any given time, no longer refractory and is capable of being excited is called the excitable gap [6,8]. Slowing of impulse conduction or shortening of refractoriness will increase the excitable gap. The longer the excitable gap, the more likely it is for an extrastimulus to enter the reentrant circuit and initiate or terminate a reentrant arrhythmia. In addition, entrainment is more likely to occur when the excitable gap is longer. TYPES OF REENTRY Reentry tachycardias have been divided into two different forms based upon the type of anatomic substrate used for the development of the arrhythmia: anatomic or functional. The original ring model requires the presence of an anatomic obstruction (due to a structural abnormality). There are also several models of functional reentry (due to electrophysiologic abnormalities) including the leading circle, anisotropic conduction, figure of eight, and spiral wave ( figure 1 and figure 2). Anatomic reentry Anatomic reentrant tachycardia most closely resembles the original description of reentry arrhythmia because it requires an anatomic obstacle, such as an area of fibrosis [1]. This discrete anatomic block creates a surrounding circular pathway, resulting in a https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 4/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate fixed length and location of the reentrant circuit. A tachycardia is initiated when a depolarization wave splits into two limbs after going around this obstacle, creating a circus movement [9,10]. Tachycardia rates are determined both by the wavelength (defined as conduction velocity and refractory period) and the length of the circuit or the pathlength. Examples of anatomic reentry are supraventricular tachycardia associated with an accessory pathway (preexcitation syndromes) called atrioventricular reentrant tachycardia (AVRT), AV nodal reentrant tachycardia (AVNRT; associated with dual AV nodal pathways), typical atrial flutter originating in the right atrium due to an area of fibrosis in the lower portion of the atrium (termed isthmus), atrial fibrillation resulting from multiple reentrant circuits in the atria, ventricular tachycardia (VT) originating within the His-Purkinje system (bundle branch tachycardia), and VT originating at the terminal portion of the His-Purkinje system or around an area of infarcted tissue (scar mediated). There is often a long excitable gap associated with anatomic reentry. Functional reentry Functional reentry depends upon the intrinsic heterogeneity of the electrophysiologic properties of cardiac muscle (ie, dispersion of excitability or refractoriness) as well as anisotropic differences in intercellular resistances. There is no anatomic obstacle present. Examples of functional reentry include atypical atrial flutter, some cases of atrial fibrillation (AF), and VT in a structurally normal heart. Functional circuits have the following properties: They tend to be small, rapidly conducting, and unstable in that the waves they generate may fragment, establishing other areas of reentry. Circuit times and hence tachycardia rates are significantly dependent upon the refractory period of the involved tissue. The location and size of these tachycardias vary due to the absence of an anatomic block. There is usually a short excitable gap associated with functional reentry. One animal study reported the following additional properties [11]: A thin layer of activation near the core or central region of the circuit is responsible for the maintenance of reentry; the remaining portion of the tissue is activated passively by the outward propagation of wavefronts away from the core. Access to the tissue near the core is essential for termination of reentry by a point stimulation. https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 5/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate To terminate reentry with a stimulus applied away from the core, the stimulus must occur at certain critical coupling intervals and the line connecting the stimulus and the core must be roughly parallel to the fiber orientation. Leading circle concept In this model, functional reentry involves the propagation of an impulse around a functionally determined region of unexcitable tissue or a refractory core and among neighboring fibers with different electrophysiologic properties [4-6]. The excitation wave then travels in the smallest possible circuit with the head of the impulse having just enough strength to excite relatively refractory tissue ahead of it. Thus, the "head of the circulating wavefront is continuously biting its tail of refractoriness" ( figure 1) [6]. There is a small excitable gap in this setting. The circulating wave activates peripheral tissue but also gives rise to wavelets that collide at the center, rendering it refractory. Anisotropic reentry Anisotropic reentry is determined by the orientation of myocardial fibers and the manner in which these fibers and muscle bundles are connected to each other [12,13]. In general, the electrical resistances between cells is dependent upon fiber orientation (ie, cell- to-cell communication is more rapid between cell that are parallel to each other), while communication is slower when cells are transverse to each other [14,15]. Anisotropic reentry occurs in myocardium composed of tissue with structural features different from those of adjacent tissue, resulting in variations in conduction velocities and repolarization properties (referred to as anisotropic myocardium) ( figure 2) [16]. As an example, an impulse propagating parallel to the long axis of the myocardial tissue will typically travel three to five times faster than the same impulse traveling in the transverse direction. Therefore, anatomic anisotropy can cause heterogeneity of electrophysiologic properties which can result in blocked impulses and slowed conduction, thereby setting the stage for reentry [17]. Figure of eight reentry This model of reentry involves two counter rotating circuits around a center that is anatomically damaged, but is common to both circuits [18]. The reentrant beat produces a wavefront that circulates in both directions around a long line of functional conduction block and rejoins on the distal side of the block. This results in two concomitant circuits, forming a "figure of eight." Spiral wave (rotor) activity In this model of reentry, there are concentric circular waves that result in reverberators or rotating vortices of electrical activity [19-21]. Spiral waves, which typically describe reentry in two dimensions, can be initiated in an inhomogeneous, excitable medium whenever there is disruption of the wavefront. Spiral waves rotate around an organizing center or core, which includes cells with a transmembrane potential that has a reduced amplitude, duration and rate of depolarization (ie, slow upstroke velocity of phase 0); https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 6/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate these cells are potentially excitable, but remain unexcited [22]. Anisotropy and anatomic obstacles can modify the characteristics and spatiotemporal behavior of the spiral. In addition, the spiral waves may give rise to daughter spirals which can result in disorganized electrical activity; this may be the mechanism for ventricular fibrillation [23]. Spirals may be stationary (the possible mechanism for monomorphic VT), or may continuously drift or migrate away from their origin (possibly the mechanism for polymorphic VT or AF), or may be anchored, initially drifting and then becoming stationary by anchoring to a small obstacle ( waveform 1) [24]. Phase two reentry Phase 2 reentry is a phenomenon largely related to Brugada syndrome and is discussed separately. (See "Brugada syndrome: Epidemiology and pathogenesis", section on 'Ventricular arrhythmias and phase 2 reentry' and "Brugada syndrome: Clinical presentation, diagnosis, and evaluation".) CLINICAL ARRHYTHMIAS DUE TO REENTRY Reentry can cause many clinically significant arrhythmias including sinus node reentry, atrial flutter, atrial fibrillation (AF), AV nodal reentry (AVNRT), AV reentry using an accessory bypass tract (AVRT), and ventricular tachyarrhythmias ( figure 3). Sinus node reentry SA nodal reentrant tachycardia is due to a reentrant circuit that is in the area of the sinus node and involves this structure and the sinoatrial junction. Thus, electrophysiologic studies reveal atrial activation and conduction that is identical to sinus rhythm, with the earliest recorded atrial activation in the reentrant tachycardia being located near the sinus node [25]. As with any reentrant arrhythmia, SA nodal reentrant tachycardia is usually initiated by a premature atrial stimulus, but also rarely by a ventricular premature stimulus [26,27]. It is clinically and electrocardiographically difficult to distinguish this arrhythmia from sinus tachycardia. Both have identical P waves at a rate that is usually less than 150 beats/min. The abrupt onset and termination of the reentrant arrhythmia are the only clinical distinctions from sinus tachycardia, which results from enhanced sympathetic tone and has an onset and termination that are gradual and not abrupt ( waveform 2). (See "Sinoatrial nodal reentrant tachycardia (SANRT)".) Atrial flutter The reentrant circuit resulting in atrial flutter is typically localized within the right atrium. It results from a circuit that is due to an area of fibrosis and slow conduction (isthmus) that is located between the tricuspid annulus and area of the inferior vena caval https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 7/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate insertion. Details regarding the electrocardiographic and electrophysiologic features of atrial flutter are discussed separately. (See "Electrocardiographic and electrophysiologic features of atrial flutter".) Atrial fibrillation AF is currently felt to be caused by multiple leading circle reentrant impulses (ie, the multiple wavelet theory) ( figure 4) [28,29]. Coarse AF, which is usually seen when the AF is more recent in onset, is thought to be caused by a relatively small number of large sized waves, while fine fibrillation (when usually indicated AF that has been present for a longer period of time) is caused by many small, fragmented waves ( waveform 3A-B). It has been estimated that a minimum of six circuits is needed to sustain AF [29]. (See "The electrocardiogram in atrial fibrillation".) AV nodal reentry AVNRT, one of the most frequent paroxysmal supraventricular tachycardias, is caused by a reentrant circuit located within the AV node. It is the result of dual AV nodal pathways (which are linked proximally and distally within the AV node), both of which conduct in an antegrade and retrograde direction [30-35]. The slow or alpha pathway typically has a slower conduction velocity and shorter refractory period (faster recovery) than the faster conducting beta pathway, which has a faster conduction velocity but a longer refractory period. These two pathways are linked proximally and distally within the AV junction. AVNRTs have been divided into two types based upon their mechanism of conduction [36]. (See "Atrioventricular nodal reentrant tachycardia".) The common type, comprising approximately 90 percent of all AVNRTs, is usually initiated by a premature atrial complex (also referred to a premature atrial beat, premature supraventricular complex, or premature supraventricular beat) that reaches the AV node when the fast pathway is still refractory and hence travels down the slow pathway to activate the ventricles in an antegrade fashion. If the impulse reaches the distal end of the circuit when the fast pathway has recovered, it enters the fast pathway and is conducted in a retrograde direction to activate the atrial in a retrograde direction and simultaneously with ventricular activation. If the slow pathway has recovered by the time the impulse reaches the proximally portion of the circuit, the impulse may also reenter the slow pathway. If this situation repeats, an AV nodal reentrant tachycardia results. As ventricular activation is via the slow pathway and retrograde atrial activation is via the fast pathway, this is termed "slow-fast" ( figure 5 and figure 6). The uncommon type of AVNRT uses the fast pathway in an antegrade manner and the slow pathway in the retrograde manner (fast-slow) ( figure 7 and figure 8). This may be initiated by a premature ventricular complex/contraction (PVC; also referred to a premature https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 8/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate ventricular beats or premature ventricular depolarizations) that is blocked in the fast pathway and hence travels up to the atrial via the slow pathway and then down to the ventricles via the fast pathway (fast-slow). Atrioventricular reentry using an accessory bypass tract The presence of an accessory bypass tract, which has electrophysiologic properties that are different from those of the normal AV node-His Purkinje system and resemble the properties of Purkinje fibers, favors the development of reentrant tachycardia by providing two limbs of a possible reentrant circuit: one limb is the AV node and His-Purkinje system; and the other is the bypass tract which directly connects an atrium and a ventricle, bypassing the AV node [37,38]. The circuit, known as a macroreentrant circuit, is formed by a proximal connection via the atria and a distal connection within the ventricular myocardium. Accessory bypass tracts can be found along the perimeter of both the mitral and tricuspid valves or within the ventricular myocardium (bundle of Kent, which links the atrium directly to the ventricular myocardium), may connect the atrium directly to the distal AV node or His Purkinje system (bundle of James), and may also connect the AV node to either the right bundle or the ventricle, termed nodofascicular and nodoventricular tracts, respectively. (See "Anatomy, pathophysiology, and localization of accessory pathways in the preexcitation syndrome".) Accessory bypass tracts may conduct reentrant impulses either in a retrograde or antegrade direction. Orthodromic AVRT is defined by conduction of the depolarization impulse to the ventricles down the AV node and His-Purkinje system in an antegrade manner and its return via the accessory tract in a retrograde manner ( waveform 4 and figure 9). The QRS complex is narrow (although it may have a typical right or left bundle branch block pattern if there is rate- related aberration) as ventricular activation is via the normal conduction pathway. Antidromic AVRT is characterized by the reverse sequence in which the depolarization wave travels down the bypass tract in an antegrade direction to activate the ventricular myocardium and returns to the atria via the His-Purkinje system and AV node ( waveform 5 and figure 10). In this situation, the QRS complex is maximally preexcited and has a wide and strange morphology as a result of direct myocardial activation via the accessory pathway. The complex has the same morphology in every lead as the preexcited complex during sinus rhythm, although it may be wider as it is maximally preexcited. Since it is wide, with a strange morphology, it may look like VT. Orthodromic AVRT is most common, occurring in approximately 90 percent of symptomatic patients with accessory bypass tracts [39]; antidromic AVRT accounts for the remaining 10 percent [40]. (See "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway".) The conduction characteristics of bypass tracts can vary significantly not only among patients, but also between retrograde and antegrade directions within the same tract in a given patient https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 9/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate [41]. As an example, a single bypass tract may be involved in both orthodromic and antidromic AVRTs. Ventricular tachycardia and fibrillation Ventricular tachycardia (VT; monomorphic) and ventricular fibrillation (VF), the two most lethal arrhythmias, are both caused by reentry ( waveform 6 and waveform 7) [42]. Pathologic changes associated with ischemic heart disease (infarction resulting in fibrosis) or cardiomyopathy (myocardial infiltration and/or fibrosis) most often produce the cardiac substrate necessary for reentrant ventricular arrhythmias: areas of unidirectional block and sufficiently slow conduction. The reentrant circuits are small, involving the distal Purkinje fibers within normal and abnormal myocardial tissue, and this has been termed "microreentry." Monomorphic VT can be initiated by appropriately timed premature ventricular impulses or by burst pacing and can be terminated by cardioversion, overdrive pacing, or antiarrhythmic drugs. VF can be initiated by appropriately timed premature ventricular impulses but can be terminated only with defibrillation. Although sustained VTs with different QRS morphologies (polymorphic VT without QT prolongation of the sinus complex) occur spontaneously (most commonly due to active ischemia) or during electrophysiologic study after a myocardial infarction, they most commonly arise from reentrant circuits located in the region of the infarction [43]. Factors responsible for different exit routes from circuits in the same region, leading to multiple morphologies include: Different direction of rotation around the same circuit Small differences in the reentrant circuit Reentrant circuits with different sizes and shapes Differences in the refractoriness of the ventricular myocardium and hence its ability to conduct the impulse While sustained VT generally involves one reentrant circuit, or perhaps a single spiral, VF results from multiple circuits simultaneously activating the ventricular myocardium. In an animal model, the most likely underlying mechanism was rotating spiral waves [44]. With the development of global ischemia during VF, the rate of VF decreases due to an increase in the rotation period of the spiral waves that results from an increase in the core area. It has frequently been observed that VF is often preceded by a variable period of VT (monomorphic or polymorphic). The transition from a sustained organized VT to disorganized VF probably involves the breakup of a single propagating wave or spiral into multiple daughter wavelets or spirals, a result of heterogeneity of myocardial electrophysiologic properties (functional block) or anatomic obstacles. This is identical to the process seen with AF. These wavelets rarely reenter themselves but can re-excite portions of the myocardium recently https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 10/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate activated by another wavefront, a process called random reentry. As a result, there are multiple wavefronts of activation that may collide with each other, extinguishing themselves or creating new wavelets or spiral and wavefronts, thereby perpetuating the arrhythmia [45,46]. Spontaneous wave breaks without apparent collision may also occur during VF; in an experimental model, procainamide can reduce the incidence of these events, decreasing the number of wavelets [46]. Spontaneously occurring reentrant arrhythmias are infrequent in a healthy ventricle, because the substrate for reentry is lacking. However, these tachyarrhythmias can occur in a normal heart in the right clinical setting. As an example, bundle branch reentry can be initiated by an early coupled premature impulse; VT may then develop based upon the difference in the refractory periods either between the two bundles or between one of the bundles and ventricular muscle ( figure 11) [47]. (See "Bundle branch reentrant ventricular tachycardia".) VF can also be induced in a healthy heart if a properly timed, strong stimulus is applied to the ventricle. The critical moment occurs immediately after the refractory period, generally at the downstroke of the T wave just after its peak, a period of time termed the vulnerable period, when a heterogeneous state of excitability and refractoriness exists [48]. A strong stimulus applied during the vulnerable period is postulated to set up a number of functional reentrant circuits. The amount of energy that provokes VF is termed the VF threshold. The VF threshold in a normal, nonischemic heart is high, while the VF threshold is low in the presence of active ischemia. In this situation, a premature ventricular complex or a pacing stimulus occurring at the downstroke of the T wave (R on T phenomenon) may have sufficient energy to provoke VF. SUMMARY Cardiac arrhythmias are generally produced by one of three mechanisms: enhanced automaticity, triggered activity, or reentry. Reentry, which occurs when a propagating impulse fails to die out after normal activation of the heart and persists to re-excite the heart after the refractory period has ended, is the electrophysiologic mechanism responsible for the majority of clinically important arrhythmias. (See 'Introduction' above.) While the one event which is crucial to the development of a reentrant tachycardia is the failure of a group of fibers to activate during a depolarization wave, the initiation of a reentrant arrhythmia also requires various electrophysiologic properties (eg, ability to conduct antegrade and retrograde, presence of unidirectional block, etc) to be present concurrently within the myocardial tissue making up the circuit. Changes in heart rate or autonomic tone, ischemia, electrolyte or pH abnormalities, or the occurrence of a https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 11/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate premature beat (which results in transient changes in the electrophysiologic properties of the myocardium) may be sufficient to initiate a reentrant tachycardia. (See 'Definition and characteristics' above.) Twelve conditions which may be seen during invasive electrophysiology study in the electrophysiology laboratory have been proposed to either prove or to identify the existence of a reentrant tachycardia. (See 'Criteria for diagnosis' above.) Reentry tachycardias have been divided into two different forms based upon the type of anatomic substrate used for the development of the arrhythmia: anatomic or functional. Anatomic reentrant tachycardia requires a discrete anatomic obstacle, such as an area of fibrosis, resulting in a fixed length and location of the reentrant circuit. Examples of anatomic reentry are supraventricular tachycardia associated with an accessory pathway (preexcitation syndromes), AV nodal reentrant tachycardia, atrial flutter, ventricular tachycardia originating within the His-Purkinje system (bundle branch tachycardia), and ventricular tachycardia originating at the terminal portion of the His- Purkinje system or around an area of infarcted tissue. (See 'Anatomic reentry' above.) Functional reentry depends upon the intrinsic heterogeneity of the electrophysiologic properties of cardiac muscle (ie, dispersion of excitability or refractoriness) as well as anisotropic differences in intercellular resistances. There is no anatomic obstacle present. Examples of functional reentry include type II (atypical) atrial flutter and atrial tachycardia. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Mayer AG. Rhythmical pulsation in scyphomedusae. Carnegie Institution of Washington Pub lication No. 47, 1906. 2. Mines GR. On dynamic equilibrium in the heart. J Physiol 1913; 46:349. 3. Lewis T. The Mechanism and Graphic Registration of the Heart Beat, & Sons, London 1925. 4. Allessie MA, Bonke FI, Schopman FJ. Circus movement in rabbit atrial muscle as a mechanism of trachycardia. Circ Res 1973; 33:54. 5. Allessie MA, Bonke FI, Schopman FJ. Circus movement in rabbit atrial muscle as a mechanism of tachycardia. II. The role of nonuniform recovery of excitability in the https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 12/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate occurrence of unidirectional block, as studied with multiple microelectrodes. Circ Res 1976; 39:168. 6. Allessie MA, Bonke FI, Schopman FJ. Circus movement in rabbit atrial muscle as a mechanism of tachycardia. III. The "leading circle" concept: a new model of circus movement in cardiac tissue without the involvement of an anatomical obstacle. Circ Res 1977; 41:9. 7. Hoffman BF. Circus movement in the AV ring. In: Cardiac Electrophysiology: A Textbook, Ros en MR, Janse MJ, Wi AL (Eds), Futura, Mt Kisco, NY 1990. p.573. 8. Waldo AL, MacLean WA, Karp RB, et al. Entrainment and interruption of atrial flutter with atrial pacing: studies in man following open heart surgery. Circulation 1977; 56:737. 9. Frame LH, Page RL, Hoffman BF. Atrial reentry around an anatomic barrier with a partially refractory excitable gap. A canine model of atrial flutter. Circ Res 1986; 58:495. 10. Gough WB, Mehra R, Restivo M, et al. Reentrant ventricular arrhythmias in the late myocardial infarction period in the dog. 13. Correlation of activation and refractory maps. Circ Res 1985; 57:432. 11. Kamjoo K, Uchida T, Ikeda T, et al. Importance of location and timing of electrical stimuli in terminating sustained functional reentry in isolated swine ventricular tissues: evidence in support of a small reentrant circuit. Circulation 1997; 96:2048. 12. Spach MS, Miller WT 3rd, Geselowitz DB, et al. The discontinuous nature of propagation in normal canine cardiac muscle. Evidence for recurrent discontinuities of intracellular resistance that affect the membrane currents. Circ Res 1981; 48:39. 13. Spach MS, Dolber PC, Heidlage JF. Influence of the passive anisotropic properties on directional differences in propagation following modification of the sodium conductance in human atrial muscle. A model of reentry based on anisotropic discontinuous propagation. Circ Res 1988; 62:811. 14. Brugada J, Boersma L, Kirchhof CJ, et al. Reentrant excitation around a fixed obstacle in uniform anisotropic ventricular myocardium. Circulation 1991; 84:1296. 15. Spach MS, Dolber PC, Heidlage JF. Interaction of inhomogeneities of repolarization with anisotropic propagation in dog atria. A mechanism for both preventing and initiating reentry. Circ Res 1989; 65:1612. 16. Allessie MA, Schalij MJ, Kirchhof CJ, et al. Experimental electrophysiology and arrhythmogenicity. Anisotropy and ventricular tachycardia. Eur Heart J 1989; 10 Suppl E:2. 17. Allessie MA, Schalij MJ, Kirchhof CJ, et al. Electrophysiology of spiral waves in two dimensions: the role of anisotropy. Ann N Y Acad Sci 1990; 591:247. https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 13/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate 18. El-Sherif N, Smith RA, Evans K. Canine ventricular arrhythmias in the late myocardial infarction period. 8. Epicardial mapping of reentrant circuits. Circ Res 1981; 49:255. 19. Davidenko JM, Kent PF, Chialvo DR, et al. Sustained vortex-like waves in normal isolated ventricular muscle. 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existence of a reentrant tachycardia. (See 'Criteria for diagnosis' above.) Reentry tachycardias have been divided into two different forms based upon the type of anatomic substrate used for the development of the arrhythmia: anatomic or functional. Anatomic reentrant tachycardia requires a discrete anatomic obstacle, such as an area of fibrosis, resulting in a fixed length and location of the reentrant circuit. Examples of anatomic reentry are supraventricular tachycardia associated with an accessory pathway (preexcitation syndromes), AV nodal reentrant tachycardia, atrial flutter, ventricular tachycardia originating within the His-Purkinje system (bundle branch tachycardia), and ventricular tachycardia originating at the terminal portion of the His- Purkinje system or around an area of infarcted tissue. (See 'Anatomic reentry' above.) Functional reentry depends upon the intrinsic heterogeneity of the electrophysiologic properties of cardiac muscle (ie, dispersion of excitability or refractoriness) as well as anisotropic differences in intercellular resistances. There is no anatomic obstacle present. Examples of functional reentry include type II (atypical) atrial flutter and atrial tachycardia. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Mayer AG. Rhythmical pulsation in scyphomedusae. Carnegie Institution of Washington Pub lication No. 47, 1906. 2. Mines GR. On dynamic equilibrium in the heart. J Physiol 1913; 46:349. 3. Lewis T. The Mechanism and Graphic Registration of the Heart Beat, & Sons, London 1925. 4. Allessie MA, Bonke FI, Schopman FJ. Circus movement in rabbit atrial muscle as a mechanism of trachycardia. Circ Res 1973; 33:54. 5. Allessie MA, Bonke FI, Schopman FJ. Circus movement in rabbit atrial muscle as a mechanism of tachycardia. II. The role of nonuniform recovery of excitability in the https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 12/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate occurrence of unidirectional block, as studied with multiple microelectrodes. Circ Res 1976; 39:168. 6. Allessie MA, Bonke FI, Schopman FJ. Circus movement in rabbit atrial muscle as a mechanism of tachycardia. III. The "leading circle" concept: a new model of circus movement in cardiac tissue without the involvement of an anatomical obstacle. Circ Res 1977; 41:9. 7. Hoffman BF. Circus movement in the AV ring. In: Cardiac Electrophysiology: A Textbook, Ros en MR, Janse MJ, Wi AL (Eds), Futura, Mt Kisco, NY 1990. p.573. 8. Waldo AL, MacLean WA, Karp RB, et al. Entrainment and interruption of atrial flutter with atrial pacing: studies in man following open heart surgery. Circulation 1977; 56:737. 9. Frame LH, Page RL, Hoffman BF. Atrial reentry around an anatomic barrier with a partially refractory excitable gap. A canine model of atrial flutter. Circ Res 1986; 58:495. 10. Gough WB, Mehra R, Restivo M, et al. Reentrant ventricular arrhythmias in the late myocardial infarction period in the dog. 13. Correlation of activation and refractory maps. Circ Res 1985; 57:432. 11. Kamjoo K, Uchida T, Ikeda T, et al. Importance of location and timing of electrical stimuli in terminating sustained functional reentry in isolated swine ventricular tissues: evidence in support of a small reentrant circuit. Circulation 1997; 96:2048. 12. Spach MS, Miller WT 3rd, Geselowitz DB, et al. The discontinuous nature of propagation in normal canine cardiac muscle. Evidence for recurrent discontinuities of intracellular resistance that affect the membrane currents. Circ Res 1981; 48:39. 13. Spach MS, Dolber PC, Heidlage JF. Influence of the passive anisotropic properties on directional differences in propagation following modification of the sodium conductance in human atrial muscle. A model of reentry based on anisotropic discontinuous propagation. Circ Res 1988; 62:811. 14. Brugada J, Boersma L, Kirchhof CJ, et al. Reentrant excitation around a fixed obstacle in uniform anisotropic ventricular myocardium. Circulation 1991; 84:1296. 15. Spach MS, Dolber PC, Heidlage JF. Interaction of inhomogeneities of repolarization with anisotropic propagation in dog atria. A mechanism for both preventing and initiating reentry. Circ Res 1989; 65:1612. 16. Allessie MA, Schalij MJ, Kirchhof CJ, et al. Experimental electrophysiology and arrhythmogenicity. Anisotropy and ventricular tachycardia. Eur Heart J 1989; 10 Suppl E:2. 17. Allessie MA, Schalij MJ, Kirchhof CJ, et al. Electrophysiology of spiral waves in two dimensions: the role of anisotropy. Ann N Y Acad Sci 1990; 591:247. https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 13/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate 18. El-Sherif N, Smith RA, Evans K. Canine ventricular arrhythmias in the late myocardial infarction period. 8. Epicardial mapping of reentrant circuits. Circ Res 1981; 49:255. 19. Davidenko JM, Kent PF, Chialvo DR, et al. Sustained vortex-like waves in normal isolated ventricular muscle. Proc Natl Acad Sci U S A 1990; 87:8785. 20. Pertsov AM, Davidenko JM, Salomonsz R, et al. Spiral waves of excitation underlie reentrant activity in isolated cardiac muscle. Circ Res 1993; 72:631. 21. Davidenko JM, Pertsov AV, Salomonsz R, et al. Stationary and drifting spiral waves of excitation in isolated cardiac muscle. Nature 1992; 355:349. 22. Athill CA, Ikeda T, Kim YH, et al. Transmembrane potential properties at the core of functional reentrant wave fronts in isolated canine right atria. Circulation 1998; 98:1556. 23. Garfinkle A, Qu Z. Nonlinear dynamics of excitation and propagation in cardiac muscle. In: C ardiac Electrophysiology: From Cell to Bedside, Zipes DP, Jalife J (Eds), WB Saunders, Philadel phia 1999. p.515. 24. Davidenko JM. Spiral wave activity: a possible common mechanism for polymorphic and monomorphic ventricular tachycardias. J Cardiovasc Electrophysiol 1993; 4:730. 25. Wathen MS, Klein GJ, Yee R, Natale A. Classification and terminology of supraventricular tachycardia. Diagnosis and management of the atrial tachycardias. Cardiol Clin 1993; 11:109. 26. Narula OS. Sinus node re-entry: a mechanism for supraventricular tachycardia. Circulation 1974; 50:1114. 27. Wu D, Amat-y-leon F, Denes P, et al. Demonstration of sustained sinus and atrial re-entry as a mechanism of paroxysmal supraventricular tachycardia. Circulation 1975; 51:234. 28. Moe, GK . On the multiple wavelet hypothesis of atrial fibrillation. Arch Int Pharmacol Dyn Ther 1962; 140:183. 29. Allessie MA, Lammers WJEP, Bonke FIM, et al. Experimental evaluation of Moe's multiple wav elet hypothesis of atrial fibrillation. In: Cardiac Arrhythmias, Zipes DP, Jalife J (Eds), Grune & Stratton, New York 1985. p.265. 30. Denes P, Wu D, Amat-y-Leon F, et al. The determinants of atrioventricular nodal re-entrance with premature atrial stimulation in patients with dual A-V nodal pathways. Circulation 1977; 56:253. 31. Denes P, Wu D, Dhingra R, et al. Dual atrioventricular nodal pathways. A common electrophysiological response. Br Heart J 1975; 37:1069. 32. Denes P, Wu D, Dhingra RC, et al. Demonstration of dual A-V nodal pathways in patients with paroxysmal supraventricular tachycardia. Circulation 1973; 48:549. https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 14/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate 33. Rosen KM, Mehta A, Miller RA. Demonstration of dual atrioventricular nodal pathways in man. Am J Cardiol 1974; 33:291. 34. Sung RJ, Waxman HL, Saksena S, Juma Z. Sequence of retrograde atrial activation in patients with dual atrioventricular nodal pathways. Circulation 1981; 64:1059. 35. Wu D, Denes P, Dhingra R, et al. New manifestations of dual A-V nodal pathways. Eur J Cardiol 1975; 2:459. 36. Sung RJ, Styperek JL, Myerburg RJ, Castellanos A. Initiation of two distinct forms of atrioventricular nodal reentrant tachycardia during programmed ventricular stimulation in man. Am J Cardiol 1978; 42:404. 37. Gallagher JJ, Sealy WC, Kasell J, Wallace AG. Multiple accessory pathways in patients with the pre-excitation syndrome. Circulation 1976; 54:571. 38. Wellens HJJ, Brugada P. Value of programmed stimulation of the heart in patients with the W olff-Parkinson-White syndrome. In: Tachycardias: Mechanisms, Diagnosis, Treatment, Josep hson ME, Wellens HJJ (Eds), Lea & Febiger, Philadelphia 1984. p.1991. 39. Newman BJ, Donoso E, Friedberg CK. Arrhythmias in the Wolff-Parkinson-White syndrome. Prog Cardiovasc Dis 1966; 9:147. 40. Bardy GH, Packer DL, German LD, Gallagher JJ. Preexcited reciprocating tachycardia in patients with Wolff-Parkinson-White syndrome: incidence and mechanisms. Circulation 1984; 70:377. 41. Wellens HJJ. Electrophysiologic properties of the accessory pathway in Wolff-Parkinson-Whit e syndrome. In: Conduction System of the Heart: Structure, Function, and Clinical Implicatio n, Wellens HJJ, Lie KI, Janse MJ (Eds), Stenfert Krose BV, Leiden 1976. p.567. 42. Josephson ME, Marchlinski FE, Buxton AE, et al. Electrophysiologic basis for sustained ventri cular tachycardia: The role of reentry. In: Tachycardias: Mechanisms, Diagnosis, Treatment, J osephson ME, Wellens HJJ (Eds), & Febiger, Philadelphia 1984. p.305. 43. Costeas C, Peters NS, Waldecker B, et al. Mechanisms causing sustained ventricular tachycardia with multiple QRS morphologies: results of mapping studies in the infarcted canine heart. Circulation 1997; 96:3721. 44. Mandapati R, Asano Y, Baxter WT, et al. Quantification of effects of global ischemia on dynamics of ventricular fibrillation in isolated rabbit heart. Circulation 1998; 98:1688. 45. Lee JJ, Kamjoo K, Hough D, et al. Reentrant wave fronts in Wiggers' stage II ventricular fibrillation. Characteristics and mechanisms of termination and spontaneous regeneration. Circ Res 1996; 78:660. https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 15/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate 46. Kwan YY, Fan W, Hough D, et al. Effects of procainamide on wave-front dynamics during ventricular fibrillation in open-chest dogs. Circulation 1998; 97:1828. 47. Akhtar M, Gilbert C, Wolf FG, Schmidt DH. Reentry within the His-Purkinje system. Elucidation of reentrant circuit using right bundle branch and His bundle recordings. Circulation 1978; 58:295. 48. Wiggers, CJ, Wegria, R . Ventricular fibrillation due to single, localized induction and condenser shocks applied during the vulnerable phase of ventricular systole. Am J Physiol 1940; 128:500. Topic 954 Version 22.0 https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 16/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate GRAPHICS Mechanisms of reentry in cardiac arrhythmias Schematic representation of possible reentrant circuits. The thick black arrow represents the circulating impulse; thin black lines represent advancing wavefronts in completely refractory tissue; speckled areas are partially refractory tissue; white areas are fully excitable tissue. A is the original model of circus movement around a fixed obstacle. There is a fully excitable gap, and the length and location of the circuit are fixed. B represents circus movement around 2 fixed anatomic obstacles. A fully excitable gap is present. C represents rapidly conducting bundles forming closed loops that serve as preferential circuits through which the impulse may travel. D is the leading circle type of reentry which does not require an anatomic obstacle. Instead, the impulse propagates around a functionally refractory core and among neighboring fibers that have different electrophysiologic properties. Since the refractoriness of the core is variable, the circuit size changes but will be the smallest possible circuit that can continue to propagate an impulse. Functional circuits tend to be small, rapid, and unstable. E represents reentry around a fixed anatomic obstacle, but a fully excitable gap is absent. F demonstrates an area of slowed conduction (hatched lines) between anatomic boundaries, while in G all areas of slowed conduction neighbor an anatomic obstacle. H represents anisotropic reentry. There are differences in the conduction of a single impulse in various fibers as a result of differences in their orientation. https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 17/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate Courtesy of Philip J Podrid, MD, FACC. Graphic 52134 Version 5.0 https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 18/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate Anisotropic reentry Panel A is an activation map of a single reentrant circuit at the epicardial border zone of a myocardial infarction. The large arrows represent the general activation pattern which occurs around a long line of block (blue arrow). Parallel isochrones 130 and 140 which are adjacent to the block suggest that activation is occurring across the block, resulting in a smaller circuit (shaded area) shown by the small black arrow. Panel B is an enlarged representation of this shaded area; the dark black rectangle represents an area of block around which there is a reentrant circuit (small arrows). Rapid activation occurs parallel to the long axis of the fiber orientation (isochrones 10-40 and 130-150), while in the transverse direction activation is slow (bunched isochrones 50-120). Graphic 54711 Version 2.0 https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 19/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate Mechanism of torsades de pointes The top panels A-F are examples of epicardial isochrone maps obtained from the surface of the anterior left ventricular (LV) wall and free wall of the right ventricle (RV) during an episode of quinidine-induced torsades de pointes. Each map corresponds to a QRS deflection of the surface ECG and simultaneous monophasic action potential (MAP). Early afterpotentials (EADs) result in triggered activity (panels A-C) which is followed by a long episode of spiral-like reentry (panels D-F). Panel C shows the first reentrant wave which is not stationary, but gradually shifts upward and to the right. This is associated with a gradual decrease in the QRS complex amplitude. Reprinted with permission from the American College of Cardiology. Journal of the American College of Cardiology, 1997; 29:831. Graphic 56857 Version 3.0 https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 20/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate Sites of reentry in supraventricular tachyarrhythmias Reentry may occur around a fixed anatomic obstacle or may be functional, developing in the absence of an anatomic obstacle and resulting from the intrinsic heterogeneity of electrophysiologic properties of the myocardial tissue. Reentrant circuits leading to a supraventricular tachyarrhythmia may develop in various parts of the heart: within and around the sinoatrial node (sinus node reentry); within the atrial myocardium (atrial tachycardia, atrial flutter, or atrial fibrillation); within the atrioventricular (AV) node due to the presence of a slow and fast pathway (atrioventricular nodal reentrant tachycardia); or involving the AV node and an accessory pathway (AP) (atrioventricular reentrant tachycardia). LAF: left anterior fascicle; LPF: left posterior fascicle. Graphic 82249 Version 4.0 https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 21/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate Single-lead electrocardiogram (ECG) showing sinoatrial (SA) nodal reentrant tachycardia Electrocardiogram showing SA nodal reentrant tachycardia. The first three beats are normal sinus beats at a rate of about 107 beats/min; the fourth beat is an atrial premature beat that is followed by a return to sinus rhythm. The eighth beat (arrow) represents the sudden onset of SA nodal reentrant tachycardia at a rate of about 145 beats/min. Since the P waves are similar to the sinus beats, the diagnosis is suggested only by the abrupt onset of the tachycardia. Courtesy of Morton F Arnsdorf, MD. Graphic 76364 Version 5.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 22/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate Two types of reentry in atrial fibrillation The isochronal activation maps demonstrate two types of reentry in atrial fibrillation. Map A shows random reentry with three simultaneous wavefronts (black arrows) activating most of the recording area. Map B also shows three simultaneous wavefronts, but they are coming from different directions than those in map A. Maps C and D show two consecutive cycles of complete reentry. The wave of activation (black arrow) spreads clockwise in a circular fashion around a line of unexcited tissue. Reproduced with permission from Holm M, Johansson R, Brandt J, et al. Eur Heart J 1997; 18:290. Graphic 73931 Version 2.0 https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 23/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate Single-lead electrocardiogram (ECG) showing atrial fibrillation Lead V1 showing coarse AF with moderate ventricular response. The two characteristic findings in AF are present: the very rapid atrial fibrillatory waves (f waves), which are variable in appearance; and the irregularly irregular ventricular response as the R-R interval between beats is unpredictable. Coarse AF may appear similar to atrial flutter. However, the variable height and duration of the f waves differentiate them from atrial flutter (F) waves, which are identical in appearance and occur at a constant rate of about 250 to 350 beats/min. AF: atrial fibrillation. Courtesy of Ary Goldberger, MD. Graphic 73958 Version 6.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 24/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate Single-lead electrocardiogram (ECG) showing atrial fibrillation with minimally apparent atrial activity F waves are not apparent in this lead, as the only finding suggestive of AF is the irregularly irrregular ventricular response. AF: atrial fibrillation. Courtesy of Morton Arnsdorf, MD. Graphic 53988 Version 4.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 25/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate Typical atrioventricular nodal reentrant tachycardia The first two complexes are normal sinus beats with a normal P wave followed by a QRS complex. The third complex, an atrial premature beat (APB), has a prolonged PR interval; it initiates a common or typical atrioventricular nodal reentrant tachycardia (AVNRT) in which antegrade conduction to the ventricle is via the slow pathway and retrograde atrial activation is by the fast pathway. Although no distinct P wave is seen, the QRS complex has a small terminal deflection, known as a pseudo r', which is the P wave superimposed upon the terminal portion of the QRS complex. Graphic 54290 Version 3.0 https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 26/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate Slow-fast form of atrioventricular nodal reentrant tachycardia (AVNRT) Representation of dual pathway physiology involving the atrioventricular (AV) node and perinodal atrial tissue in the common form of AVNRT. Left panel: A normal sinus beat (A ) is conducted through the fast pathway (F) to the final common pathway (fcp) in the AV node and into the Bundle of His. The conduction through the slow pathway (S) runs into the refractory period of the impulse through the fast pathway and is extinguished. 1 Middle panel: A critically timed atrial premature beat (A ) finds the fast pathway refractory in the antegrade direction but is able to conduct antegrade through the slow pathway, which has a shorter refractory period. If excitability in the fast pathway has recovered by 2 the time the impulse reaches the fcp, there may be retrograde activation of the fast pathway. Right panel: The retrograde impulse throws off an echo to the atrium (A*), and, if the slow pathway has recovered its excitability, the impulse reenters the slow pathway and produces ventricular depolarization (V*). If the mechanism persists, a repetitive circuit is established that creates a sustained reentrant tachycardia. The sequence of antegrade (S) and retrograde (F) conduction is called the slow-fast form of AVNRT. Graphic 79760 Version 6.0 https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 27/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate Atypical atrioventricular nodal reentrant tachycardia Shown are three simultaneous ECG leads (I, II, and III) during an uncommon or atypical form of an atrioventricular nodal reentrant tachycardia (AVNRT) in which antegrade conduction to the ventricle is via the fast pathway and retrograde atrial activation is by the slow pathway. As a result of delayed atrial activation, there is a long RP and short PR interval and a negative P wave in the inferior leads II and III. Graphic 66828 Version 2.0 https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 28/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate Uncommon fast-slow variant of atrioventricular nodal reentrant tachycardia (AVNRT) Diagrammatic representation in the circuit (left panel) and the ladder diagram (right panel) of the uncommon form of AVNRT (fast-slow variant). Antegrade conduction is through the fast (F) pathway and retrograde conduction is through the slow (S) pathway. Because of slow retrograde activation of the atrium, the P wave occurs after the QRS complex with a long RP interval and relatively short PR interval before the next QRS complex. ECG: electrocardiogram. Graphic 56806 Version 4.0 https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 29/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate 12-lead electrocardiogram (ECG) showing orthodromic atrioventricular reentrant tachycardia (AVRT) in a patient with an accessory AV pathway The 12-lead ECG from a patient with Wolff-Parkinson-White shows a regular tachycardia. However, in contrast to the QRS pattern during sinus rhythm, the QRS complexes are narrow, without evidence of a delta wave or pre-excitation; this is due to the fact that antegrade ventricular activation occurs via the normal atrioventricular node-His Purkinje pathway, while retrograde atrial activation is via the accessory pathway. Therefore, this is called an orthodromic atrioventricular reentrant tachycardia (OAVRT). Courtesy of Martin Burke, DO. Graphic 68804 Version 5.0 ECG in Wolff-Parkinson-White https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 30/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate The 12-lead ECG shows the typical features of Wolff-Parkinson-White; the PR interval is short (*) and the QRS duration prolonged as a result of a delta wave (arrow), indicating ventricular preexcitation. Courtesy of Martin Burke, DO. Graphic 67181 Version 3.0 https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 31/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate Orthodromic atrioventricular reentrant tachycardia (AVRT) in the setting of an accessory AV pathway The rhythm strip shows a sinus (S) beat that has a short PR interval and a wide QRS complex as a result of a delta wave (d). Panel A shows an atrial premature beat (APB,*) that is blocked in the accessory pathway (AP), which has a long refractory period but is conducted antegradely through the atrioventricular node (N) and the His-Purkinje system, resulting in a normal PR interval and a narrow and normal QRS complex, as seen on the rhythm strip. After normal myocardial activation, the impulse is conducted retrogradely along the AP, activating the atrium in a retrograde fashion (panel B), which results in a negative P wave. If this activation sequence repeats itself (panel C), an orthodromic atrioventricular reentrant (or reciprocating) tachycardia (AVRT) is established. Graphic 71302 Version 7.0 https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 32/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate 12-lead electrocardiogram (ECG) showing antidromic atrioventricular reentrant tachycardia (AVRT) in a patient with an accessory AV pathway The 12-lead ECG of a patient with Wolff-Parkinson-White shows a regular tachycardia. The QRS complexes are widened and are identical to the QRS complexes seen in sinus rhythm; the antegrade conduction to the ventricle is via the accessory pathway and retrograde conduction is via the normal His- atrioventricular node pathway. This is, therefore, an antidromic atrioventricular reentrant tachycardia (AVRT). Courtesy of Martin Burke, DO. Graphic 54484 Version 20.0 ECG in Wolff-Parkinson-White https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 33/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate The 12-lead ECG shows the typical features of Wolff-Parkinson-White; the PR interval is short (*) and the QRS duration prolonged as a result of a delta wave (arrow), indicating ventricular preexcitation. Courtesy of Martin Burke, DO. Graphic 67181 Version 3.0 https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 34/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate Antidromic atrioventricular reentrant tachycardia (AVRT) in the setting of an accessory AV pathway The rhythm strip shows a sinus (S) beat that has a short PR interval and a wide QRS complex as a result of a delta wave (d). Panel A shows the activation sequence with an atrial premature beat (APB,*). The impulse reaches the atrioventricular node (N) before it has repolarized and hence is blocked in this structure. However, the accessory pathway (AP), which has a short refractory period, is able to conduct the impulse antegradely, resulting in an APB with a widened QRS morphology similar to the sinus beat. As seen in panel B, following myocardial activation, the impulse is conducted retrogradely along the His-Purkinje system and AV node, resulting in retrograde atrial activation, seen on the rhythm strip as an inverted P wave. If this activation sequence repeats itself (panel C), a wide QRS complex antidromic atrioventricular reentrant (or reciprocating) tachycardia (AVRT) is established. Graphic 50433 Version 4.0 https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 35/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate Single lead electrocardiogram (ECG) showing monomorphic ventricular tachycardia Three or more successive ventricular beats are defined as ventricular tachycardia (VT). This VT is monomorphic since all of the QRS complexes have an identical appearance. Although the P waves are not distinct, they can be seen altering the QRS complex and ST-T waves in an irregular fashion, indicating the absence of a relationship between the P waves and the QRS complexes (ie, AV dissociation is present). AV: atrioventricular. Graphic 63176 Version 7.0 Normal rhythm strip Normal rhythm strip in lead II. The PR interval is 0.15 sec and the QRS duration is 0.08 sec. Both the P and T waves are upright. Courtesy of Morton F Arnsdorf, MD. Graphic 59022 Version 3.0 https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 36/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate ECG 12-lead ventricular fibrillation 12-lead ECG showing course ventricular fibrillation. ECG: electrocardiogram. Graphic 118944 Version 1.0 https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 37/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate Mechanism of bundle branch reentrant ventricular tachycardia Schematic representation of the reentrant circuit in bundle branch reentrant ventricular tachycardia (BBRVT) showing a ventricular premature beat that blocks in the right bundle branch (RBB), conducts slowly up the left bundle branch (LBB), activates the bundle of His, and returns antegradely down the RBB. If the RBB has recovered its excitability from the preceding beat, the circuit is completed, and the reentrant circuit may become repetitive. AV: atrioventricular; PVC: premature ventricular contraction. Graphic 75164 Version 5.0 https://www.uptodate.com/contents/reentry-and-the-development-of-cardiac-arrhythmias/print 38/39 7/5/23, 10:47 AM Reentry and the development of cardiac arrhythmias - UpToDate Contributor Disclosures Philip J Podrid, MD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Bernard J Gersh, MB, ChB, DPhil, FRCP, MACC Consultant/Advisory Boards: Bain Institute [CRO for trials involving Edwards percutaneous valve devices]; Cardiovascular Research Foundation [Data safety monitoring board (RELIEVE-HF Trial)]; Caristo Diagnostics Limited [Imaging and inflammation/atherosclerosis]; Philips Image Guided Therapy Corporation [Imaging]; Sirtex Med Limited [General consulting]; Thrombosis Research Institute [Data safety monitoring board (GARFIELD study)]. All of the relevant financial relationships listed have been mitigated. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. 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7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. The electrocardiogram in atrial fibrillation : Brian Olshansky, MD, Zachary D Goldberger, MD, FACC, FHRS, Steven M Pogwizd, MD : Bradley P Knight, MD, FACC : Nisha Parikh, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Sep 10, 2021. INTRODUCTION Atrial fibrillation (AF) can cause significant symptoms; impair functional status, hemodynamics, and quality of life; and increase the risk of stroke and death. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation".) Diagnosis of AF has important implications for acute and long-term management. A missed diagnosis of AF may result in a failure to appropriately anticoagulate for stroke prophylaxis or effectively treat symptoms due to AF, while overdiagnosis of AF may lead to inappropriate testing and therapy including unwarranted anticoagulation with associated risk of major bleeding. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation".) This topic will review the electrocardiographic (ECG) features of AF. The mechanisms of AF are presented separately. (See "Mechanisms of atrial fibrillation".) DIAGNOSIS OF ATRIAL FIBRILLATION AF is diagnosed by interpretation of the 12-lead ECG. In most patients, a single 12-lead ECG, recorded while the patient is in AF, is sufficient to secure the diagnosis. Examination of prior ECGs may be helpful, but prior diagnosis (or misdiagnosis) of AF should not influence interpretation of a current ECG. In some patients, AF is detected on ECG recordings from cardiac telemetry, ambulatory ECG monitor (eg, Holter monitor or loop recorder), or cardiac implantable electronic device (permanent pacemaker [PPM] or implantable cardioverter-defibrillator [ICD]). (See "Ambulatory ECG monitoring" and "Permanent cardiac pacing: Overview of devices and https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 1/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate indications" and "Implantable cardioverter-defibrillators: Overview of indications, components, and functions".) Our approach While the ECG diagnosis of AF with typical features can be straightforward in patients with characteristic features of AF (see 'Key features of atrial fibrillation' below), misdiagnosis of AF is common, as there are a significant number of AF mimics that should be excluded. (See 'Differential diagnosis' below.) The following is our approach to ECG identification of the cause of an irregularly irregular ventricular rhythm (or regular rhythm with fibrillatory or absent P waves) ( algorithm 1): Exclude artifact If artifact may be present, examine all 12 leads and examine atrial activity in the leads with the least amount of artifact-related oscillations ( waveform 1 and waveform 2). If atrial activity cannot be adequately assessed, address the cause of the artifact to the extent possible and repeat the ECG. (See 'Differential diagnosis' below.) Identify atrial activity Examine all 12 leads of the ECG closely for the presence of atrial activity, particularly the inferior leads and lead V1. Focus on areas with longer R-R intervals that display longer periods of isoelectric baseline. Increase amplitude, if needed If no atrial activity is detected or the morphology of atrial activity is not well visualized, use ECG amplification (either digital magnification or an increase in gain for the entire ECG signal) ( waveform 3). Examine atrial activity The morphology, frequency, and timing of atrial activity in relationship to QRS complexes should be assessed. Exclude AF mimics. (See 'Differential diagnosis' below.) If AF mimics are excluded, and there are fibrillatory waves or no P waves (despite ECG amplification), AF is diagnosed. Common and uncommon ECG characteristics of AF are described below. (See 'Key features of atrial fibrillation' below.) Key features of atrial fibrillation Common findings The following findings are commonly seen with AF: Atrial activity (see 'Atrial activity' below): Lack of discrete P waves ( waveform 4). https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 2/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Rapid, low-amplitude fibrillatory (or f) waves vary continuously in amplitude, morphology, and rate. The rate may be between 350 to 600 beats per minute (bpm) or unmeasurable. If present, f waves usually are best seen in the inferior leads and in V1. The f waves may be identified between QRS complexes and are sometimes visible superimposed on the ST segment and T waves. Ventricular activity (see 'Ventricular activation' below): The ventricular rhythm is described as "irregularly irregular," meaning lacking a repetitive, predictable pattern. (See 'General features' below.) The ventricular rate (especially in absence of atrioventricular [AV] nodal blocking drugs or intrinsic conduction disease) is usually 90 to 170 bpm, with higher rates seen in younger individuals (see 'General features' below). Based on the ventricular rate, AF is often characterized as having "slow" (<60 bpm), "moderate" (60 to 100 bpm), or "rapid" (>100 bpm) ventricular response ( waveform 5). The QRS complexes are narrow unless conduction through the His-Purkinje system is abnormal due to preexisting right or left bundle branch ( waveform 6), fascicular block, functional (rate-related) aberration, or ventricular preexcitation with anterograde conduction via an AV accessory pathway. (See 'With aberrant conduction' below and 'With Wolff-Parkinson-White syndrome' below.) Uncommon findings The following findings are less commonly identified in patients with AF: A regular (rather than an irregularly irregular) ventricular rhythm: Regular ventricular escape complexes in patients with complete or high-grade AV block are referred to as "regularization of AF." Complete or high-grade AV block may be caused by conduction system disease, AV node ablation, or drugs (including digoxin toxicity). (See "Etiology of atrioventricular block" and "Atrial fibrillation: Atrioventricular node ablation" and "Third-degree (complete) atrioventricular block" and "Cardiac arrhythmias due to digoxin toxicity", section on 'Digoxin-induced arrhythmias'.) Junctional escape Most commonly, the escape pacemaker is located in the AV junction above the bifurcation of the bundle branches, leading to a QRS complex that has the same morphology as if it had conducted from the atria through the AV node ( waveform 7). This pacemaker generally has a characteristic rate of approximately 60 bpm, unless it is accelerated or depressed due to pathology, ischemia, or drugs (eg, digoxin). https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 3/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Ventricular escape With less commonly seen ventricular (subjunctional or fascicular) escape rhythms, the QRS is wide and, unless accelerated, the ventricular rate is generally 30 to 50 bpm ( waveform 7). Ventricular pacing produces a regular paced ventricular rhythm with wide QRS. (See "Permanent cardiac pacing: Overview of devices and indications" and "Modes of cardiac pacing: Nomenclature and selection".) The ventricular rhythm is typically regular when there is ventricular tachycardia in the presence of AF. With very fast rates of AV conduction, the ventricular rate may appear regular. If there is conversion between AF and atrial flutter with a fixed ratio of conduction, the ventricular rate will be regular during periods of atrial flutter. Variable (rather than consistent) QRS morphology may result from varying combinations of AV conduction and native or paced ventricular beats ( waveform 8). In these unusual cases, there may be AV conduction and fusion beats (hybrid complexes produced by coincident AV conduction and ventricular or paced beats) or pseudofusion beats (QRS complexes with morphology of AV conducted beats but with superimposed pacemaker stimuli). An example is the occurrence of AF with rapid ventricular response in concert with a "competing" tachycardia (eg, ventricular tachycardia) ( waveform 9). (See "ECG tutorial: Miscellaneous diagnoses", section on 'Fusion and capture beats' and "ECG tutorial: Pacemakers", section on 'Ventricular pacing only'.) Differential diagnosis When there are no recognizable atrial deflections in any ECG lead, turning up the gain on the ECG may enable identification of f or P waves and thus help distinguish fine AF from sinus rhythm with irregularity (due to ectopy or sinus arrhythmia) ( waveform 3). AF can be confused with a number of other supraventricular arrhythmias that exhibit atrial activity (ie, sinus P waves, ectopic P waves, or flutter waves). "Coarse" AF (large-amplitude f waves, especially in lead V1) should be distinguished from atrial flutter and multifocal atrial tachycardia, as discussed below. Specific AF mimics can be subdivided based on the type of atrial activity present. One or more of the following types of rhythms may be present: Artifact Artifact from tremor, shivering, or loose lead connection superimposed on sinus rhythm (or any other non-AF rhythm) can mimic AF ( waveform 1 and waveform 2). https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 4/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial flutter Atrial flutter is characterized by flutter waves on the isoelectric baseline between longer R-R intervals and on the ST segments and/or T waves, usually best seen in inferior leads or V1 ( waveform 10). Both typical and atypical atrial flutter can mimic AF. In atrial flutter, atrial rates are generally 250 to 350 bpm (but are sometimes as low as 190 to 200 bpm). While atrial flutter with a constant degree of AV block (2:1, 3:1, 4:1) typically results in regular rhythms, atrial flutter with variable AV conduction is irregular. Some patients with AF also have episodes of atrial flutter. (See "Overview of atrial flutter", section on 'Electrocardiogram'.) We avoid use of the term "atrial fibrillation/flutter," which is commonly used when the precise type of atrial activity is unclear. The term is inaccurate and may impact care as there are differences in the short- and long-term management for AF and atrial flutter. When it is difficult to distinguish these conditions, we use alternate language such as "The atrial activity is unclear and coarse, but the likely diagnosis is AF. However, atrial flutter with variable conduction cannot be excluded." Some patients have both of these conditions. If an ECG catches a transition between AF and atrial flutter, this transition should be noted and not labeled as "atrial fibrillation/flutter." The presence of sinus P waves (upright in II, inverted in aVR, and biphasic in V1) suggests an underlying sinus rhythm. Sinus arrhythmia If all P waves are sinus, variation in PP (by >0.16 seconds) with a relatively constant PR suggests sinus arrhythmia ( waveform 11). There is progressive increase and decrease in the P-P interval (See "ECG tutorial: Rhythms and arrhythmias of the sinus node", section on 'Sinus arrhythmia' and "Normal sinus rhythm and sinus arrhythmia", section on 'Sinus arrhythmia'.) Sinus arrhythmia with competing junctional escape rhythm If there is variation in PP and there is one or more QRS complex without a preceding P wave or preceded by a shorter than normal PR interval, consider sinus arrhythmia with a competing junctional escape rhythm (also known as isorhythmic AV dissociation) ( waveform 12). This occurs when the sinus rate intermittently drops below that of the junctional escape rhythm. The inconsistent P-QRS relationship is more challenging for the standard AF algorithms of ECG machines, and the rhythm is often misinterpreted as AF. (See "ECG tutorial: Rhythms and arrhythmias of the sinus node", section on 'Types' and "ECG tutorial: Atrial and atrioventricular nodal (supraventricular) arrhythmias", section on 'Junctional escape beats'.) https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 5/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Sinus rhythm with second-degree AV block Sinus rhythm with second-degree AV block can result in an irregular rhythm with occasional dropped beats (nonconducted P waves) which may (Mobitz I) or may not (Mobitz II) be preceded by progressive PR prolongation ( waveform 13). (See "Second-degree atrioventricular block: Mobitz type I (Wenckebach block)" and "Second-degree atrioventricular block: Mobitz type II" and "ECG tutorial: Atrioventricular block".) Sinus rhythm with premature ventricular complexes (PVCs) Sinus rhythm with PVCs can result in an irregular rhythm that may be mistaken as AF when P wave amplitude is diminished or in the setting of artifact. One morphology of nonsinus P waves (along with sinus P waves): Sinus rhythm with premature atrial complexes (PACs) The combination of sinus rhythm and PACs results in an irregular rhythm that can resemble AF, especially when the P waves of sinus beats and/or PACs are superimposed on the ST segment or T waves of preceding beats . To distinguish this rhythm from AF, magnification of digitized ECG tracings may facilitate recognition of sinus and ectopic P waves and demonstrate a consistent one-to-one relationship between P waves and QRS complexes ( waveform 3). (See "ECG tutorial: Atrial and atrioventricular nodal (supraventricular) arrhythmias", section on 'Premature atrial complex'.) Runs of nonsinus P waves A shift in atrial activation arising from the sinus node to that from an ectopic atrial site (or vice versa) can lead to a sudden change in P wave morphology and, often, some irregularity that could mimic AF. Ectopic atrial rhythm Atrial rate is 100; generally, 30 to 60 bpm ( waveform 14). (See "ECG tutorial: Atrial and atrioventricular nodal (supraventricular) arrhythmias", section on 'Ectopic atrial rhythm'.) Focal atrial tachycardia Atrial tachycardia (AT) is characterized by atrial rates in the 140 to 180 bpm range ( waveform 15). In the presence of AV block, the ventricular response can be irregular and mimic AF. While AT with block has been commonly described with digoxin toxicity, it can occur in the absence of digoxin. (See "Cardiac arrhythmias due to digoxin toxicity", section on 'Digoxin-induced arrhythmias'.) Three or more P wave morphologies: Wandering atrial pacemaker or multifocal atrial rhythm is an irregular rhythm that is also characterized by P waves of at least three morphologies and is characterized by https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 6/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate ventricular rates <100 bpm ( waveform 16). (See "ECG tutorial: Atrial and atrioventricular nodal (supraventricular) arrhythmias" and "ECG tutorial: Atrial and atrioventricular nodal (supraventricular) arrhythmias", section on 'Wandering atrial pacemaker'.) Multifocal atrial tachycardia (MAT) MAT is a rapid irregularly irregular rhythm (ventricular rate 100 bpm) characterized by P waves of at least three different morphologies and with a one-to-one correspondence of P waves to QRS complexes ( waveform 17). (See "ECG tutorial: Atrial and atrioventricular nodal (supraventricular) arrhythmias", section on 'Multifocal atrial tachycardia' and "Multifocal atrial tachycardia", section on 'Clinical manifestations and diagnosis'.) Ventricular tachycardia AF with aberrant conduction may include consecutive runs of aberrantly conducted beats with wide QRS complexes, which may appear similar to ventricular tachycardia. The ventricular rate with AF is generally irregular. (See 'With aberrant conduction' below.) EXPLANATION OF ECG FEATURES Atrial activity In AF, there is no regular or organized atrial activity ( waveform 4). Numerous apparent microreentrant circuits within the atria may generate multiple waves of impulses that compete with or extinguish each other in what is termed "fibrillatory conduction." The sinus node is suppressed and cannot activate the atrium. Mechanisms causing this abnormal pattern of atrial electrical activity are discussed elsewhere. (See "Mechanisms of atrial fibrillation".) Rapid, irregular, and variable fibrillatory (f) waves may be coarse (amplitude 1 mm) or fine (<1 mm) and may not be identified. Some studies have found that fine AF is associated with older age, but age ranges for coarse and fine AF overlap widely [1,2]. The amplitude of f waves does not correlate with left atrial size [1,3]. The differential diagnosis for AF is discussed above. (See 'Differential diagnosis' above.) Ventricular activation General features In AF, the ventricular response rate is dependent on properties of the AV conduction system. As rapid and irregular atrial impulses bombard the AV node, some impulses occur in such rapid succession that they are blocked due to the refractoriness of the AV node, resulting in irregular impulse conduction through the AV node to the ventricular myocardium via https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 7/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate the His-Purkinje system. High frequency of atrial stimuli reaching the AV node does not lead to high frequency of AV conduction, as frequent impulses may cause "concealed" depolarization (ie, not evident on the surface ECG) impairing AV conduction. The large number of atrial impulses arriving at the AV node compete with each other, interfering with their penetration into and through the node, leaving this tissue variably refractory. While the ventricular rate in adults with AF is usually 90 to 170 bpm, in young, untreated individuals, rates are 160 to 200 bpm, reflecting the maximal rate at which the AV node can conduct (as determined by its refractory period in lieu of concealed conduction). Increases in the ventricular response rate to over 200 bpm may occur if the refractory period of the AV node is shortened, as with an increase in circulating catecholamines (eg, sympathetic stimulation or pheochromocytoma, hyperthyroidism, or conduction down a manifest accessory pathway). A decrease in the ventricular response rate occurs when the refractory period of the AV node is increased (eg, with aging, conduction system disease, drugs, or enhanced vagal tone) or AV conduction otherwise slows. With aberrant conduction A common cause for QRS widening during AF is aberrant conduction, which is a rate-related change in conduction. Most aberrancy is tachycardia- dependent, although bradycardia-dependent aberrancy does occur [4]. The aberrant conduction in AF involves a rate-related (tachycardia-induced) change in conduction, typically a functional bundle branch block; right bundle branch block (RBBB) is more common than left bundle branch block (LBBB), as the RBBB has a longer refractory period than the LBBB. An important property of the conducting system and myocardium is that refractoriness is longer at slow rates and shorter at faster rates. The refractoriness of the conducting system varies on a beat-by-beat basis and is related to the coupling interval of the preceding beat. As such, a long coupling interval leads to prolongation of bundle branch refractoriness (typically R>L), and if the next beat comes in early (ie, a long-short cycle), the refractoriness of the RBBB leads to a RBBB configuration and QRS widening that resembles a premature ventricular complex (PVC). This pattern of long-short cycle typically leads to RBBB morphology (known as Ashman phenomenon [5]) and can occur during sinus rhythm with appropriately timed premature atrial complexes (PACs) ( waveform 18) as well as during AF ( waveform 19). Aberrancy with LBBB morphology is less common but can occur. The QRS of aberrant beats typically exhibits an upstroke similar to those of other native supraventricular beats in leads other than V1 to V2, while PVCs typically exhibit markedly different morphology from supraventricular beats in multiple leads, as shown for sinus rhythm ( waveform 18). The approach to evaluating wide QRS complex tachycardia to distinguish supraventricular tachycardia from ventricular tachycardia is discussed separately. (See "Wide QRS complex tachycardias: Approach to the diagnosis".) https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 8/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate During AF, Ashman phenomenon is associated with frequent isolated wide-complex aberrantly conducted beats. However, aberrantly conducted beats can also occur in couplets or longer nonsustained runs that can resemble ventricular tachycardia ( waveform 19). In these situations, there is no longer a long-short cycle but rather short-short cycles of rapid AF. In this case, the functional RBBB and activation down the LBBB is followed by partial penetration up the right bundle, leading to RBBB of the subsequent beat. This represents "concealed conduction" up the right bundle (ie, not evident on the surface ECG, which solely reflects atrial and ventricular activity). This can continue for a number of consecutive beats until functional BBB resolves either despite continued short cycle length or when the cycle length lengthens. As such, AF with aberrant conduction can resemble ventricular tachycardia, and it is critical to distinguish between ventricular tachycardia and sustained aberrancy . (See 'Differential diagnosis' above.) With Wolff-Parkinson-White syndrome When AF is associated with ventricular preexcitation due to anterograde conduction down an accessory pathway in patients with Wolff- Parkinson-White syndrome (WPW), the ventricular response rate may be very rapid and may exceed 280 to 300 bpm ( waveform 20), since impulse activation bypasses the AV node. Preexcited AF is facilitated when the refractory period of the accessory pathway is very short. Accessory pathway tissue differs from that of the AV node. Specifically, the accessory pathway does not exhibit postrepolarization refractoriness but rather conducts rapidly as the tissue is dependent on sodium (rather than calcium) channel activity. Conduction down the accessory pathway typically results in a slurred QRS upstroke (ie, "delta" wave), and the QRS morphology depends on the location of the pathway and its insertion into the ventricular myocardium. The QRS complex is usually wide, with rapid activation down the accessory pathway into ventricular muscle, often in concert with some conduction down the AV node and His-Purkinje system. The more conduction proceeds through the accessory pathway, the wider and more slurred the QRS complex. (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis", section on 'Electrocardiographic findings'.) A distinguishing feature of AF with preexcitation is the relationship between heart rate and QRS duration; the faster the rate, the wider the QRS. At times, it can resemble ventricular tachycardia (based on its appearance and, often, the presence of precordial concordance). While the rhythm is irregularly irregular, variations may be difficult to measure at extremely fast rates. The clinical significance of AF with rapid ventricular response in patients with WPW is discussed separately. (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis", section on 'Ventricular fibrillation and sudden death'.) ROLE OF COMPUTER TECHNOLOGY https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 9/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Computer interpretation Each ECG computer interpretation should be overread by a trained clinician as an essential requirement for patient care and safety. Automatic computer interpretation of the ECG is common practice, with over 100 million automatic ECG interpretations yearly. Limited data are available on the accuracy of automatic computer interpretation for AF, but an estimated 10 to 30 percent of the computer ECG interpretations may misdiagnose AF, and such misdiagnosis may be frequently missed by clinicians [6,7]. Such misdiagnosis can lead to inappropriate interventions and therapies. The methodological approaches that computers utilize to determine whether or not AF is present are not well clarified. Insufficient overreading may be a growing problem as formal ECG interpretation becomes less of a focus in many training programs. Wearable consumer devices While ambulatory ECG monitoring (Holter, event, or patch- based monitors, and implantable loop recorders) is a commonly employed clinical method to detect occult AF (see "Ambulatory ECG monitoring"), there has been growing use of wearable consumer devices such as smart watches and other devices that can connect to smart phones [8,9] to monitor heart rate and rhythm [10,11]. While these widely used electronic devices have potential capabilities for detecting AF, and algorithms are improving, they are subject to limitations. Generally, the methodology (often proprietary) monitors the irregularity in ventricular response rates but does not monitor the presence and type of atrial activation. Also, some devices may require a threshold episode duration (eg, 30 seconds) to detect an arrhythmia. These limitations are likely to limit the sensitivity and specificity of these devices in detecting and diagnosing AF. Thus, all patients with suspected AF require clinician review of recordings on clinically approved ECG equipment, as described above . (See 'Our approach' above.) SUMMARY AND RECOMMENDATIONS Atrial fibrillation (AF) is diagnosed by interpretation of the 12-lead electrocardiogram (ECG). AF should be considered in patients with an irregularly irregular ventricular rhythm (or regular rhythm with fibrillatory or absent P waves). (See 'Diagnosis of atrial fibrillation' above and 'Differential diagnosis' above.) In some patients, AF is detected on ECG recordings from cardiac telemetry, ambulatory ECG monitor (eg, Holter monitor or loop recorder), or cardiac implantable electronic device (permanent pacemaker [PPM] or implantable cardioverter-defibrillator [ICD]). (See "Ambulatory ECG monitoring" and "Permanent cardiac pacing: Overview of devices and indications" and "Implantable cardioverter-defibrillators: Overview of indications, components, and functions".) https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 10/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Our approach to diagnosis of AF involves exclusion of artifact, ECG amplification (if no atrial activity is detected or the morphology of atrial activity is not well-visualized), and exclusion of AF mimics ( algorithm 1). (See 'Our approach' above and 'Differential diagnosis' above.) Common features of AF include lack of discrete P waves, presence of fibrillatory (f) waves, and irregularly irregular ventricular rhythm. QRS complexes are narrow unless there is a right or left bundle branch block, fascicular block, functional (rate-related) aberration, or antegrade conduction via an AV accessory pathway. (See 'Common findings' above.) ECG features that are uncommonly associated with AF include a regular ventricular rhythm and variable QRS morphology. (See 'Uncommon findings' above.) The differential diagnosis of AF includes artifact, atrial flutter, sinus rhythm (with sinus arrhythmia, second-degree AV block, or premature atrial complexes [PACs]), ectopic atrial rhythm, multifocal atrial tachycardia (MAT), wandering atrial pacemaker, focal atrial tachycardia with block, sinus rhythm with competing junctional rhythm, and ventricular tachycardia. (See 'Differential diagnosis' above.) Each ECG computer interpretation should be overread by a trained clinician as an essential requirement for patient care and safety. Limited data on the accuracy of automatic computer interpretation for AF suggest that 10 to 30 percent of the computer ECG interpretations may misdiagnose AF. (See 'Computer interpretation' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Pourafkari L, Baghbani-Oskouei A, Aslanabadi N, et al. Fine versus coarse atrial fibrillation in rheumatic mitral stenosis: The impact of aging and the clinical significance. Ann Noninvasive Electrocardiol 2018; 23:e12540. 2. Yilmaz MB, Guray Y, Guray U, et al. Fine vs. coarse atrial fibrillation: which one is more risky? Cardiology 2007; 107:193. 3. Li YH, Hwang JJ, Tseng YZ, et al. Clinical significance of fibrillatory wave amplitude. A clue to left atrial appendage function in nonrheumatic atrial fibrillation. Chest 1995; 108:359. 4. Fisch C, Miles WM. Deceleration-dependent left bundle branch block: a spectrum of bundle branch conduction delay. Circulation 1982; 65:1029. https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 11/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate 5. GOUAUX JL, ASHMAN R. Auricular fibrillation with aberration simulating ventricular paroxysmal tachycardia. Am Heart J 1947; 34:366. 6. Bogun F, Anh D, Kalahasty G, et al. Misdiagnosis of atrial fibrillation and its clinical consequences. Am J Med 2004; 117:636. 7. Lindow T, Kron J, Thulesius H, et al. Erroneous computer-based interpretations of atrial fibrillation and atrial flutter in a Swedish primary health care setting. Scand J Prim Health Care 2019; 37:426. 8. https://www.forbes.com/sites/paullamkin/2018/02/22/smartwatch-popularity-booms-with-fi tness-trackers-on-the-slide/#6ebca2b97d96 (Accessed on April 15, 2021). 9. http://www.pewresearch.org/fact-tank/2017/01/12/evolution-of-technology (Accessed on Ap ril 15, 2021). 10. Perez MV, Mahaffey KW, Hedlin H, et al. Large-Scale Assessment of a Smartwatch to Identify Atrial Fibrillation. N Engl J Med 2019; 381:1909. 11. D rr M, Nohturfft V, Brasier N, et al. The WATCH AF Trial: SmartWATCHes for Detection of Atrial Fibrillation. JACC Clin Electrophysiol 2019; 5:199. Topic 1014 Version 27.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 12/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate GRAPHICS Approach to diagnosis of an irregularly irregular supraventricular rhythm* This graphic describes an approach to distinguishing atrial fibrillation (identified with a thick border) from other causes of an irregularly irregular supraventricular rhythm. While atrial fibrillation is the rhythm most commonly described as irregularly irregular, mimics of atrial fibrillation should be excluded when an irregularly irregular rhythm is identified. Of note, atrial fibrillation uncommonly occurs with a regular ventricular rhythm, as described in UpToDate content on the electrocardiogram in atrial fibrillation. ECG: electrocardiogram; AV: atrioventricular; PVCs: premature ventricular complexes; PACs: premature atrial complexes. Refer to UpToDate content on distinguishing supraventricular from ventricular rhythms. https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 13/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate If no atrial activity is detected or the morphology of atrial activity is unclear, use ECG amplification (digital magnification or increase in gain for the entire ECG signal). The ventricular rhythm associated with Mobitz I or II second-degree AV block is not irregularly irregular since there is a pattern to the variation in ventricular rate, but this pattern may not be immediately recognized. Graphic 132103 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 14/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Normal sinus rhythm with artifact Normal sinus rhythm with artifact: 12-lead ECG showing sinus rhythm (best seen in lead V1) along with baseline artifact that resembles AF (most evident in leads II, III, and aVF). The best way to avoid misinterpretation of this AF mimic is to carefully review all leads of the 12-lead tracing, noting any leads with evidence of regular P waves, a consistent PR interval, and a one-to-one correspondence of P waves to QRS complexes (in this case, lead V1 along with the occasional concurrent P waves in lead II demonstrates sinus rhythm). ECG: electrocardiogram; AF: atrial fibrillation. Graphic 132168 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 15/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Normal sinus rhythm with tremor Normal sinus rhythm with tremor: Lead V1 and lead II rhythm strips show sinus rhythm, evident from typical sinus P waves in leads V1 and lead II, with superimposed 3 to 5 Hz oscillations consistent with tremor activity. Graphic 132169 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 16/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Value of increasing ECG gain with possible AF Value of increasing ECG gain with possible AF. (A) Lead V1 and lead II rhythm strips show an irregularly irregular rhythm. At first glance, the rhythm looks li with moderate ventricular response. (B) However, when the gain is increased twofold, it is now apparent that there are P waves preceding each QR th (*). Some P waves (eg, the 1 , 2 5 , 10 , 11 , 12 , and 13 P waves appear to be nonsinus, suggesting frequent atrial premature complex st nd th th th th th rd , 6 , 7 , 8 , 9 , and 14 ) appear to be sinus P waves, while the 3 , 4 th th th th th In this case, magnification of the ECG tracing facilitates recognition of a common AF mimic that could be associated with a preliminary ECG machine interpretation of AF. ECG: electrocardiogram; AF: atrial fibrillation. Graphic 132167 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 17/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate ECG atrial fibrillation Atrial fibrillation. 12-lead ECG shows an irregularly irregular rhythm. Discrete P waves are not seen, and there is fibrillatory atrial activity, best seen in lead V1. The average heart rate is 102 bpm, with a normal axis, QRS duration, and QTc interval, and with nonspecific ST-T changes. ECG: electrocardiogram; bpm: beats per minute. Graphic 132160 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 18/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial fibrillation with a slow, moderate, and rapid ventricular response Atrial fibrillation with a slow (A), moderate (B), and rapid (C) ventricular response. Lead V1 and lead II rhythm strips show irregularly irregular rhythms without discrete P waves and with fibrillatory atrial activity. Graphic 132159 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 19/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial fibrillation with left bundle branch block Atrial fibrillation with LBBB. Rhythm strip shows an irregularly irregular rhythm. Discrete P waves are not seen, and there is fibrillatory atrial activity. The QRS duration is approximately 120 ms, and a complete LBBB is seen with a QS complex in lead V1. LBBB: left bundle branch block. Graphic 132162 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 20/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial fibrillation with complete heart block AF with complete heart block. Lead V1 and lead II rhythm strips show AF with complete heart block with a na complex junctional escape rhythm (A) or with a wide complex ventricular escape rhythm (B). AF: atrial fibrillation. Graphic 132164 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 21/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial fibrillation with fully paced QRS complexes Atrial fibrillation with fully paced QRS complexes (beats 1 ,5, 6, 7, 8). Native ventricular conduction is present (beats 2, 3, 4), and there are complexes (beats 9, 10) where the pacer stimulus occurs while the native complex is being conducted, resulting in a complex that has the same morphology as the native QRS complex (pacemaker pseudofusion). Graphic 132165 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 22/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial fibrillation with ventricular tachycardia AF with ventricular tachycardia. Lead V1 and lead II rhythm strips show AF with rapid ventricular response and the onset of monomorphic ventricular tachycardia at approximately 170 bpm. AF: atrial fibrillation; bpm: beats per minute. Graphic 132166 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 23/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial flutter Atrial flutter. (A) Lead V1 and lead II ECG tracings show AFL with a moderate ventricular response and variable AV conduct with flutter waves discernable in lead II. They are uniform, and occur at a rate of 300/min. Inferiorly directed flutter waves that are positive in V1 are suggestive of typical (cavotricuspid isthmus-dependent), countercloc AFL. (B) Lead V1 and lead II ECG tracings show AFL with moderate ventricular response and variable AV conductio with flutter waves in lead II at a rate of 272 bpm, consistent with typical AFL. ECG: electrocardiogram; AFL: atrial flutter; AV: atrioventricular; bpm: beats per minute. Graphic 132170 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 24/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Sinus rhythm with sinus arrhythmia Sinus rhythm with sinus arrhythmia. Lead V1 and lead II rhythm strips show an irregular rhythm with a ventricular rate that gradually increases, and with each QRS preceded by a sinus P wave, indicating sinus rhythm with sinus arrhythmia. This can mimic AF, especially if the P wave amplitude is low. AF: atrial fibrillation. Graphic 132171 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 25/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate ECG: Sinus arrhythmia and a junctional escape rhythm Sinus arrhythmia and a junctional escape rhythm. Lead V1 and lead II rhythm strips show an irregular

ECG: electrocardiogram; AV: atrioventricular; PVCs: premature ventricular complexes; PACs: premature atrial complexes. Refer to UpToDate content on distinguishing supraventricular from ventricular rhythms. https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 13/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate If no atrial activity is detected or the morphology of atrial activity is unclear, use ECG amplification (digital magnification or increase in gain for the entire ECG signal). The ventricular rhythm associated with Mobitz I or II second-degree AV block is not irregularly irregular since there is a pattern to the variation in ventricular rate, but this pattern may not be immediately recognized. Graphic 132103 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 14/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Normal sinus rhythm with artifact Normal sinus rhythm with artifact: 12-lead ECG showing sinus rhythm (best seen in lead V1) along with baseline artifact that resembles AF (most evident in leads II, III, and aVF). The best way to avoid misinterpretation of this AF mimic is to carefully review all leads of the 12-lead tracing, noting any leads with evidence of regular P waves, a consistent PR interval, and a one-to-one correspondence of P waves to QRS complexes (in this case, lead V1 along with the occasional concurrent P waves in lead II demonstrates sinus rhythm). ECG: electrocardiogram; AF: atrial fibrillation. Graphic 132168 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 15/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Normal sinus rhythm with tremor Normal sinus rhythm with tremor: Lead V1 and lead II rhythm strips show sinus rhythm, evident from typical sinus P waves in leads V1 and lead II, with superimposed 3 to 5 Hz oscillations consistent with tremor activity. Graphic 132169 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 16/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Value of increasing ECG gain with possible AF Value of increasing ECG gain with possible AF. (A) Lead V1 and lead II rhythm strips show an irregularly irregular rhythm. At first glance, the rhythm looks li with moderate ventricular response. (B) However, when the gain is increased twofold, it is now apparent that there are P waves preceding each QR th (*). Some P waves (eg, the 1 , 2 5 , 10 , 11 , 12 , and 13 P waves appear to be nonsinus, suggesting frequent atrial premature complex st nd th th th th th rd , 6 , 7 , 8 , 9 , and 14 ) appear to be sinus P waves, while the 3 , 4 th th th th th In this case, magnification of the ECG tracing facilitates recognition of a common AF mimic that could be associated with a preliminary ECG machine interpretation of AF. ECG: electrocardiogram; AF: atrial fibrillation. Graphic 132167 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 17/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate ECG atrial fibrillation Atrial fibrillation. 12-lead ECG shows an irregularly irregular rhythm. Discrete P waves are not seen, and there is fibrillatory atrial activity, best seen in lead V1. The average heart rate is 102 bpm, with a normal axis, QRS duration, and QTc interval, and with nonspecific ST-T changes. ECG: electrocardiogram; bpm: beats per minute. Graphic 132160 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 18/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial fibrillation with a slow, moderate, and rapid ventricular response Atrial fibrillation with a slow (A), moderate (B), and rapid (C) ventricular response. Lead V1 and lead II rhythm strips show irregularly irregular rhythms without discrete P waves and with fibrillatory atrial activity. Graphic 132159 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 19/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial fibrillation with left bundle branch block Atrial fibrillation with LBBB. Rhythm strip shows an irregularly irregular rhythm. Discrete P waves are not seen, and there is fibrillatory atrial activity. The QRS duration is approximately 120 ms, and a complete LBBB is seen with a QS complex in lead V1. LBBB: left bundle branch block. Graphic 132162 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 20/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial fibrillation with complete heart block AF with complete heart block. Lead V1 and lead II rhythm strips show AF with complete heart block with a na complex junctional escape rhythm (A) or with a wide complex ventricular escape rhythm (B). AF: atrial fibrillation. Graphic 132164 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 21/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial fibrillation with fully paced QRS complexes Atrial fibrillation with fully paced QRS complexes (beats 1 ,5, 6, 7, 8). Native ventricular conduction is present (beats 2, 3, 4), and there are complexes (beats 9, 10) where the pacer stimulus occurs while the native complex is being conducted, resulting in a complex that has the same morphology as the native QRS complex (pacemaker pseudofusion). Graphic 132165 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 22/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial fibrillation with ventricular tachycardia AF with ventricular tachycardia. Lead V1 and lead II rhythm strips show AF with rapid ventricular response and the onset of monomorphic ventricular tachycardia at approximately 170 bpm. AF: atrial fibrillation; bpm: beats per minute. Graphic 132166 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 23/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial flutter Atrial flutter. (A) Lead V1 and lead II ECG tracings show AFL with a moderate ventricular response and variable AV conduct with flutter waves discernable in lead II. They are uniform, and occur at a rate of 300/min. Inferiorly directed flutter waves that are positive in V1 are suggestive of typical (cavotricuspid isthmus-dependent), countercloc AFL. (B) Lead V1 and lead II ECG tracings show AFL with moderate ventricular response and variable AV conductio with flutter waves in lead II at a rate of 272 bpm, consistent with typical AFL. ECG: electrocardiogram; AFL: atrial flutter; AV: atrioventricular; bpm: beats per minute. Graphic 132170 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 24/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Sinus rhythm with sinus arrhythmia Sinus rhythm with sinus arrhythmia. Lead V1 and lead II rhythm strips show an irregular rhythm with a ventricular rate that gradually increases, and with each QRS preceded by a sinus P wave, indicating sinus rhythm with sinus arrhythmia. This can mimic AF, especially if the P wave amplitude is low. AF: atrial fibrillation. Graphic 132171 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 25/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate ECG: Sinus arrhythmia and a junctional escape rhythm Sinus arrhythmia and a junctional escape rhythm. Lead V1 and lead II rhythm strips show an irregular rhythm that initiates with sinus rhythm with sinus arrhythmia and a gradual slowing of heart rate. When the heart rate slows below a rate of approximately 35 bpm, a junctional escape beat appears followed by an atrial premature complex (note the different P wave morphology in lead V1 compared with initial sinus beats). The variation in rate and the presence of some QRS complexes not preceded by a P wave contribute to this rhythm being incorrectly labeled as atrial fibrillation by a preliminary ECG machine interpretation. ECG: electrocardiogram; bpm: beats per minute. Graphic 132172 Version 3.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 26/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Normal sinus rhythm with Mobitz I second-degree AV block Normal sinus rhythm with Mobitz I second-degree AV block. Lead V1 and lead II rhythm strips show a regularly irregular rhythm with group beat. There are distinct P waves before each QRS as well as during the relative pauses. The P-P interval is constant, consistent with a sinus rhythm at a rate of 80 bpm. There is progressive prolongation of the PR interval followed by a dropped beat (nonconducted sinus P wave), reflective of Mobitz I second-degree AV block. AV: atrioventricular; bpm: beats per minute. Graphic 132173 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 27/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Normal sinus rhythm with an ectopic atrial rhythm Normal sinus rhythm with an ectopic atrial rhythm. Lead V1 and lead II rhythm strips show a somewhat irregular narrow QRS complex rhythm that starts off (first 3 beats) with sinus P waves, which then shift to a different (nonsinus) focus, evident by the change in P wave morphology in subsequent beats. Graphic 132174 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 28/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Atrial tachycardia with block Atrial tachycardia with block. Lead V1 and lead II rhythm strips show regular atrial activity at a rate of 160 bpm with variable AV block, consistent with atrial tachycardia with AV block. bpm: beats per minute; AV: atrioventricular. Graphic 132175 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 29/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Wandering atrial pacemaker Wandering atrial pacemaker. Lead V1 and lead II rhythm strips show an irregularly irregular rhythm. On close examination there are more than 3 different P wave morphologies preceding each QRS complex. As the rate is <100 beats per minute, the rhythm is wandering atrial pacemaker (rather than multifocal atrial tachycardia). Graphic 132176 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 30/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Multifocal atrial tachycardia Multifocal atrial tachycardia. Lead V1 and lead II rhythm strips show an irregularly irregular narrow QRS complex rhythm that, on first glance, looks like AF with rapid ventricular response. On closer examination, there are P waves preceding each QRS complex, and, overall, there are more than 3 different P wave morphologies, consistent with the diagnosis of multifocal atrial tachycardia. AF: atrial fibrillation. Graphic 132177 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 31/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Sinus rhythm with frequent PACs with aberrant conduction Sinus rhythm with frequent PACs with aberrant conduction. st rd th th th th (A) Lead V1 and lead II rhythm strips show sinus rhythm with the 1 , 3 , 5 , 7 , 9 , and 11 beats preced t by normal sinus P waves. The 2 nd th th th th th th , 4 , 6 , 8 , 10 , and 12 beats are all PACs. However, while the 4 , 10 th nd th th th and 12 beats conduct normally, the 2 aberrant conduction with a RBBB morphology evident in lead V1. In lead II, the aberrantly conducted PACs ha similar appearance to normally conducted PACs except for a deep terminal S wave and some QRS widening d to the rate-related RBBB. , 6 , 8 , and 12 beats conduct with a wide QRS complex due to rd (B) Lead V1 and lead II rhythm strips show sinus rhythm with a PAC with aberrant conduction (3 beat) and w an interpolated PVC (8 beat). th PACs: premature atrial complexes; RBBB: right bundle branch block; PVC: premature ventricular complex. Graphic 132178 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 32/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate AF with aberrant conduction and concealed conduction AF with aberrant conduction and concealed conduction. Lead V1 and lead II rhythm strips show AF with th rapid ventricular response. Note that the 5 and 6 QRS complexes, as well as the 18 and the 20 to th th th th the 30 QRS complexes, are wide with a right bundle branch pattern apparent in lead V1, while the QRS complexes for these beats in lead II are similar to native AF beats. These are all aberrantly conducted beats. th While the initial or isolated aberrant beats (5 , 18 , and 20 ) occur after a relative long-short interval th th th st th (Ashman phenomenon), the subsequent beats (6 and 21 to 30 ) occur with a short-short sequence but are aberrant due to concealed conduction. For more detail, refer to UpToDate content on the electrocardiogram in atrial fibrillation. AF: Atrial fibrillation. Graphic 132179 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 33/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate AF with Wolff-Parkinson-White syndrome AF with Wolff-Parkinson-White syndrome. 12-lead ECG showing AF with preexcitation. There is an irregular, wide-complex tachycardia, with many QRS complexes showing a slurred upstroke (delta wave). At times, the ventricular rate can be as high as 300 bpm. AF: atrial fibrillation; ECG: electrocardiogram; bpm: beats per minute. Reproduced with permission from: Nathanson LA, McClennen S, Safran C, Goldberger AL. ECG Wave-Maven: Self-Assessment Program for Students and Clinicians. Copyright 2021 Beth Israel Deaconess Medical Center. Available at: http://ecg.bidmc.harvard.edu (Accessed on August 2, 2021). Graphic 132180 Version 1.0 https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 34/35 7/5/23, 10:47 AM The electrocardiogram in atrial fibrillation - UpToDate Contributor Disclosures Brian Olshansky, MD Other Financial Interest: AstraZeneca [Member of the DSMB for the DIALYZE trial]; Medtelligence [Cardiovascular disease]. All of the relevant financial relationships listed have been mitigated. Zachary D Goldberger, MD, FACC, FHRS Other Financial Interest: Elsevier [Book royalties from Goldberger s Clinical Electrocardiography]. All of the relevant financial relationships listed have been mitigated. Steven M Pogwizd, MD No relevant financial relationship(s) with ineligible companies to disclose. Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/the-electrocardiogram-in-atrial-fibrillation/print 35/35

7/5/23, 11:13 AM Arrhythmic complications of mitral valve prolapse - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Arrhythmic complications of mitral valve prolapse : Matthew J Sorrentino, MD, FACC : Catherine M Otto, MD, Mark S Link, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Dec 02, 2021. INTRODUCTION Mitral valve prolapse (MVP) is the most common cause of primary mitral regurgitation (MR) in developed countries. The diagnosis is usually suspected from cardiac auscultation and then confirmed by echocardiography. (See "Mitral valve prolapse: Clinical manifestations and diagnosis".) Although the correlation between certain nonspecific symptoms and MVP remains unclear, many patients with this disorder present with palpitations and atrial or ventricular arrhythmias [1-5]. Some studies suggest that these patients are at increased risk of sudden cardiac death (SCD) compared with the general population, but the exact incidence is unknown. Furthermore, since atrial and ventricular arrhythmias are common in the general population, it is not clearly established that the incidence of arrhythmias and SCD are in fact increased in patients with MVP. This topic will review the incidence of arrhythmias, the risk of SCD, the electrocardiographic abnormalities that can be seen, and the treatment of arrhythmias in patients with MVP. The nonarrhythmic complications of MVP, including nonspecific symptoms and major complications, such as infective endocarditis, MR, transient ischemic attacks, and cerebrovascular accidents, are discussed separately. (See "Nonarrhythmic complications of mitral valve prolapse" and "Mitral valve prolapse syndrome".) PREVALENCE OF ARRHYTHMIAS https://www.uptodate.com/contents/arrhythmic-complications-of-mitral-valve-prolapse/print 1/11 7/5/23, 11:13 AM Arrhythmic complications of mitral valve prolapse - UpToDate Several studies report a broad range in -prevalence of the arrhythmias in patients with MVP [1- 5]: Premature atrial complex (PAC; also referred to a premature atrial beat, premature supraventricular complex, or premature supraventricular beat) 35 to 90 percent. Paroxysmal supraventricular tachycardia 3 to 32 percent. Ventricular premature beats 58 to 89 percent. Complex ventricular ectopy 30 to 56 percent. This wide variability is most likely due to selection bias and to the heterogeneity of the populations studied. Most studies have been performed in adults, but ventricular arrhythmias have also been reported in children with MVP [6,7]. What remains unclear is whether the prevalence of one or more of these arrhythmias in adults with MVP is higher than in controls. Some well-controlled studies do not show an increased prevalence of arrhythmias in MVP. The Framingham Heart Study compared 84 patients with MVP, based upon current two-dimensional echocardiographic criteria, with 3403 control subjects without MVP [8]. On average, the patients in this study had trace to mild mitral regurgitation (MR). The prevalence of atrial ectopy (3.2 versus 1.6 percent), atrial fibrillation (1.2 versus 1.7 percent), and ventricular ectopy (2.6 versus 1.4) was equivalent in the two groups. This study suggests that MVP without significant MR is not associated with excess risk of atrial or ventricular arrhythmias. Arrhythmias may be more common in patients with MVP who develop MR, a population that may be overrepresented in some studies [9]. Patients with MR and MVP have more ventricular arrhythmias than those with MVP alone [10]. The presence of moderate to severe MR is an independent predictor of ventricular arrhythmias in patients with MVP [11]; in this setting, ventricular arrhythmias are associated with significant mitral valve annular abnormalities and left ventricular dysfunction [12]. Atrial arrhythmias are also more common in those with MVP and MR than in those with MVP alone [10]. The presence of moderate to severe MR is an independent predictor of atrial arrhythmias in patients with MVP [13]. In echocardiographic series of patients with MVP, the observed frequency of atrial fibrillation (AF) has varied from 1 to 25 percent or more [14]. In a study of 246 patients with MVP with MR undergoing mitral valve surgery, the frequency of chronic AF was 15 percent, and paroxysmal AF occurred in 13 percent. Risk factors for development of AF were evaluated in 89 patients with moderate to severe MR and simple MVP and 360 patients with flail mitral leaflets [15]. In both groups, the predictors of AF were age and left atrial diameter. https://www.uptodate.com/contents/arrhythmic-complications-of-mitral-valve-prolapse/print 2/11 7/5/23, 11:13 AM Arrhythmic complications of mitral valve prolapse - UpToDate SUDDEN CARDIAC DEATH SCD in patients with MVP is usually due to ventricular fibrillation [16]. However, the relation between MVP and SCD is uncertain. Consistent with a causative role for MVP is the observation that MVP is the only cardiac abnormality in some patients at autopsy and in certain survivors of SCD [16-23]. As an example, among a cohort of 24 patients with an implantable cardioverter- defibrillator who experienced idiopathic out-of-hospital cardiac arrest (all had no evidence of myocardial ischemia, cardiomyopathy, or channelopathy), 10 patients (42 percent) were found to have bileaflet MVP [23]. Patients with MVP in this cohort were also significantly more likely to have T wave abnormalities and ventricular ectopy compared with those with normal mitral valves. (See 'Electrocardiographic abnormalities' below.) MVP is also the only cardiac abnormality found in 8 to 16 percent of patients with refractory ventricular tachycardia (VT) [1-3]. On the other hand, both SCD and VT can occur in patients without apparent structural heart disease, and it is not clear that other causes of SCD and VT were excluded in the above reports. (See "Approach to sudden cardiac arrest in the absence of apparent structural heart disease" and "Ventricular tachycardia in the absence of apparent structural heart disease".) The incidence of SCD in patients with MVP is not clearly established. One estimate of the risk of SCD in patients with MVP without MR was 1.9 per 10,000 patients per year [1]. The risk was estimated to be 50 to 100 times higher (0.9 to 1.9 percent per year) if significant MR is present; this is the rate that was later observed in patients with flail mitral leaflet (see 'Flail mitral leaflet' below). In series including patients with MVP with a spectrum of MR severity, an intermediate risk of SCD has been observed. Two such series of 237 and 300 patients, both with mean follow- up of six years, found that SCD occurred in 2.5 and 1.0 percent (0.4 and 0.2 percent per year), respectively [20,21]. Early small series of patients with MVP suggested an association between the following factors and increased risk of SCD [1-3,18,24]: history of syncope or near syncope, symptoms such as palpitations, chest pain, and dyspnea, prolonged QT interval or inferolateral repolarization abnormalities, frequent or complex ventricular premature beats, prolapse of both the anterior and posterior mitral valve leaflets, hemodynamically significant mitral regurgitation, and flail mitral leaflet. The increased risk of SCD associated with flail mitral leaflet was confirmed in a large series [25]. (See 'Flail mitral leaflet' below.) A study of 237 patients found a higher incidence of SCD (approximately 1.6 percent per year) in patients with redundant (defined as thickness of 5 mm or more) mitral valve leaflets as https://www.uptodate.com/contents/arrhythmic-complications-of-mitral-valve-prolapse/print 3/11 7/5/23, 11:13 AM Arrhythmic complications of mitral valve prolapse - UpToDate compared with the rate (approximately 0.1 percent per year) for those without redundant leaflets [20]. The increased risk of SCD associated with MR may be directly related to the valvular regurgitation, rather than MVP itself. (See "Chronic primary mitral regurgitation: General management".) Proposed pathophysiologic mechanisms for SCD include fibrosis in the papillary muscles and inferobasal wall of the left ventricle, mitral annular disjunction, and systolic curling of the mitral leaflets [26]. Premature ventricular complexes (PVCs) arising from the Purkinje tissue may be a trigger for ventricular fibrillation [27]. Risk stratification As for other patient populations, prior cardiac arrest or sustained VT are strong predictors of SCD in individuals with MVP. While other clinical risk factors for sudden death, such as the presence of flail leaflet or the presence of significant mitral regurgitation, have been proposed, no specific recommendations for risk stratification of patients with MVP have been defined. The 2017 American College of Cardiology/American Heart Association/European Society of Cardiology guidelines for ventricular arrhythmias and SCD recommended that patients with valvular heart disease and ventricular arrhythmias should be evaluated and treated following current recommendations for each disorder [28]. No specific risk stratification of patients with MVP for SCD was recommended. Flail mitral leaflet Among patients with MVP, SCD appears be more common in patients with chordal rupture resulting in a flail mitral leaflet, particularly those treated conservatively. (See "Natural history of chronic mitral regurgitation caused by mitral valve prolapse and flail mitral leaflet".) The following findings were noted in a retrospective report of 348 patients with flail mitral leaflet who were followed for a mean of four years [25]: The estimated sudden death rate at 5 and 10 years was 8.6 and 18.8 percent, respectively. The linearized rate was 1.8 percent per year. Independent predictors of sudden death were New York Heart Association class III and IV (7.8 versus 1.0 and 3.1 percent per year in class I and II, respectively), left ventricular ejection fraction (LVEF) less than 50 percent (12.7 versus approximately 1.2 percent with LVEF above 50 percent), and atrial fibrillation (4.9 versus 1.3 percent per year with sinus rhythm). https://www.uptodate.com/contents/arrhythmic-complications-of-mitral-valve-prolapse/print 4/11 7/5/23, 11:13 AM Arrhythmic complications of mitral valve prolapse - UpToDate Twenty percent of patients with sudden death had none of these risk factors; the yearly rate of sudden death in this setting was 0.8 percent. Other comorbidities prevalent in these patients may have been important. Surgical correction of the flail leaflet reduced the incidence of sudden death (adjusted hazard ratio 0.29). Causes of sudden cardiac arrest generally are discussed separately. (See "Pathophysiology and etiology of sudden cardiac arrest".) ELECTROCARDIOGRAPHIC ABNORMALITIES Several electrocardiographic abnormalities have been reported in patients with MVP, including QT interval prolongation, repolarization abnormalities, and evidence for accessory pathways. These findings, however, are not supported by all surveys of patients with MVP. As an example, some studies report that as many as 75 percent of patients with MVP have QT interval prolongation [1]. In contrast, at least two series found no increase in QT prolongation compared with control populations [1,29]. The Framingham Heart Study found no difference in the prevalence of left ventricular hypertrophy or left atrial enlargement between those with and without MVP [8]. There is also no evidence to indicate an increased prevalence of accessory pathways in patients with MVP. In addition, the claim that ST segment and T wave abnormalities are more common in MVP is controversial, as is the possible link between repolarization abnormalities and arrhythmias. One study noted greater dispersion of refractoriness in 32 patients with MVP and documented ventricular arrhythmias, although the QT interval was not prolonged [30]. This raises the possibility that regional shortening and lengthening of repolarization times may be a mechanism for arrhythmias and SCD in MVP. CMR In a cardiovascular magnetic resonance (CMR) imaging report, focal late gadolinium enhancement (LGE) in the papillary muscles was observed in patients with MVP, particularly in those with complex ventricular arrhythmias [31]. LGE at the level of the papillary muscles and inferobasal wall of the left ventricle was found in a population of MVP patients with ventricular arrhythmias, suggesting a possible correlation with histologic findings of fibrosis in some patients with MVP and SCD [32]. The clinical significance of these CMR findings has not been determined. https://www.uptodate.com/contents/arrhythmic-complications-of-mitral-valve-prolapse/print 5/11 7/5/23, 11:13 AM Arrhythmic complications of mitral valve prolapse - UpToDate ELECTROPHYSIOLOGIC TESTING Electrophysiologic (EP) testing has been used in an attempt to understand the role of arrhythmias in patients with MVP. Unfortunately, the data are again conflicting. It has been suggested that patients with symptoms or documented arrhythmias are more likely to have inducible ventricular tachycardia. However, an analysis of six fairly rigorous studies found that only 6 out of 100 patients with symptomatic or asymptomatic nonsustained ventricular tachycardia had inducible sustained monomorphic ventricular tachycardia; as a result, the association between inducibility and clinical symptoms is unlikely to be valid [33]. Similar to its role in other patient groups, EP testing is not generally performed in survivors of SCD or sustained ventricular tachycardia. (See "Cardiac evaluation of the survivor of sudden cardiac arrest", section on 'EP study'.) MANAGEMENT The treatment of arrhythmias in patients with MVP varies with the clinical setting. Survivors of SCD or sustained VT Survivors of SCD or sustained ventricular tachycardia with structural heart disease are considered to be at high risk for subsequent SCD. An implantable cardioverter-defibrillator is recommended in such patients. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".) Very symptomatic palpitations The type and presence of arrhythmias in patients with marked symptoms due to palpitations should be documented by either 24-hour Holter or transtelephonic monitoring. Treatment is then initiated based upon both the arrhythmia and the severity of symptoms. The benefit derived from the relief of symptoms with treatment must be weighed against the possible proarrhythmic and other side effects of many antiarrhythmic drugs. (See "Evaluation of palpitations in adults".) Mild palpitations from atrial or ventricular premature beats Many patients with mild palpitations from premature beats can be treated conservatively with reassurance, abstinence from alcohol or stimulants such as caffeine or nicotine, and participation in an exercise program. Beta blockers can occasionally be used; they are particularly effective in patients with inappropriate heart rate responses to stress, anxiety, or activity. (See "Premature ventricular complexes: Treatment and prognosis".) Atrial fibrillation As mentioned above, it is not clear if the incidence of atrial fibrillation (AF) is increased in patients with MVP who have no or mild mitral regurgitation (MR) [8]. The risk of https://www.uptodate.com/contents/arrhythmic-complications-of-mitral-valve-prolapse/print 6/11 7/5/23, 11:13 AM Arrhythmic complications of mitral valve prolapse - UpToDate AF is related to MR, age, and atrial size. The role of antithrombotic therapy in patients with MVP with and without AF is presented separately. (See "Chronic primary mitral regurgitation: General management".) In addition, the development of new-onset AF in patients with MVP and severe MR is an indication for corrective surgery. (See "Indications for intervention for chronic severe primary mitral regurgitation".) Asymptomatic patients without evidence of sustained arrhythmias There is no evidence that therapy will offer any survival advantage to asymptomatic patients without evidence of sustained arrhythmias. The prognosis in asymptomatic patients with nonsustained arrhythmias and structurally normal hearts is quite good. Thus, the potential deleterious effects of drug therapy probably outweigh any risk from the arrhythmia in this setting. Mitral valve surgery Although there is a risk of SCD in patients with MVP, particularly among those with flail mitral leaflet treated conservatively, the efficacy of mitral valve repair or replacement in reducing the risk of sudden death in patients with severe MR and ventricular arrhythmias is not well established [34]. Indications for surgery in patients with MVP and MR are discussed separately. (See "Indications for intervention for chronic severe primary mitral regurgitation" and "Acute mitral regurgitation in adults".) Participation in sports Recommendations for participation in sports for patients with MR are detailed separately. (See "Chronic primary mitral regurgitation: General management", section on 'Exercise'.) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Arrhythmias in adults" and "Society guideline links: Cardiac valve disease".) SUMMARY AND RECOMMENDATIONS Atrial and ventricular arrhythmias have been observed in patients with mitral valve prolapse (MVP). However, there is evidence that the prevalence of these arrhythmias is https://www.uptodate.com/contents/arrhythmic-complications-of-mitral-valve-prolapse/print 7/11 7/5/23, 11:13 AM Arrhythmic complications of mitral valve prolapse - UpToDate similar to that in the general population, at least among those with trace or mild mitral regurgitation. (See 'Prevalence of arrhythmias' above.) The risk for sudden cardiac death (SCD) in patients with MVP appears to vary with severity of accompanying mitral regurgitation. (See 'Sudden cardiac death' above.) A role for electrophysiologic testing in patients with MVP has not been established. (See 'Electrophysiologic testing' above.) Survivors of SCD or sustained ventricular tachycardia with structural heart disease are considered to be at high risk for subsequent SCD. An implantable cardioverter-defibrillator is recommended in such patients. (See 'Survivors of SCD or sustained VT' above.) Although the risk of SCD is increased in patients with flail mitral leaflet, the available evidence is insufficient to establish a role for mitral valve surgery in reducing the risk of SCD. (See 'Flail mitral leaflet' above and 'Mitral valve surgery' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Kligfield P, Levy D, Devereux RB, Savage DD. Arrhythmias and sudden death in mitral valve prolapse. Am Heart J 1987; 113:1298. 2. Schaal SF. Ventricular arrhythmias in patients with mitral valve prolapse. Cardiovasc Clin 1992; 22:307. 3. Kligfield P, Devereux RB. Is the mitral valve prolapse patient at high risk of sudden death identifiable? Cardiovasc Clin 1990; 21:143. 4. Babuty D, Cosnay P, Breuillac JC, et al. Ventricular arrhythmia factors in mitral valve prolapse. Pacing Clin Electrophysiol 1994; 17:1090. 5. Zuppiroli A, Mori F, Favilli S, et al. Arrhythmias in mitral valve prolapse: relation to anterior mitral leaflet thickening, clinical variables, and color Doppler echocardiographic parameters. Am Heart J 1994; 128:919. 6. Kavey RE, Blackman MS, Sondheimer HM, Byrum CJ. Ventricular arrhythmias and mitral valve prolapse in childhood. J Pediatr 1984; 105:885. 7. Bobkowski W, Siwi ska A, Zachwieja J, et al. A prospective study to determine the significance of ventricular late potentials in children with mitral valvar prolapse. Cardiol Young 2002; 12:333. https://www.uptodate.com/contents/arrhythmic-complications-of-mitral-valve-prolapse/print 8/11 7/5/23, 11:13 AM Arrhythmic complications of mitral valve prolapse - UpToDate 8. Freed LA, Levy D, Levine RA, et al. Prevalence and clinical outcome of mitral-valve prolapse. N Engl J Med 1999; 341:1. 9. Kim S, Kuroda T, Nishinaga M, et al. Relationship between severity of mitral regurgitation and prognosis of mitral valve prolapse: echocardiographic follow-up study. Am Heart J 1996; 132:348. 10. Kligfield P, Hochreiter C, Kramer H, et al. Complex arrhythmias in mitral regurgitation with and without mitral valve prolapse: contrast to arrhythmias in mitral valve prolapse without mitral regurgitation. Am J Cardiol 1985; 55:1545. 11. Turker Y, Ozaydin M, Acar G, et al. Predictors of ventricular arrhythmias in patients with mitral valve prolapse. Int J Cardiovasc Imaging 2010; 26:139. 12. van Wijngaarden AL, de Riva M, Hiemstra YL, et al. Parameters associated with ventricular arrhythmias in mitral valve prolapse with significant regurgitation. Heart 2021; 107:411. 13. Turker Y, Ozaydin M, Acar G, et al. Predictors of atrial arrhythmias in patients with mitral valve prolapse. Acta Cardiol 2009; 64:755. 14. Berbarie RF, Roberts WC. Frequency of atrial fibrillation in patients having mitral valve repair or replacement for pure mitral regurgitation secondary to mitral valve prolapse. Am J Cardiol 2006; 97:1039. 15. Grigioni F, Avierinos JF, Ling LH, et al. Atrial fibrillation complicating the course of degenerative mitral regurgitation: determinants and long-term outcome. J Am Coll Cardiol 2002; 40:84. 16. Boudoulas H, Schaal SF, Stang JM, et al. Mitral valve prolapse: cardiac arrest with long-term survival. Int J Cardiol 1990; 26:37. 17. Vohra J, Sathe S, Warren R, et al. Malignant ventricular arrhythmias in patients with mitral valve prolapse and mild mitral regurgitation. Pacing Clin Electrophysiol 1993; 16:387. 18. Davies MJ, Moore BP, Braimbridge MV. The floppy mitral valve. Study of incidence, pathology, and complications in surgical, necropsy, and forensic material. Br Heart J 1978; 40:468. 19. Chesler E, King RA, Edwards JE. The myxomatous mitral valve and sudden death. Circulation 1983; 67:632. 20. Nishimura RA, McGoon MD, Shub C, et al. Echocardiographically documented mitral-valve prolapse. Long-term follow-up of 237 patients. N Engl J Med 1985; 313:1305. 21. D ren DR, Becker AE, Dunning AJ. Long-term follow-up of idiopathic mitral valve prolapse in 300 patients: a prospective study. J Am Coll Cardiol 1988; 11:42. https://www.uptodate.com/contents/arrhythmic-complications-of-mitral-valve-prolapse/print 9/11 7/5/23, 11:13 AM Arrhythmic complications of mitral valve prolapse - UpToDate 22. Anders S, Said S, Schulz F, P schel K. Mitral valve prolapse syndrome as cause of sudden death in young adults. Forensic Sci Int 2007; 171:127. 23. Sriram CS, Syed FF, Ferguson ME, et al. Malignant bileaflet mitral valve prolapse syndrome in patients with otherwise idiopathic out-of-hospital cardiac arrest. J Am Coll Cardiol 2013; 62:222. 24. Alpert JS. Association between arrhythmias and mitral valve prolapse. Arch Intern Med 1984; 144:2333. 25. Grigioni F, Enriquez-Sarano M, Ling LH, et al. Sudden death in mitral regurgitation due to flail leaflet. J Am Coll Cardiol 1999; 34:2078. 26. Basso C, Iliceto S, Thiene G, Perazzolo Marra M. Mitral Valve Prolapse, Ventricular Arrhythmias, and Sudden Death. Circulation 2019; 140:952. 27. Syed FF, Ackerman MJ, McLeod CJ, et al. Sites of Successful Ventricular Fibrillation Ablation in Bileaflet Mitral Valve Prolapse Syndrome. Circ Arrhythm Electrophysiol 2016; 9. 28. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2018; 72:e91. 29. Sniezek-Maciejewska M, Dubiel JP, Piwowarska W, et al. Ventricular arrhythmias and the autonomic tone in patients with mitral valve prolapse. Clin Cardiol 1992; 15:720. 30. Tieleman RG, Crijns HJ, Wiesfeld AC, et al. Increased dispersion of refractoriness in the absence of QT prolongation in patients with mitral valve prolapse and ventricular arrhythmias. Br Heart J 1995; 73:37. 31. Han Y, Peters DC, Salton CJ, et al. Cardiovascular magnetic resonance characterization of mitral valve prolapse. JACC Cardiovasc Imaging 2008; 1:294. 32. Basso C, Perazzolo Marra M, Rizzo S, et al. Arrhythmic Mitral Valve Prolapse and Sudden Cardiac Death. Circulation 2015; 132:556. 33. Kinder C, Tamburro P, Kopp D, et al. The clinical significance of nonsustained ventricular tachycardia: current perspectives. Pacing Clin Electrophysiol 1994; 17:637. 34. European Heart Rhythm Association, Heart Rhythm Society, Zipes DP, et al. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for https://www.uptodate.com/contents/arrhythmic-complications-of-mitral-valve-prolapse/print 10/11 7/5/23, 11:13 AM Arrhythmic complications of mitral valve prolapse - UpToDate Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death). J Am Coll Cardiol 2006; 48:e247. Topic 8169 Version 23.0 Contributor Disclosures Matthew J Sorrentino, MD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Catherine M Otto, MD No relevant financial relationship(s) with ineligible companies to disclose. Mark S Link, MD No relevant financial relationship(s) with ineligible companies to disclose. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/arrhythmic-complications-of-mitral-valve-prolapse/print 11/11

7/5/23, 11:14 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Athletes: Overview of sudden cardiac death risk and sport participation : Antonio Pelliccia, MD, Mark S Link, MD : Peter J Zimetbaum, MD, Scott Manaker, MD, PhD : Todd F Dardas, MD, MS All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: May 03, 2022. INTRODUCTION Sudden cardiac death (SCD) associated with athletic activity is a rare but devastating event. Victims can be young and apparently healthy, and while many of these deaths are unexplained, a substantial number harbor underlying previously undiagnosed cardiovascular disease. As a result, there is great interest in early identification of at-risk individuals for whom appropriate activity restrictions can be implemented to minimize the risk of SCD. The majority of SCD events in athletes are due to malignant arrhythmias, usually sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). In individuals with certain cardiac disorders (eg, hypertrophic cardiomyopathy, arrhythmogenic cardiomyopathy, etc), athletics may increase the likelihood of VT/VF in two ways: In certain susceptible individuals (ie, with inherited arrhythmogenic cardiomyopathy), prolonged exercise training may induce adaptive changes in cardiac structure (eg, interstitial fibrosis, disruption of normal myocardial architecture, dilation of right and left ventricle) that may create pathologic arrhythmogenic substrate. The immediate physiologic demands of intense athletics (eg, mechanical strain, increased myocardial oxygen consumption, hemodynamic overload, catecholamine release, electrolyte imbalance) may trigger malignant arrhythmias in susceptible individuals with underlying cardiac abnormalities. https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 1/28 7/5/23, 11:14 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate The potential for SCD associated with athletic activity generates two questions: How should individuals be identified prior to initiating athletic activity? What restrictions (if any) should be placed upon individuals with known cardiovascular disease to minimize the SCD risk ? Answers to these questions are complicated and controversial and often based on limited clinical data and thus expert opinion. Answers vary based upon three factors: The age of the individual The nature of the activity (ie, competitive versus recreational athletics) The type of underlying heart disease This topic will review the major etiologies of SCD in athletes and recommendations for participation in sports in the presence of various cardiac abnormalities. The broader range of arrhythmias and conduction disturbances common in athletes, including treatment and return to participation following treatment, are discussed separately. (See "Athletes with arrhythmias: Electrocardiographic abnormalities and conduction disturbances" and "Athletes with arrhythmias: Clinical manifestations and diagnostic evaluation" and "Athletes with arrhythmias: Treatment and returning to athletic participation".) The recommended approaches to preparticipation screening of athletes are also presented separately. (See "Screening to prevent sudden cardiac death in competitive athletes".) DEFINITIONS Although definitions vary from study to study, it is important to define the populations of athletes as well as the level of competition in which the athletes are engaged. Young athletes Most commonly, "young athletes" refers to those in high school and college but applies in general to individuals under age 35 in whom SCD is usually due to a variety of congenital heart diseases. Masters athletes Adult, or "masters," athletes include individuals 35 years of age in whom SCD is most commonly associated with coronary heart disease. Such sports programs primarily include apparently normal and healthy individuals 35 years of age, although many participants are greater than 50 up to 80 years of age. Competitive/elite athletes Competitive/elite athletes engage in organized team or individual sports in which there is regular competition, placing a premium on achievement. https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 2/28 7/5/23, 11:14 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate This definition implies that individuals are regularly engaged in high-level training and competition and may not have the will or the judgment to limit their activity. This most frequently applies to high school, college, and professional sports. Recreational athletes Recreational athletes generally participate for health and/or enjoyment purposes and do not typically have the same pressures to excel. Activity levels may still be vigorous, and the distinction from competitive athletics may be elusive in the individual case. However, defining recreational athletics separately permits the development of guidelines for noncompetitive athletes with cardiovascular disease. COMPETITIVE VERSUS RECREATIONAL ATHLETICS The literature on SCD during exertion has largely focused on competitive athletics. However, some recreational athletics can be as vigorous as competitive sport, so recreational activity limitations are also important in individuals with one of the cardiovascular diseases commonly associated with SCD [1]. While the incidence of SCD appears higher in competitive versus recreational athletes, the total number of SCDs is greater in recreational athletes, due to the sheer numbers of persons engaging in recreational activity [2]. The balance between the risks and benefits of athletic activity depends upon several factors, including baseline fitness level, the nature and intensity of athletic activity, the presence and extent of cardiac disease, and the psychologic and physical benefit from sport. For patients with a congenital disorder, with either structural or arrhythmic substrate, the possible increased risk associated with participation in athletic activity generally requires some restriction on athletic activity. However, it must be acknowledged that these restrictions are usually based on expert opinion and not controlled studies. Historically, patients with known genetic disorders that may predispose to SCD (eg, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, Marfan syndrome, long QT syndrome) have been advised to avoid recreational activities with the following characteristics: "Burst" exertion, involving rapid acceleration and deceleration, as is common in sprints, basketball, tennis, and soccer. Activities with stable energy expenditure, such as jogging, biking on level terrain, and lap swimming are preferred. Extreme environmental conditions (temperature, humidity, and altitude) that impact blood volume and electrolytes. Systematic and progressive training load focused on achieving higher levels of conditioning and excellence. https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 3/28 7/5/23, 11:14 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate However, paternalistic guidance has been changed to a contemporary approach for a shared decision-making process, which involves the athlete in the discussion of risk and benefit. Patients with unusual or high-risk clinical features may require greater restriction. These features include a history of syncope or presyncope (especially during exertion), prior arrhythmic episodes, or an implantable cardioverter-defibrillator (ICD). However, for most other individuals, including those with stable coronary heart disease, the overall benefits of regular exercise far outweigh the risks. A prudent and gradually progressive exercise program is appropriate in most cases [2]. (See "Exercise and fitness in the prevention of atherosclerotic cardiovascular disease" and "The benefits and risks of aerobic exercise".) OUR APPROACH TO PARTICIPATION IN ATHLETICS (AND SPORT ACTIVITY IN GENERAL) Our approach to participation in sport activity, either recreationally or competitively, is in general agreement with that of the American Heart Association [2]: Physically active asymptomatic individuals without known cardiovascular disease These individuals may continue their usual moderate or vigorous exercise and progress gradually as tolerated. Those who develop signs or symptoms of cardiovascular disease should discontinue exercise and seek guidance from a medical professional before resuming exercise of any intensity. Physically active asymptomatic individuals with known cardiovascular disease Those who have been medically evaluated within 12 months may continue a moderate- intensity exercise program unless they develop signs or symptoms, which requires immediate cessation of exercise and medical reassessment. Physically inactive individuals without known cardiovascular disease These persons may begin light- to moderate-intensity exercise without medical guidance and, provided they remain asymptomatic, progress gradually in intensity as recommended by current American College of Sports Medicine (ACSM) guidelines. Physically inactive individuals with known cardiovascular disease or signs/symptoms that are suggestive cardiovascular disease Such patients should seek medical guidance before starting an exercise program, regardless of the intensity. INCIDENCE OF SUDDEN CARDIAC DEATH https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 4/28 7/5/23, 11:14 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate It is widely acknowledged that SCD is one of the leading medical causes of death in athletes, although its exact incidence remains controversial. The best available evidence, together with a close examination of reporting methods for case identification and population definitions, suggests that an overall incidence of between 1:50,000 and 1:100,000 per year in young athletes is a reasonable estimate based on existing information from retrospective cohort studies and prospective observational and cross-sectional studies [3-5]. This rate is notably higher in older adults, closer to 1:7000 healthy adult athletes per year [2]. Incidence data are imprecise since most are derived from retrospective analyses, and incidence varies depending upon the intensity of exercise, the athletic population considered, the time period of observation, and whether the definition of athletic SCD encompasses SCD outside of sport/exercise [6-10]. Use of media reports or catastrophic insurance claims as the primary method for case identification has been demonstrated to underestimate (by approximately 50 percent) the risk of SCD in athletes [3]. Male athletes are consistently found to be at greater risk, and there appears to be a disproportionately higher risk among male African American athletes. Using data from the Rescue Registry cardiac arrest database, which contains data from all out- of-hospital sudden cardiac arrests (SCA, which includes deaths and resuscitated arrests) attended by paramedics in the province of Ontario, Canada, investigators retrospectively reviewed the incidence of SCA between 2009 and 2014 among an estimated 350,000 competitive athletes ages 12 to 45 years (in total 2.1 million athlete-years) [4]. Among the 3825 out-of- hospital SCA presumed to be cardiac in nature that occurred over the six years, 74 were identified as occurring during or within one hour of sports activities (16 during competitive sports, 58 during recreational sports). Although the overall rate of SCA in athletes was 0.76 per 100,000 athlete-years, 44 percent survived to hospital discharge, leading to an overall rate of SCD of 0.42 per 100,000 athlete-years. The incidence rate was somewhat higher among athletes ages 12 to 17 years (SCA rate 1.17 per 100,000 athlete-years; SCD rate 0.65 per 100,000 athlete- years) but still lower than prior SCD estimates of 1:50,000 athletes per year. The magnitude of the problem and the challenges inherent in screening are illustrated in reports of arrhythmic events associated with major endurance sporting events [8,11]. As an example, in a study examining SCD in 215,413 marathon runners participating in one of two marathons over a 19-year period, the following findings were noted [8]: SCD occurred in four individuals during or immediately following the marathon, an incidence of approximately 1 in 50,000. This is substantially lower than the annual risk of premature death in the general population. None of the four subjects had prior cardiac symptoms. https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 5/28 7/5/23, 11:14 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate Two of the four had completed several previous marathons. Three of the four had coronary artery disease on autopsy, although none had a previous infarction. Although the incidence of SCD among marathon runners is low (one death per 215,000 hours), it is higher than for other types of exercise, such as noncompetitive jogging (one death per 396,000 hours), cross-country skiing (one death per 607,000 hours), or general, noncompetitive exercise (one death per 375,000 hours) [12-15]. ETIOLOGY OF SUDDEN DEATH Structural heart disease SCD in athletes often occurs in the presence of structural heart disease, although the underlying disorder is usually undetected until the presenting arrhythmic event. Structural heart disease can increase the risk for SCD by one or more of the following mechanisms: By far the most frequent mechanisms are ventricular tachyarrhythmias, which are commonly due to reentrant arrhythmias that develop in abnormal myocardium and/or areas of fibrotic replacement of myocardial tissue. Other rare but possible mechanisms include bradyarrhythmia or asystole due to extension of the pathologic process into the conduction system, causing complete heart block without a reliable escape focus. Syncope, in addition to arrhythmic causes, may result from outflow tract obstruction in hypertrophic cardiomyopathy and aortic stenosis, as well as from cyanosis during exercise in the setting of certain congenital lesions with right-to-left shunts. Dissection of the great vessels, as in patients with Marfan syndrome. Athletes <35 years of age Several large series have evaluated SCD in athletes less than 35 years of age [6,16-24] . In most cases, structural heart disease was present, although more contemporary data suggest more sudden arrhythmic death with a structural normal heart [2,22]. When present, the most common structural heart diseases include hypertrophic cardiomyopathy (HCM), anomalous origin of a coronary artery, arrhythmogenic right ventricular cardiomyopathy (ARVC, which commonly also affects the left ventricle), myocarditis, and coronary atherosclerosis, albeit with some variation among the different series. https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 6/28 7/5/23, 11:14 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate Among 1435 young competitive athletes from a United States registry in whom cardiovascular disease was evident on postmortem examination following SCD, HCM (36 percent) and anomalous origin of a coronary artery accounted for more than half of the cases [17]. A separate study showed that among 51 middle school athletes, anomalous origins of a coronary artery accounted for one-third of cases of sudden cardiac arrest and death [24]. However, among 55 college and professional athletes, cardiomyopathies (hypertrophic, arrhythmogenic, dilated, noncompaction, or restrictive) accounted for nearly half of cases. In a cohort of over six million military recruits in the United States (mean age 19, range 17 to 35), among whom 126 nontraumatic sudden deaths occurred (including 108 [86 percent] related to exercise), anomalous origin of a coronary artery (33 percent), myocarditis (20 percent), coronary atherosclerosis (16 percent), and HCM (13 percent) accounted for over three-quarters of the structural abnormalities [25]. In a series from the United Kingdom Regional Registry of 357 consecutive athletes with SCD between 1994 and 2014 (mean age 29 years), sudden arrhythmic death syndrome (SADS), likely including undiagnosed primary electrical disease, was the most prevalent cause of death (42 percent) [22]. Myocardial disease was detected in 40 percent of cases, including idiopathic left ventricular (LV) hypertrophy and/or fibrosis (16 percent), ARVC (13 percent), and HCM (6 percent). A different distribution was noted in a series of 49 athletes under age 35 with SCD from northern Italy [16]. In this series, ARVC (22 percent) was the most common abnormality, followed by coronary atherosclerosis (18 percent) and anomalous origin of a coronary artery (12 percent). Athletes 35 years of age In contrast to these series in young subjects, among those 35 years of age (so-called masters athletes), coronary artery disease is the predominant cause of SCD during exercise [23,26]. (See 'Coronary artery disease' below.) Primary electrical disease SCD during athletics also occurs in the absence of structural heart disease, a situation termed primary electrical disease. Series of patients with SCD have shown an increasing number with normal autopsies, although there is concern that cardiac abnormalities may have been missed. A number of inherited arrhythmic syndromes predispose individuals to SCD, and the heart is usually structurally normal in these patients. Examples include: Long QT syndrome (see "Congenital long QT syndrome: Epidemiology and clinical manifestations") https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 7/28 7/5/23, 11:14 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate Brugada syndrome (see "Brugada syndrome: Clinical presentation, diagnosis, and evaluation") Catecholaminergic polymorphic ventricular tachycardia (see "Catecholaminergic polymorphic ventricular tachycardia") Short QT syndrome (see "Short QT syndrome") Early repolarization syndrome (see 'Early repolarization syndrome' below) In addition, in individuals with structurally normal hearts, arrhythmic events may be precipitated by trauma or occur as sporadic/idiopathic phenomena, such as commotio cordis, in which SCD results from being struck in the precordium with a projectile object such as a baseball, hockey puck, or fist. (See "Commotio cordis".) Finally, several case reports describe SCD in young athletes who had no previously known heart disease but were taking androgens for performance enhancement; cardiac hypertrophy or myocarditis were found at autopsy [27,28]. It is not possible to establish causality in these sporadic cases. (See "Use of androgens and other hormones by athletes", section on 'Side effects and complications'.) STRUCTURAL ABNORMALITIES ASSOCIATED WITH SCD Hypertrophic cardiomyopathy Our experts agree that low- to moderate-intensity exercise can and should be regularly performed by most individuals with hypertrophic cardiomyopathy (HCM). Historically, persons with a probable or unequivocal clinical diagnosis of HCM have been advised not to participate in most competitive sports with the possible exception of those that are low intensity ( figure 1) [29,30]. A novel and less restrictive approach has been suggested by the 2020 European Society of Cardiology (ESC) sport cardiology guidelines [31]. The guidelines include the option for selective participation in recreational and competitive athletic activity in patients with HCM who have a low-risk profile (ie, without any risk factors that would place them at high risk for SCD), provided that they undergo periodic evaluation. The 2020 ESC guidelines confirm that patients with high- risk markers should not participate in competitive athletics. The 2020 American Heart Association/American College of Cardiology (AHA/ACC) HCM guidelines allow for a shared decision-making approach for patients with HCM, in which the clinician and the athlete share discussion of the potential risks and benefits of exercise [32]. https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 8/28 7/5/23, 11:14 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate Activity advice in patients with HCM has been based largely on expert opinion given limited data. Some moderate-intensity and many low-intensity recreational activities were generally considered to be safe when performed in moderation, including biking, doubles tennis, swimming laps, golf, and skating, and should be considered on a case-by-case basis [31,33]. Lifting weights with weight-training machines may be safe, but intense static (isometric) activity were discouraged because of the possible induction of a Valsalva maneuver and exacerbation of an LV outflow tract gradient. HCM is a relatively common disease, occurring in approximately 1 out of 500 individuals in the general population. In most athletes with SCD due to HCM, the diagnosis of HCM was not previously established. Patients with HCM who are at the highest risk of SCD are those with prior sudden cardiac arrest. In addition, those with unexplained syncope, massive hypertrophy (maximum LV wall thickness >30 mm), family history of SCD due to HCM, significant LV outflow tract obstruction (gradient >50 mmHg), nonsustained ventricular tachyarrhythmias observed on electrocardiogram (ECG) monitoring, including exercise-related VT, apical aneurysms, and extensive scarring on cardiovascular magnetic resonance imaging are at increased risk [31]. Moreover, age is a relevant determinant, with adolescent and young athletes being at higher risk than adult patients. Among patients with HCM, stratification as advised by the AHA and the ESC can identify patients at high and relatively low risk for SCD; however, zero risk does not exist and even patients defined as low risk have a small but nontrivial risk of SCD [34-36]. (See 'Etiology of sudden death' above and "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death".) Some data suggest a relatively low risk of ventricular arrhythmias and SCD in athletes with HCM regardless of the continuation or discontinuation of training and competition. In a cohort of 88 Italian athletes with HCM who were advised to discontinue training and competition (77 who were low risk by the ESC algorithm, 67 who were low risk by the AHA algorithm), 61 patients stopped exercising, but 27 continued to exercise against clinician advice [37]. Over an average follow-up of seven years, 1.3 percent of patients per year developed symptoms (syncope, palpitations), and only one cardiac arrest occurred (in a detrained patient and not during exercise), with no significant difference in the event rates between the sedentary and exercising groups. (See "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death".) The natural history is not well defined in individuals with a genetic diagnosis of HCM in the absence of symptoms and phenotypic expression (ie, without LV hypertrophy) of the disease (so- called genotype positive, phenotype negative carriers). At present, no compelling data are available that would preclude these patients from competitive sports, particularly in the absence of a family history of sudden death [38]. Professional societies, and our experts, agree that these https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 9/28 7/5/23, 11:14 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate individuals should have periodical clinical and imaging follow-up (annually during adolescence and eventually every two years in adulthood) [1,31,39]. Congenital coronary artery abnormalities Patients with any uncorrected anomalous coronary artery origin, regardless of the presence or absence of symptoms, should generally be advised against participation in competitive sports [40]. These patients may be considered for appropriate management, which in selected cases includes surgical correction with coronary reimplantation or bypass grafting. Participation in sports at least three months after successful operation may be considered on an individual basis for an athlete without prior infarction and in the absence of ischemia, ventricular tachyarrhythmia, or LV dysfunction during maximal exercise testing [40]. Athletes with previously infarcted myocardium need to follow appropriate guidelines for clearance and observation, which primarily depend upon the degree of LV dysfunction and exercise-associated arrhythmias. In such patients, the approach is similar to that in patients with atherosclerotic coronary artery disease [41]. (See 'Coronary artery disease' below and "Exercise and fitness in the prevention of atherosclerotic cardiovascular disease" and "Cardiac rehabilitation programs".) Anomalous origin of a coronary artery is found in 12 to 33 percent of young athletes with SCD at autopsy [16,25,42]. The most common anomalies associated with SCD are the origin of the left main coronary artery from the right sinus of Valsalva and the origin of the right coronary artery from the left coronary sinus [43-46]. (See 'Etiology of sudden death' above and "Congenital and pediatric coronary artery abnormalities", section on 'Variations of coronary artery origin from the aorta'.) High-risk coronary anomalies are those in which the anomalous coronary artery originates with a slit-like ostium, has proximal intramural course, makes an acute bend, and courses between the pulmonary artery and aorta [43,46]. The presumed mechanism of SCD involves repeated bouts of silent ischemia secondary to an exaggeration of a sharp angle in the aberrant origin that occurs with exercise, with decreased blood flow in the intramural course and/or in the interarterial course between an expanded aorta and pulmonary arterial trunk. Chronic ischemia is considered responsible for myocardial fibrosis representing the ultimate substrate for induction of tachyarrhythmias during exercise. Patients with congenital coronary anomalies may present with syncope or presyncope, especially with exercise and with angina in a limited proportion of cases. Unfortunately, SCD is often the first clinical symptom. This was illustrated in a report of 18 patients with an anomalous coronary artery origin, only six of whom had a preceding history of angina and/or syncope [45]. In another series of autopsy results on 27 patients with an anomalous coronary artery, 55 https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 10/28 7/5/23, 11:14 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate percent had no clinical manifestations during life or with testing [47]. In the remaining patients, premonitory symptoms occurred only shortly before SCD. Physical examination and diagnostic studies are usually unrevealing in the absence of myocardial infarction (MI) or symptoms of ongoing ischemia. When anomalous origin of a coronary artery is suspected (usually by echocardiography), noninvasive computed tomography coronary angiography (CTCA) is advised to define anomalous coronary anatomy. Cardiovascular magnetic resonance imaging (CMR) is a noninvasive alternative to CTCA and can include gadolinium contrast imaging for identification of intramyocardial late gadolinium enhancement (LGE). Coronary angiography had been the historical gold standard for the evaluation of the origin and course of the coronary arteries and is still recommended when other studies are not diagnostic [40]. (See "Congenital and pediatric coronary artery abnormalities", section on 'Variations of coronary artery origin from the aorta' and "Cardiac imaging with computed tomography and magnetic resonance in the adult".) Arrhythmogenic (right and/or left) ventricular cardiomyopathy Because of the evidence linking athletic participation with worsened outcomes, patients with arrhythmogenic right/left ventricular cardiomyopathy (ARVC) should not participate in competitive sports ( figure 1) [29- 31]. Similarly, patients with arrhythmogenic cardiomyopathy should not participate in high- intensity noncompetitive sports, including basketball, ice hockey, sprinting, and singles tennis [29-31]. In addition, the risks associated with impaired consciousness (ie, syncope or presyncope) should be considered with regard to activities with the potential for trauma (eg, weight training with free weights, horseback riding) or certain water activities (eg, scuba diving or snorkeling). Patients with ARVC are also advised to avoid most moderate-intensity amateur activities, including biking and doubles tennis. However, they may participate in low-intensity recreational activities (class IA), including golf, skating, and light weightlifting (with weight- training machines). (See "Arrhythmogenic right ventricular cardiomyopathy: Treatment and prognosis".) The condition was initially recognized as a predominantly right ventricular (RV) disease involving fibro-fatty or fibrous infiltration of predominantly the free wall, known as arrhythmogenic RV cardiomyopathy (ARVC). However, it is now well established that in the majority of cases both ventricles are affected, and in some it may only affect the LV. The diagnosis of ARVC is based on task force criteria that encompass electrophysiological, anatomical, functional, and clinical features of the disease. Tachyarrhythmias and SCD are as frequent in patients with ARVC compared with those with a dilated cardiomyopathy or a previous infarction [16,48]. In a cohort of patients with ARVC followed for over 10 years, the mortality rate was 20 percent [49]. ARVC is a significantly more https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 11/28 7/5/23, 11:14 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate common cause of SCD in case series from Italy than in those from the United States [16,42]. (See 'Etiology of sudden death' above.) The clinical presentation of patients with ARVC, particularly the athlete, includes exercise- induced palpitations, presyncope, and/or syncope, consistent with the catecholamine-sensitive nature of many of the associated tachyarrhythmias, as well as the wall stretch observed in the right (and left) heart in response to the increased venous return occurring with exercise [50]. The diagnostic evaluation of ARVC is discussed separately. (See "Arrhythmogenic right ventricular cardiomyopathy: Diagnostic evaluation and diagnosis".) Among a cohort of 108 patients with ARVC that included 41 competitive athletes, 48 recreational athletes, and 19 inactive patients, the risk of VT or SCD was significantly higher among competitive athletes compared with either recreational athletes (hazard ratio [HR] 2.0, 95% CI 1.2-3.3) or inactive patients (HR 2.1, 95% CI 1.1-3.9) [51]. In addition, there are increasing data that repetitive extreme conditioning/exertion enhances disease progression [51,52]. Any activity, competitive or not, that causes symptoms of palpitations, presyncope, or syncope should be avoided. Marfan syndrome Athletes with Marfan syndrome can selectively participate in low and moderate static/low dynamic competitive sports (classes IA and IIA) ( figure 1) if they do not have one or more of the following: aortic root dilatation, moderate-to-severe mitral regurgitation, or family history of dissection or sudden death in a Marfan relative [53]. These athletes should have an echocardiographic measurement of aortic root dimension repeated every 6 to 12 months (depending upon the size of the aorta, rate of growth, etc) for close surveillance of aortic enlargement. (See "Management of Marfan syndrome and related disorders", section on 'Monitoring MFS'.) Athletes with Marfan syndrome, familial aortic aneurysm or dissection, or congenital bicuspid aortic valve with any degree of ascending aortic enlargement should not participate in sports that involve the potential for bodily collision. On the other hand, some moderate-intensity and many low-intensity recreational activities are generally considered to be safe, including stationary biking, hiking, doubles tennis, swimming laps, golf, and skating. However, intense static (isometric) exertion is associated with increased wall stress; therefore, activities such as weight training with either free weights or weight machines should be avoided. Marfan syndrome is an autosomal dominant condition that is one of the most common inherited disorders of connective tissue. The full phenotype is characterized by arachnodactyly, tall stature, pectus excavatum, kyphoscoliosis, and lenticular dislocation. Malignant arrhythmias are not common in Marfan syndrome, but the cardiovascular manifestations include aortic https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 12/28 7/5/23, 11:14 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate dissection, which can lead to sudden death. The genetics, epidemiology, diagnosis, and management of Marfan syndrome are discussed in detail separately. (See "Genetics, clinical features, and diagnosis of Marfan syndrome and related disorders" and "Management of Marfan syndrome and related disorders".) Myocarditis Persons with probable or definite evidence of myocarditis should be withdrawn from all competitive and recreational sports and undergo a prudent convalescent period of between three and six months following the onset of clinical manifestations [29,31]. Athletes may return to training and competition after this period of time if LV systolic function has returned to normal (based on echocardiography and/or CMR), clinically relevant arrhythmias such as frequent and/or complex repetitive forms of ventricular or supraventricular ectopic activity are absent on ambulatory Holter monitoring and graded exercise testing, and serum markers of inflammation and heart failure have normalized. The impact that persistent LGE on CMR represents following the apparent clinical resolution of myocarditis is still uncertain [29]. As patients with previous myocarditis are at increased risk of recurrence and/or silent progressive myocardial dysfunction, periodic clinical reevaluation (at least annually) is recommended, including clinical assessment and imaging testing [31]. Patients should be advised to seek medical attention for dyspnea on exertion, syncope, or arrhythmic events. Myocarditis has been reported in 6 to 7 percent of cases of SCD in competitive athletes and 20 percent of military recruits [16,25,42]. (See 'Etiology of sudden death' above.) The clinical presentation of myocarditis is quite broad, from subclinical cases with only mild reduction of physical performance or palpitation to more severe presentations with clinical findings of heart failure in an otherwise healthy young person. The ECG usually shows diffuse repolarization abnormalities, and global or regional wall motion abnormalities are present on cardiac imaging. Active myocarditis is associated with atrial and ventricular tachyarrhythmias, bradyarrhythmias, and SCD. Healed myocarditis leading to a dilated cardiomyopathy or persistent segmental abnormalities increases the risk of SCD, and this risk may be proportional to the degree of cardiac dysfunction and severity of clinical presentation. (See "Clinical manifestations and diagnosis of myocarditis in adults".) Myocarditis and other causes of myocardial injury in individuals with coronavirus disease 2019 (COVID-19), the risk of SARS-CoV-2 vaccine-associated myocarditis, and return to play after COVID-19 are discussed separately. (See "COVID-19: Cardiac manifestations in adults" and "COVID-19: Evaluation and management of cardiac disease in adults" and "COVID-19: Arrhythmias and conduction system disease" and "COVID-19: Vaccines", section on 'Myocarditis' and "COVID-19: Return to sport or strenuous activity following infection".) https://www.uptodate.com/contents/athletes-overview-of-sudden-cardiac-death-risk-and-sport-participation/print 13/28 7/5/23, 11:14 AM Athletes: Overview of sudden cardiac death risk and sport participation - UpToDate Congenital heart diseases The estimated prevalence of congenital abnormalities in the athlete is 0.2 percent. Recommendations for athletic activity in patients with congenital heart disease, which are based primarily on expert opinion, depend upon the nature of the abnormality [40]. The approach for exercise prescription in adolescents and adults with congenital heart disease should be individualized [54]. However, there is generally a prohibition of competitive sports in those who have: Significant pulmonary hypertension Cyanosis with an arterial saturation <80 percent Symptomatic arrhythmias Symptomatic ventricular dysfunction INHERITED ARRHYTHMIA SYNDROMES There is a partial divergence of opinions on competitive athletics for individuals with inherited arrhythmias, and specifically for long QT syndrome (LQTS) [55-58]. The 2015 American Heart Association/American College of Cardiology (AHA/ACC) Scientific Statement on Eligibility and Disqualification Recommendations for Competitive Athletes discusses participation in competitive events and training sessions in patients with channelopathies (namely, LQTS) as allowable if the patient is asymptomatic and an emergency action plan with an automated external defibrillator (AED) is immediately available on site. However, a different approach is dictated by the European guidelines, which advise precautionary restriction from competitive sports in these instances. Congenital long QT syndrome Guidelines for physical activity and sports participation in congenital LQTS are presented separately. (See "Congenital long QT syndrome: Treatment", section on 'Physical activity and LQTS'.) Brugada syndrome Professional society guidelines allow sports participation in patients with Brugada syndrome who are defined as low risk based on absence of symptoms and events after the clinician and patient participate in a fully informed discussion and shared decision-making process and take all appropriate precautionary measures [55]. In contrast to other inherited arrhythmia syndromes, most moderate- and low-intensity recreational, noncompetitive sports are considered safe for patients with Brugada syndrome or Brugada pattern ECG, except for those that would incur significant risk of trauma with impaired