EHRA/HRS/APHRS expert consensus on ventricular arrhythmias (2014)

This international consensus statement of the European Heart Rhythm Association (EHRA), Heart Rhythm Society (HRS), and Asia Pacific Heart Rhythm Society is intended to provide clinical guidance for the management of patients with ventricular arrhythmias (VAs). It summarizes the consensus of the international writing group members and is based on a systematic review of the medical literature regarding VAs. The spectrum of VAs ranges from those that are benign and asymptomatic to those that produce severe symptoms including sudden cardiac death (SCD). In addition, many patients exhibit multiple forms of VAs over time. Thus, clinicians who encounter patients with VAs face important questions regarding which diagnostic tests are needed and which treatments, if any, should be offered. The Writing Committee recognizes that the manner in which patients present with VAs varies greatly. The electrocardiographic recording of a VA may be the first and only manifestation of a cardiac abnormality; alternatively, patients with a prior diagnosis of cardiac disease may later develop these arrhythmias. Thus, the specific arrhythmia and the underlying structural heart disease (SHD), if any, may have important prognostic and treatment implications. This document addresses the indications for diagnostic testing, the present state of prognostic risk stratification, and the treatment strategies that have been demonstrated to improve the clinical outcome of patients with VAs. In addition, this document includes recommendations for referral of patients to centres with specialized expertise in the management of arrhythmias. Wherever appropriate, the reader is referred to other publications regarding the indications for implantable cardioverter-defibrillator (ICD) implantation [1], [2], catheter ablation [3], inherited arrhythmia syndromes [4], [5], congenital heart disease (CHD) [6], the use of amiodarone [7], and the management of patient with ICD shocks [8], syncope [9], or those nearing end of life [10]. The consensus recommendations in this document use the standard Class I, IIa, IIb, and III classification [11] and the corresponding language: ‘is recommended’ for Class I consensus recommendation; ‘can be useful’ for a Class IIa consensus recommendation; ‘may be considered’ to signify a Class IIb consensus recommendation; ‘should not’ or ‘is not recommended’ for a Class III consensus recommendation (failure to provide any additional benefit and/or may be harmful). The level of evidence supporting these recommendations is defined as ‘A’, ‘B’, or ‘C’ depending on the number of populations studied, whether data are derived from randomized clinical trials, non-randomized studies, or, in the absence of large studies, the consensus opinions of experts from case studies or standards of care. Most medical interventions to prevent sudden death and to treat VAs were developed in an era when patient cohorts were small and the accepted standards to demonstrate effectiveness were lower than today. Many interventions to terminate or suppress VAs have since been used in many patients, and over time different treatment ‘patterns’ have developed in different regions of the world. The writing group has tried to accommodate reasonable variations in treatment in our recommendations, and have relied upon expert consensus for many of the recommendations put forward in this document. This is reflected by the relatively low level of evidence that supports the majority of our recommendations. Each of the recommendations was voted upon by the Writing Committee and only those where there was at least 80% agreement have been included. The consensus group has approached VAs by whether they are sustained or non-sustained. The first part of this document deals with non-sustained arrhythmias, discussed in two parts [premature ventricular complexes (PVCs) and non-sustained ventricular tachycardia (NSVT)]. The consensus group believes that patients with non-sustained VAs need a standardized diagnostic workup. This is summarized here, and explained in the two sections. All patients with documented non-sustained or sustained VAs should have a resting 12-lead electrocardiogram (ECG) and a transthoracic echocardiogram to detect underlying heart disease including inherited and acquired cardiomyopathies. Especially in patients in whom the arrhythmia morphology suggests such a specific aetiology, valvular and right heart morphology and function should be assessed. (IIa) LOE B Repeat 12-lead ECGs should be considered whenever an inherited arrhythmia syndrome with varying electrocardiographic manifestations or a transient condition (e.g. coronary spasm) is suspected. (IIa) LOE C In selected patients, and especially in those with sustained arrhythmias, a second imaging modality (e.g. a magnetic resonance study, stress testing with perfusion scanning, or echocardiography) should be considered to detect subtle SHD. (IIa) LOE B A test for myocardial ischaemia should be considered in all patients with VAs in whom the clinical presentation and/or the type of arrhythmia suggests the presence of coronary artery disease. IIa LOE C The risk of cardiac events is often dictated by an underlying heart disease rather than the arrhythmia. Therefore, optimal treatment of underlying cardiovascular diseases and risk factors is recommended. I LOE A Prolonged ECG monitoring by Holter ECG, prolonged ECG event monitoring, or implantable loop recorders should be considered when documentation of further, potentially longer arrhythmias would change management. IIa LOE C In patients with incompletely characterized arrhythmias with wide QRS complexes, both supraventricular and VAs should be considered in developing a care plan. IIa LOE C For treatment of patients with non-sustained VAs, we propose the following consensus recommendations. Infrequent ventricular ectopic beats, couplets, and triplets without other signs of an underlying SHD or an inherited arrhythmia syndrome should be considered as a normal variant in asymptomatic patients. IIa LOE C An invasive electrophysiological study (EPS) should be considered in patients with significant SHD and non-sustained VAs especially if accompanied by unexplained symptoms such as syncope, near-syncope, or sustained palpitations IIa LOE C No treatment other than reassurance is needed for patients with neither SHD nor an inherited arrhythmogenic disorder who have asymptomatic or mildly symptomatic PVCs. I LOE C It is recommended to treat survivors of a myocardial infarction (MI) and other patient with reduced left ventricular (LV) function and non-sustained VAs with a beta-blocker unless these agents are contraindicated. I LOE A A therapeutic trial of beta-blockers may be considered in symptomatic patients with non-sustained VAs. IIb LOE C In suitable patients without SHD, a non-dihydropyridine calcium channel antagonist may be considered as an alternative to beta-blocker treatment. IIb C In patients who suffer from symptomatic non-sustained VAs on an adequately dosed beta-blocker or a non-dihydropyridine calcium channel antagonist, treatment with an antiarrhythmic drug (AAD; amiodarone, flecainide, mexiletine, propafenone, sotalol) may be considered to improve symptoms associated with arrhythmia episodes. IIb LOE C Flecainide and propafenone are not recommended to suppress PVCs in patients with reduced LV function (unless caused by ventricular ectopy itself), myocardial ischaemia, or myocardial scar. III LOE A Sotalol should be used with caution in patients with chronic kidney disease and should be avoided in patients with a prolonged QT interval at baseline or with excessive prolongation of QT interval (>0.50 s) upon therapy initiation. I LOE B Amiodarone appears to have less overall pro-arrhythmic risk than other AADs in patients with heart failure and may be preferred to other membrane-active AADs unless a functioning defibrillator has been implanted. IIb LOE C Catheter ablation may be beneficial by improving symptoms or LV dysfunction in patients suffering from frequent non-sustained VAs (e.g. >PVC 10 000 per 24 h) in patients with significant symptoms or LV dysfunction without another detectable cause. IIa LOE B Amiodarone, sotalol, and/or other beta-blockers are useful pharmacological adjuncts to implantation of a defibrillator (e.g. to reduce shocks) and to suppress symptomatic NSVT in patients who are unsuitable for ICD therapy, in addition to optimal medical therapy for patients with heart failure. IIb LOE B Premature ventricular complexes (PVCs) are common both in patients with and without SHD and may be asymptomatic even for patients with high frequency of these beats. Other patients may be highly symptomatic with relatively few ectopic beats [12]. Although a recent meta-analysis [13] of patients without clinically apparent SHD demonstrated an increased incidence of adverse events in patients with frequent PVCs, only one of the included studies used echocardiography to establish structural disease. The independent prognostic importance of PVCs in the presence of structural disease is not clear. Early studies demonstrated an association with increased cardiovascular mortality after MI [14], [15] and with increased total mortality in patients with LV hypertrophy (LVH) [16]. However, these studies were observational and performed in an era prior to modern management [17]. In a study of patients with congestive heart failure [ejection fraction (EF) <35%], PVC frequency did not predict the risk of sudden death and did not provide prognostic information beyond other clinical variables [18]. Several studies have demonstrated an association between frequent PVCs and a potentially reversible cardiomyopathy, which in selected patients resolves after catheter ablation [19]-[24]. The number of PVCs/24 h that is associated with impaired LV function has generally been reported at burdens above 15–25% of the total cardiac beats, though this may be as low as 10% [21]-[23], [25]-[30] (Table 1). However, since PVCs may be the result of an underlying cardiomyopathy, it may be difficult to prospectively determine which of these sequences is operative in a given patient [31]. Importantly, the vast majority of patients with frequent PVCs will not go on to develop cardiomyopathy but currently available data do not allow for accurate risk prediction. A recent longitudinal study followed 239 patients with frequent PVCs (>1000 per day) and no SHD [echo and magnetic resonance imaging (MRI)] for 5.6 years with no adverse cardiac events and no decline in overall LV ejection fraction (LVEF) [32]. The presence of at least some PVCs during 24 h ambulatory monitoring is extremely common and may be considered normal. Because the finding of PVCs during 24 h ambulatory monitoring is very likely, any conclusion that they are related to symptoms requires careful correlation. In two studies in which SHD was rigorously excluded, only 2 and 4% had 0.50 or 0.100 PVCs/24 h, respectively [33], [34]. The vast majority of patients without SHD who have PVCs have a benign prognosis. An exception may be a very small subset of patients with PVCs that have a short coupling interval (<300 ms) between the premature and the preceding beats, a finding which suggests the short QT syndrome and increases the risk of malignant Vas [35]. It should be emphasized that this is a very small minority of patients with PVCs. As with other VAs, the first step in the evaluation of a patient with PVCs is to determine the presence or absence of SHD (1, 2). For patients with arrhythmic or other cardiac symptoms, a resting 12-lead ECG is very helpful to evaluate the presence of myocardial scar (Q-waves or fractionated QRS complexes), the QT interval, ventricular hyper-trophy, and other evidence of SHD. An echocardiogram provides assessment of right ventricular (RV) and LV structure and function, valvular abnormalities, and pulmonary artery systolic pressure and is recommended for patients with symptomatic PVCs, a high frequency of PVCs (>10% burden), or when the presence of SHD is suspected. Management of PVCs. a. See table for definitions of structural heart disease; b. Medical therapy+ICD; c. Absence of high scar burden suggests reversibility. CRT, cardiac resynchronisation therapy; ICD, implantable cardioverter-defibrillator; LV, left ventricular; MRI-DE, magnetic resonance imaging with delayed enhancement; PE, physical examination; PVC, premature ventricular complexes; Rx, therapy; SHD, structural heart disease; VAs, ventricular arrhythmias. Evaluation for the presence or absence of structural heart disease. CT, computed tomography; MRI-DE, magnetic resonance imaging with delayed enhancement; VA, ventricular arrhythmia. For selected patients, especially when there is a suggestion of symptoms associated with exercise, exercise stress testing should be considered to determine whether PVCs are potentiated or suppressed by exercise, to assess whether longer duration VAs are provoked. A negative exercise test can decrease the probability that catecholaminergic polymorphic ventricular tachycardia (CPVT) is the underlying cause. Premature ventricular complexes that worsen with exercise should prompt further investigation as these patients are more likely to require treatment. Although the majority of patients with PVCs can be accurately assessed with a 12-lead ECG and echocardiography, contrastenhanced MRI may provide additional diagnostic and prognostic data when the presence or absence of SHD remains in doubt [36]. While there are no large-scale studies investigating which patients should undergo MRI, the management of several forms of SHD associated with PVCs may be guided by MRI, including dilated cardiomyopathy, hypertrophic cardiomyopathy (HCM), sarcoidosis, amyloidosis, and arrhythmogenic right ventricular cardiomyopathy (ARVC) [37]-[39]. In these conditions, the presence of ventricular wall motion abnormalities or myocardial scar detected by delayed gadolinium enhancement may provide useful prognostic information. In selected patients for whom the diagnosis of ARVC is suspected, the signal-averaged ECG (SAECG) may provide useful information and forms a minor diagnostic criterion for this disorder. In the absence of SHD, the most common indication for treating PVCs remains the presence of symptoms that are not improved by explanation of their benign nature and reassurance from the physician. In addition, some patients may require treatment for frequent asymptomatic PVCs if longitudinal imaging surveillance reveals an interval decline in LV systolic function or an increase in chamber volume. For patients with >10 000 PVCs/24 h, follow-up with repeat echocardiography and Holter monitoring should be considered. In patients with fewer PVCs, further investigation is only necessary should symptoms increase. It should also be recognized that PVC burden often fluctuates over time. In patients with SHD, symptoms form the primary grounds for considering whether treatment is indicated. Elimination of high burden PVCs (>10%) in patients with impaired LV function can be associated with significant improvement of LV function, [19], [20] even when significant scarring is present [22], [23]. Catheter ablation may also be helpful when frequent PVCs interfere with cardiac resynchronization therapy [40]. For patients without SHD and mild symptoms, the first step in treatment of patients with PVCs is education of the benign nature of this arrhythmia and reassurance. No large-scale randomized trials of drug treatment for PVCs in the absence of heart disease have been performed. For patients whose symptoms are not effectively managed in this manner, a trial of beta-blockers or non-dihydropyridine calcium antagonists may be considered though the efficacy of these agents is quite limited with only 10–15% of patients achieving >90% PVC suppression, [41] similar to placebo.[42] It should also be recognized that the data supporting the use of calcium blockers are less than for beta-blockers and that these agents may themselves produce significant symptoms. While membrane-active AADs are more effective to suppress PVCs, the risk–benefit ratio has not been carefully evaluated in patients without SHD. Nevertheless, these agents are highly effective and may significantly improve symptoms in markedly symptomatic patients. Because these agents may increase the risk of mortality in patients with significant SHD, perhaps with the exception of amiodarone, caution is advised before using them for PVC suppression [41], [43]. Randomized trials of PVC suppression with catheter ablation have not been performed. However, multiple studies indicate high efficacy of ablation with PVC elimination in 74–00% of patients [44]-[57]. However, these studies have typically included highly symptomatic patients typically with a very high burden of PVCs. Thus, catheter ablation should only be considered for patients who are markedly symptomatic with very frequent PVCs. In addition, procedural success may be dependent on site of origin with lower efficacy reported for coronary venous and epicardial foci than for other sites [49], [58]. Although complete PVC elimination is the goal of ablation, it should be noted that partial success may still be associated with significant improvement in LV systolic function. The efficacy of catheter ablation may be reduced for patients with multiple morphologies of PVCs or those for whom the clinical PVC morphology cannot be induced at the time of the procedure. The published complication rates of catheter ablation for PVC suppression are generally low (~1%). Catheter ablation of PVCs is recommended for highly selected patients who remain very symptomatic despite conservative treatment or for those with very high PVC burdens associated with a decline in LV systolic function. Although several different definitions have been used, [59] NSVT is defined as runs of beats arising from the ventricles with duration between 3 beats and 30 s and with cycle length of <600 ms (>100 b.p.m.) [60]. Similar to PVCs, NSVT is a relatively common finding in patients with either structurally normal or abnormal hearts[59], [61], [62]. Non-sustained ventricular tachycardia is found in nearly 6% of patients evaluated for palpitations [63]. Diagnostic and therapeutic considerations for NSVT are included in several [3], [60], [64] recent guideline and consensus documents. In general, therapy for the underlying cardiac disease is indicated rather than for the arrhythmia itself. However, the finding of NSVT should always trigger further evaluation of the patient and a practical approach can be usefully divided into a general approach (Table 2), patients with an apparently normal heart (Table 3) and those with SHD (Table 4). Exercise-related NSVT is relatively common and appears to be associated with a worse prognosis when it occurs during recovery [65], [66]. Polymorphic NSVT requires extensive evaluation in both symptomatic and asymptomatic patients with careful assessment for the presence of coronary ischaemia. An important inherited arrhythmia which may present as exercise-induced NSVT is CPVT [72], [73]. This condition is typically manifested by polymorphic or bidirectional VT which are triggered by sympathetic stimulation and exercise (commonly occurring at an exercise level of 120–130 b.p.m.) and is associated with an increased risk of sudden death. The underlying mechanism of CPVT is calcium overload leading to delayed afterdepolarizations as a result of mutations in the genes coding for ryanodine receptor or calsequestrin proteins. Non-sustained ventricular tachycardia is a relatively common finding among athletes [67], [68]. Other causes of NSVT in the absence of SHD include QT interval prolongation caused by mutations in proteins regulating repolarizing currents drugs (LQTS) or electrolyte abnormalities. Athletes with NSVT should be evaluated for the presence of HCM, a diagnosis which may overlap with some degree of LVH as an adaptation to exercise. Because of this challenging distinction, expert consultation should be obtained if this diagnosis is suspected. Although only limited data are available regarding the significance of NSVT in athletes without a structural cardiac disease, discontinuation of training is not generally recommended. Non-sustained ventricular tachycardia is common in ischaemic heart disease and can be recorded in 30–80% of patients during long-term ECG monitoring where it is usually asymptomatic [60]. No studies have demonstrated a mortality benefit of suppressing NSVT with either AADs or catheter ablation and treatment is usually not indicated in asymptomatic patients. A range of studies have demonstrated that NSVT occurring during the first few days after an acute coronary event has no adverse long-term prognostic significance. However, when NSVT occurs 48 h or more after MI, there is an increased mortality and morbidity even when asymptomatic [74]. For a patient with non-ischaemic dilated cardiomyopathy, the prognostic significance of NSVT is uncertain and no studies have provided precise guidance for treatment in this group of patients [75]. The occurrence of NSVT in patients with an implanted ICD is associated with an increased frequency of shocks and all-cause mortality [76]. For these patients, programming the ICD to a long VT time and a high ventricular may be especially important For patients with an apparently normal the 12-lead ECG should be for evidence of 3) polymorphic VT including or an inherited arrhythmia such as the long short or syndromes 4). VAs typically have an with either or LV the is and the ratio of the and in during PVCs or VT divided by this ratio during a LV origin is In addition to the ECG, an echocardiogram to assess the presence or absence of SHD should also be considered for all patients with For where SHD is but cannot be with echocardiography, cardiac MRI may be especially useful to the presence or absence of myocardial scar or wall motion abnormalities. of NSVT should be using a similar to 3 and Evaluation in is in a ventricular (RV) coronary in long short arrhythmogenic right ventricular cardiomyopathy, hypertrophic cardiomyopathy, Most from the or LV (Table 3 and arrhythmias only require treatment if they are or produce LV death is very in patients with The treatment of these arrhythmias is either medical with a a calcium or with catheter ablation [60]. Non-sustained ventricular tachycardia with a mechanism may also from the and to beta-blockers or catheter ablation In addition, LV VT can be with though with a relatively high risk on therapy Catheter ablation is effective for LV VT and should be considered even when this sustained arrhythmia is by Catheter ablation can be recommended for patients with NSVT that is highly symptomatic and drug especially if it is The recording of polymorphic NSVT should prompt a evaluation for the presence of coronary ischaemia as the primary therapy for this arrhythmia should be to improving coronary non-sustained can be as a the risk of arrhythmia is high and therapy with of an ICD is recommended [4], In of any or electrolyte that should be Although an ICD should be considered for all patients with a significantly reduced there may be a for stimulation in selected patients with NSVT and ischaemic heart disease who have less severe LV dysfunction cardioverter-defibrillator implantation is recommended in this group of patients if or sustained VT is with stimulation [60]. if NSVT is in a patient with a prior MI, a of syncope, and is generally recommended to usually with ICD should sustained VT be Non-sustained ventricular tachycardia in an asymptomatic patient with a not usually require specific antiarrhythmic therapy, and the goal is treatment of the underlying heart disease. In the of HCM, ICD therapy is an if NSVT is present with or without other risk factors [60]. In general, therapy may be considered for patients with SHD who NSVT not by of medical therapy, or treatment of reversible consensus recommendations on A 12-lead ECG should be recorded during sustained whenever and I LOE B For patients with sustained VT and no evidence of SHD on resting ECG or echocardiography cardiac MRI may provide additional information LOE B signal-averaged ECG may provide additional information LOE C exercise testing may provide additional information LOE B For patients with a wide QRS tachycardia in whom the diagnosis is an invasive should be considered to the tachycardia (IIa) LOE C For patients with SHD and an ICD is recommended in the absence of LOE A For patients with SHD and specific treatment of Vas with AADs mexiletine, or catheter ablation, and/or from an ICD should be considered in addition to an of the underlying SHD or ischaemia will in most not be to prevent VT (IIa) LOE B For patients with an ICD as primary programming to a long VT interval and a high should be considered. (IIa) LOE VT is defined as sustained when longer than 30 s or requires to Most sustained occurs in the of but may also be occurring in patients with no detectable myocardial disease. No structural ventricular tachycardia In the absence of SHD, is generally associated with an prognosis [60], The presence of syncope or is in the absence of SHD or an inherited arrhythmia VT can have a malignant clinical usually with a very or a short coupling interval The large majority of patients with who present for therapy have significant SHD. The most frequent is ischaemic heart disease, of patients for whom an ICD is implanted or who are referred for catheter ablation VT is associated with increased mortality risk in the of reduced ventricular systolic function The mortality risk to VT in patients with ventricular function is less cardioverter-defibrillator shocks are also associated with risk and multiple studies have demonstrated that defibrillator both and are associated with increased mortality and reduced of life The association of ICD shocks and total mortality appears to be a function of cardiac disease rather than a specific of of with long VT prior to the of and rates shocks and mortality in patients an ICD for primary The of programming a long VT time in patients with a of sustained or is less Although it has not been whether suppression of VT by either pharmacological or catheter ablation in patients with sustained treatment to symptoms is and these may improve in patients with VT The to in the investigation of is to the presence or absence of SHD, A 12-lead ECG to the diagnosis of provide important into the underlying mechanism 3 and the presence of SHD, and the site of This is especially important when catheter ablation is A resting ECG should be performed in all patients with sustained The presence of or of the QRS suggests underlying structural disease ventricular tachycardia evaluation and management.