Risk for clinical thromboembolism associated with conversion to sinus rhythm in patients with atrial fibrillation lasting less than 48 hours.

Atrial fibrillation, the most common sustained arrhythmia, is responsible for an estimated 266 000 hospital admissions annually [1]. This arrhythmia is characterized by lack of coordinated electrical and mechanical activity in the atria, often with a rapid ventricular response [2]. The loss of atrial systole leads to depressed cardiac output, symptoms of dyspnea, and fatigue [2]; the resulting stasis predisposes the patient to the formation of atrial thrombi and subsequent thromboembolism [2, 3]. Cardioversion of atrial fibrillation to sinus rhythm is done in an effort to improve cardiac function, relieve symptoms, and decrease the risk for thrombus formation [2]. However, successful cardioversion may be associated with clinical thromboembolism. Patients with atrial fibrillation lasting 2 days or more have a 5% to 7% risk for clinical thromboembolism if cardioversion is not preceded by several weeks of warfarin therapy [4-7]. The risk decreases to 0% to 1.6% with 2 to 4 weeks of warfarin prophylaxis or shorter-term anticoagulation therapy and screening by transesophageal echocardiography [4, 6, 8-11]. For patients with atrial fibrillation lasting 2 days or less, the risk for thromboembolism caused by cardioversion that was not preceded by prolonged anticoagulation therapy has been presumed to be low, and early cardioversion is advocated [2, 12-18]. The assumption that atrial thrombi are rare in this patient population has recently been challenged: Transesophageal echocardiography has shown left atrial thrombi in 14% of patients with atrial fibrillation lasting 3 days or less [3]. This has led to concern about the safety of early cardioversion in this group. We sought to determine the incidence of clinical thromboembolism in a large consecutive series of patients who presented with atrial fibrillation that had lasted less than 48 hours. Methods We prospectively screened 1214 adults who were admitted to Beth Israel Hospital, Boston, from 1 January 1990 to 25 September 1995 and 608 adults who were admitted to the University of Connecticut Health Center, Farmington, Connecticut, from 28 September 1991 to 29 April 1996 with a diagnosis that included atrial fibrillation. From this group, we identified 375 patients who had atrial fibrillation that was clinically estimated (on the basis of patient symptoms, which included acute onset of palpitations, dyspnea, angina, and dizziness) to have lasted less than 48 hours. Patients were excluded if their duration of atrial fibrillation could not be clinically determined or was clinically estimated to have lasted more than 48 hours. Patients were also excluded if they initially presented with acute thromboembolism (n = 1) or if they were receiving long-term warfarin treatment and had a therapeutic prothrombin time at presentation (>1.6 times control prothrombin time). Patients who had previously had thromboembolic events were not excluded. No attempt was made to modify the practice of the patients' attending physicians. Clinical and echocardiographic data and outcomes were gathered from the patients' medical records. We recorded data on the use of cardiovascular and anticoagulant medications at admission and on the initiation or discontinuation of therapy with these medications during hospitalization. Data on transthoracic echo-cardiography were gathered from clinical studies done either at admission (n = 187) or during the previous 6 months (n = 93). Left atrial dimension was measured in the parasternal long-axis view using M-mode echocardiography [19]. Left atrial length was measured in the apical four-chamber view from the mitral annulus to the posterior left atrium. The extent of mitral regurgitation was assessed by pulsed and color Doppler ultrasonography and given a grade of 0 (none) to 3 (severe) [20]. Left ventricular systolic function was considered abnormal if evidence of global or regional hypokinesis was found. We recorded only clinical embolic events (stroke, transient neurologic event, pulmonary embolism, or systemic embolism) that occurred during the index hospitalization and within 1 month after conversion. The total duration of atrial fibrillation was estimated as the time from onset of acute symptoms to time of conversion to sinus rhythm in the hospital, as documented by 12-lead electrocardiography or rhythm strip. Conversion was considered active if an antiarrhythmic agent known to be effective in the conversion of atrial fibrillation to sinus rhythm (for example, quinidine, procainamide, amiodarone, flecainide, sotalol, or propafenone) was given or if elective direct-current cardioversion was used [2]. Conversion was considered spontaneous if it occurred without the use of such medications or procedures or if it occurred after the initiation of therapy with or an increase in the dosage of a ventricular rate-controlling agent (such as digoxin, -receptor antagonists, or calcium channel blockers) [15, 21-24]. All data are expressed as the mean SD. The effect of anticoagulation therapy on thromboembolism was assessed using the Fisher exact test (SPS for Windows, version 6.1, SAS Institute, Cary, North Carolina). Confidence intervals were determined using the method of Daly [25]. No funding sources had any role in the collection, analysis, or interpretation of the data. The funding sources did not review the manuscript at any time and were not involved in submitting the paper for publication. Results Patient Sample We studied 375 patients (214 women and 161 men; mean age, 68 16 years [range, 20 to 97 years]) who presented to the hospital with atrial fibrillation that had lasted less than 48 hours. During the index hospitalization, 357 patients (95.2%) converted to sinus rhythm; 250 (66.7%) converted spontaneously, and 107 (28.5%) were actively converted. Underlying systemic disorders that predisposed patients to atrial fibrillation were hypertension (156 patients [41.7%]), infection (25 patients [6.7%]), excessive alcohol intake (22 patients [5.9%]), rheumatic heart disease (7 patients [1.9%]), and other factors (7 patients [1.9%]). One hundred fourteen patients (30.4%) had a clinical history suggestive of coronary artery disease, as documented by previous cardiac catheterization, myocardial infarction, or angina pectoris. No underlying disorder was identified in 91 patients (24.3%). Thirty-nine patients (10.4%) had a history of myocardial infarction, 181 (48.3%) had a history of atrial fibrillation, and 23 (6.1%) had a history of thromboembolism. Medications at Presentation At the time of presentation with atrial fibrillation, some patients were receiving anticoagulant and antiplatelet medications, including aspirin (93 patients [24.8%]) and warfarin (12 patients [3.2%]). Patients receiving warfarin had subtherapeutic prothrombin times (<1.6 times control prothrombin time) at presentation. Some patients were receiving ventricular rate-controlling medications, such as digoxin (88 patients [23.5%]), -receptor antagonists (84 patients [22.4%]), and calcium channel blockers (80 patients [21.3%]). Forty-nine patients (13.1%) were receiving a type IA, IC, or III antiarrhythmic agent at presentation. Therapy Initiated at Admission and before Conversion Anticoagulation or antiplatelet therapy was initiated in more than 60% of patients after they presented with atrial fibrillation. Agents included intravenous heparin (133 patients [35.5%]), oral aspirin (69 patients [18.4%]), and oral warfarin (26 patients [6.9%]). New medications that were added to treat slowing of atrioventricular nodal conduction included digoxin (129 patients [34.4%]), calcium channel blockers (105 patients [28%], and -receptor antagonists (77 patients [20.5%]). Antiarrhythmic agents added to actively convert patients to sinus rhythm were quinidine (42 patients [11.2%]), procainamide (26 patients [6.9%]), and other antiarrhythmic agents (6 patients [1.6%]). The duration of the index hospitalization was 4.6 2.4 days. Transthoracic Echocardiography The following data were derived from transthoracic echocardiography (n = 280). Patients had a left atrial dimension of 4.2 0.7 cm (normal, 4.0 cm) and a left atrial length was 5.7 0.7 cm (normal, 5.2 cm). Left ventricular systolic function was normal in 213 patients (76.1%). Focal hypokinetic wall-motion abnormalities were seen in 49 patients (17.5%), and 18 patients (6.4%) had global hypokinesis. Mild mitral regurgitation was found in 157 patients (56.1%), and moderate or severe mitral regurgitation was found in 61 patients (21.8%). No patient had transesophageal echocardiography. Cardioversion-Related Thromboembolism Three hundred fifty-seven patients (95.2%) converted to sinus rhythm during the index hospitalization. The estimated mean total duration of atrial fibrillation before conversion was 1.7 1.4 days. Three patients (0.8% [95% CI, 0.2% to 2.4%]) had clinical thromboembolic events after conversion to sinus rhythm and are described below. Patient 1 An 86-year-old woman with a history of hypertension presented with new-onset palpitations and new atrial fibrillation (<24 hours' duration), as seen on electrocardiography at admission. At the time of admission, she was being treated with aspirin and digoxin. After presentation, therapy with diltiazem hydrochloride and metoprolol was initiated. Transthoracic echocardiography showed a left atrial dimension of 4.4 cm, mild to moderate aortic insufficiency, mild mitral leaflet thickening, mild mitral annular calcification, and moderate mitral regurgitation. Left ventricular systolic function was normal. Conversion to sinus rhythm occurred spontaneously later on the day of admission [total duration of atrial fibrillation, 24 hours]. Less than 12 hours after conversion, the patient developed Wernicke aphasia. Results of both 1) computed tomography and magnetic resonance imaging of the head and 2) neurologic examination were consistent with a left parietal embolic stroke. Patient 2 An 83-year-old woman with a