Paul Dorian

BACKGROUND: Patients surviving ventricular fibrillation (VF) or sustained ventricular tachycardia (VT) are at a high risk of death due to a recurrence of arrhythmia. The implantable cardioverter defibrillator (ICD) terminates VT or VF, but it is not known whether this device prolongs life in these patients compared with medical therapy with amiodarone. METHODS AND RESULTS: A total of 659 patients with resuscitated VF or VT or with unmonitored syncope were randomly assigned to treatment with the ICD or with amiodarone. The primary outcome measure was all-cause mortality, and the secondary outcome was arrhythmic death. A total of 328 patients were randomized to receive an ICD. A thoracotomy was done in 33, no ICD was implanted in 18, and the rest had a nonthoracotomy ICD. All 331 patients randomized to amiodarone received it initially. At 5 years, 85.4% of patients assigned to amiodarone were still receiving it at a mean dose of 255 mg/day, 28.1% of ICD patients were also receiving amiodarone, and 21.4% of amiodarone patients had received an ICD. A nonsignificant reduction in the risk of death was observed with the ICD, from 10.2% per year to 8.3% per year (19.7% relative risk reduction; 95% confidence interval, -7.7% to 40%; P=0.142). A nonsignificant reduction in the risk of arrhythmic death was observed, from 4.5% per year to 3.0% per year (32.8% relative risk reduction; 95% confidence interval, -7.2% to 57.8%; P=0.094). CONCLUSIONS: A 20% relative risk reduction occurred in all-cause mortality and a 33% reduction occurred in arrhythmic mortality with ICD therapy compared with amiodarone; this reduction did not reach statistical significance.

BACKGROUND: It is common practice to restore and maintain sinus rhythm in patients with atrial fibrillation and heart failure. This approach is based in part on data indicating that atrial fibrillation is a predictor of death in patients with heart failure and suggesting that the suppression of atrial fibrillation may favorably affect the outcome. However, the benefits and risks of this approach have not been adequately studied. METHODS: We conducted a multicenter, randomized trial comparing the maintenance of sinus rhythm (rhythm control) with control of the ventricular rate (rate control) in patients with a left ventricular ejection fraction of 35% or less, symptoms of congestive heart failure, and a history of atrial fibrillation. The primary outcome was the time to death from cardiovascular causes. RESULTS: A total of 1376 patients were enrolled (682 in the rhythm-control group and 694 in the rate-control group) and were followed for a mean of 37 months. Of these patients, 182 (27%) in the rhythm-control group died from cardiovascular causes, as compared with 175 (25%) in the rate-control group (hazard ratio in the rhythm-control group, 1.06; 95% confidence interval, 0.86 to 1.30; P=0.59 by the log-rank test). Secondary outcomes were similar in the two groups, including death from any cause (32% in the rhythm-control group and 33% in the rate-control group), stroke (3% and 4%, respectively), worsening heart failure (28% and 31%), and the composite of death from cardiovascular causes, stroke, or worsening heart failure (43% and 46%). There were also no significant differences favoring either strategy in any predefined subgroup. CONCLUSIONS: In patients with atrial fibrillation and congestive heart failure, a routine strategy of rhythm control does not reduce the rate of death from cardiovascular causes, as compared with a rate-control strategy. (ClinicalTrials.gov number, NCT00597077.)

BACKGROUND: Implantable cardioverter-defibrillator (ICD) therapy has been shown to improve survival in patients with various heart conditions who are at high risk for ventricular arrhythmias. Whether benefit occurs in patients early after myocardial infarction is unknown. METHODS: We conducted the Defibrillator in Acute Myocardial Infarction Trial, a randomized, open-label comparison of ICD therapy (in 332 patients) and no ICD therapy (in 342 patients) 6 to 40 days after a myocardial infarction. We enrolled patients who had reduced left ventricular function (left ventricular ejection fraction, 0.35 or less) and impaired cardiac autonomic function (manifested as depressed heart-rate variability or an elevated average 24-hour heart rate on Holter monitoring). The primary outcome was mortality from any cause. Death from arrhythmia was a predefined secondary outcome. RESULTS: During a mean (+/-SD) follow-up period of 30+/-13 months, there was no difference in overall mortality between the two treatment groups: of the 120 patients who died, 62 were in the ICD group and 58 in the control group (hazard ratio for death in the ICD group, 1.08; 95 percent confidence interval, 0.76 to 1.55; P=0.66). There were 12 deaths due to arrhythmia in the ICD group, as compared with 29 in the control group (hazard ratio in the ICD group, 0.42; 95 percent confidence interval, 0.22 to 0.83; P=0.009). In contrast, there were 50 deaths from nonarrhythmic causes in the ICD group and 29 in the control group (hazard ratio in the ICD group, 1.75; 95 percent confidence interval, 1.11 to 2.76; P=0.02). CONCLUSIONS: Prophylactic ICD therapy does not reduce overall mortality in high-risk patients who have recently had a myocardial infarction. Although ICD therapy was associated with a reduction in the rate of death due to arrhythmia, that was offset by an increase in the rate of death from nonarrhythmic causes.

BACKGROUND: Atrial fibrillation is a leading preventable cause of recurrent stroke for which early detection and treatment are critical. However, paroxysmal atrial fibrillation is often asymptomatic and likely to go undetected and untreated in the routine care of patients with ischemic stroke or transient ischemic attack (TIA). METHODS: We randomly assigned 572 patients 55 years of age or older, without known atrial fibrillation, who had had a cryptogenic ischemic stroke or TIA within the previous 6 months (cause undetermined after standard tests, including 24-hour electrocardiography [ECG]), to undergo additional noninvasive ambulatory ECG monitoring with either a 30-day event-triggered recorder (intervention group) or a conventional 24-hour monitor (control group). The primary outcome was newly detected atrial fibrillation lasting 30 seconds or longer within 90 days after randomization. Secondary outcomes included episodes of atrial fibrillation lasting 2.5 minutes or longer and anticoagulation status at 90 days. RESULTS: Atrial fibrillation lasting 30 seconds or longer was detected in 45 of 280 patients (16.1%) in the intervention group, as compared with 9 of 277 (3.2%) in the control group (absolute difference, 12.9 percentage points; 95% confidence interval [CI], 8.0 to 17.6; P<0.001; number needed to screen, 8). Atrial fibrillation lasting 2.5 minutes or longer was present in 28 of 284 patients (9.9%) in the intervention group, as compared with 7 of 277 (2.5%) in the control group (absolute difference, 7.4 percentage points; 95% CI, 3.4 to 11.3; P<0.001). By 90 days, oral anticoagulant therapy had been prescribed for more patients in the intervention group than in the control group (52 of 280 patients [18.6%] vs. 31 of 279 [11.1%]; absolute difference, 7.5 percentage points; 95% CI, 1.6 to 13.3; P=0.01). CONCLUSIONS: Among patients with a recent cryptogenic stroke or TIA who were 55 years of age or older, paroxysmal atrial fibrillation was common. Noninvasive ambulatory ECG monitoring for a target of 30 days significantly improved the detection of atrial fibrillation by a factor of more than five and nearly doubled the rate of anticoagulant treatment, as compared with the standard practice of short-duration ECG monitoring. (Funded by the Canadian Stroke Network and others; EMBRACE ClinicalTrials.gov number, NCT00846924.).

BACKGROUND: The restoration and maintenance of sinus rhythm is a desirable goal in patients with atrial fibrillation, because the prevention of recurrences can improve cardiac function and relieve symptoms. Uncontrolled studies have suggested that amiodarone in low doses may be more effective and safer than other agents in preventing recurrence, but this agent has not been tested in a large, randomized trial. METHODS: We undertook a prospective, multicenter trial to test the hypothesis that low doses of amiodarone would be more efficacious in preventing recurrent atrial fibrillation than therapy with sotalol or propafenone. We randomly assigned patients who had had at least one episode of atrial fibrillation within the previous six months to amiodarone or to sotalol or propafenone, given in an open-label fashion. The patients in the group assigned to sotalol or propafenone underwent a second randomization to determine whether they would receive sotalol or propafenone first; if the first drug was unsuccessful the second agent was prescribed. Loading doses of the drugs were administered and electrical cardioversion was performed (if necessary) within 21 days after randomization for all patients in both groups. The follow-up period began 21 days after randomization. The primary end point was the length of time to a first recurrence of atrial fibrillation. RESULTS: Of the 403 patients in the study, 201 were assigned to amiodarone and 202 to either sotalol (101 patients) or propafenone (101 patients). After a mean of 16 months of follow-up, 71 of the patients who were assigned to amiodarone (35 percent) and 127 of those who were assigned to sotalol or propafenone (63 percent) had a recurrence of atrial fibrillation (P<0.001). Adverse events requiring the discontinuation of drug therapy occurred in 18 percent of the patients receiving amiodarone, as compared with 11 percent of those treated with sotalol or propafenone (P=0.06). CONCLUSIONS: Amiodarone is more effective than sotalol or propafenone for the prevention of recurrences of atrial fibrillation.