A comparison of rate control and rhythm control in patients with atrial fibrillation.

BACKGROUND: There are two approaches to the treatment of atrial fibrillation: one is cardioversion and treatment with antiarrhythmic drugs to maintain sinus rhythm, and the other is the use of rate-controlling drugs, allowing atrial fibrillation to persist. In both approaches, the use of anticoagulant drugs is recommended. METHODS: We conducted a randomized, multicenter comparison of these two treatment strategies in patients with atrial fibrillation and a high risk of stroke or death. The primary end point was overall mortality. RESULTS: A total of 4060 patients (mean [+/-SD] age, 69.7+/-9.0 years) were enrolled in the study; 70.8 percent had a history of hypertension, and 38.2 percent had coronary artery disease. Of the 3311 patients with echocardiograms, the left atrium was enlarged in 64.7 percent and left ventricular function was depressed in 26.0 percent. There were 356 deaths among the patients assigned to rhythm-control therapy and 310 deaths among those assigned to rate-control therapy (mortality at five years, 23.8 percent and 21.3 percent, respectively; hazard ratio, 1.15 [95 percent confidence interval, 0.99 to 1.34]; P=0.08). More patients in the rhythm-control group than in the rate-control group were hospitalized, and there were more adverse drug effects in the rhythm-control group as well. In both groups, the majority of strokes occurred after warfarin had been stopped or when the international normalized ratio was subtherapeutic. CONCLUSIONS: Management of atrial fibrillation with the rhythm-control strategy offers no survival advantage over the rate-control strategy, and there are potential advantages, such as a lower risk of adverse drug effects, with the rate-control strategy. Anticoagulation should be continued in this group of high-risk patients.

Foods, health claims, and the law: comparisons of the United States and Europe.

Government, academia, and the food industry can play a significant role in the identification of healthy foods and ingredients important for weight management and health. The U.S. Food and Drug Administration developed regulations that define specific food categories for weight management and health. These categories include foods for special dietary uses and medical foods. Medical foods are classified for use in specific disease states and require a physician's recommendation and continuous monitoring. The European regulations specify energy-restricted foods as a subcategory of food for particular nutritional uses, which includes infant formula, medical foods, and foods for sports. European standards for energy-restricted diets have been established, leaving little flexibility for change. Three categories exist (i.e., very-low-calorie diets [450 to 800 kcal], low-calorie diets [800 to 1200 kcal], and meal replacements [200 to 400 kcal]). No claims on anticipated weight loss can be made even where significant clinical research has demonstrated long-term efficacy, thereby preventing informed choice management. Dramatic changes in lifestyle (e.g., disruption of the family unit, altered eating occasions, fast foods, and food grazing) have resulted in an epidemic of obesity and chronic disease. Regulating food selection or dietary patterns to limit the epidemic is not realistic. However, stimulating government health agencies and the food industry to increase public awareness through educational programs and regulating the definition of acceptable methods and products can provide an environment for change. A consensus is needed among academia, government, and industry for appropriate food labeling and claims. These actions are needed to help individuals make healthy food selections and maintain a healthy weight. Public health initiatives should change consumer attitudes with programs that are simple, affordable, effective, and accessible.

Life-threatening ventricular arrhythmias due to transient or correctable causes: high risk for death in follow-up.

OBJECTIVES: This study evaluated the prognosis of patients resuscitated from ventricular tachycardia (VT) or ventricular fibrillation (VF) with a transient or correctable cause suspected as the cause of the VT/VF. BACKGROUND: Patients resuscitated from VT/VF in whom a transient or correctable cause has been identified are thought to be at low risk for recurrence and often receive no primary treatment for their arrhythmias. METHODS: In the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial, patients with a potentially transient or correctable cause of VT/VF were not eligible for randomization. The mortality of these patients was compared with the mortality of patients with a known high risk of recurrence of VT/VF in the AVID registry. RESULTS: Compared with patients having high risk VT/VF, those with a transient or correctable cause for their presenting VT/VF were younger and had a higher left ventricular ejection fraction. These patients were more often treated with revascularization as the primary therapy, more commonly received a beta-blocker, less often required therapy for congestive heart failure and less commonly received either an antiarrhythmic drug or an implantable cardioverter defibrillator. Nevertheless, subsequent mortality of patients with a transient or correctable cause of VT/VF was no different or perhaps even worse than that of the primary VT/VF population. CONCLUSIONS: Patients identified with a transient or correctable cause for their VT/VF remain at high risk for death. Further research is needed to define truly reversible causes of VT/VF. Meanwhile, these patients may require more aggressive evaluation, treatment and follow-up than is currently practiced.

Comparison of dilated cardiomyopathy and coronary artery disease in patients with life-threatening ventricular arrhythmias: Differences in presentation and outcome in the AVID registry.

BACKGROUND: The etiology of structural heart disease in patients with life-threatening arrhythmias (ventricular tachycardia [VT]/ventricular fibrillation [VF]) may define clinical characteristics at presentation, may require that different therapies be administered, and may cause different mortality outcomes. METHODS: In the Antiarrhythmics Versus Implantable Defibrillators (AVID) registry, baseline clinical characteristics, treatments instituted, and ultimate mortality outcomes from the National Death Index were obtained on 3117 patients seen at participating institutions with VT/VF, irrespective of participation in the randomized trial. By use of these data, 2268 patients with coronary artery disease (CAD) were compared with 334 patients with dilated nonischemic cardiomyopathy (DCM). RESULTS: The CAD group was 7 years older and had a higher percentage of males. DCM patients were more likely to be African American, have severely compromised left ventricular function (52% vs 39%), and have a history of congestive heart failure symptoms (62% vs 44%). Patients with CAD were more likely to be treated with b-blockers and calcium channel blockers and less likely to be treated with angiotensin-converting enzyme inhibitors. Patients with DCM were more likely to be treated with diuretics, warfarin, and an implantable cardioverter defibrillator for VT/VF (54% vs 48% for CAD); the use of other antiarrhythmic therapies did not differ between the 2 groups. Two-year survival was not significantly different between the groups (76.6% [95% CI 74.6%-78.7%] vs 78.2% [95% CI 73.6%-82.9%]). CONCLUSIONS: In AVID registry patients with VT/VF, demographic and clinical characteristics were different between patients with CAD and those with DCM. Despite these differences, overall survival was similar in these 2 groups.

Relationship between rehospitalization and future death in patients treated for potentially lethal arrhythmia.

INTRODUCTION: It is generally considered that death is the only appropriate endpoint to evaluate interventions for preventing death; however, this belief may be based on the previous use of inappropriate or inadequate surrogates for death. The aim of this study was to evaluate whether rehospitalization following implementation of an intervention is a reasonable surrogate for death. METHODS AND RESULTS: The time from discharge following intervention to rehospitalization was evaluated for 997 patients discharged after baseline hospitalization in the Antiarrhythmics Versus Implantable Defibrillators Trial. The relationship between rehospitalization for various reasons and subsequent death was compared in the two treatment arms to assess the adequacy of rehospitalization as a surrogate for death. Included were rehospitalization for: any reason, a cardiac problem, a noncardiac problem, new or worsened congestive heart failure (CHF), an acute coronary syndrome, and a cardiac procedure. For all of the reasons except cardiac procedure, rehospitalization was associated with a substantially increased hazard for subsequent death. Rehospitalization for new or worsened CHF was most closely (that is, temporally) related to subsequent death and was the only reason for rehospitalization, which fully explained the treatment effect of implantable cardiac defibrillators compared with antiarrhythmic drugs on death. CONCLUSION: Rehospitalization is a significant risk factor for subsequent death. However, only rehospitalization for new or worsened CHF appears to be a potential surrogate for death in the setting of antiarrhythmic interventions.

Follow-up of patients with unexplained syncope and inducible ventricular tachyarrhythmias: analysis of the AVID registry and an AVID substudy. Antiarrhythmics Versus Implantable Defibrillators.

INTRODUCTION: A prospective registry and substudy were conducted in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Study to clarify the prognosis and recurrent event rate, risk factors, and impact of implantable cardioverter defibrillator (ICD) therapy in patients with unexplained syncope, structural heart disease, and inducible ventricular tachyarrhythmias. METHODS AND RESULTS: Included in the AVID registry were patients from all participating sites who had "out of hospital syncope with structural heart disease and EP-inducible VT/VF with symptoms." In addition, 13 collaborating sites provided more in-depth clinical and electrophysiologic data as part of a formal prospective substudy. Patients in the substudy were followed by local investigators for recurrent arrhythmic events and mortality. Registry patients were tracked for fatal outcomes by the National Death Index. A total of 429 patients with syncope were entered in the AVID registry, of whom 80 participated in the substudy. Of the substudy patients, 21 patients (26%) had inducible polymorphic ventricular tachycardia/ventricular fibrillation (VT/VF), 11 patients (14%) had sustained monomorphic VT <200 beats/min, and 48 patients (60%) had sustained monomorphic VT > or = 200 beats/min. The ICD was used as sole therapy in 75% of the syncope substudy patients (and with antiarrhythmic drug in an additional 9%) and in 59% of the syncope registry patients. Survival rates at 1 and 3 years were 93% and 74% for the substudy patients and 90% and 74% for the registry patients, respectively. Survival of the syncope substudy patients (predominantly treated by ICD) was similar to the VT patients treated by ICD and superior to the VT patients treated by an antiarrhythmic drug (P = 0.05) in the randomized main trial. Mortality events in the substudy were marginally predicted by ejection fraction (P = 0.06) but not by electrophysiologic study-induced arrhythmia. The significant predictor of increased mortality in the registry was age (P = 0.003) and of reduced mortality was treatment with ICD (P = 0.006). CONCLUSION: The results of these analyses support the role of the ICD as primary antiarrhythmic therapy in patients with unexplained syncope, structural heart disease, and inducible VT/VF at electrophysiologic study.

Central clinical research issues in electrophysiology: report of the NASPE Committee.

This article contains the results of an attempt by appointed members of the North American Society of Pacing and Electrophysiology to define the research frontier in electrophysiology and suggest areas of study as an aid in setting the research agenda.

Meta-analysis of the implantable cardioverter defibrillator secondary prevention trials. AVID, CASH and CIDS studies. Antiarrhythmics vs Implantable Defibrillator study. Cardiac Arrest Study Hamburg . Canadian Implantable Defibrillator Study.

AIMS: Three randomized trials of implantable cardioverter defibrillator (ICD) therapy vs medical treatment for the prevention of death in survivors of ventricular fibrillation or sustained ventricular tachycardia have been reported with what might appear to be different results. The present analysis was performed to obtain the most precise estimate of the efficacy of the ICD, compared to amiodarone, for prolonging survival in patients with malignant ventricular arrhythmia. METHODS AND RESULTS: Individual patient data from the Antiarrhythmics vs Implantable Defibrillator (AVID) study, the Cardiac Arrest Study Hamburg (CASH) and the Canadian Implantable Defibrillator Study (CIDS) were merged into a master database according to a pre-specified protocol. Proportional hazard modelling of individual patient data was used to estimate hazard ratios and to investigate subgroup interactions. Fixed effect meta-analysis techniques were also used to evaluate treatment effects and to assess heterogeneity across studies. The classic fixed effects meta-analysis showed that the estimates of ICD benefit from the three studies were consistent with each other (P heterogeneity=0.306). It also showed a significant reduction in death from any cause with the ICD; with a summary hazard ratio (ICD:amiodarone) of 0.72 (95% confidence interval 0.60, 0.87;P=0.0006). For the outcome of arrhythmic death, the hazard ratio was 0.50 (95% confidence interval 0.37, 0.67;P<0.0001). Survival was extended by a mean of 4.4 months by the ICD over a follow-up period of 6 years. Patients with left ventricular ejection fraction < or = 35% derived significantly more benefit from ICD therapy than those with better preserved left ventricular function. Patients treated before the availability of non-thoracotomy ICD implants derived significantly less benefit from ICD therapy than those treated in the non-thoracotomy era. CONCLUSION: Results from the three trials of the ICD vs amiodarone are consistent with each other. There is a 28% reduction in the relative risk of death with the ICD that is due almost entirely to a 50% reduction in arrhythmic death.

A comparison of biphasic and monophasic shocks for external defibrillation. Physio-Control Biphasic Investigators.

BACKGROUND AND OBJECTIVE: The ability of a shock to defibrillate the heart depends on its waveform and energy. Past studies of biphasic truncated exponential (BTE) shocks for external defibrillation focused on low energy levels. This prospective, randomized, double-blind clinical trial compared the first-shock efficacies of 200-joule (J) BTE, 130-J BTE, and 200-J monophasic damped sine wave shocks. METHODS: Ventricular fibrillation (VF) was induced in 115 patients during evaluation of implantable cardioverter-defibrillator function and 39 patients during electrophysiologic evaluation of ventricular arrhythmias. After 19 +/- 10 seconds of VF, a randomized transthoracic shock was administered. Mean first-shock success rates of the three groups were compared using a "Tukey-like" statistical test, adjusting for multiple comparisons. Blood pressures and arterial oxygen saturations were measured before VF induction and 30, 90, and 150 seconds after successful defibrillation. RESULTS: First-shock success rates were 61/68 (90%) for 200-J monophasic, 39/39 (100%) for 200-J biphasic, and 39/47 (83%) for 130-J biphasic shocks. The 200-J biphasic shocks were simultaneously superior in first-shock efficacy to both 200-J monophasic and 130-J biphasic shocks (experimentwise error rate, alpha < 0.01). There was no significant difference between the efficacies of 200-J monophasic and 130-J biphasic shocks, nor was there any significant difference between the three groups in hemodynamic parameters after successful shocks. CONCLUSIONS: Biphasic shocks of 200 J provide better first-shock defibrillation efficacy for short-duration VF than 200-J monophasic and 130-J biphasic shocks and thus may allow earlier termination of VF in cardiac arrest patients.

The implantable cardioverter-defibrillator.

Ventricular arrhythmias remain a major cause of cardiovascular mortality. Therapy for serious ventricular arrhythmias has evolved over the past decade, from treatment primarily with antiarrhythmic drugs to implanted devices. The implantable cardioverter-defibrillator (ICD) is the best therapy for patients who have experienced an episode of ventricular fibrillation not accompanied by an acute myocardial infarction or other transient or reversible cause. It is also superior therapy in patients with sustained ventricular tachycardia (VT) causing syncope or hemodynamic compromise. Controlled clinical trials have confirmed the utility of these devices. As primary prevention, the ICD is superior to conventional antiarrhythmic drug therapy in patients who have survived a myocardial infarction and who have spontaneous, nonsustained ventricular tachycardia, a low ejection fraction, inducible VT at electrophysiologic study, and whose VT is not suppressed by procainamide. The effect of the ICD on survival of other patient populations remains to be proven. The device is costly, but its price is generally accepted to be reasonable. The ICD has been a major advance in the treatment of ventricular arrhythmias.

Determinants of outcome in patients with sustained ventricular tachyarrhythmias: the antiarrhythmics versus implantable defibrillators (AVID) study registry.

BACKGROUND: The prognosis of patients with sustained ventricular tachyarrhythmias varies according to clinical characteristics. We sought to identify predictors of survival in a large population of patients with documented sustained ventricular tachyarrhythmias not related to reversible or correctable causes included in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Registry. METHODS AND RESULTS: We analyzed the impact of 36 demographic, clinical, and discharge treatment variables on the outcome for 3559 patients. Survival status was assessed with the use of the National Death Index. Multivariate analyses were performed with the use of the Cox proportional hazards model. After a mean follow-up of 17 +/- 12 months, 631 patients died. Actuarial survival was 0.86 (95% confidence interval [CI] 0.85 to 0.88), 0.79 (95% CI 0.78 to 0.81), and 0.72 (95% CI 0.70 to 0.74) at 1, 2, and 3 years. Multivariate predictors of worse survival included older age, severe left ventricular dysfunction, lower systolic blood pressure, history of congestive heart failure, diabetes, smoking or atrial fibrillation, and preexistent pacemaker. The hemodynamic impact of the qualifying arrhythmia was not a predictor of outcome. Defibrillator implantation and hospital discharge while the patient was taking a beta-blocker or an angiotensin-converting enzyme inhibitor were associated with better prognosis. CONCLUSIONS: Despite therapeutic advances, the mortality rates of patients with sustained ventricular tachyarrhythmias remain high. Prognosis depends on the severity of underlying heart disease, as reflected by the extent of left ventricular dysfunction and the presence of heart failure. Well-tolerated ventricular tachycardia in patients with structural heart disease does not carry a significantly better prognosis than ventricular tachyarrhythmia with more severe hemodynamic consequences.

In-hospital versus out-of-hospital presentation of life-threatening ventricular arrhythmias predicts survival: results from the AVID Registry. Antiarrhythmics Versus Implantable Defibrillators.

OBJECTIVES: This study describes the outcomes of patients from the Antiarrhythmics Versus Implantable Defibrillators (AVID) Study Registry to determine how the location of ventricular arrhythmia presentation influences survival. BACKGROUND: Most studies of cardiac arrest report outcome following out-of-hospital resuscitation. In contrast, there are minimal data on long-term outcome following in-hospital cardiac arrest. METHODS: The AVID Study was a multicenter, randomized comparison of drug and defibrillator strategies to treat life-threatening ventricular arrhythmias. A Registry was maintained of all patients with sustained ventricular arrhythmias at each study site. The present study includes patients who had AVID-eligible arrhythmias, both randomized and not randomized. Patients with in-hospital and out-of-hospital presentations are compared. Data on long-term mortality were obtained through the National Death Index. RESULTS: The unadjusted mortality rates at one- and two-year follow-ups were 23% and 31.1% for patients with in-hospital presentations, and 10.5% and 16.8% for those with out-of-hospital presentations (p < 0.001), respectively. The adjusted mortality rates at one- and two-year follow-ups were 14.8% and 20.9% for patients with in-hospital presentations, and 8.4% and 14.1% for those with out-of-hospital presentations (p < 0.001), respectively. The adjusted long-term relative risk for in-hospital versus out-of-hospital presentation was 1.6 (95% confidence interval [CI] 1.3-1.9). CONCLUSIONS: Compared with patients with out-of-hospital presentations of life-threatening ventricular arrhythmias not due to a reversible cause, patients with in-hospital presentations have a worse long-term prognosis. Because location of ventricular arrhythmia presentation is an independent predictor of long-term outcome, it should be considered as an element of risk stratification and when planning clinical trials.

Beta-blocker use and survival in patients with ventricular fibrillation or symptomatic ventricular tachycardia: the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial.

OBJECTIVES: To evaluate whether use of beta-adrenergic blocking agents, alone or in combination with specific antiarrhythmic therapy, is associated with improved survival in persons with ventricular fibrillation (VF) or symptomatic ventricular tachycardia (VT). BACKGROUND: The ability of beta-blockers to alter the mortality of patients with VF or VT receiving contemporary medical management is not well defined. METHODS: Survival of 1,016 randomized and 2,101 eligible, nonrandomized patients with VF or symptomatic VT followed in the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial through December 31, 1996 was assessed using Cox proportional hazards analysis. RESULTS: The 817 (28%) patients discharged from hospital receiving beta-blockers had less ventricular dysfunction, fewer symptoms of heart failure and a different pattern of medication use compared with patients not receiving beta-blockers. Before adjustment for important prognostic variables, beta-blockade was not significantly associated with survival in randomized or in eligible, nonrandomized patients treated with specific antiarrhythmic therapy. After adjustment, beta-blockade remained unrelated to survival in randomized or in eligible, nonrandomized patients treated with amiodarone alone (n = 1142; adjusted relative risk [RR] = 0.96; 95% confidence interval [CI] 0.64-1.45; p = 0.85) or a defibrillator alone (n = 1347; adjusted RR = 0.88; 95% CI 0.55 to 1.40; p = 0.58). In contrast, beta-blockade was independently associated with improved survival in eligible, nonrandomized patients who were not treated with specific antiarrhythmic therapy (n = 412; adjusted RR = 0.47; 95% CI 0.25 to 0.88; p = 0.018). CONCLUSIONS: Beta-blocker use was independently associated with improved survival in patients with VF or symptomatic VT who were not treated with specific antiarrhythmic therapy, but a protective effect was not prominent in patients already receiving amiodarone or a defibrillator.