Comparison of beta-blockers, amiodarone plus beta-blockers, or sotalol for prevention of shocks from implantable cardioverter defibrillators: the OPTIC Study: a randomized trial.

CONTEXT: Implantable cardioverter defibrillator (ICD) therapy is effective but is associated with high-voltage shocks that are painful. OBJECTIVE: To determine whether amiodarone plus beta-blocker or sotalol are better than beta-blocker alone for prevention of ICD shocks. DESIGN, SETTING, AND PATIENTS: A randomized controlled trial with blinded adjudication of events of 412 patients from 39 outpatient ICD clinical centers located in Canada, Germany, United States, England, Sweden, and Austria, conducted from January 13, 2001, to September 28, 2004. Patients were eligible if they had received an ICD within 21 days for inducible or spontaneously occurring ventricular tachycardia or fibrillation. INTERVENTION: Patients were randomized to treatment for 1 year with amiodarone plus beta-blocker, sotalol alone, or beta-blocker alone. MAIN OUTCOME MEASURE: Primary outcome was ICD shock for any reason. RESULTS: Shocks occurred in 41 patients (38.5%) assigned to beta-blocker alone, 26 (24.3%) assigned to sotalol, and 12 (10.3%) assigned to amiodarone plus beta-blocker. A reduction in the risk of shock was observed with use of either amiodarone plus beta-blocker or sotalol vs beta-blocker alone (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.28-0.68; P<.001). Amiodarone plus beta-blocker significantly reduced the risk of shock compared with beta-blocker alone (HR, 0.27; 95% CI, 0.14-0.52; P<.001) and sotalol (HR, 0.43; 95% CI, 0.22-0.85; P = .02). There was a trend for sotalol to reduce shocks compared with beta-blocker alone (HR, 0.61; 95% CI, 0.37-1.01; P = .055). The rates of study drug discontinuation at 1 year were 18.2% for amiodarone, 23.5% for sotalol, and 5.3% for beta-blocker alone. Adverse pulmonary and thyroid events and symptomatic bradycardia were more common among patients randomized to amiodarone. CONCLUSIONS: Despite use of advanced ICD technology and treatment with a beta-blocker, shocks occur commonly in the first year after ICD implant. Amiodarone plus beta-blocker is effective for preventing these shocks and is more effective than sotalol but has an increased risk of drug-related adverse effects.Clinical Trials Registration ClinicalTrials.gov Identifier: NCT00257959.

Beta-blocker therapy in atrial fibrillation.

Beta-blocking agents are a generally established therapy to achieve rate control in patients with AF. With the widely spread belief that rhythm control is the therapy of choice, their use is currently limited to patients that were considered not suitable for specific antiarrhythmic drug therapy. In contrast to that belief, recent studies show that beta-blockers do have some benefit in maintaining sinus rhythm or reducing the frequency of paroxysmal AF and that this benefit might be comparable to conventionally used antiarrhythmic drugs, with the exception of amiodarone. In addition, four prospectively randomized studies recently presented concluded that rate control may be an appropriate aim as a first line approach in patients with AF. Hence, an increased use of beta-blockers in the treatment of patients with AF is to be expected, given the proven prognostic benefit of these drugs in many cardiovascular disorders that are associated with AF. However, no prospective study has yet proven that beta-blockers do exert the same benefit in patients in AF, and one retrospective analysis suggests that there may be differences with regard to the potential benefits of beta-blocker therapy when patients are in AF compared to sinus rhythm. The article summarizes available clinical studies and reviews some experimental data examining the treatment effects of antiadrenergic therapy in AF.

Impact of rate versus rhythm control on quality of life in patients with persistent atrial fibrillation. Results from a prospective randomized study.

AIMS: Despite the high prevalence of atrial fibrillation (AF), there are only limited data on quality of life (QoL) stemming from prospective trials comparing rate versus rhythm control. This prospective study evaluated QoL in patients with symptomatic persistent AF randomized to therapy aiming at rate versus rhythm control. METHODS AND RESULTS: Patients with symptomatic persistent AF (7 to 360 days duration) were prospectively randomized to ventricular rate control (n=125) or to cardioversion and maintenance of sinus rhythm (n=127). QoL was assessed by the Medical Outcomes Study Short Form health survey (SF-36) at baseline and during 1 year of follow-up. Changes in QoL were compared on an intent-to-treat basis, and subsequently between patients in sinus rhythm versus AF. At baseline, all SF-36 scales were reduced compared to healthy controls. At 1 year, six of eight items had improved significantly in patients assigned to rate control, and five of eight items on rhythm control (p=ns). The physical component summary showed a comparable increase with both treatment strategies (rate control: p=0.004; rhythm control: p<0.001) whereas no significant changes were found for the mental component summary. At 1 year, 55% of patients reported a positive health transition with no inter-group differences. There were no significant differences in QoL in patients in sinus rhythm or AF at the end of the observation period. CONCLUSION: In patients with symptomatic persistent AF, the two treatment strategies of rate versus rhythm control are associated with similar improvements in QoL.

Heart failure complicated by atrial fibrillation: mechanistic, prognostic, and therapeutic implications.

Atrial fibrillation and congestive heart failure are two distinct clinical entities that are responsible for significant morbidity and mortality in the Western world. Hypertension, coronary artery disease, and nonischemic cardiomyopathy represent the most prevalent underlying pathologies of both diseases, implying a coincidence of both in many patients. The prevalence of atrial fibrillation with a progressive degree of congestive heart failure is increasing, as judged by New York Heart Association functional class. Moreover, the presence of congestive heart failure has been identified as one of the most powerful independent predictors of atrial fibrillation, with a sixfold increase in relative risk of its development. On the other hand, atrial fibrillation can cause or significantly aggravate symptoms of congestive heart failure in previously asymptomatic or well-compensated patients. In some patients, symptomatic dilated cardiomyopathy may develop over time entirely due to atrial fibrillation with rapid ventricular rates. Upon restoration of sinus rhythm, this type of "tachymyopathy" has been shown to be often reversible. Recent investigations of the physiologic and structural changes of the atrial myocardium ("electrical and structural remodeling") have shown that neurohumoral activation, fibrosis, and apoptosis are demonstrable with both diseases. On the other hand, experimental data suggest that the substrates of atrial fibrillation in congestive heart failure are different from those of pure atrial tachycardia-related forms of atrial fibrillation. This review highlights the clinical and pathophysiologic similarities and differences of atrial fibrillation and congestive heart failure relevant to the understanding, treatment, and prevention of these diseases in the population at risk.

Thromboembolic risk of patients referred for radiofrequency catheter ablation of typical atrial flutter without prior appropriate anticoagulation therapy.

BACKGROUND: Radiofrequency catheter ablation of isthmus dependent atrial flutter is considered the therapy of choice. There is, however, controversy with regard to the thrombogenicity of atrial flutter in comparison with atrial fibrillation. METHODS: Consecutive patients scheduled for catheter ablation of documented typical atrial flutter receiving insufficient (INR < 2.0) or no anticoagulation during the three weeks preceding the procedure underwent multiplane transesophageal echocardiography (TEE). Patients with exclusive documentation of atrial flutter were classified as group I, whereas patients with additional documentation of atrial fibrillation were classified as group II. RESULTS: The study included 201 patients, 62 of whom were not on therapeutic anticoagulation (mean age 64 +/- 9 years, 87% men). In 10 of these 62 patients (16%), TEE detected a left atrial (LA) appendage thrombus in 4, or dense spontaneous echo contrast (SEC) in 6 patients. Comparison of patients with versus without SEC or thrombus, revealed a higher incidence of valvular heart disease (60% vs 26%, P = 0.05), but no differences with respect to age, gender, LA diameter, left ventricular end-diastolic diameter, or left ventricular ejection fraction. The incidence of positive TEE findings in group I was 1 in of 36 versus 9 of 26 in group II (3% vs 35%, P < 0.001), and the relative risk for thromboembolism in group II versus group I was 12.5 (95% CI: 3-55, P < 0.001). CONCLUSION: There is a significant risk for thromboembolism in patients referred for ablation of typical atrial flutter who have not been appropriately anticoagulated.

[Pharmacological therapy of atrial fibrillation and atrial flutter]. / Pharmakologische Therapie von Vorhofflimmern und Vorhofflattern.

BACKGROUND: Despite the increasing availability of nonpharmacological treatment options for atrial fibrillation, drug therapy targeted at restoration and maintenance of sinus rhythm, or aimed at symptomatic ventricular rate control remains the mainstay of therapy for the majority of patients. METHOD: Available data suggest that these two treatment approaches yield similar responder rates with regard to symptomatic improvement. RESULTS: Detailed results from major prospective studies investigating the prognostic effects of different atrial fibrillation treatment modalities are expected to become available soon. At present, however, the choice of the primary treatment strategy, i.e. rate control or rhythm control, still remains upon the clinical decision and expertise of the treating physician. Cardioversion by means of external biphasic shock delivery has shown to effectively convert atrial fibrillation to sinus rhythm in more than 90% of patients. Pharmacological cardioversion, in contrast, has a far lower success rate and may be followed by severe complications mandating in-hospital administration with the majority of drug regimens. For the maintenance of sinus rhythm, the proarrhythmic side effects of Class I antiarrhythmic drugs currently limit their use to those patients without any structural heart disease. Clinical investigation of newer "pure" Class III drugs have shown to excite considerable prolongation of ventricular repolarization duration resulting in a significant risk for torsade-de-pointes tachycardia. Betablockers are beneficial in many clinical situations associated with the occurrence of atrial fibrillation, such as heart failure, arterial hypertension and coronary artery disease. These substances, however, do not seem to improve cardioversion rates and their effect in maintaining sinus rhythm is only moderate. Patients with structural heart disease in whom maintenance of sinus rhythm is strongly desired, therefore, are left to amiodarone therapy. The cardiac safety profile as well as the proven effectiveness are unsurpassed by any other available drug at present. This paper reviews major studies published during the last decade implementing recent guidelines regarding pharmacological rate control, cardioversion and maintenance of sinus rhythm and the approach towards patients suffering from paroxysmal atrial fibrillation.

Ventricular rate stabilization for the prevention of pause dependent ventricular tachyarrhythmias: results from a prospective study in 309 ICD recipients.

Reviews of stored electrograms from ICDs revealed a 5-30% incidence of short-long-short intervals preceding the onset of recurrent ventricular tachyarrhythmias. Rate stabilization by dedicated antibradycardia pacing algorithms has, therefore, been suggested to prevent onset of pause dependent tachyarrhythmias. However, the clinical efficacy of this approach has not been studied systematically. In a prospective multicenter crossover study, patients were randomized to activation or deactivation of an implemented ventricular rate stabilization algorithm (VRS) after first implant of a dual chamber ICD. After 3 months, all patients were crossed over to the alternate programming. The rate of appropriate spontaneous VA episodes was compared between VRS On and VRS Off. Stored electrograms were reviewed for evaluation of the mode of onset of tachyarrhythmias. Overall efficacy analysis was based on 309 patients enrolled in the study. Forty percent (124/309) of the patients experienced 4,973 VA episodes. Based on an intention-to-treat analysis, VRS Off and On arrhythmia incidence was 10.2 and 6.6 normalized to 3 months, respectively (risk reduction 35%; P = 0.18) On an on-treatment basis, a reduction from 9.0 episodes to 8.1 episodes (10% risk reduction, P = 0.24) was seen. In an extended Cox model adjusting for confounding variables, the relative risk for recurrent episodes was 0.92 during VRS On compared to Off (95% CI: 0.58-1.48; P = 0.74). During VRS Off, pause dependent onset was documented in only 36 (8%) of 427 visually analyzed episodes. There was no significant reduction in the incidence of recurrent ventricular tachyarrhythmias with VRS On compared to the Off programming in this prospective study.