High incidence of pacemaker syndrome in patients with sinus node dysfunction treated with ventricular-based pacing in the Mode Selection Trial (MOST).

OBJECTIVES: We evaluated the incidence, predictors, and treatment of pacemaker syndrome in patients with sinus node dysfunction treated with ventricular-based (VVIR) pacing in the Mode Selection Trial (MOST). BACKGROUND: Pacemaker syndrome, or intolerance to VVIR pacing, consists of cardiovascular signs and symptoms induced by VVIR pacing. METHODS: The definition of pacemaker syndrome required that a patient with single-chamber VVIR pacing develop either congestive signs and symptoms associated with retrograde conduction during VVIR pacing or a >or=20 mm Hg reduction of systolic blood pressure during VVIR pacing, associated with reproducible symptoms of weakness, lightheadedness, or syncope. RESULTS: Of 996 patients randomized to VVIR pacing, 182 (18.3%) met criteria for pacemaker syndrome in follow-up. Pacemaker syndrome occurred early in most patients (13.8% at 6 months, 16.0% at 1 year, increasing to 19.7% at 4 years). Baseline univariate predictors of pacemaker syndrome included a lower sinus rate and higher programmed pacemaker rate. Previous heart failure, ejection fraction, and drop in systolic blood pressure with VVIR pacing at implantation did not predict the development of pacemaker syndrome. Post-implantation predictors of pacemaker syndrome were a higher percentage of paced beats, higher programmed low rate, and slower underlying spontaneous sinus rate. Quality of life decreased at the time of diagnosis of pacemaker syndrome and improved with reprogramming to atrial-based pacing. CONCLUSIONS: Severe pacemaker syndrome developed in nearly 20% of VVIR-paced patients and improved with reprogramming to the dual-chamber pacing mode. Because prediction of pacemaker syndrome is difficult, the only way to prevent pacemaker syndrome is to implant atrial-based pacemakers in all patients.

Percent right ventricular pacing predicts outcomes in the DAVID trial.

BACKGROUND: The Dual-Chamber and VVI Implantable Defibrillator (DAVID) trial demonstrated a worse outcome in patients with implantable cardioverter-defibrillators (ICDs) programmed to DDDR at 70 bpm compared with patients who had ICDs programmed to VVI backup pacing at 40 bpm. Pacing was more frequent in the DDDR group. OBJECTIVES: The purpose of this study was to determine whether right ventricular pacing (RV) is an independent predictor of outcome in the DAVID trial. METHODS: We evaluated the relationship of percent RV pacing to the composite endpoint of death or hospitalization for congestive heart failure. Patients who had a 3-month follow-up and who had not yet reached an endpoint were included in the study. Using Cox regression analysis (VVI group N = 195; DDDR group N = 185), we examined multiple factors, including percent RV pacing at 3-month follow-up, that might be associated with adverse outcomes. RESULTS: Percent RV pacing as a continuous variable was correlated with the primary endpoint. As a dichotomous variable, the best separation for predicting endpoints occurred with DDDR RV pacing > 40% vs DDDR RV pacing < or = 40% (P = .025). Patients with DDDR RV pacing < or = 40% had similar or better outcomes to the VVI backup group (P = .07). Correction for baseline variables predictive of the composite outcome in the (nonpaced) VVI group (use of nitrates, increased heart rate, and increased age) did not change the findings for RV pacing (P = .008). In contrast, atrial pacing was not predictive of worse outcomes. CONCLUSION: These results suggest, but do not prove, a causal relationship between frequent RV pacing and adverse outcomes in patients with left ventricular ejection fraction < or = 40%.

Effect of surgical revascularization in patients with coronary artery disease and ventricular tachycardia or fibrillation in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Registry.

BACKGROUND: Patients who undergo resuscitation from near-fatal ventricular arrhythmias often have significant coronary artery disease, and revascularization has been shown to reduce myocardial ischemia and cardiac arrest episodes in this patient population. The magnitude of benefit attributed to revascularization has varied by study, and the use of adjunct implantable cardioverter defibrillator (ICD) therapy has not been well-characterized. METHODS AND RESULTS: The Antiarrhythmics Versus Implantable Defibrillators (AVID) registry included 3117 patients with life-threatening ventricular arrhythmias, of whom 2321 (77%) had documented coronary artery disease and 281 (17%) underwent a coronary artery bypass grafting revascularization procedure after the index event. Patients who underwent a revascularization procedure were younger, had a lower incidence rate of prior myocardial infarction and ventricular arrhythmia, had a higher left ventricular ejection fraction, had less congestive heart failure, and were more likely to have had ventricular fibrillation as the presenting arrhythmia. Patients who underwent revascularization had a better survival rate than did those who did not undergo such a procedure after the index event, and adjustment for differing baseline patient covariates did not alter the relative survival rate benefit. Further, ICD implantation offered a similar survival rate advantage to those patients in the AVID registry with coronary artery disease independent of revascularization. CONCLUSION: Coronary revascularization in the AVID registry patients with coronary artery disease effected a survival rate benefit that was not attributable to differences in baseline patient characteristics. The benefit of ICD on patient survival rate was not attenuated by a revascularization procedure.

Do arrhythmia patients improve survival by participating in randomized clinical trials? Observations from the Cardiac Arrhythmia Suppression Trial (CAST)and the Antiarrhythmics Versus Implantable Defibrillators Trial (AVID).

It is debatable whether patients benefit directly from participation in a randomized clinical trial. We attempt to address this question for participants in the Cardiac Arrhythmia Suppression Trial (CAST) and the Antiarrhythmics Versus Implantable Defibrillators (AVID) studies. Survival rates were compared between eligible patients who enrolled in the trials and eligible patients who did not enroll, adjusting for baseline covariates. In CAST, despite that the active therapy was found to confer an almost threefold increased risk of death, survival was similar between the 3163 enrolled and the 1363 nonenrolled eligible patients. However, when patients were under study management, their risk of death was approximately 20% lower than when they left study management. In AVID, overall survival was similar between the 1016 enrolled and the 1246 nonenrolled eligible patients. However, mortality was substantially higher among patients not enrolled because the referring physician mandated the type of therapy. Overall these observational analyses suggest a net improvement in survival for the participants in these two trials.

Predictors and clinical impact of atrial fibrillation after pacemaker implantation in elderly patients treated with dual chamber versus ventricular pacing.

The Pacemaker Selection in the Elderly (PASE) trial was a prospective, multicenter, single blind, randomized comparison of single chamber, rate adaptive, ventricular pacing (VVIR) with dual chamber, rate adaptive pacing (DDDR) in 407 patients aged > or =65 years(mean 76 +/- 7 years, 60% male)with standard bradycardia indications for dual chamber pacemaker implantation. The incidence, predictors, and clinical consequences of atrial fibrillation (AF) developing after pacemaker implantation in the PASE trial were studied prospectively. During a median follow-up of 18 months, AF developed in 73 (18%) patients. Kaplan-Meier estimated cumulative incidences of AF in patients with sinus node dysfunction (n=176) at 18 months were 28% in the VVIR and 16% in the DDDR groups (P=0.08). After adjustment for other clinical variables using a Cox multivariate regression model, randomization to VVIR compared with DDDR pacing mode among patients with sinus node dysfunction was independently associated with a 2.6-fold increased relative risk (RR) of developing AF after pacemaker implantation (P=0.01). Other independent clinical risk factors for development of postimplant AF included a preimplant history of hypertension (P=0.02) or supraventricular tachyarrhythmias(P<0.04). Patients who developed AF had similar health related quality of life scores and cardiovascular functional status after 18 months of pacing as patients who remained free of AF. The RR of death, stroke, or heart failure hospitalization was not increased in patients who developed AF. Thus, in the elderly patients with sinus node dysfunction requiring permanent pacing, DDDR pacing mode protected against the development of AF. However, development of AF after pacemaker implantation in this population was not associated with a significant impact on quality-of-life, functional status, or other clinical endpoints during 18 months of follow-up.