Importance of beta-blocker dose in prevention of ventricular tachyarrhythmias, heart failure hospitalizations, and death in primary prevention implantable cardioverter-defibrillator recipients: a Danish nationwide cohort study.

Aims: There is a paucity of studies investigating a dose-dependent association between beta-blocker therapy and risk of outcome. In a nationwide cohort of primary prevention implantable cardioverter-defibrillator (ICD) patients, we aimed to investigate the dose-dependent association between beta-blocker therapy and risk of ventricular tachyarrhythmias (VT/VF), heart failure (HF) hospitalizations, and death. Methods and results: Information on ICD implantation, endpoints, comorbidities, beta-blocker usage, type, and dose were obtained through Danish nationwide registers. The two major beta-blockers carvedilol and metoprolol were examined in three dose levels; low (metoprolol ≤ 25 mg; carvedilol ≤ 12.5 mg), intermediate (metoprolol 26-199 mg; carvedilol 12.6-49.9 mg), and high (metoprolol ≥ 200 mg; carvedilol ≥ 50 mg). Time to events was investigated utilizing multivariate Cox models with beta-blocker as a time-dependent variable. From 2007 to 2012, 2935 first-time ICD devices were implanted. During follow-up, 399 patients experienced VT/VF, 728 HF hospitalizations and 361 died. As compared with patients not on beta-blockers, low, intermediate, and high dose had significantly reduced risk of HF hospitalizations {hazard ratio (HR) = 0.68 [0.54-0.87], P = 0.002; HR = 0.53 [0.42-0.66], P < 0.001; HR = 0.43 [0.34-0.54], P < 0.001} and death (HR = 0.47 [0.35-0.64], P < 0.001; HR = 0.29 [0.22-0.39], P = 0.001; HR = 0.24 [0.18-0.33], P < 0.001). For the endpoint of VT/VF, only intermediate and high dose beta-blocker was associated with significantly reduced risk (HR = 0.58 [0.43-0.79], P < 0.001; HR = 0.53 [0.39-0.72], P < 0.001). No significant difference was found between comparable doses of carvedilol and metoprolol on any endpoint (P = 0.06-0.94). Conclusion: In primary prevention ICD patients, beta-blocker therapy was associated with significantly reduced risk of all endpoints, as compared with patients not on beta-blocker, with the suggestion of a dose-dependent effect. No detectable difference was found between comparable doses of carvedilol and metoprolol.

Efficacy on resynchronization and longitudinal contractile function comparing His-bundle pacing with conventional biventricular pacing: a substudy to the His-alternative study.

AIMS: His-bundle pacing has emerged as a novel method to deliver cardiac resynchronization therapy (CRT). However, there are no data comparing conventional biventricular (BiV)-CRT with His-CRT with regard to effects on mechanical dyssynchrony and longitudinal contractile function. METHODS AND RESULTS: Patients with symptomatic heart failure, left ventricular ejection fraction ≤ 35%, and left bundle branch block (LBBB) by strict ECG criteria were randomized 1:1 to His-CRT or BiV-CRT. Two-dimensional strain echocardiography was performed prior to CRT implantation and at 6 months after implantation. Differences in changes in mechanical dyssynchrony (standard deviation of time-to-peak in 12 midventricular and basal segments) and regional longitudinal strain in the six left ventricular walls were compared between the BiV-CRT and His-CRT groups.In the on-treatment analysis, 31 received BiV-CRT and 19 His-CRT. In both groups, mechanical dyssynchrony was significantly reduced after 6 months [BiV group from 120 ms (±45) to 63 ms (±22), P < 0.001, and His group from 116 ms (±54) to 49 ms (±11), P < 0.001] but no significant differences in changes could be demonstrated between groups [-9.0 ms (-36; 18), P = 0.50]. Global longitudinal strain (GLS) improved in both groups [BiV group from -9.1% (±2.7) to -10.7% (±2.6), P = 0.02, and His group from -8.6% (±2.1) to -11.1% (±2.0), P < 0.001], but no significant differences in changes could be demonstrated from baseline to follow-up [-0.9% (-2.4; -0.6), P = 0.25] between groups. There were no regional differences between groups. CONCLUSION: In heart failure, patients with LBBB, BiV-CRT, and His-CRT have comparable effects with regard to improvements in mechanical dyssynchrony and longitudinal contractile function.