Sex-Based Differences in Outcomes of Cardiac Resynchronization Therapy in Patients With Left Bundle Branch Block: A Systematic Review and Meta-Analysis

Cardiac resynchronization therapy (CRT) improves outcomes in heart failure with reduced ejection fraction and left bundle branch block (LBBB), and several studies suggest that women respond better than men.However, most evidence comes from populations that mix LBBB with other conduction disturbances.We conducted a systematic review and meta-analysis of sex-specific CRT outcomes restricted to patients with LBBB.PubMed, Scopus, and Excerpta Medica database (Embase) were searched from inception to November 2024 in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines.Twelve studies (4,072 patients; 1,564 women) were included.Studies of conventional biventricular pacing (BVP) formed the primary analysis, and left bundle branch area pacing (LBBAP) arms were added in sensitivity analyses.Random-effects models were used.In the primary analysis, women had a greater improvement in left ventricular ejection fraction (LVEF) than men (mean difference (MD) 2.83%, 95% CI 0.16-5.51;I²=81%), with a larger difference in studies published after 2010 (MD 4.07%, 95% CI 0.42-7.72).Women also had lower all-cause mortality (RR 0.68, 95% CI 0.49-0.94;I²=0%) and fewer heart failure hospitalizations (RR 0.73, 95% CI 0.54-0.99),although the latter estimate was based on only two studies.Post-CRT QRS duration did not differ by sex.Adding the single available LBBAP arm gave a similar LVEF estimate (MD 2.67%, 95% CI 0.43-4.90).However, the LVEF difference lost statistical significance when any of four of the six BVP studies were omitted; its 95% prediction interval crossed zero (-6.04% to 11.71%), and the mortality estimate depended largely on one large study.Among patients with LBBB undergoing CRT, female sex was associated with more favorable outcomes.Because women more often had non-ischemic cardiomyopathy, less often had atrial fibrillation, and had smaller ventricles, these findings reflect an association rather than an independent effect of sex.