Sex Differences in Implantation and Outcomes of Cardiac Resynchronization Therapy in Real-World Settings: A Systematic Review of Cohort Studies

Background: Evidence from randomized trials is conflicting on the effects of cardiac resynchronization therapy (CRT) by sex, and differences in access are unknown. We examined sex differences in the implantation rates and outcomes in patients treated with CRT using cohort studies.Methods: We followed a pre-specified protocol (International Prospective Register of Systematic Reviews [PROSPERO]: CRD42020204804). MEDLINE, Embase, and Web of Science were searched for cohort studies from January 2000 to June 2020 that evaluated the response to CRT in patients = 18 years old and reported sex-specific information in any language.Results: We included 97 studies (1,172,654 men and 486,553 women). Men received CRT more frequently than women (median ratio, 3.16; 25th to 75th interquartile range, 2.48-3.62). In the unadjusted analysis, men had a greater long-term all-cause mortality rate after CRT, compared with women (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.38-1.63; P < 0.001). Adjustment for confounders did not affect the strength or direction of association (HR, 1.45; 95% CI, 1.32-1.59; P < 0.001). Women achieved a greater rate of improvement in left ejection fraction compared with men (HR, 4.66; 95% CI, 4.23-5.13; P < 0.001). Men had a lower risk of a pneumothorax (relative risk, 0.21; 95% CI, 0.13-0.34; P < 0.001]); otherwise, there were no differences in complications.Conclusions: We found in this large meta-analysis that men were more often implanted with CRT than women, yet men had a higher long-term all-cause mortality following CRT, compared with women, and smaller improvement in left ventricular ejection fraction. Reasons for this difference in implantation rates of CRT in real-world practice need to be investigated.