Sex-Related Differences in Outcomes and Thresholds for Intervention in Primary Mitral Regurgitation

BACKGROUND: Evidence on sex differences in outcomes after interventions for primary mitral regurgitation (PMR) remains conflicting. The authors performed a dedicated meta-analysis to examine whether guideline-recommended thresholds for intervention may contribute to these discrepancies. METHODS: Electronic databases were searched for studies reporting long-term outcomes of patients undergoing surgical or transcatheter interventions for PMR, stratified by sex. The primary endpoint was all-cause mortality, and the secondary endpoint was major adverse cardiovascular events. Reconstructed time-to-event individual patient data were used to derive frailty-adjusted Cox models and restricted mean survival time. To investigate whether sex-based differences in baseline characteristics had a modulating effect on differences in all-cause mortality, meta-regression was performed on individual patient data-derived HRs using a linear mixed-effects model. RESULTS: Across 17 studies (N = 25,690), women comprised the minority (n = 9,632, 37.5%) and were significantly older (mean difference: 3.2 years, 95% CI: 2.2-4.3) with a greater proportion of heart failure symptoms (OR: 1.8; 95% CI: 1.6-2.1). At 15.7 years of follow-up, women had significantly greater risk of all-cause mortality compared with men (HR: 1.15; 95% CI: 1.07-1.24), corresponding to a survival deficit of 5.8 months (95% CI: 3.7-7.7). Similar results were observed in sensitivity analyses restricted to surgical intervention studies (HR: 1.18; 95% CI: 1.10-1.27). Female sex was also associated with significantly increased major adverse cardiovascular events (n = 2,775) (HR: 1.37; 95% CI: 1.11-1.70; Δ restricted mean survival time: 8.5 months, 95% CI: 2.4-14.5). Age, ≥ moderate tricuspid regurgitation (TR), and concomitant tricuspid valve repair (TVr) emerged as significant moderators of sex differences in mortality after intervention for PMR (P < 0.001, P = 0.03, and P < 0.001, respectively). A greater proportion of ≥ moderate TR and TVr in women conferred increased mortality relative to men. Neither left ventricular nor left atrial parameters significantly moderated sex differences in all-cause mortality (all P > 0.05). CONCLUSIONS: At the time of PMR intervention, women are older, have more symptoms, and worse long-term outcomes compared with men. Older female age alongside higher prevalence of ≥ moderate TR and TVr explained a significant proportion of this heterogeneity in sex-related all-cause mortality, whereas differences in left ventricular and left atrial parameters had no significant influence. A careful appraisal of current guidelines to ensure equality of health care outcomes between sexes is warranted.