JACC. Cardiovascular imaging · 2026
Sex-Related Differences in Outcomes and Thresholds for Intervention in Primary Mitral Regurgitation: A Systematic Review and Meta-Analysis.
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Long Edouard, Hahn Rebecca T, Gulati Martha, Demetrescu Camelia, Shah Benoy N, Bhattacharya Sanjeev, Moorjani Narain, Lucchese Gianluca, Bilkhu Rajdeep, Bosco Paolo, Patterson Tiffany, Redwood Simon, Pibarot Philippe, Prendergast Bernard, Rajani Ronak, Androshchuk Vitaliy
Аннотация
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.
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.