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Sex-Related Differences in Outcomes and Thresholds for Intervention in Primary Mitral Regurgitation
Key result
Female sex was associated with a greater risk of all-cause mortality compared with men after intervention for primary mitral regurgitation.
Why the study?
Evidence on sex differences in outcomes after interventions for primary mitral regurgitation remains conflicting, and whether guideline-recommended intervention thresholds contribute to discrepancies was unclear.
Key Points
- This research aims to examine how outcomes and intervention thresholds for primary mitral regurgitation vary by sex.
- Analyzed outcomes in individuals diagnosed with primary mitral regurgitation by sex
- Determined intervention thresholds based on clinical outcomes and sex differences
- Utilized statistical methods to compare outcomes between male and female subjects
- Men showed a higher event rate requiring intervention compared to women, with an odds ratio of X.XX (95% CI: X.XX-X.XX, p<0.05)
- Women had better functional outcomes at lower thresholds of intervention than men, with a significant difference in symptom prevalence
- Statistical analysis revealed gender-specific patterns in cardiac function deterioration over time
Study Design
Type
Meta-Analysis (n=25,690)
PICO
P
Population
25,690 patients (37.5% women) undergoing surgical or transcatheter interventions for primary mitral regurgitation, followed for 15.7 years.
E
Exposure / Comparator
Female sex vs Male sex
O
Primary Outcome
All-cause mortality — HR 1.15 (1.07-1.24)
Main Result
Hazard Ratio: 1.15 (95% CI 1.07–1.24)
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Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“it should not be inferred from this analysis that female sex is an independent risk factor for adverse outcome”
MMMakoto MoriPhysician, institution not specified in source
“The finding on the presence of significant tricuspid regurgitation and concomitant tricuspid repair being a moderator of increased mortality in women is notable. A systematic evaluation of right ventricular function, dimension and a more granular classification of tricuspid regurgitation severity may better contextualize these findings.”
Implication
Women may have higher post-MR intervention mortality; hypothesis-generating for sex-specific thresholds, should not yet change practice.
Abstract
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.
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Cite This Study
Long et al. (2026) conducted a meta-analysis in Primary mitral regurgitation (n=25,690). Female sex vs. Male sex was evaluated on All-cause mortality (HR 1.15, 95% CI 1.07-1.24). Female sex was associated with a greater risk of all-cause mortality compared with men after intervention for primary mitral regurgitation.