Sex-Specific Association of Left Ventricular Function With Mortality in Severe Mitral Regurgitation

Importance: The association between left ventricular (LV) systolic dysfunction and adverse outcomes in patients with severe degenerative mitral regurgitation (MR) may vary by sex. Objective: To investigate the sex-specific association of LV systolic function with mortality in patients with severe degenerative MR. Design, Setting, and Participants: This retrospective cohort study included consecutive patients who underwent surgery for severe degenerative MR at 2 tertiary hospitals in South Korea from 2006 to 2020. Preoperative LV ejection fraction (LVEF) and LV global longitudinal strain (LV-GLS) were measured, with absolute LV-GLS values reported. Patients were stratified by LVEF (≤55%, >55% to ≤60%, and >60%) and LV-GLS (<19.9%, ≥19.9% to <23.4%, and ≥23.4%) tertiles. Mortality status was verified through December 2023, with a median (IQR) follow-up duration of 8.2 (5.3-12.2) years. Data analysis was conducted in March 2024. Exposures: Surgical MV repair or replacement. Main Outcomes and Measures: The primary outcome was all-cause mortality after MV surgery. Restricted cubic spline (RCS) curves visualized the association between LVEF, LV-GLS, and mortality for each sex. Results: Among 1686 patients, 1088 (64.5%) were men and 598 (35.5%) were women. Women were older than men (median [IQR] age, 62 [51-70] vs 54 [45-63] years) and had higher LVEF and LV-GLS than men did. During the follow-up, 220 (13.0%) deaths occurred (117 men [10.8%]; 103 women [17.2%]). In Kaplan-Meier curves, mortality in men increased in the lowest LVEF (≤55%) and LV-GLS (<19.9%) groups, whereas women exhibited an earlier increase in mortality at higher LVEF (55%-60%) and LV-GLS (19.9%-23.4%) levels. Multivariable Cox analyses showed a higher mortality risk associated with LVEF less than or equal to 55% (adjusted hazard ratio [HR], 3.48; 95% CI, 1.84-6.58; P < .001) and 55% to 60% (adjusted HR, 2.21; 95% CI, 1.36-3.58; P = .001) compared with LVEF greater than 60% in women, but not in men (P for interaction by sex = .02). RCS curves showed an earlier increase in mortality risk at higher LVEF and LV-GLS levels in women. Similar trends were observed in asymptomatic patients. Conclusions and Relevance: In this cohort study of patients with severe degenerative MR, women had an earlier increase in mortality risk associated with LV systolic dysfunction, suggesting the need to consider sex-specific criteria for early surgery in asymptomatic patients.