Sex Differences in Primary Mitral Regurgitation: Insights from Cardiovascular Magnetic Resonance Study

Background: Prior studies described existing knowledge gaps in management of women with mitral regurgitation (MR). We aim to evaluate the impact of sex on assessment of MR severity and cardiac remodeling using CMR. We also explore sex differences in symptom status between women and men and compare adverse outcomes after mitral valve (MV) intervention.

Methods: Patients undergoing CMR for assessment of chronic primary MR were enrolled. Confounding conditions such as coronary artery disease, cardiomyopathy, infiltrative/inflammatory disease, LVEF< 50% and coexisting valvular disease were excluded. Symptoms related to MR were recorded at the time of CMR. Patients were followed for all-cause mortality after MV intervention.

Results: A total of 598 primary MR patients were evaluated (302 women, 296 men). Women were older (62.0±14.5vs.58.5±14.9 years, p=0.004) with smaller body surface area (BSA, 1.77±0.19vs.2.03±0.22 m², p< 0.001). Comorbidities were comparable. MV prolapse was the most common etiology in both groups. Late gadolinium enhancement was more prevalent in men than women (25.7%vs.16.9%, p=0.009). Left and right ventricular (LV/RV) volumes and LV mass were smaller in women across MR severity. After adjusted for BSA, these differences were no longer significant except for the higher LV mass index in men (Fig 1). Left atrial volume index (LAVI) and extracellular volume (ECV) increased with MR severity and greater in women at similar MR severity (Fig 2). Symptomatic MR (total 159 patients) was more frequent in women (58.3%vs.41.9%, p=0.003). Women with symptomatic MR, compared to men, had lower regurgitant volume (41.0vs.63.0 ml, p< 0.001) and LV volumes even after adjustment for BSA (LVEDV index 89.2vs.109.0 ml/m² and LVESV index 27.3vs.41.0 ml/m², both p< 0.001) while regurgitant fraction (42.0%vs.48.0%, p=0.06) and LVEF (65.5%vs.62.3%, p=0.07) were similar. Of 199 patients who underwent MV intervention, 39.7% were women vs. 60.3% were men. Women had MV intervention due to symptoms more than men (89.9%vs.67.5%, p=0.003) while men had higher proportion due to LV dilatation or systolic dysfunction as indication (32.5%vs10.1%, p< 0.001). During follow up (median 5.8 years), all-cause mortality after MV intervention occurred in 17 patients (11 women, 6 men). Female sex was associated with all-cause mortality (Fig 3) after MV intervention (unadjusted HR 3.11, [95% CI 1.15-8.45], p=0.03).

Conclusion: In primary MR patients with preserved systolic function, women demonstrated higher remodeling sequalae for a given MR severity, as manifested by LAVI and ECV while indexing for BSA largely corrected for sex differences in LV dilatation. Women developed MR symptoms at lower regurgitant volume and lesser degree of LV dilatation. Despite greater burden of symptoms, women underwent MV intervention less often than men and suffered higher adverse outcome. Our data suggest sex-specific thresholds for MV intervention may better stratify patients at risk.

Fig 1. Sex differences in cardiac remodelling across mitral regurgitation severity with absolute values (panel A-C) and adjustment for body surface area (panel D-F) depicting by quadratic prediction plots with confidence interval bands.
Fig 2. Sex differences in left atrial volume index (panel A), aortic forward flow index (panel B) and extracellular volume (panel C) across mitral regurgitation severity depicting by quadratic prediction plots with confidence interval bands.
Fig 3. Kaplan Meier curve demonstrates all-cause mortality after mitral valve intervention in women and men