Impact of sex on severity assessment and cardiac remodeling in primary mitral regurgitation due to valve prolapse

Abstract

The current recommended cut-off values for primary mitral regurgitation (MR) quantification (Effective Regurgitant Orifice Area [EROA], regurgitant volume [RegVol]) and left ventricular (LV) remodeling in MR (end-systolic diameter [ESD]) are not sex-specific. We retrospectively evaluated 470 patients (27% women, median age 63 years) with chronic significant primary MR due to prolapse who underwent echocardiography (Echo) and cardiac magnetic resonance imaging (CMR) in 3 tertiary centers between 2005 and 2022. Women were older than men, had higher NYHA class, larger left atrial volume, higher pulmonary pressure, and more symptoms-triggered MV intervention (all P < 0.035). However, both MR EROA, Echo-RegVol and CMR-RegVol were lower in women than in men (all P < 0.003), while CMR regurgitant fraction (RegFrac) values were similar (P = 0.890). Abnormally increased CMR- (> upper limit bound of UK Biobank reference values) indexed LV end-diastolic (indLVEDV), end-systolic volume (indLVESV) were observed in 55%, 29% of patients, respectively, without sex difference (P = 1, P = 0.9). The optimal cut-off values of MR EROA, Echo-RegVol and CMR-RegVol associated with enlarged indLVEDV were lower in women (40 mm2, 60 mL, 50 mL) than in men (45 mm2,77 mL, 62 mL). LVESD ≥ 40 mm showed in women and men high specificity [Sp] (91%, 79%) but poor sensitivity [Se] (40% 50%) to predict enlarged indLVESV, while the optimal threshold was slightly lower in women (35 mm, Se = 65%, Sp = 71%) than in men (37 mm, Se = 65%, Sp = 68%). Despite clear hallmarks of more advanced valve disease, women with primary MR have lower mitral RegVol and lower ventricular volumes than men. Then, cut-off values of mitral RegVol, EROA and LV dimensions for predicting abnormal LV dilatation are lower in women than in men. Hence, guideline-based criteria for grading MR and timing of intervention could be sex-specific (Fig. 1).