Sex-specific differences in left ventricular remodelling and mitral regurgitation assessment in surgically treated mitral valve prolapse: results from a pilot multimodality imaging study

Abstract Background There is growing recognition that the recommended cut-off values for evaluating mitral regurgitation (MR) may underestimate MR severity in women compared to men, leading to delayed referrals for surgical treatment and poorer postoperative outcomes. Moreover, linear ventricular dimensions (LVDs) often inadequately capture the extent of cardiac remodelling in MR [1, 2]. Purpose This study aimed to investigate sex-related differences in LVDs and ventricular volumes (VVols), as well as regurgitant volume (RVol) and regurgitant fraction (RF), in patients with mitral valve prolapse (MVP) referred for mitral valve repair (MVR) at a tertiary referral heart centre. Methods A total of 56 patients (27% female) with isolated significant MR (grade 3+/4+) due to MVP, referred for MVR, were prospectively assessed using 2D transthoracic echocardiography (TTE), 3D-TTE, and cardiac magnetic resonance (CMR). Given the smaller body size of women, parameters were evaluated relative to body surface area (BSA); RVol was additionally indexed to left ventricular end-diastolic volume (LVEDV). Results Women exhibited significantly smaller absolute LVDs and VVols than men (CMR: LVDD 58 ± 5 mm vs. 62 ± 6 mm, LVSD 34 ± 5 mm vs. 37 ± 7 mm, p < 0.05; LVEDV 188 ± 39 mL vs. 252 ± 57 mL, LVESV 68 ± 13 mL vs. 98 ± 32 mL, p < 0.05). After indexing to BSA, the difference in LVDs showed a non-significant but reversed trend, with higher values in women (CMR LVDD/BSA 34 ± 5 mm/m² vs. 32 ± 4 mm/m², LVSD/BSA 20 ± 4 mm/m² vs. 19 ± 4 mm/m²). Indexed VVols remained significantly smaller in women (CMR LVEDV/BSA 110 ± 27 mL/m² vs. 126 ± 27 mL/m², LVESV/BSA 40 ± 10 mL/m² vs. 49 ± 16 mL/m², p < 0.05). Average end-diastolic VVols indicated severe left ventricular (LV) dilatation in both sexes, while average LVDs suggested mild LV dilatation in men and moderate LV dilatation in women. Notably, only 27% of women had an LVSD ≥ 40 mm compared to 44% of men, yet 47% had an LVSD/BSA ≥ 21 mm/m² vs. 39% of men. Based on the recommended 2D-TTE cut-off values, women showed more dilated hearts (mean LVEDV > 25 mL above the severe dilatation threshold vs. > 5 mL in men; LVEDV/BSA > 10 mL/m² in women vs. > 3 mL/m² in men). Furthermore, women had significantly smaller absolute RVol than men (CMR RVol 58 ± 21 mL vs. 72 ± 27 mL; p < 0.05). However, after indexing to BSA and LVEDV, indexed RVol values and RF were comparable between sexes. These results were consistent across imaging modalities (s. Tables 1 and 2). Conclusion(s) Volume measurements may offer a more accurate assessment of LV remodelling than linear dimensions in both sexes. Women with significant MR demonstrate greater LV remodelling yet have smaller absolute VVols and RVol compared to men. Indexed RVol and RF values may serve as sex-independent indicators of MR severity. Our findings underscore the absence of sex-specific imaging thresholds for MR assessment and highlight the need for gender-specific cut-off values in clinical practice.