Impact of sex on severity assessment and cardiac remodeling in primary mitral regurgitation due to valve prolapse
Authors: Altes A , Levy F , Hanet V , De Azevedo D , Krug P , Iacuzio L , Toledano M , Silvestri V , Vancraeynest D , Pasquet A , Vincentelli A , Eker A , Marechaux S , Gerber B L 
Published: June 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
It is well known that left ventricular(LV) dimensions are influenced by body size and sex. However, current guidelines for primary mitral regurgitation(MR) valve disease propose echocardiographic cut-off values for MR quantitative parameters (effective orifice regurgitant area(EROA), regurgitant volume(RegVol)) and left heart remodeling (LV end-systolic diameter[ESD], indexed LA volume[indLAV]) which are not sex-specific.

Purpose
Therefore we aimed at evaluating how MR severity and cardiac remodeling are influenced by sex.

Methods
We retrospectively evaluated 470 patients (27% women, median age 63 [IQR: 53–71] years) with chronic significant (at least moderate to severe) primary MR due to valve prolapse who underwent transthoracic echocardiographic(Echo) and cardiac magnetic resonance imaging(CMR) in 3 tertiary centers between 2005 and 2022. The relationship between MR quantification, cardiac remodeling and sex was evaluated.

Results
Women were older than men (p&lt;0.001), had higher NYHA functional class (p = 0.035), larger Echo-indLAV (p = 0.003), higher right ventricle systolic peak pressure (p = 0.032), and more symptoms-triggered MV intervention (p = 0.029). However, both EROA (p&lt;0.001), Echo-RegVol (p = 0.003) and CMR-RegVol (p&lt;0.001) were lower in women than in men, while CMR regurgitant fraction(RegFrac) values were similar (p = 0.890). Abnormally increased CMR- (&gt;upper limit bound of UK Biobank reference values) indexed LV end-diastolic(indLVEDV), end-systolic volume(indLVESV) and indLAV were observed in 55%, 29% and 82% of patients, respectively, without sex difference (p = 1, p = 0.9 and p = 0.5). The optimal cut-off values of MR EROA, Echo-RegVol and CMR-RegVol associated with enlarged indLVEDV were lower in women (40mm2, 60ml, 50ml) than in men (45mm2, 77ml, 62ml). The threshold of LVESD ≥40mm showed in women and men high specificity[Sp] (91%, 79%) but poor sensitivity[Se] (40%, 50%) to predict enlarged indLVESV. Accordingly, the best threshold of LVESD to predict enlarged indLVESV was slightly lower in women (35mm, Se=65%, Sp = 71%, AUC=0.72) than in men (37mm, Se=65%, Sp = 68%, AUC=0.72). Replacing absolute by indexed LVESD did not improve the predictive value. In contrast, the best threshold of Echo-indLAV associated with enlarged CMR-indLAV was lower in men (47ml/m2, Se=68%, Sp = 71%, AUC=0.76) than in women (56ml/m2, Se=70%, Sp = 71%, AUC=0.73).

Conclusion
Despite clear hallmarks of more advanced valve disease, women with primary MR have lower absolute mitral regurgitant volumes and lower ventricular volumes than men. Furthermore, cut-off values of mitral regurgitant volume, effective orifice regurgitant area and LV dimensions for predicting abnormal LV dilatation by CMR are lower in women than in men. Conversely, cut-off values of indexed LA volume by echo for predicting abnormal LA dilatation by CMR are lower in men than in women. Therefore, guideline-based criteria for grading MR and timing of intervention could be sex-specific.