Background In calcific aortic valve disease on tricuspid aortic valves ( TAVs ), men have higher aortic valve calcification and less fibrosis than women. However, little is known in bicuspid aortic valves ( BAV ). We thus aimed to investigate the impact of age, sex, and valve phenotype ( TAVs versus BAVs ) on fibro‐calcific remodeling in calcific aortic valve disease. Methods and Results We included 2 cohorts: 411 patients who underwent multidetector computed tomography (37% women) for aortic valve calcification density assessment and 138 explanted aortic valves (histological cohort; 50% women). The cohorts were divided in younger (<60 years old) or older patients with BAV (≥60 years old), and TAV patients. In each group, women and men were matched. Women presented less aortic valve calcification density than men in each group of the multidetector computed tomography cohort (all P ≤0.01). Moreover, in women, younger patients with BAV had the lowest aortic valve calcification density (both P =0.02). In multivariate analysis, aortic valve calcification density correlated with age (β estimate±standard error: 6.5±1.8; P =0.0004) and male sex (109.2±18.4; P <0.0001), and there was a trend with TAVs (41.5±23.0; P =0.07). Women presented a higher collagen content than men (77.8±10.8 versus 69.9±12.9%; P <0.001) in the entire cohort. In women, younger patients with BAV had denser connective tissue than TAV and older patients with BAV (both P ≤0.05), while no difference was observed between men. Conclusions In calcific aortic valve disease, women had less calcification and more fibrotic remodeling than men, regardless of the phenotype of the valve or age of the patient. Moreover, younger women with BAVs had less valve calcification. Thus, mineralization/fibrosis of the aortic valve is likely to have sex/age‐specific mechanisms and be influenced by the valve morphology.

Objective The aim of this study was to assess the impact of sex on the management and outcome of patients according to aortic stenosis (AS) severity. Introduction Sex differences in the management and outcome of AS are poorly understood. Methods Doppler echocardiography data of patients with at least mild-to-moderate AS [aortic valve area (AVA) ≤1.5 cm2 and peak jet velocity (VPeak) ≥2.5 m/s or mean gradient (MG) ≥25 mmHg] were prospectively collected between 2005 and 2015 and retrospectively analysed. Patients with reduced left ventricular ejection fraction (&lt;50%), or mitral or aortic regurgitation &gt;mild were excluded. Results Among 3632 patients, 42% were women. The mean indexed AVA (0.48 ± 0.17 cm2/m2), VPeak (3.74 ± 0.88 m/s), and MG (35.1 ± 18.2 mmHg) did not differ between sexes (all P ≥ 0.18). Women were older (72.9 ± 13.0 vs. 70.1 ± 11.8 years) and had more hypertension (75% vs. 70%; P = 0.0005) and less coronary artery disease (38% vs. 55%, P &lt; 0.0001) compared to men. After inverse-propensity weighting (IPW), female sex was associated with higher mortality (IPW-HR: 1.91 [1.14–3.22]; P = 0.01) and less referral to valve intervention (competitive model IPW-HR: 0.88 [0.82–0.96]; P = 0.007) in the whole cohort. This excess mortality in women was blunted in concordant non-severe AS initially treated conservatively (IPW-HR = 1.03 [0.63–1.68]; P = 0.88) or in concordant severe AS initially treated by valve intervention (IPW-HR = 1.25 [0.71–2.21]; P = 0.43). Interestingly, the excess mortality in women was observed in discordant low-gradient AS patients (IPW-HR = 2.17 [1.19–3.95]; P = 0.01) where women were less referred to valve intervention (IPW-Sub-HR: 0.83 [0.73–0.95]; P = 0.009). Conclusion In this large series of patients, despite similar baseline hemodynamic AS severity, women were less referred to AVR and had higher mortality. This seemed mostly to occur in the patient subset with discordant markers of AS severity (i.e. low-gradient AS) where women were less referred to AVR.

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