Impact of Sievers morphology on fibro-calcific remodeling in severe bicuspid aortic valve stenosis: Exploratory findings from sex-stratified analyses

Abstract Aims Aortic stenosis (AS) is the most frequent valvular complication of bicuspid aortic valve (BAV), characterized by progressive fibro-calcific remodeling of the valve leaflets, but whether Sievers morphology (type 0 vs. type 1) influences tissue composition and whether these differences are sex-specific remain unclear. This study aimed to compare calcific and fibrotic remodeling between Sievers type 0 and type 1 BAV in severe AS, and to explore the effect modified by sex. Methods and results This retrospective study included 244 patients with severe BAV stenosis (type 0: n=134, type 1: n=110; 43.4% women) who underwent both echocardiography and cardiac computed tomography. Calcific and fibrotic volumes were quantified and indexed to aortic annulus area to achieve density parameters. In the overall cohort, fibrotic density was significantly higher in type 0 versus type 1 (456.5 vs. 354.3 mm3/cm2, p<0.001), whereas calcific density did not differ between groups. In exploratory sex-stratified analyses, the difference in fibrotic density between type 0 and type 1 was statistically significant in women (463.9 vs. 376.5 mm3/cm2, p=0.011) but not in men. Multivariable regression confirmed these associations in women (β=-2.2, 95% CI: -4.0 – -0.4, p=0.016), while no significant associations were observed in men. However, formal interaction testing between Sievers type and sex was not significant (p=0.140). Conclusion In severe BAV stenosis, Sievers type 0 morphology is associated with higher fibrotic density than type 1, whereas calcific density is comparable, exploratory analyses suggest a potential sex-related difference that warrants further investigation in larger cohorts.