Differential roles of calcification and fibrosis in aortic stenosis: a sex- and morphology-specific CT analysis.

AIMS: Aortic stenosis (AS) is characterized by fibrotic and calcific remodelling of the valve, but their sex- and morphology-specific contributions to disease severity remain incompletely characterized.

METHODS AND

RESULTS

This cross-sectional analysis enrolled 448 AS patients with preserved flow (left ventricular ejection fraction ≥50%, stroke volume index >35 mL/m²) who underwent comprehensive echocardiography and cardiac CT, severity was classified by both peak aortic jet velocity and indexed aortic valve area (AVA), and stratified by sex and valve morphology [bicuspid (BAV) or tricuspid (TAV) aortic valve]. Mean age was 64.6 ± 10.1 years, 48.2% were female, and 54.5% had BAV. Calcification metrics showed consistent, significant correlations with peak aortic jet velocity (e.g. Calcificvolumedensity: R = 0.571, P < 0.001) and indexed AVA (R = -0.466, P < 0.001) across all subgroups. In contrast, fibrotic volume density demonstrated minimal or non-significant correlations with severity indices and lacked a proportional association across severity stages. Pronounced sex- and morphology-specific patterns were observed. Specifically, in severe AS classified by both peak aortic jet velocity and indexed AVA, women with BAV had higher fibrotic volume density than men (P = 0.017 and 0.062), while men exhibited greater calcification (Both P < 0.001). Among TAV patients, men had higher calcific volume density (Both P < 0.001) and similar fibrotic volume density (P = 0.792 and 0.923) than women.

CONCLUSION

Valvular calcification is the tissue component more strongly and consistently associated with disease severity in AS, irrespective of whether assessed by peak aortic jet velocity or indexed AVA. Fibrosis represents a distinct phenotypic feature, particularly prominent in women with BAV.