Sex differences in hemodynamics and remodeling patterns uncovered by automated Machine-Learning 3D echocardiography in aortic stenosis with preserved ejection fraction

Women with aortic stenosis (AS) are underdiagnosed and undertreated compared to men and face a higher mortality risk despite similar symptoms and fewer comorbidities. Sex-specific differences in left ventricular (LV) remodeling may contribute to this disparity. We investigated whether a fully automated, machine-learning-based three-dimensional echocardiography (3DE) approach, the Dynamic Heart Model (DHM), improves the detection of these differences compared to conventional two-dimensional echocardiography (2DE). This study investigates sex-related differences in cardiac remodeling and hemodynamics in AS patients with a preserved ejection fraction (EF ≥ 50%), comparing results from 2D echocardiography (2DE) and 3D echocardiography (3DE) via the DHM. The study included 101 consecutive patients with AS (42% women) who were assessed with 2DE and DHM. Parameters such as LV volumes, mass (LVM), stroke volume (SV), and aortic valve area (AVA) were measured and indexed to body surface area (BSA). Sex-specific differences were analyzed, with a focus on identifying significant remodeling patterns. Women exhibited smaller LV end-diastolic volume (EDV) and end-systolic volume (ESV) by DHM compared to men (115 mL vs. 155 mL, p < 0.001; 51 mL vs. 66 mL, p < 0.001). Indexed EDV (EDVi) and ESV (ESVi) were also significantly lower in women (69 mL/m² vs. 84 mL/m², p < 0.001; 30 mL/m² vs. 34 mL/m², p = 0.002). LVM and indexed LV mass (LVMi) were significantly lower in women when measured by DHM (131 g vs. 163 g, p < 0.001; 75 g/m² vs. 89 g/m², p = 0.005), whereas 2DE did not reveal statistically significant differences. Women exhibited a more concentric LV geometry, as reflected by higher relative wall thickness than men (0.42 vs. 0.36; p = 0.04). Despite similar hemodynamic parameters, women had significantly smaller DHM-derived AVA (0.90 cm² vs. 1.20 cm², p < 0.001), correlating with reduced SV (64 mL vs. 90 mL, p < 0.001). This study highlights that significant sex-related differences in LV remodeling and AS severity are better captured by DHM than 2DE, emphasizing the importance of sex-specific considerations and accurate measurements in evaluating and managing AS.