Sex differences in aortic stenosis progression and myocardial response

Abstract

Abstract Background Aortic stenosis (AS) produces an increased afterload and consequently left ventricular (LV) remodeling. While current guidelines recommend the same echo-doppler criteria for diagnosis and grading of AS for men and women, different sex-specific patterns of cardiac remodeling, and eventually damage, have been reported. Whether these different patterns are caused by sex-related AS progression rate or myocardial response is less well known. Aim We aim to compare longitudinal changes in aortic valve and cardiac function between women and men with AS to investigate sex-related differences in AS progression and cardiac remodeling. Methods Patients with mild-to-severe AS and LV ejection fraction (LVEF) ≥ 50 % at least in 2 transthoracic echocardiograms (TTE) were retrospectively identified. Prosthetic and bicuspid valves were excluded. Serial TTEs provided a multiparametric framework to compare AS severity, progression rate and induced cardiac changes between sexes. Results 914 patients were included (median follow-up time of 6.8 years) and 52 % (473) were female. Both sexes had similar baseline aortic peak velocities (APV) (2.9±0.9 m/s), mean pressure gradient (MPG) (27±13 mmHg) and LVEF (60±5 %). Women were older (75±9 vs 73±8 years; p<0.001), had smaller body surface area (BSA) (1.70±0.15 vs 1.88±0.16 m2, p<0.001), proportionally lower stroke volume (SV) (82±19 mL vs 91±22 mL, p<0.001), lower indexed LV mass (iLVM) (118±33 g/m2 vs 125±28 g/m2, p<0.001) and higher indexed left atrial (LA) volume (39±13 vs 49±20 mL/m2, p<0.001). The average annual progression rate of APV and MPG was similar for both groups (2 mmHg/year and 0.14 m s-1 year-1). After multivariate adjustment including time-dependent aortic valve replacement, women had a higher incidence of severe LV hypertrophy as measured by iLVM (HR=1.16, CI=1.08-1.91, p<0.01), moderate-to-severe tricuspid valve regurgitation (HR=2.03, CI=1.01-4.07, p<0.05) and pulmonary hypertension (PHT) (HR=1.49, CI=1.02-2.18, p=0.04) at 5 years. Similar incidence rates were seen for LV dilation, LVEF reduction and mitral valve regurgitation. All-cause mortality rates were similar between groups (p=0.30). Conclusion This study suggests that under similar static and dynamic loading conditions, women will develop severe LV hypertrophy and PHT earlier than men, possibly reflecting sex-specific response differences intrinsic to the myocardium. This suggests that the definition of AS severity may benefit from a shift from a valve-focused to a myocardial-integrative approach taking gender into account.