Gender-specific predictors of all-cause of death in symptomatic severe aortic stenosis with preserved ejection fraction

Introduction Patients with symptomatic severe aortic stenosis (AS) are indicated for valve intervention, percutaneously or surgically. Left ventricular ejection fraction (LVEF) is widely recognized as one of the leading independent predictors of mortality in AS. However, among symptomatic AS and preserved LVEF – the most prevalent subgroup – the independent predictors of death may differ significantly between genders. Objective To analyse the independent predictors of death in AS with preserved LVEF in women and men. Methods We analysed 525 patients with AS and preserved LVEF (≥50%) with an indication for valve intervention between April 2020 and December 2024. Severe AS was confirmed by echocardiography, with criteria of mean transvalvular gradient ≥40 mmHg, aortic area ≤1.0 cm², or jet velocity ≥4.0 m/s. Clinical characteristics, echocardiographic parameters, and the presence of coronary artery disease (CAD), defined as lesions with luminal reduction >50%, were evaluated. We used Kaplan-Meier test and the Cox proportional hazards model to identify variables independently associated with all-cause death, adjusted for age, diabetes, LVEF, left ventricular mass index (LVMI), and CAD. Results The mean age was 75.4±10.6 years, and 313 (53%) were male. In a follow-up of 2.9±1.5 years, 216 (37%) deaths occurred, 170 (79%) of cardiovascular diseases and 46 (21%) to other causes. Among the patients, 91% had dyspnoea, 39% angina, and 15% syncope. Patients who died were older (77±10 vs. 75±11 years; p=0.026), had a higher prevalence of atrial fibrillation (AF) (20% vs. 14%; p=0.025), and had higher LVMI (121±31 vs. 113±30 g/m²; p=0.004). In men who died, we observed a higher prevalence of diabetes (43% vs. 27%; p=0.010) and lower LVEF (61±5 vs. 63±5; p=0.042). Among women who died, there was a higher prevalence of CAD (41% vs. 24%; p=0.007), AF (8% vs. 4%; p=0.010), and higher LVMI (118±33 vs. 109±30 g/m²; p=0.033). Cumulative mortality was higher in the presence of CAD (p=0.006) (Figure A). In the analysis by gender, this association was observed only in women (p=0.039) (Figure B). In the multivariate analysis, CAD [HR=1.53 (95% CI: 1.14-2.05); p=0.004] and LVMI [HR=1.01 (95% CI: 1.00-1.01); p=0.012] were independent variables associated with death in the total population. Among women, CAD [HR=1.85 (95% CI: 1.19-2.87); p=0.005] was the main predictor of death, while in men, diabetes [HR=1.73 (95% CI: 1.14-2.60); p=0.009]. Conclusion The results showed the need for gender-specific approaches in AS. In women, a more detailed stratification of CAD is essential, while in men, drug control of diabetes should be intensified.