Sex‐Based Differences in Coronary Physiological Assessment in Patients With Severe Aortic Stenosis

BACKGROUND: Assessing coronary artery disease in severe aortic stenosis (AS) presents unique challenges. Fractional flow reserve (FFR) may yield unreliable results due to altered coronary hemodynamics, leading to discordance with non-hyperemic indices. Women with AS develop distinct myocardial remodeling patterns that may predispose to coronary microvascular dysfunction. We investigated whether sex influences the diagnostic performance and agreement of invasive physiological indices in severe AS. METHODS: This prospective single-center study enrolled 221 patients with severe AS and intermediate coronary stenoses. We performed comprehensive physiological assessment of 416 vessels using FFR, instantaneous wave-free ratio (iFR), and quantitative flow ratio (QFR). Discordance in the detecting significant ischemia was defined using standard thresholds (FFR ≤ 0.80, iFR ≤ 0.89, QFR ≤ 0.80). Multivariable logistic regression identified predictors of discordance. RESULTS: Among 130 women and 91 men with similar angiographic disease severity, women demonstrated systematically weaker correlations between all physiological indices. FFR/iFR concordance was significantly lower in women (90.2% vs. 96.1%; p = 0.021). Discordance was predominantly FFR-negative/iFR-positive (9.8% in women vs. 3.9% in men). Female sex independently predicted FFR/iFR discordance (OR 2.70; 95% CI: 1.03-7.04; p = 0.043), along with smoking status and percent diameter stenosis. No FFR-positive/iFR-negative cases occurred. CONCLUSIONS: Female sex is an independent predictor of FFR/iFR discordance in severe AS, manifesting exclusively as the FFR-negative/iFR-positive pattern. This finding suggests sex-specific differences in coronary microvascular function that may influence revascularization decisions. Recognition of these differences might be important for optimal management of coronary disease in severe AS.