Incorporating angina into the H2FPEF score improves diagnostic performance for HFpEF in women

Background and aims The Heavy, Hypertensive, Atrial fibrillation, Pulmonary hypertension, Elder, Filling pressure (H2FPEF) score is a widely used diagnostic tool for heart failure with preserved ejection fraction (HFpEF). Angina symptoms are common in patients with HFpEF but are not included in the score. We aimed to determine whether incorporating angina into the H2FPEF score improves its diagnostic performance sex-specifically, given the well-known sex differences in both HFpEF and angina presentation.Methods We included 515 individuals from the UHFO-DM cohort with suspected HFpEF. Participants underwent standardised symptom collection, including angina using WHO questionnaires, and expert-panel adjudication of HFpEF. Following evaluation of H2FPEF, we assessed the association of angina with HFpEF independent of H2FPEF using logistic regression. By adding angina to H2FPEF, we developed a modified algorithm and evaluated it by the area under the receiver operating characteristic curve (AUC), calibration, reclassification and decision curve analysis. All analyses were stratified by sex. We also included another 751 individuals with suspected HFpEF from a Combination cohort of UHFO-COPD (n=136), STRETCH (n=331) and TREE (n=284) for regression analysis.Results In the UHFO-DM cohort, HFpEF prevalence was 24%. Overall H2FPEF discrimination (AUC) was 0.72, with 0.69 in women and 0.74 in men. Angina was independently associated with HFpEF in women (OR 3.96, 95% CI 1.72 to 9.11, p=0.001) but not in men (1.90, 0.88 to 4.10, 0.102). Adding one point for angina in a modified H2FPEF score in women improved AUC from 0.69 to 0.71 (DeLong p=0.030), increased sensitivity (0.53 to 0.60) and negative predictive value (0.80 to 0.82) and yielded a continuous net reclassification improvement of 0.449, with preserved calibration and higher net clinical benefit on decision curves. No performance gain was observed with the same modification in men. In the Combination cohort, angina was also independently associated with HFpEF only in women (women, 2.13, 1.14 to 3.97, 0.018; men, 0.85, 0.44 to 1.66, 0.638).Conclusions In women with suspected HFpEF, the presence of angina provides diagnostic information independent of H2FPEF to uncover HFpEF. A simple sex-specific modification of H2FPEF, adding one point for angina in women, may slightly improve discrimination and rule-out performance in women.