Incorporating Angina into the H ₂ FPEF Score Improves Diagnostic Performance for HFpEF in Women

Background and Aims The H 2 FPEF score is a widely used prediction tool used during the diagnostic work-up of heart failure with preserved ejection fraction (HFpEF). However, having angina symptoms is not included in the score, despite being common in patients with HFpEF. We hypothesize that incorporating angina in the H 2 FPEF score may improve its performance. Given the known sex differences in HFpEF, sex-specific analyses are warranted. Methods We included 1,266 individuals suspected HFpEF, with 515 from the UHFO-DM cohort and 751 from a combination cohort of STRETCH, TREE and UHFO-COPD. Participants underwent standardized symptom collection, including angina, using WHO questionnaires and expert-panel adjudication of HFpEF. Following evaluation of H 2 FPEF, we assessed the association of angina with HFpEF independent of H 2 FPEF using logistic regression. By adding angina to H 2 FPEF, we developed a modified algorithm and evaluated it by AUC, calibration, reclassification, and decision curve analysis. All analyses were stratified by sex. Results In the UHFO-DM cohort, HFpEF prevalence was 24%. Overall H 2 FPEF 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 1.72–9.11, P=0.001) but not in men (1.90, 0.88–4.10, 0.102). This was also found in the combination cohort (women: 2.13, 1.14–3.97, 0.018; men: 0.85, 0.44–1.66, 0.638). In the UHFO-DM cohort, adding one point for angina in a modified H 2 FPEF 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. Conclusions In women with suspected HFpEF, presence of angina provides diagnostic information independent of H 2 FPEF to uncover HFpEF. A simple sex-specific modification of H 2 FPEF, adding one point for angina in women, may slightly improve discrimination and rule-out performance in women.