Abstract / Summary
Background/Objectives: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous multisystem syndrome in which conventional cardiac measures may not fully capture systemic vulnerability. The Endothelial Activation and Stress Index (EASIX) is prognostic in other cardiovascular populations, but evidence in HFpEF remains limited. We evaluated the association of EASIX with long-term mortality and compared its prognostic value with the Prognostic Nutritional Index (PNI) and Controlling Nutritional Status (CONUT) score. Methods: This retrospective single-center study included 79 adults hospitalized with HFpEF between 2019 and 2025. EASIX, PNI, and CONUT were calculated from admission laboratory values. The endpoint was all-cause mortality. EASIX was modeled using restricted cubic splines. Incremental value beyond age, serum sodium, and B-type natriuretic peptide was assessed using likelihood-ratio tests. Harrell’s C-index was internally validated using 1000 bootstrap resamples; conventional and time-dependent receiver operating characteristic analyses were also performed. Results: During a median follow-up of 27.6 months, 45 patients (57.0%) died. EASIX was nonlinearly associated with mortality (overall and nonlinearity p < 0.001) and improved clinical model fit (Δχ2 = 24.36; p < 0.001). PNI improved the clinical model without EASIX (Δχ2 = 8.74; p = 0.003), but its contribution after EASIX was attenuated (Δχ2 = 3.54; p = 0.060); CONUT did not improve model fit (p = 0.859). Optimism-corrected C-indices were 0.728 for clinical + EASIX and 0.732 after adding PNI. Conventional AUCs were 0.753, 0.782, and 0.661 for EASIX, PNI, and CONUT, respectively. Conclusions: In this selected hospitalized HFpEF cohort, EASIX provided incremental prognostic information beyond clinical markers. These exploratory findings require confirmation in larger prospective cohorts with external validation.