Endothelial Activation and Stress Index (EASIX) Predicts In-Hospital Mortality in Acute Decompensated Heart Failure with Reduced Ejection Fraction

<b>Background:</b> Early risk stratification in acute decompensated heart failure with reduced ejection fraction (ADHF-rEF) remains challenging. The Endothelial Activation and Stress Index (EASIX)-a composite of lactate dehydrogenase, creatinine, and platelet count-reflects endothelial dysfunction, a pathophysiological contributor to early deterioration in ADHF-rEF. This study evaluated the prognostic utility of admission-based EASIX for in-hospital mortality. <b>Methods:</b> In this retrospective single-center cohort, 850 consecutive patients hospitalized with ADHF-rEF between January 2022 and June 2025 were analyzed. EASIX was calculated from first-day laboratory values. Logistic regression, ROC analysis, restricted cubic splines, and Kaplan-Meier survival methods were used to assess the association between EASIX and in-hospital mortality, and to evaluate its incremental value beyond established clinical and laboratory predictors. <b>Results</b>: In-hospital mortality was 12.4%. Higher EASIX values were significantly associated with mortality in both univariable and multivariable models (adjusted OR 1.273; <i>p</i> < 0.001). EASIX demonstrated moderate discriminative performance among evaluated biomarkers (AUC 0.751) and showed a clear dose-response risk gradient, with mortality rising from 1.4% in the lowest tertile to 26.2% in the highest. Incorporating EASIX into clinical and laboratory prediction models yielded substantial continuous net reclassification improvement (0.59 and 0.38, respectively). Survival curves diverged early and remained distinctly separated across EASIX strata. <b>Conclusions:</b> Admission EASIX is an independent predictor of in-hospital mortality in ADHF-rEF and provides complementary prognostic information beyond conventional models. This is the first study to demonstrate the prognostic value of EASIX in the ADHF-rEF setting, supporting its potential utility as an accessible endothelial stress biomarker for early risk stratification.