Endothelial Activation and Stress Index (EASIX) Predicts In-Hospital Mortality in Acute Decompensated Heart Failure with Reduced Ejection Fraction
B Ozlek, V O Tanik, A Tas, S Barutcu, B Cuvalcioglu, C Tunca, K Akbuga, Y B Sahin, M AkdoganAbstract
Background
Early risk stratification in acute decompensated heart failure with reduced ejection fraction (ADHF-rEF) remains challenging despite advances in guideline-directed therapy. Endothelial dysfunction plays a central role in acute hemodynamic deterioration and multiorgan injury. The Endothelial Activation and Stress Index (EASIX), derived from routine laboratory parameters, reflects systemic endothelial stress and may provide incremental prognostic information in this high-risk population.
Purpose
To evaluate the prognostic value of admission Endothelial Activation and Stress Index (EASIX) for predicting in-hospital mortality in patients hospitalized with ADHF-rEF.
Methods
This retrospective single-center cohort study included 850 consecutive patients hospitalized with ADHF-rEF between January 2022 and June 2025. EASIX was calculated at admission using lactate dehydrogenase, serum creatinine, and platelet count. The primary endpoint was in-hospital all-cause mortality. Prognostic performance was assessed using logistic regression, receiver operating characteristic (ROC) analysis, restricted cubic splines, net reclassification improvement (NRI), and Kaplan–Meier survival analysis. Multivariable models were adjusted for established clinical and laboratory risk factors.
Results
Overall in-hospital mortality was 12.4%. Patients with higher EASIX values had significantly increased mortality risk. In multivariable logistic regression analysis, EASIX remained independently associated with in-hospital mortality (adjusted OR 1.27, 95% CI 1.12–1.44, p<0.001). EASIX demonstrated moderate discriminative ability (AUC 0.75) and a clear dose–response relationship, with mortality rising from 1.4% in the lowest tertile to 26.2% in the highest tertile. Incorporation of EASIX into clinical and laboratory prediction models resulted in substantial improvement in risk classification (continuous NRI 0.59 and 0.38, respectively). Kaplan–Meier analysis showed early and sustained separation of survival curves in patients with elevated EASIX (HR 4.41, 95% CI 2.91–6.69, log-rank p<0.001).
Conclusion
Admission Endothelial Activation and Stress Index is a simple, inexpensive, and readily available biomarker that independently predicts in-hospital mortality in patients with ADHF-rEF. Integration of EASIX into routine clinical assessment may enhance early risk stratification and support timely identification of high-risk patients in acute heart failure settings.Restricted cubic spline analysisFor image description, please refer to the figure legend and surrounding text.Kaplan MeierFor image description, please refer to the figure legend and surrounding text.