Can Endothelin-1 Help Address the Diagnostic and Prognostic Challenges in Multimorbid Acute Heart Failure Patients?

The management of acute heart failure (AHF) is becoming increasingly complex, especially in patients with multiple comorbidities. Endothelin-1 (ET-1), a vasoconstrictive peptide, is an important mediator of neurohormonal activation, endothelial dysfunction, and cardiac remodeling-key processes involved in the pathogenesis of AHF. The aim of our study was to evaluate the diagnostic and prognostic performance of ET-1 in multimorbid AHF patients, compared to established markers such as amino terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (hs-cTnI). We conducted a single-center prospective study including 76 patients; 54 with AHF and 22 serving as controls. Upon admission, all patients underwent a comprehensive clinical, echocardiographic, and laboratory evaluation, including plasma ET-1 measurement using the enzyme-linked immunosorbent assay (ELISA) method. Receiver operating characteristic (ROC) curve and area under the curve (AUC) analysis were performed to assess the diagnostic and prognostic performance of ET-1 in comparison to NT-proBNP and hs-cTnI. ET-1 levels were considerably higher in AHF patients than in controls (<i>p</i> = 0.02), with an AUC of 0.954, showing comparable diagnostic accuracy with NT-proBNP (AUC = 0.997), alongside strong correlations with signs of systemic congestion, increased hospital stay, and ventricular dysfunction. ET-1 had the strongest predictive accuracy for in-hospital mortality (AUC = 0.781, <i>p</i> = 0.026), outperforming NT-proBNP and hs-cTnI. For 30-day mortality, ET-1 remained a reliable predictor (AUC = 0.784, <i>p</i> = 0.016). However, as the follow-up period extended to one year, its predictive power declined, confirming ET-1's prognostic efficacy only for short-term outcomes. Moreover, ET-1 levels were not influenced by the presence of comorbidities, demonstrating its potential as an independent biomarker. Our findings support that ET-1 is a valuable biomarker for both diagnosis and short-term prognosis in the assessment of multimorbid AHF patients.