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Abstract Aims Insulin‐like growth factor binding protein‐4 (IGFBP‐4) fragments have been shown to predict the risk of major adverse cardiovascular events, including segment‐elevation myocardial infarction, in patients with acute coronary syndrome. We evaluated the prognostic value of the carboxy‐terminal fragment of IGFBP‐4 (CT‐IGFBP‐4) for all‐cause mortality in emergency room patients with acute heart failure (AHF). Methods and results CT‐IGFBP‐4, N‐terminal pro brain natriuretic peptide (NT‐proBNP), and C‐reactive protein (CRP) were measured at admission from the lithium‐heparin plasma of 156 patients with AHF. All‐cause mortality was recorded for 1 year. Receiver operator characteristic (ROC) curves, Kaplan–Meier, and Cox proportional hazard ratio analyses were performed to evaluate the prognostic value of the various clinical variables, CT‐IGFBP‐4, NT‐proBNP, CRP, and their combinations. During 1 year of follow‐up, 52 (33.3%) patients died. CT‐IGFBP‐4 only weakly correlated with NT‐proBNP (Pearson correlation coefficient r = 0.16, P = 0.044) and did not correlate with CRP (r = 0.08, P = 0.35), emphasizing the different nature of these biomarkers. The receiver operator characteristic area under the curve (ROC AUC) of CT‐IGFBP‐4 for the prediction of all‐cause mortality (0.727) was significantly higher than that of NT‐proBNP (0.680, P = 0.045) and CRP (0.669, P = 0.016). The combination of CT‐IGFBP‐4, NT‐proBNP, and CRP predicted mortality significantly better (ROC AUC = 0.788) than any of the biomarkers alone (P |