Deniau B, Rehfeld L, Santos K, et al. - Among cardiogenic shock patients (n = 174), the link between circulating dipeptidyl peptidase 3 (DPP3) [cDPP3] levels and mortality was assessed. In a heart failure (HF) model in mice, the influence of high cDPP3 on organ function was also investigated. Increased short-term mortality risk and severe organ dysfunction were observed in relation to high cDPP3 levels. A favourable outcome was reported in correlation with a rapid drop in cDPP3 in cardiogenic shock patients within 24 h of admission. In this study, cDPP3 was acknowledged as a newly identified myocardial depressant factor. Admission levels of cDPP3 were found to be related to mortality in severe HF patients. Furthermore, Procizumab-induced cDPP3 inhibition resulted in improved haemodynamics in a mouse model of HF. Findings are indicative of the potential utility of DPP3 as a novel biomarker and biotarget for severe HF.