Circulating DPP3 is an early predictor of mortality and organ support in patients with cardiogenic shock: Post-hoc analyses of the ACCOST-HH trial

Dipeptidyl Peptidase 3 (DPP3) is a protease which has recently been shown to have an increased importance in the cardiovascular system. Previous studies demonstrated that elevated circulating DPP3 concentration (cDPP3) is an early predictor of short-term outcome in cardiogenic shock, mostly of ischemic origin. Whether cDPP3 is related to outcome in a more diverse cohort of cardiogenic shock remains unknown. To evaluate the association between cDPP3 levels and 30-days mortality in a mixed cardiogenic shock population. Post-hoc analysis of the ACCOST-HH cohort, a prospective, double-blind, multicentre, randomized, placebo-controlled trial on safety and efficacy of Adrecizumab, an adrenomedullin-modulating antibody, in cardiogenic shock patients, was performed. Values of cDPP3 under 40 ng/mL were considered low concentrations, and above defined as high. In all, 48% of the patient's cohort with high cDPP3 at admission died within 30 days after inclusion, whereas mortality was only 31% in the low cDPP3 group (HR = 1.8 (95% CI = 1.1–3.1), P < 0.05). Mortality in patients with non-ischemic cause of CS was much higher in the high cDPP3 group (HR 2.6, 95% CI = 1.2–5.6). The median number of days without need of cardiovascular support in the low cDPP3 group was 20.5 whereas the median in the high cDPP3 group was 3 days (P = 0.0005). There was a significant increase in need for renal replacement therapy when cDPP3 was high compared to when it was low at admission (56% vs. 22%, P < 0.05). In addition, elevated cDPP3 was associated with a higher need for invasive mechanical ventilation (90% in the high cDPP3 group vs. 74% in the low cDPP3 group, P < 0.05). Furthermore, kinetics of cDPP3 from 0 to 72 hours after admission for CS had a significant impact on outcome: when cDPP3 levels were low at both timepoints (LL-group) or when cDPP3 was initially high but low at 72 h (HL group), 30 day-mortality was significantly decreased when compared to the group with constantly high cDPP3 levels (HH). Sex- and age-adjusted HR for LL vs. HH was 0.2 (95% CI 0.1–0.4), and HR for HL vs. HH was 0.2 (95% CI 0.1–0.3). In cardiogenic shock, cDPP3 is an early predictor of mortality where low concentrations are correlated with improved survival. Moreover, monitoring cDPP3 kinetics is relevant for further assessment of patient care and therapy.