Cardiogenic shock supported with VA-ECMO: Association between cDPP3 concentrations and outcomes in a post hoc analysis of the ADRECMO cohort.

BACKGROUND: Circulating dipeptidyl peptidase-3 (cDPP3), a protease involved in angiotensin II degradation, has demonstrated prognostic properties, including organ dysfunction and/or mortality in patients with cardiogenic shock (CS) or at risk of developing CS. However, prognostic properties of cDPP3 have not yet been investigated in the most severe CS patients requiring venoarterial extra corporeal membrane oxygenation (VA-ECMO). METHOD: This is a post hoc analysis of the ADRECMO study, a prospective cohort of 50 patients primarily designed to investigate the association between inflammation and adrenoreceptor expression in patients with CS receiving VA-ECMO. cDPP3 measurements were performed before VA-ECMO implantation, 3-5 days later while VA-ECMO was ongoing, and before explantation. Associations between cDPP3 concentrations at the predefined timepoints and level of organ dysfunction and 30-day survival were investigated. RESULTS: Forty-seven patients were analysed. Median cDPP3 was 73 (IQR 46 - 151) ng/mL at VA-ECMO implantation decreasing to 47 (30 - 64) ng/mL at day 3 to 5 and 39 (29 - 50) ng/mL at the day of explantation (p<0.001). Patients with cDPP3 >73 ng/mL at VA-ECMO implantation exhibited, higher lactate concentrations (3.5 [2.5 - 5.9] vs. 1.9 [1.3 - 3] mmol/L, p<0.001), worse eGFR (26 [15 - 40] vs. 75 [48 - 102] mL/min/1.73m2, p<0.001), higher AST levels (1127 [587 - 1970] vs. 195 [50 - 646] IU/L, p<0.001) and greater norepinephrine cumulated dose (682 [326 - 2258] vs. 93 [0 - 349] μg/kg, p=0.001) compared to patients with lower cDPP3 concentrations. After adjustment for CS cause, timing of VA-ECMO implantation, and cardiac arrest before implantation, patients with high cDPP3 before implantation exhibited lower survival compared with patients with low cDPP3 (adjusted HR 4.13 [95% CI 1.55-10.98]). No significant association was observed between cDPP3 concentrations at later timepoints and 30-day survival. CONCLUSION: In a population of CS patients on VA-ECMO, high cDPP3 measured before implantation is associated with greater severity of organ dysfunction and lower 30-day survival.