Elevated Plasma Bioactive Adrenomedullin and Mortality in Cardiogenic Shock: Results from the OptimaCC Trial.

Koji Takagi,Etienne Gayat,Gad Cotter,Oliver Hartmann,Ayu Asakage,Benjamin Deniau,Janin Schulte,Antoine Kimmoun,Òscar Miró,Beth A Davison,Kévin Duarte,Bruno Levy,Alexandre Mebazaa,Alice Blet

doi:10.3390/jcm10194512

Abstract

Aims: Bioactive adrenomedullin (bio-ADM) was recently shown to be a prognostic marker in patients with acute circulatory failure. We investigate the association of bio-ADM with organ injury, functional impairment, and survival in cardiogenic shock (CS). Methods: OptimaCC was a multicenter and randomized trial in 57 patients with CS. In this post-hoc analysis, the primary endpoint was to assess the association between bio-ADM and 30-day all-cause mortality. Secondary endpoints included adverse events and parameters of organ injury or functional impairment. Results: Bio-ADM values were higher in 30-day non-survivors than 30-day survivors at inclusion (median (interquartile range) 67.0 (54.6–142.9) pg/mL vs. 38.7 (23.8–63.6) pg/mL, p = 0.010), at 24 h (p = 0.012), and up to 48 h (p = 0.027). Using a bio-ADM cutoff of 53.8 pg/mL, patients with increased bio-ADM had a HR of 3.90 (95% confidence interval 1.43–10.68, p = 0.008) for 30-day all-cause mortality, and similar results were observed even after adjustment for severity scores. Patients with the occurrence of refractory CS had higher bio-ADM value at inclusion (90.7 (59.9–147.7) pg/mL vs. 40.7 (23.0–64.7) pg/mL p = 0.005). Bio-ADM values at inclusion were correlated with pulmonary vascular resistance index, estimated glomerular filtration rate, and N-terminal pro-B-type natriuretic peptide (r = 0.49, r = –0.47, and r = 0.64, respectively; p < 0.001). Conclusions: In CS patients, the values of bio-ADM are associated with some parameters of organ injury and functional impairment and are prognostic for the occurrence of refractory CS and 30-day mortality.

Highlights

The European Society of Cardiology and the American Heart Association defined cardiogenic shock (CS) as a state of critical end-organ hypoperfusion caused by primary cardiac dysfunction [1,2,3]
There was no influence of the vasopressor infused, epinephrine, or norepinephrine, on Bioactive adrenomedullin (bio-ADM) values at any time point (Figure S1)
The present study showed that high bio-ADM at ICU admission in patients with CS complicating acute myocardial infarction (AMI) was associated with increased mortality at 30 days

Summary

Introduction

The European Society of Cardiology and the American Heart Association defined cardiogenic shock (CS) as a state of critical end-organ hypoperfusion caused by primary cardiac dysfunction [1,2,3]. A novel immunoassay has been developed, which directly measures bioactive ADM (bioADM) [21]. The latter has been shown to be a prognostic marker in patients with acute circulatory failure (e.g., septic shock, CS) [17,22]. The prognostic implication of bio-ADM and its relationship with the parameters of organ injury or functional impairment in patients with CS remain poorly characterized. The purpose of this study was to investigate the association of bio-ADM with organ injury, functional impairment, and survival to contribute to risk stratification and therapeutic decision-making in patients with CS

Objectives

Methods

Results

Conclusion