AIMS: Soluble urokinase-type plasminogen activator receptor (suPAR) is a biomarker reflecting the level of immune activation. It has been shown to have prognostic value in acute coronary syndrome and heart failure as well as in critical illness. Considering the complex pathophysiology of cardiogenic shock (CS), we hypothesized suPAR might have prognostic properties in CS as well. The aim of this study was to assess the kinetics and prognostic utility of suPAR in CS. METHODS AND RESULTS: SuPAR levels were determined in serial plasma samples (0-96 h) from 161 CS patients in the prospective, observational, multicentre CardShock study. Kinetics of suPAR, its association with 90-day mortality, and additional value in risk-stratification were investigated. The median suPAR-level at baseline was 4.4 [interquartile range (IQR) 3.2-6.6)] ng/mL. SuPAR levels above median were associated with underlying comorbidities, biomarkers reflecting renal and cardiac dysfunction, and higher 90-day mortality (49% vs. 31%; P = 0.02). Serial measurements showed that survivors had significantly lower suPAR levels at all time points compared with nonsurvivors. For risk stratification, suPAR at 12 h (suPAR12h) with a cut-off of 4.4 ng/mL was strongly associated with mortality independently of established risk factors in CS: OR 5.6 (95% CI 2.0-15.5); P = 0.001) for death by 90 days. Adding suPAR12h > 4.4 ng/mL to the CardShock risk score improved discrimination identifying high-risk patients originally categorized in the intermediate-risk category. CONCLUSION: SuPAR associates with mortality and improves risk stratification independently of other previously known risk factors in CS patients.

Cardiology Department Hospital de la Santa Creu 1 Sant Pau Universitat Autònoma de Barcelona Biomedical Research Institute IIB Sant Pau CIBER CV Spain

Cardiology University of Helsinki and Heart and Lung Centre Helsinki University Hospital Helsinki Finland

CINTESIS Center for Health Technology and Services Research Faculty of Medicine University of Porto São João University Medical Center Faculty of Medicine University of Porto Porto Portugal

Emergency Medicine University of Helsinki Department of Emergency Medicine and Services Helsinki University Hospital Helsinki Finland

ER and Heart Failure Unit Attikon University Hospital National and Kapodestrian University of Athens Athens Greece

National Institute of Cardiology Warsaw Poland

Research Direction Consorci Sanitari Integral University of Barcelona Barcelona Spain

St Ann university hospital and Medical faculty Masaryk University Brno Czech Republic

Université de Paris Inserm 942 MASCOT Paris France

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