Soluble CD146, a new endothelial biomarker of acutely decompensated heart failure Etienne Gayat a,b,c, ⁎, Anaïs Caillard a,b,c , Saïd Laribi a,b,d , Christian Mueller e , Malha Sadoune b,c , Marie-France Seronde b,f , Alan Maisel g , Jozef Bartunek h , Marc Vanderheyden h , Johan Desutter i , Paul Dendale j , Gregoire Thomas k , Miguel Tavares l , Alain Cohen-Solal b,c,m , Jane-Lise Samuel a,b , Alexandre Mebazaa a,b,c a Department of Anesthesiology and Critical Care Medicine, Saint Louis Lariboisière University Hospital, Assistance Publique — Hôpitaux de Paris, Paris, France b UMR-S 942, INSERM, Paris, France c Université Paris Diderot, Paris, France d Emergency Department, Saint Louis Lariboisière University Hospital, Assistance Publique — Hôpitaux de Paris, Paris, France e University Hospital Basel, Basel, Switzerland f Department of Cardiology EA3920, University Hospital Jean Minjoz, Besancon, France g San Diego VA Medical Center, University of California, San Diego, CA, USA h Cardiovascular Center, OLV Hospital, Moorselbaan 164, 9300 Aalst, Belgium i Department of Cardiology, AZ Maria Middelares Hospital Gent, University Gent, Belgium j Hasselt University, Heart Centre Hasselt, Hasselt, Belgium k SQU4RE, Lokeren, Belgium l Hospital Geral de Santo Antonio, Porto, Portugal m Department of Cardiology, Saint Louis Lariboisière University Hospital, Assistance Publique — Hôpitaux de Paris, France abstract article info Article history: Received 26 March 2015 Received in revised form 25 June 2015 Accepted 7 July 2015 Available online 12 July 2015 Keywords: Heart failure Biomarker Diagnosis Congestion Endothelial Background: The present study involved both human cohorts and animal experiments to explore the perfor- mance of soluble CD146 (sCD146), a marker of endothelial function, as a diagnostic marker of acutely decompen- sated heart failure (ADHF), to determine the influence of patients' characteristics on that performance and to explore the potential application of CD146 in the pathophysiology of ADHF. Methods and results: NT-proBNP and sCD146 were measured in three hundred ninety-one patients admitted to the emergency department for acute dyspnea. ROC curve analysis demonstrated that AUCs for ADHF diagnosis in dyspneic patients were 0.86 (95% CI: 0.82–0.90) for sCD146 and 0.90 (95% CI: 0.86–0.92) for NT-proBNP. Sub- group analyses demonstrated that adding sCD146 to NT-proBNP improved the diagnostic performance for pa- tients lying in the gray zone of NT-proBNP (p = 0.02) and could be especially useful for ruling-out ADHF. An experimental model of ADHF in rats using thoracic aortic constriction suggests that CD146 is expressed in the in- tima of large arteries and associated with both left ventricular function and organ congestion. Conclusions: sCD146, a marker of endothelial function, seems to be as powerful as NT-proBNP is used to detect the cardiac origin of an acute dyspnea. The combination of sCD146 and NT-proBNP may have better performance than NT-proBNP used alone in particular for patients underlying in the “gray” zone and could therefore be an im- proved option for ruling-out ADHF. Both experimental and human data suggest that CD146 is related to systolic left ventricular function and to organ congestion. © 2015 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Acutely decompensated heart failure (ADHF) is a common presenta- tion to the Emergency Department (ED) and is associated with both poor short- and long-term outcomes. Because clinical presentation may not be sufficiently discriminating in an acute setting, biomarkers have been proposed to aid in diagnosis and risk stratification [1,2]. The Natriuretic peptides (NPs), brain natriuretic peptide (BNP) and its inac- tive amino-terminal fragment (NT-proNP) are recommended by many guidelines for this purpose [3,4]. However with both NPs, there exists a gray zone where diagnosis is uncertain. In case of NT-proBNP, levels of the marker are above the cut point of 300 ng/mL for “ruling out” ADHF but below the age-adjusted diagnosis cut points for “ruling in” AHF rec- ommended by the International NT-proBNP Consensus Panel [5]. In a previous study, using a robust protein discovery platform and a sensitive antibody-free assay, we described QS0X-1 (Quiescin Q6) as a new candidate diagnostic marker of ADHF [6]. Using the same approach, a second peptide was identified as of potential interest to discriminate International Journal of Cardiology 199 (2015) 241–247 ⁎ Corresponding author at: Department of Anesthesiology and Critical Care Medicine, UMR-S 942, INSERM, Université Paris Diderot, 2 Rue Ambroise Paré, 75010 Paris, France. E-mail address: etienne.gayat@lrb.aphp.fr (E. Gayat). http://dx.doi.org/10.1016/j.ijcard.2015.07.039 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved. Contents lists available at ScienceDirect International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard