title: Soluble CD146 Is a Novel Marker of Systemic Congestion in Heart Failure Patients: An Experimental Mechanistic and Transcardiac Clinical Study.
abstract: BACKGROUND
  Soluble CD146 (sCD146), is an endothelial marker with similar diagnostic power as natriuretic peptides in decompensated heart failure (HF). While natriuretic peptides are released by the failing heart, sCD146 may be released by veins in response to stretch induced by systemic congestion in HF. This study investigated the source, effects of vascular stress on release and prognostic properties of sCD146 in HF.
  
  
  METHODS
  In a peripheral venous stress study, plasma concentrations of sCD146 and N-terminal probrain natriuretic-peptide (NT-proBNP) were measured in 44 HF patients at baseline and after 90 min of unilateral forearm venous congestion. In addition, sCD146 and NT-proBNP were measured in peripheral vein (PV) and coronary sinus (CS) blood samples of 137 HF patients and the transcardiac gradient was calculated. Those patients were followed for major adverse cardiovascular events (MACE) during 2 years.
  
  
  RESULTS
  The induction of venous stress was associated with a pronounced increase in circulating concentrations of sCD146 in the congested arm (+60 μg/L) compared to the control arm (+16 μg/L, P = 0.025), while no difference in NT-proBNP concentrations was seen. In contrast to positive transcardiac gradient for NT-proBNP, median sCD146 concentrations were lower in CS than in PV (396 vs 434, P < 0.001), indicating a predominantly extracardiac source of sCD146. Finally, increased PV concentrations of sCD146 were associated with higher risk of MACE at 2 years.
  
  
  CONCLUSIONS
  Soluble CD146 is released from the peripheral vasculature in response to venous stretch and may reflect systemic congestion in chronic HF patients.
authors.affiliation: INSERM UMR-S 942, Paris, France.|Université Paris Diderot, PRES Sorbonne Paris Cité, France; Department of Anesthesiology and Critical Care Medicine, AP-HP, Saint Louis Lariboisière University Hospitals, Paris, France.|Université Paris Diderot, PRES Sorbonne Paris Cité, France, Department of Cardiology, AP-HP, Saint Louis Lariboisière University Hospitals, Paris, France.|Department of Cardiology, University Heart Center, University Hospital Zurich, Switzerland.
authors.forename: Mattia
authors.initials: M
authors.lastname: Arrigo
authors.affiliation: Dalio Institute of Cardiovascular Imaging, New York-Presbyterian Hospital and Weill Cornell Medical College, New York, NY.|Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Quynh A
authors.initials: QA
authors.lastname: Truong
authors.affiliation: Division of Cardiology, Columbia University Medical Center, New York NY.
authors.forename: Duygu
authors.initials: D
authors.lastname: Onat
authors.affiliation: Dalio Institute of Cardiovascular Imaging, New York-Presbyterian Hospital and Weill Cornell Medical College, New York, NY.|Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Jackie
authors.initials: J
authors.lastname: Szymonifka
authors.affiliation: INSERM UMR-S 942, Paris, France.|Université Paris Diderot, PRES Sorbonne Paris Cité, France; Department of Anesthesiology and Critical Care Medicine, AP-HP, Saint Louis Lariboisière University Hospitals, Paris, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Gayat
authors.affiliation: INSERM UMR-S 942, Paris, France.
authors.forename: Heli
authors.initials: H
authors.lastname: Tolppanen
authors.affiliation: INSERM UMR-S 942, Paris, France.
authors.forename: Malha
authors.initials: M
authors.lastname: Sadoune
authors.affiliation: Division of Cardiology, Columbia University Medical Center, New York NY.
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Demmer
authors.affiliation: Division of Cardiology, Columbia University Medical Center, New York NY.
authors.forename: Ka Y
authors.initials: KY
authors.lastname: Wong
authors.affiliation: Université Paris Diderot, PRES Sorbonne Paris Cité, France, Department of Biochemistry, AP-HP, Lariboisière University Hospitals, Paris, France.
authors.forename: Jean Marie
authors.initials: JM
authors.lastname: Launay
authors.affiliation: INSERM UMR-S 942, Paris, France.
authors.forename: Jane-Lise
authors.initials: JL
authors.lastname: Samuel
authors.affiliation: INSERM UMR-S 942, Paris, France.|Université Paris Diderot, PRES Sorbonne Paris Cité, France, Department of Cardiology, AP-HP, Saint Louis Lariboisière University Hospitals, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Cohen-Solal
authors.affiliation: Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: James L
authors.initials: JL
authors.lastname: Januzzi
authors.affiliation: Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Jagmeet P
authors.initials: JP
authors.lastname: Singh
authors.affiliation: Division of Cardiology, Columbia University Medical Center, New York NY.
authors.forename: Paolo C
authors.initials: PC
authors.lastname: Colombo
authors.affiliation: INSERM UMR-S 942, Paris, France; alexandre.mebazaa@aphp.fr.|Université Paris Diderot, PRES Sorbonne Paris Cité, France; Department of Anesthesiology and Critical Care Medicine, AP-HP, Saint Louis Lariboisière University Hospitals, Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Mebazaa
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D051929:CD146 Antigen / Q000097:blood*; D015331:Cohort Studies; D054326:Coronary Sinus / Q000473:pathology*; D005260:Female; D005542:Forearm / Q000473:pathology*; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012995:Solubility
chemical_list: D015415:Biomarkers; D051929:CD146 Antigen