title: Increased mortality with elevated plasma endothelin-1 in acute heart failure: an ASCEND-HF biomarker substudy.
abstract: OBJECTIVE
  Endothelin-1 (ET-1) is an endogenous vasoconstrictor implicated in pulmonary and systemic hypertension, as well as ventricular dysfunction, through effects on vascular smooth muscle, the kidneys, and cardiomyocytes. We aimed to determine the association between serial ET-1 levels and acute heart failure patient outcomes.
  
  
  RESULTS
  We measured plasma ET-1 at baseline, 48-72 h, and 30 days in a cohort of 872 patients hospitalized with acute heart failure from the ASCEND-HF trial (randomized to nesiritide vs. placebo), and its association with 30-day mortality, 180-day mortality, in-hospital death or worsening heart failure, and 30-day mortality or rehospitalization. Median ET-1 was 7.6 [interquartile range (IQR) 5.9-10] pg/mL at baseline, 6.3 (IQR 4.9-8.1) pg/mL at 48-72 h, and 5.9 (IQR 4.7-7.9) pg/mL at 30 days (P < 0.001). Baseline and 48-72 h ET-1 were found to be independently associated with 180-day mortality in a multivariable analysis [hazard ratio (HR) 1.6, 95% confidence interval (CI) 1.3-2.0, P < 0.001 and HR 1.5, 95% CI 1.2-1.9, P = 0.001, respectively, log-transformed]. ET-1 that was measured at 48-72 h was also independently associated with death or worsening heart failure prior to discharge [odds ratio (OR) 1.6, 95% CI 1.03-2.4, P = 0.03]. These independent associations remained significant after including NT-proBNP in the multivariable analysis.
  
  
  CONCLUSIONS
  We observed an independent association between elevated ET-1 and short-term in-hospital clinical outcomes and 180-day mortality in hospitalized patients with acute heart failure ET-1 provided additional prognostic information which was incremental to that yielded by NT-proBNP.
authors.affiliation: Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Antonio L
authors.initials: AL
authors.lastname: Perez
authors.affiliation: Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Justin L
authors.initials: JL
authors.lastname: Grodin
authors.affiliation: Cleveland State University, Department of Mathematics, Cleveland, OH, USA.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Duke University Medical Center, Duke Clinical Research Institute, Durham, NC, USA.
authors.forename: Adrian F
authors.initials: AF
authors.lastname: Hernandez
authors.affiliation: Cardiovascular Division, Stony Brook University, Stony Brook, NY, USA.
authors.forename: Javed
authors.initials: J
authors.lastname: Butler
authors.affiliation: Institute of Cardiology, University of Brescia, Brescia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Metra
authors.affiliation: Duke University Medical Center, Duke Clinical Research Institute, Durham, NC, USA.
authors.forename: G Michael
authors.initials: GM
authors.lastname: Felker
authors.affiliation: University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
authors.affiliation: Department of Cardiology, University of Glasgow, Glasgow, UK.
authors.forename: John J
authors.initials: JJ
authors.lastname: McMurray
authors.affiliation: Department of Cardiology, University of Alberta, Edmonton, Canada.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Armstrong
authors.affiliation: Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Randall C
authors.initials: RC
authors.lastname: Starling
authors.affiliation: Duke University Medical Center, Duke Clinical Research Institute, Durham, NC, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: O'Connor
authors.affiliation: Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: W H Wilson
authors.initials: WH
authors.lastname: Tang
mesh_terms: D000208:Acute Disease; D000368:Aged; D015415:Biomarkers / Q000097:blood; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000401:mortality*; D017052:Hospital Mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic
chemical_list: D015415:Biomarkers; D019332:Endothelin-1; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
keywords: Acute heart failure; Endothelin-1; Prognosis