title: Prognostic Value of Baseline and Changes in Circulating Soluble ST2 Levels and the Effects of Nesiritide in Acute Decompensated Heart Failure.
abstract: OBJECTIVE
  The study sought to investigate the association between soluble growth stimulation expressed gene 2 (sST2) level and adverse outcomes in acute heart failure (HF).
  
  
  BACKGROUND
  Several studies have demonstrated the prognostic utility of sST2 levels in HF.
  
  
  METHODS
  sST2 levels were measured in sequential baseline and follow-up (48 to 72 h and 30 days) plasma samples from 858 acute HF subjects enrolled in the ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) trial biomarker substudy and were related to in-hospital and post-discharge clinical outcomes.
  
  
  RESULTS
  Higher sST2 levels were associated with increased death risk at 180 days (baseline hazard ratio [HR]: 2.21; follow-up HR: 2.64; both p < 0.001). These results were not independent of covariates and aminoterminal pro-B-type natriuretic peptide for baseline sST2 (HR: 1.29, p = 0.243), but were borderline significant for follow-up sST2 (HR: 1.61, p = 0.051). Subjects with persistently high (>60 ng/ml) sST2 levels at follow-up had higher 180-day death rates than those with lower follow-up sST2 levels (adjusted HR: 2.91, p = 0.004). Neither baseline nor follow-up sST2 levels were associated with dyspnea improvement. Changes in sST2 from baseline were less in the nesiritide versus placebo group at follow-up, but were similar at 30 days.
  
  
  CONCLUSIONS
  Elevated levels of sST2 were associated with an increased risk of adverse clinical events in acute HF, but prognostic value of baseline sST2 diminished after adjusting for clinical covariates and aminoterminal pro-B-type natriuretic peptide. In those with elevated baseline sST2 levels, persistently elevated sST2 levels at follow-up were associated with increased mortality risk. In addition, nesiritide did not demonstrate an incremental impact on sST2 levels over standard therapy.
authors.affiliation: Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio. Electronic address: tangw@ccf.org.
authors.forename: W H Wilson
authors.initials: WH
authors.lastname: Tang
authors.affiliation: Department of Mathematics, Cleveland State University, Cleveland, Ohio.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Justin L
authors.initials: JL
authors.lastname: Grodin
authors.affiliation: Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Amy P
authors.initials: AP
authors.lastname: Hsu
authors.affiliation: Duke University Medical Center, Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Adrian F
authors.initials: AF
authors.lastname: Hernandez
authors.affiliation: Cardiology Division, Department of Internal Medicine Stony Brook University, Stony Brook, New York.
authors.forename: Javed
authors.initials: J
authors.lastname: Butler
authors.affiliation: Department of Cardiology, University of Brescia, Brescia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Metra
authors.affiliation: Hanzeplein 1, University of Groningen, Groningen, the Netherlands.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
authors.affiliation: Duke University Medical Center, Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: G Michael
authors.initials: GM
authors.lastname: Felker
authors.affiliation: Department of Cardiology, University of Otago, Christchurch, New Zealand.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Troughton
authors.affiliation: Janssen Research & Development, LLC, Raritan, New Jersey.
authors.forename: Roger M
authors.initials: RM
authors.lastname: Mills
authors.affiliation: Department of Cardiology, University of Glasgow, Glasgow, United Kingdom.
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: Duke University Medical Center, Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: O'Connor
authors.affiliation: Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Randall C
authors.initials: RC
authors.lastname: Starling
mesh_terms: D000208:Acute Disease; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D053208:Kaplan-Meier Estimate; D008297:Male; D045283:Natriuretic Agents / Q000627:therapeutic use*; D020097:Natriuretic Peptide, Brain / Q000378:metabolism / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000378:metabolism; D011446:Prospective Studies; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018570:Risk Assessment / Q000379:methods; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D045283:Natriuretic Agents; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
keywords: acute decompensated heart failure; nesiritide; prognosis; soluble ST2