title: Plasma galectin-3 and heart failure outcomes in MADIT-CRT (multicenter automatic defibrillator implantation trial with cardiac resynchronization therapy).
abstract: BACKGROUND
  Elevated circulating levels of the protein galectin-3, a mediator of fibrogenesis, have previously been associated with adverse outcomes in heart failure (HF) patients and appear to modify response to certain pharmacologic therapies. This study investigated the relationship between galectin-3 level and clinical outcomes in HF patients randomized to implantable cardioverter defibrillator (ICD-only) or cardiac resynchronization therapy (CRT-D).
  
  
  RESULTS
  Plasma galectin-3 concentrations were measured in 654 New York Heart Association functional class I/II patients participating in the MADIT-CRT trial. A heterogeneity of response was detected between pre-implantation galectin-3 and randomization group (CRT-D or ICD-only) on the primary MADIT-CRT trial end point of nonfatal HF event or death (P = .045). Among patients with baseline galectin-3 levels in the top quartile of the distribution, CRT-D was associated with a 65% reduction in risk of the primary end point (hazard ratio [HR] 0.35, 95% confidence interval [CI] 0.19-0.67), whereas among patients with lower baseline galectin-3 values CRT-D was associated with a 25% decrease in risk (HR 0.75, 95% CI. 0.51-1.11). Baseline galectin-3 level also was observed to be an independent predictor of the primary end point (multivariable adjusted HR per log unit increase: 1.55; 95% CI 1.01-2.38; P = .043).
  
  
  CONCLUSIONS
  Elevated galectin-3 was found to be an independent predictor of adverse HF outcome in patients with mildly symptomatic HF. A significant interaction of device randomization group with pre-implantation galectin-3 level was detected, with HF patients with the highest baseline galectin-3 levels deriving a disproportionately larger benefit from CRT-D.
authors.affiliation: Boston Scientific Corporation, St Paul, Minnesota. Electronic address: craig.stolen@bsci.com.
authors.forename: Craig M
authors.initials: CM
authors.lastname: Stolen
authors.affiliation: BG Medicine, Waltham, Massachusetts.
authors.forename: Aram
authors.initials: A
authors.lastname: Adourian
authors.affiliation: Boston Scientific Corporation, St Paul, Minnesota.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Meyer
authors.affiliation: Boston Scientific Corporation, St Paul, Minnesota.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Stein
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Solomon
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D058406:Cardiac Resynchronization Therapy / Q000379:methods*; D017147:Defibrillators, Implantable; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D037502:Galectin 3 / Q000097:blood*; D006333:Heart Failure / Q000097:blood / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D037502:Galectin 3
keywords: Prognosis; biomarkers; cardiac resynchronization therapy; patient selection