title: Relationship between galectin-3 levels and mineralocorticoid receptor antagonist use in heart failure: analysis from HF-ACTION.
abstract: BACKGROUND
  Galectin-3 (Gal-3) is a marker of myocardial fibrosis, and elevated levels are associated with adverse outcomes. Mineralocorticoid receptor antagonists (MRAs) modulate cardiac fibrosis in heart failure (HF) patients and have been shown to improve long-term outcomes. We examined whether treatment effects from MRA use differed by Gal-3 levels in ambulatory heart failure patients enrolled in HF-ACTION.
  
  
  RESULTS
  HF-ACTION was a randomized controlled trial of exercise training versus usual care in patients with HF due to LV systolic dysfunction (New York Heart Association functional class II-IV, left ventricular ejection fraction ≤ 0.35, median follow-up 2.5 years). Galectin-3 was assessed at baseline in 895 patients. The end point was all-cause mortality or all-cause hospitalization (ACM+ACH); all-cause mortality (ACM) was a key secondary end point. A differential association of MRA use by increasing Gal-3 concentration was tested with the use of interaction terms in Cox proportional hazards models, adjusted for covariates previously identified in this cohort as well as age, sex, and race. Inverse propensity-weighted (IPW) methods were also used to assess this association. Approximately one-half (n = 401) of the patients were on an MRA. There was no significant interaction for the associations of Gal-3 levels and MRA use for either end point (adjusted interaction P = .76 for ACM+ACH; P = .26 for ACM). There was no evidence of improved outcomes for patients on an MRA compared with those not on MRA for either end point (hazard ratio [HR] 1.02, 95% confidence interval [CI] 0.85-1.23, P = .8; and HR = 1.15, 95% CI [0.82-1.61], P = .4; respectively). IPW analysis was consistent with the results of the adjusted analysis.
  
  
  CONCLUSIONS
  Our study showed no evidence of interaction between Gal-3 and treatment effect of MRA. Whether biomarkers may be used to predict which patients may benefit from an mineralocorticoid receptor antagonist in HF requires further investigation.
authors.affiliation: Division of Cardiology, Duke University Medical Center, Durham, North Carolina; Division of Cardiology, Duke Clinical Research Institute, Durham, North Carolina. Electronic address: mona.fiuzat@duke.edu.
authors.forename: Mona
authors.initials: M
authors.lastname: Fiuzat
authors.affiliation: Division of Cardiology, Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Schulte
authors.affiliation: Division of Cardiology, Duke University Medical Center, Durham, North Carolina; Division of Cardiology, Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Michael
authors.initials: M
authors.lastname: Felker
authors.affiliation: Division of Cardiology, Duke University Medical Center, Durham, North Carolina; Division of Cardiology, Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Tariq
authors.initials: T
authors.lastname: Ahmad
authors.affiliation: Division of Cardiology, Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Megan
authors.initials: M
authors.lastname: Neely
authors.affiliation: Division of Cardiology, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Kirkwood F
authors.initials: KF
authors.lastname: Adams
authors.affiliation: Division of Cardiology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Donahue
authors.affiliation: Division of Cardiology, Duke University Medical Center, Durham, North Carolina.
authors.forename: William E
authors.initials: WE
authors.lastname: Kraus
authors.affiliation: Division of Cardiology, Montefiore Medical Center, Bronx, New York.
authors.forename: Ileana L
authors.initials: IL
authors.lastname: Piña
authors.affiliation: Division of Cardiology, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: David J
authors.initials: DJ
authors.lastname: Whellan
authors.affiliation: Division of Cardiology, Duke University Medical Center, Durham, North Carolina; Division of Cardiology, Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: O'Connor
mesh_terms: D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D005081:Exercise Therapy; D005260:Female; D037502:Galectin 3 / Q000097:blood*; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy / Q000209:etiology / Q000401:mortality / Q000503:physiopathology; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D009026:Mortality; D010045:Outpatients; D011379:Prognosis; D057216:Propensity Score; D016016:Proportional Hazards Models; D012720:Severity of Illness Index; D013318:Stroke Volume; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D015415:Biomarkers; D037502:Galectin 3; D000451:Mineralocorticoid Receptor Antagonists
keywords: Heart failure; biomarkers; galectin-3; mineralocorticoid receptor antagonists