title: Galectin-3 in patients with heart failure with preserved ejection fraction: results from the Aldo-DHF trial.
abstract: OBJECTIVE
  Galectin-3 is a marker of myocardial fibrosis and mediates aldosterone-induced cardiovascular inflammation and fibrosis. Characteristics of galectin-3 and its response to spironolactone have not been evaluated in heart failure with preserved ejection fraction (HFpEF). The aim of this study was to determine the association between galectin-3 levels and patient characteristics in HFpEF; to evaluate the interaction between spironolactone and galectin-3 levels; and to assess the association between galectin-3 and clinical outcomes.
  
  
  RESULTS
  Aldo-DHF investigated spironolactone 25 mg once daily vs. placebo for 12 months in patients with NYHA class II-III, LVEF ≥50%, grade ≥ I diastolic dysfunction, and peakVO2  ≤ 25 mL/kg/min. Galectin-3 levels were obtained at baseline, and at 6 and 12 months. The association between baseline galectin-3, change in galectin-3, and all-cause death or hospitalization was evaluated, and the interaction between galectin-3 and treatment was assessed. Median baseline galectin-3 was 12.1 ng/mL. After multivariable adjustment, baseline galectin-3 inversely correlated with peak VO2 (P = 0.021), 6 min walk distance (P = 0.002), and Short Form 36 (SF-36) physical functioning (P = 0.001), and directly correlated with NYHA class (P = 0.007). Baseline NT-proBNP correlated with E/e' velocity ratio (P ≤ 0.001), left atrial volume index (P < 0.001), and LV mass index (P = 0.009). Increasing galectin-3 at 6 or 12 months was associated with all-cause death or hospitalization independent of treatment arm [hazard ratio (HR) 3.319, 95% confidence interval (CI) 1.214-9.07, P = 0.019] and NT-proBNP (HR 3.127, 95% CI 1.144-8.549, P = 0.026). Spironolactone did not influence galectin-3 levels.
  
  
  CONCLUSIONS
  Galectin-3 levels are modestly elevated in patients with stable HFpEF and relate to functional performance and quality of life. Increasing galectin-3 was associated with worse outcome, independent of treatment or NT-proBNP.
authors.affiliation: Department of Cardiology and Pneumology, Heart Center, University of Göttingen, Göttingen, Germany; German Center for Cardiovascular Research (DZHK), University of Göttingen, Göttingen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Edelmann
authors.forename: Volker
authors.initials: V
authors.lastname: Holzendorf
authors.forename: Rolf
authors.initials: R
authors.lastname: Wachter
authors.forename: Kathleen
authors.initials: K
authors.lastname: Nolte
authors.forename: Albrecht G
authors.initials: AG
authors.lastname: Schmidt
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kraigher-Krainer
authors.forename: André
authors.initials: A
authors.lastname: Duvinage
authors.forename: Ines
authors.initials: I
authors.lastname: Unkelbach
authors.forename: Hans-Dirk
authors.initials: HD
authors.lastname: Düngen
authors.forename: Carsten
authors.initials: C
authors.lastname: Tschöpe
authors.forename: Christoph
authors.initials: C
authors.lastname: Herrmann-Lingen
authors.forename: Martin
authors.initials: M
authors.lastname: Halle
authors.forename: Gerd
authors.initials: G
authors.lastname: Hasenfuss
authors.forename: Götz
authors.initials: G
authors.lastname: Gelbrich
authors.forename: Wendy Gattis
authors.initials: WG
authors.lastname: Stough
authors.forename: Burkert M
authors.initials: BM
authors.lastname: Pieske
mesh_terms: D000368:Aged; D001798:Blood Proteins; D004232:Diuretics / Q000627:therapeutic use*; D005260:Female; D037502:Galectin 3 / Q000097:blood*; D037161:Galectins; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013148:Spironolactone / Q000627:therapeutic use*; D013318:Stroke Volume / Q000502:physiology*; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling
chemical_list: D001798:Blood Proteins; D004232:Diuretics; D037502:Galectin 3; D037161:Galectins; C428445:LGALS3 protein, human; D013148:Spironolactone
keywords: Diastolic; Galectin-3; Heart failure; Morbidity; Mortality; Spironolactone