Galectin-3 in patients with heart failure with preserved ejection fraction: results from the Aldo-DHF trial

Eur J Heart Fail. 2015 Feb;17(2):214-23. doi: 10.1002/ejhf.203. Epub 2014 Nov 24.


Aims: 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.

Methods and 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.

Conclusion: 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.

Keywords: Diastolic; Galectin-3; Heart failure; Morbidity; Mortality; Spironolactone.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blood Proteins
  • Diuretics / therapeutic use*
  • Female
  • Galectin 3 / blood*
  • Galectins
  • Heart Failure / blood*
  • Heart Failure / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Spironolactone / therapeutic use*
  • Stroke Volume / physiology*
  • Ventricular Function, Left / drug effects
  • Ventricular Remodeling


  • Blood Proteins
  • Diuretics
  • Galectin 3
  • Galectins
  • LGALS3 protein, human
  • Spironolactone