Interaction of Galectin-3 Concentrations with the Treatment Effects of β-Blockers and RAS Blockade in Patients with Systolic Heart Failure: A Derivation-Validation Study from TIME-CHF and GISSI-HF

Clin Chem. 2016 Apr;62(4):605-16. doi: 10.1373/clinchem.2015.246850. Epub 2016 Mar 2.


Background: Galectin-3 predicts prognosis in heart failure (HF) and may help to select HF patients in need of intensified therapy.

Methods: This retrospective post hoc analysis included 219 patients from the Trial of Intensified versus Standard Medical Therapy in Elderly Patients with Congestive Heart Failure (TIME-HF) and 631 patients from Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca (GISSI-HF) with HF who had reduced ejection fraction and available galectin-3 plasma concentrations. The interaction between galectin-3, β-blockers, renin-angiotensin system (RAS) blockade, and spironolactone on outcome was evaluated in TIME-CHF and validated in GISSI-HF. End points were all-cause mortality and the composite of mortality with HF hospitalization or any hospitalization.

Results: High galectin-3 concentrations were associated with adverse outcome in both cohorts and remained significantly associated with death after multivariate adjustment [hazard ratio 2.42 (95% CI 1.17-5.01), P = 0.02, in TIME-CHF; 1.47 (1.02-2.10), P = 0.04, in GISSI-HF). In TIME-CHF, patients with low galectin-3 plasma concentrations had a better prognosis when β-blockers were up-titrated, whereas patients with high galectin-3 plasma concentrations did not (interaction P < 0.05 for mortality and death with or without hospitalization). Opposite trends were seen for RAS blockade but were not statistically significant. Patients with high galectin-3 plasma concentrations had neutral prognosis when receiving spironolactone, whereas patients with low galectin-3 plasma concentrations had worse prognosis when receiving spironolactone (interaction P < 0.10 for death with or without hospitalization). In the GISSI-HF validation cohort, these interactions were confirmed for β-blockers (P < 0.05 for all end points) and consistent for RAS blockade (P < 0.10 for death with or without hospitalization), but inconsistent for spironolactone.

Conclusions: Galectin-3 is a mediocre prognostic marker, and galectin-3 concentrations interact with the treatment effect of β-blockers and possibly RAS blockade in patients with systolic HF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / administration & dosage
  • Adrenergic beta-Antagonists / therapeutic use*
  • Aged
  • Blood Proteins
  • Cause of Death / trends*
  • Female
  • Galectin 3 / blood*
  • Galectins
  • Heart Failure, Systolic / blood
  • Heart Failure, Systolic / drug therapy*
  • Heart Failure, Systolic / mortality*
  • Hospitalization / statistics & numerical data
  • Humans
  • Male
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Randomized Controlled Trials as Topic
  • Renin-Angiotensin System / drug effects*
  • Retrospective Studies
  • Spironolactone / administration & dosage
  • Spironolactone / therapeutic use


  • Adrenergic beta-Antagonists
  • Blood Proteins
  • Galectin 3
  • Galectins
  • LGALS3 protein, human
  • Spironolactone