title: 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.
abstract: 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.
authors.affiliation: Maastricht University Medical Center, Maastricht, the Netherlands; sandra.van.wijk@mumc.nl.
authors.forename: Sandra
authors.initials: S
authors.lastname: Sanders-van Wijk
authors.affiliation: Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy;
authors.forename: Serge
authors.initials: S
authors.lastname: Masson
authors.affiliation: Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy;
authors.forename: Valentina
authors.initials: V
authors.lastname: Milani
authors.affiliation: Cardiology, University Hospital Bruderholz, Bruderholz, Switzerland;
authors.forename: Peter
authors.initials: P
authors.lastname: Rickenbacher
authors.affiliation: ANMCO Research Center, Florence, Italy;
authors.forename: Marco
authors.initials: M
authors.lastname: Gorini
authors.affiliation: GVM Care and Research, Maria Cecilia Hospital, Cotignola, Italy;
authors.forename: Luigi T
authors.initials: LT
authors.lastname: Tavazzi
authors.affiliation: Cardiology, University Hospital Basel, Basel, Switzerland;
authors.forename: Daniel
authors.initials: D
authors.lastname: Tobler
authors.affiliation: Cardiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors.forename: Hans
authors.initials: H
authors.lastname: Rickli
authors.affiliation: Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy;
authors.forename: Roberto
authors.initials: R
authors.lastname: Latini
authors.affiliation: Maastricht University Medical Center, Maastricht, the Netherlands; Cardiology, University Hospital Basel, Basel, Switzerland;
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Brunner-La Roccaenen
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000368:Aged; D001798:Blood Proteins; D002423:Cause of Death / Q000639:trends*; D005260:Female; D037502:Galectin 3 / Q000097:blood*; D037161:Galectins; D054143:Heart Failure, Systolic / Q000097:blood / Q000188:drug therapy* / Q000401:mortality*; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012189:Retrospective Studies; D013148:Spironolactone / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000319:Adrenergic beta-Antagonists; D001798:Blood Proteins; D037502:Galectin 3; D037161:Galectins; C428445:LGALS3 protein, human; D013148:Spironolactone