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

Sandra Sanders Van Wijk, Serge Masson, Valentina Milani, Peter Rickenbacher, Marco Gorini, Luigi T. Tavazzi, Daniel Tobler, Hans Rickli, Roberto Latini, Hans Peter Brunner La Roccaenen

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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 perlo Studio della Sopravvivenzanell '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.

Original languageEnglish
Pages (from-to)605-616
Number of pages12
JournalClinical Chemistry
Issue number4
Publication statusPublished - Apr 1 2016


ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical

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