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Randomized Controlled Trial
. 2015 Feb;17(2):214-23.
doi: 10.1002/ejhf.203. Epub 2014 Nov 24.

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

Frank Edelmann  1 , Volker Holzendorf, Rolf Wachter, Kathleen Nolte, Albrecht G Schmidt, Elisabeth Kraigher-Krainer, André Duvinage, Ines Unkelbach, Hans-Dirk Düngen, Carsten Tschöpe, Christoph Herrmann-Lingen, Martin Halle, Gerd Hasenfuss, Götz Gelbrich, Wendy Gattis Stough, Burkert M Pieske
Affiliations
Free article
Randomized Controlled Trial

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

Frank Edelmann et al. Eur J Heart Fail. 2015 Feb.
Free article

Abstract

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.

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