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Galectin-3 in patients with heart failure with preserved ejection fraction: results from the Aldo-DHF trial
Frank Edelmann1, Volker Holzendorf, Rolf Wachter
1Department of Cardiology and Pneumology, Heart Center, University of Göttingen, Göttingen, Germany; German Center for Cardiovascular Research (DZHK), University of Göttingen, Göttingen, Germany.
Insights
In heart failure with preserved ejection fraction (HFpEF), higher galectin-3 levels correlate with poorer functional capacity and increased risk of death or hospitalization. Spironolactone did not affect galectin-3 levels in this patient group.
Area of Science:
- Cardiology
- Biomarker Research
- Heart Failure Studies
Background:
- Galectin-3 is implicated in myocardial fibrosis and aldosterone-induced inflammation.
- Its role and response to spironolactone in heart failure with preserved ejection fraction (HFpEF) remain underexplored.
Purpose of the Study:
- To investigate the association between galectin-3 levels and HFpEF patient characteristics.
- To evaluate the interaction between spironolactone treatment and galectin-3 levels.
- To assess the prognostic value of galectin-3 for clinical outcomes in HFpEF.
Main Methods:
- The Aldo-DHF trial randomized NYHA class II-III HFpEF patients to spironolactone or placebo for 12 months.
- Galectin-3 levels were measured at baseline, 6, and 12 months.
- Associations between galectin-3, patient characteristics, and clinical outcomes (all-cause death/hospitalization) were analyzed.
Main Results:
- Baseline galectin-3 inversely correlated with peak VO2, 6-minute walk distance, and SF-36 physical functioning, and directly with NYHA class.
- Increasing galectin-3 levels at 6 or 12 months predicted all-cause death or hospitalization, independent of treatment and NT-proBNP.
- Spironolactone treatment did not significantly alter galectin-3 levels.
Conclusions:
- Galectin-3 is modestly elevated in stable HFpEF and linked to reduced functional capacity and quality of life.
- Elevated and increasing galectin-3 levels are associated with adverse clinical outcomes in HFpEF.
- Galectin-3 may serve as an independent prognostic biomarker in HFpEF, irrespective of spironolactone treatment.
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.
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