Abstract
Galectin-3 (Gal-3) has emerged as a potential biomarker for risk stratification in chronic heart failure (HF), given its role in cardiac fibrosis and inflammation. However, its independent prognostic value and clinical utility remain controversial. This systematic review evaluates the association between serum Gal-3 levels and mortality outcomes in chronic HF patients, addressing its consistency, interaction with treatments, and comparative performance against established biomarkers. A systematic search was conducted in PubMed, Scopus, Web of Science, and Embase, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Twelve studies meeting the inclusion criteria (original research assessing Gal-3 and mortality in chronic HF) were selected. Data on study characteristics, prognostic value, and treatment interactions were extracted. Risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool. Elevated Gal-3 levels were consistently associated with increased mortality in univariate analyses. However, its independent prognostic significance diminished in multivariate models adjusting for N-terminal pro B-type natriuretic peptide (NT-proBNP), soluble suppression of tumorigenicity-2 (ST2), or high-sensitivity troponin T (hs-TnT). Gal-3 demonstrated modifiability with therapies like sacubitril/valsartan but showed inconsistent interactions with beta-blockers (β-blockers) and mineralocorticoid receptor antagonists (MRAs). Compared to other biomarkers, Gal-3 underperformed in risk stratification, though it added value in multimarker panels. Methodological heterogeneity, particularly in assay standardization and cut-offs, was a key limitation across studies. While Gal-3 correlates with adverse outcomes in chronic HF, its incremental prognostic value is limited alongside established biomarkers. Standardization of measurements and further research into its therapeutic implications are needed. Gal-3 may currently serve best as part of a multimarker strategy rather than a standalone prognostic tool.