The Role of Soluble Suppression of Tumorigenicity-2 and Galectin-3 in Heart Failure With Preserved Ejection Fraction: A Scoping Review of the Literature

Heart failure with preserved ejection fraction (HFpEF) represents a heterogeneous clinical syndrome characterized by complex pathophysiological mechanisms and substantial diagnostic and prognostic challenges. Recently, circulating biomarkers have emerged as potential tools for improving risk stratification and disease characterization in this population. Among these biomarkers, soluble suppression of tumorigenicity-2 (sST2) and galectin-3 (Gal-3) have gained particular attention due to their association with myocardial fibrosis, inflammation, and adverse cardiac remodeling. This scoping review aimed to evaluate the current evidence on the diagnostic and prognostic roles of sST2 and Gal-3 in patients with HFpEF. A literature search was conducted in PubMed and ScienceDirect to identify studies investigating the clinical significance of these biomarkers in HFpEF. Titles and abstracts were screened, and eligible studies were assessed through full-text review according to predefined inclusion criteria. Ultimately, 11 studies were included in the qualitative synthesis. Evidence from the available literature suggests that both sST2 and Gal-3 are associated with markers of myocardial fibrosis, inflammation, and disease severity in HFpEF. Elevated circulating levels of these biomarkers have been linked to poorer clinical outcomes, including an increased risk of hospitalization and mortality. However, variability across studies in study populations, biomarker thresholds, and methodological approaches limits the direct translation of these findings into routine clinical practice. Overall, sST2 and Gal-3 appear to hold promise as complementary biomarkers for risk stratification in HFpEF. Nonetheless, further large-scale prospective studies are needed to clarify the clinical utility of these biomarkers and determine the subsequent integration into multimarker strategies for the management of patients with HFpEF.