What is the clinical evidence from this study?

Study design: Review. Population: Heart Failure with Preserved Ejection Fraction (HFpEF). Intervention: Elevated sST2 and Gal-3 levels vs. Lower biomarker levels. Primary outcome: Prognosis (hospitalization and mortality) and diagnosis.

What does this research mean for the field?

Elevated circulating levels of soluble suppression of tumorigenicity-2 (sST2) and galectin-3 (Gal-3) are associated with myocardial fibrosis, inflammation, and increased risks of hospitalization and mortality in patients with heart failure with preserved ejection fraction. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To evaluate the current literature regarding the diagnostic and prognostic significance of soluble suppression of tumorigenicity-2 (sST2) and galectin-3 (Gal-3) in heart failure with preserved ejection fraction (HFpEF).

October 1, 2026Reviews in Cardiovascular MedicineOpen Access

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

Q: What are the key findings of this study?

Elevated circulating levels of sST2 and Gal-3 are associated with poorer clinical outcomes, including an increased risk of hospitalization and mortality in patients with heart failure with preserved ejection fraction.

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Key result

Elevated sST2 and Gal-3 are linked to increased hospitalization and mortality in HFpEF.

Why the study?

Heart failure with preserved ejection fraction (HFpEF) presents diagnostic and prognostic challenges, and the roles of sST2 and Gal-3 biomarkers in this population require evaluation.

Does measurement of sST2 and Gal-3 improve diagnosis and risk stratification in patients with HFpEF?

Key Points

To evaluate the current literature regarding the diagnostic and prognostic significance of soluble suppression of tumorigenicity-2 (sST2) and galectin-3 (Gal-3) in heart failure with preserved ejection fraction (HFpEF).
Conducted a scoping review by searching PubMed and ScienceDirect, screening 4665 initial records according to PRISMA-ScR guidelines.
Assessed biomarker measurement methodologies, identifying enzyme-linked immunosorbent assay (ELISA) as the primary quantification technique in stable outpatients or acute admissions within 48 hours.
Gal-3 demonstrated diagnostic value across multiple cohorts, with reported AUCs of 0.819 (95% CI, 0.75–0.89; p=0.000) at 9.55 ng/mL, 0.763 (95% CI, 0.696–0.821; p<0.0001) at 15.974 ng/mL, and 0.927 (p<0.001) at 10.1 ng/mL.
sST2 demonstrated diagnostic and prognostic capacity, showing a diagnostic AUC of 0.717 (95% CI, 0.628–0.796; p<0.01) at 0.332 ng/mL and predicting CV death or HF hospitalization with an AUC of 0.677 (95% CI, 0.492–0.862; p=0.042) at 117 ng/mL.
Both biomarkers correlated with myocardial fibrosis and increased risk of hospitalization and death, though clinical implementation remains hindered by non-standardized assays and disparate cutoff thresholds.

Structured PICO

Does measurement of sST2 and Gal-3 improve diagnosis and risk stratification in patients with HFpEF?

Population

A scoping review of 11 studies evaluating the diagnostic and prognostic roles of circulating biomarkers sST2 and Gal-3 in patients with heart failure with preserved ejection fraction.

Exposure

Measurement of circulating biomarkers soluble suppression of tumorigenicity-2 (sST2) and galectin-3 (Gal-3)

Outcome

Diagnostic and prognostic roles (including risk of hospitalization and mortality)

sST2 and Gal-3 hold promise as complementary biomarkers for risk stratification in HFpEF, though methodological variability currently limits their routine clinical use.

Limitations

Variability across studies in study populations
Variability in biomarker thresholds
Variability in methodological approaches and lack of standardized assays
Small sample sizes in some included studies
Selection bias in included studies
Only English-language studies included
Variability across studies in study populations, biomarker thresholds, and methodological approaches
Exclusion of non-English articles
Lack of a prospectively developed or registered review protocol

Implication

May refine HFpEF prognosis; leaves open whether these biomarkers guide therapy or improve outcomes.

Abstract

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.

Discussion

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Cite This Study

Ntalekou et al. (2026) conducted a review in Heart Failure with Preserved Ejection Fraction (HFpEF). Elevated sST2 and Gal-3 levels vs. Lower biomarker levels was evaluated on Prognosis (hospitalization and mortality) and diagnosis. Elevated circulating levels of sST2 and Gal-3 are associated with poorer clinical outcomes, including an increased risk of hospitalization and mortality in patients with heart failure with preserved ejection fraction.

synapsesocial.com/papers/6abda8f14d657f10339f94f7 https://doi.org/10.31083/rcm51830

Topics

HFrEF treatment

Heart failure

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Implication

May refine HFpEF prognosis; leaves open whether these biomarkers guide therapy or improve outcomes.

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

Key Points

Structured PICO

Limitations

Implication

Abstract

Discussion

Cite This Study

Topics

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

Key Points

Structured PICO

Limitations

Implication

Abstract

Discussion

Cite This Study

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