The Clinical Value of NT-proBNP, sST2, and Galectin-3 in the Management of Heart Failure: From Diagnosis to Dynamic Monitoring: A Narrative Review

Heart failure management remains a critical clinical challenge. While modern neurohormonal therapies have significantly improved survival, standard clinical assessments often fail to capture the full complexity of underlying structural disease progression. To comprehensively synthesize the established literature regarding the biological and prognostic roles of NT-proBNP, soluble ST2 (sST2), and Galectin-3 (Gal-3) and, subsequently, to propose a hypothesis-generating multimarker framework for HF risk stratification. A narrative review of the literature (2006–2026) was conducted across PubMed, Scopus, and Google Scholar. The synthesis focused on the clinical utility, phenotypic specificities, and methodological limitations of evaluating NT-proBNP, sST2, and Gal-3 concentrations. Evidence from the literature confirms that while NT-proBNP remains the gold standard for acute hemodynamic assessment. sST2 and Gal-3 provide complementary insights into active biomechanical strain and interstitial fibrotic remodeling; however, prospective randomized clinical trials demonstrating that sST2- or Gal-3-guided management improves clinical outcomes remain lacking. Based on these established findings, we propose an investigational four-step multimarker framework spanning from acute diagnosis to dynamic outpatient monitoring. This framework hypothesizes that integrating these pathways can better identify high-risk phenotypes that remain undetected by natriuretic peptides alone. The synergistic application of NT-proBNP, sST2, and Gal-3 offers a deeper pathophysiological evaluation of HF. However, our proposed biomarker-guided framework represents a set of testable research hypotheses. It requires prospective randomized validation before integration into routine clinical protocols for therapeutic titration.