Key result
NT-proBNP reliably predicts heart failure outcomes, but common clinical confounders limit its diagnostic utility in HFpEF.
Why the study?
Accurately distinguishing HFpEF from HFrEF remains challenging using biomarkers, as NT-proBNP levels are confounded by age, renal function, and obesity in HFpEF.
While NT-proBNP remains the gold standard for prognostic assessment in heart failure, its diagnostic limitations in HFpEF highlight the need for integrating novel proteomic biomarkers for precision phenotyping.
Heart failure (HF) encompasses a spectrum of clinical syndromes with substantial global morbidity and mortality, primarily linked to coronary artery disease. Affecting over 37 million individuals worldwide, its prevalence increases with age. HF is classified into three major categories: heart failure with reduced ejection fraction (HFrEF), heart failure with preserved ejection fraction (HFpEF), and the intermediate phenotype, heart failure with mid-range ejection fraction (HFmrEF). Despite similar symptomatology, differentiating HFpEF from HFrEF remains challenging, particularly through biomarker evaluation. The diagnostic and prognostic roles of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are well established; however, an unmet need persists in accurately distinguishing HFpEF from HFrEF, as NT-proBNP levels are often influenced by age, renal function, and obesity, which confound its interpretation in HFpEF. This review uniquely integrates current evidence delineating the biomarker's pathophysiological underpinnings, clinical thresholds, and predictive capacities across HF phenotypes, while contrasting its limitations and interpretive nuances in real-world practice. For instance, while elevated NT-proBNP levels in HFrEF strongly correlate with ventricular dysfunction severity and guide therapy initiation, their diagnostic specificity in HFpEF is reduced, often necessitating adjunctive imaging or additional biomarkers for confirmation. Advances in proteomics are reshaping biomarker discovery, enabling the identification of novel cardiac stress markers such as soluble ST2 and growth differentiation factor-15 (GDF-15), which complement NT-proBNP by reflecting distinct molecular pathways of myocardial remodeling and inflammation. Although NT-proBNP remains the gold standard for prognostic assessment and risk stratification in HF, its diagnostic performance, particularly in HFpEF, must be interpreted within the broader biomarker landscape. Future directions should emphasize proteomic integration and multimarker strategies to achieve precision-based HF phenotyping and improved therapeutic outcomes.
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Kanyal et al. (2025) conducted a review in Heart Failure (HFpEF and HFrEF). NT-proBNP was evaluated. NT-proBNP is a robust prognostic biomarker across heart failure phenotypes, but its diagnostic utility in HFpEF is limited by confounding factors such as age, obesity, and renal dysfunction.
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