Circulating Biomarkers Evolve as Essential Pillars for Heart Failure Diagnosis and Prognosis

Heart failure (HF), particularly heart failure with preserved ejection fraction (HFpEF), remains a leading cause of morbidity and mortality worldwide, characterized by complex pathophysiology and heterogeneous clinical trajectories. Current diagnostic and prognostic tools often fall short in providing a comprehensive, individualized risk assessment. Circulating biomarkers offer a minimally invasive approach to reflect ongoing myocardial stress, injury, and remodeling, addressing critical gaps in understanding disease progression and optimizing therapeutic strategies beyond traditional clinical parameters.

This review synthesized the current landscape of circulating biomarkers in heart failure, evaluating their role from ancillary diagnostic tools to indispensable instruments for diagnosis, prognostication, and therapeutic guidance. The authors systematically explored established markers like natriuretic peptides and troponins, alongside emerging biomarkers reflecting novel pathways such as fibrosis, inflammation, oxidative stress, and non-coding RNAs. The review also discussed the potential of multimarker strategies and the integration of high-throughput omics platforms with artificial intelligence (AI) for precision medicine in HF.

The review identified B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) as the cornerstones of biomarker-guided HF management, despite their interpretation being influenced by factors like age, renal function, obesity, and atrial fibrillation. Cardiac troponins provide robust prognostic information by reflecting ongoing myocardial injury, while high-sensitivity C-reactive protein (hsCRP) captures systemic inflammation. > Novel biomarkers like Galectin-3 (Gal-3) and soluble suppression of tumorigenicity-2 (sST2) are established mediators of fibrosis and remodeling, offering incremental prognostic value beyond natriuretic peptides. Growth differentiation factor-15 (GDF-15), myeloperoxidase (MPO), and mid-regional pro-adrenomedullin (MR-proADM) integrate systemic stress, congestion, and oxidative injury into risk assessment. Furthermore, non-coding RNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), have emerged as pathophysiologically grounded biomarkers with diagnostic, prognostic, and potential therapeutic implications. The review concluded that multimarker strategies combining complementary pathways provide a multidimensional perspective on HF progression and therapeutic response.