Metabolomic Biomarkers in Heart Failure: A Systematic Review of Diagnostic and Prognostic Significance

This systematic review evaluates the role of metabolomic biomarkers in the diagnosis, prognosis, and risk stratification of patients with heart failure (HF) across various phenotypes. A comprehensive literature search identified randomized controlled trials, cohort studies, and clinical trials that utilized validated metabolomic platforms, such as liquid chromatography-tandem mass spectrometry (LC-MS), gas chromatography-tandem mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR) spectroscopy. Eligible studies assessed the relationship between metabolite profiles and key clinical outcomes, including NT-proBNP levels, six-minute walk distance (6MWD), hospitalization, and mortality. The included trials consistently identified significant associations between branched-chain amino acids (BCAAs), acylcarnitines, and phenylalanine with markers of HF severity and prognosis. Metabolomic profiling provided insight into altered energy metabolism, amino acid catabolism, and lipid oxidation pathways that underpin HF pathophysiology. Collectively, these findings highlight the potential of metabolomic biomarkers as valuable tools for early diagnosis, disease monitoring, and prognostic assessment in HF. Further large-scale, longitudinal studies are warranted to validate these biomarkers and facilitate their integration into precision cardiology.