Increased branched-chain amino acid levels are associated with long-term adverse cardiovascular events in patients with STEMI and acute heart failure

Aims: The long-term prognosis of ST-segment elevation myocardial infarction (STEMI) with acute heart failure (AHF) is poor. Identification of metabolic changes could provide understanding of the underlying pathological progress associated with adverse events in patients with STEMI and AHF. Therefore, the study aimed to identify new plasm metabolites associated with long-term adverse cardiovascular events in patients with STEMI and AHF. Materials and methods: Mass spectrometry measurements of 26 amino acids were performed in 138 patients with STEMI and AHF. Endpoints were adverse cardiac events (composite of death and heart failure hospitalization). Survival analysis was performed to determine independent predictors of amino acids. Key findings: During a 3-year follow-up, there were 32 deaths and 21 hospitalizations for heart failure (HF). Multivariable Cox regression analysis showed that branched-chain amino acid (BCAA) levels were independent predictors for adverse cardiovascular events in patients with STEMI and AHF (adjusted HR: 2.67, p < 0.001). The prognostic value of BCAA was better than that of N-terminal pro-B-type natriuretic peptide (area under the curve: 0.77 vs. 0.72) and Kaplan-Meier curves for adverse cardiac events (log-rank: 14.91 vs. 10.05). The combination of BCAAs and NT-proBNP yielded a stronger predictive value (area under the curve: 0.81, log-rank: 27.14). Importantly, addition of BCAAs and NT-pro BNP to the Global Registry of Acute Coronary Events score increased the C-statistic from 0.707 to 0.813, with a net reclassification improvement of 0.714. Significance: Our study shows that increased plasma BCAA levels are associated with long-term adverse cardiovascular events in patients with STEMI and AHF. These findings suggest that dysregulated BCAA metabolism pathways affect clinical outcome after STEMI with AHF.