High-throughput untargeted metabolomic profiling of urinary biomarkers in acute myocarditis patients: a cross-sectional study

Acute myocarditis, characterized by inflammatory myocardial injury, significantly risks heart failure and sudden death. Despite its severity, specific biomarkers are lacking. This study applied metabolomic analysis to urine samples from 21 acute myocarditis patients and 21 controls using UPLC-MS/MS, revealing 728 increased and 820 decreased metabolites in patients. The affected pathways were predominantly related to the amino acid metabolism, lipid metabolism, carbohydrate metabolism, nucleotide metabolism, and others. We have validated 19 metabolites with an area under the receiver operating characteristic curve (AUC-ROC) greater than 0.7 and a high level of identification confidence. Potential biomarkers upregulated in acute myocarditis patients included phytosphingosine, N-acetylneuraminic acid, indolelactic acid, L-glutamic acid, 4-pyridoxic acid, N1-methyl-2-pyridone-5-carboxamide, palmitic acid, hydroxyphenyllactic acid, riboflavin, nicotinic acid, choline, N-formylkynurenine, guanine, and hypoxanthine. Conversely, sebacic acid, 4-vinylphenol sulfate, capryloylglycine, 4-ethylphenylsulfate, and azelaic acid were found to be decreased. Collectively, the metabolomic profiling has uncovered distinct metabolic signatures in patients with acute myocarditis. The amino acid metabolism appears to play a pivotal role in the pathogenesis of acute myocarditis, offering potential avenues for diagnostic and therapeutic development.