Altered Carnitine Metabolism in Ischemic and Non-Ischemic Cardiomyopathy: A Comparative Metabolomics Study Using...

Cardiomyopathy is a major cause of heart failure. Ischemic cardiomyopathy (IC) and non-ischemic cardiomyopathy (NIC) have distinct pathophysiological mechanisms. Carnitine plays a critical role in transporting long-chain fatty acids into mitochondria for β-oxidation. Disruptions in carnitine and acylcarnitine homeostasis have been implicated in cardiomyopathy; however, comparative profiling between IC and NIC remains limited.

Serum samples were obtained from 40 IC patients, 40 NIC patients, and 40 age- and sex-matched controls. Free carnitine and 27 acylcarnitine species were quantified using LC-MS/MS. Multivariate analyses (PCA, PLS-DA), univariate statistics (ANOVA with Tukey's HSD), and ROC curve analyses were performed to identify discriminatory metabolites and assess their diagnostic performance.

Compared with controls, IC patients exhibited reduced levels of short- and medium-chain acylcarnitines (C2, C4DC, C6, C8, C10, and C14), whereas NIC patients showed elevations in medium- and long-chain species (C6DC and C16). Heatmaps demonstrated clear group clustering. PCA and PLS-DA revealed partial separation, with C2, C6DC, and C16 emerging as the most influential metabolites (highest VIP scores). ROC analysis indicated modest diagnostic performance, with AUC values ranging from 0.623 to 0.635.

IC and NIC are characterized by distinct alterations in serum carnitine profiles, reflecting differential metabolic remodeling. These findings may clarify disease mechanisms and highlight potential metabolic biomarkers or therapeutic targets. Acylcarnitine profiling could support differential diagnosis and personalized management in cardiomyopathy.