Metabolic Adaptation during Cardiac Exercise Rehabilitation in Patients after a First Myocardial Infarction

Cardiac rehabilitation (CR) is highly beneficial in postmyocardial infarction (MI) patients; however, its metabolic impact remains underexplored. This study investigated metabolic and lipidomic adaptations to an intensive CR program in 25 nondiabetic male patients (<75 years) following a first uncomplicated ST-elevation MI (STEMI). CR involved 24 ± 3 sessions, with baseline and final clinical assessments, and, in a subgroup of 17 patients, longitudinal dried blood spots (DBS) were collected, and metabolomics/lipidomics analysis was also performed. CR significantly improved clinical outcomes, including the 6 min walk test, B-type natriuretic peptide (BNP), left ventricular ejection fraction (LVEF%), C-reactive protein (CRP), and homocysteine levels. Metabolomic analysis showed sustained metabolic adaptations, notably increased N-acetyl-l-tyrosine (NAT), suggesting a mitohormesis response to exercise-induced mitochondrial stress. The third training session exhibited the highest metabolic adaptation, primarily in energy metabolism pathways like the TCA cycle, indicating enhanced oxidative energy generation and improved exercise performance. The lipidome displayed an acute response to the first training, with upregulation of phosphatidylserines (PS). Predicted increased activity of phosphatidylserine synthase-1 (PSS1), enzymes vital for PS synthesis, underscores PS's protective role in myocardial damage and its contribution to muscle activity. These findings highlight CR's beneficial metabolic adaptations, potentially via mitohormesis, and suggest possible mechanistic targets and candidate biomarkers requiring investigation in future controlled intervention studies.