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

## TL;DR

This study explores how intensive cardiac rehabilitation affects metabolism in patients recovering from a first heart attack, revealing beneficial metabolic changes and potential biomarkers.

## Contribution

The study identifies specific metabolic and lipidomic adaptations during cardiac rehabilitation, including mitohormesis and phosphatidylserine responses.

## Key findings

- Cardiac rehabilitation significantly improved clinical outcomes like 6 min walk test and BNP levels.
- Metabolomic analysis revealed increased N-acetyl-l-tyrosine, suggesting a mitohormesis response to exercise-induced stress.
- Phosphatidylserines increased acutely after the first training session, indicating a protective role in myocardial recovery.

## Abstract

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.