Exercise‐Based Cardiac Rehabilitation Improves Left Ventricular Dysfunction, Mitophagy, and Oxidative Stress Postmyocardial Infarction

Aim: Left ventricular dysfunction, disturbed mitophagy, and persistent oxidative stress after myocardial infarction (MI) are critical drivers of myocardial injury and cardiac remodeling. Exercise‐based cardiac rehabilitation (CR) is a cornerstone of post‐MI treatment and management, yet its mechanistic effects on myocardial repair remain incompletely elucidated. This study aimed to the effect of exercise‐based CR on the left ventricular dysfunction, mitophagy, and oxidative stress post‐MI. Methods: Mendelian randomization analysis elucidated causal relationship between six physical activities and MI. Subsequently, 70 MI patients were randomized to control or exercise‐based CR groups (moderate‐to‐vigorous physical activity intensity, 3 days/week, 10–50 min/day, 12 weeks); left ventricular function, cardiopulmonary function, and SF‐36 quality of life scale were assessed pre‐/postintervention using standardized protocols. Additionally, 21 rats were allocated to Sham, MI, or MI + treadmill running groups (high‐intensity interval exercise training, 5 days/week, 30–50 min/day, 10–25 m/min, 4 weeks); left ventricular function, mitophagy, and oxidative stress were detected postintervention. Results: Genetically predicted moderate‐to‐vigorous intensity physical activity was significantly associated with lower risk of MI (IVW OR = 0.66, 95% CI: 0.54–0.81), with no causal links for other activities. Critically, clinical and animal studies demonstrated that exercise‐based CR improved left ventricular systolic function (LVEF) after MI. Four‐week exercise in MI rats enhanced mitophagy levels (LC3, FUNDC1, PINK1, and Parkin) and attenuated oxidative injury (MDA, GSH, SOD2, and GPX4) post‐MI. Additionally, exercise‐based CR also improved cardiopulmonary function (peak VO 2 /kg, peakVO 2 /pred%, and MET) in patients with MI and ameliorated mitochondrial damage in MI rats. However, GLS, secondary cardiopulmonary parameters (Wmax, HRR1min, peakVO 2 /HR, and peakVO 2 /HRpred%), and SF‐36 (PCS and MCS) showed no significant changes, which may be associated with shorter duration of exercise intervention. Conclusion: Exercise‐based CR significantly ameliorated left ventricular dysfunction, enhanced mitophagy levels, and attenuated oxidative stress post‐MI, establishing its role in critical pathological mechanisms. Future studies should validate long‐term sustainability of exercise‐based CR and explore the interaction mechanism between mitophagy and oxidative stress in cardiac remodeling, providing personalized and precise exercise protocols for people at high risk of exercise.