Abnormalities in Skeletal Muscle Mitochondrial Function Linked to Exercise Intolerance in HFpEF Patients: JAMA

USA: A ground-breaking study published JAMA: Cardiology has shed light on the pathophysiology of exercise intolerance in patients with heart failure with preserved ejection fraction (HFpEF), uncovering the crucial role of abnormal skeletal muscle metabolism.

The research, conducted by a team of experts, aimed to evaluate the associations between skeletal muscle mitochondrial function and exercise performance in HFpEF patients.

The study was a cross-sectional analysis, that involved the examination of muscle fiber bundles obtained from fresh vastus lateralis biopsies. High-resolution respirometry was employed to assess mitochondrial oxidative phosphorylation, including the capacity and contributions of complex I–linked and complex II–linked respiration.

72 patients with stable chronic HFpEF, aged 60 and above, were compared with age-matched healthy control participants who were not enrolled in regular exercise or diet programs.

The study revealed the following clinical takeaways:

1. Skeletal muscle mitochondrial function measures were significantly lower in patients with heart failure with preserved ejection fraction (HFpEF) compared to healthy controls (HC), even after adjusting for age, sex, and body mass index.

2. Maximal capacity of skeletal muscle mitochondria was strongly and significantly correlated with peak exercise oxygen consumption, 6-minute walk distance, and the Short Physical Performance Battery score.

3. The p-values were all less than 0.001, indicating a highly significant association between maximal capacity and exercise performance measures.

4. The correlation coefficients (R) were 0.69 for peak exercise oxygen consumption, 0.70 for a 6-minute walk distance, and 0.46 for the Short Physical Performance Battery score.

The abnormalities in skeletal muscle mitochondrial function can be regarded as promising therapeutic targets. It provides valuable insights into the mechanisms underlying metabolic dysfunction in HFpEF patients, a phenomenon that has remained incompletely understood until now.

“By identifying skeletal muscle mitochondrial abnormalities as key contributors to exercise intolerance, this research opens new avenues for potential interventions and treatment strategies for HFpEF patients. Further exploration in this field may lead to improved quality of life and enhanced management of this debilitating condition,” said Dr. Lina Scandalis lead author of the study.

Reference:

Scandalis L, Kitzman DW, Nicklas BJ, et al. Skeletal Muscle Mitochondrial Respiration and Exercise Intolerance in Patients With Heart Failure With Preserved Ejection Fraction. JAMA Cardiol. Published online May 10, 2023. doi:10.1001/jamacardio.2023.0957