Article Impact Level: HIGH Data Quality: STRONG Summary of JAMA Cardiology. https://doi.org/10.1001/jamacardio.2023.0957 Dr. Lina Scandalis et al.
Points
- Patients with heart failure with preserved ejection fraction (HFpEF) exhibited markedly reduced skeletal muscle mitochondrial function compared to healthy controls.
- The impaired mitochondrial function in HFpEF patients was strongly correlated with exercise performance measures, including peak exercise oxygen consumption, 6-minute walk distance, and Short Physical Performance Battery score.
- Maximal capacity of mitochondrial function showed significant positive associations with exercise performance measures in HFpEF patients.
- Skeletal muscle mitochondrial dysfunction appears to play a role in the exercise intolerance observed in HFpEF patients.
- Targeting mitochondrial dysfunction in skeletal muscle could be a promising therapeutic strategy for improving exercise capacity in individuals with HFpEF.
Summary
This cross-sectional study investigated the association between skeletal muscle mitochondrial function and exercise performance in patients with heart failure with preserved ejection fraction (HFpEF). The study included 72 participants, of whom 50 were women, with a mean age of 69.6 years. Muscle fiber bundles obtained from vastus lateralis biopsies were analyzed using high-resolution respirometry to assess mitochondrial oxidative phosphorylation. The results demonstrated markedly lower measures of skeletal muscle mitochondrial function in HFpEF patients compared to age-matched healthy controls, even after adjusting for age, sex, and body mass index.
The findings revealed a strong correlation between the maximal capacity of mitochondrial function and exercise performance measures. Maximal capacity showed significant positive associations with peak exercise oxygen consumption (R = 0.69; P < 0.001), 6-minute walk distance (R = 0.70; P < 0.001), and Short Physical Performance Battery score (R = 0.46; P < 0.001). These results suggest that the impaired mitochondrial function observed in HFpEF patients is closely related to exercise intolerance.
The study emphasizes the potential therapeutic significance of targeting mitochondrial dysfunction in skeletal muscle to improve exercise capacity in HFpEF patients. The severely reduced maximal capacity and impaired complex I- and complex II-linked respiration identified in this study serve as promising targets for therapeutic interventions. By elucidating the role of skeletal muscle mitochondrial dysfunction in HFpEF-related exercise intolerance, this research contributes valuable insights that can inform the development of targeted therapeutic strategies to alleviate the burden of HFpEF on patients’ physical functioning and overall well-being.
Link to the article: https://jamanetwork.com/journals/jamacardiology/fullarticle/2804714
References Scandalis, L., Kitzman, D. W., Nicklas, B. J., Lyles, M., Brubaker, P., Nelson, M. B., Gordon, M., Stone, J., Bergstrom, J., Neufer, P. D., Gnaiger, E., & Molina, A. J. A. (2023). Skeletal muscle mitochondrial respiration and exercise intolerance in patients with heart failure with preserved ejection fraction. JAMA Cardiology. https://doi.org/10.1001/jamacardio.2023.0957
