Skeletal Muscle Mitochondrial Respiration and Exercise Intolerance in HFpEF
- In a study of 27 HFpEF patients and matched 45 healthy controls, skeletal muscle biopsy showed that all measures of skeletal muscle mitochondrial function were lower in HFpEF patients.
- Measures of skeletal muscle strength correlated with skeletal muscle mitochondrial respiration, suggesting that mitochondrial dysfunction is associated with impaired exercise tolerance in HFpEF.
- Skeletal muscle mitochondrial dysfunction in HFpEF patients persisted despite adjustment for age, sex, and BMI, suggesting that other factors not linked to obesity contribute to exercise intolerance in this population.
Does mitochondrial dysfunction contribute to altered skeletal muscle metabolism and result in exercise intolerance in patients with heart failure with preserved ejection fraction (HFpEF)?
Individuals over 60 years old with HFpEF (HF symptoms with EF ≥50%) without other conditions that may explain symptoms were enrolled with age matched, healthy sedentary persons serving as controls. Vastus lateralis muscle biopsy was performed for all individuals and analyzed using high resolution respirometry that provides details on mitochondrial respiratory function (oxidative phosphorylation and contributions of complex I and complex II linked respiration). Exercise performance was assessed for all individuals with peak O2 consumption (peak VO2), 6-minute walk test (6MWT), and short physical performance battery (SPPB).
Overall, 27 patients with HFpEF and 45 matched controls were recruited, which included 50 women with a mean age of 70 years. Compared with controls, HFpEF patients had severely reduced peak VO2 despite similar respiratory exchange ratio (≥1.08) with lower 6MWT, SPPB scores, and left leg strength. All assessed skeletal muscle mitochondrial function measures were lower in HFpEF patients despite adjustment for age, sex, and body mass index (BMI). Peak VO2 consumption, 6MWT, SPPB, and leg muscle strength correlated with skeletal muscle mitochondrial respiration, suggesting that mitochondrial dysfunction is associated with impaired exercise tolerance in HFpEF.
In a study of 27 individuals with HFpEF and 45 matched healthy cohorts, respirometry of biopsied skeletal muscle fibers suggests that exercise intolerance in HFpEF is secondary to mitochondrial dysfunction.
Exercise intolerance is a cardinal manifestation of HFpEF patients but mechanisms behind this remain poorly understood. Accordingly, trials with medications known to have cardiovascular benefits in HFrEF have not resulted in benefits in HFpEF patients. In this study, the authors report results of mitochondrial function assessments in skeletal muscle fibers from HFpEF patients and contrast it with healthy, age matched, sedentary controls. All measures of mitochondrial respiratory function were lower in HFpEF patients compared with controls. This in turn correlated with poorer skeletal muscle functioning as assessed by several different measures including a peak VO2, muscle strength, 6MWT, and the SPPB, which is a composite of several different measures of muscle strength and function. Interestingly, these differences persisted despite adjustment for BMI, as obesity is often assumed to be a contributor, suggesting that factors unrelated to obesity contribute to exercise impairment in HFpEF patients. Although the authors only assessed mitochondrial respiratory function in skeletal muscle at rest and not with exercise, these results suggest that interventions targeting mitochondrial abnormalities may help HFpEF patients.
Clinical Topics: Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Exercise
Keywords: Biopsy, Body Mass Index, Exercise, Exercise Tolerance, Heart Failure, Mitophagy, Muscle, Skeletal, Muscle Strength, Obesity, Oxidative Phosphorylation, Respiration, Secondary Prevention, Stroke Volume
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