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Abnormal skeletal muscle bioenergetics in familial hypertrophic cardiomyopathy
C H Thompson1, G J Kemp, D J Taylor
1MRC Biochemical and Clinical Magnetic Resonance Unit, John Radcliffe Hospital, Oxford, UK.
Insights
Familial hypertrophic cardiomyopathy affects skeletal muscle metabolism. Abnormal beta myosin heavy chain protein is linked to decreased muscle oxidative capacity and impaired exercise response.
Area of Science:
- Cardiology
- Biochemistry
- Muscle Physiology
Background:
- Familial hypertrophic cardiomyopathy (FHC) is a genetic heart condition.
- Skeletal muscle involvement in FHC is not fully understood.
- Investigating muscle metabolism can reveal FHC's systemic effects.
Purpose of the Study:
- To investigate skeletal muscle metabolic differences in patients with FHC.
- To compare metabolic profiles based on the specific genetic abnormality (beta myosin heavy chain vs. troponin T).
Main Methods:
- Case-control study using 31P magnetic resonance spectroscopy (MRS) on calf muscle.
- Compared five patients with beta myosin heavy chain abnormality, five with troponin T abnormality, and 16 healthy controls.
- Assessed high-energy phosphate metabolism at rest and during exercise.
Main Results:
- Beta myosin heavy chain group showed higher resting phosphocreatine/ATP ratio.
- Both patient groups exhibited greater phosphocreatine depletion and acidification during exercise.
- Slower phosphocreatine recovery post-exercise in the beta myosin heavy chain group indicated reduced oxidative capacity.
Conclusions:
- Exercise metabolism is altered in FHC patients, influenced by the specific protein abnormality.
- Beta myosin heavy chain abnormality is associated with decreased muscle oxidative capacity.
- Findings align with previous muscle biopsy studies showing mitochondrial reduction.
Objective:
To determine the skeletal muscle metabolic manifestations of familial hypertrophic cardiomyopathy.
Design:
A case-control study.
Setting:
31P magnetic resonance spectroscopy of the calf muscle was performed on volunteers from a centre specialising in familial hypertrophic cardiomyopathy.
Patients:
Five patients with abnormal beta myosin heavy chain protein in cardiac and skeletal muscle and five patients with a troponin T abnormality in cardiac muscle were compared with healthy controls.
Results:
High energy phosphate metabolism in vivo was examined in a non-invasive manner. In resting muscle, the beta myosin heavy chain group had a higher ratio of phosphocreatine to ATP concentration (4.51 (SD 0.17)) than either the troponin T group (3.88 (0.42)) or controls (n = 16; 4.04 (0.40)). Exercise duration was reduced compared to controls, and during the fourth minute of exercise phosphocreatine depletion and muscle acidification were greater in both patient groups. After exercise, the recovery of phosphocreatine-an index of oxidative metabolic capacity of the muscle-was slower in the beta myosin heavy chain group (mean half time 0.65 (0.08) minutes) than in the troponin T group (0.60 (0.17) minutes) or controls (0.48 (0.14) minutes).
Conclusions:
Exercise metabolism was abnormal in both groups of subjects, and the affected contractile protein determined the metabolic changes in muscle at rest and during recovery. In patients with abnormal beta myosin heavy chain protein, there was a decrease in oxidative capacity consistent with the reduction in mitochondria reported in muscle biopsy studies of similar patients.