Skeletal muscle abnormalities in heart failure with preserved ejection fraction.
Almost half of all heart failure (HF) disease burden is due to HF with preserved ejection fraction (HFpEF). The primary symptom in patients with HFpEF, even when well compensated, is severe exercise intolerance and is associated with their reduced quality of life. Recently, studies showed that HFpEF patients have multiple skeletal muscle (SM) abnormalities, and these are associated with decreased exercise intolerance. The SM abnormalities are likely intrinsic to the HFpEF syndrome, not a secondary consequence of an epiphenomenon. These abnormalities are decreased muscle mass, reduced type I (oxidative) muscle fibers, and reduced type I-to-type II fiber ratio as well as a reduced capillary-to-fiber ratio, abnormal fat infiltration into the thigh SM, increased levels of atrophy genes and proteins, reduction in mitochondrial content, and rapid depletion of high-energy phosphate during exercise with markedly delayed repletion of high-energy phosphate during recovery in mitochondria. In addition, patients with HFpEF have impaired nitric oxide bioavailability, particularly in the microvasculature. These SM abnormalities may be responsible for impaired diffusive oxygen transport and/or impaired SM oxygen extraction. To date, exercise training (ET) and caloric restriction are some of the interventions shown to improve outcomes in HFpEF patients. Improvements in exercise tolerance following aerobic ET are largely mediated through peripheral SM adaptations with minimal change in central hemodynamics and highlight the importance of targeting SM to improve exercise intolerance in HFpEF. Focusing on the abnormalities mentioned above may improve the clinical condition of patients with HFpEF.
Duke Scholars
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Related Subject Headings
- Stroke Volume
- Quality of Life
- Phosphates
- Oxygen Consumption
- Oxygen
- Muscle, Skeletal
- Humans
- Heart Failure
- Exercise Tolerance
- Cardiovascular System & Hematology
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Stroke Volume
- Quality of Life
- Phosphates
- Oxygen Consumption
- Oxygen
- Muscle, Skeletal
- Humans
- Heart Failure
- Exercise Tolerance
- Cardiovascular System & Hematology