Impaired Exercise Tolerance in Heart Failure: Role of Skeletal Muscle Morphology and Function

Abstract

Both HFrEF and HFpEF patients exhibit a reduction in percent of type I (oxidative) muscle fibers and oxidative enzymes coupled with abnormal mitochondrial respiration. These skeletal muscle abnormalities contribute to impaired oxidative metabolism with an earlier shift towards glycolytic metabolism during exercise that is strongly associated with exercise intolerance. In both HFrEF and HFpEF patients, peripheral "non-cardiac" factors are important determinants of the improvement in exercise tolerance following aerobic exercise training. Adjunctive strategies that include nutritional supplementation with amino acids and/or anabolic drugs to stimulate anabolic molecular pathways in skeletal muscle show great promise for improving exercise tolerance and treating heart failure-associated sarcopenia, but these efforts remain early in their evolution, with no immediate clinical applications. There is consistent evidence that heart failure is associated with multiple skeletal muscle abnormalities which impair oxygen uptake and utilization and contribute greatly to exercise intolerance. Exercise training induces favorable adaptations in skeletal muscle morphology and function that contribute to improvements in exercise tolerance in patients with HFrEF. The contribution of skeletal muscle adaptations to improved exercise tolerance following exercise training in HFpEF remains unknown and warrants further investigation.

Serum Brain-Derived Neurotrophic Factor Levels Are Associated with Skeletal Muscle Function but Not with Muscle Mass in Patients with Heart Failure

“…eart failure (HF) has become highly prevalent, characterized by reduced activities of daily living and repeated hospitalizations in addition to high mortality rates, comprising a major public health problem. 1) Aberrant skeletal muscle alterations are involved in HF; 2,3) these alterations include muscle atrophy, a reduction in muscular strength, a switch in myofibers from slow type I to fast type II, and impaired energy metabolism due to a reduction in mitochondrial density and oxidative function. [4][5][6] These changes have been considered important factors that lead to skeletal muscle impairments, related not only to worse symptoms but also to the severity of HF and the prognosis of patients with HF.…”

“…Given that skeletal muscle, i.e., muscle mass, strength and mitochondrial function is an important factor that determines exercise capacity in HF patients, 2,20) we hypothesized that the measurement of serum BDNF may show a close relationship between muscle mass and/or strength. The association between BDNF and skeletal muscle function in patients with HF has not been established; we therefore aimed to examine the relationship between serum BDNF and skeletal muscle mass as well as muscle strength in HF patients.…”

Muscle Wasting and Sarcopenia in Heart Failure—The Current State of Science

“…In the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF) [62], which enrolled 200 chronic HF patients, the prevalence of sarcopenia in HF patients with reduced ejection fraction (HFrEF) was nearly 20% higher than in healthy adults of the same age [62,63]. Similar results have been observed in HF patients with a preserved ejection fraction [64,65]. Therefore, sarcopenia and chronic HF seem to be intertwined, complicating the progression and outcome of each other [66].…”

Exercise as a Therapeutic Strategy for Sarcopenia in Heart Failure: Insights into Underlying Mechanisms

“…The prevalence of HF increases sharply in patients aged ≥65 years, and the disease is strongly associated with a number of pathophysiological complications, including pulmonary hypertension, renal disease, vascular dysfunction, and stroke [ 2 , 3 ]. Additionally, patients with HF often demonstrate a reduced exercise capacity that restricts daily activity and mobility [ 4 ]. There are several causes of exercise intolerance in HF patients, including systemic impairment of blood perfusion, blood flow, oxygen supply, and diffusivity of blood to skeletal muscle tissues [ 4 ].…”

“…Additionally, patients with HF often demonstrate a reduced exercise capacity that restricts daily activity and mobility [ 4 ]. There are several causes of exercise intolerance in HF patients, including systemic impairment of blood perfusion, blood flow, oxygen supply, and diffusivity of blood to skeletal muscle tissues [ 4 ]. Such chronic impairments of the cardiovascular system, along with limited physical activity, may cause quantitative and qualitative loss of skeletal muscle and accelerate the onset of sarcopenia [ 5 ].…”