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

  • Pathophysiology: Neuroendocrine, Vascular, and Metabolic Factors (S. Katz, Section Editor)
  • Published:
Current Heart Failure Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

To discuss the impact of deleterious changes in skeletal muscle morphology and function on exercise intolerance in patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), as well as the utility of exercise training and the potential of novel treatment strategies to preserve or improve skeletal muscle morphology and function.

Recent Findings

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.

Summary

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.

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Abbreviations

a-vO2diff:

Arterial-venous oxygen content difference

CO:

Cardiac output

HF:

Heart failure

HFpEF:

Heart failure with preserved ejection fraction

HFrEF:

Heart failure with reduced ejection fraction

NYHA:

New York Heart Association

PCr:

Phosphocreatine

VO2peak :

Cardiorespiratory fitness

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Funding

Dr. Tucker is financially supported by the American Heart Association (AHA) Postdoctoral Fellowship Grant (AHA Award Number: 18POST33990210). Dr. Haykowsky is financially supported by the Moritz Chair in Geriatrics at the University of Texas at Arlington, and the National Institutes of Health (NIH) R15NR016826-01 grant. Dr. Forman is financially supported by the National Institute of Health grants R01AG060499-01 (NIA), R01AG051376 (NIA), U01 AR071130 (Commonwealth Fund), and P30 AG024827 (NIA). He is also funded by the Veterans Affairs (VA) Rehabilitation Research and Development Service (RR&D) F0834-R grant.

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Authors and Affiliations

  1. The University of Texas at Arlington, Arlington, TX, USA

    Wesley J. Tucker, Mark J. Haykowsky, Yaewon Seo & Elisa Stehling

  2. Department of Medicine, Section of Geriatric Cardiology, Veterans Affairs Geriatric Research Education, and Clinical Center, University of Pittsburgh, 3471 Fifth Avenue, Suite 500, Pittsburgh, PA, 15213, USA

    Daniel E. Forman

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  1. Wesley J. Tucker
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  2. Mark J. Haykowsky
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  3. Yaewon Seo
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Correspondence to Daniel E. Forman.

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This article is part of the Tropical Collection on Pathophysiology: Neuroendocrine, Vascular, and Metabolic Factors

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Tucker, W.J., Haykowsky, M.J., Seo, Y. et al. Impaired Exercise Tolerance in Heart Failure: Role of Skeletal Muscle Morphology and Function. Curr Heart Fail Rep 15, 323–331 (2018). https://doi.org/10.1007/s11897-018-0408-6

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