Making the Case for Skeletal Muscle Myopathy and Its Contribution to Exercise Intolerance in Heart Failure With Preserved Ejection Fraction
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- exercise intolerance
- heart failure
- magnetic resonance spectroscopy
- mitochondrial function
- skeletal muscle
See Article by Weiss et al
Thirty-five years ago, Robert Luchi provided the first description of heart failure (HF) with preserved ejection fraction (HFpEF). HFpEF is now the most common form of HF in older adults, particularly women, and its prevalence is increasing and its prognosis is worsening. The primary symptom in chronic HFpEF, even when patients are well compensated and nonedematous, is severe exercise intolerance, characterized by exertional fatigue and dyspnea, associated with reduced quality of life.1 Thus, understanding the pathophysiology of exercise intolerance in HFpEF is critical for improving patient-centered outcomes.
Exercise intolerance can be objectively and reproducibly measured as reduced peak exercise oxygen consumption (VO2) by expired gas analysis. Using this technique, we and others have shown that the reduction in peak VO2 in HFpEF is at least as severe as in age-matched people with HF with severely reduced ejection fraction (HFrEF; mean ejection fraction, 30%).1 By the Fick equation, reduced peak VO2 must be because of either reduced cardiac output (CO), reduced arteriovenous oxygen content difference (A-VO2Diff), or a combination of these factors.2 It has conventionally been assumed that reduced exercise CO is the sole driver of exercise intolerance in HFpEF. However, we showed that reduced exercise A-VO2Diff accounts for at least 50% of the reduction in peak VO2 and is a stronger independent predictor of peak VO2 than exercise CO,3 results confirmed by several others.4
Reduced A-VO2Diff during exercise can be caused by reduced convective and diffusive oxygen delivery to exercising skeletal muscle, impaired oxygen utilization by the exercising skeletal muscle, or a combination of these factors.2 Indeed, it is now known that, as has been previously established in HFrEF, there are multiple skeletal muscle abnormalities in HFpEF …