Aerobic Exercise and Pharmacological Therapies for Skeletal Myopathy in Heart Failure: Similarities and Differences

Abstract

Skeletal myopathy has been identified as a major comorbidity of heart failure (HF) affecting up to 20% of ambulatory patients leading to shortness of breath, early fatigue, and exercise intolerance. Neurohumoral blockade, through the inhibition of renin angiotensin aldosterone system (RAS) and β-adrenergic receptor blockade (β-blockers), is a mandatory pharmacological therapy of HF since it reduces symptoms, mortality, and sudden death. However, the effect of these drugs on skeletal myopathy needs to be clarified, since exercise intolerance remains in HF patients optimized with β-blockers and inhibitors of RAS. Aerobic exercise training (AET) is efficient in counteracting skeletal myopathy and in improving functional capacity and quality of life. Indeed, AET has beneficial effects on failing heart itself despite being of less magnitude compared with neurohumoral blockade. In this way, AET should be implemented in the care standards, together with pharmacological therapies. Since both neurohumoral inhibition and AET have a direct and/or indirect impact on skeletal muscle, this review aims to provide an overview of the isolated effects of these therapeutic approaches in counteracting skeletal myopathy in HF. The similarities and dissimilarities of neurohumoral inhibition and AET therapies are also discussed to identify potential advantageous effects of these combined therapies for treating HF.

Effects of aerobic and inspiratory training on skeletal muscle microRNA‐1 and downstream‐associated pathways in patients with heart failure

“…The reduction in PTEN in our study favoured the increase in p‐AKT stimulating protein synthesis by mTOR upregulation. Moreover, these responses seem to contribute to an improvement in anabolic/catabolic balance expressed by the enhancement in the muscle fibre cross‐sectional area . At this point, the explanation for the differences in the microRNA‐1 expression provoked by exercise training in healthy individuals and patients with chronic HFrEF remains uncertain.…”

“…Exercise intolerance in patients with chronic HFrEF has been attributed, in great part, to skeletal myopathy. Exercise training has been shown to counteract the muscular alterations in this syndrome by improving many of the key features of the skeletal myopathy . This nonpharmacological strategy increases muscle capillarization, muscle blood flow, and flow‐mediated dilation, which facilitate oxygen diffusion and oxidative energy production .…”

“…Exercise training has been shown to counteract the muscular alterations in this syndrome by improving many of the key features of the skeletal myopathy. 3,5,26,27 This nonpharmacological strategy increases muscle capillarization, muscle blood flow, and flow-mediated dilation, which facilitate oxygen diffusion and oxidative energy production. 3,5,26,27 In addition, exercise training ameliorates protein degradation pathways by downregulating the ubiquitin-proteasome system and stimulating insulin-like growth factor-1 (IGF-1) signalling pathway.…”

“…3,5,26,27 In addition, exercise training ameliorates protein degradation pathways by downregulating the ubiquitin-proteasome system and stimulating insulin-like growth factor-1 (IGF-1) signalling pathway. 3,5,26,27 These changes contribute to the restoration in anabolic/catabolic imbalance. 3,5,26,27 The present study extends the knowledge that AET improves the microRNA-1 downstream-associated pathways in patients with chronic HFrEF, which seems to improve skeletal myopathy and exercise capacity in this set of patients.…”

“…Aerobic exercise training (AET) has been shown to provoke a remarkable reduction in muscle sympathetic nerve activity and vasoconstriction . In skeletal muscle, AET reduces inflammation, oxidative stress, and energy metabolism and improves the balance between muscle protein synthesis and degradation . Moreover, there are data supporting the notion that AET can increase and/or decrease skeletal muscle myomiRs and, in consequence, alter skeletal muscle phenotype in cardiovascular diseases …”