Skeletal Muscle Myopathy in Heart Failure: the Role of Ejection Fraction

Paneroni, Mara; Pasini, Evasio; Comini, Laura; Vitacca, Michele; Schena, Federico; Venturelli, Massimo

doi:10.1007/s11886-018-1056-x

Cited by 11 publications

(10 citation statements)

References 79 publications

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“…56 Both HFpEF and HFrEF patients with exercise intolerance manifest early exercise-induced declines in skeletal muscle highenergy phosphates and reduced oxidative capacity compared with healthier and low-fatigability HF patients. 57,58…”

Section: Skeletal Myopathymentioning

confidence: 99%

The continuous heart failure spectrum: moving beyond an ejection fraction classification

Triposkiadis

Butler

Abboud

et al. 2019

European Heart Journal

214

206

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Randomized clinical trials initially used heart failure (HF) patients with low left ventricular ejection fraction (LVEF) to select study populations with high risk to enhance statistical power. However, this use of LVEF in clinical trials has led to oversimplification of the scientific view of a complex syndrome. Descriptive terms such as ‘HFrEF’ (HF with reduced LVEF), ‘HFpEF’ (HF with preserved LVEF), and more recently ‘HFmrEF’ (HF with mid-range LVEF), assigned on arbitrary LVEF cut-off points, have gradually arisen as separate diseases, implying distinct pathophysiologies. In this article, based on pathophysiological reasoning, we challenge the paradigm of classifying HF according to LVEF. Instead, we propose that HF is a heterogeneous syndrome in which disease progression is associated with a dynamic evolution of functional and structural changes leading to unique disease trajectories creating a spectrum of phenotypes with overlapping and distinct characteristics. Moreover, we argue that by recognizing the spectral nature of the disease a novel stratification will arise from new technologies and scientific insights that will shape the design of future trials based on deeper understanding beyond the LVEF construct alone.

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Section: Skeletal Myopathymentioning

confidence: 99%

The continuous heart failure spectrum: moving beyond an ejection fraction classification

Triposkiadis

Butler

Abboud

et al. 2019

European Heart Journal

214

206

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show abstract

“…Another myopathy with elevated heme is present in patients with chronic heart failure is skeletal muscle myopathy, and this is considered as a main cause of exercise intolerance in these patients [30]. However, the molecular pathophysiology of skeletal muscle myopathy is not well understood.…”

Section: Discussionmentioning

confidence: 99%

Heme-Induced Oxidation of Cysteine Groups of Myofilament Proteins Leads to Contractile Dysfunction of Permeabilized Human Skeletal Muscle Fibres

Alvarado

Tóth

Csősz

et al. 2020

IJMS

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Background: Heme released from red blood cells targets a number of cell components including the cytoskeleton. The purpose of the present study was to determine the impact of free heme (20–300 µM) on human skeletal muscle fibres made available during orthopedic surgery. Methods: Isometric force production and oxidative protein modifications were monitored in permeabilized skeletal muscle fibre segments. Results: A single heme exposure (20 µM) to muscle fibres decreased Ca2+-activated maximal (active) force (Fo) by about 50% and evoked an approximately 3-fold increase in Ca2+-independent (passive) force (Fpassive). Oxidation of sulfhydryl (SH) groups was detected in structural proteins (e.g., nebulin, α-actinin, meromyosin 2) and in contractile proteins (e.g., myosin heavy chain and myosin-binding protein C) as well as in titin in the presence of 300 µM heme. This SH oxidation was not reversed by dithiothreitol (50 mM). Sulfenic acid (SOH) formation was also detected in the structural proteins (nebulin, α-actinin, meromyosin). Heme effects on SH oxidation and SOH formation were prevented by hemopexin (Hpx) and α1-microglobulin (A1M). Conclusions: These data suggest that free heme has a significant impact on human skeletal muscle fibres, whereby oxidative alterations in structural and contractile proteins limit contractile function. This may explain and or contribute to the weakness and increase of skeletal muscle stiffness in chronic heart failure, rhabdomyolysis, and other hemolytic diseases. Therefore, therapeutic use of Hpx and A1M supplementation might be effective in preventing heme-induced skeletal muscle alterations.

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“…Most patients with HF have developed skeletal muscle abnormalities. Skeletal muscle wasting, such as sarcopenia and myopathy occurs in 30-50% of patients with HFrEF, as a result of impaired mobility and symptoms (11,34). Moreover there is a mitochondrial dysfunction, fewer muscle fibers type 1 (switch from type 1 to type 2 fiber), and decreased muscular capillary network which leads to impaired, both exercise and functional, capacity (28,34,35).…”

Section: Skeletal Musclementioning

confidence: 99%

Exercise training and testing in patients with heart failure

Lans

2021

Linköping University Medical Dissertations

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Skeletal Muscle Myopathy in Heart Failure: the Role of Ejection Fraction

Cited by 11 publications

References 79 publications

The continuous heart failure spectrum: moving beyond an ejection fraction classification

The continuous heart failure spectrum: moving beyond an ejection fraction classification

Heme-Induced Oxidation of Cysteine Groups of Myofilament Proteins Leads to Contractile Dysfunction of Permeabilized Human Skeletal Muscle Fibres

Exercise training and testing in patients with heart failure

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