Sarcopenia is primarily characterized by skeletal muscle disturbances such as loss of muscle mass, quality, strength, and physical performance. It is commonly seen in elderly patients with chronic ...diseases. The prevalence of sarcopenia in chronic heart failure (HF) patients amounts to up to 20% and may progress into cardiac cachexia. Muscle wasting is a strong predictor of frailty and reduced survival in HF patients. Despite many different techniques and clinical tests, there is still no broadly available gold standard for the diagnosis of sarcopenia. Resistance exercise and nutritional supplementation represent the currently most used strategies against wasting disorders. Ongoing research is investigating skeletal muscle mitochondrial dysfunction as a new possible target for pharmacological compounds. Novel agents such as synthetic ghrelin and selective androgen receptor modulators (SARMs) seem promising in counteracting muscle abnormalities but their effectiveness in HF patients has not been assessed yet. In the last decades, many advances have been accomplished but sarcopenia remains an underdiagnosed pathology and more efforts are needed to find an efficacious therapeutic plan. The purpose of this review is to illustrate the current knowledge in terms of pathogenesis, diagnosis, and treatment of sarcopenia in order to provide a better understanding of wasting disorders occurring in chronic heart failure.
Body wasting is a serious complication that affects a large proportion of patients with heart failure. Muscle wasting, also known as sarcopenia, is the loss of muscle mass and strength, whereas ...cachexia describes loss of weight. After reaching guideline-recommended doses of heart failure therapies, the most promising approach to treating body wasting seems to be combined therapy that includes exercise, nutritional counselling, and drug treatment. Nutritional considerations include avoiding excessive salt and fluid intake, and replenishment of deficiencies in trace elements. Administration of omega-3 polyunsaturated fatty acids is beneficial in selected patients. High-calorific nutritional supplements can also be useful. The prescription of aerobic exercise training that provokes mild or moderate breathlessness has good scientific support. Drugs with potential benefit in the treatment of body wasting that have been tested in clinical studies in patients with heart failure include testosterone, ghrelin, recombinant human growth hormone, essential amino acids, and β
-adrenergic receptor agonists. In this Review, we summarize the pathophysiological mechanisms of muscle wasting and cachexia in heart failure, and highlight the potential treatment strategies. We aim to provide clinicians with the relevant information on body wasting to understand and treat these conditions in patients with heart failure.
Sarcopenia (loss of muscle mass and muscle function) is a strong predictor of frailty, disability and mortality in older persons and may also occur in obese subjects. The prevalence of sarcopenia is ...increased in patients suffering from chronic heart failure. However, there are currently few therapy options. The main intervention is resistance exercise, either alone or in combination with nutritional support, which seems to enhance the beneficial effects of training. Also, testosterone has been shown to increased muscle power and function; however, a possible limitation is the side effects of testosterone. Other investigational drugs include selective androgen receptor modulators, growth hormone, IGF‐1, compounds targeting myostatin signaling, which have their own set of side effects. There are abundant prospective targets for improving muscle function in the elderly with or without chronic heart failure, and the continuing development of new treatment strategies and compounds for sarcopenia and cardiac cachexia makes this field an exciting one.
Patients suffering from chronic heart failure (CHF) show an increased prevalence (~20% in elderly CHF patients) of loss of muscle mass and muscle function (i.e. sarcopenia) compared with healthy ...elderly people. Sarcopenia, which can also occur in obese patients, is considered a strong predictor of frailty, disability, and mortality in older persons and is present in 5–13% of elderly persons aged 60–70 years and up to 50% of all octogenarians. In a CHF study, sarcopenia was associated with lower strength, reduced peak oxygen consumption (peak VO2, 1173 ± 433 vs. 1622 ± 456 mL/min), and lower exercise time (7.7 ± 3.8 vs. 10.22 ± 3.0 min, both P < 0.001). Unfortunately, there are only very limited therapy options. Currently, the main intervention remains resistance exercise. Specialized nutritional support may aid the effects of resistance training. Testosterone has significant positive effects on muscle mass and function, and low endogenous testosterone has been described as an independent risk factor in CHF in a study with 618 men (hazard ratio 0.929, P = 0.042). However, the use of testosterone is controversial because of possible side effects. Selective androgen receptor modulators have been developed to overcome these side effects but are not yet available on the market. Further investigational drugs include growth hormone, insulin‐like growth factor 1, and several compounds that target the myostatin pathway. The continuing development of new treatment strategies and compounds for sarcopenia, muscle wasting regardless of CHF, and cardiac cachexia makes this a stimulating research area.
Cardiac cachexia: hic et nunc Loncar, Goran; Springer, Jochen; Anker, Markus ...
Journal of cachexia, sarcopenia and muscle,
June 2016, 2016-06-00, 20160601, Letnik:
7, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Cardiac cachexia (CC) is the clinical entity at the end of the chronic natural course of heart failure (HF). Despite the efforts, even the most recent definition of cardiac cachexia has been ...challenged, more precisely, the addition of new criteria on top of obligatory weight loss. The pathophysiology of CC is complex and multifactorial. A better understanding of pathophysiological pathways in body wasting will contribute to establish potentially novel treatment strategies. The complex biochemical network related with CC and HF pathophysiology underlines that a single biomarker cannot reflect all of the features of the disease. Biomarkers that could pick up the changes in body composition before they convey into clinical manifestations of CC would be of great importance. The development of preventive and therapeutic strategies against cachexia, sarcopenia, and wasting disorders is perceived as an urgent need by healthcare professionals. The treatment of body wasting remains an unresolved challenge to this day. As CC is a multifactorial disorder, it is unlikely that any single agent will be completely effective in treating this condition. Among all investigated therapeutic strategies, aerobic exercise training in HF patients is the most proved to counteract skeletal muscle wasting and is recommended by treatment guidelines for HF.
Muscle wasting in heart failure: An overview von Haehling, Stephan; Steinbeck, Lisa; Doehner, Wolfram ...
The international journal of biochemistry & cell biology,
10/2013, Letnik:
45, Številka:
10
Journal Article
Recenzirano
Patients with heart failure are frequently limited in their exercise capacity. Although this clinical phenomenon is mostly attributed to the failing myocardium, the effects of skeletal muscle wasting ...should not be underestimated. Muscle wasting may present in the form of loss of muscle mass and function, termed sarcopenia in healthy aging, or in the form of cachexia. Only cachexia is associated with loss of body weight. The mechanisms involved embrace an anabolic-/catabolic imbalance with increased degradation of myofibrils and myocyte apoptosis. Clinical effects include reduced muscle mass, strength and consequently reduced exercise capacity. This article describes the terminology, molecular pathways, prevalence, clinical implications and possible treatment approaches to muscle wasting in patients with heart failure.
This article is part of a Directed Issue entitled: Molecular basis of muscle wasting.
Background:Kynurenine is a circulating metabolite from the essential amino acid tryptophan. Accelerated degradation of kynurenine in skeletal muscle has been reported to provide an anti-inflammatory ...effect. The aim of this study was to investigate the association between blood kynurenine and muscle mass/function in patients with heart failure (HF), in whom diseased muscle mass/function plays a pathophysiological role.Methods and Results:Plasma kynurenine was assessed in 249 patients with HF (67±11 years, 21% women) and in 45 controls from the SICA-HF study. Kynurenine was higher in 173 HF patients with reduced ejection fraction (EF) and in 76 patients with preserved EF than controls (3.5±1.5, 3.4±1.3, and 2.4±1.1 μmol/L, P<0.001). In HF patients, kynurenine had an inverse association with handgrip strength (r=–0.26, P<0.01), peak oxygen consumption (r=–0.29, P<0.01), 6-min walk distance (r=–0.23, P<0.01), and had a positive association with kidney and liver function parameters. No correlation was observed between kynurenine and lean mass. On multivariable linear regression analysis, a significant association was noted between kynurenine and peak oxygen consumption even after adjustment for age, gender, BMI, and hemoglobin (β=–0.23, P<0.001). Patients with higher kynurenine were at higher risk of death (adjusted HR, 1.46 per 1 μmol/L, P<0.01).Conclusions:In stable HF patients, plasma kynurenine was inversely correlated with muscle strength and functional capacity as well as with liver and kidney function.
MicroRNAs in muscle wasting Suzuki, Tsuyoshi; Springer, Jochen
Journal of cachexia, sarcopenia and muscle,
December 2018 Supplement, 2018-12-00, 20181201, 2018-12-01, Letnik:
9, Številka:
7
Journal Article
Recenzirano
Odprti dostop
In patients with COPD with a low fat free mass, an increased expression of miR‐675 in quadricep muscle was shown to repress muscle regeneration in vitro. ...quadricep expression of miR‐422a was ...positively associated with muscle strength (maximal voluntary contraction r = 0.59, P < 0.001 and r = 0.51, P = 0.004, for COPD and aortic surgery, respectively) and inversely associated with the amount of muscle that would be lost in the first post‐operative week (r = −0.57, P < 0.001). Differential regulation of miR expression in skeletal muscle after exercise miR up‐regulated miR down‐regulated Exercise type Exercise duration Reference miR‐1, miR‐133a, miR‐133b, miR181a miR‐9, miR‐23a, miR‐23b, miR‐31 Acute exercise Acute bout of moderate‐intensity endurance cycling Russel et al. miR‐1, miR‐133a Acute resistance exercise 45 min of one‐legged knee extensor exercise Ringholm et al. miR‐1 12 weeks of training with two weekly resistance exercise sessions 12 weeks of training with two weekly resistance exercise sessions Mueller et al. miR‐1, miR‐133a, miR‐133b, miR‐206 Endurance Cycle ergometer five times per week frequency for 12 weeks Nielsen et al. miR‐1, miR‐29b Endurance 10 days of endurance training Russel et al. miR‐136, miR‐200c, miR‐376, miR‐377, miR‐499b, miR‐558 miR‐28, miR‐30d, miR‐204, miR‐330, miR‐345, miR‐375, miR‐449c, miR‐483, miR‐509, miR‐520a, miR‐548, miR‐628, miR‐653, miR‐670, miR‐889, miR‐1245a, miR‐1270, miR‐1280, miR‐1322, miR‐3180 Chronic resistance exercise 12‐week lower body resistance exercise Ogasawara et al. miR‐451 miR‐26a, miR‐29a, miR‐378 Resistance exercise 12‐week resistance exercise training program (pushing, pulling, and leg exercises, with 60 weight‐lifting sessions in total Davidsen et al. miR‐133a, miR‐378, miR‐486 Resistance exercise 8 × 5 unilateral leg press repetitions on each leg at 80% of the 1repitition maximum Fyfe et al. miRs can be actively secreted from a cell or leaking through the membrane in response to various stimuli and insults resulting in varying circulating miR levels in the blood, which are relatively stable making miRs interesting for the use as biomarkers and therapeutic targets. Resistance exercise has been of particular interest in sarcopenia and also in cachexia. ...exercise mimetics such as trimetazidine are of interest in the therapy of muscle atrophy, but also need companion biomarkers.
The role of myostatin in muscle wasting: an overview Elkina, Yulia; von Haehling, Stephan; Anker, Stefan D. ...
Journal of cachexia, sarcopenia and muscle,
September 2011, Letnik:
2, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Myostatin is an extracellular cytokine mostly expressed in skeletal muscles and known to play a crucial role in the negative regulation of muscle mass. Upon the binding to activin type IIB receptor, ...myostatin can initiate several different signalling cascades resulting in the upregulation of the atrogenes and downregulation of the important for myogenesis genes. Muscle size is regulated via a complex interplay of myostatin signalling with the insulin-like growth factor 1/phosphatidylinositol 3-kinase/Akt pathway responsible for increase in protein synthesis in muscle. Therefore, the regulation of muscle weight is a process in which myostatin plays a central role but the mechanism of its action and signalling cascades are not fully understood. Myostatin upregulation was observed in the pathogenesis of muscle wasting during cachexia associated with different diseases (i.e. cancer, heart failure, HIV). Characterisation of myostatin signalling is therefore a perspective direction in the treatment development for cachexia. The current review covers the present knowledge about myostatin signalling pathways leading to muscle wasting and the state of therapy approaches via the regulation of myostatin and/or its downstream targets in cachexia.
Interleukin-6 (IL-6) is an important player in chronic inflammation associated with heart failure and tumor-induced cachexia. Fibroblasts are salient mediators of both inflammation and fibrosis. ...Whereas the general outcome of IL-6 on the heart’s function and muscle wasting has been intensively studied, the influence of IL-6 on fibroblasts of the heart and skeletal muscle (SM) has not been analyzed so far. We illustrate that SM-derived fibroblasts exhibit higher basal mRNA expression of α-SMA, extracellular matrix molecules (collagen1a1/3a1/5a1), and chemokines (CCL2, CCL7, and CX3CL1) as compared to the left ventricle (LV)-derived fibroblasts. IL-6 drives the transdifferentiation of fibroblasts into myofibroblasts as indicated by an increase in α-SMA expression and upregulates NLRP3 inflammasome activity in both LV- and SM-derived fibroblasts. IL-6 increases the release of CCL7 to CX3CL1 in the supernatant of SM-derived fibroblasts associated with the attraction of more pro(Ly6C
hi
) versus anti(Ly6C
lo
) inflammatory monocytes as compared to unstimulated fibroblasts. IL-6-stimulated LV-derived fibroblasts attract less Ly6C
hi
to Ly6C
lo
monocytes compared to IL-6-stimulated SM-derived fibroblasts. In addition, SM-derived fibroblasts have a higher mitochondrial energy turnover and lower glycolytic activity versus LV-derived fibroblasts under basal and IL-6 conditions. In conclusion, IL-6 modulates the inflammatory and metabolic phenotype of LV- and SM-originated fibroblasts.
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