The influence of muscle mass, strength, fatigability and blood flow on exercise capacity in cachectic and non-cachectic patients with chronic heart failure

Anker, Stefan D.; Swan, Jonathan W.; Volterrani, Maurizio; Chua, Tuan Peng; Clark, Andrew L.; Poole‐Wilson, Philip A.; Coats, Andrew J.S.

doi:10.1093/oxfordjournals.eurheartj.a015229

Cited by 184 publications

(128 citation statements)

References 28 publications

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“…The weight loss affects all body compartments, and is important because muscle bulk is strongly related to exercise capacity, and hence a patient's symptoms,1 and because both decreasing weight and weight loss are strongly related to an adverse prognosis 2…”

Section: Introductionmentioning

confidence: 99%

Effect of beta‐adrenergic blockade with carvedilol on cachexia in severe chronic heart failure: results from the COPERNICUS trial

Clark

Coats

Krum

et al. 2017

J cachexia sarcopenia muscle

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BackgroundCardiac cachexia frequently accompanies the progression of heart failure despite the use of effective therapies for left ventricular dysfunction. Activation of the sympathetic nervous system has been implicated in the pathogenesis of weight loss, but the effects of sympathetic antagonism on cachexia are not well defined.MethodsWe prospectively evaluated changes in body weight in 2289 patients with heart failure who had dyspnoea at rest or on minimal exertion and a left ventricular ejection fraction <25%. Patients were randomly assigned (double‐blind) to receive either placebo (n = 1133) or carvedilol (n = 1156) and were followed for the occurrence of major clinical events for up to 29 months (COPERNICUS trial). Patients were not enrolled if they had signs of clinically significant fluid retention due to heart failure.ResultsPatients in the carvedilol group were 33% less likely than patients in the placebo group to experience a further significant loss of weight (>6%) (95% confidence interval: 14–48%, P = 0.002) and were 37% more likely to experience a significant gain in weight (≥5%) (95% confidence interval: 12–66%, P = 0.002). Carvedilol's ability to prevent weight loss was most marked in patients with increased body mass index at baseline, whereas its ability to promote weight gain was most marked in patients with decreased body mass index at baseline. Increases in weight were not accompanied by evidence of fluid retention. Baseline values for body mass index and change in body weight were significant predictors of survival regardless of treatment.ConclusionsCarvedilol attenuated the development and promoted a partial reversal of cachexia in patients with severe chronic heart failure, supporting a role for prolonged sympathetic activation in the genesis of weight loss.

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Section: Introductionmentioning

confidence: 99%

Effect of beta‐adrenergic blockade with carvedilol on cachexia in severe chronic heart failure: results from the COPERNICUS trial

Clark

Coats

Krum

et al. 2017

J cachexia sarcopenia muscle

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“…9 -12 Excessive production of free radicals partially contributes to the impairment of muscle function and apoptosis of SM fibers, with the consequent loss in muscle bulk. 1,[13][14][15][16] Nevertheless, SM contains an enzymatic antioxidative system encompassing copper-zinc superoxide dismutase (CuZnSOD), manganese superoxide dismutase (Mn-SOD), glutathione peroxidase (GPX), and catalase (Cat), which protect the cells from attacks by ROS. 17 Currently, it is unknown whether this enzyme system adapts to the enhanced production of ROS or whether the impaired activity of radical scavenger enzymes leads to a further increase in local oxidative stress.…”

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confidence: 99%

Antioxidative Effects of Exercise Training in Patients With Chronic Heart Failure

et al. 2005

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Background-In chronic heart failure (CHF), cross-talk between inflammatory activation and oxidative stress has been anticipated in skeletal muscle (SM). The role of the radical scavenger enzymes superoxide dismutase (SOD), catalase (Cat), and glutathione peroxidase (GPX), which remove oxygen radicals, has never been assessed in the SM in this context. Moreover, it remains unknown whether exercise training augments the activity of these enzymes in CHF. Methods and Results-Twenty-three patients with CHF were randomized to either 6 months of exercise training (T) or a sedentary lifestyle (C); 12 age-matched healthy subjects (HS) were studied in parallel. Activity of Cat, SOD, and GPX was assessed in SM biopsies before and after 6 months (6 months). Oxidative stress was determined by measuring nitrotyrosine formation. SOD, Cat, and GPX activity was reduced by 31%, 57%, and 51%, respectively, whereas nitrotyrosine formation was increased by 107% in SM in CHF (PϽ0.05 versus HS). In CHF, exercise training augmented GPX and Cat activity in SM by 41% (PϽ0.05 versus before and group C) and 42% (PϽ0.05 versus before and group C), respectively, and decreased nitrotyrosine production by 35% (from 3.8Ϯ0.4% tissue area before to 2.5Ϯ0.3% after 6 months; PϽ0.05 versus before). Conclusions-The reduced activity of major antioxidative enzymes in the SM of CHF patients is associated with increased local oxidative stress. Exercise training exerts antioxidative effects in the SM in CHF, in particular, due to an augmentation in activity of radical scavenger enzymes.

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“…1,2 Endothelial function 3 and vasodilator reactivity to exercise 4 have been shown to be significantly reduced in patients with CHF. One major factor responsible for the impaired regulation of vascular tone in CHF is the increase in oxidative stress, leading to a premature breakdown of endotheliumderived vasoactive nitric oxide (NO).…”

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confidence: 99%

Effects of Xanthine Oxidase Inhibition With Allopurinol on Endothelial Function and Peripheral Blood Flow in Hyperuricemic Patients With Chronic Heart Failure

et al. 2002

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Background-In patients with chronic heart failure (CHF), hyperuricemia is a common finding and is associated with reduced vasodilator capacity and impaired peripheral blood flow. It has been suggested that the causal link of this association is increased xanthine oxidase (XO)-derived oxygen free radical production and endothelial dysfunction. We therefore studied the effects of XO inhibition with allopurinol on endothelial function and peripheral blood flow in CHF patients after intra-arterial infusion and after oral administration in 2 independent placebo-controlled studies. Methods and Results-In 10 CHF patients with normal serum uric acid (UA) levels (315Ϯ42 mol/L) and 9 patients with elevated UA (535Ϯ54 mol/L), endothelium-dependent (acetylcholine infusion) and endothelium-independent (nitroglycerin infusion) vasodilation of the radial artery was determined. Coinfusion of allopurinol (600 g/min) improved endothelium-dependent but not endothelium-independent vasodilation in hyperuricemic patients (PϽ0.05). In a double-blind, crossover design, hyperuricemic CHF patients were randomly allocated to allopurinol 300 mg/d or placebo for 1 week. In 14 patients (UA 558Ϯ21 mol/L, range 455 to 743 mol/L), treatment reduced UA by Ͼ120 mol/L in all patients (mean reduction 217Ϯ15 mol/L, PϽ0.0001). Compared with placebo, allopurinol improved peak blood flow (venous occlusion plethysmography) in arms (ϩ24%, Pϭ0.027) and legs (ϩ23%, Pϭ0.029). Flow-dependent flow improved by 58% in arms (Pϭ0.011). Allantoin, a marker of oxygen free radical generation, decreased by 20% after allopurinol treatment (PϽ0.001). There was a direct relation between change of UA and improvement of flow-dependent flow after allopurinol treatment (rϭ0.63, PϽ0.05). Conclusions-In hyperuricemic CHF patients, XO inhibition with allopurinol improves peripheral vasodilator capacity and blood flow both locally and systemically.

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The influence of muscle mass, strength, fatigability and blood flow on exercise capacity in cachectic and non-cachectic patients with chronic heart failure

Abstract: The predictors of exercise capacity change with the development of cardiac cachexia from age and strength to peak blood flow. This shift may be caused by additional endocrine or catabolic, abnormalities active in end stage heart failure.

Cited by 184 publications

References 28 publications

Effect of beta‐adrenergic blockade with carvedilol on cachexia in severe chronic heart failure: results from the COPERNICUS trial

Effect of beta‐adrenergic blockade with carvedilol on cachexia in severe chronic heart failure: results from the COPERNICUS trial

Antioxidative Effects of Exercise Training in Patients With Chronic Heart Failure

Effects of Xanthine Oxidase Inhibition With Allopurinol on Endothelial Function and Peripheral Blood Flow in Hyperuricemic Patients With Chronic Heart Failure

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