Exercise training reduces sympathetic nerve activity in heart failure patients treated with carvedilol

Fraga, Raffael F.; Franco, Fabio; Roveda, Fabiana; Matos, Laís Lopes Machado de; Braga, Adriano H.; Rondon, Maria Urbana Pinto Brandão; Rotta, Daniel R.; Brum, Patrícia Chakur; Barretto, Antônio Carlos Pereira; Middlekauff, Holly R.; Negräo, Carlos Eduardo

doi:10.1016/j.ejheart.2007.03.003

Cited by 116 publications

(120 citation statements)

References 54 publications

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“…Second, the effects of carvedilol on body weight may not have reflected a specific adrenergic effect on the metabolism of adipose tissue or skeletal muscle but may have been related to an increase in physical activity25, 26 or improvement in nutrition27 that might accompany a reduction in symptoms in heart failure. However, exercise tolerance has not been consistently improved with carvedilol in clinical trials in heart failure,28, 29, 30 and treatments that have improved symptoms and exercise tolerance have not produced striking effects on cachexia.…”

Section: Discussionmentioning

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: Discussionmentioning

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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“…The FBF was measured during 10 min of rest by venous occlusion plethysmography as previously described 28, 29. The nondominant arm was elevated above heart level to ensure adequate venous drainage.…”

Section: Methodsmentioning

confidence: 99%

Cardiac and peripheral autonomic control in restrictive cardiomyopathy

et al. 2017

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AimsAutonomic dysfunction determines the advance of dilated cardiomyopathy (DCM) and is related to poor outcomes. However, this autonomic imbalance is unknown in patients with restrictive cardiomyopathy (RCM) even though they have similar symptoms and poor quality of life as DCM patients have. The aim of this study was to evaluate if autonomic and neurovascular controls were altered in RCM patients.Methods and resultsFifteen RCM patients, 10 DCM patients, and 10 healthy subjects were evaluated. Heart rate and blood pressure (BP) were recorded. Peripheral sympathetic activity [muscle sympathetic nerve activity (MSNA)] by microneurography and cardiac sympathetic activity by power spectrum analysis of heart rate variability. Spontaneous baroreflex sensitivity (BRS) was evaluated by the sequence method and forearm blood flow by venous occlusion plethysmography. Both cardiomyopathy groups had higher MSNA frequency (P < 0.001) and MSNA incidence (P < 0.001), higher cardiac sympathovagal balance (P < 0.02), reduced BRS for increase (P = 0.002) and for decrease in BP (P = 0.002), and lower forearm blood flow (P < 0.001) compared with healthy subjects. We found an inverse correlation between BRS for increase and decrease in BP and peripheral sympathetic activity (r = −0.609, P = 0.001 and r = −0.648, P < 0.001, respectively) and between BRS for increase and decrease in BP and cardiac sympathetic activity (r = −0.503, P = 0.03 and r = −0.487, P = 0.04, respectively).ConclusionsThe RCM patients had cardiac and peripheral autonomic dysfunctions associated with peripheral vasoconstriction. Nonetheless, the presence of normal ejection fraction underestimates the evolution of the disease and makes clinical treatment difficult. These alterations could lead to a similar cardiovascular risk as that observed in DCM patients.

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“…The reduction of sympathetic activity by exercise training in HF patients is associated with a better clinical outcome (14,15). We have demonstrated by direct assessment of muscular sympathetic nerve activity that a 4-month period of moderate exercise training leads to a significant reduction in resting sympathetic activity (Figure 1) associated with improved peak oxygen uptake and exercise tolerance in class II and III New York Heart Association chronic HF patients (15).…”

Section: Effects Of Exercise Training On the Sympathetic Nervous Systemmentioning

confidence: 99%

“…Therefore, HF therapies that increase cholinergic activity (28) and/or decrease adrenergic hyperactivity (9) should combine exercise training to optimize the benefits on the cardiovascular system. In this context, we have demonstrated an additional reduction in muscular sympathetic nerve activity by exercise training in HF patients optimized with carvedilol, a third generation β-blocker (β 1 -and β 2 -blockade) with an α-blockade and vasodilatory effect (14). Additionally, while β-blocker therapy had no impact on exercise capacity in humans or animals with HF (6,9), a β-blocker combined with exercise training improved exercise capacity (14,19).…”

Section: Effects Of Exercise Training On the Sympathetic Nervous Systemmentioning

confidence: 99%

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Aerobic exercise training in heart failure: impact on sympathetic hyperactivity and cardiac and skeletal muscle function

Brum

Bacurau

Medeiros

et al. 2011

Braz J Med Biol Res

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Heart failure is a common endpoint for many forms of cardiovascular disease and a significant cause of morbidity and mortality. Chronic neurohumoral excitation (i.e., sympathetic hyperactivity) has been considered to be a hallmark of heart failure and is associated with a poor prognosis, cardiac dysfunction and remodeling, and skeletal myopathy. Aerobic exercise training is efficient in counteracting sympathetic hyperactivity and its toxic effects on cardiac and skeletal muscles. In this review, we describe the effects of aerobic exercise training on sympathetic hyperactivity, skeletal myopathy, as well as cardiac function and remodeling in human and animal heart failure. We also discuss the mechanisms underlying the effects of aerobic exercise training.

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Exercise training reduces sympathetic nerve activity in heart failure patients treated with carvedilol

Cited by 116 publications

References 54 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

Cardiac and peripheral autonomic control in restrictive cardiomyopathy

Aerobic exercise training in heart failure: impact on sympathetic hyperactivity and cardiac and skeletal muscle function

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