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

Abstract

Background: Evidence suggests that carvedilol decreases muscle sympathetic nerve activity (MSNA) in patients with heart failure (HF) but carvedilol fails to improve forearm vascular resistance and overall functional capacity. Exercise training in HF reduces MSNA and improves forearm vascular resistance and functional capacity. Aims: To investigate whether the beneficial effects exercise training on MSNA are maintained in the presence of carvedilol. Methods and results: Twenty seven HF patients, NYHA Class II-III, EF b 35%, peak VO 2 b20 ml/kg/min, treated with carvedilol were randomly divided into two groups: exercise training (n = 15) and untrained (n = 12). MSNA was recorded by microneurography. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. The four-month training program consisted of three 60-min exercise/ week on a cycloergometer. Baseline parameters were similar between groups. Exercise training reduced MSNA (− 14 ± 3.3 bursts / 100 HB, p = 0.001) and increased forearm blood flow (0.6 ± 0.1 mL/min/100 g, p b 0.001) in HF patients on carvedilol. In addition, exercise training improved peak VO 2 in HF patients (20 ± 6%, p = 0.002). MSNA, FBF and peak VO 2 were unchanged in untrained HF patients on carvedilol. Conclusion: Exercise training reduces MSNA in heart failure patients treated with carvedilol. In addition, the beneficial effects of exercise training on muscle blood flow and functional capacity are still realized in patients on carvedilol.

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

“…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.…”

Cardiac and peripheral autonomic control in restrictive cardiomyopathy

“…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.…”

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

“…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).…”

“…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).…”

“…These effects include reduction of sympathetic outflow in exercised humans (14,15) and animals (16)(17)(18) with HF. The sympathetic toxicity of cardiac (17)(18)(19)(20)(21) and skeletal (22)(23)(24) muscles in HF is also reduced by exercise training.…”