Fabiana Roveda

The effects of exercise training on sympathetic neural activation in advanced heart failure ☆: A randomized controlled trial

OBJECTIVES The goal of this study was to test the hypothesis that exercise training reduces resting sympathetic neural activation in patients with chronic advanced heart failure. BACKGROUND Exercise training in heart failure has been shown to be beneficial, but its mechanisms of benefit remain unknown. METHODS Sixteen New York Heart Association class II to III heart failure patients, age 35 to 60 years, ejection fraction < or =40% were divided into two groups: 1) exercise-trained (n = 7), and 2) sedentary control (n = 9). A normal control exercise-trained group was also studied (n = 8). The four-month supervised exercise training program consisted of three 60 min exercise sessions per week, at heart rate levels that corresponded up to 10% below the respiratory compensation point. Muscle sympathetic nerve activity (MSNA) was recorded directly from peroneal nerve using the technique of microneurography. Forearm blood flow was measured by venous plethysmography. RESULTS Baseline MSNA was greater in heart failure patients compared with normal controls; MSNA was uniformly decreased after exercise training in heart failure patients (60 +/- 3 vs. 38 +/- 3 bursts/100 heart beats), and the mean difference in the change was significantly (p < 0.05) greater than the mean difference in the change in sedentary heart failure or trained normal controls. In fact, resting MSNA in trained heart failure patients was no longer significantly greater than in trained normal controls. In heart failure patients, peak VO(2) and forearm blood flow, but not left ventricular ejection fraction, increased after training. CONCLUSIONS These findings demonstrate that exercise training in heart failure patients results in dramatic reductions in directly recorded resting sympathetic nerve activity. In fact, MSNA was no longer greater than in trained, healthy controls.

Increased muscle sympathetic nerve activity predicts mortality in heart failure patients

BACKGROUND Previous studies have associated neurohumoral excitation, as estimated by plasma norepinephrine levels, with increased mortality in heart failure. However, the prognostic value of neurovascular interplay in heart failure (HF) is unknown. We tested the hypothesis that the muscle sympathetic nerve activity (MSNA) and forearm blood flow would predict mortality in chronic heart failure patients. METHODS One hundred and twenty two heart failure patients, NYHA II-IV, age 50+/-1 ys, LVEF 33+/-1%, and LVDD 7.1+/-0.2 mm, were followed up for one year. MSNA was directly measured from the peroneal nerve by microneurography. Forearm blood flow was obtained by venous occlusion plethysmography. The variables were analyzed by using univariate, stepwise multivariate Cox proportional hazards analysis, and Kaplan-Meier analysis. RESULTS After one year, 34 pts died from cardiac death. The univariate analysis showed that MSNA, forearm blood flow, LVDD, LVEF, and heart rate were significant predictors of mortality. The multivariate analysis showed that only MSNA (P=0.001) and forearm blood flow (P=0.003) were significant independent predictors of mortality. On the basis of median levels of MSNA, survival rate was significantly lower in pts with >49 bursts/min. Similarly, survival rate was significantly lower in pts with forearm blood flow <1.87 ml/min/100 ml (P=0.002). CONCLUSION MSNA and forearm blood flow predict mortality rate in patients with heart failure. It remains unknown whether therapies that specifically target these abnormalities will improve survival in heart failure.

Exercise Training Restores Baroreflex Sensitivity in Never-Treated Hypertensive Patients

The effects of exercise training on baroreflex control of sympathetic nerve activity in human hypertension are unknown. We hypothesized that exercise training would improve baroreflex control of muscle sympathetic nerve activity (MSNA) and heart rate (HR) in patients with hypertension and that exercise training would reduce MSNA and blood pressure (BP) in hypertensive patients. Twenty never-treated hypertensive patients were randomly divided into 2 groups: exercise-trained (n=11; age: 46±2 years) and untrained (n=9; age: 42±2 years) patients. An age-matched normotensive exercise-trained group (n=12; age: 42±2 years) was also studied. Baroreflex control of MSNA (microneurography) and HR (ECG) was assessed by stepwise intravenous infusions of phenylephrine and sodium nitroprusside and analyzed by linear regression. BP was monitored on a beat-to-beat basis. Exercise training consisted of three 60-minute exercise sessions per week for 4 months. Under baseline conditions (before training), BP and MSNA were similar between hypertensive groups but significantly increased when compared with the normotensive group. Baroreflex control of MSNA and HR was similar between hypertensive groups but significantly decreased when compared with the normotensive group. In hypertensive patients, exercise training significantly reduced BP (P<0.01) and MSNA (P<0.01) levels and significantly increased baroreflex control of MSNA and HR during increases (P<0.01 and P<0.03, respectively) and decreases (P<0.01 and P<0.03, respectively) in BP. The baseline (preintervention) difference in baroreflex sensitivity between hypertensive patients and normotensive individuals was no longer observed after exercise training. No significant changes were found in untrained hypertensive patients. In conclusion, exercise training restores the baroreflex control of MSNA and HR in hypertensive patients. In addition, exercise training normalizes MSNA and decreases BP levels in these patients.

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

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.

Exercise training improves neurovascular control and functional capacity in heart failure patients regardless of age

Background: Exercise training is a non-pharmacological strategy for treatment of heart failure. Exercise training improves functional capacity and quality of life in patients. Moreover, exercise training reduces muscle sympathetic nerve activity (MSNA) and peripheral vasoconstriction. However, most of these studies have been conducted in middle-aged patients. Thus, the effects of exercise training in older patients are much less understood. The present study was undertaken to investigate whether exercise training improves functional capacity, muscular sympathetic activation and muscular blood flow in older heart failure patients, as it does in middle-aged heart failure patients. Design: Fifty-two consecutive outpatients with heart failure from the database of the Unit of Cardiovascular Rehabilitation and Physiology Exercise were divided by age (middle-aged, defined as 45–59 years, and older, defined as 60–75 years) and exercise status (trained and untrained). Methods: MSNA was recorded directly from the peroneal nerve using the microneurography technique. Forearm Blood Flow (FBF) was measured by venous occlusion plethysmography. Functional capacity was evaluated by cardiopulmonary exercise test. Results: Exercise training significantly and similarly increased FBF and peak VO2 in middle-aged and older heart failure patients. In addition, exercise training significantly and similarly reduced MSNA and forearm vascular resistance in these patients. No significant changes were found in untrained patients. Conclusion: Exercise training improves neurovascular control and functional capacity in heart failure patients regardless of age.