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European Journal of Heart Failure 2006 8(8):851-855; doi:10.1016/j.ejheart.2006.02.009
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© 2006 European Society of Cardiology

Effects of home-based exercise training on neurovascular control in patients with heart failure

Fábio Gazelato de Mello Francoa,*, Amilton C. Santosa, Maria Urbana P. Rondona, Ivani C. Trombettaa, Célia Strunza, Ana Maria W. Bragaa, Holly Middlekauffb, Carlos E. Negrãoa and Antônio C. Pereira Barrettoa

a Heart Institute (InCor), University of São Paulo Medical School São Paulo, Brazil
b Department of Cardiology, University of California Los Angeles, California

* Corresponding author. Tel.: +55 11 3069 5043. E-mail address: fabio.franco{at}incor.usp.br


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 
Background: The effect of home-based exercise training on neurovascular control in heart failure patients is unknown.

Aims: To test the hypothesis that home-based training would maintain the reduction in muscle sympathetic nerve activity (MSNA) and forearm vascular resistance (FVR) acquired after supervised training.

Methods and results: Twenty-nine patients (54±1.9 years, EF<40%) were randomised into two groups: untrained control (n=12) and exercise trained (n=17). Both groups underwent assessment of Quality of Life (QoL), MSNA, and forearm blood flow. The exercise group underwent a 4-month supervised training program followed by 4 months of home-based training. After the initial 4 months of training, patients in the exercise group showed a significant increase in peak VO2 and reduction in MSNA, compared to the untrained group, but this was not maintained during 4 months of home-based training. In contrast, the decrease in FVR (56±3 vs. 46±4 vs. 40±2 U, p=0.008) and the improvement in QOL that were achieved during supervised training were maintained during home-based training.

Conclusions: Home-based training following supervised training is a safe strategy to maintain improvements in QoL and reduction in FVR in chronic heart failure patients, but is an inadequate strategy to maintain fitness as estimated by peak VO2 or reduction in neurohumoral activation.

Key Words: Heart failure • Cardiopulmonary • Exercise training

Received October 2, 2005; Revised January 2, 2006; Accepted February 13, 2006


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 References
 
Several studies have demonstrated the benefits of supervised exercise training in patients with heart failure. Exercise training restores autonomic control [1,2], improves the oxidative capacity of peripheral muscles [3,4], and decreases the expression of some inflammatory markers [5,6]. These physiological adaptations seem to explain, at least in part, the improvement in functional capacity in patients with cardiac dysfunction. Bellardinelli et al. [7] showed that supervised training is also effective in improving quality of life (QoL) and prognosis in patients with heart failure. In addition, a supervised walking training program can maintain the benefits in QoL for at least 52 weeks in the absence of a formal home-based program [8].

Despite the accumulated knowledge about the benefits of exercise training in heart failure, the effects of home-based training on neurohumoral activation and peripheral blood flow, which are clinically important, are largely unknown. Firstly, norepinephrine levels correlate with mortality rate in heart failure patients, and muscle sympathetic nerve activity (MSNA) is an independent predictor of mortality in heart failure patients [9,10]. Secondly, supervised exercise training dramatically reduces MSNA in chronic heart failure patients [1]. Thirdly, home-based exercise training following a supervised exercise training period is the most realistic strategy for many chronic heart failure patients.

Data from the few studies dealing with home-based training in heart failure are controversial. The Exercise Rehabilitation Trial study (EXERT) [11] showed that a 9-month home-based training program was ineffective in maintaining gains in arm and leg strength achieved with supervised training in patients with heart failure, suggesting some degree of supervision is necessary. Conversely, Kiilavuori et al. [12] reported that home-based exercise training preserved improvements in exercise capacity and gas exchange for 3 months, after a 3-month supervised training program. In the present study, we describe the effects of 4 months of supervised exercise training followed by 4 months of home-based exercise training, on sympathetic activation, peripheral vascular resistance and quality of life (QoL) in patients with heart failure.

We hypothesized that 4 months of home-based exercise training, following 4 months of supervised training, would be sufficient to maintain fitness as estimated by peak oxygen uptake (VO2), as well as improvements in MSNA, forearm vascular resistance (FVR), and QoL in patients with heart failure.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 References
 
2.1. Study population
Twenty-nine patients with clinically stable heart failure, aged 35 to 60 years, NYHA Functional Class II-III, and ejection fraction ≤40% were invited to participate in the study. All patients had severe systolic heart dysfunction as determined by 2-dimensional echocardiography. Patients with unstable angina, a recent myocardial infarction (less than 3 months), severe chronic obstructive pulmonary disease, uncontrolled systemic arterial hypertension, and/or neurological or orthopaedic disabilities were excluded. The investigation conforms with the principles outlined in the Declaration of Helsinki. All patients gave written informed consent for this study, which was approved by the Human Subject Protection Committee of the Heart Institute (InCor) and Clinical Hospital, University of São Paulo Medical School.

2.2. Measurements and procedures
2.2.1. Blood pressure and heart rate
Baseline and exercise blood pressures were monitored non-invasively and intermittently from an automatic and oscillometric cuff (Dixtal, DX 2710, Brazil, Manaus). The cuff inflated every minute. Heart rate was monitored continuously through lead II of the ECG.

2.2.2. Muscle sympathetic nerve activity
MSNA was recorded directly from the peroneal nerve using the technique of microneurography [13,14]. Multiunit post-ganglionic muscle sympathetic nerve recordings were made using a tungsten microelectrode. Signals were amplified by a factor of 50,000 to 100,000 and bandpass filtered (700 to 2000 Hz). Nerve activity was rectified and integrated (time constant 0.1 second) to obtain a mean voltage display of sympathetic nerve activity that was recorded on paper.

2.2.3. Forearm blood flow
Forearm blood flow (FBF) was measured by venous occlusion plethysmography. The non-dominant arm was elevated above heart level to ensure adequate venous drainage. A mercury-filled silastic tube attached to a low-pressure transducer was placed around the forearm and connected to a plethysmograph (Hokanson, Bellevue, WA). Sphygmomanometer cuffs were placed around the wrist and upper arm. At 15-s intervals, the upper cuff was inflated above venous pressure for 7 to 8 s. Forearm vascular resistance (FVR) was calculated by dividing mean arterial pressure by FBF.

2.2.4. Exercise training protocol
The eligible patients were randomised into two groups: exercise trained (n=17) and untrained control group (n=12). The exercise trained group underwent 4 months of supervised exercise training. This phase consisted of three 60-min exercise sessions/week. Each session consisted of a 5-min warm-up period, 25 to 40 min of aerobic exercise on a cycle ergometer, 10 min of local strengthening exercises, and a 5-min cool-down period. The intensity of this supervised phase was determined by a cardiopulmonary exercise test, which established heart rate levels corresponding to an anaerobic threshold up to 10% below the respiratory compensation point [1]. The untrained patients were followed-up for 4 months during regularly scheduled clinic appointments.

After 4 months, exercise trained patients began exercise at home, at the same frequency and intensity as that performed during the supervised phase. The intensity of the home-based exercise training was controlled by heart rate. Fig. 1 summarizes the patient selection and follow-up.


Figure 1
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  		Fig. 1 Patient selection and dropouts TG=exercise trained group, UG=untrained control group.

 
2.2.5. Cardiopulmonary exercise testing
Maximal exercise capacity was determined by means of maximal exercise test on an electromagnetically braked cycle ergometer (Medifit 400 L, Medical Fitness Equipment, Maarn, Netherlands), using a ramp protocol with work rate increments of 5-10 W every minute until exhaustion. VO2 and carbon dioxide production was measured on a breath-by-breath basis using a computerized system (SensorMedics, Model Vmax 229, Buena Vista, CA, USA). Peak oxygen uptake (VO2) was defined as the maximum attained VO2 at the end of the exercise period in which the patient could not maintain the cycle ergometer velocity at 60 rpm. The anaerobic threshold was determined by the V-slope technique [15] or the point at which the ventilatory equivalent for oxygen and end-tidal oxygen partial pressure curves reached their respective minimum values and began to rise [16]. Respiratory compensation was determined to occur at the point at which the ventilatory equivalent for carbon dioxide was lowest before a systematic increase and when end-tidal carbon dioxide partial pressure reached a maximum and began to decrease [17].

2.2.6. Quality of life
QoL was evaluated using the Minnesota Living With Heart Failure questionnaire [18]. This instrument assesses how heart failure influences aspects of patients' daily life (e.g., psychological state, socioeconomic status, level of physical activity). Scores range from 0 to 100 points, with lower scores representing a better QoL.

2.2.7. Statistical analysis
Statistical analysis was performed using paired Student's t tests to compare within-group values before and after intervention, and unpaired Student's t tests to make between-group comparisons. One-way analysis of variance with repeated measures was used to evaluate multiple comparisons within exercise trained group. Chi-square or Fisher exact test was used for dichotomous variables. A p value of ≤0.05 was considered statistically significant. The data are presented as the mean±S.E.M.


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 References
 
Characteristics of the trained and untrained heart failure patients are shown in Table 1. There were no differences between heart failure patients randomised to the exercise training and the untrained groups for any of the parameters studied.


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  		Table 1 Baseline physiological parameters

 
3.1. Effects of supervised training
Supervised exercise training significantly increased QoL, peak VO2 and FBF (p=0.003, p=0.04 and p=0.01, respectively), and significantly decreased MSNA and FVR (p=0.007 and p=0.04, respectively). Left ventricular ejection fraction, mean blood pressure and heart rate did not change in the exercise trained patients. Parameters in the untrained patients were unchanged (Table 2).


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  		Table 2 Physiological parameters after supervised exercise training

 
3.2. Effects of home-based exercise training
The improvement in peak VO2 achieved during supervised training was not maintained during home-based training (Table 3). Similarly, the reduction in MSNA was no longer significant following the home-based training. QoL was maintained above baseline after 4 months of home-based exercise training (p=0.002, Table 3). FBF was maintained above and FVR below baseline after 4 months of home-based exercise training (p=0.03 and p=0.002, respectively, Table 3). Left ventricular ejection fraction, mean blood pressure, and heart rate were unchanged following the home-based exercise training when compared to baseline.


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  		Table 3 Physiological parameters at baseline, after 4 months of supervised exercise training and 4 months of home-based exercise training in heart failure patients

 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
References
 
The purpose of this study was to establish the effect of home-based exercise training following a supervised phase of training, on physical capacity as estimated by peak VO2 in heart failure patients. In addition, parameters of neurovascular control and QoL were measured. It was hypothesized that these parameters would change synchronously with changes in physical capacity. We found that the 4-month home-based exercise program was inadequate to maintain the improvements in physical capacity achieved during the 4-month supervised training program. Similarly, the reduction in MSNA levels was not maintained during the home-based program. Surprisingly, the reduction in FVR and improvement in QoL acquired after supervised exercise training were maintained following home-based exercise training.

The improvement in forearm blood flow after exercise training in heart failure patients has been previously demonstrated [1,19]. Our present study extends this observation by demonstrating that this effect can be maintained during home-based exercise training. This is an important finding because forearm blood flow, besides MSNA, is an independent predictor of mortality in heart failure patients [10]. This peripheral vascular adaptation may predominantly reflect an increase in endothelial function rather than a reduction in sympathetic activation, since the reduction in MSNA was not maintained.

The improvement in QoL has clinical implications for the role of home-based exercise training in heart failure patients. Kiilavuori [12] found that home-based training was effective in maintaining benefits in physical capacity obtained with supervised training in patients with heart dysfunction. Surprisingly, the EXERT study [11] failed to improve QoL in patients with heart failure after supervised exercise training and home-based training. It is possible that the duration of home-based training may explain the difference between studies. In Kiilavuori's [12] study home-based training was maintained for 3 months, while in the EXERT study it was maintained for 9 months. Although not addressed in the design of the present study, it would be interesting to know whether the beneficial effects on QOL and FVR derived from a supervised training program, would be maintained for 4 months in the absence of any formal home-based program.

The puzzle in this study is the loss of the effect on MSNA after home-based training. Why does MSNA tend to increase towards baseline levels, although compliance with the home-based training was very good? One explanation is that the patients did not maintain the same level of exercise intensity during the home training period. In fact, peak VO2 was reduced towards baseline levels during home-based training, which is consistent with this explanation. This finding raises some uncertainties about the maintenance of exercise training at home. It is also possible that the effects of exercise training on MSNA are progressively lost, in this group of sick patients. These are interesting issues for future investigation.

Resting bradycardia is a marker of exercise training adaptation in humans [20]. In our study, no reduction in resting heart rate was found. This finding can be attributed to the fact that most of our patients were receiving β-blocker treatment. It is unlikely that our training strategy was insufficient to provoke heart rate adaptation, because the same exercise training strategy significantly reduced resting heart rate in a previous study of heart failure patients [1].

4.1. Limitations
We recognize many limitations in our study. Although our patients reported that they followed the exercise training program precisely, there was no guarantee that the exercise intensity was maintained during the home-based exercise program. We do not know the effects of home-based exercise training on sympathetic activation and muscle vascular resistance without prior supervised exercise training period. The patients involved in home-based training were not randomised into home-based training or continued supervised training groups. Although the Minnesota Living with Heart Failure questionnaire is a well accepted instrument to assess the effect of heart failure on daily activity, there is some degree of subjectivity in this evaluation.

4.2. Perspectives
Home-based exercise training seems to be a safe and an inexpensive strategy for cardiac rehabilitation in chronic heart failure patients. Although home-based exercise training failed to maintain the reduction in MSNA and the increase in functional capacity, it sustained the improvement in QoL and the reduction in muscle peripheral resistance. These findings are particularly important in developing countries, where the incidence of heart failure is high and the public budget to treat patients suffering from heart failure is limited. Our findings demonstrate that home-based exercise training is, in fact, a safe non-pharmacological intervention for heart dysfunction. However, the effectiveness of home-based exercise training may depend upon a previous supervised training period and, in addition, the maintenance of exercise intensity.

In conclusion, home-based exercise training maintains the muscle vascular resistance reduction and QoL improvement acquired after 4 months of supervised exercise training and should be recommended in the treatment of patients with chronic heart failure.


   Acknowledgements
 
This study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP # 01/09476-0), and, in part, by Fundação Zerbini.


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 

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