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J Am Coll Cardiol, 2002; 40:1602-1608
© 2002 by the American College of Cardiology Foundation
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CLINICAL STUDY: CONGESTIVE HEART FAILURE

Selective low-level leg muscle training alleviates dyspnea in patients with heart failure

Ainat Beniaminovitz, MD*, Chim C. Lang, MD, FACC*, John LaManca, PhD* and Donna M. Mancini, MD*,*

* Division of Circulatory Physiology, Columbia Presbyterian Medical Center, New York, New York, USA

Manuscript received February 12, 2002; revised manuscript received April 24, 2002, accepted June 24, 2002.

* Reprint requests and correspondence: Dr. Donna M. Mancini, Division of Circulatory Physiology, Department of Medicine, Columbia Presbyterian Medical Center, 622 West 168th Street, New York, New York 10032, USA.
dmm31{at}columbia.edu


   Abstract
Top
 Abstract
Methods
 Results
 Discussion
 References
 
OBJECTIVES: The purpose of this study was to demonstrate in patients with moderate to severe heart failure that exertional dyspnea can be alleviated by improving muscle function.

BACKGROUND: Dyspnea is a frequent limiting symptom in patients with chronic heart failure (CHF). This sensation may originate from activation of receptors in the musculature rather than the lung.

METHODS: To investigate whether dyspnea could be alleviated by selective changes in leg muscle function, we performed isolated lower-limb training in 17 patients with severe CHF. Eight patients learned guided imagery relaxation techniques and served as an active control group. Exercise training consisted of three months of low-level bicycle and treadmill exercise such that minute ventilation was <25 l/min. Leg calisthenics were also performed. Maximal and submaximal exercise performance, respiratory and quadriceps muscle strength and endurance and quality-of-life and dyspnea scales were measured before and after each intervention. Metabolic stress testing (VO2), pulmonary function tests and isokinetic strength testing were also performed.

RESULTS: In the active control group, no changes in leg muscle function, pulmonary function, maximal and submaximal exercise performance or quality-of-life questionnaires were observed. In the training group, peak torque of leg flexors (pre: 39 ± 15 ft-lb; post: 50 ± 13 ft-lb; p < 0.002) increased and the fatigue ratio decreased, indicating improved strength and endurance of the leg muscles. Maximal inspiratory and expiratory mouth pressures and maximum voluntary ventilation were unchanged. Peak VO2 was increased (pre:12 ± 2.2 ml/kg/min; post: 14 ± 2.6 ml/kg/min) as well as the duration of exercise at 70% peak VO2 increased (pre: 11.5 ± 3.1 min; post: 21.5 ± 5.4 min; p < 0.003). Perceived dyspnea during the submaximal testing was decreased. Minnesota Living with Heart Failure Score, Guyatt Dyspnea Scale, and the Transitional Dyspnea Index were all improved with training (all p < 0.05).

CONCLUSIONS: We concluded that improvement of limb muscle function alleviates dyspnea and improves exercise performance in patients with CHF.

Abbreviations and Acronyms
  BP
  blood pressure
  CHF
  chronic heart failure
  HF
  heart failure
  HR
  heart rate
  MRT
  mean response time
  VO2
  oxygen consumption

Dyspnea is a frequent limiting symptom in patients with heart failure (HF). The main stimulus for dyspnea in these patients is unclear and is a subject of intense study. In acute HF, activation of J receptors in the lung by elevated pulmonary pressures and/or hypoxia are the primary stimuli (1). In chronic heart failure (CHF), it has been proposed that dyspnea originates from the stimulation of metaboreceptors in muscles, resulting in increased respiratory drive through central or peripheral mechanisms (2,3). Marked metabolic, histochemic and morphologic changes have been repeatedly demonstrated in the limb musculature of patients with HF, including a shift from oxidative to glycolytic metabolism with significant atrophy (4,5). Piepoli et al. (2) have demonstrated an exaggerated ventilatory response to stimulation of ergoreceptors that can be ameliorated with muscle training. Previously we have focused on the respiratory muscles and their role in producing dyspnea in patients with HF. Deoxygenation of the accessory respiratory muscles during exercise (6), increased work of breathing (7), diminished endurance (8), and decreased strength of the respiratory muscles (9) have been demonstrated in these patients. In addition, selective respiratory muscle training was associated with diminished dyspnea during submaximal exercise (10). However, it should be noted that these aerobic exercise-training programs often condition both respiratory and peripheral muscles, which can diminish the excessive ventilatory response to exercise (11,12). What is not known is whether selective training of limb muscles would have the same effects. The purpose of this study was to investigate whether dyspnea could be alleviated by selective exercise of leg muscles at a low level that does not condition the respiratory muscles. To do this, patients were carefully trained at a work load that did not increase the minute ventilation beyond 25 l/min.


   Methods
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 Abstract
 Methods
Results
 Discussion
 References
 
Patient population.   Twenty-nine patients were recruited and gave their written informed consent to participate in this study, which was approved by the Human Studies Committee at Columbia Presbyterian Hospital. A 2:1 randomization was performed for training versus active control groups. Nine patients were enrolled in an active control group and 20 patients in the training group. One patient did not complete the study in the control group and three in the training group; therefore, a total of 25 patients were studied. The baseline clinical characteristics of the patients are shown in Table 1. Age, gender, etiology of CHF, oxygen consumption (VO2), and left ventricular ejection fraction were similar in both groups.


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  		Table 1 Baseline Characteristics of Control and Training Groups

 
Active control group
To overcome the problem of patient bias, an active control group of patients with CHF learned guided imagery techniques, the results of which have been previously published (13). The patients attended 90-min, weekly therapist-guided sessions for 1 month and were taught a series of relaxation/imagery exercises that promoted stress reduction. The participants were provided with a 15-min tape of the images learned during the session and were instructed to listen to the tapes on an audiocassette at least twice daily. Patients were encouraged to perform the mental exercises twice daily.

Exercise training.   Supervised training sessions were conducted 3 times/week and consisted of 15 min each of bicycle and treadmill exercise at a workload corresponding to 50% of peak VO2 with a minute ventilation <25 l/min and a heart rate (HR) <120 beats/min. A series of leg calisthenics were performed, including hip flexion and extension with ankle weights (5 lb/leg) and thigh muscle contraction using therabands. Each month, an additional set of exercises was added and ankle weights were increased by 2 lb/leg. The resistance of the theraband was also increased.

Measurements before and after intervention.   A series of tests were performed before and after each intervention, including measures of maximal and submaximal exercise capacity, leg and respiratory muscle strength and endurance, muscle mass and assessment of dyspnea.

Cardiopulmonary testing
Maximal bicycle testing was performed by the patient in the fasting state. Respiratory gas analysis was measured continuously using a metabolic cart (Medical Graphics 2001, Minneapolis, Minnesota) via a disposable pneumotach. After we collected 3 min of rest data, exercise began at 0 W and increased by 25 W every 3 min until the patient reached exhaustion. Heart rate was monitored continuously and blood pressure (BP) recorded with each stage of exercise by cuff sphygmomanometry. Level of perceived dyspnea and fatigue using the modified Borg Scale (14) was recorded during each stage of exercise and at maximum exercise.

Submaximal exercise capacity was evaluated by measuring the duration of single load of exercise. The selected workload corresponded to 70% of peak VO2. Perceived dyspnea and fatigue was recorded every 5 min using the modified Borg scale. Oxygen kinetics (O2 kinetics) was determined using the O2 kinetics software (Medgraphics). The O2 deficit incurred between exercise initiation and the achievement of steady-state oxygen uptake during submaximal exercise was determined as previously described (15). It is calculated as the difference between the oxygen uptake apparently required and the actual oxygen uptake for the duration of the low level exercise. The mean response time (MRT) characterizes the ability of a subject to respond to a step change in work. MRT is calculated as the inverse of k, rate constant of the rise in O2 in the dimension of time (16), expressed in seconds. An unencouraged 6-min walk test was also performed.

Respiratory and leg muscle testing
Respiratory muscle strength was assessed by measuring maximum mouth pressures. Maximum inspiratory pressure was measured at residual volume whereas maximum expiratory pressure was assessed at total lung capacity. Maximum inspiratory and expiratory pressure were recorded in triplicate or until a stable value was achieved. A 15-s maximum voluntary ventilation was recorded to assess respiratory muscle endurance.

Leg muscle strength and endurance were assessed by isokinetic testing using a dynanonometer (Cybex, Ronkonkama, New York) as previously described (17). The resistance of the lever arm is automatically adjusted to the dynamic tension produced by the muscle throughout its range of motion and the device records torque during muscle contraction at a selected angular velocity. In this study, the dominant leg was tested. The subjects were positioned in the Cybex at 0° and their upper body movement restricted with a series of straps. The exercise protocol consisted of five maximal knee extensions and flexions at an angular velocity of 60° and 120°. The patient then performed 25 rapid contractions at the 120 speed. The fatigue ratio was defined as the average torque of the last three repetitions divided by the first three repetitions.

Anthropometric measurements were performed using Lange calipers (Cambridge Science Instruments, Cambridge, Massachusetts), and a standard tape measure was used to assess skeletal muscle mass. Skinfold thickness of the triceps and biceps of the nondominant arm, subscapular, suprailiac, and midthigh of the nondominant leg were recorded. Each skinfold measurement was estimated to the nearest 1 mm and the mean was calculated from three readings. The circumference of the thigh at one-half and two-thirds the distance from the iliac crest to the top of the patella were also recorded.

Dyspnea testing
Dyspnea was assessed using three different quality-of-life questionnaires (18–21). The Minnesota Living with Heart Failure Questionnaire queried patients on all aspects of life with CHF. The score for this 20-question questionnaire ranges from 0 to 100 with a lower score associated with a better quality-of-life. The Guyatt Respiratory Scale questionnaire was developed to assess specific areas of function important to patients with airflow limitations. A higher score denotes a better quality-of-life. The Transitional Dyspnea Scale specifically addresses a change in dyspnea from baseline function. Magnitude of effort task and function are assessed. A higher score denotes better functional capacity.

Statistical analysis.   Intragroup differences were compared by paired t testing and intergroup differences by unpaired t testing. A p value of <0.05 was considered statistically significant. All results are reported as mean ± standard error of the mean.


   Results
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 Abstract
 Methods
 Results
Discussion
 References
 
Cardiopulmonary parameters during maximal and submaximal exercise.   Peak VO2 and VO2 at anaerobic threshold was unchanged in the control group. However, significant increases were observed in training group. The HR and BP response to exercise was unchanged in both groups. The ventilatory response to exercise assessed as the ventilatory equivalent for carbon dioxide production at 1 l was also unchanged in both groups (Table 2) .


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  		Table 2 Maximal and Submaximal Exercise Performance in Control and Training Groups

 
Submaximal exercise performance assessed by the duration of a single load of exercise was unchanged in the control group but markedly improved in the training group (Fig. 1). During submaximal testing, O2 kinetics was only determinable in a subgroup of the patients (training, n = 5; and control, n = 4). MRT was significantly shorter (p = 0.05) and O2 deficit tended to be less in the training group when compared with the control group (Table 2). The 6-min walk test was significantly improved in the training but not in the control group (Table 2).



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  		Figure 1 Single-load exercise duration in the control and training groups before and after the intervention. The single workload corresponded to 70% peak oxygen consumption. Filled diamond = pretraining; filled square= post-training. *p < 0.001 pretraining versus post-training.

 
Leg and respiratory muscle strength and endurance.   Maximal inspiratory pressure and maximal expiratory pressure were unchanged in both the training or control groups. Similarly, respiratory muscle endurance assessed by a 15-s maximum voluntary ventilation was also unchanged in both groups (Table 3) .


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  		Table 3 Leg and Respiratory Muscle Strength, Endurance, and Anthropomorphic Measurements of Control and Training Groups

 
Peak flexor and extensor torque at 60° and 120° velocities at baseline were not significantly different between both groups. With training, peak flexor and extensor torque significantly increased in the training but not in the control group (Table 3). Endurance reflected by the fatigue ratio was unchanged for both flexors and extensors in the control group but was significantly improved with training (Table 3). Anthropometric measurements reflecting muscle mass and fat were unchanged in both groups.

Dyspnea testing.   Guided imagery did not significantly affect the scoring for the Minnesota Living with Heart Failure or Guyatt Respiratory Scales. Low-level training did significantly improve both quality-of-life scores (Table 4). The mean change in the Minnesota Living with Heart Failure score for the control group was 7 versus 13 in the low-level training group. The improvement in the transition score was significantly greater in the low-level training than the active control group.


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  		Table 4 Quality-of-Life Scales in the Control and Training Groups

 
Perceived dyspnea and fatigue during maximal exercise testing was unchanged in both groups. However, perceived dyspnea and fatigue were significantly lower during single load exercise in the training group (Fig. 2).



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  		Figure 2 Perceived dyspnea using the modified Borg scale during submaximal testing in the training group before and after training. Diamond = pretraining; square = post-training. *p < 0.05, pretraining versus post-training.

 

   Discussion
Top
 Abstract
 Methods
 Results
 Discussion
References
 
This study had the following main findings. First, low-intensity lower extremity training significantly improved lower-extremity strength and endurance and did not alter respiratory muscle function. Second, this selective exercise-induced change in lower-leg muscle function improved submaximal and maximal exercise performance and alleviated dyspnea in these patients with HF. Perceived dyspnea during a single load of exercise was significantly decreased with training. Quality-of-life scores were all improved by training. Thus, our study demonstrates that isolated modulation of peripheral skeletal muscle function favorably affects the sensation of dyspnea.

Muscle changes in CHF.   Skeletal muscle metabolic, histochemic, and morphologic changes have been described in patients with CHF (4,5). Similar changes have also been recently described in patients with severe obstructive lung disease (22,23). These skeletal muscle changes may result from a combination of deconditioning, malnutrition, inflammatory cytokine responses associated with chronic disease and/or episodic hypoxia to the muscle (4,5). In both CHF and chronic lung disease, the peripheral muscle may be the key transducer of the sensation of dyspnea and fatigue rather than the primary failing organ. Accumulation of metabolites during exercise in the skeletal muscle may lead to stimulation of metaboreceptors. Stimulation of interstitial nerve afferents can increase BP, increase vasoconstriction, alter skeletal muscle blood flow, and increase ventilatory response (2). Potential chemostimulants include adenosine, lactate, hydrogen ion, potassium, phosphate, and hypoxia (2,3). The muscle metaboreceptor has not been well characterized in patients with HF. Conflicting data exist whether hyperactivity of these metaboreceptors occur in patients with HF (2,3).

Mode of training in CHF.   Our low-intensity training protocol selectively improved lower-limb skeletal muscle strength and endurance without affecting ventilatory and respiratory muscle function. The absence of any detectable changes in any of the respiratory muscle strength and endurance parameters, such as maximal inspiratory pressure, maximal expiratory pressure, and MVV, supports a lack of a conditioning effect on respiratory muscles. Low-intensity training had significant benefits on both submaximal and maximal exercise performance. This is in agreement with previous studies that have shown aerobic training at 50% of peak VO2 to be efficacious in these patients (24–27). Hambrecht et al. (25) also demonstrated significant histochemic changes in the skeletal muscle with low-intensity training. The improvement in a single load of endurance, the shift in the anaerobic threshold and the reduction in O2 deficit observed in this study are consistent with improved oxidative capacity of the peripheral muscle.

The results of low-level training on sympathetic function has been variable, with some authors describing a decrease in resting heart rate and others reporting no change (25–27). In our study, HR and BP response was not affected suggesting absence of any autonomic effects.

Previous studies have suggested that low-intensity training may be beneficial for patients with HF by preventing a marked increase in myocardial wall stress with left ventricle overload, leading to further ventricular dilation (27). This caveat for high-intensity training does not have much clinical support (28) but in the extremely ill populations, low-level and/or small muscle mass training may be the only possible therapeutic approach. In patients with class IV CHF, a preliminary small muscle mass training program preceding aerobic training may indeed be beneficial.

The exercise program used in this study combined elements of isotonic and isometric exercise. The calisthenics and leg exercises using resistive bands impacted significantly on the peak muscle strength. The benefit of purely isometric training in patients with HF is unclear (29), although given the widespread muscle atrophy of these patients, it should impact favorably on both function and quality of life.

Effect of selective lower extremity training on dyspnea.   Quality-of-life scores were improved and perception of dyspnea alleviated by selective leg training, suggesting improved muscle metabolism as the underlying mechanism. Absence of significant changes in anthropometric measurements before and after training suggest that an increase in muscle mass did not produce these findings. The ventilatory response to exercise and respiratory muscle function again were not affected by this protocol, thus suggesting that local muscle changes accounted for the alleviation of dyspnea.

Previously, we reported on the benefit of selective respiratory muscle training in alleviation the sensation of dyspnea in patients with HF (10). How can we reconcile the findings of these two studies? Both studies support the importance of muscle function in determining the perception of dyspnea and fatigue during exercise. Whether both studies illustrate the effect of learning and the ability to adapt our personal discomfort threshold is unclear.

Active control group.   In this study, the active control group learned guided imagery techniques. Volitional central mechanisms can affect respiratory control and thus the sensation of dyspnea. On a physiologic level, mind-body techniques can decrease the resting metabolism of the body (30). Respiratory rate and oxygen consumption during the meditative state have been shown in some studies to be reduced (31). The use of yoga in a small group of patients with HF (32) demonstrated a significant improvement in exercise performance. Guided imagery is similar to meditation in its use of mental focusing to connect the mind and body and initiate a relaxation response and regulate respiration. Additionally, the control group had the benefit of group interaction with specialized attention. Despite this intervention, the sensation of dyspnea during submaximal or maximal exercise was unaffected confirming the reproducibility of the techniques.

Study limitations.   This study had several limitations. First, muscle biopsy data would have provided additional evidence to support leg muscle training effects. However, the efficacy of low-level training on muscle using biopsy techniques has been demonstrated in several studies (26,27). Accordingly, to increase patient recruitment and compliance, we opted for a totally noninvasive protocol. The increase in exercise endurance, muscle strength, and shift in anaerobic threshold in the trained but not in the control group supports a training effect. Second, any study focusing on an alteration in perception is limited by the lack of suitable instruments that can objectively measure sensations. We attempted to compensate for this by using multiple dyspnea scales and by using an active control group. Third, this study is limited in that it is not able to distinguish between alterations in metaboreceptors from alterations in the stimuli resulting from increased active muscle. However, in a recent study by Scott and colleagues (33), it was shown that the metaboreceptor component is probably more important than mechanoreceptors in the ventilatory response in patients with CHF. Lastly, one component of the exercise-training regimen included treadmill exercise and thus global involvement of the skeletal muscle system. However, the low levels of exercise should limit upper body activity.

Clinical implications.   This study provides additional evidence of the importance of the skeletal muscle in generating the symptoms of CHF. Therapeutic interventions targeted at altering muscle function such as those that improve muscle oxidative capacity (34,35), mass (36,37), and/or substrate utilization (38) may improve the quality of life and exercise performance in patients with CHF.


   Footnotes
 
Supported by a grant from the New York City American Heart Association Grant-in-Aid and the Division of Research Resources, General Clinical Research Centers Program, N.I.H. 5 M01 RR00645. Dr. Lang is a recipient of a Fulbright Visiting Scholar Award.


   References
Top
 Abstract
 Methods
 Results
 Discussion
 References
 

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