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European Journal of Heart Failure 2001 3(1):47-52; doi:10.1016/S1388-9842(00)00087-8
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© 2001 European Society of Cardiology

Comprehensive local muscle training increases aerobic working capacity and quality of life and decreases neurohormonal activation in patients with chronic heart failure

Raija Tyni-Lennéa,*, Kerstin Denckera, Allan Gordonb, Eva Janssonc and Christer Sylvénb

a Department of Physical Therapy, Karolinska Institutet and Huddinge University Hospital Stockholm, Sweden
b Department of Cardiology, Karolinska Institutet and Huddinge University Hospital Stockholm, Sweden
c Departments of Clinical Physiology, Karolinska Institutet and Huddinge University Hospital Stockholm, Sweden

* Corresponding author. Department of Physical Therapy, Huddinge University Hospital, S-141 86 Stockholm, Sweden. Tel.: +46-8-5858-1941; fax: +46-8-5858-2190. E-mail address: raija.tyni-lenne{at}physio.hs.sll.se (R. Tyni-Lenné).


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 
Background: Beneficial training outcomes have been reported in patients with chronic heart failure (CHF) following leg exercise training. However, data from more comprehensive training programs are limited. The aim of this study was to test the hypothesis that exercise training applying the concept of comprehensive local muscle training can improve aerobic and functional working capacity as well as quality of life in patients with CHF.

Methods: Twenty-four men and women [age 63 ± 9 years (mean ± S.D.)] with stable, moderate chronic heart failure (left ventricular ejection fraction 30 ± 10%), were investigated in a randomized controlled study with a training group of 16 patients and a control group of 8 patients. The training was performed as an aerobic resistance training by activating all the main muscle groups, one at a time. The patients exercised for 1 h, three times per week for 8 weeks.

Results: Patient groups did not differ at baseline. Peak oxygen uptake (8%, P < 0.03), the distance walked in a 6-min walking test (11%, P < 0.002), the health-related quality of life (P < 0.001) and plasma norepinephrine levels at rest (32%, P < 0.003) and at submaximal intensities (P < 0.03) improved after training. No changes were found in the control group, except for decreased peak oxygen uptake (P < 0.02) and quality of life scores (P < 0.03).

Conclusions: Since comprehensive physical training activating a minor muscle mass at a time markedly improves exercise capacity and quality of life and reduces catecholamine levels, it can be recommended for the rehabilitation of patients with CHF under supervision of a physical therapist.

Key Words: Chronic heart failure • Exercise training

Received September 23, 1999; Revised March 20, 2000; Accepted April 25, 2000


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 References
 
Heart failure syndrome is rapidly becoming one of the most common cardiovascular disorders with considerable consequences for the costs of healthcare [1]. Heart failure is recognized by a constellation of signs and symptoms produced by complex circulatory and neurohormonal responses to cardiac dysfunction [1]. Despite advanced pharmacological therapy, patients with chronic heart failure (CHF) are still characterized by exercise intolerance [2,3], excessive sympathetic activation associated with prognostically unfavorable effects [4,5] and poor quality of life [6].

The exercise intolerance in these patients is suggested as a consequence of a complex interaction between central hemodynamic and peripheral factors [2,7]. Different modes of aerobic exercise training activating lower extremities have shown to improve exercise capacity in men and women with CHF [3,6,8,9]. Improvements have been suggested to be due mainly to peripheral adaptations, like in the pathway of delivery of oxygen to the exercising muscles [3,8], raising the possibility of improving exercise tolerance by peripherally acting exercise training.

Local muscle training allows close to maximal skeletal muscle training with beneficial peripheral adaptations without pushing the cardiac capacity to its limits in patients with CHF [6,7]. However, since training-induced adaptations in skeletal muscle and vascular function occur mainly in the region of the trained muscles [10,11], all the major muscle groups should be trained. This might be done safely by applying the concept of local muscle training in a comprehensive training program. Our group has previously shown improved exercise capacity and quality of life as well as decreased plasma catecholamines following local muscle training in patients with CHF [6,12]. Training involving a minor muscle mass at a time was found to be even more efficient than training involving a large muscle mass at a time [12].

As of yet, the most appropriate forms of exercise therapy for patients with CHF are not known [3]. The aim of this study was to test the hypothesis that comprehensive exercise training, applying the concept of local training, can increase aerobic and functional working capacity and quality of life in patients with stable CHF.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 References
 
2.1. Patients and study design
Twenty-four consecutive patients with moderate CHF gave their informed consent to participate in the trial approved by the local Ethics Committee. The patients were allocated to either exercise training or control group using a 2:1 randomization strategy.

The diagnosis of chronic heart failure had been based on symptoms of dyspnea, general fatigue and congestion; medication with diuretics, angiotensin-converting enzyme inhibitors and digoxin; and an echocardiographically determined ejection fraction at rest of <40%. The main inclusion criteria were medically stable, chronic heart failure in New York Heart Association (NYHA) class II or III [13] for at least 3 months before the study. The exclusion criteria were angina pectoris, valvular heart disease determined by Doppler echocardiography, and co-morbidity such as intermittent claudication, diabetes mellitus, chronic obstructive pulmonary disease, or any other disorder limiting physical performance other than heart failure.

2.2. Patient characteristics
Patient characteristics were similar in the training and control groups (Table 1) and the variables did not differ between the groups at baseline.


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  		Table 1 Baseline characteristicsa

 
The patients had received ordinary medical care and counseling concerning drug use, diet, alcohol consumption, smoking and physical activities prior to the study and were encouraged not to change their lifestyle during the study period. The pharmacological treatment generally remained stable. However, the dose of diuretics was increased during the training period in one of the female patients.

2.3. Exercise test protocol
The patients performed symptom-limited cardiopulmonary exercise test on an upright cycle ergometer. Stepwise work rate increments of 10 W every minute to exhaustion were employed [14]. The respiratory gas exchange was recorded continuously by an on-line system (Ametek, Thermox, Instr. Div., Pittsburgh, PA, USA), with ventilation measured by an impeller.

Blood samples were taken from an antecubital vein before, every other minute during, and at the end of the incremental cycle ergometer exercise test to determine circulating blood lactate and plasma norepinephrine concentrations. The blood lactate concentration was determined in neutralized perchloric acid extracts using an enzymatic fluorometric technique [15] and plasma norepinephrine using HPLC with electrochemical detection [16]. Blood samples were not adequate for analysis in two of the training patients and in one of the controls.

2.4. Six-minute walk test
A standardized 6-min corridor walking test was performed [6,17] and the heart rate (determined by Sport Tester, Polar Electro Oy, Kempele, Finland), the perceived exertion rated on the Borg RPE scale [18], and the distance walked were recorded.

2.5. Quality of life measurement
Self-reported data on the perceived quality of life was collected with the disease-specific Minnesota Living with Heart Failure Questionnaire (LIhfe) [19]. Lower LIhfe scores are indicative of a better quality of life.

2.6. Training protocol
Exercise training was carried out as an outpatient activity in a group under the supervision of a physical therapist three times per week for 8 weeks.

The exercise started with a warm-up period of 6 min consisting of easy arm and leg movements without resistance. This was followed by 45 min of actual training. After that a cool-down period of 9 min with easy arm and leg movements with no resistance and stretching of the engaged muscle groups took place. This gives a total training time of 60 min.

In the training protocol the patients performed continuously repetitive muscle contractions against a resistance provided by the rubber band (Thera-Band). One muscle group at a time was trained without any rest. The protocol started with 25 repetitions of an exercise for a muscle group in the right arm and was directly followed by the same exercise of the left arm. This was repeated one more time so that each separate exercise was performed two times 25 repetitions/side. The protocol was continued alternating exercises for different arm, leg and trunk muscles. The frequency was 70 b.p.m. set by the pace of the music played during the training session.

The patients were instructed to have such a work load that their central exertion was scored 13 or less and peripheral muscular exertion from 13 to 16 on the Borg RPE Scale [18]. When the peripheral exertion was scored less than 13, the resistance was increased individually by changing Thera-Band. Thera-Bands are available in six different colors corresponding to six different grades of resistance allowing individually suitable resistance and thus graded increase in workload.

2.7. Statistical analysis
Unless otherwise stated, data are presented as the mean±S.D. and the median and (range). An unpaired Student's t-test and Mann–Whitney U-test were used to compare baseline characteristics between the groups. For physiological variables, two-factor (before/after measure, group) analyses of variance (ANOVA) was used to evaluate inter-group differences in change and paired Student's t-test to evaluate change within the group. To evaluate treatment effect in quality of life variables, the Wilcoxon's signed ranks test was used. Statistical significance was defined as P<0.05.


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 References
 
3.1. Exercise capacity
The resting and peak heart rate and systolic blood pressure did not change in any of the groups (Table 2). Peak work rate (13%), and peak oxygen uptake (8%) increased in the training group, while peak oxygen uptake decreased (10%) in the control group during the period of 8 weeks (Table 2, Fig. 1).


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  		Table 2 Exercise capacitya

 


Figure 01
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  		Fig. 1 Peak oxygen uptake before (open bars) and after (solid bars) the control (left panel) and training periods (right panel). Values are given as mean±S.D. Training improved peak oxygen uptake (P<0.03) with intergroup difference in improvement (P<0.005).

 
In the training and in the control group, respectively, plasma lactate levels at rest (from 0.9±0.2 to 1.0±0.2 and from 1.1±0.3 to 1.0±0.2 mmol/l, respectively) and at the 50% intensity of baseline peak performance (from 1.1±0.2 to 1.2±0.2 and from 1.4±0.6 to 1.3±0.5 mmol/l, respectively) did not change.

3.2. Catecholamines
Plasma norepinephrine levels decreased at rest (26%) and at submaximal intensities of 25 and 50% of baseline peak performance in the training group, while no change was found in the control group (Fig. 2).


Figure 02
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  		Fig. 2 Plasma norepinephrine concentrations at rest and during incremental cycle ergometer exercise tests before (open circles) and after (solid circles) the control (left panel) and training periods (right panel). Mean±S.D. are given for work rates corresponding to rest and 25, 50, 75 and 100% of the baseline peak work rate. Training improved norepinephrine concentrations (**P<0.01).

 
3.3. Functional capacity and quality of life
The distance walked during a 6-min walking test increased (11%) in the training group, while no change was found in the control group (Table 3). Peak heart rate increased in the training group, while Borg ratings remained unchanged in both groups after the 6-min walking (Table 3). The health-related quality of life showed improvement in the training group, contrary to the control group, which showed deterioration during the same period (Table 3).


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  		Table 3 Functional capacity and quality of lifea

 
3.4. Compliance
All the patients completed the trial. No adverse effects occurred during the period of 8 weeks, apart from increased edema in one of the patients in the training group. Compliance, assessed as a percentage of the total number of training sessions attended, was 95%.


   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
References
 
The main muscle groups, one group at a time, can favorably be exercised in patients with CHF, by applying the concept of local muscle training as a comprehensive exercise program. Improved aerobic and functional working capacity and quality of life as well as decreased neurohormonal activation could be achieved without pushing the limited cardiac capacity to its limits by a training period of only 8 weeks.

Training adaptation in a healthy population usually requires a minimum of 4–6 weeks [20]. However, Kavanagh et al. [21] have suggested 16 weeks as the time required to attain peak training response in patients with CHF, indicating that a longer training period in this study might have further improved the outcomes. The average age of the patients in the present study was higher than in previous studies conducted by other investigators [3,8,9]. Since younger individuals tend to have a greater capacity for training adaptation than older individuals [20], the results of this study might have been even better in the population comparable in age with previous studies [3,8,9]. This study differed regarding the gender of the population as well. Previous studies mainly included male patients [3,8,9,22,23]. Although left ventricular dysfunction is more common in the male population than in the female, the prevalence of heart failure is similar in both genders [1]. Therefore, and since we have previously demonstrated effectiveness of physical training in women with CHF as well as in men [6,24,25], exclusion of women from training cannot be motivated any longer.

A reduction of hormonal stress, as indicated by reduced plasma norepinephrine concentrations, was noted at submaximal work intensities in the present study as previously demonstrated by us [6] and others [8,9,24]. A decrease in plasma norepinephrine concentration at rest was also found. Some previous studies have shown similar changes [8,25], while we and others applying a shorter training time and duration have previously failed to lower plasma norepinephrine concentration at rest [6,9]. Hambrecht et al. [8] showed remarkable reduction in plasma norepinephrine concentration at rest, after daily exercise lasting more than 40 min during a 6-month period. The reduction in plasma norepinephrine concentration at rest may reflect the total training time. Even though the training period in the present study as well as in our previous studies was only 8 weeks, the exercise time in each training session in this study was three times the time of our previous studies [6]. No relation between neurohormonal activation during exercise and improved exercise capacity has been suggested [8,25–28]. However, a reduction in plasma norepinephrine concentration at rest is an important training outcome, since sympathetic overactivity, found in patients with CHF, has been demonstrated to contribute to the further progression of the heart failure syndrome [4,5].

In contrast to our previous findings of local muscle training, when only quadriceps muscles were activated followed by relaxation after each contraction [24], the patients in the present program did not improve in blood lactate levels. In the present training program, the concentric contraction was followed by an eccentric contraction without relaxation. Increase of the relaxation component during or at the end of the program during the cool down period might be of value for lactate levels and should be tested in further studies.

The present study shows improvement in exercise capacity and in the health-related quality of life after physical training while non-training patients deteriorated during the same 8-week period. The exercise mode should reflect the purpose of the program [20]. Since patients with CHF suffer from physical and psychosocial limitations caused by reduced exercise capacity and disability in different activities [6], all the major muscle groups used in daily life should be trained. Improvement in aerobic working capacity as well as in specific activities of the daily life may be of great impact on the quality of life.

Local muscle training allows close to maximal skeletal muscle work with beneficial peripheral adaptations without pushing the cardiac capacity to its limits [7] in patients with CHF. This type of training program can be tailored to improve endurance in specific activities of daily living. It could not improve only ability in activities of the lower extremities like walking, but also activities of the upper extremities and other parts of the body needed in daily life.

4.1. Limitation of the study
The training time in this study was only 8 weeks, which can be considered as the main limitation of the study. However, a shorter training time like this allows high compliance and makes it possible to keep medical and other conditions stable during the study period. Further studies with a similar type of program but with longer training period are motivated.

4.2. Conclusions
The aim of physical training in patients with CHF should be to improve quality of life and exercise capacity. This comprehensive training program applying the concept of aerobic local muscle training improved aerobic as well as functional capacity and the health-related quality of life, while neurohormonal activation was reduced. Therefore, it can be recommended for men and women with stable CHF.


   Acknowledgements
 
This study was supported by grants from the Medical Research Council and the Committee for Health and Caring Sciences, Karolinska Institutet, Sweden.


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

  1. Mosterd A., Hoes A.W., de Bryune M.C., et al. Prevalence of heart failure and left ventricular dysfunction in the general population. The Rotterdam study. Eur Heart J (1999) 20:447–455.[Abstract/Free Full Text]
  2. Sullivan M.J., Hawthorne M.H. Exercise intolerance in patients with chronic heart failure. Prog Cardiovasc Dis (1995) 38:1–22.[CrossRef][Web of Science][Medline]
  3. Coats A.J.S. Optimizing exercise training for subgroups of patients with chronic heart failure. Eur Heart J (1998) 19(Suppl_O):O29–O34.[Web of Science][Medline]
  4. Rector S.T., Olivari M.T., Levine T.B., Francis G.S., Cohn J.N. Predicting survival for an individual with congestive heart failure using plasma norepinephrine. Am Heart J (1987) 114:148–152.[CrossRef][Web of Science][Medline]
  5. Cohn J., Levine T., Olivari M. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl Med (1984) 311:819–823.[Abstract]
  6. Tyni-Lenné R., Gordon A., Europe E., Jansson E., Sylvén C. Exercise-based rehabilitation improves skeletal muscle capacity, exercise tolerance and quality of life in women as well as in men with chronic heart failure. J Card Failure (1998) 4:9–17.[Medline]
  7. Sylvén C. Skeletal muscle in heart failure. Cardiologia (1997) 42:1139–1144.[Medline]
  8. Hambrecht R., Niebauer J., Fiehn E., et al. Physical training in patients with chronic heart failure: effects of cardiorespiratory fitness and ultrastructural abnormalities of leg muscles. J Am Coll Cardiol (1995) 25(6):1239–1249.[Abstract]
  9. Belardinelli R., Georgiou D., Scocco V., Barstow T., Pucaro A. Low intensity exercise training in patients with chronic heart failure. J Am Coll Cardiol (1995) 26:975–982.[Abstract]
  10. Åstrand P.-O. Why exercise? Med Sci Sports Exerc (1991) 24:153–162.[Web of Science]
  11. Huonker M., Halle M., Keul J. Structural and functional adaptations of the cardiovascular system by training. Int J Sports Med (1996) 3(Suppl 17):164–172.
  12. Tyni-Lenné R., Gordon A., Jensen-Urstad M., Dencker K., Jansson E., Sylvén C. Aerobic training involving a minor muscle mass shows greater efficiency than training involving a major muscle mass in chronic heart failure patients. J Card Failure (1999) 5:300–307.[CrossRef][Web of Science][Medline]
  13. The Criteria Committee of the New York Heart Association, Inc. Diseases of the heart and blood vessels; Nomeclature and criteria for diagnosis, 6th ed. Boston: Little, Brown, 1964.
  14. Åström H., Jonsson B. Designed exercise test with special reference to heart patients. Br Heart J (1976) 3:289–296.
  15. Lowry O.H., Passoneau J.V. A flexible system for enzymatic analysis (1972) New York: Academic Press.
  16. Hjemdahl P. Catecholamine measurements in plasma by high-performance liquid chromatography with electrochemical detection. Methods Enzymol (1987) 142:521–534.[Web of Science][Medline]
  17. Guyatt G. Use of the six-minute walk test as an outcome measure in clinical trials in chronic heart failure. Heart Failure (1987) 21:211–217.
  18. Sylvén C., Borg G., Holmgren A., Åström H. Psychophysical power functions of exercise limiting symptoms in coronary heart disease. Med Sci Sports Exerc (1991) 23:1050–1054.[Web of Science][Medline]
  19. Rector S.T., Kubo S.H., Cohn J.N. Validity of the Minnesota Living with Heart Failure Questionnaire as a measure of therapeutic response to enalapril or placebo. Am J Cardiol (1993) 71:1106–1107.[CrossRef][Web of Science][Medline]
  20. Fardy P.S., Yanowitz F.G. Cardiac rehabilitation, adult fitness, and exercise testing (1995) Baltimore: Williams & Wilkins.
  21. Kavanagh T., Myers M.G., Baigrie R.S., Mertens D.J., Sawyer P., Shephard R.J. Quality of life and cardiorespiratory function in chronic heart failure: effects of 12 months aerobic training. Heart (1996) 76:42–49.[Abstract/Free Full Text]
  22. Belardinelli R., Georgiou D., Scocco V., Barstow T.J., Purcaro A. Low intensity exercise training in patients with chronic heart failure. J Am Coll Cardiol (1995) 26:975–982.[Abstract]
  23. Demopoulos L., Bijou R., Fergus I., Jones M., Strom J., LeJemtel T. Exercise training in patients with severe congestive heart failure: enhancing peak aerobic capacity whilst minimizing the increase in ventricular wall stress. J Am Coll Cardiol (1997) 29:597–603.[Abstract]
  24. Tyni-Lenné R., Gordon A., Janssson E., Bermann G., Sylvén C. Skeletal muscle endurance training improves peripheral oxidative capacity, exercise tolerance and health-related quality of life in women with chronic congestive heart failure secondary to either ischemic cardiomyopathy or idiopathic dilated cardiomyopathy. Am J Cardiol (1997) 80:1025–1029.[CrossRef][Web of Science][Medline]
  25. Tyni-Lenné R., Jansson E., Sylvén C. Female-related skeletal muscle phenotype in patients with moderate chronic heart failure before and after dynamic exercise training. Cardiovasc Res (1999) 42:99–103.[Abstract/Free Full Text]
  26. Coats A., Adamopoulos S., Radaelli A., et al. Controlled trial of physical training in chronic heart failure. Exercise performance, hemodynamics, ventilation and autonomic function. Circulation (1992) 85:2119–2131.[Abstract/Free Full Text]
  27. Sullivan M., Higginbotham M., Cobb F. Exercise training in patients with severe left ventricular dysfunction. Circulation (1988) 78:506–515.[Abstract/Free Full Text]
  28. Kiilavuori K., Sovijärvi A., Näveri H., Ikonen T., Leinonen H. Effect of physical training on exercise capacity and gas exchange in patients with chronic heart failure. Chest (1996) 110:985–991.[CrossRef][Web of Science][Medline]

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