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(Circulation. 1995;91:559-561.)
© 1995 American Heart Association, Inc.

Articles

Exercise Intolerance in Heart Failure

Importance of Skeletal Muscle

John R. Wilson, MD

From the Cardiology Division, Vanderbilt University Medical Center, Nashville, Tenn.

Correspondence to John R. Wilson, MD, Cardiology Division, RM CC-2218 MCN, Vanderbilt University Medical Center, Nashville, TN 37232-2170.

Key Words: Editorials • heart failure • muscles • exercise • respiration

	Introduction

Top Introduction References

 
For over a century, investigators have sought to define the mechanisms responsible for exercise intolerance in heart failure. At the outset, this mission appeared a simple one. Exertional dyspnea was attributed to exercise-induced increases in pulmonary wedge pressure. Exertional fatigue was attributed to an inadequate cardiac output. Over the past decade, however, it has become clear that the link between cardiac dysfunction and exertional symptoms in heart failure is far more complex. This understanding has led investigators to explore novel treatment options in heart failure. In this issue of Circulation, Mancini and coworkers describe one such new treatment option: selective respiratory muscle training.

At first glance, respiratory muscle training would appear of little value since it targets the skeletal muscle rather than the circulatory system. However, recent observations increasingly suggest that abnormalities of the skeletal muscle system are important contributors to exertional symptoms in patients with heart failure. Indeed, there is growing evidence that the sensations of exertional fatigue and dyspnea are linked, in part, via the skeletal muscle system. The first evidence that noncirculatory factors contribute to exertional symptoms in heart failure came from observations that acutely altering hemodynamic parameters did not alter exertional symptoms. The traditional presumption that dyspnea is caused by elevated intrapulmonary pressures was tested by measuring symptomatic and ventilatory responses to exercise before and after pharmacologic manipulation of the pulmonary wedge pressure; excessive ventilatory levels during exercise have been viewed as a hallmark of lung dysfunction during exercise. Acute reductions in the pulmonary wedge pressure during exercise had no effect on ventilatory responses.¹ Moreover, the level of excessive ventilation during exercise had no relation to the resting or exercise-induced pulmonary wedge pressure.^{1 2}

Investigators have also noted a weak relation between flow abnormalities and the sensation of fatigue. Although as a group patients with heart failure have reduced leg blood flow during exercise,^{3 4} a substantial number of patients with fatigue exhibit normal leg flow responses to exercise.⁵ Acute pharmacologically induced increases in cardiac output do not improve exertional fatigue in heart failure. A variety of interventions have been tested, including angiotensin converting enzyme inhibitors, -blockers, hydralazine, and inotropic agents.^{6 7 8 9 10 11} In these studies, patients typically underwent maximal exercise testing before and after the interventions. Although such interventions increased both cardiac output and leg blood flow, patients had no improvement in their maximal exercise capacity, sensation of leg fatigue, or leg lactate release.

Further evidence that exertional fatigue in heart failure is not wholly due to inadequate muscle flow comes from studies of skeletal muscle metabolism. Using ³¹P magnetic resonance spectroscopy, several investigators have examined forearm and calf metabolic responses to local limb exercise.^{12 13 14 15 16} They observed that muscle pH and phosphocreatinine concentration decreased more rapidly in patients with heart failure than in normal subjects. When flow to the exercising limb was measured, however, there was no evidence of inadequate muscle perfusion, leading to the general suspicion that the skeletal muscle of patients with heart failure is somehow altered by heart failure.

These suspicions were subsequently confirmed by biopsy studies. Several groups independently reported abnormal histochemistry and enzyme levels in the leg muscles of patients with heart failure. These abnormalities included shifts from slow-twitch to fast-twitch fiber types, atrophy of the fast-twitch type II fibers, reduced levels of mitochondrial enzymes, and reduced mitochondrial size.^{14 17 18 19} Minotti et al²⁰ also noted that quadriceps muscle endurance was impaired in patients with heart failure independent of limb blood flow.

Similar abnormalities have been observed in respiratory muscle of patients with heart failure. Lindsay et al²¹ observed a variety of histological abnormalities in the diaphragmatic muscle of patients with heart failure. Both Hammond et al²² and McParland et al²³ noted reductions in maximal inspiratory and expiratory pressures that were consistent with respiratory muscle weakness.

These observations raised the possibility that exertional symptoms in heart failure could be improved by altering skeletal muscle performance. This hypothesis was initially tested by using whole-body exercise training, an obvious intervention since the leg muscle changes noted in heart failure were thought to be caused by deconditioning. Sullivan et al²⁴ enrolled a group of patients in a standard cardiac rehabilitation program and noted that this intervention significantly improved peak exercise oxygen consumption, skeletal muscle lactate release during exercise, and ventilatory responses to exercise. No change in hemodynamic responses to exercise was found. Coats et al²⁵ randomized 17 patients to a home bicycle exercise program in a randomized crossover study and noted that even this unsupervised approach led to improved maximal exercise capacity, reduced ventilatory responses to exercise, and patients' subjective feelings of improvement during normal daily activities.

Mancini and coworkers sought to apply the same approach to the respiratory muscles. In a previous study, they observed²⁶ that maximal voluntary ventilation is decreased in patients with heart failure, whereas diaphragmatic work during exercise is markedly increased. They speculated, therefore, that an intervention designed to improve the strength of respiratory muscle might reduce the sensation of dyspnea. Their results basically support this hypothesis. Although only a relatively small number of patients were studied, a carefully designed respiratory muscle training regimen significantly increased maximal inspiratory and expiratory pressure, maximal voluntary ventilation, and both 6-minute walk time and peak exercise O₂. The effect on maximum sustainable ventilatory capacity was particularly striking, with average increases of almost 50% and a dramatic reduction in the sensation of dyspnea during the test.

Taken together, these changes represent an important finding and raise the possibility that a home-based program designed to train respiratory muscles may improve the exercise capacity of selected patients. The training program used in the study was aggressive and difficult, as shown by the fact that 6 of the 14 study patients elected to drop out of the study. However, it is possible that a less aggressive program could achieve the same results. For example, home use of a small inspiratory muscle trainer alone may have beneficial effects.

We hope that a randomized, controlled study of such a simplified regimen will be undertaken. In the meantime, it is important to emphasize that, although impressive, the findings of the present study by Mancini et al must be interpreted with caution until confirmed by additional studies. Although peak exercise capacity was improved by respiratory muscle training, the ventilatory response to exercise and the degree of dyspnea noted during bicycle exercise were unchanged. As emphasized by Mancini et al, the lack of a true control group is also cause for concern. It is possible that the improvements observed in exercise performance and symptoms were primarily due to the close attention given to the patients. Indeed, a number of placebo-controlled studies of pharmacologic agents have demonstrated improvements in exercise performance in the placebo group similar to those noted following respiratory muscle training.

Despite these potential limitations, the results of the trial are sufficiently intriguing to warrant continuing work. The results also serve to emphasize that exercise intolerance in heart failure must be viewed as a product of both skeletal muscle and cardiovascular dysfunction. To optimally treat exercise intolerance in heart failure, improving skeletal muscle characteristics may be just as important as altering the cardiovascular system.

	Footnotes

 
The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.

	References

Top Introduction References

 

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3. Wilson JR, Martin JL, Schwartz D, Ferraro N. Exercise intolerance in patients with chronic heart failure: role of impaired nutritive flow to skeletal muscle. Circulation. 1984;69:1079-1087. [Abstract/Free Full Text]
   
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