Skeletal muscle dysfunction and exercise intolerance in heart failure
- Wilson S Colucci, MD
Wilson S Colucci, MD
- Section Editor — Heart Failure
- Professor of Medicine
- Boston University School of Medicine
The hallmark of heart failure (HF) is exercise intolerance due to dyspnea and fatigue. These symptoms were, in the past, thought to result entirely from central hemodynamic derangements, which might be reversed by inotropic agents and/or vasodilators. (See "Inotropic agents in heart failure with reduced ejection fraction" and "ACE inhibitors in heart failure with reduced ejection fraction: Therapeutic use".)
However, it is now clear that significant skeletal muscular pathology is also present in HF and may contribute to the associated symptoms . The evidence associating skeletal muscular abnormalities and exercise intolerance, and the beneficial effects of cardiac rehabilitation for patients with HF will be reviewed here. An overview of normal exercise physiology, the use of measurement of peak oxygen uptake (peak Vo2) to assess exercise capacity and prognosis, and the ability of cardiac rehabilitation to improve exercise capacity in patients with mild to moderate HF are discussed separately. (See "Exercise physiology" and "Exercise capacity and VO2 in heart failure" and "Cardiac rehabilitation in patients with heart failure".)
IMPACT OF MEDICAL THERAPY ON EXERCISE TOLERANCE
Exercise capacity is reduced even in mild heart failure. Exercise intolerance and fatigue may be the result of a reduction in cardiac output, which is due primarily to impaired myocardial function, and may be exaggerated by decreased plasma and blood volumes caused by excessive diuresis . Although the cardiac output may be relatively normal at rest, it is usually unable to increase adequately with even mild exertion . As in normal subjects, peak Vo2 in patients with heart failure (HF) is directly related to peak exercise cardiac output and muscle blood flow (figure 1). However, the inability to appropriately increase cardiac output in HF results in an insufficient increase in perfusion to exercising muscle, which can cause early anaerobic metabolism, an inadequate increase in muscle strength, and muscle fatigue .
With the success of medical therapy for HF in the early 1980s, several investigators evaluated the acute impact of inotropic agents and vasodilators on exercise capacity in patients with HF. As an example, one study evaluated 11 patients with New York Heart Association (NYHA) class III HF and a mean left ventricular ejection fraction (LVEF) of 20 percent who underwent exercise on a bicycle ergometer before and during infusion of dobutamine . Although dobutamine improved peak exercise cardiac output (6.5 versus 7.4 L/min, p <0.01) and reduced pulmonary capillary wedge pressure (PCWP), it failed to significantly increase exercise duration (5.5 versus 5.8 minutes).
Another study investigated the effect of the potent vasodilator hydralazine on blood flow to exercising skeletal muscle and exercise capacity in 10 patients with NYHA class III HF and a mean LVEF of 19 percent . Hydralazine, administered intravenously, substantially increased peak cardiac output during exercise on a bicycle ergometer (5.6 versus 6.7 L/min, p <0.01) and improved femoral venous flow, indicating improved femoral arterial flow and delivery of oxygen to the exercising skeletal muscle. However, maximal oxygen consumption (Vo2max) was unaffected because of a reduction in systemic and leg oxygen extraction after hydralazine administration.
- Kokkinos PF, Choucair W, Graves P, et al. Chronic heart failure and exercise. Am Heart J 2000; 140:21.
- Feigenbaum MS, Welsch MA, Mitchell M, et al. Contracted plasma and blood volume in chronic heart failure. J Am Coll Cardiol 2000; 35:51.
- Reddy HK, Weber KT, Janicki JS, McElroy PA. Hemodynamic, ventilatory and metabolic effects of light isometric exercise in patients with chronic heart failure. J Am Coll Cardiol 1988; 12:353.
- Harrington D, Anker SD, Chua TP, et al. Skeletal muscle function and its relation to exercise tolerance in chronic heart failure. J Am Coll Cardiol 1997; 30:1758.
- Wilson JR, Martin JL, Ferraro N. Impaired skeletal muscle nutritive flow during exercise in patients with congestive heart failure: role of cardiac pump dysfunction as determined by the effect of dobutamine. Am J Cardiol 1984; 53:1308.
- Wilson JR, Martin JL, Ferraro N, Weber KT. Effect of hydralazine on perfusion and metabolism in the leg during upright bicycle exercise in patients with heart failure. Circulation 1983; 68:425.
- Kugler J, Maskin C, Frishman WH, et al. Regional and systemic metabolic effects of angiotensin-converting enzyme inhibition during exercise in patients with severe heart failure. Circulation 1982; 66:1256.
- Wilson JR, Ferraro N. Effect of the renin-angiotensin system on limb circulation and metabolism during exercise in patients with heart failure. J Am Coll Cardiol 1985; 6:556.
- Franciosa JA, Goldsmith SR, Cohn JN. Contrasting immediate and long-term effects of isosorbide dinitrate on exercise capacity in congestive heart failure. Am J Med 1980; 69:559.
- Wilson JR, Ferraro N, Wiener DH. Effect of the sympathetic nervous system on limb circulation and metabolism during exercise in patients with heart failure. Circulation 1985; 72:72.
- Schaufelberger M, Andersson G, Eriksson BO, et al. Skeletal muscle changes in patients with chronic heart failure before and after treatment with enalapril. Eur Heart J 1996; 17:1678.
- Vescovo G, Dalla Libera L, Serafini F, et al. Improved exercise tolerance after losartan and enalapril in heart failure: correlation with changes in skeletal muscle myosin heavy chain composition. Circulation 1998; 98:1742.
- Clark AL, Poole-Wilson PA, Coats AJ. Exercise limitation in chronic heart failure: central role of the periphery. J Am Coll Cardiol 1996; 28:1092.
- Belardinelli R, Barstow TJ, Nguyen P, Wasserman K. Skeletal muscle oxygenation and oxygen uptake kinetics following constant work rate exercise in chronic congestive heart failure. Am J Cardiol 1997; 80:1319.
- Chati Z, Zannad F, Jeandel C, et al. Physical deconditioning may be a mechanism for the skeletal muscle energy phosphate metabolism abnormalities in chronic heart failure. Am Heart J 1996; 131:560.
- Toth MJ, Miller MS, Ward KA, Ades PA. Skeletal muscle mitochondrial density, gene expression, and enzyme activities in human heart failure: minimal effects of the disease and resistance training. J Appl Physiol (1985) 2012; 112:1864.
- Southern WM, Ryan TE, Kepple K, et al. Reduced skeletal muscle oxidative capacity and impaired training adaptations in heart failure. Physiol Rep 2015; 3.
- Vescovo G, Volterrani M, Zennaro R, et al. Apoptosis in the skeletal muscle of patients with heart failure: investigation of clinical and biochemical changes. Heart 2000; 84:431.
- Duscha BD, Kraus WE, Keteyian SJ, et al. Capillary density of skeletal muscle: a contributing mechanism for exercise intolerance in class II-III chronic heart failure independent of other peripheral alterations. J Am Coll Cardiol 1999; 33:1956.
- Tsutsui H, Ide T, Hayashidani S, et al. Enhanced generation of reactive oxygen species in the limb skeletal muscles from a murine infarct model of heart failure. Circulation 2001; 104:134.
- Pette D. Metabolic heterogeneity of muscle fibres. J Exp Biol 1985; 115:179.
- Mancini DM, Coyle E, Coggan A, et al. Contribution of intrinsic skeletal muscle changes to 31P NMR skeletal muscle metabolic abnormalities in patients with chronic heart failure. Circulation 1989; 80:1338.
- De Sousa E, Veksler V, Bigard X, et al. Heart failure affects mitochondrial but not myofibrillar intrinsic properties of skeletal muscle. Circulation 2000; 102:1847.
- Massie B, Conway M, Yonge R, et al. Skeletal muscle metabolism in patients with congestive heart failure: relation to clinical severity and blood flow. Circulation 1987; 76:1009.
- Okita K, Yonezawa K, Nishijima H, et al. Skeletal muscle metabolism limits exercise capacity in patients with chronic heart failure. Circulation 1998; 98:1886.
- Massie BM, Simonini A, Sahgal P, et al. Relation of systemic and local muscle exercise capacity to skeletal muscle characteristics in men with congestive heart failure. J Am Coll Cardiol 1996; 27:140.
- Schaufelberger M, Eriksson BO, Grimby G, et al. Skeletal muscle alterations in patients with chronic heart failure. Eur Heart J 1997; 18:971.
- Chua TP, Ponikowski PP, Harrington D, et al. Contribution of peripheral chemoreceptors to ventilation and the effects of their suppression on exercise tolerance in chronic heart failure. Heart 1996; 76:483.
- Millard RW, Higgins CB, Franklin D, Vatner SF. Regulation of the renal circulation during severe exercise in normal dogs and dogs with experimental heart failure. Circ Res 1972; 31:881.
- Riede UN, Förstermann U, Drexler H. Inducible nitric oxide synthase in skeletal muscle of patients with chronic heart failure. J Am Coll Cardiol 1998; 32:964.
- Hambrecht R, Adams V, Gielen S, et al. Exercise intolerance in patients with chronic heart failure and increased expression of inducible nitric oxide synthase in the skeletal muscle. J Am Coll Cardiol 1999; 33:174.
- Walsh JT, Andrews R, Johnson P, et al. Inspiratory muscle endurance in patients with chronic heart failure. Heart 1996; 76:332.
- Meyer FJ, Borst MM, Zugck C, et al. Respiratory muscle dysfunction in congestive heart failure: clinical correlation and prognostic significance. Circulation 2001; 103:2153.
- Tikunov B, Levine S, Mancini D. Chronic congestive heart failure elicits adaptations of endurance exercise in diaphragmatic muscle. Circulation 1997; 95:910.
- Sullivan MJ, Higginbotham MB, Cobb FR. Increased exercise ventilation in patients with chronic heart failure: intact ventilatory control despite hemodynamic and pulmonary abnormalities. Circulation 1988; 77:552.
- Buller NP, Poole-Wilson PA. Mechanism of the increased ventilatory response to exercise in patients with chronic heart failure. Br Heart J 1990; 63:281.