Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Mechanisms by which exercise training benefits patients with heart failure

Nature Reviews Cardiology volume 6, pages 292–300 (2009)Cite this article

Abstract

Clinical consequences of heart failure are fatigue, dyspnea, and progressive impairment of exercise tolerance. Regular exercise training is associated with health-improving effects. In patients with stable heart failure, exercise training can relieve symptoms, improve exercise capacity and quality of life, as well as reduce hospitalization and, to some extent, risk of mortality. Progressive exercise training is associated with pulmonary, cardiovascular, and skeletal muscle metabolic adaptations that increase oxygen delivery and energy production. This Review focuses on current knowledge of mechanisms by which progressive and moderate exercise training can have sustained beneficial effects on patients with heart failure.

Key Points

  • Exercise training is associated with reduction of sympathetic activity, an increase in parasympathetic tone, and reduced levels of circulating neurohormones in patients with stable heart failure

  • Exercise training can decrease generation of reactive oxygen species, restore endothelial function, and reduce peripheral resistance with improved left ventricular ejection fraction in patients with stable heart failure

  • Regular exercise training can have an anti-inflammatory effect in patients with stable heart failure by reducing inflammatory cytokines, platelet-related inflammatory mediators, and peripheral markers of endothelial dysfunction

  • Exercise training improves oxygen consumption and lactate threshold, and delays onset of anaerobic metabolism in skeletal muscle of patients with stable heart failure

  • Exercise training improves left ventricular ejection fraction, end-diastolic and systolic volumes, maximal heart rate, systolic blood pressure and cardiac output in patients with stable heart failure

  • Endurance and strength training, and moderate continuous training, are less effective than high intensity interval training, but training involving resistance and aerobic exercise might be the most beneficial regimen

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Pathobiological pathways induced by exercise training in patients with heart failure.

Similar content being viewed by others

References

  1. Jeger, R. V. et al. Ten-year trends in the incidence and treatment of cardiogenic shock. Ann. Intern. Med. 149, 618–626 (2008).

    Article  PubMed  Google Scholar 

  2. Remme, W. J. et al. Guidelines for the diagnosis and treatment of chronic heart failure. Eur. Heart J. 22, 1527–1560 (2001).

    Article  CAS  PubMed  Google Scholar 

  3. Franciosa, J. A., Park, M. & Levine, T. B. Lack of correlation between exercise capacity and indexes of resting left ventricular performance in heart failure. Am. J. Cardiol. 47, 33–39 (1981).

    Article  CAS  PubMed  Google Scholar 

  4. Piña, I. L. et al. Exercise and heart failure: A statement from the American Heart Association Committee on exercise, rehabilitation, and prevention. Circulation 107, 1210–1225 (2003).

    Article  PubMed  Google Scholar 

  5. Okita, K. et al. Skeletal muscle metabolism limits exercise capacity in patients with chronic heart failure. Circulation 98, 1886–1891 (1998).

    Article  CAS  PubMed  Google Scholar 

  6. Meyer, F. J. et al. Respiratory muscle dysfunction in congestive heart failure: clinical correlation and prognostic significance. Circulation 103, 2153–2158 (2001).

    Article  CAS  PubMed  Google Scholar 

  7. Thompson, P. D. et al. Exercise and physical activity in the prevention and treatment of atherosclerotic cardiovascular disease: a statement from the Council on Clinical Cardiology (Subcommittee on Exercise, Rehabilitation, and Prevention) and the Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity). Circulation 107, 3109–3116 (2003).

    Article  PubMed  Google Scholar 

  8. Myers, J. et al. Exercise capacity and mortality among men referred for exercise testing. N. Engl. J. Med. 346, 793–801 (2002).

    Article  PubMed  Google Scholar 

  9. Dorn, J., Naughton, J., Imamura, D. & Trevisan, M. Results of a multicenter randomized clinical trial of exercise and long-term survival in myocardial infarction patients: the National Exercise and Heart Disease Project (NEHDP). Circulation 100, 1764–1769 (1999).

    Article  CAS  PubMed  Google Scholar 

  10. Piepoli, M. F., Davos, C., Francis, D. P. & Coats, A. J. Exercise training meta-analysis of trials in patients with chronic heart failure (ExTraMATCH). BMJ. 328, 189 (2004).

    Article  CAS  PubMed  Google Scholar 

  11. Hunt, S. A. et al. ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society. Circulation 112, e154–e235 (2005).

    Article  PubMed  Google Scholar 

  12. van Tol, B. A., Huijsmans, R. J., Kroon, D. W., Schothorst, M. & Kwakkel, G. Effects of exercise training on cardiac performance, exercise capacity and quality of life in patients with heart failure: a meta-analysis. Eur. J. Heart Fail. 8, 841–850 (2006).

    Article  PubMed  Google Scholar 

  13. Ignarro, L. J., Balestrieri, M. L. & Napoli, C. Nutrition, physical activity, and cardiovascular disease: an update. Cardiovasc. Res. 73, 326–340 (2007).

    Article  CAS  PubMed  Google Scholar 

  14. Anand, I. S. Changes in brain natriuretic peptide and norepinephrine over time and mortality and morbidity in the Valsartan Heart Failure Trial (Val-HeFT). Circulation 107, 1278–1283 (2003).

    Article  CAS  PubMed  Google Scholar 

  15. Azevedo, E. R., Newton, G. E., Floras, J. S. & Parker, J. D. Reducing cardiac filling pressure lowers norepinephrine spillover in patients with chronic heart failure. Circulation 101, 2053–2059 (2000).

    Article  CAS  PubMed  Google Scholar 

  16. Benedict, C. R. et al. Relation of neurohumoral activation to clinical variables and degree of ventricular dysfunction: a report from the Registry of Studies of Left Ventricular Dysfunction. SOLVD Investigators. J. Am. Coll. Cardiol. 23, 1410–1420 (1994).

    Article  CAS  PubMed  Google Scholar 

  17. Ferrara, R. et al. Neurohormonal modulation in chronic heart failure. Eur. Heart J. Supplements 4, D3–D11 (2002).

    Article  CAS  Google Scholar 

  18. Nolan, J. et al. Decreased cardiac parasympathetic activity in chronic heart failure and its relation to left ventricular function. Br. Heart J. 67, 482–485 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ponikowski, P. et al. Depressed heart rate variability as an independent predictor of death in chronic congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am. J. Cardiol. 79, 1645–1650 (1997).

    Article  CAS  PubMed  Google Scholar 

  20. Ferguson, D. W., Berg, W. J., Roach, P. J., Oren, R. M. & Mark, A. L. Effects of heart failure on baroreflex control of sympathetic neural activity. Am. J. Cardiol. 69, 523–531 (1992).

    Article  CAS  PubMed  Google Scholar 

  21. Wang, W., Chen, J. S. & Zucker, I. H. Carotid sinus baroreceptor reflex in dogs with experimental heart failure. Circ. Res. 68, 1294–1301 (1991).

    Article  CAS  PubMed  Google Scholar 

  22. Ponikowski, P. et al. Augmented peripheral chemosensitivity as a potential input to baroreflex impairment and autonomic imbalance in chronic heart failure. Circulation 96, 2586–2594 (1997).

    Article  CAS  PubMed  Google Scholar 

  23. Malliani, A. & Montano, N. Emerging excitatory role of cardiovascular sympathetic afferents in pathophysiological conditions. Hypertension 39, 63–68 (2002).

    Article  CAS  PubMed  Google Scholar 

  24. Gao, L. et al. Superoxide mediates sympathoexcitation in heart failure: roles of angiotensin II and NAD(P)H oxidase. Circ. Res. 95, 937–944 (2004).

    Article  CAS  PubMed  Google Scholar 

  25. Liu, D., Gao, L., Roy, S. K., Cornish, K. G. & Zucker, I. H. Role of oxidant stress on AT1 receptor expression in neurons of rabbits with heart failure and in cultured neurons. Circ. Res. 103, 186–193 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Zhang, K., Li, Y. F. & Patel, K. P. Blunted nitric oxide-mediated inhibition of renal nerve discharge within PVN of rats with heart failure. Am. J. Physiol. Heart Circ. Physiol. 281, H995–H1004 (2001).

    Article  CAS  PubMed  Google Scholar 

  27. Liu, J. L., Irvine, S., Reid, I. A., Patel, K. P. & Zucker, I. H. Chronic exercise reduces sympathetic nerve activity in rabbits with pacing-induced heart failure: A role for angiotensin II. Circulation 102, 1854–1862 (2000).

    Article  CAS  PubMed  Google Scholar 

  28. Liu, J. L., Kulakofsky, J. & Zucker, I. H. Exercise training enhances baroreflex control of heart rate by a vagal mechanism in rabbits with heart failure. J. Appl. Physiol. 92, 2403–2408 (2002).

    Article  PubMed  Google Scholar 

  29. Mousa, T. M., Liu, D., Cornish, K. G. & Zucker, I. H. Exercise training enhances baroreflex sensitivity by an angiotensin II-dependent mechanism in chronic heart failure. J. Appl. Physiol. 104, 616–624 (2008).

    Article  CAS  PubMed  Google Scholar 

  30. Pliquett, R. U. et al. Amelioration of depressed cardiopulmonary reflex control of sympathetic nerve activity by short-term exercise training in male rabbits with heart failure. J. Appl. Physiol. 95, 1883–1888 (2003).

    Article  CAS  PubMed  Google Scholar 

  31. Schultz, H. D. & Sun, S. Y. Chemoreflex function in heart failure. Heart Fail. Rev. 5, 45–56 (2000).

    Article  CAS  PubMed  Google Scholar 

  32. Gao, L., Wang, W., Liu, D. & Zucker, I. H. Exercise training normalizes sympathetic outflow by central antioxidant mechanisms in rabbits with pacing-induced chronic heart failure. Circulation 115, 3095–3102 (2007).

    Article  PubMed  Google Scholar 

  33. Zheng, H., Li, Y. F., Cornish, K. G., Zucker, I. H. & Patel, K. P. Exercise training improves endogenous nitric oxide mechanisms within the paraventricular nucleus in rats with heart failure. Am. J. Physiol. Heart Circ. Physiol. 288, H2332–H2341 (2005).

    Article  CAS  PubMed  Google Scholar 

  34. Kleiber, A. C., Zheng, H., Schultz, H. D., Peuler, J. D. & Patel, K. P. Exercise training normalizes enhanced glutamate-mediated sympathetic activation from the PVN in heart failure. Am. J. Physiol. Regul. Integr. Comp. Physiol. 294, R1863–R1872 (2008).

    Article  CAS  PubMed  Google Scholar 

  35. Ponikowski, P. P. et al. Muscle ergoreceptor overactivity reflects deterioration in clinical status and cardiorespiratory reflex control in chronic heart failure. Circulation 104, 2324–2330 (2001).

    Article  CAS  PubMed  Google Scholar 

  36. Gademan, M. G. et al. Effect of exercise training on autonomic derangement and neurohumoral activation in chronic heart failure. J. Card. Fail. 13, 294–303 (2007).

    Article  PubMed  Google Scholar 

  37. Coats, A. J. et al. Controlled trial of physical training in chronic heart failure. Exercise performance, hemodynamics, ventilation, and autonomic function. Circulation 85, 2119–2131 (1992).

    Article  CAS  PubMed  Google Scholar 

  38. 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. 26, 975–982 (1995).

    Article  CAS  PubMed  Google Scholar 

  39. Shemesh, J. et al. Norepinephrine and atrial natriuretic peptide responses to exercise testing in rehabilitated and nonrehabilitated men with ischemic cardiomyopathy after healing of anterior wall acute myocardial infarction. Am. J. Cardiol. 75, 1072–1074 (1995).

    Article  CAS  PubMed  Google Scholar 

  40. Gordon, A. et al. Improved ventilation and decreased sympathetic stress in chronic heart failure patients following local endurance training with leg muscles. J. Card. Fail. 3, 3–12 (1997).

    Article  CAS  PubMed  Google Scholar 

  41. Hambrecht, R. et al. Effects of exercise training on left ventricular function and peripheral resistance in patients with chronic heart failure: A randomized trial. JAMA 283, 3095–3101 (2000).

    Article  CAS  PubMed  Google Scholar 

  42. Passino, C. et al. Aerobic training decreases B-type natriuretic peptide expression and adrenergic activation in patients with heart failure. J. Am. Coll. Cardiol. 47, 1835–1839 (2006).

    Article  CAS  PubMed  Google Scholar 

  43. Roveda, F. et al. The effects of exercise training on sympathetic neural activation in advanced heart failure: a randomized controlled trial. J. Am. Coll. Cardiol. 42, 854–860 (2003).

    Article  PubMed  Google Scholar 

  44. de Mello Franco, F. G. et al. Effects of home-based exercise training on neurovascular control in patients with heart failure. Eur. J. Heart Fail. 8, 851–855 (2006).

    Article  PubMed  Google Scholar 

  45. Adamopoulos, S. et al. Circadian pattern of heart rate variability in chronic heart failure patients. Effects of physical training. Eur. Heart J. 16, 1380–1386 (1995).

    Article  CAS  PubMed  Google Scholar 

  46. Kiilavuori, K., Toivonen, L., Näveri, H. & Leinonen, H. Reversal of autonomic derangements by physical training in chronic heart failure assessed by heart rate variability. Eur. Heart J. 16, 490–495 (1995).

    Article  CAS  PubMed  Google Scholar 

  47. Pietilä, M. et al. Exercise training in chronic heart failure: beneficial effects on cardiac 11C-hydroxyephedrine PET, autonomic nervous control, and ventricular repolarization. J. Nucl. Med. 43, 773–779 (2002).

    PubMed  Google Scholar 

  48. Braith, R. W., Welsch, M. A., Feigenbaum, M. S., Kluess, H. A. & Pepine, C. J. Neuroendocrine activation in heart failure is modified by endurance exercise training. J. Am. Coll. Cardiol. 34, 1170–1175 (1999).

    Article  CAS  PubMed  Google Scholar 

  49. Wisløff, U. et al. Superior cardiovascular effect of aerobic interval training versus moderate continuous training in heart failure patients: a randomized study. Circulation 115, 3086–3094 (2007).

    Article  PubMed  Google Scholar 

  50. Katz, S. D. et al. Decreased activity of the L-arginine-nitric oxide metabolic pathway in patients with congestive heart failure. Circulation. 99, 2113–2117 (1999).

    Article  CAS  PubMed  Google Scholar 

  51. Ramsey, M. W. et al. Endothelial control of arterial distensibility is impaired in chronic heart failure. Circulation 92, 3212–3219 (1995).

    Article  CAS  PubMed  Google Scholar 

  52. Lerman, A., Kubo, S. H., Tschumperlin, L. K. & Burnett, J. C. Jr. Plasma endothelin concentrations in humans with end-stage heart failure and after heart transplantation. J. Am. Coll. Cardiol. 20, 849–853 (1992).

    Article  CAS  PubMed  Google Scholar 

  53. Rush, J. W., Denniss, S. G. & Graham, D. A. Vascular nitric oxide and oxidative stress: determinants of endothelial adaptations to cardiovascular disease and to physical activity. Can. J. Appl. Physiol. 30, 442–474 (2005).

    Article  CAS  PubMed  Google Scholar 

  54. Linke, A., Recchia, F., Zhang, X. & Hintze, T. H. Acute and chronic endothelial dysfunction: implications for the development of heart failure. Heart Fail. Rev. 8, 87–97 (2003).

    Article  CAS  PubMed  Google Scholar 

  55. Napoli, C. et al. Long-term combined beneficial effects of physical training and metabolic treatment on atherosclerosis in hypercholesterolemic mice. Proc. Natl Acad. Sci. USA 101, 8797–8802 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Napoli, C. et al. Physical training and metabolic supplementation reduce spontaneous atherosclerotic plaque rupture and prolong survival in hypercholesterolemic mice. Proc. Natl Acad. Sci. USA 103, 10479–10484 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Watanabe, T. et al. Reduction in hemoglobin–oxygen affinity results in the improvement of exercise capacity in mice with chronic heart failure. J. Am. Coll. Cardiol. 52, 779–786 (2008).

    Article  CAS  PubMed  Google Scholar 

  58. Arany, Z. et al. HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1alpha. Nature 451, 1008–1012 (2008).

    Article  CAS  PubMed  Google Scholar 

  59. Bjørnstad, H. H. et al. Exercise training decreases plasma levels of soluble CD40 ligand and P-selectin in patients with chronic heart failure. Eur. J. Cardiovasc. Prev. Rehabil. 15, 43–48 (2008).

    Article  PubMed  Google Scholar 

  60. Sarto, P. et al. Effects of exercise training on endothelial progenitor cells in patients with chronic heart failure. J. Card. Fail. 13, 701–708 (2007).

    Article  CAS  PubMed  Google Scholar 

  61. Sessa, W. C., Pritchard, K., Seyedi, N., Wang, J. & Hintze, T. H. Chronic exercise in dogs increases coronary vascular nitric oxide production and endothelial cell nitric oxide synthase gene expression. Circ. Res. 74, 349–353 (1994).

    Article  CAS  PubMed  Google Scholar 

  62. Woodman, C. R., Muller, J. M., Laughlin, M. H. & Price, E. M. Induction of nitric oxide synthase mRNA in coronary resistance arteries isolated from exercise-trained pigs. Am. J. Physiol. 273, H2575–H2579 (1997).

    CAS  PubMed  Google Scholar 

  63. Varin, R. et al. Exercise improves flow-mediated vasodilatation of skeletal muscle arteries in rats with chronic heart failure. Role of nitric oxide, prostanoids, and oxidant stress. Circulation 99, 2951–2957 (1999).

    Article  CAS  PubMed  Google Scholar 

  64. Fukai, T. et al. Regulation of the vascular extracellular superoxide dismutase by nitric oxide and exercise training. J. Clin. Invest. 105, 1631–1639 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Adams, V. et al. Impact of regular physical activity on the NAD(P)H oxidase and angiotensin receptor system in patients with coronary artery disease. Circulation 111, 555–562 (2005).

    Article  CAS  PubMed  Google Scholar 

  66. Niebauer, J., Clark, A. L., Webb-Peploe, K. M., Böger, R. & Coats, A. J. Home-based exercise training modulates pro-oxidant substrates in patients with chronic heart failure. Eur. J. Heart Fail. 7, 183–188 (2005).

    Article  CAS  PubMed  Google Scholar 

  67. Linke, A. et al. Antioxidative effects of exercise training in patients with chronic heart failure: increase in radical scavenger enzyme activity in skeletal muscle. Circulation 111, 1763–1770 (2005).

    Article  CAS  PubMed  Google Scholar 

  68. Hambrecht, R. et al. Regular physical exercise corrects endothelial dysfunction and improves exercise capacity in patients with chronic heart failure. Circulation 98, 2709–2715 (1998).

    Article  CAS  PubMed  Google Scholar 

  69. Hambrecht, R. et al. Correction of endothelial dysfunction in chronic heart failure: additional effects of exercise training and oral L-arginine supplementation. J. Am. Coll. Cardiol. 35, 706–713 (2000).

    Article  CAS  PubMed  Google Scholar 

  70. Belardinelli, R., Capestro, F., Misiani, A., Scipione, P. & Georgiou, D. Moderate exercise training improves functional capacity, quality of life, and endothelium-dependent vasodilation in chronic heart failure patients with implantable cardioverter defibrillators and cardiac resynchronization therapy. Eur. J. Cardiovasc. Prev. Rehabil. 13, 818–825 (2006).

    Article  PubMed  Google Scholar 

  71. Belardinelli, R. et al. Coenzyme Q10 and exercise training in chronic heart failure. Eur. Heart J. 27, 2675–2681 (2006).

    Article  CAS  PubMed  Google Scholar 

  72. Adamopoulos, S., Parissis, J. T. & Kremastinos, D. T. A glossary of circulating cytokines in chronic heart failure. Eur. J. Heart Fail. 3, 517–526 (2001).

    Article  CAS  PubMed  Google Scholar 

  73. Blum, A. & Miller, H. Pathophysiological role of cytokines in congestive heart failure. Annu. Rev. Med. 52, 15–27 (2001).

    Article  CAS  PubMed  Google Scholar 

  74. Torre-Amione, G. et al. Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: a report from the Studies of Left Ventricular Dysfunction (SOLVD). J. Am. Coll. Cardiol. 27, 1201–1206 (1996).

    Article  CAS  PubMed  Google Scholar 

  75. Tsutamoto, T. et al. Interleukin-6 spillover in the peripheral circulation increases with the severity of heart failure, and the high plasma level of interleukin-6 is an important prognostic predictor in patients with congestive heart failure. J. Am. Coll. Cardiol. 31, 391–398 (1998).

    Article  CAS  PubMed  Google Scholar 

  76. Aukrust, P. et al. Elevated circulating levels of C-C chemokines in patients with congestive heart failure. Circulation 97, 1136–1143 (1998).

    Article  CAS  PubMed  Google Scholar 

  77. Ferdinandy, P., Danial, H., Ambrus, I., Rothery, R. A. & Schulz, R. Peroxynitrite is a major contributor to cytokine-induced myocardial contractile failure. Circ. Res. 87, 241–247 (2000).

    Article  CAS  PubMed  Google Scholar 

  78. McTiernan, C. F. et al. Interleukin-1 beta inhibits phospholamban gene expression in cultured cardiomyocytes. Circ. Res. 81, 493–503 (1997).

    Article  CAS  PubMed  Google Scholar 

  79. Bozkurt, B. et al. Pathophysiologically relevant concentrations of tumor necrosis factor-alpha promote progressive left ventricular dysfunction and remodeling in rats. Circulation 97, 1382–1391 (1998).

    Article  CAS  PubMed  Google Scholar 

  80. Clapp, B. R. et al. Inflammation-induced endothelial dysfunction involves reduced nitric oxide bioavailability and increased oxidant stress. Cardiovasc. Res. 64, 172–178 (2004).

    Article  CAS  PubMed  Google Scholar 

  81. Rössig L. et al. The pro-apoptotic serum activity is an independent mortality predictor of patients with heart failure. Eur. Heart J. 25, 1620–1625 (2004).

    Article  PubMed  Google Scholar 

  82. Noutsias, M., Seeberg, B., Schultheiss, H. P. & Kühl, U. Expression of cell adhesion molecules in dilated cardiomyopathy: evidence for endothelial activation in inflammatory cardiomyopathy. Circulation 99, 2124–2131 (1999).

    Article  CAS  PubMed  Google Scholar 

  83. Hambrecht, R. et al. Reduction of insulin-like growth factor-I expression in the skeletal muscle of noncachectic patients with chronic heart failure. J. Am. Coll. Cardiol. 39, 1175–1181 (2002).

    Article  CAS  PubMed  Google Scholar 

  84. Adams, V. et al. Induction of iNOS expression in skeletal muscle by IL-1beta and NFkappaB activation: an in vitro and in vivo study. Cardiovasc. Res. 54, 95–104 (2002).

    Article  CAS  PubMed  Google Scholar 

  85. Hambrecht, R. 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. 33, 174–179 (1999).

    Article  CAS  PubMed  Google Scholar 

  86. Anker, S. D. et al. Cytokines and neurohormones relating to body composition alterations in the wasting syndrome of chronic heart failure. Eur. Heart J. 20, 683–693 (1999).

    Article  CAS  PubMed  Google Scholar 

  87. Nunes, R. B. et al. Physical exercise improves plasmatic levels of IL-10, left ventricular end-diastolic pressure, and muscle lipid peroxidation in chronic heart failure rats. J. Appl. Physiol. 104, 1641–1647 (2008).

    Article  CAS  PubMed  Google Scholar 

  88. Batista, M. L. Jr., Santos, R. V., Oliveira, E. M., Seelaender, M. C. & Costa Rosa, L. F. Endurance training restores peritoneal macrophage function in post-MI congestive heart failure rats. J. Appl. Physiol. 102, 2033–2039 (2007).

    Article  CAS  PubMed  Google Scholar 

  89. Batista, M. L. Jr et al. Endurance training modulates lymphocyte function in rats with post-MI CHF. Med. Sci. Sports. Exerc. 40, 549–556 (2008).

    Article  PubMed  Google Scholar 

  90. Adamopoulos, S. et al. Physical training modulates proinflammatory cytokines and the soluble Fas/soluble Fas ligand system in patients with chronic heart failure. J. Am. Coll. Cardiol. 39, 653–663 (2002).

    Article  CAS  PubMed  Google Scholar 

  91. Conraads, V. M. et al. Combined endurance/resistance training reduces plasma TNF-alpha receptor levels in patients with chronic heart failure and coronary artery disease. Eur. Heart J. 23, 1854–1860 (2002).

    Article  CAS  PubMed  Google Scholar 

  92. Adamopoulos, S. et al. Physical training reduces peripheral markers of inflammation in patients with chronic heart failure. Eur. Heart J. 22, 791–797 (2001).

    Article  CAS  PubMed  Google Scholar 

  93. LeMaitre, J. P., Harris, S., Fox, K. A. & Denvir, M. Change in circulating cytokines after 2 forms of exercise training in chronic stable heart failure. Am. Heart J. 147, 100–105 (2004).

    Article  CAS  PubMed  Google Scholar 

  94. Gielen, S. et al. Exercise training in chronic heart failure: correlation between reduced local inflammation and improved oxidative capacity in the skeletal muscle. Eur. J. Cardiovasc. Prev. Rehabil. 12, 393–400 (2005).

    Article  PubMed  Google Scholar 

  95. Damy, T. et al. Increased neuronal nitric oxide synthase-derived NO production in the failing human heart. Lancet 363, 1365–1367 (2004).

    Article  CAS  PubMed  Google Scholar 

  96. Drexler, H. et al. Expression, activity and functional significance of inducible nitric oxide synthase in the failing human heart. J. Am. Coll. Cardiol. 32, 955–963 (1998).

    Article  CAS  PubMed  Google Scholar 

  97. Riede, U. N., Förstermann, U. & Drexler, H. Inducible nitric oxide synthase in skeletal muscle of patients with chronic heart failure. J. Am. Coll. Cardiol. 32, 964–969 (1998).

    Article  CAS  PubMed  Google Scholar 

  98. Kokkinos, P. F., Choucair, W., Graves, P., Papademetriou, V. & Ellahham, S. Chronic heart failure and exercise. Am. Heart J. 140, 21–28 (2000).

    Article  CAS  PubMed  Google Scholar 

  99. Vescovo, G. et al. Apoptosis of skeletal muscle myofibers and interstitial cells in experimental heart failure. J. Moll. Cell. Cardiol. 30, 2449–2459 (1998).

    Article  CAS  Google Scholar 

  100. Sinoway, L. I. & Li, J. A perspective on the muscle reflex: implication for congestive heart failure. J. Appl. Physiol. 99, 5–22 (2005).

    Article  CAS  PubMed  Google Scholar 

  101. Piepoli, M. F., Dimopoulos K., Concu, A. & Crisafulli, A. Cardiovascular and ventilatory control during exercise in chronic heart failure: role of muscle reflexes. Int. J. Cardiol. 130, 3–10 (2008).

    Article  PubMed  Google Scholar 

  102. Smith, S. A., Mitchell, J. H., Naseem, R. H. & Garry, M. G. Mechanoreflex mediates the exaggerated exercise pressor reflex in heart failure. Circulation 112, 2293–2300 (2005).

    Article  PubMed  Google Scholar 

  103. Ventura-Clapier, R., Mettauer, B. & Bigard, X. Beneficial effects of endurance training on cardiac and skeletal muscle energy metabolism in heart failure. Cardiovasc. Res. 73, 10–18 (2007).

    Article  CAS  PubMed  Google Scholar 

  104. De Sousa, E. et al. Cardiac and skeletal muscle energy metabolism in heart failure: beneficial effects of voluntary activity. Cardiovasc. Res. 56, 260–268 (2002).

    Article  CAS  PubMed  Google Scholar 

  105. Brunotte, F. et al. Rat skeletal muscle metabolism in experimental heart failure: effects of physical training. Acta. Physiol. Scand. 154, 439–447 (1995).

    Article  CAS  PubMed  Google Scholar 

  106. Lawler, J. M., Kwak, H. B., Song, W. & Parker, J. L. Exercise training reverses downregulation of HSP70 and antioxidant enzymes in porcine skeletal muscle after chronic coronary artery occlusion. Am. J. Physiol. Regul. Integr. Comp. Physiol. 291, R1756–R1763 (2006).

    Article  CAS  PubMed  Google Scholar 

  107. Gustafsson, T. et al. Increased expression of VEGF following exercise training in patients with heart failure. Eur. J. Clin. Invest. 31, 362–366 (2001).

    Article  CAS  PubMed  Google Scholar 

  108. Hambrecht, R. et al. Effects of endurance training on mitochondrial ultrastructure and fiber type distribution in skeletal muscle of patients with stable chronic heart failure. J. Am. Coll. Cardiol. 29, 1067–1073 (1997).

    Article  CAS  PubMed  Google Scholar 

  109. Hambrecht, R. et al. Physical training in patients with stable chronic heart failure: effects on cardiorespiratory fitness and ultrastructural abnormalities of leg muscles. J. Am. Coll. Cardiol. 25, 1239–1249 (1995).

    Article  CAS  PubMed  Google Scholar 

  110. Minotti, J. R. et al. Skeletal muscle response to exercise training in congestive heart failure. J. Clin. Invest. 86, 751–758 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Keteyian, S. J. et al. Differential effects of exercise training in men and women with chronic heart failure. Am. Heart J. 145, 912–918 (2003).

    PubMed  Google Scholar 

  112. Larsen, A. I. et al. Effect of exercise training on skeletal muscle fibre characteristics in men with chronic heart failure. Correlation between skeletal muscle alterations, cytokines and exercise capacity. Int. J. Cardiol. 83, 25–32 (2002).

    Article  PubMed  Google Scholar 

  113. Hambrecht, R. et al. Effects of exercise training on insulin-like growth factor-I expression in the skeletal muscle of non-cachectic patients with chronic heart failure. Eur. J. Cardiovasc. Prev. Rehabil. 12, 401–406 (2005).

    Article  PubMed  Google Scholar 

  114. Kenchaiah, S., Sesso, H. D. & Gaziano, J. M. Body mass index and vigorous physical activity and the risk of heart failure among men. Circulation 119, 44–52 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  115. Arena, R. et al. Prognostic characteristics of cardiopulmonary exercise testing in caucasian and African American patients with heart failure. Congest. Heart Fail. 14, 310–315 (2008).

    Article  PubMed  Google Scholar 

  116. Arena, R. et al. The partial pressure of resting end-tidal carbon dioxide predicts major cardiac events in patients with systolic heart failure. Am. Heart J. 156, 982–988 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  117. Di Valentino, M. et al. Prognostic value of cycle exercise testing prior to and after outpatient cardiac rehabilitation. Int. J. Cardiol. doi:10.1016/j.ijcard.2008.10.034 (2008).

  118. Myers, J. et al. A cardiopulmonary exercise testing score for predicting outcomes in patients with heart failure. Am. Heart J. 156, 1177–1183 (2008).

    Article  PubMed  Google Scholar 

  119. Nilsson, B. B., Westheim, A. & Risberg, M. A. Long-term effects of a group-based high-intensity aerobic interval-training program in patients with chronic heart failure. Am. J. Cardiol. 102, 1220–1224 (2008).

    Article  PubMed  Google Scholar 

  120. Chase, P. et al. Prognostic usefulness of dyspnea versus fatigue as reason for exercise test termination in patients with heart failure. Am. J. Cardiol. 102, 879–882 (2008).

    Article  PubMed  Google Scholar 

  121. Bensimhon, D. R. et al. Reproducibility of peak oxygen uptake and other cardiopulmonary exercise testing parameters in patients with heart failure (from the Heart Failure and A Controlled Trial Investigating Outcomes of exercise traiNing). Am. J. Cardiol. 102, 712–717 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  122. Beckers, P. J. et al. Combined endurance-resistance training vs. endurance training in patients with chronic heart failure: a prospective randomized study. Eur. Heart J. 29, 1858–1866 (2008).

    Article  PubMed  Google Scholar 

  123. Rolim, N. P. et al. Exercise training improves the net balance of cardiac Ca2+ handling protein expression in heart failure. Physiol. Genomics 29, 246–252 (2007).

    Article  CAS  PubMed  Google Scholar 

  124. Medeiros, A. et al. Exercise training delays cardiac dysfunction and prevents calcium handling abnormalities in sympathetic hyperactivity-induced heart failure mice. J. Appl. Physiol. 104, 103–109 (2008).

    Article  CAS  PubMed  Google Scholar 

  125. Lu, L. et al. Exercise training normalizes altered calcium-handling proteins during development of heart failure. J. Appl. Physiol. 92, 1524–1530 (2002).

    Article  CAS  PubMed  Google Scholar 

  126. de Waard, M. C. et al. Early exercise training normalizes myofilament function and attenuates left ventricular pump dysfunction in mice with a large myocardial infarction. Circ. Res. 100, 1079–1088 (2007).

    Article  CAS  PubMed  Google Scholar 

  127. Haykowsky, M. J. et al. A meta-analysis of the effect of exercise training on left ventricular remodeling in heart failure patients: the benefit depends on the type of training performed. J. Am. Coll. Cardiol. 49, 2329–2336 (2007).

    Article  PubMed  Google Scholar 

  128. van Tol, B. A., Huijsmans, R. J., Kroon, D. W., Schothorst, M. & Kwakkel, G. Effects of exercise training on cardiac performance, exercise capacity and quality of life in patients with heart failure: a meta-analysis. Eur. J. Heart Fail. 8, 841–850 (2006).

    Article  PubMed  Google Scholar 

  129. Abete, P. et al. Angina-induced protection against myocardial infarction in adult and elderly patients: a loss of preconditioning mechanism in the aging heart? J. Am. Coll. Cardiol. 30, 947–954 (1997).

    Article  CAS  PubMed  Google Scholar 

  130. Napoli, C. et al. “Warm-up” phenomenon detected by electrocardiographic ambulatory monitoring in adult and older patients. J. Am. Geriatr. Soc. 47, 1114–1117 (1999).

    Article  CAS  PubMed  Google Scholar 

  131. Abete, P. et al. High level of physical activity preserves the cardioprotective effect of preinfarction angina in elderly patients. J. Am. Coll. Cardiol. 38, 1357–1365 (2001).

    Article  CAS  PubMed  Google Scholar 

  132. Abete, P. et al. Exercise training restores ischemic preconditioning in the aging heart. J. Am. Coll. Cardiol. 36, 643–650 (2000).

    Article  CAS  PubMed  Google Scholar 

  133. Polcaro, P. et al. Left-ventricular function and physical performance on the 6-min walk test in older patients after inpatient cardiac rehabilitation. Am. J. Phys. Med. Rehabil. 87, 46–52 (2008).

    Article  PubMed  Google Scholar 

  134. Conraads, V. M. et al. Exercise-induced biphasic increase in circulating NT-proBNP levels in patients with chronic heart failure. Eur. J. Heart Fail. 10, 793–795 (2008).

    Article  CAS  PubMed  Google Scholar 

  135. Kallistratos, M. S., Dristas, A., Laoutaris, I. D. & Cokkinos, D. V. Incremental value of N-terminal pro-brain natriuretic peptide over left ventricle ejection fraction and aerobic capacity for estimating prognosis in heart failure patients. J. Heart Lung Transplant. 27, 1251–1256 (2008).

    Article  PubMed  Google Scholar 

  136. Hurley, B. F. & Roth, S. M. Strength training in the elderly: effects on risk factors for age-related diseases. Sports. Med. 30, 249–268 (2000).

    Article  CAS  PubMed  Google Scholar 

  137. Braith, R. W. et al. Effect of resistance exercise on skeletal muscle myopathy in heart transplant recipients. Am. J. Cardiol. 95, 1192–1198 (2005).

    Article  PubMed  Google Scholar 

  138. Meyer, K. Resistance exercise in chronic heart failure—landmark studies and implications for practice. Clin. Invest. Med. 29, 166–169 (2006).

    PubMed  Google Scholar 

  139. Green, D. J., Watts, K., Maiorana, A. J. & O'Driscoll, J. G. A comparison of ambulatory oxygen consumption during circuit training and aerobic exercise in patients with chronic heart failure. J. Cardiopulm. Rehabil. 21, 167–174 (2001).

    Article  CAS  PubMed  Google Scholar 

  140. Belardinelli, R. et al. Exercise training improves left ventricular diastolic filling in patients with dilated cardiomyopathy. Clinical and prognostic implications. Circulation 91, 2775–2784 (1995).

    Article  CAS  PubMed  Google Scholar 

  141. Belardinelli, R., Georgiou, D., Cianci, G. & Purcaro, A. Randomized, controlled trial of long-term moderate exercise training in chronic heart failure: effects on functional capacity, quality of life, and clinical outcome. Circulation 99, 1173–1182 (1999).

    Article  CAS  PubMed  Google Scholar 

  142. Coats, A. J., Adamopoulos, S., Meyer, T. E., Conway, J. & Sleight, P. Effects of physical training in chronic heart failure. Lancet 335, 63–66 (1990).

    Article  CAS  PubMed  Google Scholar 

  143. Gottlieb, S. S. et al. Effects of exercise training on peak performance and quality of life in congestive heart failure patients. J. Card. Fail. 5, 188–194 (1999).

    Article  CAS  PubMed  Google Scholar 

  144. Jetté, M., Heller, R., Landry, F. & Blümchen, G. Randomized 4-week exercise program in patients with impaired left ventricular function. Circulation 84, 1561–1567 (1991).

    Article  PubMed  Google Scholar 

  145. Keteyian, S. J. et al. Exercise training in patients with heart failure. A randomized, controlled trial. Ann. Intern. Med. 124, 1051–1057 (1996).

    Article  CAS  PubMed  Google Scholar 

  146. 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 110, 985–991 (1996).

    Article  CAS  PubMed  Google Scholar 

  147. McKelvie, R. S. et al. Effects of exercise training in patients with heart failure: the Exercise Rehabilitation Trial (EXERT). Am. Heart J. 144, 23–30 (2002).

    Article  PubMed  Google Scholar 

  148. Wielenga, R. P. et al. Safety and effects of physical training in chronic heart failure. Results of the Chronic Heart Failure and Graded Exercise study (CHANGE). Eur. Heart J. 20, 872–879 (1999).

    Article  CAS  PubMed  Google Scholar 

  149. Willenheimer, R., Erhardt, L., Cline, C., Rydberg, E. & Israelsson, B. Exercise training in heart failure improves quality of life and exercise capacity. Eur. Heart J. 19, 774–781 (1998).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Supported in part by a grant from the Italian Ministery of University and Research 2006 (PRIN 2006, Principal Investigator: Prof Napoli) and Ricerca Finalizzata from Italian Ministery of Health 2006 (Principal Investigator: Dr Cacciatore).

Author information

Authors and Affiliations

  1. Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Ettore Crimi

  2. Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA

    Louis J. Ignarro

  3. Cardiovascular Rehabilitation, Fondazione Salvatore Maugeri, IRCCS, Istituto Scientifico di Telese Terme e Campoli (BN), Italy

    Francesco Cacciatore

  4. Department of General Pathology, Clinical Pathology and Excellence Research Center on Cardiovascular Diseases, 1st School of Medicine, II University of Naples, Naples, Italy

    Claudio Napoli

Authors
  1. Ettore Crimi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Louis J. Ignarro
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Francesco Cacciatore
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Claudio Napoli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Ettore Crimi or Claudio Napoli.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Crimi, E., Ignarro, L., Cacciatore, F. et al. Mechanisms by which exercise training benefits patients with heart failure. Nat Rev Cardiol 6, 292–300 (2009). https://doi.org/10.1038/nrcardio.2009.8

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrcardio.2009.8

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing