Skip to main content

Advertisement

Log in

Unraveling new mechanisms of exercise intolerance in chronic heart failure. Role of exercise training

  • Published:
Heart Failure Reviews Aims and scope Submit manuscript

Abstract

Despite remarkable progress in the therapeutic approach of patients with chronic heart failure (CHF), exercise intolerance remains one of the hallmarks of the disease. During the past two decades, evidence has accumulated to underscore the key role of both endothelial dysfunction and skeletal muscle wasting in the process that gradually leads to physical incapacity. Whereas reverse ventricular remodeling has been attributed to aerobic exercise training, the vast majority of studies conducted in this specific patient population emphasize the reversal of peripheral abnormalities. In this review, we provide a general overview on underlying pathophysiological mechanisms. In addition, emphasis is put on recently identified pathways, which contribute to a deeper understanding of the main causes of exercise tolerance and the potential for reversal through exercise training. Recently, deficient bone marrow-related endothelial repair mechanisms have received considerable attention. Both acute exercise bouts, as well as exercise training, affect the mobilization of endothelial progenitor cells and their function. The observed changes following exercise training are believed to significantly contribute to improvement of peripheral endothelial function, as well as exercise capacity. With regard to skeletal muscle dysfunction and energy deprivation, adiponectin has been suggested to play a significant role. The demonstration of local skeletal muscle adiponectin resistance may provide an interesting and new link between the insulin resistant state and skeletal muscle wasting in CHF patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) (2001) The survival of patients with heart failure with preserved or reduced left ventricular ejection fraction: an individual patient data meta-analysis. Eur Heart J [Epub ahead of print]

  2. Dickstein K, Cohen-Solal A Filippatos G. McMurray JJ, Ponikowski P, Poole-Wilson P A, Stromberg A, van Veldhuisen DJ., Atar D, Hoes AWKeren A, Mebazaa A, Nieminen M, Priori SG, Swedberg K, Vahanian A, Camm J, De Caterina R, Dean V, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL (2008) ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the task force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Developed in collaboration with the heart failure association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J 29:2388–2442

  3. Coats AJ, Clark AL, Piepoli M, Volterrani M, Poole-Wilson PA (1994) Symptoms and quality of life in heart failure: the muscle hypothesis. Br Heart J 72:S36–S39

    Article  PubMed  CAS  Google Scholar 

  4. Piepoli MF, Conraads V, Corra U, Dickstein K, Francis DP. Jaarsma T, McMurray J, Pieske B, Piotrowicz E, Schmid JP, Anker SD, Solal AC. Filippatos GS, Hoes AW, Gielen, S, Giannuzzi P, Ponikowski PP (2011) Exercise training in heart failure: from theory to practice. A consensus document of the heart failure association and the European association for cardiovascular prevention and rehabilitation. Eur J Heart Fail 13:347–357

    Google Scholar 

  5. Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, Jessup M, Konstam MA, Mancini DM, Michl K, Oates JA, Rahko PS, Silver MA, Stevenson LW, Yancy CW (2009) Focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and management of heart failure in adults a report of the American college of cardiology foundation/American Heart Association task force on practice guidelines developed in collaboration with the international society for heart and lung transplantation. J Am Coll Cardiol 53:e1–e90

    Google Scholar 

  6. Davies P, Taylor F, Beswick A, Singh S, Coats AJ, Ebrahim S, Lough F, Taylor RS (2010) Promoting patient uptake and adherence in cardiac rehabilitation. Cochrane Database Syst Rev;7:CD007131

    Google Scholar 

  7. O’Connor CM, Whellan DJ, Lee KL, Keteyian SJ, Cooper LS, Ellis SJ, Leifer ES, Kraus WE, Kitzman DW, Blumenthal JA, Rendall DS, Miller NH, Fleg JL, Schulman KA, McKelvie RS, Zannad F, Pina IL (2009) Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial. JAMA 301:1439–1450

    Article  PubMed  Google Scholar 

  8. Flynn KE, Piña IL, Whellan DJ, Lin L, Blumenthal JA, Ellis SJ, Fine LJ, Howlett JG, Keteyian SJ, Kitzman DW, Kraus WE, Miller NH, Schulman KA, Spertus JA, O’Connor CM, Weinfurt KP, HF-ACTION Investigators (2009) Effects of exercise training on health status in patients with chronic heart failure: HF-ACTION randomized controlled trial. JAMA 301:1451–1459

    Article  PubMed  CAS  Google Scholar 

  9. Haykowsky MJ, Liang Y, Pechter D, Jones LW, McAlister FA, Clark AM (2007) 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

    Article  PubMed  Google Scholar 

  10. Beckers PJ, Denollet J, Possemiers NM, Wuyts FL, Vrints CJ, Conraads VM (2008) Combined endurance-resistance training versus endurance training in patients with chronic heart failure: a prospective randomized study. Eur Heart J 29:1858–1866

    Article  PubMed  Google Scholar 

  11. Wisløff U, Støylen A, Loennechen JP, Bruvold M, Rognmo Ø, Haram PM, Tjønna AE, Helgerud J, Slørdahl SA, Lee SJ, Videm V, Bye A, Smith GL, Najjar SM, Ellingsen Ø, Skjaerpe T (2007) Superior cardiovascular effect of aerobic interval training versus moderate continuous training in heart failure patients: a randomized study. Circulation 115:3086–3094

    Article  PubMed  Google Scholar 

  12. Stoylen A, Conraads V, Halle M, Linke A, Prescott E, Ellingsen O (2011) Controlled study of myocardial recovery after interval training in heart failure: SMARTEX-HF: rationale and design. Eur J Cardiovasc Prev Rehabil; Mar 21 [Epub ahead of print]

  13. Chiappa GR, Roseguini BT, Vieira PJ, Alves CN, Tavares A, Winkelmann ER, Ferlin EL, Stein R, Ribeiro JP (2008) Inspiratory muscle training improves blood flow to resting and exercising limbs in patients with chronic heart failure. J Am Coll Cardiol 51:1663–1671

    Article  PubMed  Google Scholar 

  14. Conraads VM, Bosmans JM, Vrints CJ (2002) Chronic heart failure: an example of a systemic chronic inflammatory disease resulting in cachexia. Int J Cardiol 85:33–49

    Article  PubMed  Google Scholar 

  15. Franciosa JA, Park M, Levine TB (1981) Lack of correlation between exercise capacity and indexes of resting left ventricular performance in heart failure. Am J Cardiol 47:33–39

    Article  PubMed  CAS  Google Scholar 

  16. Hambrecht R, Fiehn E, Weigl C, Gielen S, Hamann C, Kaiser R, Yu J, Adams V, Niebauer J, Schuler G (1998) Regular physical exercise corrects endothelial dysfunction and improves exercise capacity in patients with chronic heart failure. Circulation 98:2709–2715

    Article  PubMed  CAS  Google Scholar 

  17. Hambrecht R, Gielen S, Linke A, Fiehn E, Yu J, Walther C, Schoene N, Schuler G (2000) Effects of exercise training on left ventricular function and peripheral resistance in patients with chronic heart failure: a randomized trial. JAMA 283:3095–3101

    Article  PubMed  CAS  Google Scholar 

  18. Kojda G, Hambrecht R (2005) Molecular mechanisms of vascular adaptations to exercise. Physical activity as an effective antioxidant therapy? Cardiovasc Res 67:187–197

    Article  PubMed  CAS  Google Scholar 

  19. Linke A, Adams V, Schulze PC, Erbs S, Gielen S, Fiehn E, Möbius-Winkler S, Schubert A, Schuler G, Hambrecht R (2005) Antioxidative effects of exercise training in patients with chronic heart failure: increase in radical scavenger enzyme activity in skeletal muscle. Circulation 111:1763–1770

    Article  PubMed  CAS  Google Scholar 

  20. Conraads VM, Bosmans JM, Schuerwegh AJ, De Clerck LS, Bridts CH, Wuyts FL, Stevens WJ, Vrints CJ (2003) Association of lipoproteins with cytokines and cytokine receptors in heart failure patients. Differences between ischaemic versus idiopathic cardiomyopathy. Eur Heart J 24:2221–2226

    Article  PubMed  CAS  Google Scholar 

  21. Rauchhaus M, Doehner W, Francis DP, Davos C, Kemp M, Liebenthal C, Niebauer J, Hooper J, Volk HD, Coats AJ, Anker SD (2000) Plasma cytokine parameters and mortality in patients with chronic heart failure. Circulation 102:3060–3067

    Article  PubMed  CAS  Google Scholar 

  22. Van Craenenbroeck EM, Conraads VM (2010) Endothelial progenitor cells in vascular health: focus on lifestyle. Microvasc Res 79:184–192

    Article  PubMed  Google Scholar 

  23. Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275:964–967

    Article  PubMed  CAS  Google Scholar 

  24. Hill JM, Zalos G, Halcox JP, Schenke WH, Waclawiw MA, Quyyumi AA, Finkel T (2003) Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med 348:593–600

    Article  PubMed  Google Scholar 

  25. Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A, Böhm M, Nickenig G (2005) Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med 353:999–1007

    Article  PubMed  CAS  Google Scholar 

  26. Dimmeler S, Aicher A, Vasa M, Mildner-Rihm C, Adler K, Tiemann M, Rütten H, Fichtlscherer S, Martin H, Zeiher AM (2001) HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway. J Clin Invest 108:391–397

    PubMed  CAS  Google Scholar 

  27. Dimmeler S, Zeiher AM (2004) Vascular repair by circulating endothelial progenitor cells: the missing link in atherosclerosis? J Mol Med (Berl) 82:671–677

    Article  Google Scholar 

  28. Dimmeler S (2010) Regulation of bone marrow-derived vascular progenitor cell mobilization and maintenance. Arterioscler Thromb Vasc Biol 30:1088–1093

    Article  PubMed  CAS  Google Scholar 

  29. Everaert BR, Van Craenenbroeck EM, Hoymans VY, Haine SE, Van Nassauw L, Conraads VM, Timmermans JP, Vrints CJ, Hoymans VY et al (2010) Current perspective of pathophysiological and interventional effects on endothelial progenitor cell biology: focus on PI3 K/AKT/eNOS pathway. Int J Cardiol 144:350–366

    Article  PubMed  Google Scholar 

  30. Hambrecht R, Adams V, Erbs S, Linke A, Kränkel N, Shu Y, Baither Y, Gielen S, Thiele H, Gummert JF, Mohr FW, Schuler G (2003) Regular physical activity improves endothelial function in patients with coronary artery disease by increasing phosphorylation of endothelial nitric oxide synthase. Circulation 107:3152–3158

    Article  PubMed  CAS  Google Scholar 

  31. Ennezat PV, Malendowicz SL, Testa M, Colombo PC, Cohen-Solal A, Evans T, LeJemtel T (2001) Physical training in patients with chronic heart failure enhances the expression of genes encoding antioxidative enzymes. J Am Coll Cardiol 38:194–198

    Article  PubMed  CAS  Google Scholar 

  32. Laufs U, Werner N, Link A, Endres M, Wassmann S, Jürgens K, Miche E, Böhm M, Nickenig G (2004) Physical training increases endothelial progenitor cells, inhibits neointima formation, and enhances angiogenesis. Circulation 109:220–226

    Article  PubMed  CAS  Google Scholar 

  33. Sandri M, Adams V, Gielen S, Linke A, Lenk K, Kränkel N, Lenz D, Erbs S, Scheinert D, Mohr FW, Schuler G, Hambrecht R (2005) Effects of exercise and ischemia on mobilization and functional activation of blood-derived progenitor cells in patients with ischemic syndromes: results of 3 randomized studies. Circulation 111:3391–3399

    Article  PubMed  Google Scholar 

  34. Erbs S, Höllriegel R, Linke A, Beck EB, Adams V, Gielen S, Möbius-Winkler S, Sandri M, Kränkel N, Hambrecht R, Schuler G (2010) Exercise training in patients with advanced chronic heart failure (NYHA IIIb) promotes restoration of peripheral vasomotor function, induction of endogenous regeneration, and improvement of left ventricular function. Circ Heart Fail 3:486–494

    Article  PubMed  Google Scholar 

  35. Van Craenenbroeck EM, Hoymans VY, Beckers PJ, Possemiers NM, Wuyts K, Paelinck BP, Vrints CJ, Conraads VM (2010) Exercise training improves function of circulating angiogenic cells in patients with chronic heart failure. Basic Res Cardiol 105:665–676

    Article  PubMed  Google Scholar 

  36. Haram PM, Kemi OJ, Wisloff U (2008) Adaptation of endothelium to exercise training: insights from experimental studies. Front Biosci 13:336–346

    Article  PubMed  CAS  Google Scholar 

  37. Suvorava T, Kojda G (2007) Prevention of transient endothelial dysfunction in acute exercise: a friendly fire? Thromb Haemost 97:331–333

    PubMed  CAS  Google Scholar 

  38. Rehman J, Li J, Parvathaneni L, Karlsson G, Panchal VR, Temm CJ, Mahenthiran J, March KL (2004) Exercise acutely increases circulating endothelial progenitor cells and monocyte-/macrophage-derived angiogenic cells. J Am Coll Cardiol 43:2314–2318

    Article  PubMed  Google Scholar 

  39. Thorell D, Borjesson M, Larsson P, Ulfhammer E, Karlsson L, DuttaRoy S (2009) Strenuous exercise increases late outgrowth endothelial cells in healthy subjects. Eur J Appl Physiol 107:481–488

    Article  PubMed  CAS  Google Scholar 

  40. Van Craenenbroeck EM, Vrints CJ, Haine SE, Vermeulen K, Goovaerts I, Van Tendeloo VF, Hoymans VY, Conraads VM (2008) A maximal exercise bout increases the number of circulating CD34+/KDR+ endothelial progenitor cells in healthy subjects. Relation with lipid profile. J Appl Physiol Apr 104 1006–1013

    Google Scholar 

  41. Adams V, Lenk K, Linke A, Lenz D, Erbs S, Sandri M, Tarnok A, Gielen S, Emmrich F, Schuler G, Hambrecht R (2004) Increase of circulating endothelial progenitor cells in patients with coronary artery disease after exercise-induced ischemia. Arterioscler Thromb Vasc Biol 24:684–690

    Article  PubMed  CAS  Google Scholar 

  42. Van Craenenbroeck EM, Bruyndonckx L, Van Berckelaer C, Hoymans VY, Vrints CJ, Conraads VM (2011) The effect of acute exercise on endothelial progenitor cells is attenuated in chronic heart failure. Eur J Appl Physiol 111:2375–2379

    Article  PubMed  Google Scholar 

  43. Kissel CK, Lehmann R, Assmus B, Aicher A, Honold J, Fischer-Rasokat U, Heeschen C, Spyridopoulos I, Dimmeler S, Zeiher AM (2007) Selective functional exhaustion of hematopoietic progenitor cells in the bone marrow of patients with postinfarction heart failure. J Am Coll Cardiol 49:2341–2349

    Article  PubMed  Google Scholar 

  44. Van Craenenbroeck EM, Beckers PJ, Possemiers NM, Wuyts K, Frederix G, Hoymans VY, Wuyts F, Paelinck BP, Vrints CJ, Conraads VM (2010) Exercise acutely reverses dysfunction of circulating angiogenic cells in chronic heart failure. Eur Heart 31:1924–1934

    Article  Google Scholar 

  45. Sarto P, Balducci E, Balconi G, Fiordaliso F, Merlo L, Tuzzato G, Pappagallo GL, Frigato N, Zanocco A, Forestieri C, Azzarello G, Mazzucco A, Valenti MT, Alborino F, Noventa D, Vinante O, Pascotto P, Sartore S, Dejana E, Latini R (2007) Effects of exercise training on endothelial progenitor cells in patients with chronic heart failure. J Card Fail 13:701–708

    Article  PubMed  CAS  Google Scholar 

  46. Balligand JL, Feron O, Dessy C (2009) eNOS activation by physical forces: from short-term regulation of contraction to chronic remodeling of cardiovascular tissues. Physiol Rev 89:481–534

    Article  PubMed  CAS  Google Scholar 

  47. Anker SD, Ponikowski P, Varney S, Chua TP, Clark AL, Webb-Peploe KM, Harrington D, Kox WJ, Poole-Wilson PA, Coats AJ (1997) Wasting as independent risk factor for mortality in chronic heart failure. Lancet 349:1050–1053

    Article  PubMed  CAS  Google Scholar 

  48. Evans WJ, Morley JE, Argilés J, Bales C, Baracos V, Guttridge D, Jatoi A, Kalantar-Zadeh K, Lochs H, Mantovani G, Marks D, Mitch WE, Muscaritoli M, Najand A, Ponikowski P, Rossi Fanelli F, Schambelan M, Schols A, Schuster M, Thomas D, Wolfe R, Anker S (2008) Cachexia: a new definition. Clin Nutr 27:793–799

    Article  PubMed  CAS  Google Scholar 

  49. Cicoira M, Zanolla L, Franceschini L, Rossi A, Golia G, Zamboni M, Tosoni P, Zardini P (2001) Skeletal muscle mass independently predicts peak oxygen consumption and ventilatory response during exercise in noncachectic patients with chronic heart failure. J Am Coll Cardiol 37:2080–2085

    Article  PubMed  CAS  Google Scholar 

  50. Harrington D, Clark AL, Chua TP, Anker SD, Poole-Wilson PA, Coats AJ (1997) Effect of reduced muscle bulk on the ventilatory response to exercise in chronic congestive heart failure secondary to idiopathic dilated and ischemic cardiomyopathy. Am J Cardiol 80:90–93

    Article  PubMed  CAS  Google Scholar 

  51. Middlekauff HR (2010) Making the case for skeletal myopathy as the major limitation of exercise capacity in heart failure. Circ Heart Fail 3:537–546

    Article  PubMed  Google Scholar 

  52. Filippatos GS, Kanatselos C, Manolatos DD, Vougas B, Sideris A, Kardara D, Anker SD, Kardaras F, Uhal B (2003) Studies on apoptosis and fibrosis in skeletal musculature: a comparison of heart failure patients with and without cardiac cachexia. Int J Cardiol 90:107–113

    Article  PubMed  Google Scholar 

  53. Adams V, Jiang H, Yu J, Möbius-Winkler S, Fiehn E, Linke A, Weigl C, Schuler G, Hambrecht R (1999) Apoptosis in skeletal myocytes of patients with chronic heart failure is associated with exercise intolerance. J Am Coll Cardiol 33:959–965

    Article  PubMed  CAS  Google Scholar 

  54. Hambrecht R, Fiehn E, Yu J, Niebauer J, Weigl C, Hilbrich L, Adams V, Riede U, Schuler G (1997) 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

    Article  PubMed  CAS  Google Scholar 

  55. Drexler H, Riede U, Munzel T, Konig H, Funke E, Just H (1992) Alterations of skeletal muscle in chronic heart failure. Circulation 85:1751–1759

    Article  PubMed  CAS  Google Scholar 

  56. Mancini DM, Walter G, Reichek N, Lenkinski R, McCully KK, Mullen JL, Wilson J (1992) Contribution of skeletal muscle atrophy to exercise intolerance and altered muscle metabolism in heart failure. Circulation 85:1364–1373

    Article  PubMed  CAS  Google Scholar 

  57. Mettauer B, Zoll J, Garnier A, Ventura-Clapier R (2006) Heart failure: a model of cardiac and skeletal muscle energetic failure. Pflugers Arch 452:653–666

    Article  PubMed  CAS  Google Scholar 

  58. Mettauer B, Zoll J, Sanchez H, Lampert E, Ribera F, Veksler V, Bigard X, Mateo P, Epailly E, Lonsdorfer J, Ventura-Clapier R (2001) Oxidative capacity of skeletal muscle in heart failure patients versus sedentary or active control subjects. J Am Coll Cardiol 38:947–954

    Article  PubMed  CAS  Google Scholar 

  59. Garnier A, Fortin D, Zoll J, N’Guessan B, Mettauer B, Lampert E, Veksler V, Ventura-Clapier R (2005) Coordinated changes in mitochondrial function and biogenesis in healthy and diseased human skeletal muscle. FASEB J 19:43–52

    Article  PubMed  CAS  Google Scholar 

  60. Lunde PK, Sejersted OM, Thorud HM, Tønnessen T, Henriksen UL, Christensen G, Westerblad H, Bruton J (2006) Effects of congestive heart failure on Ca2+ handling in skeletal muscle during fatigue. Circ Res 98:1514–1519

    Article  PubMed  CAS  Google Scholar 

  61. Bekedam MA, van Beek-Harmsen BJ, van Mechelen W, Boonstra A, Visser FC, van der Laarse WJ (2009) Sarcoplasmic reticulum ATPase activity in type I and II skeletal muscle fibres of chronic heart failure patients. Int J Cardiol 133:185–190

    Article  PubMed  Google Scholar 

  62. Ashrafian H, Frenneaux MP, Opie LH (2007) Metabolic mechanisms in heart failure. Circulation 116:434–448

    Article  PubMed  CAS  Google Scholar 

  63. Doehner W, von Haehling S, Anker SD (2008) Insulin resistance in chronic heart failure. J Am Coll Cardiol 52:239

    Article  PubMed  Google Scholar 

  64. Coats AJ, Anker SD (2000) Insulin resistance in chronic heart failure. J Cardiovasc Pharmacol 35:S9–S14

    Article  PubMed  CAS  Google Scholar 

  65. Anker SD, Volterrani M, Pflaum CD, Strasburger CJ, Osterziel KJ, Doehner W, Ranke MB, Poole-Wilson PA, Giustina A, Dietz R, Coats A (2001) Acquired growth hormone resistance in patients with chronic heart failure: implications for therapy with growth hormone. J Am Coll Cardiol 38:443–452

    Article  PubMed  CAS  Google Scholar 

  66. Niebauer J, Pflaum CD, Clark AL, Strasburger CJ, Hooper J, Poole-Wilson PA, Coats AJ, Anker S (1998) Deficient insulin-like growth factor I in chronic heart failure predicts altered body composition, anabolic deficiency, cytokine and neurohormonal activation. J Am Coll Cardiol 32:393–397

    Article  PubMed  CAS  Google Scholar 

  67. Van Berendoncks AM, Conraads VM (2011) Functional adiponectin resistance and exercise intolerance in heart failure. Curr Heart Fail Rep 8:113–122

    Article  PubMed  Google Scholar 

  68. Krause MP, Liu Y, Vu V, Chan L, Xu A, Riddell MC, Sweeney G, Hawke T (2008) Adiponectin is expressed by skeletal muscle fibers and influences muscle phenotype and function. Am J Physiol Cell Physiol 295:C203–C212

    Article  PubMed  CAS  Google Scholar 

  69. Tsutamoto T, Tanaka T, Sakai H, Ishikawa C, Fujii M, Yamamoto T, Horie M (2007) Total and high molecular weight adiponectin, haemodynamics, and mortality in patients with chronic heart failure. Eur Heart J 28:1723–1730

    Article  PubMed  Google Scholar 

  70. Van Berendoncks AM, Beckers P, Hoymans VY, Possemiers N, Coenen S, Elseviers MM, Vrints CJ, Conraads V (2010) Beta-blockers modify the prognostic value of adiponectin in chronic heart failure. Int J Cardiol 150:296–300

    Article  PubMed  Google Scholar 

  71. McEntegart MB, Awede B, Petrie MC, Sattar N, Dunn FG, MacFarlane NG, McMurray J (2007) Increase in serum adiponectin concentration in patients with heart failure and cachexia: relationship with leptin, other cytokines, and B-type natriuretic peptide. Eur Heart J 28:829–835

    Article  PubMed  CAS  Google Scholar 

  72. Kintscher U (2007) Does adiponectin resistance exist in chronic heart failure? Eur Heart J 28:1676–1677

    Article  PubMed  Google Scholar 

  73. Van Berendoncks AM, Garnier A, Beckers P, Hoymans VY, Possemiers N, Fortin D, Martinet W, Van Hoof V, Vrints CJ, Ventura-Clapier R, Conraads VM (2010) Functional adiponectin resistance at the level of the skeletal muscle in mild to moderate chronic heart failure. Circ Heart Fail 3:185–194

    Article  PubMed  Google Scholar 

  74. Conraads V (2002) 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

    Article  PubMed  CAS  Google Scholar 

  75. Gielen S, Adams V, Möbius-Winkler S, Linke A, Erbs S, Yu J, Kempf W, Schubert A, Schuler G, Hambrecht R (2003) Anti-inflammatory effects of exercise training in the skeletal muscle of patients with chronic heart failure. J Am Coll Cardiol 42:861–868

    Article  PubMed  CAS  Google Scholar 

  76. Conraads VM, Beckers P, Vaes J, Martin M, Van Hoof V, De Maeyer C, Possemiers N, Wuyts FL, Vrints C (2004) Combined endurance/resistance training reduces NT-proBNP levels in patients with chronic heart failure. Eur Heart J 25:1797–1805

    Article  PubMed  CAS  Google Scholar 

  77. Braith RW, Welsch MA, Feigenbaum MS, Kluess HA, Pepine CJ (1999) Neuroendocrine activation in heart failure is modified by endurance exercise training. J Am Coll Cardiol 34:1170–1175

    Article  PubMed  CAS  Google Scholar 

  78. Van Berendoncks AM, Beckers P, Hoymans VY, Possemiers N, Wuytss FL, Vrints CJ, Conraads VM (2009) Exercise training reduces circulating adiponectin levels in patients with chronic heart failure. Clin Sci (Lond) 118:281–289

    Article  Google Scholar 

  79. Van Berendoncks AM, Garnier A, Beckers P, Hoymans VY, Possemiers N, Fortin D, Van Hoof V, Dewilde S, Vrints CJ, Ventura-Clapier R, Conraads VM (2011) Exercise training reverses adiponectin resistance in skeletal muscle of patients with chronic heart failure. Heart 97:1403–1409

    Article  PubMed  Google Scholar 

  80. Höllriegel R, Beck EB, Linke A, Adams V, Möbius-Winkler S, Mangner N, Sandri M, Gielen S, Gutberlet M, Hambrecht R, Schuler G, Erbs S (2012) Anabolic effects of exercise training in patients with advanced chronic heart failure (NYHA IIIb): Impact on ubiquitin-protein ligases expression and skeletal muscle size. Int J Cardiol [Epub ahead of print]

  81. Conraads VM, Vrints CJ, Rodrigus IE, Hoymans VY, Van Craenenbroeck EM, Bosmans J, Claeys MJ, Van Herck P, Linke A, Schuler G, Adams V (2009) Depressed expression of MuRF1 and MAFbx in areas remote of recent myocardial infarction: a mechanism contributing to myocardial remodeling? Basic Res Cardiol 105:219–226

    Article  PubMed  Google Scholar 

  82. Zhou Q, Du J, Hu Z, Walsh K, Wang XH (2007) Evidence for adipose-muscle cross talk: opposing regulation of muscle proteolysis by adiponectin and Fatty acids. Endocrinology 148:5696–5705

    Article  PubMed  CAS  Google Scholar 

  83. Adams V, Yu J, Möbius-Winkler S, Linke A, Weigl C, Hilbrich L, Schuler G, Hambrecht R (1997) Increased inducible nitric oxide synthase in skeletal muscle biopsies from patients with chronic heart failure. Biochem Mol Med 61:152–160

    Article  PubMed  CAS  Google Scholar 

  84. Heineke J, Auger-Messier M, Xu J, Sargent M, York A, Welle S, Molkentin J (2010) Genetic deletion of myostatin from the heart prevents skeletal muscle atrophy in heart failure. Circulation 121:419–425

    Article  PubMed  CAS  Google Scholar 

  85. Lenk K, Schur R, Linke A, Erbs S, Matsumoto Y, Adams V, Schuler G (2009) Impact of exercise training on myostatin expression in the myocardium and skeletal muscle in a chronic heart failure model. Eur J Heart Fail 11:342–348

    Article  PubMed  CAS  Google Scholar 

  86. Aucello M, Dobrowolny G, Musarò A (2009) Localized accumulation of oxidative stress causes muscle atrophy through activation of an autophagic pathway. Autophagy 5:527–529

    Article  PubMed  CAS  Google Scholar 

  87. Lenk K, Erbs S, Höllriegel R, Beck E, Linke A, Gielen S, Möbius Winkler S, Sandri M, Hambrecht R, Schuler G, Adams V (2011) Exercise training leads to a reduction of elevated myostatin levels in patients with chronic heart failure. Eur J Cardiovasc Prev Rehabil 19:404–411

  88. Hambrecht R, Schulze PC, Gielen S, Linke A, Möbius-Winkler S, Erbs S, Kratzsch J, Schubert A, Adams V, Schuler G (2005) 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

    Article  PubMed  Google Scholar 

  89. Adams V, Linke A, Gielen S, Erbs S, Hambrecht R, Schuler G (2008) Modulation of Murf-1 and MAFbx expression in the myocardium by physical exercise training. Eur J Cardiovasc Prev Rehabil. 15:293–299

    Article  PubMed  Google Scholar 

  90. Conraads VM, Beckers PJ (2010) Exercise training in heart failure: practical guidance. Heart 96:2025–2031

    Article  PubMed  Google Scholar 

  91. Beckers PJ, Possemiers NM, Van Craenenbroeck EM, Van Berendoncks AM, Wuyts K, Vrints CJ, Conraads VM (2011) Impact of exercise testing mode on exercise parameters in patients with chronic heart failure. Eur J Cardiovasc Prev Rehabil 19:389–395

    Google Scholar 

  92. Spruit MA, Eterman RM, Hellwig VA, Janssen PP, Wouters EF, Uszko-Lencer NH (2009) Effects of moderate-to-high intensity resistance training in patients with chronic heart failure. Heart 95:1399–1408

    Article  PubMed  CAS  Google Scholar 

  93. Feiereisen P, Delagardelle C, Vaillant M, Lasar Y, Beissel J (2007) Is strength training the more efficient training modality in chronic heart failure. Med Sci Sports Exerc 39:1910–1917

    Article  PubMed  Google Scholar 

  94. Maiorana A, O’Driscoll G, Dembo L, Cheetham C, Goodman C, Taylor R, Green D (2000) Effect of aerobic and resistance exercise training on vascular function in heart failure. Am J Physiol Heart Circ Physiol 279:H1999–H2005

    PubMed  CAS  Google Scholar 

  95. Maiorana A, O’Driscoll G, Cheetham C, Collis J, Goodman C, Rankin S, Taylor R, Green D (2000) Combined aerobic and resistance exercise training improves functional capacity and strength in CHF. J Appl Physiol 88:1565–1570

    PubMed  CAS  Google Scholar 

  96. Dall’Ago P, Chiappa GR, Guths H, Stein R, Ribeiro JP (2006) Inspiratory muscle training in patients with heart failure and inspiratory muscle weakness: a randomized trial. J Am Coll Cardiol 47:757–763

    Article  PubMed  Google Scholar 

  97. Winkelmann ER, Chiappa GR, Lima CO, Viecili PR, Stein R, Ribeiro JP (2009) Addition of inspiratory muscle training to aerobic training improves cardiorespiratory responses to exercise in patients with heart failure and inspiratory muscle weakness. Am Heart J 158:768 e1–768 e7

    Google Scholar 

  98. Smart N, Haluska B, Jeffriess L, Marwick TH (2007) Exercise training in systolic and diastolic dysfunction: effects on cardiac function, functional capacity, and quality of life. Am Heart J 153:530–536

    Article  PubMed  Google Scholar 

  99. Kitzman DW, Brubaker PH, Morgan TM, Stewart KP, Little WC (2010) Exercise training in older patients with heart failure and preserved ejection fraction: a randomized, controlled, single-blind trial. Circ Heart Fail 3:659–667

    Article  PubMed  Google Scholar 

  100. Edelmann F, Gelbrich G, Düngen HD, Fröhling S, Wachter R, Stahrenberg R, Binder L, Töpper A, Lashki DJ, Schwarz S, Herrmann-Lingen C, Löffler M, Hasenfuss G, Halle M, Pieske B (2011) Exercise training improves exercise capacity and diastolic function in patients with heart failure with preserved ejection fraction: results of the Ex-DHF (exercise training in diastolic heart failure) pilot study. J Am Coll Cardiol 58:1780–1791

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

Drs. C, VC, DM, VB, B and V have no conflicts of interest or financial ties to disclose in relation to this research paper.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Viviane M. Conraads.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Conraads, V.M., Van Craenenbroeck, E.M., De Maeyer, C. et al. Unraveling new mechanisms of exercise intolerance in chronic heart failure. Role of exercise training. Heart Fail Rev 18, 65–77 (2013). https://doi.org/10.1007/s10741-012-9324-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10741-012-9324-0

Keywords

Navigation