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01-12-2018 | Pathophysiology: Neuroendocrine, Vascular, and Metabolic Factors (S. Katz, Section Editor)

Impaired Exercise Tolerance in Heart Failure: Role of Skeletal Muscle Morphology and Function

Published in: Current Heart Failure Reports | Issue 6/2018

Abstract

Purpose of Review

To discuss the impact of deleterious changes in skeletal muscle morphology and function on exercise intolerance in patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), as well as the utility of exercise training and the potential of novel treatment strategies to preserve or improve skeletal muscle morphology and function.

Recent Findings

Both HFrEF and HFpEF patients exhibit a reduction in percent of type I (oxidative) muscle fibers and oxidative enzymes coupled with abnormal mitochondrial respiration. These skeletal muscle abnormalities contribute to impaired oxidative metabolism with an earlier shift towards glycolytic metabolism during exercise that is strongly associated with exercise intolerance. In both HFrEF and HFpEF patients, peripheral “non-cardiac” factors are important determinants of the improvement in exercise tolerance following aerobic exercise training. Adjunctive strategies that include nutritional supplementation with amino acids and/or anabolic drugs to stimulate anabolic molecular pathways in skeletal muscle show great promise for improving exercise tolerance and treating heart failure-associated sarcopenia, but these efforts remain early in their evolution, with no immediate clinical applications.

Summary

There is consistent evidence that heart failure is associated with multiple skeletal muscle abnormalities which impair oxygen uptake and utilization and contribute greatly to exercise intolerance. Exercise training induces favorable adaptations in skeletal muscle morphology and function that contribute to improvements in exercise tolerance in patients with HFrEF. The contribution of skeletal muscle adaptations to improved exercise tolerance following exercise training in HFpEF remains unknown and warrants further investigation.

Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, Cheng S, et al. Heart Disease and Stroke Statistics-2018 update: a report from the American Heart Association. Circulation. 2018;137(12):e67–e492.PubMed

• Haykowsky MJ, Tomczak CR, Scott JM, Paterson DI, Kitzman DW. Determinants of exercise intolerance in patients with heart failure and reduced or preserved ejection fraction. J Appl Physiol (1985). 2015;119(6):739–44. This review covers the mechanisms responsible for exercise intolerance in patients with heart failure and reduced or preserved ejection fraction.

Upadhya B, Kitzman DW. Heart Failure with preserved ejection fraction in older adults. Heart Fail Clin. 2017;13(3):485–502.PubMedPubMedCentral

Borlaug BA, Melenovsky V, Russell SD, Kessler K, Pacak K, Becker LC, et al. Impaired chronotropic and vasodilator reserves limit exercise capacity in patients with heart failure and a preserved ejection fraction. Circulation. 2006;114(20):2138–47.PubMed

Borlaug BA, Olson TP, Lam CS, Flood KS, Lerman A, Johnson BD, et al. Global cardiovascular reserve dysfunction in heart failure with preserved ejection fraction. J Am Coll Cardiol. 2010;56(11):845–54.PubMedPubMedCentral

•• Haykowsky MJ, Brubaker PH, John JM, Stewart KP, Morgan TM, Kitzman DW. Determinants of exercise intolerance in elderly heart failure patients with preserved ejection fraction. J Am Coll Cardiol. 2011;58(3):265–74. This cross-sectional study investigated the mechanisms responsible for reduced exercise tolerance in heart failure with preserved ejection fraction. Reduced peak exercise VO ₂ was associated with reduced peak cardiac output and reduced peak arteriovenous oxygen content difference (a-vO ₂ diff); however, the change in a-vO ₂ diff was the strongest independent predictor of peak VO ₂ during exercise. PubMedPubMedCentral

Sullivan MJ, Knight JD, Higginbotham MB, Cobb FR. Relation between central and peripheral hemodynamics during exercise in patients with chronic heart failure. Muscle blood flow is reduced with maintenance of arterial perfusion pressure. Circulation. 1989;80(4):769–81.PubMed

Wilson JR, Mancini DM, Dunkman WB. Exertional fatigue due to skeletal muscle dysfunction in patients with heart failure. Circulation. 1993;87(2):470–5.PubMed

•• Dhakal BP, Malhotra R, Murphy RM, Pappagianopoulos PP, Baggish AL, Weiner RB, et al. Mechanisms of exercise intolerance in heart failure with preserved ejection fraction: the role of abnormal peripheral oxygen extraction. Circ Heart Fail. 2015;8(2):286–94. First study to directly measure arteriovenous oxygen content (a-vO ₂ diff) throughout exercise in heart failure with reduced ejection fraction (HFrEF), preserved ejection fraction (HFpEF), or normal individuals. Reduced peak exercise a-vO ₂ diff was the major determinant of exercise capacity in HFpEF. PubMed

10.

Esposito F, Mathieu-Costello O, Shabetai R, Wagner PD, Richardson RS. Limited maximal exercise capacity in patients with chronic heart failure: partitioning the contributors. J Am Coll Cardiol. 2010;55(18):1945–54.PubMedPubMedCentral

11.

Forman DE, Arena R, Boxer R, Dolansky MA, Eng JJ, Fleg JL, et al. Prioritizing functional capacity as a principal end point for therapies oriented to older adults with cardiovascular disease: a scientific statement for healthcare professionals from the American Heart Association. Circulation. 2017;135(16):e894–918.PubMed

12.

Poole DC, Richardson RS, Haykowsky MJ, Hirai DM, Musch TI. Exercise limitations in heart failure with reduced and preserved ejection fraction. J Appl Physiol (1985). 2018;124(1):208–24.

13.

Houstis NE, Eisman AS, Pappagianopoulos PP, Wooster L, Bailey CS, Wagner PD, et al. Exercise intolerance in heart failure with preserved ejection fraction: diagnosing and ranking its causes using personalized O2 pathway analysis. Circulation. 2018;137(2):148–61.PubMed

14.

Kitzman DW, Higginbotham MB, Cobb FR, Sheikh KH, Sullivan MJ. Exercise intolerance in patients with heart failure and preserved left ventricular systolic function: failure of the Frank-Starling mechanism. J Am Coll Cardiol. 1991;17(5):1065–72.PubMed

15.

Sullivan MJ, Green HJ, Cobb FR. Altered skeletal muscle metabolic response to exercise in chronic heart failure. Relation to skeletal muscle aerobic enzyme activity. Circulation. 1991;84(4):1597–607.PubMed

16.

•• Weiss K, Schar M, Panjrath GS, Zhang Y, Sharma K, Bottomley PA, et al. Fatigability, exercise intolerance, and abnormal skeletal muscle energetics in heart failure. Circ Heart Fail. 2017;10(7). This cross-sectional study showed that patients with heart failure with reduced or preserved ejection fraction with exercise intolerance exhibit an accelerated rate of phosphocreatine depletion during plantar flexion exercise compared with healthy controls and HFrEF patients without exercise intolerance.

17.

Anker SD, Ponikowski P, Varney S, Chua TP, Clark AL, Webb-Peploe KM, et al. Wasting as independent risk factor for mortality in chronic heart failure. Lancet. 1997;349(9058):1050–3.PubMed

18.

Cicoira M, Zanolla L, Franceschini L, Rossi A, Golia G, Zamboni M, et al. Skeletal muscle mass independently predicts peak oxygen consumption and ventilatory response during exercise in noncachectic patients with chronic heart failure. J Am Coll Cardiol. 2001;37(8):2080–5.PubMed

19.

Fulster S, Tacke M, Sandek A, Ebner N, Tschope C, Doehner W, et al. Muscle wasting in patients with chronic heart failure: results from the studies investigating co-morbidities aggravating heart failure (SICA-HF). Eur Heart J. 2013;34(7):512–9.PubMed

20.

Mancini DM, Walter G, Reichek N, Lenkinski R, McCully KK, Mullen JL, et al. Contribution of skeletal muscle atrophy to exercise intolerance and altered muscle metabolism in heart failure. Circulation. 1992;85(4):1364–73.PubMed

21.

Minotti JR, Christoph I, Oka R, Weiner MW, Wells L, Massie BM. Impaired skeletal muscle function in patients with congestive heart failure. Relationship to systemic exercise performance. J Clin Invest. 1991;88(6):2077–82.PubMedPubMedCentral

22.

Drexler H, Riede U, Munzel T, Konig H, Funke E, Just H. Alterations of skeletal muscle in chronic heart failure. Circulation. 1992;85(5):1751–9.PubMed

23.

Magnusson G, Kaijser L, Rong H, Isberg B, Sylven C, Saltin B. Exercise capacity in heart failure patients: relative importance of heart and skeletal muscle. Clin Physiol. 1996;16(2):183–95.PubMed

24.

Massie BM, Simonini A, Sahgal P, Wells L, Dudley GA. Relation of systemic and local muscle exercise capacity to skeletal muscle characteristics in men with congestive heart failure. J Am Coll Cardiol. 1996;27(1):140–5.PubMed

25.

Schaufelberger M, Andersson G, Eriksson BO, Grimby G, Held P, Swedberg K. Skeletal muscle changes in patients with chronic heart failure before and after treatment with enalapril. Eur Heart J. 1996;17(11):1678–85.PubMed

26.

Sullivan MJ, Green HJ, Cobb FR. Skeletal muscle biochemistry and histology in ambulatory patients with long-term heart failure. Circulation. 1990;81(2):518–27.PubMed

27.

Minotti JR, Pillay P, Oka R, Wells L, Christoph I, Massie BM. Skeletal muscle size: relationship to muscle function in heart failure. J Appl Physiol (1985). 1993;75(1):373–81.

28.

Piepoli MF, Kaczmarek A, Francis DP, Davies LC, Rauchhaus M, Jankowska EA, et al. Reduced peripheral skeletal muscle mass and abnormal reflex physiology in chronic heart failure. Circulation. 2006;114(2):126–34.PubMed

29.

Lang CC, Chomsky DB, Rayos G, Yeoh TK, Wilson JR. Skeletal muscle mass and exercise performance in stable ambulatory patients with heart failure. J Appl Physiol (1985). 1997;82(1):257–61.

30.

Haykowsky MJ, Brubaker PH, Morgan TM, Kritchevsky S, Eggebeen J, Kitzman DW. Impaired aerobic capacity and physical functional performance in older heart failure patients with preserved ejection fraction: role of lean body mass. J Gerontol A Biol Sci Med Sci. 2013;68(8):968–75.PubMedPubMedCentral

31.

•• Kitzman DW, Nicklas B, Kraus WE, Lyles MF, Eggebeen J, Morgan TM, et al. Skeletal muscle abnormalities and exercise intolerance in older patients with heart failure and preserved ejection fraction. Am J Physiol Heart Circ Physiol. 2014;306(9):H1364–70. Using needle biopsies of the vastus lateralis, this cross-sectional study demonstrated that older patients with heart failure and preserved ejection fraction exhibit multiple skeletal muscle abnormalities characterized by a shift in muscle fiber type distribution with reduced type I oxidative muscle fibers and a reduced capillary-to-fiber ratio that are both associated with reduced VO _2peak. PubMedPubMedCentral

32.

Duscha BD, Kraus WE, Keteyian SJ, Sullivan MJ, Green HJ, Schachat FH, 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(7):1956–63.PubMed

33.

•• Molina AJ, Bharadwaj MS, Van Horn C, Nicklas BJ, Lyles MF, Eggebeen J, et al. Skeletal muscle mitochondrial content, oxidative capacity, and mfn2 expression are reduced in older patients with heart failure and preserved ejection fraction and are related to exercise intolerance. JACC Heart Fail. 2016;4(8):636–45. Using needle biopsies of the vastus lateralis, this cross-sectional study demonstrates that skeletal muscle oxidative capacity, mitochondrial content, and mitochondrial fusion are abnormal in older patients with heart failure and preserved ejection fraction and may contribute to severe exercise intolerance in this patient population. PubMedPubMedCentral

34.

Martin WH 3rd, Berman WI, Buckey JC, Snell PG, Blomqvist CG. Effects of active muscle mass size on cardiopulmonary responses to exercise in congestive heart failure. J Am Coll Cardiol. 1989;14(3):683–94.PubMed

35.

Bhella PS, Prasad A, Heinicke K, Hastings JL, Arbab-Zadeh A, Adams-Huet B, et al. Abnormal haemodynamic response to exercise in heart failure with preserved ejection fraction. Eur J Heart Fail. 2011;13(12):1296–304.PubMedPubMedCentral

36.

Abudiab MM, Redfield MM, Melenovsky V, Olson TP, Kass DA, Johnson BD, et al. Cardiac output response to exercise in relation to metabolic demand in heart failure with preserved ejection fraction. Eur J Heart Fail. 2013;15(7):776–85.PubMedPubMedCentral

37.

Chati Z, Zannad F, Robin-Lherbier B, Escanye JM, Jeandel C, Robert J, et al. Contribution of specific skeletal muscle metabolic abnormalities to limitation of exercise capacity in patients with chronic heart failure: a phosphorus 31 nuclear magnetic resonance study. Am Heart J. 1994;128(4):781–92.PubMed

38.

Lipkin DP, Jones DA, Round JM, Poole-Wilson PA. Abnormalities of skeletal muscle in patients with chronic heart failure. Int J Cardiol. 1988;18(2):187–95.PubMed

39.

Mancini DM, Coyle E, Coggan A, Beltz J, Ferraro N, Montain S, et al. Contribution of intrinsic skeletal muscle changes to 31P NMR skeletal muscle metabolic abnormalities in patients with chronic heart failure. Circulation. 1989;80(5):1338–46.PubMed

40.

Massie BM, Conway M, Yonge R, Frostick S, Sleight P, Ledingham J, et al. 31P nuclear magnetic resonance evidence of abnormal skeletal muscle metabolism in patients with congestive heart failure. Am J Cardiol. 1987;60(4):309–15.PubMed

41.

van der Ent M, Jeneson JA, Remme WJ, Berger R, Ciampricotti R, Visser F. A non-invasive selective assessment of type I fibre mitochondrial function using 31P NMR spectroscopy. Evidence for impaired oxidative phosphorylation rate in skeletal muscle in patients with chronic heart failure. Eur Heart J. 1998;19(1):124–31.PubMed

42.

Esposito F, Reese V, Shabetai R, Wagner PD, Richardson RS. Isolated quadriceps training increases maximal exercise capacity in chronic heart failure: the role of skeletal muscle convective and diffusive oxygen transport. J Am Coll Cardiol. 2011;58(13):1353–62.PubMedPubMedCentral

43.

Haykowsky MJ, Kouba EJ, Brubaker PH, Nicklas BJ, Eggebeen J, Kitzman DW. Skeletal muscle composition and its relation to exercise intolerance in older patients with heart failure and preserved ejection fraction. Am J Cardiol. 2014;113(7):1211–6.PubMedPubMedCentral

44.

Haykowsky MJ, Nicklas BJ, Brubaker PH, Hundley WG, Brinkley TE, Upadhya B, et al. Regional adipose distribution and its relationship to exercise intolerance in older obese patients who have heart failure with preserved ejection fraction. JACC Heart Fail. 2018.

45.

Delmonico MJ, Harris TB, Visser M, Park SW, Conroy MB, Velasquez-Mieyer P, et al. Longitudinal study of muscle strength, quality, and adipose tissue infiltration. Am J Clin Nutr. 2009;90(6):1579–85.PubMedPubMedCentral

46.

Haykowsky MJ, Liang Y, Pechter D, Jones LW, McAlister FA, Clark AM. 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. 2007;49(24):2329–36.PubMed

47.

Weston KS, Wisloff U, Coombes JS. High-intensity interval training in patients with lifestyle-induced cardiometabolic disease: a systematic review and meta-analysis. Br J Sports Med. 2014;48(16):1227–34.PubMed

48.

Erbs S, Hollriegel R, Linke A, Beck EB, Adams V, Gielen S, et al. 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. 2010;3(4):486–94.PubMed

49.

Hambrecht R, Fiehn E, Yu J, Niebauer J, Weigl C, Hilbrich L, 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. 1997;29(5):1067–73.PubMed

50.

Hambrecht R, Niebauer J, Fiehn E, Kalberer B, Offner B, Hauer K, 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. 1995;25(6):1239–49.PubMed

51.

Magnusson G, Gordon A, Kaijser L, Sylven C, Isberg B, Karpakka J, et al. High intensity knee extensor training, in patients with chronic heart failure. Major skeletal muscle improvement. Eur Heart J. 1996;17(7):1048–55.PubMed

52.

Wisloff U, Stoylen A, Loennechen JP, Bruvold M, Rognmo O, Haram PM, et al. Superior cardiovascular effect of aerobic interval training versus moderate continuous training in heart failure patients: a randomized study. Circulation. 2007;115(24):3086–94.PubMed

53.

Pu CT, Johnson MT, Forman DE, Hausdorff JM, Roubenoff R, Foldvari M, et al. Randomized trial of progressive resistance training to counteract the myopathy of chronic heart failure. J Appl Physiol (1985). 2001;90(6):2341–50.

54.

Bouchla A, Karatzanos E, Dimopoulos S, Tasoulis A, Agapitou V, Diakos N, et al. The addition of strength training to aerobic interval training: effects on muscle strength and body composition in CHF patients. J Cardiopulm Rehabil Prev. 2011;31(1):47–51.PubMed

55.

Jankowska EA, Wegrzynowska K, Superlak M, Nowakowska K, Lazorczyk M, Biel B, et al. The 12-week progressive quadriceps resistance training improves muscle strength, exercise capacity and quality of life in patients with stable chronic heart failure. Int J Cardiol. 2008;130(1):36–43.PubMed

56.

Minotti JR, Johnson EC, Hudson TL, Zuroske G, Murata G, Fukushima E, et al. Skeletal muscle response to exercise training in congestive heart failure. J Clin Invest. 1990;86(3):751–8.PubMedPubMedCentral

57.

Senden PJ, Sabelis LW, Zonderland ML, Hulzebos EH, Bol E, Mosterd WL. The effect of physical training on workload, upper leg muscle function and muscle areas in patients with chronic heart failure. Int J Cardiol. 2005;100(2):293–300.PubMed

58.

•• Kitzman DW, Brubaker P, Morgan T, Haykowsky M, Hundley G, Kraus WE, et al. Effect of caloric restriction or aerobic exercise training on peak oxygen consumption and quality of life in obese older patients with heart failure with preserved ejection fraction: a randomized clinical trial. JAMA. 2016;315(1):36–46. This randomized, attention-controlled, 2 × 2 factorial trial investigated whether 20 weeks of caloric restriction, exercise, or both improves exercise capacity in obese older patients with heart failure and preserved ejection fraction. Exercise training and caloric restriction both yielded similar improvements in VO _2peak , while a combination of both caused an additive effect on VO _2peak . Both exercise training and caloric restriction reduced body weight and fat mass, while caloric restriction improved muscle leg muscle quality. In addition, the change in VO _2peak was positively correlated with both the change in percent lean mass and the change in thigh muscle to intermuscular fat ratio. PubMedPubMedCentral

59.

Tyni-Lenne R, Gordon A, Jensen-Urstad M, Dencker K, Jansson E, Sylven C. Aerobic training involving a minor muscle mass shows greater efficiency than training involving a major muscle mass in chronic heart failure patients. J Card Fail. 1999;5(4):300–7.PubMed

60.

Dubach P, Myers J, Dziekan G, Goebbels U, Reinhart W, Muller P, et al. Effect of high intensity exercise training on central hemodynamic responses to exercise in men with reduced left ventricular function. J Am Coll Cardiol. 1997;29(7):1591–8.PubMed

61.

Sullivan MJ, Higginbotham MB, Cobb FR. Exercise training in patients with severe left ventricular dysfunction. Hemodynamic and metabolic effects. Circulation. 1988;78(3):506–15.PubMed

62.

Fu TC, Yang NI, Wang CH, Cherng WJ, Chou SL, Pan TL, et al. Aerobic interval training elicits different hemodynamic adaptations between heart failure patients with preserved and reduced ejection fraction. Am J Phys Med Rehabil. 2016;95(1):15–27.PubMed

63.

•• Haykowsky MJ, Brubaker PH, Stewart KP, Morgan TM, Eggebeen J, Kitzman DW. Effect of endurance training on the determinants of peak exercise oxygen consumption in elderly patients with stable compensated heart failure and preserved ejection fraction. J Am Coll Cardiol. 2012;60(2):120–8. This single-blind, randomized controlled trial in elderly heart failure with preserved ejection fraction patients showed that the improvement in peak exercise VO ₂ (exercise capacity) following 4 months of exercise training was driven primarily by peripheral adaptations with little to no changes in peak exercise cardiac output. PubMedPubMedCentral

64.

Adamopoulos S, Coats AJ, Brunotte F, Arnolda L, Meyer T, Thompson CH, et al. Physical training improves skeletal muscle metabolism in patients with chronic heart failure. J Am Coll Cardiol. 1993;21(5):1101–6.PubMed

65.

Ohtsubo M, Yonezawa K, Nishijima H, Okita K, Hanada A, Kohya T, et al. Metabolic abnormality of calf skeletal muscle is improved by localised muscle training without changes in blood flow in chronic heart failure. Heart. 1997;78(5):437–43.PubMedPubMedCentral

66.

Stratton JR, Dunn JF, Adamopoulos S, Kemp GJ, Coats AJ, Rajagopalan B. Training partially reverses skeletal muscle metabolic abnormalities during exercise in heart failure. J Appl Physiol (1985). 1994;76(4):1575–82.

67.

Giuliano C, Karahalios A, Neil C, Allen J, Levinger I. The effects of resistance training on muscle strength, quality of life and aerobic capacity in patients with chronic heart failure - a meta-analysis. Int J Cardiol. 2017;227:413–23.PubMed

68.

Jewiss D, Ostman C, Smart NA. The effect of resistance training on clinical outcomes in heart failure: a systematic review and meta-analysis. Int J Cardiol. 2016;221:674–81.PubMed

69.

Maiorana A, O’Driscoll G, Cheetham C, Collis J, Goodman C, Rankin S, et al. Combined aerobic and resistance exercise training improves functional capacity and strength in CHF. J Appl Physiol (1985). 2000;88(5):1565–70.

70.

Tucker W, Beaudry RI, Liang Y, Clark AM, Tomczak CR, Nelson MD, et al. Meta-analysis of exercise training on left ventricular ejection fraction in heart failure with reduced ejection fraction: a 10–year update. Prog Cardiovasc Dis. 2018. Accepted for publiation: In press.

71.

Dieberg G, Ismail H, Giallauria F, Smart NA. Clinical outcomes and cardiovascular responses to exercise training in heart failure patients with preserved ejection fraction: a systematic review and meta-analysis. J Appl Physiol (1985). 2015;119(6):726–33.

72.

Pandey A, Parashar A, Kumbhani D, Agarwal S, Garg J, Kitzman D, et al. Exercise training in patients with heart failure and preserved ejection fraction: meta-analysis of randomized control trials. Circ Heart Fail. 2015;8(1):33–40.PubMed

73.

Taylor RS, Davies EJ, Dalal HM, Davis R, Doherty P, Cooper C, et al. Effects of exercise training for heart failure with preserved ejection fraction: a systematic review and meta-analysis of comparative studies. Int J Cardiol. 2012;162(1):6–13.PubMed

74.

Tucker WJ, Nelson MD, Beaudry RI, Halle M, Sarma S, Kitzman DW, et al. Impact of exercise training on peak oxygen uptake and its determinants in heart failure with preserved ejection fraction. Card Fail Rev. 2016;2(2):95–101.PubMedPubMedCentral

75.

• Tucker WJ, Lijauco CC, Hearon CM Jr, Angadi SS, Nelson MD, Sarma S, et al. Mechanisms of the Improvement in peak VO2 with exercise training in heart failure with reduced or preserved ejection fraction. Heart Lung Circ. 2018;27(1):9–21. This review covers the central and peripheral mechanisms responsible for exercise intolerance in patients with heart failure and reduced or preserved ejection fraction. PubMed

76.

Angadi SS, Mookadam F, Lee CD, Tucker WJ, Haykowsky MJ, Gaesser GA. High-intensity interval training vs. moderate-intensity continuous exercise training in heart failure with preserved ejection fraction: a pilot study. J Appl Physiol (1985). 2015;119(6):753–8.

77.

Edelmann F, Gelbrich G, Dungen HD, Frohling S, Wachter R, Stahrenberg R, et al. 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. 2011;58(17):1780–91.PubMed

78.

Kitzman DW, Brubaker PH, Morgan TM, Stewart KP, Little WC. Exercise training in older patients with heart failure and preserved ejection fraction: a randomized, controlled, single-blind trial. Circ Heart Fail. 2010;3(6):659–67.PubMedPubMedCentral

79.

Smart NA, Haluska B, Jeffriess L, Leung D. Exercise training in heart failure with preserved systolic function: a randomized controlled trial of the effects on cardiac function and functional capacity. Congest Heart Fail. 2012;18(6):295–301.PubMed

80.

Lin H, Zhang H, Lin Z, Li X, Kong X, Sun G. Review of nutritional screening and assessment tools and clinical outcomes in heart failure. Heart Fail Rev. 2016;21(5):549–65.PubMed

81.

de Lucia C, Gambino G, Petraglia L, Elia A, Komici K, Femminella GD, et al. Long-term caloric restriction improves cardiac function, remodeling, adrenergic responsiveness, and sympathetic innervation in a model of postischemic heart failure. Circ Heart Fail. 2018;11(3):e004153.PubMed

82.

Longo VD, Antebi A, Bartke A, Barzilai N, Brown-Borg HM, Caruso C, et al. interventions to slow aging in humans: are we ready? Aging Cell. 2015;14(4):497–510.PubMedPubMedCentral

83.

• Aquilani R, Viglio S, Iadarola P, Opasich C, Testa A, Dioguardi FS, et al. Oral amino acid supplements improve exercise capacities in elderly patients with chronic heart failure. Am J Cardiol. 2008;101(11a):104e–10e. This randomized, double-blind, placebo-controlled study showed that 30 days of supplementation with amino acids increased exercise capacity in elderly patients with heart failure. PubMed

84.

• Lombardi C, Carubelli V, Lazzarini V, Vizzardi E, Bordonali T, Ciccarese C, et al. Effects of oral administration of orodispersible levo-carnosine on quality of life and exercise performance in patients with chronic heart failure. Nutrition. 2015;31(1):72–8. This prospective, open-label, randomized controlled, parallel group study showed that 6 months of amino acid supplementation (levo-carnosine) improved exercise capacity and quality of life in heart failure patients with reduced ejection fraction. PubMed

85.

Lombardi C, Carubelli V, Lazzarini V, Vizzardi E, Quinzani F, Guidetti F, et al. Effects of oral amino acid supplements on functional capacity in patients with chronic heart failure. Clin Med Insights Cardiol. 2014;8:39–44.PubMedPubMedCentral

86.

Lopez-Otin C, Galluzzi L, JMP F, Madeo F, Kroemer G. Metabolic control of longevity. Cell. 2016;166(4):802–21.PubMed

87.

Beavers KM, Miller ME, Rejeski WJ, Nicklas BJ, Kritchevsky SB. Fat mass loss predicts gain in physical function with intentional weight loss in older adults. J Gerontol A Biol Sci Med Sci. 2013;68(1):80–6.PubMed

88.

de las Fuentes L, Waggoner AD, Mohammed BS, Stein RI, Miller BV 3rd, Foster GD, et al. Effect of moderate diet-induced weight loss and weight regain on cardiovascular structure and function. J Am Coll Cardiol. 2009;54(25):2376–81.PubMedPubMedCentral

89.

Haufe S, Utz W, Engeli S, Kast P, Bohnke J, Pofahl M, et al. Left ventricular mass and function with reduced-fat or reduced-carbohydrate hypocaloric diets in overweight and obese subjects. Hypertension. 2012;59(1):70–5.PubMed

90.

Normandin E, Houston DK, Nicklas BJ. Caloric restriction for treatment of geriatric obesity: Do the benefits outweigh the risks? Curr Nutr Rep. 2015;4(2):143–55.PubMedPubMedCentral

91.

Haass M, Kitzman DW, Anand IS, Miller A, Zile MR, Massie BM, et al. Body mass index and adverse cardiovascular outcomes in heart failure patients with preserved ejection fraction: results from the Irbesartan in Heart Failure with Preserved Ejection Fraction (I-PRESERVE) trial. Circ Heart Fail. 2011;4(3):324–31.PubMedPubMedCentral

92.

Sharma A, Lavie CJ, Borer JS, Vallakati A, Goel S, Lopez-Jimenez F, et al. Meta-analysis of the relation of body mass index to all-cause and cardiovascular mortality and hospitalization in patients with chronic heart failure. Am J Cardiol. 2015;115(10):1428–34.PubMed

93.

Jasuja R, LeBrasseur NK. Regenerating skeletal muscle in the face of aging and disease. Am J Phys Med Rehabil. 2014;93(11 Suppl 3):S88–96.PubMed

94.

Morvan F, Rondeau JM, Zou C, Minetti G, Scheufler C, Scharenberg M, et al. Blockade of activin type II receptors with a dual anti-ActRIIA/IIB antibody is critical to promote maximal skeletal muscle hypertrophy. Proc Natl Acad Sci U S A. 2017;114(47):12448–53.PubMedPubMedCentral

95.

Bianchi VE. Testosterone, myocardial function, and mortality. Heart Fail Rev. 2018.

96.

Borst SE, Shuster JJ, Zou B, Ye F, Jia H, Wokhlu A, et al. Cardiovascular risks and elevation of serum DHT vary by route of testosterone administration: a systematic review and meta-analysis. BMC Med. 2014;12:211.PubMedPubMedCentral

97.

Springer J, Springer JI, Anker SD. Muscle wasting and sarcopenia in heart failure and beyond: update 2017. ESC Heart Fail. 2017;4(4):492–8.PubMedPubMedCentral

Title: Impaired Exercise Tolerance in Heart Failure: Role of Skeletal Muscle Morphology and Function
Publication date: 01-12-2018
Published in: Current Heart Failure Reports / Issue 6/2018
Print ISSN: 1546-9530
Electronic ISSN: 1546-9549
DOI: https://doi.org/10.1007/s11897-018-0408-6

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Hyperkalaemia in Heart Failure—Pathophysiology, Implications and Therapeutic Perspectives

Depression, Anxiety, and Cognitive Impairment

Setting Up a Heart Failure Program in 2018: Moving Towards New Paradigm(s)

Improving Provider Adherence to Guideline Recommendations in Heart Failure

Role of the Wearable Defibrillator in Newly Diagnosed Heart Failure

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page