When comparing individuals with heart failure to healthy age-matched controls, which is not true?

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Research Methods & Reporting BMJ 2016; 352 doi: https://doi.org/10.1136/bmj.i969 (Published 25 February 2016) Cite this as: BMJ 2016;352:i969

1. Kitzman DW. Exercise Intolerance. Prog Cardiovasc Dis. 2005;47:367–379. [PubMed] [Google Scholar]

2. Higginbotham MB, Morris KG, Williams RS, McHale PA, Coleman RD, Cobb FR. Regulation of stroke volume during submaximal and maximal upright exercise in normal man. Circ Res. 1986;58:281–291. [PubMed] [Google Scholar]

3. Higginbotham MB, Morris KG, Williams RS. Physiologic basis for the age-related decline in aerobic work capacity. Am J Cardiol. 1986;57:1374–1379. [PubMed] [Google Scholar]

4. Orso F, Baldasseroni S, Maggioni A. Heart rate in coronary syndromes and heart failure. Prog Cardiovasc Dis. 2009;52:38–45. [PubMed] [Google Scholar]

5. Kannel WB. New perspectives on cardiovascular risk factors. Am Heart J. 1987;114:213–219. [PubMed] [Google Scholar]

6. Tardif JC. Heart rate as a treatable cardiovascular risk factor. Br Med Bull. 2009;90:71–84. [PubMed] [Google Scholar]

7. Fox K, Ford I, Steg PG, Tendera M, Robertson M, Ferrari R, BEAUTIFUL investigators Heart rate as a prognostic risk factor in patients with coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a subgroup analysis of a randomised controlled trial. Lancet. 2008;372:817–821. [PubMed] [Google Scholar]

8. Lauer MS. Autonomic function and prognosis. Cleve Clin J of Med. 2009;76:S18–S22. [PubMed] [Google Scholar]

9. Vivekananthan DP, Blackstone EH, Pothier CE, Lauer MS. Heart rate recovery after exercise is a predictor of mortality, independent of angiographic severity of coronary disease. J Am Coll Cardiol. 2003;42:831–838. [PubMed] [Google Scholar]

10. Cole CR, Foody JM, Blackstone EH, Lauer MS. Heart rate recovery after submaximal exercise testing as a predictor of mortality in a cardiovascularly healthy cohort. Ann Intern Med. 2000;132:552–555. [PubMed] [Google Scholar]

11. Imai K, Sato H, Hori M, Kusuoka H, Ozaki H, Yokoyama H, Takeda H, Inoue M, Kamada T. Vagally mediated heart rate recovery after exercise is accelerated in athletes but blunted in patients with chronic heart failure. J Am Coll Cardiol. 1994;24:1529–1535. [PubMed] [Google Scholar]

12. Morshedi-Meibodi A, Larson MG, Levy D, O'Donnell CJ, Vasan RS. Heart rate recovery after treadmill exercise testing and risk of cardiovascular disease events (The Framingham Heart Study) Am J Cardiol. 2002;90:848–852. [PubMed] [Google Scholar]

13. Adabag AS, Grandits GA, Prineas RJ, Crow RS, Bloomfield HE, Neaton JD, MRFIT Research Group Relation of heart rate parameters during exercise test to sudden death and all-cause mortality in asymptomatic men. Am J Cardiol. 2008;101:1437–1443. [PMC free article] [PubMed] [Google Scholar]

14. Jouven X, Empana JP, Schwartz PJ. Heart-rate profile during exercise as a predictor of sudden death. N Engl J Med. 2005;352:1951–1958. [PubMed] [Google Scholar]

15. Kitzman DW, Taffet G. Effects of aging on cardiovascular structure and function. In: Halter JB, Ouslander JG, Tinetti ME, Studenski SA, High KP, Asthana S, editors. Hazzard's Geriatric Medicine and Gerontology. McGraw Hill; New York: 2009. [Google Scholar]

16. Haidet GC. Dynamic exercise in senescent beagles: oxygen consumption and hemodynamic responses. Am J Physiol. 1989;257:H1428–H1437. [PubMed] [Google Scholar]

17. Tate CA, Taffet GE, Hudson EK, Blaylock SL, McBride RP, Michael LH. Enhanced calcium uptake of cardiac sarcoplasmic reticulum in exercise-trained old rats. Am J Physiol Heart Circ Physiol. 1990;258:H431–H435. [PubMed] [Google Scholar]

18. Ogawa T, Spina RJ, Martin WH, Kohrt WM, Schechtman KB. Effect of aging, sex, and physical training on cardiovacular responses to exercise. Circulation. 1992;86:494–503. [PubMed] [Google Scholar]

19. Gulati M, Shaw LJ, Thisted RA, Black HR, Bairey CN, Arnsdorf MF. Heart rate response to exercise stress testing in asymptomatic women. The St. James Women Take Heart Project. Ciculation. 2010;122:130–137. [PubMed] [Google Scholar]

20. Astrand PO. Physical performance as a function of age. JAMA. 1968;205:729–733. [PubMed] [Google Scholar]

21. Tanaka H, Monahan KD, Seals DR. Age-predicted maximal heart rate revisited. Journal of the American College of Cardiology. 2001;37:153–156. [PubMed] [Google Scholar]

22. Brawner CA, Ehrman JK, Schairer JR, Cao JJ, Keteyian SJ. Predicting maximum heart rate among patients with coronary heart disease receiving beta-adrenergic blockade therapy. Am Heart J. 2004;148:910–914. [PubMed] [Google Scholar]

23. Corbelli R, Masterson M, Milkoff BL. Chronotropic response to exercise in patients with atrial fibrillation. Pacing Clin Electrophysiol. 1990;13:179–187. [PubMed] [Google Scholar]

24. Coyne JC, Rohrbaugh MJ, Shoham V, Sonnega JS, Nicklas JM, Cranford JA. Prognostic importance of marital quality for survival of congestive heart failure. Am J Cardiol. 2001;88:526–529. [PubMed] [Google Scholar]

25. Gwinn N, Leman R, Kratz J, White JK, Gillette P. Chronotropic incompetence: a common and progressive finding in pacemaker patients. Am Heart J. 1992;123:1216–1219. [PubMed] [Google Scholar]

26. Lamas GA, Knight JD, Sweeney M, Mianulli M, Jorapur V, Khalighi K, Cook JR, Silverman R, Rosenthal L, Clapp-Channing N, Lee KL, Mark DB. Impact of rate-modulated pacing on quality of life and exercise capacity--evidence from the Advanced Elements of Pacing Randomized Controlled Trial (ADEPT) Heart Rhythm. 2007;4:1125–1132. [PubMed] [Google Scholar]

27. Coman J, Freedman R, Koplan BA, Reeves R, Santucci P, Stolen KQ, Kraus SM, Meyer TE, LIFE Study Results A blended sensor restores chronotropic response more favorable than an accelerometer alone in pacemaker patients: the LIFE study results. 2008;31(11):1442. [PubMed] [Google Scholar]

28. Lauer MS, Francis GS, Okin PM, Pashkow FJ, Snader CE, Marwick TH. Impaired chronotropic response to exercise stress testing as a predictor of mortality [see comments] JAMA. 1999;281:524–529. [PubMed] [Google Scholar]

29. Dresing TJ, Blackstone EH, Pashkow FJ. Usefulness of impaired chronotropic response to exercise as a predictor of mortality, independent of the severity of coronary artery disease. Am J Cardiol. 2000;86:602–609. [PubMed] [Google Scholar]

30. Elhendy A, van Domburg RT, Bax JJ, Nierop PR, Geleijnse ML, Ibrahim MM, Roelandt JR. The functional significance of chronotropic incompetence during dobutamine stress test. Heart. 1999;81:398–403. [PMC free article] [PubMed] [Google Scholar]

31. Okin PM, Lauer MS, Kligfield P. Chronotropic response to exercise. Improved performance of ST-depression criteria after adjustment for heart rate reserve. Circulation. 1996;94:3226–3231. [PubMed] [Google Scholar]

32. Wilkoff BL, Miller RE. Exercise testing for chronotropic assessment. Cardiology Clinics. 1992;10:705–717. [PubMed] [Google Scholar]

33. Savonen KP, Kiviniemi V, Laukkanen JA, Lakka TA, Rauramaa TH, Salonen JT, Rauramaa R. Chronotropic incompetence and mortality in middle-aged men with known or suspected coronary heart disease. Eur Heart J. 2008;29:1896–1902. [PubMed] [Google Scholar]

34. Savonen KP, Lakka TA, Laukkanen JA, Rauramaa TH, Salonen JT, Rauramaa R. Usefulness of chronotropic incompetence in response to exercise as a predictor of myocardial infarction in middle-aged men without cardiovascular disease. Am J Cardiol. 2008;101:992–998. [PubMed] [Google Scholar]

35. Leeper NJ, Dewey FE, Ashley EA, Sandri M, Tan SY, Hadley D, Myers J, Froelicher V. Prognostic value of heart rate increase at onset of exercise testing. Circulation. 2007;115:468–474. [PubMed] [Google Scholar]

36. Gauri AJ, Raxwal V, Roux L. Effects of chronotropic incompetence and beta blocker use on the treadmill test in men. Am Heart J. 2001;142:136–141. [PubMed] [Google Scholar]

37. Witte KK, Cleland J, Clark AL. Chronic heart failure, chronotropic incompetence, and the effects of beta blockers. Heart. 2006;92:481–486. [PMC free article] [PubMed] [Google Scholar]

38. Khan ME, Pothier CE, Lauer MS. Chronotropic incompetence asa predictor of death among patients with normal electrocardiograms taking beta blockers. Am J Cardiol. 2005;96:1328–1333. [PubMed] [Google Scholar]

39. Kass DA, Kitzman DW, Alvarez GE. The Restoration of Chronotropic CompEtence in Heart Failure PatientS with Normal Ejection FracTion (RESET) Study: Rationale and Design. J Card Fail. 2010;16:17–24. [PMC free article] [PubMed] [Google Scholar]

40. Magri D, Palermo P, Cauti FM, Contini M, Farina S, Cattadori G, Apostolo A, Salvioni E, Magini A, Vignati C, Vignati C, Alimento M, Sciomer S, Bussotti M, Agostoni P. Chronotropic incompetence and functional capacity in chronic heart failure: no role of beta-blockers and beta-blocker dose. Cardiovasc Ther. 2010 Online Ahead of Print. [PubMed] [Google Scholar]

41. Jorde UP, Vittorio T, Kasper ME, Arezzi E, Colombo PC, Goldsmith RI, Ahuja K, Tseng CH, Haas F, Hirsh DS. Chronotropic incompetence, beta-blockers, and functional capacity in advanced congestive heart failure: time to pace? Eur J Heart Fail. 2008;10:96–101. [PubMed] [Google Scholar]

42. Phan T, Shivu G, Weaver R, Ahmed I, Frenneaux M. Impaired heart rate recovery and chronotropic incompetence in patients with heart failure with preserved ejection fraction. Circ Heart Fail. 2010;3:29–34. [PubMed] [Google Scholar]

43. Vittorio T, Lanier G, Zolty R, Sarswat N, Tseng CH, Colombo PC, Jorde UP. Association between endothelial function and chronotropic incompetence in subjects with chronic heart failure receiving optimal medical therapy. Echocardiography. 2010;27:294–299. [PubMed] [Google Scholar]

44. Hinkle LE, Carver ST, Plakum A. Slow heart rates and increased risk of death cardiac death in middle aged men. Arch Intern Med. 1972;129:58–8. [PubMed] [Google Scholar]

45. Creager MA, Massie BM, Faxon DP, Friedman SD, Kramer BL, Weiner DA, Ryan TJ, Topic N, Melidossian CD. Acute and long-term effects of enalapril on the cardiovascular response to exercise and exercise tolerance in patients with congestive heart failure. J Am Coll Cardiol. 1985;6:163–173. [PubMed] [Google Scholar]

46. Eckberg DL, Brabinsky M, Braumwald E. Defective cardiac parasympathetic control in patients with heart disease. N Engl J Med. 1971;285:877–883. [PubMed] [Google Scholar]

47. Ellestad MH, Wan MK. Predictive implications of stress testing. Follow-up of 2700 subjects after maximum treadmill stress testing. Circulation. 1975;51:363–369. [PubMed] [Google Scholar]

48. Lauer MS, Okin PM, Larson MG, Evans JC, Levy D. Impaired heart rate response to graded exercise: prognostic implications of chronotropic incompetence in the Framingham Heart Study. Circulation. 1996;93:1520–1526. [PubMed] [Google Scholar]

49. Ellestad MH. Chronotropic incompetence: The implications of heart rate response to exercise (compensatory parasympathetic hyperactivity?) Circulation. 1996;93:1485–1487. [PubMed] [Google Scholar]

50. Azarbal B, Hayes SW, Lewin HC, Hachamovitch R, Cohen I, Berman DS. The incremental prognostic value of percentage of heart rate reserve achieved over myocardial perfusion single-photon emission computed tomography in the prediction of cardiac death and all-cause mortality: superiority over 85% of maximal age-predicted heart rate. J Am Coll Cardiol. 2004;44:423–430. [PubMed] [Google Scholar]

51. Kligfield P, Lauer MS. Exercise electrocardiogram testing: beyond the ST segment. Circulation. 2006;114:2070–2082. [PubMed] [Google Scholar]

52. Myers J, Tan SY, Abella J, Aleti V, Froelicher V. Comparison of the chronotropic response to exercise and heart rate recovery in predicting cardiovascular mortality. 2007;14(2):221. [PubMed] [Google Scholar]

53. Thom T, Haase N, Rosamond W, Howard VJ, Rumsfeld J, Manolio T, Zheng ZJ, Flegal K, O'Donnell C, Kittner S, Lloyd-Jones D, Goff DC, Hong YL, Adams R, Friday G, Furie K, Gorelick P, Kissela B, Marler J, Meigs J, Roger V, Sidney S, Sorlie P, Steinberger J, Wasserthiel-Smoller S, Wilson M, Wolf P. Heart disease and stroke statistics - 2006 update - A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2006;113:E85–E151. [PubMed] [Google Scholar]

54. Senni M, Tribouilloy CM, Rodeheffer RJ, Jacobsen SJ, Evans JM, Bailey KR, Redfield MM. Congestive heart failure in the community: a study of all incident cases in Olmsted County, Minnesota, in 1991. Circulation. 1998;98:2282–2289. [PubMed] [Google Scholar]

55. Vasan RS, Larson MG, Benjamin EJ, Evans JC, Reiss CK, Levy D. Congestive heart failure in subjects with normal versus reduced left ventricular ejection fraction: prevalence and mortality in a population-based cohort. J Am Coll Cardiol. 1999;33:1948–1955. [PubMed] [Google Scholar]

56. Devereux RB, Roman MJ, Liu JE, Welty TK, Lee ET, Rodeheffer R, Fabsitz RR, Howard BV. Congestive heart failure despite normal left ventricular systolic function in a population-based sample: the Strong Heart Study*. Am J Cardiol. 2000;86:1090–1096. [PubMed] [Google Scholar]

57. Sullivan MJ, Hawthorne M. Exercise intolerance in patients with chronic heart failure. Prog Cardiovasc Dis. 1995;28:1–22. [PubMed] [Google Scholar]

58. Kitzman DW, Little WC, Brubaker PH, Anderson RT, Hundley WG, Marburger CT, Brosnihan B, Morgan TM, Stewart KP. Pathophysiological characterization of isolated diastolic heart failure in comparison to systolic heart failure. JAMA. 2002;288:2144–2150. [PubMed] [Google Scholar]

59. Moore B, Brubaker PH, Stewart KP, Kitzman DW. VE/VCO2 Slope in Older Heart Failure Patients With Normal Versus Reduced Ejection Fraction Compared With Age-Matched Healthy Controls. J Card Fail. 2007;13:259–262. [PubMed] [Google Scholar]

60. Brubaker PH, Marburger CT, Morgan TM, Fray B, Kitzman DW. Exercise responses of elderly patients with diastolic versus systolic heart failure. Med Sci Sports Exerc. 2003;35:1477–1485. [PubMed] [Google Scholar]

61. Maldonado-Martin S, Brubaker PH, Kaminsky LA, Moore JB, Stewart KP, Kitzman DW. The relationship of a 6-min walk to VO(2 peak) and VT in older heart failure patients. Med Sci Sports Exerc. 2006;38:1047–1053. [PubMed] [Google Scholar]

62. Smart N, Haluska B, Jeffriess L, Marwick TH. Exercise training in systolic and diastolic dysfunction: Effects on cardiac function, functional capacity, and quality of life. American Heart Journal. 2007;153:530–536. [PubMed] [Google Scholar]

63. Williams AG, Rayson MP, Jubb M, World M, Woods DR, Hayward M, Martin J, Humphries SE, Montgomery HE. The ACE gene and muscle performance. Nature. 2000;403:614. [PubMed] [Google Scholar]

64. De Cort SS, Innes JA, Barstow T, Guz A. Cardiac output, oxygen consumption and arteriovenous oxygen difference following a sudden rise in exercise level in human. J Physiol. 1991;441:501–512. [PMC free article] [PubMed] [Google Scholar]

65. Myers J, Froelicher V. Hemodynamic determinants of exercise capacity in chronic heart failure. Ann Intern Med. 1991;115:377–386. [PubMed] [Google Scholar]

66. Higginbotham MB, Morris KG, Conn E, Coleman RE, Cobb FR. Determinants of variable exercise performance among patients with severe left ventricular dysfunction. Am J Cardiol. 1983;51:52–60. [PubMed] [Google Scholar]

67. Pina IL, Apstein CS, Balady GJ, Belardinelli R, Chaitman BR, Duscha BD, Fletcher BJ, Fleg JL, Myers JN, Sullivan MJ. Exercise and heart failure: A statement from the American Heart Association Committee on exercise, rehabilitation, and prevention. Circulation. 2003;107:1210–1225. [PubMed] [Google Scholar]

68. Brubaker PH, Joo KC, Stewart KP, Fray B, Moore B, Kitzman DW. Chronotropic incompetence and its contribution to exercise intolerance in older heart failure patients. J Cardiopulm Rehabil. 2006;26:86–89. [PubMed] [Google Scholar]

69. Borlaug BA, Melenovsky V, Russell SD, Kessler K, Pacak K, Becker LC, Kass DA. Impaired Chronotropic and Vasodilator Reserves Limit Exercise Capacity in Patients With Heart Failure and a Preserved Ejection Fraction. Circulation. 2006;114:2138–2147. [PubMed] [Google Scholar]

70. Clark AL, Coats AJ. Chronotropic incompetence in chronic heart failure. Int J Cardiol. 1995;49:225–231. [PubMed] [Google Scholar]

71. Roche F, Pichot V, Da Costa A. Chronotropic Incompetence response to exercise in congestive heart failure, relationship with autonomic status. Clinical Physiology. 2001;3:335–342. [PubMed] [Google Scholar]

72. Bristow MR, Hershberger RE, Port JD. Beta-adrenergic pathways in non-failing and failing human ventricular myocardium. Circulation. 1990;82:12–25. [PubMed] [Google Scholar]

73. Colucci WS, Ribeiro JP, Rocco MB, Quigg RJ, Creager MA, Marsh JD, Gauthier DF, Hartley LH. Impaired chronotropic response to exercise in patients wtih congestive heart failure. Circulation. 1989;80:314–323. [PubMed] [Google Scholar]

74. Samejima H, Omiya K, Uno M. Relationship between impaired chronotropic response, cardiac output during exercise, exercise tolerance in patients with chronic heart failure. Jpn Heart J. 2003;44:515–525. [PubMed] [Google Scholar]

75. Sanders P, Kistler PM, Morton JB, Spence SJ, Kalman JM. Remodeling of sinus node function in patients with congestive heart failure: reduction in sinus node reserve. Circulation. 2004;110:897–903. [PubMed] [Google Scholar]

76. Gademan MG, Swenne CA, Verwey HF, van der Laarse A, Maan AC, van de Vooren H, van Pelt J, van Exel HF, Lucas C, Cleuren GV, Somer S, Schalij MJ, van der Wall EE. Effect of exercise training on autonomic derangement and neurohumoral activation in chronic heart failure. J Card Fail. 2007;13:294–303. [PubMed] [Google Scholar]

77. Whellan DJ, O'Connor CM, Lee KL, Keteyian SJ, Cooper LS, Ellis SJ, Leifer ES, Kraus WE, Kitzman DW, Blumenthal JA. Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing (HF-ACTION): Design and rationale. American Heart Journal. 2007;153:201–211. [PubMed] [Google Scholar]

78. Grossman GB, Rohde LE, Clausell N. Evidence for increased peripheral production of tumor necrosis factor-alpha in advanced congestive heart failure. Am J Cardiol. 2001;88:578–581. [PubMed] [Google Scholar]

79. Hambrecht R, Gielen S, Linke A, Fiehn E, Yu J, Walther C, Schoene N, Schuler G. Effects of exercise training on left ventricular function and peripheral resistance in patients with chronic heart failure. JAMA. 2000;283:3095–3101. [PubMed] [Google Scholar]

80. Belardinelli R, Georgiou D, Cianci G, Purcaro A. Randomized, controlled trial of long-term moderate exercise training in chronic heart failure: effects of functional capacity, quality of life, and clinical outcome. Circulation. 1999;99:1173–1182. [PubMed] [Google Scholar]

81. Kavanaugh T, Myers MG, Baigrie R. Quality of life and cardiorespiratory function in chronic heart failure: effects of 12 months of aerobic training. Heart. 1996;76:42–49. [PMC free article] [PubMed] [Google Scholar]

82. van Tol BA, Huijsmans RJ, Kroon DW, 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. 2006;8:841–850. [PubMed] [Google Scholar]

83. Keteyian SJ, Brawner CA, Schairer JR. Effects of exercise training on chronotropic incompetence in patients with heart failure. Am Heart J. 1999;138:233–240. [PubMed] [Google Scholar]

84. McElroy PA, Janicki JS, Weber KT. Physiologic correlates of the heart rate response to upright isotonic exercise; relevance to rate-responsive pacemakers. J Am Coll Cardiol. 1988;11:94–99. [PubMed] [Google Scholar]

85. Kappenberger L, Herpers L. Rate responsive dual chamber pacing. Pacing Clin Electrophysiol. 1986;9:987–991. [PubMed] [Google Scholar]

86. Buckingham TA. Effects of ventricular function on exercise hemodynamics of variable rate pacing. J Am Coll Cardiol. 1998;11:1269–1277. [PubMed] [Google Scholar]

87. Freedman RA. Assessment of pacemaker chronotropic response: implementation of the wilkoff mathematical model. Pacing Clin Electrophysiol. 2001;24:1748–1754. [PubMed] [Google Scholar]

88. Tse HF, Siu CW, Lee KLF, Fan K, Chan HW, Tang MO, Tsang V, Lee SWL, Lau CP. The Incremental Benefit of Rate-Adaptive Pacing on Exercise Performance During Cardiac Resynchronization Therapy. Journal of the American College of Cardiology. 2005;46:2292–2297. [PubMed] [Google Scholar]

89. Kawasaki T, Kalmoto S, Sakatani T, Miki S, Kamitani T, Kuribayashi T, Matsubara H, Sugihara II Chronotropic incompetence and autonomic dysfunction in patients without structural heart disease. Eurospace. 2010;12:561–566. [PubMed] [Google Scholar]

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Influence of parasympathetic tone on heart rate recovery. A. Absolute heart rates (after log transformation) during the first 3 minutes ater exercise in 3 groups of subjects. Among athlets and normal subjects, there is a biexponential relationship which is absent in heart failure patients. B. After atropine, the initial steep slope is absent. From Lauer MS, Cleve Clin J of Med. 2009;76:S18-S22.8

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