Journal of Cardiac Failure
Volume 16, Issue 1 , Pages 17-24 , January 2010

The Restoration of Chronotropic CompEtence in Heart Failure PatientS with Normal Ejection FracTion (RESET) Study: Rationale and Design

  • David A. Kass, MD

      Affiliations

    • Division of Cardiology, Department of Medicine, Johns Hopkins Medical Institutions Baltimore, MD
    • Corresponding Author InformationReprint requests: David A. Kass, MD, Ross 858, Division of Cardiology, Johns Hopkins University Medical Institutions, 720 Rutland Avenue, Baltimore, MD 21205. Tel: (410) 955-7153; Fax: (410) 502-2558.
    • ,
  • Dalane W. Kitzman, MD

      Affiliations

    • Sections of Cardiology and Geriatrics, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC
    • ,
  • Guy E. Alvarez, PhD

      Affiliations

    • Boston Scientific CRM, St. Paul, MN

Received 15 June 2009 ,Revised 12 August 2009 ,Accepted 17 August 2009.

References 

  1. Jessup M, Brozena S. Heart failure. N Engl J Med. 2003;348:2007–2018
  2. Rosamond W, Flegal K, Furie K, et al. Heart disease and stroke statistics—2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2008;117:e25–e146
  3. Bursi F, Weston SA, Redfield MM, et al. Systolic and diastolic heart failure in the community. JAMA. 2006;296:2209–2216
  4. Kitzman DW, Gardin JM, Gottdiener JS, et al. Importance of heart failure with preserved systolic function in patients > or = 65 years of age. CHS Research Group. Cardiovascular Health Study. Am J Cardiol. 2001;87:413–419
  5. Redfield MM, Jacobsen SJ, Burnett JC, et al. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA. 2003;289:194–202
  6. Senni M, Tribouilloy CM, Rodeheffer RJ, et al. Congestive heart failure in the community: a study of all incident cases in Olmsted County, Minnesota, in 1991. Circulation. 1998;98:2282–2289
  7. Vasan RS, Larson MG, Benjamin EJ, et al. 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
  8. Bhatia RS, Tu JV, Lee DS, et al. Outcome of heart failure with preserved ejection fraction in a population-based study. N Engl J Med. 2006;355:260–269
  9. Grigorian Shamagian L, Gonzalez-Juanatey JR, Roman AV, et al. The death rate among hospitalized heart failure patients with normal and depressed left ventricular ejection fraction in the year following discharge: evolution over a 10-year period. Eur Heart J. 2005;26:2251–2258
  10. Hogg K, Swedberg K, McMurray J. Heart failure with preserved left ventricular systolic function; epidemiology, clinical characteristics, and prognosis. J Am Coll Cardiol. 2004;43:317–327
  11. Liao L, Jollis JG, Anstrom KJ, et al. Costs for heart failure with normal vs reduced ejection fraction. Arch Intern Med. 2006;166:112–118
  12. Owan TE, Hodge DO, Herges RM, et al. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006;355:251–259
  13. Tribouilloy C, Rusinaru D, Mahjoub H, et al. Prognosis of heart failure with preserved ejection fraction: a 5 year prospective population-based study. Eur Heart J. 2008;29:339–347
  14. Kitzman DW, Higginbotham MB, Cobb FR, et al. Exercise intolerance in patients with heart failure and preserved left ventricular systolic function: failure of the Frank-Starling mechanism. J Am Coll Cardiol. 1991;17:1065–1072
  15. Kitzman DW, Little WC, Brubaker PH, et al. Pathophysiological characterization of isolated diastolic heart failure in comparison to systolic heart failure. JAMA. 2002;288:2144–2150
  16. Colucci WS, Ribeiro JP, Rocco MB, et al. Impaired chronotropic response to exercise in patients with congestive heart failure. Role of postsynaptic beta-adrenergic desensitization. Circulation. 1989;80:314–323
  17. Fleg JL, O'Connor F, Gerstenblith G, et al. Impact of age on the cardiovascular response to dynamic upright exercise in healthy men and women. J Appl Physiol. 1995;78:890–900
  18. Nussbacher A, Gerstenblith G, O'Connor FC, et al. Hemodynamic effects of unloading the old heart. Am J Physiol. 1999;277:H1863–H1871
  19. Lam CS, Roger VL, Rodeheffer RJ, et al. Cardiac structure and ventricular-vascular function in persons with heart failure and preserved ejection fraction from Olmsted County, Minnesota. Circulation. 2007;115:1982–1990
  20. Melenovsky V, Borlaug BA, Rosen B, et al. Cardiovascular features of heart failure with preserved ejection fraction versus nonfailing hypertensive left ventricular hypertrophy in the urban Baltimore community: the role of atrial remodeling/dysfunction. J Am Coll Cardiol. 2007;49:198–207
  21. Borlaug BALC, Olson TP, Flood KS, Johnson BD, Redfield MM. Cardiovascular reserve function in heart failure with preserved ejection fraction: systolic versus diastolic determinants. [abstract 5884] Circulation. 2008;(S_1022):118
  22. Borlaug BA, Melenovsky V, Russell SD, et al. Impaired chronotropic and vasodilator reserves limit exercise capacity in patients with heart failure and a preserved ejection fraction. Circulation. 2006;114:2138–2147
  23. Brubaker PH, Joo KC, Stewart KP, et al. Chronotropic incompetence and its contribution to exercise intolerance in older heart failure patients. J Cardiopulm Rehabil. 2006;26:86–89
  24. Freedman RA, Hopper DL, Mah J, et al. Assessment of pacemaker chronotropic response: implementation of the Wilkoff mathematical model. Pacing Clin Electrophysiol. 2001;24:1748–1754
  25. Kappenberger LJ, Herpers L. Rate responsive dual chamber pacing. Pacing Clin Electrophysiol. 1986;9:987–991
  26. Wilkoff BLCJ, Blackburn G. A mathematical model of the cardiac chronotropic response to exercise. J Electrophysiol. 1989;3:176–180
  27. Wilkoff BL, Miller RE. Exercise testing for chronotropic assessment. Cardiol Clin. 1992;10:705–717
  28. Lau CP, Butrous GS, Ward DE, et al. Comparison of exercise performance of six rate-adaptive right ventricular cardiac pacemakers. Am J Cardiol. 1989;63:833–838
  29. Lau CP, Wong CK, Leung WH, et al. A comparative evaluation of a minute ventilation sensing and activity sensing adaptive-rate pacemakers during daily activities. Pacing Clin Electrophysiol. 1989;12:1514–1521
  30. Bacharach DW, Hilden TS, Millerhagen JO, et al. Activity-based pacing: comparison of a device using an accelerometer versus a piezoelectric crystal. Pacing Clin Electrophysiol. 1992;15:188–196
  31. Lau C. Clinical comparison of currently available sensor-based rate-adaptive pacing systems. Boston: Blackwell Scientific; 1993;
  32. Matula M, Alt E, Fotuhi P, et al. Rate adaptation of activity pacemakers under various types of means of locomotion. Eur J Cardiac Pacing Electrophysiol. 1992;2(Supp 1A):A49
  33. Kay GN, Bubien RS, Epstein AE, et al. Rate-modulated cardiac pacing based on transthoracic impedance measurements of minute ventilation: correlation with exercise gas exchange. J Am Coll Cardiol. 1989;14:1283–1289
  34. Lau CP, Antoniou A, Ward DE, et al. Reliability of minute ventilation as a parameter for rate responsive pacing. Pacing Clin Electrophysiol. 1989;12:321–330
  35. Erol-Yilmaz A, Schrama TA, Tanka JS, et al. Individual optimization of pacing sensors improves exercise capacity without influencing quality of life. Pacing Clin Electrophysiol. 2005;28:17–24
  36. Aurigemma GP, Gaasch WH. Clinical practice. Diastolic heart failure. N Engl J Med. 2004;351:1097–1105
  37. Gaasch WH, Zile MR. Left ventricular diastolic dysfunction and diastolic heart failure. Annu Rev Med. 2004;55:373–394
  38. Little WC, Warner JG, Rankin KM, et al. Evaluation of left ventricular diastolic function from the pattern of left ventricular filling. Clin Cardiol. 1998;21:5–9
  39. Zile MR, Baicu CF, Gaasch WH. Diastolic heart failure—abnormalities in active relaxation and passive stiffness of the left ventricle. N Engl J Med. 2004;350:1953–1959
  40. Gottdiener JS, Massie BM, Carson PE, Bhaumik A, Ptaszynska A, Komajda M, et al. Cardiac structural changes and diastolic function in heart failure with preserved ejection fraction—importance of left atrial volume: the iPRESERVE Study. Circulation. 2006;114:II-816, abstract 3814
  41. Liu CP, Ting CT, Lawrence W, et al. Diminished contractile response to increased heart rate in intact human left ventricular hypertrophy. Systolic versus diastolic determinants. Circulation. 1993;88:1893–1906
  42. Sullivan MJ, Knight JD, Higginbotham MB, et al. 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;80:769–781
  43. Wilson JR, Martin JL, Schwartz D, et al. Exercise intolerance in patients with chronic heart failure: role of impaired nutritive flow to skeletal muscle. Circulation. 1984;69:1079–1087
  44. Wiens RD, Lafia P, Marder CM, et al. Chronotropic incompetence in clinical exercise testing. Am J Cardiol. 1984;54:74–78
  45. Azarbal B, Hayes SW, Lewin HC, et al. 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
  46. Clark AL, Coats AJ. Chronotropic incompetence in chronic heart failure. Int J Cardiol. 1995;49:225–231
  47. Fei L, Keeling PJ, Sadoul N, et al. Decreased heart rate variability in patients with congestive heart failure and chronotropic incompetence. Pacing Clin Electrophysiol. 1996;19:477–483
  48. Jorde UP, Vittorio TJ, Kasper ME, et al. Chronotropic incompetence, beta-blockers, and functional capacity in advanced congestive heart failure: time to pace?. Eur J Heart Fail. 2008;10:96–101
  49. Witte KK, Cleland JG, Clark AL. Chronic heart failure, chronotropic incompetence, and the effects of beta blockade. Heart. 2006;92:481–486
  50. Heart Failure Society of America . Section 11: evaluation and management of patients with heart failure and preserved left ventricular ejection fraction. J Cardiac Failure. 2006;12:e80
  51. Swedberg K, Cleland J, Dargie H, et al. Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. Eur Heart J. 2005;26:1115–1140
  52. Cheng CP, Igarashi Y, Little WC. Mechanism of augmented rate of left ventricular filling during exercise. Circ Res. 1992;70:9–19
  53. Little WC, Brucks S. Therapy for diastolic heart failure. Prog Cardiovasc Dis. 2005;47:380–388
  54. Kass DA, Wolff MR, Ting CT, et al. Diastolic compliance of hypertrophied ventricle is not acutely altered by pharmacologic agents influencing active processes. Ann Intern Med. 1993;119:466–473
  55. Bangalore S, Messerli FH, Kostis JB, et al. Cardiovascular protection using beta-blockers: a critical review of the evidence. J Am Coll Cardiol. 2007;50:563–572
  56. Ciulla MM, Paliotti R, Esposito A, et al. Different effects of antihypertensive therapies based on losartan or atenolol on ultrasound and biochemical markers of myocardial fibrosis: results of a randomized trial. Circulation. 2004;110:552–557
  57. Dahlof B, Pennert K, Hansson L. Reversal of left ventricular hypertrophy in hypertensive patients. A metaanalysis of 109 treatment studies. Am J Hypertens. 1992;5:95–110
  58. Ting CT, Brin KP, Lin SJ, et al. Arterial hemodynamics in human hypertension. J Clin Invest. 1986;78:1462–1471
  59. Borlaug BA, Kass DA. In:  Vannan M,  Pitt B,  Baliga RR,  Young JB editor. Heart failure clinics: diastolic dysfunction and heart failure. Ventricular-vascular interaction in heart failure. Vol. 4:Philadelphia, PA: W.B. Saunders Company; 2008;p. 23–36
  60. Khan MN, Pothier CE, Lauer MS. Chronotropic incompetence as a predictor of death among patients with normal electrograms taking beta blockers (metoprolol or atenolol). Am J Cardiol. 2005;96:1328–1333
  61. Alt EU, Schlegl MJ, Matula MM. Intrinsic heart rate response as a predictor of rate-adaptive pacing benefit. Chest. 1995;107:925–930
  62. Buckingham TA, Woodruff RC, Pennington DG, et al. Effect of ventricular function on the exercise hemodynamics of variable rate pacing. J Am Coll Cardiol. 1988;11:1269–1277
  63. Tse HF, Siu CW, Lee KL, et al. The incremental benefit of rate-adaptive pacing on exercise performance during cardiac resynchronization therapy. J Am Coll Cardiol. 2005;46:2292–2297
  64. Westermann D, Kasner M, Steendijk P, et al. Role of left ventricular stiffness in heart failure with normal ejection fraction. Circulation. 2008;117:2051–2060
  65. Kitzman DW. Diastolic dysfunction: one piece of the heart failure with normal ejection fraction puzzle. Circulation. 2008;117:2044–2046
  66. DeMaria AN, Neumann A, Schubart PJ, et al. Systematic correlation of cardiac chamber size and ventricular performance determined with echocardiography and alterations in heart rate in normal persons. Am J Cardiol. 1979;43:1–9
  67. Aroesty JM, McKay RG, Heller GV, et al. Simultaneous assessment of left ventricular systolic and diastolic dysfunction during pacing-induced ischemia. Circulation. 1985;71:889–900
  68. Dehmer GJ, Firth BG, Nicod P, et al. Alterations in left ventricular volumes and ejection fraction during atrial pacing in patients with coronary artery disease: assessment with radionuclide ventriculography. Am Heart J. 1983;106:114–124
  69. Erbel R, Schweizer P, Krebs W, et al. Effects of heart rate changes on left ventricular volume and ejection fraction: a 2-dimensional echocardiographic study. Am J Cardiol. 1984;53:590–597
  70. Feldman MD, Alderman JD, Aroesty JM, et al. Depression of systolic and diastolic myocardial reserve during atrial pacing tachycardia in patients with dilated cardiomyopathy. J Clin Invest. 1988;82:1661–1669
  71. Hung J, Kelly DT, Hutton BF, et al. Influence of heart rate and atrial transport on left ventricular volume and function: relation to hemodynamic changes produced by supraventricular arrhythmia. Am J Cardiol. 1981;48:632–638
  72. Rozenman Y, Weiss AT, Atlan H, et al. Left ventricular function during atrial pacing: a radionuclide angiographic study. Clin Cardiol. 1984;7:349–355
  73. Ferrari AU. Modifications of the cardiovascular system with aging. Am J Geriatr Cardiol. 2002;11:30–33
  74. Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: part I: aging arteries: a “set up” for vascular disease. Circulation. 2003;107:139–146
  75. Chen CH, Nakayama M, Nevo E, et al. Coupled systolic-ventricular and vascular stiffening with age: implications for pressure regulation and cardiac reserve in the elderly. J Am Coll Cardiol. 1998;32:1221–1227
  76. Gandhi SK, Powers JC, Nomeir AM, et al. The pathogenesis of acute pulmonary edema associated with hypertension. N Engl J Med. 2001;344:17–22
  77. Kawaguchi M, Hay I, Fetics B, et al. Combined ventricular systolic and arterial stiffening in patients with heart failure and preserved ejection fraction: implications for systolic and diastolic reserve limitations. Circulation. 2003;107:714–720
  78. Redfield MM, Jacobsen SJ, Borlaug BA, et al. Age- and gender-related ventricular-vascular stiffening: a community-based study. Circulation. 2005;112:2254–2262

 Drs. Kass and Kitzman have received honoraria as consultants from Boston Scientific CRM. Dr. Alvarez is an employee of Boston Scientific CRM.

PII: S1071-9164(09)01036-7

doi: 10.1016/j.cardfail.2009.08.008

Journal of Cardiac Failure
Volume 16, Issue 1 , Pages 17-24 , January 2010

Article Tools

* Image Usage & Resolution