The American Journal of Medicine
Volume 122, Issue 8 , Pages 713-723 , August 2009

Heart Failure with Preserved Ejection Fraction in Older Adults

  • Michael A. Chen, MD, PhD

      Affiliations

    • Corresponding Author InformationRequests for reprints should be address to Michael A. Chen, MD, PhD, Harborview Medical Center/Cardiology, 325 9th Avenue, Box 359748, Seattle, WA 98104

References 

  1. American Heart Association. Heart disease and stroke statistics—2007 update. Dallas, TX: American Heart Association; 2007;[updated 2007; cited September 10, 2007]. Available at: http://www.americanheart.org. Accessed June 10, 2008.
  2. Kozak L, DeFrances C, Hall M. National Hospital Discharge Survey: 2004 Summary. Vital Health Stat. 2004;13:1–209
  3. Thomas S, Rich M. Epidemiology, pathophysiology, and prognosis of heart failure in the elderly. Clin Geriatr Med. 2007;23:1–10
  4. Field J. CHF Prevalence to Nearly Double by Year 2030 as US Population Ages. In:  Field JL editors. Beyond Four Walls: Research Summary for Clinicians and Administrators on CHF Management (Cardiology Preeminence Round Table). Washington, DC: Advisory Board Company; 1994;
  5. Andersson B, Waagstein F. Spectrum and outcome of congestive heart failure in a hospitalized population. Am Heart J. 1993;632–640
  6. Paulus W, Tschope C, Sanderson J, et al. How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Eur Heart J. 2007;28:2539–2550
  7. Zile M. Heart failure with preserved ejection fraction: is this diastolic heart failure?. J Am Coll Cardiol. 2003;41:1519–1522
  8. Burkoff D, Maurer M, Packer M. Heart failure with a normal ejection fraction: Is it really a disorder of diastolic function?. Circulation. 2003;107:656–658
  9. Chatterjee K. Neurohormonal activation in congestive heart failure and the role of vasopressin. Am J Cardiol. 2005;95(Suppl):8B–13B
  10. Fonarow G ADHERE Scientific Advisory Committee. The Acute Decompensated Heart Failure National Registry (ADHERE): opportunities to improve care of patients hospitalized with acute decompensated heart failure. Rev Cardiovasc Med. 2003;4(Suppl 7):S21–S30
  11. Cleland J, Swedberg K, Follath F, et al. The EuroHeart Failure survey programme—a survey on the quality of care among patients with heart failure in Europe (Part 1: patient characteristics and diagnosis). Eur Heart J. 2003;24:442–463
  12. Kitzman D, Gardin J, Gottdiener J, et al. Importance of heart failure with preserved systolic function in patients>or=65 years of age. Am J Cardiol. 2001;87:413–419
  13. Vasan R, Larson M, Benjamin E, 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
  14. Kitzman D, Little W, Brubaker P, et al. Pathophysiological characterization of isolated diastolic heart failure in comparison to systolic heart failure. JAMA. 2002;288:2144–2150
  15. Lakatta E, 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
  16. Olivetti G, Capasso J, Meggs L, et al. Cellular basis of chronic ventricular remodeling after myocardial infarction in rats. Circ Res. 1991;68:856–869
  17. Lakatta E. Diminished beta-adrenergic modulation of cardiovascular function in advanced age. Cardiol Clin. 1986;4:185–200
  18. Iriarte M, Perez O, Sagastagoitia D, et al. Congestive heart failure due to hypertensive ventricular diastolic dysfunction. Am J Cardiol. 1995;76:43D–47D
  19. Gandhi S, Powers J, Nomeir A, et al. The pathogenesis of acute pulmonary edema associated with hypertension. N Engl J Med. 2001;344:17–22
  20. Gong L, Zhang W, Zhu Y, et al. Shanghai Trial of Nifedipine in the Elderly (STONE). J Hypertens. 1996;14:1237–1245
  21. Staessen J, Fagard R, Thijs L, et al. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension (The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators). Lancet. 1997;350:757–764
  22. Amery A, Birkenhager W, Brixko P, et al. Mortality and morbidity results from the European Working Party on High Blood Pressure in the Elderly Trial. Lancet. 1985;I:1349–1354
  23. Coope J, Warrender T. Randomised trial of treatment of hypertension in elderly patients in primary care. Br Med J (Clin Res Ed). 1986;1145–1151
  24. Dahlof B, Lindholm L, Hannson L, et al. Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension). Lancet. 1991;338:1281–1285
  25. The Systolic Hypertension in the Elderly Program (SHEP) Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: final results of SHEP. JAMA. 1991;265:3255–3264
  26. Beckett N, Peters R, Fletcher AE, et al. HYVET Study Group Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008;358:1887–1898
  27. Gottdiener J, Arnold A, Aurigemma G, et al. Predictors of congestive heart failure in the elderly: the Cardiovascular Health Study. J Am Coll Cardiol. 2000;35:1628–1637
  28. Krumholz H, Larson M, Levy D. Sex differences in cardiac adaptation to isolated systolic hypertension. Am J Cardiol. 1993;72:310–313
  29. Gerdts E, Zabalgoitia M, Björnstad H, et al. Gender differences in systolic left ventricular function in hypertensive patients with electrocardiographic left ventricular hypertrophy (the LIFE study). Am J Cardiol. 2001;87:980–983
  30. Givertz M, Colucci W, Braunwald E. Clinical aspects of heart failure; pulmonary edema, high-output failure. In: 7th ed..  Zipes DP,  Libby P,  Bonow RO, et al. editor. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine. vol. 1:Philadelphia: Elsevier/Saunders; 2005;
  31. Ommen S, Nishimura R, Appleton C, et al. Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: a comparative simultaneous Doppler-catheterization study. Circulation. 2000;102:1788–1794
  32. Celermajer D, Sorensen K, Spiegelhalter D, et al. Aging is associated with endothelial dysfunction in healthy men years before the age-related decline in women. J Am Coll Cardiol. 1994;24:471–476
  33. Nesto R, Kowalchuk G. The ischemic cascade: temporal sequence of hemodynamic, electrocardiographic and symptomatic expressions of ischemia. J Am Coll Cardiol. 1987;59:23C–30C
  34. Brubaker P, Stewart K, Fray B, et al. Chronotropic incompetence and its contribution to exercise intolerance in older heart failure patients. J Cardiopul Rehabil. 2006;26:86–89
  35. Feinberg W, Blackshear J, Laupacis A, et al. Prevalence, age distribution and gender of patients with atrial fibrillation: analysis and implications. Arch Intern Med. 1995;155:469–473
  36. Aronow W. Epidemiology, pathophysiology, prognosis and treatment of systolic and diastolic heart failure. Cardiol Rev. 2006;14:108–124
  37. Roger V, Weston S, Redfield M, et al. Trends in heart failure incidence and survival in a community-based population. JAMA. 2004;292:344–350
  38. Smith G, Masoudi F, Vaccarino V, et al. Outcomes in heart failure patients with preserved ejection fraction: mortality, readmission, and functional decline. J Am Coll Cardiol. 2003;41:15108
  39. Philbin E, Rocco T, Lindenmuth N, et al. Systolic versus diastolic heart failure in community practice: clinical features, outcomes, and the use of angiotensin-converting enzyme inhibitors. Am J Med. 2000;109:605–613
  40. Rodeheffer R, Jacobsen S, Gersh B, et al. The incidence and prevalence of congestive heart failure in Rochester, Minnesota. Mayo Clin Proc. 1993;68:1143–1150
  41. Redfield M, Jacobsen S, Burnett J, 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
  42. Owan T, Hodge D, Herges R, et al. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006;355:251–259
  43. Chavey W, Bleske B, Van Harrison R, et al. University of Michigan Health System Heart Failure Guideline. 2006;1–18Available at http://www.med.umich.edu/1info/FHP/practiceguides/heart/HF06.pdf. Accessed July 16, 2007
  44. Oh J, Hatle L, Tajik A, et al. Diastolic heart failure can be diagnosed by comprehensive two-dimensional and Doppler echocardiography. J Am Coll Cardiol. 2006;47:500–506
  45. The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med. 1991;325:303–310
  46. Garg R, Yusuf S Collaborative Group on ACE Inhibitor Trials. Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. JAMA. 1995;273:1450–1456
  47. Arnold J, Yusuf S, Young J, et al. Prevention of Heart Failure in Patients in the Heart Outcomes Prevention Evaluation (HOPE) Study. Circulation. 2003;107:1284–1290
  48. Fox K EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease Investigators. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet. 2003;362:782–788
  49. Adams K, Lindenfeld J, Arnold J, et al. HFSA 2006 Comprehensive Heart Failure Practice Guideline. J Card Fail. 2006;12:e1–e122
  50. Hunt S, Abraham W, Chin M, et al. ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure). J Am Coll Cardiol. 2005;46:e1–e82
  51. Friedrich S, Lorell B, Douglas P, et al. Intracardiac ACE inhibition improves diastolic distensibility in patients with left ventricular hypertrophy due to aortic stenosis. Circulation. 1992;86(suppl 1):1–119
  52. Lorell B, Grossman W. Cardiac hypertrophy: the consequences for diastole. J Am Coll Cardiol. 1987;9:1189–1193
  53. Aronow W, Kronzon I. Effect of enalapril on congestive heart failure treated with diuretics in elderly patients with prior myocardial infarction and normal left ventricular ejection fraction. Am J Cardiol. 1993;71:602–604
  54. Lakatta E. Cardiovascular aging research: the next horizons. J Am Geriatr Soc. 1999;47:613–625
  55. Philbin E, Rocco T. Use of angiotensin-converting enzyme inhibitors in heart failure with preserved left ventricular systolic function. Am Heart J. 1997;134(2 pt 1):188–195
  56. Anand A, Mooss A, Hee T, et al. Meta-analysis: inhibition of renin-angiotensin system prevents new-onset atrial fibrillation. Am Heart J. 2006;152:217–222
  57. Cleland J, Tendera M, Adamus J, et al. Perindopril for elderly people with chronic heart failure: the PEP-CHF study. Eur J Heart Fail. 1999;1:211–217
  58. Warner J, Metzger D, Kitzman D, et al. Losartan improves exercise tolerance in patients with diastolic dysfunction and a hypertensive response to exercise. J Am Coll Cardiol. 1999;33:1567–1572
  59. Little W, Wesley-Farrington D, Hoyle J, et al. Effect of candesartan and verapamil on exercise tolerance in diastolic dysfunction. J Cardiovasc Pharmacol. 2004;43:288–293
  60. Yusuf S, Pfeffer M, Swedberg K, et al. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. Lancet. 2003;362:777–781
  61. Massie B, Carson P, McMurray J, et al. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med. 2008;359:1–12
  62. Pitt B, Zannad F, Remme W, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure (Randomized Aldactone Evaluation Study Investigators). N Engl J Med. 1999;341:709–717
  63. Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003;348:1309–1321
  64. Rajagopalan S, Pitt B. Aldosterone as a target in congestive heart failure. Med Clin North Am. 2003;87:441–457
  65. Pitt B, Reichek N, Willenbrock R, et al. Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: the 4E-left ventricular hypertrophy study. Circulation. 2003;108:1831–1838
  66. Zannad F, Alla F, Dousset B, et al. Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure: insights from the randomized Aldactone evaluation study (RALES). Circulation. 2000;102:2700–2706
  67. Daniel K, Wells G, Fray B, et al. The effect of spironolactone on exercise tolerance and quality of life in elderly women with diastolic heart failure. Am J Geriatr Cardiol. 2003;12:131
  68. Aldosterone Antagonist Therapy for Adults with Heart Failure and Preserved Systolic Function (TOPCAT). http://www.clinicaltrials.gov/ct/gui/show/NCT00094302Accessed June 10, 2008
  69. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet. 1999;353:9–13
  70. Packer M, Coats A, Fowler M, et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001;344:1651–1658
  71. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet. 1999;353:2001–2007
  72. Cheng C, Igarashi Y, Little W. Mechanism of augmented rate of left ventricle filling during exercise. Circ Res. 1992;70:9–19
  73. Blaustein A, Gaasch W. VI (Effects of beta-adrenergic tone and asynchrony on LV relaxation rate). Am J Physiol. 1983;244:H417–H422
  74. Colin P, Ghaleh B, Hittinger L, et al. Differential effects of heart rate reduction and beta-blockade on left ventricular relaxation during exercise. Am J Physiol Heart Circ Physiol. 2002;282:H672–H679
  75. Grogan M, Smith H, Gersh B, et al. Left ventricular dysfunction due to atrial fibrillation in patients initially believed to have idiopathic dilated cardiomyopathy. Am J Cardiol. 1992;69:1570–1573
  76. Flather M, Shibata M, Coats A, et al. Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure. Eur Heart J. 2005;26:215–225
  77. Alvares R, Goodwin J. Non-invasive assessment of diastolic function in hypertrophic cardiomyopathy on and off beta adrenergic blocking drugs. Br Heart J. 1982;48:204–212
  78. Cohen L, Braunwald E. Amelioration of angina pectoris in idiopathic hypertrophic subaortic stenosis with beta-adrenergic blockade. Circulation. 1967;35:847–851
  79. Thompson D, Naqvi N, Juul S, et al. Effects of propranolol on myocardial oxygen consumption, substrate extraction, and hemodynamics in hypertrophic obstructive cardiomyopathy. Br Heart J. 1980;44:488–498
  80. Lee D, Johnson R, Bingham J, et al. Heart failure in outpatients: a randomized trial of digoxin versus placebo. N Engl J Med. 1982;306:699–705
  81. Guyatt G, Sullivan M, Fallen E, et al. A controlled trial of digoxin in congestive heart failure. Am J Cardiol. 1988;61:371–375
  82. Ahmed A, Rich M, Love T, et al. Digoxin and reduction in mortality and hospitalization in heart failure: a comprehensive post hoc analysis of the DIG trial. Eur Heart J. 2006;27:178–186
  83. Packer M, Gheorghiade M, Young J, et al. Withdrawal of digoxin from patients with chronic heart failure treated with angiotensin-converting-enzyme inhibitors (RADIANCE Study). N Engl J Med. 1993;329:1–7
  84. Uretsky B, Young J, Shahidi F, et al. Randomized study assessing the effect of digoxin withdrawal in patients with mild to moderate chronic congestive heart failure: results of the PROVED trial (PROVED Investigative Group). J Am Coll Cardiol. 1993;22:955–962
  85. Gheorghiade M, Ferguson D. Digoxin (A neurohormonal modulator in heart failure?). Circulation. 1991;84:2181–2186
  86. Terra S, Washam J, Dunham G, et al. Therapeutic range of digoxin's efficacy in heart failure: what is the evidence?. Pharmacotherapy. 1999;19:1123–1126
  87. Ahmed A, Rich M, Fleg J, et al. Effects of digoxin on morbidity and mortality in diastolic heart failure: the ancillary digitalis investigation group trial. Circulation. 2006;114:397–403
  88. Wilson J, Reichek N, Dunkman W, et al. Effect of diuresis on the performance of the failing left ventricle in man. Am J Med. 1981;70:234–239
  89. Page J, Henry D. Consumption of NSAIDs and the development of congestive heart failure in elderly patients: an underrecognized public health problem. Arch Intern Med. 2000;160:777–784
  90. Cohn J, Johnson G, Ziesche S, et al. A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med. 1991;325:303–310
  91. Fogari R, Zoppi A, Mugellini A, et al. Effects of lisinopril vs hydralazine on left ventricular hypertrophy and ambulatory blood pressure monitoring in essential hypertension. Eur Heart J. 1995;16:1120–1125
  92. Taylor A, Ziesche S, Yancy C, et al. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med. 2004;344:20049–20057
  93. Cohn J, Johnson G. Heart failure with normal ejection fraction (The V-HeFT Study. Veterans Administration Cooperative Study Group). Circulation. 1990;81(2 Suppl):III48–III53
  94. Goldstein R, Boccuzzi S, Cruess D, et al. Diltiazem increases late-onset congestive heart failure in postinfarction patients with early reduction in ejection fraction. Circulation. 1991;83:52–60
  95. Elkayam U, Amin J, Mehra A, et al. A prospective, randomized, double-blind, crossover study to compare the efficacy and safety of chronic nifedipine therapy with that of isosorbide dinitrate and their combination in the treatment of chronic congestive heart failure. Circulation. 1990;82:1954–1961
  96. Godfraind T, Salomone S, Dessy C, et al. Selectivity scale of calcium antagonists in the human cardiovascular system based on in vitro studies. J Cardiovasc Pharmacol. 1992;20(Suppl 5):s34–s41
  97. Packer M, O'Connor C, Ghali J, et al. Effect of amlodipine on morbidity and mortality in severe chronic heart failure. N Engl J Med. 1996;335:1107–1114
  98. Nathan S, Pepine C, Bakris G. Calcium antagonists: effects on cardio-renal risk in hypertensive patients. Hypertension. 2005;46:637–642
  99. Chen C, Nakayama M, Talbot M, et al. Verapamil acutely reduces ventricular-vascular stiffening and improves aerobic exercise performance in elderly individuals. J Am Coll Cardiol. 1999;33:1602–1609
  100. Bonow R, Dilsizian V, Rosing D, et al. Verapamil-induced improvement in left ventricular diastolic filling and increased exercise tolerance in patients with hypertrophic cardiomyopathy: short- and long-term effects. Circulation. 1985;72:853–864
  101. Setaro J, Zaret B, Schulman D, et al. Usefulness of verapamil for congestive heart failure associated with abnormal left ventricular diastolic filling and normal left ventricular systolic performance. Am J Cardiol. 1990;66:981–986
  102. Go A, Lee W, Yang J, et al. Statin therapy and risks for death and hospitalization in chronic heart failure. JAMA. 2006;296:2105–2111
  103. Mozaffarian D, Nye R, Levy W. Statin therapy is associated with lower mortality among patients with severe heart failure. Am J Cardiol. 2004;93:1124–1129
  104. Foody J, Shah R, Galusha D, et al. Statins and mortality among elderly patients hospitalized with heart failure. Circulation. 2006;113:1086–1092
  105. Kjekshus J, Apetrei E, Barrios V, et al. Rosuvastatin in older patients with systolic heart failure. N Engl J Med. 2007;357:2248–2261
  106. Fukuta H, Sane D, Brucks S, et al. Statin therapy may be associated with lower mortality in patients with diastolic heart failure: a preliminary report. Circulation. 2005;112:357–363
  107. Patel R, Nagueh S, Tsybouleva N, et al. Simvastatin induces regression of cardiac hypertrophy and fibrosis and improves cardiac function in a transgenic rabbit model of human hypertrophic cardiomyopathy. Circulation. 2001;104:317–324
  108. Bauersachs J, Galuppo P, Fraccarollo D, et al. Improvement of left ventricular remodeling and function by hydroxymethylglutaryl coenzyme A reductase inhibition with cerivastatin in rats with heart failure after myocardial infarction. Circulation. 2001;104:982–985
  109. Ferrier K, Muhlmann M, Baguet J, et al. Intensive cholesterol reduction lowers blood pressure and large artery stiffness in isolated systolic hypertension. J Am Coll Cardiol. 2002;39:1020–1025
  110. Ramasubbu K, Estep J, White DL, et al. Experimental and clinical basis for the use of statins in patients with ischemic and nonischemic cardiomyopathy. J Am Coll Cardiol. 2008;51:415–426
  111. Rees K, Taylor R, Singh S, et al. Exercise based rehabilitation for heart failure. Cochrane Database Syst Rev. 2004;3:CD003331
  112. Bensimhon D, Adams G, Whellan D, et al. Effect of exercise training on ventricular function, dyssynchrony, resting myocardial perfusion, and clinical outcomes in patients with heart failure: a nuclear ancillary study of Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing (FH-ACTION); design and rationale. Am Heart J. 2007;154:46–53
  113. O'Connor CM, Whellan DJ, Lee KL, et al. Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial. JAMA. 2009;301:1439–1450
  114. Whellan D, O'Connor C, Lee K, et al. Heart failure and a controlled trial investigating outcomes of exercise training (HF-ACTION): design and rationale. Am Heart J. 2007;153:201–211
  115. Whellan D, Hasselblad V, Peterson E, et al. Metaanalysis and review of heart failure disease management randomized controlled clinical trials. Am Heart J. 2005;149:722–729
  116. Rich M, Beckham V, Wittenberg C, et al. A multidisciplinary intervention to prevent the readmission of elderly patients with congestive heart failure. N Engl J Med. 1995;333:1190–1195
  117. Riegel B, Carlson B, Kopp Z, et al. Effect of a standardized nurse case-management telephone intervention on resource use in patients with chronic heart failure. Arch Intern Med. 2002;162:705–712
  118. Dickstein K, Cohen-Solal A, Filippatos G, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008. Eur Heart J. 2008;29:2388–2442

 Funding: None.

 Conflict of Interest: None.

 Authorship: Author had access to the data and played a role in writing this manuscript.

PII: S0002-9343(09)00397-0

doi: 10.1016/j.amjmed.2009.01.038

The American Journal of Medicine
Volume 122, Issue 8 , Pages 713-723 , August 2009