Aging and Optimal Therapy of Systolic Heart Failure in the Elderly

  • Nakul Chander SharmaEmail author
  • Bodh I. Jugdutt


Aging is a biological process that affects everyone with the passage of time. Several factors affect the rate of cardiovascular aging. Cardiovascular changes that occur with aging may predispose the elderly population (age ≥65 years) to diastolic and systolic dysfunction with heart failure (HF). In developed countries, the number of elderly people is expected to increase. Concurrently, the number of elderly patients with systolic heart failure (SHF) is expected to increase. This has been driven, in part, by an overall increase in life expectancy associated with improved health care and medical therapy in younger subsets and cumulative effects of lifelong exposure to cardiovascular disease risk factors. The elderly are at higher risk for HF, with higher mortality rates for SHF and diastolic HF (DHF). Several issues hinder optimization of HF therapy in the elderly. Foremost is lack of randomized clinical trial data on the efficacy and safety of prescribed therapy for SHF and DHF in the elderly. With a few exceptions, most guidelines proposed for management of SHF in the elderly come from extrapolation of data from past trials in younger patients and community registries. Novel therapies targeting the elderly may be needed. As the prevalences of SHF and DHF in elderly patients continue to rise, it is imperative that practicing physicians who care for them become familiar with ways to optimize therapy using available drugs/strategies while recognizing the issues and limitations with these and the need for more research to identify specific targets for the growing elderly population with SHF.


Heart Failure Heart Failure Patient Acute Heart Failure Mortality Benefit Systolic Heart Failure 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Lakatta EG, Gerstenblith G, Weisfeldt ML. The aging heart: structure, function, and disease. In: Braunwald E, editor. Heart disease. Philadelphia: Saunders; 1997. p. 1687–700.Google Scholar
  2. 2.
    Lakatta EG. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises. Part I. Circulation. 2003;107:139–46.PubMedCrossRefGoogle Scholar
  3. 3.
    Lakatta EG. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises. Part II. Circulation. 2003;107:346–54.PubMedCrossRefGoogle Scholar
  4. 4.
    Lakatta EG, Wang M, Najjar SS. Arterial aging and subclinical arterial disease are fundamentally intertwined at macroscopic and molecular levels. Med Clin North Am. 2009;93:583–604.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Centers for Disease Control and Prevention. Public health and aging: trends in aging: United States and worldwide. Morb Mortal Wkly Rep. 2003;52:101–6. Available at: Accessed 18 Aug 2011.Google Scholar
  6. 6.
    He W, Sengupta M, Velkoff VA, DeBarros KA. 65+ in the United States: 2005. Current population reports. Washington, DC: Government Printing Office; 2005. p. 23–209. Accessed 18 Aug 2011.
  7. 7.
    Hunt SA, Abraham WT, Chin MH, et al. 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. Circulation. 2009;119:e391–479.PubMedCrossRefGoogle Scholar
  8. 8.
    Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, et al. Heart disease and stroke statistics-2012 update: a report from the American Heart Association. Circulation. 2012;125:e2–220.PubMedCrossRefGoogle Scholar
  9. 9.
    McMurray J, Adamopoulos S, Anker S, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012- The task force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2012;14:803–69.PubMedCrossRefGoogle Scholar
  10. 10.
    Jugdutt BI. Aging and heart failure: changing demographics and implications for therapy in the elderly. Heart Fail Rev. 2010;15:401–5.PubMedCrossRefGoogle Scholar
  11. 11.
    Jugdutt BI. Heart failure in the elderly: advances and challenges. Expert Rev Cardiovasc Ther. 2010;8:695–715.PubMedCrossRefGoogle Scholar
  12. 12.
    Jugdutt BI. Aging and remodeling during healing of the wounded heart: current therapies and novel drug targets. Curr Drug Targets. 2008;9:325–44.PubMedCrossRefGoogle Scholar
  13. 13.
    Alexander KP, Newby LK, Armstrong PW, et al. American Heart Association Council on Clinical Cardiology; Society of Geriatric Cardiology. Acute coronary care in the elderly, part II: ST-segment-elevation myocardial infarction: a scientific statement for healthcare professionals from the American Heart Association Council on Clinical Cardiology: in collaboration with the Society of Geriatric Cardiology. Circulation. 2007;115:2570–89.PubMedCrossRefGoogle Scholar
  14. 14.
    Jessup M, Abraham WT, Casey DE, et al. Focused update: ACCF/AHA 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. Circulation. 2009;119:1977–2016.PubMedCrossRefGoogle Scholar
  15. 15.
    Cheng JW, Nayar M. A review of heart failure management in the elderly population. Am J Geriatr Pharmacother. 2009;7:233–49.PubMedCrossRefGoogle Scholar
  16. 16.
    Komajda M, Hanon O, Hochadel M, et al. Contemporary management of octogenarians hospitalized for heart failure in Europe: Europe Heart Failure Survey II. Eur Heart J. 2009;30:478–86.PubMedCrossRefGoogle Scholar
  17. 17.
    Kawaguchi M, Hay I, Fetics B, Kass DA. Combined ventricular systolic and diastolic reserve limitations. Circulation. 2003;107:714–20.PubMedCrossRefGoogle Scholar
  18. 18.
    Ho KK, Pinsky JL, Kannel WB, Levy D. The epidemiology of heart failure: the Framingham study. J Am Coll Cardiol. 1993;22:6A–13.PubMedCrossRefGoogle Scholar
  19. 19.
    Stevenson LW. Projecting heart failure into bankruptcy in 2012? Am Heart J. 2011;161:1007–11.PubMedCrossRefGoogle Scholar
  20. 20.
    Arnold MO, Liu P, Demers C, et al. Canadian Cardiovascular Society consensus conference recommendations on heart failure 2006: Diagnosis and treatment. Can J Cardiol. 2006;22:23–45.PubMedCrossRefGoogle Scholar
  21. 21.
    Jugdutt BI. Prevention of heart Failure in the elderly: when, where and how to begin? Heart Fail Rev. 2012;17:531–44.PubMedCrossRefGoogle Scholar
  22. 22.
    Goldberg RJ, McCormick D, Gurwitz JH, et al. Age-related trends in short- and long-term survival after acute myocardial infarction: A 20-year population-based perspective (1975-1995). Am J Cardiol. 1998;82:1311–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Yusuf S, Hawken S, Ounpuu S, et al. INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364:937–52.PubMedCrossRefGoogle Scholar
  24. 24.
    Hulsmann M, Berger R, Mortl D, Pacher R. Influence of age and in-patient care on prescription rate and long-term outcome in chronic heart failure: a data-based sub study of the EuroHeart Failure Survey. Eur J Heart Fail. 2005;7:657–61.PubMedCrossRefGoogle Scholar
  25. 25.
    Barsheshet A, Shotan A, Cohen E, et al. Predictors of long-term (4 year) mortality in elderly and young patients with acute heart failure. Eur J Heart Fail. 2010;12:833–40.PubMedCrossRefGoogle Scholar
  26. 26.
    Manzano L, Babalis D, Roughton M, et al. Predictors of clinical outcomes in elderly patients with heart failure. Eur J Heart Fail. 2011;13:528–36.PubMedCrossRefGoogle Scholar
  27. 27.
    Mogensen UM, Ersboll M, Andersen M, et al. Clinical characteristics and major comorbidities in heart failure patients more than 85 years of age compared to younger age groups. Eur J Heart Fail. 2011;13:1216–23.PubMedCrossRefGoogle Scholar
  28. 28.
    Abraham WT, Fonarow GC, Albert NM, et al. Predictors of in-hospital mortality in patients hospitalized for heart failure: insights from the Organized Program to initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF). J Am Coll Cardiol. 2008;52:347–56.PubMedCrossRefGoogle Scholar
  29. 29.
    Fonarow GC. Epidemiology and risk stratification in acute heart failure. Am Heart J. 2008;155:200–2007.PubMedCrossRefGoogle Scholar
  30. 30.
    Pocock SJ, Wang D, Pfeffer MA, et al. Predictors of mortality and morbidity in patients with chronic heart failure. Eur Heart J. 2006;27:65–75.PubMedCrossRefGoogle Scholar
  31. 31.
    Jelani A, Jugdutt BI. STEMI and heart failure in the elderly: role of adverse remodeling. Heart Fail Rev. 2010;15:513–21.PubMedCrossRefGoogle Scholar
  32. 32.
    Rich MW. Epidemiology, pathophysiology, and etiology of congestive heart failure in older adults. J Am Geriatr Soc. 1997;45:968–74.PubMedGoogle Scholar
  33. 33.
    Rich MW, Kitzman D. Heart failure in octogenarians: a fundamentally different disease. Am J Geriatr Cardiol. 2000;9(suppl):97–104.Google Scholar
  34. 34.
    Shih H, Lee B, Lee RJ, Boyle AJ. The aging heart and post-infarction left ventricular remodeling. J Am Coll Cardiol. 2011;57:9–17.PubMedCrossRefGoogle Scholar
  35. 35.
    Olivetti G, Melissari M, Capasso JM, Anversa P. Cardiomyopathy of the aging human heart. Myocyte loss and reactive cellular hypertrophy. Circ Res. 1991;68:1560–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Wong LS, van der Harst P, de Boer RA, Huzen J, van Gilst WH, van Veldhuisen DJ. Aging, telomeres and heart failure. Heart Fail Rev. 2010;15:479–86.PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Zile MR, Brutsaert DL. New concepts in diastolic dysfunction and diastolic heart failure. Part II: causal mechanisms and treatment. Circulation. 2002;105:2503–1508.Google Scholar
  38. 38.
    Nieminen MS, Brutsaert D, Dickstein K, et al. EuroHeart Failure Survey II (EHFSII): a survey on hospitalized acute heart failure patients: description of population. Eur Heart J. 2006;27:2725–36.PubMedCrossRefGoogle Scholar
  39. 39.
    Forman DE, Cannon CP, Hernandez AF, Liang L, Yancy C, Fonarow GC. Influence of age on the management of heart failure: findings from Get With the Guidelines-Heart Failure (GWTG-HF). Am Heart J. 2009;157:1010–7.PubMedCrossRefGoogle Scholar
  40. 40.
    Redfield MM, Jacobsen SJ, Burnett Jr JC, Mahoney DW, Bailey KR, Rodeheffer RJ. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA. 2003;289:194–202.PubMedCrossRefGoogle Scholar
  41. 41.
    Jugdutt BI. Aging and remodeling during healing of the wounded heart: Current therapies and novel drug targets. Curr Drug Targets. 2008;9:325–44.PubMedCrossRefGoogle Scholar
  42. 42.
    Cieslick KA, Taffet GE, Carlson S, Hermosillo J, Trial J, Entman ML. Immune-inflammatory dysregulation modulates the incidence of progressive fibrosis and diastolic stiffness in the aging heart. J Mol Cell Cardiol. 2011;50:248–56.CrossRefGoogle Scholar
  43. 43.
    Ho D, Yan L, Iwatsubo K, Vatner DE, Vatner SF. Modulation of β-adrenergic receptor signaling in heart failure and longevity: targeting adenyl cyclase type 5. Heart Fail Rev. 2010;15:495–512.PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Janczewski AM, Lakatta EG. Modulation of Ca2+ cycling in systolic and diastolic heart failure associated with aging. Heart Fail Rev. 2010;15:431–45.PubMedCentralPubMedCrossRefGoogle Scholar
  45. 45.
    Dhalla NS, Rangi S, Babick AP, Zieroth S, Elimban V. Cardiac remodeling and subcellular defects in heart failure due to myocardial infarction and aging. Heart Fail Rev. 2012;671–681.Google Scholar
  46. 46.
    Collerton J, Martin-Ruiz C, Kenny A, et al. Telomere length is associated with left ventricular function in the oldest old: the Newcastle 85+ study. Eur Heart J. 2007;28:172–6.PubMedCrossRefGoogle Scholar
  47. 47.
    Marti CN, Gheorghiade M, Kalogeropoulos AP, Georgiopoulou VV, Quyyumi AA, Butler J. Endothelial dysfunction, arterial stiffness, and heart failure. J Am Coll Cardiol. 2012;60(16):1455–69.PubMedCrossRefGoogle Scholar
  48. 48.
    Fleg J, Strait J. Age-associated changes in cardiovascular structure and function: ma fertile milieu for future disease. Heart Fail Rev. 2012;17:545–54.PubMedCrossRefGoogle Scholar
  49. 49.
    Jugdutt BI. Clinical effectiveness of telmisartan alone or in combination therapy for controlling blood pressure and vascular risk in the elderly. Clin Interv Aging. 2010;5:403–16.PubMedCentralPubMedCrossRefGoogle Scholar
  50. 50.
    Kazemian P, Oudit G, Jugdutt BI. Atrial fibrillation and heart failure in the elderly. Heart Fail Rev. 2012;17:597–613.PubMedCrossRefGoogle Scholar
  51. 51.
    Chae CU, Albert CM, Glynn RJ, Guralnik JM, Curhan GC. Mild renal insufficiency and risk of heart failure in men and women > or = age 70 years of age. Am J Cardiol. 2003;92:682–6.PubMedCrossRefGoogle Scholar
  52. 52.
    Rich MW. Office management of heart failure in the elderly. Am J Med. 2005;118:342–8.PubMedCrossRefGoogle Scholar
  53. 53.
    Maisel AS, Krishnaswamy P, Nowak RM, et al. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med. 2002;347:161–7.PubMedCrossRefGoogle Scholar
  54. 54.
    McClellan WM, Flanders WD, Langston RD, Jurovitz C, Presely R. Anemia and renal insufficiency are independent risk factors for death among patients with congestive heart failure admitted to community hospitals: a population- based study. J Am Soc Nephrol. 2002;13:1928–36.PubMedCrossRefGoogle Scholar
  55. 55.
    Krumholz HM, Chen YT, Vaccarino V, et al. Correlates and impact on outcomes of worsening renal function in patients > 65 years of age with heart failure. Am J Cardiol. 2000;85:1110–3.PubMedCrossRefGoogle Scholar
  56. 56.
    Vogels RL, Scheltens P, Schroeder-Tanka JM, Weinstein HC. Cognitive impairment in heart failure: a systemic review of the literature. Eur J Heart Fail. 2007;9:440–9.PubMedCrossRefGoogle Scholar
  57. 57.
    Robinson T, Gariballa S, Fancourt G, Potter J, Castleden M. The acute effects of a single dopamine infusion in elderly patients with congestive cardiac failure. Br J Clin Pharmacol. 1994;37:261–3.PubMedCentralPubMedCrossRefGoogle Scholar
  58. 58.
    Rich MW. Pharmacotherapy of heart failure in the elderly: adverse events. Heart Fail Rev. 2012;17:589–95.PubMedCrossRefGoogle Scholar
  59. 59.
    Hauptman PJ, Rich MW, Heidenreich PA, et al. The heart failure clinic: a consensus statement of the Heart Failure Society of America. J Card Fail. 2008;14(10):801–15.PubMedCrossRefGoogle Scholar
  60. 60.
    Howlett JG, McKelvie RS, Costigan J, et al. The 2010 Canadian Cardiovascular Society guidelines for the diagnosis and management of heart failure update: Heart Failure in ethnic minority populations, heart failure and pregnancy, disease management, and quality improvement/assurance programs. Can J Cardiol. 2010;26(4):185–202.PubMedCrossRefGoogle Scholar
  61. 61.
    Garg R, Yusuf S. Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. Collaborative group ACE inhibitor Trials. JAMA. 1995;273:1450–6.PubMedCrossRefGoogle Scholar
  62. 62.
    Giles TD, Katz R, Sullivan JM, et al. Short and long acting angiotensin- converting enzyme inhibitors: a randomized trial of lisinopril versus captopril in the treatment of congestive heart failure. J Am Coll Cardiol. 1989;13:1240–7.PubMedCrossRefGoogle Scholar
  63. 63.
    Israili ZH, Hall WD. Cough and angioneurotic edema associated with angiotensin- converting enzyme inhibitor therapy. A review of literature and pathophysiology. Ann Intern Med. 1992;117:234–42.PubMedCrossRefGoogle Scholar
  64. 64.
    Ryden L, Armstrong PW, Cleland JG, et al. Efficacy and safety on high dose lisinopril in chronic heart failure patients at high cardiovascular risk, including those with diabetes mellitus. Results from the ATLAS trial. Eur Heart J. 2000;21:1967–78.PubMedCrossRefGoogle Scholar
  65. 65.
    Ahmed A, Kiefe CI, Allman RM, et al. Survival benefits of angiotensin-converting enzyme inhibitors in older heart failure patients with perceived contraindications. J Am Geriatr Soc. 2002;50:1659–66.PubMedCrossRefGoogle Scholar
  66. 66.
    Granger CB, McMurray JJ, Yusuf S, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting enzyme inhibitors: the CHARM-alternative trial. Lancet. 2003;362:772–6.PubMedCrossRefGoogle Scholar
  67. 67.
    Cohn JN, Tognoni G. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001;345:1667–75.PubMedCrossRefGoogle Scholar
  68. 68.
    Pitt B, Remme W, Zannad F, et al. The effect of spironolactone or morbidity and mortality in patients with severe heart failure. Randomized aldactone evaluation study investigators. N Engl J Med. 1999;341:709–17.PubMedCrossRefGoogle Scholar
  69. 69.
    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;348:1309–21.PubMedCrossRefGoogle Scholar
  70. 70.
    Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, Vincent J, Pocock SJ, Pitt B, EMPHASIS-HF Study Group. Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms. N Engl J Med. 2011;364:11–21.PubMedCrossRefGoogle Scholar
  71. 71.
    Dulin BR, Haas SJ, Abraham WT, Krum H. Do elderly systolic heart failure patients benefit from beta blockers to the same extent as the non-elderly? Meta analysis of > 12000 patients in large-scale clinical trials. Am J Cardiol. 2005;95:896–8.PubMedCrossRefGoogle Scholar
  72. 72.
    Ghio S, Magrini G, Serio A, et al. Effects of nebivolol in elderly heart failure patients with or without systolic left ventricular dysfunction: results of the SENIORS echocardiographic sub study. Eur Heart J. 2006;27:5672–678.Google Scholar
  73. 73.
    Effects of Metoprolol CR/XL in chronic heart failure: metoprolol CR/XL randomized intervention trial in congestive heart failure (MERIT-HF). Lancet. 1999;353:2001–207.Google Scholar
  74. 74.
    Short PM, Lipworth S, Elder DHJ, Schembri S, Lipworth BJ. Effect of beta blockers in treatment of chronic obstructive pulmonary disease: a retrospective cohort study. BMJ. 2011;342:d2549.PubMedCentralPubMedCrossRefGoogle Scholar
  75. 75.
    Swedberg K, Komajda PM, Böhm M, et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomized placebo-controlled study. Lancet. 2010;376:875–85.PubMedCrossRefGoogle Scholar
  76. 76.
    Brater DC. Diuretic therapy. N Engl J Med. 1998;351:543–51.Google Scholar
  77. 77.
    Schrier RW, Gross P, Gheorghiade M, SALT Investigators, et al. Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med. 2006;355:2099–112.PubMedCrossRefGoogle Scholar
  78. 78.
    Taylor AL, Ziesche S, Yancy C, et al. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med. 2004;351:1547–52.CrossRefGoogle Scholar
  79. 79.
    Jugdutt BI. Nitrates as anti-ischemic and cardio-protective agents. In: Singh BN, Dzau VJ, Vanhoutte P, Woosley RL, editors. Cardiovascular pharmacology and therapeutics. New York: Churchill Livingstone; 1993. p. 449–65.Google Scholar
  80. 80.
    Jugdutt BI. Intravenous nitroglycerin unloading in acute myocardial infarction. Am J Cardiol. 1991;68:52D–63.PubMedCrossRefGoogle Scholar
  81. 81.
    Rector TS, Johnson G, Dunkman WB, Daniels G, Farrell L, Henrick A, Smith B, Cohn JN. Evaluation by patients with heart failure of the effects of enalapril compared with hydralazine plus isosorbide dinitrate on quality of life. V-HeFT II. The V-HeFT VA Cooperative Studies Group. Circulation. 1993;87(6 Suppl):VI71–7.PubMedGoogle Scholar
  82. 82.
    O’Connor CM, Starling RC, Hernandez AF, Armstrong PW, Dickstein K. Effect of Nesiritide in Patients with Acute Decompensated Heart Failure. N Engl J Med. 2001;365:32–43.CrossRefGoogle Scholar
  83. 83.
    The Digitalis Investigation Group. The effect of Digoxin on mortality and morbidity in patients with heart failure. N Engl J Med. 1997;336:525–33.CrossRefGoogle Scholar
  84. 84.
    The PROMISE Study Research Group. Effect of oral milrinone on mortality in severe chronic heart failure. N Engl J Med. 1991;325:1486–75.Google Scholar
  85. 85.
    Oliva F, Latini R, Politi A, et al. Intermittent 6-month low-dose dobutamine infusion in severe heart failure. DICE multicenter trial. Am Heart J. 1999;138:247–53.PubMedCrossRefGoogle Scholar
  86. 86.
    Homma S, Thompson JL, Pullicino PM, Investigators WARCEF, et al. Warfarin and aspirin in patients with heart failure and sinus rhythm. N Engl J Med. 2012;366:1859–69.PubMedCentralPubMedCrossRefGoogle Scholar
  87. 87.
    Patterson ME, Grant WC, Glickman SW, et al. Resource use and costs of treatment with anticoagulation and antiplatelet agents: results of the WATCH trial economic evaluation. J Card Fail. 2009;10:819–27.CrossRefGoogle Scholar
  88. 88.
    Epstein AE, DiMarco JP, Ellenbogen KA, et al. ACC/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology/American Heart Association task force on practice guidelines. Circulation. 2008;117:e350–408.PubMedCrossRefGoogle Scholar
  89. 89.
    Strimel W, Koplik S, Chen HR, Song J, Huang SK. Safety and effectiveness of primary prevention cardioverter defibrillators in octogenarians. Pacing Clin Electrophysiol. 2011;34:900–6.PubMedCrossRefGoogle Scholar
  90. 90.
    Tang AS, Wells GA, Resynchronization–Defibrillation for Ambulatory Heart Failure Trial (RAFT) Investigators, et al. Cardiac-resynchronization therapy for mild-to-moderate heart failure. N Engl J Med. 2010;363:2385–95.PubMedCrossRefGoogle Scholar
  91. 91.
    Marielli D, Kobashigawa J, Hamilton M, et al. Long term outcomes of heart transplantation in older recipients. J Heart Lung Transplant. 2008;27:830–4.CrossRefGoogle Scholar
  92. 92.
    Adamson RM, Stahovich M, Chillcott S, et al. Clinical strategies and outcomes in advanced heart failure patients older than 70 years of age receiving the HeartMate II left ventricular assist device: a community hospital experience. J Am Coll Cardiol. 2011;57:2487–95.PubMedCrossRefGoogle Scholar
  93. 93.
    Butler CR, Jugdutt BI. Mechanical circulatory support for elderly heart failure patients. Heart Fail Rev. 2012;17:663–9.PubMedCrossRefGoogle Scholar
  94. 94.
    Kostis JB, Packer M, Black HR, Schmieder R, Henry D, Levy E. Omapatrilat and enalapiril in patients with hypertension: the omapatrilat cardiovascular treatment vs. enalapril (OCTAVE) trial. Am J Hypertens. 2004;17:103–11.PubMedCrossRefGoogle Scholar
  95. 95.
    Solomon SD, Skali H, Bourgoun M, Fang J, Ghali JK, Martelet M, Wojciechowski D, Ansmite B, Skards J, Laks T, Henry D, Packer M, Pfeffer MA, OVERTURE Investigators. Effect of angiotensin-converting enzyme or vasopeptidase inhibition on ventricular size and function in patients with heart failure: the omapatrilat versus enalapril randomized trial of utility in reducing events (OVERTURE) ehocardiographic study. Am Heart J. 2005;150:257–62.PubMedCrossRefGoogle Scholar
  96. 96.
    Solomon SD, Zile M, Pieske B, Voors A, Shah A, Kraigher-Krainer E, Shi V, Bransford T, Takeuchi M, Gong J, Lefkowitz M, Packer M, McMurray JJV, PARAMOUNT Investigators. The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomized clinical trial. Lancet. 2012;380(9851):1387–95. doi: 10.1016/S0140-6736(12)61227-6. Accessed Aug 2012.PubMedCrossRefGoogle Scholar
  97. 97. Prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in patients with heart failure (PARADIGM-HF). 2012. Accessed Aug 2012Google Scholar
  98. 98.
    Pitt B, Segal R, Martinez FA, et al. Randomized trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the elderly Study, ELITE). Lancet. 1997;349:2338–45.Google Scholar
  99. 99.
    Flather MD, Shibata MC, Coats AJ, et al. Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur Heart J. 2005;26:215–25.PubMedCrossRefGoogle Scholar
  100. 100.
    Cleland JG, Tendera M, Adamus J, Investigators PEP-CHF, et al. The perindopril in elderly people with chronic heart failure (PEP-CHF). Eur Heart J. 2006;27:2338–45.PubMedCrossRefGoogle Scholar
  101. 101.
    Massie BM, Carson PE, McMurray JJ, et al. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med. 2008;359:2456–67.PubMedCrossRefGoogle Scholar
  102. 102.
    Dungen HD, Apostolovic S, Inkrot S, et al. Titration to target dose of bisoprolol vs. Carvedilol in elderly patients with heart failure: the CIBIS-ELD trial. Eur J Heart Fail. 2011;13:670–80.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Division of Cardiology, Department of MedicineMazankowski Heart InstituteEdmontonCanada
  2. 2.2C2 W.C. Mackenzie Health Sciences Centre, Division of Cardiology, Department of Medicine, Mazankowski Alberta Heart InstituteUniversity of Alberta and HospitalsEdmontonCanada

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