Drugs & Aging

, Volume 23, Issue 4, pp 299–308 | Cite as

Diastolic Heart Failure in the Elderly and the Potential Role of Aldosterone Antagonists

  • Ashwani Kumar
  • Gary Meyerrose
  • Vineeta Sood
  • Chanwit Roongsritong
Review Article


The overall incidence of heart failure increases with age, affecting up to 10% of people >65 years of age. Diastolic heart failure is also age-dependent, increasing from <15% in middle-aged patients to >40% in patients ≥;70 years of age. Elderly patients usually have other co-morbid conditions such as hypertension, diabetes mellitus, coronary artery disease and atrial fibrillation that can adversely affect the diastolic properties of the heart.

The clinical manifestations of diastolic heart failure are similar to those of systolic heart failure. In practice, the diagnosis is generally based on the finding of typical symptoms and signs of heart failure with preserved left ventricular ejection fraction and no valvular abnormalities on echocardiography.

Altered ventricular relaxation and abnormal ventricular filling are the hallmarks of diastolic heart failure. Cardiac fibrosis and cellular disarray lead to the alterations in the diastolic properties of the heart. Diffuse foci of fibrosis in the myocardium have been reported with advancing age. Aldosterone has been shown to play a crucial role in the development of cardiac fibrosis via a direct effect on the mineralocorticoid receptors within the myocardium.

Unlike the situation with treatment of systolic heart failure, few clinical trials are available to guide the management of patients with diastolic heart failure. In the absence of controlled clinical trials, patient management is based on control of the physiological factors (blood pressure, heart rate, blood volume and myocardial ischaemia) that are known to exert important effects on ventricular relaxation. Aldosterone antagonists inhibit the deposition of collagen matrix in the myocardium, thereby targeting the basic pathophysiological mechanism of diastolic dysfunction. Thus, they appear to represent a promising therapeutic approach for this condition. Currently, only small clinical trials supporting this therapy are available and large clinical trials evaluating long-term outcomes in diastolic dysfunction are therefore needed.


Aldosterone Leave Ventricular Hypertrophy Diastolic Dysfunction Diastolic Function Brain Natriuretic Peptide 
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.



No work resembling the enclosed article has been published or is submitted for publication elsewhere. We certify that we have each made a substantial contribution so as to qualify for authorship. We did not receive any financial support for our work and do not have any potential conflicts of interest.


  1. 1.
    Kannel WB, Belanger AJ. Epidemiology of heart failure. Am Heart J 1991; 121: 951–7PubMedCrossRefGoogle Scholar
  2. 2.
    Kannel WB. Epidemiology and prevention of cardiac failure: Framingham Study insights. Eur Heart J 1987; 8Suppl. F: 23–6PubMedCrossRefGoogle Scholar
  3. 3.
    Hunt SA, Abraham WT, Chin MH, 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–e82PubMedCrossRefGoogle Scholar
  4. 4.
    Gaasch WH, Zile MR. Left ventricular diastolic dysfunction and diastolic heart failure. Annu Rev Med 2004; 55: 373–94PubMedCrossRefGoogle Scholar
  5. 5.
    Redfield MM, Jacobsen SJ, Burnett Jr JC, et al. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA 2003; 289: 194–202PubMedCrossRefGoogle Scholar
  6. 6.
    Zile MR, Brutsaert DL. New concepts in diastolic dysfunction and diastolic heart failure: Part I. Diagnosis, prognosis, and measurements of diastolic function. Circulation 2002; 105: 1387–93PubMedCrossRefGoogle Scholar
  7. 7.
    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: 1953–9PubMedCrossRefGoogle Scholar
  8. 8.
    Vasan RS, Benjamin EJ, Levy D. Prevalence, clinical features and prognosis of diastolic heart failure: an epidemiologic perspective. J Am Coll Cardiol 1995; 26: 1565–74PubMedCrossRefGoogle Scholar
  9. 9.
    Kitzman DW, Gardin JM, Gottdiener JS, et al. Importance of heart failure with preserved systolic function in patients ≥65 years of age. Am J Cardiol 2001; 87: 413–9PubMedCrossRefGoogle Scholar
  10. 10.
    Aurigemma GP, Gottdiener JS, Shemanski L, et al. Predictive value of systolic and diastolic function for incident congestive heart failure in the elderly: the Cardiovascular Health Study. J Am Coll Cardiol 2001; 37: 1042–8PubMedCrossRefGoogle Scholar
  11. 11.
    Vasan R, 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: 1948–55PubMedCrossRefGoogle Scholar
  12. 12.
    O’Conner CM, Gattis WA, Shaw L, et al. Clinical characteristics and long-term outcomes of patients with heart failure and preserved systolic function. Am J Cardiol 2000; 86: 863–7CrossRefGoogle Scholar
  13. 13.
    Judge KW, Pawitan Y, Caldwell J, et al. Congestive heart failure symptoms in patients with preserved left ventricular systolic function: analysis of the CASS registry. J Am Coll Cardiol 1991; 18: 377–82PubMedCrossRefGoogle Scholar
  14. 14.
    Aurigemma GP, Williams HG. Diastolic heart failure. N Engl J Med 2004; 351: 1097–105PubMedCrossRefGoogle Scholar
  15. 15.
    Zile MR, Gaasch WH, Carroll JD, et al. Heart failure with a normal ejection fraction: is measurement of diastolic function necessary to make the diagnosis of diastolic heart failure? Circulation 2001; 104: 779–82PubMedCrossRefGoogle Scholar
  16. 16.
    European Study Group on Diastolic Heart Failure. How to diagnose diastolic heart failure. Eur Heart J 1998; 19: 990–1003CrossRefGoogle Scholar
  17. 17.
    Vasan RS, Levy D. Defining diastolic heart failure: a call for standardized diagnostic criteria. Circulation 2000; 101: 2118–21PubMedCrossRefGoogle Scholar
  18. 18.
    Bryg RJ, Williams GA, Labovitz AJ. Effect of aging on left ventricular diastolic filling in normal subjects. Am J Cardiol 1987; 59: 971–4PubMedCrossRefGoogle Scholar
  19. 19.
    Rakowski H, Appleton C, Chan KL, et al. Canadian consensus recommendations for the measurement and reporting of diastolic dysfunction by echocardiography from the Investigators of Consensus on Diastolic Dysfunction by Echocardiography. J Am Soc Echocardiogr 1996; 9: 736–60PubMedCrossRefGoogle Scholar
  20. 20.
    Garcia MJ, Thomas JD, Klein AL. New Doppler echocardiographic applications for the study of diastolic function. J Am Coll Cardiol 1998; 32: 865–75PubMedCrossRefGoogle Scholar
  21. 21.
    Yamaguchi H, Yoshida J, Yamamoto K, et al. Elevation of plasma brain natriuretic peptide is a hallmark of diastolic heart failure independent of ventricular hypertrophy. J Am Coll Cardiol 2004; 43: 55–60PubMedCrossRefGoogle Scholar
  22. 22.
    Lubien E, DeMaria A, Krishnaswamy P, et al. Utility of B-natriuretic peptide in detecting diastolic dysfunction, comparison with Doppler velocity recordings. Circulation 2002; 105: 595–601PubMedCrossRefGoogle Scholar
  23. 23.
    Krishnaswamy P, Lubien E, Clopton P, et al. Utility of B-natriuretic peptide levels in identifying patients with left ventricular systolic and diastolic dysfunction. Am J Med 2001; 111: 274–9PubMedCrossRefGoogle Scholar
  24. 24.
    Roongsritong C, Qaddour A, Cox SL, et al. Brain natriuretic peptide and diastolic dysfunction in the elderly: influence of gender. Congest Heart Fail 2005; 11: 65–7PubMedCrossRefGoogle Scholar
  25. 25.
    Kitzman DW. Diastolic function in the elderly, genesis and diagnostic and therapeutic implications. Cardiol Clin 2000; 18: 597–617PubMedCrossRefGoogle Scholar
  26. 26.
    Gaasch WH, Izzi G. Clinical diagnosis and management of left ventricular diastolic dysfunction. In: Hori M, Suga H, Baan J, et al., editors. Cardiac mechanics and function in the normal and diseased heart. New York: Springer-Verlag, 1989: 296Google Scholar
  27. 27.
    Gaasch WH, Blaustein AS, LeWinter MM. Heart failure and clinical disorders of left ventricular diastolic dysfunction. In: Gaasch WH, LeWinter MM, editors. Left ventricular diastolic dysfunction and heart failure. Philadelphia (PA): Lea and Febiger, 1994: 245–58Google Scholar
  28. 28.
    Abd-Allah NM, Hassan FH, Esmat AY, et al. Age dependence of the levels of plasma norepinephrine, aldosterone, renin activity and urinary vanillylmandelic acid in normal and essential hypertensives. Biol Res 2004; 37: 95–106PubMedCrossRefGoogle Scholar
  29. 29.
    Daniel KR, Brosnihan B, Fray B, et al. Renin-angiotensin-aldosterone system activation in diastolic heart failure: comparison with systolic heart failure and age-matched normal subjects [abstract]. J Am Coll Cardiol 2005; 45: 130AGoogle Scholar
  30. 30.
    Zannad F, Dousset B, Alla F. Treatment of congestive heart failure: interfering the aldosterone-cardiac extracellular matrix relationship. Hypertension 2001; 38: 1227–32PubMedCrossRefGoogle Scholar
  31. 31.
    Brilla C, Weber K. Reactive and reparative myocardial fibrosis in arterial hypertension in rats. Cardiovasc Res 1992; 26: 671–7PubMedCrossRefGoogle Scholar
  32. 32.
    Young M, Funder J. Determinants of cardiac fibrosis in experimental hypermineralocorticoid states. Am J Physiol 1995; 269: E657–62PubMedGoogle Scholar
  33. 33.
    Delcayre C, Silvestre JS. Aldosterone and the heart: towards a physiological function? Cardiovasc Res 1999; 43: 7–12PubMedCrossRefGoogle Scholar
  34. 34.
    Brilla CG. Renin-angiotensin-aldosterone system and myocardial fibrosis. Cardiovasc Res 2000; 47: 1–3PubMedCrossRefGoogle Scholar
  35. 35.
    Rocha R, Rudolph AE, Frierdich GE, et al. Aldosterone induces a vascular inflammatory phenotype in the rat heart. Am J Physiol Heart Circ Physiol 2002; 283: 802–10Google Scholar
  36. 36.
    Connell MC, Davies E. The new biology of aldosterone. J Endocrinol 2005; 186: 1–20PubMedCrossRefGoogle Scholar
  37. 37.
    Soylu A, Temizhan A, Duzenli MA, et al. The influence of aldosterone on development of left ventricular geometry and hypertrophy in patients with essential hypertension. Jpn Heart J 2004; 45: 807–21PubMedCrossRefGoogle Scholar
  38. 38.
    Bravo EL. Aldosterone and specific aldosterone receptor antagonists in hypertension and cardiovascular disease. Curr Hypertens Rep 2003; 5: 122–5PubMedCrossRefGoogle Scholar
  39. 39.
    Stier Jr CT, Koenig S, Lee DY, et al. Aldosterone and aldosterone antagonism in cardiovascular disease: focus on eplerenone (Inspra). Heart Dis 2003; 5: 102–18PubMedCrossRefGoogle Scholar
  40. 40.
    Jaffe IZ, Mendelsohn ME. Angiotensin II and aldosterone regulate gene transcription via functional mineralocorticoid receptors in human coronary artery smooth muscle cells. Circ Res 2005; 96: 610–1CrossRefGoogle Scholar
  41. 41.
    Gaasch WH, Schick EC, Zile MR. Management of left ventricular diastolic dysfunction. In: Smith TW, editor. Cardiovascular therapeutics: a companion to Braunwald’s Heart Disease. Philadelphia (PA): WB Saunders, 1996: 237–42Google Scholar
  42. 42.
    Gottdiener JS, Reda DJ, Massie BM, et al. Effect of single-drug therapy on reduction of left ventricular mass in mild to moderate hypertension: comparison of six antihypertensive agents. The Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents. Circulation 1997; 95: 2007–14PubMedCrossRefGoogle Scholar
  43. 43.
    Mathew J, Sleight P, Lonn E, et al. Reduction of cardiovascular risk by regression of electrocardiographic markers of left ventricular hypertrophy by the angiotensin-converting enzyme inhibitor ramipril. Circulation 2001; 104: 1615–21PubMedCrossRefGoogle Scholar
  44. 44.
    Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999; 341: 709–17PubMedCrossRefGoogle Scholar
  45. 45.
    Yusuf S, Pfeffer MA, 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: 777–81PubMedCrossRefGoogle Scholar
  46. 46.
    Brilla C, Matsubara LS, Weber KT. Antifibrotic effects of spironolactone in preventing myocardial fibrosis in systemic arterial hypertension. Am J Cardiol 1993; 71: 12A–16APubMedCrossRefGoogle Scholar
  47. 47.
    Lijnen P, Petrov V. Antagonism of the renin-angiotensin-aldosterone system and collagen metabolism in cardiac fibroblasts. Method Find Exp Clin Pharmacol 1999; 21: 215–27CrossRefGoogle Scholar
  48. 48.
    Silvestre J, Heymes C, Oubenaissa A, et al. Activation of cardiac aldosterone production in rat myocardial infarction: effect of angiotensin II receptor blockade and role in cardiac fibrosis. Circulation 1999; 99: 2694–701PubMedCrossRefGoogle Scholar
  49. 49.
    Lacolley P, Safer ME, Lucet B, et al. Prevention of aortic and cardiac fibrosis by spironolactone in old normotensive rats. J Am Coll Cardiol 2001; 37: 662–7PubMedCrossRefGoogle Scholar
  50. 50.
    Degre S, Detry JM, Unger P, et al. Effects of spironolactonealtizide on left ventricular hypertrophy. Acta Cardiol 1998; 53: 261–7PubMedGoogle Scholar
  51. 51.
    Grandi AM, Imperiale D, Santillo R, et al. Aldosterone antagonist improves diastolic function in essential hypertension. Hypertension 2002; 40: 647–52PubMedCrossRefGoogle Scholar
  52. 52.
    Sato A, Hayashi M, Saruta T. Relative long-term effects of spironolactone in conjunction with an angiotensin-converting enzyme inhibitor on left ventricular mass and diastolic function in patients with essential hypertension. Hypertens Res 2002; 25: 837–42PubMedCrossRefGoogle Scholar
  53. 53.
    Pitt B, Reichek N, Willenbrock R, et al. Effects of eplerenone, enalapril and eplerenone/enalapril combination in patients with essential hypertension and left ventricular hypertrophy: 4E Left Ventricular Hypertrophy Study. Circulation 2003; 108: 1831–8PubMedCrossRefGoogle Scholar
  54. 54.
    Mottram PM, Haluska B, Leano R, et al. Effect of aldosterone antagonism on myocardial dysfunction in hypertensive patients with diastolic heart failure. Circulation 2004; 110: 558–65PubMedCrossRefGoogle Scholar
  55. 55.
    Roongsritong C, Sutthiwan P, Bradley J, et al. Spironolactone improves diastolic function in the elderly. Clin Cardiol 2005; 28: 484–7PubMedCrossRefGoogle Scholar
  56. 56.
    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: 2700–6PubMedCrossRefGoogle Scholar
  57. 57.
    Mahmud A, Feely J. Arterial stiffness and the renin-angiotensin-aldosterone system. J Renin Angiotensin Aldosterone Syst 2004; 5: 102–8PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2006

Authors and Affiliations

  • Ashwani Kumar
    • 1
  • Gary Meyerrose
    • 2
  • Vineeta Sood
    • 1
  • Chanwit Roongsritong
    • 2
  1. 1.Department of Internal MedicineTexas Tech University Health Sciences CenterLubbockUSA
  2. 2.Department of Internal Medicine, Division of CardiologyTexas Tech University Health Sciences CenterLubbockUSA

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