The less familiar side of heart failure: Symptomatic diastolic dysfunction

,; ,; ,

Applied Evidence

The less familiar side of heart failure: Symptomatic diastolic dysfunction

J Fam Pract. 2005 June;54(6):501-511

PDF Download

References

1. American Heart Association. Heart Disease and Stroke Statistics—2004 Update. Dallas, Texas: American Heart Association; 2003.

2. Popvic JR, Hall MJ. 1999 National Hospital Discharge Survey. Advance data from vital and health statistics; no. 319. Hyattsville, Maryland: Nation Center for Health Statistics, 2001.

3. Krumholz HM, Parent EM, Tu N, et al. Readmission after hospitalization for congestive heart failure among Medicare beneficiaries. Arch Intern Med 1997;157:99-104.

4. Krum H, Gilbert RE. Demographics and concomitant disorders in heart failure. Lancet 2003;362:147-158.

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.-

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.-

8. Kitzman DW, Gardin JM, Arnold A, et al. Heart failure with preserved LV function in the elderly: clinical and echocardiographic correlates from the Cardiovascular Health Study. Circulation 1999;94:1433.-

9. Hunt SA, Baker DW, Chin MH, et al. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: full text: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to revise the 1995 Guidelines for the Evaluation and Management of Heart Failure). Available at: http://www.acc.org/clinical/guidelines/failure/pdfs/hf_fulltext.pdf.

10. Gaasch WH. Diagnosis and treatment of heart failure based on left ventricular systolic or diastolic dysfunction. JAMA 1994;271:1276-1280.

11. Vasan RS, Levy D. Defining diastolic heart failure: a call for standardized diagnostic criteria. Circulation 2000;101:2118-2121.

12. Grossman W. Defining diastolic dysfunction. Circulation 2000;101:2020-2021.

13. Brozena SC, Jessup M. The new staging system for heart failure: what every primary care physician should know. Geriatrics 2003;58:31-36.

14. McDermott MM, Feinglas J, Sy J, et al. Hospitalized congestive heart failure patients with preserved versus abnormal left ventricular systolic function; clinical characteristics and drug therapy. Am J Med 1995;99:629-635.

15. 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.-

16. Kitzman DW, Gardin JM, Gottdiener JS, et al. for the CHS Research Group. Importance of heart failure with preserved systolic function in patients >65 years of age. Am J Cardiol 2001;87:413-419.

17. Masoudi FA, Havranek EP, Smith G, et al. Gender, age and heart failure with preserved left ventricular systolic function. J Am Coll Cardiol 2003;41:217-223.

18. Hellermann JP, Jacobsen SJ, Reeder GS, et al. Heart failure after myocardial infarction: Prevalence of preserved left ventricular systolic function in the community. Am Heart J 2003;145:742-748.

19. Bonow RO, Udelson JE. Left ventricular diastolic dysfunction as a cause of congestive heart failure: mechanisms and management. Ann Intern Med 1992;117:502-510.

20. Zile MR, Brutsaert DL. New concepts in diastolic dysfunction and diastolic heart failure: Part II: causal mechanisms and treatment. Circulation 2002;105:1503-1508.

21. Levy D, Larson MG, Vasan RS, Kannel WB, Ho KK. The progression from hypertension to congestive heart failure. JAMA 1996;275:1557-1562.

22. Vasan RS, Benjamin EJ, Levy D. Congestive heart failure with normal left ventricular systolic function: clinical approaches to the diagnosis and treatment of diastolic heart failure. Arch Intern Med 1996;156:146-157.

23. Zile MR, Brutsaert DL. New concepts in diastolic dysfunction and diastolic heart failure: Part I: diagnosis, prognosis, and measurements of diastolic function. Circulation 2002;105:1387-1393.

24. How to diagnose diastolic heart failure. European Study Group on Diastolic Heart Failure. Eur Heart J 1998;19:990.-

25. 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;104:779-782.

26. McKee PA, Castelli WP, McNamara PM, et al. The natural history of congestive heart failure: the Framingham study. N Engl J Med 1971;285:1441-1446.

27. Gandi SK, Powers JC, Nomeir A, et al. The pathogenesis of acute pulmonary edema associated with hypertension. N Engl J Med 2001;344:17-60.

28. Kitzman DW, Little WC, Brubaker PH, et al. Pathophysiological characterization of isolated dias-tolic heart failure in comparison to systolic heart failure. JAMA 2002;288:2144-2150.

29. Zile MR, Baicu CF, Gaasch WH. Diastolic heart fail-ure—abnormalities in active relaxation and passive stiffness of the left ventricle. N Engl J Med 2004;350:1953-1959.

30. Elesber AA, Redfield MM. Approach to patients with heart failure and normal ejection fraction. Mayo Clin Proc 2001;76:1047-1052.

31. Angeja BG, Grossman W. Evaluation and management of diastolic heart failure. Circulation 2003;107:659.-

32. Lubien E, DeMaria A, Krishnaswamy P, et al. Utility of b-natriuretic peptide in detecting diastolic dysfunction: comparison with Doppler velocity recordings. Circulation 2002;105:595-601.

33. Garg R, Yusuf S. Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. JAMA 1995;273:1450-1456.

34. Foody JM, Farrell MH, Krumholz HM. β-blocker therapy in heart failure: scientific review. JAMA 2002;287:883-889.

35. Pitt B, Zannad F, Remme WJ. The effect of spirono-lactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999;341:709-717.

36. Pitt B, Remme W, Zannad F. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003;348:1309-1321.

37. Yusuf S, Pfeffer MA, Swedberg, 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.

38. Aronow WS, Ahn C, Kronzon I. Effects of propranolol versus no propranolol on total mortality plus nonfatal myocardial infarction in older patients with prior myocardial infarction, congestive heart failure, and left ventricular ejection fraction >40% treated with diuretics plus angiotensin-converting enzyme inhibitors. Am J Cardiol 1997;80:207-209.

39. The Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med 1997;336:525.-

40. Vasan RS. Diastolic heart failure: the condition exists and needs to be recognized, prevented, and treated. BMJ 2003;327:1181-1182.

41. Aronow WS, 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.

42. Wilson JR, Reichek N, Dunkman WB, Golberg S. Effect of diuresis on the performance of the failing left ventricle in man. Am J Med 1981;70:234-239.

43. Faris R, Flather M, Purcell H, et al. Current evidence supporting the role of diuretics in heart failure: a meta analysis of randomized controlled trials. Int J Cardiol 2002;82:149-158.

44. Cowie MR, Zaphiriou A. Management of chronic heart failure. Br Med J 2002;325:422-425.

45. Cody RJ, Kubo SH, Pickworth KK. Diuretic treatment for the sodium retention of congestive heart failure. Arch Intern Med 1994;154:1905-1914.

46. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial Lancet 1999;353:9-13.

47. 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.

48. Packer M, Coats AJ, Fowler MB, et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 2001;344:1651-1658.

49. Levine HJ. Optimum heart rate of large failing hearts. Am J Cardiol 1988;61:633-636.

50. O’Connor CM, Carson PE, Miller AB, et al. Effect of amlodipine on mode of death among patients with advanced heart failure in the PRAISE trial. Prospective Randomized Amlodipine Survival Evaluation. Am J Cardiol 1998;82:881-887.

51. Amabile CM, Spencer AP. Keeping your patient with heart failure safe: a review of potentially dangerous medications. Arch Intern Med 2004;164:709-720.

52. Setaro J, Zaret BL, Schueman Ds, et al. Usefulness of verapamil for congestive heart failure associated with abnormal left ventricular diastolic performance. Am J Cardiol 1990;66:981-986.

53. Rathore SS, Wang Y, Krumholz HM. Sex-based differences in the effect of digoxin for the treatment of heart failure. N Engl J Med 2002;347:1403-1411.

54. Yamani MH. When should digoxin be used in patients with diastolic dysfunction? Cleve Clin J Med 2001;68:481,-485.

55. Vasan RS, Benjamin EJ. Diastolic heart failure—no time to relax. N Engl J Med 2001;344:56-58.

56. Carson P, Massie B. I-PRESERVE (Irbesartan in Heart Failure with Preserved Systolic Function) Study initiation presented at the European Society of Cardiology Annual Meeting, September 3, 2002, Berlin.

57. Cleland JG, Tendera M, Adamus J, et al. Perindopril for elderly people with chronic heart failure: the PEP-CHF study.

	LEVEL OF EVIDENCE*
FEATURE	SYSTOLIC HEART FAILURE	DIASTOLIC HEART FAILURE
Prevalence and risk factors	III	III
Non-invasive diagnostic methodologies	I - assessment of LVEF	IV, VII^†
Non-invasive diagnostic methodologies	I - measurement of BNP levels	IV, VII^†
Prognosis	I - II	II, III
Treatment with ACE inhibitor, ARB, beta-blockers, and digitalis	I^‡	II, V-VII
Prevention trials (treatment of asymptomatic precursor condition)	I	None
* evidence from several large, well-conducted randomized controlled trials evidence from a single large, randomized controlled trial or small, well-conducted randomized controlled studies evidence from well-conducted cohort studies evidence from well-conducted case-control studies evidence from uncontrolled or poorly controlled studies conflicting evidence, but tending to favor the recommendation expert opinion
† Diagnosis is primarily by exclusion of systolic heart failure; measurement of LVEF and BNP is also useful.
‡ Cochrane review and meta-analysis.
ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; LVEF, left ventricular ejection fraction; BNP, b-type natriuretic peptide. Adapted and reproduced with permission from the BMJ Publishing Group and Dr. Ramachandran S. Vasan. BMJ 2003; 327:1181-1182.⁴⁰

TABLE 5
Diastolic heart failure outcome trials

TRIAL	BACKGROUND AND CONTEXT	REPRESENTATIVE PATIENT POPULATION	AVG LVEF OF PARTICIPANTS	NNT	SOR* (LOE)
CHARM-Preserved	Candesartan added to standard heart failure therapy in patients with LVEF >40%	N=3023	54%	36^†	A (1b)
		60% NYHA Class II		42^‡
		38% NYHA Class III
		2% NYHA Class IV
DIG Ancillary Trial	Digoxin + ACE inhibitors and diuretics in patients with LVEF >45%	N=988	Not reported	N/A^§	B (1b)
DIG Ancillary Trial		NYHA classification not specified	Not reported	N/A^§	B (1b)
Propranolol Study, Aronow et al	Propranolol added to ACE inhibitors and diuretics in post-MI patients with LVEF 40%	N=158	56%	5^¶	A (1b)
		52% NYHA Class II
		48% NYHA Class III
*Based on the guidelines for evidence quality outlined by the Center for Evidence-Based Medicine, available at: www.cebm.net/levels_ of_evidence.asp. A(1b) = consistent level 1 studies; individual randomized controlled trial (with narrow confidence interval). B(1b) = consistent level 2 or 3 studies or extrapolations from level 1 studies; individual randomized controlled trial (with narrow confidence interval)
† For the composite of cardiovascular death, hospital admission for heart failure, MI, or cerebrovascular accident over 3 years
‡ For recurrent admissions for heart failure exacerbations over 3 years
§ No statistical differences between groups in rates of hospitalization or mortality over 3 years
¶ All-cause mortality over a mean of 32 months
NNT, number needed to treat to prevent one death or other specified endpoint; LVEF, left ventricular ejection fraction; ACE, angiotensin-converting enzyme; NYHA, New York Heart Association classification; CHARM, Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity; DIG, Digitalis Investigation Group.

Medications to control blood pressure

Hypertension is a major risk factor for DHF, and the ACC/AHA heart failure guidelines recommend a lower blood pressure goal for patients with diastolic heart failure than for those with uncomplicated hypertension (ie, <130/80 mm Hg).⁹ Angiotensin receptor blockers (ARBs), ACE inhibitors, beta-blockers, calcium channel blockers, and diuretics may all be employed to achieve this blood pressure goal.

FAST TRACK

Guidelines recommend a lower blood pressure goal for patients with DHF than those with uncomplicated hypertension (ie, <130/80 mm Hg)

Angiotensin II receptor blockers. The use of ARBs in the treatment of DHF was recently evaluated in the CHARM-Preserved Study. Candesartan, 32 mg once daily, when added to a background therapy of mostly diuretics and beta-blockers (initially excluding the use of ACE inhibitors but later permitted in appropriate patients following the release of the HOPE trial results), was found to have a modest impact in preventing recurrent admissions for heart failure exacerbations (number needed to treat [NNT]=42 over 3 years).³⁷ Candesartan also demonstrated a more favorable impact on the composite end-point of cardiovascular death, hospitalization for heart failure, MI, and stroke (NNT=36).

ACE inhibitors. For post-MI patients with DHF, ACE inhibitors have improved treadmill duration and NYHA functional class.⁴¹ Further studies are needed to determine whether an ACE inhibitor or an ARB is preferred or whether they may be used safely together in the management of DHF.

Beta-blockers. Propranolol, when added to an ACE inhibitor and diuretic, has been shown to significantly reduce mortality in a small prospective study of 158 post-MI patients with an average LVEF of 56% and NYHA Class II or III symptoms.³⁸ Seventy percent of the study patients were women (n=111) and the mean age was 81 years. The dose of pro-pranolol in this study was increased in 10-mg increments at 10-day intervals up to a total daily dose of 30 mg 3 times daily.

All 79 patients randomized to receive propranolol successfully reached the target dose; however, 14% (n=11) discontinued therapy due to worsening heart failure or hypotension. The absolute reduction in total mortality among patients receiving propranolol was 20%, compared with the study group receiving only standard heart failure therapy (NNT=5 for a median of 32 months of follow-up, P=.007). The positive effect of beta-blocker therapy in this small study merits another larger, complementary trial to confirm its benefits in a bigger patient population with the same characteristics.