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Treatment of patients with heart failure and preserved ejection fraction

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Opinion statement

Of the more than 5 million Americans who have heart failure (HF), 30% to 50% have HF with preserved ejection fraction (HF-PEF). HF-PEF commonly occurs in elderly patients, especially women, with comorbidities of hypertension, left ventricular hypertrophy, diabetes, myocardial ischemia, and obesity. HF-PEF is associated with high morbidity and mortality. Although two large multicenter randomized, placebo-controlled trials evaluating an angiotensin-converting enzyme inhibitor (ACEI) and an angiotensin receptor blocker (ARB) in patients with HFPEF did not demonstrate any statistically significant benefit in their primary end points, they did suggest that these agents may have a modest role in reducing HF hospitalizations. Although calcium channel blockers and β-blockers may be of benefit in patients with HF-PEF, large clinical trial data are not available to support their routine use in all patients with HF-PEF. Subgroup analysis does not support the use of digoxin in patients with HF-PEF in sinus rhythm. Current therapeutic recommendations for HF-PEF are aimed at 1) management of HF symptoms with sodium and fluid restriction along with diuretics for volume overload and 2) treatment of concomitant comorbidities, especially hypertension, rate and possibly rhythm control of atrial fibrillation, and evaluation and treatment of myocardial ischemia and anemia. ACEIs, ARBs, calcium channel blockers, and β-blockers are recommended for HF-PEF patients who have other established indications for their use. Results are awaited from ongoing clinical trials with another ARB, irbesartan, and an aldosterone blocker, spironolactone.

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References and Recommended Reading

  1. 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.

    Article  PubMed  Google Scholar 

  2. Gaasch WH, Zile MR: Left ventricular diastolic dysfunction and diastolic heart failure. Annu Rev Med 2004, 55:373–394.

    Article  PubMed  CAS  Google Scholar 

  3. 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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  5. 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.

    Article  PubMed  CAS  Google Scholar 

  6. 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.

    Article  PubMed  CAS  Google Scholar 

  7. Dahlstrom U: Can natriuretic peptides be used for the diagnosis of diastolic heart failure? Eur J Heart Fail 2004, 6:281–287.

    Article  PubMed  CAS  Google Scholar 

  8. Yamamoto K, Burnett JC Jr, Jougasaki M, et al.: Superiority of brain natriuretic peptide as a hormonal marker of ventricular systolic and diastolic dysfunction and ventricular hypertrophy. Hypertension 1996, 28:988–994.

    PubMed  CAS  Google Scholar 

  9. Macin SM, Perna ER, Cimbaro Canella JP, et al.: Increased levels of cardiac troponin-T in outpatients with heart failure and preserved systolic function are related to adverse clinical findings and outcome. Coron Artery Dis 2006, 17:685–691.

    Article  PubMed  Google Scholar 

  10. Heart Failure Society of America: Executive summary: HFSA 2006 Comprehensive Heart Failure Practice Guideline. J Card Fail 2006, 12:10–38.

    Article  Google Scholar 

  11. Redfield MM: Heart failure with normal ejection fraction. In Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine. Edited by Libby P, Bonow RO, Mann DL, et al.: Philadelphia: WB Saunders; 2007:641–657.

    Google Scholar 

  12. Zile MR, Brutsaert DL: New concepts in diastolic dysfunction and diastolic heart failure: part II: causal mechanisms and treatment. Circulation 2002, 105:1503–1508.

    Article  PubMed  Google Scholar 

  13. Kass DA, Bronzwaer JG, Paulus WJ: What mechanisms underlie diastolic dysfunction in heart failure? Circ Res 2004, 94:1533–1542.

    Article  PubMed  CAS  Google Scholar 

  14. Hoit BD, Walsh RA: Diastolic function in hypertensive heart disease. In Left Ventricular Diastolic Dysfunction and Heart Failure. Edited by Gaasch WH, LeWinter MM. Philadelphia: Lea and Febiger; 1994:354–372.

    Google Scholar 

  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, 104:779–782.

    Article  PubMed  CAS  Google Scholar 

  16. Brutsaert DL, Sys SU, Gillebert TC: Diastolic failure: pathophysiology and therapeutic implications. J Am Coll Cardiol 1993, 22:318–325.

    Article  PubMed  CAS  Google Scholar 

  17. 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.

    Article  PubMed  Google Scholar 

  18. 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.

    Article  PubMed  Google Scholar 

  19. Maurer MS, King DL, El Khoury RL, et al.: Left heart failure with a normal ejection fraction: identification of different pathophysiologic mechanisms. J Card Fail 2005, 11:177–187.

    Article  PubMed  Google Scholar 

  20. Yamamoto K, Masuyama T, Sakata Y, et al.: Roles of renin-angiotensin and endothelin systems in development of diastolic heart failure in hypertensive hearts. Cardiovasc Res 2000, 47:274–283.

    Article  PubMed  CAS  Google Scholar 

  21. Klapholz M, Maurer M, Lowe AM, et al.: Hospitalization for heart failure in the presence of a normal left ventricular ejection fraction: results of the New York Heart Failure Registry. J Am Coll Cardiol 2004, 43:1432–1438.

    Article  PubMed  Google Scholar 

  22. Little WC, Ohno M, Kitzman DW, et al.: Determination of left ventricular chamber stiffness from the time for deceleration of early left ventricular filling. Circulation 1995, 92:1933–1939.

    PubMed  CAS  Google Scholar 

  23. Devereux RB, Palmieri V, Sharpe N, et al.: Effects of once-daily angiotensin-converting enzyme inhibition and calcium channel blockade-based antihypertensive treatment regimens on left ventricular hypertrophy and diastolic filling in hypertension: the prospective randomized enalapril study evaluating regression of ventricular enlargement (preserve) trial. Circulation 2001, 104:1248–1254.

    Article  PubMed  CAS  Google Scholar 

  24. Solomon SD, Janardhanan R, Verma A, et al.: Effect of angiotensin receptor blockade and antihypertensive drugs on diastolic function in patients with hypertension and diastolic dysfunction: a randomised trial. Lancet 2007, 369:2079–2087.

    Article  PubMed  CAS  Google Scholar 

  25. Collins SP, Mielniczuk LM, Whittingham HA, et al.: The use of noninvasive ventilation in emergency department patients with acute cardiogenic pulmonary edema: a systematic review. Ann Emerg Med 2006, 48:260–269, 269.e1–269.e4.

    Article  PubMed  Google Scholar 

  26. Cheng CP, Suzuki M, Ohte N, et al.: Altered ventricular and myocyte response to angiotensin II in pacing-induced heart failure. Circ Res 1996, 78:880–892.

    PubMed  CAS  Google Scholar 

  27. Dagenais GR, Pogue J, Fox K, et al.: Angiotensin-converting-enzyme inhibitors in stable vascular disease without left ventricular systolic dysfunction or heart failure: a combined analysis of three trials. Lancet 2006, 368:581–588.

    Article  PubMed  CAS  Google Scholar 

  28. 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, 362:777–781.

    Article  PubMed  CAS  Google Scholar 

  29. Cleland JG, Tendera M, Adamus J, et al.: The perindopril in elderly people with chronic heart failure (PEP-CHF) study. Eur Heart J 2006, 27:2338–2345.

    Article  PubMed  CAS  Google Scholar 

  30. Yip GW, Wang M, Wang T, et al.: The Hong Kong diastolic heart failure study: a randomized control trial of diuretics, irbesartan and ramipril on quality of life, exercise capacity, left ventricular global and regional function in heart failure with a normal ejection fraction. Heart 2008, 94:573–580.

    Article  PubMed  CAS  Google Scholar 

  31. Carson P, Massie BM, McKelvie R, et al.: The irbesartan in heart failure with preserved systolic function (I-PRESERVE) trial: rationale and design. J Card Fail 2005, 11:576–585.

    Article  PubMed  CAS  Google Scholar 

  32. 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): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society. Circulation 2005, 112:e154–e235.

    Article  PubMed  Google Scholar 

  33. Brilla CG, Janicki JS, Weber KT: Impaired diastolic function and coronary reserve in genetic hypertension. Role of interstitial fibrosis and medial thickening of intramyocardial coronary arteries. Circ Res 1991, 69:107–115.

    PubMed  CAS  Google Scholar 

  34. Brilla CG, Matsubara LS, Weber KT: Anti-aldosterone treatment and the prevention of myocardial fibrosis in primary and secondary hyperaldosteronism. J Mol Cell Cardiol 1993, 25:563–575.

    Article  PubMed  CAS  Google Scholar 

  35. Staessen J, Lijnen P, Fagard R, et al.: Rise in plasma concentration of aldosterone during long-term angiotensin II suppression. J Endocrinol 1981, 91:457–465.

    Article  PubMed  CAS  Google Scholar 

  36. Struthers AD: Aldosterone escape during angiotensin-converting enzyme inhibitor therapy in chronic heart failure. J Card Fail 1996, 2:47–54.

    Article  PubMed  CAS  Google Scholar 

  37. Little WC, Brucks S: Therapy for diastolic heart failure. Prog Cardiovasc Dis 2005, 47:380–388.

    Article  PubMed  CAS  Google Scholar 

  38. 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, 26:215–225.

    Article  PubMed  CAS  Google Scholar 

  39. Rationale and design of a randomized trial to assess the effects of beta-blocker in diastolic heart failure; Japanese Diastolic Heart Failure Study (J-DHF). J Card Fail 2005, 11:542–547.

  40. Dauterman K, Pak PH, Maughan WL, et al.: Contribution of external forces to left ventricular diastolic pressure: implications for the clinical use of the Starling law. Ann Intern Med 1995, 122:737–742.

    PubMed  CAS  Google Scholar 

  41. Massie BM, Abdalla I: Heart failure in patients with preserved left ventricular systolic function: do digitalis glycosides have a role? Prog Cardiovasc Dis 1998, 40:357–369.

    Article  PubMed  CAS  Google Scholar 

  42. Ahmed A, Rich MW, Fleg JL, et al.: Effects of digoxin on morbidity and mortality in diastolic heart failure: the Ancillary Digitalis Investigation Group Trial. Circulation 2006, 114:397–403.

    Article  PubMed  CAS  Google Scholar 

  43. Zile MR: Treating diastolic heart failure with statins: “phat” chance for pleiotropic benefits. Circulation 2005, 112:300–303.

    Article  PubMed  Google Scholar 

  44. Fukuta H, Sane DC, 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.

    Article  PubMed  CAS  Google Scholar 

  45. Fraser H, Belardinelli L, Wang L, et al.: Ranolazine decreases diastolic calcium accumulation caused by ATX-II or ischemia in rat hearts. J Mol Cell Cardiol 2006, 41:1031–1038.

    Article  PubMed  CAS  Google Scholar 

  46. Zile M, Gaasch W, Little W, et al.: A phase II, double-blind, randomized, placebo-controlled, dose comparative study of the efficacy, tolerability, and safety of MCC-135 in subjects with chronic heart failure, NYHA class II/III (MCC-135-GO1 study): rationale and design. J Card Fail 2004, 10:193–199.

    Article  PubMed  CAS  Google Scholar 

  47. Kass DA, Shapiro EP, Kawaguchi M, et al.: Improved arterial compliance by a novel advanced glycation end-product crosslink breaker. Circulation 2001, 104:1464–1470.

    Article  PubMed  CAS  Google Scholar 

  48. McMurray JJ, Carson PE, Komajda M, et al.: Heart failure with preserved ejection fraction: clinical characteristics of 4133 patients enrolled in the I-PRESERVE trial. Eur J Heart Fail 2008, 10:149–156.

    Article  PubMed  Google Scholar 

  49. ClinicalTrials.gov website. Available at www.clinicaltrials.gov. Accessed June 4, 2008.

  50. Hori M, Kitabatake A, Tsutsui H, et al.: Rationale and design of a randomized trial to assess the effects of betablocker in diastolic heart failure; Japanese Diastolic Heart Failure Study (J-DHF). J Card Fail 2005, 11:542–547.

    Article  PubMed  CAS  Google Scholar 

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  1. Michael E. DeBakey VA Medical Center (111B), 2002 Holcombe Boulevard, Houston, TX, 77030, USA

    Biykem Bozkurt

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  1. Anita Deswal
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Correspondence to Biykem Bozkurt.

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Deswal, A., Bozkurt, B. Treatment of patients with heart failure and preserved ejection fraction. Curr Treat Options Cardio Med 10, 516–528 (2008). https://doi.org/10.1007/s11936-008-0044-7

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