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Update on Heart Failure with Preserved Ejection Fraction

  • Elderly and Heart Disease (J Wei and G Azhar, Section Editors)
  • Published:
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Abstract

Heart failure with preserved ejection fraction (HFPEF) is the most common form of heart failure (HF) in older adults, and is increasing in prevalence as the population ages. Morbidity and long-term mortality in HFPEF are substantial and can be similar to HF with reduced ejection fraction (HFREF), yet HFPEF therapy remains empirical and treatment guidelines are based primarily on expert consensus. Neurohormonal blockade has revolutionized the management of HFREF, but trials in HFPEF based on this strategy have been disappointing to date. However, many recent studies have increased knowledge about HFPEF. The concept of HFPEF has evolved from a ‘cardio-centric’ model to a syndrome that may involve multiple cardiovascular and non-cardiovascular mechanisms. Emerging data highlight the importance of non-pharmacological management strategies and assessment of non-cardiovascular comorbidities. Animal models, epidemiological cohorts, and small human studies suggest that oxidative stress and inflammation contribute to HFPEF, potentially leading to development of new therapeutic targets.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, et al. Heart disease and stroke statistics—2013 update: a report from the American Heart Association. Circulation. 2013;127(1):e6–e245. doi:10.1161/CIR.0b013e31828124ad.

    Article  PubMed  Google Scholar 

  2. •• Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction.[see comment]. N Engl J Med. 2006;355(3):251–9. This report showed that, in contrast to HFREF which is decreasing, the prevalence of HFPEF is increasing and outcomes are worsening.

    Article  PubMed  CAS  Google Scholar 

  3. Tribouilloy C, Rusinaru D, Mahjoub H, Souliere V, Levy F, Peltier M, et al. Prognosis of heart failure with preserved ejection fraction: a 5 year prospective population-based study. Eur Heart J. 2008;29(3):339–47. doi:10.1093/eurheartj/ehm554.

    Article  PubMed  Google Scholar 

  4. Fonarow GC, Stough WG, Abraham WT, Albert NM, Gheorghiade M, Greenberg BH, et al. Characteristics, treatments, and outcomes of patients with preserved systolic function hospitalized for heart failure: a report from the OPTIMIZE-HF Registry. J Am Coll Cardiol. 2007;50(8):768–77.

    Article  PubMed  Google Scholar 

  5. Lam CSP, Lyass A, Kraigher-Krainer E, Massaro JM, Lee DS, Ho JE, et al. Cardiac dysfunction and noncardiac dysfunction as precursors of heart failure with reduced and preserved ejection fraction in the community / clinical perspective. Circulation. 2011;124(1):24–30. doi:10.1161/circulationaha.110.979203.

    Article  PubMed  CAS  Google Scholar 

  6. Mohammed SF, Borlaug BA, Roger VL, Mirzoyev SA, Rodeheffer RJ, Chirinos JA, et al. Comorbidity and ventricular and vascular structure and function in heart failure with preserved ejection fraction: a community-based study. Circ Heart Fail. 2012;5(6):710–9. doi:10.1161/circheartfailure.112.968594.

    Article  PubMed  Google Scholar 

  7. Hummel SL, DeFranco AC, Skorcz S, Montoye CK, Koelling TM. Recommendation of low-salt diet and short-term outcomes in heart failure with preserved systolic function. Am J Med. 2009;122(11):1029–36.

    Article  PubMed  Google Scholar 

  8. Yancy CW, Lopatin M, Stevenson LW, De Marco T, Fonarow GC. Adhere Scientific Advisory Committee and I. Clinical presentation, management, and in-hospital outcomes of patients admitted with acute decompensated heart failure with preserved systolic function: a report from the Acute Decompensated Heart Failure National Registry (ADHERE) Database.erratum appears in J Am Coll Cardiol. 2006 Apr 7;47(7):1502. J Am Coll Cardiol. 2006;47(1):76–84.

    Article  PubMed  Google Scholar 

  9. Packer M. Can brain natriuretic peptide be used to guide the management of patients with heart failure and a preserved ejection fraction? The wrong way to identify new treatments for a nonexistent disease. Circ Heart Fail. 2011;4(5):538–40. doi:10.1161/circheartfailure.111.963710.

    Article  PubMed  Google Scholar 

  10. Campbell RT, Jhund PS, Castagno D, Hawkins NM, Petrie MC, McMurray JJV. What have we learned about patients with heart failure and preserved ejection fraction from DIG-PEF, CHARM-Preserved, and I-PRESERVE? J Am Coll Cardiol. 2012;60(23):2349–56. doi:10.1016/j.jacc.2012.04.064.

    Article  PubMed  Google Scholar 

  11. • Ather S, Chan W, Bozkurt B, Aguilar D, Ramasubbu K, Zachariah AA, et al. Impact of noncardiac comorbidities on morbidity and mortality in a predominantly male population with heart failure and preserved versus reduced ejection fraction. J Am Coll Cardiol. 2012;59(11):998–1005. doi:10.1016/j.jacc.2011.11.040. This report showed that non-cardiac comorbidties are very common in HFPEF and drive a majority of the adverse outcomes.

  12. Chan MMY, Lam CSP. How do patients with heart failure with preserved ejection fraction die? Eur J Heart Fail. 2013;15(6):604–13. doi:10.1093/eurjhf/hft062.

    Article  PubMed  Google Scholar 

  13. Yancy CW, Jessup M, Bozkurt B, Masoudi FA, Butler J, McBride PE et al. 2013 ACCF/AHA Guideline for the Management of Heart FailureA Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013. doi:10.1016/j.jacc.2013.05.019.

  14. McMurray JJV, Adamopoulos S, Anker SD, Auricchio A, Böhm M, Dickstein K et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012. Eur Heart J. 2012;8:803–69.

    Google Scholar 

  15. Lindenfeld J, Albert N, Boehmer J, Collins S, Ezekowitz J, Givertz M, et al. HFSA 2010 comprehensive heart failure practice guideline. J Card Fail. 2010;16(6):e1–194.

    Article  PubMed  Google Scholar 

  16. Kitzman DW, Higginbotham MB, Cobb FR, Sheikh KH, Sullivan MJ. Exercise intolerance in patients with heart failure and preserved left ventricular systolic function: failure of the Frank-Starling mechanism.[see comment]. J Am Coll Cardiol. 1991;17(5):1065–72.

    Article  PubMed  CAS  Google Scholar 

  17. 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(19):1953–9.

    Article  PubMed  CAS  Google Scholar 

  18. Lam CSP, Roger VL, Rodeheffer RJ, Bursi F, Borlaug BA, Ommen SR, et al. Cardiac structure and ventricular-vascular function in persons with heart failure and preserved ejection fraction from Olmsted County. Minnesota Circulation. 2007;115(15):1982–90.

    Article  Google Scholar 

  19. AlJaroudi W, Alraies MC, Halley C, Rodriguez L, Grimm RA, Thomas JD, et al. Impact of progression of diastolic dysfunction on mortality in patients with normal ejection fraction / clinical perspective. Circulation. 2012;125(6):782–8. doi:10.1161/circulationaha.111.066423.

    Article  PubMed  Google Scholar 

  20. Persson H, Lonn E, Edner M, Baruch L, Lang CC, Morton JJ, et al. Diastolic dysfunction in heart failure with preserved systolic function: need for objective evidence:results from the CHARM Echocardiographic Substudy-CHARMES. J Am Coll Cardiol. 2007;49(6):687–94.

    Article  PubMed  Google Scholar 

  21. Westermann D, Kasner M, Steendijk P, Spillmann F, Riad A, Weitmann K, et al. Role of left ventricular stiffness in heart failure with normal ejection fraction. Circulation. 2008;117(16):2051–60. doi:10.1161/circulationaha.107.716886.

    Article  PubMed  Google Scholar 

  22. Borlaug BA, Jaber WA, Ommen SR, Lam CSP, Redfield MM, Nishimura RA. Diastolic relaxation and compliance reserve during dynamic exercise in heart failure with preserved ejection fraction. Heart. 2011;97(12):964–9. doi:10.1136/hrt.2010.212787.

    Article  PubMed  Google Scholar 

  23. Kawaguchi M, Hay I, Fetics B, Kass DA. 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(5):714–20.

    Article  PubMed  Google Scholar 

  24. • Hundley WG, Kitzman DW, Morgan TM, Hamilton CA, Darty SN, Stewart KP, et al. Cardiac cycle-dependent changes in aortic area and distensibility are reduced in older patients with isolated diastolic heart failure and correlate with exercise intolerance. J Am Coll Cardiol. 2001;38(3):796–802. This was the first report of increased vascular stiffness and its contribution to exercise intolerance in HFPEF.

    Article  PubMed  CAS  Google Scholar 

  25. Kitzman DW, Herrington DM, Brubaker PH, Moore JB, Eggebeen J, Haykowsky MJ. Carotid arterial stiffness and its relationship to exercise intolerance in older patients with heart failure and preserved ejection fraction. Hypertension. 2013;61(1):112–9. doi:10.1161/hypertensionaha.111.00163.

    Article  PubMed  CAS  Google Scholar 

  26. Borlaug BA, Lam CSP, Roger VL, Rodeheffer RJ, Redfield MM. Contractility and ventricular systolic stiffening in hypertensive heart disease: insights into the pathogenesis of heart failure with preserved ejection fraction. J Am Coll Cardiol. 2009;54(5):410–8. doi:10.1016/j.jacc.2009.05.013.

    Article  PubMed  Google Scholar 

  27. Zhong L. Attenuation of stress-based ventricular contractility in patients with heart failure and normal ejection fraction. Ann Acad Med Singapore. 2011;40(4):179–85.

    PubMed  Google Scholar 

  28. Tartière-Kesri L, Tartière J-M, Logeart D, Beauvais F, Cohen SA. Increased proximal arterial stiffness and cardiac response with moderate exercise in patients with heart failure and preserved ejection fraction. J Am Coll Cardiol. 2012;59(5):455–61. doi:10.1016/j.jacc.2011.10.873.

    Article  PubMed  Google Scholar 

  29. Borlaug BA, Olson TP, Lam CSP, Flood KS, Lerman A, Johnson BD, et al. Global cardiovascular reserve dysfunction in heart failure with preserved ejection fraction. J Am Coll Cardiol. 2010;56(11):845–54.

    Article  PubMed  Google Scholar 

  30. Hundley WG, Bayram E, Hamilton CA, Hamilton EA, Morgan TM, Darty SN, et al. Leg flow-mediated arterial dilation in elderly patients with heart failure and normal left ventricular ejection fraction. Am J Physiol Heart Circ Physiol. 2007;292(3):H1427–34. doi:10.1152/ajpheart.00567.2006.

    Article  PubMed  CAS  Google Scholar 

  31. Haykowsky MJ, Herrington DM, Brubaker PH, Morgan TM, Hundley WG, Kitzman DW. Relationship of flow-mediated arterial dilation and exercise capacity in older patients with heart failure and preserved ejection fraction. J Gerontol A Biol Sci Med Sci. 2013;68(2):161–7. doi:10.1093/gerona/gls099.

    Article  PubMed  Google Scholar 

  32. Maurer MS, Burkhoff D, Fried LP, Gottdiener J, King DL, Kitzman DW. Ventricular structure and function in hypertensive participants with heart failure and a normal ejection fraction: The Cardiovascular Health Study. J Am Coll Cardiol. 2007;49(9):972–81.

    Article  PubMed  Google Scholar 

  33. Noumi B, Teruya S, Salomon S, Helmke S, Maurer MS. Blood volume measurements in patients with heart failure and a preserved ejection fraction: implications for diagnosing anemia. Congest Heart Fail. 2011;17(1):14–8. doi:10.1111/j.1751-7133.2010.00208.x.

    Article  PubMed  Google Scholar 

  34. McKie PM, Schirger JA, Costello-Boerrigter LC, Benike SL, Harstad LK, Bailey KR, et al. Impaired natriuretic and renal endocrine response to acute volume expansion in pre-clinical systolic and diastolic dysfunction. J Am Coll Cardiol. 2011;58(20):2095–103. doi:10.1016/j.jacc.2011.07.042.

    Article  PubMed  CAS  Google Scholar 

  35. Colombo PC, Ganda A, Lin J, Onat D, Harxhi A, Iyasere JE, et al. Inflammatory activation: cardiac, renal, and cardio-renal interactions in patients with the cardiorenal syndrome. Heart Fail Rev. 2012;17(2):177–90. doi:10.1007/s10741-011-9261-3.

    Article  PubMed  CAS  Google Scholar 

  36. Brubaker PH, Joo KC, Stewart KP, Fray B, Moore B, Kitzman DW. Chronotropic incompetence and its contribution to exercise intolerance in older heart failure patients. J Cardiopulm Rehabil. 2006;26(2):86–9.

    Article  PubMed  Google Scholar 

  37. Brubaker PH, Kitzman DW. Chronotropic incompetence: causes, consequences, and management. Circulation. 2011;123(9):1010–20. doi:10.1161/circulationaha.110.940577.

    Article  PubMed  Google Scholar 

  38. Kurt M, Wang J, Torre-Amione G, Nagueh SF. Left atrial function in diastolic heart failure. Circ Cardiovasc Imag. 2009;2(1):10–5. doi:10.1161/circimaging.108.813071.

    Article  Google Scholar 

  39. Obokata M, Negishi K, Kurosawa K, Arima H, Tateno R, Ui G, et al. Incremental diagnostic value of LA strain with leg lifts in heart failure with preserved ejection fraction. JACC Cardiovasc Imaging. 2013;6(7):749–58. doi:10.1016/j.jcmg.2013.04.006.

    Article  PubMed  Google Scholar 

  40. Chaudhry SI, McAvay G, Chen S, Whitson H, Newman AB, Krumholz HM, et al. Risk factors for hospital admission among older persons with newly diagnosed heart failure: findings from the Cardiovascular Health Study. J Am Coll Cardiol. 2013;61(6):635–42. doi:10.1016/j.jacc.2012.11.027.

    Article  PubMed  Google Scholar 

  41. Duscha BD, Annex BH, Green HJ, Pippen AM, Kraus WE. Deconditioning fails to explain peripheral skeletal muscle alterations in men with chronic heart failure. J Am Coll Cardiol. 2002;39(7):1170–4.

    Article  PubMed  Google Scholar 

  42. Simonini A, Long CS, Dudley GA, Yue P, McElhinny J, Massie BM. Heart failure in rats causes changes in skeletal muscle morphology and gene expression that are not explained by reduced activity. Circ Res. 1996;79(1):128–36.

    Article  PubMed  CAS  Google Scholar 

  43. Edelmann F, Gelbrich G, Düngen H-D, Fröhling S, Wachter R, Stahrenberg R, et al. Exercise training improves exercise capacity and diastolic function in patients with heart failure with preserved ejection fraction: results of the Ex-DHF (Exercise training in Diastolic Heart Failure) Pilot Study. J Am Coll Cardiol. 2011;58(17):1780–91. doi:10.1016/j.jacc.2011.06.054.

    Article  PubMed  Google Scholar 

  44. Kitzman D, Brubaker P, Morgan T, Stewart K, Little W. Exercise training in older patients with heart failure and preserved ejection fraction: a randomized, controlled. Single-Blind Trial Circ Heart Fail. 2010;3(6):659–67.

    Article  Google Scholar 

  45. Kitzman DW, Brubaker PH, Herrington DM, Morgan TM, Stewart KP, Hundley WG et al. Effect of endurance exercise training on endothelial function and arterial stiffness in older patients with heart failure and preserved ejection fraction: a randomized, controlled, single-blind trial. J Am Coll Cardiol. 2013. doi:10.1016/j.jacc.2013.04.033.

  46. Fujimoto N, Prasad A, Hastings JL, Bhella PS, Shibata S, Palmer D, et al. Cardiovascular effects of 1 year of progressive endurance exercise training in patients with heart failure with preserved ejection fraction. Am Heart J. 2012;164(6):869–77. doi:10.1016/j.ahj.2012.06.028.

    Article  PubMed  Google Scholar 

  47. •• Haykowsky MJ, Brubaker PH, Stewart KP, Morgan TM, Eggebeen J, Kitzman DW. Effect of endurance training on the determinants of peak exercise oxygen consumption in elderly patients with stable compensated heart failure and preserved ejection fraction. J Am Coll Cardiol. 2012;60(2):120–8. doi:10.1016/j.jacc.2012.02.055. This group first showed that peripheral factors accounted for about 50% of the reduction in peak exercise VO2 in HFPEF compared to normals. In this report, they showed that peripheral factors accounted for nearly 100% of the improvement in peak VO2 with exercise training.

  48. Haykowsky MJ, Brubaker PH, Morgan TM, Kritchevsky S, Eggebeen J, Kitzman DW. Impaired aerobic capacity and physical functional performance in older heart failure patients with preserved ejection fraction: role of lean body mass. J Gerontol A Biol Sci Med Sci. 2013;68(8):968–75. doi:10.1093/gerona/glt011.

    Article  PubMed  CAS  Google Scholar 

  49. Gottdiener JS, Arnold AM, Aurigemma GP, Polak JF, Tracy RP, Kitzman DW, et al. Predictors of congestive heart failure in the elderly: the Cardiovascular Health Study. J Am Coll Cardiol. 2000;35(6):1628–37.

    Article  PubMed  CAS  Google Scholar 

  50. Kalogeropoulos A, Georgiopoulou V, Psaty BM, Rodondi N, Smith AL, Harrison DG, et al. Inflammatory markers and incident heart failure risk in older adults: The health ABC (Health, Aging, and Body Composition) study. J Am Coll Cardiol. 2010;55(19):2129–37.

    Article  PubMed  CAS  Google Scholar 

  51. Rickard A, Morgan J, Tesch G, Funder J, Fuller P, Young M. Deletion of mineralocorticoid receptors from macrophages protects against deoxycorticosterone/salt-induced cardiac fibrosis and increased blood pressure. Hypertension. 2009;54(3):537–43.

    Article  PubMed  CAS  Google Scholar 

  52. Klotz S, Hay I, Zhang G, Maurer M, Wang J, Burkhoff D. Development of heart failure in chronic hypertensive Dahl rats: focus on heart failure with preserved ejection fraction.see comment. Hypertension. 2006;47(5):901–11.

    Article  PubMed  CAS  Google Scholar 

  53. Matsui H, Ando K, Kawarazaki H, Nagae A, Fujita M, Shimosawa T, et al. Salt excess causes left ventricular diastolic dysfunction in rats with metabolic disorder. Hypertension. 2008;52(2):287–94.

    Article  PubMed  CAS  Google Scholar 

  54. Munagala VK, Hart CY, Burnett Jr JC, Meyer DM, Redfield MM. Ventricular structure and function in aged dogs with renal hypertension: a model of experimental diastolic heart failure. Circulation. 2005;111(9):1128–35.

    Article  PubMed  Google Scholar 

  55. Tian N, Moore RS, Phillips WE, Lin L, Braddy S, Pryor JS, et al. NADPH oxidase contributes to renal damage and dysfunction in Dahl salt-sensitive hypertension. Am J Physiol Regul Integr Comp Physiol. 2008;295(6):R1858–65. doi:10.1152/ajpregu.90650.2008.

    Article  PubMed  CAS  Google Scholar 

  56. Usher MG, Duan SZ, Ivaschenko CY, Frieler RA, Berger S, Schütz G, et al. Myeloid mineralocorticoid receptor controls macrophage polarization and cardiovascular hypertrophy and remodeling in mice. J Clin Invest. 2010;120(9):3350–64.

    Article  PubMed  CAS  Google Scholar 

  57. Bayorh MA, Mann G, Walton M, Eatman D. Effects of enalapril, tempol, and eplerenone on salt-induced hypertension in Dahl Salt-Sensitive Rats. Clin Exp Hypertens. 2006;28(2):121–32.

    Article  PubMed  CAS  Google Scholar 

  58. Vanegas V, Ferrebuz A, Quiroz Y, Rodriguez-Iturbe B. Hypertension in Page (cellophane-wrapped) kidney is due to interstitial nephritis. Kidney Int. 2005;68(3):1161–70.

    Article  PubMed  Google Scholar 

  59. Westermann D, Lindner D, Kasner M, Zietsch C, Savvatis K, Escher F, et al. Cardiac inflammation contributes to changes in the extracellular matrix in patients with heart failure and normal ejection fraction / clinical perspective. Circ Heart Fail. 2011;4(1):44–52. doi:10.1161/circheartfailure.109.931451.

    Article  PubMed  Google Scholar 

  60. Tamaki S, Mano T, Sakata Y, Ohtani T, Takeda Y, Kamimura D, et al. Interleukin-16 promotes cardiac fibrosis and myocardial stiffening in heart failure with preserved ejection fraction. PLoS ONE. 2013;8(7):e68893. doi:10.1371/journal.pone.0068893.

    Article  PubMed  CAS  Google Scholar 

  61. Brinkley TE, Leng X, Miller ME, Kitzman DW, Pahor M, Berry MJ, et al. Chronic inflammation is associated with low physical function in older adults across multiple comorbidities. J Gerontol A Biol Sci Med Sci. 2009;64(4):455–61. doi:10.1093/gerona/gln038.

    Article  PubMed  Google Scholar 

  62. van Heerebeek L, Hamdani N, Falcao-Pires I, Leite-Moreira AF, Begieneman MP, Bronzwaer JG, et al. Low myocardial protein kinase g activity in heart failure with preserved ejection fraction. Circulation. 2012;126(7):830–9. doi:10.1161/circulationaha.111.076075.

    Article  PubMed  Google Scholar 

  63. Paulus WJ, Tschöpe C. A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. J Am Coll Cardiol. 2013;62(4):263–71. doi:10.1016/j.jacc.2013.02.092.

    Article  PubMed  Google Scholar 

  64. • Bhella PS, Prasad A, Heinicke K, Hastings JL, Arbab-Zadeh A, Adams-Huet B, et al. Abnormal haemodynamic response to exercise in heart failure with preserved ejection fraction. Eur J Heart Fail. 2011;13(12):1296–304. doi:10.1093/eurjhf/hfr133. First report of skeletal muscle abnormalities in HFPEF.

    Google Scholar 

  65. Yusuf S, Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, et al. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial.[see comment]. Lancet. 2003;362(9386):777–81.

    Article  PubMed  CAS  Google Scholar 

  66. Massie BM, Carson PE, McMurray JJ, Komajda M, McKelvie R, Zile MR, et al. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med. 2008;359(23):2456–67.

    Article  PubMed  CAS  Google Scholar 

  67. Cleland JG, Tendera M, Adamus J, Freemantle N, Polonski L, Taylor J, et al. The perindopril in elderly people with chronic heart failure (PEP-CHF) study.see comment. Eur Heart J. 2006;27(19):2338–45.

    Article  PubMed  CAS  Google Scholar 

  68. Groban L, Pailes NA, Bennett CD, Carter CS, Chappell MC, Kitzman DW, et al. Growth hormone replacement attenuates diastolic dysfunction and cardiac angiotensin II expression in senescent rats. J Gerontol A Biol Sci Med Sci. 2006;61(1):28–35.

    Article  PubMed  Google Scholar 

  69. Groban L, Yamaleyeva LM, Westwood BM, Houle TT, Lin M, Kitzman DW, et al. Progressive diastolic dysfunction in the female mRen(2). Lewis rat: influence of salt and ovarian hormones. J Gerontol A Biol Sci Med Sci. 2008;63(1):3–11.

    Article  PubMed  Google Scholar 

  70. Warner Jr JG, Metzger DC, Kitzman DW, Wesley DJ, Little WC. Losartan improves exercise tolerance in patients with diastolic dysfunction and a hypertensive response to exercise. J Am Coll Cardiol. 1999;33(6):1567–72. doi:10.1016/S0735-1097(99)00048-0.

    Article  PubMed  CAS  Google Scholar 

  71. Little WC, Wesley-Farrington DJ, Hoyle J, Brucks S, Robertson S, Kitzman DW, et al. Effect of candesartan and verapamil on exercise tolerance in diastolic dysfunction. J Cardiovasc Pharmacol. 2004;43(2):288–93.

    Article  PubMed  CAS  Google Scholar 

  72. Kitzman DW, Hundley WG, Brubaker PH, Morgan TM, Moore JB, Stewart KP, et al. A randomized double-blind trial of enalapril in older patients with heart failure and preserved ejection fraction: effects on exercise tolerance and arterial distensibility. Circ Heart Fail. 2010;3(4):477–85. doi:10.1161/circheartfailure.109.898916.

    Article  PubMed  Google Scholar 

  73. Lund LH, Benson L, Dahlström U, Edner M. Association between use of renin-angiotensin system antagonists and mortality in patients with heart failure and preserved ejection fraction. JAMA. 2012;308(20):2108–17. doi:10.1001/jama.2012.14785.

    Article  PubMed  CAS  Google Scholar 

  74. Solomon SD, Zile M, Pieske B, Voors A, Shah A, Kraigher-Krainer E et al. The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomised controlled trial. Lancet. 2013;380(9851):1387–95. doi:10.1016/S0140-6736(12)61227-6.

    Google Scholar 

  75. Deswal A, Richardson P, Bozkurt B, Mann DL. Results of the Randomized Aldosterone Antagonism in Heart Failure With Preserved Ejection Fraction Trial (RAAM-PEF). J Card Fail. 2011;17(8):634–42. doi:10.1016/j.cardfail.2011.04.007.

    Article  PubMed  Google Scholar 

  76. • Edelmann F, Wachter R, Schmidt AG, et al. Effect of spironolactone on diastolic function and exercise capacity in patients with heart failure with preserved ejection fraction: the ALDO-DHFrandomized controlled trial. JAMA. 2013;309(8):781–91. doi:10.1001/jama.2013.905. The randomized trial of aldosterone antagonism in HFPEF.

  77. Patel K, Fonarow GC, Kitzman DW, Aban IB, Love TE, Allman RM, et al. Aldosterone antagonists and outcomes in real-world older patients with heart failure and preserved ejection fraction. JACC: Heart Failure. 2013;1(1):40–7. doi:10.1016/j.jchf.2012.08.001.

    Article  PubMed  Google Scholar 

  78. Shah SJ, Heitner JF, Sweitzer NK, Anand IS, Kim H-Y, Harty B, et al. Baseline Characteristics of Patients in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) Trial. Circ Heart Fail. 2012. doi:10.1161/circheartfailure.112.972794.

    Google Scholar 

  79. Lam CSP, Roger VL, Rodeheffer RJ, Borlaug BA, Enders FT, Redfield MM. Pulmonary hypertension in heart failure with preserved ejection fraction: a community-based study. J Am Coll Cardiol. 2009;53(13):1119–26.

    Article  PubMed  Google Scholar 

  80. Guazzi M, Vicenzi M, Arena R, Guazzi MD. Pulmonary hypertension in heart failure with preserved ejection fraction: a target of phosphodiesterase-5 inhibition in a 1-year study. Circulation. 2011;124(2):164–74. doi:10.1161/circulationaha.110.983866.

    Article  PubMed  CAS  Google Scholar 

  81. Redfield MM, Chen HH. Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: A randomized clinical trial. JAMA. 2013;309(12):1268–77. doi:10.1001/jama.2013.2024.

    Article  PubMed  CAS  Google Scholar 

  82. Kosmala W, Holland DJ, Rojek A, Wright L, Przewlocka-Kosmala M, Marwick TH. Effect of If-channel inhibition on hemodynamics and exercise tolerance in heart failure with preserved ejection fraction: a randomized trial. J Am Coll Cardiol. 2013. doi:10.1016/j.jacc.2013.06.043.

    PubMed  Google Scholar 

  83. Maurer MS, Teruya S, Chakraborty B, Helmke S, Mancini D. Treating anemia in older adults with heart failure with a preserved ejection fraction with epoetin alfa: single-blind randomized clinical trial of safety and efficacy. Circ Heart Fail. 2013;6(2):254–63. doi:10.1161/circheartfailure.112.969717.

    Article  PubMed  Google Scholar 

  84. Jacobshagen C, Belardinelli L, Hasenfuss G, Maier LS. Ranolazine for the treatment of heart failure with preserved ejection fraction: background, aims, and design of the RALI-DHF study. Clin Cardiol. 2011;34(7):426–32. doi:10.1002/clc.20897.

    Article  PubMed  Google Scholar 

  85. Teerlink JR, Cotter G, Davison BA, Felker GM, Filippatos G, Greenberg BH, et al. Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial. Lancet. 2013;381(9860):29–39. doi:10.1016/s0140-6736(12)61855-8.

    Article  PubMed  CAS  Google Scholar 

  86. Smart N, Haluska B, Jeffriess L, Marwick TH. Exercise training in systolic and diastolic dysfunction: effects on cardiac function, functional capacity, and quality of life. Am Heart J. 2007;153(4):530–6. doi:10.1016/j.ahj.2007.01.004.

    Article  PubMed  Google Scholar 

  87. Mudge AM, Denaro CP, Scott AC, Atherton JJ, Meyers DE, Marwick TH, et al. Exercise training in recently hospitalized heart failure patients enrolled in a disease management programme: design of the EJECTION-HF randomized controlled trial. Eur J Heart Fail. 2011;13(12):1370–5. doi:10.1093/eurjhf/hfr139.

    Article  PubMed  Google Scholar 

  88. Al-Solaiman Y, Jesri A, Zhao Y, Morrow JD, Egan BM. Low-sodium DASH reduces oxidative stress and improves vascular function in salt-sensitive humans. J Hum Hypertens. 2009;12:826–35.

    Google Scholar 

  89. Levitan EB, Wolk A, Mittleman MA. Consistency with the DASH diet and incidence of heart failure. Arch Intern Med. 2009;169(9):851–7. doi:10.1001/archinternmed.2009.56.

    Article  PubMed  CAS  Google Scholar 

  90. Hummel SL, Seymour EM, Brook RD, Kolias TJ, Sheth SS, Rosenblum HR, et al. Low-sodium dietary approaches to stop hypertension diet reduces blood pressure, arterial stiffness, and oxidative stress in hypertensive heart failure with preserved ejection fraction / novelty and significance. Hypertension. 2012;60(5):1200–6. doi:10.1161/hypertensionaha.112.202705.

    Article  PubMed  CAS  Google Scholar 

  91. Hummel SL, Seymour EM, Brook RD, Sheth SS, Ghosh E, Zhu S et al. Low-Sodium DASH Diet Improves Diastolic Function and Ventricular-Arterial Coupling in Hypertensive Heart Failure with Preserved Ejection Fraction. Circ Heart Fail. 2013;(accepted for publication August 16, 2013).

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Scott L. Hummel and Dalane W. Kitzman declare that they have no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Department of Internal Medicine, Section of Cardiovascular Medicine, University of Michigan School of Medicine, Ann Arbor, USA

    Scott L. Hummel

  2. Ann Arbor Veterans Affairs Health System, Ann Arbor, MI, USA

    Scott L. Hummel

  3. Department of Internal Medicine, Section on Cardiology, Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC, USA

    Dalane W. Kitzman

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  1. Scott L. Hummel
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  2. Dalane W. Kitzman
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Correspondence to Dalane W. Kitzman.

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Supported in part by: NIH grant R3718915, NIH grant K23HL109176

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Hummel, S.L., Kitzman, D.W. Update on Heart Failure with Preserved Ejection Fraction. Curr Cardiovasc Risk Rep 7, 495–502 (2013). https://doi.org/10.1007/s12170-013-0350-9

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