Heart Failure with Preserved Ejection Fraction: Current Management and Future Strategies

  • Enrico Agabiti RoseiEmail author
  • Damiano Rizzoni
Part of the Updates in Hypertension and Cardiovascular Protection book series (UHCP)


Hypertension (HTN) represents the most important attributable risk factor for heart failure (HF). The measurement of left ventricular (LV) ejection fraction (EF) is the basis for the description of HF in different patients, from those with normal EF (above 50% HF with preserved EF (HFpEF)) to those with reduced EF (below 40%, HF with reduced EF (HFrEF)) [1]. Recent ESC guidelines have identified patients with an LVEF in the range 40–49%, defined as HFmrEF, which in different studies have been considered in the group with HFpEF [2]. HFpEF accounts for about 50% of HF cases, but its prevalence relative to HFrEF continues to rise. HFpEF carries similar risk of morbidity/mortality as HFrEF. Patients with HFpEF are frequently old women with HTN, usually also with diabetes and obesity, characterized by concentric LV hypertrophy (LVH), increased left atrial (LA) size, diastolic dysfunction, pulmonary hypertension, and elevated levels of natriuretic peptides.


  1. 1.
    Agabiti-Rosei E, Muiesan ML, Schmieder RE. Cardiac damage and progression to heart failure. In: Mancia G, Grassi G, Redon J, editors. Manual of hypertension of the European Society of Hypertension. London: Informa Healthcare; 2014. p. 159–75.CrossRefGoogle Scholar
  2. 2.
    Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, González-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P, Authors/Task Force Members. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Eur Heart J. 2016;37:2129–200.CrossRefGoogle Scholar
  3. 3.
    Rosei EA, Mancia G, editors. Assessment of preclinical organ damage in hypertension. Cham: Springer International; 2015. p. 3–37.CrossRefGoogle Scholar
  4. 4.
    Perrone-Filardi P, Coca A, Galderisi M, Paolillo S, Alpendurada F, de Simone G, Donal E, Kahan T, Mancia G, Redon J, Schmieder R, Williams B, Agabiti-Rosei E. Non-invasive cardiovascular imaging for evaluating subclinical target organ damage in hypertensive patients: a consensus paper from the European Association of Cardiovascular Imaging (EACVI), the European Society of Cardiology Council on hypertension, and the European Society of Hypertension (ESH). Eur Heart J Cardiovasc Imaging. 2017;18:945–60.CrossRefGoogle Scholar
  5. 5.
    Tschöpe C, Birner C, Böhm M, Bruder O, Frantz S, Luchner A, Maier L, Störk S, Kherad B, Laufs U. Heart failure with preserved ejection fraction: current management and future strategies: expert opinion on the behalf of the nucleus of the “Heart Failure Working Group” of the German Society of Cardiology (DKG). Clin Res Cardiol. 2018;107:1–19.CrossRefGoogle Scholar
  6. 6.
    Yip GW, Wang M, Wang T, Chan S, Fung JW, Yeung L, Yip T, Lau ST, Lau CP, Tang MO, Yu CM, Sanderson JE. The Hong Kong diastolic heart failure study: a randomised controlled 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;94:573–80.CrossRefGoogle Scholar
  7. 7.
    Khan MS, Fonarow GC, Khan H, Greene SJ, Anker SD, Gheorghiade M, Butler J. Renin-angiotensin blockade in heart failure with preserved ejection fraction: a systematic review and meta-analysis. ESC Heart Fail. 2017;4:402–8.CrossRefGoogle Scholar
  8. 8.
    Butler J, Fonarow GC, Zile MR, Lam CS, Roessig L, Schelbert EB, Shah SJ, Ahmed A, Bonow RO, Cleland JG, Cody RJ, Chioncel O, Collins SP, Dunnmon P, Filippatos G, Lefkowitz MP, Marti CN, McMurray JJ, Misselwitz F, Nodari S, O’Connor C, Pfeffer MA, Pieske B, Pitt B, Rosano G, Sabbah HN, Senni M, Solomon SD, Stockbridge N, Teerlink JR, Georgiopoulou VV, Gheorghiade M. Developing therapies for heart failure with preserved ejection fraction: current state and future directions. JACC Heart Fail. 2014;2:97–112.CrossRefGoogle Scholar
  9. 9.
    Shah SJ, Kitzman DW, Borlaug BA, van Heerebeek L, Zile MR, Kass DA, Paulus WJ. Phenotype-specific treatment of heart failure with preserved ejection fraction: a multiorgan roadmap. Circulation. 2016;134:73–90.CrossRefGoogle Scholar
  10. 10.
    Zakeri R, Cowie MR. Heart failure with preserved ejection fraction: controversies, challenges and future directions. Heart. 2018;104(5):377–84. Scholar
  11. 11.
    van Veldhuisen DJ, Cohen-Solal A, Bohm M, Anker SD, Babalis D, Roughton M, Coats AJ, Poole-Wilson PA, Flather MD, SENIORS Investigators. Beta-blockade with nebivolol in elderly heart failure patients with impaired and preserved left ventricular ejection fraction: data from SENIORS (study of effects of nebivolol intervention on outcomes and rehospitalization in seniors with heart failure). J Am Coll Cardiol. 2009;53:2150–8.CrossRefGoogle Scholar
  12. 12.
    Maier LS, Layug B, Karwatowska-Prokopczuk E, Belardinelli L, Lee S, Sander J, Lang C, Wachter R, Edelmann F, Hasenfuss G, Jacobshagen C. RAnoLazIne for the treatment of diastolic heart failure in patients with preserved ejection fraction: the RALI-DHF proof-of-concept study. JACC Heart Fail. 2013;1:115–22.CrossRefGoogle Scholar
  13. 13.
    Fukuta H, Goto T, Wakami K, Ohte N. The effect of statins on mortality in heart failure with preserved ejection fraction: a meta-analysis of propensity score analyses. Int J Cardiol. 2016;214:301–6.CrossRefGoogle Scholar
  14. 14.
    American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Writing Committee Members, Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, PE MB, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines. Circulation. 2013;128:e240–327.Google Scholar
  15. 15.
    Edelmann F, Gelbrich G, Dungen HD, Frohling S, Wachter R, Stahrenberg R, Binder L, Topper A, Lashki DJ, Schwarz S, Herrmann-Lingen C, Loffler M, Hasenfuss G, Halle M, Pieske B. 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. 2012;58:1780–91.CrossRefGoogle Scholar
  16. 16.
    Pandey A, Parashar A, Kumbhani DJ, Agarwal S, Garg J, Kitzman D, Levine BD, Drazner M, Berry JD. Exercise training in patients with heart failure and preserved ejection fraction: meta-analysis of randomized control trials. Circ Heart Fail. 2015;8:33–40.CrossRefGoogle Scholar
  17. 17.
    Hummel SL, Seymour EM, Brook RD, Sheth SS, Ghosh E, Zhu S, Weder AB, Kovacs SJ, Kolias TJ. Low-sodium DASH diet improves diastolic function and ventricular-arterial coupling in hypertensive heart failure with preserved ejection fraction. Circ Heart Fail. 2013;6:1165–71.CrossRefGoogle Scholar
  18. 18.
    Kitzman DW, Brubaker P, Morgan T, Haykowsky M, Hundley G, Kraus WE, Eggebeen J, Nicklas BJ. Effect of caloric restriction or aerobic exercise training on peak oxygen consumption and quality of life in obese older patients with heart failure with preserved ejection fraction: a randomized clinical trial. JAMA. 2016;315:36–46.CrossRefGoogle Scholar
  19. 19.
    Borlaug BA, Koepp KE, Melenovsky V. Sodium nitrite improves exercise hemodynamics and ventricular performance in heart failure with preserved ejection fraction. J Am Coll Cardiol. 2015;66:1672–82.CrossRefGoogle Scholar
  20. 20.
    Simon MA, Vanderpool RR, Nouraie M, Bachman TN, White PM, Sugahara M, Gorcsan J III, Parsley EL, Gladwin MT. Acute hemodynamic effects of inhaled sodium nitrite. in pulmonary hypertension associated with heart failure with preserved ejection fraction. JCI Insight. 2016;1(18):e89620.CrossRefGoogle Scholar
  21. 21.
    Eggebeen J, Kim-Shapiro DB, Haykowsky M, Morgan TM, Basu S, Brubaker P, Rejeski J, Kitzman DW. One week of daily dosing with beetroot juice improves submaximal endurance and blood pressure in older patients with heart failure and preserved ejection fraction. JACC Heart Fail. 2016;4(6):428–37.CrossRefGoogle Scholar
  22. 22.
    Redfield MM, Chen HH, Borlaug BA, Semigran MJ, Lee KL, Lewis G, LeWinter MM, Rouleau JL, Bull DA, Mann DL, Deswal A, Stevenson LW, Givertz MM, Ofili EO, O’Connor CM, Felker GM, Goldsmith SR, Bart BA, McNulty SE, Ibarra JC, Lin G, Oh JK, Patel MR, Kim RJ, Tracy RP, Velazquez EJ, Anstrom KJ, Hernandez AF, Mascette AM, Braunwald E, Trial R. Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial. JAMA. 2013;309:1268–77.CrossRefGoogle Scholar
  23. 23.
    Van Tassell BW, Arena R, Biondi-Zoccai G, McNair Canada J, Oddi C, Abouzaki NA, Jahangiri A, Falcao RA, Kontos MC, Shah KB, Voelkel NF, Dinarello CA, Abbate A. Effects of interleukin-1 blockade with anakinra on aerobic exercise capacity in patients with heart failure and preserved ejection fraction (from the D-HART pilot study). Am J Cardiol. 2014;113:321–7.CrossRefGoogle Scholar
  24. 24.
    van der Meer RW, Rijzewijk LJ, de Jong HW, Lamb HJ, Lubberink M, Romijn JA, Bax JJ, de Roos A, Kamp O, Paulus WJ, Heine RJ, Lammertsma AA, Smit JW, Diamant M. Pioglitazone improves cardiac function and alters myocardial substrate metabolism without affecting cardiac triglyceride accumulation and high-energy phosphate metabolism in patients with well-controlled type 2 diabetes mellitus. Circulation. 2009;119:2069–77.CrossRefGoogle Scholar
  25. 25.
    Scalzo RL, Moreau KL, Ozemek C, Herlache L, McMillin S, Gilligan S, Huebschmann AG, Bauer TA, Dorosz J, Reusch JE, Regensteiner JG. Exenatide improves diastolic function and attenuates arterial stiffness but does not alter exercise capacity in individuals with type 2 diabetes. J Diabetes Complications. 2017;31:449–55.CrossRefGoogle Scholar
  26. 26.
    Connelly KA, Bowskill BB, Advani SL, Thai K, Chen LH, Kabir MG, Gilbert RE, Advani A. Dipeptidyl peptidase-4 inhibition improves left ventricular function in chronic kidney disease. Clin Invest Med. 2014;37:E172.CrossRefGoogle Scholar
  27. 27.
    Dong S, Ma W, Hao B, Hu F, Yan L, Yan X, Wang Y, Chen Z, Wang Z. microRNA-21 promotes cardiac fibrosis and development of heart failure with preserved left ventricular ejection fraction by up-regulating Bcl-2. Int J Clin Exp Pathol. 2014;7:565–74.PubMedPubMedCentralGoogle Scholar
  28. 28.
    Nair N, Gupta S, Collier IX, Gongora E, Vijayaraghavan K. Can microRNAs emerge as biomarkers in distinguishing HFpEF versus HFrEF? Int J Cardiol. 2014;175:395–9.CrossRefGoogle Scholar
  29. 29.
    Sondergaard L, Reddy V, Kaye D, Malek F, Walton A, Mates M, Franzen O, Neuzil P, Ihlemann N, Gustafsson F. Transcatheter treatment of heart failure with preserved or mildly reduced ejection fraction using a novel interatrial implant to lower left atrial pressure. Eur J Heart Fail. 2014;16:796–801.CrossRefGoogle Scholar
  30. 30.
    Hasenfuss G, Hayward C, Burkhoff D, Silvestry FE, McKenzie S, Gustafsson F, Malek F, Van der Heyden J, Lang I, Petrie MC, Cleland JG, Leon M, Kaye DM, REDUCE LAP-HF Study Investigators. A transcatheter intracardiac shunt device for heart failure with preserved ejection fraction (REDUCE LAP-HF): a multicentre, open-label, single-arm, phase 1 trial. Lancet. 2016;387:1298–304.CrossRefGoogle Scholar
  31. 31.
    Abraham WT, Zile MR, Weaver FA, Butter C, Ducharme A, Halbach M, Klug D, Lovett EG, Muller-Ehmsen J, Schafer JE, Senni M, Swarup V, Wachter R, Little WC. Baroreflex activation therapy for the treatment of heart failure with a reduced ejection fraction. JACC Heart Fail. 2015;3:487–96.CrossRefGoogle Scholar
  32. 32.
    Patel HC, Rosen SD, Hayward C, Vassiliou V, Smith GC, Wage RR, Bailey J, Rajani R, Lindsay AC, Pennell DJ, Underwood SR, Prasad SK, Mohiaddin R, Gibbs JS, Lyon AR, Di Mario C. Renal denervation in heart failure with preserved ejection fraction (RDT-PEF): a randomized controlled trial. Eur J Heart Fail. 2016;18:703–12.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Clinica Medica, Department of Clinical and Experimental SciencesUniversity of BresciaBresciaItaly

Personalised recommendations