Approach to the Treatment of Heart Failure With Preserved Ejection Fraction and Mid- Range Ejection Fraction

Ewa A Jankowska, Andrew JS Coats, Stefan D Anker


In this article we discuss the treatment of heart failure (HF) with preserved ejection fraction (HFpEF) and of HF with mid-range ejection fraction (HFmrEF) as has received considerable interest since the publciation of the 2016 European Society of Cardiology (ESC) heart failure guidelines. Since clinical trials on HFpEF have included also patients with HFmrEF, due to the lack of an agreed definition, the ESC recommendations here described apply to both phenotypes. As a consequence of the recent characterisation of this HF syndrome, it is expected that upcoming research will provide data specifically regarding HFmrEF and tailored recommendations will be developed in the future.


heart failure, cardiology, guidelines, treatment, HFrEF, HFmrEF

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Ponikowski, P., A. A. Voors, S. D. Anker, H. Bueno, J. Cleland, A. Coats, V. Falk, J. R. Gonzalez-Juanatey, V. Harjola, E. Jankowska, M. Jessup, C. Linde, P. Nihoyannopoulos, J. T. Parissis, B. Pieske, J. Riley, G. M. C. Rosano, L. Ruilope, F. Ruschitzka, F. H. Rutten and P. van der Meer (2016). 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. European Heart Journal.

Maggioni, A. P., S. D. Anker, U. Dahlstrom, G. Filippatos, P. Ponikowski, F. Zannad, O. Amir, O. Chioncel, M. C. Leiro, J. Drozdz, A. Erglis, E. Fazlibegovic, C. Fonseca, F. Fruhwald, P. Gatzov, E. Goncalvesova, M. Hassanein, J. Hradec, A. Kavoliuniene, M. Lainscak, D. Logeart, B. Merkely, M. Metra, H. Persson, P. Seferovic, A. Temizhan, D. Tousoulis, L. Tavazzi and E. S. C. Heart Failure Association of the (2013). Are hospitalized or ambulatory patients with heart failure treated in accordance with European Society of Cardiology guidelines? Evidence from 12,440 patients of the ESC Heart Failure Long-Term Registry. Eur J Heart Fail 15(10): 1173-1184.

Lewis, E. F., G. A. Lamas, E. O’Meara, C. B. Granger, M. E. Dunlap, R. S. McKelvie, J. L. Probstfield, J. B. Young, E. L. Michelson, K. Halling, J. Carlsson, B. Olofsson, J. J. McMurray, S. Yusuf, K. Swedberg, M. A. Pfeffer and C. Investigators (2007). Characterization of health-r elated quality of life in heart failure patients with preserved versus low ejection fraction in CHARM. Eur J Heart Fail 9(1): 83–91.

Fukuta, H., T. Goto, K. Wakami and N. Ohte (2016). Effects of drug and exercise intervention on functional capacity and quality of life in heart failure with preserved ejection fraction: A meta-analysis of randomized controlled trials. Eur J Prev Cardiol 23(1): 78-85.

Faris, R., M. Flather, H. Purcell, M. Henein, P. Poole- Wilson and A. Coats (2002). Current evidence supporting the role of diuretics in heart failure: a meta analysis of randomised controlled trials. Int J Cardiol 82(2): 149–158

Yusuf, S., M. A. Pfeffer, K. Swedberg, C. B. Granger, P. Held, J. J. McMurray, E. L. Michelson, B. Olofsson, J. Ostergren, C. Investigators and Committees (2003). Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. Lancet 362(9386): 777-781.

Massie, B. M., P. E. Carson, J. J. McMurray, M. Komajda, R. McKelvie, M. R. Zile, S. Anderson, M. Donovan, E. Iverson, C. Staiger, A. Ptaszynska and I. P. Investigators (2008). Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med 359(23): 2456-2467.

Cleland, J. G., M. Tendera, J. Adamus, N. Freemantle, L. Polonski, J. Taylor and P.-C. Investigators (2006). The perindopril in elderly people with chronic heart failure (PEP-CHF) study. Eur Heart J 27(19): 2338-2345.

Flather, M. D., M. C. Shibata, A. J. Coats, D. J. Van Veldhuisen, A. Parkhomenko, J. Borbola, A. Cohen-Solal, D. Dumitrascu, R. Ferrari, P. Lechat, J. Soler-Soler, L. Tavazzi, L. Spinarova, J. Toman, M. Bohm, S. D. Anker, S. G. Thompson, P. A. Poole-Wilson and S. Investigators (2005). Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur Heart J 26(3): 215-225.

van Veldhuisen, D. J., A. Cohen-Solal, M. Bohm, S. D. Anker, D. Babalis, M. Roughton, A. J. Coats, P. A. Poole-Wilson, M. D. Flather and S. Investigators (2009). 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 53(23): 2150-2158.

Mulder, B. A., D. J. van Veldhuisen, H. J. Crijns, M. Bohm, A. Cohen-Solal, D. Babalis, M. Roughton, M. D. Flather, A. J. Coats and I. C. Van Gelder (2012). Effect of nebivolol on outcome in elderly patients with heart failure and atrial fibrillation: insights from SENIORS. Eur J Heart Fail 14(10): 1171-1178.

Ahmed, A., M. W. Rich, J. L. Fleg, M. R. Zile, J. B. Young, D. W. Kitzman, T. E. Love, W. S. Aronow, K. F. Adams, Jr. and M. Gheorghiade (2006). Effects of digoxin on morbidity and mortality in diastolic heart failure: the ancillary digitalis investigation group trial. Circulation 114(5): 397-403.

Pitt, B., M. A. Pfeffer, S. F. Assmann, R. Boineau, I. S. Anand, B. Claggett, N. Clausell, A. S. Desai, R. Diaz, J. L. Fleg, I. Gordeev, B. Harty, J. F. Heitner, C. T. Kenwood, E. F. Lewis, E. O'Meara, J. L. Probstfield, T. Shaburishvili, S. J. Shah, S. D. Solomon, N. K. Sweitzer, S. Yang, S. M. McKinlay and T. Investigators (2014). Spironolactone for heart failure with preserved ejection fraction. N Engl J Med 370(15): 1383-1392.

Edelmann, F., G. Gelbrich, H. D. Dungen, S. Frohling, R. Wachter, R. Stahrenberg, L. Binder, A. Topper, D. J. Lashki, S. Schwarz, C. Herrmann-Lingen, M. Loffler, G. Hasenfuss, M. Halle and B. Pieske (2011). 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 58(17): 1780-1791.

Windecker, S., P. Kolh, F. Alfonso, J. P. Collet, J. Cremer, V. Falk, G. Filippatos, C. Hamm, S. J. Head, P. Juni, A. P. Kappetein, A. Kastrati, J. Knuuti, U. Landmesser, G. Laufer, F. J. Neumann, D. J. Richter, P. Schauerte, M. Sousa Uva, G. G. Stefanini, D. P. Taggart, L. Torracca, M. Valgimigli, W. Wijns and A. Witkowski (2015). 2014 ESC/EACTS guidelines on myocardial revascularization. EuroIntervention 10(9): 1024-1094.

Beckett, N. S., R. Peters, A. E. Fletcher, J. A. Staessen, L. Liu, D. Dumitrascu, V. Stoyanovsky, R. L. Antikainen, Y. Nikitin, C. Anderson, A. Belhani, F. Forette, C. Rajkumar, L. Thijs, W. Banya, C. J. Bulpitt and H. S. Group (2008). Treatment of hypertension in patients 80 years of age or older. N Engl J Med 358(18): 1887-1898.

Mancia, G., R. Fagard, K. Narkiewicz, J. Redon, A. Zanchetti, M. Bohm, T. Christiaens, R. Cifkova, G. De Backer, A. Dominiczak, M. Galderisi, D. E. Grobbee, T. Jaarsma, P. Kirchhof, S. E. Kjeldsen, S. Laurent, A. J. Manolis, P. M. Nilsson, L. M. Ruilope, R. E. Schmieder, P. A. Sirnes, P. Sleight, M. Viigimaa, B. Waeber, F. Zannad and M. Task Force (2013). 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 31(7): 1281-1357.

Sakata, Y., K. Nochioka, M. Miura, T. Takada, S. Tadaki, S. Miyata, N. Shiba and H. Shimokawa (2013). Supplemental benefit of an angiotensin receptor blocker in hypertensive patients with stable heart failure using olmesartan (SUPPORT) trial--rationale and design. J Cardiol 62(1): 31-36.

Ryden, L., E. Standl, M. Bartnik, G. Van den Berghe, J. Betteridge, M. J. de Boer, F. Cosentino, B. Jonsson, M. Laakso, K. Malmberg, S. Priori, J. Ostergren, J. Tuomilehto, I. Thrainsdottir, I. Vanhorebeek, M. Stramba-Badiale, P. Lindgren, Q. Qiao, S. G. Priori, J. J. Blanc, A. Budaj, J. Camm, V. Dean, J. Deckers, K. Dickstein, J. Lekakis, K. McGregor, M. Metra, J. Morais, A. Osterspey, J. Tamargo, J. L. Zamorano, J. W. Deckers, M. Bertrand, B. Charbonnel, E. Erdmann, E. Ferrannini, A. Flyvbjerg, H. Gohlke, J. R. Juanatey, I. Graham, P. F. Monteiro, K. Parhofer, K. Pyorala, I. Raz, G. Schernthaner, M. Volpe, D. Wood, D. Task Force on, C. Cardiovascular Diseases of the European Society of and D. European Association for the Study of (2007). Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary. The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD). Eur Heart J 28(1): 88-136.

Zinman, B., C. Wanner, J. M. Lachin, D. Fitchett, E. Bluhmki, S. Hantel, M. Mattheus, T. Devins, O. E. Johansen, H. J. Woerle, U. C. Broedl, S. E. Inzucchi and E.-R. O. Investigators (2015). Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med 373(22): 2117-2128.

Gilbert, R. E. and H. Krum (2015). Heart failure in diabetes: effects of anti-hyperglycaemic drug therapy. Lancet 385(9982): 2107-2117.

Udell, J. A., M. A. Cavender, D. L. Bhatt, S. Chatterjee, M. E. Farkouh and B. M. Scirica (2015). Glucose-lowering drugs or strategies and cardiovascular outcomes in patients with or at risk for type 2 diabetes: a meta-analysis of randomised controlled trials. Lancet Diabetes Endocrinol 3(5): 356-366.

Ambrosio, G., M. D. Flather, M. Bohm, A. Cohen-Solal, A. Murrone, F. Mascagni, G. Spinucci, M. G. Conti, D. J. van Veldhuisen, L. Tavazzi and A. J. Coats (2011). beta-blockade with nebivolol for prevention of acute ischaemic events in elderly patients with heart failure. Heart 97(3): 209-214.

Domanski, M., J. Norman, B. Pitt, M. Haigney, S. Hanlon, E. Peyster and D. Studies of Left Ventricular (2003). Diuretic use, progressive heart failure, and death in patients in the Studies Of Left Ventricular Dysfunction (SOLVD). J Am Coll Cardiol 42(4): 705-708.

Oghlakian, G. O., I. Sipahi and J. C. Fang (2011). Treatment of heart failure with preserved ejection fraction: have we been pursuing the wrong paradigm? Mayo Clin Proc 86(6): 531-539.

Senni, M., W. J. Paulus, A. Gavazzi, A. G. Fraser, J. Diez, S. D. Solomon, O. A. Smiseth, M. Guazzi, C. S. Lam, A. P. Maggioni, C. Tschope, M. Metra, S. L. Hummel, F. Edelmann, G. Ambrosio, A. J. Stewart Coats, G. S. Filippatos, M. Gheorghiade, S. D. Anker, D. Levy, M. A. Pfeffer, W. G. Stough and B. M. Pieske (2014). New strategies for heart failure with preserved ejection fraction: the importance of targeted therapies for heart failure phenotypes. Eur Heart J 35(40): 2797-2815.

Shewan L.G., Coats A.J.S., Henein M. Requirements for Ethical Publishing in Biomedical Journals. International Cardiovascular Forum Journal. 2015;2:2.


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