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Cardiovascular & Hematological Disorders-Drug Targets

Editor-in-Chief

ISSN (Print): 1871-529X
ISSN (Online): 2212-4063

Mini-Review Article

Current Updates in the Pharmacotherapy of Heart Failure with a Preserved Ejection Fraction

Author(s): Ranjan Dahal*, Nils Nickel, Debabrata Mukherjee and Haider Alkhateeb

Volume 22, Issue 2, 2022

Published on: 22 August, 2022

Page: [87 - 95] Pages: 9

DOI: 10.2174/1871529X22666220630164630

Price: $65

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Abstract

Background: Heart failure is the leading cause of morbidity and mortality worldwide. With improved longevity, the incidence and prevalence of heart failure continue to rise with an estimated prevalence of around 26 million worldwide. Heart failure with preserved ejection fraction (HFpEF) constitutes around 50% of the total heart failure cases and is the most common cause of heart failure in the elderly population. The cost of heart failure care continues to rise with care for heart failure hospitalization taking the major bulk. The cost was around 30 billion in the US in 2012 and is projected to reach 70 billion by 2030.

Objective: This study aims to provide updated pharmacotherapy of heart failure with a preserved ejection fraction (HFpEF).

Methods: We performed a comprehensive literature review to examine the available pharmacotherapeutics in the management of heart failure with a preserved ejection fraction using online databases (PubMed and Embase).

Results: We reviewed multiple studies examining pharmacotherapeutics in the management of HFpEF and reducing heart failure hospitalizations in this cohort. Until recently, our management mainly focused on aggressively managing diabetes, hypertension, atrial fibrillation, and coronary artery disease anticipating improving the outcome. Beta-blockers, Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, sildenafil, digoxin, vericiguat, praliciguat, and Ivabradine did not improve heart failure hospitalization in this cohort.

Conclusion: EMPEROR-PRESERVED (Empagliflozin) and PRESERVED-HF (Dapagliflozin) results in the management of HFpEF look promising irrespective of diabetes status. Sacubitrilvalsartan and Empagliflozon are the only medications approved for its management as per the PARAGON-HF and EMPEROR-PRESERVED studies, respectively.

Keywords: Heart failure with preserved ejection fraction (HFpEF), diastolic heart failure, diuretics, angiotensin receptor neprilysin inhibitor (ARNI), SGLT-2 inhibitors, pharmacotherapy.

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[1]
Virani, S.S.; Alonso, A.; Aparicio, H.J.; Benjamin, E.J.; Bittencourt, M.S.; Callaway, C.W.; Carson, A.P.; Chamberlain, A.M.; Cheng, S.; Delling, F.N.; Elkind, M.S.V.; Evenson, K.R.; Ferguson, J.F.; Gupta, D.K.; Khan, S.S.; Kissela, B.M.; Knutson, K.L.; Lee, C.D.; Lewis, T.T.; Liu, J.; Loop, M.S.; Lutsey, P.L.; Ma, J.; Mackey, J.; Martin, S.S.; Matchar, D.B.; Mussolino, M.E.; Navaneethan, S.D.; Perak, A.M.; Roth, G.A.; Samad, Z.; Satou, G.M.; Schroeder, E.B.; Shah, S.H.; Shay, C.M.; Stokes, A.; VanWagner, L.B.; Wang, N.Y.; Tsao, C.W. Heart disease and stroke statistics-2021 update: A report from the American heart association. Circulation, 2021, 143(8), e254-e743.
[http://dx.doi.org/10.1161/CIR.0000000000000950] [PMID: 33501848]
[2]
Savarese, G.; Lund, L.H. Global public health burden of heart failure. Card. Fail. Rev., 2017, 3(1), 7-11.
[http://dx.doi.org/10.15420/cfr.2016:25:2] [PMID: 28785469]
[3]
Heidenreich, P.A.; Albert, N.M.; Allen, L.A.; Bluemke, D.A.; Butler, J.; Fonarow, G.C.; Ikonomidis, J.S.; Khavjou, O.; Konstam, M.A.; Maddox, T.M.; Nichol, G.; Pham, M.; Piña, I.L.; Trogdon, J.G. Forecasting the impact of heart failure in the United States: A policy statement from the American Heart Association. Circ. Heart Fail., 2013, 6(3), 606-619.
[http://dx.doi.org/10.1161/HHF.0b013e318291329a] [PMID: 23616602]
[4]
Cook, C.; Cole, G.; Asaria, P.; Jabbour, R.; Francis, D.P. The annual global economic burden of heart failure. Int. J. Cardiol., 2014, 171(3), 368-376.
[http://dx.doi.org/10.1016/j.ijcard.2013.12.028] [PMID: 24398230]
[5]
Dunlay, S.M.; Roger, V.L.; Redfield, M.M. Epidemiology of heart failure with preserved ejection fraction. Nat. Rev. Cardiol., 2017, 14(10), 591-602.
[http://dx.doi.org/10.1038/nrcardio.2017.65] [PMID: 28492288]
[6]
Shah, A.M.; Claggett, B.; Loehr, L.R.; Chang, P.P.; Matsushita, K.; Kitzman, D.; Konety, S.; Kucharska-Newton, A.; Sueta, C.A.; Mosley, T.H.; Wright, J.D.; Coresh, J.; Heiss, G.; Folsom, A.R.; Solomon, S.D. Heart failure stages among older adults in the community: The atherosclerosis risk in communities study. Circulation, 2017, 135(3), 224-240.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.116.023361] [PMID: 27881564]
[7]
Gerges, M.; Gerges, C.; Pistritto, A.M.; Lang, M.B.; Trip, P.; Jakowitsch, J.; Binder, T.; Lang, I.M. Pulmonary hypertension in heart failure. Epidemiology, right ventricular function, and survival. Am. J. Respir. Crit. Care Med., 2015, 192(10), 1234-1246.
[http://dx.doi.org/10.1164/rccm.201503-0529OC] [PMID: 26181215]
[8]
Shah, K.S.; Xu, H.; Matsouaka, R.A.; Bhatt, D.L.; Heidenreich, P.A.; Hernandez, A.F.; Devore, A.D.; Yancy, C.W.; Fonarow, G.C. Heart failure with preserved, borderline, and reduced ejection fraction: 5-Year outcomes. J. Am. Coll. Cardiol., 2017, 70(20), 2476-2486.
[http://dx.doi.org/10.1016/j.jacc.2017.08.074] [PMID: 29141781]
[9]
Cheng, R.K.; Cox, M.; Neely, M.L.; Heidenreich, P.A.; Bhatt, D.L.; Eapen, Z.J.; Hernandez, A.F.; Butler, J.; Yancy, C.W.; Fonarow, G.C. Outcomes in patients with heart failure with preserved, borderline, and reduced ejection fraction in the medicare population. Am. Heart J., 2014, 168(5), 721-730.
[http://dx.doi.org/10.1016/j.ahj.2014.07.008] [PMID: 25440801]
[10]
Owan, T.E.; Hodge, D.O.; Herges, R.M.; Jacobsen, S.J.; Roger, V.L.; Redfield, M.M. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N. Engl. J. Med., 2006, 355(3), 251-259.
[http://dx.doi.org/10.1056/NEJMoa052256] [PMID: 16855265]
[11]
McDonagh, T.A.; Metra, M.; Adamo, M.; Gardner, R.S.; Baumbach, A.; Böhm, M.; Burri, H.; Butler, J.; Čelutkienė, J.; Chioncel, O.; Cleland, J.G.F.; Coats, A.J.S.; Crespo-Leiro, M.G.; Farmakis, D.; Gilard, M.; Heymans, S.; Hoes, A.W.; Jaarsma, T.; Jankowska, E.A.; Lainscak, M.; Lam, C.S.P.; Lyon, A.R.; McMurray, J.J.V.; Mebazaa, A.; Mindham, R.; Muneretto, C.; Francesco Piepoli, M.; Price, S.; Rosano, G.M.C.; Ruschitzka, F.; Kathrine Skibelund, A.; de Boer, R.A.; Christian Schulze, P.; Abdelhamid, M.; Aboyans, V.; Adamopoulos, S.; Anker, S.D.; Arbelo, E.; Asteggiano, R.; Bauersachs, J.; Bayes-Genis, A.; Borger, M.A.; Budts, W.; Cikes, M.; Damman, K.; Delgado, V.; Dendale, P.; Dilaveris, P.; Drexel, H.; Ezekowitz, J.; Falk, V.; Fauchier, L.; Filippatos, G.; Fraser, A.; Frey, N.; Gale, C.P.; Gustafsson, F.; Harris, J.; Iung, B.; Janssens, S.; Jessup, M.; Konradi, A.; Kotecha, D.; Lambrinou, E.; Lancellotti, P.; Landmesser, U.; Leclercq, C.; Lewis, B.S.; Leyva, F.; Linhart, A.; Løchen, M-L.; Lund, L.H.; Mancini, D.; Masip, J.; Milicic, D.; Mueller, C.; Nef, H.; Nielsen, J-C.; Neubeck, L.; Noutsias, M.; Petersen, S.E.; Sonia Petronio, A.; Ponikowski, P.; Prescott, E.; Rakisheva, A.; Richter, D.J.; Schlyakhto, E.; Seferovic, P.; Senni, M.; Sitges, M.; Sousa-Uva, M.; Tocchetti, C.G.; Touyz, R.M.; Tschoepe, C.; Waltenberger, J.; Adamo, M.; Baumbach, A.; Böhm, M.; Burri, H.; Čelutkienė, J.; Chioncel, O.; Cleland, J.G.F.; Coats, A.J.S.; Crespo-Leiro, M.G.; Farmakis, D.; Gardner, R.S.; Gilard, M.; Heymans, S.; Hoes, A.W.; Jaarsma, T.; Jankowska, E.A.; Lainscak, M.; Lam, C.S.P.; Lyon, A.R.; McMurray, J.J.V.; Mebazaa, A.; Mindham, R.; Muneretto, C.; Piepoli, M.F.; Price, S.; Rosano, G.M.C.; Ruschitzka, F.; Skibelund, A.K. 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur. Heart J., 2021, 42(36), 3599-3726.
[http://dx.doi.org/10.1093/eurheartj/ehab368] [PMID: 34447992]
[12]
Borlaug, B.A.; Nishimura, R.A.; Sorajja, P.; Lam, C.S.; Redfield, M.M. Exercise hemodynamics enhance diagnosis of early heart failure with preserved ejection fraction. Circ. Heart Fail., 2010, 3(5), 588-595.
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.109.930701] [PMID: 20543134]
[13]
Reddy, Y.N.V.; Carter, R.E.; Obokata, M.; Redfield, M.M.; Borlaug, B.A. A simple, evidence-based approach to help guide diagnosis of heart failure with preserved ejection fraction. Circulation, 2018, 138(9), 861-870.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.118.034646] [PMID: 29792299]
[14]
Barandiarán Aizpurua, A.; Sanders-van Wijk, S.; Brunner-La Rocca, H.P.; Henkens, M.; Heymans, S.; Beussink-Nelson, L.; Shah, S.J.; van Empel, V.P.M. Validation of the HFA-PEFF score for the diagnosis of heart failure with preserved ejection fraction. Eur. J. Heart Fail., 2020, 22(3), 413-421.
[http://dx.doi.org/10.1002/ejhf.1614] [PMID: 31472035]
[15]
Eckel, R.H.; Farooki, A.; Henry, R.R.; Koch, G.G.; Leiter, L.A. Cardiovascular outcome trials in type 2 diabetes: What do they mean for clinical practice? Clin. Diabetes, 2019, 37(4), 316-337.
[http://dx.doi.org/10.2337/cd19-0001] [PMID: 31660005]
[16]
Rosano, G.M.; Vitale, C.; Seferovic, P. Heart failure in patients with diabetes mellitus. Card. Fail. Rev., 2017, 3(1), 52-55.
[http://dx.doi.org/10.15420/cfr.2016:20:2] [PMID: 28785476]
[17]
Meagher, P.; Adam, M.; Civitarese, R.; Bugyei-Twum, A.; Connelly, K.A. Heart failure with preserved ejection fraction in diabetes: Mechanisms and management. Can. J. Cardiol., 2018, 34(5), 632-643.
[http://dx.doi.org/10.1016/j.cjca.2018.02.026] [PMID: 29731023]
[18]
Perkovic, V.; Jardine, M.J.; Neal, B.; Bompoint, S.; Heerspink, H.J.L.; Charytan, D.M.; Edwards, R.; Agarwal, R.; Bakris, G.; Bull, S.; Cannon, C.P.; Capuano, G.; Chu, P.L.; de Zeeuw, D.; Greene, T.; Levin, A.; Pollock, C.; Wheeler, D.C.; Yavin, Y.; Zhang, H.; Zinman, B.; Meininger, G.; Brenner, B.M.; Mahaffey, K.W. Canagliflozin and renal outcomes in Type 2 diabetes and nephropathy. N. Engl. J. Med., 2019, 380(24), 2295-2306.
[http://dx.doi.org/10.1056/NEJMoa1811744] [PMID: 30990260]
[19]
McMurray, J.J.V.; Solomon, S.D.; Inzucchi, S.E.; Køber, L.; Kosiborod, M.N.; Martinez, F.A.; Ponikowski, P.; Sabatine, M.S.; Anand, I.S.; Bělohlávek, J.; Böhm, M.; Chiang, C.E.; Chopra, V.K.; de Boer, R.A.; Desai, A.S.; Diez, M.; Drozdz, J.; Dukát, A.; Ge, J.; Howlett, J.G.; Katova, T.; Kitakaze, M.; Ljungman, C.E.A.; Merkely, B.; Nicolau, J.C.; O’Meara, E.; Petrie, M.C.; Vinh, P.N.; Schou, M.; Tereshchenko, S.; Verma, S.; Held, C.; DeMets, D.L.; Docherty, K.F.; Jhund, P.S.; Bengtsson, O.; Sjöstrand, M.; Langkilde, A.M. Dapagliflozin in patients with heart failure and reduced ejection fraction. N. Engl. J. Med., 2019, 381(21), 1995-2008.
[http://dx.doi.org/10.1056/NEJMoa1911303] [PMID: 31535829]
[20]
Packer, M.; Anker, S.D.; Butler, J.; Filippatos, G.; Pocock, S.J.; Carson, P.; Januzzi, J.; Verma, S.; Tsutsui, H.; Brueckmann, M.; Jamal, W.; Kimura, K.; Schnee, J.; Zeller, C.; Cotton, D.; Bocchi, E.; Böhm, M.; Choi, D.J.; Chopra, V.; Chuquiure, E.; Giannetti, N.; Janssens, S.; Zhang, J.; Gonzalez Juanatey, J.R.; Kaul, S.; Brunner-La Rocca, H.P.; Merkely, B.; Nicholls, S.J.; Perrone, S.; Pina, I.; Ponikowski, P.; Sattar, N.; Senni, M.; Seronde, M.F.; Spinar, J.; Squire, I.; Taddei, S.; Wanner, C.; Zannad, F. Cardiovascular and renal outcomes with empagliflozin in heart failure. N. Engl. J. Med., 2020, 383(15), 1413-1424.
[http://dx.doi.org/10.1056/NEJMoa2022190] [PMID: 32865377]
[21]
Cannon, C.P.; Pratley, R.; Dagogo-Jack, S.; Mancuso, J.; Huyck, S.; Masiukiewicz, U.; Charbonnel, B.; Frederich, R.; Gallo, S.; Cosentino, F.; Shih, W.J.; Gantz, I.; Terra, S.G.; Cherney, D.Z.I.; McGuire, D.K. Cardiovascular outcomes with ertugliflozin in Type 2 diabetes. N. Engl. J. Med., 2020, 383(15), 1425-1435.
[http://dx.doi.org/10.1056/NEJMoa2004967] [PMID: 32966714]
[22]
Anker, S.D.; Butler, J.; Filippatos, G.; Ferreira, J.P.; Bocchi, E.; Böhm, M.; Brunner-La Rocca, H.P.; Choi, D.J.; Chopra, V.; Chuquiure-Valenzuela, E.; Giannetti, N.; Gomez-Mesa, J.E.; Janssens, S.; Januzzi, J.L.; Gonzalez-Juanatey, J.R.; Merkely, B.; Nicholls, S.J.; Perrone, S.V.; Piña, I.L.; Ponikowski, P.; Senni, M.; Sim, D.; Spinar, J.; Squire, I.; Taddei, S.; Tsutsui, H.; Verma, S.; Vinereanu, D.; Zhang, J.; Carson, P.; Lam, C.S.P.; Marx, N.; Zeller, C.; Sattar, N.; Jamal, W.; Schnaidt, S.; Schnee, J.M.; Brueckmann, M.; Pocock, S.J.; Zannad, F.; Packer, M. Empagliflozin in heart failure with a preserved ejection fraction. N. Engl. J. Med., 2021, 385(16), 1451-1461.
[http://dx.doi.org/10.1056/NEJMoa2107038] [PMID: 34449189]
[23]
Nassif, M.E.; Windsor, S.L.; Borlaug, B.A.; Kitzman, D.W.; Shah, S.J.; Tang, F.; Khariton, Y.; Malik, A.O.; Khumri, T.; Umpierrez, G.; Lamba, S.; Sharma, K.; Khan, S.S.; Chandra, L.; Gordon, R.A.; Ryan, J.J.; Chaudhry, S.P.; Joseph, S.M.; Chow, C.H.; Kanwar, M.K.; Pursley, M.; Siraj, E.S.; Lewis, G.D.; Clemson, B.S.; Fong, M.; Kosiborod, M.N. The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: A multicenter randomized trial. Nat. Med., 2021, 27(11), 1954-1960.
[http://dx.doi.org/10.1038/s41591-021-01536-x] [PMID: 34711976]
[24]
Cleland, J.G.; Tendera, M.; Adamus, J.; Freemantle, N.; Polonski, L.; Taylor, J. The perindopril in elderly people with chronic heart failure (PEP-CHF) study. Eur. Heart J., 2006, 27(19), 2338-2345.
[http://dx.doi.org/10.1093/eurheartj/ehl250] [PMID: 16963472]
[25]
Yusuf, S.; Pfeffer, M.A.; Swedberg, K.; Granger, C.B.; Held, P.; McMurray, J.J.; Michelson, E.L.; Olofsson, B.; Ostergren, J. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: The CHARM-Preserved Trial. Lancet, 2003, 362(9386), 777-781.
[http://dx.doi.org/10.1016/S0140-6736(03)14285-7] [PMID: 13678871]
[26]
Massie, B.M.; Carson, P.E.; McMurray, J.J.; Komajda, M.; McKelvie, R.; Zile, M.R.; Anderson, S.; Donovan, M.; Iverson, E.; Staiger, C.; Ptaszynska, A. Irbesartan in patients with heart failure and preserved ejection fraction. N. Engl. J. Med., 2008, 359(23), 2456-2467.
[http://dx.doi.org/10.1056/NEJMoa0805450] [PMID: 19001508]
[27]
Solomon, S.D.; McMurray, J.J.V.; Anand, I.S.; Ge, J.; Lam, C.S.P.; Maggioni, A.P.; Martinez, F.; Packer, M.; Pfeffer, M.A.; Pieske, B.; Redfield, M.M.; Rouleau, J.L.; van Veldhuisen, D.J.; Zannad, F.; Zile, M.R.; Desai, A.S.; Claggett, B.; Jhund, P.S.; Boytsov, S.A.; Comin-Colet, J.; Cleland, J.; Düngen, H.D.; Goncalvesova, E.; Katova, T.; Kerr Saraiva, J.F.; Lelonek, M.; Merkely, B.; Senni, M.; Shah, S.J.; Zhou, J.; Rizkala, A.R.; Gong, J.; Shi, V.C.; Lefkowitz, M.P. Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction. N. Engl. J. Med., 2019, 381(17), 1609-1620.
[http://dx.doi.org/10.1056/NEJMoa1908655] [PMID: 31475794]
[28]
Solomon, S.D.; Zile, M.; Pieske, B.; Voors, A.; Shah, A.; Kraigher-Krainer, E.; Shi, V.; Bransford, T.; Takeuchi, M.; Gong, J.; Lefkowitz, M.; Packer, M.; McMurray, J.J. The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: A phase 2 double-blind randomised controlled trial. Lancet, 2012, 380(9851), 1387-1395.
[http://dx.doi.org/10.1016/S0140-6736(12)61227-6] [PMID: 22932717]
[29]
Pitt, B.; Pfeffer, M.A.; Assmann, S.F.; Boineau, R.; Anand, I.S.; Claggett, B.; Clausell, N.; Desai, A.S.; Diaz, R.; Fleg, J.L.; Gordeev, I.; Harty, B.; Heitner, J.F.; Kenwood, C.T.; Lewis, E.F.; O’Meara, E.; Probstfield, J.L.; Shaburishvili, T.; Shah, S.J.; Solomon, S.D.; Sweitzer, N.K.; Yang, S.; McKinlay, S.M. Spironolactone for heart failure with preserved ejection fraction. N. Engl. J. Med., 2014, 370(15), 1383-1392.
[http://dx.doi.org/10.1056/NEJMoa1313731] [PMID: 24716680]
[30]
Pfeffer, M.A.; Claggett, B.; Assmann, S.F.; Boineau, R.; Anand, I.S.; Clausell, N.; Desai, A.S.; Diaz, R.; Fleg, J.L.; Gordeev, I.; Heitner, J.F.; Lewis, E.F.; O’Meara, E.; Rouleau, J.L.; Probstfield, J.L.; Shaburishvili, T.; Shah, S.J.; Solomon, S.D.; Sweitzer, N.K.; McKinlay, S.M.; Pitt, B. Regional variation in patients and outcomes in the treatment of preserved cardiac function heart failure with an aldosterone antagonist (TOPCAT) trial. Circulation, 2015, 131(1), 34-42.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.114.013255] [PMID: 25406305]
[31]
Flather, M.D.; Shibata, M.C.; Coats, A.J.; Van Veldhuisen, D.J.; Parkhomenko, A.; Borbola, J.; Cohen-Solal, A.; Dumitrascu, D.; Ferrari, R.; Lechat, P.; Soler-Soler, J.; Tavazzi, L.; Spinarova, L.; Toman, J.; Böhm, M.; Anker, S.D.; Thompson, S.G.; Poole-Wilson, P.A. 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(3), 215-225.
[http://dx.doi.org/10.1093/eurheartj/ehi115] [PMID: 15642700]
[32]
Cleland, J.G.F.; Bunting, K.V.; Flather, M.D.; Altman, D.G.; Holmes, J.; Coats, A.J.S.; Manzano, L.; McMurray, J.J.V.; Ruschitzka, F.; van Veldhuisen, D.J.; von Lueder, T.G.; Böhm, M.; Andersson, B.; Kjekshus, J.; Packer, M.; Rigby, A.S.; Rosano, G.; Wedel, H.; Hjalmarson, Å.; Wikstrand, J.; Kotecha, D. Beta-blockers for heart failure with reduced, mid-range, and preserved ejection fraction: An individual patient-level analysis of double-blind randomized trials. Eur. Heart J., 2018, 39(1), 26-35.
[http://dx.doi.org/10.1093/eurheartj/ehx564] [PMID: 29040525]
[33]
The effect of digoxin on mortality and morbidity in patients with heart failure. N. Engl. J. Med., 1997, 336(8), 525-533.
[http://dx.doi.org/10.1056/NEJM199702203360801] [PMID: 9036306]
[34]
Ahmed, A.; Rich, M.W.; Fleg, J.L.; Zile, M.R.; Young, J.B.; Kitzman, D.W.; Love, T.E.; Aronow, W.S.; Adams, K.F., Jr; Gheorghiade, M. Effects of digoxin on morbidity and mortality in diastolic heart failure: The ancillary digitalis investigation group trial. Circulation, 2006, 114(5), 397-403.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.106.628347] [PMID: 16864724]
[35]
Hoendermis, E.S.; Liu, L.C.; Hummel, Y.M.; van der Meer, P.; de Boer, R.A.; Berger, R.M.; van Veldhuisen, D.J.; Voors, A.A. Effects of sildenafil on invasive haemodynamics and exercise capacity in heart failure patients with preserved ejection fraction and pulmonary hypertension: A randomized controlled trial. Eur. Heart J., 2015, 36(38), 2565-2573.
[http://dx.doi.org/10.1093/eurheartj/ehv336] [PMID: 26188003]
[36]
Redfield, M.M.; Chen, H.H.; Borlaug, B.A.; Semigran, M.J.; Lee, K.L.; Lewis, G.; LeWinter, M.M.; Rouleau, J.L.; Bull, D.A.; Mann, D.L.; Deswal, A.; Stevenson, L.W.; Givertz, M.M.; Ofili, E.O.; O’Connor, C.M.; Felker, G.M.; Goldsmith, S.R.; Bart, B.A.; McNulty, S.E.; Ibarra, J.C.; Lin, G.; Oh, J.K.; Patel, M.R.; Kim, R.J.; Tracy, R.P.; Velazquez, E.J.; Anstrom, K.J.; Hernandez, A.F.; Mascette, A.M.; Braunwald, E. RELAX Trial, 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), 1268-1277.
[http://dx.doi.org/10.1001/jama.2013.2024] [PMID: 23478662]
[37]
Redfield, M.M.; Anstrom, K.J.; Levine, J.A.; Koepp, G.A.; Borlaug, B.A.; Chen, H.H.; LeWinter, M.M.; Joseph, S.M.; Shah, S.J.; Semigran, M.J.; Felker, G.M.; Cole, R.T.; Reeves, G.R.; Tedford, R.J.; Tang, W.H.; McNulty, S.E.; Velazquez, E.J.; Shah, M.R.; Braunwald, E. Isosorbide mononitrate in heart failure with preserved ejection fraction. N. Engl. J. Med., 2015, 373(24), 2314-2324.
[http://dx.doi.org/10.1056/NEJMoa1510774] [PMID: 26549714]
[38]
Borlaug, B.A.; Anstrom, K.J.; Lewis, G.D.; Shah, S.J.; Levine, J.A.; Koepp, G.A.; Givertz, M.M.; Felker, G.M.; LeWinter, M.M.; Mann, D.L.; Margulies, K.B.; Smith, A.L.; Tang, W.H.W.; Whellan, D.J.; Chen, H.H.; Davila-Roman, V.G.; McNulty, S.; Desvigne-Nickens, P.; Hernandez, A.F.; Braunwald, E.; Redfield, M.M. Effect of inorganic nitrite vs. placebo on exercise capacity among patients with heart failure with preserved ejection fraction: The INDIE-HFpEF randomized clinical trial. JAMA, 2018, 320(17), 1764-1773.
[http://dx.doi.org/10.1001/jama.2018.14852] [PMID: 30398602]
[39]
Udelson, J.E.; Lewis, G.D.; Shah, S.J.; Zile, M.R.; Redfield, M.M.; Burnett, J., Jr; Parker, J.; Seferovic, J.P.; Wilson, P.; Mittleman, R.S.; Profy, A.T.; Konstam, M.A. Effect of Praliciguat on peak rate of oxygen consumption in patients with heart failure with preserved ejection fraction: The capacity HFpEF randomized clinical trial. JAMA, 2020, 324(15), 1522-1531.
[http://dx.doi.org/10.1001/jama.2020.16641] [PMID: 33079154]
[40]
Armstrong, P.W.; Lam, C.S.P.; Anstrom, K.J.; Ezekowitz, J.; Hernandez, A.F.; O’Connor, C.M.; Pieske, B.; Ponikowski, P.; Shah, S.J.; Solomon, S.D.; Voors, A.A.; She, L.; Vlajnic, V.; Carvalho, F.; Bamber, L.; Blaustein, R.O.; Roessig, L.; Butler, J. Effect of Vericiguat vs. placebo on quality of life in patients with heart failure and preserved ejection fraction: The VITALITY-HFpEF randomized clinical trial. JAMA, 2020, 324(15), 1512-1521.
[http://dx.doi.org/10.1001/jama.2020.15922] [PMID: 33079152]
[41]
Pieske, B.; Maggioni, A.P.; Lam, C.S.P.; Pieske-Kraigher, E.; Filippatos, G.; Butler, J.; Ponikowski, P.; Shah, S.J.; Solomon, S.D.; Scalise, A.V.; Mueller, K.; Roessig, L.; Gheorghiade, M. Vericiguat in patients with worsening chronic heart failure and preserved ejection fraction: Results of the SOluble guanylate Cyclase stimulatoR in heArT failurE patientS with PRESERVED EF (SOCRATES-PRESERVED) study. Eur. Heart J., 2017, 38(15), 1119-1127.
[http://dx.doi.org/10.1093/eurheartj/ehw593] [PMID: 28369340]
[42]
Komajda, M.; Isnard, R.; Cohen-Solal, A.; Metra, M.; Pieske, B.; Ponikowski, P.; Voors, A.A.; Dominjon, F.; Henon-Goburdhun, C.; Pannaux, M.; Böhm, M. Effect of ivabradine in patients with heart failure with preserved ejection fraction: The EDIFY randomized placebo-controlled trial. Eur. J. Heart Fail., 2017, 19(11), 1495-1503.
[http://dx.doi.org/10.1002/ejhf.876] [PMID: 28462519]
[43]
Kosmala, W.; Holland, D.J.; Rojek, A.; Wright, L.; Przewlocka-Kosmala, M.; Marwick, T.H. Effect of If-channel inhibition on hemodynamic status and exercise tolerance in heart failure with preserved ejection fraction: A randomized trial. J. Am. Coll. Cardiol., 2013, 62(15), 1330-1338.
[http://dx.doi.org/10.1016/j.jacc.2013.06.043] [PMID: 23916925]
[44]
Pal, N.; Sivaswamy, N.; Mahmod, M.; Yavari, A.; Rudd, A.; Singh, S.; Dawson, D.K.; Francis, J.M.; Dwight, J.S.; Watkins, H.; Neubauer, S.; Frenneaux, M.; Ashrafian, H. Effect of selective heart rate slowing in heart failure with preserved ejection fraction. Circulation, 2015, 132(18), 1719-1725.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.115.017119] [PMID: 26338956]
[45]
Lewis, G.A.; Dodd, S.; Clayton, D.; Bedson, E.; Eccleson, H.; Schelbert, E.B.; Naish, J.H.; Jimenez, B.D.; Williams, S.G.; Cunnington, C.; Ahmed, F.Z.; Cooper, A. Rajavarma Viswesvaraiah; Russell, S.; McDonagh, T.; Williamson, P.R.; Miller, C.A. Pirfenidone in heart failure with preserved ejection fraction: A randomized phase 2 trial. Nat. Med., 2021, 27(8), 1477-1482.
[http://dx.doi.org/10.1038/s41591-021-01452-0] [PMID: 34385704]
[46]
Adamson, P.B.; Abraham, W.T.; Bourge, R.C.; Costanzo, M.R.; Hasan, A.; Yadav, C.; Henderson, J.; Cowart, P.; Stevenson, L.W. Wireless pulmonary artery pressure monitoring guides management to reduce decompensation in heart failure with preserved ejection fraction. Circ. Heart Fail., 2014, 7(6), 935-944.
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.113.001229] [PMID: 25286913]
[47]
United States Food and Drug Administration. PMA P100045: FDA summary of safety and effectiveness data, Available from:. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P100045
[48]
Lindenfeld, J.; Zile, M.R.; Desai, A.S.; Bhatt, K.; Ducharme, A.; Horstmanshof, D.; Krim, S.R.; Maisel, A.; Mehra, M.R.; Paul, S.; Sears, S.F.; Sauer, A.J.; Smart, F.; Zughaib, M.; Castaneda, P.; Kelly, J.; Johnson, N.; Sood, P.; Ginn, G.; Henderson, J.; Adamson, P.B.; Costanzo, M.R. Haemodynamic-guided management of heart failure (GUIDE-HF): A randomised controlled trial. Lancet, 2021, 398(10304), 991-1001.
[http://dx.doi.org/10.1016/S0140-6736(21)01754-2] [PMID: 34461042]
[49]
Jackson, A.M.; Jhund, P.S.; Anand, I.S.; Düngen, H.D.; Lam, C.S.P.; Lefkowitz, M.P.; Linssen, G.; Lund, L.H.; Maggioni, A.P.; Pfeffer, M.A.; Rouleau, J.L.; Saraiva, J.F.K.; Senni, M.; Vardeny, O.; Wijkman, M.O.; Yilmaz, M.B.; Saito, Y.; Zile, M.R.; Solomon, S.D.; McMurray, J.J.V. Sacubitril-valsartan as a treatment for apparent resistant hypertension in patients with heart failure and preserved ejection fraction. Eur. Heart J., 2021, 42(36), 3741-3752.
[http://dx.doi.org/10.1093/eurheartj/ehab499] [PMID: 34392331]
[50]
Martin, N.; Manoharan, K.; Davies, C.; Lumbers, R.T. Beta-blockers and inhibitors of the renin-angiotensin aldosterone system for chronic heart failure with preserved ejection fraction. Cochrane Database Syst. Rev., 2021, 5(5), CD012721.
[PMID: 34022072]
[51]
Wiviott, S.D.; Raz, I.; Bonaca, M.P.; Mosenzon, O.; Kato, E.T.; Cahn, A.; Silverman, M.G.; Zelniker, T.A.; Kuder, J.F.; Murphy, S.A.; Bhatt, D.L.; Leiter, L.A.; McGuire, D.K.; Wilding, J.P.H.; Ruff, C.T.; Gause-Nilsson, I.A.M.; Fredriksson, M.; Johansson, P.A.; Langkilde, A.M.; Sabatine, M.S. Dapagliflozin and cardiovascular outcomes in Type 2 diabetes. N. Engl. J. Med., 2019, 380(4), 347-357.
[http://dx.doi.org/10.1056/NEJMoa1812389] [PMID: 30415602]
[52]
Scheffer, M.; Driessen-Waaijer, A.; Hamdani, N.; Landzaat, J.W.D.; Jonkman, N.H.; Paulus, W.J.; van Heerebeek, L. Stratified treatment of heart failure with preserved ejection fraction: Rationale and design of the STADIA-HFpEF trial. ESC Heart Fail., 2020, 7(6), 4478-4487.
[http://dx.doi.org/10.1002/ehf2.13055] [PMID: 33073523]
[53]
Solomon, S.D.; de Boer, R.A.; DeMets, D.; Hernandez, A.F.; Inzucchi, S.E.; Kosiborod, M.N.; Lam, C.S.P.; Martinez, F.; Shah, S.J.; Lindholm, D.; Wilderäng, U.; Öhrn, F.; Claggett, B.; Langkilde, A.M.; Petersson, M.; McMurray, J.J.V. Dapagliflozin in heart failure with preserved and mildly reduced ejection fraction: Rationale and design of the DELIVER trial. Eur. J. Heart Fail., 2021, 23(7), 1217-1225.
[http://dx.doi.org/10.1002/ejhf.2249] [PMID: 34051124]
[54]
Tromp, J.; Ponikowski, P.; Salsali, A.; Angermann, C.E.; Biegus, J.; Blatchford, J.; Collins, S.P.; Ferreira, J.P.; Grauer, C.; Kosiborod, M.; Nassif, M.E.; Psotka, M.A.; Brueckmann, M.; Teerlink, J.R.; Voors, A.A. Sodium-glucose co-transporter 2 inhibition in patients hospitalized for acute decompensated heart failure: Rationale for and design of the EMPULSE trial. Eur. J. Heart Fail., 2021, 23(5), 826-834.
[http://dx.doi.org/10.1002/ejhf.2137] [PMID: 33609072]

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