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Open Access 27-02-2024 | Heart Failure

Heart failure with mildly reduced and preserved ejection fraction: A review of disease burden and remaining unmet medical needs within a new treatment landscape

Authors: Nihar Desai, Elzbieta Olewinska, Agata Famulska, Cécile Remuzat, Clément Francois, Kerstin Folkerts

Published in: Heart Failure Reviews | Issue 3/2024

Abstract

This review provides a comprehensive overview of heart failure with mildly reduced and preserved ejection fraction (HFmrEF/HFpEF), including its definition, diagnosis, and epidemiology; clinical, humanistic, and economic burdens; current pharmacologic landscape in key pharmaceutical markets; and unmet needs to identify key knowledge gaps. We conducted a targeted literature review in electronic databases and prioritized articles with valuable insights into HFmrEF/HFpEF. Overall, 27 randomized controlled trials (RCTs), 66 real-world evidence studies, 18 clinical practice guidelines, and 25 additional publications were included. Although recent heart failure (HF) guidelines set left ventricular ejection fraction thresholds to differentiate categories, characterization and diagnosis criteria vary because of the incomplete disease understanding. Recent epidemiological data are limited and diverse. Approximately 50% of symptomatic HF patients have HFpEF, more common than HFmrEF. Prevalence varies with country because of differing definitions and study characteristics, making prevalence interpretation challenging. HFmrEF/HFpEF has considerable mortality risk, and the mortality rate varies with study and patient characteristics and treatments. HFmrEF/HFpEF is associated with considerable morbidity, poor patient outcomes, and common comorbidities. Patients require frequent hospitalizations; therefore, early intervention is crucial to prevent disease burden. Recent RCTs show promising results like risk reduction of composite cardiovascular death or HF hospitalization. Costs data are scarce, but the economic burden is increasing. Despite new drugs, unmet medical needs requiring new treatments remain. Thus, HFmrEF/HFpEF is a growing global healthcare concern. With improving yet incomplete understanding of this disease and its promising treatments, further research is required for better patient outcomes.

Available only for authorised users

Authors analyzed the KCCQ total symptom score as a composite outcome based on the rank of the change in score from baseline to moth 8, with a corresponding win ratio used to estimate the magnitude of the treatment effect.

McDonagh TA, Metra M, Adamo M et al (2021) 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) With the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 42(36):3599–3726. https://doi.org/10.1093/eurheartj/ehab368CrossRefPubMed

Heidenreich PA, Bozkurt B, Aguilar D et al (2022) 2022 AHA/ACC/HFSA guideline for the management of heart failure: A report of the American College of Cardiology/American Heart Association Joint Committee on clinical practice guidelines. Circulation 145(18):e895–e1032. https://doi.org/10.1161/CIR.0000000000001063CrossRefPubMed

Tsutsui H, Ide T, Ito H et al (2021) JCS/JHFS 2021 guideline focused update on diagnosis and treatment of acute and chronic heart failure. Circ J 85(12):2252–2291. https://doi.org/10.1253/circj.CJ-21-0431CrossRefPubMed

Teramoto K, Teng T-HK, Chandramouli C, Tromp J, Sakata Y, Lam CSP (2022) Epidemiology and clinical features of heart failure with preserved ejection fraction. Card Fail Rev 8:e27. https://doi.org/10.15420/cfr.2022.06CrossRefPubMedPubMedCentral

Shah SJ, Borlaug BA, Kitzman DW et al (2020) Research priorities for heart failure with preserved ejection fraction. Circulation 141(12):1001–1026. https://doi.org/10.1161/CIRCULATIONAHA.119.041886CrossRefPubMedPubMedCentral

European Medicines Agency (2022) Jardiance Summary of Product Characteristics. Boehringer Ingelheim. https://www.ema.europa.eu/en/documents/product-information/jardiance-epar-product-information_en.pdf. Accessed 7 Nov 2023

US Food and Drug Administration (2023) Jardiance prescribing information. Boehringer Ingelheim. https://content.boehringer-ingelheim.com/DAM/7d9c411c-ec33-4f82-886f-af1e011f35bb/jardiance-us-pi.pdf. Accessed 7 Nov 2023

European Medicines Agency (2023) Forxiga Summary of Product Characteristics. AstraZeneca. https://www.ema.europa.eu/en/documents/product-information/forxiga-epar-product-information_en.pdf

US Food and Drug Administration (2023) Farxiga prescribing information AstraZeneca. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/202293s026lbl.pdf. Accessed 7 Nov 2023

10.

US Food and Drug Administration (2021) Entresto prescribing information. Novartis. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/207620s018lbl.pdf. Accessed 7 Nov 2023

11.

Groenewegen A, Rutten FH, Mosterd A, Hoes AW (2020) Epidemiology of heart failure. Eur J Heart Fail 22(8):1342–1356. https://doi.org/10.1002/ejhf.1858CrossRefPubMed

12.

Dunlay SM, Roger VL, Redfield MM (2017) Epidemiology of heart failure with preserved ejection fraction. Nat Rev Cardiol 14(10):591–602. https://doi.org/10.1038/nrcardio.2017.65CrossRefPubMed

13.

Savarese G, Hage C, Benson L et al (2021) Eligibility for sacubitril/valsartan in heart failure across the ejection fraction spectrum: real-world data from the Swedish Heart Failure Registry. J Intern Med 289(3):369–384. https://doi.org/10.1111/joim.13165CrossRefPubMed

14.

Higgins J, Thomas J, Chandler J, Cumpston M, Li T, Page M, Welch V (2022) Cochrane Handbook for Systematic Reviews of Interventions version 6.3 (updated February 2022). Cochrane. www.training.cochrane.org/handbook. Accessed 7 Nov 2023

15.

Centre for Reviews and Dissemination (2009) Systematic Reviews: CRD’s guidance for undertaking reviews in health care. CRD, University of York. https://www.york.ac.uk/media/crd/Systematic_Reviews.pdf. Accessed 7 Nov 2023

16.

Shea B, O’Connell D, Peterson J, Welch V, Losos M, Tugwell P (2012) The Newcastle-Ottawa Scale (NOS) for assessing the quality if nonrandomized studies in meta-analyses. The Ottawa Hospital. http://www.hrica/programs/clinical_epidemiology/oxfordasp. Accessed 7 Nov 2023

17.

DGK (2021) Acute and chronic HF, Version 2021. German Cardiac Society, Düsseldorf, Germany

18.

HAS (2014) Guide Du Parcours De Soins. Insuffisance cardiaque. https://www.has-sante.fr/upload/docs/application/pdf/2012-04/guide_parcours_de_soins_ic_web.pdf. Accessed 7 Nov 2023

19.

IQWiG (2021) Leitliniensynopse für die Aktualisierung des DMP Herzinsuffizienz. Auftrag: V20-05, Version: 1.0, Stand: 19.07.2021. https://www.iqwig.de/download/v20-05_dmp-herzinsuffizienz_vorbericht_v1-0.pdf. Accessed 7 Nov 2023

20.

LOK nätverket för Sveriges läkemedelskommittéer (2022) Drug treatment in chronic HF. Pharmaceutical Committees’ National Network, Stockholm

21.

NBHW (2018) National guidelines for cardiac care. National Board of Health and Welfare (Socialstyrelsen), Stockholm

22.

NICE (2018) Chronic heart failure in adults: diagnosis and management. National Institute for Health and Care Excellence, London

23.

NVL (2019) National care guideline: chronic health failure. National Health Care Guidelines, Berlin

24.

SKS (2021) Person-centred and integrated care course in HF. Swedish Knowledge Support, Stockholm

25.

SMA (2015) HF: therapy recommendations (se. Hjärtsvikt). Swedish Medicines Agency. https://lakemedelsboken.se/kapitel/hjarta-karl/hjartsvikt.html. Accessed 7 Nov 2023

26.

Pieske B, Tschope C, de Boer RA et al (2020) How to diagnose heart failure with preserved ejection fraction: the HFA-PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). Eur J Heart Fail 22(3):391–412. https://doi.org/10.1002/ejhf.1741CrossRefPubMed

27.

Edelmann F, Knosalla C, Mörike K, Muth C, Prien P, Störk S (2018) Clinical Practice Guideline Chronic Heart Failure. Dtsch Arztebl Int 115(8):124–130. https://doi.org/10.3238/arztebl.2018.0124CrossRefPubMedPubMedCentral

28.

Hanon O, Belmin J, Benetos A et al (2021) Consensus of experts from the French Society of Geriatrics and Gerontology on the management of heart failure in very old subjects. Arch Cardiovasc Dis 114(3):246–259. https://doi.org/10.1016/j.acvd.2020.12.001CrossRefPubMed

29.

HAS (2015) Heart failure with preserved systolic function Acts and benefits–long-term condition. French National Authority for Health, Paris

30.

Kasiakogias A, Rosei EA, Camafort M et al (2021) Hypertension and heart failure with preserved ejection fraction: position paper by the European Society of Hypertension. J Hypertens 39(8):1522–1545. https://doi.org/10.1097/HJH.0000000000002910CrossRefPubMed

31.

CaReMeUK-HF (2022) HF management algorithm. British Cardiovascular Society. https://www.britishcardiovascularsociety.org/resources/careme. Accessed 7 Nov 2023

32.

Pieske B, Wachter R, Shah SJ et al (2021) Effect of sacubitril/valsartan vs standard medical therapies on plasma NT-proBNP concentration and submaximal exercise capacity in patients with heart failure and preserved ejection fraction: The PARALLAX randomized clinical trial. JAMA 326(19):1919–1929. https://doi.org/10.1001/jama.2021.18463CrossRefPubMedPubMedCentral

33.

Sakata Y, Shiba N, Takahashi J et al (2015) Clinical impacts of additive use of olmesartan in hypertensive patients with chronic heart failure: the supplemental benefit of an angiotensin receptor blocker in hypertensive patients with stable heart failure using olmesartan (SUPPORT) trial. Eur Heart J 36(15):915–923. https://doi.org/10.1093/eurheartj/ehu504CrossRefPubMedPubMedCentral

34.

Bhatt DL, Szarek M, Pitt B et al (2020) Sotagliflozin in patients with diabetes and chronic kidney disease. N Engl J Med 384(2):129–139. https://doi.org/10.1056/NEJMoa2030186CrossRefPubMed

35.

Feng M, He B, Wang B, Chen X, Chu H (2022) Clinical study of heart failure with left ventricular ejection fraction regimen treated with entresto. Contrast Media Mol Imaging 2022:4164089. https://doi.org/10.1155/2022/4164089CrossRefPubMedPubMedCentral

36.

Uijl A, Savarese G, Vaartjes I et al (2021) Identification of distinct phenotypic clusters in heart failure with preserved ejection fraction. Eur J Heart Fail 23(6):973–982. https://doi.org/10.1002/ejhf.2169CrossRefPubMed

37.

Harmon D, Rathousky J, Choudhry F et al (2020) Readmission risk factors and heart failure with preserved ejection fraction. J Am Osteopath Assoc 120(12):831–838. https://doi.org/10.7556/jaoa.2020.154CrossRefPubMed

38.

Hage C, Svedlund S, Saraste A et al (2020) Association of coronary microvascular dysfunction with heart failure hospitalizations and mortality in heart failure with preserved ejection fraction: A follow-up in the PROMIS-HFpEF study. J Card Fail 26(11):1016–1021. https://doi.org/10.1016/j.cardfail.2020.08.010CrossRefPubMed

39.

Shah SJ, Lam CSP, Svedlund S et al (2018) Prevalence and correlates of coronary microvascular dysfunction in heart failure with preserved ejection fraction: PROMIS-HFpEF. Eur Heart J 39(37):3439–3450. https://doi.org/10.1093/eurheartj/ehy531CrossRefPubMedPubMedCentral

40.

Takahari K, Hidaka T, Ueda Y et al (2019) H(2)FPEF score for the prediction of exercise intolerance and abnormal hemodynamics in Japanese–evaluation by exercise stress echocardiography combined with cardiopulmonary exercise testing. Circ J 83(12):2487–2493. https://doi.org/10.1253/circj.CJ-19-0699CrossRefPubMed

41.

Yoshihisa A, Sato Y, Kanno Y et al (2020) Prognostic impacts of changes in left ventricular ejection fraction in heart failure patients with preserved left ventricular ejection fraction. Open Heart 7(1):e001112. https://doi.org/10.1136/openhrt-2019-001112CrossRefPubMedPubMedCentral

42.

Hornsby WE, Sareini MA, Golbus JR, Willer CJ, McNamara JL, Konerman MC, Hummel SL (2019) Lower extremity function is independently associated with hospitalization burden in heart failure with preserved ejection fraction. J Card Fail 25(1):2–9. https://doi.org/10.1016/j.cardfail.2018.09.002CrossRefPubMed

43.

Fudim M, Kelly JP, Brophy TJ et al (2020) Trends in treatment for patients hospitalized with heart failure with preserved ejection fraction before and after treatment of preserved cardiac function heart failure with an aldosterone antagonist (TOPCAT). Am J Cardiol 125(11):1655–1660. https://doi.org/10.1016/j.amjcard.2020.02.038CrossRefPubMed

44.

Meyer M, Du Fay LJ, Benson L, Savarese G, Dahlström U, Lund LH (2021) Association between β-blockers and outcomes in heart failure with preserved ejection fraction: current insights from the SwedeHF registry. J Card Fail 27(11):1165–1174. https://doi.org/10.1016/j.cardfail.2021.04.015CrossRefPubMedPubMedCentral

45.

Bekfani T, Pellicori P, Morris D et al (2019) Iron deficiency in patients with heart failure with preserved ejection fraction and its association with reduced exercise capacity, muscle strength and quality of life. Clin Res Cardiol 108(2):203–211. https://doi.org/10.1007/s00392-018-1344-xCrossRefPubMed

46.

Perry AS, Mudigonda P, Huang GS, Qureshi B, Cheng RK, Levy WC, Li S (2022) Long-term outcomes and risk stratification of patients with heart failure with recovered ejection fraction. Am J Cardiol 173:80–87. https://doi.org/10.1016/j.amjcard.2022.03.006CrossRefPubMed

47.

Wenzel JP, Nikorowitsch J, Bei der Kellen R et al (2022) Heart failure in the general population and impact of the 2021 European Society of Cardiology Heart Failure Guidelines. ESC Heart Fail 9(4):2157–2169. https://doi.org/10.1002/ehf2.13948CrossRefPubMedPubMedCentral

48.

Davies DR, Redfield MM, Scott CG et al (2022) A simple score to identify increased risk of transthyretin amyloid cardiomyopathy in heart failure with preserved ejection fraction. JAMA Cardiol 7(10):1036–1044. https://doi.org/10.1001/jamacardio.2022.1781CrossRefPubMedPubMedCentral

49.

Brann A, Janvanishstaporn S, Greenberg B (2020) Association of prior left ventricular ejection fraction with clinical outcomes in patients with heart failure with midrange ejection fraction. JAMA Cardiol 5(9):1027–1035. https://doi.org/10.1001/jamacardio.2020.2081CrossRefPubMed

50.

Li DL, Quispe R, Onyekwelu C, Faillace RT, Taub CC (2019) Racial differences of heart failure with midrange ejection fraction (HFmrEF): a large urban centre-based retrospective cohort study in the USA. BMJ Open 9(4):e026479. https://doi.org/10.1136/bmjopen-2018-026479CrossRefPubMedPubMedCentral

51.

Cosentino F, Cannon CP, Cherney DZI et al (2020) Efficacy of ertugliflozin on heart failure-related events in patients with type 2 diabetes mellitus and established atherosclerotic cardiovascular disease: Results of the VERTIS CV trial. Circulation 142(23):2205–2215. https://doi.org/10.1161/circulationaha.120.050255CrossRefPubMedPubMedCentral

52.

Cannon CP, Pratley R, Dagogo-Jack S et al (2020) Cardiovascular outcomes with ertugliflozin in type 2 diabetes. N Engl J Med 383(15):1425–1435. https://doi.org/10.1056/NEJMoa2004967CrossRefPubMed

53.

Kato ET, Silverman MG, Mosenzon O et al (2019) Effect of dapagliflozin on heart failure and mortality in type 2 diabetes mellitus. Circulation 139(22):2528–2536. https://doi.org/10.1161/CIRCULATIONAHA.119.040130CrossRefPubMed

54.

Szarek M, Bhatt DL, Steg PG et al (2021) Effect of Sotagliflozin on Total Hospitalizations in Patients With Type 2 Diabetes and Worsening Heart Failure : A Randomized Trial. Ann Intern Med 174(8):1065–1072. https://doi.org/10.7326/m21-0651CrossRefPubMed

55.

Miura M, Sakata Y, Miyata S et al (2016) Influence of left ventricular ejection fraction on the effects of supplemental use of angiotensin receptor blocker olmesartan in hypertensive patients with heart failure. Circ J 80(10):2155–2164. https://doi.org/10.1253/circj.CJ-16-0577CrossRefPubMed

56.

Tromp J, Lim SL, Tay WT et al (2019) Microvascular disease in patients with diabetes with heart failure and reduced ejection versus preserved ejection fraction. Diabetes Care 42(9):1792–1799. https://doi.org/10.2337/dc18-2515CrossRefPubMed

57.

Subramaniam AV, Weston SA, Killian JM et al (2022) Development of advanced heart failure: a population-based study. Circ Heart Fail 15(5):e009218. https://doi.org/10.1161/circheartfailure.121.009218CrossRefPubMedPubMedCentral

58.

Ho JE, Redfield MM, Lewis GD, Paulus WJ, Lam CSP (2020) Deliberating the diagnostic dilemma of heart failure with preserved ejection fraction. Circulation 142(18):1770–1780. https://doi.org/10.1161/CIRCULATIONAHA.119.041818CrossRefPubMedPubMedCentral

59.

Garg P, Dakshi A, Assadi H et al (2021) Characterisation of the patients with suspected heart failure: experience from the SHEAF Registry. Open Heart 8(1):e001448. https://doi.org/10.1136/openhrt-2020-001448CrossRefPubMedPubMedCentral

60.

Cohen-Solal A, Philip JL, Picard F et al (2022) Iron deficiency in heart failure patients: the French CARENFER prospective study. ESC Heart Fail 9(2):874–884. https://doi.org/10.1002/ehf2.13850CrossRefPubMedPubMedCentral

61.

Lindberg F, Lund LH, Benson L et al (2022) Patient profile and outcomes associated with follow-up in specialty vs. primary care in heart failure. ESC Heart Fail 9(2):822–833. https://doi.org/10.1002/ehf2.13848CrossRefPubMedPubMedCentral

62.

Lorenzo CJ, Conte JI, Villasmil RJ, Abdelal QK, Pierce D, Wiese-Rometsch W, Garcia-Fernandez JA (2022) Heart failure ejection fraction class conversions: impact of biomarkers, co-morbidities, and pharmacotherapy. ESC Heart Fail 9(4):2538–2547. https://doi.org/10.1002/ehf2.13965CrossRefPubMedPubMedCentral

63.

Shiga T, Suzuki A, Haruta S et al (2019) Clinical characteristics of hospitalized heart failure patients with preserved, mid-range, and reduced ejection fractions in Japan. ESC Heart Fail 6(3):475–486. https://doi.org/10.1002/ehf2.12418CrossRefPubMedPubMedCentral

64.

An M, Mehta A, Min BH et al (2023) Sequential pembrolizumab cooperates with platinum/5FU to remodel the tumor microenvironment in advanced gastric cancer: a phase II chemoimmunotherapy trial. medRxiv. https://doi.org/10.1101/2023.04.03.23288062

65.

Ibrahim NE, Song Y, Cannon CP et al (2019) Heart failure with mid-range ejection fraction: characterization of patients from the PINNACLE Registry^®. ESC Heart Fail 6(4):784–792. https://doi.org/10.1002/ehf2.12455CrossRefPubMedPubMedCentral

66.

Göbel S, Prochaska JH, Tröbs SO et al (2021) Rationale, design and baseline characteristics of the MyoVasc study: A prospective cohort study investigating development and progression of heart failure. Eur J Prev Cardiol 28(9):1009–1018. https://doi.org/10.1177/2047487320926438CrossRefPubMed

67.

Aizawa N, Konishi M, Kitai T et al (2022) Infrequent use of nighttime dialysis for emergency admission due to worsening heart failure in patients on maintenance hemodialysis. Ther Apher Dial 26(1):85–93. https://doi.org/10.1111/1744-9987.13644CrossRefPubMed

68.

Tsukamoto K, Suzuki A, Shiga T, Arai K, Hagiwara N (2021) Changes in the left ventricular ejection fraction and outcomes in hospitalized heart failure patients with mid-range ejection fraction: a prospective observational study. Intern Med 60(10):1509–1518. https://doi.org/10.2169/internalmedicine.6388-20CrossRefPubMed

69.

Yoshihisa A, Ichijo Y, Sato Y et al (2020) Comprehensive clinical characteristics of hospitalized patients with mid-range left ventricular ejection fraction. Eur J Prev Cardiol 27(19):2084–2088. https://doi.org/10.1177/2047487319859689CrossRefPubMed

70.

Tromp J, Tay WT, Ouwerkerk W et al (2018) Multimorbidity in patients with heart failure from 11 Asian regions: A prospective cohort study using the ASIAN-HF registry. PLoS Med 15(3):e1002541. https://doi.org/10.1371/journal.pmed.1002541CrossRefPubMedPubMedCentral

71.

Abraham WT, Lindenfeld J, Ponikowski P et al (2021) Effect of empagliflozin on exercise ability and symptoms in heart failure patients with reduced and preserved ejection fraction, with and without type 2 diabetes. Eur Heart J 42(6):700–710. https://doi.org/10.1093/eurheartj/ehaa943CrossRefPubMed

72.

Greenberg B, Peterson ED, Berger JS et al (2019) Ejection fraction, B-type natriuretic peptide and risk of stroke and acute myocardial infarction among patients with heart failure. Clin Cardiol 42(2):277–284. https://doi.org/10.1002/clc.23140CrossRefPubMedPubMedCentral

73.

Jentzer JC, Reddy YN, Rosenbaum AN, Dunlay SM, Borlaug BA, Hollenberg SM (2022) Outcomes and predictors of mortality among cardiac intensive care unit patients with heart failure. J Card Fail 28(7):1088–1099. https://doi.org/10.1016/j.cardfail.2022.02.015CrossRefPubMed

74.

Fayol A, Wack M, Livrozet M et al (2022) Aetiological classification and prognosis in patients with heart failure with preserved ejection fraction. ESC Heart Fail 9(1):519–530. https://doi.org/10.1002/ehf2.13717CrossRefPubMed

75.

Alasdair H, Jingzhou H, Alice C, Stelios I, Phil K (2020) The impact of an integrated heart failure service in a medium-sized district general hospital. Open Heart 7(1):e001218. https://doi.org/10.1136/openhrt-2019-001218CrossRef

76.

Seki T, Kubota Y, Matsuda J, Tokita Y, Iwasaki YK, Shimizu W (2022) Clinical features and long-term prognosis of patients with congestive heart failure taking tolvaptan: a comparison of patients with preserved and reduced left ventricular ejection fraction. Heart Vessels 37(4):574–582. https://doi.org/10.1007/s00380-021-01957-1CrossRefPubMed

77.

Arnold SV, Echouffo-Tcheugui JB, Lam CSP et al (2018) Patterns of glucose-lowering medication use in patients with type 2 diabetes and heart failure. Insights from the Diabetes Collaborative Registry (DCR). Am Heart J 203:25–29. https://doi.org/10.1016/j.ahj.2018.05.016CrossRefPubMed

78.

Butler J, Filippatos G, Jamal Siddiqi T et al (2022) Empagliflozin, health status, and quality of life in patients with heart failure and preserved ejection fraction: The EMPEROR-Preserved Trial. Circulation 145(3):184–193. https://doi.org/10.1161/circulationaha.121.057812CrossRefPubMed

79.

Solomon SD, McMurray JJV, Claggett B et al (2022) Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med 387(12):1089–1098. https://doi.org/10.1056/NEJMoa2206286CrossRefPubMed

80.

Nassif ME, Windsor SL, Borlaug BA et al (2021) The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial. Nat Med 27(11):1954–1960. https://doi.org/10.1038/s41591-021-01536-xCrossRefPubMedPubMedCentral

81.

Anker SD, Siddiqi TJ, Filippatos G et al (2022) Outcomes with empagliflozin in heart failure with preserved ejection fraction using DELIVER-like endpoint definitions. Eur J Heart Fail 24(8):1400–1405. https://doi.org/10.1002/ejhf.2558CrossRefPubMed

82.

Anker SD, Butler J, Filippatos G et al (2021) Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med 385(16):1451–1461. https://doi.org/10.1056/NEJMoa2107038CrossRefPubMed

83.

Yusuf S, Pfeffer MA, Swedberg K et al (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. https://doi.org/10.1016/s0140-6736(03)14285-7CrossRefPubMed

84.

Cleland JG, Tendera M, Adamus J, Freemantle N, Polonski L, Taylor J (2006) The perindopril in elderly people with chronic heart failure (PEP-CHF) study. Eur Heart J 27(19):2338–2345. https://doi.org/10.1093/eurheartj/ehl250CrossRefPubMed

85.

Solomon SD, McMurray JJV, Anand IS et al (2019) Angiotensin–neprilysin inhibition in heart failure with preserved ejection fraction. N Engl J Med 381(17):1609–1620. https://doi.org/10.1056/NEJMoa1908655CrossRefPubMed

86.

Pitt B, Pfeffer MA, Assmann SF et al (2014) Spironolactone for heart failure with preserved ejection fraction. N Engl J Med 370(15):1383–1392. https://doi.org/10.1056/NEJMoa1313731CrossRefPubMed

87.

Afzal A, van Zyl J, Nisar T et al (2022) Trends in hospital admissions for systolic and diastolic heart failure in the United States between 2004 and 2017. Am J Cardiol 171:99–104. https://doi.org/10.1016/j.amjcard.2022.01.047CrossRefPubMed

88.

Clark KAA, Reinhardt SW, Chouairi F et al (2022) Trends in heart failure hospitalizations in the US from 2008 to 2018. J Card Fail 28(2):171–180. https://doi.org/10.1016/j.cardfail.2021.08.020CrossRefPubMed

89.

Reinhardt SW, Chouairi F, Miller PE et al (2021) National trends in the burden of atrial fibrillation during hospital admissions for heart failure. J Am Heart Assoc 10(11):e019412. https://doi.org/10.1161/jaha.120.019412CrossRefPubMedPubMedCentral

90.

Ambrosy AP, Parikh RV, Sung SH et al (2021) A natural language processing-based approach for identifying hospitalizations for worsening heart failure within an integrated health care delivery system. JAMA Netw Open 4(11):e2135152. https://doi.org/10.1001/jamanetworkopen.2021.35152CrossRefPubMedPubMedCentral

91.

Desai RJ, Mahesri M, Chin K et al (2021) Epidemiologic characterization of heart failure with reduced or preserved ejection fraction populations identified using Medicare claims. Am J Med 134(4):e241–e251. https://doi.org/10.1016/j.amjmed.2020.09.038CrossRefPubMed

92.

Desai RJ, Solomon SD, Vaduganathan M (2022) Rates of spironolactone initiation and subsequent hyperkalemia hospitalizations in patients with heart failure with preserved ejection fraction following the TOPCAT trial: A cohort study of Medicare beneficiaries. J Card Fail 28(6):1035–1039. https://doi.org/10.1016/j.cardfail.2022.01.012CrossRefPubMed

93.

European Medicines Agency (2017) Guideline on clinical investigation of medicinal products for the treatment of chronic heart failure CPMP/EWP/235/95, Rev.2. 7 Nov 2023. https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-clinical-investigation-medicinal-products-treatment-chronic-heart-failure-revision-2_en.pdf

94.

Spertus J (2016) Medical Device Development Tool (MDDT) qualification decision summary for Kansas City Cardiomyopathy Questionnaire (KCCQ). St Luke's Mid America Heart Institute. https://www.fda.gov/media/108301/download. Accessed 7 Nov 2023

95.

Huang W, Teng TK, Tay WT et al (2020) Patient-reported outcomes in heart failure with preserved vs. reduced ejection fraction: focus on physical independence. ESC Heart Fail 7(5):2051–2062. https://doi.org/10.1002/ehf2.12950CrossRefPubMedPubMedCentral

96.

Joseph SM, Novak E, Arnold SV et al (2013) Comparable performance of the Kansas City Cardiomyopathy Questionnaire in patients with heart failure with preserved and reduced ejection fraction. Circ Heart Fail 6(6):1139–1146. https://doi.org/10.1161/circheartfailure.113.000359CrossRefPubMedPubMedCentral

97.

Spertus JA, Jones PG, Sandhu AT, Arnold SV (2020) Interpreting the Kansas City Cardiomyopathy Questionnaire in clinical trials and clinical care: JACC state-of-the-art review. J Am Coll Cardiol 76(20):2379–2390. https://doi.org/10.1016/j.jacc.2020.09.542CrossRefPubMed

98.

Lewis EF, Kim HY, Claggett B et al (2016) Impact of spironolactone on longitudinal changes in health-related quality of life in the treatment of preserved cardiac function heart failure with an aldosterone antagonist trial. Circ Heart Fail 9(3):e001937. https://doi.org/10.1161/circheartfailure.114.001937CrossRefPubMed

99.

Streng KW, Nauta JF, Hillege HL et al (2018) Non-cardiac comorbidities in heart failure with reduced, mid-range and preserved ejection fraction. Int J Cardiol 271:132–139. https://doi.org/10.1016/j.ijcard.2018.04.001CrossRefPubMed

100.

Lam CSP, Wood R, Vaduganathan M et al (2021) Contemporary economic burden in a real-world heart failure population with Commercial and Medicare supplemental plans. Clin Cardiol 44(5):646–655. https://doi.org/10.1002/clc.23585CrossRefPubMedPubMedCentral

101.

Kiuchi S, Hisatake S, Kabuki T, Oka T, Dobashi S, Fujii T, Ikeda T (2020) Comparable effect of tolvaptan in heart failure patients with preserved or reduced ejection fraction. Clin Exp Hypertens 42(2):110–117. https://doi.org/10.1080/10641963.2019.1583244CrossRefPubMed

102.

Center for Drug Evaluation and Research (2015) Approval package for application number 207620Orig1s018. Trade name: Entresto. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207620Orig1s000Approv.pdf. Accessed 7 Nov 2023

103.

Stewart J (2021) Entresto FDA approval history 2023. https://www.drugs.com/history/entresto.html. Accessed 7 Nov 2023

104.

European Medicines Agency (2023) Entresto Summary of Product Characteristics. 7 Nov 2023. https://www.ema.europa.eu/en/documents/product-information/entresto-epar-product-information_en.pdf.

105.

US Food and Drug Administration (2023) Drugs@FDA: FDA-Approved Drugs. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm. Accessed 7 Nov 2023

106.

Boehringer Ingelheim (2022) Jardiance^® (empagliflozin) becomes the first and only approved treatment in Europe for adults with symptomatic chronic heart failure regardless of ejection fraction (Press Release). https://www.boehringer-ingelheim.com/human-health/heart-diseases/heart-failure/preserved-heart-failure-treatment-approval-europe. Accessed 7 Nov 2023

107.

Eckford C (European Pharmaceutical Review) (2022) Dapagliflozin approved for heart failure across LVEFs. https://www.europeanpharmaceuticalreview.com/news/177359/dapagliflozin-approved-for-heart-failure-across-lvefs/. Accessed 7 Nov 2023

108.

Gallagher A (2023) FDA approves expanded label for dapagliflozin to reduce risk of cardiovascular death, hospitalization from heart failure. PharmacyTimes. https://www.pharmacytimes.com/view/fda-approves-expanded-label-for-dapagliflozin-to-reduce-risk-of-cardiovascular-death-hospitalization-from-heart-failure. Accessed 7 Nov 2023

109.

Pharmaceuticals and Medical Devices Agency (2020) New Drugs Approved in FY 2020. 7 Nov 2023. https://www.pmda.go.jp/files/000242574.pdf

110.

Pharmaceutical and Medical Devices Agency (2021) New Drugs Approved in FY 2021. 7 Nov 2023. https://www.pmda.go.jp/files/000250462.pdf

111.

Wohlfahrt P, Nativi-Nicolau J, Zhang M et al (2021) Quality of life in patients with heart failure with recovered ejection fraction. JAMA Cardiol 6(8):957–962. https://doi.org/10.1001/jamacardio.2021.0939CrossRefPubMed

112.

Borlaug BA, Sharma K, Shah SJ, Ho JE (2023) Heart Failure with preserved ejection fraction: JACC scientific statement. J Am Coll Cardiol 81(18):1810–1834. https://doi.org/10.1016/j.jacc.2023.01.049CrossRefPubMed

113.

Savarese G, Becher PM, Lund LH, Seferovic P, Rosano GMC, Coats AJS (2023) Global burden of heart failure: a comprehensive and updated review of epidemiology. Cardiovasc Res 118(17):3272–3287. https://doi.org/10.1093/cvr/cvac013CrossRefPubMed

114.

Dunlay SM, Roger VL, Weston SA, Jiang R, Redfield MM (2012) Longitudinal changes in ejection fraction in heart failure patients with preserved and reduced ejection fraction. Circ Heart Fail 5(6):720–726. https://doi.org/10.1161/circheartfailure.111.966366CrossRefPubMedPubMedCentral

115.

Cintron G, Johnson G, Francis G, Cobb F, Cohn JN (1993) Prognostic significance of serial changes in left ventricular ejection fraction in patients with congestive heart failure. The V-HeFT VA Cooperative Studies Group. Circulation 87(6 Suppl):Vi17–23PubMed

116.

Basuray A, French B, Ky B et al (2014) Heart failure with recovered ejection fraction: clinical description, biomarkers, and outcomes. Circulation 129(23):2380–2387. https://doi.org/10.1161/circulationaha.113.006855CrossRefPubMedPubMedCentral

117.

Kalogeropoulos AP, Fonarow GC, Georgiopoulou V et al (2016) Characteristics and outcomes of adult outpatients with heart failure and improved or recovered ejection fraction. JAMA Cardiol 1(5):510–518. https://doi.org/10.1001/jamacardio.2016.1325CrossRefPubMed

118.

Chamberlain AM, Boyd CM, Manemann SM et al (2020) Risk factors for heart failure in the community: Differences by age and ejection fraction. Am J Med 133(6):e237–e248. https://doi.org/10.1016/j.amjmed.2019.10.030CrossRefPubMed

119.

Chamberlain AM, St Sauver JL, Gerber Y et al (2015) Multimorbidity in heart failure: a community perspective. Am J Med 128(1):38–45. https://doi.org/10.1016/j.amjmed.2014.08.024CrossRefPubMed

120.

Murtaza G, Paul TK, Rahman ZU, Kelvas D, Lavine SJ (2020) Clinical characteristics, comorbidities and prognosis in patients with heart failure with mid-range ejection fraction. Am J Med Sci 359(6):325–333. https://doi.org/10.1016/j.amjms.2020.03.008CrossRefPubMed

121.

European Medicines Agency (2022) EMA/954956/2022 – Forxiga European Public Assessment Report, 2022, https://www.ema.europa.eu/en/documents/variation-report/forxiga-h-c-ws-2299-epar-assessment-report-variation_en.pdf. Accessed 7 Nov 2023.

122.

Center for Drug Evaluation and Research (2015) Approval package for application number 204629Orig1s001. Trade name: Jardiance. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/204629Orig1s001.pdf. Accessed 7 Nov 2023

123.

European Medicines Agency (2022) CHMP extension of indication variation assessment report: Jardiance. 7 Nov 2023. https://www.ema.europa.eu/en/documents/variation-report/jardiance-h-c-002677-ii-0060-epar-assessment-report-variation_en.pdf

124.

JCS/JHFS (2023) Recommendations for the appropriate use of SGLT2 inhibitors in the treatment of heart failure. https://www.j-circ.or.jp/cms/wp-content/uploads/2023/06/jcs_jhfs_Recommendation_SGLT2_Inhibitors__HF.pdf. Accessed 7 Nov 2023

125.

McDonagh TA, Metra M, Adamo M et al (2023) 2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) With the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J:ehad195. 7 Nov 2023. https://doi.org/10.1093/eurheartj/ehad195

126.

ClinicalTrials.gov (2023) A study of tirzepatide (LY3298176) in participants with heart failure with preserved ejection fraction and obesity (SUMMIT) (ClinicalTrials.gov ID: NCT04847557). https://clinicaltrials.gov/ct2/show/NCT04847557. Accessed 7 Nov 2023

127.

ClinicalTrials.gov (2023) Research study to look at how well semaglutide works in people living with heart failure, obesity and type 2 diabetes (STEP HFpEF DM) (ClinicalTrials.gov ID: NCT04916470). https://clinicaltrials.gov/ct2/show/NCT04916470. Accessed 7 Nov 2023

128.

ClinicalTrials.gov (2023) A research study to look at how ziltivekimab works compared to placebo in people with heart failure and inflammation (HERMES) (ClinicalTrials.gov ID: NCT05636176). https://clinicaltrials.gov/ct2/show/NCT05636176. Accessed 7 Nov 2023

129.

ClinicalTrials.gov (2023) Study to evaluate the efficacy and safety of AZD4831 in participants with heart failure with left ventricular ejection fraction > 40% (ENDEAVOR) (ClinicalTrials.gov ID: NCT04986202). https://clinicaltrials.gov/ct2/show/NCT04986202. Accessed 7 Nov 2023

130.

Hashemi H, Mechanick J (2021) The Pooled SCORED and SOLOIST-WHF Analysis. https://accessmedicine.mhmedical.com/updatesContent.aspx?gbosid=556865. Accessed 7 Nov 2023

131.

Edelmann F, Wachter R, Schmidt AG et al (2013) Effect of spironolactone on diastolic function and exercise capacity in patients with heart failure with preserved ejection fraction: the Aldo-DHF randomized controlled trial. JAMA 309(8):781–791. https://doi.org/10.1001/jama.2013.905CrossRefPubMed

132.

Ueda T, Kasama S, Yamamoto M et al (2021) Effect of the sodium-glucose cotransporter 2 inhibitor canagliflozin for heart failure with preserved ejection fraction in patients with type 2 diabetes. Circ Rep 3(8):440–448. https://doi.org/10.1253/circrep.CR-21-0030CrossRefPubMedPubMedCentral

133.

ClinicalTrials.gov (2021) DETERMINE-preserved-dapagliflozin effect on exercise capacity using a 6-minute walk test in patients with heart failure with preserved ejection fraction. https://classic.clinicaltrials.gov/ct2/show/NCT03877224. Accessed 7 Nov 2023

134.

Massie BM, Carson PE, McMurray JJ et al (2008) Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med 359(23):2456–2467. https://doi.org/10.1056/NEJMoa0805450CrossRefPubMed

135.

Kosmala W, Rojek A, Przewlocka-Kosmala M, Wright L, Mysiak A, Marwick TH (2016) Effect of aldosterone antagonism on exercise tolerance in heart failure with preserved ejection fraction. J Am Coll Cardiol 68(17):1823–1834. https://doi.org/10.1016/j.jacc.2016.07.763CrossRefPubMed

136.

Upadhya B, Hundley WG, Brubaker PH, Morgan TM, Stewart KP, Kitzman DW (2017) Effect of spironolactone on exercise tolerance and arterial function in older adults with heart failure with preserved ejection fraction. J Am Geriatr Soc 65(11):2374–2382. https://doi.org/10.1111/jgs.14940CrossRefPubMedPubMedCentral

137.

Yip GW, Wang M, Wang T et al (2008) 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 94(5):573–580. https://doi.org/10.1136/hrt.2007.117978CrossRefPubMed

138.

Yuksek U, Cerit L, Eren NK, Ergene O (2019) The effect of perindopril on echocardiographic parameters, NYHA functional class and serum NT-proBNP values in patients with diastolic heart failure. Cardiovasc J Afr 30(4):222–227. https://doi.org/10.5830/cvja-2019-022CrossRefPubMed

139.

Zi M, Carmichael N, Lye M (2003) The effect of quinapril on functional status of elderly patients with diastolic heart failure. Cardiovasc Drugs Ther 17(2):133–139. https://doi.org/10.1023/a:1025387702212CrossRefPubMed

140.

Davis BR, Kostis JB, Simpson LM et al (2008) Heart failure with preserved and reduced left ventricular ejection fraction in the antihypertensive and lipid-lowering treatment to prevent heart attack trial. Circulation 118(22):2259–2267. https://doi.org/10.1161/circulationaha.107.762229CrossRefPubMedPubMedCentral

141.

Tanaka A, Hisauchi I, Taguchi I et al (2020) Effects of canagliflozin in patients with type 2 diabetes and chronic heart failure: a randomized trial (CANDLE). ESC Heart Fail 7(4):1585–1594. https://doi.org/10.1002/ehf2.12707CrossRefPubMedPubMedCentral

142.

Spertus JA, Birmingham MC, Nassif M et al (2022) The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial. Nat Med 28(4):809–813. https://doi.org/10.1038/s41591-022-01703-8CrossRefPubMedPubMedCentral

143.

Tamisier R, Damy T, Davy JM et al (2020) Cohort profile: FACE, prospective follow-up of chronic heart failure patients with sleep-disordered breathing indicated for adaptive servo ventilation. BMJ Open 10(7):e038403. https://doi.org/10.1136/bmjopen-2020-038403CrossRefPubMedPubMedCentral

144.

Hawley A, He J, Crabtree A, Iacovides S, Keeling P (2020) The impact of an integrated heart failure service in a medium-sized district general hospital. Open Heart 7(1). https://doi.org/10.1136/openhrt-2019-001218

145.

Verdu-Rotellar JM, Vaillant-Roussel H, Abellana R et al (2020) Precipitating factors of heart failure decompensation, short-term morbidity and mortality in patients attended in primary care. Scand J Prim Health Care 38(4):473–480. https://doi.org/10.1080/02813432.2020.1844387CrossRefPubMedPubMedCentral

146.

Arora S, Jaswaney R, Jani C et al (2020) Catheter ablation for atrial fibrillation in patients with concurrent heart failure. Am J Cardiol 137:45–54. https://doi.org/10.1016/j.amjcard.2020.09.035CrossRefPubMed

147.

Buckallew AR, Tellor KB, Watson R et al (2021) Evaluation of the safety and tolerability of spironolactone in patients with heart failure and chronic kidney disease. Eur J Clin Pharmacol 77(7):955–960. https://doi.org/10.1007/s00228-020-03069-7CrossRefPubMed

148.

Contreras JP, Hong KN, Castillo J et al (2019) Anticoagulation in patients with atrial fibrillation and heart failure: Insights from the NCDR PINNACLE-AF registry. Clin Cardiol 42(3):339–345. https://doi.org/10.1002/clc.23142CrossRefPubMedPubMedCentral

149.

Dunlay SM, Roger VL, Killian JM et al (2021) Advanced heart failure epidemiology and outcomes: A population-based study. JACC Heart Fail 9(10):722–732. https://doi.org/10.1016/j.jchf.2021.05.009CrossRefPubMedPubMedCentral

150.

Hamo CE, Fonarow GC, Greene SJ et al (2021) Temporal trends in risk profiles among patients hospitalized for heart failure. Am Heart J 232:154–163. https://doi.org/10.1016/j.ahj.2020.11.015CrossRefPubMed

151.

Joyce E, Chung C, Badloe S et al (2016) Variable contribution of heart failure to quality of life in ambulatory heart failure with reduced, better, or preserved ejection fraction. JACC Heart Fail 4(3):184–193. https://doi.org/10.1016/j.jchf.2015.12.011CrossRefPubMed

152.

Lopuszynski JB, Downing AJ, Finley CM, Zahid M (2021) Prognosticators of All-cause mortality in patients with heart failure with preserved ejection fraction. Am J Cardiol 158:66–73. https://doi.org/10.1016/j.amjcard.2021.07.044CrossRefPubMedPubMedCentral

153.

Luo N, Xu H, Jneid H et al (2018) Use of oral anticoagulation in eligible patients discharged with heart failure and atrial fibrillation. Circ Heart Fail 11(10):e005356. https://doi.org/10.1161/circheartfailure.118.005356CrossRefPubMedPubMedCentral

154.

Navid P, Nguyen L, Jaber D et al (2021) Attitudes toward deprescribing among adults with heart failure with preserved ejection fraction. J Am Geriatr Soc 69(7):1948–1955. https://doi.org/10.1111/jgs.17204CrossRefPubMedPubMedCentral

155.

Patel RB, Fonarow GC, Greene SJ et al (2021) Kidney function and outcomes in patients hospitalized with heart failure. J Am Coll Cardiol 78(4):330–343. https://doi.org/10.1016/j.jacc.2021.05.002CrossRefPubMedPubMedCentral

156.

Regmi MR, Bhattarai M, Parajuli P et al (2020) Heart failure with preserved ejection fraction and 30-day readmission. Clin Med Res 18(4):126–132. https://doi.org/10.3121/cmr.2020.1521CrossRefPubMedPubMedCentral

157.

Yee D, Novak E, Platts A, Nassif ME, LaRue SJ, Vader JM (2019) Comparison of the Kansas City Cardiomyopathy Questionnaire and Minnesota Living With Heart Failure Questionnaire in predicting heart failure outcomes. Am J Cardiol 123(5):807–812. https://doi.org/10.1016/j.amjcard.2018.11.037CrossRefPubMed

158.

Kinugawa K, Sato N, Inomata T, Yasuda M, Shimakawa T, Fukuta Y (2019) A prospective, multicenter, post-marketing surveillance study to evaluate the safety and effectiveness of tolvaptan in patients with reduced, preserved, and mid-range ejection fraction heart failure. Int Heart J 60(5):1123–1130. https://doi.org/10.1536/ihj.18-671CrossRefPubMed

159.

Suzuki S, Motoki H, Minamisawa M et al (2019) Prognostic significance of high-sensitivity cardiac troponin in patients with heart failure with preserved ejection fraction. Heart Vessels 34(10):1650–1656. https://doi.org/10.1007/s00380-019-01393-2CrossRefPubMed

160.

Tomii D, Horiuchi Y, Gonda Y et al (2021) The role of the renal resistance index in patients with heart failure with reduced or preserved ejection fraction. J Cardiol 78(4):301–307. https://doi.org/10.1016/j.jjcc.2021.05.007CrossRefPubMed

161.

Chandramouli C, Tay WT, Bamadhaj NS et al (2019) Association of obesity with heart failure outcomes in 11 Asian regions: A cohort study. PLoS Med 16(9):e1002916. https://doi.org/10.1371/journal.pmed.1002916CrossRefPubMedPubMedCentral

162.

Kapelios CJ, Laroche C, Crespo-Leiro MG et al (2020) Association between loop diuretic dose changes and outcomes in chronic heart failure: observations from the ESC-EORP Heart Failure Long-Term Registry. Eur J Heart Fail 22(8):1424–1437. https://doi.org/10.1002/ejhf.1796CrossRefPubMed

Title: Heart failure with mildly reduced and preserved ejection fraction: A review of disease burden and remaining unmet medical needs within a new treatment landscape
Authors: Nihar Desai
Elzbieta Olewinska
Agata Famulska
Cécile Remuzat
Clément Francois
Kerstin Folkerts
Publication date: 27-02-2024
Publisher: Springer US
Keywords: Heart Failure
Valsartan
Published in: Heart Failure Reviews / Issue 3/2024
Print ISSN: 1382-4147
Electronic ISSN: 1573-7322
DOI: https://doi.org/10.1007/s10741-024-10385-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Heart failure with mildly reduced and preserved ejection fraction: A review of disease burden and remaining unmet medical needs within a new treatment landscape

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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