Skip to main content

Advertisement

SpringerLink
Log in

Advance in the pharmacological and comorbidities management of heart failure with preserved ejection fraction: evidence from clinical trials

  • Published:
Heart Failure Reviews Aims and scope Submit manuscript

Abstract

The prevalence of heart failure with preserved ejection fraction (HFpEF) accounts for approximately 50% of the total heart failure population, and with the aging of the population and the increasing prevalence of hypertension, obesity, and type 2 diabetes (T2DM), the incidence of HFpEF continues to rise and has become the most common subtype of heart failure. Compared with heart failure with reduced ejection fraction, HFpEF has a more complex pathophysiology and is more often associated with hypertension, T2DM, obesity, atrial fibrillation, renal insufficiency, pulmonary hypertension, obstructive sleep apnea, and other comorbidities. HFpEF has generally been considered a syndrome with high phenotypic heterogeneity, and no effective treatments have been shown to reduce mortality to date. Diuretics and comorbidity management are traditional treatments for HFpEF; however, they are mostly empirical due to a lack of clinical evidence in the setting of HFpEF. With the EMPEROR-Preserved and DELIVER results, sodium-glucose cotransporter 2 inhibitors become the first evidence-based therapies to reduce rehospitalization for heart failure. Subgroup analyses of the PARAGON-HF, TOPCAT, and CHARM-Preserved trials suggest that angiotensin receptor-neprilysin inhibitors, spironolactone, and angiotensin II receptor blockers may be beneficial in patients at the lower end of the ejection fraction spectrum. Other potential pharmacotherapies represented by non-steroidal mineralocorticoid receptor antagonists finerenone and antifibrotic agent pirfenidone also hold promise for the treatment of HFpEF. This article intends to review the clinical evidence on current pharmacotherapies of HFpEF, as well as the comorbidities management of atrial fibrillation, hypertension, T2DM, obesity, pulmonary hypertension, renal insufficiency, obstructive sleep apnea, and iron deficiency, to optimize the clinical management of HFpEF.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Availability of data and material

Not applicable.

References

  1. Becher PM, Lund LH, Coats AJS, Savarese G (2022) An update on global epidemiology in heart failure. Eur heart J

  2. Tsao CW, Aday AW, Almarzooq ZI, Alonso A, Beaton AZ, Bittencourt MS, Boehme AK, Buxton AE, Carson AP, Commodore-Mensah Y et al (2022) Heart disease and stroke statistics-2022 update: a report from the American Heart Association. Circulation 145(8):e153–e639

    Article  PubMed  Google Scholar 

  3. Mentz RJ, Kelly JP, von Lueder TG, Voors AA, Lam CS, Cowie MR, Kjeldsen K, Jankowska EA, Atar D, Butler J et al (2014) Noncardiac comorbidities in heart failure with reduced versus preserved ejection fraction. J Am Coll Cardiol 64(21):2281–2293

    Article  PubMed  PubMed Central  Google Scholar 

  4. Streng KW, Nauta JF, Hillege HL, Anker SD, Cleland JG, Dickstein K, Filippatos G, Lang CC, Metra M, Ng LL et al (2018) Non-cardiac comorbidities in heart failure with reduced, mid-range and preserved ejection fraction. Int J Cardiol 271:132–139

    Article  PubMed  Google Scholar 

  5. Pieske B, Tschöpe C, de Boer RA, Fraser AG, Anker SD, Donal E, Edelmann F, Fu M, Guazzi M, Lam CSP et al (2019) 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 Heart J 40(40):3297–3317

    Article  PubMed  Google Scholar 

  6. Uijl A, Savarese G, Vaartjes I, Dahlström U, Brugts JJ, Linssen GCM, van Empel V, Brunner-La Rocca HP, Asselbergs FW, Lund LH et al (2021) Identification of distinct phenotypic clusters in heart failure with preserved ejection fraction. Eur J Heart Fail 23(6):973–982

    Article  PubMed  Google Scholar 

  7. Palazzuoli A, Buono MGD, Ruocco G, Caravita S, Abbate A, Lavie CJ (2023) The conundrum of HFpEF definition: non-invasive assessment uncertainties and alternative diagnostic strategies. Curr Probl Cardiol 48(1):101433

    Article  PubMed  Google Scholar 

  8. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O et al (2021) 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 42(36):3599–3726

    Article  CAS  PubMed  Google Scholar 

  9. Solomon SD, McMurray JJV, Anand IS, Ge J, Lam CSP, Maggioni AP, Martinez F, Packer M, Pfeffer MA, Pieske B et al (2019) Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction. N Engl J Med 381(17):1609–1620

    Article  CAS  PubMed  Google Scholar 

  10. Raschi E, Diemberger I, Sabatino M, Poluzzi E, De Ponti F, Potena L (2022) Evaluating sacubitril/valsartan as a treatment option for heart failure with reduced ejection fraction and preserved ejection fraction. Expert Opin Pharmacother 23(3):303–320

    Article  CAS  PubMed  Google Scholar 

  11. Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Böhm M, Brunner-La Rocca HP, Choi DJ, Chopra V, Chuquiure-Valenzuela E et al (2021) Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med 385(16):1451–1461

    Article  CAS  PubMed  Google Scholar 

  12. Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR et al (2022) 2022 AHA/ACC/HFSA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology/American Heart Association Joint Committee on clinical practice guidelines. J Am Coll Cardiol 79(17):1757–1780

    Article  PubMed  Google Scholar 

  13. Solomon SD, McMurray JJV, Claggett B, de Boer RA, DeMets D, Hernandez AF, Inzucchi SE, Kosiborod MN, Lam CSP, Martinez F et al (2022) Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med 387(12):1089–1098

    Article  PubMed  Google Scholar 

  14. Filippatos G, Anker SD, Agarwal R, Ruilope LM, Rossing P, Bakris GL, Tasto C, Joseph A, Kolkhof P, Lage A et al (2022) Finerenone reduces risk of incident heart failure in patients with chronic kidney disease and type 2 diabetes: analyses from the FIGARO-DKD trial. Circulation 145(6):437–447

    Article  CAS  PubMed  Google Scholar 

  15. Lewis GA, Dodd S, Clayton D, Bedson E, Eccleson H, Schelbert EB, Naish JH, Jimenez BD, Williams SG, Cunnington C et al (2021) Pirfenidone in heart failure with preserved ejection fraction: a randomized phase 2 trial. Nat Med 27(8):1477–1482

    Article  CAS  PubMed  Google Scholar 

  16. Palau P, Seller J, Domínguez E, Sastre C, Ramón JM, de La Espriella R, Santas E, Miñana G, Bodí V, Sanchis J et al (2021) Effect of β-blocker withdrawal on functional capacity in heart failure and preserved ejection fraction. J Am Coll Cardiol 78(21):2042–2056

    Article  CAS  PubMed  Google Scholar 

  17. Singh A, Agarwal A, Wafford QE, Shah SJ, Huffman M, Khan S (2022) Efficacy and safety of diuretics in heart failure with preserved ejection fraction: a scoping review. Heart 108(8):593–605

    Article  CAS  PubMed  Google Scholar 

  18. Verbrugge FH, Menon V (2022) In perspective: torsemide comparison with furosemide for management of heart failure (TRANSFORM-HF) trial. Eur Heart J Acute Cardiovasc Care

  19. Faselis C, Arundel C, Patel S, Lam PH, Gottlieb SS, Zile MR, Deedwania P, Filippatos G, Sheriff HM, Zeng Q et al (2020) Loop diuretic prescription and 30-day outcomes in older patients with heart failure. J Am Coll Cardiol 76(6):669–679

    Article  PubMed  PubMed Central  Google Scholar 

  20. Ter Maaten JM, Rao VS, Hanberg JS, Perry Wilson F, Bellumkonda L, Assefa M, Sam Broughton J, D’Ambrosi J, Wilson Tang WH, Damman K et al (2017) Renal tubular resistance is the primary driver for loop diuretic resistance in acute heart failure. Eur J Heart Fail 19(8):1014–1022

    Article  PubMed  Google Scholar 

  21. Montero D, Flammer AJ (2017) Exercise intolerance in heart failure with preserved ejection fraction: time to scrutinize diuretic therapy? Eur J Heart Fail 19(8):971–973

    Article  PubMed  Google Scholar 

  22. van Kraaij DJ, Jansen RW, Bouwels LH, Gribnau FW, Hoefnagels WH (2000) Furosemide withdrawal in elderly heart failure patients with preserved left ventricular systolic function. Am J Cardiol 85(12):1461–1466

    Article  PubMed  Google Scholar 

  23. Brisco-Bacik MA, Ter Maaten JM, Houser SR, Vedage NA, Rao V, Ahmad T, Wilson FP, Testani JM (2018) Outcomes associated with a strategy of adjuvant metolazone or high-dose loop diuretics in acute decompensated heart failure: a propensity analysis. J Am Heart Assoc 7(18):e009149

    Article  PubMed  PubMed Central  Google Scholar 

  24. Khan SS, Huffman MD, Shah SJ (2021) Could a low-dose diuretic polypill improve outcomes in heart failure with preserved ejection fraction? Circ Heart Fail 14(3):e008090

    Article  PubMed  PubMed Central  Google Scholar 

  25. Pabel S, Hamdani N, Singh J, Sossalla S (2021) Potential mechanisms of SGLT2 inhibitors for the treatment of heart failure With preserved ejection fraction. Front Physiol 12:752370

    Article  PubMed  PubMed Central  Google Scholar 

  26. Wei J, Du J (2023) Mechanisms of sodium-glucose cotransporter 2 inhibitors in heart failure. Cardiovasc Innov Appl 8(1)

  27. Packer M, Butler J, Zannad F, Filippatos G, Ferreira JP, Pocock SJ, Carson P, Anand I, Doehner W, Haass M et al (2021) Effect of empagliflozin on worsening heart failure events in patients with heart failure and preserved ejection fraction: EMPEROR-Preserved trial. Circulation 144(16):1284–1294

    Article  PubMed  PubMed Central  Google Scholar 

  28. Ferreira JP, Butler J, Zannad F, Filippatos G, Schueler E, Steubl D, Zeller C, Januzzi JL, Pocock S, Packer M et al (2022) Mineralocorticoid receptor antagonists and empagliflozin in patients with heart failure and preserved ejection fraction. J Am Coll Cardiol 79(12):1129–1137

    Article  CAS  PubMed  Google Scholar 

  29. Amerena JJH (2022) Outcomes of empagliflozin in patients with heart failure with a preserved ejection fraction and atrial fibrillation or atrial flutter: insights from EMPEROR-Preserved. Lung Circ 31:S93-S94

  30. Nicholls SJH (2022) Empagliflozin improves cardiovascular and renal outcomes in patients with preserved ejection fraction irrespective of blood pressure–the EMPEROR-Preserved trial. Lung, Circ 31:S81-S82

  31. Böhm M, Butler J, Filippatos G, Ferreira JP, Pocock SJ, Abdin A, Mahfoud F, Brueckmann M, Gollop ND, Iwata T et al (2022) Empagliflozin improves outcomes in patients with heart failure and preserved ejection fraction irrespective of age 80(1):1–18

    Google Scholar 

  32. Yang M, Butt JH, Kondo T, Jering KS, Docherty KF, Jhund PS, de Boer RA, Claggett BL, Desai AS, Hernandez AF et al (2022) Dapagliflozin in patients with heart failure with mildly reduced and preserved ejection fraction treated with a mineralocorticoid receptor antagonist or sacubitril/valsartan. Eur J Heart Fail

  33. Nassif ME, Windsor SL, Borlaug BA, Kitzman DW, Shah SJ, Tang F, Khariton Y, Malik AO, Khumri T, Umpierrez G et al (2021) The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial. Nat Med 27(11):1954–1960

    Article  PubMed  PubMed Central  Google Scholar 

  34. Spertus JA, Birmingham MC, Nassif M, Damaraju CV, Abbate A, Butler J, Lanfear DE, Lingvay I, Kosiborod MN, Januzzi JL (2022) The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial. Nat Med 28(4):809–813

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Mone P, Lombardi A, Gambardella J, Pansini A, Macina G, Morgante M, Frullone S, Santulli G (2022) Empagliflozin improves cognitive impairment in frail older adults with type 2 diabetes and heart failure with preserved ejection fraction. Diabetes Care 45(5):1247–1251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Bhatt DL, Szarek M, Steg PG, Cannon CP, Leiter LA, McGuire DK, Lewis JB, Riddle MC, Voors AA, Metra M et al (2021) Sotagliflozin in patients with diabetes and recent worsening heart failure. N Engl J Med 384(2):117–128

    Article  CAS  PubMed  Google Scholar 

  37. McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K et al (2014) Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med 371(11):993–1004

    Article  PubMed  Google Scholar 

  38. Solomon SD, Zile M, Pieske B, Voors A, Shah A, Kraigher-Krainer E, Shi V, Bransford T, Takeuchi M, Gong J et al (2012) The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomised controlled trial. Lancet (London, England) 380(9851):1387–1395

    Article  CAS  PubMed  Google Scholar 

  39. Solomon SD, Vaduganathan ML, Claggett B, Packer M, Zile M, Swedberg K, Rouleau J, A. Pfeffer M, Desai A, Lund L, Kober L et al (2020) Sacubitril/valsartan across the spectrum of ejection fraction in heart failure. Circulation 141(5):352–361

    Article  PubMed  Google Scholar 

  40. Vaduganathan M, Claggett BL, Desai AS, Anker SD, Perrone SV, Janssens S, Milicic D, Arango JL, Packer M, Shi VC et al (2020) Prior heart failure hospitalization, clinical outcomes, and response to sacubitril/valsartan compared with valsartan in HFpEF. J Am Coll Cardiol 75(3):245–254

    Article  CAS  PubMed  Google Scholar 

  41. Gori M, Senni M, Claggett B, Liu J, Maggioni AP, Zile M, Prescott MF, Van Veldhuisen DJ, Zannad F, Pieske B et al (2021) Integrating high-sensitivity troponin T and sacubitril/valsartan treatment in HFpEF: the PARAGON-HF trial. JACC Heart failure 9(9):627–635

    Article  PubMed  Google Scholar 

  42. Vaduganathan M, Cunningham JW, Claggett BL, Causland FM, Barkoudah E, Finn P, Zannad F, Pfeffer MA, Rizkala AR, Sabarwal S et al (2021) Worsening heart failure episodes outside a hospital setting in heart failure with preserved ejection fraction: the PARAGON-HF trial. JACC Heart failure 9(5):374–382

    Article  PubMed  Google Scholar 

  43. Codina P, Domingo M, Barceló E, Gastelurrutia P, Casquete D, Vila J, Abdul-Jawad Altisent O, Spitaleri G, Cediel G, Santiago-Vacas E et al (2022) Sacubitril/valsartan affects pulmonary arterial pressure in heart failure with preserved ejection fraction and pulmonary hypertension. ESC heart failure 9(4):2170–2180

    Article  PubMed  PubMed Central  Google Scholar 

  44. Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B, Clausell N, Desai AS, Diaz R, Fleg JL et al (2014) Spironolactone for heart failure with preserved ejection fraction. N Engl J Med 370(15):1383–1392

    Article  CAS  PubMed  Google Scholar 

  45. Pfeffer MA, Claggett B, Assmann SF, Boineau R, Anand IS, Clausell N, Desai AS, Diaz R, Fleg JL, Gordeev I et al (2015) Regional variation in patients and outcomes in the treatment of preserved cardiac function heart failure with an aldosterone antagonist (TOPCAT) trial. Circulation 131(1):34–42

    Article  CAS  PubMed  Google Scholar 

  46. Solomon SD, Claggett B, Lewis EF, Desai A, Anand I, Sweitzer NK, O’Meara E, Shah SJ, McKinlay S, Fleg JL et al (2016) Influence of ejection fraction on outcomes and efficacy of spironolactone in patients with heart failure with preserved ejection fraction. Eur Heart J 37(5):455–462

    Article  CAS  PubMed  Google Scholar 

  47. Choy M, Liang W, He J, Fu M, Dong Y, He X, Liu C (2022) Phenotypes of heart failure with preserved ejection fraction and effect of spironolactone treatment. ESC Heart Fail

  48. Elkholey K, Papadimitriou L, Butler J, Thadani U, Stavrakis S (2021) Effect of obesity on response to spironolactone in patients with heart failure with preserved ejection fraction. Am J Cardiol 146:36–47

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Kintscher U, Bakris GL, Kolkhof P (2022) Novel non-steroidal mineralocorticoid receptor antagonists in cardiorenal disease. Br J Pharmacol 179(13):3220–3234

    Article  CAS  PubMed  Google Scholar 

  50. Lorente-Ros M, Aguilar-Gallardo JS, Shah A, Narasimhan B, Aronow WS (2022) An overview of mineralocorticoid receptor antagonists as a treatment option for patients with heart failure: the current state-of-the-art and future outlook. Expert Opin Pharmacother 23(15):1737–1751

    Article  CAS  PubMed  Google Scholar 

  51. Bakris GL, Agarwal R, Anker SD, Pitt B, Ruilope LM, Rossing P, Kolkhof P, Nowack C, Schloemer P, Joseph A et al (2020) Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med 383(23):2219–2229

    Article  CAS  PubMed  Google Scholar 

  52. Pitt B, Filippatos G, Agarwal R, Anker SD, Bakris GL, Rossing P, Joseph A, Kolkhof P, Nowack C, Schloemer P et al (2021) Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N Engl J Med 385(24):2252–2263

    Article  CAS  PubMed  Google Scholar 

  53. Georgianos PI, Agarwal R (2022) The non-steroidal MRA finerenone in cardiorenal medicine: a state-of-the-art review of the literature. Am J Hypertens

  54. Bayer (2020) Study to evaluate the efficacy (effect on disease) and safety of finerenone on morbidity (events indicating disease worsening) and mortality (death rate) in participants with heart failure and left ventricular ejection fraction (proportion of blood expelled per heart stroke) greater or equal to 40%(FINEARTS-HF)

  55. Yusuf S, Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, Olofsson B, Ostergren J (2003) Effects of Candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved trial. Lancet (London, England) 362(9386):777–781

    Article  CAS  PubMed  Google Scholar 

  56. Lund LH, Claggett B, Liu J, Lam CS, Jhund PS, Rosano GM, Swedberg K, Yusuf S, Granger CB, Pfeffer MA et al (2018) Heart failure with mid-range ejection fraction in CHARM: characteristics, outcomes and effect of candesartan across the entire ejection fraction spectrum. Eur J Heart Fail 20(8):1230–1239

    Article  CAS  PubMed  Google Scholar 

  57. Martin N, Manoharan K, Davies C, Lumbers RT (2021) Beta-blockers and inhibitors of the renin-angiotensin aldosterone system for chronic heart failure with preserved ejection fraction. Cochrane Database Syst Rev 5(5):Cd012721

  58. Meyer M, LeWinter MM (2019) Heart rate and heart failure with preserved ejection fraction: time to slow β-blocker use? Circ Heart Fail 12(8):e006213

    Article  PubMed  PubMed Central  Google Scholar 

  59. Zweerink A, van der Lingen ACJ, Handoko ML, van Rossum AC, Allaart CP (2018) Chronotropic incompetence in chronic heart failure. Circ Heart Fail 11(8):e004969

    Article  PubMed  Google Scholar 

  60. Silverman DN, Plante TB, Infeld M, Callas PW, Juraschek SP, Dougherty GB, Meyer M (2019) Association of β-blocker use with heart failure hospitalizations and cardiovascular disease mortality among patients with heart failure with a preserved ejection fraction: a secondary analysis of the TOPCAT trial. JAMA Netw Open 2(12):e1916598

    Article  PubMed  PubMed Central  Google Scholar 

  61. Fauchier L, Bodin A, Bisson A (2022) Beta-blocker withdrawal and chronotropic incompetence in heart failure with preserved ejection fraction. J Am Coll Cardiol 79(9):e195

    Article  CAS  PubMed  Google Scholar 

  62. Aimo A, Cerbai E, Bartolucci G, Adamo L, Barison A, Lo Surdo G, Biagini S, Passino C, Emdin M (2020) Pirfenidone is a cardioprotective drug: mechanisms of action and preclinical evidence. Pharmacol Res 155:104694

    Article  CAS  PubMed  Google Scholar 

  63. Kotecha D, Lam CS, Van Veldhuisen DJ, Van Gelder IC, Voors AA, Rienstra M (2016) Heart failure with preserved ejection fraction and atrial fibrillation: vicious twins. J Am Coll Cardiol 68(20):2217–2228

    Article  PubMed  Google Scholar 

  64. Cikes M, Planinc I, Claggett B, Cunningham J, Milicic D, Sweitzer N, Senni M, Gori M, Linssen G, Shah SJ et al (2022) Atrial fibrillation in heart failure with preserved ejection fraction: the PARAGON-HF trial. JACC Heart failure 10(5):336–346

    Article  PubMed  Google Scholar 

  65. Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomström-Lundqvist C, Boriani G, Castella M, Dan GA, Dilaveris PE et al (2021) 2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): the task force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J 42(5):373–498

    Article  PubMed  Google Scholar 

  66. Prystowsky EN (2022) Rate versus rhythm control for atrial fibrillation: has the debate been settled? Circulation 146(21):1561–1563

    Article  PubMed  Google Scholar 

  67. Kelly JP, DeVore AD, Wu J, Hammill BG, Sharma A, Cooper LB, Felker GM, Piccini JP, Allen LA, Heidenreich PA et al (2019) Rhythm control versus rate control in patients with atrial fibrillation and heart failure with preserved ejection fraction: insights from get with the guidelines-heart failure. J Am Heart Assoc 8(24):e011560

    Article  PubMed  PubMed Central  Google Scholar 

  68. Machino-Ohtsuka T, Seo Y, Ishizu T, Yamamoto M, Hamada-Harimura Y, Machino T, Yamasaki H, Sekiguchi Y, Nogami A, Aonuma K et al (2019) Relationships between maintenance of sinus rhythm and clinical outcomes in patients with heart failure with preserved ejection fraction and atrial fibrillation. J Cardiol 74(3):235–244

    Article  PubMed  Google Scholar 

  69. Rillig A, Magnussen C, Ozga AK, Suling A, Brandes A, Breithardt G, Camm AJ, Crijns H, Eckardt L, Elvan A et al (2021) Early rhythm control therapy in patients with atrial fibrillation and heart failure. Circulation 144(11):845–858

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Rillig A, Borof K, Breithardt G, Camm AJ, Crijns H, Goette A, Kuck KH, Metzner A, Vardas P, Vettorazzi E et al (2022) Early rhythm control in patients with atrial fibrillation and high comorbidity burden. Circulation 146(11):836–847

    Article  PubMed  Google Scholar 

  71. Packer DL, Piccini JP, Monahan KH, Al-Khalidi HR, Silverstein AP, Noseworthy PA, Poole JE, Bahnson TD, Lee KL, Mark DB (2021) Ablation versus drug therapy for atrial fibrillation in heart failure: results from the CABANA trial. Circulation 143(14):1377–1390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Sugumar H, Nanayakkara S, Vizi D, Wright L, Chieng D, Leet A, Mariani JA, Voskoboinik A, Prabhu S, Taylor AJ et al (2021) A prospective study using invasive haemodynamic measurements following catheter ablation for AF and early HFpEF: STALL AF-HFpEF. Eur J Heart Fail 23(5):785–796

    Article  CAS  PubMed  Google Scholar 

  73. Kotecha D, Bunting KV, Gill SK, Mehta S, Stanbury M, Jones JC, Haynes S, Calvert MJ, Deeks JJ, Steeds RP et al (2020) Effect of digoxin vs bisoprolol for heart rate control in atrial fibrillation on patient-reported quality of life: the RATE-AF randomized clinical trial. JAMA 324(24):2497–2508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Wright JT Jr, Williamson JD, Whelton PK, Snyder JK, Sink KM, Rocco MV, Reboussin DM, Rahman M, Oparil S, Lewis CE et al (2015) A randomized trial of intensive versus standard blood-pressure control. N Engl J Med 373(22):2103–2116

    Article  CAS  PubMed  Google Scholar 

  75. Zhang W, Zhang S, Deng Y, Wu S, Ren J, Sun G, Yang J, Jiang Y, Xu X, Wang TD et al (2021) Trial of intensive blood-pressure control in older patients with hypertension. N Engl J Med 385(14):1268–1279

    Article  CAS  PubMed  Google Scholar 

  76. Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, DePalma SM, Gidding S, Jamerson KA, Jones DW et al (2018) 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines. Circulation 138(17):e426–e483

    PubMed  Google Scholar 

  77. Kasiakogias A, Rosei EA, Camafort M, Ehret G, Faconti L, Ferreira JP, Brguljan J, Januszewicz A, Kahan T, Manolis A 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

    Article  CAS  PubMed  Google Scholar 

  78. 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

    Article  CAS  PubMed  Google Scholar 

  79. Jackson AM, Rørth R, Liu J, Kristensen SL, Anand IS, Claggett BL, Cleland JGF, Chopra VK, Desai AS, Ge J et al (2022) Diabetes and pre-diabetes in patients with heart failure and preserved ejection fraction. Eur J Heart Fail 24(3):497–509

    Article  CAS  PubMed  Google Scholar 

  80. Benko J, Samoš M, Bolek T, Prídavková D, Jurica J, Péč MJ, Galajda P, Mokáň M (2022) Diabetic heart failure with preserved left ventricular ejection fraction: review of current pharmacotherapy. J Diabetes Res 2022:3366109

    Article  PubMed  PubMed Central  Google Scholar 

  81. Davies MJ, Aroda VR, Collins BS, Gabbay RA, Green J, Maruthur NM, Rosas SE, Del Prato S, Mathieu C, Mingrone G et al (2022) Management of hyperglycemia in type 2 diabetes, 2022. a consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care

  82. Carbone S, Dixon DL, Buckley LF, Abbate A (2018) Glucose-lowering therapies for cardiovascular risk reduction in type 2 diabetes mellitus: state-of-the-art review. Mayo Clin Proc 93(11):1629–1647

    Article  CAS  PubMed  Google Scholar 

  83. Yagi K, Imamura T, Tada H, Chujo D, Liu J, Shima Y, Ohbatake A, Miyamoto Y, Okazaki S, Ito N et al (2021) Diastolic cardiac function improvement by liraglutide is mainly body weight reduction dependent but independently contributes to B-type natriuretic peptide reduction in patients with type 2 diabetes with preserved ejection fraction. J Diabetes Res 2021:8838026

    Article  PubMed  PubMed Central  Google Scholar 

  84. Margulies KB, Hernandez AF, Redfield MM, Givertz MM, Oliveira GH, Cole R, Mann DL, Whellan DJ, Kiernan MS, Felker GM et al (2016) Effects of liraglutide on clinical stability among patients with advanced heart failure and reduced ejection fraction: a randomized clinical trial. JAMA 316(5):500–508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Jorsal A, Kistorp C, Holmager P, Tougaard RS, Nielsen R, Hänselmann A, Nilsson B, Møller JE, Hjort J, Rasmussen J et al (2017) Effect of liraglutide, a glucagon-like peptide-1 analogue, on left ventricular function in stable chronic heart failure patients with and without diabetes (LIVE)-a multicentre, double-blind, randomised, placebo-controlled trial. Eur J Heart Fail 19(1):69–77

    Article  CAS  PubMed  Google Scholar 

  86. Halabi A, Sen J, Huynh Q, Marwick TH (2020) Metformin treatment in heart failure with preserved ejection fraction: a systematic review and meta-regression analysis. Cardiovasc Diabetol 19(1):124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Mgbemena O, Zhang Y, Velarde G (2021) Role of diabetes mellitus in heart failure with preserved ejection fraction: a review article. Cureus 13(11):e19398

    PubMed  PubMed Central  Google Scholar 

  88. Obokata M, Reddy YNV, Pislaru SV, Melenovsky V, Borlaug BA (2017) Evidence supporting the existence of a distinct obese phenotype of heart failure with preserved ejection fraction. Circulation 136(1):6–19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Powell-Wiley TM, Poirier P, Burke LE, Després JP, Gordon-Larsen P, Lavie CJ, Lear SA, Ndumele CE, Neeland IJ, Sanders P et al (2021) Obesity and cardiovascular disease: a scientific statement from the American Heart Association. Circulation 143(21):e984–e1010

    Article  PubMed  PubMed Central  Google Scholar 

  90. Kitzman DW, Brubaker P, Morgan T, Haykowsky M, Hundley G, Kraus WE, Eggebeen J, Nicklas BJ (2016) 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 315(1):36–46

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Brubaker PH, Nicklas BJ, Houston DK, Hundley WG, Chen H, Molina M, Lyles WM, Nelson B, Upadhya B, Newland R et al (2022) A randomized, controlled trial of resistance training added to caloric restriction plus aerobic exercise training in obese heart failure with preserved ejection fraction. Circ Heart Fail

  92. Fukuta H, Goto T, Wakami K, Kamiya T, Ohte N (2019) Effects of exercise training on cardiac function, exercise capacity, and quality of life in heart failure with preserved ejection fraction: a meta-analysis of randomized controlled trials. Heart Fail Rev 24(4):535–547

    Article  PubMed  Google Scholar 

  93. Kreiner FF, Hovingh GKK, von Scholten BJ (2022) The potential of glucagon-like peptide-1 receptor agonists in heart failure. Front Physiol 13:983961

    Article  PubMed  PubMed Central  Google Scholar 

  94. Rubino DM, Greenway FL, Khalid U, O’Neil PM, Rosenstock J, Sørrig R, Wadden TA, Wizert A, Garvey WT (2022) Effect of weekly subcutaneous semaglutide vs daily liraglutide on body weight in adults with overweight or obesity without diabetes: the STEP 8 randomized clinical trial. JAMA 327(2):138–150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. le Roux C, Steen O, Lucas KJ, Startseva E, Unseld A, Hennige AM (2023) 51-OR: a phase 2, randomized, double-blind, placebo-controlled, dose-finding study of BI 456906 in people with overweight/obesity. Diabetes 72(Supplement_1)

  96. Garvey WT, Frias JP, Jastreboff AM, le Roux CW, Sattar N, Aizenberg D, Mao H, Zhang S, Ahmad NN, Bunck MC et al (2023) Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet (London, England)

  97. Rosenstock J, Frias J, Jastreboff AM, Du Y, Lou J, Gurbuz S, Thomas MK, Hartman ML, Haupt A, Milicevic Z et al (2023) Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA. Lancet (London, England)

  98. Knop FK, Aroda VR, do Vale RD, Holst-Hansen T, Laursen PN, Rosenstock J, Rubino DM, Garvey WT (2023) Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet (London, England)

  99. Frias JP, Hsia S, Eyde S, Liu R, Ma X, Konig M, Kazda C, Mather KJ, Haupt A, Pratt E et al (2023) Efficacy and safety of oral orforglipron in patients with type 2 diabetes: a multicentre, randomised, dose-response, phase 2 study. Lancet (London, England)

  100. Packer M, Kitzman DW (2018) Obesity-related heart failure with a preserved ejection fraction: the mechanistic rationale for combining inhibitors of aldosterone, neprilysin, and sodium-glucose cotransporter-2. JACC Heart failure 6(8):633–639

    Article  PubMed  Google Scholar 

  101. Ayinapudi K, Samson R, Le Jemtel TH, Marrouche NF, Oparil S (2020) Weight reduction for obesity-induced heart failure with preserved ejection fraction. Curr Hypertens Rep 22(8):47

    Article  PubMed  Google Scholar 

  102. Mikhalkova D, Holman SR, Jiang H, Saghir M, Novak E, Coggan AR, O’Connor R, Bashir A, Jamal A, Ory DS et al (2018) Bariatric surgery-induced cardiac and lipidomic changes in obesity-related heart failure with preserved ejection fraction. Obesity (Silver Spring, Md) 26(2):284–290

    Article  CAS  PubMed  Google Scholar 

  103. van de Wouw J, Broekhuizen M, Sorop O, Joles JA, Verhaar MC, Duncker DJ, Danser AHJ, Merkus D (2019) Chronic kidney disease as a risk factor for heart failure with preserved ejection fraction: a focus on microcirculatory factors and therapeutic targets. Front Physiol 10:1108

    Article  PubMed  PubMed Central  Google Scholar 

  104. Mullens W, Martens P, Testani JM, Tang WHW, Skouri H, Verbrugge FH, Fudim M, Iacoviello M, Franke J, Flammer AJ et al (2022) Renal effects of guideline-directed medical therapies in heart failure: a consensus document from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 24(4):603–619

    Article  PubMed  Google Scholar 

  105. Tsujimoto T, Kajio H (2018) Efficacy of renin-angiotensin system inhibitors for patients with heart failure with preserved ejection fraction and mild to moderate chronic kidney disease. Eur J Prev Cardiol 25(12):1268–1277

    Article  PubMed  Google Scholar 

  106. Voors AA, Gori M, Liu LC, Claggett B, Zile MR, Pieske B, McMurray JJ, Packer M, Shi V, Lefkowitz MP et al (2015) Renal effects of the angiotensin receptor neprilysin inhibitor LCZ696 in patients with heart failure and preserved ejection fraction. Eur J Heart Fail 17(5):510–517

    Article  CAS  PubMed  Google Scholar 

  107. Mc Causland FR, Lefkowitz MP, Claggett B, Anavekar NS, Senni M, Gori M, Jhund PS, McGrath MM, Packer M, Shi V et al (2020) Angiotensin-neprilysin inhibition and renal outcomes in heart failure with preserved ejection fraction. Circulation 142(13):1236–1245

    Article  CAS  PubMed  Google Scholar 

  108. Peikert A, Vaduganathan M, Mc Causland F, Claggett BL, Chatur S, Packer M, Pfeffer MA, Zannad F, Lefkowitz MP, Pieske B et al (2022) Effects of sacubitril/valsartan versus valsartan on renal function in patients with and without diabetes and heart failure with preserved ejection fraction: insights from PARAGON-HF. Eur J Heart Fail 24(5):794–803

    Article  CAS  PubMed  Google Scholar 

  109. Jia R, Zhang X, Xu Y, Zheng Z, Jiang L, Zhang X, Sun C, Wu X, Li S, Raj A et al (2022) Effect of sacubitril/valsartan on renal function in patients with chronic kidney disease and heart failure with preserved ejection fraction: a real-world 12-week study. Eur J Pharmacol 928:175053

    Article  CAS  PubMed  Google Scholar 

  110. Heerspink HJL, Stefánsson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, Mann JFE, McMurray JJV, Lindberg M, Rossing P et al (2020) Dapagliflozin in patients with chronic kidney disease. N Engl J Med 383(15):1436–1446

    Article  CAS  PubMed  Google Scholar 

  111. Packer M, Zannad F, Butler J, Filippatos G, Ferreira JP, Pocock SJ, Brueckmann M, Zeller C, Hauske S, Anker SD (2021) Influence of endpoint definitions on the effect of empagliflozin on major renal outcomes in the EMPEROR-Preserved trial. Eur J Heart Fail 23(10):1798–1799

    Article  CAS  PubMed  Google Scholar 

  112. Packer M, Butler J, Zannad F, Pocock SJ, Filippatos G, Ferreira JP, Brueckmann M, Jamal W, Zeller C, Wanner C et al (2021) Empagliflozin and major renal outcomes in heart Failure. N Engl J Med 385(16):1531–1533

    Article  PubMed  Google Scholar 

  113. Ryan DK, Banerjee D, Jouhra F (2022) Management of heart failure in patients with chronic kidney disease. Eur Cardiol 17

    Article  PubMed  PubMed Central  Google Scholar 

  114. Méndez AB, Azancot MA, Olivella A, Soler MJ (2022) New aspects in cardiorenal syndrome and HFpEF. Clin Kidney J 15(10):1807–1815

    Article  PubMed  PubMed Central  Google Scholar 

  115. Lam CS, Roger VL, Rodeheffer RJ, Borlaug BA, Enders FT, Redfield MM (2009) Pulmonary hypertension in heart failure with preserved ejection fraction: a community-based study. J Am Coll Cardiol 53(13):1119–1126

    Article  PubMed  PubMed Central  Google Scholar 

  116. Inampudi C, Silverman D, Simon MA, Leary PJ, Sharma K, Houston BA, Vachiéry JL, Haddad F, Tedford RJ (2021) Pulmonary hypertension in the context of heart failure with preserved ejection fraction. Chest 160(6):2232–2246

    Article  PubMed  PubMed Central  Google Scholar 

  117. Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RMF, Brida M, Carlsen J, Coats AJS, Escribano-Subias P, Ferrari P et al (2022) ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J

  118. Vachiéry JL, Tedford RJ, Rosenkranz S, Palazzini M, Lang I, Guazzi M, Coghlan G, Chazova I, De Marco T (2019) Pulmonary hypertension due to left heart disease. Eur Respir J 53(1)

  119. Koller B, Steringer-Mascherbauer R, Ebner CH, Weber T, Ammer M, Eichinger J, Pretsch I, Herold M, Schwaiger J, Ulmer H et al (2017) Pilot study of endothelin receptor blockade in heart failure with diastolic dysfunction and pulmonary hypertension (BADDHY-trial). Heart Lung Circ 26(5):433–441

    Article  CAS  PubMed  Google Scholar 

  120. Hoendermis ES, Liu LC, Hummel YM, van der Meer P, de Boer RA, Berger RM, van Veldhuisen DJ, Voors AA (2015) 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 36(38):2565–2573

    Article  CAS  PubMed  Google Scholar 

  121. Guazzi M, Vicenzi M, Arena R, Guazzi MD (2011) Pulmonary hypertension in heart failure with preserved ejection fraction: a target of phosphodiesterase-5 inhibition in a 1-year study. Circulation 124(2):164–174

    Article  CAS  PubMed  Google Scholar 

  122. Kramer T, Dumitrescu D, Gerhardt F, Orlova K, Ten Freyhaus H, Hellmich M, Baldus S, Rosenkranz S (2019) Therapeutic potential of phosphodiesterase type 5 inhibitors in heart failure with preserved ejection fraction and combined post- and pre-capillary pulmonary hypertension. Int J Cardiol 283:152–158

    Article  PubMed  Google Scholar 

  123. Opitz CF, Hoeper MM, Gibbs JS, Kaemmerer H, Pepke-Zaba J, Coghlan JG, Scelsi L, D’Alto M, Olsson KM, Ulrich S et al (2016) Pre-capillary, combined, and post-capillary pulmonary hypertension: a pathophysiological continuum. J Am Coll Cardiol 68(4):368–378

    Article  PubMed  Google Scholar 

  124. Reddy YNV, Obokata M, Koepp KE, Egbe AC, Wiley B, Borlaug BA (2019) The β-adrenergic agonist albuterol improves pulmonary vascular reserve in heart failure with preserved ejection fraction. Circ Res 124(2):306–314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Burkhoff D, Borlaug BA, Shah SJ, Zolty R, Tedford RJ, Thenappan T, Zamanian RT, Mazurek JA, Rich JD, Simon MA et al (2021) Levosimendan improves hemodynamics and exercise tolerance in PH-HFpEF: results of the randomized placebo-controlled HELP trial. JACC Heart failure 9(5):360–370

    Article  PubMed  Google Scholar 

  126. Zhang H, Zhang J, Chen M, Xie DJ, Kan J, Yu W, Li XB, Xu T, Gu Y, Dong J et al (2019) Pulmonary artery denervation significantly increases 6-min walk distance for patients with combined pre- and post-capillary pulmonary hypertension associated with left heart failure: the PADN-5 study. JACC Cardiovasc Interv 12(3):274–284

    Article  PubMed  Google Scholar 

  127. (2021) A study of sotatercept for the treatment of Cpc-PH due to HFpEF (MK-7962-007/A011-16) (CADENCE) - full text view - ClinicalTrials.gov [Internet]. [cited 2023 Jul 11]. Available from: https://clinicaltrials.gov/ct2/show/NCT04945460

  128. Hoeper MM, Badesch DB, Ghofrani HA, Gibbs JSR, Gomberg-Maitland M, McLaughlin VV, Preston IR, Souza R, Waxman AB, Grünig E et al (2023) Phase 3 trial of sotatercept for treatment of pulmonary arterial hypertension. N Engl J Med 388(16):1478–1490

    Article  CAS  PubMed  Google Scholar 

  129. Bitter T, Faber L, Hering D, Langer C, Horstkotte D, Oldenburg O (2009) Sleep-disordered breathing in heart failure with normal left ventricular ejection fraction. Eur J Heart Fail 11(6):602–608

    Article  PubMed  Google Scholar 

  130. Herrscher TE, Akre H, Øverland B, Sandvik L, Westheim AS (2011) High prevalence of sleep apnea in heart failure outpatients: even in patients with preserved systolic function. J Card Fail 17(5):420–425

    Article  PubMed  Google Scholar 

  131. Sanderson JE, Fang F, Lu M, Ma CY, Wei YX (2021) Obstructive sleep apnoea, intermittent hypoxia and heart failure with a preserved ejection fraction. Heart 107(3):190–194

    Article  CAS  PubMed  Google Scholar 

  132. Abdullah A, Eigbire G, Salama A, Wahab A, Nadkarni N, Alweis R (2018) Relation of obstructive sleep apnea to risk of hospitalization in patients with heart failure and preserved ejection fraction from the national inpatient sample. Am J Cardiol 122(4):612–615

    Article  PubMed  Google Scholar 

  133. Patil SP, Ayappa IA, Caples SM, Kimoff RJ, Patel SR, Harrod CG (2019) Treatment of adult obstructive sleep apnea with positive airway pressure: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med : JCSM : Offic Publication Am Acad Sleep Med 15(2):335–343

    Google Scholar 

  134. Randerath W, Verbraecken J, de Raaff CAL, Hedner J, Herkenrath S, Hohenhorst W, Jakob T, Marrone O, Marklund M, McNicholas WT et al (2021) European Respiratory Society guideline on non-CPAP therapies for obstructive sleep apnoea. Eur Res Rev : Offic J Eur Respir Soc 30(162)

  135. Khattak HK, Hayat F, Pamboukian SV, Hahn HS, Schwartz BP, Stein PK (2018) Obstructive sleep apnea in heart failure: review of prevalence, treatment with continuous positive airway pressure, and prognosis. Tex Heart Inst J 45(3):151–161

    Article  PubMed  PubMed Central  Google Scholar 

  136. Yoshihisa A, Suzuki S, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y (2013) Impact of adaptive servo-ventilation on cardiovascular function and prognosis in heart failure patients with preserved left ventricular ejection fraction and sleep-disordered breathing. Eur J Heart Fail 15(5):543–550

    Article  CAS  PubMed  Google Scholar 

  137. O’Connor CM, Whellan DJ, Fiuzat M, Punjabi NM, Tasissa G, Anstrom KJ, Benjafield AV, Woehrle H, Blase AB, Lindenfeld J et al (2017) Cardiovascular outcomes with minute ventilation-targeted adaptive servo-ventilation therapy in heart failure: the CAT-HF trial. J Am Coll Cardiol 69(12):1577–1587

    Article  PubMed  Google Scholar 

  138. McEvoy RD, Antic NA, Heeley E, Luo Y, Ou Q, Zhang X, Mediano O, Chen R, Drager LF, Liu Z et al (2016) CPAP for prevention of cardiovascular events in obstructive sleep apnea. N Engl J Med 375(10):919–931

    Article  PubMed  Google Scholar 

  139. Mokhlesi B, Ayas NT (2016) Cardiovascular events in obstructive sleep apnea - can CPAP therapy save lives? N Engl J Med 375(10):994–996

    Article  PubMed  Google Scholar 

  140. Kittleson MM, Panjrath GS, Amancherla K, Davis LL, Deswal A, Dixon DL, Januzzi JL, Yancy CW (2023) ACC expert consensus decision pathway on management of heart failure with preserved ejection fraction. 0(0)

  141. Savarese G, von Haehling S, Butler J, Cleland JGF, Ponikowski P, Anker SD (2023) Iron deficiency and cardiovascular disease. Eur Heart J 44(1):14–27

    Article  CAS  PubMed  Google Scholar 

  142. Shamsi A, Cannata A, Piper S, Bromage DI, McDonagh TA (2023) Treatment of iron deficiency in heart failure. Curr Cardiol Rep 25(7):649–661

    Article  PubMed  PubMed Central  Google Scholar 

  143. Barandiarán Aizpurua A, Sanders-van Wijk S, Brunner-La Rocca HP, Henkens M, Weerts J, Spanjers MHA, Knackstedt C, van Empel VPM (2021) Iron deficiency impacts prognosis but less exercise capacity in heart failure with preserved ejection fraction. ESC heart failure 8(2):1304–1313

    Article  PubMed  PubMed Central  Google Scholar 

  144. Beale AL, Warren JL, Roberts N, Meyer P, Townsend NP, Kaye D (2019) Iron deficiency in heart failure with preserved ejection fraction: a systematic review and meta-analysis. Open heart 6(1):e001012

    Article  PubMed  PubMed Central  Google Scholar 

  145. Gevaert AB, Mueller S, Winzer EB, Duvinage A, Van de Heyning CM, Pieske-Kraigher E, Beckers PJ, Edelmann F, Wisløff U, Pieske B et al (2021) Iron deficiency impacts diastolic function, aerobic exercise capacity, and patient phenotyping in heart failure with preserved ejection fraction: a subanalysis of the OptimEx-Clin study. Front Physiol 12:757268

    Article  PubMed  Google Scholar 

  146. Verelst FR, Van Craenenbroeck EM, Gevaert AB (2023) Iron deficiency in heart failure across the spectrum of left ventricular ejection fraction: dotting the i’s. Eur Heart J 44(16):1383–1385

    Article  PubMed  Google Scholar 

  147. López-Vilella R, Lozano-Edo S, Arenas Martín P, Jover-Pastor P, Ezzitouny M, Sorolla Romero J, Calvo Asensio M, Martínez-Solé J, Guerrero Cervera B, Sánchez Martínez JC et al (2022) Impact of intravenous ferric carboxymaltose on heart failure with preserved and reduced ejection fraction. ESC heart failure 9(1):133–145

    Article  PubMed  Google Scholar 

  148. Rull JLM (2019) Effects of iron therapy in heart failure with preserved ejection fraction and iron deficiency (PREFER-HF) - full text view - ClinicalTrials.gov [Internet]. [cited 2022 Oct 16]. Available from: https://clinicaltrials.gov/ct2/show/study/NCT03833336

  149. Doehner W (2020) Effect of IV iron in patients with heart failure with preserved ejection fraction - full text view - ClinicalTrials.gov [Internet]. [cited 2022 Oct 16]. Available from: https://clinicaltrials.gov/ct2/show/NCT03074591

  150. Kim MN, Park SM (2021) Current status of pharmacologic and nonpharmacologic therapy in heart failure with preserved ejection fraction. Heart Fail Clin 17(3):463–482

    Article  PubMed  Google Scholar 

  151. Gevaert AB, Kataria R, Zannad F, Sauer AJ, Damman K, Sharma K, Shah SJ, Van Spall HGC (2022) Heart failure with preserved ejection fraction: recent concepts in diagnosis, mechanisms and management. Heart 108(17):1342–1350

    Article  PubMed  Google Scholar 

  152. Zawadzka MM, Grabowski M, Kapłon-Cieślicka A (2022) Phenotyping in heart failure with preserved ejection fraction: a key to find effective treatment. Adv Clin Exp Med : Offic organ Wroclaw Med University

Download references

Funding

This study was supported by grants from the National Natural Science Foundation of China (Grant no. 81800278) and the Fujian Provincial Health Technology Project (Grant no. 2022CXA057) to Liming Lin; the Natural Science Foundation of Fujian Province to Kaizu Xu (Grant no. 2020J011259), Ying Wu (Grant no. 2021J01122508), Meifang Wu (Grant no. 2022J011433), Wen Chen (Grant no. 2022J011438), and Liming Lin (Grant no. 2022J011431); and the Education and scientific research project of young and middle-aged teachers in Fujian Education Department to Ying Wu (Grant no. JAT190553).

Author information

Author notes

  1. Wu Meifang and Wu Ying contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, School of Clinical Medicine, Fujian Medical University, Affiliated Hospital of Putian University, Putian, 351100, Fujian, China

    Wu Meifang, Wu Ying, Chen Wen, Xu Kaizu, Song Meiyan & Lin Liming

Authors
  1. Wu Meifang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wu Ying
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chen Wen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xu Kaizu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Song Meiyan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lin Liming
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Song Meiyan, Wu Ying, and Chen Wen wrote the manuscript, and Xu Kaizu, Wu Meifang, and Lin Liming examined the final draft.

Corresponding author

Correspondence to Lin Liming.

Ethics declarations

Ethics approval

Not applicable.

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Meifang, W., Ying, W., Wen, C. et al. Advance in the pharmacological and comorbidities management of heart failure with preserved ejection fraction: evidence from clinical trials. Heart Fail Rev 29, 305–320 (2024). https://doi.org/10.1007/s10741-023-10338-x

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10741-023-10338-x

Keywords

Search

Navigation