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Heart failure with preserved ejection fraction: recent concepts in diagnosis, mechanisms and management
  1. Andreas B Gevaert1,2,3,
  2. Rachna Kataria4,
  3. Faiez Zannad5,6,
  4. Andrew J Sauer7,
  5. Kevin Damman2,
  6. Kavita Sharma8,
  7. Sanjiv J Shah9,
  8. Harriette G C Van Spall10,11,12
  1. 1 Research Group Cardiovascular Diseases, GENCOR Department, University of Antwerp, Antwerp, Belgium
  2. 2 Department of Cardiology, University Medical Centre Groningen, Groningen, The Netherlands
  3. 3 Department of Cardiology, Antwerp University Hospital (UZA), Edegem, Belgium
  4. 4 Department of Cardiology-Advanced Heart Failure and Cardiac Transplantation, Corrigan Minehan Heart Center, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA
  5. 5 Université de Lorraine, INSERM, Centre d'Investigations Cliniques-1433 and INSERM U1116, Centre Hospitalier Regional Universitaire de Nancy, Nancy, France
  6. 6 Investigation Network Initiative-Cardiovascular and Renal Clinical Trialists, French Clinical Research Infrastructure Network, Nancy, France
  7. 7 Center for Advanced Heart Failure and Heart Transplantation, The University of Kansas Health System, Kansas City, Kansas, USA
  8. 8 Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  9. 9 Division of Cardiology, Department of Medicine and Bluhm Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
  10. 10 Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
  11. 11 Research Institute of St. Joe's and Population Health Research Institute, Hamilton, Ontario, Canada
  12. 12 Department of Medicine, McMaster University, Hamilton, Ontario, Canada
  1. Correspondence to Dr Harriette G C Van Spall, Department of Medicine, McMaster University, Suite C3-117, 20 Copeland Avenue, David Braley Research Institute Bldg, Hamilton, Ontario, Canada; harriette.vanspall{at}


It is estimated that half of all patients with heart failure (HF) have HF with preserved ejection fraction (HFpEF). Yet this form of HF remains a diagnostic and therapeutic challenge. Differentiating HFpEF from other causes of dyspnoea may require advanced diagnostic methods, such as exercise echocardiography, invasive haemodynamics and investigations for ‘HFpEF mimickers’. While the classification of HF has relied heavily on cut-points in left ventricular ejection fraction (LVEF), recent evidence points towards a gradual shift in underlying mechanisms, phenotypes and response to therapies as LVEF increases. For example, among patients with HF, the proportion of hospitalisations and deaths due to cardiac causes decreases as LVEF increases. Medication classes that are efficacious in HF with reduced ejection fraction (HFrEF) have been less so at higher LVEF ranges, decreasing the risk of HF hospitalisation but not cardiovascular or all-cause death in HFpEF. These observations reflect the burden of non-cardiac comorbidities as LVEF increases and highlight the complex pathophysiological mechanisms, both cardiac and non-cardiac, underpinning HFpEF. Treatment with sodium-glucose cotransporter 2 inhibitors reduces the risk of composite cardiovascular events, driven by a reduction in HF hospitalisations; renin-angiotensin-aldosterone blockers and angiotensin-neprilysin inhibitors result in smaller reductions in HF hospitalisations among patients with HFpEF. Comprehensive management of HFpEF includes exercise as well as treatment of risk factors and comorbidities. Classification based on phenotypes may facilitate a more targeted approach to treatment than LVEF categorisation, which sets arbitrary cut-points when LVEF is a continuum. This narrative review summarises the pathophysiology, diagnosis, classification and management of patients with HFpEF.

  • heart failure
  • diastolic
  • pharmacology
  • clinical
  • diagnostic imaging
  • outcome assessment
  • health care

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  • ABG and RK are joint first authors.

  • Twitter @rachkataria, @kevin_damman, @HFpEF, @hvanspall

  • Contributors HGCV was invited by the journal to provide this review and assumes responsibility for project supervision. ABG, RK and HGCV contributed to the conception or design of the work. ABG, RK, AS and HGCV drafted the manuscript. FZ, KD, KS and SJS critically revised the manuscript. All authors gave final approval and are accountable for the integrity and accuracy of the work.

  • Funding The study was funded by the Canadian Institutes of Health Research to HGCV, and the Heart and Stroke Foundation of Canada to HGCV.

  • Competing interests FZ has received fees for serving on the board of Boston Scientific; consulting fees from Novartis, Takeda, AstraZeneca, Boehringer Ingelheim, GE Healthcare, Relypsa, Servier, Boston Scientific, Bayer, Johnson & Johnson, and Resmed; and speaking fees from Pfizer and AstraZeneca. KD received consultancy fees from Abbott and an investigator-initiated study grant from Boehringer Ingelheim; and is supported by the Netherlands Heart Institute (ICIN) and an ESC Heart Failure Association Research Grant. KS is an advisory board member and consultant for Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Janssen, Novartis and Novo Nordisk, and receives honoraria. SJS has received research grants from Actelion, AstraZeneca, Corvia, Novartis and Pfizer, and has received consulting fees from Abbott, Actelion, AstraZeneca, Amgen, Aria CV, Axon Therapies, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardiora, CVRx, Cytokinetics, Edwards Lifesciences, Eidos, Eisai, Imara, Impulse Dynamics, Intellia, Ionis, Ironwood, Lilly, Merck, MyoKardia, Novartis, Novo Nordisk, Pfizer, Prothena, Regeneron, Rivus, Sanofi, Shifamed, Tenax, Tenaya and United Therapeutics. The other authors report no conflicts of interest with regard to this manuscript.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Commissioned; externally peer reviewed.