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The continuous heart failure spectrum: moving beyond an ejection fraction classification.

  • Triposkiadis, Filippos1
  • Butler, Javed2
  • Abboud, Francois M3
  • Armstrong, Paul W4
  • Adamopoulos, Stamatis5
  • Atherton, John J6
  • Backs, Johannes7
  • Bauersachs, Johann8
  • Burkhoff, Daniel9
  • Bonow, Robert O10
  • Chopra, Vijay K11
  • de Boer, Rudolf A12
  • de Windt, Leon13
  • Hamdani, Nazha14
  • Hasenfuss, Gerd15
  • Heymans, Stephane16
  • Hulot, Jean-Sébastien17, 18, 19
  • Konstam, Marvin20
  • Lee, Richard T21
  • Linke, Wolfgang A22
  • And 22 more
  • 1 Department of Cardiology, Larissa University Hospital, Larissa, Greece. , (Greece)
  • 2 Department of Medicine-L650, University of Mississippi Medical Center, Jackson, MS, USA.
  • 3 Abboud Cardiovascular Research Center, University of Iowa, Iowa City, IA, USA.
  • 4 Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada. , (Canada)
  • 5 Transplant and Mechanical Circulatory Support Unit, Onassis Cardiac Surgery Center, Athens, Greece. , (Greece)
  • 6 Department of Cardiology, Royal Brisbane and Women's Hospital, University of Queensland School of Medicine, Brisbane, Australia. , (Australia)
  • 7 Department of Molecular Cardiology and Epigenetics, Heidelberg University, Heidelberg, Germany. , (Germany)
  • 8 Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany. , (Germany)
  • 9 Cardiovascular Research Foundation, New York, NY, USA.
  • 10 Bluhm Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Northwestern Memorial Hospital, Chicago, IL, USA.
  • 11 Department of Cardiology, Medanta Medicity, Gurugram, Haryana, India. , (India)
  • 12 Department of Cardiology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands. , (Netherlands)
  • 13 Department of Cardiology, Faculty of Health, Medicine and Life Sciences, School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands. , (Netherlands)
  • 14 Department of Systems Physiology, Ruhr University Bochum, Bochum, Germany. , (Germany)
  • 15 Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany. , (Germany)
  • 16 Department of Cardiology, CARIM School for Cardiovascular Diseases Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands. , (Netherlands)
  • 17 Université Paris-Descartes, Sorbonne Paris Cité, Paris, France. , (France)
  • 18 Paris Cardiovascular Research Center, INSERM UMR 970, Paris, France. , (France)
  • 19 Hôpital Européen Georges Pompidou, AP-HP, Paris, France. , (France)
  • 20 The CardioVascular Center of Tufts Medical Center, Boston, MA, USA.
  • 21 Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.
  • 22 Institute of Physiology II, University of Münster, Münster, Germany. , (Germany)
  • 23 Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway. , (Norway)
  • 24 Cardiovascular Research Centre, Royal Brompton Hospital, London, UK.
  • 25 National Heart and Lung Institute, Imperial College London, London, UK.
  • 26 Comprehensive Heart Failure Center, University Clinic Würzburg, Würzburg, Germany. , (Germany)
  • 27 Department of Medicine, Center for Cardiovascular Research, Washington University School of Medicine, St. Louis Missouri, MO, USA.
  • 28 Department of Anaesthesiology and Critical Care Medicine, AP-HP, Saint Louis and Lariboisière University Hospitals, Inserm U 942, Paris, France. , (France)
  • 29 Duke Clinical Research Institute, Durham, NC, USA.
  • 30 Imperial College London, NHLI, National Heart & Lung Institute, London, UK.
  • 31 Division of Clinical Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. , (Hungary)
  • 32 Heart Failure Unit, Department of Cardiology, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece. , (Greece)
  • 33 Experimental Cardiology Unit, Department of Cardiovascular Medicine, University of Lausanne Medical School, Lausanne, Switzerland. , (Switzerland)
  • 34 Department of Medical Sciences, IRCCS San Raffaele, Centre for Clinical and Basic Research, Pisana Rome, Italy. , (Italy)
  • 35 Montreal Heart Institute and University of Montreal, Montreal, Quebec, Canada. , (Canada)
  • 36 School of Medicine, Belgrade University, Belgrade, Serbia. , (Serbia)
  • 37 School of Cardiovascular Medicine & Sciences, British Heart Foundation Centre, King's College London, London, UK.
  • 38 Cleveland Clinic, Heart and Vascular Institute, Cleveland, OH, USA.
  • 39 Department of Translational Medical Sciences, Federico II University, Naples, Italy. , (Italy)
  • 40 CIC INSERM 1413, Institut du thorax, UMR INSERM 1087, University Hospital of Nantes, Nantes, France. , (France)
  • 41 Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Hanover, Germany. , (Germany)
  • 42 Inserm CIC 1433, Université de Lorrain, CHU de Nancy, Nancy, France. , (France)
  • 43 Antwerp University, Antwerp, Belgium. , (Belgium)
  • 44 Laboratory of Physiopharmacology, Antwerp University, Universiteitsplein 1, Building T, Wilrijk, Antwerp, Belgium. , (Belgium)
  • 45 Division of Cardiology, Antwerp University Hospital, Edegem, Belgium. , (Belgium)
  • 46 ZNA Hartcentrum, Antwerp, Belgium. , (Belgium)
Published Article
European Heart Journal
Oxford University Press
Publication Date
Jul 01, 2019
DOI: 10.1093/eurheartj/ehz158
PMID: 30957868


Randomized clinical trials initially used heart failure (HF) patients with low left ventricular ejection fraction (LVEF) to select study populations with high risk to enhance statistical power. However, this use of LVEF in clinical trials has led to oversimplification of the scientific view of a complex syndrome. Descriptive terms such as 'HFrEF' (HF with reduced LVEF), 'HFpEF' (HF with preserved LVEF), and more recently 'HFmrEF' (HF with mid-range LVEF), assigned on arbitrary LVEF cut-off points, have gradually arisen as separate diseases, implying distinct pathophysiologies. In this article, based on pathophysiological reasoning, we challenge the paradigm of classifying HF according to LVEF. Instead, we propose that HF is a heterogeneous syndrome in which disease progression is associated with a dynamic evolution of functional and structural changes leading to unique disease trajectories creating a spectrum of phenotypes with overlapping and distinct characteristics. Moreover, we argue that by recognizing the spectral nature of the disease a novel stratification will arise from new technologies and scientific insights that will shape the design of future trials based on deeper understanding beyond the LVEF construct alone. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: [email protected]

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