The Continuous Heart Failure Spectrum: Moving Beyond an Ejection Fraction Classification

LVEF, left ventricular ejection fraction.

cGMP, cyclic guanosine monophosphate.

Authors and Disclosures

Filippos Triposkiadis¹, Javed Butler², Francois M. Abboud³, Paul W. Armstrong⁴, Stamatis Adamopoulos⁵, John J. Atherton⁶, Johannes Backs⁷, Johann Bauersachs⁸, Daniel Burkhoff⁹, Robert O. Bonow¹⁰, Vijay K. Chopra¹¹, Rudolf A. de Boer¹², Leon deWindt¹³, Nazha Hamdani¹⁴, Gerd Hasenfuss¹⁵, Stephane Heymans¹⁶, Jean-Sébastien Hulot^17,18,19, Marvin Konstam²⁰, Richard T. Lee²¹, Wolfgang A. Linke²², Ida G. Lunde²³, Alexander R. Lyon^24,25, Christoph Maack²⁶, Douglas L. Mann²⁷, Alexandre Mebazaa²⁸, Robert J. Mentz²⁹, Petros Nihoyannopoulos³⁰, Zoltan Papp³¹, John Parissis³², Thierry Pedrazzini³³, Giuseppe Rosano³⁴, Jean Rouleau³⁵, Petar M. Seferovic³⁶, Ajay M. Shah³⁷, Randall C. Starling³⁸, Carlo G. Tocchetti³⁹, Jean-Noel Trochu⁴⁰, Thomas Thum⁴¹, Faiez Zannad⁴², Dirk L. Brutsaert⁴³, Vincent F. Segers^44,45 and Gilles W. De Keulenaer^44,46*

¹Department of Cardiology, Larissa University Hospital, Larissa, Greece; ²Department of Medicine-L650, University of Mississippi Medical Center, Jackson, MS, USA; ³Abboud Cardiovascular Research Center, University of Iowa, Iowa City, IA, USA; ⁴Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada; ⁵Transplant and Mechanical Circulatory Support Unit, Onassis Cardiac Surgery Center, Athens, Greece; ⁶Department of Cardiology, Royal Brisbane and Women's Hospital, University of Queensland School of Medicine, Brisbane, Australia; ⁷Department of Molecular Cardiology and Epigenetics, Heidelberg University, Heidelberg, Germany; ⁸Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany; ⁹Cardiovascular Research Foundation, New York, NY, USA; ¹⁰Bluhm Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Northwestern Memorial Hospital, Chicago, IL, USA; ¹¹Department of Cardiology, Medanta Medicity, Gurugram, Haryana, India; ¹²Department of Cardiology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands; ¹³Department of Cardiology, Faculty of Health, Medicine and Life Sciences, School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands; ¹⁴Department of Systems Physiology, Ruhr University Bochum, Bochum, Germany; ¹⁵Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover 30625, Germany; ¹⁶Department of Cardiology, CARIM School for Cardiovascular Diseases Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands; ¹⁷Université Paris-Descartes, Sorbonne Paris Cité, Paris, France; ¹⁸Paris Cardiovascular Research Center, INSERM UMR 970, Paris, France; ¹⁹Hôpital Européen Georges Pompidou, AP-HP, Paris, France; ²⁰The CardioVascular Center of Tufts Medical Center, Boston, MA, USA; ²¹Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA; ²²Institute of Physiology II, University of Münster, Münster, Germany; ²³Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway; ²⁴Cardiovascular Research Centre, Royal Brompton Hospital, London, UK; ²⁵National Heart and Lung Institute, Imperial College London, London, UK; ²⁶Comprehensive Heart Failure Center, University Clinic Würzburg, Würzburg, Germany; ²⁷Department of Medicine, Center for Cardiovascular Research, Washington University School of Medicine, St. Louis Missouri, MO, USA; ²⁸Department of Anaesthesiology and Critical Care Medicine, AP-HP, Saint Louis and Lariboisière University Hospitals, Inserm U 942, Paris, France; ²⁹Duke Clinical Research Institute, Durham, NC, USA; ³⁰Imperial College London, NHLI, National Heart & Lung Institute, London, UK; ³¹Division of Clinical Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary; ³²Heart Failure Unit, Department of Cardiology, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece; ³³Experimental Cardiology Unit, Department of Cardiovascular Medicine, University of Lausanne Medical School, Lausanne, Switzerland; ³⁴Department of Medical Sciences, IRCCS San Raffaele, Centre for Clinical and Basic Research, Pisana Rome, Italy; ³⁵Montreal Heart Institute and University of Montreal, Montreal, Quebec, Canada; ³⁶School of Medicine, Belgrade University, Belgrade, Serbia; ³⁷School of Cardiovascular Medicine & Sciences, British Heart Foundation Centre, King's College London, London, UK; ³⁸Cleveland Clinic, Heart and Vascular Institute, Cleveland, OH, USA; ³⁹Department of Translational Medical Sciences, Federico II University, Naples, Italy; ⁴⁰CIC INSERM 1413, Institut du thorax, UMR INSERM 1087, University Hospital of Nantes, Nantes, France; ⁴¹Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Hanover, Germany; ⁴²Inserm CIC 1433, Université de Lorrain, CHU de Nancy, Nancy, France; ⁴³Antwerp University, Antwerp, Belgium; ⁴⁴Laboratory of Physiopharmacology, Antwerp University, Universiteitsplein 1, Building T, Wilrijk, Antwerp 2610, Belgium; ⁴⁵Division of Cardiology, Antwerp University Hospital, Edegem, Belgium; and ⁴⁶ZNA Hartcentrum, Antwerp, Belgium

* Corresponding author
Tel: +3232652338, Fax: +3232652412, Email: gilles.dekeulenaer@uantwerpen.be

Conflict of interest
J. Bu. reports to be consultant for Amgen, Array, Astra Zeneca, Bayer, Boehringer Ingelheim, Bristol Mayers Squib, CVRx, G3 Pharmaceutical, Innolife, Janssen, Luitpold, Medtronic, Merck, Novartis, Relypsa, StealthPeptide, SC Pharma, Vifor, ZS Pharma, outside the submitted work. J. Ba. reports personal fees from Novartis, grants and personal fees from Bayer, personal fees from Servier, personal fees from Orion, grants and personal fees from Abiomed, grants and personal fees from CVRx, grants and personal fees from Medtronic, grants from Zoll, grants and personal fees from Vifor, personal fees from Abbott, personal fees from AstraZeneca, outside the submitted work; R.D.B. reports grants from AstraZeneca, grants from Bristol Myers Squibb, grants from Trevena, grants from Novo Nordisk, personal fees from AstraZeneca, personal fees from Novartis, personal fees from Vifor, personal fees from MandalMed, Inc, and other types of support from scPharmaceuticals, Inc, other from ThermoFisher, other from Roche, all outside the submitted work; L.D.W. reports to be co-founder and stockholder of Mirabilis Therapeutics BV, a spin-off Biotech aimed to develop new therapeutics for heart failure; G.H. reports personal fees from Corvia Medical, Servier, Impulse Dynamics, Novartis, AstraZeneca, Vifor Pharma, and Springer all outside the submitted work; J.-S.H. reports personal fees from Servier and Novartis, outside the submitted work; M.K. reports personal fees from Amgen, BMS, Boehringer-Ingelheim, Novartis and grants and personal fees from Ironwood, LivaNova, SCPharma, outside the submitted work; R.L. reports to be a founder of a startup biotechnology company named Elevian, Inc., which has heart failure as one of its target diseases; A.L. reports personal fees from Servier, grants and personal fees from Pfizer, personal fees from Novartis, personal fees from Roche, personal fees from Takeda, personal fees from Boehringer Ingelheim, personal fees from Amgen, personal fees from Clinigen Group, personal fees from Ferring Pharmaceuticals, personal fees from Eli Lily, personal fees from Bristol Myers Squibb, personal fees from Eisai Ltd, outside the submitted work; C.M. reports grants from Deutsche Forschungsgemeinschaft, during the conduct of the study; personal fees from Servier, personal fees from Boehringer Ingelheim, personal fees from Novartis, personal fees from Bayer, personal fees from Bristol Myer Squibb (BMS), personal fees from Berlin Chemie, personal fees from Daiichi Sankyo, outside the submitted work; A.M. reports personal fees from Novartis, personal fees from Orion, personal fees from Roche, personal fees from Servier, grants and personal fees from Adrenomed, grants and personal fees from Abbott, personal fees from Sanofi, outside the submitted work; R.M. reports grants and personal fees from Amgen, grants and personal fees from Bayer, grants and personal fees from Merck, grants and personal fees from AstraZeneca, grants and personal fees from Novartis, grants from Akros, grants from Luitpold, personal fees from Boehringer Ingelheim; J.P. reports horonaria for advisory boards and lectures from Novartis, Servier, Pfizer, Orion Pharma and Roche diagnostics; T.P. has a patent PCT/EP2014/078868 issued; P.M.S. reports grants/research supports from the ministry of education, science and technological development of Republic of Serbia. Receipt of honoraria or consultation fees from Servier, Boehringher Ingelheim, Hemofarm, Novartis, Astra Zeneca. Participation in a company sponsored speaker's bureau: Fondazione Internationale Menarini; R.C.S. reports grants from Novartis, grants from Amgen, other from Abbott, grants from Corvia, other from Novartis, outside the submitted work; C.G.T. reports grants from Federico II University-Ricerca d'Ateneo, personal fees from speaker honoraria from Alere, outside the submitted work; In addition, Dr. Tocchetti has a patent Canadian patent no. 2,613,477: "Thiol Sensitive Positive Inotropes", with royalties paid; J.-N.T. reports personal fees from Amgen, personal fees from Bayer, personal fees from Resmed, grants and personal fees from Abott, grants and personal fees from Novartis, grants and personal fees from Carmat, outside the submitted work; T.T. is the founder and shareholder of Cardior. He also filed and licensed a number of non-coding RNA based patents in the cardiovascular disease era; F.Z. reports personal fees from Janssen, personal fees from Bayer, personal fees from Novartis, personal fees from Boston Scientific, personal fees from Resmed, personal fees from Amgen, personal fees from CVRx, personal fees from Quantum Genomics, personal fees from General Electric, personal fees from Boehringer, other from cardiorenal, other from CVCT, personal fees from AstraZeneca, personal fees from Vifor Fresenius, outside the submitted work.