The continuous heart failure spectrum: Moving beyond an ejection fraction classification

Filippos Triposkiadis, Javed Butler, Francois M. Abboud, Paul W. Armstrong, Stamatis Adamopoulos, John J. Atherton, Johannes Backs, Johann Bauersachs, Daniel Burkhoff, Robert O. Bonow, Vijay K. Chopra, Rudolf A. De Boer, Leon De Windt, Nazha Hamdani, Gerd Hasenfuss, Stephane Heymans, Jean Sébastien Hulot, Marvin Konstam, Richard T. Lee, Wolfgang A. LinkeIda G. Lunde, Alexander R. Lyon, Christoph Maack, Douglas L. Mann, Alexandre Mebazaa, Robert J. Mentz, Petros Nihoyannopoulos, Zoltan Papp, John Parissis, Thierry Pedrazzini, Giuseppe Rosano, Jean Rouleau, Petar M. Seferovic, Ajay M. Shah, Randall C. Starling, Carlo G. Tocchetti, Jean Noel Trochu, Thomas Thum, Faiez Zannad, Dirk L. Brutsaert, Vincent F. Segers, Gilles W. De Keulenaer

Research output: Contribution to journalReview articlepeer-review

190 Scopus citations


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.

Original languageEnglish
Pages (from-to)2155-2163B
JournalEuropean heart journal
Issue number26
StatePublished - Jul 7 2019


  • Ejection fraction
  • Endothelium
  • Heart failure
  • Pathophysiology


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