@article{3105822,
    title = "The continuous heart failure spectrum: Moving beyond an ejection fraction classification",
    author = "Triposkiadis, F. and Butler, J. and Abboud, F.M. and Armstrong, P.W. and Adamopoulos, S. and Atherton, J.J. and Backs, J. and Bauersachs, J. and Burkhoff, D. and Bonow, R.O. and Chopra, V.K. and De Boer, R.A. and De Windt, L. and Hamdani, N. and Hasenfuss, G. and Heymans, S. and Hulot, J.-S. and Konstam, M. and Lee, R.T. and Linke, W.A. and Lunde, I.G. and Lyon, A.R. and Maack, C. and Mann, D.L. and Mebazaa, A. and Mentz, R.J. and Nihoyannopoulos, P. and Papp, Z. and Parissis, J. and Pedrazzini, T. and Rosano, G. and Rouleau, J. and Seferovic, P.M. and Shah, A.M. and Starling, R.C. and Tocchetti, C.G. and Trochu, J.-N. and Thum, T. and Zannad, F. and Brutsaert, D.L. and Segers, V.F. and De Keulenaer, G.W.",
    journal = "EUROPEAN HEART JOURNAL-CARDIOVASCULAR PHARMACOTHERAPY",
    year = "2019",
    volume = "40",
    number = "26",
    pages = "2155-2163B",
    publisher = "Oxford University Press",
    doi = "10.1093/eurheartj/ehz158",
    keywords = "cardiac muscle cell;  cell damage;  clinical feature;  comorbidity;  disease classification;  disease exacerbation;  endothelial dysfunction;  heart disease;  heart ejection fraction;  heart failure;  heart failure with reduced ejection fraction;  heart left atrial dysfunction;  heart left ventricle ejection fraction;  heart muscle fibrosis;  heart right ventricle failure;  heart ventricular dyssynchrony;  human;  left ventricular diastolic dysfunction;  left ventricular systolic dysfunction;  myopathy;  pathophysiology;  phenotype;  priority journal;  QRS interval;  Review;  risk factor;  sudden cardiac death;  classification;  heart failure;  heart left ventricle function;  heart stroke volume;  heart ventricle remodeling;  pathology;  physiology;  reference value;  vascular endothelium, Comorbidity;  Disease Progression;  Endothelium, Vascular;  Heart Failure;  Humans;  Myocytes, Cardiac;  Reference Values;  Stroke Volume;  Ventricular Dysfunction, Left;  Ventricular Remodeling",
    abstract = "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. © The Author(s) 2019."
}