Left Ventricular Ejection Fraction and the Future of Heart Failure Phenotyping
- PMID: 38099892
- DOI: 10.1016/j.jchf.2023.11.005
Left Ventricular Ejection Fraction and the Future of Heart Failure Phenotyping
Abstract
Heart failure (HF) is a complex syndrome traditionally classified by left ventricular ejection fraction (LVEF) cutpoints. Although LVEF is prognostic for risk of events and predictive of response to some HF therapies, LVEF is a continuous variable and cutpoints are arbitrary, often based on historical clinical trial enrichment decisions rather than physiology. Holistic evaluation of the treatment effects for therapies throughout the LVEF range suggests the standard categorization paradigm for HF merits modification. The multidisciplinary Heart Failure Collaboratory reviewed data from large-scale HF clinical trials and found that many HF therapies have demonstrated therapeutic benefit across a large range of LVEF, but specific treatment effects vary across that range. Therefore, HF should practically be classified by association with an LVEF that is reduced or not reduced, while acknowledging uncertainty around the precise LVEF cutpoint, and future research should evaluate new therapies across the continuum of LVEF.
Keywords: classification; heart failure; left ventricular ejection fraction; phenotyping.
Published by Elsevier Inc.
Conflict of interest statement
Funding Support and Author Disclosures Dr Ibrahim has received consulting fees from Cytokinetics. Dr McMurray discloses payments to his employer, Glasgow University, for his work on clinical trials, consulting, and other activities: Alnylam, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Cardurion, Cytokinetics, Dal-Cor, GlaxoSmithKline, Ionis, KBP Biosciences, Novartis, Pfizer, and Theracos; and personal payments: Abbott, Alkem Metabolics, Eris Lifesciences, Hikma, Ionis, Lupin, ProAdWise Communications, Sun Pharmaceuticals, and Servier. Dr Lindenfeld has received consulting fees from Abbott, Alleviant, Boston Scientific, Cordio, CRVx, Edwards Lifesciences, Medtronic, Merck, Whiteswell, Vascular Dynamics, and V-Wave. Dr Bozkurt has received consulting fees from Amgen, AstraZeneca, Bristol Myers Squibb, scPharmaceuticals, Baxter, Sanofi, Relypsa, Vifor, Roche, and Boehringer Ingelheim; has served on the steering committees of Relypsa and Renovacor; has served on a Clinical Event Committee for Abbott Pharmaceuticals; and has served on the Data Safety Monitoring Board for LivaNova Pharmaceuticals. Dr Bristow has served as a director, officer, partner, advisor, consultant, or trustee for ARCA biopharma; has received research grants from the American Heart Association and National Institute of Allergy and Infectious Diseases; and has received personal payments from ARCA biopharma. Dr Butler has received consulting fees from Boehringer Ingelheim, Cardior, CVRx, Foundry, G3 Pharma, Imbria, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, Roche, Sanofi, Sequana Medical, V-Wave Ltd, and Vifor; and is a Trial Executive Committee member of the Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance (trial sponsor). Dr Carson has received consulting fees from Boehringer Ingelheim and IQVIA related to work on Clinical Events Committees. Dr Felker has received research grants from the National Heart, Lung, and Blood Institute, American Heart Association, Amgen, Bayer, BMS, Novartis, Daxor, Merck, Cytokinetics, and CSL-Behring; has acted as a consultant to Novartis, Amgen, BMS, Cytokinetics, Innolife, Medtronic, Cardionomic, Boehringer Ingelheim, American Regent, Abbott, AstraZeneca, Regeneron, Reprieve, Myovant, Sequana, Windtree Therapuetics, Rocket Pharma, and Whiteswell; and has served on clinical endpoint committees/data safety monitoring boards for Amgen, Merck, Medtronic, EBR Systems, V-Wave, and LivaNova. Dr Murillo is an employee and stockholder of UnitedHealth Group. Dr Kondo has received grants from the Uehara Memorial Foundation and the Japanese Heart Failure Society Tsuchiya Foundation for research activity at the University of Glasgow; and has received lecture fees from Ono Pharmaceutical Co, Ltd, Otsuka Pharmaceutical Co, Ltd, Novartis Pharma K.K., AstraZeneca K.K., Bristol Myers Squibb Co, Abiomed Japan K.K., and Boehringer Ingelheim. Dr Solomon has received research grants from Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, BMS, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lone Star Heart, Mesoblast, MyoKardia, National Institutes of Health/National Heart, Lung and Blood Institute, Novartis, Sanofi Pasteur, and Theracos; and has consulted for Akros, Alnylam, Amgen, AstraZeneca, Bayer, BMS, Cardior, Corvia, Cytokinetics, Gilead, GlaxoSmithKline, Ironwood, Merck, MyoKardia, Novartis, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, AoBiome, Janssen, Cardiac Dimensions, and Tenaya. Dr Abraham has received consulting fees from Boehringer Ingelheim, Cardionomic, Zoll Respicardia, scPharmaceuticals, Sensible Medical, and Vectorious; has received salary support from V-Wave Medical; and has served as a speaker for Edwards Lifesciences. Dr O’Connor has received grant or research support from Merck; and consulting fees from Merck, Bayer, and Abiomed. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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