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Review
. 2023 Jan 31;81(4):413-424.
doi: 10.1016/j.jacc.2022.11.023.

Worsening Heart Failure: Nomenclature, Epidemiology, and Future Directions: JACC Review Topic of the Week

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Free article
Review

Worsening Heart Failure: Nomenclature, Epidemiology, and Future Directions: JACC Review Topic of the Week

Stephen J Greene et al. J Am Coll Cardiol. .
Free article

Abstract

Heart failure (HF) is a progressive disease characterized by variable durations of symptomatic stability often punctuated by episodes of worsening despite continued therapy. These periods of clinical worsening are increasingly recognized as a distinct phase in the history of HF, termed worsening HF (WHF). The definition of WHF continues to evolve from a historical focus solely on hospitalization to now include nonhospitalization events (eg, need for intravenous diuretic therapy in the emergency or outpatient setting). Most HF clinical trials to date have had HF hospitalization and death as primary endpoints, and only recently, some studies have included other WHF events regardless of location of care. This article reviews the evolution of the WHF definition, highlights the importance of considering the onset of WHF as an event that marks a new phase of HF, summarizes the latest clinical trials investigating novel therapies, and outlines unmet needs regarding identification and treatment of WHF.

Keywords: biologic definition; biomarkers; clinical trial endpoints; diuretic therapy; hemodynamic monitoring; worsening heart failure.

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Conflict of interest statement

Funding Support and Author Disclosures This work was supported by Bayer AG, Germany. Dr Greene has received research support from the Duke University Department of Medicine Chair’s Research Award, American Heart Association, National Heart, Lung, and Blood Institute, Amgen, AstraZeneca, Bristol Myers Squibb, Cytokinetics, Merck, Novartis, Pfizer, and Sanofi; has served on advisory boards for Amgen, AstraZeneca, Boehringer Ingelheim and Eli Lilly, Bristol Myers Squibb, Cytokinetics, Roche Diagnostics, scPharmaceuticals, and Sanofi; has served as a consultant for Amgen, Bayer, Boehringer Ingelheim and Eli Lilly, Bristol Myers Squibb, Corteria Pharmaceuticals, CSL Vifor, Merck, PharmaIN, Roche Diagnostics, Sanofi, Tricog Health, and Urovant Pharmaceuticals; and has received speaker fees from Boehringer Ingelheim and Cytokinetics. Dr Bauersachs has received honoraria for lectures/consulting from Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Cardior, Corvia, CVRx, Novartis, Pfizer, and Vifor; and has received institutional research support from Zoll, CVRx, and Abiomed. Dr Brugts has received research grants from Abbott and Vifor Pharma; and has received speaker fees from or has served on advisory boards for Abbott, Bayer, Boehringer, Novartis, and Vifor Pharma. Dr Ezekowitz has received research grants from Bayer, Merck, Servier, Amgen, Sanofi, Novartis, Cytokinetics, American Regent, and Applied Therapeutics; and has received consulting fees from Bayer, Merck, Servier, Amgen, Sanofi, Novartis, Cytokinetics, American Regent, and Applied Therapeutics. Dr Lam is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from Bayer and Roche Diagnostics; has served as consultant or on advisory boards/steering committees/executive committees for Actelion, Alleviant Medical, Allysta Pharma, Amgen, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Darma Inc, EchoNous Inc, Eli Lilly, Impulse Dynamics, Ionis Pharmaceutical, Janssen Research & Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, ProSciento Inc, Radcliffe Group Ltd, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics and Us2.ai; and serves as cofounder and nonexecutive director of Us2.ai. Dr Lund has received grants from AstraZeneca, Vifor Pharma, Boston Scientific, Boehringer Ingelheim, and Novartis; has served as a consultant for Merck, Vifor Pharma, AstraZeneca, Bayer, Pharmacosmos, MedScape, Sanofi, Lexicon Pharmaceuticals Inc, Myokardia, Boehringer Ingelheim, and Servier; has received speaker honoraria from Abbott, MedScape, Radcliffe, AstraZeneca, Novartis, and AnaCardio AB; and owns stock in AnaCardio AB. Dr Ponikowski has served as consultant or on advisory boards/steering committees/executive committees for Abbott Vascular, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Impulse Dynamics, Merck, Novartis, Radcliffe Group Ltd, Servier, and Vifor Pharma. Dr Zieroth has received research grant support, served on advisory boards, or been a speaker for Abbott, Akcea Therapeutics, Inc., AstraZeneca, Amgen, Alnylam, Bayer, BMS, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novartis, Novo Nordisk, Otsuka, Pfizer, Servier, and Vifor Pharma; and has served on a clinical trial steering committee or as a national lead for studies sponsored by AstraZeneca, Bayer, Boehringer Ingelheim, Merck, and Novartis. Dr Butler has served as a consultant for Abbott, Adrenomed AG, Amgen, American Regent, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CVRx, G3 Pharmaceutical, Impulse Dynamics, Innolife, Janssen Pharmaceuticals, LivaNova, Medtronic, Merck, Novartis, NovoNordisk, Pfizer, Roche, and Vifor Pharma. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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