NYMC Faculty Publications

Heart Failure With Preserved Ejection Fraction: Key Stumbling Blocks for Experimental Drugs in Clinical Trials

Author Type(s)

Faculty

DOI

10.1080/13543784.2022.2069009

Journal Title

Expert Opinion on Investigational Drugs

First Page

463

Last Page

474

Document Type

Article

Publication Date

5-1-2022

Department

Medicine

Abstract

INTRODUCTION: Heart failure with preserved ejection fraction (HFpEF) is a disease with a high prevalence. Accounting for more than 50% of all heart failure cases, it carries a significant mortality. There is a lack of therapeutic options that show improvement in morbidity and mortality. Certain novel therapies have shown a decrease in heart failure hospitalizations; however, this beneficial effect was more pronounced for heart failure patients with mildly reduced ejection fraction (EF). AREAS COVERED: This review summarizes the pathophysiology of the disease to help elucidate the differences between heart failure with reduced ejection fraction (HFrEF), and HFpEF, which could explain why therapies are successful in one (rather than the other). This review focuses on non-standardized nomenclature across major trials, the challenges of finding a therapeutic agent for such a heterogeneous population, and identification of specific phenotypes that have different outcomes and could be a target for future therapies. EXPERT OPINION: Lack of standardized diagnostic criteria, associated with population heterogeneity, might explain why trials have failed to improve outcomes for patients with HFpEF. Standardizing phenotypes, recapitulating these phenotypes in animal models, and understanding the mechanisms of the disease at the molecular level could be the first steps in identifying promising therapeutic options.

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