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Talking Therapeutics: Preserving Hope for Patients With HFpEF

March 10, 2021

By Douglas L. Jennings, PharmD, FACC, FAHA, FCCP, FHFSA, BCPS

Volume 1, Issue 2

talking therapeutics doug jennings“A rose by any other name would smell as sweet”

When it comes to managing patients with heart failure (HF), it’s all in the name. For patients classified as heart failure with reduced ejection fraction (HFrEF), there are many options for guideline-directed medical therapies (GDMT) that can unequivocally reduce morbidity and prolong life. Conversely, for patients with a preserved ejection fraction (HFpEF), there are no treatments that have conclusively proven effective. This fact is quite staggering when one considers that nearly half of the roughly six million Americans with heart failure have a preserved ejection fraction. In this week’s issue of “Talking Therapeutics,” we take a look at the latest updates on how heart failure is classified and explore a novel treatment option for patients with HFpEF.

Point 1: A Universal Definition for Heart Failure Has Finally Been Established

While we may think that the current heart failure classifications are uniform, there is actually significant variability in the definitions used for the various HFrEF and HFpEF clinical trials. Fortunately, the American, European, and Japanese heart failure societies recently convened to develop the Universal Definition and Classification of Heart Failure. In this document, standardized definitions for heart failure according to ejection fraction have been proposed:

  • HF with reduced EF (HFrEF): HF with an LVEF of ≤40%;
  • HF with mildly reduced EF (HFmrEF): HF with an LVEF of 41% to 49%;
  • HF with preserved EF (HFpEF): HF with an LVEF of ≥50%;
  • HF with improved EF (HFimpEF): HF with a baseline LVEF of ≤40%, a >10-point increase from baseline LVEF, and a second measurement of LVEF of >40%.

Having standardized cuff offs for ejection fraction is critical for accurately classifying patients for appropriate therapy, a fact which is even more important because….

Point 2: The FDA Just Approved sacubitril/valsartan (Entresto) for Patients With HFpEF

This news, which is based on data from the PARAGON study, expands the approved label for Entresto to include patients with heart failure whose ejection fraction is “not normal.” Who exactly falls into the category of “not normal” is somewhat up for debate, especially since the PARAGON trial defined HFpEF as an ejection fraction of ≥45%. Digging a little deeper into the data, the benefits seen in PARAGON were primarily in those with ejection fractions between 45% to 57%. This may seem like a narrow range, but expanding Entresto use to these patients would actually cover two-thirds of Americans with HFpEF, which translates into roughly 2 million new candidates. Given the relative lack of effective therapies, this change in the FDA labelling is very significant for patients afflicted with HFpEF.  

The bottom line for this week’s column: thanks to a world-wide collaboration of experts, we now have a clear classification schema for patients with heart failure; furthermore, all symptomatic heart failure patients with a confirmed ejection fraction less than 57% should be evaluated for therapy with Entresto.


Dr Jennings is currently an Associate Professor of Pharmacy at Long Island University and the clinical pharmacist for the Heart Transplant and LVAD teams at NewYork- Presbyterian Hospital Columbia University Irving Medical Center.  He is an active researcher in his field, and he has published over 120 peer-reviewed abstracts and manuscripts, primarily focusing on the pharmacotherapy of patients under mechanical circulatory support. As a recognized expert in this area, he has been invited to speak at numerous national and international venues, including meetings in France, Saudia Arabia, India. Finally, Dr. Jennings has been active in professional organizations throughout his career. He is a fellow of the American College of Clinical Pharmacy, the American College of Cardiology, the Heart Failure Society of America, and the American Heart Association.  

Disclaimer: The views and opinions expressed are those of the authors and do not necessarily reflect the official policy or position of Population Health Learning Network. Any content provided by our bloggers or authors are of their opinion and are not intended to malign any religion, ethnic group, club, organization, company, individual or anyone or anything.

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