Clinical Heart and Vascular Center

HFpEF: Mechanism and Management

By Joseph A. Hill, M.D., Ph.D.

Professor of Internal Medicine

Editor-in-Chief, Circulation

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Dr. Joseph A. Hill

Heart failure with preserved ejection fraction (HFpEF) accounts for approximately 50% of all heart failure and is associated with significant morbidity, mortality, and health care expenditures. Sadly, there are no evidence-based therapies with demonstrated efficacy in HFpEF. None. We have no therapies to treat these tens of millions of individuals worldwide; rather, we are relegated to treating symptoms and comorbidities. It has been said that HFpEF is the single greatest unmet need in cardiovascular medicine.

At UT Southwestern, we have mounted a comprehensive, multidisciplinary attack on HFpEF. At a basic science level, we engineered an animal model that faithfully recapitulates the myriad features we see in our HFpEF patients. We did this in response to the sad reality that existing preclinical models do not reflect the clinical realities of the syndrome. Working with mice that “look like patients with HFpEF” – hypertensive and obese – we unveiled novel molecular mechanisms never reported previously in cardiovascular disease. Importantly, we confirmed our surprising findings – meta-inflammation – in endomyocardial biopsy specimens from HFpEF patients. These findings were published recently in a landmark paper in Nature.

“We are tackling the challenge of HFpEF across a spectrum spanning fundamental molecular research all the way to clinical trials. This is coupled with an ever-expanding emphasis on the care of this growing group of patients.”

Joseph A. Hill, M.D., Ph.D.

In addition to continuing our molecular studies (presented by Gabriele Schiattarella, M.D., Ph.D., in the Melvin L. Marcus Early Career Investigator Award competition), work is underway to develop a large animal model of HFpEF. In parallel, we are launching a first-in-human clinical trial based on our findings. All of this is occurring in the context of a growing clinical focus in our division on this burgeoning population of patients.

We are tackling the challenge of HFpEF across a spectrum spanning fundamental molecular research all the way to clinical trials. This is coupled with an ever-expanding emphasis on the care of this growing group of patients. There are few cardiology programs in the world capable of harnessing so vast a spectrum of science coupled with outstanding clinical care, fostering bidirectional collaborations to advance the field. Looking to the future, we believe we are on the verge of significant advances in the care of patients with HFpEF.

Follow Dr. Joseph Hill:

Twitter: @josephahill

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