ESC William Harvey Lecture on Basic Science: Prof. Joseph Hill
HFpEF: Malady, model, meta-inflammatory mechanisms
29 Aug 2021
Cardiologist-scientist, Professor Joseph Hill, Professor of Internal Medicine and Molecular Biology and Director, Harry S. Moss Heart Center, and Chief of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA, has played a key role in elucidating mechanisms of heart failure with preserved ejection fraction (HFpEF) to facilitate the development of urgently required treatments for this difficult-to-manage condition.
What inspired you to become a cardiologist-scientist?
Originally, I planned to be a physical chemist. I then realised that while I was committed to doing research, I wanted it to have more of a direct human impact. Becoming a physician-scientist allowed me to combine taking care of patients and doing research at the same time.
For me, cardiology was attractive as a specialty for two reasons. Firstly, diagnosis centres on the physical examination and talking to the patient about their symptoms, whereas, in other specialties, the focus is more on laboratory tests. Secondly, the science of cardiology and the medicine of cardiology are very closely aligned, and the effects of scientific developments can often be seen in the clinical setting within just a few years.
How did you become interested in studying HFpEF?
My interest in HFpEF really developed a few years ago when the cardiologist-scientist Gabriele Schiattarella joined our department to complete his PhD. Both practising cardiologists, he and I agreed that meeting the enormous clinical challenge of HFpEF has been hampered by the fact that preclinical models of the syndrome do not always faithfully represent the clinical realities. This has very likely contributed to the many disappointing results we have seen with the translation of HFpEF research into the clinic. We developed a mouse model that better resembles the HFpEF seen in patients and used this model to uncover some of the mechanisms involved.
It is important to recognise that HFpEF and heart failure with reduced ejection fraction (HFrEF) are two entirely different, mechanistically distinct conditions, with only a very modest overlap in mechanism. We discovered that HFpEF has critical elements involving metabolic and inflammatory pathways, so-called meta-inflammation. We have since observed these events in human tissue samples. Subsequent to the publication of our findings,1 the message of ‘metabolism plus inflammation’ for HFpEF seems to be taking off. Indeed, we have evidence of this here at ESC Congress 2021, with the positive findings emerging from the EMPEROR-Preserved trial with empagliflozin.
What are the current challenges in your field?
One of the major challenges is that we have brilliant scientists, who are trained to uncover mechanisms but sometimes do not understand the clinical realities, and brilliant clinicians, who know the clinical problems very well but do not have the scientific expertise. We need to bring these professionals together if we are to conduct research more effectively.
Where do you think research in your field is heading in the future?
Robust successes in cardiology over the last 30 years have led us to a situation that is similar to that seen with HIV/AIDS. Improved treatments have allowed us to transform cardiac disease from something that used to be characterised regularly by acute death into a chronic disorder – heart failure – that people can survive with for years. My view is that much of the future of cardiac medicine will centre around trying to relieve the burden of heart failure and other chronic manifestations of heart disease.
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1. Schiattarella GG, et al. Nature. 2019;568:351–356.