Physician Update: AHA Special Edition
Read more articles from our most relevant research presented at the 2023 AHA Scientific Sessions.
Clinical Heart and Vascular Center
HFpEF: Insights from Preclinical Models
By Joseph A. Hill, M.D., Ph.D.
Professor of Internal Medicine and Molecular Biology
As we have become increasingly successful in treating acute cardiovascular events, attention has turned to heart failure (HF) as the next major hurdle in cardiovascular medicine; more and more people are surviving the acutely lethal manifestations of cardiovascular diseases, returning to family and society with an injured heart, often culminating in HF. HFpEF (heart failure with preserved ejection fraction) is now the most common form of HF and a significant public health concern for which limited effective therapies exist.
A growing therapeutic arsenal has improved outcomes in HFrEF (heart failure with reduced ejection fraction), yet our ability to treat HFpEF remains only modestly effective. In light of significant morbidity/mortality associated with HFpEF, coupled with the fact that it is now the most prevalent form of HF, deciphering the molecular underpinnings of this syndrome is of paramount importance. Leveraging these findings to promote development of new therapies is critical for improving patient outcomes.
For some years, the clinical trial space in HFpEF has been littered with multiple – numerous – failures. One explanation for this is lack of communication between clinicians, experts in the realities of HFpEF but often not equipped to glean underlying mechanisms, and scientists who are expert at deciphering molecular mechanisms but are often unfamiliar with the clinical realities of the syndrome. Recently, our group developed a rather simplistic animal model of HFpEF that involved “making a mouse that looks like a patient with cardiometabolic HFpEF”: obese with metabolic syndrome and hypertension. In work we published in Nature in 2019, we reported that these mice do, in fact, recapitulate most of the numerous features of human HFpEF, and our work went on to glean underlying mechanisms never previously reported in cardiovascular science – meta-inflammation.
“In light of significant morbidity/mortality associated with HFpEF, coupled with the fact that it is now the most prevalent form of HF, deciphering the molecular underpinnings of this syndrome is of paramount importance.”
At #AHA23, I presented these findings in my delivery of the Thomas W. Smith Memorial Lecture. Now, I’m pleased that our work has been replicated numerous times in both academia and industry, and the HFpEF field is advancing again. I am optimistic that insights with clinical relevance will emerge with time.
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