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.