Heart failure with preserved ejection fraction (HFpEF) is, in many ways, a fascinating tale of modern cardiovascular medicine that, according to lead author Dr. Joshua Hare (University of Miami Miller School of Medicine), has taught cardiovascular researchers and clinicians a lot of humility. Understanding HFpEF in a variety of animal models has led to a paradigm shift away from heart failure linked to low ejection fraction. In this episode Associate Editor Dr. Jonathan Kirk (Loyola University Chicago Stritch School of Medicine) interviews Dr. Hare along with expert Dr. Julie McMullen (Baker Heart and Diabetes Institute, Melbourne, Australia) about the latest study by Kanashiro-Takeuchi et al. The Hare Lab was originally attracted to a cardiometabolic model of HFpEF pioneered by Dr. Joseph Hill, because in a large proportion of human patients, HFpEF is due to metabolic syndrome, which is a combination of obesity, diabetes, and hypertension. Armed with the ability to create this cardiometabolic HFpEF model, Hare and co-authors decided to test growth hormone-releasing hormone-agonist using a powerhouse of methods to determine if exercise intolerance could be improved. Kanashiro-Takeuchi et al. found that diastolic function and exercise performance improved, and myocyte hypertrophy and fibrosis were restored. Essentially all of the features of cardiometabolic HFpEF responded to treatment with GHRH-agonist. The authors did not see a reduction in blood pressure or weight, indicating a direct myocardial effect. In a wide-ranging discussion that touches on skeletal muscle, aging, sarcomeric proteins, and the technical complexities of running titin gels and PV loops, our experts explain why HFpEF is such a challenging syndrome to treat and why this translational research is so important. Listen now.

Rosemeire M. Kanashiro-Takeuchi, Lauro M. Takeuchi, Raul A. Dulce, Katarzyna Kazmierczak, Wayne Balkan, Renzhi Cai, Wei Sha, Andrew V. Schally, Joshua M. Hare Efficacy of a Growth Hormone-Releasing Hormone Agonist in a Murine Model of Cardiometabolic Heart Failure with Preserved Ejection Fraction Am J Physiol Heart Circ Physiol, published April 25, 2023. DOI: 10.1152/ajpheart.00601.2022.