Semaglutide's Hypothesized Modulation of Epicardial Adipose Tissue Composition to Improve HFpEF Outcomes

Heart Failure with Preserved Ejection Fraction (HFpEF) is a complex syndrome characterized by stiff heart muscle and impaired relaxation, leading to fluid buildup despite normal pumping function. Current therapies often fall short in addressing its diverse underlying mechanisms, particularly in cardiometabolic subtypes. Epicardial adipose tissue (EAT), the fat surrounding the heart, is increasingly recognized as an active endocrine organ that can secrete proinflammatory factors, contributing to myocardial dysfunction and fibrosis in HFpEF. Understanding EAT composition, beyond just volume, offers a novel avenue for diagnosis and targeted therapy. GLP-1 receptor agonists like semaglutide have shown broad cardiometabolic benefits, suggesting a potential role in modulating EAT and improving HFpEF outcomes.

This study outlines a protocol to develop and apply advanced cardiac MRI (CMR) methods for quantifying EAT fat attenuation coefficient (FAC) in human subjects. The first aim is to develop a rapid free-breathing 3D EAT FAC MRI method to improve resolution and reproducibility. The second aim involves individuals with known or suspected HFpEF undergoing CMR, echocardiography, and other tests to diagnose cardiometabolic HFpEF, characterize severity, and assess EAT volume and FAC. The third aim focuses on cardiometabolic HFpEF and pre-HFpEF subjects, who will undergo baseline and 3-month follow-up imaging, serving as a self-control. They will then undergo repeat imaging 6 months after semaglutide (SEMA) initiation, with changes in FAC compared.