Heart Failure Preserved Ejection Fraction, Epicardial Adipose Tissue
Conditions
Keywords
HFpEF, Heart Failure preserved Ejection Fraction, Cardiac MRI, Epicardial Adipose Tissue, GLP-1, EAT FAC, cardiovascular function
Brief summary
This study seeks to develop improved cardiac MRI (CMR) methods to quantify epicardial adipose tissue (EAT) composition and to demonstrate the advantages of EAT composition imaging (a) in advancing the understanding of the relationship between EAT and heart failure with preserved ejection fraction (HFpEF) and (b) for understanding mechanisms of and guiding medical therapy in HFpEF. The investigators recently developed the first method for quantifying EAT FAC in human subjects, utilizing a rate-6 accelerated radial 2D multi-echo gradient-echo breathhold acquisition with a local low rank reconstruction. In this project the first specific aim is to develop a rapid free-breathing 3D EAT FAC MRI method that reduces motion-related artifacts, increases coverage, and facilitates higher spatial resolution and improved FAC reproducibility. The second specific aim is to show that EAT FAC is more strongly associated than EAT volume with cardiometabolic HFpEF. In this context, individuals with known or suspected HFpEF will undergo CMR, echocardiography, and other testing to (a) diagnose cardiometabolic HFpEF; (b) characterize features associated with the severity of HFpEF; and (c) assess EAT volume and FAC. The investigators will determine if EAT FAC is more strongly associated than EAT volume with HFpEF and with features associated with the severity of HFpEF. The third specific aim is to show, in the context of cardiometabolic HFpEF and pre-HFpEF, (a) that GLP-1 receptor agonism with semaglutide (SEMA) shifts the EAT FAC to a less proinflammatory profile and (b) that baseline EAT FAC is a stronger predictor than EAT volume of improved cardiovascular function due to SEMA. Cardiometabolic HFpEF and pre-HFpEF subjects will undergo echocardiography and CMR with EAT FAC at baseline and after 3 months to serve as a self-control. Subjects will then undergo repeat imaging 6 months after the initiation of SEMA. The change in FAC after treatment with SEMA will be compared to the change in FAC prior to SEMA. Data will be analyzed to show that SEMA changes EAT FAC, and that baseline EAT FAC is a stronger predictor than EAT volume of improvements in severity of HFpEF.
Interventions
DRUGGLP-1RA
Receive 6 months of GLP-1RA (Semaglutide) treatment starting at 0.25mg once weekly and then the dose will be up titrated as tolerated every four weeks to once-weekly doses of 0.5, 1.0, 1.7, and 2.4 mg until a target dose of 2.4mg is reached after 16 weeks.
Sponsors
National Institutes of Health (NIH)
University of Virginia
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years - 90 years; * LVEF ≥ 50%; * ≥ 2 risk factors for HFpEF or symptoms that could be related to HFpEF (e.g., dyspnea, orthopnea, paroxysmal nocturnal dyspnea, lower extremity edema, pulmonary edema, etc); * Not currently being treated with GLP-1RA therapy or SGLT2i therapy.
Exclusion criteria
* • Previously or currently reduced EF (\<50%), including heart transplant; (2) Obstructive un-revascularized coronary disease by coronary CT or invasive coronary angiography; * MI/PCI/CABG within the past 6 months; * Untreated severe stenotic or regurgitant valvular disease; * Infiltrative cardiomyopathy (Fabry/HCM/sarcoid/amyloid, etc); * Myocarditis; * Claustrophobia/inability to tolerate MRI; * Implants that are a contraindication for MRI or may negatively impact image quality (e.g. pacemakers and ICDs); * Active systemic inflammatory disorder; * Atrial fibrillation with rapid ventricular response at time of study; and * Hemodynamic instability * Pregnancy * Prisoners * Inability to provide informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Epicardial adipose tissue (EAT) fatty acid composition (FAC) | Baseline, 3 months (self-control period), and 9-months (6 months post semaglutide treatment) | The longitudinal change in epicardial adipose tissue (EAT) fatty acid composition (FAC) \[quantified in terms of the fraction of saturated fatty acids (SFA) in units of %\] that occur after 6 months of treatment with semaglutide will be compared to the change in SFA that occurred during 3 month period prior to the initiation of semaglutide. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| EAT Volume | Baseline, 3months (self-control period), and 9-months (6 months post semaglutide treatment) | The longitudinal change in epicardial adipose tissue (EAT) volume (ml) that occurs after 6 months of treatment with semaglutide will be compared to the change in SFA that occurred during 3 month period prior to the initiation of semaglutide. |
| Baseline Saturated Fatty Acid Composition of Epicaridal Adipose Tissue and Change in Myocardial Deformation | Baseline, 3months (self-control period), and 9-months (6 months post semaglutide treatment) | The cohort will be divided into 2 groups based on the median value of the epicardial adipose tissue saturated fatty acid composition. The change in global strain (%) following treatment with semaglutide will be compared between the groups. |
| Baseline Saturated Fatty Acid Composition of Epicaridal Adipose Tissue and Change in diastolic dysfunction grade | Baseline, 3months (self-control period), and 9-months (6 months post semaglutide treatment) | The cohort will be divided into 2 groups based on the median value of the epicardial adipose tissue saturated fatty acid composition. The change in diastolic dysfunction grade following treatment with semaglutide will be compared between the groups. |
Countries
United States
Contacts
Primary ContactShuo Wang
Outcome results
None listed