Epicardial Adipose Tissue Composition and Heart Failure With Preserved Ejection Fraction

NCT ID: NCT07178145

Last Updated: 2025-09-17

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 192 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-30
• Study Completion Date: 2029-12-31

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.

Conditions

Heart Failure Preserved Ejection Fraction; Epicardial Adipose Tissue

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

3D EAT FAC CMR imaging

non-contrast MRI to debug/test 3D MRI techniques for quantifying EAT FAC

Group Type: NO_INTERVENTION

No interventions assigned to this group

Imaging acquisition and medical condition overview

Will undergo Cardiac MRI, exercise echocardiography, 12 lead ECG, medical history review, bloodwork, physical exam, and optional stress cardiac MRI.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Imaging acquisition and GLP-1RA treatment

Will undergo all testing before and after a 6-month treatment of GLP-1RA

Group Type: EXPERIMENTAL

GLP-1RA

Intervention Type: DRUG

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.

Interventions

GLP-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.

Intervention Type: DRUG

Eligibility Criteria

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

• allergy to gadolinium-based contrast agents
• Acute kidney injury
• Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m²
• Hepatorenal syndrome
• History of liver transplant
• High-grade atrioventricular (AV) block
• Active asthma exacerbation
• Known allergy to vasodilator agents
• Recent seizure

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

University of Virginia

OTHER

Sponsor Role: lead

Responsible Party

Amit R. Patel

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Amit Patel, MD

Role: PRINCIPAL_INVESTIGATOR

University of Virginia

Locations

University of Virginia

Charlottesville, Virginia, United States

Countries

United States

Central Contacts

Shuo Wang

Role: CONTACT

VJR7CE@uvahealth.org

434-982-1058

Facility Contacts

Shuo Wang

Role: primary

JR7CE@uvahealth.org

434-982-1058

References

Pfeffer MA, Shah AM, Borlaug BA. Heart Failure With Preserved Ejection Fraction In Perspective. Circ Res. 2019 May 24;124(11):1598-1617. doi: 10.1161/CIRCRESAHA.119.313572.

Reference Type: BACKGROUND

PMID: 31120821 (View on PubMed)

Bozkurt B, Ahmad T, Alexander KM, Baker WL, Bosak K, Breathett K, Fonarow GC, Heidenreich P, Ho JE, Hsich E, Ibrahim NE, Jones LM, Khan SS, Khazanie P, Koelling T, Krumholz HM, Khush KK, Lee C, Morris AA, Page RL 2nd, Pandey A, Piano MR, Stehlik J, Stevenson LW, Teerlink JR, Vaduganathan M, Ziaeian B; Writing Committee Members. Heart Failure Epidemiology and Outcomes Statistics: A Report of the Heart Failure Society of America. J Card Fail. 2023 Oct;29(10):1412-1451. doi: 10.1016/j.cardfail.2023.07.006. Epub 2023 Sep 26. No abstract available.

Reference Type: BACKGROUND

PMID: 37797885 (View on PubMed)

Shah SA, Reagan CE, Bresticker JE, Wolpe AG, Good ME, Macal EH, Billcheck HO, Bradley LA, French BA, Isakson BE, Wolf MJ, Epstein FH. Obesity-Induced Coronary Microvascular Disease Is Prevented by iNOS Deletion and Reversed by iNOS Inhibition. JACC Basic Transl Sci. 2023 Feb 1;8(5):501-514. doi: 10.1016/j.jacbts.2022.11.005. eCollection 2023 May.

Reference Type: BACKGROUND

PMID: 37325396 (View on PubMed)

Echols JT, Wang S, Patel AR, Hogwood AC, Abbate A, Epstein FH. Fatty acid composition MRI of epicardial adipose tissue: Methods and detection of proinflammatory biomarkers in ST-segment elevation myocardial infarction patients. Magn Reson Med. 2025 Feb;93(2):519-535. doi: 10.1002/mrm.30285. Epub 2024 Sep 25.

Reference Type: BACKGROUND

PMID: 39323040 (View on PubMed)

Shah SA, Echols JT, Sun C, Wolf MJ, Epstein FH. Accelerated fatty acid composition MRI of epicardial adipose tissue: Development and application to eplerenone treatment in a mouse model of obesity-induced coronary microvascular disease. Magn Reson Med. 2022 Oct;88(4):1734-1747. doi: 10.1002/mrm.29348. Epub 2022 Jun 20.

Reference Type: BACKGROUND

PMID: 35726367 (View on PubMed)

Martel D, Leporq B, Saxena A, Belmont HM, Turyan G, Honig S, Regatte RR, Chang G. 3T chemical shift-encoded MRI: Detection of altered proximal femur marrow adipose tissue composition in glucocorticoid users and validation with magnetic resonance spectroscopy. J Magn Reson Imaging. 2019 Aug;50(2):490-496. doi: 10.1002/jmri.26586. Epub 2018 Dec 12.

Reference Type: BACKGROUND

PMID: 30548522 (View on PubMed)

Martel D, Leporq B, Bruno M, Regatte RR, Honig S, Chang G. Chemical shift-encoded MRI for assessment of bone marrow adipose tissue fat composition: Pilot study in premenopausal versus postmenopausal women. Magn Reson Imaging. 2018 Nov;53:148-155. doi: 10.1016/j.mri.2018.07.001. Epub 2018 Jul 10.

Reference Type: BACKGROUND

PMID: 30006022 (View on PubMed)

Leporq B, Lambert SA, Ronot M, Boucenna I, Colinart P, Cauchy F, Vilgrain V, Paradis V, Van Beers BE. Hepatic fat fraction and visceral adipose tissue fatty acid composition in mice: Quantification with 7.0T MRI. Magn Reson Med. 2016 Aug;76(2):510-8. doi: 10.1002/mrm.25895. Epub 2015 Nov 3.

Reference Type: BACKGROUND

PMID: 26527483 (View on PubMed)

Schneider M, Janas G, Lugauer F, Hoppe E, Nickel D, Dale BM, Kiefer B, Maier A, Bashir MR. Accurate fatty acid composition estimation of adipose tissue in the abdomen based on bipolar multi-echo MRI. Magn Reson Med. 2019 Apr;81(4):2330-2346. doi: 10.1002/mrm.27557. Epub 2018 Oct 28.

Reference Type: BACKGROUND

PMID: 30368904 (View on PubMed)

Bydder M, Girard O, Hamilton G. Mapping the double bonds in triglycerides. Magn Reson Imaging. 2011 Oct;29(8):1041-6. doi: 10.1016/j.mri.2011.07.004. Epub 2011 Aug 24.

Reference Type: BACKGROUND

PMID: 21868182 (View on PubMed)

Berglund J, Ahlstrom H, Kullberg J. Model-based mapping of fat unsaturation and chain length by chemical shift imaging--phantom validation and in vivo feasibility. Magn Reson Med. 2012 Dec;68(6):1815-27. doi: 10.1002/mrm.24196. Epub 2012 Feb 14.

Reference Type: BACKGROUND

PMID: 22334300 (View on PubMed)

Peterson P, Trinh L, Mansson S. Quantitative 1 H MRI and MRS of fatty acid composition. Magn Reson Med. 2021 Jan;85(1):49-67. doi: 10.1002/mrm.28471. Epub 2020 Aug 25.

Reference Type: BACKGROUND

PMID: 32844500 (View on PubMed)

Ren J, Dimitrov I, Sherry AD, Malloy CR. Composition of adipose tissue and marrow fat in humans by 1H NMR at 7 Tesla. J Lipid Res. 2008 Sep;49(9):2055-62. doi: 10.1194/jlr.D800010-JLR200. Epub 2008 May 28.

Reference Type: BACKGROUND

PMID: 18509197 (View on PubMed)

Johnson LF, Shoolery JN. Determination of Unsaturation and Average Molecular Weight of Natural Fats by Nuclear Magnetic Resonance. Analytical Chemistry 1962;34:1136-1139.

Reference Type: BACKGROUND

Zou Q, Torres LA, Fain SB, Higano NS, Bates AJ, Jacob M. Dynamic imaging using motion-compensated smoothness regularization on manifolds (MoCo-SToRM). Phys Med Biol. 2022 Jul 4;67(14):10.1088/1361-6560/ac79fc. doi: 10.1088/1361-6560/ac79fc.

Reference Type: BACKGROUND

PMID: 35714617 (View on PubMed)

Daude P, Roussel T, Troalen T, Viout P, Hernando D, Guye M, Kober F, Confort Gouny S, Bernard M, Rapacchi S. Comparative review of algorithms and methods for chemical-shift-encoded quantitative fat-water imaging. Magn Reson Med. 2024 Feb;91(2):741-759. doi: 10.1002/mrm.29860. Epub 2023 Oct 10.

Reference Type: BACKGROUND

PMID: 37814776 (View on PubMed)

Daude P, Troalen T, Mackowiak ALC, Royer E, Piccini D, Yerly J, Pfeuffer J, Kober F, Gouny SC, Bernard M, Stuber M, Bastiaansen JAM, Rapacchi S. Trajectory correction enables free-running chemical shift encoded imaging for accurate cardiac proton-density fat fraction quantification at 3T. J Cardiovasc Magn Reson. 2024 Winter;26(2):101048. doi: 10.1016/j.jocmr.2024.101048. Epub 2024 Jun 13.

Reference Type: BACKGROUND

PMID: 38878970 (View on PubMed)

Franz D, Diefenbach MN, Treibel F, Weidlich D, Syvari J, Ruschke S, Wu M, Holzapfel C, Drabsch T, Baum T, Eggers H, Rummeny EJ, Hauner H, Karampinos DC. Differentiating supraclavicular from gluteal adipose tissue based on simultaneous PDFF and T2 * mapping using a 20-echo gradient-echo acquisition. J Magn Reson Imaging. 2019 Aug;50(2):424-434. doi: 10.1002/jmri.26661. Epub 2019 Jan 25.

Reference Type: BACKGROUND

PMID: 30684282 (View on PubMed)

Reeder SB, Hu HH, Sirlin CB. Proton density fat-fraction: a standardized MR-based biomarker of tissue fat concentration. J Magn Reson Imaging. 2012 Nov;36(5):1011-4. doi: 10.1002/jmri.23741. Epub 2012 Jul 6. No abstract available.

Reference Type: BACKGROUND

PMID: 22777847 (View on PubMed)

Ma J. Dixon techniques for water and fat imaging. J Magn Reson Imaging. 2008 Sep;28(3):543-58. doi: 10.1002/jmri.21492.

Reference Type: BACKGROUND

PMID: 18777528 (View on PubMed)

Liu J, Yu Q, Li Z, Zhou Y, Liu Z, You L, Tao L, Dong Q, Zuo Z, Gao L, Zhang D. Epicardial adipose tissue density is a better predictor of cardiometabolic risk in HFpEF patients: a prospective cohort study. Cardiovasc Diabetol. 2023 Mar 4;22(1):45. doi: 10.1186/s12933-023-01778-8.

Reference Type: BACKGROUND

PMID: 36870978 (View on PubMed)

Ciuffo L, Nguyen H, Marques MD, Aronis KN, Sivasambu B, de Vasconcelos HD, Tao S, Spragg DD, Marine JE, Berger RD, Lima JAC, Calkins H, Ashikaga H. Periatrial Fat Quality Predicts Atrial Fibrillation Ablation Outcome. Circ Cardiovasc Imaging. 2019 Jun;12(6):e008764. doi: 10.1161/CIRCIMAGING.118.008764. Epub 2019 Jun 10.

Reference Type: BACKGROUND

PMID: 31177816 (View on PubMed)

Takahashi N, Abe I, Kira S, Ishii Y. Role of epicardial adipose tissue in human atrial fibrillation. J Arrhythm. 2023 Feb 19;39(2):93-110. doi: 10.1002/joa3.12825. eCollection 2023 Apr.

Reference Type: BACKGROUND

PMID: 37021018 (View on PubMed)

Klein C, Brunereau J, Lacroix D, Ninni S, Brigadeau F, Klug D, Longere B, Montaigne D, Pontana F, Coisne A. Left atrial epicardial adipose tissue radiodensity is associated with electrophysiological properties of atrial myocardium in patients with atrial fibrillation. Eur Radiol. 2019 Jun;29(6):3027-3035. doi: 10.1007/s00330-018-5793-4. Epub 2018 Nov 6.

Reference Type: BACKGROUND

PMID: 30402702 (View on PubMed)

El Mahdiui M, Simon J, Smit JM, Kuneman JH, van Rosendael AR, Steyerberg EW, van der Geest RJ, Szaraz L, Herczeg S, Szegedi N, Geller L, Delgado V, Merkely B, Bax JJ, Maurovich-Horvat P. Posterior Left Atrial Adipose Tissue Attenuation Assessed by Computed Tomography and Recurrence of Atrial Fibrillation After Catheter Ablation. Circ Arrhythm Electrophysiol. 2021 Apr;14(4):e009135. doi: 10.1161/CIRCEP.120.009135. Epub 2021 Mar 15.

Reference Type: BACKGROUND

PMID: 33720759 (View on PubMed)

Mahabadi AA, Balcer B, Dykun I, Forsting M, Schlosser T, Heusch G, Rassaf T. Cardiac computed tomography-derived epicardial fat volume and attenuation independently distinguish patients with and without myocardial infarction. PLoS One. 2017 Aug 24;12(8):e0183514. doi: 10.1371/journal.pone.0183514. eCollection 2017.

Reference Type: BACKGROUND

PMID: 28837682 (View on PubMed)

Goeller M, Achenbach S, Marwan M, Doris MK, Cadet S, Commandeur F, Chen X, Slomka PJ, Gransar H, Cao JJ, Wong ND, Albrecht MH, Rozanski A, Tamarappoo BK, Berman DS, Dey D. Epicardial adipose tissue density and volume are related to subclinical atherosclerosis, inflammation and major adverse cardiac events in asymptomatic subjects. J Cardiovasc Comput Tomogr. 2018 Jan-Feb;12(1):67-73. doi: 10.1016/j.jcct.2017.11.007. Epub 2017 Nov 24.

Reference Type: BACKGROUND

PMID: 29233634 (View on PubMed)

Marwan M, Hell M, Schuhback A, Gauss S, Bittner D, Pflederer T, Achenbach S. CT Attenuation of Pericoronary Adipose Tissue in Normal Versus Atherosclerotic Coronary Segments as Defined by Intravascular Ultrasound. J Comput Assist Tomogr. 2017 Sep/Oct;41(5):762-767. doi: 10.1097/RCT.0000000000000589.

Reference Type: BACKGROUND

PMID: 28914752 (View on PubMed)

Monti CB, Codari M, De Cecco CN, Secchi F, Sardanelli F, Stillman AE. Novel imaging biomarkers: epicardial adipose tissue evaluation. Br J Radiol. 2020 Sep 1;93(1113):20190770. doi: 10.1259/bjr.20190770. Epub 2019 Dec 11.

Reference Type: BACKGROUND

PMID: 31782934 (View on PubMed)

Ebadi M, Field CJ, Lehner R, Mazurak VC. Chemotherapy diminishes lipid storage capacity of adipose tissue in a preclinical model of colon cancer. Lipids Health Dis. 2017 Dec 19;16(1):247. doi: 10.1186/s12944-017-0638-8.

Reference Type: BACKGROUND

PMID: 29258509 (View on PubMed)

Li W, Liu M, Yu F, Jiang T, Zhu W, Liu H. Changes in epicardial adipose tissue among women treated with trastuzumab for breast cancer. Int J Cardiol. 2022 Feb 1;348:163-168. doi: 10.1016/j.ijcard.2021.12.006. Epub 2021 Dec 8.

Reference Type: BACKGROUND

PMID: 34890762 (View on PubMed)

Hales CM. Prevalence of Obesity and Severe Obesity Among Adults: US Department of Health and Human Services, Centers for Disease Control and …, 2020.

Reference Type: BACKGROUND

Kennedy A, Martinez K, Chuang CC, LaPoint K, McIntosh M. Saturated fatty acid-mediated inflammation and insulin resistance in adipose tissue: mechanisms of action and implications. J Nutr. 2009 Jan;139(1):1-4. doi: 10.3945/jn.108.098269. Epub 2008 Dec 3.

Reference Type: BACKGROUND

PMID: 19056664 (View on PubMed)

Robblee MM, Kim CC, Porter Abate J, Valdearcos M, Sandlund KL, Shenoy MK, Volmer R, Iwawaki T, Koliwad SK. Saturated Fatty Acids Engage an IRE1alpha-Dependent Pathway to Activate the NLRP3 Inflammasome in Myeloid Cells. Cell Rep. 2016 Mar 22;14(11):2611-23. doi: 10.1016/j.celrep.2016.02.053. Epub 2016 Mar 10.

Reference Type: BACKGROUND

PMID: 26971994 (View on PubMed)

Packer M. Epicardial Adipose Tissue May Mediate Deleterious Effects of Obesity and Inflammation on the Myocardium. J Am Coll Cardiol. 2018 May 22;71(20):2360-2372. doi: 10.1016/j.jacc.2018.03.509.

Reference Type: BACKGROUND

PMID: 29773163 (View on PubMed)

Walker ME, Matthan NR, Goldbaum A, Meng H, Lamon-Fava S, Lakshman S, Jang S, Molokin A, Solano-Aguilar G, Urban JF Jr, Lichtenstein AH. Dietary patterns influence epicardial adipose tissue fatty acid composition and inflammatory gene expression in the Ossabaw pig. J Nutr Biochem. 2019 Aug;70:138-146. doi: 10.1016/j.jnutbio.2019.04.013. Epub 2019 May 14.

Reference Type: BACKGROUND

PMID: 31202119 (View on PubMed)

Gaborit B, Sengenes C, Ancel P, Jacquier A, Dutour A. Role of Epicardial Adipose Tissue in Health and Disease: A Matter of Fat? Compr Physiol. 2017 Jun 18;7(3):1051-1082. doi: 10.1002/cphy.c160034.

Reference Type: BACKGROUND

PMID: 28640452 (View on PubMed)

Iacobellis G. Epicardial adipose tissue in contemporary cardiology. Nat Rev Cardiol. 2022 Sep;19(9):593-606. doi: 10.1038/s41569-022-00679-9. Epub 2022 Mar 16.

Reference Type: BACKGROUND

PMID: 35296869 (View on PubMed)

Other Identifiers

302641

Identifier Type: -

Identifier Source: org_study_id