Epicardial Adipose Tissue Composition and Heart Failure With Preserved Ejection Fraction

Официальное название

MRI of Epicardial Adipose Tissue Composition: Development of Methods and Application to Heart Failure With Preserved Ejection Fraction

Обзор

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.

Вмешательства

• Препарат 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 maximum dose of 2.4mg (or the subject's maximally tolerated dose, if the subject's maximally tolerated dose is \<2.4 mg) is reached after 16 weeks.

Первичные конечные точки

• Epicardial adipose tissue (EAT) fatty acid composition (FAC) [Срок оценки: Baseline, 3 months (self-control period), and 9-months (6 months post semaglutide treatment)]

Вторичные конечные точки (3)

• EAT Volume [Срок оценки: Baseline, 3months (self-control period), and 9-months (6 months post semaglutide treatment)]
• Baseline Saturated Fatty Acid Composition of Epicaridal Adipose Tissue and Change in Myocardial Deformation [Срок оценки: Baseline, 3months (self-control period), and 9-months (6 months post semaglutide treatment)]
• Baseline Saturated Fatty Acid Composition of Epicaridal Adipose Tissue and Change in diastolic dysfunction grade [Срок оценки: Baseline, 3months (self-control period), and 9-months (6 months post semaglutide treatment)]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• • 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

Exclusion Criteria for Optional Cardiac Stress Imaging Procedure

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Диагностика

Центры проведения

США · 1 центр

• University of Virginia — Charlottesville

Публикации

• 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. PMID 31120821
• 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 He PMID 37797885
• 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. PMID 37325396
• 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. PMID 39323040
• 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. PMID 35726367
• 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. PMID 30548522
• 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. PMID 30006022
• 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. PMID 26527483

Идентификаторы

NCT: NCT07178145 · 302641

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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