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Randomized Controlled Trial
. 2025 Feb 25;85(7):699-706.
doi: 10.1016/j.jacc.2024.11.001. Epub 2024 Nov 18.

Tirzepatide Reduces LV Mass and Paracardiac Adipose Tissue in Obesity-Related Heart Failure: SUMMIT CMR Substudy

Christopher M Kramer  1 , Barry A Borlaug  2 , Michael R Zile  3 , Dustin Ruff  4 , Joseph M DiMaria  5 , Venu Menon  6 , Yang Ou  4 , Angela M Zarante  7 , Karla C Hurt  4 , Masahiro Murakami  4 , Milton Packer  8 ; SUMMIT Trial Study Group
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Free article
Randomized Controlled Trial

Tirzepatide Reduces LV Mass and Paracardiac Adipose Tissue in Obesity-Related Heart Failure: SUMMIT CMR Substudy

Christopher M Kramer et al. J Am Coll Cardiol. .
Free article

Abstract

Background: Obesity is a known risk factor for heart failure with preserved ejection fraction (HFpEF) and is considered a distinct phenotype with more concentric remodeling. Epicardial adipose tissue (EAT) is also increased in obesity-related HFpEF and is associated with adverse events.

Objectives: The cardiac magnetic resonance (CMR) substudy of the SUMMIT trial aimed to examine the effects of tirzepatide on cardiac structure and function with the underlying hypothesis that it would reduce left ventricular (LV) mass and EAT in obesity-related HFpEF.

Methods: A total of 175 patients with obesity-related HFpEF from the parent study of tirzepatide (2.5 mg subcutaneously weekly, increasing to a maximum of 15 mg weekly) or matching placebo underwent CMR at baseline, which consisted of multiplanar cine imaging. A total of 106 patients completed the CMR and had adequate image quality for analysis of LV and left atrial structure and function and paracardiac (epicardial plus pericardial) adipose tissue at both baseline and 52 weeks. The prespecified primary endpoint of this substudy was between-group changes in LV mass.

Results: LV mass decreased by 11 g (95% CI: -19 to -4 g) in the treated group (n = 50) when corrected for placebo (n = 56) (P = 0.004). Paracardiac adipose tissue decreased in the treated group by 45 mL (95% CI: -69 to -22 mL) when corrected for placebo (P < 0.001). The change in LV mass in the treated group correlated with changes in body weight (P < 0.02) and tended to correlate with changes in waist circumference and blood pressure (P = 0.06 for both). The LV mass change also correlated with changes in LV end-diastolic volume and left atrial end-diastolic and end-systolic volumes (P < 0.03 for all).

Conclusions: The CMR substudy of the SUMMIT trial demonstrated that tirzepatide therapy in obesity-related HFpEF led to reduced LV mass and paracardiac adipose tissue as compared with placebo, and the change in LV mass paralleled weight loss. These physiologic changes may contribute to the reduction in heart failure events seen in the main SUMMIT trial. (A Study of Tirzepatide [LY3298176] in Participants With Heart Failure With Preserved Ejection Fraction [HFpEF] and Obesity: The SUMMIT Trial; NCT04847557).

Keywords: GLP1 agonist; HFpEF; LV mass; cardiac MRI; obesity.

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Conflict of interest statement

Funding Support and Author Disclosures Dr Kramer has served as a consultant for Eli Lilly and Co; and has received research grant support from Eli Lilly and Co, Bristol Myers Squibb, and Cytokinetics. Dr Borlaug has received research grant support from the National Institutes of Health and the U.S. Department of Defense, AstraZeneca, Axon, Corvia, Novo Nordisk, and Tenax Therapeutics; has served as a consultant for Actelion, Amgen, Aria, Axon Therapies, BD, Boehringer Ingelheim, Cytokinetics, Edwards Lifesciences, Lilly, Imbria, Janssen, Merck, Novo Nordisk, NGM, NXT, and VADovations; and is a named inventor (U.S. Patent No. 10,307,179) for the tools and approach for a minimally invasive pericardial modification procedure to treat heart failure. Dr Zile has received research support from the U.S. Department of Veterans Affairs (Project Nos. BX005943, BX005848); and has served as a consultant for Abbott, Adona Medical, Aria CV, Avery Therapeutics, Boehringer Ingelheim, Boston Scientific, Cardiovascular Research Foundation Clinical Trials Center, CVRx, DIASTOL Therapeutics, EBR, Edwards, Lilly, GenKardia, Innoventric, KestraMedical, Medtronic, Merck, Morphic Therapeutics, Novartis, Pulnova, Salubris Biotherapeutics, Sonata, SRNALYTICS, V-WAVE, and Vectorious. Dr Ruff, Dr Ou, Ms Hurt, and Dr Murakami are employees of Eli Lilly and Co. Dr Packer has served as a consultant for 89bio, AbbVie, Actavis, Altimmune, Alnylam, Amarin, Amgen, Ardelyx, ARMGO, AstraZeneca, Attralus, Biopeutics, Boehringer Ingelheim, Caladrius, Casana, CSL Behring, Cytokinetics, Lilly, Imara, Medtronic, Moderna, Novartis, Pharmacocosmos, Reata, Regeneron, Roche, and Salamandra. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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