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Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jun 15, 2023; 14(6): 724-740
Published online Jun 15, 2023. doi: 10.4239/wjd.v14.i6.724
Targeting epicardial adipose tissue: A potential therapeutic strategy for heart failure with preserved ejection fraction with type 2 diabetes mellitus
Yu-Jiao Shi, Guo-Ju Dong, Ming Guo
Yu-Jiao Shi, Guo-Ju Dong, Ming Guo, Department of Cardiovascular Medicine, Xiyuan Hospital, Chinese Academy of Traditional Chinese Medicine, Beijing 100091, China
Author contributions: Shi YJ performed most of the writing and prepared the figures and tables; Dong GJ and Ming G performed data accusation and writing; Dong GJ and Ming G designed the outline and coordinated the writing of the paper.
Conflict-of-interest statement: There are no conflicts of interest associated with the senior author or coauthor who contributed their efforts to this manuscript.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Guo-Ju Dong, MD, PhD, Chief Physician, Department of Cardiovascular Medicine, Xiyuan Hospital, Chinese Academy of Traditional Chinese Medicine, No. 1 Xiyuan Playground, Haidian District, Beijing 100091, China. 13691393589@163.com
Received: December 28, 2022
Peer-review started: December 28, 2022
First decision: February 8, 2023
Revised: February 10, 2023
Accepted: April 24, 2023
Article in press: April 24, 2023
Published online: June 15, 2023
Processing time: 169 Days and 4.1 Hours
Abstract

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with various comorbidities, multiple cardiac and extracardiac pathophysiologic abnormalities, and diverse phenotypic presentations. Since HFpEF is a heterogeneous disease with different phenotypes, individualized treatment is required. HFpEF with type 2 diabetes mellitus (T2DM) represents a specific phenotype of HFpEF, with about 45%-50% of HFpEF patients suffering from T2DM. Systemic inflammation associated with dysregulated glucose metabolism is a critical pathological mechanism of HFpEF with T2DM, which is intimately related to the expansion and dysfunction (inflammation and hypermetabolic activity) of epicardial adipose tissue (EAT). EAT is well established as a very active endocrine organ that can regulate the pathophysiological processes of HFpEF with T2DM through the paracrine and endocrine mechanisms. Therefore, suppressing abnormal EAT expansion may be a promising therapeutic strategy for HFpEF with T2DM. Although there is no treatment specifically for EAT, lifestyle management, bariatric surgery, and some pharmaceutical interventions (anti-cytokine drugs, statins, proprotein convertase subtilisin/kexin type 9 inhibitors, metformin, glucagon-like peptide-1 receptor agonists, and especially sodium-glucose cotransporter-2 inhibitors) have been shown to attenuate the inflammatory response or expansion of EAT. Importantly, these treatments may be beneficial in improving the clinical symptoms or prognosis of patients with HFpEF. Accordingly, well-designed randomized controlled trials are needed to validate the efficacy of current therapies. In addition, more novel and effective therapies targeting EAT are needed in the future.

Keywords: Epicardial adipose tissue; Heart failure with preserved ejection fraction; Type 2 diabetes mellitus; Inflammation; Anti-hyperglycemic drugs; Sodium-glucose cotransporter-2 inhibitors

Core Tip: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome requiring individualized treatment depending on phenotypic differences. HFpEF with type 2 diabetes mellitus is strongly associated with the expansion, inflammation, and hypermetabolic activity of epicardial adipose tissue (EAT). Thus, targeting EAT may be a promising therapeutic strategy for HFpEF with type 2 diabetes mellitus. Lifestyle management, bariatric surgery, and certain drugs may suppress the accumulation of EAT and improve the clinical symptoms and prognosis of HFpEF. More studies are required to validate the efficacy of current treatments and to develop new effective therapies.