Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Jun 12;121(6):860-870.
doi: 10.1093/cvr/cvaf056.

The role of epicardial adipose tissue remodelling in heart failure with preserved ejection fraction

Carolina Janssen-Telders  1   2 , Etto C Eringa  2   3   4 , Joris R de Groot  1   2 , Frances S de Man  2   4 , M Louis Handoko  1   5   6
Affiliations
Review

The role of epicardial adipose tissue remodelling in heart failure with preserved ejection fraction

Carolina Janssen-Telders et al. Cardiovasc Res. .

Abstract

Heart failure with preserved ejection fraction (HFpEF) is a growing global health problem characterized by high morbidity and mortality, with limited effective therapies available. Obesity significantly influences haemodynamic and structural changes in the myocardium and vasculature, primarily through the accumulation and action of visceral adipose tissue. Particularly, epicardial adipose tissue (EAT) contributes to HFpEF through inflammation and lipotoxic infiltration of the myocardium. However, the precise signalling pathways leading to diastolic stiffness in HFpEF require further elucidation. This review explores the dynamic role of EAT in health and disease. Drawing upon insights from studies in other conditions, we discuss potential EAT-mediated inflammatory pathways in HFpEF and how they may contribute to functional and structural myocardial and endothelial derangements, including intramyocardial lipid infiltration, fibrosis, endothelial dysfunction, cardiomyocyte stiffening, and left ventricular hypertrophy. Lastly, we propose potential targets for novel therapeutic avenues.

Keywords: Epicardial adipose tissue; Heart failure with preserved ejection fraction; Inflammation; Inflammatory pathways.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest: none declared.

Figures

Graphical Abstract
Graphical Abstract
Figure 1
Figure 1
Risk factors and hallmarks of HFpEF. The four circles represent levels contributing to HFpEF pathophysiology. The outer circle shows risk factors/comorbidities that can influence an increase in EAT. In turn, EAT creates a proinflammatory state and induces oxidative stress. Lastly, this drives cellular hallmarks of HFpEF: cardiomyocyte stiffening, fibrosis, and endothelial dysfunction (inner circle). cGMP, cyclic guanosine monophosphate; EAT, epicardial adipose tissue; NO, nitric oxide; ROS, reactive oxygen species; PKG, protein kinase G; TGF-β, transforming growth factor-β. Created in BioRender.com.
Figure 2
Figure 2
Physiological and pathophysiological role of EAT on myocardial function. The outer fatty layer represents the EAT that lies in direct contact to the myocardial layer of the heart. Due to the lack of separation between the two entities, EAT can have a direct effect on the functioning of the heart. Created in BioRender.com.
Figure 3
Figure 3
Secretion of proinflammatory adipokines by remodelled EAT and inflammatory pathways in HFpEF. Pathologically remodelled EAT shifts its secretome towards proinflammatory molecules while decreasing anti-inflammatory ones. The arrows describe the molecular pathways of different adipokines. The bottom section illustrates the hypothetical effects that these pathways have on the myocardium in HFpEF. Downward arrows depict a decrease, upward arrows depict an increase. FABP-4, fatty-acid-binding protein-4; FFA, free fatty acids; GLUT-4, glucose transporter type-4; LV, left ventricle; NO, nitric oxide; PKG, protein kinase K; RBP4, retinol-binding protein-4; ROS, reactive oxygen species; TLR4, toll-like receptor-4. Created in BioRender.com.
See this image and copyright information in PMC

References

    1. Shah SJ, Borlaug BA, Kitzman DW, McCulloch AD, Blaxall BC, Agarwal R, Chirinos JA, Collins S, Deo RC, Gladwin MT, Granzier H, Hummel SL, Kass DA, Redfield MM, Sam F, Wang TJ, Desvigne-Nickens P, Adhikari BB. Research priorities for heart failure with preserved ejection fraction: National Heart, Lung, and Blood Institute Working Group Summary. Circulation 2020;141:1001–1026. - PMC - PubMed
    1. Dunlay SM, Roger VL, Redfield MM. Epidemiology of heart failure with preserved ejection fraction. Nat Rev Cardiol 2017;14:591–602. - PubMed
    1. McDonagh TA, Metra M, Adamo M, Baumbach A, Böhm M, Burri H, Čelutkiene J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gardner RS, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Piepoli MF, Price S, Rosano GMC, Ruschitzka F, Skibelund AK; ESC Scientific Document Group . 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021;42:4901. - PubMed
    1. Borlaug BA, Paulus WJ. Heart failure with preserved ejection fraction: pathophysiology, diagnosis, and treatment. Eur Heart J 2011;32:670–679. - PMC - PubMed
    1. Redfield MM, Borlaug BA. Heart failure with preserved ejection fraction. JAMA 2023;329:827. - PubMed

MeSH terms

Substances