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Clinical Trial
. 2025 Mar 22;24(1):134.
doi: 10.1186/s12933-025-02688-7.

Exploring the impact of metabolic comorbidities on epicardial adipose tissue in heart failure with preserved ejection fraction

Nassiba Menghoum #  1   2 , Maria Chiara Badii #  1   2 , Martin Leroy  1 , Marie Parra  1 , Clotilde Roy  1 , Sibille Lejeune  1   2 , David Vancraeynest  1   2 , Agnes Pasquet  1   2 , Dulce Brito  3   4 , Barbara Casadei  5   6 , Christophe Depoix  1   2 , Gerasimos Filippatos  7 , Damien Gruson  1   2 , Frank Edelmann  8 , Vanessa M Ferreira  9 , Renaud Lhommel  1   2 , Masliza Mahmod  8 , Stefan Neubauer  8 , Alexandre Persu  1   2 , Stefan Piechnik  8 , Kristian Hellenkamp  10 , Ignatios Ikonomidis  7 , Bartosz Krakowiak  11   12 , Burkert Pieske  13 , Elisabeth Pieske-Kraigher  14 , Fausto Pinto  3   4 , Piotr Ponikowski  11 , Michele Senni  15 , Jean-Noël Trochu  16 , Nancy Van Overstraeten  2 , Rolf Wachter  17 , Bernhard L Gerber  1   2 , Jean-Luc Balligand  1   2 , Christophe Beauloye  1   2 , Anne-Catherine Pouleur  18   19
Affiliations
Clinical Trial

Exploring the impact of metabolic comorbidities on epicardial adipose tissue in heart failure with preserved ejection fraction

Nassiba Menghoum et al. Cardiovasc Diabetol. .

Abstract

Background: Heart failure (HF) with preserved ejection fraction (HFpEF) is increasingly prevalent worldwide due to aging and comorbidities. Epicardial adipose tissue (EAT), favored by diabetes and obesity, was shown to contribute to HFpEF pathophysiology and is an emerging therapeutic target. This study explored the relationship between ventricular EAT measured by cardiovascular magnetic resonance (CMR), metabolic factors, and imaging characteristics in controls, pre-HF patients, and HFpEF patients.

Methods: Patients from a Belgian cohort enrolled from December 2015 to June 2017 were categorized by HF stage: pre-HF (n = 16), HFpEF (n = 104) and compared to matched controls (n = 26) and to pre-HF (n = 191) from the Beta3-LVH cohort. Biventricular EAT volume was measured in end-diastolic short-axis cine stacks. In the Belgian cohort, associations between EAT, HF stage, and various biological and imaging markers were explored. The clinical endpoint was a composite of mortality or first HF hospitalization in the HFpEF group.

Results: EAT significantly differed between groups, with higher values in HFpEF patients compared to pre-HF and controls (72.4 ± 20.8ml/m2vs. 55.0 ± 11.8ml/m2 and 48 ± 8.9ml/m2, p < 0.001) from the Belgian cohort and to pre-HF (52.0 ± 15.0 ml/m2, p < 0.001) from the Beta3-LVH cohort. Subsequent analyses focused on the Belgian cohort. In contrast to atrial fibrillation, diabetes prevalence and body mass index (BMI) did not differ between pre-HF and HFpEF patients. Multivariable logistic regression and random forest classification identified EAT, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and H2FPEF score as strong markers of HFpEF status. EAT was significantly correlated with H2FPEF score (r = 0.41, p = 0.003), BMI (r = 0.30, p < 0.001), high-sensitive troponin T (r = 0.41, p < 0.001), NT-proBNP (r = 0.37, p < 0.001), soluble suppression of tumorigenicity-2 (sST2) (r = 0.30, p < 0.001), E/e' ratio (r = 0.33, p < 0.001), and left ventricular global longitudinal strain (r = 0.35, p < 0.001). In HFpEF patients, diabetes, ischemic cardiomyopathy, and elevated sST2 were independently associated with elevated EAT. In contrast with diabetes and BMI, increased EAT was not associated with prognosis.

Conclusions: EAT assessed by CMR was significantly higher in HFpEF patients compared to controls and pre-HF patients, irrespective of diabetes and BMI. EAT was moderately associated with HFpEF status. HFpEF patients with elevated EAT exhibited a marked diabetic, ischemic, and inflammatory profile, highlighting the potential role of drugs targeting EAT.

Trial registration: Characterization of Heart Failure With Preserved Ejection Fraction; Assessment of Efficacy of Mirabegron, a New beta3-adrenergic Receptor in the Prevention of Heart Failure (Beta3_LVH).

Trial registration number: ClinicalTrials.gov. Identifier: NCT03197350; NCT02599480.

Keywords: Cardiovascular magnetic resonance (CMR); Diabetes; Epicardial adipose tissue; Heart failure with preserved ejection fraction; Inflammation; Metabolic syndrome; Obesity; Soluble ST2.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The study was approved by the Institutional Review Board of the Cliniques universitaires Saint-Luc, Université Catholique de Louvain, and all participants gave written consent to participate in the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Boxplot, indexed EAT volume of controls, pre-HF (stage B) patients, and HFpEF (stage C) patients in the Belgian and Beta3-LVH cohorts. Comparison by ANOVA and Dunnett’s post-hoc analysis
Fig. 2
Fig. 2
Distribution of H2FPEF score category within control, pre-HF, and HFpEF patients A in the Belgian cohort; Associated factors of HFpEF illustrated by multivariable logistic regression analysis B and random forest classification analysis C in the Belgian cohort. EAT Epicardial adipose tissue, HF Heart failure, HFpEF Heart failure with preserved ejection fraction
Fig. 3
Fig. 3
Scatter plot of H2FPEF score, LV global longitudinal strain, high-sensitive troponin T, soluble ST2, and indexed EAT volume in the Belgian cohort. EAT Epicardial adipose tissue, LV Left ventricular
Fig. 4
Fig. 4
Forest plot, multivariable Cox regression analysis of all-causes mortality and heart failure hospitalization in the Belgian cohort
Fig. 5
Fig. 5
Boxplot, EAT volume of non-diabetic and diabetic HFpEF patients in the Belgian cohort A Scatter plot of metabolic score and indexed EAT volume B in the Belgian cohort
See this image and copyright information in PMC

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