Journal Article

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

Wachter, Rolf, Menghoum, Nassiba, Leroy, Martin, Edelmann, Frank, Neubauer, Stefan, Gruson, Damien, Pouleur, Anne-Catherine, Filippatos, Gerasimos, Ikonomidis, Ignatios, Gerber, Bernhard L., Roy, Clotilde, Pasquet, Agnes, Mahmod, Masliza, Lejeune, Sibille, Badii, Maria Chiara, Pinto, Fausto, Senni, Michele, Brito, Dulce, Pieske-Kraigher, Elisabeth, Casadei, Barbara, Trochu, Jean-Noël, Vancraeynest, David, Krakowiak, Bartosz, Persu, Alexandre, Ponikowski, Piotr, Beauloye, Christophe, Hellenkamp, Kristian, Van Overstraeten, Nancy, Parra, Marie, Depoix, Christophe, Balligand, Jean-Luc, Lhommel, Renaud, Piechnik, Stefan, Pieske, Burkert, Ferreira, Vanessa M.

2025

Overview

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/m 2 vs. 55.0 ± 11.8ml/m 2 and 48 ± 8.9ml/m 2 , p < 0.001) from the Belgian cohort and to pre-HF (52.0 ± 15.0 ml/m 2 , 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 H 2 FPEF score as strong markers of HFpEF status. EAT was significantly correlated with H 2 FPEF 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. Graphical abstract

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Adipose tissue / Adipose Tissue - diagnostic imaging / Adipose Tissue - metabolism / Adipose Tissue - physiopathology / Adiposity / Adrenergic receptors / Aged / Angiology / Belgium - epidemiology / Biomarkers / Biomarkers - blood / Body fat / Body mass index / Brain natriuretic peptide / Cardiac arrhythmia / Cardiac stress tests / Cardiology / Cardiometabolic HFpEF with focus on type 2 diabetes mellitus / Cardiomyopathy / Cardiovascular disease / Case-Control Studies / Chronic illnesses / Comorbidity / Congestive heart failure / Diabetes / Diabetes mellitus / Diabetes Mellitus - epidemiology / Diabetes Mellitus - mortality / Drug delivery / Drug development / Ejection fraction / Enzymes / Epicardial Adipose Tissue / Female / Heart failure / Heart Failure - diagnostic imaging / Heart Failure - epidemiology / Heart Failure - mortality / Heart Failure - physiopathology / Heart Failure - therapy / Heart failure with preserved ejection fraction / Hospitalization / Humans / Hypertension / Hypotheses / Inflammation / Ischemia / Kidney diseases / Magnetic Resonance Imaging, Cine / Male / Medical prognosis / Medicine / Medicine & Public Health / Metabolic syndrome / Metabolism / Middle Aged / Obesity / Obesity - epidemiology / Obesity - mortality / Obesity - physiopathology / Pathophysiology / Pericardium / Pericardium - diagnostic imaging / Pericardium - physiopathology / Predictive Value of Tests / Prognosis / Risk Assessment / Risk Factors / Stroke Volume / Therapeutic targets / Troponin / Troponin T / Tumorigenicity / Ventricle / Ventricular Function, Left