Thick but safe: revisiting the role of epicardial adipose tissue in chemotherapy-induced cardiac dysfunction

Abstract Background Epicardial adipose tissue (EAT) is increasingly recognized as a cardiometabolic risk factor, known to promote oxidative stress, contractile dysfunction, and myocardial fibrosis through its paracrine and endocrine activity. These mechanisms are also implicated in chemotherapy-related cardiac dysfunction (CTRCD), suggesting a potential link. Conversely, EAT may exert cardioprotective effects under physiological conditions by secreting beneficial adipokines and providing metabolic support to the myocardium. Given this dual role, the influence of EAT on CTRCD susceptibility remains unclear. Purpose To investigate whether baseline EAT thickness is associated with the development of CTRCD in breast cancer patients and to evaluate longitudinal changes in EAT during chemotherapy. Methods A total of 131 consecutive breast cancer patients (mean age 51.0 ± 9.3 years) who received chemotherapy were included. Baseline echocardiography was performed within 1 day before chemotherapy and repeated at 3, 6, and 12 months thereafter. CTRCD was defined as a ≥5% decline in LVEF to <55% with symptoms of heart failure, or a ≥10% decline to <55% without symptoms. EAT thickness (EATt) was measured by transthoracic echocardiography according to ASE recommendations. Results Over 12 months, CTRCD developed in 10 patients (7.6%). There were no significant differences in age, BMI, or cardiovascular risk factors, such as hypertension, diabetes, smoking, and dyslipidemia, between patients with and without CTRCD. The cumulative anthracycline dose (p=0.186) and trastuzumab use (p=0.613) were not different between the groups. Baseline EATt was significantly greater in patients who did not develop CTRCD compared to those who did (4.60 ± 1.61 mm vs. 3.58 ± 0.99 mm, p=0.021), and this difference persisted throughout follow-up. EATt significantly increased over time in patients without CTRCD (p<0.001), but remained unchanged in those with CTRCD (p=0.458). On multivariate analysis, lower baseline EATt was independently associated with CTRCD development (OR 0.560, 95% CI 0.31–0.99, p=0.05), after adjustment for age, BMI, and cardiovascular risk factors. Conclusion Lower baseline EATt may be associated with an increased risk of chemotherapy-related cardiac dysfunction in breast cancer patients. Moreover, the progressive increase in EATt among patients without CTRCD may reflect a potential adaptive or cardioprotective remodeling response. These findings challenge the conventional view of EAT as purely harmful and suggest a more nuanced role in cancer therapy–induced cardiotoxicity. Further studies in larger cohorts are warranted to validate these observations.Comparison of the change of EAT thicknes