Delayed late ventricular depolarization is associated with inflammation in epicardial Fat Among females: a New avenue in cardiac electrophysiology

Background Epicardial adipose tissue (EAT) has been linked to cardiac conduction through direct myocardium interaction and endocrine activity. We investigated sex-specific associations between ventricular electrical activity and the molecular composition of EAT. Methods EAT biopsies from 146 cardiac surgery patients were analysed for inflammatory cell markers (CD16, DEFA3, CXCR2, CD68, CD14), fatty acid transporters (FABP4, CD36), fibroblast-related markers (COL1A2 and PREF1), and neuroreceptor-related markers (CHRM3, CHRM2, ADRB3) using real-time PCR. High-quality electrocardiograms (ECGs) from 100 patients were analysed for 36 ventricular depolarization and repolarization parameters. Principal component analysis was used to explore the internal ECG structure. Spearman correlation with Benjamini-Hochberg correction and sex-stratified linear regression assessed ECG-EAT associations, adjusting for clinical covariates. Results In females, EAT fibrotic and inflammatory profile were correlated with delayed late anteroseptal depolarization (prolonged S-wave upstroke time) in V2 (COL1A2, p = 0.642, adj. p  = 0.025; DEFA3, p  = 0.572, adj. p  = 0.038), and V3 (COL1A2, p  = 0.592; DEFA3, p  = 0.629; CD16, p  = 0.642; CD14, p  = 0.596; CHRM3, p  = 0.600; all adj. p  ≤ 0.027). Linear regression models confirmed strong positive associations between the interaction ECGxSex and CD14, CD16, DEFA3, and COL1A2 ( β  = 1 to 5, all p  ≤ 0.02). Clinical factors reduced but did not eliminate sex dependent effects. Akaike information criteria (AIC)-refined models identified coronary artery disease, hypertension, and valvular heart disease as key covariates, yet inflammatory markers (CD14 and CD16) retained sex-specific explanatory power (adjusted R 2  = 0.13–0.20). Conclusion Despite similar absolute ECG values, females exhibited a stronger electrical response to the EAT inflammatory profile. These findings highlight inflammation-driven sex-specific depolarization alterations and support ECG as a simple tool to indicate adverse EAT phenotypes.