Delayed late ventricular depolarisation is associated with inflammation in epicardial fat among women: a new avenue in cardiac electrophysiology
N Ahmed, D Sanchez-Lopez, R Basdas, J R Nunez-Caamano, J M Martinez-Cereijo, L Reija-Lopez, A L.Fernandez, M Rodriguez-Manero, J R Gonzalez-Juanatey, S EirasAbstract
Background
Epicardial adipose tissue (EAT) volume has been linked to arrhythmias and conduction abnormalities, due to its direct interaction and endocrine activity with the myocardium.
Purpose
In this study, we aimed to investigate the association between ventricular electrical activity, and EAT molecular composition, particularly in a sex-specific manner.
Methods
We retrospectively included consecutive cardiac surgery patients from whom EAT biopsies were obtained (n=146). Finally, ninety-five electrocardiograms (ECGs), 65 men and 30 women, were analysed for thirty-six different depolarization and repolarization parameters. Biopsies were analysed by real time-PCR for detecting inflammatory cell-related markers (CD16, DEFA3, CXCR2, CD68 and CD14), fatty acid transporters-related markers (FABP4 and CD36), fibroblast-related markers (COL1A2 and PREF1), and neuroreceptor-related markers (mAChR3, mAChR2 and ADRB3). ECG parameters were analysed using principal component analysis (PCA) to explore their internal structure. Associations between ECG parameters and EAT molecular markers were assessed using Spearman correlation with Benjamini–Hochberg correction. Linear regression models were used to further examine ECG-EAT pairs showing sex-related divergence. Clinical factors were evaluated to determine their effects on the sex-dependent ECG-EAT associations.
Results
Higher inflammatory-cell infiltration in EAT, particularly among women, showed strong associations with slower late anteroseptal depolarization, reflected by prolonged S-wave upstroke time in V2 (COL1A2, ρ=0.642, FDR=0.025; DEFA3, ρ=0.572, FDR=0.038) and in V3 (CD16, ρ=0.642; DEFA3, ρ=0.629; CD14, ρ=0.596; mAChR3, ρ=0.600; COL1A2, ρ=0.592; all FDR ≤ 0.027). Sex interaction regression showed consistently strong, positive, and significant ECG-EAT slopes in women for S-wave upstroke time in V2 and V3 with CD14, CD16, DEFA3, and COL1A2 (β up to ~ 2.23, all p ≤ 0.027), while male slopes were uniformly weak and non-significant. Clinical factors modestly influenced the interaction β (↓ 1 - 3 units) but did not eliminate or substantially attenuate the sex-dependent effect. AIC refined models identified coronary artery disease (CAD), hypertension (HTN), and valvular disease (VD) as the most influential covariates, yet sex dependent interactions persisted for inflammatory markers (CD14, CD16 and DEFA3), showing modest but consistent explanatory power (adjusted R² = 0.13 - 0.20).
Conclusion
Despite similar absolute ECG values, the electrical response to EAT inflammation differs markedly between sexes. EAT inflammatory activity was strongly associated with delayed late depolarization, particularly in women, highlighting inflammation as a key driver of electrical abnormalities. These results support the potential use of ECG as a simple tool to identify adverse EAT phenotypes and to better understand sex-specific cardiac-adipose interactions.Graphical Abstract