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

Figures

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  Figure 1. Ventricular electrical activity in ECG. (A) QRS duration represents the ventricular depolarization, QT interval represents the ventricular action potential duration, JT interval represents the ventricular repolarization phase. (B) Tpe (T peak- T end) represents the repolarization dispersion or the difference in repolarization time across the ventricular wall. Since M cells have the longest repolarization time, T peak corresponds to the end of repolarization in the epicardium, and T end corresponds to the end of repolarization in the M cell. (C) ECG parameters scheme showing both depolarization and repolarization parameters used in the study.

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  Figure 2. Linear correlations between the manually measured values of QTc (A) and QRS (B) and the automated values.

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  Figure 3. Patient sample inclusion and exclusion criteria. ADRB3, B3 adrenergic receptor; COL1A2, collagen type I alpha 2 chain; CXCR2, CXC chemokine receptor 2; DEFA3, defensin alpha 3; EAT, epicardial adipose tissue; ECG, electrocardiogram; FABP4, fatty acid binding protein 4; mAChR2, M2 muscarinic acetylcholine receptor; mAChR3, M3 muscarinic acetylcholine receptor; PREF1, preadipocyte factor-1.

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  Figure 4. PCA space markers by sex [(A) depolarization, (B) repolarization]. Data points are coloured by sex. Ellipses represent the 95% confidence regions for each group. PC1 and PC2 define the two-dimensional PCA space summarizing the major patterns of variation in markers.

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  Figure 5. Clustered heatmaps of ECG-EAT correlations in the total population and by sex after FDR correction. Each panel displays a clustered heatmap of Spearman correlation coefficients between EAT markers and ECG depolarization parameters (left panels) or repolarization parameters (right panel), after FDR adjustment for multiple testing, shown for total population (top raw), males (middle row), and females (bottom raw). Asterisks indicate statistically significant associations. ADRB3, B3 adrenergic receptor; COL1A2, collagen type I alpha 2 chain; CXCR2, CXC chemokine receptor 2; DEFA3, defensin alpha 3; dTpe, dispersion of T peak—T end; FABP4, fatty acid binding protein 4; JTc, corrected JT; JTcd, dispersion of corrected JT; JT R/L, JT right (V1 + V2 + V3)-to-left (V4 + V5 + V6) ratio; JTc R/L, corrected JT right (V1 + V2 + V3)-to-left (V4 + V5 + V6) ratio; mAChR2, M2 muscarinic acetylcholine receptor; mAChR3, M3 muscarinic acetylcholine receptor; PREF1, preadipocyte factor-1; QRSd, QRS dispersion; QRS R/L, QRS right (V1 + V2 + V3)-to-left (V4 + V5 + V6) ratio; QTc, corrected QT; QTcd, dispersion of corrected QT; QT R/L, QT right (V1 + V2 + V3)-to-left (V4 + V5 + V6) ratio; QTc R/L,…

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  Figure 6. Comparisons of sex-specific ECG-EAT interactions across all ECG-EAT studied pairs. Red circles represent the regression sex-interaction slopes (b) and their 95% confidence intervals for females, and blue triangles for males, across all S2 UT and S3 UT associations with EAT markers (CD14, CD16, DEFA3, COL1A2, and mAChR3). COL1A2, collagen type I alpha 2 chain; DEFA3, defensin alpha 3; mAChR3, M3 muscarinic acetylcholine receptor; S2 UT, S-wave upstroke time in V2; S3 UT, S-wave upstroke time in V3.

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  Figure 7. Stability of interaction effects after adding clinical factors. Each horizontal line represents the interaction effect obtained from a single-covariate regression model in which one clinical factor was added to the base interaction model. “Raw” refers to the unadjusted interaction estimated (no clinical factor included). Points represent the shifts in b and reflect the changes in the strength of the sex-dependent interaction, while lines represent the changes in 95% confidence interval width which reflect the differences in the precision of the estimate after adjusting for each clinical factor. AF, atrial fibrillation; BMI, body mass index; CAD, coronary artery disease; DLP, Dyslipidaemia; DM, diabetes mellitus; HFpEF, heart failure with preserved ejection fraction; HTN, hypertension; VHD, valvular heart disease.

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  Figure 8. A Forest plot of the estimated interaction coefficients b and their 95% confidence intervals for each ECG × Sex interaction after adding each clinical factor individually to the model. Each horizontal line represents the interaction estimate obtained from a single-covariate regression model. The points indicate the adjusted interaction b, and the horizontal bars represent the 95% confidence intervals. AF, atrial fibrillation; BMI, body mass index; CAD, coronary artery disease; DLP, Dyslipidaemia; DM, diabetes mellitus; HFpEF, heart failure with preserved ejection fraction; HTN, hypertension; VHD, valvular heart disease.