Body Surface Mapping of Ventricular Repolarization Heterogeneity: An Ex-vivo Multiparameter Study

Abstract

Background: Increased heterogeneity of ventricular repolarization is associated with life-threatening arrhythmia and sudden cardiac death (SCD). T-wave analysis through body surface potential mapping (BSPM) is a promising tool for risk stratification, but the clinical effectiveness of current electrocardiographic indices is still unclear, with limited experimental validation. This study aims to investigate performance of non-invasive state-of-the-art and novel T-wave markers for repolarization dispersion in an ex vivo model.

Methods: Langendorff-perfused pig hearts (N = 7) were suspended in a human-shaped 256-electrode torso tank. Tank potentials were recorded during sinus rhythm before and after introducing repolarization inhomogeneities through local perfusion with dofetilide and/or pinacidil. Drug-induced repolarization gradients were investigated from BSPMs at different experiment phases. Dispersion of electrical recovery was quantified by duration parameters, i.e., the time interval between the peak and the offset of T-wave (T_PEAK-T_END) and QT interval, and variability over time and electrodes was also assessed. The degree of T-wave symmetry to the peak was quantified by the ratio between the terminal and initial portions of T-wave area (Asy). Morphological variability between left and right BSPM electrodes was measured by dynamic time warping (DTW). Finally, T-wave organization was assessed by the complexity of repolarization index (CR), i.e., the amount of energy non-preserved by the dominant eigenvector computed by principal component analysis (PCA), and the error between each multilead T-wave and its 3D PCA approximation (NMSE). Body surface indices were compared with global measures of epicardial dispersion of repolarization, and with local gradients between adjacent ventricular sites.

Results: After drug intervention, both regional and global repolarization heterogeneity were significantly enhanced. On the body surface, T_PEAK-T_END was significantly prolonged and less stable in time in all experiments, while QT interval showed higher variability across the interventions in terms of duration and spatial dispersion. The rising slope of the repolarization profile was steeper, and T-waves were more asymmetric than at baseline. Interventricular shape dissimilarity was enhanced by repolarization gradients according to DTW. Organized T-wave patterns were associated with abnormal repolarization, and they were properly described by the first principal components.

Conclusion: Repolarization heterogeneity significantly affects T-wave properties, and can be non-invasively captured by BSPM-based metrics.

Keywords: T-wave; body surface potential mapping; electrocardiology; sudden cardiac death; ventricular repolarization heterogeneity.

FIGURE 1

A representative single-lead QRST sequence from a tank potential recorded from an experiment from Dof & Pin Group before (Baseline, blue trace) and after induction of repolarization gradients through injection of dofetilide (Dof, green trace) and simultaneous perfusion with dofetilide and pinacidil (Dof + Pin, red trace).

FIGURE 2

Time evolution of signal features and their variations with respect to baseline conditions for experiments from Pin Group, computed before and during progressive injection with pinacidil. (A) Invasive epicardial metrics of heterogeneity of repolarization and changes from baseline computed as global differences in RTs between Pin- and not-Pin sites (RTG_GLOBAL and ΔRTG_GLOBAL, left), global differences in RTs between LV and RV (RTG(LV/RV)_GLOBAL and ΔRTG(LV/RV)_GLOBAL, middle), and local RT gradients between neighboring epicardial sock nodes (RTG_LOCAL and ΔRTG_LOCAL, right). (B) BSPM indices and changes from baseline of T-wave duration (T_PEAK-T_END and ΔT_PEAK-T_END, left) and corrected QT interval (QT_C and ΔQT_C, right). (C) BSPM indices and changes from baseline of temporal variability of T-wave duration [SD(T_PEAK-T_END) and ΔSD(T_PEAK-T_END), left] and QT_C spatial dispersion (QTD and ΔQTD, right). (D) BSPM indices and changes from baseline of T-wave symmetry (Asy and ΔAsy, left) and shape (d_LV/RV and Δd_LV/RV, right). (E) BSPM indices and changes from baseline of T-wave complexity (CR and ΔCR, left, and NMSE and ΔNMSE, right). a.u., arbitrary units.

FIGURE 3

BA plots of the differences z_D between BSPM markers of T-wave and invasive RT dispersion measures vs. their mean z_M for the assessment of the agreement between the two approaches for experiments from Pin Group before and during progressive injection with pinacidil. The mean difference between methods (horizontal continuous black line) and upper and lower 95% LoA (dashed magenta and green lines, respectively) are also displayed. (A) BSPM indices and T-wave duration (T_PEAK-T_END, left) and corrected QT interval (QT_C, right). (B) BSPM indices of temporal variability of T-wave duration [SD(T_PEAK-T_END), left] and QT_C spatial dispersion (QTD, right). (C) BSPM indices of T-wave symmetry (Asy, left) and shape (d_LV/RV, right). (D) BSPM indices of T-wave complexity (CR, left, and NMSE, right). a.u., arbitrary units.

FIGURE 4

Time evolution of signal features and their variations with respect to baseline conditions for experiments from Dof & Pin Group, computed before and during progressive injection with dofetilide and pinacidil. (A) Invasive epicardial metrics of heterogeneity of repolarization and changes from baseline computed as global differences in RTs between Pin- and not-Pin sites (RTG_GLOBAL and ΔRTG_GLOBAL, left), global differences in RTs between LV and RV (RTG(LV/RV)_GLOBAL and ΔRTG(LV/RV)_GLOBAL, middle), and local RT gradients between neighboring epicardial sock nodes (RTG_LOCAL and ΔRTG_LOCAL, right). (B) BSPM indices and changes from baseline of T-wave duration (T_PEAK-T_END and ΔT_PEAK-T_END, left) and corrected QT interval (QT_C and ΔQT_C, right). (C) BSPM indices and changes from baseline of temporal variability of T-wave duration [SD(T_PEAK-T_END) and ΔSD(T_PEAK-T_END), left] and QT_C spatial dispersion (QTD and ΔQTD, right). (D) BSPM indices and changes from baseline of T-wave symmetry (Asy and ΔAsy, left) and shape (d_LV/RV and Δd_LV/RV, right). (E) BSPM indices and changes from baseline of T-wave complexity (CR and ΔCR, left, and NMSE and ΔNMSE, right). a.u., arbitrary units.

FIGURE 5

BA plots of the differences z_D between BSPM markers of T-wave and invasive RT dispersion measures vs. their mean z_M for the assessment of the agreement between the two approaches for experiments from Dof & Pin Group before and during progressive injection with dofetilide and pinacidil. The mean difference between methods (horizontal continuous black line) and upper and lower 95% LoA (dashed magenta and green lines, respectively) are also displayed. (A) BSPM indices and T-wave duration (T_PEAK-T_END, left) and corrected QT interval (QT_C, right). (B) BSPM indices of temporal variability of T-wave duration [SD(T_PEAK-T_END), left] and QT_C spatial dispersion (QTD, right). (C) BSPM indices of T-wave symmetry (Asy, left) and shape (d_LV/RV, right). (D) BSPM indices of T-wave complexity (CR, left, and NMSE, right). a.u., arbitrary units.