Orthogonal bipolar approach to detect cardiac repolarization changes related to activation direction
Authors: Masse S , Niri A , Azam M A , Lai P F H , Asta J , Nanthakumar K 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
In addition to wave propagation, tissue anisotropy is thought to determine repolarization (repol). This may explain PVC-induced vulnerability to re-entry, based on change of activation setting up arrhythmogenic repol gradients. However, differential repolarization effects produced by waves propagating in various directions has not been studied. Though this effect could be measured with optical mapping it is unknown whether egm-based methods can detect these differences.

Purpose
The objective of this study was to determine the effect of wave direction on cardiac repol as measured by optical mapping. We recently proposed a novel method of assessing repol with the use of equi-spaced array catheters that allow integration of orthogonal bipolar egms and we sought to compare the performance of unipolar-based ARI methods and orthogonal bipolar egms in detecting the changes shown in optical mapping.

Methods
Simultaneous optical mapping and epicardial mapping with equi-spaced array catheters (Optrell and HD Grid) was performed in 6 rabbit Langendorff experiments. Unipolar egms from 4 electrodes forming a square in the middle of the array were recorded. A compound egm, called rEGM was created from orthogonal bipolar egms derived from the unipolar egms. Optical mapping was performed with a sampling rate of 3333 frames/s. Epicardial waves propagating in different directions were produced by point stimulation (CL = 200ms) at various location respective to the electrode array: Left (anterior LV, Pace B), right (lateral LV, Pace A), catheter distal (apex, Pace D) and catheter proximal (anterior base, Pace C). An endocardial source located transmurally across the electrode array was also evaluated. APD80 from optical data was measured from an algorithm described before. An APD estimate from rEGM, APDc was measured from the onset of QRS to baseline return of rEGM. For each method (optical, APDc and ARI) a statistical analysis evaluating the effect of wave propagation was performed.

Results
a) Gold Standard, optical mapping: Left column on figure shows the APD80 measurements respective to wave direction for two of the experiments. Kruskal-Wallis analysis showed a significant effect of wave direction on APD80 (p &lt; 0.01 for both experiments 3 & 4). Multiple comparisons showed most notable effect from Pace A (lateral side). b) APDc shown in middle column successfully detected the changes (p &lt; 0.01). c) Unipolar ARI: Right column shows the ARI measurements from the same experiments that failed to detect a directional repolarization difference (Exp3 p=0.10; Exp4 p =0.62).

Conclusions
Changes in direction of wave front propagation can change repol timing of as much as 30msec. These changes were not detectable by ARI method. However subtle changes of repolarization were successfully detected by orthogonal bipolar approach using equi-spaced array catheters, enabling a reliable method to assess minute repolarization changes locally.