Repolarization and depolarization abnormalities are preferentially impaired by ajmaline in Brugada patients compared to controls

Abstract Background Repolarization hypothesis states that a transmural repolarization dispersion in right ventricular outflow tract (RVOT) determines type-1 ECG phenotype in Brugada syndrome (BrS). So far only few evidences support it, whilst depolarization impairment has been widely described. Purpose To investigate the changes in depolarization mapping through endocardial unipolar J-elevation mapping of RVOT in BrS patients and in controls undergoing ajmaline and their relations with activation time (AT), marker of local depolarization. Methods Consecutive BrS patients with spontaneous type-1 ECG pattern and controls underwent RV endocardial mapping with the CARTO3 system. Mapping in both groups was performed before (pre) and after (post) ajmaline administration as none expressed a baseline type-1 ECG pattern. Data were exported and converted into Matlab format using OpenEP. J-elevation for each point was calculated as the amplitude in mV of the unipolar signal at J-point from zero-line. For each point AT was defined as the difference between local depolarization (minimum -dV/dt of the unipolar signal) and surface ECG depolarization (minimum of V2). Corresponding pre and post points were selected; patients having <200 corresponding points were discarded. In each patient, pre and post AT and J-elevation maps were created; a region of interest (ROI) covering the RVOT was selected based on the tricuspid valve position. For each ROI point delta-J and delta-AT were calculated as the difference between post and pre, and interpolated to obtain RVOT differential maps. A point-by-point correlation analysis was performed between delta-J and delta-AT. A maximum and a minimum variation area (ROImax and ROImin, respectively) within RVOT were identified for both delta-J and delta-AT. Results 24 BrS patients and 2 controls were included (1092±633 average corresponding points); all BrS patients presented type-1 ECG after ajmaline, while no control did. Examples of RV maps, ROI selection and RVOT pre, post and differential maps can be seen in Figure 1. In BrS, ROImax delta-J was significantly higher with respect to ROImin (1.68 vs 0.6 mV, p<0.001) while delta-AT ROImax was significantly longer compared to delta-AT ROImin (24.1 vs 8.72 ms, p=0.004). In controls no differences between ROImax and ROImin were observed for delta-J, nor for delta-AT. (Figure 2). In BrS population, a point-by-point correlation between delta-J and delta-AT was present in patient BrS4 (Pearson R coefficient=0.61, p<0.001) and in patient BrS20 (R=0.53, p> 0.001). Conclusions Localized repolarization and depolarization abnormalities in the RVOT are typically found in BrS patients but not in controls. High-density unipolar endocardial mapping pre and post-ajmaline unveils the critical electrophysiological substrate unmasking local repolarization and depolarization dispersion area. In BrS, higher repolarization dispersion area, located in the RVOT, correlates to slow-conducting zones.Methods Results