High-density unipolar endocardial mapping before and after ajmaline challenge to assess transmural repolarization gradients in Brugada syndrome: comparison with controls
A Rossi, V Hartwig, S Latrofa, A Giannoni, M Nesti, G Mirizzi, S Garibaldi, L Panchetti, U Startari, M Piacenti, N VanelloAbstract
Background
Transmural repolarization dispersion in the right ventricular outflow tract (RVOT) is thought to underlie the type-1 ECG phenotype in Brugada syndrome (BrS). Repolarization abnormalities generate localized slow-conduction areas on the RVOT epicardium, forming the arrhythmogenic substrate and the target for ablation. However, data on electrical substrate characterization using high-density unipolar endocardial mapping are lacking.
Purpose
To evaluate repolarization changes through endocardial unipolar J-point mapping of the RVOT in BrS patients and controls undergoing ajmaline testing, and to explore their relationship with local activation time (AT) and potential implications for substrate assessment.
Methods
Consecutive BrS patients with spontaneous type-1 ECG and controls underwent high-density endocardial right ventricular mapping before and after ajmaline (AjT). None exhibited baseline type-1 ECG. J-point amplitude was defined as unipolar signal voltage at the surface ECG J-point; AT as the delay between local depolarization (minimum –dV/dt) and surface V2 depolarization. Corresponding points before and after AjT were analyzed within the RVOT region. ΔJ-point and ΔAT maps were generated, and point-by-point correlation assessed.
Results
Twenty-three BrS patients and five controls were included; one underwent combined endo-epicardial mapping and epicardial RVOT ablation. After AjT, all BrS patients but no controls developed type-1 ECG. Baseline RVOT J-point and AT values were similar in BrS and controls. AjT induced a significant J-point amplitude reduction (0.91±0.81 vs 0.44±0.94 mV, p=0.02) and AT prolongation (1.63±17.09 vs 16.93±20.7 ms, p<0.001) in BrS, but not in controls. Both ΔJ-point and ΔAT were significantly greater in BrS (p<0.05), with maximal variations localized to the anterior sub-pulmonary RVOT. ΔJ-point and ΔAT correlated in 10/23 BrS subjects (Spearman R = 0.2–0.51). SCN5A P/LP variant carriers showed greater ΔJ-point and ΔAT changes than non-carriers (p≈0.05).
Conclusions
Ajmaline induces marked endocardial unipolar J-point reduction and AT prolongation in BrS, predominantly in the anterior sub-pulmonary RVOT, but not in controls. These changes co-localize with the epicardial arrhythmogenic substrate and are accentuated in SCN5A variant carriers, suggesting a potential endocardial marker of transmural repolarization heterogeneity and arrhythmogenic substrate in BrS.IMAGE 1IMAGE 2