TY - JOUR
T1 - Mechanism of the effects of sodium channel blockade on the arrhythmogenic substrate of Brugada syndrome
AU - Nademanee, Koonlawee
AU - Veerakul, Gumpanart
AU - Nogami, Akihiko
AU - Lou, Qing
AU - Hocini, M. lèze
AU - Coronel, Ruben
AU - Behr, Elijah R.
AU - Wilde, Arthur
AU - Boukens, Bastiaan J.
AU - Haissaguerre, Michel
N1 - Funding Information: Funding Sources: This work was partially supported by the National Research Council of Thailand and Grant in Aid from Bumrungrad Hospital, Bangkok, Thailand, and Medtronic Inc. (to Dr Nademanee) and by the Leducq Foundation (RHYTHM, 16CVD02; to Drs Hocini, Haissaguerre, and Coronel) and Predict 2 (to Dr Wilde). Dr Boukens was supported by the Dutch Heart Foundation (2016T047).Disclosures: Drs Nademanee and Haissaguerre have received research grants from Biosense Webster and Medtronic. Dr Lou is an employee of CardioInsight Medtronic Inc. The rest of the authors report no conflicts of interest. Funding Information: Disclosures: Drs Nademanee and Haissaguerre have received research grants from Biosense Webster and Medtronic. Dr Lou is an employee of CardioInsight Medtronic Inc. The rest of the authors report no conflicts of interest. Funding Information: Funding Sources: This work was partially supported by the National Research Council of Thailand and Grant in Aid from Bumrungrad Hospital, Bangkok, Thailand, and Medtronic Inc. (to Dr Nademanee) and by the Leducq Foundation (RHYTHM, 16CVD02; to Drs Hocini, Haissaguerre, and Coronel) and Predict 2 (to Dr Wilde). Dr Boukens was supported by the Dutch Heart Foundation (2016T047). Publisher Copyright: © 2021 Heart Rhythm Society
PY - 2022
Y1 - 2022
N2 - Background: The mechanisms by which sodium channel blockade and high-rate pacing modify electrogram (EGM) substrates of Brugada syndrome (BrS) have not been elucidated. Objective: The purpose of this study was to determine the effect of ajmaline and high pacing rate on the BrS substrates. Methods: Thirty-two patients with BrS (mean age 40 ± 12 years) and frequent ventricular fibrillation episodes underwent right ventricular outflow tract substrate electroanatomical and electrocardiographic imaging (ECGI) mapping before and after ajmaline administration and during high-rate atrial pacing. In 4 patients, epicardial mapping was performed using open thoracotomy with targeted biopsies. Results: Ajmaline increased the activation time delay in the substrate (33%; P = .002), ST-segment elevation in the right precordial leads (74%; P < .0001), and the area of delayed activation (170%; P < .0001), coinciding with the increased substrate size (75%; P < .0001). High atrial pacing rate increased the abnormal EGM duration at the right ventricular outflow tract areas from 112 ± 48 to 143 ± 66 ms (P = .003) and produced intermittent conduction block and/or excitation failure at the substrate sites, especially after ajmaline administration. Biopsies from the 4 patients with thoracotomy showed epicardial fibrosis where EGMs were normal at baseline but became fractionated after ajmaline administration. In some areas, local activation was absent and unipolar EGMs had a monophasic morphology resembling the shape of the action potential. Conclusion: Sodium current reduction with ajmaline severely compromises impulse conduction at the BrS fibrotic substrates by producing fractionated EGMs, conduction block, or excitation failure, leading to the Brugada ECG pattern and favoring ventricular fibrillation genesis.
AB - Background: The mechanisms by which sodium channel blockade and high-rate pacing modify electrogram (EGM) substrates of Brugada syndrome (BrS) have not been elucidated. Objective: The purpose of this study was to determine the effect of ajmaline and high pacing rate on the BrS substrates. Methods: Thirty-two patients with BrS (mean age 40 ± 12 years) and frequent ventricular fibrillation episodes underwent right ventricular outflow tract substrate electroanatomical and electrocardiographic imaging (ECGI) mapping before and after ajmaline administration and during high-rate atrial pacing. In 4 patients, epicardial mapping was performed using open thoracotomy with targeted biopsies. Results: Ajmaline increased the activation time delay in the substrate (33%; P = .002), ST-segment elevation in the right precordial leads (74%; P < .0001), and the area of delayed activation (170%; P < .0001), coinciding with the increased substrate size (75%; P < .0001). High atrial pacing rate increased the abnormal EGM duration at the right ventricular outflow tract areas from 112 ± 48 to 143 ± 66 ms (P = .003) and produced intermittent conduction block and/or excitation failure at the substrate sites, especially after ajmaline administration. Biopsies from the 4 patients with thoracotomy showed epicardial fibrosis where EGMs were normal at baseline but became fractionated after ajmaline administration. In some areas, local activation was absent and unipolar EGMs had a monophasic morphology resembling the shape of the action potential. Conclusion: Sodium current reduction with ajmaline severely compromises impulse conduction at the BrS fibrotic substrates by producing fractionated EGMs, conduction block, or excitation failure, leading to the Brugada ECG pattern and favoring ventricular fibrillation genesis.
KW - Brugada syndrome
KW - Catheter ablation
KW - Fibrosis
KW - Sodium channel blocker
KW - Ventricular fibrillation
UR - http://www.scopus.com/inward/record.url?scp=85120413034&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.hrthm.2021.10.031
DO - https://doi.org/10.1016/j.hrthm.2021.10.031
M3 - Article
C2 - 34742919
SN - 1547-5271
VL - 19
SP - 407
JO - Heart Rhythm
JF - Heart Rhythm
IS - 3
ER -