Nademanee Koonlawee, Veerakul Gumpanart, Nogami Akihiko, Lou Qing, Hocini Mélèze, Coronel Ruben, Behr Elijah R, Wilde Arthur, Boukens Bastiaan J, Haissaguerre Michel
Center of Excellence in Arrhythmia Research Chulalongkorn University, Bangkok, Thailand; Pacific Rim Electrophysiology Research Institute at Bumrungrad Hospital, Bangkok, Thailand.
Bhumibol Adulyadej RTAF Hospital, Bangkok, Thailand.
Heart Rhythm. 2022 Mar;19(3):407-416. doi: 10.1016/j.hrthm.2021.10.031. Epub 2021 Nov 4.
The mechanisms by which sodium channel blockade and high-rate pacing modify electrogram (EGM) substrates of Brugada syndrome (BrS) have not been elucidated.
The purpose of this study was to determine the effect of ajmaline and high pacing rate on the BrS substrates.
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.
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.
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.
钠通道阻滞和高频率起搏改变Brugada综合征（BrS）心电图（EGM）基质的机制尚未阐明。
本研究旨在确定阿义马林和高起搏频率对BrS基质的影响。
32例BrS患者（平均年龄40±12岁）且有频发室颤发作，在给予阿义马林前后以及高频率心房起搏期间，进行右心室流出道基质电解剖和心电图成像（ECGI）标测。4例患者采用开胸手术进行心外膜标测并进行靶向活检。
阿义马林增加了基质中的激活时间延迟（33%；P = 0.002）、右胸前导联的ST段抬高（74%；P < 0.0001）以及延迟激活面积（170%；P < 0.0001），同时基质大小增加（75%；P < 0.0001）。高心房起搏频率使右心室流出道区域异常EGM持续时间从112±48毫秒增加至143±66毫秒（P = 0.003），并在基质部位产生间歇性传导阻滞和/或兴奋衰竭，尤其是在给予阿义马林后。4例开胸患者的活检显示心外膜纤维化，这些区域的EGM在基线时正常，但在给予阿义马林后变为碎裂。在一些区域，局部激活缺失，单极EGM具有类似于动作电位形状的单相形态。
阿义马林使钠电流减少，通过产生碎裂的EGM、传导阻滞或兴奋衰竭，严重损害BrS纤维化基质处的冲动传导，导致Brugada心电图模式并有利于室颤的发生。
