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.

中文翻译：

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钠通道阻滞剂对 Brugada 综合征致心律失常底物的影响机制

背景

钠通道阻滞和高速起搏改变 Brugada 综合征 (BrS) 的电图 (EGM) 底物的机制尚未阐明。

客观的

本研究的目的是确定阿马林和高起搏率对 BrS 底物的影响。

方法

32 名 BrS 患者（平均年龄 40 ± 12 岁）和频繁的心室颤动发作在给予阿吉马林之前和之后以及在高速心房起搏期间接受了右心室流出道基质电解剖和心电图成像 (ECGI) 映射。在 4 名患者中，使用开胸手术和靶向活检进行心外膜标测。

结果

Ajmaline 增加了基底层的激活时间延迟 (33%; P = .002)、右胸前导联 ST 段抬高 (74%; P < .0001) 和延迟激活区域 (170%; P < .0001)，与增加的基板尺寸一致 (75%; P < .0001)。高心房起搏率使右心室流出道区域的异常 EGM 持续时间从 112 ± 48 增加到 143 ± 66 ms ( P= .003) 并在底物部位产生间歇性传导阻滞和/或激发失败，尤其是在阿马林给药后。来自 4 名开胸手术患者的活检显示心外膜纤维化，其中 EGM 在基线时正常，但在给予阿吉马林后变得分裂。在某些区域，局部激活不存在，单极 EGM 具有类似于动作电位形状的单相形态。

结论

用ajmaline降低钠电流通过产生分级EGM、传导阻滞或兴奋失败，严重损害BrS纤维化底物的脉冲传导，导致Brugada心电图模式并有利于心室颤动的发生。