Repolarization Heterogeneity in Human Post-Infarct Ventricular Tachycardia.
Repolarization Heterogeneity in Human Post-Infarct Ventricular Tachycardia.
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DOI：
10.1016/j.jacep.2022.03.002
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发表时间：
2022-06
影响因子：
7
通讯作者：
Donahue, Kevin
中科院分区：
文献类型：
--
作者：
Callans, David J.;Donahue, Kevin
本研究的目的是确定人类梗死后室性心动过速（VT）的折返回路是否与复极异质性相关。由存活的肌细胞之间的纤维化和连接蛋白重塑引起的慢传导是梗死后VT的重要先决条件;然而，慢传导存在于整个梗死区，而VT回路数量有限且离散。在猪室性心动过速模型中，折返回路发生在由钾通道β亚基KCNE 3（增加复极电流）和KCNE 4（减少复极电流）上调引起的显著复极异质性区域，导致动作电位时程异质性。在6例患者中，在诱发室性心动过速期间进行左心室标测，以识别室性心动过速回路内的部位。随后，进行单极标测（3.5 mm头端消融导管）以表征激动-恢复间期（阿里斯），其是VT回路峡部（IN）内记录的部位与梗死瘢痕内但VT回路外（OUT）部位的局部动作电位时程的替代。与OUT部位相比，IN部位的阿里斯明显更短（420.2 ± 79.3 vs 462 ± 52.8 ms; P = 0.01）。全组与电路相关的部位的ARI值总是比从OUT区域采样的部位的ARI值短。人梗死后室性心动过速的室性心动过速回路部位与复极异质性相关，与先前在猪模型中报道的相似。这表明人类和猪梗死后VT模型之间存在共同机制的可能性，并且开发消融策略或小分子或遗传疗法以恢复正常复极动力学可能是抗心律失常的。
This study was designed to determine whether re-entrant circuits in human post infarction ventricular tachycardia (VT) are associated with repolarization heterogeneity. Slow conduction, caused by fibrosis between surviving myocytes and connexin remodeling, is an important prerequisite for post infarction VT; however, slow conduction is present throughout the infarct whereas VT circuits are finite in number and discrete. In a porcine model of VT, re-entrant circuits occur at region of significant repolarization heterogeneity caused by up-regulation of potassium channel β-subunits KCNE3 (increasing repolarization current) and KCNE4 (decreasing repolarization current), causing heterogeneous action potential durations. In 6 patients, left ventricular mapping was performed during induced VT to identify sites within the VT circuit. Subsequently, unipolar mapping (3.5-mm tip ablation catheter) was performed to characterize activation-recovery intervals (ARIs), which are surrogates for local action potential durations, at sites documented within the VT circuit isthmus (IN) compared to sites within the infarct scar but outside of the VT circuit (OUT). ARIs were significantly shorter in the IN compared with the OUT sites (420.2 ± 79.3 vs 462 ± 52.8 ms; P = 0.01). In all patients. sites that were associated with the circuit always had shorter ARI values than did those sampled from OUT regions. VT circuit sites in human post infarct VT are associated with repolarization heterogeneity, similar to what was previously reported in a porcine model. This suggests the possibility of a common mechanism between humans and the porcine model of post infarct VT, and that development of ablation strategies or small molecule or genetic therapies to restore normal repolarization kinetics may be antiarrhythmic.
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影响因子：
16.6
作者：
Kelemen K;Greener ID;Wan X;Parajuli S;Donahue JK
通讯作者：
Donahue JK
影响因子：
8.4
作者：
Berruezo, Antonio;Fernandez-Armenta, Juan;Mont, Lluis
通讯作者：
Mont, Lluis
影响因子：
37.8
作者：
DEBAKKER, JMT;VANCAPELLE, FJL;HAUER, RNW
通讯作者：
HAUER, RNW
影响因子：
37.8
作者：
KIENZLE, MG;MILLER, J;JOSEPHSON, ME
通讯作者：
JOSEPHSON, ME
影响因子：
5.5
作者：
Orini, Michele;Graham, Adam J.;Lambiase, Pier D.
通讯作者：
Lambiase, Pier D.