Mexiletine Shortens the QT Interval in Patients With Potassium Channel-Mediated Type 2 Long QT Syndrome
Mexiletine Shortens the QT Interval in Patients With Potassium Channel-Mediated Type 2 Long QT Syndrome
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DOI：
10.1161/circep.118.007280
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发表时间：
2019-05-01
影响因子：
8.4
通讯作者：
Ackerman, Michael J.
中科院分区：
文献类型：
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作者：
Bos, J. Martijn;Crotti, Lia;Ackerman, Michael J.
背景：长QT综合征是一种潜在的致死性但高度可治疗的心脏通道病。虽然β受体阻滞剂治疗是大多数患者的标准治疗，但钠通道阻滞剂（如美西律）的伴随治疗通常用于钠通道介导的3型长QT综合征（LQT 3）患者。尚未详细研究钠通道阻滞剂在钾通道介导的长QT综合征（即LQT 1和LQT 2）患者中的潜在作用。方法：我们对12名患者进行了回顾性病历审查（5名女性;诊断时的中位年龄为14.1岁（四分位距[IQR]，7.7-23;范围，0-59，诊断时的中位心率校正QT间期[QTc] 557 ms（IQR，529-605），具有遗传学确定的LQT 2（10）或LQT 1/LQT 2（1）或LQT 2/LQT 3（1）组合，谁收到墨西哥。在诊断和开始治疗后，收集症状状态、治疗和突破性心脏事件的数据。此外，在诊断时、开始美西律治疗前和美西律治疗后收集12导联ECG，以评价药物对QTc的影响。研究结果：诊断前，6例患者有症状，在开始美西律治疗前，4例患者在β受体阻滞剂治疗时发生≥ 1起突破性心脏事件。美西律首次给药时的中位年龄为24.3岁（IQR，14-32.4）。对于所有患者，美西律给药后，中位QTc下降了65 +/- 45 ms，从美西律前的547 ms（IQR，488-558）降至美西律后的470 ms（IQR，409-529）（P= 0.0005）。8例患者（67%）的QTc缩短≥ 40 ms，平均缩短91 ms（P < 0.008）。对于11例维持美西律治疗的患者，在随访期间没有发生突破性心脏事件。结论：尽管美西律通常用于LQT 3患者，但在三分之二的钾通道介导的LQT 2患者中，美西律也显著缩短了QTc。在LQT 2患者中，生理性晚期钠电流的药理学靶向可能会为β受体阻滞剂治疗提供额外的治疗功效。
BACKGROUND: Long QT syndrome is a potentially lethal yet highly treatable cardiac channelopathy. Although ss-blocker therapy is standard for most patients, concomitant therapy with sodium channel blockers, like mexiletine, is often utilized for patients with sodium channel-mediated type 3 long QT syndrome (LQT3). The potential role of sodium channel blockers in patients with potassium channel-mediated long QT syndrome (ie, LQT1 and LQT2) has not been investigated in detail. METHODS: We performed a retrospective chart review on 12 patients (5 females; median age at diagnosis 14.1 years (interquartile range [IQR], 7.7-23; range, 0-59, median heart rate-corrected QT interval [QTc] at diagnosis 557 ms (IQR, 529-605) with genetically established LQT2 (10) or a combination of LQT1/LQT2 (1) or LQT2/LQT3 (1), who received mexiletine. Data were collected on symptomatic status, treatments, and breakthrough cardiac events after diagnosis and initiation of treatment. Additionally, 12-lead ECGs were collected at diagnosis, before initiation of mexiletine and following mexiletine to evaluate the drug's effect on QTc. RESULTS: Before diagnosis, 6 patients were symptomatic and, before initiation of mexiletine, 4 patients experienced = 1 breakthrough cardiac event on beta-blocker. Median age at first mexiletine dose was 24.3 years (IQR, 14-32.4). After mexiletine, the median QTc decreased by 65 +/- 45 ms from 547 ms (IQR, 488-558) premexiletine to 470 ms (IQR, 409-529) postmexiletine (P= 0.0005) for all patients. In 8 patients (67%), the QTc decreased by = 40 ms with a mean decrease in QTc of 91 ms (P < 0.008). For the 11 patients maintained on mexiletine therapy, there have been no breakthrough cardiac events during follow-up. CONCLUSIONS: Although commonly prescribed in patients with LQT3, mexiletine also shortens the QTc significantly in two-thirds of a small subset of patients with potassium channel-mediated LQT2. In patients with LQT2, pharmacological targeting of the physiological late sodium current may provide added therapeutic efficacy to beta-blocker therapy.