"Pill-in-the-Pocket" Treatment of Propafenone Unmasks ECG Brugada Pattern in an Atrial Fibrillation Patient With a Common SCN5A R1193Q Polymorphism
"Pill-in-the-Pocket" Treatment of Propafenone Unmasks ECG Brugada Pattern in an Atrial Fibrillation Patient With a Common SCN5A R1193Q Polymorphism
复制标题
– 普罗帕酮治疗揭示了具有常见 SCN5A R1193Q 多态性的心房颤动患者的心电图 Brugada 模式
DOI：
10.3389/fphys.2019.00353
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发表时间：
2019-03-29
影响因子：
4
通讯作者：
Ma, Changsheng
中科院分区：
文献类型：
--
作者：
Li, Linling;Ruan, Yanfei;Ma, Changsheng
背景：指南中推荐使用 IC 类药物进行“口袋药丸”(PIP) 治疗，用于对新发心房颤动 (AF) 进行复律。主要不良反应经常被报道，其潜在机制被认为与遗传背景有关。方法和结果：一名男性患者接受 PIP 方法（普罗帕酮 600 mg.po）治疗，以转变新发 AF。他的症状变得更严重，并被送往急诊室；心电图显示典型的布鲁格达综合征（BrS）I 型心电图模式，伴窦性心律。基因筛查发现了常见的SCN5A多态性R1193Q。使用膜片钳技术在表达 SCN5A R1193Q 通道和 WT 通道的 HEK293 细胞中研究了普罗帕酮对 I-Na 的阻断。 R1193Q 和 WT 基线时的峰值电流和稳态门控参数没有显着差异。在临床相关浓度 2 μmol/L 普罗帕酮下，R1193Q 与 WT 中 I-Na 的使用依赖性阻断 (UDB) 更为明显（频率为 2 Hz 时分别为 44.2 +/- 7.2 % 与 24.8 +/- 5.7%，P < 0.05）； R1193Q 的 UDB 的 IC50 为 2.9 +/- 0.7 μmol/L，WT 的 UDB 的 IC50 为 8.1 +/- 1.8 μmol/L。与 WT 相比，普罗帕酮在 R1193Q 中产生更多的稳态失活左移，并且从失活恢复更慢。结论：常见的 SCN5A 多态性 R1193Q 增强普罗帕酮的 UDB，并使患者在 PIP 治疗时易患药物诱导的 BrS。我们的数据表明，R1193Q 多态性可能是与普罗帕酮 PIP 方法治疗 AF 患者相关的主要不良反应的遗传标记。对于被确定具有 R1193Q 多态性的 AF 患者，在普罗帕酮 PIP 治疗之前，应考虑进行 Ajmaline 挑战以排除 BrS 的存在。
Background: "Pill-in-the-pocket" (PIP) treatment with type IC drugs for cardioversion of recent-onset atrial fibrillation (AF) has been recommended in guidelines. Major adverse effects have been often reported, and the underlying mechanisms are proposed to be associated with the genetic backgrounds.Methods and Results: A male patient was treated with PIP approach (propafenone 600 mg.po) for the conversion of new onset AF. His symptoms got worse and referred to emergency room; ECG showed a typical Brugada syndrome (BrS) type I ECG pattern with sinus rhythm. Genetic screening identified a common SCN5A polymorphism R1193Q. Propafenone blockade of I-Na was studied in HEK293 cells expressed SCN5A R1193Q channel and WT channel using patch clamp techniques. There was no significant difference in peak current and steady-state gating parameters between R1193Q and WT at baseline. At clinically relevant concentration of 2 mu mol/L propafenone, use-dependent block (UDB) of I-Na was more pronounced in R1193Q versus WT (44.2 +/- 7.2 versus 24.8 +/- 5.7% at the frequency of 2 Hz, P < 0.05); IC50 of UDB was 2.9 +/- 0.7 mu mol/L for R1193Q and 8.1 +/- 1.8 mu mol/L for WT, respectively. Propafenone produced more left shift of steady-state inactivation and slower recovery from inactivation in R1193Q compared with WT.Conclusion: A common SCN5A polymorphism R1193Q enhances UDB by propafenone and predisposes the patients to drug-induced BrS with PIP treatment. Our data suggest that R1193Q polymorphism is likely to be a genetic marker for the major adverse effects associated with propafenone PIP approach for AF patients' management. Ajmaline challenge to rule out the presence of BrS should be considered prior to propafenone PIP therapy in AF patients who are identified to have R1193Q polymorphism.