Lehtonen Annukka, Fodstad Heidi, Laitinen-Forsblom Päivi, Toivonen Lauri, Kontula Kimmo, Swan Heikki
Research Program in Molecular Medicine, Biomedicum Helsinki, Helsinki, Finland.
Heart Rhythm. 2007 May;4(5):603-7. doi: 10.1016/j.hrthm.2007.01.019. Epub 2007 Jan 18.
Pathophysiologically significant ion-channel mutations have been detected in only a minority of cases of acquired long QT syndrome (LQTS).
The aim of this study was to clarify the putative role of subclinical inherited LQTS in drug-associated torsades de pointes (TdP) and to assess the concomitant proarrhythmic factors.
We evaluated 16 consecutive cases with documented, antiarrhythmic drug-induced TdP who were referred to the Laboratory of Molecular Medicine at Helsinki University for LQTS genetic testing between September 2000 and August 2005.
A prolonged QTc interval was observed in 56% of the patients before administration of the drug. TdP was associated with amiodarone in seven, sotalol in six, flecainide in two, and propafenone in one of the cases. Except for the culprit drug, one or more risk factors such as female sex, congestive heart failure, and atrial fibrillation were present in each drug-associated TdP. DNA samples were screened for the four common Finnish founder mutations (KCNQ1 G589D and IVS7-2A-->G, HERG L552S, and R176W), which are known to account for the majority of inherited LQTS in Finland. A total of three (19%) individuals carried one of these four mutations.
Our data show that previously unsuspected LQTS mutations may be present in patients with antiarrhythmic drug-associated TdPs. A normal QTc interval does not exclude the risk of proarrhythmia.
在获得性长QT综合征（LQTS）病例中，仅少数病例检测到具有病理生理意义的离子通道突变。
本研究旨在阐明亚临床遗传性LQTS在药物相关性尖端扭转型室性心动过速（TdP）中的假定作用，并评估伴随的促心律失常因素。
我们评估了2000年9月至2005年8月期间连续16例有记录的抗心律失常药物诱发TdP的病例，这些病例被转诊至赫尔辛基大学分子医学实验室进行LQTS基因检测。
56%的患者在服用药物前观察到QTc间期延长。7例TdP与胺碘酮有关，6例与索他洛尔有关，2例与氟卡尼有关，1例与普罗帕酮有关。除了致病药物外，每种药物相关性TdP病例中均存在一种或多种危险因素，如女性、充血性心力衰竭和心房颤动。对DNA样本进行了芬兰四种常见的始祖突变（KCNQ1 G589D和IVS7-2A→G、HERG L552S和R176W）筛查，已知这些突变占芬兰遗传性LQTS的大部分。共有3例（19%）个体携带这四种突变中的一种。
我们的数据表明，抗心律失常药物相关性TdP患者可能存在先前未被怀疑的LQTS突变。正常的QTc间期并不能排除促心律失常的风险。
