Verduyn S C, Winckels S K G, Gorgels A P M, Doevendans P A, Vos M A
Neth Heart J. 2003 Feb;11(2):70-76.
In the US, the FDA requires in-hospital institution of class III drugs. This study retrospectively assessed whether these criteria, which differ markedly from the Dutch exclusion criteria, could predict sotalol-induced torsade de pointes arrhythmias (TdP).
Oral sotalol effect in a control group (50 patients, 62±12 years, 23 men, 27 women) was compared with five patients developing TdP (75±5years, all women), using known and new (JTU area measured in lead V2) risk parameters. Paroxysmal atrial fibrillation was the most common indication for sotalol treatment.
At baseline the strict US regulations would have identified four of five TdP patients on the basis of individual K levels, creatinine clearance and QT. However, 7 of 49 controls would also have been excluded, although they did not develop documented TdP in the >2 years follow-up. Sotalol slightly increased QT (361±34 to 387±33ms) in controls, due to heart rate reduction. In the TdP group, sotalol dramatically increased QT (467±33 to 626±52 ms, +35%, p<0.05) accompanied by deep negative TU waves and an increased JTU area and all could be identified as risk patients.
Patients developing TdP on oral sotalol can be identified using the FDA risk criteria and hospitalisation may therefore be appropriate. A European prospective study is required to investigate the costs, sensitivity and specificity of this strategy.
在美国，美国食品药品监督管理局（FDA）要求在医院使用III类药物。本研究回顾性评估了这些与荷兰排除标准明显不同的标准是否能够预测索他洛尔诱发的尖端扭转型室性心动过速（TdP）。
使用已知和新的（V2导联测量的JTU面积）风险参数，将对照组（50例患者，年龄62±12岁，男性23例，女性27例）口服索他洛尔的效果与5例发生TdP的患者（年龄75±5岁，均为女性）进行比较。阵发性房颤是索他洛尔治疗最常见的适应症。
在基线时，严格的美国法规会根据个体的血钾水平、肌酐清除率和QT间期识别出5例TdP患者中的4例。然而，49例对照组患者中有7例也会被排除，尽管在超过2年的随访中他们未发生有记录的TdP。在对照组中，由于心率降低，索他洛尔使QT间期略有增加（从361±34毫秒增至387±33毫秒）。在TdP组中，索他洛尔使QT间期显著增加（从467±33毫秒增至626±52毫秒，增加35%，p<0.05），伴有深的负向TU波和JTU面积增加，所有这些患者均可被识别为风险患者。
使用FDA风险标准可以识别口服索他洛尔时发生TdP的患者，因此住院治疗可能是合适的。需要进行一项欧洲前瞻性研究来调查该策略的成本、敏感性和特异性。
