Segan Louise, Beekman Ashley, Parfrey Shane, Perrin Mark
Department of Cardiology, Barwon Health, Bellerine Street, Geelong, VIC 3220, Australia.
Eur Heart J Case Rep. 2019 Dec 31;4(1):1-5. doi: 10.1093/ehjcr/ytz230. eCollection 2020 Feb.
Poly ADP-ribose polymerase (PARP) inhibitors target pathogenic mutations in chemotherapy-resistant malignancies. PARP inhibitors cause modest dose-dependent QT prolongation in the setting of a normal baseline QT interval.
We describe a case of PARP inhibitor-induced torsades de pointes (TdP) in an 86-year-old gentleman prescribed rucaparib due to chemotherapy-resistant, metastatic prostate cancer with pre-existing long QT, with an apparent dose-dependent increase in QT interval. The patient presented with syncope and recurrent TdP requiring direct cardioversion reversion (200 J biphasic) and an isoprenaline infusion (2 μg/min). There were no other QT prolonging agents and no electrolyte or metabolic disturbance to account for this arrhythmia. Improvement in QT interval was observed within 72 h of rucaparib cessation.
PARP inhibitors cause a modest, dose-dependent increase in QT interval in patients with a normal baseline. The safety of PARP inhibitors in patients with pre-existing long QT has not been evaluated. This is the first reported case of rucaparib-associated TdP in a patient with pre-existing long QT, highlighting the amplified effect of this agent in individuals with pre-existing QT prolongation and the risk of fatal arrhythmias.
聚（ADP - 核糖）聚合酶（PARP）抑制剂可靶向化疗耐药恶性肿瘤中的致病突变。在基线QT间期正常的情况下，PARP抑制剂会引起适度的剂量依赖性QT间期延长。
我们描述了一例86岁男性因化疗耐药的转移性前列腺癌且存在长QT间期而服用鲁卡帕尼后发生PARP抑制剂诱导的尖端扭转型室性心动过速（TdP）的病例，其QT间期呈明显的剂量依赖性增加。患者出现晕厥和反复的TdP，需要进行直接心脏复律（200 J双相波）和静脉输注异丙肾上腺素（2μg/min）。不存在其他导致QT间期延长的药物，也没有电解质或代谢紊乱可解释这种心律失常。在停用鲁卡帕尼72小时内观察到QT间期有所改善。
PARP抑制剂在基线正常的患者中会引起适度的、剂量依赖性的QT间期增加。PARP抑制剂在已有长QT间期患者中的安全性尚未得到评估。这是首例报道的已有长QT间期患者发生鲁卡帕尼相关TdP的病例，突出了该药物在已有QT间期延长个体中的放大效应以及致命性心律失常的风险。
