Low Ashlea, Leong Kai'En, Sharma Anand, Oqueli Ernesto
Cardiology Department, Ballarat Health Services, 1 Drummond Street, Ballarat, VIC, Australia.
Cardiology Department, Royal Melbourne Hospital, 300 Grattan Street, Parkville, VIC, Australia.
Eur Heart J Case Rep. 2018 Dec 28;3(1):yty156. doi: 10.1093/ehjcr/yty156. eCollection 2019 Mar.
Ticagrelor is an oral anti-platelet agent that is a reversible and direct inhibitor of the adenosine diphosphate P2Y12 receptor. Ticagrelor's brady-arrhythmic potential was investigated in a sub-study of the PLATO trial, which concluded that the effects were transient and not clinically significant beyond the acute initiation phase. Since then, there have been emerging reports of ticagrelor-associated high-degree heart block, requiring drug discontinuation and pacemaker insertion. We present a case of symptomatic ventricular pauses in a patient loaded with ticagrelor post-percutaneous coronary intervention (PCI) for non-ST elevation acute coronary syndrome (NSTEACS) and review the literature relating to ticagrelor and its brady-arrhythmic potential.
A 59-year-old female presented to our hospital with NSTEACS and received an oral load of ticagrelor 180 mg following PCI to her mid-left circumflex coronary artery. Three hours after, four pauses were observed on telemetry over a 20 min period, the longest being 18.5 s in duration. Ticagrelor was ceased and clopidogrel commenced in place. No arrhythmic events were recorded on loop recorder interrogation following ticagrelor discontinuation.
The exact mechanism of ticagrelor-induced brady-arrhythmia is unclear, although inhibition of adenosine reuptake is proposed as likely due to structural similarities between ticagrelor and adenosine. In the setting of acute coronary syndrome treated with ticagrelor, extracellular adenosine concentrations are amplified by the ischaemic milieu with myocardial adenosine release and blunted cellular reuptake. This leads to enhanced agonism of adenosine A1 receptors, causing negative chronotropy and dromotropy. This case report highlights ticagrelor's brady-arrhythmic potential even in the absence of baseline conduction disease or concurrent confounding medications.
替格瑞洛是一种口服抗血小板药物，是二磷酸腺苷P2Y12受体的可逆性直接抑制剂。在PLATO试验的一项子研究中对替格瑞洛的缓慢性心律失常可能性进行了调查，该研究得出结论，这些影响是短暂的，在急性起始阶段之后无临床意义。从那时起，不断有关于替格瑞洛相关高度房室传导阻滞的报道，需要停药并植入起搏器。我们报告一例在经皮冠状动脉介入治疗（PCI）后接受替格瑞洛负荷剂量治疗的非ST段抬高型急性冠状动脉综合征（NSTEACS）患者出现有症状的心室停搏的病例，并回顾与替格瑞洛及其缓慢性心律失常可能性相关的文献。
一名59岁女性因NSTEACS就诊于我院，在左回旋支冠状动脉中段进行PCI后口服180mg替格瑞洛负荷剂量。三小时后，在20分钟的遥测中观察到4次停搏，最长持续时间为18.5秒。停用替格瑞洛并开始使用氯吡格雷。停用替格瑞洛后，动态心电图记录仪检查未记录到心律失常事件。
尽管由于替格瑞洛与腺苷在结构上的相似性，有人提出抑制腺苷再摄取可能是替格瑞洛诱发缓慢性心律失常的确切机制，但尚不清楚。在用替格瑞洛治疗急性冠状动脉综合征的情况下，细胞外腺苷浓度因缺血环境、心肌腺苷释放和细胞再摄取减弱而升高。这导致腺苷A1受体激动增强，引起负性变时性和变传导性。本病例报告强调了即使在没有基线传导疾病或同时使用混淆药物的情况下，替格瑞洛也有诱发缓慢性心律失常的可能性。
