Entrectinib-Induced Brugada Syndrome Leading to Ventricular Tachycardia in A Patient with ROS1 Fusion-Positive Lung Adenocarcinoma.

Abstract

A 65-year-old male presented to the emergency room after experiencing syncope while driving, causing a self-inflicted accident. He had previously been diagnosed with stage IV A (cTXN2M1a) lung adenocarcinoma with C-ROS oncogene 1 (ROS1) fusion gene, wherein entrectinib (a multikinase inhibitor of ROS1, 600 mg orally once daily) was initiated as the first-line chemotherapy 12 days prior. He presented with haemodynamically unstable conditions without fever (blood pressure 89/42 mmHg; heart rate, 180/min). The 12-lead electrocardiogram revealed ventricular tachycardia (VT) with a left bundle branch block and right axis deviation. Synchronised electrical cardioversion terminated the sustained VT, and the post-electrocardiogram exhibited coved-type ST-segment elevation in V1 to V3. An emergency coronary angiography showed no abnormal findings. Coved-type ST-segment elevation in V1 to V3 persisted for two days following cessation of entrectinib; however, electrocardiogram findings gradually normalised, with no recurrence of clinical VT. Catheter ablation for VT was initially planned; however, the consultant pulmonologist considered that entrectinib could induce Brugada syndrome (BrS), resulting in sustained VT. Therefore, the plan was suspended and entrectinib was discontinued. Electrophysiological examination with programmed electrical and pilsicainide infusion for risk stratification failed to induce clinical VT, and the patient was considered at low risk for VT recurrence following entrectinib discontinuation. Accordingly, we opted for close observation. At the one-year follow-up, no ventricular arrhythmias were noted. The relationship between entrectinib and drug-induced BrS remains unclear, with few reported cases. Continuous or frequent electrocardiogram monitoring during hospitalisation post entrectinib initiation may help detect entrectinib-induced BrS.

Learning points: The relationship between entrectinib and drug-induced Brugada syndrome remains unclear, and reports of entrectinib-induced Brugada syndrome are rare.We performed risk stratification using electrophysiological examinations in a case of entrectinib-induced Brugada syndrome in a patient with ROS1 fusion-positive lung adenocarcinoma.Our results suggest that continuous electrocardiogram monitoring or frequent electrocardiogram recording at least once a day several days following entrectinib initiation may help detect entrectinib-induced Brugada syndrome irrespective of being in or out of hospital.