DOI: 10.12890/2025_005232

Entrectinib-induced Brugada syndrome leading to ventricular tachycardia in a patient with ROS1 fusion-positive lung adenocarcinoma

Authors

  • Nobuo Ishiguro Department of Cardiology, Nagoya Tokushukai General Hospital, Nagoya, Japan
  • Takeshi Mori Department of Cardiology, Nagoya Tokushukai General Hospital, Nagoya, Japan
  • Makito Kaneshiro Department of Cardiology, Nagoya Tokushukai General Hospital, Nagoya, Japan
  • Shin Hasegawa Department of Cardiology, Nagoya Tokushukai General Hospital, Nagoya, Japan
  • Akimitsu Tanaka Department of Cardiology, Nagoya Tokushukai General Hospital, Nagoya, Japan
  • Miyuki Ando Department of Cardiology, Nagoya Tokushukai General Hospital, Nagoya, Japan
  • Kazuo Kato Department of Cardiology, Nagoya Tokushukai General Hospital, Nagoya, Japan

ishiguronobuo0707@gmail.com

Keywords

Entrectinib, drug-induced Brugada syndrome, ventricular tachycardia, ROS1 fusion-positive non-small-cell lung cancer

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.

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References

  1. Drilon A, Siena S, Dziadziuszko R, Barlesi F, Krebs MG, Shaw AT, et al. trial investigators. Entrectinib in ROS1 fusion-positive non-small-cell lung cancer: integrated analysis of three phase 1–2 trials. Lancet Oncol 2020;21:261–270. Erratum in: Lancet Oncol 2020;21:e70. Erratum in: Lancet Oncol 2020;21:e341.
  2. Kubota M, Iso Y, Mori H, Suzuki H. Entrectinib-induced Brugada phenocopy in a patient with metastatic non-small cell lung cancer. Eur Heart J Case Rep 2023;7:ytad324.
  3. Futamura K, Hase T, Tanaka A, Sakai Y, Okachi S, Shibata H, et al. Lethal ventricular arrhythmia due to entrectinib-induced Brugada syndrome: a case report and literature review. Int Cancer Conf J 2023;12:299–304.
  4. Wellens HJ, Bär FW, Lie KI. The value of the electrocardiogram in the differential diagnosis of a tachycardia with a widened QRS complex. Am J Med 1978;64:27–33.
  5. Kindwall KE, Brown J, Josephson ME. Electrocardiographic criteria for ventricular tachycardia in wide complex left bundle branch block morphology tachycardias. Am J Cardiol 1988;61:1279–1283.
  6. Ueoka A, Morita H, Watanabe A, Morimoto Y, Kawada S, Tachibana M, et al. Prognostic significance of the sodium channel blocker test in patients with Brugada syndrome. J Am Heart Assoc 2018;7:e008617.
  7. Tisdale JE, Chung MK, Campbell KB, Hammadah M, Joglar JA, Leclerc J, et al. American Heart Association Clinical Pharmacology Committee of the Council on Clinical Cardiology and Council on Cardiovascular and Stroke Nursing. Drug-induced arrhythmias: a scientific statement from the American Heart Association. Circulation 2020;142:e214–e233.
  8. Konigstein M, Rosso R, Topaz G, Postema PG, Friedensohn L, Heller K, et al. Drug-induced Brugada syndrome: clinical characteristics and risk factors. Heart Rhythm 2016;13:1083–1087.
  9. Russo V, Caturano A, Migliore F, Guerra F, Francia P, Nesti M, et al. Long-term clinical outcomes of patients with drug-induced type 1 Brugada electrocardiographic pattern: a nationwide cohort registry study. Heart Rhythm 2024;21:555–561.
  10. Nakano Y, Shimizu W. Brugada syndrome as a major cause of sudden cardiac death in Asians. JACC Asia 2022;2:412–421.
  11. Milman A, Sabbag A, Conte G, Postema PG, Andorin A, Gourraud JB, et al. Characteristics of patients with spontaneous versus drug-induced Brugada electrocardiogram: sub-analysis from the SABRUS. Circ Arrhythm Electrophysiol 2023;16:e011360.

Published

2025-04-02

Issue

Vol. 12 No. 5 (2025)

Categories

How to Cite

1.
Ishiguro N, Mori T, Kaneshiro M, Hasegawa S, Tanaka A, Ando M, et al. Entrectinib-induced Brugada syndrome leading to ventricular tachycardia in a patient with ROS1 fusion-positive lung adenocarcinoma. EJCRIM [Internet]. 2025 Apr. 2 [cited 2026 Nov. 3];12(5). Available from: https://ejcrim.com/index.php/ejcrim/article/view/5232

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