Tyrosine kinase inhibitor-associated ventricular arrhythmias: a case series and review of literature

Abstract

Background: Tyrosine kinase inhibitors (TKIs) have been increasingly used as first-line therapy in hematologic and solid-organ malignancies. Multiple TKIs have been linked with the development of cardiovascular complications, especially atrial arrhythmias, but data on ventricular arrhythmias (VAs) is scarce.

Methods: Herein we describe five detailed cases of VAs related to TKI use in patients with varied baseline cardiovascular risk factors between 2019 and 2022 at three centers. Individual chart review was conducted retrospectively.

Results: Patient ages ranged from 43 to 83 years. Three patients were on Bruton's TKI (2 ibrutinib and 1 zanubrutinib) at the time of VAs; other TKIs involved were afatinib and dasatinib. Three patients had a high burden of non-sustained ventricular tachycardia (NSVT) requiring interventions, whereas two patients had sustained VAs. While all patients in our case series had significant improvement in VA burden after TKI cessation, two patients required new long-term antiarrhythmic drug therapy, and one had an implantable defibrillator cardioverter (ICD) placed due to persistent VAs after cessation of TKI therapy. One patient reinitiated TKI therapy after control of arrhythmia was achieved with antiarrhythmic drug therapy.

Conclusions: Given the expanding long-term use of TKIs among a growing population of cancer patients, it is critical to acknowledge the association of TKIs with cardiovascular complications such as VAs, to characterize those at risk, and deploy preventive and therapeutic measures to avoid such complications and interference with oncologic therapy. Further efforts are warranted to develop monitoring protocols and optimal treatment strategies for TKI-induced VAs.

Keywords: Arrhythmia; Sudden cardiac death; Tyrosine kinase inhibitors; Ventricular fibrillation; Ventricular tachycardia.

Fig. 1

a A 14-day cardiac event monitor showed 2376 ventricular tachycardia runs, with fastest interval (lasting 5 beats) at a rate of 272 bpm and longest (shown in the figure) lasting 16 beats at a rate of 211 bpm. b There were 314,232 premature ventricular contractions at a total burden of 34.2% with two dominant morphologies at 28.6% and 5.6% burden. c Presenting electrocardiogram showing ventricular bigeminy

Fig. 2

A 12-lead electrocardiogram showing normal sinus rhythm with premature atrial contractions followed by a short run of likely atrial tachycardia with aberrancy, followed by two premature ventricular contractions

Fig. 3

a Normal baseline electrocardiogram. b, c, d Temporal progression of QRS changes. f Short-coupled premature ventricular complex initiating polymorphic ventricular tachycardia degenerating into ventricular fibrillation

Fig. 4

a A 12-lead electrocardiogram showed sinus rhythm with non-sustained ventricular tachycardia (NSVT) with right bundle branch block and left superior axis. b Inpatient showing frequent ventricular ectopy and NSVT runs. c Telemetry strip in normal sinus rhythm is shown here for reference, which was rare throughout this hospitalization

Fig. 5

Device interrogation shows detection of sustained ventricular tachycardia (VT) by the implantable defibrillator cardioverter (ICD), continuation of VT following a 41 J ICD shock, followed by self-termination, and reinitiation of a non-sustained VT episode. Atrial lead had been turned off due to permanent atrial fibrillation