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

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.

Cardiotoxicity Surveillance and Risk of Heart Failure During HER2 Targeted Therapy.

BACKGROUND: Guidelines recommend left ventricular ejection fraction (LVEF) assessments every 3 months for cardiotoxicity monitoring during human epidermal growth factor receptor 2 (HER2) targeted therapy. Evidence in support of this practice is lacking. OBJECTIVES: This study examines the association between adherence to cardiotoxicity surveillance guidelines and heart failure (HF) in HER2-positive breast cancer patients. METHODS: A case-control study was performed in 53 patients who developed cardiotoxicity during HER2 targeted therapy, and 159 controls matched by age, anthracycline exposure, and year of treatment. Cardiotoxicity was defined as HF (New York Heart Association functional class III or IV) or cardiac death. Adherence to cardiotoxicity surveillance guidelines was ascertained from the beginning of HER2 targeted therapy to the diagnosis date of HF for cases or the corresponding timepoint for matched controls. Conditional logistic regression was used for case-control comparisons. RESULTS: Eighty-one percent of cases and controls were previously treated with an anthracycline. Adherence to cardiotoxicity surveillance guidelines during the entire observation period or during the first 6 months of treatment was not associated with lower risk of HF. An LVEF <55% at any surveillance timepoint was identified in 49% of cases and 3% of controls, and an LVEF <55% during the final surveillance timepoint before developing HF was identified in 54% of cases and 4% of controls. In multivariable-adjusted analyses, LVEF <55% at any timepoint or during the final surveillance timepoint (odds ratio: 27.0; 95% confidence interval: 9.3 to 78.8 and odds ratio: 25.6; 95% confidence interval: 7.3 to 90.3, respectively) was associated with HF. CONCLUSIONS: Patients with LVEF <55% on routine surveillance during HER2 targeted therapy are at increased risk for HF. Additional studies to define their optimal management are warranted.