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

Fazal, Muhammad; Wei, Chen; Chuy, Katherine Lee; Hussain, Kifah; Gomez, Sofia; Ba, Shayena Shah; Pietrasik, Grzegorz; Yadav, Neha; Ghazizadeh, Zaniar; Kapoor, Ridhima; Witteles, Ronald; Blackmon, Amanda; Wang, Paul J.; John, Roy M.; Narayan, Sanjiv M.; Cheng, Paul; Rhee, June‐Wha; Baykaner, Tina

doi:10.1007/s10840-022-01400-z

Cited by 11 publications

(3 citation statements)

References 23 publications

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“…Furthermore, our study showed that induced VA in the heart of IBR-treated rats exhibited greater spatial disorganization than seen in hearts from the ABR group, making them more likely to cause insurmountable hemodynamic instability [ 20 ]. This finding aligns with the existing published literature on the characteristics of VA in patients treated with IBR and ABR [ 13 , 21 , 22 , 23 ]. The different impacts of IBR and ABR on ventricular membrane voltage, as demonstrated in our study, may underlie the varying vulnerability to VA and the distinct VA characteristics observed between these two agents [ 9 ].…”

Section: Discussionsupporting

confidence: 92%

Arrhythmogenic Ventricular Remodeling by Next-Generation Bruton’s Tyrosine Kinase Inhibitor Acalabrutinib

Zhao,

Chakraborty,

Tomassetti

et al. 2024

IJMS

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Cardiac arrhythmias remain a significant concern with Ibrutinib (IBR), a first-generation Bruton’s tyrosine kinase inhibitor (BTKi). Acalabrutinib (ABR), a next-generation BTKi, is associated with reduced atrial arrhythmia events. However, the role of ABR in ventricular arrhythmia (VA) has not been adequately evaluated. Our study aimed to investigate VA vulnerability and ventricular electrophysiology following chronic ABR therapy in male Sprague–Dawley rats utilizing epicardial optical mapping for ventricular voltage and Ca2+ dynamics and VA induction by electrical stimulation in ex-vivo perfused hearts. Ventricular tissues were snap-frozen for protein analysis for sarcoplasmic Ca2+ and metabolic regulatory proteins. The results show that both ABR and IBR treatments increased VA vulnerability, with ABR showing higher VA regularity index (RI). IBR, but not ABR, is associated with the abbreviation of action potential duration (APD) and APD alternans. Both IBR and ABR increased diastolic Ca2+ leak and Ca2+ alternans, reduced conduction velocity (CV), and increased CV dispersion. Decreased SERCA2a expression and AMPK phosphorylation were observed with both treatments. Our results suggest that ABR treatment also increases the risk of VA by inducing proarrhythmic changes in Ca2+ signaling and membrane electrophysiology, as seen with IBR. However, the different impacts of these two BTKi on ventricular electrophysiology may contribute to differences in VA vulnerability and distinct VA characteristics.

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Section: Discussionsupporting

confidence: 92%

Arrhythmogenic Ventricular Remodeling by Next-Generation Bruton’s Tyrosine Kinase Inhibitor Acalabrutinib

Zhao,

Chakraborty,

Tomassetti

et al. 2024

IJMS

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“…In addition, afatinib inhibits HER2 expression [ 21 ]. There has been a report of heart failure caused by afatinib in 1.88% of patients and a case of suspected medication for PVC [ 22 , 23 ]. Erlotinib, on the other hand, has been reported to cause thrombotic complications and not heart failure or cardiac conduction defects [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Successful Rechallenge with Osimertinib following Osimertinib-Induced Ventricular Tachycardia: A Case Report

Saito,

Imakita,

Ito

et al. 2023

Case Rep Oncol

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Osimertinib, a third-generation tyrosine kinase inhibitor, is the first-line treatment for metastatic non-small cell lung cancer (NSCLC) with sensitizing epidermal growth factor receptor (EGFR) mutations. It is known to cause drug-induced cardiotoxicity, including QT prolongation syndrome, heart failure, and ventricular arrhythmias, which can lead to sudden death. Once severe arrhythmias occur, it is difficult to continue osimertinib treatment. We report a case of a 66-year-old woman with recurrent NSCLC after concurrent chemoradiotherapy who experienced osimertinib-induced ventricular arrhythmia-causing syncope. The patient was initially treated with concurrent chemoradiotherapy, and genetic testing revealed EGFR exon 19 deletion. Three years following treatment initiation, the primary tumor progressed, and new bone metastases developed. The patient was diagnosed with recurrent NSCLC and was treated with targeted therapy with osimertinib. On the 10th day of osimertinib administration, syncope occurred. Electrocardiography showed polymorphic non-sustained ventricular tachycardia, which was believed to be the cause of syncope. The patient was switched to erlotinib. Two and a half years later, disease progression in the primary lesion was observed. A liquid biopsy revealed an EGFR T790M resistance mutation. Therefore, osimertinib (40 mg) was administered every alternate day. After confirming the absence of palpitations and arrhythmias on electrocardiogram, the osimertinib dosing was increased to 40 mg daily. Thereafter, no further events occurred, and tumor shrinkage was observed. Low-dose osimertinib rechallenge after induced ventricular arrhythmia may be considered an option under close monitoring; however, osimertinib rechallenge must be carefully selected based on the risk-benefit analysis.

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“…The toxicities associated with ibrutinib, a BTK inhibitor, include atrial fibrillation in up to 38% of patients [ 149 ], ventricular arrhythmias, HF, and hypertension [ 20 ]. Recent evidence indicates that newer BTK inhibitors, such as acalabrutinib and zanubrutinib, have less cardiac activity and are more selective for BTK [ 16 ].…”

Section: Tyrosine Kinase Inhibitorsmentioning

confidence: 99%

Cardiovascular Toxicity of Antineoplastic Treatments in Hematological Diseases: Focus on Molecular Mechanisms to Improve Therapeutic Management

Barachini,

Buda,

Petrini

2024

JCM

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In recent years, advancements in the treatment of hematologic neoplasms have led to more effective and less toxic therapeutic schemes, resulting in prolonged patient life expectancy. However, the success of these treatments has also brought about an increased prevalence of cardiovascular adverse events, becoming a significant concern for the growing population of cancer survivors. Antineoplastic therapies, targeting both tumor and organ vessels, contribute to vascular toxicity, influenced by genetic factors and pre-existing vascular diseases. Chemotherapeutic agents and targeted treatments can induce cardiovascular toxicity by affecting endothelial cells and cardiomyocytes through various mechanisms, including hypoxia, vasculature abnormalities, and direct effects on cardiomyocytes. Cardiovascular adverse events encompass a wide range, from cardiac dysfunction to an elevated risk of arrhythmias. While early cardiac events are well-described in clinical trials, delayed toxicities are gaining relevance due to prolonged patient survival. The review focuses on the cardiac and vascular toxicity of antineoplastic drugs in hematological disorders, providing insights into the molecular physiopathology of cancer therapy-associated cardiotoxicity. Understanding how these drugs interact with the heart and blood vessels is essential for predicting, detecting, and managing chemotherapy-related heart issues.

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

Cited by 11 publications

References 23 publications

Arrhythmogenic Ventricular Remodeling by Next-Generation Bruton’s Tyrosine Kinase Inhibitor Acalabrutinib

Arrhythmogenic Ventricular Remodeling by Next-Generation Bruton’s Tyrosine Kinase Inhibitor Acalabrutinib

Successful Rechallenge with Osimertinib following Osimertinib-Induced Ventricular Tachycardia: A Case Report

Cardiovascular Toxicity of Antineoplastic Treatments in Hematological Diseases: Focus on Molecular Mechanisms to Improve Therapeutic Management

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