Atrial Fibrillation and Ibrutinib: Understanding the Cardiovascular Toxicity of Bruton Tyrosine Kinase Inhibitors in Lymphoma

Introduction

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the elderly. In recent years, Bruton tyrosine kinase (BTK) inhibitors have been increasingly used in the treatment of various lymphomas. However, concerns have been raised about the cardiovascular toxicity of these therapies, including the development of AF. In this article, we explore the relationship between BTK inhibitors and AF, highlighting the importance of careful monitoring and management of cardiovascular risks.

The Mechanism of BTK Inhibitors

BTK is involved in the signaling pathways of B-cell receptors, which play a critical role in the survival and proliferation of malignant B cells. BTK inhibitors, such as ibrutinib, irreversibly bind to the BTK active site, preventing downstream signaling and inducing apoptosis of malignant B cells.

BTK Inhibitors and AF

A recent meta-analysis showed that the use of BTK inhibitors was associated with an increased risk of AF, with an incidence ranging from 6.4% to 16.2%. The underlying mechanism of AF induced by BTK inhibitors remains unclear, but it may be related to the effect of ibrutinib on ion channels and cardiac conduction systems.

Ion channels

BTK inhibitors, such as ibrutinib, have been shown to block the hERG potassium channel, which is critical for cardiac repolarization. This blockade can cause prolongation of the QT interval and increase the risk of arrhythmias, including AF.

Cardiac conduction system

Ibrutinib can also affect the cardiac conduction system by inhibiting the L-type calcium channel and the delayed rectifier potassium channel. These channels play a critical role in the regulation of cardiac action potential and conduction. Inhibition of these channels by ibrutinib can cause conduction abnormalities, including AF.

Management of Cardiovascular Risks

Given the potential cardiovascular toxicity of BTK inhibitors, including the development of AF, careful monitoring and management of cardiovascular risks are crucial in patients receiving these therapies. Patients should be regularly assessed for cardiac function, and ECG monitoring should be performed during treatment. In addition, consideration should be given to the use of alternative treatments in patients with cardiovascular risk factors or a history of arrhythmias.

Conclusion

AF is a common arrhythmia in the elderly, and its incidence may be increased by the use of BTK inhibitors in the treatment of lymphomas. While the underlying mechanism of AF induced by BTK inhibitors is not well understood, it is likely to be related to the effect of these therapies on ion channels and cardiac conduction systems. Thus, careful monitoring and management of cardiovascular risks are essential in patients receiving these therapies.

Originally Post From https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2024.1408983/abstract

The Dangers of Bruton Tyrosine Kinase Inhibitor-Related Atrial Fibrillation – A Treatment Wake-up Call