Advanced Cardiac Conduction Abnormalities in Patients on Ibrutinib Therapy

Abstract

Background: Bruton tyrosine kinase inhibitors, such as ibrutinib, are medications that are actively used for Chronic Lymphocytic Leukemia (CLL) and several lymphomas. They work by inhibiting Bruton’s tyrosine kinase therefore affecting B cell proliferation. Ibrutinib itself is associated with multiple cardiotoxicities including atrial fibrillation, ventricular arrhythmias, heart failure, and bleeding. There are well-established studies that show the incidence of atrial fibrillation with ibrutinib therapy. However, only a few reports show an association between ibrutinib therapy and advanced heart block. Case presentation: We present two unique cases of patients who presented to the emergency room with syncope while being on ibrutinib therapy for CLL. At presentation, the patients were found to have conduction abnormalities seen on their EKG that included complete heart block in one patient and sick sinus syndrome in the other. Ultimately, each patient was treated with a pacemaker, ibrutinib therapy was discontinued, and they were started on alternative therapy for their CLL. Discussion: No clear mechanism has been established for how ibrutinib therapy causes these conduction abnormalities. This case series proposes a possible mechanism of advanced conduction abnormalities that is caused by ibrutinib therapy that is associated with the NOTCH gene. We propose that the downregulation of the NOTCH gene may prevent cardiac myocyte remodeling and therefore can cause conduction abnormalities as seen in our patients along with others that presented with advanced heart block with ibrutinib therapy.