Sudden Death and Asymptomatic Arrhythmia in Chronic Lymphocytic Leukemia Patients Treated with Ibrutinib.

BACKGROUND Ibrutinib (IBR) is a first-in-class Bruton's tyrosine kinase inhibitor (BTKi) approved in multiple hematologic conditions for indefinite use until disease progression or toxicity. Hypertension (HTN) and atrial fibrillation are well-recognized cardiac complications of BTKi; more recently, heart failure, additional arrhythmias, and sudden cardiac death (SCD) have been attributed to IBR. Next-generation covalent BTKi are also associated with cardiovascular complications, including SCD, albeit to a lesser degree. OBJECTIVE The incidence and clinical features of patients experiencing SCD and asymptomatic arrhythmias on IBR remain ill-defined. We aim to characterize the incidence of SCD and asymptomatic arrhythmias on IBR. METHODS We report: 1) a retrospective cohort analysis of 131 patients with a median of 66.5 months on IBR utilizing available cardiac testing, genetic sequencing, and autopsy review; 2) a cross-sectional cardiac analysis of 21 asymptomatic patients on IBR including ambulatory EKG, stress tests, and transthoracic echocardiograms. RESULTS The incidence of SCD in patients on IBR (n=5) was 801 per 100,000 patient-years, approximately 2-4x higher than the general population. All patients with SCD on IBR had at least one cardiac risk factor. Autopsies conducted in 3 of 5 patients with SCD did not reveal acute pathologic processes, but did demonstrate evolving cardiac pathology. Cardiovascular testing in asymptomatic patients on IBR revealed previously unknown clinically significant arrhythmias in 4 (19%) patients, leading to precautionary IBR discontinuation in 2 patients. CONCLUSION IBR increases the risk of SCD among patients with cardiac risk factors. Stress and ambulatory EKG on IBR identified asymptomatic arrhythmias altering clinical management in 19% of patients. These data highlight the need for risk-mitigation strategies for patients starting or receiving IBR, and possibly extending to other BTKis.

• Publication year

  2025

• Venue

  Heart Rhythm

• Publication date

  2025-10-01

• Fields of study

  Medicine

• Identifiers
  DOI 10.1016/j.hrthm.2025.10.014PMID 41077373
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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