Left atrial abnormality (LAA) as a predictor of ibrutinib-associated atrial fibrillation in patients with chronic lymphocytic leukemia

ABSTRACT

Results from several recent studies in chronic lymphocytic leukemia (CLL) have demonstrated an association between ibrutinib exposure and the development of atrial fibrillation, estimated incidence of 11% with long-term follow up. This is a common cause of ibrutinib discontinuation. Risk factors for atrial fibrillation include advanced age, hypertension (HTN), mitral valve disease (MVD), left atrial remodeling, coronary artery disease (CAD) and risk factors for cardiovascular dysfunction We conducted a retrospective case control study using the presence of left atrial abnormality identified on pre-ibrutinib EKGs, defined as either (1) Lead II-bifed p wave, with 40 mcsec between peaks for ≥ 2.5 mm wide ≥ 100 msec in duration, (2) Lead V1-biphasic P wave with terminal portion ≥ 40 msec in duration or terminal portion ≥ 1 mm deep or (3) PR interval ≥ 200 msec (intra-atrial conduction delay) as a predictor for development of atrial fibrillation. 183 consecutively CLL patients treated with ibrutinib were identified. 44 patients met inclusion criteria (20 cases, 24 controls). 20 (11.3%) of patients developed atrial fibrillation. Left atrial enlargement was identified as a significant predictor of development of atrial fibrillation (OR 9.1, 95% CI 2.2–37.3, p=0.02). Age, baseline HTN, CAD, diabetes, age and sex were not significant predictors. Area under the ROC curve for the model was estimated to be 75%. LAA identified by EKG is a moderately specific and sensitive finding that can identify patients at increased risk for this toxicity.

KEYWORDS:

• ibrutinib
• atrial fibrillation
• chronic lymphocytic leukemia
• left atrial abnormality
• EKG
• toxicity
• arrhythmia
• Clinical Trials
• Receptor Signaling