Atrial fibrillation burden and clinical outcomes following BTK inhibitor initiation
John Alan Gambril, Sanam Ghazi, Stephen Sansoterra, Mussammat Ferdousi, Onaopepo Kola‐Kehinde, Patrick Ruz, Adam S. Kittai, Kerry A. Rogers, Michael R. Grever, Seema A. Bhat, Tracy Wiczer, John C. Byrd, Jennifer A. Woyach, Daniel Addison
Abstract
Bruton's tyrosine kinase inhibitors (BTKi) have dramatic efficacy against B-cell malignancies, but link with cardiotoxicity, including atrial fibrillation (AF). Burden, severity, and implications of BTKi-related AF are unknown. Leveraging a large-cohort of consecutive B-cell malignancy patients initiated on BTKi from 2009-2020, we identified patients with extended ambulatory rhythm monitoring. The primary outcome was AF burden after BTKi-initiation. Secondary outcomes included ventricular arrhythmia burden and other arrhythmias. Observed incident-AF rates and burden with next-generation BTKi's were compared to ibrutinib. Multivariable regression defined association between rhythm measures and major adverse cardiac events (MACE), and mortality. There were 98 BTKi-treated patients [38.8% next-generation BTKi's, 14.3% prior-AF], with 28,224 h of monitoring. Median duration BTKi-use was 34 months. Over mean duration 12 days monitoring, 72.4% developed arrhythmias (16.3% incident-AF, 31.6% other SVTs, 14.3% ventricular tachycardia). 14.3% had high AF-burden. AF-burden was similar between ibrutinib and next-generation BTKi's. No single antiarrhythmic-therapy prevented BTKi-related AF. However, antiarrhythmic initiation associated with reduction in arrhythmic burden (P = 0.009). In a multivariable model accounting for traditional cardiovascular risk factors, prior-AF associated with increased post-BTKi AF-burden. In follow-up, high AF burden associated with MACE (HR 3.12, P = 0.005) and mortality (HR 2.97, P = 0.007). Among BTKi-treated patients, high AF burden prognosticates future MACE and mortality risk.