Pericardial effusion and tamponade as a rare cardiac toxicity of covalent BTK inhibitors in CLL–a multi-modality study

Bruton tyrosine kinase inhibitors (BTKi) have a unique cardiovascular toxicity profile. We investigated pericardial effusion and tamponade (PE/T) as a potential cardiac complication associated with BTKi therapy. We employed a multi-modal approach: (1) a case series (2) a prevalence analysis using institutional and National Health Oragnization Maintanance (HMO) registry data; and (3) a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing BTKi- and non-BTKi-based regimens in CLL. We identified 15 cases of PE/T during BTKi therapy. In our institutional cohort (<i>n</i> = 750), PE/T prevalence was 2.6% among BTKi-treated patients vs. 0.17% in non-BTKi-treated patients (RR 15.48; <i>p</i> = 0.0072). In the HMO registry (<i>n</i> = 5917), BTKi-associated PE/T prevalence was 0.78%, with an RR of 3.09 (<i>p</i> = 0.029). The meta-analysis showed a significantly increased risk of PE/T with BTKi therapy (OR 3.25; 95% CI 1.02-10.35; <i>p</i> = 0.01; I²=0%). These results suggest that PE/T may represent a rare but clinically meaningful cardiac toxicity of BTKi therapy.