Asymptomatic atrial fibrillation in patients treated with BTK inhibitors in hematologic malignancies: a systematic review and metanalysis

BACKGROUND: Atrial fibrillation (AF) is a frequent complication of Bruton's tyrosine kinase inhibitor (BTKi) therapy, yet the proportion of asymptomatic AF events in this setting remains poorly defined. OBJECTIVES: We aimed to estimate the proportion of asymptomatic AF among patients who develop AF during BTKi treatment and to explore factors influencing its detection. METHODS: We conducted a systematic literature review and meta-analysis following international guidelines. Studies reporting AF occurrence and symptom status according to the Common Terminology Criteria for Adverse Events (CTCAE) in BTKi-treated patients with hematologic malignancies were included. Asymptomatic AF was defined as CTCAE grade 1. RESULTS: Twenty-three studies including 2839 patients were analyzed. Overall, 292 AF events were reported, yielding a pooled AF prevalence of 9% (95% CI: 6-13%; I² = 77%). Among these, 49 events were asymptomatic, corresponding to a pooled proportion of 14% (95% CI: 8-24%) with low heterogeneity (I² = 23%). Subgroup analyses demonstrated a significantly higher proportion of asymptomatic AF in the study employing extended rhythm monitoring with a 7-day patch (64%; 95% CI: 38-84%), compared with health care record-based ascertainment or scheduled electrocardiographic evaluation (p for subgroup differences = 0.001). Age, sex, duration of follow-up, BTKi type, and study design were not significantly associated with the proportion of asymptomatic AF. CONCLUSIONS: Approximately one in seven AF episodes occurring during BTKi therapy are asymptomatic. This proportion is influenced by the method of rhythm monitoring and may be higher when prolonged monitoring strategies are employed.