Longitudinal changes in left atrial function during chronic ibrutinib therapy: a prospective observational study.

BACKGROUND: Ibrutinib is effective for B-cell malignancies but is associated with cardiovascular adverse events, including atrial fibrillation (AF) and hypertension. Longitudinal data on left atrial (LA) remodeling during treatment are limited. We characterized serial changes in LA size and function during chronic ibrutinib therapy. METHODS: In this prospective observational cohort, 40 patients starting ibrutinib underwent clinical assessment, 24-72-hour Holter monitoring, and echocardiography with LA strain at baseline and 3, 6, 12, and long-term (nominal 36-month) follow-up. Primary analyses used observed paired data, random-intercept mixed models, standardized response means (SRMs), and Benjamini-Hochberg adjustment across 24 primary contrasts. RESULTS: Median age was 65 years and 53% were female. Paired mean LAVI changes were +1.52 mL/m² at 3 months (n = 38), +1.68 at 6 months (n = 36), +2.62 at 12 months (n = 33), and +2.15 at long-term follow-up (n = 31; all q ≤ 0.020). LA reservoir strain worsened from 6 months onward (all q ≤ 0.031), while LA contractile strain, LA lateral-wall TDI, and LV GLS worsened at every follow-up (all q ≤ 0.009). Results were materially unchanged after adjustment for time-varying hypertension and in complete-case sensitivity analyses. Incident AF occurred in 5/40 patients (12.5%; 95% CI 5.5%-26.1%). CONCLUSION: During chronic ibrutinib therapy, longitudinal imaging showed modest LA enlargement and consistent deterioration in several LA deformation indices. These treatment-associated observations require confirmation in controlled cohorts. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT03751410.