Clonal haematopoiesis of indeterminate potential predicts recurrence of atrial arrhythmias after surgical ablation for atrial fibrillation

Abstract Background Clonal haematopoiesis of indeterminate potential (CHIP), characterized by the presence of somatic blood cell clone expanding without other haematological abnormalities, was recently shown to be significantly associated with the development and progression of atrial fibrillation (AF). However, the clinical relevance of CHIP in patients underwent surgical atrial ablation remained unexplored. Aims This study investigated the potential role of CHIP in the recurrence of atrial arrhythmias after surgical ablation in patients with AF. Methods Deep-target sequencing of 74 CHIP (a mean depth of coverage = 4051x) was performed in 132 patients with AF (mean age, 60 years; 75.8% male; mean left atrial diameter, 47mm) who underwent surgical ablation without previous atrial ablation between December 2014 and September 2021. Variant allele fraction (VAF) ≥ 2.0% of any targeted genes indicated the presence of CHIP mutations. The primary outcome is the recurrence of any atrial arrhythmias for >30s after a blanking period of 3 months within a year. The clinical significance of CHIP was determined by multivariable Cox proportional hazards regression. Results A total of 17.4% (23 of 132) patients with AF carried CHIP mutations (DNMT3A, 8.3% and TET2, 3.8%). CHIP prevalence varied among AF types, with paroxysmal, persistent, and long-lasting AF counting for 12.5%, 16.5%, and 36.4%, respectively. During one-year follow-up after blanking period, recurrent atrial arrhythmia was documented in 15 (65.2%) and 37 (33.4%) patients in the CHIP and non-CHIP groups, respectively (p = 0.005 for log-rank test). The association of CHIP with atrial arrhythmias recurrence remained significant after fully adjustment (hazard ratio, [95% confidence interval], 1.92 [1.02-3.63]). Conclusions CHIP mutations with a VAF ≥ 2.0% were identified in 17.4% AF patients undertaken surgical ablation and was associated with poor prognosis. CHIP assessment may be useful in the personalized management of patients who planned to perform surgical ablation for AF.