Abstract
Atrial fibrillation (AF) recurrence following radiofrequency ablation (RFA) remains a significant clinical challenge, and pacemaker implantation may influence outcomes. However, the underlying molecular mechanisms are not well understood. This study aimed to investigate whether pacemaker implantation is statistically associated with of AF recurrence and to identify proteomic biomarkers associated with this statistical relationship. We conducted a propensity score-matched cohort study and performed Cox proportional hazards analysis to assess the association between pacemaker implantation and AF recurrence. Exploratory plasma proteomic profiling was performed to identify differentially expressed proteins (DEPs) in a pilot cohort of paroxysmal AF patients with and without pacemakers. An independent validation cohort was used to confirm the findings via Cox analysis and biomarker quantification, followed by statistical mediation analysis. In the discovery cohort, pacemaker implantation was identified as an independent risk factor for post-ablation AF recurrence (adjusted hazard ratio: 2.349, 95% CI: 1.065–5.179, p = 0.034). Exploratory proteomic analysis revealed significantly elevated levels of cartilage intermediate layer protein 1 (CILP1) in pacemaker patients. In the validation cohort, pacemaker implantation remained an independent predictor of AF recurrence, and plasma CILP1 levels were significantly statistically associated with recurrence risk (AUC: 0.737, 95% CI: 0.633–0.842, p = 0.0005). Statistical mediation analysis indicated that elevated CILP1 levels were indirectly associated with the relationship between pacemaker implantation and AF recurrence (p = 0.022). Pacemaker implantation is associated with an increased risk of AF recurrence following RFA. This risk appears to be partially statistically mediated by elevated plasma CILP1 levels. These findings suggest CILP1 may serve as a potential biomarker for AF risk stratification. Given the pilot nature of the proteomic screening, further large-scale studies are warranted to validate these associations.
Data availability
All data are available in the main text or the supplementary materials.
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Funding
This work was supported by Shanghai Arrhythmia Research Center Project (grant number 2022ZZ01008).
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Jingmeng Liu, Taojie Zhou and Changjian Lin contributed equally to this work. Liqun Wu, Qi Jin and Yangyang Bao proposed the study design. Jingmeng Liu, Taojie Zhou and Changjian Lin performed data analysis, data interpretation and manuscript writing. Ning Zhang, Yun Xie, Yue Wei, Qingzhi Luo, Xiang Li, Zimo Sha, Guanhua Wu, Yalan Deng, Tianyou Ling, Wenqi Pan, Lin Lu performed data collection. Yangyang Bao performed manuscript revision. All authors have read and agreed to the published version of the manuscript.
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This research and involved experimental procedures were received approval by Institutional Review Board of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (approval no. RJH201656). Written informed consents were obtained from all participants.
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Liu, J., Zhou, T., Lin, C. et al. Pacemaker implantation is associated with post-ablation atrial fibrillation recurrence mediated by plasma CILP1. Sci Rep (2026). https://doi.org/10.1038/s41598-026-44907-5
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DOI: https://doi.org/10.1038/s41598-026-44907-5
