Pacemaker implantation is associated with post-ablation atrial fibrillation recurrence mediated by plasma CILP1

Figures

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  Fig. 1. Flowchart describing the schematic overview of the study design. Through the follow-up of a clinical cohort comprising 70 patients with paroxysmal atrial fibrillation (parox-AF) and 48 propensity score-matched parox-AF patients with implanted pacemakers, we observed a higher recurrence rate in the pacemaker group. To investigate the underlying biomarkers, we collected plasma samples from both groups for proteomic analysis, focusing on elevated levels of the extracellular matrix protein CILP1 in the parox-AF patients with pacemakers. Subsequent validation with an expanded sample size confirmed that CILP1 levels were significantly higher in parox-AF patients with pacemakers, establishing CILP1 as an independent risk factor for AF recurrence post-ablation. Mediation analysis further indicated that the increased recurrence rate in parox-AF patients with implanted pacemakers after ablation is partially mediated by elevated plasma CILP1 levels.

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  Fig. 2. Recurrence of atrial fibrillation in the patients with or without pacemaker. (A) LAD of patients with PM was higher than those without PM. (B) Kaplan-Meier curves demonstrated AF recurrence across with or without PM. LAD, left atrial diameter; PM, pacemaker; AF, atrial fibrillation.

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  Fig. 3. Identification of differentially expressed proteins in plasma using quantitative proteomics. (A) PCA score plot of the plasma samples displaying separation of patients without PM from patients with PM. (B) Heatmap of the differentially expressed proteins (DEPs) (C) Volcano plot showing the DEPs between no-PM and PM groups. (D) Gene Ontology (GO) enrichment analysis of the DEPs. The top 5 enriched terms in the biological process (BP), cellular component (CC), and molecular function (MF) are listed. (E) Comparison of up- and down-regulated terms in GO enrichment analysis.

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  Fig. 4. Elevated plasma CILP1 levels in patients with cardiac pacemaker and its association with recurrence of atrial fibrillation after catheter ablation. (A) Plasma CILP1 levels were higher in patients with implanted cardiac pacemaker. (B) Patients with implanted cardiac pacemaker presented larger left atrial diameter (LAD). (C) Plasma CILP1 levels were moderately correlated with LAD in patients with or without pacemaker. (D) Plasma CILP1 levels were higher in patients with recurrent atrial fibrillation after radiofrequency ablation. (E) Receiver operating characteristic curve (ROC) analysis to verify the predictive value of plasma CILP1 level and LAD for AF recurrence. (F) Kaplan-Meier curves demonstrated AF recurrence across plasma CILP1 level.

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  Fig. 5. Plasma CILP1 level as a mediator in the associations between paroxysmal fibrillation with implanted pacemaker and recurrence after radiofrequency ablation. (A,B) Plasma CILP1 levels partially mediate the association between paroxysmal fibrillation with implanted pacemakers and recurrence after radiofrequency ablation. (C) A schematic diagram illustrating increased atrial fibrillation recurrence post radiofrequency ablation in paroxysmal atrial fibrillation patients with implanted pacemakers.