Plasma proteomic profiling reveals potential biomarkers for sinus node dysfunction in persistent atrial fibrillation
TL;DR
Integrated data-independent acquisition-based proteomics and WGCNA revealed a distinct plasma proteomic signature associated with prolonged SNRT in patients with PerAF, characterized by enrichment of extracellular matrix remodeling and metabolic reprogramming pathways.
Abstract
Aims: In patients with persistent atrial fibrillation (PerAF), detecting sinus node dysfunction (SND) before rhythm control therapy is challenging, which may increase the risk of post-cardioversion bradyarrhythmia and complicate clinical management. This study aimed to identify plasma proteomic signatures associated with prolonged sinus node recovery time (SNRT) and to explore potential predictors of SND in PerAF patients. Methods: A total of 226 consecutive patients with PerAF undergoing catheter ablation were screened, and 177 eligible patients were included. SNRT was measured after cardioversion, with 1,500 ms used as the cutoff to define prolonged SNRT. Propensity score matching was applied to select matched controls. Plasma samples were analyzed using proteomic techniques to compare protein expression profiles between the prolonged-SNRT and normal-SNRT groups. A weighted gene co-expression network analysis (WGCNA) was conducted to determine the most significant module and hub proteins associated with SNRT. An enzyme-linked immunosorbent assay was used for further assessment of candidate biomarkers. Results: Proteomic analysis identified 435 differentially expressed proteins, including 138 upregulated and 297 downregulated proteins in the prolonged-SNRT group. Integrated data-independent acquisition-based proteomics and WGCNA revealed a distinct plasma proteomic signature associated with prolonged SNRT in patients with PerAF, characterized by enrichment of extracellular matrix remodeling and metabolic reprogramming pathways. Acid phosphatase 5 (ACP5) was selected as a candidate biomarker, which was significantly elevated in patients complicated by SND in the validation set. Conclusions: This study revealed distinct plasma proteomic features in PerAF patients with prolonged SNRT. ACP5 may serve as a potential biomarker to assess sinoatrial node function in PerAF patients prior to rhythm control therapy.