{"doi":"10.1093/europace/euaf085.795","title":"Atrial fibrillation-induced autonomic remodeling is reversed by noninvasive vagus nerve stimulation","abstract":"Abstract Background Atrial fibrillation (AF) is the most common sustained arrhythmia, yet its underlying mechanisms remain poorly understood, leaving treatment options often suboptimal. The autonomic nervous system, and particularly the ganglionated plexi (GP) within the heart, may hold a critical role in AF pathogenesis. Emerging evidence points to structural and functional remodeling in GP neurons in AF, but the physiology of human GP is still inadequately described. Transcutaneous vagus nerve stimulation (tVNS) has surfaced as a potential therapy to mitigate AF by modulating neural activity, with preliminary findings indicating its antiarrhythmic and anti-inflammatory effects. Purpose The primary goal of this study is to examine AF-induced changes in human GP tissue markers related to adrenergic, cholinergic and glial functions, and to evaluate the ability of tVNS to modulate these neural characteristics. We hypothesize that tVNS can reverse AF-associated changes in GP, offering a potential therapeutic approach to AF treatment. Methods In a randomized controlled design, adult patients undergoing elective open-heart surgery received either 1-hour tVNS or no stimulation intraoperatively. Biopsy tissues from the right anterior GP were collected from all patients. Confocal imaging was used to quantify specific neuronal markers and cellular architecture changes in cholinergic and adrenergic neurons, as well as glial cells within GP. Tissue samples were analyzed to assess the threshold area of each marker per cell, comparing patients with vs. without history of AF, as well as tVNS-treated patients vs controls. Results In patients with AF (n = 7), confocal imaging revealed a significant increase in the adrenergic marker tyrosine hydroxylase (TH) and the cholinergic marker vesicular acetylcholine transporter (VAchT) compared to patients without AF (n = 17). Additionally, the glial marker S100B was reduced in AF patients, suggesting a shift in neural composition associated with AF pathology. In the tVNS group, VAchT and neuronal nitric oxide synthase (nNOS) were significantly reduced, while S100B levels were increased, indicating that tVNS may partially reverse AF-induced changes in GP by normalizing neuronal and glial marker levels (Figure 1). Conclusions This study highlights the structural and functional heterogeneity within cardiac GP neurons associated with AF and supports the potential of tVNS to modulate these alterations. By reducing adrenergic and cholinergic activity and enhancing glial cell presence, tVNS may promote autonomic balance restoration within the heart, comprising a non-invasive therapeutic strategy to AF treatment.","journal":"EP Europace","year":2025,"id":566586,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9576,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1470641,"name":"T Venkatesan","orcid":null,"position":1,"is_corresponding":false},{"id":240659,"name":"Lynsie Morris","orcid":"0000-0003-0701-271X","position":2,"is_corresponding":false},{"id":1470642,"name":"Scott Whyte","orcid":null,"position":3,"is_corresponding":false},{"id":999752,"name":"Kulsoom Farhat","orcid":null,"position":4,"is_corresponding":false},{"id":243651,"name":"Khaled Elkholey","orcid":null,"position":5,"is_corresponding":false},{"id":1470643,"name":"L Harveille","orcid":null,"position":6,"is_corresponding":false},{"id":240658,"name":"Stavros Stavrakis","orcid":"0000-0002-4370-8135","position":7,"is_corresponding":false},{"id":1470231,"name":"Maria Toumpourleka","orcid":"0000-0002-9708-7864","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:56:36.440192Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}