title: Characterization of the left atrial neural network and its impact on autonomic modification procedures.
abstract: BACKGROUND
  Left atrial (LA) ganglionated plexi (GP) are part of the intrinsic cardiac autonomic nervous system and implicated in the pathogenesis of atrial fibrillation. High frequency stimulation is used to identify GP sites in humans. The effect of ablation on neural pathways connecting GPs in humans is unknown.
  
  
  RESULTS
  Thirty patients undergoing LA ablation with autonomic modification were recruited. In patients with persistent atrial fibrillation, endocardial continuous high frequency stimulation identified GP sites producing AV block. After right lower GP ablation (N=5), 2 of 15 sites remained positive, whereas after ablation of other GPs (N=5), leaving right lower GP intact, all 19 sites remained positive (right lower GP versus other GP, P<0.005), indicating that neural pathways between LAGPs and the AV node are via the right lower GP. In 20 patients with paroxysmal atrial fibrillation, synchronized high frequency stimulation identified sites initiating pulmonary vein (PV) ectopy. After PV isolation (N=8), no sites remained positive. After local GP ablation (N=9), 3 of 14 sites remained positive, suggesting neural connections to the PV were disrupted by both PV isolation and GP ablation. Heart rate variability indices reduced significantly after right upper GP ablation alone, suggesting that neural pathways from the LA to the SA node travel via the right upper GP.
  
  
  CONCLUSIONS
  We have demonstrated neural pathways connecting LA GPs with the PVs, AV node, and SA node. The effects of high frequency stimulation at GP sites can be prevented by ablating the GP site or the neural pathway. This further delineates the mechanism via which PV isolation prevents atrial fibrillation and highlights important caveats for autonomic modification end points.
authors.affiliation: Imperial College London and Imperial Healthcare NHS Trust, London, United Kingdom.
authors.forename: Louisa C
authors.initials: LC
authors.lastname: Malcolme-Lawes
authors.forename: Phang Boon
authors.initials: PB
authors.lastname: Lim
authors.forename: Ian
authors.initials: I
authors.lastname: Wright
authors.forename: Pipin
authors.initials: P
authors.lastname: Kojodjojo
authors.forename: Michael
authors.initials: M
authors.lastname: Koa-Wing
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Jamil-Copley
authors.forename: Hakim-Moulay
authors.initials: HM
authors.lastname: Dehbi
authors.forename: Darrel P
authors.initials: DP
authors.lastname: Francis
authors.forename: D Wyn
authors.initials: DW
authors.lastname: Davies
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Peters
authors.forename: Prapa
authors.initials: P
authors.lastname: Kanagaratnam
mesh_terms: D000328:Adult; D000368:Aged; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000601:surgery*; D017776:Autonomic Pathways / Q000503:physiopathology / Q000601:surgery; D016022:Case-Control Studies; D017115:Catheter Ablation / Q000379:methods*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D005725:Ganglia, Autonomic / Q000503:physiopathology / Q000601:surgery*; D006329:Heart Conduction System / Q000503:physiopathology / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000502:physiology; D011667:Pulmonary Veins / Q000601:surgery*; D018570:Risk Assessment; D012849:Sinoatrial Node / Q000503:physiopathology / Q000601:surgery; D016896:Treatment Outcome
keywords: ablation; atrial fibrillation; autonomic nervous system; ganglionated plexi; pulmonary vein isolation