title: M2-muscarinic acetylcholine receptor autoantibody levels predict left atrial fibrosis severity in paroxysmal lone atrial fibrillation patients undergoing cryoablation.
abstract: OBJECTIVE
  Atrial fibrosis has been found to be associated with recurrent atrial fibrillation (AF) following catheter ablation. Autoantibodies against M2-muscarinic receptors (anti-M2-R) may play a role in the development of AF by inducing left atrial (LA) fibrosis. In this study, we aim to compare anti-M2-R levels between paroxysmal lone AF patients and healthy control subjects and to investigate the relationship between pre-ablation anti-M2-R level, LA fibrosis quantified by delayed enhancement magnetic resonance imaging (DE-MRI), and AF recurrence following cryoablation.
  
  
  RESULTS
  Thirty-one patients with paroxysmal lone AF (53.4 ± 8.0 years, 61% male), who underwent cryoballoon-based ablation, along with 31 healthy control subjects were included. Enzyme-linked immunosorbent assay tests to measure serum anti-M2-R levels were performed in both groups and DE-MRI was done to quantify LA fibrosis prior to the ablation in the patients. Anti-M2-R levels were higher in the study population when compared with control subjects [212.4 (103.2-655.5) vs. 73.0 (39.5-299.1) ng/mL, P < 0.001]. Anti-M2-R level predicted moderate-extensive LA fibrosis independent of other measures [odds ratio: 1.26 (95% confidence interval (CI): 1.04-1.53), P = 0.017]. At a mean follow-up of 35.2 ± 3.5 months, nine patients (29.0%) had AF recurrence. In the Cox regression model including pre-ablation anti-M2-R level, LA diameter, LA volume index, and moderate-extensive LA fibrosis, only moderate-extensive LA fibrosis predicted late AF recurrence independent of other measures [hazard ratio: 29.41 (95% CI: 3.52-250.00), P = 0.002].
  
  
  CONCLUSIONS
  Serum anti-M2-R levels may be associated with the severity of LA fibrosis and may be implicated in the pathophysiology of AF recurrence following cryoablation. Detection of anti-M2-R levels may help select appropriate patients for the procedure.
authors.affiliation: Department of Cardiology, Hacettepe University Faculty of Medicine, 06100 Ankara, Turkey.
authors.forename: Kadri Murat
authors.initials: KM
authors.lastname: Gurses
authors.affiliation: Department of Cardiology, Hacettepe University Faculty of Medicine, 06100 Ankara, Turkey.
authors.forename: Muhammed Ulvi
authors.initials: MU
authors.lastname: Yalcin
authors.affiliation: Department of Cardiology, Hacettepe University Faculty of Medicine, 06100 Ankara, Turkey kocyigitduygu@yahoo.com.
authors.forename: Duygu
authors.initials: D
authors.lastname: Kocyigit
authors.affiliation: Department of Basic Oncology and Immunology, Hacettepe University Faculty of Medicine, 06100 Ankara, Turkey.
authors.forename: Sacit Altug
authors.initials: SA
authors.lastname: Kesikli
authors.affiliation: Department of Cardiology, Yuksek Ihtisas Heart-Education and Research Hospital, 06230 Ankara, Turkey.
authors.forename: Ugur
authors.initials: U
authors.lastname: Canpolat
authors.affiliation: Department of Cardiology, Hacettepe University Faculty of Medicine, 06100 Ankara, Turkey.
authors.forename: Hikmet
authors.initials: H
authors.lastname: Yorgun
authors.affiliation: Department of Cardiology, Hacettepe University Faculty of Medicine, 06100 Ankara, Turkey.
authors.forename: Mehmet Levent
authors.initials: ML
authors.lastname: Sahiner
authors.affiliation: Department of Cardiology, Hacettepe University Faculty of Medicine, 06100 Ankara, Turkey.
authors.forename: Ergun Baris
authors.initials: EB
authors.lastname: Kaya
authors.affiliation: Department of Radiology, Hacettepe University Faculty of Medicine, 06100 Ankara, Turkey.
authors.forename: Tuncay
authors.initials: T
authors.lastname: Hazirolan
authors.affiliation: Department of Cardiology, Hacettepe University Faculty of Medicine, 06100 Ankara, Turkey.
authors.forename: Necla
authors.initials: N
authors.lastname: Ozer
authors.affiliation: Department of Cardiology, Hacettepe University Faculty of Medicine, 06100 Ankara, Turkey.
authors.forename: Mehmet Ali
authors.initials: MA
authors.lastname: Oto
authors.affiliation: Department of Basic Oncology and Immunology, Hacettepe University Faculty of Medicine, 06100 Ankara, Turkey.
authors.forename: Dicle
authors.initials: D
authors.lastname: Guc
authors.affiliation: Department of Cardiology, Hacettepe University Faculty of Medicine, 06100 Ankara, Turkey.
authors.forename: Kudret
authors.initials: K
authors.lastname: Aytemir
mesh_terms: D001281:Atrial Fibrillation / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D001323:Autoantibodies / Q000276:immunology*; D016022:Case-Control Studies; D003452:Cryosurgery; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005355:Fibrosis; D006325:Heart Atria / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D016016:Proportional Hazards Models; D043585:Receptor, Muscarinic M2 / Q000276:immunology*; D012008:Recurrence; D012720:Severity of Illness Index
chemical_list: D001323:Autoantibodies; D043585:Receptor, Muscarinic M2
keywords: Atrial fibrillation; Atrial fibrosis; Cryoablation; M2-muscarinic receptor autoantibodies