title: The role of fibroblasts in complex fractionated electrograms during persistent/permanent atrial fibrillation: implications for electrogram-based catheter ablation.
abstract: BACKGROUND
  Electrogram-based catheter ablation, targeting complex fractionated atrial electrograms (CFAEs), is empirically known to be effective in halting persistent/permanent atrial fibrillation (AF). However, the mechanisms underlying CFAEs and electrogram-based ablation remain unclear.
  
  
  OBJECTIVE
  Because atrial fibrosis is associated with persistent/permanent AF, we hypothesized that electrotonic interactions between atrial myocytes and fibroblasts play an important role in CFAE genesis and electrogram-based catheter ablation.
  
  
  RESULTS
  We used a human atrial tissue model in heart failure and simulated propagation and spiral wave reentry with and without regionally proliferated fibroblasts. Coupling of fibroblasts to atrial myocytes resulted in shorter action potential duration, slower conduction velocity, and lower excitability. Consequently, heterogeneous fibroblast proliferation in the myocardial sheet resulted in frequent spiral wave breakups, and the bipolar electrograms recorded at the fibroblast proliferation area exhibited CFAEs. The simulations demonstrated that ablation targeting such fibroblast-derived CFAEs terminated AF, resulting from the ablation site transiently pinning the spiral wave and then pushing it out of the fibroblast proliferation area. CFAEs could not be attributed to collagen accumulation alone.
  
  
  CONCLUSIONS
  Fibroblast proliferation in atria might be responsible for the genesis of CFAEs during persistent/permanent AF. Our findings could contribute to better understanding of the mechanisms underlying CFAE-targeted AF ablation.
authors.affiliation: Department of Cardiovascular Medicine, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu 520-2192, Japan. ash@belle.shiga-med.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Ashihara
authors.forename: Ryo
authors.initials: R
authors.lastname: Haraguchi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nakazawa
authors.forename: Tsunetoyo
authors.initials: T
authors.lastname: Namba
authors.forename: Takanori
authors.initials: T
authors.lastname: Ikeda
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nakazawa
authors.forename: Tomoya
authors.initials: T
authors.lastname: Ozawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Ito
authors.forename: Minoru
authors.initials: M
authors.lastname: Horie
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Trayanova
mesh_terms: D000200:Action Potentials; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology / Q000601:surgery*; D002304:Cardiac Pacing, Artificial; D017115:Catheter Ablation; D002450:Cell Communication; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism; D003198:Computer Simulation; D022062:Electrophysiologic Techniques, Cardiac; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005355:Fibrosis; D006325:Heart Atria / Q000378:metabolism / Q000601:surgery; D006333:Heart Failure / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008955:Models, Cardiovascular; D032342:Muscle Cells / Q000378:metabolism* / Q000473:pathology; D011237:Predictive Value of Tests; D013997:Time Factors
chemical_list: D003094:Collagen