title: Diverse Fibrosis Architecture and Premature Stimulation Facilitate Initiation of Reentrant Activity Following Chronic Atrial Fibrillation.
abstract: BACKGROUND
  Patients with paroxysmal atrial fibrillation (AF) often transition between sinus rhythm and AF. For AF to initiate there must be both a trigger and a substrate that facilitates reentrant activity. This trigger is often caused by a premature atrial contraction or focal activations within the atrium. We hypothesize that specific architectures of fibrosis alter local conduction to enable AF.
  
  
  RESULTS
  Control goats (n = 13) and goats in chronic AF (for an average of 6 months, n = 6) had a high-density electrode plaque placed on the LA appendage. Conduction patterns following a premature atrial contraction, caused by an electrical stimulation, were quantified to determine regions of conduction slowing. These regions were compared to architecture, either diffuse fibrosis or regions of obstructive fibrosis, and overall fibrosis levels as determined by histology from the mapped region. The chronic AF goats had more obstructive fibrosis than the controls (17.5 ± 8.0 fibers/mm(2) vs. 8.6 ± 3.0 fibers/mm(2)). Conduction velocity of the AF goats was significantly slowed compared to the control goats in the transverse direction (0.40 ± 0.04 m/s vs. 0.53 ± 0.15 m/s) but not in the longitudinal direction (0.70 ± 0.27 m/s vs. 0.76 ± 0.18 m/s).
  
  
  CONCLUSIONS
  AF-induced atrial remodeling leads to increased obstructive fibrosis and conduction velocity slowing transverse to fiber orientation following premature stimuli. The decrease in conduction velocity causes a decrease in the cardiac wavelength, and increases the likelihood of reentry and AF onset.
authors.affiliation: Comprehensive Arrhythmia Research & Management Center, Division of Cardiovascular Medicine, Salt Lake City, Utah, USA.|Department of Bioengineering, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Angel
authors.affiliation: Comprehensive Arrhythmia Research & Management Center, Division of Cardiovascular Medicine, Salt Lake City, Utah, USA.
authors.forename: L I
authors.initials: LI
authors.lastname: Li
authors.affiliation: Comprehensive Arrhythmia Research & Management Center, Division of Cardiovascular Medicine, Salt Lake City, Utah, USA.|Department of Bioengineering, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Rob S
authors.initials: RS
authors.lastname: Macleod
authors.affiliation: Comprehensive Arrhythmia Research & Management Center, Division of Cardiovascular Medicine, Salt Lake City, Utah, USA.|Center for Engineering Innovation, Salt Lake City, Utah, USA.
authors.forename: Nassir
authors.initials: N
authors.lastname: Marrouche
authors.affiliation: Comprehensive Arrhythmia Research & Management Center, Division of Cardiovascular Medicine, Salt Lake City, Utah, USA.|Department of Bioengineering, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Ranjan
authors.affiliation: Comprehensive Arrhythmia Research & Management Center, Division of Cardiovascular Medicine, Salt Lake City, Utah, USA.|Center for Engineering Innovation, Salt Lake City, Utah, USA.|Department of Bioengineering, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Dosdall
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*; D018880:Atrial Premature Complexes / Q000150:complications / Q000209:etiology / Q000503:physiopathology; D064752:Atrial Remodeling; D002908:Chronic Disease; D004558:Electric Stimulation; D004562:Electrocardiography; D022062:Electrophysiologic Techniques, Cardiac; D055724:Electrophysiological Phenomena; D005355:Fibrosis; D006041:Goats; D006325:Heart Atria / Q000473:pathology*; D006329:Heart Conduction System; D010138:Pacemaker, Artificial
keywords: atrial fibrillation; conduction; electrophysiological mapping; fibrosis; remodeling