title: Human atrial fibrillation initiates via organized rather than disorganized mechanisms.
abstract: BACKGROUND
  It is unknown how atrial fibrillation (AF) is actually initiated by triggers. Based on consistencies in atrial structure and function in individual patients between episodes of AF, we hypothesized that human AF initiates when triggers interact with deterministic properties of the atria and may engage organized mechanisms.
  
  
  RESULTS
  In 31 patients with AF, we mapped AF initiation after spontaneous triggers or programmed stimulation. We used 64-pole basket catheters to measure regional dynamic conduction slowing and to create biatrial activation maps during transitions to AF. Sixty-two AF initiations were recorded (spontaneous, n=28; induced, n=34). Notably, AF did not initiate by disorganized mechanisms, but by either a dominant reentrant spiral wave (76%) or a repetitive focal driver. Both mechanisms were located 21±17 mm from their triggers. AF-initiating spirals formed at the site showing the greatest rate-dependent slowing in each patient. Accordingly, in 10 of 12 patients with multiple observed AF episodes, AF initiated using spatially conserved mechanisms despite diverse triggers.
  
  
  CONCLUSIONS
  Human AF initiates from triggers by organized rather than disorganized mechanisms, either via spiral wave re-entry at sites of dynamic conduction slowing or via repetitive focal drivers. The finding that diverse triggers initiate AF at predictable, spatially conserved functional sites in each individual provides a novel deterministic paradigm for AF with therapeutic implications.
authors.affiliation: From the Division of Cardiovascular Medicine, Department of Medicine, University of California, San Diego and the Veterans Administration San Diego Healthcare System, San Diego, CA (A.A.S., G.G.L., D.E.K., S.M.N.), and the Center for Theoretical Biological Physics, Department of Physics, University of California, San Diego, CA (W.J.R.).
authors.forename: Amir A
authors.initials: AA
authors.lastname: Schricker
authors.affiliation: From the Division of Cardiovascular Medicine, Department of Medicine, University of California, San Diego and the Veterans Administration San Diego Healthcare System, San Diego, CA (A.A.S., G.G.L., D.E.K., S.M.N.), and the Center for Theoretical Biological Physics, Department of Physics, University of California, San Diego, CA (W.J.R.).
authors.forename: Gautam G
authors.initials: GG
authors.lastname: Lalani
authors.affiliation: From the Division of Cardiovascular Medicine, Department of Medicine, University of California, San Diego and the Veterans Administration San Diego Healthcare System, San Diego, CA (A.A.S., G.G.L., D.E.K., S.M.N.), and the Center for Theoretical Biological Physics, Department of Physics, University of California, San Diego, CA (W.J.R.).
authors.forename: David E
authors.initials: DE
authors.lastname: Krummen
authors.affiliation: From the Division of Cardiovascular Medicine, Department of Medicine, University of California, San Diego and the Veterans Administration San Diego Healthcare System, San Diego, CA (A.A.S., G.G.L., D.E.K., S.M.N.), and the Center for Theoretical Biological Physics, Department of Physics, University of California, San Diego, CA (W.J.R.).
authors.forename: Wouter-Jan
authors.initials: WJ
authors.lastname: Rappel
authors.affiliation: From the Division of Cardiovascular Medicine, Department of Medicine, University of California, San Diego and the Veterans Administration San Diego Healthcare System, San Diego, CA (A.A.S., G.G.L., D.E.K., S.M.N.), and the Center for Theoretical Biological Physics, Department of Physics, University of California, San Diego, CA (W.J.R.). sanjiv1@stanford.edu.
authors.forename: Sanjiv M
authors.initials: SM
authors.lastname: Narayan
mesh_terms: D000200:Action Potentials; D000368:Aged; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D016279:Atrial Function, Left; D016280:Atrial Function, Right; D002140:California; D002304:Cardiac Pacing, Artificial; D004562:Electrocardiography; D022062:Electrophysiologic Techniques, Cardiac; D005260:Female; D006325:Heart Atria / Q000503:physiopathology; D006329:Heart Conduction System / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013997:Time Factors
keywords: arrhythmias, cardiac; atrial fibrillation; cardiac electrophysiology; spiral waves