title: Repolarization alternans reveals vulnerability to human atrial fibrillation.
abstract: BACKGROUND
  The substrates for human atrial fibrillation (AF) are poorly understood, but involve abnormal repolarization (action potential duration [APD]). We hypothesized that beat-to-beat oscillations in APD may explain AF substrates, and why vulnerability to AF forms a spectrum from control subjects without AF to patients with paroxysmal then persistent AF.
  
  
  RESULTS
  In 33 subjects (12 with persistent AF, 13 with paroxysmal AF, and 8 controls without AF), we recorded left (n=33) and right (n=6) atrial APD on pacing from cycle lengths 600 to 500 ms (100 to 120 bpm) up to the point where AF initiated. Action potential duration alternans required progressively faster rates for patients with persistent AF, patients with paroxysmal AF, and controls (cycle length 411±94 versus 372±72 versus 218±33 ms; P<0.01). In AF patients, APD alternans occurred at rates as slow as 100 to 120 bpm, unrelated to APD restitution (P>0.10). In this milieu, spontaneous ectopy initiated AF. At fast rates, APD alternans disorganized to complex oscillations en route to AF. Complex oscillations also arose at progressively faster rates for persistent AF, paroxysmal AF, and controls (cycle length: 316±99 versus 266±19 versus 177±16 ms; P=0.02). In paroxysmal AF, APD oscillations amplified before AF (P<0.001). In controls, APD alternans arose only at very fast rates (cycle length <250 ms; P<0.001 versus AF groups) just preceding AF. In 4 AF patients in whom rapid pacing did not initiate AF, APD alternans arose transiently then extinguished.
  
  
  CONCLUSIONS
  Atrial APD alternans reveals dynamic substrates for AF, arising most readily (at lower rates and higher magnitudes) in persistent AF then paroxysmal AF, and least readily in controls. APD alternans preceded all AF episodes and was absent when AF did not initiate. The cellular mechanisms for APD alternans near resting heart rates require definition.
authors.affiliation: VAMC/Cardiology, University of California-San Diego, 3350 La Jolla Village Dr., San Diego, CA 92161, USA. snarayan@ucsd.edu
authors.forename: Sanjiv M
authors.initials: SM
authors.lastname: Narayan
authors.forename: Michael R
authors.initials: MR
authors.lastname: Franz
authors.forename: Paul
authors.initials: P
authors.lastname: Clopton
authors.forename: Etienne J
authors.initials: EJ
authors.lastname: Pruvot
authors.forename: David E
authors.initials: DE
authors.lastname: Krummen
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000328:Adult; D000368:Aged; D001281:Atrial Fibrillation / Q000503:physiopathology*; D002304:Cardiac Pacing, Artificial; D022062:Electrophysiologic Techniques, Cardiac; D005260:Female; D006325:Heart Atria / Q000503:physiopathology*; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012189:Retrospective Studies; D013997:Time Factors