title: Unmasking atrial repolarization to assess alternans, spatiotemporal heterogeneity, and susceptibility to atrial fibrillation.
abstract: BACKGROUND
  Detection of atrial repolarization waves free of far-field signal contamination by ventricular activation would allow investigation of atrial electrophysiology and factors that influence susceptibility to atrial tachycardia and atrial fibrillation (AF).
  
  
  OBJECTIVE
  The purpose of this study was to identify means for high-resolution intracardiac recording of atrial repolarization (Ta) waves using standard clinical electrocatheters and to assess fundamental electrophysiologic properties relevant to AF risk.
  
  
  METHODS
  In alpha-chloralose anesthetized Yorkshire pigs, we studied effects of vagus nerve stimulation (VNS) on PTa and QT intervals and effects of acute atrial ischemia or administration of intrapericardial acetylcholine followed by intravenous epinephrine on susceptibility to AF.
  
  
  RESULTS
  Electrocatheters with closely spaced (1-mm) electrode pairs yielded high-resolution tracings of atrial repolarization waves. These recordings permitted detection of differential effects of right or left VNS, which shortened atrial PTa interval by 30% vs. 21% (P <.01) and lengthened QT interval by 1.5% vs. 9%, respectively (P < .05). During atrial ischemia, STa segments were elevated 3.4-fold (P < .01), and the threshold for inducing AF was reduced 3.1-fold (P = .004). Ischemia amplified atrial T-wave alternans (TWAa) and spatiotemporal heterogeneity (TWHa) by 23- and 13-fold, respectively, in inverse correlation to AF threshold (r = 0.74, P <.01; r = 0.61, P = .03). TWAa and TWHa increased by 4.5- and 2-fold shortly before autonomically triggered atrial premature beats and AF.
  
  
  CONCLUSIONS
  This study used standard electrocatheters to demonstrate that TWAa and TWHa analysis provides means to assess vulnerability to AF without provocative electrical stimuli. These parameters could be evaluated in the clinical electrophysiology laboratory to determine risk for this prevalent arrhythmia and efficacy of contemporary and new agents.
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts. Electronic address: rverrier@bidmc.harvard.edu.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Verrier
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, Massachusetts; Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Henrique
authors.initials: H
authors.lastname: Fuller
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, Massachusetts; Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Justo
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Nearing
authors.affiliation: Gilead Sciences, Inc., Foster City and Fremont, California.
authors.forename: Sridharan
authors.initials: S
authors.lastname: Rajamani
authors.affiliation: Gilead Sciences, Inc., Foster City and Fremont, California.
authors.forename: Luiz
authors.initials: L
authors.lastname: Belardinelli
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001281:Atrial Fibrillation / Q000503:physiopathology* / Q000628:therapy; D004195:Disease Models, Animal; D022062:Electrophysiologic Techniques, Cardiac / Q000379:methods*; D006325:Heart Atria / Q000503:physiopathology; D006329:Heart Conduction System / Q000503:physiopathology; D008297:Male; D013552:Swine; D055536:Vagus Nerve Stimulation / Q000379:methods*
keywords: Atrial fibrillation; Cardiac electrophysiologic testing; Catecholamines; Electrode catheter; Electrophysiologic mapping; Monophasic action potential; Myocardial ischemia; Repolarization alternans; Repolarization heterogeneity; Vagus nerve stimulation