Document Detail

Repolarization alternans reveals vulnerability to human atrial fibrillation.
MedLine Citation:
PMID:  21646498     Owner:  NLM     Status:  MEDLINE    
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.
METHODS AND 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.
Sanjiv M Narayan; Michael R Franz; Paul Clopton; Etienne J Pruvot; David E Krummen
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-06-06
Journal Detail:
Title:  Circulation     Volume:  123     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-06-28     Completed Date:  2011-09-01     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2922-30     Citation Subset:  AIM; IM    
VAMC/Cardiology, University of California-San Diego, 3350 La Jolla Village Dr., San Diego, CA 92161, USA.
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MeSH Terms
Action Potentials / physiology*
Atrial Fibrillation / physiopathology*
Cardiac Pacing, Artificial
Electrophysiologic Techniques, Cardiac
Heart Atria / physiopathology*
Heart Rate / physiology
Middle Aged
Prospective Studies
Retrospective Studies
Time Factors
Grant Support
HL70529/HL/NHLBI NIH HHS; HL83359/HL/NHLBI NIH HHS; K23 HL070529-03/HL/NHLBI NIH HHS; K23 HL070529-04/HL/NHLBI NIH HHS; K23 HL070529-05/HL/NHLBI NIH HHS; K24 HL103800-01/HL/NHLBI NIH HHS; R01 HL083359-01A1/HL/NHLBI NIH HHS; R01 HL083359-02/HL/NHLBI NIH HHS; R01 HL083359-03/HL/NHLBI NIH HHS
Comment In:
Circulation. 2012 Jan 31;125(4):e320; author reply e321   [PMID:  22294715 ]

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