Promotion of atrial fibrillation by heart failure in dogs: atrial remodeling of a different sort.
BACKGROUND
Studies of atrial fibrillation (AF) due to atrial tachycardia have provided insights into the remodeling mechanisms by which "AF begets AF" but have not elucidated the substrate that initially supports AF before remodeling occurs. We studied the effects of congestive heart failure (CHF), an entity strongly associated with clinical AF, on atrial electrophysiology in the dog and compared the results with those in dogs subjected to rapid atrial pacing (RAP; 400 bpm) with a controlled ventricular rate (AV block plus ventricular pacemaker at 80 bpm).


RESULTS
CHF induced by 5 weeks of rapid ventricular pacing (220 to 240 bpm) increased the duration of AF induced by burst pacing (from 8+/-4 seconds in control dogs to 535+/-82 seconds; P<0.01), similar to the effect of 1 week of RAP (713+/-300 seconds). In contrast to RAP, CHF did not alter atrial refractory period, refractoriness heterogeneity, or conduction velocity at a cycle length of 360 ms; however, CHF dogs had a substantial increase in the heterogeneity of conduction during atrial pacing (heterogeneity index in CHF dogs, 2. 76+/-0.16 versus 1.46+/-0.10 for control and 1.51+/-0.06 for RAP dogs; P<0.01) owing to discrete regions of slow conduction. Histological examination revealed extensive interstitial fibrosis (connective tissue occupying 12.8+/-1.9% of the cross-sectional area) in CHF dogs compared with control (0.8+/-0.3%) and RAP (0. 9+/-0.2%) dogs.


CONCLUSIONS
Experimental CHF strongly promotes the induction of sustained AF by causing interstitial fibrosis that interferes with local conduction. The substrates of AF in CHF are very different from those of atrial tachycardia-related AF, with important potential implications for understanding, treating, and preventing AF related to CHF.
Li
D
D
Research Center, Department of Medicine, Montreal Heart Institute and University of Montreal, Canada.
Fareh
S
S
Leung
T K
TK
Nattel
S
S
D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D002304:Cardiac Pacing, Artificial; D004285:Dogs; D004562:Electrocardiography; D005355:Fibrosis; D006321:Heart / Q000503:physiopathology; D006325:Heart Atria / Q000473:pathology; D006329:Heart Conduction System / Q000503:physiopathology*; D006333:Heart Failure / Q000150:complications* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006984:Hypertrophy; D009206:Myocardium / Q000473:pathology; D013610:Tachycardia / Q000150:complications* / Q000503:physiopathology