Long-term frequency gradients during persistent atrial fibrillation in sheep are associated with stable sources in the left atrium.
BACKGROUND
Dominant frequencies (DFs) of activation are higher in the atria of patients with persistent than paroxysmal atrial fibrillation (AF), and left atrial (LA)-to-right atrial (RA) DF gradients have been identified in both. However, whether such gradients are maintained as long-term persistent AF is established remains unexplored. We aimed at determining in vivo the time course in atrial DF values from paroxysmal to persistent AF in sheep and testing the hypothesis that an LA-to-RA DF difference is associated with LA drivers in persistent AF.


RESULTS
AF was induced using RA tachypacing (n=8). Electrograms were obtained weekly from an RA lead and an implantable loop recorder implanted near the LA. DFs were determined for 5-second-long electrograms (QRST subtracted) during AF in vivo and in ex vivo optical mapping. Underlying structural changes were compared with weight-matched controls (n=4). After the first AF episode, DF increased gradually during a 2-week period (7±0.21 to 9.92±0.31 Hz; n=6; P<0.05). During 9 to 24 weeks of AF, the DF values on the implantable loop recorder were higher than the RA (10.6±0.08 versus 9.3±0.1 Hz, respectively; n=7; P<0.0001). Subsequent optical mapping confirmed a DF gradient from posterior LA-to-RA (9.1±1.0 to 6.9±0.9 Hz; P<0.05) and demonstrated patterns of activation compatible with drifting rotors in the posterior LA. Persistent AF sheep showed significant enlargement of the posterior LA compared with controls.


CONCLUSIONS
In the sheep, transition from paroxysmal to persistent AF shows continuous LA-to-RA DF gradients in vivo together with enlargement of the posterior LA, which harbors the highest frequency domains and patterns of activation compatible with drifting rotors.
Center for Arrhythmia Research, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
David
D
Filgueiras-Rama
Nicholas F
NF
Price
Raphael P
RP
Martins
Masatoshi
M
Yamazaki
Uma Mahesh R
UM
Avula
Kuljeet
K
Kaur
Jérôme
J
Kalifa
Steven R
SR
Ennis
Elliot
E
Hwang
Vijay
V
Devabhaktuni
Jose
J
Jalife
Omer
O
Berenfeld
D000818:Animals; D001281:Atrial Fibrillation / Q000503:physiopathology*; D002304:Cardiac Pacing, Artificial; D004195:Disease Models, Animal; D018450:Disease Progression; D022062:Electrophysiologic Techniques, Cardiac; D006325:Heart Atria / Q000503:physiopathology*; D006329:Heart Conduction System / Q000503:physiopathology*; D012756:Sheep; D013997:Time Factors; D056969:Voltage-Sensitive Dye Imaging