Long-Term Frequency Gradients During Persistent Atrial Fibrillation in Sheep Are Associated With Stable Sources in the Left Atrium

Abstract

Background Dominant frequencies (DFs) of activation are higher in the atria of patients with persistent than paroxysmal atrial fibrillation (AF) and left-to-right atrial (LA-to-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 test the hypothesis that a LA-to-RA DF difference is associated with LA drivers in persistent AF. Methods and Results AF was induced using RA tachypacing (N=8). Electrograms were obtained weekly from a RA lead and a loop recorder (ILR) implanted near the LA. DFs were determined for 5-sec-long electrograms (QRST subtracted) during AF in-vivo and in ex-vivo optical mapping. Underlying structural changes were compared to weight-matched controls (N=4). Following the first AF episode, DF increased gradually over a 2-week period (7±0.21 to 9.92±0.31 Hz, N=6, p<0.05). During 9–24 weeks of AF the DF values on the ILR were higher than the RA (10.6±0.08 vs. 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 (PLA). Persistent AF sheep showed significant enlargement of the PLA compared to 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 PLA, which harbors the highest frequency domains and patterns of activation compatible with drifting rotors.

Human Persistent Atrial Fibrillation Is Maintained by Rotors

“…Electrograms at FIRM-identified ablation sites were not found to differ in dominant frequency or Shannon entropy values compared with the atrial regions that did not harbor focal AF drivers. Conversely, in both animal models 10,[27][28][29] and other human studies, rotor sites have demonstrated a higher frequency 11,12 than other atrial regions. Intuitively, if a rotor is to be a driver of fibrillation it would be expected to have a higher frequency than surrounding atrial myocardium, [30][31][32] with a negative activation frequency gradient away from the high-frequency source as part of fibrillatory conduction.…”

Role of atrial tissue remodeling on rotor dynamics: an in vitro study

“…A critical obstacle for the elucidation of mechanisms responsible for chronic AF lies in the practical challenges associated with the development of experimental models that reproduce the electrophysiological characteristics of atrial remodeling. Animal models involve subjecting animals to weeks or months of sustained atrial arrhythmias, which implies significant economical, ethical, and time burdens (11,20). Other experimental models include in vitro cell cultures, which are typically obtained from neonatal rat hearts.…”

Mechanisms of Atrial Fibrillation

“…22 To establish the patterns of activation underlying the DF max values in the LA we used phase movies 13 to correlate those with reentries in the PLA and LAA. 23 In Figure 3A a dynamic combination of breakthroughs (BTs) and reentries is seen in the PLA and LAA during AF, with a rotor drifting from the PLA towards the LAA (See Video).…”