Stable Microreentrant Sources as a Mechanism of Atrial Fibrillation in the Isolated Sheep Heart

Abstract

Background-Atrial fibrillation (AF) has traditionally been described as aperiodic or random. Yet, ongoing sources of high-frequency periodic activity have recently been suggested to underlie AF in the sheep heart. Our objective was to use a combination of optical and bipolar electrode recordings to identify sites of periodic activity during AF and elucidate their mechanism. Methods and Results-AF was induced by rapid pacing in the presence of 0.1 to 0.5 mol/L acetylcholine in 7Langendorff-perfused sheep hearts. We used simultaneous optical mapping of the right and left atria (RA and LA) and frequency sampling of optical and bipolar electrode recordings (including a roving electrode) to identify sites having the highest dominant frequency (DF). Rotors were identified from optical recordings, and their rotation period, core area, and perimeter were measured. In all, 35 AF episodes were analyzed. Mean LA and RA DFs were 14.7Ϯ3.8 and 10.3Ϯ2.1 Hz, respectively. Spatiotemporal periodicity was seen in the LA during all episodes. In 5 of 7 experiments, a single site having periodic activity at the highest DF was localized. The highest DF was most often (80%) localized to the posterior LA, near or at the pulmonary vein ostium. Rotors (nϭ14) were localized on the LA. The mean core perimeter and area were 10.4Ϯ2.8 mm and 3.8Ϯ2.8 mm 2 , respectively. Conclusions-Frequency sampling allows rapid identification of discrete sites of high-frequency periodic activity during AF. Stable microreentrant sources are the most likely underlying mechanism of AF in this model. (Circulation.

Not all rotors, effective ablation targets for nonparoxysmal atrial fibrillation, are included in areas suggested by conventional indirect indicators of atrial fibrillation drivers: ExTRa Mapping project

“…Even for basic research, in terms of the excitation wave dynamics during AF, several hypotheses, that is, multiple wavelets,7, 8 meandering rotors,9 and stationary stable rotors,10 have been proposed; therefore, it is natural that the mechanisms of non‐PAF persistency in clinical practice are still unclear.…”

Atrial fibrillation: the role of common and rare genetic variants

“…23 In line with this, clinical and animal studies have demonstrated that ectopic foci of electrical activity arising from within the pulmonary veins and posterior left atrium have a substantial role in initiating and maintaining fibrillatory activity. 24,25 In contrast to studies indicating a structural role of PITX2c, a recently published study of heterozygous knockout (PITX2c þ / À ) mice showed that these mice have a normal cardiac morphology and function, whereas expression of calcium ion binding proteins, gap-and tight junctions and ion channels was changed. They furthermore showed that isolated PITX2c þ / À mice hearts were susceptible to AF during programmed pacing, because of shortening of atrial action potential durations (APDs) and the effective refractory period (ERP).…”

2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS

“…Mechanizmem tej ogniskowej aktywności może być zarówno aktywność wyzwalana, jak i ogniskowo występujące zjawisko re-entry [109,110]. Hierarchiczną organizację AF z szybką aktywacją obszarów napędzających arytmię udokumentowano u pacjentów z napadowym AF [111,112], ale jest mniej oczywista u nieselekcjonowanych pacjentów z przetrwałym AF [113].…”