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.

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Abstract-Short QT syndrome (SQTS) leads to an abbreviated QTc interval and predisposes patients to life-threatening arrhythmias. To date, two forms of the disease have been identified: SQT1, caused by a gain of function substitution in the HERG (I Kr ) channel, and SQT2, caused by a gain of function substitution in the KvLQT1 (I Ks ) channel. Here we identify a new variant, "SQT3", which has a unique ECG phenotype characterized by asymmetrical T waves, and a defect in the gene coding for the inwardly rectifying Kir2.1 (I K1 ) channel. The affected members of a single family had a G514A substitution in the KCNJ2 gene that resulted in a change from aspartic acid to asparagine at position 172 (D172N). Whole-cell patch-clamp studies of the heterologously expressed human D172N channel demonstrated a larger outward I K1 than the wild-type (PϽ0.05) at potentials between Ϫ75 mV and Ϫ45 mV, with the peak current being shifted in the former with respect to the latter (WT, Ϫ75 mV; D172N, Ϫ65 mV). Coexpression of WT and mutant channels to mimic the heterozygous condition of the proband yielded an outward current that was intermediate between WT and D172N. In computer simulations using a human ventricular myocyte model the increased outward I K1 greatly accelerated the final phase of repolarization, and shortened the action potential duration. Hence, unlike the known mutations in the two other SQTS forms (N588K in HERG and V307L in KvLQT1), simulations using the D172N and WT/D172N mutations fully accounted for the ECG phenotype of tall and asymmetrically shaped T waves. Although we were unable to test for inducibility of arrhythmia susceptibility due to lack of patients' consent, our computer simulations predict a steeper steady-state restitution curve for the D172N and WT/D172N mutation, compared with WT or to HERG or KvLQT1 mutations, which may predispose SQT3 patients to a greater risk of reentrant arrhythmias. (Circ Res. 2005;96:800-807.)

Reentry in anatomically or functionally determined circuits forms the basis of spatiotemporal periodic activity during AF. The cycle length of sources in the LA determines the dominant peak in the frequency spectra in this experimental model of AF.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and the major cardiac cause of stroke. Recent studies in patients with paroxysmal AF have shown that the arrhythmia is triggered by focal sources localized usually in one of the cardiac veins. However, in chronic AF, the prevailing theory is that multiple random wavelets of activation coexist to create an unorganized atrial rhythm. Experiments in isolated hearts have demonstrated that stable, self-sustained rotors can exist in the atria and that high frequency activation by such rotors results in the complex patterns of activation that characterize AF. Studies in animals and patients support the view that at least some cases of paroxysmal and chronic AF are the result of the uninterrupted periodic activity of discrete reentrant sites. In this brief review article, we examine historical data and more recent experimental evidence behind the hypothesis that AF may be organized by one, or a small number of high-frequency reentrant sources localized in the left atrium. We then discuss the potential implications and evidence supporting such a hypothesis for human AF. Finally, we suggest future studies designed to unravel the detailed molecular, cellular and pathophysiological mechanisms responsible for AF initiation and maintenance. The work discussed may open potentially exciting new diagnostic and therapeutic possibilities.

Background-Spectral analysis identifies localized sites of high-frequency activity during atrial fibrillation (AF). We determined the effectiveness of using real-time dominant frequency (DF) mapping for radiofrequency ablation of maximal DF (DFmax) sites and elimination of left-to-right frequency gradients in the long-term maintenance of sinus rhythm (SR) in AF patients.

Background-The identification of sites of dominant activation frequency during atrial fibrillation (AF) in humans and the effect of ablation at these sites have not been reported. Methods and Results-Thirty-two patients undergoing AF ablation (19 paroxysmal, 13 permanent) during ongoing arrhythmia were studied. Electroanatomic mapping was performed, acquiring 126Ϯ13 points per patient throughout both atria and coronary sinus. At each point, 5-second electrograms were obtained to determine the highest-amplitude frequency on spectral analysis and to construct 3D dominant frequency (DF) maps. The temporal stability of the recording interval was confirmed in a subset. Ablation was performed with the operator blinded to the DF maps. The effect of ablation at sites with or without high-frequency DF sites (maximal frequencies surrounded by a decreasing frequency gradient Ն20%) was evaluated by determining the change in AF cycle length (AFCL) and the termination and inducibility of AF. The spatial distribution of the DF sites was different in patients with paroxysmal and permanent AF; paroxysmal AF patients were more likely to harbor the DF site within the pulmonary vein, whereas in permanent AF, atrial DF sites were more prevalent. Ablation at a DF site resulted in significant prolongation of the AFCL (180Ϯ30 to 198Ϯ40 ms; PϽ0.0001; ϭ 0.77), whereas in the absence of a DF site, there was no change in AFCL (169Ϯ22 to 170Ϯ22 ms; Pϭ0.4). AF terminated during ablation in 17 of 19 patients with paroxysmal and 0 of 13 with permanent AF (PϽ0.0001). When 2 patients with nonsustained AF during mapping were excluded, 13 of 15 (87%) had AF termination at DF sites (54% at the initially ablated DF site): 11 pulmonary veins and 2 atrial. In addition, AF could no longer be induced in 69% with termination of AF at a DF site. There were no significant differences in the number or percentage of DF sites detected (5.4Ϯ1.6 versus 4.9Ϯ2.1; Pϭ0.3) and ablated (1.9Ϯ1.0 versus 2.4Ϯ1.0; Pϭ0.3) in those with and without AF termination. The duration of radiofrequency ablation to achieve termination was significantly shorter than that delivered in those with persisting AF (34.8Ϯ24.0 versus 73.5Ϯ22.9 minutes; Pϭ0.0002). All patients with persisting AF had additional DF sites outside the ablated zones. Conclusions-Spectral

Background-Recent studies demonstrated spatiotemporal organization in atrial fibrillation (AF). We hypothesized that waves emanating from sources in the left atrium (LA) undergo fragmentation, resulting in left-to-right frequency gradient. Our objective was to characterize impulse propagation across Bachmann's bundle (BB) and the inferoposterior pathway (IPP) during AF.