Background-Specific noninvasive signal processing was applied to identify drivers in distinct categories of persistent atrial fibrillation (AF). Methods and Results-In 103 consecutive patients with persistent AF, accurate biatrial geometry relative to an array of 252 body surface electrodes was obtained from a noncontrast computed tomography scan. The reconstructed unipolar AF electrograms acquired at bedside from multiple windows (duration, 9±1 s) were signal processed to identify the drivers (focal or reentrant activity) and their cumulative density map. The driver domains were catheter ablated by using AF termination as the procedural end point in comparison with the stepwise-ablation control group. The maps showed incessantly changing beat-to-beat wave fronts and varying spatiotemporal behavior of driver activities. Reentries were not sustained (median, 2.6 rotations lasting 449±89 ms), meandered substantially but recurred repetitively in the same region.In total, 4720 drivers were identified in 103 patients: 3802 (80.5%) reentries and 918 (19.5%) focal breakthroughs; most of them colocalized. Of these, 69% reentries and 71% foci were in the left atrium. Driver ablation alone terminated 75% and 15% of persistent and long-lasting AF, respectively. The number of targeted driver regions increased with the duration of continuous AF: 2 in patients presenting in sinus rhythm, 3 in AF lasting 1 to 3 months, 4 in AF lasting 4 to 6 months, and 6 in AF lasting longer. The termination rate sharply declined after 6 months. The mean radiofrequency delivery to AF termination was 28±17 minutes versus 65±33 minutes in the control group (P<0.0001). At 12 months, 85% patients with AF termination were free from AF, similar to the control population (87%,); P=not significant. Conclusions-Persistent Methods Study PopulationThis is a hospital-based study of patients with persistent AF. All consecutive patients referred for ablation of persistent AF were enrolled between May 2012 and June 2013. Persistent AF was defined as continuous AF from 7 days to 12 months and long-lasting AF beyond 12 months. There were no exclusion criteria based on the left atrial size, ventricular ejection fraction, or structural heart disease. All patients gave written informed consent to participate in the study, which involved the use of an investigational system for mapping. The study protocol was approved by the institutional Clinical Research and Ethics Committee. Noninvasive MappingIf patients presented in ongoing AF, mapping was performed bedside, within 24 hours preceding the invasive procedure. For those presenting in sinus rhythm, AF was induced in the electrophysiological laboratory by rapid atrial pacing decrementing up to 200-ms cycle length at the beginning of the invasive procedure and before transseptal puncture. Induced AF was analyzed after >30 minutes of sustenance (during this time, intracardiac catheter placement and invasive mapping were undertaken). Isoproterenol was not used to facilitate induction.The noninvasive mapping techniq...

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