Atrial Fibrillation Organization Research Articles

Atrial fibrillation initiation and organization in a mechanistic model of atrial remodeling and calcium homeostatic regulation

Atrial fibrillation initiation and organization in a mechanistic model of atrial remodeling and calcium homeostatic regulation

Abstract 17206: Targeted Ablation at Regions of High Oxidative Injury in Persistent Atrial Fibrillation in a Canine Model — A New Electrogram Based Therapeutic Strategy in Atrial Fibrillation?

Introduction: Oxidative stress (OS) plays an important role in the development of atrial fibrillation (AF). However, it is currently not possible to detect regions of high OS in the atria of individual AF patients. Hypothesis: We hypothesized that in persistent AF, electrograms (EGMs) at sites of high OS, are uniquely sensitive to acute reactive oxygen species (ROS) scavenging with N-acetylcysteine (NAC), both in a large animal model and in patients and that ablation at these NAC-sensitive ‘hotspots’ can terminate or slow AF. Methods: We performed high-density mapping (both atria, pre/post-NAC, intravenous, 100mg/kg) in 17 persistent AF dogs (3-14 weeks rapid atrial pacing) using an epicardial mapping-plaque (6 regions, both atria, 130 electrodes, electrode-distance 2.5mm) (Figure 1) and in 5 patients (HD-grid, Abbott). We analyzed cycle length (CL) and dominant frequency (DF) in ‘hot spot’-sub-regions (>10% change pre vs. post-NAC). In 4 dogs we performed epicardial ablation (Atricure) at 3 quadrants of the mapping fields with the largest NAC hotspots of all 6 mapped regions (Figure 2). Results: NAC led to preferential organization of AF (>10% DF decrease) at several sites in both atria (NAC hot spots). In patients, NAC (Figure 3) increased CL in the left atrium in the left lateral wall and in the right atrium in the posterior lateral wall. The largest DF hotspots were in the left atrium in the superior wall. In dogs, ablation at the largest hotspots terminated AF in 50% of the cases (2/4). In all cases, ablation significantly increased CL in the left atrium and decreased DF in all atrial regions (Figure 2). Conclusions: Acute administration of NAC preferentially organizes AF electrograms in subregions of both atria (‘hotspots’). Ablation at these NAC-sensitive hotspot regions terminated or slowed AF. We have discovered a unique method to target identified atrial sub-regions of high OS in the atria. These ‘hotspots’ may be a new therapeutic target in patients with persistent AF.

PO-01-170 PHARMACOLOGICAL AND GENE-THERAPY BASED INHIBITION OF NOX2-GENERATED ROS ATTENUATES DISRUPTION OF MICROTUBULE NETWORK AND EMERGENCE OF TRIGGERED CA2+WAVES IN ATRIAL MYOCYTES AND IN CHRONIC AF CANINE MODEL

Recent research indicate an important role for derailed proteostasis in atrial fibrillation (AF). Major pathways of derailed proteostasis include disruption of microtubule network (MTN). Experimental and clinical studies have documented a significant contribution of histone deactylase 6 (HDAC6) mediated disruption of MTN. Another major causative factor for AF is excessive oxidative stress (OS). However, a clear connection of disruption of MTN with OS is not known in atrial myocytes and chronic model of AF. In particular, it remains elusive whether disruption of MTN by NOX2-generated reactive oxygen species (ROS) contributes to the emergence of triggered Ca2+ waves (TCWs), which can cause membrane depolarization and promote early-afterdepolarization (EAD). To establish the connection between OS and disruption of MTN in isolated canine atrial myocytes and in atrial myocardium of a canine model of chronic AF Normal atrial myocytes were isolated from 4 dogs and pre-incubated in Colchicine (a microtubule disruptor) and H2O2. While myocytes, loaded with Ca2+ sensitive dye, were paced at different cycle lengths (1000ms to 200ms), line-scan confocal Ca2+ imaging were performed in the presence of gp91-tat (a NOX2 inhibitor) and TSA (a HDAC6 inhibitor). In the same cells, MTN was examined by Immunofluorescence. To determine the MTN organization in chronic AF, immunohischemistry was performed in atrial tissue sections from 3 normal animals, 4 control rapid atrial pacing (RAP) animals, and 4 NOX2-shRNA injected RAP animals. In Colchicine treated- isolated atrial myocytes, acute application of gp91-tat and TSA attenuated the disruption of MTN (a) and the generation of TCWs (b). Similarly, gp91-tat and TSA attenuated the disruption of MTN in H2O2 pretreated atrial myocytes (data not shown). Notably, while distinctive MTN was abolished in RAP induced chronic AF atrial sections, there was an attenuation of expected MTN decrease in atrial sections from NOX2-shRNA injected RAP dogs (c). Inhibition of NOX2 by either NOX2 shRNA injection in the chronic AF model or acute application of NOX2 inhibitor as well as HDAC6 inhibitor in atrial myocytes is associated with attenuation of the disruption of MTN and generation of TCWs. Identifying the connection between OS and derailed proteostasis not only sheds light on the molecular mechanisms underlying AF, but also may allow to develop novel therapeutic approach for AF.

Organization of atrial fibrillation using a pure sodium channel blocker: Implications of rotor ablation therapy.

Rotors are the source of atrial fibrillation (AF). However, the ablation of rotors for persistent AF is challenging. The purpose of this study was to identify the dominant rotor by accelerating the organization of AF using a sodium channel blocker and detecting the rotor's preferential area that governs AF. Overall, 30 consecutive patients with persistent AF who underwent pulmonary vein isolation and still sustained AF were enrolled. Pilsicainide 50 mg was administered. An online real-time phase mapping system (ExTRa Mapping™) was used to identify the meandering rotors and multiple wavelets in 11 left atrial segments. The time ratio of non-passive activation (%NP) was evaluated as the frequency of rotor activity in each segment. Conduction velocity became slower-from 0.46 ± 0.14 to 0.35 ± 0.14 mm/ms (p = .004)-and the rotational period of the rotor was significantly prolonged-156 ± 21 to 193 ± 28 ms/cycle (p < .001). AF cycle length was prolonged from 169 ± 19 to 223 ± 29 ms (p < .001). A decrease in %NP was observed in seven segments. Additionally, 14 patients had at least one complete passive activation area. Of them, the use of high %NP area ablation resulted in atrial tachycardia and sinus rhythm in two patients each. A sodium channel blocker organized persistent AF. In selective patients with a wide organized area, high %NP area ablation could convert AF into atrial tachycardia or terminate AF.

CA-529-03 NOVEL DETECTION OF ATRIAL TACHYCARDIA-LIKE ISLANDS DURING ATRIAL FIBRILLATION PREDICTS RESPONSE TO ABLATION

A major limitation of identifying organized activity in atrial fibrillation (AF) has been the use of analytics that are difficult to confirm visually by experts. An intuitive metric of AF organization that does not require frequency, phase, or complex mathematical constructs may better guide therapy.

Stepwise endo-/epicardial catheter ablation for atrial fibrillation: the Mediterranea approach

Abstract Background Outcomes of catheter ablation (CA) among patients with non-paroxysmal atrial fibrillation (AF) are largely disappointing. Purpose We sought to evaluate the feasibility, effectiveness, and safety of a single-stage stepwise endo-/epicardial approach in patients with persistent/longstanding-persistent AF. Methods We enrolled 25 consecutive patients with symptomatic persistent (n=4) or longstanding-persistent (n=21) AF and at least one prior endocardial procedure, who underwent CA using an endo-/epicardial approach. Our anatomical stepwise protocol included multiple endocardial as well as epicardial (Bachmann's bundle [BB] and ligament of Marshall ablations) components, and entailed ablation of atrial tachycardias emerging during the procedure. The primary outcome was freedom from any AF/atrial tachycardia episode after a 3-month blanking period. The secondary outcome was patients' symptom status during follow-up. Results The stepwise endo-/epicardial approach allowed sinus rhythm restoration in 72% of patients, either directly (n=6, 24%) or after AF organization into atrial tachycardia (n=12, 48%). BB's ablation was commonly implicated in arrhythmia termination. After a median follow-up of 266 days (interquartile range, 96 days), survival free from AF/atrial tachycardia was 88%. Antiarrhythmic drugs could be discontinued in 22 patients (88%). As compared to baseline, more patients were asymptomatic at 9-month follow-up (0% vs- 56%, p=0.02). Five patients (20%) developed mild medical complications, whereas one subject (4%) had severe kidney injury requiring dialysis. Conclusion A single-stage endo-/epicardial CA resulted in favorable rhythm and symptom outcomes in a cohort of patients with symptomatic persistent/longstanding-persistent AF and one or more prior endocardial procedures. Epicardial ablation of BB was commonly implicated in procedural success. Funding Acknowledgement Type of funding sources: None.

Stepwise endo-/epicardial catheter ablation for atrial fibrillation: The Mediterranea approach.

BackgroundOutcomes of catheter ablation (CA) among patients with nonparoxysmal atrial fibrillation (AF) are largely disappointing.ObjectiveWe sought to evaluate the feasibility, effectiveness, and safety of a single‐stage stepwise endo‐/epicardial approach in patients with persistent/longstanding‐persistent AF.MethodsWe enrolled 25 consecutive patients with symptomatic persistent (n = 4) or longstanding‐persistent (n = 21) AF and at least one prior endocardial procedure, who underwent CA using an endo‐/epicardial approach. Our anatomical stepwise protocol included multiple endocardial as well as epicardial (Bachmann's bundle [BB] and ligament of Marshall ablations) components, and entailed ablation of atrial tachycardias emerging during the procedure. The primary outcome was freedom from any AF/atrial tachycardia episode after a 3‐month blanking period. The secondary outcome was patients' symptom status during follow‐up.ResultsThe stepwise endo‐/epicardial approach allowed sinus rhythm restoration in 72% of patients, either directly (n = 6, 24%) or after AF organization into atrial tachycardia (n = 12, 48%). BB's ablation was commonly implicated in arrhythmia termination. After a median follow‐up of 266 days (interquartile range, 96 days), survival free from AF/atrial tachycardia was 88%. Antiarrhythmic drugs could be discontinued in 22 patients (88%). As compared to baseline, more patients were asymptomatic at 9‐month follow‐up (0% vs. 56%, p = .02). Five patients (20%) developed mild medical complications, whereas one subject (4%) had severe kidney injury requiring dialysis.ConclusionA single‐stage endo‐/epicardial CA resulted in favorable rhythm and symptom outcomes in a cohort of patients with symptomatic persistent/longstanding‐persistent AF and one or more prior endocardial procedures. Epicardial ablation of BB was commonly implicated in procedural success.

Effective termination of atrial fibrillation by SK channel inhibition is associated with a sudden organization of fibrillatory conduction.

AimsPharmacological termination of atrial fibrillation (AF) remains a challenge due to limited efficacy and potential ventricular proarrhythmic effects of antiarrhythmic drugs. SK channels are proposed as atrial-specific targets in the treatment of AF. Here, we investigated the effects of the new SK channel inhibitor AP14145.Methods and resultsEight goats were implanted with pericardial electrodes for induction of AF (30 days). In an open-chest study, the atrial conduction velocity (CV) and effective refractory period (ERP) were measured during pacing. High-density mapping of both atrial free-walls was performed during AF and conduction properties were assessed. All measurements were performed at baseline and during AP14145 infusion [10 mg/kg/h (n = 1) or 20 mg/kg/h (n = 6)]. At an infusion rate of 20 mg/kg/h, AF terminated in five of six goats. AP14145 profoundly increased ERP and reduced CV during pacing. AP14145 increased spatiotemporal instability of conduction at short pacing cycle lengths. Atrial fibrillation cycle length and pathlength (AF cycle length × CV) underwent a strong dose-dependent prolongation. Conduction velocity during AF remained unchanged and conduction patterns remained complex until the last seconds before AF termination, during which a sudden and profound organization of fibrillatory conduction occurred.ConclusionAP14145 provided a successful therapy for termination of persistent AF in goats. During AF, AP14145 caused an ERP and AF cycle length prolongation. AP14145 slowed CV during fast pacing but did not lead to a further decrease during AF. Termination of AF was preceded by an abrupt organization of AF with a decline in the number of fibrillation waves.

Sequential ultrahigh-density contact mapping of persistent atrial fibrillation: An efficient technique for driver identification.

Literature supports the existence of drivers as maintainers of atrial fibrillation (AF). Whether ultrahigh density (UHD) contact mapping may detect them is unknown. We sequentially mapped the left atrial (LA) activation during spontaneous persistent AF and performed circumferential pulmonary vein isolation (CPVI), followed by remapping and ablation of potential drivers (rotational and focal propagation sites) with Rhythmia™ in 90 patients. The time reference was an LA appendage (LAA) electrogram (EGM). Regions with uniform color were defined as "organized." Only patients (51) with no previous ablation were considered for acute results and follow-up reporting. LA maps (175 ± 28 ml, 43578 ± 18013 EGM) were acquired in 23 ± 7 min. In all post-CPVI maps potential drivers (7.3 ± 3.2/patient) were visualized: 85% with rotational propagation and continuous low voltage in the center; the remaining with focal propagation and an organized EGM at the site of earliest activation. The RF delivery time for extra-PV driver ablation was 12.2 ± 7.9 min. There was a progressive increase of AF organization: the LAA cycle length prolonged, the number of potential drivers decreased, and the organized LA surface in AF increased from 14 ± 6% to 28 ± 16% (p = .0007). Termination of AF without cardioversion was obtained in 67%. AF recurrence rate at 15 ± 7.3 months was 17.6% after the first procedure. Sequential UHD contact activation mapping of persistent AF allows visualization of potential drivers. A sequential strategy of CPVI followed by ablation of potential drivers with limited RF time resulted in an increasing organization of AF and good acute and long-term results.

Relationship between dominant frequency, organization index, and left atrial size in patients with atrial fibrillation.

Frequency domain analysis is a methodology for quantifying the organization of atrial fibrillation (AF) pattern to understand the pathophysiology of the electrical mechanism. We aimed to investigate whether the dominant frequency (DF) and organization index (OI) can indicate left atrial (LA) dilatation in patients with AF. This observational, retrospective, single-center cohort study assessed 100 patients with persistent AF. The study population was divided into two groups based on an anterior-posterior LA dimension (LAD of 50 mm) measured by transthoracic echocardiography. The groups were one-to-one propensity score-matched. Frequency domain analysis was performed using signals at leads II and V1 on surface electrocardiogram to calculate the DF and OI. In all patients, the DF was shown to have an inverse relationship with LAD (R = -.369, p < .001 in lead II; R = -.330, p = .001 in lead V1), while the OI was directly associated with LAD (R = .234, p = .190 in lead II; R = .283, p = .004 in lead V1). However, no significant relationship between the signal amplitude and LAD was observed. Compared to patients with LAD ≤ 50 mm, those with LAD > 50 mm had a lower DF (5.057 ± 0.740 vs. 4.542 ± 0.898, p = .002) and higher OI (0.261 ± 0.104 vs. 0.322 ± 0.116, p = .007) in lead V1. These findings were consistent with those found in lead II. Patients with persistent AF and a larger LA size had a significantly higher OI and lower DF than those with a smaller LA size. Atrial electrical properties of structural remodeling are associated with increased organization of atrial signals.

Focal impulse and rotor modulation of atrial rotors during atrial fibrillation leads to organization of left atrial activation as reflected by waveform morphology recurrence quantification analysis and organizational index.

BackgroundFocal impulse and rotor modulation (FIRM) can cause slowing, organization, and occasionally termination of atrial fibrillation (AF), although results have been mixed. To further characterize changes in AF during rotor ablation, we quantified morphologic and temporal activation changes following FIRM.MethodsIn patients undergoing FIRM ablation for AF, we retrospectively analyzed coronary sinus bipolar EGMs before and after rotor ablation, including EGM activation frequency and regularity, dominant frequency (DF), and organizational index (OI). Changes in EGM waveform morphology were determined with recurrence quantification analysis (RQA) consisting of recurrence rate (RR), determinism (DET), laminarity (LAM), average diagonal line length (L), and trapping time (TT) using Wilcoxon signed‐rank testing.ResultsOverall, 36 rotors from 21 patients undergoing FIRM ablation were analyzed. All morphology RQA parameters demonstrated significant organization of atrial activation after rotor ablation (RR P = .03, DET P = .005, LAM P = .03, L P = .005, TT P = .009). The organizational index also showed a significant increase after rotor ablation (P = .01), and the change in OI correlated with changes in all morphology parameters. Of the rotors, 14/36 (39%) rotors showed organizational changes in all morphology parameters and OI, and an additional 5 rotors (19/36, 53%) showed organizational changes in 4 of 5 morphology parameters and OI.ConclusionsCoronary sinus EGM waveform morphologies and activation patterns are significantly altered after FIRM ablation even when there is no fibrillatory slowing. RQA morphology analysis and organizational index may impart important information regarding underlying AF organization and may be useful in quantifying the acute response to ablation.

Noninvasive Assessment of Complexity of Atrial Fibrillation: Correlation With Contact Mapping and Impact of Ablation.

It is difficult to noninvasively phenotype atrial fibrillation (AF) in a way that reflects clinical end points such as response to therapy. We set out to map electrical patterns of disorganization and regions of reentrant activity in AF from the body surface using electrocardiographic imaging, calibrated to panoramic intracardiac recordings and referenced to AF termination by ablation. Bi-atrial intracardiac electrograms of 47 patients with AF at ablation (30 persistent, 29 male, 63±9 years) were recorded with 64-pole basket catheters and simultaneous 57-lead body surface ECGs. Atrial epicardial electrical activity was reconstructed and organized sites were invasively and noninvasively tracked in 3-dimension using phase singularity. In a subset of 17 patients, sites of AF organization were targeted for ablation. Body surface mapping showed greater AF organization near intracardially detected drivers than elsewhere, both in phase singularity density (2.3±2.1 versus 1.9±1.6; P=0.02) and number of drivers (3.2±2.3 versus 2.7±1.7; P=0.02). Complexity, defined as the number of stable AF reentrant sites, was concordant between noninvasive and invasive methods (r2=0.5; CC=0.71). In the subset receiving targeted ablation, AF complexity showed lower values in those in whom AF terminated than those in whom AF did not terminate (P<0.01). AF complexity tracked noninvasively correlates well with organized and disorganized regions detected by panoramic intracardiac mapping and correlates with the acute outcome by ablation. This approach may assist in bedside monitoring of therapy or in improving the efficacy of ongoing ablation procedures.

Long-Term Outcome of Additional Superior Vena Cava to Septal Linear Ablation in Catheter Ablation of Atrial Fibrillation.

BackgroundWe previously reported the benefit of linear ablation from the superior vena cava to the right atrial septum (SVC‐L) within a year after circumferential pulmonary vein isolation (CPVI) in patients with paroxysmal atrial fibrillation (AF). We explored the long‐term effects of SVC‐L and its potential related mechanisms.Methods and ResultsAmong 2140 consecutive patients with AF ablation, we included 614 patients (73.3% male, aged 57.8±10.7 years, 13.7% with persistent AF) who did not undergo an extra–pulmonary vein left atrial ablation after propensity score matching; of those, 307 had additional SVC‐L and 307 had CPVI alone. We evaluated the heart rate variability and computational modeling study to explore mechanisms. Although the procedure time was longer in the SVC‐L group than the CPVI group (P<0.001), the complication rates did not differ (P=0.560). During 40.5±24.4 months of follow‐up, the rhythm outcome was significantly better in the SVC‐L group than the CPVI group (log rank, P<0.001). At 2‐year follow‐up of heart rate variability, a significantly higher mean heart rate (P=0.018) and a lower ratio of low/high‐frequency components (P=0.011) were found with SVC‐L than CPVI alone. In realistic in silico biatrial modeling, which reflected the electroanatomies of 10 patients, SVC‐L significantly reduced biatrial dominant frequency compared with CPVI alone (P<0.001) and increased AF termination and defragmentation rates (P=0.033).Conclusions SVC‐L ablation in addition to CPVI significantly improved the long‐term rhythm outcome over 2 years after AF catheter ablation by mechanisms involving autonomic modulation and AF organization.

Kolmogorov Complexity of Coronary Sinus Atrial Electrograms before Ablation Predicts Termination of Atrial Fibrillation after Pulmonary Vein Isolation

Atrial fibrillation (AF) is related to a very complex local electrical activity reflected in the rich morphology of intracardiac electrograms. The link between electrogram complexity and efficacy of the catheter ablation is unclear. We test the hypothesis that the Kolmogorov complexity of a single atrial bipolar electrogram recorded during AF within the coronary sinus (CS) at the beginning of the catheter ablation may predict AF termination directly after pulmonary vein isolation (PVI). The study population consisted of 26 patients for whom 30 s baseline electrograms were recorded. In all cases PVI was performed. If AF persisted after PVI, ablation was extended beyond PVs. Kolmogorov complexity estimated by Lempel–Ziv complexity and the block decomposition method was calculated and compared with other measures: Shannon entropy, AF cycle length, dominant frequency, regularity, organization index, electrogram fractionation, sample entropy and wave morphology similarity index. A 5 s window length was chosen as optimal in calculations. There was a significant difference in Kolmogorov complexity between patients with AF termination directly after PVI compared to patients undergoing additional ablation (p < 0.01). No such difference was seen for remaining complexity parameters. Kolmogorov complexity of CS electrograms measured at baseline before PVI can predict self-termination of AF directly after PVI.

Which patients recur as atrial tachycardia rather than atrial fibrillation after catheter ablation of atrial fibrillation?

IntroductionThe ablation gaps have been known as the main mechanism of recurrence as atrial tachycardia (AT) rather than atrial fibrillation (AF) after AF catheter ablation. However, AF organization due to reduction of critical mass or focal trigger may also be the mechanism of AT recurrence. We sought to find out the main clinical factors of recurrence as AT rather than AF after AF ablation in the absence of antiarrhythmic drug effect.MethodsWe analyzed 521 patients (70.8% men, 64.1% paroxysmal AF) who experienced AT or AF recurrence without antiarrhythmic drug effect during 44.7 ± 25.4 months follow-up.ResultsAmong 521 patients with recurrence, 42.0% (219 of 521) recurred with AT. The proportion of AT recurrence was not different between the pulmonary vein isolation only group and additional linear ablation group (45.1% vs. 38.1%, p = 0.128). The absence of hypertension (odds ratio [OR] 0.49, 95% confidence interval [CI] 0.29–0.83, p = 0.007), small left atrial (LA) volume index (OR 0.89 per 10 mL/m2, 95% CI 0.79–1.00, p = 0.049), and high mean LA bipolar voltage (OR 2.03 per 1 mV, 95% CI 1.30–3.16, p = 0.002) were independently associated with AT recurrence, whereas additional linear ablation was not. Among 90 patients who underwent repeat ablation procedure, rates of PV reconnection (p = 0.358) and gap in prior linear ablations (p = 0.269) were not significantly different between AT recurrence group and AF recurrence group.ConclusionThe degree of LA remodeling is significantly associated with recurrence as AT after AF ablation, irrespective of potential ablation gap in linear lesion.

P1437Time course of electrogram organization of sustained versus non-sustained atrial fibrillation

P1437Time course of electrogram organization of sustained versus non-sustained atrial fibrillation

P335High level of atrial ECG organization in persistent atrial fibrillation remaining in sinus rhythm after a single ablation procedure

P335High level of atrial ECG organization in persistent atrial fibrillation remaining in sinus rhythm after a single ablation procedure

Electrocardiographic spatial loops indicate organization of atrial fibrillation minutes before ablation-related transitions to atrial tachycardia

BackgroundDuring ablation for atrial fibrillation (AF), it is challenging to anticipate transitions to organized tachycardia (AT). Defining indices of this transition may help to understand fibrillatory conduction and help track therapy. ObjectiveTo determine the timescale over which atrial fibrillation (AF) organizes en route to atrial tachycardia (AT) using the ECG referenced to intracardiac electrograms. MethodsIn 17 AF patients at ablation (58.7±9.6years; 53% persistent AF) we analyzed spatial loops of atrial activity on the ECG and intracardiac electrograms over successive timepoints. Loops were tracked at precisely 15, 10, 5, 3 and 1min prior to defined transitions of AF to AT. ResultsOrganizational indices reliably quantified changes from AF to AT. Spatiotemporal AF organization on the ECG was identifiable at least 15min before AT was established (p=0.02). ConclusionsAF shows anticipatory global organization on the ECG minutes before AT is clinically evident. These results offer a foundation to establish when AF therapy is on an effective path, and for a quantitative classification separating AT from AF.

Acute and early outcomes of focal impulse and rotor modulation (FIRM)-guided rotors-only ablation in patients with nonparoxysmal atrial fibrillation

Focal impulse and rotor modulation (FIRM)-guided ablation targets sites that are thought to sustain atrial fibrillation (AF). The purpose of this study was to evaluate the acute and mid-term outcomes of FIRM-guided only ablation in patients with nonparoxysmal AF. We prospectively enrolled patients with persistent and long-standing persistent (LSP) AF at three centers to undergo FIRM-guided only ablation. We evaluated acute procedural success (defined as AF termination, organization, or ≥10% slowing), safety (incidence of periprocedural complications), and long-term success (single-procedure freedom from atrial tachycardia [AT]/AF off antiarrhythmic drugs [AAD] after a 2-month blanking period). Twenty-nine patients with persistent (N = 20) and LSP (N = 9) AF underwent FIRM mapping. Rotors were presents in all patients, with a mean of 4 ± 1.2 per patient (62% were left atrial); 1 focal impulse was identified. All sources were successfully ablated, and overall acute success rate was 41% (0 AF termination, 2 AF slowing, 10 AF organization). There were no major procedure-related adverse events. After a mean 5.7 months of follow-up, single-procedure freedom from AT/AF without AADs was 17%. In nonparoxysmal AF patients, targeted ablation of FIRM-identified rotors is not effective in obtaining AF termination, organization, or slowing during the procedure. After mid-term follow-up, the strategy of ablating FIRM-identified rotors alone did not prevent recurrence from AT/AF.

Phase synchrony reveals organization in human atrial fibrillation.

It remains unclear if human atrial fibrillation (AF) is spatially nonhierarchical or exhibits a hierarchy of organization sustained by sources. We utilize activation times obtained at discrete locations during AF to compute the phase synchrony between tissue regions, to examine underlying spatial dynamics throughout both atria. We construct a binary synchronization network and show that this network can accurately define regions of coherence in coarse-grained in silico data. Specifically, domains controlled by spiral waves exhibit regions of high phase synchrony. We then apply this analysis to clinical data from patients experiencing cardiac arrhythmias using multielectrode catheters to simultaneously record from a majority of both atria. We show that pharmaceutical intervention with ibutilide organizes activation by increasing the size of the synchronized domain in AF and quantify the increase in temporal organization when arrhythmia changes from fibrillation to tachycardia. Finally, in recordings from 24 patients in AF we show that the level of synchrony is spatially broad with some patients showing large spatially contiguous regions of synchronization, while in others synchrony is localized to small pockets. Using computer simulations, we show that this distribution is inconsistent with distributions obtained from simulations that mimic multiwavelet reentry but is consistent with mechanisms in which one or more spatially conserved spiral waves is surrounded by tissue in which activation is disorganized.