Rotors In Atrial Fibrillation Research Articles

Adenosine and Adenosine Receptors: Advances in Atrial Fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia in the world. Because the key to developing innovative therapies that limit the onset and the progression of AF is to fully understand the underlying molecular mechanisms of AF, the aim of the present narrative review is to report the most recent advances in the potential role of the adenosinergic system in the pathophysiology of AF. After a comprehensive approach describing adenosinergic system signaling and the mechanisms of the initiation and maintenance of AF, we address the interactions of the adenosinergic system's signaling with AF. Indeed, adenosine release can activate four G-coupled membrane receptors, named A1, A2A, A2B and A3. Activation of the A2A receptors can promote the occurrence of delayed depolarization, while activation of the A1 receptors can shorten the action potential's duration and induce the resting membrane's potential hyperpolarization, which promote pulmonary vein firing, stabilize the AF rotors and allow for functional reentry. Moreover, the A2B receptors have been associated with atrial fibrosis homeostasis. Finally, the adenosinergic system can modulate the autonomous nervous system and is associated with AF risk factors. A question remains regarding adenosine release and the adenosine receptors' activation and whether this would be a cause or consequence of AF.

Understanding the origins of the basic equations of statistical fibrillatory dynamics.

The mechanisms governing cardiac fibrillation remain unclear; however, it most likely represents a form of spatiotemporal chaos with conservative system dynamics. Renewal theory has recently been suggested as a statistical formulation with governing equations to quantify the formation and destruction of wavelets and rotors in fibrillatory dynamics. In this perspective Review, we aim to explain the origin of the renewal theory paradigm in spatiotemporal chaos. The ergodic nature of pattern formation in spatiotemporal chaos is demonstrated through the use of three chaotic systems: two classical systems and a simulation of cardiac fibrillation. The logistic map and the baker's transformation are used to demonstrate how the apparently random appearance of patterns in classical chaotic systems has macroscopic parameters that are predictable in a statistical sense. We demonstrate that the renewal theory approach developed for cardiac fibrillation statistically predicts pattern formation in these classical chaotic systems. Renewal theory provides governing equations to describe the apparently random formation and destruction of wavelets and rotors in atrial fibrillation (AF) and ventricular fibrillation (VF). This statistical framework for fibrillatory dynamics provides a holistic understanding of observed rotor and wavelet dynamics and is of conceptual significance in informing the clinical and mechanistic research of the rotor and multiple-wavelet mechanisms of AF and VF.

The impact of the atrial wall thickness in normal/mild late-gadolinium enhancement areas on atrial fibrillation rotors in persistent atrial fibrillation patients.

BackgroundSome of atrial fibrillation (AF) drivers are found in normal/mild late‐gadolinium enhancement (LGE) areas, as well as moderate ones. The atrial wall thickness (AWT) has been reported to be important as a possible AF substrate. However, the AWT and degree of LGEs as an AF substrate has not been fully validated in humans.ObjectiveThe purpose of this study was to evaluate the impact of the AWT in normal/mild LGE areas on AF drivers.MethodsA total of 287 segments in 15 persistent AF patients were assessed. AF drivers were defined as non‐passively activated areas (NPAs), where rotational activation was frequently observed, and were detected by the novel real‐time phase mapping (ExTRa Mapping), mild LGE areas were defined as areas with a volume ratio of the enhancement voxel of 0% to <10%. The AWT was defined as the minimum distance from the manually determined endocardium to the epicardial border on the LGE‐MRI.ResultsNPAs were found in 20 (18.0%) of 131 normal/mild LGE areas where AWT was significantly thicker than that in the passively activated areas (PAs) (2.5 ± 0.3 vs. 2.2 ± 0.3 mm, p < .001). However, NPAs were found in 41 (26.3%) of 156 moderate LGE areas where AWT was thinner than that of PAs (2.1 ± 0.2 mm vs. 2.23 ± 0.3 mm, p = .02). An ROC curve analysis yielded an optimal cutoff value of 2.2 mm for predicting the presence of an NPA in normal/mild LGE areas.ConclusionThe location of AF drivers in normal/mild LGE areas might be more accurately identified by evaluating AWT.

B-PO05-081 SIMULTANEOUS ULTRA-HIGH RESOLUTION OPTICAL MAPPING AND CATHETER MAPPING IN A LANGENDORFF-PERFUSED SWINE HEART MODEL TO IDENTIFY ATRIAL FIBRILLATION ROTORS BY CATHETER MAPPING

The accuracy of atrial fibrillation (AF) rotor identification by catheter mapping (CM) has not been validated. To obtain simultaneous ultra-high resolution optical mapping (OM) and high resolution CM during AF in a Langendorff perfused swine heart model to test the feasibility of identifying AF rotors by CM. Langendorff preparation was performed in 3 swine. The isolated heart was stained with a voltage-sensitive dye, illuminated by LED. Two high resolution CCD cameras (26,624 pixels, each) simultaneously recorded fluorescence from the RA and LA free-wall (spatial resolution <0.1mm). Two mapping catheters (48 electrodes, 2 mm spacing, and one central non-contact reference electrode for close unipolar EGMs, OCTARAY, Biosense Webster, Fig) was sutured on the RA and LA, covering 3x3 cm area, respectively (total 96 close unipolar EGMs). An anatomical shell of RA and LA was formed using the CARTO3 system. AF was induced by rapid atrial pacing during atrial stretch. Optical signals (membrane potential map and phase map) and catheter epicardial atrial EGMs (AF activation map) were recorded simultaneously during AF. (Fig.) During AF, OM identified stable and/or unstable rotors in all 14 AF episodes (all 3 swine), often located at the base of RA or LA appendage. Compared to unstable rotors, stable rotors had shorter cycle length (median 105 ms vs 114 ms, p<0.05). CM identified corresponding rotational activities (spiral reentry) when the rotor was located close to the center of the electrodes. There was no false positive rotor detection by CM. Close unipolar CM identifies AF rotors, but only when rotor centers are located within the mapping area.

B-PO02-089 NON-PAROXYSMAL ATRIAL FIBRILLATION IN YOUNGER PATIENTS ARE REFRACTORY TO SPATIOTEMPORAL ELECTROGRAM DISPERSION ABLATION TARGETING ROTORS?

Modulating atrial fibrillation (AF) drivers has been proposed as one of the effective ablation strategies for non-paroxysmal AF (non-PAF). However, the optimal non-PAF ablation strategy is still controversial because the exact mechanisms of AF persistency, e.g., rotor and/or focal source, are not well understood. Recently, spatiotemporal electrogram dispersion (STED) assumed to indicate rotor in forms of rotational activity is proposed as the effective target for non-PAF ablation. To clarify the effectiveness of STED ablation for modulating AF drivers. STED ablation plus pulmonary vein isolation was applied to consecutive 161 non-PAF patients not undergoing previous ablation (66±10 years old, 74% male, 44% long-standing persistent AF). STED areas within the whole left and right atria were identified and ablated during AF. After procedures, we investigated the long-term outcome and the relationship of clinical and intraoperative characteristics to the recurrence of atrial tachyarrhythmias (ATA). (1) Kaplan-Meier curves estimated that the ratio of 24-month freedom from AF and ATA was 63% and 43%, respectively. (2) With a cox regression proportional hazards, we found that both younger age and long-standing persistent AF were independently associated with the recurrence of AF (Figure, top). (3) Adjusted survival curves showed that main cause of higher ATA recurrence in younger patients was not the recurrence of atrial tachycardia, but AF (Figure, bottom). Younger non-PAF patients had refractory to STED ablation targeting rotors due to difficulty in AF control. The main mechanism of AF persistency might change with aging.

Late-gadolinium enhancement properties associated with atrial fibrillation rotors in patients with persistent atrial fibrillation.

A computational model demonstrated that atrial fibrillation (AF) rotors could be distributed in patchy late-gadolinium enhancement (LGE) areas and play an important role in AF drivers. However, this was not validated in humans. The purpose of this study was to evaluate the LGE properties of AF rotors in patients with persistent AF. A total of 287 segments in 15 patients with persistent AF (long-standing persistent AF in 9 patients) that underwent AF ablation were assessed. Non-passively activated areas (NPAs), where rotational activation (AF rotor) was frequently observed, were detected by the novel real-time phase mapping (ExTRa Mapping). The properties of the LGE areas were assessed using the LGE heterogeneity and the density which was evaluated by the entropy (LGE-entropy) and the volume ratio of the enhancement voxel (LGE-volume ratio), respectively. NPAs were found in 61 (21%) of 287 segments and were mostly found around the pulmonary vein antrum. A receiver operating characteristic curve analysis yielded an optimal cutoff value of 5.7% and 10% for the LGE-entropy and LGE-volume ratio, respectively. The incidence of NPAs was significantly higher at segments with an LGE-entropy of >5.7 and LGE-volume ratio of >10% than at the other segments (38 [30%] of 126 vs. 23 [14%] of 161 segments; p = .001). No NPAs were found at segments with an LGE-volume ratio of >50% regardless of the LGE-entropy. Of five patients with AF recurrence, NPAs outside the PV antrum were not ablated in three patients and the remaining NPAs were ablated, but their LGE-entropy and LGE-volume ratio were low. AF rotors are mostly distributed in relatively weak and much more heterogenous LGE areas.

Focal Impulse and Rotor Modulation Ablation vs. Pulmonary Vein isolation for the treatment of paroxysmal Atrial Fibrillation: results from the FIRMAP AF study.

AimsPulmonary vein isolation (PVI) is the gold standard for atrial fibrillation (AF) ablation. Recently, catheter ablation targeting rotors or focal sources has been developed for treatment of AF. This study sought to compare the safety and effectiveness of Focal Impulse and Rotor Modulation (FIRM)-guided ablation as the sole ablative strategy with PVI in patients with paroxysmal AF.Methods and resultsWe conducted a multicentre, randomized trial to determine whether FIRM-guided radiofrequency ablation without PVI (FIRM group) was non-inferior to PVI (PVI group) for treatment of paroxysmal AF. The two primary efficacy end points were (i) acute success defined as elimination of AF rotors (FIRM group) or isolation of all pulmonary veins (PVI group) and (ii) long-term success defined as single-procedure freedom from AF/atrial tachycardia (AT) recurrence 12 months after ablation. The study was closed early by the sponsor. At the time of study closure, any pending follow-up visits were waived. A total of 51 patients (mean age 63 ± 10.6 years, 57% male) were enrolled. All PVs were successfully isolated in the PVI group and all rotors were successfully eliminated in the FIRM group. Single-procedure effectiveness was 31.3% (5/16) in the FIRM group and 80% (8/10) in the PVI group at 12 months. Three vascular access complications occurred in the FIRM group.ConclusionThese partial study effectiveness results reinforce the importance of PVI in paroxysmal AF patients and indicate that FIRM-guided ablation alone (without PVI) is not an effective strategy for treatment of paroxysmal AF in most patients.

Abstract 16564: Location of Persistent Atrial Fibrillation Drivers Based on Body Surface Mapping: A Systematic Review and Metanalysis

Introduction: Body Surface Mapping (BSM) is a non-invasive electrocardiogram-based mapping system that is used to identify localized drivers in patients with persistent Atrial Fibrillation (AF). Mapping of local drivers is becoming increasingly important in guiding treatment of atrial fibrillation but may not be readily available. We conducted a systematic review to determine the most prevalent atrial regions of AF driver activity identified with BSM. Methods: Electronic literature searches were performed across PubMed, Google Scholar, Cochrane, CINAHL, Web of science, EMBASE databases up to January 2019, for studies that utilized BSM to identify and report localized focal and rotor (reentrant) driver activity. Prevalence of drivers, as a percentage, were recorded for every region according to the Bordeaux Biatrial Schema. Random-effects model was used to calculate weighted averages with the corresponding 95% confidence interval (CI). Results: Total of 468 unique studies were identified and reviewed. 4 prospective cohort studies were included in the final analysis—of which 3 were single-center and 1 was multi-centered; totaling 336 patients. The mean age was 62.8 (±5.41) and 73% were males. The three most prevalent regions with persistent AF foci activity were region 1 (left pulmonary veins and left appendage): 59% (CI 48-71), followed by region 4 (upper half of right atrium and appendage): 31% (CI 12-54), and region 2 (right pulmonary veins and posterior interatrial groove): 19% (CI 7-34). The three most prevalent regions of persistent AF rotor activity were region 3 (inferior and posterior left atrium): 71% (CI 32-98), region 1: 70% (CI 21-100), and region 2: 70% (CI 25-99). Conclusion: In patients with persistent AF, majority of localized drivers seem to originate from specific atrial regions based on BSM.

Locating Atrial Fibrillation Rotor and Focal Sources Using Iterative Navigation of Multipole Diagnostic Catheters

PurposeMulti-polar diagnostic catheters are used to construct the 3D electro-anatomic mapping of the atrium during atrial fibrillation (AF) ablation procedures; however, it remains unclear how to use the electrograms recorded by these catheters to locate AF-driving sites known as focal and rotor source types. The purpose of this study is to present the first algorithm to iteratively navigate a circular multi-polar catheter to locate AF focal and rotor sources without the need to map the entire atria.MethodsStarting from an initial location, the algorithm, which was blinded to the location and type of the AF source, iteratively advanced a Lasso catheter based on its electrogram characteristics. The algorithm stopped the catheter when it located of an AF source and identified the type. The efficiency of the algorithm is validated using a set of simulated focal and rotor-driven arrhythmias in fibrotic human 2D and 3D atrial tissue.ResultsOur study shows the feasibility of locating AF sources with a success rate of greater than 95.25% within average 7.56 ± 2.28 placements independently of the initial position of the catheter and the source type.ConclusionsThe algorithm could play a critical role in clinical electrophysiology laboratories for mapping patient-specific ablation of AF sources located outside the pulmonary veins and improving the procedure success.

Developing an Iterative Tracking Algorithm to Guide a Catheter Towards Atrial Fibrillation Rotor Sources in Simulated Fibrotic Tissue.

Locating atrial fibrillation (AF) rotor sources can help target ablation therapy for AF. Our aim was to develop a catheter-tracking algorithm to locate AF rotor sources using a conventional 20-electrode circular catheter. We simulated rotor-driven arrhythmias in homogeneous and fibrotic human atrial tissue and evaluated the algorithm for different initial catheter positions. The algorithm guided and detected a rotor with a success rate of greater than 97.9% independently of the initial position of the catheter with an accuracy of greater than 2.3±1.4 mm.

1008Effectiveness of atrial fibrillation rotor ablation is dependent on conduction velocity: an in-silico 3-dimensional modeling study

1008Effectiveness of atrial fibrillation rotor ablation is dependent on conduction velocity: an in-silico 3-dimensional modeling study

P1387Developement of an independent approach to detect electrical rotors in atrial fibrillation based on the phase mapping of the electrograms

P1387Developement of an independent approach to detect electrical rotors in atrial fibrillation based on the phase mapping of the electrograms

Simulation of Spiral Waves and Point Sources in Atrial Fibrillation with Application to Rotor Localization.

Cardiac simulations play an important role in studies involving understanding and investigating the mechanisms of cardiac arrhythmias. Today, studies of arrhythmogenesis and maintenance are largely being performed by creating simulations of a particular arrhythmia with high accuracy comparable to the results of clinical experiments. Atrial fibrillation (AF), the most common arrhythmia in the United States and many other parts of the world, is one of the major field where simulation and modeling is largely used. AF simulations not only assist in understanding its mechanisms but also help to develop, evaluate and improve the computer algorithms used in electrophysiology (EP) systems for ablation therapies. In this paper, we begin with a brief overeview of some common techniques used in simulations to simulate two major AF mechanisms - spiral waves (or rotors) and point (or focal) sources. We particularly focus on 2D simulations using Nygren et al.'s mathematical model of human atrial cell. Then, we elucidate an application of the developed AF simulation to an algorithm designed for localizing AF rotors for improving current AF ablation therapies. Our simulation methods and results, along with the other discussions presented in this paper is aimed to provide engineers and professionals with a working-knowledge of application-specific simulations of spirals and foci.

Spatial relationship of organized rotational and focal sources in human atrial fibrillation to autonomic ganglionated plexi

BackgroundOne approach to improve ablation for atrial fibrillation (AF) is to focus on physiological targets including focal or rotational sources or ganglionic plexi (GP). However, the spatial relationship between these potential mechanisms has never been studied. We tested the hypothesis that rotors and focal sources for AF may co-localize with ganglionated plexi (GP). MethodsWe prospectively identified locations of AF rotors and focal sources, and correlated these to GP sites in 97 consecutive patients (age 59.9±11.4, 73% persistent AF). AF was recorded with 64-pole catheters with activation/phase mapping, and related to anatomic GP sites on electroanatomic maps. ResultsAF sources arose in 96/97 (99%) patients for 2.6±1.4 sources per patient (left atrium: 1.7±0.9 right atrium: 1.1±0.8), each with an area of 2–3cm2. On area analyses, the probability of an AF source randomly overlapping a GP area was 26%. Left atrial sources were seen in 94 (97%) patients, in whom ≥1 source co-localized with GP in 75 patients (80%; p<0.05). AF sources were more likely to colocalize with left vs right GPs (p<0.05), and colocalization was more likely in patients with higher CHADS2VASc scores (age>65, diabetes; p<0.05). ConclusionsThis is the first study to demonstrate that clinically detected AF focal and rotational sources in the left atrium often colocalize with regions of autonomic innervation. Studies should define if the role of AF sources differs by their anatomical location.

Atrial Heterogeneity Generates Re-entrant Substrate during Atrial Fibrillation and Anti-arrhythmic Drug Action: Mechanistic Insights from Canine Atrial Models

Anti-arrhythmic drug therapy is a frontline treatment for atrial fibrillation (AF), but its success rates are highly variable. This is due to incomplete understanding of the mechanisms of action of specific drugs on the atrial substrate at different stages of AF progression. We aimed to elucidate the role of cellular, tissue and organ level atrial heterogeneities in the generation of a re-entrant substrate during AF progression, and their modulation by the acute action of selected anti-arrhythmic drugs. To explore the complex cell-to-organ mechanisms, a detailed biophysical models of the entire 3D canine atria was developed. The model incorporated atrial geometry and fibre orientation from high-resolution micro-computed tomography, region-specific atrial cell electrophysiology and the effects of progressive AF-induced remodelling. The actions of multi-channel class III anti-arrhythmic agents vernakalant and amiodarone were introduced in the model by inhibiting appropriate ionic channel currents according to experimentally reported concentration-response relationships. AF was initiated by applied ectopic pacing in the pulmonary veins, which led to the generation of localized sustained re-entrant waves (rotors), followed by progressive wave breakdown and rotor multiplication in both atria. The simulated AF scenarios were in agreement with observations in canine models and patients. The 3D atrial simulations revealed that a re-entrant substrate was typically provided by tissue regions of high heterogeneity of action potential duration (APD). Amiodarone increased atrial APD and reduced APD heterogeneity and was more effective in terminating AF than vernakalant, which increased both APD and APD dispersion. In summary, the initiation and sustenance of rotors in AF is linked to atrial APD heterogeneity and APD reduction due to progressive remodelling. Our results suggest that anti-arrhythmic strategies that increase atrial APD without increasing its dispersion are effective in terminating AF.

A novel catheter-guidance algorithm for localization of atrial fibrillation rotor and focal sources.

Locating atrial fibrillation (AF) focal and rotor sources can help improve target ablation therapy for AF. However, it remains unclear how to use the information provided by multi-polar diagnostic catheters (MPDC) to locate AF sources. Our aim was to develop a catheter-guidance algorithm to locate AF focal and rotor sources using a conventional MPDC. We simulated a 10 cm × 10 cm atrial tissue with focal and rotor sources using the Nygren et al. ionic model. We modeled a Lasso MPDC with 20-unipole electrodes placed with a spacing of 4.5-1-4.5 mm (diameter, d=15 mm) along a circle to obtain 10-bipole electrograms. Staring from an initial location, the algorithm, which was blinded to the location and type of the AF source, iteratively advanced the MPDC by moving its center to the location of the first activated bipole (FAB). The algorithm located an AF source if a stopping condition for either source was satisfied using bipole electrogram characteristics extracted from the MPDC placement. We tested the algorithm for a single rotor and focal source for all possible initial positions on the simulated tissue and repeated it for a random placement with a maximum of 20 possible placements at every trial. The algorithm located the AF source for 100% of trials and on average required 5.99 ± 1.92 placements to an AF source. This algorithm may be used to iteratively direct an MPDC towards an AF source and allow the AF source to be localized for customized AF ablation.

Identification and annotation of multiple periodic pulse trains using dominant frequency and graph search: Applications in atrial fibrillation rotor detection.

Biological signals, such as intracardiac electrograms during atrial fibrillation (AF), can contain multiple periodic components or peaks. We propose a method for identifying individual periodic peak trains in signals containing multiple such periodic sequences. We use dominant frequency-based periodicity detection along with a graph search algorithm to identify the most dominant periodic activation set or peaks of interest. We then remove these peaks and iterate until all periodic sequences are identified. The proposed method is tested on simulated AF intra-cardiac electrograms with periodic activation trains of three distinct frequencies corrupted by noise and complex aperiodic signal features. The method is shown to have high accuracy (up to 100% sensitivity and 100% specificity) in detecting the three individual periodic peak trains. The method has application in biomedical signal analysis, such as detecting the periodic activations of a rotor, amidst other periodic activations during AF.

Presence and stability of rotors in atrial fibrillation: evidence and therapeutic implications.

Rotor-guided ablation has opened new perspectives into the therapy of atrial fibrillation (AF). Analysis of the spatio-temporal cardiac excitation patterns in the frequency and phase domains has demonstrated the importance of rotors in research models of AF, however, the dynamics and role of rotors in human AF are still controversial. In this review, the current knowledge gained through research models and patient data that support the notion that rotors are key players in AF maintenance is summarized. We report and discuss discrepancies regarding rotor prevalence and stability in various studies, which can be attributed in part to methodological differences among mapping systems. Future research for validation and improvement of current clinical electrophysiology mapping technologies will be crucial for developing mechanistic-based selection and application of the best therapeutic strategy for individual AF patient, being it, pharmaceutical, ablative, or other approach.

The Major Role of IK1 in Mechanisms of Rotor Drift in the Atria: A Computational Study.

Maintenance of paroxysmal atrial fibrillation (AF) by fast rotors in the left atrium (LA) or at the pulmonary veins (PVs) is not fully understood. This review describes the role of the heterogeneous distribution of transmembrane currents in the PVs and LA junction (PV-LAJ) in the localization of rotors in the PVs. Experimentally observed heterogeneities in IK1, IKs, IKr, Ito, and ICaL in the PV-LAJ were incorporated into models of human atrial kinetics to simulate various conditions and investigate rotor drifting mechanisms. Spatial gradients in the currents resulted in shorter action potential duration, less negative minimum diastolic potential, slower upstroke and conduction velocity for rotors in the PV region than in the LA. Rotors under such conditions drifted toward the PV and stabilized at the less excitable region. Our simulations suggest that IK1 heterogeneity is dominant in determining the drift direction through its impact on the excitability gradient. These results provide a novel framework for understanding the complex dynamics of rotors in AF.

Abstract 18637: Recurrence Quantification Analysis to Distinguish Active From Passive Mechanisms of CFAEs During Catheter Ablation of Atrial Fibrillation

Background: Ablation of complex fractionated atrial electrograms (CFAEs) is controversial, primarily because of difficulty in visually distinguishing CFAEs representing an active site of driver activity from a passive site of double potentials, wave break, and/or slow conduction. We hypothesized that CFAEs within rotors in atrial fibrillation (AF) would exhibit highly recurrent behavior compared with CFAEs remote from these driver regions. Methods: Active and passive mechanisms of CFAE formation were simulated in several 2D 7.5 x 7.5 cm modified Luo-Rudy 1 models. CFAEs within areas of rotors were considered active, while those caused by wave break, slow conduction or double potentials remote from rotors were considered passive. Clinical signals were also collected during catheter ablation of paroxysmal AF (n=8 patients). An active driver CFAE site was defined by termination of AF with ablation followed by non-inducibility. A passive site was defined as CFAE occurring remotely. Detection of CFAEs was based on mean cycle length (MCL) calculated from 4 second windows using -dV/dt for detection (40ms refractory period/10ms maximum EGM width for simulations; 45ms/15ms respectively for clinical signals). Recurrence quantification analysis (RQA) was performed on discrete time series of simulated and clinical CFAE activations. Results: RQA was performed on 20 simulated EGMs. MCL was similar in both active and passive CFAEs (74±11ms and 78±6ms respectively, p=NS), but recurrence was significantly higher in active compared to passive sites (%recurrence: 61±22% active, 4±6% passive, p&lt;0.01). In patients with AF, the driver sites were all located within the pulmonary vein antra while passive CFAEs were remote. The MCL of CFAEs at active driver sites was similar to that of passive sites (100±13ms active, 98±17ms passive, p=NS), but recurrence was significantly higher in the active driver sites (%recurrence: 18±15% active, 2±1% passive, p=0.02). Conclusion: CFAEs may occur due to either active or passive mechanisms. Sites within rotors or focal drivers of AF are more likely to exhibit recurrent patterns. RQA may be a powerful tool to differentiate driver from bystander CFAEs enabling more efficient targeting for ablation.