An interactive platform to guide catheter ablation in human persistent atrial fibrillation using dominant frequency, organization and phase mapping

Background and Objective: Optimal targets for persistent atrial fibrillation (persAF) ablation are still debated. Atrial regions hosting high dominant frequency (HDF) are believed to participate in the initiation and maintenance of persAF and hence are potential targets for ablation, while rotor ablation has shown promising initial results. Currently, no commercially available system offers the capability to automatically identify both these phenomena. This paper describes an integrated 3D software platform combining the mapping of both frequency spectrum and phase from atrial electrograms (AEGs) to help guide persAF ablation in clinical cardiac electrophysiological studies. Methods: 30 s of 2048 non-contact AEGs (EnSite Array, St. Jude Medical) were collected and analyzed per patient. After QRST removal, the AEGs were divided into 4 s windows with a 50% overlap. Fast Fourier transform was used for DF identification. HDF areas were identified as the maximum DF to 0.25 Hz below that, and their centers of gravity (CGs) were used to track their spatiotemporal movement. Spectral organization measurements were estimated. Hilbert transform was used to calculate instantaneous phase. Results: The system was successfully used to guide catheter ablation for 10 persAF patients. The mean processing time was 10.4 ± 1.5 min, which is adequate comparing to the normal electrophysiological (EP) procedure time (120∼180 min). Conclusions: A customized software platform capable of measuring different forms of spatiotemporal AEG analysis was implemented and used in clinical environment to guide persAF ablation. The modular nature of the platform will help electrophysiological studies in understanding of the underlying AF mechanisms

Minimizing discordances in automated classification of fractionated electrograms in human persistent atrial fibrillation

Ablation of persistent atrial fibrillation (persAF) targeting complex fractionated atrial electrograms (CFAEs) detected by automated algorithms has produced conflicting outcomes in previous electrophysiological studies. We hypothesize that the differences in these algorithms could lead to discordant CFAE classifications by the available mapping systems, giving rise to potential disparities in CFAE-guided ablation. This study reports the results of a head-to-head comparison of CFAE detection performed by NavX (St. Jude Medical) versus CARTO (Biosense Webster) on the same bipolar electrogram data (797 electrograms) from 18 persAF patients. We propose revised thresholds for both primary and complementary indices to minimize the differences in CFAE classification performed by either system. Using the default thresholds [NavX: CFEMean ≤ 120 ms; CARTO: ICL ≥ 7], NavX classified 70 % of the electrograms as CFAEs, while CARTO detected 36 % (Cohen’s kappa κ ≈ 0.3, P < 0.0001). Using revised thresholds found using receiver operating characteristic curves [NavX: CFE-Mean ≤ 84 ms, CFE-SD ≤ 47 ms; CARTO: ICL ≥ 4, ACI ≤ 82 ms, SCI ≤ 58 ms], NavX classified 45 %, while CARTO detected 42 % (κ ≈ 0.5, P < 0.0001). Our results show that CFAE target identification is dependent on the system and thresholds used by the electrophysiological study. The thresholds found in this work counterbalance the differences in automated CFAE classification performed by each system. This could facilitate comparisons of CFAE ablation outcomes guided by either NavX or CARTO in future works

Three-dimensional dominant frequency mapping using autoregressive spectral analysis of atrial electrograms of patients in persistent atrial fibrillation

Background: Areas with high frequency activity within the atrium are thought to be ‘drivers’ of the rhythm in patients with atrial fibrillation (AF) and ablation of these areas seems to be an effective therapy in eliminating DF gradient and restoring sinus rhythm. Clinical groups have applied the traditional FFT-based approach to generate the three-dimensional dominant frequency (3D DF) maps during electrophysiology (EP) procedures but literature is restricted on using alternative spectral estimation techniques that can have a better frequency resolution that FFT-based spectral estimation. Methods: Autoregressive (AR) model-based spectral estimation techniques, with emphasis on selection of appropriate sampling rate and AR model order, were implemented to generate high-density 3D DF maps of atrial electrograms (AEGs) in persistent atrial fibrillation (persAF). For each patient, 2048 simultaneous AEGs were recorded for 20.478 s-long segments in the left atrium (LA) and exported for analysis, together with their anatomical locations. After the DFs were identified using AR-based spectral estimation, they were colour coded to produce sequential 3D DF maps. These maps were systematically compared with maps found using the Fourier-based approach. Results: 3D DF maps can be obtained using AR-based spectral estimation after AEGs downsampling (DS) and the resulting maps are very similar to those obtained using FFT-based spectral estimation (mean 90.23%). There were no significant differences between AR techniques (p=0.62). The processing time for AR-based approach was considerably shorter (from 5.44 to 5.05 s) when lower sampling frequencies and model order values were used. Higher levels of DS presented higher rates of DF agreement (sampling frequency of 37.5Hz). Conclusion: We have demonstrated the feasibility of using AR spectral estimation methods for producing 3D DF maps and characterised their differences to the maps produced using the FFT technique, offering an alternative approach for 3D DF compu- tation in human persAF studies

Atrial Electrogram Complexity as a Clinical Instrument for Measuring Temporal Fractionation Variability during Atrial Fibrillation

Regions of the atria with complex fractionated atrial electrograms (CFEs) have been suggested to represent remodelled atrial substrate, and hence important sites for ablation in patients with persistent AF. However, temporal behaviour of complex fractionated atrial electrograms (CFEs) remains ill defined. In this study we introduce Negentropy (NegEn) as a measurement of electrogram (EGM) complexity and compare its use in measuring CFEs temporal behaviour with current algorithms based on time domain. [Taken from the Introduction

Distinctive Patterns of Dominant Frequency Trajectory Behaviour in Persistent Atrial Fibrillation: Characterisation of Spatio-Temporal Instability

Background: Substrates for maintenance of persistent atrial fibrillation (persAF) remain poorly understood. The use of dominant frequency (DF) mapping to guide catheter ablation has been proposed as a potential strategy, but the characteristics of high DF sites have not been extensively studied. Methods and Results: We assessed the temporal stability of DF using both contact and non-contact mapping of persAF. A total of 18 patients were included in the study. Group 1 consisted of 8 patients with contact and non-contact mapping and group 2 consisted of 10 patients who had contact mapping only. The percentage of stable DF points from both AF contact and virtual electrograms decreased rapidly over time in an exponential fashion. Sites with highest DF did not remain spatially stable and periodic DF behaviour was noted, occurring within 10 s in most cases. Tracking of the centre of gravity of highest DF areas revealed 3 types of propagation characteristics, namely i) local, ii) cyclical and iii) chaotic activity, with the former 2 patterns accounting for most of the observed events. Conclusions: DF of AF electrograms are not spatiotemporally stable and targeting sites of peak DF alone is unlikely to be a reliable ablation strategy. There appears to be a predominance of local and cyclical activity when centre of gravity of highest DF areas are tracked, which provides further mechanistic insights into maintenance of persAF

Distinctive Patterns of Dominant Frequency Trajectory Behavior in Drug-Refractory Persistent Atrial Fibrillation: Preliminary Characterization of Spatiotemporal Instability

The role of substrates in the maintenance of persistent atrial fibrillation (persAF) remains poorly understood. The use of dominant frequency (DF) mapping to guide catheter ablation has been proposed as a potential strategy, but the characteristics of high DF sites have not been extensively studied. This study aimed to assess the DF spatiotemporal stability using high density noncontact mapping (NCM) in persAF. Methods and Results: Eight persAF patients were studied using NCM during AF. Ventricular far-field cancellation was performed followed by the calculation of DF using Fast Fourier Transform. Analysis of DF stability and spatiotemporal behavior were investigated including characteristics of the highest DF areas (HDFAs). A total of 16,384 virtual electrograms (VEGMs) and 232 sequential high density 3-dimensional DF maps were analyzed. The percentage of DF stable points decreased rapidly over time. Repetition or reappearance of DF values were noted in some instances, occurring within 10 seconds in most cases. Tracking the HDFAs’ center of gravity revealed 3 types of propagation behavior, namely (i) local, (ii) cyclical, and (iii) chaotic activity, with the former 2 patterns accounting for most of the observed events. Conclusions: DF of individual VEGMs was temporally unstable, although reappearance of DF values occurred at times. Hence, targeting sites of ‘peak DF’ from a single time frame is unlikely to be a reliable ablation strategy. There appears to be a predominance of local and cyclical activity of HDFAs hinting a potentially nonrandom temporally periodic behavior that provides further mechanistic insights into the maintenance of persAF

A Platform to guide Catheter Ablation of Persistent Atrial Fibrillation using Dominant Frequency Mapping

Introduction: Dominant frequency (DF) analysis has been widely used to understand the pathophysiology of atrial fibrillation (AF). An interactive digital platform was developed to provide real-time DF mapping during DF-guided AF ablation. Methods: A user oriented graphic interface was developed in Matlab for real-time analysis of data exported from the non-contact balloon array (St. Jude Ensite Velocity System). The platform performs QRST subtraction on all electrograms (EGM) and Fast Fourier transform with 4 seconds windows (50% overlap) to compute DF, organization index (OI), regularity index (RI) and phase. DF, OI and RI of each window can be colour-coded and plotted on a 3D left atrium mesh, and 3D phase movies can also be played using a slider. High DF areas and the trajectory of their centres of gravity can be shown per individual window. Also any EGM of interest on the 3D mesh is easily accessible using the mouse. Results: 30 seconds of EGM data sampled at 2034.5 Hz with 2048 chan-nels are processed within 10 mins, which is acceptable for practical use dur-ing catheter ablation. The figure shows the percentage of processing time of each part of the program. Till now the software was tested and used success-fully in 5 catheter ablation cases. Conclusion: The proposed platform is fully automated with user-oriented graphic interface that provides a 3 dimensional representation of the left atrium with the DF behaviour. This software might provide further online information to relate DF to remodelled atrial substrate

Characterization of human persistent atrial fibrillation electrograms using recurrence quantification analysis

Atrial fibrillation (AF) is regarded as a complex arrhythmia, with one or more co-existing mechanisms, resulting in an intricate structure of atrial activations. Fractionated atrial electrograms (AEGs) were thought to represent arrhythmogenic tissue and hence have been suggested as targets for radiofrequency ablation. However, current methods for ablation target identification have resulted in suboptimal outcomes for persistent AF (persAF) treatment, possibly due to the complex spatiotemporal dynamics of these mechanisms. In the present work, we sought to characterize the dynamics of atrial tissue activations from AEGs collected during persAF using recurrence plots (RPs) and recurrence quantification analysis (RQA). 797 bipolar AEGs were collected from 18 persAF patients undergoing pulmonary vein isolation (PVI). Automated AEG classification (normal vs. fractionated) was performed using the CARTO criteria (Biosense Webster). For each AEG, RPs were evaluated in a phase space estimated following Takens' theorem. Seven RQA variables were obtained from the RPs: recurrence rate; determinism; average diagonal line length; Shannon entropy of diagonal length distribution; laminarity; trapping time; and Shannon entropy of vertical length distribution. The results show that the RQA variables were significantly affected by PVI, and that the variables were effective in discriminating normal vs. fractionated AEGs. Additionally, diagonal structures associated with deterministic behavior were still present in the RPs from fractionated AEGs, leading to a high residual determinism, which could be related to unstable periodic orbits and suggesting a possible chaotic behavior. Therefore, these results contribute to a nonlinear perspective of the spatiotemporal dynamics of persAF. Biological markers that better explain atrial fibrillation (AF) behavior and provide a definitive answer for persistent atrial fibrillation (persAF) therapy are still in debate due to its complex underlying pathophysiology and spatiotemporal behavior. As such, the role of low dimensional structures for explaining AF has been the subject of many investigations, showing that recurrence quantification analysis (RQA) might be useful to explore the underlying AF dynamics. However, a consistent set of RQA variables taking into account the specificities of the signals and of the theoretical methodology is still needed. In the present work, we propose rigorous steps for a proper reconstruction of the recurrence plots (RPs) and for the estimation of RQA-based variables extracted from atrial electrograms (AEGs) collected from persAF patients undergoing a clinical procedure for AF therapy. We demonstrate that these RQA-based variables are sensitive to important electrophysiologic characteristics of the atrial tissue and could potentially be used as biological markers to guide the clinical procedure. Additionally, a high residual determinism was found in the RPs from AEGs with seemingly turbulent characteristics, which implies that the spatiotemporal dynamics of persAF mechanisms is not necessarily associated to a random structure

Contributing Factors Concerning Inconsistencies in Persistent Atrial Fibrillation Ablation Outcomes

Abstract In the present work, we investigated current methods for complex fractionated atrial electrogram (CFAE