High-density activation mapping of fractionated electrograms in the atria of patients with paroxysmal atrial fibrillation

BACKGROUND: Areas of complex fractionated atrial electrograms (CFAEs) have been implicated in the atrial substrate of atrial fibrillation (AF). The mechanisms underlying CFAE in humans are not well investigated. OBJECTIVES: The purpose of this study was to investigate the regional activation pattern associated with CFAE using a high-density contact mapping catheter. METHODS: Twenty patients with paroxysmal AF were mapped using a high-density multielectrode catheter. CFAE were mapped at 10 different sites (left atrium [LA]: inferior, posterior, roof, septum, anterior, lateral; right atrium [RA]: anterior, lateral, posterior, septum). Local atrial fibrillation cycle length (AFCL) was measured immediately before and after the occurrence of CFAE, and the longest electrogram duration (CFAEmax) was assessed. RESULTS: Longer electrogram durations were recorded in the LA compared with the RA (CFAEmax 118 +/- 21 ms vs 104 +/- 23 ms, P = .001). AFCL significantly shortened before the occurrence of CFAEmax compared with baseline (LA: 174 +/- 32 ms vs 186 +/- 32 ms, P = .0001; RA: 177 +/- 31 ms vs 188 +/- 31 ms, P = .0001) and returned to baseline afterwards. AFCL shortened by >or=10 ms in 91% of mapped sites. Two different local activation patterns were associated with occurrence of CFAEmax: a nearly simultaneous activation in all spines in 84% indicating passive activation, and a nonsimultaneous activation sequence suggesting local complex activation or reentry. CONCLUSION: Fractionated atrial electrograms during AF demonstrate dynamic changes that are dependent on regional AFCL. Shortening of AFCL precedes the development of CFAE; thus, cycle length is a major determinant of fractionation during AF. High-density mapping in AF may help to differentiate passive activation of CFAE from CFAE associated with an active component of the AF process.     

Consistency of the CFAE phenomena using custom software for automated detection of complex fractionated atrial electrograms (CFAEs) in the left atrium during atrial fibrillation

Introduction: Complex fractionated atrial electrograms (CFAEs) have been described as a potential target for ablation of atrial fibrillation (AF). The purpose of this study is to assess the consistency of the CFAE phenomena using custom software for automated detection of CFAEs in the left atrium during AF. Methods and Results: This prospective study included 10 patients referred for catheter ablation of symptomatic drug‐refractory AF. Ten consecutive points at a single location (cluster) were acquired as electroanatomical points every 3 seconds. Atrial signals were automatically classified as CFAEs by the software algorithm. The number of intervals between 50 ms and 110 ms and in the voltage range 0.05–0.15 mV during the 2.5‐second recordings was determined and referred to as the interval confidence level (ICL). A total of 2,226 points were acquired during mapping of AF. A dominant group of ICL using one of two different configurations of ICL fractionation was identified. A dominant group was defined as the ICL categorization occurring with greatest frequency in a given cluster of points. The results show the consistency ranged from 73%± 21 for the three‐group configuration (ICL ≤ 4; 4 < ICL ≤ 7; ICL > 7) to 84%± 16 for the two‐group configuration (ICL ≤ 5; ICL > 5). Conclusion: This novel software offers an objective method for CFAE analysis during atrial fibrillation. CFAE consistency ranged from 73% to 84% with wide standard deviation. Automated detection of CFAEs may remove the pitfalls associated with subjective visual detection, thus removing one variable in comparative studies of using CFAEs as AF ablation targets.     

A new approach for catheter ablation of atrial fibrillation: mapping of the electrophysiologic substrate

OBJECTIVES: We sought to test the hypothesis that complex fractionated electrograms (CFAEs) recorded during atrial fibrillation (AF) could be used as target sites for catheter ablation of AF. BACKGROUND: Mapping of AF in humans has shown that areas of CFAEs correlate with areas of slowed conduction and pivot points of reentrant wavelets. We hypothesized that such areas of CFAEs could be identified in patients with AF and might serve as target sites for catheter ablation to maintain sinus rhythm. METHODS: The study population included 121 patients (29 females; mean age, 63 years) with refractory AF (57 paroxysmal, 64 chronic). All patients underwent nonfluoroscopic electroanatomic mapping (CARTO) during AF. Using CARTO, the biatrial replica, displayed in a three-dimensional color-coded voltage map, was created during AF, and areas associated with CFAEs were identified. Radiofrequency ablation of the area with CFAEs was performed, aiming to eliminate CFAE and/or convert to sinus rhythm. RESULTS: Complex fractionated atrial electrograms were found in seven of nine regions of both atria, but were mainly confined to the interatrial septum, pulmonary veins, roof of left atrium, and left posteroseptal mitral annulus and coronary sinus ostium. Ablations of the areas associated with CFAEs resulted in termination of AF without external cardioversion in 115 of the 121 patients (95%); 32 (28%) required concomitant ibutilide treatment. At the one-year follow-up, 110 (91%) patients were free of arrhythmia and symptoms, 92 after one ablation and 18 after two. CONCLUSIONS: Areas with CFAEs represent a defined electrophysiologic substrate and are ideal target sites for ablations to eliminate AF and maintain normal sinus rhythm.     

Characteristics of Complex Fractionated Electrograms in Nonpulmonary Vein Ectopy Initiating Atrial Fibrillation/Atrial Tachycardia

Background: Nonpulmonary vein (PV) ectopy initiating atrial fibrillation (AF)/atrial tachycardia (AT) is not uncommon in patients with AF. The relationship of complex fractionated atrial electrograms (CFAEs) and non‐PV ectopy initiating AF/AT has not been assessed. We aimed to characterize the CFAEs in the non‐PV ectopy initiating AF/AT. Methods: Twenty‐three patients (age 53 ± 11 y/o, 19 males) who underwent a stepwise AF ablation with coexisting PV and non‐PV ectopy initiating AF or AT were included. CFAE mapping was applied before and after the PV isolation in both atria by using a real‐time NavX electroanatomic mapping system. A CFAE was defined as a fractionation interval (FI) of less than 120 ms over 8‐second duration. A continuous CFAE (mostly, an FI < 50 ms) was defined as electrogram fractionation or repetitive rapid activity lasting for more than 8 seconds. Results: All patients (100%) with non‐PV ectopy initiating AF or AT demonstrated corresponding continuous CFAEs at the firing foci. There was no significant difference in the FI among the PV ostial or non‐PV atrial ectopy or other atrial CFAEs (54.1 ± 5.6, 58.3 ± 11.3, 52.8 ± 5.8 ms, P = 0.12). Ablation targeting those continuous CFAEs terminated the AF and AT and eliminated the non‐PV ectopy in all patients (100%). During a follow‐up of 7 months, 22% of the patients had an AF recurrence with PV reconnections. There was no recurrence of any ablated non‐PV ectopy during the follow‐up. Conclusion: The sites of the origin of the non‐PV ectopies were at the same location as those of the atrial continuous CFAEs. Those non‐PV foci were able to initiate and sustain AF/AT. By limited ablation targeting all atrial continuous CFAEs, the AF could be effectively eliminated.     

The Optimal Automatic Algorithm for the Mapping of Complex Fractionated Atrial Electrograms in Patients With Atrial Fibrillation

CFAEs and the Voltage.   Introduction: Catheter ablation of atrial fibrillation (AF) can be guided by the identification of complex fractionated atrial electrograms (CFAEs). We aimed to study the prediction of the CFAEs defined by an automatic algorithm in different atrial substrates (high voltage areas vs low voltage areas).
Methods and Results: This study included 13 patients (age = 56 ± 12 years, paroxysmal AF = 8 and persistent AF = 5), who underwent mapping and catheter ablation of AF with a NavX system. High-density voltage mapping of the left atrium (LA) was performed during sinus rhythm (SR) (248 ± 75 sites per patient) followed by that during AF (88 ± 24 sites per patient). The CFAE maps were based on the automatic-detection algorithm. "Operator-determined CFAEs" were defined according to Nademannee's criteria. A low-voltage zone (LVZ) was defined as a bipolar voltage of less than 0.5 mV during SR. Among a total of 1150 mapping sites, 459 (40%) were categorized as "operator-determined CFAE sites," whereas 691 (60%) were categorized as "operator-determined non-CFAE sites." The sensitivity and negative predictive value increased as the fractionated interval (FI) value of the automatic algorithm increased, but the specificity and positive predictive value decreased. The automatic CFAE algorithm exhibited the highest combined sensitivity and specificity with an FI of <60 ms for the sites inside the LVZ and FI < 70 ms for the sites outside the LVZ, when compared with a single threshold for both the high- and low-voltage groups combined (i.e., no regard for voltage) (ROC: 0.89 vs 0.86).
Conclusions: The clinical relevance of the CFAE map would be improved if the calculated index values were accordingly scaled by the electrogram peak-to-peak amplitude. (J Cardiovasc Electrophysiol, Vol. 21, pp. 21–26, January 2010)     

Measuring the Complexity of Atrial Fibrillation Electrograms

AF Electrogram Complexity. Introduction: Complex fractionated atrial electrograms (CFAE) have been identified as targets for atrial fibrillation (AF) ablation. Robust automatic algorithms to objectively classify these signals would be useful. The aim of this study was to evaluate Shannon's entropy (ShEn) and the Kolmogorov‐Smirnov (K‐S) test as a measure of signal complexity and to compare these measures with fractional intervals (FI) in distinguishing CFAE from non‐CFAE signals. Methods and Results: Electrogram recordings of 5 seconds obtained from multiple atrial sites in 13 patients (11 M, 58 ± 10 years old) undergoing AF ablation were visually examined by 4 independent reviewers. Electrograms were classified as CFAE if they met Nademanee criteria. Agreement of 3 or more reviewers was considered consensus and the resulting classification was used as the gold standard. A total of 297 recordings were examined. Of these, 107 were consensus CFAE, 111 were non‐CFAE, and 79 were equivocal or noninterpretable. FIs less than 120 ms identified CFAEs with sensitivity of 87% and specificity of 79%. ShEn, with optimal parameters using receiver‐operator characteristic curves, resulted in a sensitivity of 87% and specificity of 81% in identifying CFAE. The K‐S test resulted in an optimal sensitivity of 100% and specificity of 95% in classifying uninterpretable electrogram from all other electrograms. Conclusions: ShEn showed comparable results to FI in distinguishing CFAE from non‐CFAE without requiring user input for threshold levels. Thus, measuring electrogram complexity using ShEn may have utility in objectively and automatically identifying CFAE sites for AF ablation. (J Cardiovasc Electrophysiol, Vol. 21, pp. 649‐655, June 2010)     

The effect of electrogram duration on quantification of complex fractionated atrial electrograms and dominant frequency

Introduction: Sites of complex fractionated atrial electrograms (CFAEs) and highest dominant frequency (DF) have been proposed as critical regions maintaining atrial fibrillation (AF). This study aimed to determine the minimum electrogram recording duration that accurately characterizes CFAE or DF sites for ablation without unduly lengthening the procedure.
Methods and Results: Fourteen patients with AF undergoing catheter ablation had high-density (498 ± 174 points) biatrial mapping performed during AF before ablation. At each point, 8-second electrograms were recorded. CFAE characterization using the NavX software provided a representation of electrogram complexity (CFE-mean). CFE-mean for each point from 7-, 6-, 5-, 4-, 3-, 2-, and 1-second subsamples were compared with the index 8-second CFE-mean. Offline spectral analysis defined DF as the frequency with greatest power, and DF of subsamples were compared with index DF. Index 8-second electrogram CFE-mean was 114 ± 20 ms for right atria and 102 ± 17 ms for left atria (P = 0.01); DF was 5.7 ± 0.8 Hz for right atria and 6.0 ± 0.8 Hz for left atria (P = 0.02). Means from shorter electrograms were nonsignificantly decreased for CFE-mean and overestimated for DF (P < 0.001). Mean absolute differences between subsampled and index values ranged from 3.3 to 20.1 ms for CFE-mean and 0.11 to 1.18 Hz for DF. Subsampled electrograms deviating >10% from index values ranged from 2.5 to 56% for CFE-mean and 3.5 to 41% for DF. Intraclass correlation coefficients ranged from 0.992 to 0.788 for CFE-mean and 0.897 to 0.233 for DF. Unacceptable differences from index values were found with CFE-mean and DF from electrograms <5 seconds.
Conclusion: Electrograms of ≥5-second duration are required to accurately characterize CFAE and DF sites for ablation.     

Automated detection and characterization of complex fractionated atrial electrograms in human left atrium during atrial fibrillation

BACKGROUND: Complex fractionated atrial electrograms (CFAEs) have been reported as ablative targets for the treatment of atrial fibrillation (AF). However, the process of CFAE identification is highly dependent on the operator's judgment. OBJECTIVE: It is the aim of the study to report our initial experience with a novel software algorithm designed to automatically detect CFAEs. METHODS: Nineteen patients (6 female, 58 +/- 8 years) who underwent catheter ablation of paroxysmal (n = 11) or persistent (n = 8) AF were included in the study. During ongoing AF, 100 +/- 15 left atrial (LA) endocardial locations were sampled under the guidance of integrated electroanatomical mapping with computed tomographic images. Bipolar electrograms recorded throughout the LA were analyzed using custom software that allows for automated detection of CFAEs. Interval confidence level (ICL), defined as the number of intervals between consecutive CFAE complexes during 2.5-second recordings, was used to characterize CFAEs. The CFAE sites with an ICL >/=5 were considered as sites with highly repetitive CFAEs, which are thought to be potential ablation targets. For purposes of analysis, the LA was divided into 6 areas: pulmonary vein (PV) ostia, posterior wall, interatrial septum, roof, mitral annulus area, and appendage. RESULTS: Among a total of 1,904 LA locations sampled in 19 patients, 1,644 (86%) were categorized as CFAE sites, whereas 260 (14%) were categorized as as non-CFAE sites. Thirty-four percent of all CFAE sites were identified as sites with highly repetitive CFAEs. Of these, 24% were located at the interatrial septum, 22% on the posterior wall, 20% at the PV ostia, 18% at the mitral annulus area, 14% on the roof, and 2.7% at the LA appendage. In all patients, highly repetitive CFAE sites were distributed in 4 or more areas of the LA. Persistent AF patients had more highly repetitive CFAE sites on the posterior wall than paroxysmal AF patients (30% +/- 7.3% vs 14% +/- 8.2%, P < .001). There was a strong trend toward more highly repetitive CFAE sites located at the PV ostia in patients with paroxysmal AF compared with persistent AF patients (24% +/- 13% vs 13% +/- 7.7%, P = .05). CONCLUSION: With the use of custom software, CFAE complexes were identified in more than 80% of the LA endocardial locations. LA sites with highly repetitive CFAE sites were located predominately in the septum, posterior wall, and PV ostia. Patients with persistent AF had a different anatomical distribution pattern of highly repetitive CFAE sites from those with paroxysmal AF, with a greater prevalence of highly repetitive CFAEs located on the posterior wall. Further studies are warranted to determine the clinical significance of these findings.     

不同部位刺激诱发心房颤动时碎裂电位的出现与分布

目的 探讨在心房和肺静脉不同部位行电刺激诱发心房颤动（简称房颤）时碎裂电位（CFAEs）的出现与分布。方法 22只成年健康杂种犬,常规麻醉,气管插管,切断双侧颈迷走神经干,破坏颈交感神经节,建立动物的去自主神经模型。双侧开胸,分别在右心耳、左心耳和四支肺静脉的近、中、远段行电刺激诱发房颤,观察在基础刺激、双侧强迷走刺激两种诱发条件下,房颤发作时CFAEs的分布情况。结果 刺激诱发房颤的部位与CFAEs出现的部位并不完全一致。双侧心房（心耳）及肺静脉口附近是房颤时CFAEs出现的高频部位。当伴有迷走神经刺激时,房颤的诱发率提高,CFAEs的出现频率也随之明显增加。结论 房颤时CFAEs的分布并不局限于心房或肺静脉的某一局部区域,而是在多个部位可同时标测到。迷走刺激条件下标测到CFAEs的频率增加。     

Automatic 3D mapping of complex fractionated atrial electrograms (CFAE) in patients with paroxysmal and persistent atrial fibrillation

Background: Complex fractionated atrial electrograms (CFAE) are a possible target for atrial fibrillation (AF) ablation and can be visualized in three‐dimensional (3D) mapping systems with specialized software. Objective: To use the new CFAE software of CartoXP® (Biosense Webster, Diamond Bar, CA, USA) for analysis of spatial distribution of CFAE in paroxysmal and persistent AF. Methods: We included 16 consecutive patients (6 females; mean 59.3 years) with AF (6 paroxysmal and 10 persistent) undergoing AF ablation. Carto maps of left atrium (LA) were reconstructed. Using the new CFAE software, the degree of local electrogram fractionation was displayed color‐coded on the map surface. LA was divided into four regions: anterior wall, inferior wall, septum, and pulmonary veins (PV). The relationship among regions with CFAE visualized and CFAE ablation regions (persistent AF only) was analyzed retrospectively. Results: In paroxysmal and persistent AF, CFAE were observed in all four LA regions. In paroxysmal AF, the density of CFAE around the PV was significantly higher than in other regions (P < 0.05) and higher than in persistent AF (P < 0.05). In persistent AF, CFAE were evenly distributed all over the LA. Of 40 effective ablation sites with significant AF cycle length prolongation, 33 (82.5%) were judged retrospectively by CFAE map as CFAE sites. Conclusion: CFAE software can visualize the spatial distribution of CFAE in AF. CFAE in persistent AF were observed in more regions of LA compared to paroxysmal AF in which CFAE concentrated on the PV. Automatically detected CFAE match well with ablation sites targeted by operators.     

Time- and frequency-domain characteristics of atrial electrograms during sinus rhythm and atrial fibrillation

Ablation and Spectral Characteristics of Fibrillation. Background: Complex fractionated atrial electrograms (CFAE) have been considered to be helpful during catheter ablation of atrial fibrillation (AF). The purpose of this study was to analyze the characteristics of CFAEs recorded during sinus rhythm (SR) and AF, and to determine their relationship to perpetuation of AF and clinical outcome. Methods and Results: Antral pulmonary vein isolation (APVI) was performed in 34 consecutive patients (age = 59 ± 10 years) with paroxysmal AF who presented in SR. Time‐ and frequency‐domain characteristics of electrograms recorded from the same sites in the coronary sinus (CS) were analyzed during SR and AF, before and during isoproterenol infusion. There was a modest correlation in fractionation index (FI: change in the direction of depolarization, r = 0.40, P = 0.001) and complexity index (CI: change in the polarity of depolarization, r = 0.41, P = 0.001), but not in the dominant frequency (DF) between SR and AF. There was no relationship between the DF and CI or FI during AF. Isoproterenol was associated with an increase in DF during AF (6.6 ± 0.9 vs 5.1 ± 0.6 Hz, P < 0.001) but had no effect on CI or FI (P = 0.6). A higher CI (58.3 ± 21.0/s vs 38.0 ± 21.0/s, P < 0.01), and FI (123.5 ± 44.8/s vs 75.6 ± 44.6/s, P < 0.01) during AF were associated with a lower likelihood of termination of AF during APVI and a higher probability of recurrent AF after ablation. Ratio of FI during AF to SR was also higher when AF persisted than terminated after APVI (29.7 ± 12.4 vs 19.1 ± 9.7, P = 0.002). However, time‐ or frequency‐domain parameters during SR were not predictive of termination or clinical outcome. Conclusions: Structural and functional properties of the atrial myocardium during AF contribute to electrogram complexity, which may indicate the presence of extra‐PV mechanisms of AF that are not eliminated by APVI. Mapping of complex electrograms in SR is not likely to be sufficient to identify drivers of AF. (J Cardiovasc Electrophysiol, Vol. 22, pp. 851‐857, August 2011)     

Termination of persistent atrial fibrillation during left atrial mapping

Termination of Persistent AF During Mapping. Complex fractionated atrial electrograms (CFAEs) may represent critical areas for the maintenance of atrial fibrillation (AF). While AF organization and termination have been reported with CFAE ablation, no reports of arrhythmia termination during left atrial mapping exist. We report a case of reproducible AF termination with catheter pressure at a site of CFAE remote from the site of AF. (J Cardiovasc Electrophysiol, Vol. 22, pp. 1171‐1173, October 2011)     

Histogram analysis: a novel method to detect and differentiate fractionated electrograms during atrial fibrillation

Histogram Analysis for CFAE Detection. Introduction: Complex fractionated atrial electrograms (CFAEs) might identify the critical substrate maintaining AF. We developed a method based upon histogram analysis of interpeak intervals (IPIs) to automatically quantify fractionation and differentiate between subtypes of CFAEs. Methods: Two experts classified 1,681 fibrillatory electrograms recorded in 13 patients with persistent AF into 3 categories (gold standard): normal electrograms, discontinuous CFAEs, or continuous CFAEs. Histogram analysis of IPI was performed to calculate the P5, P50, P95, and the mean of IPIs, in addition to the total number of IPI (N_Total), and the number of IPI within predetermined ranges: 10–60 (N_Short), 60–120 (N_Intermediate), and >120 ms (N_Long). Results: P50 and N_Long were higher in the normal electrograms compared to the other 2 categories (P < 0.001). N_Intermediate was higher in the discontinuous CFAE category compared to the other 2 categories. P95, mean IPI, N_Total, and N_Short were all significantly different among the 3 categories (P < 0.001) and correlated with the degree of fractionation (r =?0.52, ?0.55, 0.68, and 0.67, respectively). Receiver operating characteristic (ROC) curves showed good diagnostic accuracy (area under curve, AUC > 0.8) of P50 and N_Long to detect normal electrograms. An algorithm using N_Intermediate showed good diagnostic accuracy (AUC > 0.7) to detect discontinuous CFAEs, whereas P95, mean, N_Total, and N_Short all revealed high diagnostic accuracy (AUC > 0.85) to detect continuous CFAEs. This was confirmed in a prospective data set. Conclusions: Histogram analysis of IPI can differentiate between normal electrograms, discontinuous and continuous fractionated electrograms. This method might be used to standardize and optimize ablation strategies in AF . (J Cardiovasc Electrophysiol, Vol. 22, pp. 781‐790, July 2011)     

Long- and Short-Term Temporal Stability of Complex Fractionated Atrial Electrograms in Human Left Atrium During Atrial Fibrillation

Background: Complex fractionated atrial electrograms (CFAEs) have been reported as targets for catheter ablation of atrial fibrillation (AF). However, the temporal stability of CFAE sites remains poorly defined.
Methods and Results: The study consisted of two phases. In the initial phase, two automated software algorithms, namely the interval confidence level (ICL) and the average interpotential interval (AIPI) were assessed for their diagnostic accuracy for automated CFAE detection. The AIPI was found to be superior to the ICL, and an AIPI of ≤100 ms was associated with a sensitivity and specificity of both 92% for detection of CFAEs. In the second phase of the study, 12 patients (2 females, mean age 54 ± 12 years) who underwent catheter ablation for persistent AF were studied to investigate the temporal stability of CFAEs. Two consecutive left atrial (LA) three-dimensional CFAE maps coded with AIPI readings were reconstructed during ongoing AF in each study patient, with a mean time difference of 34.3 ± 8.7 minutes between the two maps. Among a total of 149 CFAE sites and 238 non-CFAE sites on the first CFAE map that were precisely revisited during the repeat mapping process, 135 (90.6%) and 225 (94.5%) remained as CFAE sites and non-CFAE sites, respectively. RF ablation at the selected stable CFAE sites significantly prolonged AF cycle length (181 ± 26 ms to 199 ± 29 ms, P < 0.0001).
Conclusion: CFAEs recorded in the LA during AF display high temporal stability in patients with persistent AF. The clinical significance of our findings warrants further investigation.     

Characteristics and distribution of complex fractionated atrial electrograms and the dominant frequency during atrial fibrillation: relationship to the response and outcome of circumferential pulmonary vein isolation

Background

Although sites of complex fractionated electrograms (CFAEs) and dominant frequency (DF) are known to be critical for the maintenance of atrial fibrillation (AF), spatial distribution of CFAEs and DF and their impact on the outcome of AF ablation remain unclear.

Methods

We created CFAE and DF maps of the left atrium (LA), right atrium, and pulmonary veins (PVs) with a NavX mapping system and simultaneously calculated the DF values with a Bard LabSystem Pro in 40 patients with AF (nonparoxysmal, n?=?16).

Results

In 19 patients in whom circumferential PV isolation (CPVI) terminated AF, there was a high DF in the PVs (Bard-based DF value, 6.70?±?1.01?Hz), low DF in the LA body (5.94?±?0.75?Hz), and a significant PV-to-LA body DF gradient (0.76?±?0.65?Hz), and the CFAEs were located mainly in the PV antrum. In the 21 patients not responding to CPVI, a high DF was located in both the PVs (7.04?±?0.81?Hz) and LA body (6.75?±?0.81?Hz), and therefore, the PV-to-LA body DF gradient was smaller than that in the CPVI responders (0.29?±?0.52?Hz, P?=?0.0160), and the CFAEs extended to the LA body. The higher DF in the LA body, nonparoxysmal AF, and longer AF duration remained as independent predictors of a post-ablation AF recurrence by using a multivariate analysis.

Conclusions

A higher LA-DF value, smaller PV-to-LA DF gradient, and wider LA-CFAE distribution were noted more often in the nonresponders to CPVI than in the responders. This suggested the presence of an arrhythmogenic substrate in the LA beyond the PVs in patients whose AF persisted after CPVI, which was further associated with post-ablation AF recurrence.     

Diagnostic accuracy of a new software for complex fractionated electrograms identification in patients with persistent and permanent atrial fibrillation

Introduction: The elimination of complex fractionated atrial electrograms (CFAEs) has been proposed as a potential target for guiding successful AF substrate ablation. The possibility to efficiently map the atria and rapidly identify CFAEs sites is necessary, before the CFAEs ablation becomes a routine approach. The aims of this study, conducted in patients with persistent and permanent atrial fibrillation (AF), were to analyze by CARTO mapping in the right (RA) and in the left atrium (LA) during AF: (1) the diagnostic accuracy of a new software for CFAEs analysis, (2) the spatial distribution of CFAEs, (3) the regional beat to beat AF intervals (FF). Methods and Results: Twenty‐five consecutive patients (four women, 58.8 ± 11.4 years) undergoing radiofrequency catheter ablation for persistent and permanent AF were enrolled in the study. The CFAE software showed a high sensitivity (90%) and specificity (91%) in the identification of CFAEs, using a specific setting of parameters. The LA had a significantly higher prevalence of CFAEs as compared with the RA (30.5% vs 20.3%, P = 0.016). The CFAEs were mostly present in the septum and in the area of coronary sinus ostium (CS os). The FF intervals were significantly shorter in the LA than in the RA (P < 0.01). Conclusion: CARTO system has a high diagnostic accuracy in the identification of CFAEs. Atrial electrical activity (CFAEs, mean FF intervals) during AF showed a significant spatial inhomogeneity.     

Autonomic mechanism for complex fractionated atrial electrograms: evidence by fast fourier transform analysis

Introduction: The mechanism(s) underlying complex fractionated atrial electrograms (CFAE) is not well understood. We hypothesized that CFAE may be caused by enhanced activity of the intrinsic cardiac autonomic nervous system.
Methods and Results: In 35 anesthetized dogs, via a right or left thoracotomy, sustained atrial fibrillation was induced by local application of acetylcholine (ACh; 10, 100 mM) to the surface of the atrial appendage (AA) or by injection of ACh (10 mM) into the ganglionated plexi (GP). Fast Fourier transform analysis was performed from recordings at AA, atrial sites near the AA, mid portion of the atrium, atrial sites near the GP, and the pulmonary veins. After AF was induced with ACh either by topical application to the AA or by direct injection into the GP, CFAE exhibited a significant gradient of progressively decreasing dominant frequency and incidence of CFAE (CFAE%) from the GP toward distant sites, while regularity index progressively decreased in the opposite direction. Ablation of GP markedly attenuated CFAE and eliminated these gradients.
Conclusions: These results suggest CFAE may result from activation of the intrinsic cardiac autonomic nervous system in these animal models of sustained AF. Ablation of GP attenuates CFAE and eliminates the DF gradient.     

The Novel Electrophysiology of Complex Fractionated Atrial Electrograms: Insight from Noncontact Unipolar Electrograms

Unipolar Characteristics of CFAEs. Background: The noncontact mapping (NCM) system possesses the merit of global endocardial recording for unipolar and activation mapping. Objective: We aimed to evaluate the unipolar electrogram characteristics and activation pattern over the bipolar complex fractionated atrial electrogram (CFAE) sites during atrial fibrillation (AF). Methods: Twenty patients (age 55 ± 11 years old, 15 males) who underwent NCM and ablation of AF (paroxysmal/persistent = 13/7) were included. Both contact bipolar (32–300 Hz) and NCM virtual unipolar electrograms (0.5–300 Hz) were simultaneously recorded along with the activation pattern (total 223 sites, 11 ± 4 sites/patient). A CFAE was defined as a mean bipolar cycle length of ≤ 120 ms with an intervening isoelectric interval of more than 50 ms (Group 1A, n = 63, rapid repetitive CFAEs) or continuous fractionated activity (Group 1B, n = 59, continuous fractionated CFAEs), measured over a 7.2‐second duration. Group 2 consisted of those with a bipolar cycle length of more than 120 ms (n = 101). Results: The Group 1A CFAE sites exhibited a shorter unipolar electrogram cycle length (129 ± 11 vs 164 ± 20 ms, P < 0.001), and higher percentage of an S‐wave predominant pattern (QS or rS wave, 63 ± 13% vs 35 ± 13%, P < 0.001) than the Group 2 non‐CFAE sites. There was a linear correlation between the bipolar and unipolar cycle lengths (P < 0.001, R = 0.87). Most of the Group 1A CFAEs were located over arrhythmogenic pulmonary vein ostia or nonpulmonary vein ectopy with repetitive activations from those ectopies (62%) or the pivot points of the turning wavefronts (21%), whereas the Group 1B CFAEs exhibited a passive activation (44%) or slow conduction (31%). Conclusions: The bipolar repetitive and continuous fractionated CFAEs represented different activation patterns. The former was associated with an S wave predominant unipolar morphology which may represent an important focus for maintaining AF. (J Cardiovasc Electrophysiol, Vol. 21, pp. 640‐648, June 2010)     

Catheter ablation of persistent atrial fibrillation: The importance of substrate modification

Accumulating data have shown that elimination of atrial fibrillation (AF) sources should be the goal in persistent AF ablation. Pulmonary vein isolation, linear lesions and complex fractionated atrial electrograms (CFAEs) ablation have shown limited efficacy in patients with persistent AF. A combined approach using voltage, CFAEs and dominant frequency (DF) mapping may be helpful for the identification of AF sources and subsequent focal substrate modification. The fibrillatory activity is maintained by intramural reentry centered on fibrotic patches. Voltage mapping may assist in the identification of fibrotic areas. Stable rotors display the higher DF and possibly drive AF. Furthermore, the single rotor is usually consistent with organized AF electrograms without fractionation. It is therefore quite possible that rotors are located at relatively “healthy islands” within the patchy fibrosis. This is supported by the fact that high DF sites have been negatively correlated to the amount of fibrosis. CFAEs are located in areas adjacent to high DF. In conclusion, patchy fibrotic areas displaying the maximum DF along with high organization index and the lower fractionation index are potential targets of ablation. Prospective studies are required to validate the efficacy of substrate modification in left atrial ablation outcomes.     

Complex fractionated electrograms in the right atrial free wall and the superior/posterior wall of the left atrium are affected by activity of the autonomic nervous system

CFAEs and Autonomic Nervous System . Background: Complex fractionated atrial electrograms (CFAEs) are supposed to be related to structural and electrical remodeling. Animal studies suggest a role of the autonomic nervous system (ANS). However, this has never been studied in humans. Objective: The goal of this study was to investigate the influence of ANS on CFAEs in patients with idiopathic atrial fibrillation (AF). Methods: Thirty‐six patients (28 men, 55 ± 9 years) were included before undergoing catheter ablation. In the 24 hours preceding the procedure, 20 patients were in AF (group 1) and 16 were in sinus rhythm (SR, group 2). With 2 decapolar catheters, 1 in the right atrium (RA) and 1 in the left atrium (LA), 20 unipolar electrograms were simultaneously recorded during a 100‐second AF‐period (in group 2 after induction of AF). After atropine and metoprolol administration, a second 100‐second AF‐period was recorded 30 minutes later. Five patients of group 2 served as controls and did not receive atropine and metoprolol prior to the second recording. CFAEs were assessed and the prevalence of CFAEs was expressed as percentage of the recording time. Results: The prevalence of CFAEs was greater in group 1 than in group 2 in both RA and LA (P = 0.026, P < 0.001, respectively). Atropine and metoprolol significantly reduced CFAEs in group 1 (P < 0.001) and prevented the time‐dependent increase of CFAEs in group 2. Conclusion: The prevalence of CFAEs is greater in long‐lasting AF episodes. Atropine and metoprolol administration reduces CFAEs in both atria. Thus, CFAEs are at least partly influenced by the ANS. (J Cardiovasc Electrophysiol, Vol. 23, pp. 26‐33, January 2012)