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.     

Impact of Pharmacological Autonomic Blockade on Complex Fractionated Atrial Electrograms

Autonomic Blockade During Atrial Fibrillation . Introduction: The influence of the autonomic nervous system on the pathogenesis of complex fractionated atrial electrograms (CFAE) during atrial fibrillation (AF) is incompletely understood. This study evaluated the impact of pharmacological autonomic blockade on CFAE characteristics. Methods and Results: Autonomic blockade was achieved with propanolol and atropine in 29 patients during AF. Three‐dimensional maps of the fractionation degree were made before and after autonomic blockade using the Ensite Navx^® system. In 2 patients, AF terminated following autonomic blockade. In the remaining 27 patients, 20,113 electrogram samples of 5 seconds duration were collected randomly throughout the left atrium (10,054 at baseline and 10,059 after autonomic blockade). The impact of autonomic blockade on fractionation was assessed by blinded investigators and related to the type of AF and AF cycle length. Globally, CFAE as a proportion of all atrial electrogram samples were reduced after autonomic blockade: 61.6 ± 20.3% versus 57.9 ± 23.7%, P = 0.027. This was true/significant for paroxysmal AF (47 ± 23% vs 40 ± 22%, P = 0.003), but not for persistent AF (65 ± 22% vs 62 ± 25%, respectively, P = 0.166). Left atrial AF cycle length prolonged with autonomic blockade from 170 ± 33 ms to 180 ± 40 ms (P = 0.001). Fractionation decreases only in the 14 of 27 patients with a significant (>6 ms) prolongation of the AF cycle length (64 ± 20% vs 59 ± 24%, P = 0.027), whereas fractionation did not reduce when autonomic blockade did not affect the AF cycle length (58 ± 21% vs 56 ± 25%, P = 0.419). Conclusions: Pharmacological autonomic blockade reduces CFAE in paroxysmal AF, but not persistent AF. This effect appears to be mediated by prolongation of the AF cycle length. (J Cardiovasc Electrophysiol, Vol. pp. 766‐772, July 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 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)     

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.     

Electrophysiologic Characteristics of Complex Fractionated Atrial Electrograms in Patients with Atrial Fibrillation

Introduction: The underlying mechanisms of complex fractionated atrial electrogram (CFAE) during radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) have not yet been clearly elucidated. We explored the relationships between CFAE and left atrial (LA) voltage, or conduction velocity (CV).
Methods and Results: In 50 patients with AF (23 paroxysmal AF [PAF], 41 males, mean age 55.76 ± 10.16 years), the CFAE (average index of fractionation of electrograms during AF by interval-analysis algorithm, cycle length [CL]≤ 120 ms) areas, voltage, and CV were measured at eight different quadrants in each patient's LA by analyzing a NavX-guided, color-coded CFAE CL map, a voltage map, and an isochronal map (500 ms pacing) generated by contact bipolar electrograms (70–100 points in the LA). The results were: (1) CFAE areas were predominantly located in the septum, roof, and LA appendage; (2) CFAE area had lower voltage than those in non-CFAE area and was surrounded by the areas of high voltage (P < 0.0001); (3) The CFAE areas had low CVs compared with non-CFAE areas (P < 0.001); and (4) The percentage of CFAE area was lower in patients with persistent atrial fibrillation (PeAF) compared with those with PAF (P < 0.05).
Conclusions: The CFAE area, which is primarily located at the septum, has a low voltage with a lower CV, and is surrounded by high-voltage areas. Underlying electroanatomical complexity is associated with clustering of CFAEs.     

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.     

The Relationship Between Electrogram Cycle Length and Dominant Frequency in Patients with Persistent Atrial Fibrillation

Introduction: Sites of complex fractionated atrial electrograms (CFAE) with a short mean cycle length (MCL) and sites with a high dominant frequency (DF) have been advocated as targets for ablation in patients with persistent atrial fibrillation (AF). However, there are little data on the relationship between theses 2 markers. This study assessed the relationship between the DF and electrogram MCL after pulmonary vein (PV) isolation in patients with persistent AF. Methods and Results: A total of 44 patients with persistent AF were studied. Four‐second bipolar electrograms were obtained with a multielectrode mapping catheter at regions throughout the left atrium after isolation of the pulmonary veins, with analysis of the MCL and DF at each site. The DF was defined as the largest frequency peak within a 2.5‐ to 16‐Hz spectral profile generated with fast Fourier transformation of the electrogram. A total of 9,262 electrograms from the 44 patients were analyzed. The average MCL and DF post‐PV isolation were 135 ± 24 ms and 6.1 ± 0.6 Hz, respectively. There was a statistically significant but weak correlation between the MCL and DF (r = 0.21, P < 0.001). Additionally, analysis of this relationship within each patient did not demonstrate a strong correlation (range of r values per patient =?0.18 to 0.47). Conclusions: There is a poor correlation between the electrogram MCL and DF in patients with persistent AF. Ablation strategies targeting DF and those targeting CFAE are therefore unlikely to direct ablation toward similar left atrial sites. Comparative studies are necessary to determine the effectiveness of each strategy in guiding catheter ablation of persistent AF.     

Optimized Measurement of Activation Rate at Left Atrial Sites with Complex Fractionated Electrograms During Atrial Fibrillation

Local Activation Rate in Atrial Fibrillation. Background: Complex fractionated atrial electrograms (CFAE) have become targets for catheter ablation of atrial fibrillation (AF). Frequency components of AF signals have also become important markers for identifying potential mechanisms of AF, yet inaccuracies exist, particularly in standard dominant frequency (SDF) calculations especially at CFAE sites. We developed new methodology to improve accuracy of AF rate determinations at such recording sites. Objective: To develop optimal methods for estimating activation rates in paroxysmal and persistent AF. Methods: Electrograms were obtained from one right atrial, coronary sinus, and 6 left atrial (LA) endocardial regions manifesting CFAEs in paroxysmal (N = 7) and persistent (N = 7) AF patients. SDF was measured from 8.4 s intervals and compared to (1) optimized DF (ODF) calculated by optimizing the filter coefficients which maximized dominant frequency power, (2) autocorrelation (AC), with the rate estimated as the inverse of the signal phase shift generating the largest autocorrelation coefficient, and (3) ensemble average (EA), with the rate estimated by summing successive signal segments and selecting segment length yielding maximum power. Rate measurements were compared between groups, at baseline and with additive interference, having similar frequency content to the electrograms, to test the robustness of the different methods. Results: From pooled data (N = 168 recording sites), a significantly higher LA dominant frequency was found in persistent versus paroxysmal patients using each method (P < 0.001), with a mean value for all methods of 6.23 ± 0.08 Hz versus 5.32 ± 0.10 Hz, respectively. At the highest additive interference level, the rate measurement error was significantly greater in SDF as compared with EA (P = 0.010) and ODF (P = 0.035), and at all interference levels SDF had the largest error of any method. Conclusions: SDF appears less robust to additive interference, compared to the ODF and EA methods of estimating the activation rate at CFAE sites in this small group of patients. Use of optimized filter coefficients for DF measurement, or use of correlative methods such as EA, that reinforce the signal rather than filtering the noise, may improve calculation of activation rates. (J Cardiovasc Electrophysiol, Vol. 21, pp. 133‐143, February 2010)     

Intraprocedural Use of Ibutilide to Organize and Guide Ablation of Complex Fractionated Atrial Electrograms: Preliminary Assessment of a Modified Step‐Wise Approach to Ablation of Persistent Atrial Fibrillation

Ibutilide Guided CFAE Ablation. Introduction: While able to achieve clinical success, the current step‐wise approach to persistent atrial fibrillation (AF) ablation requires considerable “substrate” ablation and frequently mandates multiple procedures to address consequent atrial tachycardias (ATs). An alternative strategy minimizing the amount of ablation while maintaining clinical success would be desirable. We hypothesize that intraprocedural administration of a low‐dose antiarrhythmic drug (AAD) during AF will organize areas of passive activation and not affect areas critical to AF maintenance, thereby potentially minimizing the ablation lesion set. Methods and Results: Eleven patients (age = 55 ± 6 years; LA = 48 ± 15 mm; median AF duration = 3 years) with persistent AF undergoing catheter ablation were enrolled in this exploratory prospective observational study. After pulmonary vein (PV) isolation, a mean cycle length (mCL) map was created and areas with mCL <120 ms were considered to represent complex fractionated atrial electrograms (CFAE). Ibutilide (0.25–1.0 mg) was then administered and a second mCL map created. Ablation lesions were placed at CAFE sites identified after ibutilide administration. Activation and/or entrainment mapping was employed to address ATs. The endpoint of ablation was achieving sinus rhythm. The average LA mCL increased (146 vs 165 ms, P = 0.01) and the LA CFAE surface area decreased after ibutilide administration. Additional ablation organized AF to either sinus rhythm or AT in 10/11 (91%) patients. After a median follow up of 455 days, 8 of 11 (72%) patients were free from AF. Three patients underwent a repeat ablation procedure (average 1.27 ablations/patient). Conclusions: Ibutilide administration may organize atrial activity and facilitate AF termination during ablation while minimizing the ablation lesion set. (J Cardiovasc Electrophysiol, Vol. 21, pp. 608‐616, June 2010)     

High-density mapping of atrial fibrillation in humans: relationship between high-frequency activation and electrogram fractionation

Introduction: Sites of complex fractionated atrial electrograms (CFAE) and dominant frequency (DF) have been implicated in maintaining atrial fibrillation (AF); however, their relationship is poorly understood. Methods and Results: Twenty patients underwent biatrial high‐density contact mapping (507 ± 150 points/patient) during AF. CFAE were characterized using software to quantify electrogram complexity (CFE‐mean). Spectral analysis determined the frequency with greatest power and sites of high DF with a frequency gradient. CFE‐mean was higher (less fractionated) for right compared with left atria (P < 0.001) and in paroxysmal compared with persistent AF (P < 0.001). DF was lower for right compared with left atria (P = 0.02) and in paroxysmal compared with persistent AF (P < 0.001). There was significant regional variation in DF in paroxysmal (P < 0.001) but not persistent AF. Highest DF points clustered together with 5.2 ± 1.7 clusters/patient. Correlation between CFE‐mean and DF was poor on a point‐by‐point basis (r =?0.17, P < 0.001), but moderate on an individual basis (r =?0.50, P = 0.03). Exploration of their spatial relationship demonstrated CFAE areas in close proximity (median 5 mm, IQR 2–10) to high DF sites; within 10 mm in 80% and 10–20 mm in 10%. Simultaneous activation mapping at these sites further supports this observation. Conclusion: Greater fractionation and higher DF are seen in persistent AF and left atria during AF. Preferential areas of high DF are observed in paroxysmal but not persistent AF. CFAE and DF correlate within an individual but not point‐by‐point. Exploration of their spatial relationship demonstrates CFAE in areas adjacent to high DF, and this is supported by activation mapping at these sites.     

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.     

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.     

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.     

Incidence of asymptomatic cerebral microthromboembolism after atrial fibrillation ablation guided by complex fractionated atrial electrogram

Cerebral Microthromboembolism After CFAE Ablation . Background: The incidence of cerebral thromboembolism after pulmonary vein isolation (PVI) ranges from 2% to 14%. This study investigated the incidence of cerebral thromboembolism after complex fractionated atrial electrogram (CFAE) ablation with or without PVI. Methods: One hundred consecutive atrial fibrillation (AF) patients (50 paroxysmal and 50 persistent, including 10 longstanding) who underwent CFAE ablation combined with (n = 41, PVI+CFAE group) or without (n = 59, CFAE group) PVI were studied. Coronary angiography (CAG) was conducted with AF ablation in 5 cases in which coronary artery stenosis was suspected on 3D‐computed tomography. PVI was performed before CFAE ablation without circular catheter during AF. After termination of AF, additional ablation was performed to complete PVI with a circular catheter. All patients underwent cerebral magnetic resonance imaging (MRI) including diffusion‐weighted MRI and T2‐weighted MRI the day after ablation. Results: New thromboembolism was detected in 7.0%, and there was no significant difference between the 2 strategies (7.3% in PVI+CFAE group, 6.8% in CFAE group). CHADS2 score (1.6 ± 1.0 vs 0.8 ± 0.9, P < 0.05), left atrial volume (LAV; 83.8 ± 27.1 vs 67.8 ± 21.8, P < 0.05), and left ventricular ejection fraction (LVEF, 53.1 ± 9.2 vs 65.1 ± 9.7, P < 0.01) were significantly different when comparing patients with or without thromboembolism. In multivariate analysis, LVEF (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.84–0.99; P < 0.05) and concomitant CAG (OR 18.82; 95% CI, 1.77–200.00; P < 0.05) were important predictors of new cerebral thromboembolism. Conclusions: The incidence of cerebral microthromboembolism after CFAE ablation was not greater than previous reports in PVI. Cautious management is required during AF ablation, especially in the patients with low LVEF. (J Cardiovasc Electrophysiol, Vol. 23, pp. 567–573, June 2012)     

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.     

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)     

Identifying the relationship between the non-PV triggers and the critical CFAE sites post-PVAI to curtail the extent of atrial ablation in longstanding persistent AF

Relationship Between the Non‐PV Triggers and the Critical CFAE Sites. Background: Complex fractionated atrial electrograms (CFAE) ablation has been performed in addition to pulmonary veins (PV) isolation to increase the success rate of atrial fibrillation (AF) ablation in patients with longstanding (LS) persistent AF. The mechanism underlying the clinical benefit of CFAE ablation remains, however, poorly understood. Objective: We compared the impact of CFAE ablation on the prevalence of non‐PV atrial triggers inducing AF in 2 groups of patients with LS persistent AF. One group underwent PVAI alone, and the other group underwent PVAI plus CFAE ablation. In addition, we correlated the site of non‐PV triggers with the presence of CFAE. Methods: A total of 98 consecutive patients with symptomatic drug refractory LS persistent AF presenting for ablation had a preablation electroanatomic CFAE map. Patients randomized to either isolation of the PVs and posterior wall (PVAI) (group I, n = 48 pts) or PVAI and biatrial ablation of CFAEs (group II, 50 pts). After ablation, infusion of isoproterenol up to 30 mcg/min was given to reveal non PV foci inducing AF. Those foci were mapped and correlated with CFAE regions and ablated. Results: A total of 19 patients (76%) with PV foci inducing AF were associated with either stable or transient CFAE after PVAI, respectively, in 12 patients (48%) and 7 patients (28%). A total of 20 (42%) non‐PV triggers were observed in group I versus 5 (10%) in group II (P < 0.001) in 18 and 5 patients, respectively. After a mean f/u of 17.2 ± 5.2 months, 33 (69%) patients in group I and 36 (72%) patients in group II were in SR (P = NS). Conclusion: Non‐PV triggers inducing AF post‐PVAI were associated with the presence of stable or transient CFAE in 48% and 28% of cases, respectively, in LS persistent AF. CFAE ablation after PVAI was associated with a significantly higher elimination of those non‐PV triggers. This suggests that at least part of the beneficial effect achieved by CFAE ablation reflects elimination of non‐PV AF triggers. (J Cardiovasc Electrophysiol, Vol. pp. 1‐7)     

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)     

Substrate modification by pulmonary vein isolation and left atrial linear ablation in patients with persistent atrial fibrillation: its impact on complex-fractionated atrial electrograms

PV and Linear Ablation for CFAEs . Introduction: Linear ablations in the left atrium (LA), in addition to pulmonary vein (PV) isolation, have been demonstrated to be an effective ablation strategy in patients with persistent atrial fibrillation (PsAF). This study investigated the impact of LA linear ablation on the complex‐fractionated atrial electrograms (CFAEs) of PsAF patients. Methods and Results: A total of 40 consecutive PsAF patients (age: 54 ± 10 years, 39 males) who underwent catheter ablation were enrolled in this study. Linear ablation of both roofline between the right and left superior PVs and the mitral isthmus line joining from the mitral annulus to the left inferior PV were performed following PV isolation during AF. High‐density automated CFAE mapping was performed using the NAVX, and maps were obtained 3 times during the procedure (prior to ablation, after PV isolation, and after linear ablations) and were compared. PsAF was terminated by ablation in 13 of 40 patients. The mean total LA surface area and baseline CFAEs area were 120.8 ± 23.6 and 88.0 ± 23.5 cm² (74.2%), respectively. After PV isolation and linear ablations in the LA, the area of CFAEs area was reduced to 71.6 ± 22.6 cm² (58.7%) (P < 0.001) and 44.9 ± 23.0 cm² (39.2%) (P < 0.001), respectively. The LA linear ablations resulted in a significant reduction of the CFAEs area percentage in the region remote from ablation sites (from 56.3 ± 20.6 cm² (59.6%) to 40.4 ± 16.5 cm² (42.9%), P < 0.0001). Conclusion: Both PV isolation and LA linear ablations diminished the CFAEs in PsAF patients, suggesting substrate modification by PV and linear ablations. (J Cardiovasc Electrophysiol, Vol. 23, pp. 962‐970, September 2012)