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.     

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)     

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)     

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.     

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)     

Incidence and Significance of Early Recurrences Associated with Different Ablation Strategies for AF: A STAR‐AF Substudy

Early Recurrence in STAR‐AF. Background: Early recurrences of atrial tachyarrhythmias (ERAT) are common after atrial fibrillation (AF) ablation, and predict late recurrences (LR). We sought to determine the impact of different ablation strategies on ERAT and LR. Methods and Results: The STAR‐AF trial randomized 100  patients with paroxysmal or persistent AF to ablation of complex fractionated electrograms (CFAE) alone, pulmonary vein isolation (PVI) alone, or combined PVI + CFAE. Patients were followed for 12  months. ERAT was defined as any recurrence of AF, atrial tachycardia, or flutter (AT/AFL) >30 seconds during the first 3  months of follow‐up. LR was defined as any recurrence of AF/AT/AFL >30 seconds 3–12  months post. Forty‐nine patients experienced ERAT. The index ablation strategy was the only independent predictor of ERAT on multivariate analysis (HR 2.24 PVI vs PVI + CFAE; and HR 2.65 CFAE vs PVI + CFAE). Fifty‐two patients experienced LR. The presence of ERAT (HR 3.23), the use of antiarrhythmic drug (AAD) in the first 3  months postablation (HR 2.85), and the index ablation strategy were independently associated with LR (HR 3.42 PVI vs PVI + CFAE; HR 4.72 CFAE vs PVI + CFAE). Thirty‐five of 49 (71%) patients with ERAT and 17 (33%) of 51  patients without ERAT had LR (P  < 0.0001). Among patients with ERAT, increased left atrium size (HR 1.08), the use of AAD in the first 3  months postablation (HR 2.86) and the index ablation strategy were independently associated with LR (HR 4.77 PVI vs PVI + CFAE; HR 4.45 CFAE vs PVI + CFAE). Conclusion: ERAT is common following AF ablation and is strongly associated with LR. Although CFAE ablation alone results in higher rates of early and LR, the addition of CFAE to PVI results in increased long‐term success without an increase in ERAT. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1295‐1301, December 2012)     

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.     

The Modified Ablation Guided by Ibutilide Use in Chronic Atrial Fibrillation (MAGIC-AF) Study: clinical background and study design

The MAGIC‐AF Study. Background: Beyond pulmonary vein isolation (PVI), adjuvant ablation at the sites of complex fractionated atrial electrograms (CFAE) has been shown to improve the long‐term success of catheter ablation of persistent atrial fibrillation (AF). However, this approach often requires extensive ablation due to the widespread distribution of CFAE within the left atrium. An optimal strategy would identify areas of CFAE which, when selectively targeted with ablation, result in AF termination with an acceptable long‐term freedom from AF. It is possible that the intraprocedural administration of an antiarrhythmic drug may help accomplish this. Objective: The Modified Ablation Guided by Ibutilide Use in Chronic AF (MAGIC‐AF) Study is an international multicenter prospective randomized double‐blinded clinical trial assessing the utility of the intraprocedural administration of 0.25 mg of intravenous ibutilide before performing CFAE ablation. The primary efficacy endpoint of this study will be the freedom from AF at 1 year after a single procedure off antiarrhythmic agents. Safety endpoints will include procedural and radiofrequency ablation time as well as overall procedural complication rate. Methods: Patients undergoing a first ever catheter ablation procedure for persistent AF will be included. Individuals with hypertrophic cardiomyopathy, complex congenital heart disease including atrial septal defects, and ejection fraction <35% will be excluded from the study. All patients will first undergo PVI. Those patients who remain in AF will then be randomized in a 1:1 fashion to receive either 0.25 mg intravenous ibutilide or saline placebo followed by a CFAE based ablation strategy. Two hundred randomized patients will be enrolled in this study—100 in each study arm. Conclusion: The MAGIC‐AF study will assess the utility of a combined pharmaco‐ablative strategy in patients with persistent AF undergoing a CFAE based ablation strategy.     

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.     

Selective CFAE targeting for atrial fibrillation study (SELECT AF): clinical rationale, design, and implementation

SELECT AF Methodology & Rationale. Background: Adjuvant ablation of complex fractionated atrial electrograms (CFAE) in addition to pulmonary vein isolation (PVI) likely improves procedural outcome compared to PVI alone, particularly in patients with persistent atrial fibrillation (AF). However, CFAE regions can be extensive, occasionally requiring a large amount of extra ablation. Some CFAE regions may also represent passive wavefront collision and may not require ablation. Thus, there is interest in identifying more selective CFAE sites that are critical to AF perpetuation, minimizing the amount of adjuvant ablation that must be performed. Objective: The SELECT AF study is a prospective, multicenter, randomized trial comparing a strategy of PVI plus generalized CFAE ablation versus a strategy of PVI plus selective CFAE ablation, focusing on regions of continuous electrical activity (CEA). The primary efficacy endpoint is freedom from atrial arrhythmia at 1 year and the primary safety endpoint is total radiofrequency (RF) delivery time per procedure. Methods: Patients undergoing a first time ablation procedure for symptomatic persistent AF will be included. Patients with permanent AF or with left atrial size ≥55 mm will be excluded. Patients will all receive PVI at the time of their ablation, but will be randomized 1:1 to receive adjuvant CFAE ablation using the traditional “generalized” approach, or a “selective” approach targeting only CEA regions. Both strategies will be guided by automated mapping algorithms. This study will enroll a minimum of 80 evaluable subjects; 40 in each randomization group. Conclusions: SELECT AF is a randomized trial in patients with persistent AF to evaluate the efficacy of selective versus generalized CFAE ablation in addition to traditional PVI. (J Cardiovasc Electrophysiol, Vol. 22, pp. 541‐547 May 2011)     

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)     

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.     

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)     

Complex electrograms within the coronary sinus: time- and frequency-domain characteristics, effects of antral pulmonary vein isolation, and relationship to clinical outcome in patients with paroxysmal and persistent atrial fibrillation

Background: The mechanistic and clinical significance of complex fractionated atrial electrograms (CFAE) in the coronary sinus (CS) has been unclear. Methods and Results: Antral pulmonary vein isolation (APVI) was performed in 77 patients with paroxysmal (32) or persistent AF (45). CS electrograms recorded for 60 seconds before and after APVI were analyzed in the time‐ and frequency‐domains. Dominant frequency (DF), complexity index (CI: change in polarity of depolarization), and fractionation index (FI: change in direction of depolarization slope) were determined. Before APVI, there was no difference in DF, CI, or FI between paroxysmal and persistent AF. APVI resulted in a significant decrease in DF, CI, and FI in all patients. Baseline CI (43 ± 13/s vs 54 ± 14/s, P = 0.03) and FI (64 ± 23/s vs 87 ± 30/s, P = 0.02) were lower in patients with paroxysmal AF who had AF terminated by ablation than who did not. At 10 ± 2 months, 69% of patients with paroxysmal AF and 49% of patients with persistent AF were free from AF after single ablation. Baseline CI was higher among patients with paroxysmal AF who had AF after APVI (56 ± 20/s vs 44 ± 10/s, P = 0.03). In patients with persistent AF, there was a larger decrease in DF after APVI among patients who remained free from AF (13 ± 11% vs 7 ± 9%, P < 0.05). Conclusions: Complexity of CS electrograms may reflect drivers of AF that perpetuate paroxysmal AF after APVI. In persistent AF, the extent to which APVI decreases DF in the CS correlates with efficacy, suggesting that DF identifies patients who may require additional ablation beyond APVI.     

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)     

Efficacy of cardiac autonomic denervation for atrial fibrillation: a meta-analysis

Cardiac Autonomic Denervation and AF. Introduction : Adjunctive complex fractionated atrial electrograms (CFAE) ablation or ganglionated plexi (GP) ablation have been proposed as new strategies to increase the elimination of AF, but the difference between CFAE/GP ablation and pulmonary vein isolation (PVI), as well as the combined effect of CFAE/GP plus PVI ablation were unclear. This meta‐analysis was designed to determine whether adjunctive cardiac autonomic denervation (CAD) was effective for the elimination of AF, and whether CAD alone was superior to PVI in AF patients. Methods: A systemic literature search in MEDLINE, EMBASE, and Cochrane Controlled Trials Register (CCRT) was performed and controlled trials comparing the effect of PVI plus CFAE/GP ablation with PVI, as well as CFAE/GP ablation with PVI were collected. Results : A total of 15 trials including 1,147 patients with AF were qualified for this meta‐analysis. CAD plus PVI significantly increased the freedom from AF/ATs (OR 1.85, 95% CI: 1.33–2.59, P = 0.29). Subgroup analysis showed that additional CAD increased the ratio of sinus rhythm maintenance in both paroxysmal AF (OR 1.69; 95% CI: 1.09–2.62, P = 0.41) and nonparoxysmal AF (OR 2.11, 95% CI: 1.14–3.90, P = 0.14). Besides, when compared respectively, adjunctive CAD was not superior to PVI (OR 0.31; 95% CI: 0.11–0.86, P = 0.002). Conclusion : This study suggested that CAD plus PVI significantly increase the freedom from recurrence of AF both in paroxysmal and nonparoxysmal patients. However, when compared alone, the benefit of CAD was not superior to PVI. (J Cardiovasc Electrophysiol, Vol. 23, pp. 592–600, June 2012)