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.     

Spectral profiles of complex fractionated atrial electrograms are different in longstanding and acute onset atrial fibrillation atrial electrogram spectra

Spectral Profiles of CFAE. Background: Spectral analysis of complex fractionated atrial electrograms (CFAE) may be useful for gaining insight into mechanisms underlying paroxysmal and longstanding atrial fibrillation (AF). The commonly used dominant frequency (DF) measurement has limitations. Method: CFAE recordings were acquired from outside the 4 pulmonary vein ostia and at 2 left atrial free wall sites in 10 paroxysmal and 10 persistent AF patients. Two consecutive 8s‐series were analyzed from recordings >16s in duration. Power spectra were computed for each 8s‐series in the range 3–12 Hz and normalized. The mean and standard deviation of normalized power spectra (MPS and SPS, respectively) were compared for paroxysmal versus persistent CFAE. Also, the DF and its peak amplitude (ADF) were compared for pulmonary vein sites only. Power spectra were computed using ensemble average and Fourier methods. Results: No significant changes occurred in any parameter from the first to second recording sequence. For both sequences, MPS and SPS were significantly greater, and DF and ADF were significantly less, in paroxysmals versus persistents. The MPS and ADF measurements from ensemble spectra produced the most significant differences in paroxysmals versus persistents (P < 0.0001). DF differences were less significant, which can be attributed to the relatively high variability of DF in paroxysmals. The MPS was correlated to the duration of uninterrupted persistent AF prior to electrophysiologic study (P = 0.01), and to left atrial volume for all AF (P < 0.05). Conclusions: The MPS and ADF measurements introduced in this study are probably superior to DF for discerning power spectral differences in paroxysmal versus longstanding CFAE. (J Cardiovasc Electrophysiol, Vol. 23, pp. 971‐979, September 2012)     

Prospective study of atrial fibrillation termination during ablation guided by automated detection of fractionated electrograms

Introduction: Complex fractionated atrial electrograms (CFAE) may identify critical sites for perpetuation of atrial fibrillation (AF) and provide useful targets for ablation. Current assessment of CFAE is subjective; automated detection algorithms may improve reproducibility, but their utility in guiding ablation has not been tested.
Methods and Results: In 67 patients presenting for initial AF ablation (42 paroxysmal, 25 persistent), LA and CS mapping were performed during induced or spontaneous AF. CFAE were identified by an online automated computer algorithm and displayed on electroanatomical maps. A mean of 28 ± 18 sites/patient were identified (20 ± 13% of mapped sites), and were more frequent during persistent AF. CFAE occurred most commonly within the CS, on the atrial septum, and around the pulmonary veins. Ablation initially targeting CFAE terminated AF in 88% of paroxysmal AF, but only 20% of persistent AF (P < 0.001). Subsequently, additional ablation was performed in all patients (PV isolation for paroxysmal AF, PV isolation + mitral and roof lines for persistent AF). Minimum follow-up was 1 year. One-year freedom from recurrent atrial arrhythmias without antiarrhythmic drug therapy after a single procedure was 90% for paroxysmal AF, and 68% for persistent AF.
Conclusions: Ablation guided by automated detection of CFAE proved feasible, and was associated with a high AF termination rate in paroxysmal, but not persistent AF. As an adjunct to conventional techniques, it was associated with excellent long-term single procedure outcomes in both groups. Criteria for identifying optimal CFAE sites for ablation, and selection of patients most likely to benefit, require additional study.     

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)     

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 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.     

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.     

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.     

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)     

Radiofrequency ablation of complex fractionated atrial electrograms (CFAE): preferential sites of acute termination and regularization in paroxysmal and persistent atrial fibrillation

Introduction: Complex fractionated atrial electrograms (CFAE) have been described as a new target for ablation of atrial fibrillation (AF). This prospective study evaluates the acute effects of CFAE ablation in patients with paroxysmal or persistent AF and analyzes the preferential anatomic sites where these effects occur.
Methods and Results: Ablation of CFAE was performed in 66 symptomatic patients (mean age of 58 ± 12 years) with paroxysmal (n = 36) or persistent AF (n = 30). Termination or regularization of AF during ablation of CFAE was achieved in 56 of 66 patients (84%), with termination in 28 of 66 patients (42%) and regularization of AF in 28 of 66 patients (42%). Ablation of CFAE showed no effect in 10 of 66 patients (16%). Termination of AF occurred at 53 sites and AF regularization at 81 sites. The preferential sites of AF termination or regularization were found around the pulmonary veins (termination n = 15; regularization n = 22), at the anterior wall (termination n = 14; regularization n = 19) and at the interatrial septum (termination n = 8; regularization n = 17).
Conclusion: Termination or regularization of AF was achieved acutely in 84% of patients by ablation of CFAE. The preferential sites of AF termination or regularization were found around the pulmonary veins, at the anterior wall of the LA and at the interatrial septum. These findings may have implications for future ablation concepts.     

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)     

Prevalence and characteristics of continuous electrical activity in patients with paroxysmal and persistent atrial fibrillation

Background: Complex fractionated atrial electrograms (CFAEs) may play a role in the genesis of atrial fibrillation (AF). One type of CFAE is continuous electrical activity (CEA). The prevalence and characteristics of CEA in patients with paroxysmal and persistent AF are unclear.
Methods and Results: In 44 patients (age = 59 ± 8 years) with paroxysmal (25) or persistent (19) AF, bipolar electrograms were systematically recorded for ≥5 seconds at 24 left atrial (LA) sites, including 8 antral sites, and 2 sites within the coronary sinus (CS). CEA was defined as continuous depolarization for > 1 second with no isoelectric interval. CEA was recorded at the LA septum (79%), antrum (66%), posterior (68%) and anterior walls (67%), roof (66%), base of the LA appendage (61%), inferior wall (61%), posterior mitral annulus (48%), CS (41%), and in the LA appendage (14%). Antral CEA was equally prevalent in patients with paroxysmal (63%) and persistent AF (70%, P = 0.12). In patients with paroxysmal AF, the prevalence of CEA was similar among antral and nonantral LA sites, except for the LA appendage. However, in patients with persistent AF, CEA was more prevalent at the nonantral (80%) than antral sites (70%, P = 0.03). CEA at nonantral sites except the CS was more prevalent in persistent than in paroxysmal AF (80% vs 57%, P < 0.001). The mean duration of intermittent episodes of CEA was longer in persistent than in paroxysmal AF (P < 0.001).
Conclusions: The higher prevalence and duration of CEA at nonantral sites in persistent than in paroxysmal AF is consistent with a greater contribution of LA reentrant mechanisms in persistent AF. However, the high prevalence of CEA at nonantral sites in paroxysmal atrial fibrillation (PAF) suggests that CEA alone is a nonspecific marker of appropriate target sites for ablation of AF. The characteristics of CEA that most accurately identify drivers of AF remain to be determined.     

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.     

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)     

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)     

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)