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Introduction: The optimal substrate ablation approach in patients with persistent atrial fibrillation (Per AF) remains unclear. This was a prospective randomized study comparing the efficacy of limited (continuous complex fractionated atrial electrogram, CFAE: <60 milliseconds) versus extensive (continuous CFAE plus variable CFAE: <120 milliseconds) atrial substrate modification in Per AF patients., Methods and Results: We enrolled 120 Per AF patients in the study, and 30 patients with AF termination after pulmonary vein isolation (PVI) were excluded. In the remaining 90 patients, 45 were treated with limited approach (Group 1) and 45 with an extensive approach (Group 2). The end point of the study was the incidence of an atrial arrhythmia recurrence postblanking period. The patients were followed up for 15 months with 3-month clinical reviews, electrograms (ECGs), Holter recordings, and echocardiographic monitoring. Procedural AF termination and the single procedural efficacy were statistically comparable between the 2 groups (48.9% vs. 63.4% in Groups 1 and 2, respectively, P = 0.289). During the follow-up, patients who received limited ablation had a lower incidence of recurrent AFL (P = 0.04), and better reverse remodeling of the left atrium (LA, P = 0.04). After 2 procedures, the freedom from any atrial arrhythmia was better in Group 2 (62.2% vs. 87.8%, P = 0.009). Those with longstanding AF and a larger baseline LA size responded better to the extensive ablation., Conclusions: In the Per AF patients who failed to achieve AF termination after PVI alone, a specific atrial substrate modification approach targeting only continuous CFAEs could be considered as an initial ablation strategy., (© 2014 Wiley Periodicals, Inc.)

Introduction: Pulmonary vein isolation (PVI) is the primary ablation therapy in patients with atrial fibrillation (AF). We hypothesized that high dominant frequency (DF) sites (AF nests during sinus rhythm [SR]) adjacent to the PV ostia are associated with the atrial substrate that maintains AF, and PVI incorporating the high-frequency AF nests may have a higher efficacy., Methods and Results: In a prospective and randomized comparison, 126 symptomatic paroxysmal AF patients that underwent PVI were enrolled. We compared the efficacy of a modified PVI (ablation line: 1.0-1.5 cm from the PV ostium with encircling the AF nests [spectral analysis with DF >70 Hz during SR, Group II]) versus the anatomy-guided conventional PVI (Group I). In Group II, the DF value along the PV ostium was lower than 70 Hz after the PVI. The primary endpoint was the freedom from symptomatic atrial arrhythmias after a single procedure. We also followed the autonomic function by a time-domain analysis of the heart rate variability. In both groups, AF nests were observed and electric isolation was successfully obtained in all patients. With a mean duration of 16 ± 6.1 months of follow-up, Group II had a higher single procedure efficacy without drugs (78.7% vs 66.1%, log-rank test: P = 0.02), and fewer repeat procedures (6.6% vs 23%; P = 0.04), as compared to Group I., Conclusion: PVI incorporating the high frequency AF nests adjacent to the PV ostia had a better single procedure efficacy., (© 2012 Wiley Periodicals, Inc.)

Background: Sinus node (SN) activity is difficult to assess during atrial fibrillation (AF). The aim of the present study was to investigate SN activity by frequency analysis during AF., Methods: Thirteen patients with paroxysmal AF and atrial flutter in the right atrium (RA) underwent 3-dimensional noncontact mapping. The fibrillatory activity was recorded from a multielectrode array in the RA. A frequency analysis with 2- and 6-second time-segment lengths was performed. Spectral characteristics (dominant frequency and harmonic index) and isopotential activation maps were used to investigate the spatiotemporal activity of the SN region and the rest of the RA (crista terminalis, septum, and free wall) during the initiation, while ongoing, and before the termination of AF., Results: With duration of 6 seconds, the whole RA had similar trends of frequency distribution. With duration of 2 seconds prior to termination, the SN region exhibited a trend of low-frequency pattern and high-organization distribution, compared with the segments for the 2 to 4 and 4 to 6 seconds before termination. The isopotential activation maps showed the spontaneous earliest activities had wave front propagation patterns similar to those during sinus rhythm (after termination)., Conclusions: The fibrillatory activity of the SN region was organized, and slow activation was detected, by frequency analysis and isopotential mapping, within 2 seconds just prior to AF termination., (Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: There is a paucity of data regarding the mechanism of maintaining atrial fibrillation (AF) after pulmonary vein isolation (PVI) in patients with AF. The aim of this study was to examine the impact of circumferential PVI on the left atrial (LA) substrate characteristics., Methods and Results: Seventy-two AF patients (age, 53+/-11 years) underwent mapping and catheter ablation using an NavX system. The biatrial characteristics such as the complex fractionated atrial electrograms (CFEs; based on fractionated intervals) and frequency analysis (based on dominant frequencies) were mapped before and after PVI. PVI with electric isolation was performed in all patients. In the 45 patients who did not respond to PVI, the continuous CFEs (>8 seconds, 18+/-18% and 12+/-17% of the LA sites, before and after PVI, respectively, P=0.02), degree of LA fractionation (mean fractionated interval: 75.6+/-14.3 msec versus 87.3+/-16.7 msec, P=0.001), and mean LA dominant frequencies (6.92+/-0.88 Hz versus 6.58+/-0.91 Hz, P=0.001) decreased after PVI. Complete PVI altered the distribution of the CFEs toward the LA anteroseptum, mitral annulus, and LA appendage regions. A persistent presence of continuous CFEs in the vicinity of the dominant frequencies sites (observed in 53% patients) correlated with a higher procedural AF termination rate for the CFE ablation (63% versus 23%, P<0.05)., Conclusions: Complete PVI eliminated some CFEs in the LA and altered the distribution of the CFEs. The persistent presence of CFEs before and after PVI in the vicinity of the high frequency sites is important for AF maintenance after PVI.

Background: The efficacy of ablation of complex fractionated atrial electrograms (CFEs) in the single ablation procedure for nonparoxysmal atrial fibrillation (AF) patients is not well demonstrated. The aim of this study was to compare the ablation strategies of pulmonary vein isolation (PVI) plus linear ablation with and without additional ablation ofCFEs in these patients., Methods: Consecutive 60 patients (49 +/- 11 years old, 50 male, 10 female) with nonparoxysmal AF underwent catheter ablation guided by a NavX mapping system. A stepwise approach included a circumferential PVI and left atrial (LA) linear ablation followed by either the additional ablation of continuous CFEs in the LA/coronary sinus (the first 30 patients) or not (the second 30 patients), detected by an automatic algorithm., Results: There was no difference in the baseline characteristics between the two groups. Complete PVI eliminated some continuous CFEs and altered the distribution of CFEs. Following PVI and linear ablation,the remaining continuous CFEs were identified in 7.9 +/-10% mapping sites of the LA and CS, and were ablated successfully with a procedural AF termination rate of 53%. With a follow-up of 19 +/-11 months, a Kaplan-Meier analysis showed that the patients with additional ablation of the CFEs had a higher rate of sinus rhythm maintenance. Multivariate analysis showed the single procedure success could be predicted by the procedural AF termination and the additional ablation of continuous CFEs in the LA/CS., Conclusions: Ablation of continuous CFEs after PVI and LA linear ablation had a better long-term efficacy based on the results of single-ablation procedure.

Background: Termination of atrial fibrillation (AF) can be achieved by catheter ablation. It has been used as one of the procedural endpoints for AF ablation., Objective: The purpose of this study was to investigate the factors that predict AF termination and the association with long-term outcomes., Methods: Eighty-five consecutive AF patients (33 paroxysmal, 52 nonparoxysmal) underwent three-dimensional mapping and catheter ablation. A stepwise ablation approach included circumferential pulmonary vein (PV) isolation and left atrial (LA) linear ablation, followed by LA and right atrial (RA) electrogram-based (complex fractionated atrial electrogram) ablation. Clinical and electrophysiologic characteristics were assessed to evaluate the predictors of acute AF termination., Results: In univariate analysis, a diagnosis of paroxysmal AF, shorter AF history, absence of history of heart failure, smaller LA diameter, longer postablation coronary sinus cycle length, lower LA and RA mean dominant frequencies, lower RA max dominant frequency, and higher LA voltage were related to acute termination of AF during ablation. Multivariate analysis showed that smaller LA diameter and lower preablation mean RA dominant frequency were independent predictors of AF termination. Multivariate analysis also showed that larger LA diameter and the presence of RA non-PV ectopy during the index procedure could predict late recurrence during long-term (13 +/- 8 months) follow-up., Conclusion: LA size and RA non-PV drivers are important for acute termination of AF and for long-term success. Careful selection of patients, extensive RA mapping, and LA ablation may enhance long-term ablation efficacy.

Background: Regions of rapid and multiple deflections can be identified with high dominant frequency (DF) during sinus rhythm (SR). These areas may play a role in the perpetuation of atrial fibrillation (AF) and indicate an atrial substrate abnormality., Objective: The purpose of this study was to investigate the atrial substrate properties of the high-frequency sites in patients with paroxysmal AF., Methods: Forty patients (52 +/- 12 years of age) with paroxysmal AF were studied using a three-dimensional mapping system. Spectral analysis was performed on the bipolar electrograms in the left atrium (LA) during SR. Overall, 7708 electrograms were analyzed, and the DFs higher than 70 Hz were labeled as abnormal., Results: The regional distribution of the high-DF sites in the LA could be divided into two types. Type 1 includes high-DF sites existing only in the pulmonary veins (PVs; n = 19, 6.6 +/- 3.4 sites/patient). Type 2 includes high-DF sites in the LA or LA plus the PVs (n = 21, 11 +/- 5.6 sites/patient). In type 1, PV isolation (PVI) could eliminate the AF with negative AF inducibility testing after the PVI in 89% of patients. In type 2, additional LA substrate modification was needed in 81% of patients because sustained AF was induced after the PVI (P<.001, compared with type 1). Multivariate analysis showed that the lower mean voltage of the LA and high-frequency sites distribution both independently predicted a positive AF inducibility after the PVI (P<.05)., Conclusions: Spectral analysis during SR can detect an abnormal atrial substrate. A regional distribution of the high-DF sites predicts the efficacy of the PVI.

Aims: Fibrillatory waves observed in the surface electrograms may be a direct reflection of the electrophysiologic mechanism of the atrial fibrillation (AF). This study compared the fibrillatory waves in the surface ECG and the individual intracardiac mapping sites in different types of paroxysmal AF., Methods and Results: Thirty patients with paroxysmal AF originating from the pulmonary veins (PVs) or superior vena cava (SVC) were enrolled. Frequency analysis was performed on the intracardiac electrograms recorded from various mapping sites in both atria sequentially with simultaneous surface electrogram recordings. The SVC-AF patients had a trend toward a higher DF in ECG lead V1 when compared with the PV-AF patients (7.35 +/- 2.09 vs. 5.89 +/- 0.79 Hz, P = 0.018). The mean dominant frequency (DF) of the LA mapping sites in the PV-AF patients was higher than that in the SVC-AF patients (7.06 +/- 0.66 vs. 6.13 +/- 0.96 Hz, P = 0.009), whereas the mean DF of the RA mapping sites was similar between the two groups (5.84 +/- 0.80 vs. 6.26 +/- 1.11 Hz, P = NS). The intra-class correlation coefficient (ICC) between the mean DF of the RA sites and V1 was higher (r = 0.21, P = 0.02) when compared with the mean DF of the LA sites (r = -0.007, P > 0.05). Furthermore, the maximal ICC was observed in the anterolateral RA free wall (r = 0.84, P < 0.001) and not the other anatomic sites of the RA and LA., Conclusion: The fibrillatory activity observed in ECG lead V1 correlated primarily with the activity of the anterolateral RA free wall and thus may be useful for detecting the AF source if it is close to that area.

Background: Temporal variation in complex fractionated atrial electrograms (CFAEs) exists during atrial fibrillation (AF)., Objective: This study sought to quantify the variation in CFAEs using a fractionation interval (FI) algorithm and to define the shortest optimal recording duration required to consistently characterize the magnitude of the fractionation., Methods: Twenty-seven patients undergoing AF mapping in the left atrium were studied. The FI and frequency analysis were performed at each mapped site for recording durations of 1 to 8 seconds. The magnitude of the fractionation was quantified by the FI algorithm, which calculated the mean interval between multiple, discrete deflections during AF. The results from each duration were statistically compared with the maximal-duration recording, as a standard. The FI values were compared with the dominant frequency values obtained from the associated frequency spectra., Results: The FIs obtained from recording durations between 5 and 8 seconds had a smaller variation in the FI (P < .05) and, for those sites with a FI < 50 ms, the fractionation was typically continuous. The fast-Fourier Transform spectra obtained from the CFAE sites with recording durations of >5 seconds harbored higher dominant frequency values than those with shorter recording durations (8.1 +/- 2.5 Hz vs. 6.8 +/- 0.98 Hz, P < .05). The CFAE sites with continuous fractionation were located within the pulmonary veins and their ostia in 77% of patients with paroxysmal AF, and in only 29% of patients with nonparoxysmal AF (P < .05)., Conclusion: The assessment of fractionated electrograms requires a recording duration of > or =5 seconds at each site to obtain a consistent fractionation. Sites with the shortest FIs consistently identified sites with the fastest electrogram activity throughout the entire left atrium and pulmonary veins.

Introduction: Noncontact mapping (NCM) can record virtual unipolar electrograms (Egs) from multiple sites simultaneously; therefore, it has the potential to perform simultaneous frequency mapping during atrial fibrillation (AF). The aim of this study was to validate the frequency spectra of the noncontact unipolar Egs in both atria., Methods: This study enrolled 12 patients (age = 61 +/- 16 years) with paroxysmal or persistent AF who underwent catheter ablation guided by NCM. Noncontact and contact unipolar Egs were recorded simultaneously. The cross-correlation of the Eg morphology, activation time difference of the time-domain signals, and resultant frequency spectra were compared via dominant frequency (DF) and magnitude-squared coherence (MSC)., Results: A total of 159 sites were analyzed during AF. The variables that independently predicted a higher correlation between the contact and noncontact electrogram morphology were a smaller activation timing difference P < 0.01), smaller distance of the mapping sites to the array center (P = 0.01), and higher atrial voltage (P = 0.03). However, the average MSC of the frequency band within the physiologic range of AF (2 to 15 Hz) was only affected by the activation timing difference (P = 0.002). The DF value between the contact and noncontact unipolar signals correlated well with each other throughout the right atria and left atria in 94% of the mapping sites (r = 0.87, P < 0.001)., Conclusion: The accuracy of the noncontact unipolar Eg morphology decreased when the mapping sites harbored a smaller atrial voltage and longer distance to the array center. The DF difference between the contact and noncontact unipolar Eg was not affected by the distance to the array center.

Objectives: This study sought to investigate the regional frequency distribution from multiple bi-atrial sites in different types of paroxysmal atrial fibrillation (AF)., Background: A previous study showed a left atrium (LA) to right atrium (RA) frequency gradient in patients with paroxysmal AF., Methods: Forty-four patients (age = 60 +/- 16, male patients = 27) with paroxysmal AF originating from the pulmonary veins (PVs) (n = 31) or superior vena cava (SVC) (n = 13) were included. Frequency analysis was performed on the intracardiac electrograms (7 s, 1 kHz/channel) recorded from PV, posterior LA, coronary sinus (CS), posterolateral RA, and SVC. The largest peak frequency was identified as the dominant frequency (DF)., Results: In the PV-AF patients, there was a frequency gradient from the PV ostium to the LA, RA, and SVC (8.5 +/- 3.3 Hz vs. 5.9 +/- 1.1 Hz vs. 5.2 +/- 0.85 Hz vs. 5.5 +/- 0.48 Hz, respectively, p < 0.001). The highest DFs were mostly located at the arrhythmogenic PV ostium (58%). The DFs of the arrhythmogenic PV and PV ostium were significantly higher than those of the non-arrhythmogenic PVs and PV ostia (p < 0.05). In the SVC-AF patients, there was a frequency gradient from the SVC to the RA, LA, and PV (8.0 +/- 2.4 Hz vs. 5.9 +/- 1.1 Hz vs. 5.9 +/- 0.7 Hz vs. 5.8 +/- 0.7 Hz, respectively, p = 0.001). The highest DFs were mostly located inside the SVC (77%) instead of the SVC ostium (as compared with PV-AF patients, p = 0.035)., Conclusions: The location of the highest DF depended on the arrhythmogenic PV or SVC. A frequency gradient was present between the arrhythmogenic thoracic vein and atrium in all patients.

Background: Catheter ablation of the right atrial (RA) substrate has had variable efficacy in curing paroxysmal atrial fibrillation (PAF), suggesting that RA substrate ablation can play an important role in the treatment of atrial fibrillation (AF) in some patients. The aim of this study was to investigate the electrophysiological characteristics and ablation strategy and its results in a specific group of patients with paroxysmal RA-AF., Methods and Results: The study population consisted of 13 patients (8 men; age, 64+/-15 years) with drug-refractory (2+/-1 drugs), frequent episodes of PAF. Provocation maneuvers did not reveal any ectopic beat-initiating AF. However, rapid atrial pacing easily induced AF. Activation mapping during sinus rhythm, atrial pacing, and AF was visualized by using a noncontact mapping system. Noncontact mapping revealed RA reentry (6 patients with single-loop circuits and 7 with double-loop circuits) with conduction through channels between lines of block, crista terminalis gaps, and the cavotricuspid isthmus, which could be identified during sinus rhythm and atrial pacing, resulting in fibrillatory conduction in other parts of the RA. The consistency of wavefront activation was confirmed by frequency analysis from equally distributed mapping sites in the RA. Short lines of ablation lesions were aimed at the conduction channels between the lines of block, crista terminalis gaps, and the cavotricuspid isthmus, resulting in bidirectional block. AF was eliminated in 11 (85%) of 13 patients, and those 11 patients with acute success were free of AF without any antiarrhythmic drugs during the long-term follow-up period (16+/-6 months)., Conclusions: RA ablation still can cure selected patients with PAF. Linear ablation of the RA substrate guided by the electrophysiological characteristics of RA-AF is an effective approach for treating this specific group of patients with AF.

The average rate of fibrillatory activity may reflect the global activation pattern of AF. Electrical cardioversion is the most effective method of converting chronic AF to sinus rhythm. The aim of this study was to investigate the relation between the minimal defibrillation energy requirement and the dominant frequency of chronic AF. Twenty-nine patients with chronic AF (mean duration 57.9 +/- 7.7 months) underwent external electrical cardioversion. Before cardioversion, the frequency content of the 60-second AF in ECG lead V1 was quantified using digital signal processing. After band-pass filtering, QRST complexes were cancelled using a recursive lease squares algorithm. The resulting fibrillatory baseline signal was subjected to fast Fourier transform and was displayed as a power spectrum. The dominant AF frequency was found to range from 4.9 to 8.7 Hz (mean 6.7 +/- 0.9 Hz). Twenty-six patients had successful conversion of AF to sinus rhythm without immediate recurrence. There was a positive correlation between the minimal defibrillation energy and the dominant frequency of chronic AF (rho = 0.414, P = 0.035). Thus, power spectral analysis of AF using the surface ECG is feasible and may be useful in predicting the minimal shock energy required for successful cardioversion of chronic AF.