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.     

A novel finding of the atrial substrate properties and long-term results of catheter ablation in chronic atrial fibrillation patients with left atrial spontaneous echo contrast

Atrial Substrate Properties in Chronic AF Patients with LASEC. Background: The atrial substrate in chronic atrial fibrillation (AF) patients with a left atrial spontaneous echo contrast (LASEC) has not been previously reported. The aim of this study was to investigate the atrial substrate properties and long‐term follow‐up results in the patients who received catheter ablation of chronic AF. Methods: Of 36 consecutive patients with chronic AF who received a stepwise ablation approach, 18 patients with an LASEC (group I) were compared with 18 age‐gender‐left atrial volume matched patients without an LASEC (group II). The atrial substrate properties including the weighted peak‐to‐peak voltage, total activation time during sinus rhythm (SR), dominant frequency (DF), and complex fractionated electrograms (CFEs) during AF in the bi‐atria were evaluated. Result: The left atrial weighted bipolar peak‐to‐peak voltage (1.0 ± 0.6 vs 1.6 ± 0.7 mV, P = 0.04), total activation time (119 ± 20 vs 103 ± 13 ms, P < 0.001) and DF (7.3 ± 1.3 vs 6.6 ± 0.7 Hz, P < 0.001) differed between group I and group II, respectively. Those parameters did not differ in the right atrium. The bi‐atrial CFEs (left atrium: 89 ± 24 vs 92 ± 25, P = 0.8; right atrium: 92 ± 25 vs 102 ± 3, P = 0.9) did not differ between group I and group II, respectively. After a mean follow‐up of 30 ± 13 month, there were significant differences in the antiarrhythmic drugs (1.1 ± 0.3 vs 0.7 ± 0.5, P = 0.02) needed after ablation, and recurrence as persistent AF (92% vs 50%, P = 0.03) between group I and group II, respectively. After multiple procedures, there were more group II patients that remained in SR, when compared with group I (78% vs 44%, P = 0.04). Conclusion: There was a poorer atrial substrate, lesser SR maintenance after catheter ablation and need for more antiarrhythmic drugs in the chronic AF patients with an LASEC when compared with those without an LASEC. (J Cardiovasc Electrophysiol, Vol. pp. 1‐8)     

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.     

Relationship between complex fractionated electrograms (CFE) and dominant frequency (DF) sites and prospective assessment of adding DF-guided ablation to pulmonary vein isolation in persistent atrial fibrillation (AF)

Dominant Frequency Mapping and Ablation . Background: Sites of high DF are potential targets for AF ablation, but it is unknown if addition of DF ablation can improve procedural outcome. Objectives: We sought to (1) examine the relationship between DF sites and complex fractionated electrograms (CFE) and (2) prospectively assess the long‐term outcome of adding DF ablation to pulmonary vein antral isolation (PVAI) for persistent AF. Methods: First, 20 patients with persistent AF who underwent previous CFE‐guided ablation and who had AF terminate during ablation were studied retrospectively (group I). Bipolar, 8‐second electrograms were collected by a circular catheter (288 ± 86 points/map). The EnSite NavX system allows for automated display of both CFE and DF maps. Electrograms with cycle length <120 ms were considered CFE and were compared to DF sites > 8 Hz (direct inverse relationship). Sites of AF termination were related to CFE and DF sites. Based on these observations, 30 different patients (group II) with persistent AF prospectively underwent DF‐guided ablation plus PVAI. They were followed every 3 months for 1 year (visit, Holter, ECG). These patients were compared to case‐matched controls undergoing PVAI alone (group III). Results: In group I, there was a significant, inverse correlation between DF and CFE values at each point (r =–0.24, P < 0.001). DF surface area was less than CFE area (27 ± 5 cm² vs 34 ± 4 cm², P = 0.03). CFE sites overlapped 48 ± 27% with the DF surface area. Nonoverlapping CFE sites were contiguous to DF sites. AF termination occurred where DF and CFE overlapped, and at these sites, DF was always greater than the mean DF for the map. In group II, all DF sites above the mean value were prospectively ablated during AF. AF termination was noted in only 2/30 (7%) patients. After DF ablation, PVAI was performed and termination increased to 4/30 patients (14%). At 1 year, freedom from atrial arrhythmia > 30 seconds occurred in 57% of DF+PVAI compared to 60% in patients receiving PVAI alone (P = 0.18). Conclusions: DF and CFE regions overlap only about 50%. AF termination retrospectively occurred on overlapping CFE/DF sites where DF was above the mean. However, prospective ablation of DF sites plus PVAI resulted in low AF termination rates, and did not improve 1 year success over PVAI alone. (J Cardiovasc Electrophysiol, Vol. 22, pp. 1309‐1316, December 2011)     

Relationship between arrhythmogenic pulmonary veins and the surrounding atrial substrate in patients with paroxysmal atrial fibrillation

Arrhythmogenic PVs and the Fibrillatory Activities . Introduction: The relationship between pulmonary veins (PVs) with atrial fibrillation (AF) initiating triggers and their surrounding atrial substrate has not been elucidated. We aimed to clarify the atrial substrate properties around the PVs. Methods and Results: Twenty‐three paroxysmal AF patients were studied with the identification of PV initiating triggers. High‐density mapping of the dominant frequency (DF, 1200 Hz) and the mean degree of the complex fractionated electrograms (CFE mean interval over 6 seconds) was evaluated in 2 zones (zone 1: < 5 mm, zone 2: 5–15 mm from the PVs) and the left atrial (LA) using a NavX system prior to the PV isolation. High‐DFs (>8 Hz) and continuous CFEs (<50 ms) were identified in 1.5 ± 0.9 and 2.3 ± 1.1 regions per patient, respectively. Most of the high‐DF regions (86%) and continuous CFE regions (77%) were located within 15 mm of the PV ostia. Of those, 75% of the high‐DF regions and 54% of the continuous CFE regions were related to arrhythmogenic PVs. There was a significant DF gradient from arrhythmogenic PV zone 1 to zone 2, while the mean CFE exhibited a significant gradient between arrhythmogenic PV zone 2 and the rest of the LA. Additionally, 69% of the procedural AF termination sites were at arrhythmogenic PV zone 2. Conclusion: Evaluation of the atrial substrate properties may be useful for locating arrhythmogenic PVs during AF and defining the extent of the circumferential PV isolation. (J Cardiovasc Electrophysiol, Vol. 22, pp. 405‐410)     

Impact of heart rhythm status on registration accuracy of the left atrium for catheter ablation of atrial fibrillation

Introduction: Registration accuracy is of crucial importance to the successful use of image integration technique to facilitate atrial fibrillation (AF) ablation. It is well known that a patient's heart rhythm can switch from sinus rhythm (SR) to AF or vice versa during an AF ablation procedure. However, the impact of the heart rhythm change on the accuracy of left atrium (LA) registration has not been studied. Methods: This study included 10 patients who underwent AF ablation. Prior to the ablation procedure, the patients had contrast‐enhanced cardiac CT scan obtained during SR (n = 7) or AF (n = 3). Using an image integration system (CartoMerge, Biosense Webster Inc.), LA CT surface reconstruction was registered to the real‐time mapping space represented by the LA electroanatomic map. To determine the effect of rhythm change on registration accuracy, LA registration was performed during both SR and AF in each study subject. The distance between the surface of the registered LA CT reconstruction and multiple real‐time LA electroanatomic map points (surface‐to‐point distance) was used as an index for LA registration error. The position error after rhythm change was defined as the surface‐to‐point distance between the surface of the LA CT reconstruction registered in the initial rhythm and the LA electroanatomic map points sampled during the second rhythm. Results: A total of 90 ± 12 and 92 ± 9.5 LA electroanatomic map points were sampled for registration during SR and AF, respectively. No significant difference was found in surface‐to‐point distance when comparing SR with AF as the underlying rhythm during registration (1.91 ± 0.24 vs 1.84 ± 0.38 mm, P = 0.60). The position error after rhythm change was not different from the surface‐to‐point distance of LA registration conducted during the initial rhythm (2.05 ± 0.39 vs 1.96 ± 0.29 mm, P = 0.4). The surface‐to‐point distance did not differ when comparing LA registration conducted during the same versus different rhythm from that during CT imaging (1.96 ± 0.29 vs 1.79 ± 0.32 mm, P = 0.13). Conclusions: Registration error did not differ between LA registrations conducted during the same versus different rhythm as was present during CT imaging. Rhythm changes between SR and AF did not introduce significant error to the LA registration process for catheter ablation of AF. These findings are reassuring and suggest that reregistration is not needed if a patient's rhythm changes from SR to AF or vice versa during an ablation procedure.     

Clinical Value of Noninducibility by High-Dose Isoproterenol Versus Rapid Atrial Pacing After Catheter Ablation of Paroxysmal Atrial Fibrillation

Noninducibility by High‐Dose Isoproterenol. Objective: To determine the relative clinical value of noninducibility of atrial fibrillation (AF) by isoproterenol (ISO) and by rapid atrial pacing (RAP) in patients with paroxysmal AF (PAF). Background: AF can be induced by RAP or ISO in >85% of patients with PAF. Methods: ISO was administered in escalating doses of 5, 10, 15, and 20 μg/min in 112 patients (age = 56 ± 13 years) with PAF before radiofrequency catheter ablation. AF was inducible in 97 of 112 patients (87%) at a mean dose of 15 ± 5 μg/min. RAP induced AF in the remaining 14 of 15 patients. Antral pulmonary vein (PV) isolation (APVI) was followed by ablation of complex fractionated atrial electrograms (CFAEs) as necessary to terminate AF and render AF noninducible in response to ISO. Results: AF terminated during APVI in 72 of 111 patients (65%) and after APVI plus ablation of CFAEs in 11 of 111 patients (10%). In the remaining 28 patients (25%), sinus rhythm was restored by transthoracic cardioversion. RAP was performed in the last 61 consecutive patients who were rendered noninducible by ISO. RAP initiated AF in 20 of 61 patients (33%) and atrial flutter in 6 patients (10%). No additional ablation was performed if AF was induced with RAP; however, atrial flutter was targeted. At 12 ± 5 months, 63/75 patients (84%) who were noninducible by ISO and 2 of 8 (25%) who still were reinducible by ISO were free from recurrent AF after a single ablation procedure without antiarrhythmic drugs (P = 0.001). AF recurred in 20 of 36 patients (56%) who required cardioversion for persistent AF after ablation (P < 0.001). Among the 61 patients who also underwent RAP, 12 of 20 (60%) who were, and 31 of 41 (76%) who were not inducible by RAP were free from recurrent AF (P = 0.21). The accuracy of noninducibility as a predictor of clinical outcome was 83% with ISO and 64% by RAP (P = 0.03). Conclusions: The response to isoproterenol after catheter ablation of PAF more accurately predicts clinical outcome than the response to RAP. (J Cardiovasc Electrophysiol, Vol. 21, pp. 13–20, January 2010)     

Neural mechanism of atrial fibrillation: insight from global high density frequency mapping

Frequency Mapping During Neurally Mediated AF. Background: It has been demonstrated that intrinsic cardiac autonomic activation of ganglionated plexi (GPs) exhibits a frequency gradient from the center to the periphery with limited mapping. Objective: We aimed to use a global mapping tool (Ensite Array) to identify the frequency distribution and clarify the interaction between the extrinsic/intrinsic autonomic systems. Methods: A mid sternal thoractomy was performed in anesthetized dogs. High frequency stimulation (20 Hz, 0.1 ms duration) was applied to locate the GPs and achieve vagosympathetic stimulation (VNS). There were 4 major GPs, which were located near the 4 pulmonary vein (PV) ostia, and a third fat pad (SVC‐Ao) GP that was located near the superior vena cava (SVC)‐right atrial (RA) junction. Results: Without VNS (n = 12), the left atrial (LA) mean (8.20 ± 0.11 vs 7.95 ± 0.30 Hz, P = 0.04) and max (9.86 ± 0.28 vs 9.43 ± 0.29 Hz, P = 0.03) DFs were higher during the PV ostial GP stimulation than the SVC‐Ao GP stimulation. The LA max DFs were located not only at the primary GPs but also the nearby secondary PV ostial GPs. The RA mean DF (8.36 ± 0.05 vs 7.99 ± 0.19 Hz, P = 0.04) was higher during SVC‐Ao GP stimulation than PV ostial GP stimulation. The max DF was located inside the SVC during SVC‐Ao GP stimulation and at the RA septum during PV ostial GP stimulation. With VNS (n = 12), the LA mean and max DFs between the PV ostial and SVC‐Ao GP stimulation were similar. The DF distribution shifted to non‐GP LA sites during both the PV ostial and SVC‐Ao GP stimulation. Conclusion: The findings indicate that the AF was caused by an interaction between the PV ostial GPs during intrinsic autonomic stimulation, whereas the non‐GP LA sites were responsible for the AF induced by an extrinsic neural input. (J Cardiovasc Electrophysiol, Vol. 22, pp. 1049‐1056, September 2011)     

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.     

Clinical mapping approach to diagnose electrical rotors and focal impulse sources for human atrial fibrillation

Computational Mapping of Rotors and Focal Impulses in Human AF. Introduction: The perpetuating mechanisms for human atrial fibrillation (AF) remain undefined. Localized rotors and focal beat sources may sustain AF in elegant animal models, but there has been no direct evidence for localized sources in human AF using traditional methods. We developed a clinical computational mapping approach, guided by human atrial tissue physiology, to reveal sources of human AF. Methods and Results: In 49 AF patients referred for ablation (62 ± 9 years; 30 persistent), we defined repolarization dynamics using monophasic action potentials (MAPs) and recorded AF activation from 64‐pole basket catheters in left atrium and, in n = 20 patients, in both atria. Careful positioning of basket catheters was required for optimal mapping. AF electrograms at 64–128 electrodes were combined with repolarization and conduction dynamics to construct spatiotemporal AF maps. We observed sustained sources in 47/49 patients, in the form of electrical rotors (n = 57) and focal beats (n = 11) that controlled local atrial activation with peripheral wavebreak (fibrillatory conduction). Patients with persistent AF had more sources than those with paroxysmal AF (2.1 ± 1.0 vs 1.5 ± 0.8, P = 0.02), related to shorter cycle length (163 ± 19 milliseconds vs 187 ± 25 milliseconds, P < 0.001). Approximately one‐quarter of sources lay in the right atrium. Conclusions: Physiologically guided computational mapping revealed sustained electrical rotors and repetitive focal beats during human AF for the first time. These localized sources were present in 96% of AF patients, and controlled AF activity. These results provide novel mechanistic insights into human AF and lay the foundation for mechanistically tailored approaches to AF ablation. (J Cardiovasc Electrophysiol, Vol. 23, pp. 447‐454, May 2012)     

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)     

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)     

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)     

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.     

Long‐Term Outcome of Catheter Ablation in Patients with Atrial Fibrillation Originating from Nonpulmonary Vein Ectopy

Long‐Term Outcome of NPV AF Ablation . Introduction: Data regarding the long‐term outcome of catheter ablation in patients with nonpulmonary vein (NPV) ectopy initiating atrial fibrillation (AF) are limited. We aimed to evaluate the long‐term result of patients with AF who had NPV triggers and underwent catheter ablation. Methods and Results: The study included 660 consecutive patients (age 54 ± 11 years old, 477 males) who had undergone catheter ablation for AF. Group 1 consisted of 132 patients with AF initiating from the NPV, and group 2 consisted of 528 patients with AF initiating from pulmonary vein (PV) triggers only. Patients from Group 1 were younger than those from Group 2 (51 ± 12 years old vs 54 ± 11 years old, P = 0.001) and were more likely to be females (34.4% vs 25.8%, P = 0.049). The incidences of nonparoxysmal AF (36.4% vs 16.3%, P < 0.001) and right atrial (RA) enlargement (31.3% vs 19%, P = 0.004) were higher, and the biatrial substrates were worse in Group 1 than those in Group 2 (left atrial voltage 1.5 ± 0.7 mV vs 1.9 ± 0.7 mV, P < 0.001, RA voltage 1.6 ± 0.5 mV vs 1.8 ± 0.6 mV, P = 0.014). During a follow‐up period of 46 ± 23 months, there was a higher AF recurrence rate in Group 1 than in Group 2 (57.6% vs 38.8%, P < 0.001). The independent predictors of AF recurrence were NPV trigger (P < 0.001, HR 2, 95% CI 1.4–2.85), nonparoxysmal AF (P = 0.021, HR 1.55, 95% CI 1.07–2.24), larger left atrial diameter (P = 0.002, HR 1.04, 95% CI 1.02–1.07) and worse left atrial substrate (P = 0.028, HR 1.3, 95% CI 1.03–1.64). Conclusion: Compared to AF originating from the PV alone, AF originating from the NPV ectopy showed a worse outcome. (J Cardiovasc Electrophysiol, Vol. 24, pp. 250‐258, March 2013)     

The mechanisms of an increased dominant frequency in the left atrial posterior wall during atrial fibrillation in acute atrial dilatation

BACKGROUND: Previous studies have shown that the highest dominant frequency (DF) is located in the left atrium (LA) during atrial fibrillation (AF) in pacing-induced AF. However, there have been few studies on the mechanisms of the increased DF of AF during acute atrial dilatation. The purpose of this study was to investigate the mechanisms of the increased maximal DF (max DF) in pacing-induced AF during acute atrial dilatation. METHODS: In eight Langendorff-perfused canine hearts (26 +/- 2 kg), noncontact balloon catheters were placed into the right atrium (RA) and LA, respectively. AF was induced by extrastimulation pre- and postdilatation in the atrium (0 and 15 cm H(2)O, respectively). Fast Fourier transformation analysis was performed to analyze the max DF and harmonic index (HI) from the bi-atrial unipolar virtual electrograms during AF. The fibrillation cycle lengths were obtained from different atrial sites. The number of wavefronts was analyzed during AF. The frequency of regional splitting was defined as the number of wavefront splits per second in different atrial regions during AF. The percentage of the low-voltage zones (<0.5 mV) was defined as the ratio of the area of the low-voltage zones to the total atrial surface area. RESULTS: The DF was measured during AF. The shortest fibrillation cycle length was located in the LA posterior wall and became shorter during acute atrial dilatation. The max DF was located in the LA posterior wall and increased during acute atrial dilatation (7.1 +/- 0.8 vs 8.8 +/- 2.1, P = 0.02). The max DF of the LA correlated with the wavefront number (r = 0.797, P < 0.001 predilatation; r = 0.860, P < 0.001 postdilatation). The splitting of wavefronts facilitated the formation of new wavefronts. During acute atrial dilatation, the frequency of regional splitting was closely correlated with the percentage of the low-voltage zones (r = 0.876, P < 0.001). Furthermore, the LA posterior wall had a higher percentage of the low-voltage zones than the other sites. CONCLUSION: In acute atrial dilatation, the percentage of the low-voltage zones increased, especially in the LA posterior wall, which correlated with the regional splitting of the AF wavefronts. The increase in the splitting facilitated the formation of new wavefronts and resulted in a higher max DF during acute atrial dilatation.     

A Prospective,Randomized Comparison of Modified Pulmonary Vein Isolation Versus Conventional Pulmonary Vein Isolation in Patients with Paroxysmal Atrial Fibrillation

Modified Pulmonary Vein Isolation in AF Ablation. 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. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1155–1162, November 2012)     

Catheter ablation of atrial fibrillation in octogenarians: safety and outcomes

AF Ablation in Octogenarians. Introduction: Radiofrequency catheter ablation (RFCA) is an effective treatment for atrial fibrillation (AF), although studies evaluating the role of RFCA have largely excluded elderly patients. We report the safety and outcomes of RFCA of AF in octogenarians. Methods and Results: From 2008 to 2011, out of 2,754 consecutive patients undergoing RFCA of AF, 103 (3.7%) had ≥80 years (age 85 ± 3 years, 4 with >90 years). Pulmonary vein (PV) antrum isolation was performed in paroxysmal AF. In nonparoxysmal AF, ablation was extended to the entire left atrial posterior wall and to complex fractionated electrograms. Non‐PV triggers were disclosed by isoproterenol challenge at the end of the procedure and targeted for ablation. Octogenarians presented a high rate of non‐PV triggers (84% vs 69%, P = 0.001), especially in patients with paroxysmal AF (62% vs 19%, P < 0.001); non‐PV triggers were most commonly mapped in the coronary sinus (54%), left atrial appendage (32%), interatrial septum and superior vena cava (14%). After a mean follow‐up of 18 ± 6 months, 71 (69%) octogenarians remained free from AF recurrence off antiarrhythmic drugs after a single procedure (vs 71% in patients <80 years, P = 0.65). The success rate reached 87% after 2 procedures. Total periprocedural complication rates also did not differ between the 2 age groups. Conclusions: RFCA of AF is safe and effective in octogenarians. A high rate of non‐PV triggers is present in these patients, and targeting multiple structures other than the pulmonary veins is often necessary to achieve long‐term success. (J Cardiovasc Electrophysiol, Vol. 23, pp. 687‐693, July 2012)     

Atrial electrical and structural remodeling associated with longstanding pulmonary hypertension and right ventricular hypertrophy in humans

Atrial Remodeling in Pulmonary Hypertension . Introduction: Pulmonary hypertension (PH) is common to a range of cardiopulmonary conditions and is associated with atrial arrhythmias. However, little is known of the isolated atrial effects of PH and right atrial dilatation (RA) in humans. To avoid the confounding effects of PH‐associated disease states, we performed detailed electrophysiological (EP) and electroanatomic (EA) mapping of the RA in patients with idiopathic PH. Methods and Results: Eight PH patients (mean pulmonary arterial [PA] pressure 39.0 ± 15.8 mmHg) and 16 age‐matched controls (mean PA pressure 11.5 ± 4.1 mmHg, P < 0.0001) were studied. Corrected sinus node recovery times (cSNRT), atrial effective refractory periods (ERPs), conduction delay at the crista terminalis (CT), and inducibility of atrial fibrillation (AF) were evaluated. EA mapping (pacing cycle length 600 and 300 milliseconds) was performed to determine RA global and regional voltage, conduction velocities, atrial activation times, fractionated electrograms and double potentials. Patients with PH demonstrated a prolongation in cSNRT without significant change in atrial ERP and an increase in AF inducibility. PH was associated with lower tissue voltage (1.8 ± 0.4 mV in PH vs 2.2 ± 0.4 mV in controls, P = 0.02), increased low voltage areas (13.7 ± 8.2% in PH vs 6.2 ± 3.7% in controls, P < 0.01) and the presence of electrically silent areas. Conduction velocities were slower (global 67.3 ± 5.6 cm/s vs 92.8 ± 4.0 cm/s, P < 0.001) and fractionated electrograms and double potentials were more prevalent (14.7 ± 4.4% vs 6.3 ± 4.1, P < 0.01) in PH compared with controls, respectively. Conclusion: Idiopathic PH is associated with RA remodeling characterized by: generalized conduction slowing with marked regional abnormalities; reduced tissue voltage; and regions of electrical silence. These changes provide important insights into the isolated effects of PH fundamental to a range of clinical conditions associated with AF. (J Cardiovasc Electrophysiol, Vol. 23, pp. 614–620, June 2012)     

Different patterns of atrial remodeling after catheter ablation of chronic atrial fibrillation

Atrial Substrate Remodeling After Chronic AF Ablation . Background: Multiple remodeling patterns have been observed after catheter ablation of atrial fibrillation (AF). Objective: We aimed to clarify the electrical/structural properties associated with recurrences after ablation of chronic AF. Methods: After a stepwise ablation procedure in 120 consecutive patients with persistent/long‐lasting persistent AF, 36 had a recurrence of AF (Group 1/Group 2: recurrence with paroxysmal/persistent AF, n = 16/20). Results: During the first procedure, the left atrial (LA) bipolar voltage did not differ between the 2 groups, and the LA volume was smaller in Group 1 than in Group 2 and it was the only factor predicting the recurrent types (P = 0.009, OR = 1.04). In the second procedure, the bipolar voltage of the global left atrium increased (1.33 ± 0.11 mV vs 1.76 ± 0.16 mV, P = 0.001) in Group 1 and decreased (1.31 ± 0.14 mV vs 0.90 ± 0.12 mV, P = 0.01) in Group 2, when compared with that of the first procedure. The LA low‐voltage area (<0.5 mV) decreased in Group 1, and increased in Group 2. The LA volume (90 ± 8 cm³ vs 72 ± 8 cm³, P = 0.002) decreased in the second procedure in Group 1. It remained the same in Group 2. The right atrial substrates did not change between the procedures. After a follow‐up of 27 ± 3 months, all patients in Group 1 and 14 patients in Group 2 remained in sinus rhythm (P = 0.02). Conclusion: A better outcome with reverse electrical and structural remodeling occurred after the ablation of chronic AF when the recurrence was paroxysmal AF. Progressive electrical remodeling without any structural remodeling developed in those with a recurrence involving persistent AF. (J Cardiovasc Electrophysiol, Vol. 22, pp. 385‐393)