Complex Fractionated Atrial Electrograms Areas Research Articles

Ablation of persistent atrial fibrillation based on high density voltage mapping and complex fractionated atrial electrograms: A randomized controlled trial.

Introduction:Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) catheter ablation. However, a PVI alone has been considered insufficient for persistent AF. This study aimed to evaluate the efficacy of persistent AF ablation targeting complex fractionated atrial electrogram (CFAE) areas within low voltage zones identified by high-resolution mapping in addition to the PVI.Methods:We randomized 50 patients (mean age 58.4 ± 9.5 years old, 86.0% males) with persistent AF to a PVI + CFAE group and PVI only group in a 1:1 ratio. CFAE and voltage mapping was performed simultaneously using a Pentaray Catheter with the CARTO3 CONFIDENSE module (Biosense Webster, CA, USA). The PVI + CFAE group, in addition to the PVI, underwent ablation targeting low voltage areas (<0.5 mV during AF) containing CFAEs.Results:The mean persistent AF duration was 24.0 ± 23.1 months and mean left atrial dimension 4.9 ± 0.5 cm. In the PVI + CFAE group, AF converted to atrial tachycardia (AT) or sinus rhythm in 15 patients (60%) during the procedure. The PVI + CFAE group had a higher 1-year AF free survival (84.0% PVI + CFAE vs 44.0 PVI only, P = .006) without antiarrhythmic drugs. However, there was no difference in the AF/AT free survival (60.0% PVI + CFAE vs 40.0% PVI only, P = .329).Conclusion:Persistent AF ablation targeting CFAE areas within low voltage zones using high-density voltage mapping had a higher AF free survival than a PVI only. Although recurrence with AT was frequent in the PVI+CFAE group, the sinus rhythm maintenance rate after redo procedures was 76%.

The extent of complex fractionated atrial electrograms in the left atrium reflects age-related electrical remodeling in patients with persistent atrial fibrillation.

BackgroundsAlterations in the atrial structure and function associated with aging result in electric remodeling of the left atrium (LA) in patients with persistent atrial fibrillation (AF). We performed this study to evaluate the influence of age on electric remodeling as assessed by the extent of complex fractionated atrial electrograms (CFAEs) in the LA.MethodsA total of 122 patients (mean age, 55.9 ± 10.4 years; range, 31‐79; 106 males) who underwent catheter ablation for drug‐refractory persistent AF were included in the study. The extent of CFAE was measured by CFAE area and its index (CFAE area/LA surface area × 100) using three‐dimensional automated software of NavX system.ResultsThe mean value of CFAE extent was significantly different among age groups; the CFAE area decreased significantly with increasing age (30 seconds [43.2 ± 14.5 mm2] vs 40 seconds [28.6 ± 6.0 mm2] vs 50 seconds [22.8 ± 3.4 mm2] vs 60 seconds [15.3 ± 2.6 mm2] vs 70 seconds [10.3 ± 3.2 mm2]; P = .010). A similar significant decrease was observed in the CFAE area index (30 seconds [22.9 ± 7.4] vs 40 seconds [14.9 ± 3.4] vs 50 seconds [10.4 ± 1.6] vs 60 seconds [6.9 ± 1.2] vs 70 seconds [4.6 ± 1.4]; P = .002). Age had a significantly negative correlation with the CFAE area (r = −0.322, P < .001) and CFAE area index (r = −0.357, P < .001).ConclusionsIncreasing age is associated with electric remodeling in the LA characterized by a decrease in the extent of CFAE area and its index.

Recurrence quantification analysis of complex-fractionated electrograms differentiates active and passive sites during atrial fibrillation.

To differentiate electrograms representing sites of active atrial fibrillation (AF) drivers from passive ones. Ablation of complex-fractionated atrial electrograms (CFAEs) is controversial due to difficulty in distinguishing CFAEs representing sites of active AF drivers from passive mechanisms. We hypothesized that active CFAE sites exhibit repetitive wavefront directionality, thereby inscribing an electrogram conformation (Egm-C) that is more recurrent compared with passive CFAE sites; and that can be differentiated from passive CFAEs using nonlinear recurrence quantification analysis (RQA). We developed multiple computer models of active CFAE mechanisms (ie, rotors) and passive CFAE mechanisms (ie,wavebreak, slow conduction, and double potentials). CFAE signals were converted into discrete time-series representing Egm-C. The RQA algorithm was used to compare signals derived from active CFAE sites to those from passive CFAEs sites. The RQA algorithm was then applied to human CFAE signals collected during AF ablation (n = 17 patients). RQA was performed in silico on simulated bipolar CFAEs within active (n = 45) and passive (n = 60) areas. Recurrence of Egm-C was significantly higher in active compared with passive CFAE sites (31.8% ± 19.6% vs 0.3% ± 0.5%, respectively, P < .0001) despite no difference in mean cycle length (CL). Similarly, for human AF (n = 39 signals), Egm-C recurrence was higher in active vs passive CFAE areas despite similar CLs (%recurrence 13.6% ± 15.5% vs 0.1% ± 0.3%, P < .002; mean CL 102.5 ± 14.3 vs 106.6 ± 14.4, P = NS). Active CFAEs critical to AF maintenance exhibit higher Egm-C recurrence and can be differentiated from passive bystander CFAE sites using RQA.

Efficacy of Complex Fractionated Atrial Electrogram-Guided Extensive Encircling Pulmonary Vein Isolation for Persistent Atrial Fibrillation.

Background: In persistent AF, the effect of adjunctive ablation in addition to PV isolation (PVI) is controversial. We considered a new modified PVI including complex fractionated atrial electrogram (CFAE) area.Methods and Results: In 57 patients with persistent AF undergoing first ablation, CFAE were mapped before ablation and CFAE-guided extensive encircling PVI (CFAE-guided EEPVI) was performed. The PVI line was designed to include the CFAE area near PV or to cross the minimum cycle length points of the CFAE area near PV (CFAE-guided EEPVI group). The outcome was compared with conventional PVI in 34 patients with persistent AF (conventional PVI group). During a mean follow-up of 365±230 days after the first procedure, AF in 13 and atrial tachycardia (AT) in 9 patients recurred in the CFAE-guided EEPVI group, while only AF in 17 patients recurred in the conventional PVI group. Eight of 9 AT in the CFAE-guided EEPVI group were successfully ablated at second procedure. After first and second procedures, the recurrence of atrial tachyarrhythmia in the CFAE-guided EEPVI group was significantly reduced compared with the conventional PVI group (8 patients, 14% vs. 11 patients, 32%, respectively; P<0.01, log-rank test).Conclusions: CFAE-guided EEPVI was more effective for persistent AF compared with conventional PVI after first and second procedures, because recurring AT as well as re-conduction of PV was successfully ablated.

Left atrial posterior wall isolation affects complex fractionated atrial electrograms in persistent atrial fibrillation.

BackgroundThe impact of left atrial posterior wall isolation (LAPWI) on the complex fractionated atrial electrogram (CFAE) is unknown.Methods CFAE mapping was performed before and after LAPWI in 46 patients with persistent atrial fibrillation (AF).Results LAPWI decreased both the variable (fractionated index ≤ 120 ms; from 60 ± 4 cm2 to 50 ± 4 cm2, P < 0.001) and continuous (fractionated index ≤ 50 ms; from 4.2 ± 1.0 cm2 to 3.5 ± 0.9 cm2, P = 0.036) CFAE areas. Especially, the CFAE areas on the bottom and roof walls of the left atrium and on the posterior and bottom walls of the right atrium significantly decreased after LAPWI. The distribution of variable CFAE areas was not different between the AF‐recurrence (n = 9) and AF‐free (n = 37) groups before LAPWI; however, it was larger in the anterior and septal walls of the right atrium in the AF‐recurrence group than in the AF‐free group after LAPWI (anterior wall, 8% ± 2% vs 5% ± 1%, P = 0.048; septal wall, 23% ± 4% vs 16% ± 1%, P = 0.043). The distribution of continuous CFAE areas on the bottom wall of the right atrium was larger in the AF‐recurrence group than in the AF‐free group both before LAPWI (30% ± 20% vs 4% ± 2%, P = 0.008) and after LAPWI (25% ± 25% vs 3% ± 1%, P = 0.027).Conclusions LAPWI decreased the CFAE areas and affected their distribution, which contributed to AF recurrence.

Correlation between atrial fibrillation driver locations and complex fractionated atrial electrograms in patients with persistent atrial fibrillation.

The aim of this study was to evaluate a spatial correlation between active atrial fibrillation (AF) drivers measured by electrocardiographic imaging and complex fractionated atrial electrograms (CFAEs) in patients with persistent AF. Sixteen patients with persistent AF were included. A biatrial geometry relative to an array of 252-body-surface-electrodes was obtained from a noncontrast computed tomography scan. The reconstructed unipolar AF electrograms were signal-processed (ECVUE™, CardioInsight Technologies Inc., Cleveland, OH, USA) to identify AF drivers. Before driver ablation, a biatrial mapping using the NavX system (St. Jude Medical, St. Paul, MN, USA) was performed to identify CFAEs. CFAE and driver regions were then quantified and compared. AF was terminated by driver ablation in 11/16 (70%) patients. The mean number of ablated driver regions was 4±1 per patient. The most frequent driver locations were the inferior left atrium and coronary sinus, the right pulmonary veins, and the right atrium. In 49/63 (78%) of the driver locations, more than 75% of the driver site showed CFAEs. The mean ablated driver area was 58±24cm2 (19±11% of total surface area). The mean CFAE area was 178±59cm2 (49±16%). The percentage of non-ablated CFAE area was 76±13% of total CFAEs. In 9/11 patients with AF termination, the termination site showed CFAEs. There is a significant overlap between AF driver regions identified by the ECVUE™ system and CFAE areas identified by the NavX system. AF driver regions are smaller and mostly embedded in larger CFAE areas. Selective ablation of drivers in CFAE areas seems sufficient to terminate persistent AF in the majority of patients.

Diabetes mellitus and atrial remodelling in patients with paroxysmal atrial fibrillation: Role of electroanatomical mapping and catheter ablation.

Complex fractionated atrial electrograms (CFAEs) are related to atrial fibrosis, but their ablation has not yet shown superiority. The aim of the study was to compare, in terms of clinical outcome, two strategies of paroxysmal atrial fibrillation (AF) ablation in patients with type 1 diabetes mellitus (DM): pulmonary vein isolation (PVI) vs. PVI + CFAEs. Compared to an historical population of patient with paroxysmal AF and without DM, a higher percentage of patients with DM showed more than 25% of atrial area interested by CFAEs (study population, 58% vs historical group, 15%; p < 0.05). In PVI group, recurrences rate was similar in patients with HbA1c ⩽ 7.5% vs HbA1c > 7.5% (30% vs 22%; p = not significant), but a greater AF burden was observed in patients with HbA1c > 7.5% (6 ± 2 vs 1 ± 2; p < 0.05). In hazard ratios analysis PVI+CFAEs seems more effective than PVI alone in patients with HbA1c > 7.5% (hazard ratio, 1.28; p < 0.05), more than 25 years from DM diagnosis (hazard ratio, 1.25; p < 0.05) and more than five AF episodes/year (hazard ratio, 1.2; p < 0.05). Type 1 DM patients had complex atrial 'substrate', as documented by wider CFAEs areas. Despite this, 1-year follow-up recurrence rate was similar between two ablation approaches (PVI 27% vs. PVI+CFAEs 21%; p = not significant). In our study, only specific subgroups, like patients with disglycaemic state (HbA1c > 7.5%), long diabetes mellitus history and high AF burden, benefit from PVI+ CFAEs approach.

073_16740-H5 Impact of Extensive Encircling of Pulmonary Vein Isolation Guided by Complex Fractionated Atrial Electrograms (CFAE-guided EEPVI) for Persistent Atrial Fibrillation

In patients with persistent atrial fibrillation(PeAF), complex fractionated atrial electrograms(CFAE) ablation after pulmonary vein isolation(PVI) could not reduce the rate of recurrence. In 57 of 91 patients with PeAF, extensive encircling PVI including CFAE area mapped before ablation(CFAE-guided

Combined Cryoballoon and Radiofrequency Ablation Versus Radiofrequency Ablation Alone for Long-Standing Persistent Atrial Fibrillation

BackgroundTo achieve sinus rhythm, ablation of long-standing persistent atrial fibrillation (LSPAF) usually requires substrate modification in addition to pulmonary vein isolation (PVI). In the present article, we aimed to compare clinical and substrate modification effects of 2 distinct PVI strategies during stepwise ablation in patients with LSPAF: (1) Combined approach: cryoballoon (CB) for PVI and radiofrequency (RF) ablation for substrate modification and (2) RF-only approach: RF ablation for both PVI and substrate modification. Materials and MethodsA total of 34 patients were divided into 2 groups: 19 in the combined group and 15 in the RF group. Left atrial (LA) complex fractionated atrial electrogram (CFAE) maps were acquired before and after PVI and compared between groups. The groups were compared for acute atrial fibrillation termination (AFT) rates and long-term arrhythmia-free survival. ResultsA significant reduction on total LA CFAE area was observed with PVI in both groups. In the CB group, when pulmonary veins were excluded, the reduction of LA CFAE area was the most significant on the posterior wall of left atrium and which was greater than in the RF group. Although the ratio of AFT was higher in the CB group (44% versus 33%, respectively), single-procedure arrhythmia-free survival at 1 year was comparable between groups (68% in the CB group versus 66% in the RF group). Times of total procedure, fluoroscopy and post-PVI RF were all shorter in the CB group. ConclusionsCB may cause greater substrate modification on the posterior wall and increase AFT rate during LSPAF ablation.

Comparison of Direct Current Synchronized Cardioversion to Ibutilide-Guided Catheter Ablation for Long-Term Sinus Rhythm Maintenance After Isolated Pulmonary Vein Isolation of Persistent Atrial Fibrillation

Use of the antiarrhythmic ibutilide after isolated pulmonary vein isolation (PVI) might distinguish atrial remodeling severity and cases requiring further substrate modification, thereby improving efficacy of persistent atrial fibrillation (AF) treatment. Ninety-six consecutive patients with persistent AF were randomized after PVI to either direct current synchronized cardioversion (DCC group, n= 48) or 1mg of intravenous ibutilide (ibutilide group, n= 48) followed by no further intervention if AF converted to sinus rhythm (SR) within 30minutes (ibutilide conversion subgroup) or by complex fractionated atrial electrogram (CFAE) ablation until SR recovery or complete CFAE elimination (ibutilide nonconversion subgroup). With similarly distributed baseline characteristics and no serious postablation complications, the primary end point of 12-month SR maintenance rate after PVI was significantly higher for ibutilide versus the DCC group before (75% vs 56%; p=0.042) or after (83% vs 60%; p= 0.011) reablation at physician's discretion for recurrence beyond 3months after PVI. After ibutilide administration, 21 of 48 patients (44%) converted to SR at 17 ± 8minutes (mean ± SD); those in the ibutilide nonconversion subgroup had larger atrial size (47 ± 4 vs 45 ± 4; p= 0.025) and CFAE area (29 ± 8 vs 12 ± 5; p= 0.001) and longer AF duration (27 ± 6 vs 21 ± 10; p= 0.026). Among ibutilide conversion and nonconversion subgroups and DCC group, procedure, ablation, and x-ray exposure times differed significantly, as did 12-month SR maintenance rate before (81% vs 70% vs 56%; p= 0.043) or after reablation (86% vs 81% vs 60%; p= 0.042). In conclusion, in persistent AF treatment, ibutilide-guided ablation after PVI yields higher 1-year SR maintenance rate than PVI only.

Ganglionated plexi stimulation induces pulmonary vein triggers and promotes atrial arrhythmogenecity: In silico modeling study.

BackgroundThe role of the autonomic nervous system (ANS) on atrial fibrillation (AF) is difficult to demonstrate in the intact human left atrium (LA) due to technical limitations of the current electrophysiological mapping technique. We examined the effects of the ANS on the initiation and maintenance of AF by employing a realistic in silico human left atrium (LA) model integrated with a model of ganglionated plexi (GPs).MethodsWe incorporated the morphology of the GP and parasympathetic nerves in a three-dimensional (3D) realistic LA model. For the model of ionic currents, we used a human atrial model. GPs were stimulated by increasing the IK[ACh], and sympathetic nerve stimulation was conducted through a homogeneous increase in the ICa-L. ANS-induced wave-dynamics changes were evaluated in a model that integrated a patient’s LA geometry, and we repeated simulation studies using LA geometries from 10 different patients.ResultsThe two-dimensional model of pulmonary vein (PV) cells exhibited late phase 3 early afterdepolarization-like activity under 0.05μM acetylcholine (ACh) stimulation. In the 3D simulation model, PV tachycardia was induced, which degenerated to AF via GP (0.05μM ACh) and sympathetic (7.0×ICa-L) stimulations. Under sustained AF, local reentries were observed at the LA-PV junction. We also observed that GP stimulation reduced the complex fractionated atrial electrogram (CFAE)-cycle length (CL, p<0.01) and the life span of phase singularities (p<0.01). GP stimulation also increased the overlap area of the GP and CFAE areas (CFAE-CL≤120ms, p<0.01). When 3 patterns of virtual ablations were applied to the 3D AF models, circumferential PV isolation including the GP was the most effective in terminating AF.ConclusionCardiac ANS stimulations demonstrated triggered activity, automaticity, and local reentries at the LA-PV junction, as well as co-localized GP and CFAE areas in the 3D in silico GP model of the LA.

Does Additional Electrogram-Guided Ablation After Linear Ablation Reduce Recurrence After Catheter Ablation for Longstanding Persistent Atrial Fibrillation? A Prospective Randomized Study.

BackgroundAlthough circumferential pulmonary vein isolation (CPVI) catheter ablation may not be sufficient for long‐standing persistent atrial fibrillation (L‐PeAF), it is not clear which ablation strategy is beneficial in addition to CPVI. We sought to investigate whether additional complex fractionated atrial electrogram (CFAE)‐guided ablation improves clinical outcomes in L‐PeAF patients who exhibit continuous atrial fibrillation (AF) after CPVI and linear ablation (Line).Methods and ResultsThis study enrolled 137 L‐PeAF patients (71.4% male, 61.6±10.9 years old) who underwent radiofrequency catheter ablation. We conducted CPVI+Line based on the Dallas lesion set (posterior box+anterior line) after baseline CFAE mapping in all patients. If AF was defragmented (terminated or changed to atrial tachycardia), the procedure was stopped (AF‐Defrag group, n=29). If AF was maintained after CPVI+Line, we mapped the CFAE again and randomly assigned the patient to the CPVI+Line group (n=54) or the additional CFAE ablation group (CPVI+Line+CFAE group, n=54). L‐PeAF was defragmented during CPVI+Line in 21.2% of patients (29/137, AF‐Defrag group). The mean CFAE cycle length was prolonged (P<0.001), and CFAE area (CFAE cycle length <120 milliseconds) was reduced (P<0.001) after CPVI+Line in the remaining patients. Procedure time was longer in the CPVI+Line+CFAE group than the CPVI+Line group (P=0.023), but procedure‐related complication rates did not vary. During 22.3±13.2 months of follow‐up, the clinical recurrence rates were 17.2% in the AF‐Defrag group, 18.5% in the CPVI+Line group, and 32.1% in the CPVI+Line+CFAE group (log rank, P=0.166).ConclusionsAlthough CPVI+Line reduces and localizes CFAE area, additional CFAE ablation after CPVI+Line does not improve the clinical outcomes of catheter ablation in patients with L‐PeAF.

The modified stepwise ablation guided by low-dose ibutilide in chronic atrial fibrillation trial (The MAGIC-AF Study).

Complex fractionated atrial electrograms (CFAE) are targeted during persistent atrial fibrillation (AF) ablation. However, many CFAE sites are non-specific resulting in extensive ablation. Ibutilide has been shown to reduce left atrial surface area exhibiting CFAE. We hypothesized that ibutilide administration prior to CFAE ablation would identify sites critical for persistent AF maintenance allowing for improved procedural efficacy and long-term freedom from atrial arrhythmias. Two hundred patients undergoing a first-ever persistent AF catheter ablation procedure were randomly assigned to receive either 0.25 mg of intravenous ibutilide or saline placebo upon completion of pulmonary vein isolation. Complex fractionated atrial electrogram sites were then targeted with ablation. The primary efficacy endpoint was the 1-year single procedure freedom from atrial arrhythmia off anti-arrhythmic drugs. Similar procedural characteristics (procedure, fluoroscopy, and ablation times) were observed with both strategies despite a greater reduction in left atrial surface area with CFAE sites (8 vs. 1%, P < 0.0001) and AF termination during CFAE ablation with ibutilide compared with placebo (75 vs. 57%, P = 0.007). The primary efficacy endpoint was achieved in 56% of patients receiving ibutilide and 49% receiving placebo (P = 0.35). No significant differences in peri-procedural complications were observed in both groups. Despite a reduction in CFAE area and greater AF termination during CFAE ablation, procedural characteristics and clinical outcomes were unchanged when CFAE ablation was guided by ibutilide administration. ClinicalTrials.gov number: NCT01014741.

Abstract 17457: Does Additional Complex Fractionated Atrial Elecrogram Guided Ablation After Linear Ablation Improve Clinical Outcome of Catheter Ablation for Longstanding Persistent Atrial Fibrillation? A Prospective Randomized Study

Introduction: Although long-lasting circumferential pulmonary vein isolation (CPVI) is a corner stone of catheter ablation for atrial fibrillation (AF), it is not clear whether additional linear or complex fractionated atrial electrogram (CFAE)-guided ablations improve clinical outcome in patients with long-standing persistent AF (L-PeAF). Hypothesis: The purposes of this study were to compare CFAE maps before and after linear ablation, and to test whether additional CFAE ablation after linear ablation improves clinical outcome of L-PeAF. Methods: This study enrolled 119 consecutive L-PeAF patients (male 72.8%, 61.7±10.6 years old) who underwent RFCA. After baseline CFAE mapping, we conducted CPVI and linear ablations (posterior box lesion and anterior line). If AF maintained after linear ablation, we mapped CFAE again, and randomly assigned the patients to linear ablation group (Line, n=45) and additional CFAE ablation group (CFAE+Line, n=48). The patients whose AF terminated or changed to AT were excluded from randomization and classified as AF-Stop group (n=26). We compared pre- and post-linear ablation CFAE maps and clinical outcomes of CFAE+Line, Line, and AF-Stop groups. Results: 1. Mean CFAE-cycle length (CL) was significantly prolonged (203.65±40.35 ms to 264.17±39.03 ms, p&lt;0.001) and CFAE area was reduced (15.49±14.95% to 7.95±9.36%, p&lt;0.001) after linear ablation. Post-linear ablation CFAE was mainly located at left atrial (LA) appendage, septum, and posterior inferior LA. 2. There were no differences in total procedure time (p=0.441), ablation time (p=0.144), and procedure-related complication rate (p=0.955) among three groups. 3. During 17.4±10.5 month follow-up period, clinical recurrence rates were 30.4% in CFAE+Line group, 12.8% in Line group, and 16.7% in AF-Stop groups, respectively (Log rank, p=0.138). 4. Additional CFAE ablation after linear ablation did not improve clinical outcome of catheter ablation at all in patients with L-PeAF (HR 2.11, 95% CI 0.91 - 4.89, p=0.082). Conclusions: Linear ablation prolonged CFAE-CL and localized CFAE area in patients with L-PeAF. However, CFAE guided ablation in addition to linear ablation and CPVI did not improve clinical outcome of catheter ablation.

Effect of ablation of complex fractionated atrial electrogram on vagal modulation in dogs.

Clinical observations have shown that the complex fractionated atrial electrogram (CFAE) associates with ganglionated plexus activity in the cardiac autonomic nervous system. This study aimed to investigate the impact of CFAE ablation on vagal modulation to atria and vulnerability to develop atrial fibrillation (AF). Ten adult mongrel dogs were involved. Cervical sympathovagal trunks were decentralized and sympathetic effects were blocked. CFAE was color tagged on the atrial 3-dimensional image and ablated during AF induced by S1S2 programmed stimulation plus sympathovagal trunk stimulation. Atrial effective refractory period (ERP) and vulnerability window (VW) of AF were measured on baseline and at vagal stimulation at 4 atrium sites. Serial tissue sections from ablative and control specimens received hematoxylin and eosin staining for microscopic examination. Most CFAE areas were localized at the right superior pulmonary quadrant, distal coronary sinus (CS(d)) quadrant, and proximal coronary sinus (CS(p)) quadrant (21.74%, separately). Sinus rhythm cycle length (SCL) shortening did not decrease significantly after ablation at the sites, including right atrial appendage, left atrial appendage, CS(d), and CS(p) (P > 0.05). ERP shortening during vagal stimulation significantly decreased after ablation (P < 0.01); the VW to vagal stimulation significantly decreased after ablation (P < 0.05). The architecture of individual ganglia altered after ablation. CFAE has an autonomic basis in dogs. The decreased SCL and ERP shortening to vagal stimulation after CFAE ablation demonstrate that CFAE ablation attenuates vagal modulation to the atria, thereby suppressing AF mediated by enhanced vagal activity. CFAE ablation could suppress AF mediated by enhanced vagal activity.

Interatrial septal thickness is associated with the extent of left atrial complex fractionated atrial electrograms and acute procedural outcome in patients with persistent atrial fibrillation.

The interatrial septal thickness (IAST) reflects the changes of the atrial wall in patients with atrial fibrillation (AF). Complex fractionated atrial electrograms (CFAEs) were consistently positioned on the interatrial septum, especially in the remodelled left atrium (LA). We sought to characterize the relationship between IAST and LA CFAE area, as well as the acute procedural and clinical outcomes of catheter ablation in persistent AF patients. This study included 71 patients who underwent catheter ablation for drug-refractory persistent AF. A stepwise ablation approach included circumferential pulmonary vein isolation followed by LA and right atrial CFAE-guided ablation. Interatrial septal thickness was measured 1 cm inferior to the fossa ovalis on cardiac computed tomography (CT). The extent of LA CFAEs was assessed by CFAE area and index (CFAE area/LA surface area × 100). Patients were grouped into tertiles according to the value of IAST. The mean IAST of the first, second, and third tertile was 4.69 ± 0.79, 6.44 ± 0.45, and 9.12 ± 1.42 mm, respectively (P < 0.001). The mean CFAE areas (5.6 ± 6.9, 18.5 ± 20.3, and 24.3 ± 26.6 mm(2), P = 0.005) and CFAE indexes (3.1 ± 4.2, 9.2 ± 10.7, and 11.8 ± 15.3, P = 0.025) in LA were significantly different among the three groups. More patients in the highest IAST tertile did not terminate AF during catheter ablation (12.5% vs. 26.1% vs. 37.5%, P = 0.048). Interatrial septal thickness measured by cardiac CT is associated with the extent of CFAE area within the LA and is related to acute procedural success of catheter ablation. These findings suggest that IAST reflects the degree of atrial substrate and remodelling in patients with persistent AF.

Complex Fractionated Atrial Electrograms Related to Left Atrial Wall Thickness

The mechanism of complex fractionated atrial electrogram (CFAE) in patients with atrial fibrillation (AF) remains controversial. This study investigated the relationship between CFAE and left atrial (LA) wall thickness. LA muscular wall thickness (excluding fat) was measured by cardiac computed tomography in 31 patients with AF (12 paroxysmal, 19 persistent) prior to catheter ablation procedures. Measurements were performed at 31 distinct LA locations: 3 at roof, 3 at floor, 9 at anterior wall, 9 at posterior wall, 3 at lateral wall, 3 at septum, and 1 at base of the anterior appendage. The range of LA wall thickness (LAWT) varied widely (average 2.4 ± 0.4 mm, range 1.5-3.1 mm) between patients. In addition, there were significant regional differences in LAWT. Each patient had an average of 7.3 ± 3.5 CFAE sites. The LA wall was thicker at CFAE sites (227 sites, 3.0 ± 1.0 mm) than at non-CFAE sites (734 sites, 2.2 ± 0.9 mm, P < 0.001). In 23 of 31 (74%) patients, the LA wall was thicker at CFAE area than at non-CFAE area. There was no difference in LAWT between sites where CFAE vanished and those where CFAE persisted after pulmonary vein isolation (PVI) among sites with CFAE before PVI. The LAWT > 2.5 mm predicted CFAE with a sensitivity of 70% and a specificity of 70%. The LAWT correlates well with CFAE areas, suggesting that one of the mechanisms of CFAE might be related to LAWT.

Importance of pericardial fat in the formation of complex fractionated atrial electrogram region in atrial fibrillation

Background/ObjectivesPericardial fat (PF) and complex fractionated atrial electrogram (CFAE) are both associated with atrial fibrillation (AF). Therefore, we examined the relation between PF and CFAE area in AF. MethodsThe study population included 120 control patients without AF and 120 patients with AF (80 paroxysmal AF and 40 persistent AF) who underwent catheter ablation. Total cardiac PF volume, representing all adipose tissue within the pericardial sac, was measured by contrast-enhanced computed tomography. The location and distribution of CFAE region were identified by left atrial endocardial mapping using a three-dimensional mapping system. We analyzed the significance of total cardiac PF volume and total area of CFAE region on AF, persistence of AF from paroxysmal to persistent form, and the relation between total cardiac PF volume and total CFAE area. We also evaluated the regional distribution of PF volume and CFAE area in five areas of the left atrium (LA). ResultsTotal cardiac PF volume correlated with AF (odds ratio [OR]: 1.024, p<0.001). Total cardiac PF volume and total CFAE area were both independently associated with persistence of AF (OR: 1.018, p=0.018, OR: 1.144, p=0.002, respectively). Multivariate linear regression analysis identified total cardiac PF volume as a significant and independent determinant of total CFAE area (r=0.488, p<0.001). Furthermore, regional PF volume correlated with local CFAE area in an each LA area. ConclusionsPF volume correlated significantly with CFAE area in patients with AF. This finding suggests that PF is directly related to the progression of CFAE area and promotes the pathogenic process of AF.

Relationship Between Complex Fractionated Atrial Electrograms During Atrial Fibrillation and the Critical Site of Atrial Tachycardia That Develops After Catheter Ablation for Atrial Fibrillation

Complex fractionated atrial electrograms (CFAEs) are a substrate modification target in patients with atrial fibrillation (AF). However, whether CFAEs can be also arrhythmogenic grounds of atrial tachycardia (AT) presenting after AF ablation remains to be determined. We investigated the relationship between CFAEs and the critical site of AT after CFAE-guided AF ablation. Seventy-two patients showing AT after pulmonary vein isolation and further CFAE-guided ablation were included. The termination sites of the 95 distinct ATs were annotated on color-coded CFAE cycle maps. Of the 95 ATs, 61 (64.2%) had a termination site at the border zone of CFAE or in a highly dense CFAE area. The cycle length (CL) of the ATs terminated in the CFAE area was significantly shorter than the CL of those terminated in the non-CFAE area. The cut-off CL for ATs terminated at the CFAE area was 270 milliseconds, with sensitivity/specificity of 70%/75%. In 67.2% of the ATs terminating at the CFAE-related area, the major termination sites were the anterior wall near the LA appendage, septum and roof, whereas the peri-mitral isthmus was the most common termination site of ATs in the non-CFAE area. The areas showing CFAE and their border zones were frequently associated with termination of ATs presenting after AF ablation. The mean CL of ATs originating near CFAEs was significantly shorter than that of those terminated in non-CFAE areas. The targeted CFAE areas also provided the arrhythmogenic milieu for AT developing after AF ablation.

Automated Detection of Complex Fractionated Atrial Electrograms In Substrate-Based Atrial Fibrillation Ablation: Better Discrimination with a New Setting of CARTO® Algorithm.

Background and purpose: Up until recently complex fractionated atrial electrogram (CFAE) ablation has been considered as time consuming and its achievement as challenging, especially for non experimented operators. Moreover, results of substrate ablation based on CFAE detection in atrial fibrillation (AF) are very disparate, mainly because of the operator's subjective electrogram visual analysis and the difficult distinction between CFAEs really involved in AF perpetuation from other CFAE. Automatic detection provided by 3D mapping system (CARTO® algorithm) can be helpful but is not selective enough, drawing too wide CFAE areas. We sought to demonstrate a better selectivity of a new CFAE algorithm setting in order to better discriminate CFAEs really involved in AF perpetuation from other CFAE. Methods and subjects: A population of 32 patients (60.4±12.7 years) with paroxysmal (n=3) AF (PAF), persistent (n=16) AF (PeAF) or long-standing persistent (n=13) AF (LSPeAF), and AF history =56±65 months, underwent CFAE ablation based on visual analysis. Before ablation, left atrium CFAE mapping was performed on CARTO® shortest complex interval (SCI) algorithm and reanalyzed after ablation with the two different settings: nominal (SCI 60-120ms/0.05-0.15mV) vs. customized setting (SCI 30-40ms/0,04-0.15mV). CFAE areas automatically detected by both settings (CFAE-CARTO® areas) were respectively measured. The decision to ablate CFAE was only based upon the operator's electrogram visual analysis taken as reference because of high AF termination rate (93.7%) due to operator's CFAE selection experience. These ablation points drawn reference-CFAE areas involved in AF perpetuation (ablation point=60mm2) allowing to compare the selectivity of the two previous automatic maps. Results: With the customized CARTO® SCI setting, we observed a significant reduction of CFAE areas detected by CARTO® (CFAE-CARTO® areas) and of the ablated CFAE surface inside non-CFAE CARTO® areas, (30.6±20.5cm2 vs. 68.8±24.5cm2, p<0.0001, and 1.86±1.82% vs. 3±3%, p=0.003). Furthermore the proportion of ablated areas/detected CFAE-CARTO® areas were higher with customized setting (38.2±19.6% vs. 20.4±17.5%, p=0.008). Conclusions: This new customized CFAE algorithm setting is significantly more selective than the nominal one and allows an automated detection of CFAE really involved in AF perpetuation truer to an efficient experienced operator's electrogram visual analysis.