Complex Fractionated Atrial Electrograms Areas Research Articles

The Spatial Distribution of Atrial Fibrillation Termination Sites in the Right Atrium During Complex Fractionated Atrial Electrograms‐Guided Ablation in Patients with Persistent Atrial Fibrillation

The role of right atrial (RA) ablation guided by complex fractionated atrial electrograms (CFAE) in atrial fibrillation (AF) has been debated. This study evaluated the spatial distribution of RA CFAE, the critical sites, and the predictors of successful termination of longstanding persistent AF during RA ablation. A total of 97 patients with persistent AF who received automated detection of CFAE mapping and ablation at the RA for sustained AF after pulmonary vein isolation and left atrial (LA) CFAE-guided ablation were analyzed. The AF termination patterns and CFAE areas were analyzed. Forty-eight (49%) patients successfully converted to atrial tachycardia (AT) or sinus rhythm (SR) during CFAE-guided ablation at the RA. Of these, 7 (15%) patients converted directly to SR, and 41 (85%) converted via AT. The crista terminalis (CT) was the most common site for AT conversion during RA CFAE ablation, followed by the RA appendage and RA septum. Patients with larger RA volumes (> 145 mm3) had lower rates of SR or AT conversion during RA CFAE ablation. Patients with AF termination during RA CFAE ablation had less late recurrence than those without AF termination (P = 0.003). A half of patients with persistent AF refractory to LA ablation successfully converted to AT or SR during automated CFAE-guided ablation at the RA. The most common critical sites for AF termination were the CT and RA appendage and septum. Patients with AF termination during procedure whether LA CFAE only or after RA CFAE ablation had better outcome with less late recurrence of atrial tachyarrhythmia compared to those without AF termination.

Detection of Complex Fractionated Atrial Electrograms Using Recurrence Quantification Analysis

Atrial fibrillation (AF) is the most common cardiac arrhythmia but its proarrhythmic substrate remains unclear. Reentrant electrical activity in the atria may be responsible for AF maintenance. Over the last decade, different catheter ablation strategies targeting the electrical substrate of the left atrium have been developed in order to treat AF. Complex fractionated atrial electrograms (CFAEs) recorded in the atria may represent not only reentry mechanisms, but also a large variety of bystander electrical wave fronts. In order to identify CFAE involved in AF maintenance as a potential target for AF ablation, we have developed an algorithm based on nonlinear data analysis using recurrence quantification analysis (RQA). RQA features make it possible to quantify hidden structures in a signal and offer clear representations of different CFAE types. Five RQA features were used to qualify CFAE areas previously tagged by a trained electrophysiologist. Data from these analyzes were used by two classifiers to detect CFAE periods in a signal. While a single feature is not sufficient to properly detect CFAE periods, the set of five RQA features combined with a classifier were highly reliable for CFAE detection.

Areas with complex fractionated atrial electrograms recorded after pulmonary vein isolation represent normal voltage and conduction velocity in sinus rhythm

Although complex fractionated atrial electrograms (CFAEs) are purported to represent critical sites for atrial fibrillation (AF) perpetuation, the mechanism and the significance of CFAE in the genesis of AF remain poorly understood. This study evaluated the relationship between CFAE and areas of abnormal atrial tissue defined by low-voltage electrograms (LVE) and signal average of the P-wave (SAPW). Complex fractionated atrial electrogram maps were obtained after pulmonary vein isolation in 15 patients with persistent AF. Patients were then cardioverted and voltage/activation maps were acquired in normal sinus rhythm (NSR). Total left atrium (LA), CFAE and LVE areas were measured as % of total LA area (mean ± SD). Conduction velocities of normal, LVE and CFAE areas were also measured during NSR. Patients underwent signal averaged ECG of the P-wave in NSR within 24 h of the procedure. Complex fractionated atrial electrograms areas accounted for 33 ± 24% of total LA. In NSR, only 12 ± 10% of LA area had LVE. There was no anatomic correlation between CFAE sites and LVE; the area of overlap between CFAE and LVE was only 1.6 ± 1.5%. Conduction velocity was faster in CFAE areas (2.3 ± 1.4 m/s) than in normal voltage areas (1.3 ± 0.3 m/s), and LVE areas (1.1 ± 0.7 m/s, P = 0.06). A positive correlation was only found between LVE areas and SAPW duration (r = 0.7, P = 0.04). Areas of CFAEs correspond to areas of normal atrial voltage and normal conduction velocity during NSR. Complex fractionated atrial electrogram probably represents the response of normal healthy atrial tissue to rapid pulmonary vein activation.

Substrate Modification by Pulmonary Vein Isolation and Left Atrial Linear Ablation in Patients with Persistent Atrial Fibrillation: Its Impact on Complex‐Fractionated Atrial Electrograms

PV and Linear Ablation for CFAEs. Linear ablations in the left atrium (LA), in addition to pulmonary vein (PV) isolation, have been demonstrated to be an effective ablation strategy in patients with persistent atrial fibrillation (PsAF). This study investigated the impact of LA linear ablation on the complex-fractionated atrial electrograms (CFAEs) of PsAF patients. A total of 40 consecutive PsAF patients (age: 54 ± 10 years, 39 males) who underwent catheter ablation were enrolled in this study. Linear ablation of both roofline between the right and left superior PVs and the mitral isthmus line joining from the mitral annulus to the left inferior PV were performed following PV isolation during AF. High-density automated CFAE mapping was performed using the NAVX, and maps were obtained 3 times during the procedure (prior to ablation, after PV isolation, and after linear ablations) and were compared. PsAF was terminated by ablation in 13 of 40 patients. The mean total LA surface area and baseline CFAEs area were 120.8 ± 23.6 and 88.0 ± 23.5 cm(2) (74.2%), respectively. After PV isolation and linear ablations in the LA, the area of CFAEs area was reduced to 71.6 ± 22.6 cm(2) (58.7%) (P < 0.001) and 44.9 ± 23.0 cm(2) (39.2%) (P < 0.001), respectively. The LA linear ablations resulted in a significant reduction of the CFAEs area percentage in the region remote from ablation sites (from 56.3 ± 20.6 cm(2) (59.6%) to 40.4 ± 16.5 cm(2) (42.9%), P < 0.0001). Both PV isolation and LA linear ablations diminished the CFAEs in PsAF patients, suggesting substrate modification by PV and linear ablations. (J Cardiovasc Electrophysiol, Vol. 23, pp. 962-970, September 2012).

Ganglionated Plexi Ablation Directed by High‐Frequency Stimulation and Complex Fractionated Atrial Electrograms for Paroxysmal Atrial Fibrillation

The effectiveness of ganglionated plexi (GP) ablation in patients with atrial fibrillation (AF) is ambiguous. Some researchers had already suggested that additional identification of complex fractionated atrial electrograms (CFAE) around the areas with a positive reaction to high-frequency stimulation (HFS) might improve the accuracy of GP's boundaries location, then enhancing the success rate of ablation. The purpose of this study was to assess the safety and efficacy of GP ablation directed by HFS and CFAE in patients with paroxysmal AF (PAF). Sixty-two patients with PAF (age 57±8 years) underwent GP ablation. Ablation targets were the sites where vagal reflexes were evoked by HFS and additional extended ablation CFAE area around the areas where vagal reflexes were evoked. At 12 months, 71% of patients were free of symptomatic AF. At 3 months after ablation the root mean square successive differences and HF were significantly lower in patients without AF recurrence (P < 0.0001 and P = 0.004). The LF/HF ratio was significantly higher in patients without AF recurrence (P = 0.02). Enhanced GP ablation directed by HFS and CFAE can be safely performed and enables maintenance of sinus rhythm in the majority of patients with PAF for a 12-month period. Denervation of the intrinsic cardiac autonomic nervous system may be the preferable target of catheter ablation of AF.

Mapping of Complex Fractionated Atrial Electrograms (CFAE) as Target Sites for AF Ablation

The myriad pathologies leading to and resulting from atrial fibrillation (AF) have led to many theories regarding how substrate should be defined and how to reconcile substrate ablation with trigger ablation. The identification of spatiotemporally stable areas of very low amplitude short cycle length CFAE, in a sea of otherwise discrete normal amplitude and relatively longer cycle length electrograms, led to ablate the CFAE as a marker of abnormal substrate.1&nbsp;This pure substrate-based ablation strategy has resulted in remarkable success with great benefits, which include stroke and mortality reduction in high-risk patients with very long standing persistent AF. In this review, we discuss the prevailing mechanisms underlying CFAE, how to map and ablate CFAE sites, correlation of CFAE areas to those of ganglionic plexi, clinical outcomes of the approach, and the controversy surrounding targeting CFAE as substrate sites for AF ablation.

Relationship between clinical outcomes and unintentional pulmonary vein isolation during substrate ablation of atrial fibrillation guided solely by complex fractionated atrial electrogram mapping

Controversy exists as to whether atrial fibrillation (AF) ablation guided solely by complex fractionated atrial electrogram (CFAE) has a good outcome despite not requiring pulmonary vein isolation (PVI). The purpose of this study was to evaluate the effectiveness of AF ablation guided solely by targeting CFAE areas, and to determine whether its clinical efficacy has any relationship with unintentionally isolating the PV. We studied 100 consecutive patients (ages 59 ± 11 years; 54 with paroxysmal, 35 persistent, and 11 long-standing persistent AF), who underwent CFAE-ablation. PV potential (PVP) was recorded before and after ablation. After excluding 39 patients in whom sinus rhythm could not be maintained before ablation by internal cardioversion and/or who had a history of PVI(s), PVPs were analyzed. AF was terminated during ablation in 98% of paroxysmal, 80% of persistent, and 55% of long-standing persistent AF patients. Nifekalant (0.3-0.6 mg/kg) was administered in 30%, 57%, and 83%, respectively. The common areas of CFAE around the PVs were anterior to the right PVs, posterior to the left PVs, and at the ridge of the left atrial appendage. Among 215 PVs in 61 patients (42 paroxysmal, 19 persistent), only 17 PVs (8%) were unintentionally isolated. The atrial potential to PVP was prolonged (>30 ms) in 13% of PVs. After at least 12 months of follow-up (23 ± 5 months), 65% of paroxysmal (11% with drug), 54% of persistent (37% with drug), and 45% of long-standing (60% with drug) AF patients were free from atrial arrhythmia after one session. CFAE-ablation terminates AF without isolating PVs in a high percentage of patients, and yields excellent clinical outcomes.

The Contrast between the Area of the Ganglionated Plexi and Complex Fractionated Atrial Electrograms

The Ganglionated Plexi (GP) and complex fractionated atrial electrograms (CFAE) play the important role as the perpetuator of atrial fibrillation (AF). GP ablation is known as alternative procedure for AF. The aim of this study was to evaluate the contrast between the area of the GP and CFAE. Method: Ten consecutive patients with AF were studied. For patients with sinus rhythm, AF was induced by rapid atrial pacing. The geometry of Left atrium (LA) was reconstructed with electroanatomical mapping system (CARTO XP). Bipolar electrograms recorded during 2.5 second were analyzed using CFAE software module. The algorism was customized to demonstrate the classification as follows in Interval confidence level (ICL) map. Sites with continuous or transient fractionated atrial potentials were colored red. Sites with irregular amplitude, polarity, cycle length but not rapid were colored green. Sites with slow organized atrial potential were purple. The sites where vagal response was evoked by high-frequency stimulation were identified as GP sites and marked on the geometry. Result: A total of 1,107 points were taken in LA. Among a total of 197 GP points, 139 (77.2%) points were in colored red and categorized as in CFAE area. GP points in colored purple categorized as in slow organized area were only 4 points (2.3%). Conclusion: The Ganglionated Plexi is strongly related to CFAE.

Mechanisms of Complex Fractionated Electrogram-Targeted Ablation in a Model for Chronic Atrial Fibrillation

Background: We have recently demonstrated in computer simulations that electrotonic interactions between atrial myocytes and heterogeneously-distributed fibroblasts result in the genesis of complex fractionated atrial electrograms (CFAEs) during chronic atrial fibrillation (AF). However, previous research has not provided sufficient evidence that ablation targeting such fibroblast-derived CFAEs can terminate AF. Methods: To clarify this issue, we repeated simulations of CFAE-targeted ablation in the model of human chronic AF under heart failure, and we analyzed details of the excitation propagation until the AF was terminated by the application of CFAE-targeted ablation. Results: (1) Sustained spiral wave reentry, as a model of chronic AF, was found to terminate earlier as the number of ablation sites increased. (2) CFAE-targeted ablation site transiently pinned the spiral wave, preventing wave breakup by blocking the shortcut of the reentry. (3) The spiral wave drifted between ablation sites, and after a short time the spiral wave was pushed out of the CFAE area, resulting in AF termination. (4) For more effective CFAE-targeted ablation, avoiding collagen accumulation area and keeping an appropriate distance between ablation sites were required. Conclusion: Our findings might contribute to better understanding of the mechanisms of CFAE-targeted AF ablation.

Technical and Electrophysiologic Points of View of Exclusive CFAE-Guided Biatrial Ablation for CAF

Atrial fibrillation (AF) is a complex arrhythmia in which the interplay between initiating events and subsequent maintenance of the rhythm has resulted in a multitude of approaches to the cure. Ablation has traveled full circle from substrate focused catheter based analogs of the Cox Maze procedure to initiating event focused strategies targeting the pulmonary veins and once again back to substrate based ablation. The myriad pathologies leading to and resulting from AF have led to many theories regarding how substrate should be defined and how to reconcile substrate ablation with trigger ablation. The identification of spatiotemporally stable areas of very low amplitude short cycle length complex fractionated atrial electrograms (CFAE) in a sea of otherwise discrete normal amplitude and relatively longer cycle length electrograms led to use CFAE with a much shorter cycle length as a marker of abnormal substrate and target sites for AF ablation. This pure substrate based ablation strategy has resulted in reasonably success, even in high risk patients with very long standing persistent AF. In this review, I will discuss in details the prevailing mechanisms underlying CFAE, how to map and ablate CFAE sites, correlation of CFAE areas to those of ganglionic plexi and controversy of clinical outcomes of the approach.

Feasibility and Usefulness of Catheter Ablation for Atrial Fibrillation Using the Navx System

The aim of this study was to investigate the feasibility and usefulness of catheter ablation for atrial fibrillation (AF) guided by the NavX system. Thirty-nine patients (28 male, 60.9±8.4 years) who underwent radiofrequency catheter ablation with symptomatic paroxysmal (n=25), persistent (n=7) or long-lasting (n=7) AF were investigated. In all patients, extensive encircling pulmonary vein isolation (EEPVI) was performed after constructing the three-dimensional (3D) geometry of left atrium and four PVs, and fusion with CT imaging using the NavX system. When AF persisted, or AF or atrial tachycardia (AT) was induced by atrial burst pacing after bilateral EEPVI, complex fractionated atrial electrogram (CFAE) ablation and/or left atrial linear ablation was added. Simultaneous mapping by multipolar catheter in the NavX system was able to construct 3D activation map or CFAE map quickly, and helpful in detecting the gap of PVI or linear ablation line, or identifying CFAE areas. After a mean follow-up period of 7.1±4.4 months, 29 (74.3%) patients (18 in paroxysmal, 6 in persistent, 5 in long-lasting) were free of arrhythmia and symptoms (21 without antiarrhythmic agents (AA), 8 with AA), 27 after one session and 2 after two sessions. In conclusion, catheter ablation using NavX is feasible and useful for curing AF patients.

Combined use of cryoballoon and focal open-irrigation radiofrequency ablation for treatment of persistent atrial fibrillation: Results from a pilot study

Pulmonary vein isolation (PVI) achieved using a cryoballoon has been shown to be safe and effective. This treatment modality has limited effectiveness for treatment of persistent atrial fibrillation (AF). The purpose of this study was to evaluate a combined approach using a cryoballoon for treatment of PVI and focal radiofrequency (RF) left atrial substrate ablation for treatment of persistent AF. Twenty-two consecutive patients with persistent AF were included in the study. PVI initially was performed with a cryoballoon. Left atrial complex fractionated atrial electrograms (CFAEs) then were ablated using an RF catheter. Finally, linear ablations using the RF catheter were performed. Eighty-three PVs, including five with left common ostia, were targeted and isolated (100%). Seventy-seven (94%) of 82 PVs targeted with the cryoballoon were isolated, and 5 (6%) required use of RF energy to complete isolation. A mean of 9.7 +/- 2.6 cryoablation applications per patient was needed to achieve PVI. Median time required for cryoablation per vein was 600 seconds, and mean number of balloon applications per vein was 2.5 +/- 1.0. In 19 (86%) patients in whom AF persisted after PVI, CFAE areas were ablated using the RF catheter. Two cases of transient phrenic nerve paralysis occurred. After a single procedure and mean follow-up of 6.0 +/- 2.9 months, 86.4% of patients were AF-free without antiarrhythmic drugs. A combined approach of cryoablation and RF ablation for treatment of persistent AF is feasible and is associated with a favorable short-term outcome.

Catheter ablation of atrial fibrillation guided by complex fractionated atrial electrogram mapping of atrial fibrillation substrate

Cardiologists and physicians have witnessed a significant change in the management of atrial fibrillation (AF): antiarrhythmic agents are no longer considered more effective than just merely using compounds that control ventricular response of the arrhythmia with anticoagulation in high-risk patients. Catheter ablation has grown into wider acceptance as an important therapeutic modality in treating tachyarrhythmias. And over the past decade, several studies have clearly established that catheter ablation of atrial fibrillation is safe and effective and is an important alternative therapeutic option to the pharmacological approach. In general, there are two approaches to AF ablation: The anatomical approach, the most popular one, relies on isolation of electrical connections of all four pulmonary veins to the left atrium with or without adjuvant ablations, i.e. additional linear ablations. The second approach is the electrogram-guided approach by mapping and targeting areas of complex fractionated atrial electrograms (CFAE) which is the main topic of this review. The myriad pathologies leading to and resulting from AF have led to many theories regarding how substrate should be defined and how to reconcile substrate ablation with trigger ablation. The identification of spatiotemporally stable areas of very low amplitude short cycle length CFAE in a sea of otherwise discrete normal amplitude and relatively longer cycle length electrograms led to ablate the CFAE as a marker of abnormal substrate. This pure substrate-based ablation strategy has resulted in remarkable success, including mortality benefit, even in high-risk patients with very long standing persistent AF. In this review, we discuss in detail the prevailing mechanisms underlying CFAE, how to map and ablate CFAE sites, correlation of CFAE areas to those of ganglionic plexi, clinical outcomes of the approach, and the role of CFAE in the hybrid approach of AF ablation using a combination of pulmonary vein isolation and targeting CFAE areas.

Electrophysiologic Characteristics of Complex Fractionated Atrial Electrograms in Patients with Atrial Fibrillation

The underlying mechanisms of complex fractionated atrial electrogram (CFAE) during radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) have not yet been clearly elucidated. We explored the relationships between CFAE and left atrial (LA) voltage, or conduction velocity (CV). In 50 patients with AF (23 paroxysmal AF [PAF], 41 males, mean age 55.76 +/- 10.16 years), the CFAE (average index of fractionation of electrograms during AF by interval-analysis algorithm, cycle length [CL]<or= 120 ms) areas, voltage, and CV were measured at eight different quadrants in each patient's LA by analyzing a NavX-guided, color-coded CFAE CL map, a voltage map, and an isochronal map (500 ms pacing) generated by contact bipolar electrograms (70-100 points in the LA). The results were: (1) CFAE areas were predominantly located in the septum, roof, and LA appendage; (2) CFAE area had lower voltage than those in non-CFAE area and was surrounded by the areas of high voltage (P < 0.0001); (3) The CFAE areas had low CVs compared with non-CFAE areas (P < 0.001); and (4) The percentage of CFAE area was lower in patients with persistent atrial fibrillation (PeAF) compared with those with PAF (P < 0.05). The CFAE area, which is primarily located at the septum, has a low voltage with a lower CV, and is surrounded by high-voltage areas. Underlying electroanatomical complexity is associated with clustering of CFAEs.

High‐Density Mapping of Atrial Fibrillation in Humans: Relationship Between High‐Frequency Activation and Electrogram Fractionation

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. 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. 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.

Abstract 1034: Complex Fractionated Atrial Electrograms Are Often Due to Wavefront Collision or Functional Block Rather than Focal Triggers in a Canine Model of Atrial Fibrillation

Complex fractionated atrial electrograms (CFEs) have been described as a target during atrial fibrillation (AF) ablation, however, the mechanism leading to CFEs is poorly understood. We used noncontact mapping in a canine model of AF to determine the activation patterns in areas characterized by CFEs. Sustained AF was induced in 5 canines with 12 weeks of atrial tachy-pacing. A noncontact Multielctrode Array (MEA) was deployed in the left atrium (LA) and a contact bipolar CFE map was constructed. Areas of CFE were outlined on the map, and the MEA was then used to reconstruct wavefront propagation through CFE areas during 3 separate recording segments for each CFE site. There were 18 CFE regions identified (3.8/dog) and 54 noncontact CFE activation sequences studied. Activation patterns during the three recoding segments over time were consistent in 11/18 CFE regions (61%). The CFE regions were stereotypically located at the PV/LA junctions and the LA roof. Thirty-five CFE regions were characterized by wavefront collision, usually between circulating LA wavefronts and entry/exit from the PVs. Thirteen CFE regions were noted to be the central functional barrier of a rotor (Figure ) or partial rotor. Five regions were characterized by repeated conduction through a central isthmus with wavebreak. In this pacing-induced AF model, common causes of CFEs include collision between circulating LA wavefronts conduction through channels of functional block, the central vortex of a circulating rotor. The vast majority of these CFE regions were caused by heterogeneous anatomy and areas of functional block rather than true “drivers” of AF.