The Novel Electrophysiology of Complex Fractionated Atrial Electrograms: Insight from Noncontact Unipolar Electrograms

Unipolar Characteristics of CFAEs. Background: The noncontact mapping (NCM) system possesses the merit of global endocardial recording for unipolar and activation mapping. Objective: We aimed to evaluate the unipolar electrogram characteristics and activation pattern over the bipolar complex fractionated atrial electrogram (CFAE) sites during atrial fibrillation (AF). Methods: Twenty patients (age 55 ± 11 years old, 15 males) who underwent NCM and ablation of AF (paroxysmal/persistent = 13/7) were included. Both contact bipolar (32–300 Hz) and NCM virtual unipolar electrograms (0.5–300 Hz) were simultaneously recorded along with the activation pattern (total 223 sites, 11 ± 4 sites/patient). A CFAE was defined as a mean bipolar cycle length of ≤ 120 ms with an intervening isoelectric interval of more than 50 ms (Group 1A, n = 63, rapid repetitive CFAEs) or continuous fractionated activity (Group 1B, n = 59, continuous fractionated CFAEs), measured over a 7.2‐second duration. Group 2 consisted of those with a bipolar cycle length of more than 120 ms (n = 101). Results: The Group 1A CFAE sites exhibited a shorter unipolar electrogram cycle length (129 ± 11 vs 164 ± 20 ms, P < 0.001), and higher percentage of an S‐wave predominant pattern (QS or rS wave, 63 ± 13% vs 35 ± 13%, P < 0.001) than the Group 2 non‐CFAE sites. There was a linear correlation between the bipolar and unipolar cycle lengths (P < 0.001, R = 0.87). Most of the Group 1A CFAEs were located over arrhythmogenic pulmonary vein ostia or nonpulmonary vein ectopy with repetitive activations from those ectopies (62%) or the pivot points of the turning wavefronts (21%), whereas the Group 1B CFAEs exhibited a passive activation (44%) or slow conduction (31%). Conclusions: The bipolar repetitive and continuous fractionated CFAEs represented different activation patterns. The former was associated with an S wave predominant unipolar morphology which may represent an important focus for maintaining AF. (J Cardiovasc Electrophysiol, Vol. 21, pp. 640‐648, June 2010)     

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.     

Measuring the Complexity of Atrial Fibrillation Electrograms

AF Electrogram Complexity. Introduction: Complex fractionated atrial electrograms (CFAE) have been identified as targets for atrial fibrillation (AF) ablation. Robust automatic algorithms to objectively classify these signals would be useful. The aim of this study was to evaluate Shannon's entropy (ShEn) and the Kolmogorov‐Smirnov (K‐S) test as a measure of signal complexity and to compare these measures with fractional intervals (FI) in distinguishing CFAE from non‐CFAE signals. Methods and Results: Electrogram recordings of 5 seconds obtained from multiple atrial sites in 13 patients (11 M, 58 ± 10 years old) undergoing AF ablation were visually examined by 4 independent reviewers. Electrograms were classified as CFAE if they met Nademanee criteria. Agreement of 3 or more reviewers was considered consensus and the resulting classification was used as the gold standard. A total of 297 recordings were examined. Of these, 107 were consensus CFAE, 111 were non‐CFAE, and 79 were equivocal or noninterpretable. FIs less than 120 ms identified CFAEs with sensitivity of 87% and specificity of 79%. ShEn, with optimal parameters using receiver‐operator characteristic curves, resulted in a sensitivity of 87% and specificity of 81% in identifying CFAE. The K‐S test resulted in an optimal sensitivity of 100% and specificity of 95% in classifying uninterpretable electrogram from all other electrograms. Conclusions: ShEn showed comparable results to FI in distinguishing CFAE from non‐CFAE without requiring user input for threshold levels. Thus, measuring electrogram complexity using ShEn may have utility in objectively and automatically identifying CFAE sites for AF ablation. (J Cardiovasc Electrophysiol, Vol. 21, pp. 649‐655, June 2010)     

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

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

心房复杂碎裂电图的发生机制及临床意义

心房颤动(房颤)时心房电图会呈现特征性的复杂碎裂电图。多个研究认为复杂碎裂电图反映了局部折返激动,且与心脏自主神经兴奋有密切的关系。目前复杂碎裂电图指导临床射频消融治疗房颤已取得较高成功率,进一步证实复杂碎裂电图代表了房颤的基质。     

Nonlinear Analysis of Fibrillatory Electrogram Similarity to Optimize the Detection of Complex Fractionated Electrograms During Persistent Atrial Fibrillation

Nonlinear Analysis of Atrial Fibrillation . Introduction: Currently, the identification of complex fractionated atrial electrograms (CFEs) in the substrate modification is mostly based on cycle length‐derived algorithms. The characteristics of the fibrillation electrogram morphology and their consistency over time are not clear. The aim of this study was to optimize the detection algorithm of crucial CFEs by using nonlinear measure electrogram similarity. Methods and Results: One hundred persistent atrial fibrillation patients that underwent catheter ablation were included. In patients who required CFE ablation (79%), the time‐domain fibrillation signals (6 seconds) were acquired for a linear analysis (mean fractionation interval and dominant frequency [DF]) and nonlinear‐based waveform similarity analysis of the local electrograms, termed the similarity index (SI). Continuous CFEs were targeted with an endpoint of termination. Predictors of the various signal characteristics on the termination and clinical outcome were investigated. Procedural termination was observed in 39% and long‐term sinus rhythm maintenance in 67% of the patients. The targeted CFEs didn't differ based on the linear analysis modalities between the patients who responded and did not respond to CFE ablation. In contrast, the average SI of the targeted CFEs was higher in termination patients, and they had a better outcome. Multivariate regression analysis showed that a higher SI independently predicted sites of termination (≥0.57; OR = 4.9; 95% CI = 1.33–18.0; P = 0.017). Conclusions: In persistent AF patients, a cycle length‐based linear analysis could not differentiate culprit CFEs from bystanders. This study suggested that sites with a high level of fibrillation electrogram similarity at the CFE sites were important for AF maintenance. (J Cardiovasc Electrophysiol, Vol. 24, pp. 280‐289, March 2013)     

Efficacy of Additional Ablation of Complex Fractionated Atrial Electrograms for Catheter Ablation of Nonparoxysmal Atrial Fibrillation

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

Optimized Measurement of Activation Rate at Left Atrial Sites with Complex Fractionated Electrograms During Atrial Fibrillation

Local Activation Rate in Atrial Fibrillation. Background: Complex fractionated atrial electrograms (CFAE) have become targets for catheter ablation of atrial fibrillation (AF). Frequency components of AF signals have also become important markers for identifying potential mechanisms of AF, yet inaccuracies exist, particularly in standard dominant frequency (SDF) calculations especially at CFAE sites. We developed new methodology to improve accuracy of AF rate determinations at such recording sites. Objective: To develop optimal methods for estimating activation rates in paroxysmal and persistent AF. Methods: Electrograms were obtained from one right atrial, coronary sinus, and 6 left atrial (LA) endocardial regions manifesting CFAEs in paroxysmal (N = 7) and persistent (N = 7) AF patients. SDF was measured from 8.4 s intervals and compared to (1) optimized DF (ODF) calculated by optimizing the filter coefficients which maximized dominant frequency power, (2) autocorrelation (AC), with the rate estimated as the inverse of the signal phase shift generating the largest autocorrelation coefficient, and (3) ensemble average (EA), with the rate estimated by summing successive signal segments and selecting segment length yielding maximum power. Rate measurements were compared between groups, at baseline and with additive interference, having similar frequency content to the electrograms, to test the robustness of the different methods. Results: From pooled data (N = 168 recording sites), a significantly higher LA dominant frequency was found in persistent versus paroxysmal patients using each method (P < 0.001), with a mean value for all methods of 6.23 ± 0.08 Hz versus 5.32 ± 0.10 Hz, respectively. At the highest additive interference level, the rate measurement error was significantly greater in SDF as compared with EA (P = 0.010) and ODF (P = 0.035), and at all interference levels SDF had the largest error of any method. Conclusions: SDF appears less robust to additive interference, compared to the ODF and EA methods of estimating the activation rate at CFAE sites in this small group of patients. Use of optimized filter coefficients for DF measurement, or use of correlative methods such as EA, that reinforce the signal rather than filtering the noise, may improve calculation of activation rates. (J Cardiovasc Electrophysiol, Vol. 21, pp. 133‐143, February 2010)     

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)     

Intraprocedural Use of Ibutilide to Organize and Guide Ablation of Complex Fractionated Atrial Electrograms: Preliminary Assessment of a Modified Step‐Wise Approach to Ablation of Persistent Atrial Fibrillation

Ibutilide Guided CFAE Ablation. Introduction: While able to achieve clinical success, the current step‐wise approach to persistent atrial fibrillation (AF) ablation requires considerable “substrate” ablation and frequently mandates multiple procedures to address consequent atrial tachycardias (ATs). An alternative strategy minimizing the amount of ablation while maintaining clinical success would be desirable. We hypothesize that intraprocedural administration of a low‐dose antiarrhythmic drug (AAD) during AF will organize areas of passive activation and not affect areas critical to AF maintenance, thereby potentially minimizing the ablation lesion set. Methods and Results: Eleven patients (age = 55 ± 6 years; LA = 48 ± 15 mm; median AF duration = 3 years) with persistent AF undergoing catheter ablation were enrolled in this exploratory prospective observational study. After pulmonary vein (PV) isolation, a mean cycle length (mCL) map was created and areas with mCL <120 ms were considered to represent complex fractionated atrial electrograms (CFAE). Ibutilide (0.25–1.0 mg) was then administered and a second mCL map created. Ablation lesions were placed at CAFE sites identified after ibutilide administration. Activation and/or entrainment mapping was employed to address ATs. The endpoint of ablation was achieving sinus rhythm. The average LA mCL increased (146 vs 165 ms, P = 0.01) and the LA CFAE surface area decreased after ibutilide administration. Additional ablation organized AF to either sinus rhythm or AT in 10/11 (91%) patients. After a median follow up of 455 days, 8 of 11 (72%) patients were free from AF. Three patients underwent a repeat ablation procedure (average 1.27 ablations/patient). Conclusions: Ibutilide administration may organize atrial activity and facilitate AF termination during ablation while minimizing the ablation lesion set. (J Cardiovasc Electrophysiol, Vol. 21, pp. 608‐616, June 2010)     

Long- and Short-Term Temporal Stability of Complex Fractionated Atrial Electrograms in Human Left Atrium During Atrial Fibrillation

Background: Complex fractionated atrial electrograms (CFAEs) have been reported as targets for catheter ablation of atrial fibrillation (AF). However, the temporal stability of CFAE sites remains poorly defined.
Methods and Results: The study consisted of two phases. In the initial phase, two automated software algorithms, namely the interval confidence level (ICL) and the average interpotential interval (AIPI) were assessed for their diagnostic accuracy for automated CFAE detection. The AIPI was found to be superior to the ICL, and an AIPI of ≤100 ms was associated with a sensitivity and specificity of both 92% for detection of CFAEs. In the second phase of the study, 12 patients (2 females, mean age 54 ± 12 years) who underwent catheter ablation for persistent AF were studied to investigate the temporal stability of CFAEs. Two consecutive left atrial (LA) three-dimensional CFAE maps coded with AIPI readings were reconstructed during ongoing AF in each study patient, with a mean time difference of 34.3 ± 8.7 minutes between the two maps. Among a total of 149 CFAE sites and 238 non-CFAE sites on the first CFAE map that were precisely revisited during the repeat mapping process, 135 (90.6%) and 225 (94.5%) remained as CFAE sites and non-CFAE sites, respectively. RF ablation at the selected stable CFAE sites significantly prolonged AF cycle length (181 ± 26 ms to 199 ± 29 ms, P < 0.0001).
Conclusion: CFAEs recorded in the LA during AF display high temporal stability in patients with persistent AF. The clinical significance of our findings warrants further investigation.     

碎裂电位的自主神经机制

碎裂电位是心房颤动发生和持续的因和果,其机制与心脏自主神经密切相关。心脏内源性和外源性自主神经共同作用,增加心房的早期后除极和钙瞬变,导致碎裂电位和心房颤动发生。因此碎裂电位与自主神经节丛或脂肪垫分布一致。针对自主神经节丛消融,可以减少或消除碎裂电位。     

Catheter Ablation for Long-Standing Persistent Atrial Fibrillation

Atrial fibrillation (AF) is the most common sustained arrhythmia worldwide and represents a major burden to health care systems. Atrial fibrillation is associated with a 4- to 5-fold increased risk of thromboembolic stroke. The pulmonary veins have been identified as major sources of atrial triggers for AF. This is particularly true in patients with paroxysmal AF but not always the case for those with long-standing persistent AF (LSPAF), in which other locations for ectopic beats have been well recognized. Structures with foci triggering AF include the coronary sinus, the left atrial appendage (LAA), the superior vena cava, the crista terminalis, and the ligament of Marshall. More than 30 studies reporting results on radiofrequency ablation of LSPAF have been published to date. Most of these are observational studies with very different methodologies using different strategies. As a result, there has been remarkable variation in short- and long-term success, which suggests that the optimal ablation technique for LSPAF is still to be elucidated. In this review we discuss the different approaches to LSPAF catheter ablation, starting with pulmonary vein isolation (PVI) through ablation lines in different left atrial locations, the role of complex fractionated atrial electrograms, focal impulses and rotor modulation, autonomic modulation (ganglionated plexi), alcohol ablation, and the future of epicardial mapping and ablation for this arrhythmia. A stepwise ablation approach requires several key ablation techniques, such as meticulous PVI, linear ablation at the roof and mitral isthmus, electrogram-targeted ablation with particular attention to triggers in the coronary sinus and LAA, and discretionary right atrial ablation (superior vena cava, intercaval, or cavotricuspid isthmus lines).     

Ablating Atrial Fibrillation: Customizing Lesion Sets Guided by Rotor Mapping

Ablation occupies an increasing role in the contemporary management of atrial fibrillation (AF), but results are suboptimal, particularly for persistent AF. While an anatomic approach to ablation is a highly efficacious and safe method to isolate pulmonary vein (PV) triggers, recurrence of AF is not always associated with PV reconnection, and there is compelling evidence that non-PV sites sustain AF after it is triggered. Recent developments in wide-area mapping and signal processing now identify rotors in the vast majority of AF patients that sustain AF and whose elimination improves long-term freedom from AF in multicenter studies. Investigators have now demonstrated rotor and focal sources for AF that show many analogous properties between approaches: they lie in spatially reproducible regions temporally over hours to days, and they are amenable to targeted ablation. This review outlines the rationale and technical developments supporting this mechanistic paradigm for human AF, and discusses how rotor mapping may be implemented for individual patient customization of lesion sets. Mechanistic studies are required to explain why rotor elimination (or other ablation approaches) producing long-term elimination of AF may not always terminate AF acutely, how AF correlates with structural changes on magnetic resonance imaging, and how these findings can be integrated clinically with current ablation strategies to improve patient outcomes.