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)     

Left Ventricular Lateral Annulus and Left Atrial Free‐Wall Velocity Time Integral Indicate Thromboembolism in Patients with Rheumatic Atrial Fibrillation

Background: Low wall motion and stasis increase the likelihood of clot formation. We hypothesized that tissue Doppler indices of left atrial (LA) motion are reduced in the presence of LA thrombi and may be predictive for clot formation in patients with atrial fibrillation (AF). Methods: We did an observational study for 3 years in 118 patients with rheumatic mitral valve disease in chronic AF who had not received anticoagulation, with (Group 1, n = 36) and without (Group 2, n = 82) thromboembolism. Pulsed tissue Doppler systolic velocities and velocity time integrals (VTIs) were measured in all four chambers. A mean LA VTI was calculated. LA strain during ventricular systole was calculated using VTI and distance between two LA locations. Results: Logistic regression analysis showed that, after adjusting for age, gender, diabetes, hypertension, LA size, and left ventricular (LV) ejection fraction, mean LA VTI [Odds ratio (OR) 0.69, 95%CI (0.56–0.86, P = 0.03)] and lateral mitral annulus VTI [OR 0.15 (0.04–0.56, P = 0.03)] were associated with clot formation. The addition of these two parameters to the conventional risk factors increased the ability to predict thromboembolism (Nagelkerke R²= 0.32–0.50, P = 0.01; area under the curve 0.83 by receiver operating characteristic analysis, P = 0.01). LA strain also had potential to indicate clot formation (0.9 ± 13.8 vs. ?8.2 ± 15.1%, group 1 vs. 2, respectively, P = 0.01). Conclusion: Patients with chronic AF and thromboembolism have reduced LA and LV motion independently of LA size and LV ejection fraction. Tissue Doppler parameters may have potential to predict clot formation in these patients. (Echocardiography 2010;27:1038‐1048)     

Right Atrial Appendage Function in Different Etiologies of Permanent Atrial Fibrillation: A Transesophageal Echocardiography and Tissue Doppler Imaging Study

Objectives: Several studies exist on the left atrial appendage function (LAA) in permanent atrial fibrillation (AF). However, knowledge about the right atrial appendage (RAA) function is limited. We investigated RAA function with TEE and tissue Doppler imaging (TDI) in permanent AF patients with different etiologies and evaluated predictive parameters of right atrial spontaneous echo contrast (SEC) and thrombi. Methods: Patients with permanent AF developed due to three different etiologies (20 mitral stenosis, 44 hypertension, 20 hyperthyroidism) and 23 subjects with sinus rhythm were included into the study. RAA was examined with TEE and pulsed‐wave and TDI velocities of RAA were measured. Results: Both PW‐Doppler and TDI velocities were significantly impaired in all AF groups compared to controls. The lowest velocities were recorded in mitral stenosis patients. Right atrial moderate–severe SEC was observed in 75% of the mitral stenosis patients, in 25% of hypertensive patients, and in 30% of hyperthyroidism patients. Right atrial thrombus was observed in 25% of mitral stenosis, 4.5% of hypertension, and in none of the hyperthyroidism patients. In the multivariate analysis, the most important parameter associated with the severity of RAA SEC was the percent change in RAA area (B =−0.034, P = 0.03). Conclusion: In patients with permanent AF, impairment of RAA function and development of right atrial SEC‐thrombus are closely related to the underlying etiology. These results suggested that evaluation of RAA functions may have an incremental value over the assessment of the LAA for determining thromboembolic risk. (Echocardiography 2010;27:384‐393)     

The Optimal Automatic Algorithm for the Mapping of Complex Fractionated Atrial Electrograms in Patients With Atrial Fibrillation

CFAEs and the Voltage.   Introduction: Catheter ablation of atrial fibrillation (AF) can be guided by the identification of complex fractionated atrial electrograms (CFAEs). We aimed to study the prediction of the CFAEs defined by an automatic algorithm in different atrial substrates (high voltage areas vs low voltage areas).
Methods and Results: This study included 13 patients (age = 56 ± 12 years, paroxysmal AF = 8 and persistent AF = 5), who underwent mapping and catheter ablation of AF with a NavX system. High-density voltage mapping of the left atrium (LA) was performed during sinus rhythm (SR) (248 ± 75 sites per patient) followed by that during AF (88 ± 24 sites per patient). The CFAE maps were based on the automatic-detection algorithm. "Operator-determined CFAEs" were defined according to Nademannee's criteria. A low-voltage zone (LVZ) was defined as a bipolar voltage of less than 0.5 mV during SR. Among a total of 1150 mapping sites, 459 (40%) were categorized as "operator-determined CFAE sites," whereas 691 (60%) were categorized as "operator-determined non-CFAE sites." The sensitivity and negative predictive value increased as the fractionated interval (FI) value of the automatic algorithm increased, but the specificity and positive predictive value decreased. The automatic CFAE algorithm exhibited the highest combined sensitivity and specificity with an FI of <60 ms for the sites inside the LVZ and FI < 70 ms for the sites outside the LVZ, when compared with a single threshold for both the high- and low-voltage groups combined (i.e., no regard for voltage) (ROC: 0.89 vs 0.86).
Conclusions: The clinical relevance of the CFAE map would be improved if the calculated index values were accordingly scaled by the electrogram peak-to-peak amplitude. (J Cardiovasc Electrophysiol, Vol. 21, pp. 21–26, January 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.     

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)     

Magnetic Resonance Imaging‐Confirmed Ablative Debulking of the Left Atrial Posterior Wall and Septum for Treatment of Persistent Atrial Fibrillation: Rationale and Initial Experience

LA Debulking for Atrial Fibrillation. Introduction: Though pulmonary vein (PV) isolation has been widely adopted for treatment of atrial fibrillation (AF), recurrence rates remain unacceptably high with persistent and longstanding AF. As evidence emerges for non‐PV substrate changes in the pathogenesis of AF, more extensive ablation strategies need further study. Methods: We modified our PV antrum isolation procedure to include abatement of posterior and septal wall potentials. We also employed recently described image‐processing techniques using delayed‐enhancement (DE) MRI to characterize tissue injury patterns 3 months after ablation, to assess whether each PV was encircled with scar, and to assess the impact of these parameters on procedural success. Results: 118 consecutive patients underwent debulking procedure and completed follow‐up, of which 86 underwent DE‐MRI. The total left atrial (LA) radiofrequency delivery correlated with percent LA scarring by DE‐MRI (r = 0.6, P < 0.001). Based on DE patterns, complete encirclement was seen in only 131 of 335 PVs (39.1%). As expected, Cox regression analysis showed a significant relationship between the number of veins encircled by delayed enhancement and clinical success (hazard ratio of 0.62, P = 0.015). Also, progressive quartile increases in postablation posterior and septal wall scarring reduced recurrences rates with a HR of 0.65, P = 0.022 and 0.66, P = 0.026, respectively. Conclusion: Pathologic remodeling in the septal and posterior walls of the LA helps form the pathogenic substrate for AF, and these early results suggest that more aggressive treatment of these regions appears to correlate with improved ablation outcomes. Noninvasive imaging to characterize tissue changes after ablation may prove essential to stratifying recurrence risk. (J Cardiovasc Electrophysiol, Vol. 21, pp. 126‐132, February 2010)     

Left Atrial Appendage Wall‐Motion Velocity Associates with Recurrence of Nonparoxysmal Atrial Fibrillation after Catheter Ablation

Catheter ablation (CA) for nonparoxysmal atrial fibrillation (AF) is controversial due to its high recurrence rate. The aim of this study was to assess retrospectively the diagnostic value of preprocedural left atrial appendage (LAA) wall‐motion velocity in predicting recurrence of AF within 1 year after CA. We hypothesized that tissue Doppler‐derived measurement of LAA wall‐motion velocity associate with recurrence of AF within 1 year after CA. We retrospectively reviewed 47 consecutive patients with nonparoxysmal AF (defined as AF lasting for 1 week or longer) who underwent both transthoracic and transesophageal echocardiography before their first treatment by CA in a single center. Forty‐one patients aged 58 ± 10 years were included, and variables predicting the recurrence of AF within 1 year after CA were evaluated. Seventeen patients (41%) developed recurrence of AF within 1 year after CA. Univariate analyses showed that preprocedural LAA upward wall‐motion velocity at the apex assessed by transesophageal echocardiography was significantly lower in patients with recurrence of AF than those without recurrence (OR = 1.45, 95% CI: 1.13–2.01, P = 0.009). Multivariate logistic analyses including other potential predictors (duration of AF, left ventricular ejection fraction, E‐wave deceleration time, and left atrial wall‐motion velocity) identified LAA upward wall‐motion velocity at the apex as an independent predictor of outcome. These data suggest in patients with nonparoxysmal AF, preprocedural LAA upward wall‐motion velocity at the apex, as determined by tissue Doppler imaging during transesophageal echocardiography, may be a useful indicator for predicting recurrence of AF within 1 year after CA.     

心房颤动重构机制研究进展

心房颤动是最常见快速型心律失常性疾病。目前心房颤动发生机制研究分神经、重构、压力、炎症机制等临床方面和基因、分子生物学水平上的进展。其中重构机制是适应性代偿作用,又是心房颤动发生和维持的重要因素。现主要综述电生理、形态结构、功能上的重构与心房颤动的关系。     

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).     

Right Atrial Remodeling is More Advanced in Patients with Atrial Flutter Than with Atrial Fibrillation

Atrial Remodeling in Atrial Flutter. Introduction: Atrial fibrillation (AF) and atrial flutter (AFL) are related arrhythmias with common triggers, yet in individual patients either AF or AFL often predominates. We performed detailed electrophysiologic (EP) and electroanatomic (EA) studies of the right atrium (RA) in patients with AF and AFL to determine substrate differences that may explain the preferential expression of AF/AFL in individual patients. Methods: Patients with AF (n = 13) were compared to patients with persistent AFL (n = 10). Detailed studies were performed, and 3‐dimensional electroanatomic mapping studies were created and the RA was divided into 4 segments for regional analysis. Global, septal, lateral, anterior, and posterior segments were compared for analysis of: bipolar voltage; proportion of low‐voltage areas and areas of electrical silence; conduction times; and proportion of abnormal signals (fractionated signals and double potentials). Results: Compared to patients with AF, patients with AFL had (1) lower bipolar voltage and an increase in the proportion of low‐voltage areas; (2) an increase in the proportion of complex signals; and (3) prolongation of activation times. Conclusions: Patients with AFL showed more advanced remodeling than patients with AF with slowed conduction, lower voltage areas with regions of electrical silence, and a greater proportion of complex signals, particularly in the posterior RA. These changes facilitate the stabilization of AFL and may explain why some patients are more likely to develop AFL as a sustained clinical arrhythmia. (J Cardiovasc Electrophysiol, Vol. 23 pp. 1067‐1072, October 2012)     

心房颤动发生与维持的重构机制

心房颤动是一种以房律紊乱为特点的常见室上性心律失常,可导致严重临床症状和并发症。重构机制参与心房颤动的发生与维持,它包括电重构、神经重构、收缩重构和结构重构等。目前,心房颤动的重构机制不完全清楚。     

Catheter Ablation of Long‐Standing Persistent Atrial Fibrillation: A Lesson from Circumferential Pulmonary Vein Isolation

Catheter Ablation of Long‐Standing Persistent AF. Introduction: Circumferential pulmonary vein isolation (CPVI) is associated with a high success rate in patients with paroxysmal and persistent atrial fibrillation (AF). However, in patients with long‐standing persistent AF, the ideal ablation strategy still remains a matter of debate. Methods and Results: Two‐hundred and five patients underwent catheter ablation for long‐standing persistent AF defined as continuous AF of more than 1‐year duration. In a first step, all patients underwent CPVI. If direct‐current cardioversion failed following CPVI, ablation of complex fractionated atrial electrograms (CFAEs) was performed. The goal was conversion into sinus rhythm (SR) or, alternatively, atrial tachycardia (AT) with subsequent ablation. A total of 340 procedures were performed. CPVI alone was performed during 165 procedures in 124 of 205 (60.5%) patients. In the remaining 81 patients, additional CFAE ablation was performed in 45, left linear lesions for recurrent ATs in 44 and SVC isolation in 15 patients, respectively, resulting in inadvertent left atrial appendage isolation in 9 (4.4%) patients. After the initial ablation procedure, 67 of 199 patients remained in SR during a mean follow‐up of 19 ± 11 months. Six patients were lost to follow‐up. After a mean of 1.7 ± 0.8 procedures, 135 of 199 patients (67.8%) remained in SR. Eighty‐six patients (43.2%) remained in SR following CPVI performed as the sole ablative strategy. Conclusions: CPVI alone is sufficient to restore SR in 43.2% of patients with long‐standing persistent AF. Multiple procedures and additional ablation strategies with a significant risk of inadvertent left atrial appendage isolation are often required to maintain stable SR. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1085‐1093)     

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.