Atrial Electrogram Fractionation Distribution before and after Pulmonary Vein Isolation in Human Persistent Atrial Fibrillation-A Retrospective Multivariate Statistical Analysis.
ABSTRACT: Purpose: Complex fractionated atrial electrograms (CFAE)-guided ablation after pulmonary vein isolation (PVI) has been used for persistent atrial fibrillation (persAF) therapy. This strategy has shown suboptimal outcomes due to, among other factors, undetected changes in the atrial tissue following PVI. In the present work, we investigate CFAE distribution before and after PVI in patients with persAF using a multivariate statistical model. Methods: 207 pairs of atrial electrograms (AEGs) were collected before and after PVI respectively, from corresponding LA regions in 18 persAF patients. Twelve attributes were measured from the AEGs, before and after PVI. Statistical models based on multivariate analysis of variance (MANOVA) and linear discriminant analysis (LDA) have been used to characterize the atrial regions and AEGs. Results: PVI significantly reduced CFAEs in the LA (70 vs. 40%; P < 0.0001). Four types of LA regions were identified, based on the AEGs characteristics: (i) fractionated before PVI that remained fractionated after PVI (31% of the collected points); (ii) fractionated that converted to normal (39%); (iii) normal prior to PVI that became fractionated (9%) and; (iv) normal that remained normal (21%). Individually, the attributes failed to distinguish these LA regions, but multivariate statistical models were effective in their discrimination (P < 0.0001). Conclusion: Our results have unveiled that there are LA regions resistant to PVI, while others are affected by it. Although, traditional methods were unable to identify these different regions, the proposed multivariate statistical model discriminated LA regions resistant to PVI from those affected by it without prior ablation information.
Project description:Ablation of persistent atrial fibrillation (persAF) targeting complex fractionated atrial electrograms (CFAEs) detected by automated algorithms has produced conflicting outcomes in previous electrophysiological studies. We hypothesize that the differences in these algorithms could lead to discordant CFAE classifications by the available mapping systems, giving rise to potential disparities in CFAE-guided ablation. This study reports the results of a head-to-head comparison of CFAE detection performed by NavX (St. Jude Medical) versus CARTO (Biosense Webster) on the same bipolar electrogram data (797 electrograms) from 18 persAF patients. We propose revised thresholds for both primary and complementary indices to minimize the differences in CFAE classification performed by either system. Using the default thresholds [NavX: CFE-Mean ? 120 ms; CARTO: ICL ? 7], NavX classified 70 % of the electrograms as CFAEs, while CARTO detected 36 % (Cohen's kappa ? ? 0.3, P < 0.0001). Using revised thresholds found using receiver operating characteristic curves [NavX: CFE-Mean ? 84 ms, CFE-SD ? 47 ms; CARTO: ICL ? 4, ACI ? 82 ms, SCI ? 58 ms], NavX classified 45 %, while CARTO detected 42 % (? ? 0.5, P < 0.0001). Our results show that CFAE target identification is dependent on the system and thresholds used by the electrophysiological study. The thresholds found in this work counterbalance the differences in automated CFAE classification performed by each system. This could facilitate comparisons of CFAE ablation outcomes guided by either NavX or CARTO in future works.
Project description:Pulmonary vein isolation (PVI) is recognized as a potentially curative treatment for atrial fibrillation (AF). Ablation of complex fractionated atrial electrograms (CFAEs) in addition to PVI has been advocated as a means to improve procedural outcomes, but the benefit remains unclear.This study sought t synthesize the available data testing the incremental benefit of adding CFAE ablation to PVI.We performed a meta-analysis of controlled studies comparing the effect of PVI with CFAE ablation vs. PVI alone in patients with paroxysmal and nonparoxysmal AF.Of the 481 reports identified, 8 studies met our inclusion criteria. There was a statistically significant increase in freedom from atrial tachyarrhythmia (AT) with the addition of CFAE ablation (relative risk [RR] 1.15, P = .03). In the 5 reports of nonparoxysmal AF (3 randomized controlled trials, 1 controlled clinical trial, and 1 trial using matched historical controls), addition of CFAE ablation resulted in a statistically significant increase in freedom from AT (n = 112 of 181 [62%] for PVI+CFAE vs. n = 84 of 179 [47%] for PVI alone; RR 1.32, P = .02). In trials of paroxysmal AF (3 randomized controlled trials and 1 trial using matched historical controls), addition of CFAE ablation did not result in a statistically significant increase in freedom from AT (n = 131 of 166 [79%] for PVI+CFAE vs. n = 122 of 164 [74%] for PVI alone; RR 1.04, P = .52).In these studies of patients with nonparoxysmal AF, addition of CFAE ablation to PVI results in greater improvement in freedom from AF. No additional benefit of this combined approach was observed in patients with paroxysmal AF.
Project description:The unstable temporal behavior of atrial electrical activity during persistent atrial fibrillation (persAF) might influence ablation target identification, which could explain the conflicting persAF ablation outcomes in previous studies. We sought to investigate the temporal behavior and consistency of atrial electrogram (AEG) fractionation using different segment lengths. Seven hundred ninety-seven bipolar AEGs were collected with three segment lengths (2.5, 5,and 8 s) from 18 patients undergoing persAF ablation. The AEGs with 8-s duration were divided into three 2.5-s consecutive segments. AEG fractionation classification was applied off-line to all cases following the CARTO criteria; 43% of the AEGs remained fractionated for the three consecutive AEG segments, while nearly 30% were temporally unstable. AEG classification within the consecutive segments had moderate correlation (segment 1 vs 2: Spearman's correlation ? = 0.74, kappa score ? = 0.62; segment 1 vs 3: ? = 0.726, ? = 0.62; segment 2 vs 3: ? = 0.75, ? = 0.68). AEG classifications were more similar between AEGs with 5 and 8 s (? = 0.96, ? = 0.87) than 2.5 versus 5 s (? = 0.93, ? = 0.84) and 2.5 versus 8 s (? = 0.90, ? = 0.78). Our results show that the CARTO criteria should be revisited and consider recording duration longer than 2.5 s for consistent ablation target identification in persAF.
Project description:Atrial anatomy and thickness may affect the electrical wave-dynamics of atrial fibrillation (AF). We explored the relationship between left atrial (LA) wall thickness (LAWT) or LA geometry and AF wave-dynamics.We included 15 patients with persistent AF (age, 62.3 ± 11.9 years) who underwent AF catheter ablation. We measured the LAWT, LA endocardial curvature, and SD-curvature (surface bumpiness) from preprocedural computed tomography images. We compared those anatomical characteristics with electrophysiologic parameters such as dominant frequency (DF), Shannon entropy (ShEn), or complex fractionated atrial electrogram (CFAE)-cycle length (CL), calculated from intracardiac bipolar electrograms (300-500 points, 5 s), acquired during ablation procedures.1. LAWT (excluding fat) varied widely among patients, locations, and types of AF. LAWT was inversely correlated with LA volume (r = -0.565, p = 0.028) and positively correlated with SD-curvature (r = 0.272, p < 0.001). 2. LAWT was positively correlated with ShEn (r = 0.233, p < 0.001) and negatively correlated with CFAE-CL (r = -0.107, p = 0.038). 3. In the multivariate linear regression analyses for AF wave-dynamics parameters, DF (β = -0.29 [95% CI -0.44--0.14], p < 0.001), ShEn (β = 0.19 [95% CI 0.12-0.25], p < 0.001), and CFAE-CL (β = 7.49 [95% CI 0.65-14.34], p = 0.032) were independently associated with LAWT.Regional LAWT is associated with LA structural features, and has significant correlations with the wave-dynamics parameters associated with electrical wavebreaks or rotors in patients with persistent AF.
Project description:Several clinically relevant outcomes post atrial substrate modification in patients with atrial fibrillation (AF) have not been systematically analyzed among published studies on adjunctive cardiac ganglionated plexi (GP) or complex fractionated atrial electograms (CFAE) ablation vs. pulmonary vein isolation (PVI) alone. Out of 176 reports identified, the present meta-analysis included 14 randomized and non-randomized controlled trials (1613 patients) meeting inclusion criteria. Addition of GP ablation to PVI significantly increased freedom from atrial tachyarrhythmia in short- (OR: 1.72; P = 0.003) and long-term (OR: 2.0, P = 0.0006) follow-up, while adjunctive CFAE ablation did not after one or repeat procedure (P<0.05). The percentage of atrial tachycardia or atrial flutter (AT/AFL) after one procedure was higher for CFAE than GP ablation. In sub-analysis of non-paroxysmal AF, relative to PVI alone, adjunctive GP but not CFAE ablation significantly increased sinus rhythm maintenance (OR: 1.88, P = 0.01; and OR:1.24, P = 0.18, respectively). Meta regression analysis of the 14 studies indicated that sample size was significant source of heterogeneity either in outcomes after one or repeat procedure. In conclusion, in patients with AF, adjunctive GP but not CFAE ablation appeared to significantly add to the beneficial effects on sinus rhythm maintenance of PVI ablation alone; and CFAE ablation was associated with higher incidence of subsequent AT/AFL.
Project description:Although 3D-complex fractionated atrial electrogram (CFAE) mapping is useful in radiofrequency catheter ablation for persistent atrial fibrillation (AF), the directions and configuration of the bipolar electrodes may affect the electrogram. This study aimed to compare the spatial reproducibility of CFAE by changing the catheter orientations and electrode distance in an in-silico left atrium (LA). We conducted this study by importing the heart CT image of a patient with AF into a 3D-homogeneous human LA model. Electrogram morphology, CFAE-cycle lengths (CLs) were compared for 16 different orientations of a virtual bipolar conventional catheter (conv-cath: size 3.5 mm, inter-electrode distance 4.75 mm). Additionally, the spatial correlations of CFAE-CLs and the percentage of consistent sites with CFAE-CL<120 ms were analyzed. The results from the conv-cath were compared with that obtained using a mini catheter (mini-cath: size 1 mm, inter-electrode distance 2.5 mm). Depending on the catheter orientation, the electrogram morphology and CFAE-CLs varied (conv-cath: 11.5±0.7% variation, mini-cath: 7.1±1.2% variation), however the mini-cath produced less variation of CFAE-CL than conv-cath (p<0.001). There were moderate spatial correlations among CFAE-CL measured at 16 orientations (conv-cath: r=0.3055±0.2194 vs. mini-cath: 0.6074±0.0733, p<0.001). Additionally, the ratio of consistent CFAE sites was higher for mini catheter than conventional one (38.3±4.6% vs. 22.3±1.4%, p<0.05). Electrograms and CFAE distribution are affected by catheter orientation and electrode configuration in the in-silico LA model. However, there was moderate spatial consistency of CFAE areas, and narrowly spaced bipolar catheters were less influenced by catheter direction than conventional catheters.
Project description:Complex fractionated atrial electrograms (CFAE) are targets of atrial fibrillation (AF) ablation. Serial high-density maps were evaluated to understand the impact of activation direction and rate on electrogram (EGM) fractionation.Eighteen patients (9 persistent) underwent high-density, 3-dimensional, left-atrial mapping (>400 points/map) during AF, sinus (SR), and CS-paced (CSp) rhythms. In SR and CSp, fractionation was defined as an EGM with ?4 deflections, although, in AF, CFE-mean <80 ms was considered as continuous CFAE. The anatomic distribution of CFAE sites was assessed, quantified, and correlated between rhythms. Mechanisms underlying fractionation were investigated by analysis of voltage, activation, and propagation maps. A minority of continuous CFAE sites displayed EGM fractionation in SR (15+/-4%) and CSp (12+/-8%). EGM fractionation did not match between SR and CSp at 70+/-10% sites. Activation maps in SR and CSp showed that wave collision (71%) and regional slow conduction (24%) caused EGM fractionation. EGM voltage during AF (0.59+/-0.58 mV) was lower than during SR and CSp (>1.0 mV) at all sites. During AF, the EGM voltage was higher at continuous CFAE sites than at non-CFAE sites (0.53 mV (Q1, Q3: 0.33 to 0.83) versus 0.30 mV (Q1, Q3: 0.18 to 0.515), P<0.00001). Global LA voltage in AF was lower in patients with persistent AF versus patients with paroxysmal AF (0.6+/-0.59 mV versus 1.12+/-1.32 mV, P<0.01).The distribution of fractionated EGMs is highly variable, depending on direction and rate of activation (SR versus CSp versus AF). Fractionation in SR and CSp rhythms mostly resulted from wave collision. All sites with continuous fractionation in AF displayed normal voltage in SR, suggesting absence of structural scar. Thus, many fractionated EGMs are functional in nature, and their sites dynamic.
Project description:Effects of nonparoxysmal atrial fibrillation (non-PAF) ablation targeting complex fractionated atrial electrogram (CFAE) areas and/or low voltage areas (LVAs) are still controversial.A recently developed online real-time phase mapping system (ExTRa Mapping) was used to conduct LVA mapping and simultaneous ExTRa and CFAE mapping in 28 non-PAF patients after pulmonary vein isolation (PVI). Nonpassively activated areas, in the form of meandering rotors and/or multiple wavelets assumed to contain non-PAF drivers, partly overlapped with CFAE/LVAs but not always coincided with them.Real-time rotor imaging, rather than conventional indirect indicators only, might be very useful for detecting non-PAF drivers.
Project description:This multicentre, randomized trial compared three strategies of AF ablation: ablation of complex fractionated electrograms (CFE) alone, pulmonary vein isolation (PVI) alone, and combined PVI + CFE ablation, using standardized automated mapping software.Patients with drug-refractory, high-burden paroxysmal (episodes >6 h, >4 in 6 months) or persistent atrial fibrillation (AF) were enrolled at eight centres. Patients (n = 100) were randomized to one of three arms. For CFE alone (n = 34), spontaneous/induced AF was mapped using validated, automated CFE software and all sites <120 ms were ablated until AF termination/non-inducibility. For PVI (n = 32), all four PV antra were isolated and confirmed using a circular catheter. For PVI + CFE (n = 34), all four PV antra were isolated, followed by AF induction and ablation of all CFE sites until AF termination/non-inducibility. Patients were followed at 3, 6, and 12 months with a visit, ECG, 48 h Holter. Atrial fibrillation symptoms were confirmed by loop recording. Repeat procedures were allowed within the first 6 months. The primary endpoint was freedom from AF >30 s at 1 year. Patients (age 57 +/- 10 years, LA size 42 +/- 6 mm) were 35% persistent AF. In CFE, ablation terminated AF in 68%. Only 0.4 PVs per patient were isolated as a result of CFE. In PVI, 94% had all four PVs successfully isolated. In PVI + CFE, 94% had all four PVs isolated, 76% had inducible AF with additional CFE ablation, with 73% termination of AF. There were significantly more repeat procedures in the CFE arm (47%) vs. PVI (31%) or PVI + CFE (15%) (P = 0.01). After one procedure, PVI + CFE had a significantly higher freedom from AF (74%) compared with PVI (48%) and CFE (29%) (P = 0.004). After two procedures, PVI + CFE still had the highest success (88%) compared with PVI (68%) and CFE (38%) (P = 0.001). Ninety-six percent of these patients were off anti-arrhythmics. Complications were two tamponades, no PV stenosis, and no mortality.In high-burden paroxysmal/persistent AF, PVI + CFE has the highest freedom from AF vs. PVI or CFE alone after one or two procedures. Complex fractionated electrogram alone has the lowest one and two procedure success rates with a higher incidence of repeat procedures. ClinicalTrials.gov identifier number NCT00367757.
Project description:Electrogram-based catheter ablation, targeting complex fractionated atrial electrograms (CFAEs), is empirically known to be effective in halting persistent/permanent atrial fibrillation (AF). However, the mechanisms underlying CFAEs and electrogram-based ablation remain unclear.Because atrial fibrosis is associated with persistent/permanent AF, we hypothesized that electrotonic interactions between atrial myocytes and fibroblasts play an important role in CFAE genesis and electrogram-based catheter ablation.We used a human atrial tissue model in heart failure and simulated propagation and spiral wave reentry with and without regionally proliferated fibroblasts. Coupling of fibroblasts to atrial myocytes resulted in shorter action potential duration, slower conduction velocity, and lower excitability. Consequently, heterogeneous fibroblast proliferation in the myocardial sheet resulted in frequent spiral wave breakups, and the bipolar electrograms recorded at the fibroblast proliferation area exhibited CFAEs. The simulations demonstrated that ablation targeting such fibroblast-derived CFAEs terminated AF, resulting from the ablation site transiently pinning the spiral wave and then pushing it out of the fibroblast proliferation area. CFAEs could not be attributed to collagen accumulation alone.Fibroblast proliferation in atria might be responsible for the genesis of CFAEs during persistent/permanent AF. Our findings could contribute to better understanding of the mechanisms underlying CFAE-targeted AF ablation.