Complex Fractionated Atrial Electrograms Sites Research Articles

High Dominant Frequencies and Fractionated Potentials Do Not Indicate Focal or Rotational Activation During AF

BackgroundDominant frequencies (DFs) or complex fractionated atrial electrograms (CFAEs), indicative of focal sources or rotational activation, are used to identify target sites for atrial fibrillation (AF) ablation in clinical studies, although the relationship among DF, CFAE, and activation patterns remains unclear. ObjectivesThis study sought to investigate the relationship between patterns of activation underlying DF and CFAE sites during AF. MethodsEpicardial high-resolution mapping of the right and left atrium including Bachmann’s bundle was performed in 71 participants. We identified the highest dominant frequency (DFmax) and highest degree of CFAE (CFAEmax) with the use of existing clinical criteria and classified patterns of activation as focal or rotational activation and smooth propagation, conduction block (CB), collision and remnant activity, and fibrillation potentials as single, double, or fractionated potentials containing, respectively, 1, 2, or 3 or more negative deflections. Relationships among activation patterns, DFmax, and potential types were investigated. ResultsDFmax were primarily located at the left atrioventricular groove and did not harbor focal activation (proportion focal waves: 0% [IQR: 0%-2%]). Compared with non-DFmax sites, DFmax were characterized by more frequent smooth propagation (22% [IQR: 7%-48%] vs 17% [IQR: 11%-24%]; P = 0.001), less frequent conduction block (69% [IQR: 51%-81%] vs 74% [IQR: 69%-78%]; P = 0.006), a higher proportion of single potentials (72% [IQR: 55%-84%] vs 6%1 [IQR: 55%-65%]; P = 0.003), and a lower proportion of fractionated potentials (4% [IQR: 1%-11%] vs 12% [IQR: 9%-15%]; P = 0.004). CFAEmax were mainly found at the pulmonary veins area, and only 1% [IQR: 0%-2%] of all CFAEmax contained focal activation. Compared with non-CFAEmax sites, CFAEmax sites were characterized by less frequent smooth propagation (1% [IQR: 0%-1%] vs 17% [IQR: 12%-24%]; P < 0.001) and more frequent remnant activity (20% [IQR: 12%-29%] vs 8% [IQR: 5%-10%]; P < 0.001), and harbored predominantly fractionated potentials (52% [IQR: 43%-66%] vs 12% [IQR: 9%-14%]; P < 0.001). ConclusionsFocal or rotational patterns of activation were not consistently detected at DFmax domains and CFAEmax sites. These findings do not support the concept of targeting DFmax or CFAEmax according to existing criteria for AF ablation.

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.

Complex fractionated atrial electrograms, high dominant frequency regions, and left atrial voltages during sinus rhythm and atrial fibrillation

BackgroundAblation targeting complex fractionated atrial electrograms (CFAEs) or high dominant frequency (DF) sites is generally effective for persistent atrial fibrillation (AF). CFAEs and/or high DF sites may exist in low-voltage regions, which theoretically represent abnormal substrates. However, whether CFAEs or high DF sites reflect low voltage substrates during sinus rhythm (SR) is unknown. MethodsSixteen patients with AF (8 with paroxysmal AF; 8, persistent AF) underwent high-density mapping of the left atrium (LA) with a 3-dimensional electroanatomic mapping system before ablation. The LA was divided into 7 segments and the mean bipolar voltage recorded during AF and SR, CFAEs (cycle lengths of 50–120ms), and DF sites were assessed in each segment with either a duo-decapolar ring catheter (n=10) or a 64-pole basket catheter (n=6). Low-voltage areas were defined as those of <0.5mV during AF and <1.0mV during SR. ResultsRegional mean voltage recorded from the basket catheter showed good correlation between AF and SR (r=0.60, p<0.01); however, the % low-voltage area in the LA recorded from the ring catheter showed weak correlation (r=0.34, p=0.05). Mean voltage was lower during AF than during SR (1.0mV [IQR, 0.5–1.4] vs. 2.6mV [IQR, 1.8–3.6], p<0.01). The regional and overall % low-voltage area of the LA was greater during AF than during SR (20% vs. 11%, p=0.05). CFAEs and high DF sites (>8Hz) did not correlate with % low-voltage sites during SR; however, CFAEs sites were located in high-voltage regions during AF and high DF sites were located in low voltage regions during AF. ConclusionsCFAEs and high DF areas during AF do not reflect damaged atrial myocardium as shown by the SR voltage. However, CFAEs and high DF sites may demonstrate different electrophysiologic properties because of different voltage amplitude during AF.

Anatomical proximity between ganglionated plexi and epicardial adipose tissue in the left atrium: implication for 3D reconstructed epicardial adipose tissue-based ablation.

We sought to better understand the association between and clinical implications of ganglionated plexi (GPs), epicardial adipose tissue (EAT) in the left atrium (LA), and the initiation and maintenance of atrial fibrillation (AF). Three-dimensional (3D) computed tomography (CT) reconstruction images of the LA, PVs, and LA-EAT were merged with the LA geometry for 25 with paroxysmal AF (PAF) and 15 with persistent AF (PerAF) scheduled for ablation. High-frequency stimulation (20Hz, 25mA, 10ms) was performed at three sites within each of the five major anatomical LA GPs (superior left, inferior left, anterior right, inferior right, and Marshall tract GPs) to elicit vagal responses. Correspondence between the five GP areas and vagal response sites, LA-EAT, and complex fractionated atrial electrograms (CFAEs) was examined. The long-term outcomes of adjuvant LA-EAT-based ablation were assessed in 31 patients with PAF and 102 with PerAF. LA-EAT overlapped 93 ± 14% of five major anatomical GP areas, and the vagal response sites and CFAE sites corresponded to 77 ± 23 and 76 ± 25%, respectively (p < 0.05 for both vs. LA-EAT locations). The EAT-based ablation eliminated 97.6% of the vagal response sites and lengthened the AF cycle from 160 ± 26 to 193 ± 27ms (p < 0.001). The 2-year arrhythmia-free rate after EAT-based ablation was 72% in the PAF group and 73% in the PerAF group (p = 0.614). LA-EAT tends to overlie the major anatomical GP areas including most of the active GP response sites and CFAEs associated with AF. Ablation of GPs and CFAEs may explain the long-term efficacy of EAT-based ablation following extensive encircling pulmonary vein isolation (EEPVI) for AF.

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.

A Decade of CFAE Mapping: Still Seeking More Specific Tools to Identify Sources and Substrate of Persistent Atrial Fibrillation.

A decade after its first description as ‘the electrophysiological substrate’ of atrial fibrillation,1 mapping complex fractionated atrial electrogram (CFAE) as an ablation target for atrial fibrillation (AF) remains highly controversial. Early high-density mapping studies of induced AF in humans revealed distinct mechanisms that underlie electrogram fractionation: collision areas of distinct wavefronts, sites of wavelet pivoting, anisotropic/slow conduction and conduction block.2 Further mapping studies revealed the functional nature of electrogram fractionation that implies important variations in distribution of fractionated activity within the same atria during different rhythms (AF versus sinus rhythm or paced rhythm).3 The recent multicentre randomised trial STAR-AF II failed to reveal any added benefit of CFAE ablation when performed in addition to pulmonary vein isolation in patients with persistent AF.4 Importantly, in that study only CFAE sites were targeted by ablation that were detected by the NavX ‘CFEmean’ algorithm (St Jude Medical). Previous studies have shown that the CFEmean algorithm detects fractionated activity at high voltage (>0.5 mV) – i.e. underdetecting CFAE within low voltage sites.3 Similarly, another randomised clinical study failed to show an added value of CFAE ablation when using the CFEmean algorithm.5 Multiple distinct types of CFAE may be observed during AF or regular rhythms. Although some CFAE patterns as continuous activity or presence of activation gradients between neighbouring bipoles6 have been described to have a greater impact with regard to AF termination or cycle length prolongation, their identification depends on the subjective judgment of the operator, because automatic CFAE algorithms fail to specifically differentiate these active CFAE types from passive ones. CFAE may be intermittent versus continuous versus high voltage (>0.5 mV) versus low voltage (<0.5 mV).7 Identification of the active CFAE sites that correspond to active AF driver sites remains a major challenge of future mapping techniques and developments. In this issue of the journal Sohal and colleagues8 give a comprehensive overview of the distinct CFAE types and difficulties in their distinction that depends on the electrode size, the mode of electrogram filtering/recording (unipolar vs bipolar) and the CFAE detection algorithm used. They provide a future perspective on a novel, promising non-invasive mapping tool enabling detection of sources and drivers of AF: the ECVUE Mapping System (CardioInsight Technologies).8,9 Recent clinical data have identified AF drivers to CFAE sites within low voltage areas that display prolonged electrical activity when using simultaneous regional mapping with multi-electrode catheters with smaller electrodes and higher local mapping resolution than a 4 mm tip ablation catheter.7,10 Future studies on persistent AF need to assess clinical efficacy of the novel AF mapping tools to identify the active CFAE sites from the passive ones, as well as impact of novel voltage-based substrate mapping/ablation strategies on rate of arrhythmia freedom.7,10,11

Connexin and fibrosis related microRNAs in complex fractionated atrial electrograms.

Connexin and fibrosis related microRNAs in complex fractionated atrial electrograms.

Spatial and temporal variability of the complex fractionated atrial electrogram activity and dominant frequency in human atrial fibrillation

BackgroundThe presence of complex fractionated atrial electrograms (CFAEs) and high dominant frequencies (DFs) during atrial fibrillation (AF) have been demonstrated to be related to AF maintenance. Therefore, sequential mapping of CFAEs and DFs have been used for target sites of AF ablation. However, such mapping strategies are valid only if the CFAEs and DFs are spatiotemporally stable during the mapping procedure. We obtained spatially stable multi-electrode recordings to assess the spatiotemporal stability of CFAEs and DFs. MethodsWe recorded electrical activity during AF for 10min with a 64-electrode basket catheter (48 bipole electrode pairs) placed in the left atrium in 36 patients with AF (paroxysmal AF [PAF], n=16; persistent AF [PerAF], n=20). The spatial and temporal distribution of the CFAEs (fractionation interval <120ms) and high DFs (>8Hz) at 1-min intervals for 10min were compared for each of the 48 bipoles. ResultsThe baseline CFAEs were located at 68.5±14.0% (32.9±6.7) of the 48 bipoles; however, the high DF sites were fewer (9.6±8.6% [4.6±4.1 bipoles]). The CFAEs sites did not change significantly during the 10-min recording period (kappa statistic: 0.71±0.24); however, the high DF sites changed significantly (kappa statistic: 0.07±0.19). These spatiotemporal changes in the CFAEs and high DFs did not differ between patients with PAF and PerAF. ConclusionsRegardless of the AF type, CFAEs sites, but not high DF sites, showed a high degree of spatial and temporal stability.

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.

Selective Complex Fractionated Atrial Electrograms Targeting for Atrial Fibrillation Study (SELECT AF)

Background— This study compared generalized complex fractionated atrial electrograms (CFAE) ablation versus a selective CFAE ablation strategy targeting areas of continuous electric activity. Methods and Results— Subjects with symptomatic, persistent/high-burden paroxysmal atrial fibrillation (AF) were enrolled at 6 centers (n=86) and randomized to 1 of 2 arms. For group I, all CFAE regions with an interval confidence level &gt;7 were ablated followed by pulmonary vein isolation (PVI). For group II, only CFAE sites with continuous electric activity were ablated followed by PVI. For PVI, all 4 PV antra were isolated with confirmed entrance block. Subjects were followed for 1 year with a visit, ECG, and 48-hour Holter every 3 months. Symptoms were confirmed by loop recording. The primary end point was freedom from arrhythmia &gt;30 seconds at 1 year. For both group I and II, CFAE ablation prolonged AF cycle length (25±33 versus 23±33 ms; P =0.78) and resulted in similar rates of AF termination (37% versus 28%; P =0.42). Radiofrequency duration during CFAE ablation was significantly less in group II (23±20 versus 38±20 minutes; P =0.002). At 1-year follow-up, freedom from AF/atrial flutter/atrial tachycardia recurrence was significantly higher in group I versus group II after 1 procedure (50% versus 28%; P =0.03). There were also significantly fewer repeat procedures in group I (13% versus 36%; P =0.021). Conclusions— Continuous electric activity ablation+PVI result in a similar incidence of acute AF termination with significantly less radiofrequency time. However, incidence of repeat procedures and long-term recurrence of AF/atrial flutter/atrial tachycardia are significantly lower using generalized CFAE ablation+PVI. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00926783

Amiodarone reduces the amount of ablation during catheter ablation for persistent atrial fibrillation

The step-wise approach to catheter ablation for persistent atrial fibrillation (AF) requires considerable substrate modification targeting at complex fractionated atrial electrograms (CFAEs) in addition to pulmonary vein (PV) isolation. An alternative strategy that minimizes the amount of ablation would be desirable. The aim of this study was to investigate whether the use of pre-procedural amiodarone affects: (i) the amount of ablation required to achieve procedural success, and (ii) long-term outcomes. We studied 121 consecutive patients with persistent AF who underwent catheter ablation. The patients were divided into two groups: Group 1, amiodarone (n = 31); Group 2, other antiarrhythmic drugs or rate control (n = 90). All the patients underwent a step-wise ablation procedure beginning with PV isolation, then proceeding with ablation of the CFAEs and linear lesions until sinus rhythm was achieved. Mean left atrial cycle length of AF (AFCL) was recorded at each step. The number of CFAE ablation sites was recorded. The number of CFAE sites in Group 1 was significantly less than that in Group 2 (P = 0.0121). The AFCLs after each step in Group 1 were significantly longer than those in Group 2. The procedure time and the radiofrequency time of CFAE ablation in Group 1 were significantly shorter than that in Group 2 (P = 0.0276 and P = 0.0458, respectively). There was no significant difference between the two groups in early and long-term outcomes. Use of pre-procedural amiodarone prolongs AFCL during catheter ablation and reduces the number of CFAE sites requiring ablation to achieve procedural success while maintaining equivalent long-term results.

Combined Dominant Frequency and Complex Fractionated Atrial Electrogram Ablation After Circumferential Pulmonary Vein Isolation of Atrial Fibrillation

Atrial substrates with high-dominant frequency (DF) and complex fractionated atrial electrogram (CFAE) sites have sources maintaining atrial fibrillation (AF) and are potential AF ablation targets. This study aimed to evaluate an approach of circumferential pulmonary vein isolation (PVI) followed by a DF and CFAE site ablation. Fifty consecutive AF patients (23 paroxysmal, 9 persistent, and 18 longstanding persistent) underwent ablation, using NavX. When AF continued after circumferential PVI, high-DF sites of ≥ 8 Hz and then continuous left atrial (LA) CFAE sites defined by fractionated intervals (FI) of ≤50 milliseconds including the coronary sinus and right atrium were targeted. A total of 45.1% of high-DF and 48.1% of continuous CFAE sites significantly decreased after PVI (P < 0.001). The mean LA DF and FI significantly decreased and prolonged, respectively, after PVI (P < 0.001). Only 14.1% of all high-DF sites after PVI overlapped with continuous CFAE sites. AF terminated at high-DF sites in 11 (22%) patients and continuous CFAE sites in 1 (2%). AF could be induced in only 8% of patients after the procedure. The mean LA DF value before ablation was significantly lower in those without recurrence (P = 0.003). AF freedom on antiarrhythmic drugs was 96% and 59%, respectively, in the paroxysmal and nonparoxysmal AF patients (89% persistent and 44% longstanding persistent) after 1 procedure over a 12-month follow-up. A combined high-DF and continuous CFAE site ablation in all chambers after circumferential PVI may be effective in the paroxysmal and persistent AF patients.

Panoramic electrophysiological mapping but not electrogram morphology identifies stable sources for human atrial fibrillation: stable atrial fibrillation rotors and focal sources relate poorly to fractionated electrograms.

The foundation for successful arrhythmia ablation is the mapping of electric propagation to identify underlying mechanisms. In atrial fibrillation (AF), however, mapping is difficult so that ablation has often targeted electrogram features, with mixed results. We hypothesized that wide field-of-view (panoramic) mapping of both atria would identify causal mechanisms for AF and allow interpretation of local electrogram features, including complex fractionated atrial electrograms (CFAE). Contact mapping was performed using biatrial multipolar catheters in 36 AF subjects (29 persistent). Stable AF rotors (spiral waves) or focal sources were seen in 35 of 36 cases and targeted for ablation (focal impulse and rotor modulation) before pulmonary vein isolation. In 31 of 36 subjects (86.1%), AF acutely terminated (n=20; 16 to sinus rhythm) or organized (n=11; 19±8% slowing) with 2.5 minutes focal impulse and rotor modulation (interquartile range, 1.0-3.1) at one source, defined as the primary source. Subjects exhibited 2.1±1.0 concurrent AF sources of which the primary, by phase mapping, precessed in limited areas (persistent 2.5±1.7 versus paroxysmal 1.7±0.5 cm(2); P=0.30). Notably, source regions showed mixed electrogram amplitudes and CFAE grades that did not differ from surrounding atrium (P=NS). AF sources were not consistently surrounded by CFAE (P=0.67). Stable rotors and focal sources for human AF were revealed by contact panoramic mapping (focal impulse and rotor modulation mapping), but not by electrogram footprints. AF sources precessed within areas of ≈2 cm(2), with diverse voltage characteristics poorly correlated with CFAE. Most CFAE sites lie remote from AF sources and are not suitable targets for catheter ablation of AF.

Substrate of complex fractionated atrial electrograms: evidence by pathologic analysis

Ablation of complex fractionated atrial electrograms (CFAE) is an important adjunctive therapy in atrial fibrillation (AF). The present study was to elucidate the substrate underlying CFAE. Nine adult mongrel dogs were involved in the present study. AF was induced through rapid atrial pacing with vagosympathetic nerve stimulation. CFAE was recorded during AF. Ablation was performed at CFAE sites. Based on the location of the ablation scar, the atrial specimens were divided into CFAE and non-CFAE sites. Serial sections of the atrium were stained respectively with hematoxylin-eosin (HE) and the general neural marker protein gene product 9.5 (PGP9.5). We compared the characteristics of the myocardium and the ganglionated plexus (GPs) distribution between the CFAE and non-CFAE sites. The myocardium of non-CFAE sites was well-organized with little intercellular substance. However, the myocardium in the CFAE site was disorganized with more interstitial tissue ((61.7 ± 24.3)% vs. (34.1 ± 9.2)%, P < 0.01). GPs in the CFAE site were more abundant than in non-CFAE sites ((34.45 ± 37.46) bundles/cm(2) vs. (6.73 ± 8.22) bundles/cm(2), P < 0.01). The heterogeneity of the myocardium and GPs distribution may account for the substrate of CFAE and serve as a potential target of ablation.

Catheter Ablation for Persistent Atrial Fibrillation

A new era of atrial fibrillation (AF) treatment began in 1997–1998 with the discovery that triggers within the pulmonary veins initiate AF and reports that elimination of these triggers is successful in treating AF in its paroxysmal form.1–3 However, in patients with persistent AF, the success rate of exclusive pulmonary vein isolation is substantially lower.4,5 To improve the outcome of persistent AF ablation, different ablation strategies have been explored, but to date the optimal strategy has not been defined. Although some groups argue that limited ablation, including pulmonary vein isolation and, if present, ablation of nonpulmonary vein triggers, is sufficient for persistent AF ablation, other groups, including ours, favor more extensive, substrate-based ablation in addition to pulmonary vein isolation. In this review, we will discuss the rationale for a substrate-based ablation strategy to treat persistent AF and show why elimination of triggers is not sufficient in most patients with persistent AF. Response by Roten et al on p 1232 In a simple model, an electric impulse in AF can form because of abnormalities in impulse generation (triggers) or can result from abnormal impulse propagation (reentry). By a strict definition, a trigger is a focal source of new impulse generation. The mechanism by which a new impulse can form is either abnormal automaticity or triggered activity. Trigger-ablation protocols target these sources of new impulse generation. Abnormal impulse propagation, on the other hand, depends on altered substrate properties causing nonuniform or slowed conduction. This in turn causes multiple forms of wave reentry thought to be responsible for AF perpetuation: random reentry (multiple wavelets), macro- and microreentry, or functional reentry (rotors). Substrate-based ablation strategies aim to abate abnormal impulse propagation and interrupt any form of atrial reentry. Triggers of paroxysmal AF are mainly located in the pulmonary …

Comparative distribution of complex fractionated atrial electrograms, high dominant frequency (HDF) sites during atrial fibrillation and HDF sites during sinus rhythm

Complex fractionated atrial electrograms (CFAEs) and high dominant frequency sites during atrial fibrillation (AF-HDF) are related to the maintenance of atrial fibrillation (AF). HDF sites in sinus rhythm (SR-HDF; as defined by frequencies of >70 Hz) are suggested to be abnormal atrial tissue. Relations between these electrophysiologic signals have not been elucidated. We investigated the relations between SR-HDF and CFAE and AF-HDF sites during AF. NavX-based maps of CFAE and left atrium (LA)/pulmonary vein (PV) dominant frequency (DF) during AF and DF maps during SR were created for 23 patients with AF (paroxysmal AF (PAF), n = 14; persistent AF (PerAF), n = 9). The extent of overlap between SR-HDF and CFAE sites was 51 ± 18 % (as calculated by the LA/PV segments containing both an SR-HDF site and a CFAE site/total LA/PV segments containing an CFAE site) and the extent of overlap between SR-HDF and AF-HDF sites was 50 ± 35 % (P = 0.7464). However, statistically poor agreement was noted for both (kappa values, 0.07 ± 0.19 and 0.08 ± 0.24, P = 0.8794). The extent of overlap did not differ between PAF and PerAF patients (SR-HDF and CFAE, 52 % (interquartile range (IQR), 42-59) versus 57 % (IQR, 33-67), P = 0.5842; SR-HDF and AF-HDF, 43 % (IQR, 25-85) versus 55 % (IQR, 13-83), P = 0.9465). The bipolar voltage amplitudes of SR-HDF, CFAE, and AF-HDF sites revealed normal voltage areas (1.6 mV (IQR, 0.8-2.7), 1.9 mV (IQR, 1.1-2.8), and 1.5 mV (IQR, 1.7-2.7), respectively). In both PAF and PerAF, most CFAE and AF-HDF sites did not correspond to the SR-HDF sites or low-voltage area during SR. Thus, most CFAE and DF signals during AF represent functional electrical activities rather than structural remodeling of the atria.

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.

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

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. 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). 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.

Usefulness of ablation of complex fractionated atrial electrograms using nifekalant in persistent atrial fibrillation

BackgroundAdditional ablation of complex fractionated atrial electrograms (CFAE) after pulmonary vein isolation (PVI) has been shown to improve the success of ablation of persistent atrial fibrillation (AF). However, extensive ablation is often necessary to eliminate all CFAE or to terminate AF. We assessed the usefulness of the administration of an antiarrhythmic drug (AAD) before CFAE ablation. Methods and resultsOne-hundred and ten patients with persistent AF first underwent PVI, roof and floor linear ablation (box isolation). One hundred patients who remained in AF after box isolation were then randomized to either receive (AAD group, n=50) or not receive (no-AAD group, n=50) intravenous nifekalant (0.3mg/kg) followed by a CFAE ablation. In the AAD group, nifekalant terminated AF in 19 (38%) patients and ablation of localized CFAE was performed in 31 patients who remained in AF after nifekalant, and terminated AF in 11 (35%) patients. In the no-AAD group, ablation of CFAE terminated AF in 13 (26%) patients. The AAD group had a significantly lesser number of radio frequency applications at CFAE sites (18±12 versus 36±10, p<0.0001) and shorter procedure time (162±34 versus 197±29min, p<0.0001) compared with the no-AAD group. However, there was no significant difference in success rate at 12months after a single ablation procedure between the two groups (AAD group, 74% versus no-AAD group, 76%). ConclusionsAn approach to ablation using nifekalant may be useful in localizing areas of CFAE, reducing the number of applications at CFAE sites and procedure time. Ablation of only CFAE localized with nifekalant may be sufficient for clinical outcome.

THE SUBSTRATE OF COMPLEX FRACTIONATED ATRIAL ELECTROGRAMS: EVIDENCE BY PATHOLOGIC ANALYSIS

ObjectivesAblation of complex fractionated atrial electrograms (CFAE) is an important adjunctive therapy in atrial fibrillation (AF). The present study was to elucidate the substrate underlying CFAE.MethodsNine adult mongrel dogs were...