Author + information
- Received March 14, 2016
- Revision received July 20, 2016
- Accepted August 4, 2016
- Published online November 1, 2016.
- Yenn-Jiang Lin, MD, PhDa,b,∗,
- Men-Tzung Lo, PhDc,d,
- Shih-Lin Chang, MDa,b,
- Li-Wei Lo, MDa,b,
- Yu-Feng Hu, MDa,b,
- Tze-Fan Chao, MDa,b,
- Fa-Po Chung, MDa,b,
- Jo-Nan Liao, MDa,b,
- Chin-Yu Lin, MDa,b,
- Huan-Yu Kuoc,d,
- Yi-Chung Change,
- Chen Lin, PhDc,d,
- Ta-Chuan Tuan, MDa,b,
- Hsu-Wen Vincent Young, PhDd,
- Kazuyoshi Suenari, MDb,
- Van Buu Dan Do, MDb,
- Suunu Budhi Raharjo, MDb,
- Norden E. Huang, PhDd and
- Shih-Ann Chen, MDa,b,∗ ()
- aFaculty of Medicine and Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
- bDivision of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- cDepartment of Biomedical Sciences and Engineering, National Central University, Jhong-Li, Taoyuan, Taiwan
- dCenter for Dynamical Biomarkers and Translational Medicine, National Central University, Jhong-Li, Taoyuan, Taiwan
- eInstitute of Communication Engineering, National Taiwan University, Taipei, Taiwan
- ↵∗Reprint requests and correspondence:
Drs. Yenn-Jiang Lin and Shih-Ann Chen, Division of Cardiology, Taipei Veterans General Hospital, No. 201, Section 2, Shipai Road, Beitou District, Taipei 112, Taiwan.
Objectives This prospective study compared the efficacy of atrial substrate modification guided by a nonlinear phase mapping technique with that of conventional substrate ablation.
Background The optimal ablation strategy for persistent atrial fibrillation (AF) was unknown.
Methods In phase 1 study, we applied a cellular automation technique to simulate the electrical wave propagation to improve the phase mapping algorithm, involving analysis of high-similarity electrogram regions. In addition, we defined rotors and focal AF sources, using the physical parameters of the divergence and curvature forces. In phase 2 study, we enrolled 68 patients with persistent AF undergoing substrate modification into 2 groups, group-1 (n = 34) underwent similarity index (SI) and phase mapping techniques; group-2 (n = 34) received complex fractionated atrial electrogram ablation with commercially available software. Group-1 received real-time waveform similarity measurements in which a phase mapping algorithm was applied to localize the sources. We evaluated the single-procedure freedom from AF.
Results In group-1, we identified an average of 2.6 ± 0.89 SI regions per chamber. These regions involved rotors and focal sources in 65% and 77% of patients in group-1, respectively. Group-1 patients had shorter ablation procedure times, higher termination rates, and significant reduction in AF recurrence compared to group-2 and a trend toward benefit for all atrial arrhythmias. Multivariate analysis showed that substrate mapping using nonlinear similarity and phase mapping was the independent predictor of freedom from AF recurrence (hazard ratio: 0.26; 95% confidence interval: 0.09 to 0.74; p = 0.01).
Conclusions Our study showed that for persistent AF ablation, a specified substrate modification guided by nonlinear phase mapping could eliminate localized re-entry and non-pulmonary focal sources after pulmonary vein isolation.
Atrial fibrillation (AF) is the most frequently occurring, sustained arrhythmia, which causes significant morbidity and mortality (1). AF may not always be a totally random process. It can be maintained by stable and rapid re-entrant circuits resulting in fibrillatory conduction throughout the atria (2–4). During mapping of AF, difficulty is frequently encountered in the identification of culprit sites and an analysis of the wave propagation particularly when the electrogram signals demonstrate wide temporal and spatial disparities. Catheter ablation targeting regions with fractionated potentials or high frequencies during AF has been previously proposed as a treatment strategy (3,5–7). However, the benefit of adjunctive complex fractionated atrial electrograms (CFAEs) or linear ablation after successful pulmonary vein isolation (PVI) is controversial based on recent data from the STAR AF 2 (Substrate and Trigger Ablation for Reduction of Atrial Fibrillation Trial Part II) trial (8). Therefore, the optimal ablation strategy for persistent AF remains undetermined, and an alternative approach must be explored.
Several recent studies have demonstrated successful rotor identification by phase mapping of simultaneous recordings using a basket catheter (9–11). Rotors have been demonstrated in animal models of AF, with spatiotemporally organized activity in the presence of the spiral waves (12–14). In our laboratory, we applied a nonlinear processing technique to identify the morphological repetitiveness of waveform patterns in fractionated electrograms at the sources of AF (9,15). In these regions, phase mapping of highly fractionated and nonstationary electrograms could provide additional insight into the AF mechanism. In phase 1, we studied the feasibility of rotor quantification by using a phase mapping methodology in a computer simulation model. In phase 2, we performed a prospective, single-center, randomized, controlled trial to compare the efficacy of substrate ablation using high electrogram similarity mapping plus phase mapping for the identification and elimination of AF sources (group-1) versus that of CFAE ablation alone (group-2). The primary endpoint of the study was AF recurrence after the first ablation procedure.
This study included 95 symptomatic, drug refractory, nonparoxysmal AF patients who received radiofrequency ablation guided by NavX or Velocity (St. Jude Medical, Inc., St. Paul, Minnesota) or Carto system (Biosense Webster, South Diamond Bar, California) systems. The 27 AF patients (28%) who had spontaneous termination of AF before a substrate ablation were excluded from this study (Figure 1). All patients presented with persistent AF at the onset of the procedure. The patients were excluded from the study if they were in sinus rhythm (SR) before the ablation.
This study was conducted at the Taipei Veterans General Hospital in Taipei after approval by the institutional review board of the Taipei Veterans General Hospital (IRB: 2011-09-026IB, 2014-01-004B) and the Department of Health, Taiwan. Written informed consent was obtained from all patients.
This study was designed to determine the efficacy of substrate ablation by comparing similarity mapping and phase mapping with extensive substrate ablation in patients with persistent AF who did not have procedural AF termination after PVI. A crossover of the 2 groups was not performed in the index or repeat procedures.
Patients with persistent AF (sustained >7 days or lasting ≤7 days but necessitating pharmacologic or electrical cardioversion) and those with symptomatic, refractory AF, or intolerance to at least one class I or III antiarrhythmic medication were included in the study.
Patients who had previously undergone catheter ablation for AF or a Maze procedure, those with the presence of a left atrial (LA) thrombus, and those who were responsive to PVI in terms of procedural AF termination in the first step of ablation were excluded from the study (6,7).
An electrophysiological study and catheter ablation in the fasting state were performed in each patient after obtaining informed consent. All antiarrhythmic drugs, except for amiodarone, were discontinued for at least 5 half-lives before initiation of the procedure, because these patients were highly symptomatic. Amiodarone therapy was held 2 weeks before procedure. None of the patients received amiodarone during the electrophysiological procedure. Electroanatomical mapping was performed in all patients, and the details have been described previously (7,9).
Waveform analysis of fibrillation electrogram similarities
Substrate mapping was performed using an irrigated 3.5-mm-tip deflectable catheter during AF after PVI in each patient in order to identify the signal characteristics, which were acquired and characterized by linear and nonlinear analysis modalities. Linear analyses were based mostly on an interval analysis for fractionation (frequency, CFAE), and an electrogram similarity index was derived from a nonlinear method (Online Figure 1, Figure 2, Online Video 2) (6,13,16–18). The step-by-step nonlinear analysis was used to quantify the beat-to-beat morphological repetitiveness of the waveform patterns in the fractionated electrograms (similarity index [SI]) was demonstrated (Figures 2 and 3, Online Methods A, Online Figure 1) (9,15). According to the validation study, the threshold of SI was higher than 0.5 (9). Briefly, the fibrillation electrogram was filtered by first band pass (10 to 300 Hz) for preprocessing with a recording duration of 5 s. The associated envelope was subsequently obtained by a proposed order-statistic filter, which only took into account the algorithmically identified local activity during the limited time window and could highlight the important activation of the local electrograms, namely local activation wave (LAW) (15). Because the reconstructed envelop function could effectively attenuate noise and far-field contamination, it could be used to estimate the dynamical phase change between 2 consecutive activations (see the phase mapping section, Online Methods B for details). Also, distribution of the SI was displayed in the 3-dimensional (3D) system in real time. Please also see supplementary material for the consistency of SI value and mapping density (Online Methods F). By using a multiprobe type catheter, a vector field (namely SI vector field) obtained from the SI between a pair of the nearest electrodes could be used to show the average wave propagation (see details in Online Methods B). Two physical operators (curl and divergence) were then applied in order to analyze the SI vector field (Online Methods C). The curl indicates whether a vector field is rotational, whereas divergence (Div) represents how a vector field spreads out from a source or converges toward a sink. Rotor identification index (RI) was mathematically defined as the product of divergence and curl, as follows: .
A higher RI indicates that the wave propagation is rotating around the center of a rotor and spreading outward to the rotor’s periphery. The propagation pattern will be stable within the high-SI region, and the propagation types such as rotor, focal sources, traveling wave, and random fractionated can be defined.
Phase I: Validation study
In the computer simulation model, a cellular automaton model consisting of a 2-dimensional excitable medium was developed to simulate a clinical substrate (19,20). Using this model, we generated 20 realizations with stable rotors surrounded by chaotic wave breaks. We examined the changes in RI dependent on rotor size, catheter size, and distance from the center of the rotor. Then we determined the thresholds for curl and divergence for rotor and focal source identification. The spatial and temporal changes of the SI vector filed around and within the metastable rotors were characterized and tracked in a cellular automaton mode, and then we determined the thresholds of curl and divergence for rotor and focal source identification (Online Methods D, Figure 4A, Online Video 1).
Phase 2: Catheter ablation and rationale for substrate ablation
In phase 2, we initially identified the high electrogram similarity regions across the entire chamber of the atrium as the first step of substrate analysis, using point-by-point mapping. Second, the regions were subclassified according to the SI level (9). The definition of a high SI (>0.5) was based on previous studies (9,15), and multiple electrode catheters, such as the circular duo-decapolar high density catheter (St. Jude Medical, St. Paul, Minnesota) were used for the high-density phase mapping. The RI derived from the curl and divergence was subsequently calculated in order to locate the rotors.
The patients were randomly assigned to either the nonlinear phase mapping-guided substrate ablation (group-1) or extensive CFAE ablation (group-2). In the index procedure, only PVI and substrate ablation were performed.
For patients with inducible, organized atrial tachycardia (AT) after the substrate modification, a left atrium (LA) linear ablation was performed if necessary. When we repeated the procedures, the types of substrate targeted were in accordance with the first ablation procedure, and no crossover of the substrate modification was done in any of the patients (details in Online Methods E).
If AF did not stop after PVI (step 1), an additional substrate mapping was performed sequentially based on post-PVI substrate maps, using the NavX or Carto 3 V4 software with user defined map (UDM) module. In the first step, we selected a relatively broad cutoff for the primary CFAE (<120 ms) (10). Areas outside the primary CFAEs were not considered important. In group-1, within the primary CFAE region, we subdivided the importance of each subanatomic region by the level of the SI. We assessed the SI, the curl, the divergence, and the RI index calculation during catheter ablation. We set up an RI value of >0.5 to highlight the detection sources as rotors, based on computer simulation models, decreased electrogram voltage (<0.1 mV), or synchronized wavefront propagation. The RI derived from the curl and divergence was subsequently calculated in order to locate the rotors. Those areas were targeted first and followed by the high-SI regions in terms of procedure termination. The endpoint of local ablation site was AF organization, decreased SI (<0.5, similar to the nearby region). After location ablation, the regional SI value usually decreased, and there were no regional SI gradients. Re-mapping with all parameters was feasible for SI, RI index, curl, and divergence calculation after local ablation (Online Videos 2 and 3). In group-2, extensive CFAE ablation was performed. In both groups, the procedural endpoint was procedural AF termination and organization. If procedure termination could not be achieved after substrate ablation, cardioversion was performed, and SR was restored. Additionally, the endpoints of the ablation site were described in Online Appendix (15,21).
The primary endpoint of the study was single-procedure freedom from AF after a blanking period based on a single procedure. The secondary endpoints of this study were the: 1) procedural termination; 2) recurrence of all atrial arrhythmias after the first procedure; 3) safety (complication of the procedure, ablation procedure time, and fluoroscopic time); and 4) efficacy of multiple ablation procedures or the absence of drugs at the end of the follow-up.
Follow-up of AF recurrence
After discharge, the patients were followed (2 weeks after the catheter ablation, then every 1 to 3 months) at our cardiology clinic or with the referring physician. During each follow-up, 24-h Holter monitoring, or cardiac event recording was performed for a week. Recurrence was defined as any atrial arrhythmia recurrence, including AF and atrial tachycardia, and was defined as an episode lasting >1 min and confirmed by electrocardiography, 3 months after the ablation (7,9,15).
Values are mean ± SD if the data were normally distributed. Non-normally distributed data are quartiles (median, Q1 to Q3). The normally distributed continuous variables were compared using one-way ANOVA, whereas non-normally distributed variables were compared using the Kruskal-Wallis test with a Bonferroni correction. The recurrence-free survival curve was examined using the Kaplan-Meier method with the log-rank test. A multivariate Cox proportional hazards regression analysis was performed using variables with a p value of <0.20 in the univariate analysis for a hazard ratio. The level of statistical significance was set at a p value of <0.05.
In the phase I study, we used a computer simulation model of rotors to characterize the wave dynamic (Online Video 1). Figure 4A shows a rotor on an excitable substrate of 135 × 135 mm2 obtained from a cellular automaton model. A double-spiral medical device, 20-mm in diameter, consisting of 20 electrodes, was constructed to investigate the simulated rotors for human AF therapies. The double-spiral catheter was attached to different sites of the substrate, mimicking the mapping procedure. The vector field shown as the averaged waveform propagation was used to quantify the rotors in the high-similarity electrogram region. To calculate curl and divergence at the center of the rotor, an integrating path was first determined (Figure 4, red circle) that indicated the range covered by the catheter. When the diameter of an integrating path increases, the values of curl (integral of tangential components of SI vector field over a circle) and divergence (integral of normal components of SI vector field over a circle) were changed, so did the value of RI (Figure 4B). We observed that the maximal RI occurred at a diameter of 26 mm in the model, thus the precise model of the size of the rotor was defined. When the radius of the integrating path became greater than the rotor size, the value of the curl decreased, whereas the value of the divergence remained high. In Figure 4C, the double-spiral catheter is shown as it was placed in the simulation model of rotors. RI was calculated at each site and formed an RI map of the substrate. Apparently, the RI reaches the maximum if the catheter is very close to the rotor’s center (within 5 mm). On the contrary, high levels of curl and divergence barely occurred in the areas occupied by wave breaks. Using this model, we defined the RI of 0.5 to optimize the detection (Online Methods D). In addition to the rotor size, it was shown that the RI decreased as the double-spiral deviated away from the center of rotor. To study how the RI would change as the alternations of rotor size and the deviations of the catheter from the rotor center, we used a simulation model to show the relationship among the RI, rotor size, and catheter positioning in Figure 4D.
Pulmonary vein ablation and substrate mapping
We performed PVI in all 95 patients (Figure 1). Procedural AF termination was observed in 27 patients (28%) during the PVI, and sustained AF was difficult to induce. Therefore, these patients were excluded from the analysis. The remaining 68 patients were randomized to 2 groups and received either the SI plus phase mapping-guided substrate modification (group-1, n = 34) (Figure 1) or conventional CFAE ablation (group-2, n = 34). There were similar baseline characteristics between the 2 groups (Table 1). Substrate mapping was performed successfully after the PVI in both groups. Figure 3, Online Figure 4, and Online Video 3 illustrate the substrate mapping in both groups.
Critical atrial substrate after the PVI
In group-1, an average of 2.6 ± 0.89 regions per chamber of the high-SI regions were identified with each mean area (3.2 ± 2.1 cm2, 89% in the LA and 11% in right atrium [RA]). The regional distribution is shown in Table 2. The critical subregions with high SI were selected for phase mapping. Phase mapping determined the wavefront dynamics and consistency of the activation over time. There were a total of 26 consistent rotors (65% of all the patients, 2 rotors in 12% patients, 0.76 ± 0.34 per patient or chamber) (Online Video 2) and 42 consistent focal activations (with 2 foci in 18% patients, 1.24 ± 0.55 per patient) (Figure 5B). In the consistent rotor region, a high SI, curl, and divergence and high RI were observed. In contrast, a high SI, low curl, and high divergence were observed in the region of focal sources. Figure 5A shows the distribution of the high-SI region in the LA and RA. Consistent wavefront dynamics included mostly rotors and focal sources. Table 3 shows the clinical characteristics with and without rotors. Patients with rotors were mostly in persistent AF (p = 0.04), which was rarely observed in the patients with long-lasting AF. The other characteristics were similar between the 2 groups. Most of the rotors were localized within an abnormal substrate: either the bipolar low voltage zone border (0.5 mV, 4 of 22, 18%, or low voltage zone (18 of 22, 82%), but none in the scar (<0.1 mV) (Figure 2, Online Figure 4) (22).
Substrate ablation and procedural termination
We targeted all SI regions in group-1 and all CFAEs in group-2 patients. The procedural termination rate was higher in group-1 than in group-2 (23 [68%] vs. 9 [27%], respectively; p = 0.001). In group-1 patients, the termination rate was higher in the patients in whom more rotors were identified (100%, 67%, and 50%, with 2, 1, and 0 rotors, respectively; p = 0.06). Figure 2 demonstrates the identification of 2 rotors in the same patient. Overall, 32 patients (47%) had procedural AF termination (23 patients from group-1 [68% of 34] and 9 patients from group-2 [27% of 34]; p = 0.001) to SR (n = 29 [91%]). There were 3 patients with procedural termination to AT (group-1, n = 2, and group-2, n = 1). In between, a roof line was necessary to terminate the AT in 2 patients, and a septal scar line was needed to terminate the atypical flutter in 1 patient. In the remaining 36 patients (53%), cardioversion was performed to restore SR after substrate modification. Finally, LA linear ablation (lateral mitral line and roof line) for AT was performed in 6 patients (18%) and 9 patients (27%) patients in group-1 and group-2, respectively (p = 0.28). During SR, non-PVI triggers were noted in 9 patients (27%) and 12 patients (35%) in group-1 and group-2, respectively (p = 0.43). Cardiac tamponade was observed with pericardial drainage in 1 patient (2.9%) in group-2. Higher procedural AF termination rates (65% vs. 28%, respectively; p = 0.01), less ablation lesions (86 ± 38 vs. 128 ± 63, respectively; p = 0.01) (Online Figure 5), and shorter ablation times (97 ± 33 min vs. 141 ± 47 min, respectively; p < 0.01) were observed in group-1 than in group-2 patients. We also observed that the presence of high-SI sites in the subanatomic region of the PV vicinity and left atrial appendage (LAA) vicinity correlated with a procedural AF termination site (Table 2).
Follow-up of recurrences
Early recurrence within 2 months of an index procedure was more frequent in patients without procedural termination (n = 15 [46% of 34] vs. n = 6 [19% of 34]; p = 0.04; no differences between group-1 and 2; p > 0.05). During a mean follow-up of 17.7 ± 8.17 months, the Kaplan-Meier survival curves showed more AF recurrences in group-2 than in group-1 (log-rank: p = 0.03) (Figure 6A).
There was a significant reduction in AF recurrence in group-1 compared to group-2, and although there was a trend toward less atrial arrhythmia recurrence, it was not significant (p = 0.06). Patients with rotors in group-1 had a significantly reduced rate of AF and all atrial arrhythmias compared to group-2, whereas those without rotors did not. The differences between group-1 patients with rotors and those without were not statistically significant because of a low number of patients. Recurrences of any atrial arrhythmias were similar after a single ablation procedure (Figure 6B). Recurrences of AT (5 of 9 [56%] vs. 1 of 15 [94%]; p = 0.04) were significantly more frequent in patients with SI mapping (n = 32) than in patients without procedural terminations (n = 36; no differences between group-1 and -2; p > 0.05).
Univariate and multivariate analyses (Table 4) showed that the substrate mapping using similarity/phase mapping was the only independent predictor of AF recurrence (hazard ratio: 0.26; 95% confidence interval: 0.09 to 0.74; p = 0.01). (Details of the repeat procedure are described in Online Methods H.)
Analysis of patients with long-lasting AF
In this study, a rotor was rarely identified in patients with long-lasting AF. The success rates of AF ablation for both groups were similar in long-lasting persistent AF (Online Methods G). On the other hand, AT recurrence was higher in the SI group than in the CFAE group (Online Figure 6C). This study showed a propensity for rotors in patients with persistent AF compared to patients with long-lasting AF. However, only 32% of patients were in the long-lasting AF group, and more prospective trials are necessary to confirm the results.
This study demonstrated an improved method for identifying critical regions in patients with persistent AF. First, phase mapping could provide additional insight into the AF mechanism within the region of a similar repetitive bipolar electrogram configuration region. Second, AF rotors and focal sources could be more precisely identified by quantification of the curvature and divergence forces derived from the wave dynamics during phase mapping. Rotor identification was enhanced with optimal size matching between the spiral ablation catheter and rotor. Third, in a randomized controlled trial, patients with high-SI region targets and phase mapping had shorter ablation procedure times, higher termination rates, less need for repeat procedures, and a better long-term AF-free survival (but only a trend for all atrial arrhythmias) based on a single procedure.
Comparison with previous studies
Previously, our approach was based on a fibrillatory electrogram configuration analysis with spatially stable, small-radius reentries for maintaining AF (9). Mechanisms of rotors were found in a limited number of patients. Those areas were characterized by rapid repetitive activity with a high degree of electrogram similarity. Compared with previous observations (23), the application of multiple electrode catheters and phase mapping offered a way to identify the AF sources, and the detection rate of rotors was higher (2 of 3 patients), and only the identification and elimination of rotors were associated with a better AF-free outcome.
In this study, a rotor was rarely identified in patients with long-lasting AF. Also, success rate of AF ablation of both groups was similar in long-lasting persistent AF (Online Methods G). On the other hand, the AT recurrence was higher in the SI group, as compared to the CFAE group. This study showed a propensity of rotors in patients compared to long-lasting AF patients. However, only 32% of patients were in the long-lasting AF group, and more prospective trials are necessary to confirm the results.
Technical consideration of the electrogram similarity and phase mapping
The optimal ablation strategy for persistent AF remains undetermined, and an alternative approach must be explored. Previously, we demonstrated that AF-localized sources displayed regular, fast, and organized activities with a similar repetitive bipolar electrogram configuration. In this prospective study, we identified regions with high electrogram similarity as the first step during AF. In the region of consistent LAWs of the high-SI region, the electrogram voltages were decreased and often mixed with far-field electrograms. Therefore, signal decomposition and mapping using the instantaneous phase with an automatic algorithm offered a way to identify AF-localized sources. The consistency of the LAW of the high-SI region confirmed the reproducibility over time.
Identifying rotors using phase mapping and the corresponding phase singularities was previously proposed and reported by many groups (11,24). However, it is difficult to perform a phase reconstruction for complex arrhythmia, and the irregular and transient patterns further increase the difficulty to interpret instantaneous phase mapping. Here, we propose using vector fields to characterize how the electrical wave propagates around AF drivers. Phase singularity of the phase mapping has simply been identified as the pivot of a rotor in most previous studies, whereas our approach was based on high mathematical, stationary, repetitive electrogram configuration. The rotor identification index, including the divergence and curvature forces, can distinguish a rotor from a focal source and enable a more systematic observation and classification of the different mechanisms of AF.
Technical consideration of the rotor dimension
The rotor size in the most general but hard to quantify sense is a span of rotational activities. In this study, the SI vector field was used to depict rotational and spreading activities. Both activities contribute significantly to the existence of rotors, and the quantified parameter, the RI, decreased when the area being investigated was inside or far from the rotors. Therefore, the rotor size can be defined as the radius of an integrated path that renders the maximal value of the RI (Figure 4), where both the rotational and spreading activities are substantial. For clinical applications, it is mainly the spiral catheter size that determines the critical radius. A predefined RI threshold will set a limit on the detectable rotor size as the relationship between the RI and the rotor size-to-catheter size ratio is parabolic (Online Methods I).
First, the interelectrode size of the bipolar recording may affect the recording of different catheters and a spiral catheter to map the high-SI regions. In the region that the catheter configuration made it difficult to reach with optical contact or most of the electrograms and phase mapping were difficult to interpret, an empirical high-SI ablation was applied. Second, the incidence of meandering rotors could have been underestimated in this study. The application of more simultaneous recording devices may facilitate the real-time phase mapping process not specified to rotors, as well as uncover the pathological mechanism in these patients. Last, the study patients were not stratified to long-lasting and persistent patients. We need more prospective studies to confirm the role of SI ablation in long-lasting patients.
We demonstrated the effectiveness of applying electrogram configuration similarity mapping and a real-time wave dynamic analysis as auxiliary tools in patients with persistent AF after the PVI. Rotors were identified by quantification of the rotor curvature force and divergence force within regions of a high degree of electrogram similarity. Compared with conventional substrate ablation, our novel specific substrate ablation strategy showed a higher AF termination rate and fewer substrate ablation lesions. During the long-term follow-up, the AF recurrences were lower, the results on recurrence of all atrial arrhythmias were inconclusive.
COMPETENCY IN MEDICAL KNOWLEDGE: Phase mapping could provide additional insight into AF mechanisms. We studied a novel 2-step approach to improve the identification and ablation of localized AF sources. Step 1 involved an analysis of high similarity electrogram regions during AF. Step 2 involved the application of phase mapping with an automatic algorithm to define the mechanism of rotors. We demonstrated the effectiveness of applying the electrogram similarity and real-time phase mapping as auxiliary tools in patients with persistent AF after PVI.
TRANSLATIONAL OUTLOOK 1: An automatic algorithm is feasible for the electrogram similarity/phase mapping to guide the substrate ablation in persistent AF. The rotor size could be quantified. Localized sources of AF as rotors and focal sources could be defined by physical parameters.
TRANSLATIONAL OUTLOOK 2: In a single center randomized control trial, specified substrate modification guided by nonlinear phase mapping was an alternative strategy to eliminate localized AF focal sources after pulmonary vein ablation. Future multicenter trials are needed to confirm the results.
For an expanded Method section as well as supplemental figures and videos and their legends, please see the online version of this article.
This work was supported by Ministry of Science and Technology of Taiwan for National Yang-Ming University (MOST 104-2314-B-010-063-MY2), Clinical Trial of IIS No. 290 (C13-092), Biosense Webster Inc. (Diamond Bar, CA, USA), and Biosense Webster Ltd. (Israel), supported for Dell 3610 workstation, and CARTO® 3 V4 Software with pre-installed UDM 2 feature.
Dr. Lin has received funding from Biosense Webster; and speakers honoraria from St. Jude Medical and Biosense-Webster. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Drs. Yenn-Jiang Lin and Men-Tzung Lo contributed equally to this work.
- Abbreviations and Acronyms
- atrial fibrillation
- atrial tachycardia
- complex fractionated atrial electrograms
- left atrium
- left atrial appendage
- pulmonary vein isolation
- rotor identification index
- similarity index
- sinus rhythm
- Received March 14, 2016.
- Revision received July 20, 2016.
- Accepted August 4, 2016.
- American College of Cardiology Foundation
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