Atrial fibrillation termination as a procedural endpoint during ablation in long-standing persistent atrial fibrillation

Atrial fibrillation termination as a procedural endpoint during ablation in long-standing persistent atrial fibrillation Claude S. Elayi, MD,* Luigi Di Biase, MD,†‡§ Conor Barrett, MD,储 Chi Keong Ching, MD,¶ Moataz al Aly, MD,** Maria Lucciola, MD,†† Rong Bai, MD,‡‡ Rodney Horton, MD,† Tamer S. Fahmy, MD,** Atul Verma, MD,§§ Yaariv Khaykin, MD,§§ Jignesh Shah, MD,* Gustavo Morales, MD,* Richard Hongo, MD," Steven Hao, MD," Salwa Beheiry, RN," Mauricio Arruda, MD,¶¶ Robert A. Schweikert, MD,*** Jennifer Cummings, MD,*** J. David Burkhardt, MD,† Paul Wang, MD,††† Amin Al-Ahmad, MD,††† Bruno Cauchemez, MD,‡‡‡ Fiorenzo Gaita, MD,†† Andrea Natale, MD, FACC, FHRS†§"††† From the *University of Lexington, Lexington, Kentucky, †Texas Cardiac Arrhythmia Institute at St. David’s Medical Center, Austin, Texas, ‡Department of Cardiology, University of Foggia, Foggia, Italy, §Department of Biomedical Engineering University of Texas, Austin, Texas, 储Cardiac Arrhythmia Service, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, ¶National Heart Centre Singapore, Singapore, **University of Cairo, Cairo, Egypt, ††University of Turin, Turin, Italy, ‡‡Tong-Ji Hospital, Huazhong University of Science and Technology, Wuhan, China, §§Southlake Regional Health Center, Newmarket, Ontario, Canada, "California Pacific Medical Center, San Francisco, California, ¶¶Case Western Reserve University, Cleveland, Ohio, ***Akron General Hospital, Akron, Ohio, †††Stanford University, Palo Alto, California, and ‡‡‡Ambroise pare Clinic, Neuilly, France. BACKGROUND Ablation of long-standing persistent atrial fibrillation (AF) remains challenging, with a lower success rate than paroxysmal AF. A reliable ablation endpoint has not been demonstrated yet, although AF termination during ablation may be associated with higher long-term maintenance of sinus rhythm (SR). OBJECTIVE The purpose of this study was to determine whether the method of AF termination during ablation predicts mode of recurrence or long-term outcome. METHODS Three hundred six patients with long-standing persistent AF, free of antiarrhythmic drugs (AADs), undergoing a first radiofrequency ablation (pulmonary vein [PV] antrum isolation and complex fractionated atrial electrograms) were prospectively included. Organized atrial tachyarrhythmias (AT) that occurred during AF ablation were targeted. AF termination mode during ablation was studied in relation to other variables (characteristics of arrhythmia recurrence, redo procedures, the use of adenosine/isoproterenol for redo, and comparison of focal versus macroreentrant ATs). Long-term maintenance of SR was assessed during the follow-up. RESULTS During AF ablation, six of 306 patients converted directly to SR, 172 patients organized into AT (with 38 of them converting in SR with further ablation), and 128 did not organize or terminate and were cardioverted. Two hundred eleven of 306 patients (69%) maintained in long-term SR without AADs after a mean follow-up of 25 ⫾ 6.9 months, with no statistical difference between the various AF termination modes during ablation. Presence or absence of organi-

zation during ablation clearly predicted the predominant mode of recurrence, respectively, AT or AF (P ⫽ .022). Among the 74 redo ablation patients, 24 patients (32%) had extra PV triggers revealed by adenosine/isoproterenol. Termination of focal ATs was correlated with higher long-term success rate (24/29, 83%) than termination of macroreentrant ATs (20/35, 57%; P ⫽ .026). CONCLUSION AF termination during ablation (conversion to AT or SR) could predict the mode of arrhythmia recurrence (AT vs. AF) but did not impact the long-term SR maintenance after one or two procedures. AT termination with further ablation did not correlate with better long-term outcome, except with focal ATs, for which termination seems critical. KEYWORDS Atrial fibrillation ablation; Pulmonary vein isolation; Complex fragmented atrial electrograms; Persistent atrial fibrillation; Atrial fibrillation termination ABBREVIATIONS AADs ⫽ antiarrhythmic drugs; AF ⫽ atrial fibrillation; AT ⫽ atrial tachyarrhythmia; CFAE ⫽ complex fragmented and/or rapid atrial electrograms; CL ⫽ cycle length; CS ⫽ coronary sinus; LA ⫽ left atrial atrium; PAF ⫽ paroxysmal atrial fibrillation; PAC ⫽ premature atrial ectopies; PV ⫽ pulmonary vein; PVAI ⫽ pulmonary vein antrum isolation; RA ⫽ right atrial atrium; SR ⫽ sinus rhythm; SVC ⫽ superior vena cava (Heart Rhythm 2010;7:1216 –1223) © 2010 Heart Rhythm Society. All rights reserved.

Introduction Address reprint requests and correspondence: Andrea Natale, M.D., Executive Medical Director, Texas Cardiac Arrhythmia Institute at St. David’s Medical Center, 1015 East 32nd Street, Suite 516, Austin, Texas 78705. E-mail address: [email protected]. (Received August 25, 2009; accepted January 26, 2010.)

After Haissaguerre et al1 pointed out the pulmonary veins’ (PVs) role in initiating atrial fibrillation (AF), the ablation approach then consisted of ostial ablation of PV foci. Over the years, the AF population treated by ablation has become larger, including patients with persistent or permanent AF,2,3 presence of structural heart disease,4 or congestive

1547-5271/$ -see front matter © 2010 Heart Rhythm Society. All rights reserved.

doi:10.1016/j.hrthm.2010.01.038

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heart failure.5 To achieve a better success rate, more sites are targeted during ablation, particularly in the left atrium (LA). Currently, both atria and their thoracic veins are considered a target for ablation using various methods and tools: antrum isolation,6 complex fragmented and/or rapid atrial electrograms (CFAEs),7 atrial lines,8,9 ganglionated plexi,10 AF nests,11 and dominant frequency analysis.12,13 For paroxysmal AF (PAF), PV isolation is known to be effective. For non-PAF, the most effective lesion set is not determined. An ablation endpoint correlated with successful outcome is lacking. During ablation of non-PAF with various strategies (including wide circular isolation, linear lesions, and defragmentation), the arrhythmia often organizes into a regular atrial tachyarrhythmia (AT) and sometimes even terminates into sinus rhythm (SR). These parameters (AF organization/termination during ablation) appear to be intuitively ideal endpoints, and some data support this hypothesis.2,14,15 We prospectively assessed the AF termination mode during radiofrequency ablation in 306 patients with longstanding persistent AF and whether it predicts long-term SR maintenance.

Methods Study population This prospective study included 306 consecutive patients with long-standing non-PAF who were referred for their first ablation at the participant institutions. All patients presented in the lab in AF. Patients had previously failed at least two different antiarrhythmic drugs (AADs) and had symptomatic AF. To have a patient population that was as homogenous as possible, patients were not considered for the study if (1) they had paroxysmal AF, (2) they presented in the electrophysiology lab in SR, (3) they were ⬍18 years or ⬎80 years of age, (4) the presenting arrhythmia was already organized (related, for instance, to a previous heart surgery, including a Maze surgery), or (5) they ever had had an AF ablation, either endovascular or surgical. Long-standing persistent AF was defined as AF being persistent for more than 1 year as defined in the expert consensus statement on catheter and surgical ablation of AF.16 All rhythm tracings that required interpretation or measurement for this study were analyzed in a blinded fashion by two physicians from the enrolling institution.

Study protocol/parameters assessed All patients signed an informed consent before the study.

AF ablation strategy: the hybrid approach (pulmonary vein antrum isolation [PVAI] and ablation of the CFAE) This strategy was used in all patients. The sequence of ablation was PVAI followed by CFAE ablation. 1. PVAI Our PVAI technique has been recently described in detail.17 It includes isolation of the posterior wall with right and left

1217 antrum defragmentation. PVAI potentially targets triggers (including the superior vena cava [SVC])18 and possible antral rotors/drivers and abolishes vagal ganglia mediated reflex.19,20 We used a 3.5-mm irrigated-tip catheter (ThermoCool, Diamond Bar, California) guided by a circular Lasso mapping catheter to ablate the ostia and posterior antra of the PVs. The catheter was irrigated using heparinized saline infused at a rate of 30 mL/min. Radiofrequency energy output was limited to 45 W with a maximum temperature of 41°C and a maximum power of 35 W when applying energy on the posterior left atrial (LA) wall facing the esophagus. An esophageal temperature probe was placed to monitor and titrate the power delivered on the posterior LA wall during the procedure. Ablation was discontinued when the temperature probe reached 39°C. Intracardiac echocardiography was helpful to assist during the septal puncture and to define the PV anatomy. An electroanatomic mapping system was used for additional guidance when requested by the physician. The endpoint of the procedure was electrical isolation of the PV antra. An entry block was verified when no PV potentials were recorded along the antrum or in the vein. The antrum included the entire posterior wall and extended anterior to the right PVs along the left septum. Occasionally, a dissociated firing was seen for some veins after isolation, demonstrating an exit block. Isolation of the SVC along the ostium was also performed if mapping revealed PV-like potentials around this region, providing that high-output pacing (at least 30 mA) did not capture the phrenic nerve. 2. CFAE ablation CFAE criteria were those previously defined by Nademanee et al:7 (1) atrial electrograms with fractionation and composed of two defections or more and/or with continuous activity of the baseline or (2) atrial electrograms with a cycle length (CL) ⱕ120 ms. The ablation catheter was in a stable position when recording these electrograms for at least 10 seconds (to avoid artifact due to instability of the catheter). The CFAE detection and ablation were guided by visual inspection. However, all operators assessed sample CFAEs to ensure uniformity in selecting ablation sites. The intracardiac bipolar electrograms filter ranged from 30 to 500 Hz. Areas of CFAE were identified in both the atria and the coronary sinus (CS). These fractionated areas were ablated until complete elimination of the fractionated atrial electrograms (using the same ablation modalities described above except for ablation into the CS, where the power was limited to 30 W).

Mean and fastest preablation AF CL The initial CL was measured for all patients. The fastest CL was obtained within a 10-second preablation period (duration chosen arbitrarily). It was the shortest CL measured on any of the catheters dipoles present in the heart including the RA and LA (sites with continuous activity were excluded).

1218 The mean CL was obtained from a preablation sample of 10 consecutive beats. Three mean values were calculated from 10 consecutive beats on the dipoles present in the RA, the CS, and the LAA. These three values were then averaged to obtain the mean AF CL.

AF termination mode during ablation During ablation, the categories of AF termination were (1) direct conversion to SR; (2) organization into an AT (as defined in the next paragraph) that converted secondarily in SR with further ablation or (3) required a direct current cardioversion (DCC) to restore SR at the end of the procedure. In the remaining patients, AF more or less organized as persisted, requiring a (4) cardioversion after ablation to restore SR. Drug therapy had no influence on organization in this study as all AADs were stopped at least five halflives before ablation (amiodarone was discontinued at least 6 months before the procedure). No AADs were used during ablation.

Atrial tachyarrhythmia During ablations, the initial AF CL prolonged and displayed some degree of organization. However, it was characterized as regular AT only if atrial electrograms (1) were regular with less than 15 ms of fluctuation (during the nonablation period), (2) were stable over time or exhibited a repetitive pattern, and (3) had the same morphology and global activation sequence in the LA and RA with a monomorphic P wave pattern.

Ablation strategy for patients in AT We tried to define the mechanism of every AT using activation sequence and entrainment mapping. Electroanatomic mapping systems were used to delineate the AT. The first step was to try defining whether it was focal/microreentrant versus macroreentrant (for example, a centrifugal activation from a localized region in favor of a focal mechanism or the entire CL within the LA or RA favored macroreentrant mechanism). Then entrainment maneuvers were performed (postpacing interval from various sites in both atria searching for a postpacing interval of ⬍20 ms to identify the circuit, sequence of activation during entrainment compared with spontaneous AT sequence, and so on). Subsequently, further ablation was performed to terminate these ATs at optimal ablations sites when they could be defined. When the patient had more than one stable AT during the procedure, we attempted to map and ablate all the ATs. When a critical isthmus was defined and termination achieved, bidirectional conduction block across the isthmus was pursued. However, if the AT could not be terminated within 60 minutes (e.g., AT activation sequence changing frequently) or the mechanism could not be defined appropriately, the AT was finally cardioverted. This strategy was applied when the patient organized into AT(s) during the first or redo ablation or when patients presented in AT for a redo procedure.

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Second procedure PV antrum recovery and residual CFAE were ablated again when necessary. AT(s) were mapped and targeted as indicated above. Finally, adenosine (12 mg) and isoproterenol (up to 20 ␮g/min) were given to search for non-PV triggers. Further ablation was performed to eliminate consistent and repetitive atrial premature beats, regardless of whether AF or AT was induced. Burst pacing was never tested in this study.

Postablation management and follow-up All the patients were on warfarin with a therapeutic international normalized ratio (INR) between 2 and 3 before and during the procedure and pursued the same anticoagulation after discharge. The AADs, previously stopped at least five half-lives before the procedure, were resumed for a 2-month blanking period. Amiodarone was never resumed. Patients were followed up with event recorder(s), outpatient visits with 12-lead electrocardiogram, and 48-hour Holter monitoring. They were asked to record daily even if they were asymptomatic and anytime they experienced symptoms over the first 5 months. A 48-hour Holter monitoring was obtained at 3, 6, 12, 18, and 24 months postablation. Anticoagulation duration was determined by the operator but was often maintained for a minimum of 6 months in most patients because of the nonparoxysmal nature of AF in this study. Device interrogation in patients with implanted devices was also used to document arrhythmia recurrence. The procedure was considered successful if the patient was free of AT/AF during the follow-up. Freedom from AF/AT was defined as having no episodes of AF/AT that lasted more than 1 minute during the follow-up period. AF/AT episodes that occurred during the 2-month blanking period after the first or second procedure while the patient was on AADs were not considered as recurrence. The patients were encouraged to repeat ablation if they had arrhythmia recurrence after the blanking period. The mode of recurrence was depicted as AT only if no AF was observed during the follow-up. When a patient had both AF and AT during the follow-up, the recurrence mode was considered as AF.

Statistical analysis Continuous variables are reported as a mean ⫾ standard deviation, and categorical variables as a percentage. Categorical variables comparison used ␹2 analysis. An unpaired Student’s t-test was used to compare the continuous variables from two groups. P ⬍ .05 was considered statistically significant for all determinations.

Results Patients and procedure characteristics Baseline characteristics are presented in Table 1 for the 306 patients. Isolation of the PVs could be achieved in all patients. CFAE ablation was performed in AF after PVAI. The mean procedure time was 249 ⫾ 93 minutes. The mean fluoroscopic time was 97.5 ⫾ 27.7 minutes. Five pericardial effusions occurred; three of them required percuta-

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Table 1 Patient’s characteristics in patients with AF termination and no termination during ablation

No. Age Male Hypertension Heart disease AF duration, years Mean sustained AF duration, months AADs failed/patient LA size, mm LA size, cm2 LVEF, %

AF termination

AF no termination

P

178 60.2 ⫾ 9.2 122 86 64 7.9 ⫾ 4.7 25.9 ⫾ 14.7

128 60.6 ⫾ 10.1 89 58 49 8.4 ⫾ 5.3 26.4 ⫾ 14.2

.52 .1 .35 .38 .27 .35 .55

⫾ ⫾ ⫾ ⫾

.18 .23 .25

2.7 46 28 52

⫾ ⫾ ⫾ ⫾

0.4 7.3 6.9 7

2.4 47 29 54

0.7 8.2 5.9 9

neous drainage. Five patients had asymptomatic PV stenosis on the computed tomography scan assessment after ablation that remained stable over time (narrowing less than 50%). Two patients had a transient ischemic attack (TIA). Both patients had subtherapeutic INR at the time of ablation. No esophageal fistulae occurred.

Mean and shortest preablation CL The shortest preablation CL was 93 ⫾ 13 ms (for 178 patients with AF termination during radiofrequency) versus 83 ⫾ 17 ms (for 128 patients with non–AF termination; P ⫽ NS). Similarly, the shortest CL was 87 ⫾ 15 ms (for 211

Figure 1

patients with no AF recurrence during the follow-up) versus 85 ⫾ 16 ms (for 95 patients with AF recurrence; P ⫽ NS). The shortest CL therefore had no clinical significance in predicting acute and long-term outcomes. The mean preablation CL was 128 ⫾ 21 ms (for 178 patients with AF termination during ablation) versus 104 ⫾ 18 ms (for 128 patients without AF termination during ablation; P ⫽ .036). However, the mean CL was 119 ⫾ 19 ms (for 211 patients without AF recurrence) versus 115 ⫾ 22 ms (for 95 patients with AF recurrence; P ⫽ NS). Therefore, a longer mean CL at the beginning of the procedure was more likely to organize during the ablation but had no impact on long-term SR maintenance.

AF termination mode during ablation and CFAE characteristics The results are presented in Figure 1. Characteristics of patients who had AF termination during ablation were compared with those who did not have AF termination. There was no significant difference in terms of sex, age, presence of heart disease, ejection fraction, LA size, and fluoroscopic time (except for the AF preablation mean CL as described above). One hundred seventy-two patients organized into AT, with 38 of them converting in SR with further ablation. The mechanism of these 38 ATs was perimitral (n ⫽ 20), cavotricuspid isthmus dependent (n ⫽ 3), and focal (n ⫽ 15).

Study design and results (AF termination mode and success rate after the first with ADDs and second procedure with and without AADs).

1220 Overall, patients had between one and six different ATs, with a mean of 2.4 ATs per patient. The mean AT CL before termination or DCC was 248 ⫾ 32 ms. Among the 172 patients with AT, 102 patients had AF organization to AT after PVAI. In the additional 70 patients, AF organized to AT during subsequent CFAE ablation. There were no preferential areas that terminated AF during ablation. CFAE sites were located on the septum (83%), on the anterior wall (78%), in the RA (73%), in the CS (66%), on the roof (58%), on the LA floor (37%), and on the mitral isthmus (29%). CFAE sites at the base of the LA appendage were typically not ablated to avoid appendage disconnection and long-term mechanical dysfunction of the LA, unless this area appeared critical in the maintenance of AF (e.g., being the fastest CL in both atria).

AF termination mode and long-term SR maintenance after one or two procedures The results are summarized in Figure 1. After one procedure, the long-term SR maintenance off AADs was 69% (211/306) after a mean follow-up of 25 ⫾ 6.9 months (12 of those patients were on AADs). There was no statistical difference between patients with AF termination during

Heart Rhythm, Vol 7, No 9, September 2010 ablation (121/178, 68%) and patients without AF termination (90/128, 70%; P ⫽ NS). When patients with AF termination during ablation were divided in two subgroups (conversion in SR during ablation or with a DCC), no statistical difference was observed among patients who converted in SR during ablation (30/44, 68%), those who organized and required a DCC (91/134, 68%), and those who did not organize at all (90/128, 70%; P ⫽ NS). Pairwise statistical comparisons among the three subgroups were also not significant. After two procedures, the long-term outcome was still statistically not different whether AF terminated or not during the first procedure, without AADs (147/178, 83% vs. 105/128, 82%; P ⫽ NS) or with AADs (161/178, 90 % vs. 114/128, 89%; P ⫽ NS). An example of organization and termination is shown Figure 2.

Correlation AF termination mode/recurrence mode The results are presented in Table 2. Ninety-five patients had AF/AT recurrence. Presence or absence of organization during ablation clearly predicted the predominant mode of recurrence, respectively, AT or AF (P ⫽ .012).

Figure 2 Example of AF termination (organization into AT) during ablation with conversion in SR. A: AF with a CL around 140 –150 ms (lasso close to LA appendage and CS from proximal 9,10 to distal 1,2). B: AF moderate organization and slowing. C: Occurrence of AT (250 ms). D: AT termination with prolongation during ablation at the mitral isthmus.

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Table 2 Mode of termination/mode of recurrence correlation (among the 95 patients with AT/AF recurrence)

Recurrence as AT Recurrence as AF

Organization to AT during ablation (n ⫽ 57)

No organization during ablation (n ⫽ 38)

40 17

17 21

Pa .012

a

Comparing 40/57 versus 17/38.

Redo procedures characteristics Among the 95 patients with AT/AF recurrence, 74 patients had a redo procedure (25 with AF recurrence and 49 with AT recurrence). Thirty-five patients (35/49) with AT recurrence presented to the electrophysiology lab in AT and the remaining 14 in SR. PV reconnections with the LA and the response to administration of adenosine/isoproterenol were assessed in all 74 patients. Fourteen patients had no PV recovery from the previous procedure (20%). Premature atrial ectopies (PAC) burst and/or repetitive PACs consistent with a single origin were observed and targeted in these patients. In the remaining 60 patients, 21 patients had PV recovery in one vein (35%), 26 in two veins (43%), seven in three veins (12%), and six in all veins (10%). The left inferior PV had the lowest rate of recovery (19 patients, 32%), followed by the right superior (23 patients, 38%), the right inferior PV (32 patients, 53%), and finally the left superior PV (44 patients, 73%). Four patients had a common left-sided ostium previously isolated. Adenosine and isoproterenol were used in redo patients after isolation of the reconnected veins. Consistent PACs or atrial burst were induced and ablated in 24 patients. After the 2-month blanking period, and after a mean follow-up of 18.6 ⫾ 5.9 months, 41/74 (55%) of the redo patients were in SR with no AT/AF documented off AADs.

Figure 3

Focal ATs versus macroreentrant ATs The flow of patients is presented in Figure 3. A total of 38 ATs with a clearly identified mechanism (focal versus macroreentrant) were terminated during ablation at the time of the first procedure. In addition, 26 ATs were terminated during a second procedure (total of 64 ATs among 62 patients). Of them, 29 ATs were focal and 35 were macroreentrant. Their CLs were, respectively, 285 ⫾ 61 and 327 ⫾ 52 ms. For macroreentrant ATs, bidirectional conduction block across the critical isthmus was documented acutely in 97% of cases. More than 70% of focal ATs presenting for the second ablation reoccurred within a week after the first ablation. The success rate of focal ATs terminated during ablation was 83% (24/29) versus 57% (20/35) for macroreentrant ATs (P ⫽ .026). An example of focal AT is shown in Figure 4.

Discussion In the past few years, as patients with persistent AF and heart disease have been increasingly considered for catheter ablation, the lesion sets have become more aggressive and complex. The rationale for more extensive ablation relates to the prominent electrophysiologic and structural alterations of the atrial myocardium in non-PAF (the so-called atrial substrate). The extent of substrate modification required to maintain long-term SR is unknown. In this context, AF termination during ablation appears intuitively to be an ideal endpoint for this AF population. Our study combined PVAI and CFAE ablation, which increases the procedural success rate in non-PAF compared with PVAI.2,21 PVAI typically targets mainly AF triggers, whereas ablation of CFAE could target areas responsible for AF perpetuation and may indicate sites of ganglionated plexi.10 CFAE ablation after the PVAI significantly increased the AF termination ratio. It remains unclear, however, whether

Flow of patients with focal versus macroreentant AT after one or two procedures.

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Figure 4 A: AT occurring after first ablation (12-lead electrocardiogram). B: AT originating from the CS (RA crista from proximal 9,10 low to distal 1,2; CS from proximal 9,10 to distal 1,2). C: AT termination during ablation (same leads as in panel B).

AF termination during CFAE ablation results from the ablation of areas critical to SR maintenance and/or simply from the decrease of excitable atrium myocardial mass and atrial debulking (limiting the AF wavefronts propagation more around the anatomical or scar-related boundaries).22–25 With further ablation, AF sometimes organized by turning into several atrial circuits as demonstrated by the different ATs recorded during ablation (up to six different ATs could be seen in the same patient). This may occur either by reducing the amount of atrial tissue capable of fibrillating or by creating areas of slow conduction. However, these multiple ATs appear to be not clinically relevant in most cases. Indeed, AF and AT procedural termination generally did not correlate with a better clinical outcome in our study, similar to the results of Estner et al,26 which included 35 patients. Although previous studies2,27 found a correlation between AF termination during ablation and better success rate, the study from O’Neill et al15 was to date the only prospective study evaluating AF termination as a procedural endpoint of persistent AF using a “stepwise” AF ablation approach.14 The AF termination was predictive of subsequent maintenance of SR in this study. Several factors may contribute to the apparent discrepancy with the O’Neill et al15 study.

The absence of AAD interference (especially amiodarone, which was present in 25% of patients in O’Neill et al’s study) may account for our initial shorter AF CL preablation and the subsequent lower AF termination rate during ablation. Indeed, amiodarone prolongs the AF CL (maybe by reducing the amount of fractionation) and increases the AF termination ratio during ablation.28 It may be more effective to “pretreat” persistent AF with AADs to decrease the fibrillatory sites and decrease the amount of ablation, but this warrants further study. The ablation technique may also have contributed to generating different results between these two studies. Systematic creation of linear lesions during the stepwise approach achieved a high rate of AF termination (85% of SR) but may have created more atrial segmentation with the risk of conduction gap through the lines. This increases the occurrence of recurrent organized arrhythmias, as evidenced by the fact that the majority of arrhythmia recurrence was macroreentrant in the O’Neill et al15 study. Although their outcomes were better after a second procedure in AF termination patients, this was not the case after the first procedure (sustained arrhythmia recurrence was documented in 44% of AF termination patients vs. in 50% of non–AF termination patients; P ⫽ NS). The success after a repeat ablation could be due to the effective atrial substrate

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segmentation where the atria can no longer fibrillate (achieved after the first procedure) or sustain AT (achieved after the second procedure). In our study, on the contrary, outcomes were not better after the first or second ablation for patients with AF termination compared with those without AF termination during the first procedure, despite a success rate similar to that of O’Neill et al.15 Segmentation of the atrium and AF/AT termination may become less critical with more AF trigger elimination (using challenge with isoproterenol and adenosine). We recognize, however, that ablation and achievement of bidirectional block can be critical if triggers are still present and a macroreentrant flutter is the last possible circuit in the atria. Finally, focal AT was observed in a significant proportion of patients during or after ablation. Focal AT mechanisms include triggered activity, automaticity, and localized microreentry.29,30 Termination of those focal ATs correlated with better outcomes independently of the underlying focal AT mechanism.

Study limitations Some patient characteristics were underrepresented in this study such as patients with severely enlarged LA. Nevertheless, our study demographics reflect a significant proportion of permanent AF patients seen in clinical practice. Certain AF termination criteria were not assessed: progressive AF CL prolongation versus abrupt termination and minor/moderate AF CL prolongation versus important prolongation. Even though follow-up was thoroughly performed, asymptomatic AF relapses might have been missed.

Conclusion In long-standing persistent AF patients, the arrhythmia present at the end of the procedure (AT or AF) predicts the mode of recurrence (AT vs. AF) but not long-term outcomes after one or two procedures. Our study suggests that, in general, it is not worth pursuing aggressive ablation to try to organize AF or terminate the AT(s), mainly because it does not impact long-term SR maintenance. An exception would be focal ATs during the first or redo procedure.

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