Linear ablation in addition to circumferential pulmonary vein isolation (Dallas lesion set) does not improve clinical outcome in patients with paroxysmal atrial fibrillation: a prospective randomized study

Introduction

Circumferential pulmonary vein isolation (CPVI) is considered to be the cornerstone technique of atrial fibrillation (AF) catheter ablation, especially in patients with paroxysmal AF.¹ From experience with the surgical maze procedure, the addition of linear lesions to CPVI has been suggested to modify the substrate for AF and improve clinical outcomes.² However, patients in these studies underwent concomitant maze surgery with significant structural heart disease. With the development of new surgical devices, stand-alone maze surgery, mini-maze surgery, and hybrid AF surgery have become popular.³ Edgerton et al.⁴ recently reported a totally thoracoscopic surgical ablation with an added linear ablation technique, the so called Dallas lesion set, and achieved excellent clinical outcomes in patients with persistent or longstanding persistent AF. However, the appropriate lesion set for patients with paroxysmal AF has not yet been clearly defined. Although our group and others have reported no additional benefit of ablations for roof lines, posterior box lesions, or complex fractionate atrial electrograms in patients with paroxysmal AF by prospective randomized clinical studies,^5–7 recurrence rates after CPVI alone remain substantial. Therefore, we hypothesized that the Dallas lesion set generated by radiofrequency catheter ablation (RFCA) improves clinical outcome after catheter ablation of paroxysmal AF compared with that of CPVI alone. We conducted this study with a prospective randomized trial design and compared clinical outcomes of catheter Dallas lesion vs. CPVI to evaluate if addition of linear lesions and the achievement of a complete bidirectional block improves clinical outcome in patients with paroxysmal AF.

Methods

Study population

The study protocol adhered to the principles of the Declaration of Helsinki and was approved by the Institutional Review Board at the Yonsei University Health System. All patients provided written informed consent to be included in the Yonsei AF Ablation Cohort Database and to be randomized by a table of random numbers into two groups. The study population included 100 consecutive paroxysmal AF patients (male 74.7%, 56.4 ± 11.4 years old) who underwent RFCA. Exclusion criteria were as follows: (i) AF with rheumatic valvular disease, (ii) structural heart disease other than left ventricular hypertrophy, (iii) history of prior RFCA, and (iv) history of cardiac surgery. We chose the sample size on the basis of a statistical analysis to prove the superiority of additional linear ablation with CPVI, which was described in a previous study comparing ablation strategies in patients with paroxysmal AF.⁸ A two-sided significance level of 5% was used against an estimated difference between the groups of 25%, and at least 47 patients in each group was required. Considering a potential drop out of 5%, a total study cohort of 100 patients was calculated. Before all ablation procedures, the absence of a left atrial (LA) thrombus was confirmed by transoesophageal echocardiography, and the anatomy of the LA and pulmonary veins (PVs) was visually defined by 3D-CT scans (64 Channel, Light Speed Volume CT, Philips, Brilliance 63). All anti-arrhythmic drugs were discontinued for a period of at least five half-lives. Patients were prospectively and randomly assigned to two groups according to the RFCA method: the CPVI alone group (CPVI; n = 50) or the catheter Dallas lesion group (CPVI, posterior box lesion, and anterior linear ablation; n = 50).

Electrophysiological mapping

Intracardiac electrograms were recorded using the Prucka CardioLab™ Electrophysiology system (General Electric Medical Systems, Inc.), and RFCA was performed in all patients using three-dimensional (3D) electroanatomical mapping (NavX, St Jude Medical, Inc.) merged with 3D spiral computed tomography (CT). The high right atrium (RA), low RA, and coronary sinus were mapped with a decapolar catheter (Bard Electrophysiology Inc.) and duo-decapolar catheter (St Jude Medical Inc.) inserted via the left femoral vein. A quadripolar catheter was also placed in the superior vena cava. Double transseptal punctures were made, and multi-view pulmonary venograms were obtained. After securing transseptal access, a circumferential PV mapping catheter (Lasso; Biosense-Webster Inc.) was introduced with a long sheath (Schwartz left 1, St Jude Medical, Inc.). Systemic anticoagulation was performed with intravenous heparin to maintain an activated clotting time of 350–400 s during the procedure. For electroanatomical mapping, 3D geometry of both the LA and PV was generated using the NavX system and then merged with 3D spiral CT images.

Radiofrequency catheter ablation

Details of the RFCA technique and strategy were described previously in our studies.⁵ Briefly, for CPVI ablation, continuous circumferential lesions were created at the level of the LA antrum (∼1 cm from the PV ostia) encircling the right and left PV guided by the NavX system using an open irrigation, 3.5 mm tip deflectable catheter (Celsius, Johnson & Johnson, Inc.; irrigation flow rate 20–30 mL/min, 30–35 W, 47°C; Figure 1A). We conducted CPVI and cavotricuspid isthmus ablation in all patients. The endpoints of both CPVI and cavotricuspid isthmus block were defined by bidirectional pacing. Circumferential pulmonary vein isolation was verified during isoproterenol infusion after a waiting time of 30 min. For the catheter Dallas lesion group, additional linear ablations of posterior box lesions and anterior linear ablations were performed. To generate the posterior box lesion, linear ablations on the roof and posterior inferior wall were made by connecting both sides of the CPVI at the top and bottom levels, respectively (Figure 1B). Anterior linear ablation was generated by ablation from the mitral annulus at the 12 o'clock direction towards the LA roof line (Figure 1B).⁹ Bidirectional block of roof lines was confirmed by differential pacing from LA appendage vs. LA posterior wall (Figure 2), and successful generation of posterior box lesions was defined as no endocardial electrogram in the LA posterior wall with a roof line block (Figure 1B). Bidirectional block of anterior lines was confirmed by differential pacing from LA appendage vs. LA septum (Figure 3).

Figure 1

Ablation lesions for the two strategies and voltage map after catheter Dallas lesion ablation. (A) For CPVI ablation, continuous circumferential lesions were created at the level of the LA antrum (∼1 cm from the PV ostia) encircling the right and left PV. (B) For catheter Dallas lesion ablation, we generated posterior box lesion and anterior linear ablation in addition to CPVI. The posterior box lesion was generated by an additional LA roof line connecting the tops of two encircling lesions (RL) and a posterior inferior line connecting the lower margins of the right and left CPVI lines. Anterior linear ablation was created by ablation from the mitral annulus in the 12 o'clock direction to the LA roof line. Achievement of the electrical isolation of posterior box lesion was confirmed by the absence of potential in the LA posterior wall in the voltage map or activation map (B). Activation map of catheter Dallas lesion group (B) shows significant conduction block or delay along the anterior linear ablation. RL, roof line.

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Figure 2

Confirmation of bidirectional block of the roof line by differential pacing from the LA appendage (ring catheter) and LA posterior wall (ABL). (A) Locations of pacing catheters. (B) Electrogram conduction patterns during differential pacing. LAA, left atrial appendage; ABL, ablation catheter; CS, coronary sinus catheter; ds, distal electrode; px, proximal electrode.

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Figure 3

Confirmation of bidirectional block of the anterior linear ablation by differential pacing from the LA appendage (ring catheter) and LA septum (ABL). (A) Locations of pacing catheters. (B) Electrogram conduction patterns during differential pacing. LAA, left atrial appendage; ABL, ablation catheter; CS, coronary sinus catheter; ds, distal electrode; px, proximal electrode.

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Post-ablation management and follow-up

Following RFCA procedures, anti-arrhythmic drugs were discontinued in all patients. Patients visited the outpatient clinic regularly at 1, 3, 6, and 12 months and then every 6 months thereafter or whenever symptoms occurred after RFCA. All patients underwent electrocardiography (ECG) during every visit and 24 h Holter recording at 3 and 6 months and every 6 months, according to the 2012 HRS/EHRA/ECAS Expert Consensus Statement guidelines.¹⁰ However, whenever patients reported symptoms of palpitations, Holter monitor or event monitor recordings were obtained and evaluated for the possibility of arrhythmia recurrence. We defined recurrence of AF as any episode of AF or atrial tachycardia lasting for at least 30 s in duration.¹⁰ Any ECG documentation of AF recurrence after 3 months of the blanking period was diagnosed as clinical recurrence.¹⁰

Statistical analysis

Statistical analysis was performed using SPSS (Statistical Package for Social Sciences) software for Windows (version 18.0). Continuous variables were expressed as mean ± standard deviation and were compared using Student's t-test. Categorical variables were reported as frequencies (percentage) and compared by the χ² test and Fisher's exact test. A Kaplan–Meier analysis was used to analyse the probability of freedom from AF recurrences after RFCA. A P < 0.05 (two-sided) was considered statistically significant.

Results

Baseline characteristics

The 100 patients were randomly assigned to undergo CPVI (n = 50) or catheter Dallas lesion (CPVI, posterior box lesion, and anterior linear ablation, n = 50). A total of 75 patients (75.0%) were male, and the mean age of all patients was 56.4 ± 11.6 years. Table 1 shows characteristics of the study population and compares the patients by group. The two ablation groups were well balanced with regard to baseline characteristics, except for CHADS₂ score (0.56 ± 0.93 vs. 1.14 ± 1.25, P = 0.010) and history of ischaemic stroke or transient ischaemic attack (6.0 vs. 28.0%, P = 0.003).

Procedural results and clinical outcomes

Table 2 summarizes the procedural results and clinical outcomes. The total procedure time (161.1 ± 30.3 vs. 190.3 ± 46.3 min, P < 0.001) and RF energy delivery time (4027.2 ± 878.0 vs. 5345.4 ± 676.4 s, P < 0.001) were significantly shorter in the CPVI group compared with the catheter Dallas lesion group. The procedure-related complication rate was 2.0% in the overall patient population. Two patients in the CPVI group (4%) had pericardial effusions, which spontaneously resolved without pericardiocentesis. None of the patients in the catheter Dallas lesion group experienced complications, but there was no statistical difference in the complication rates between the two groups. During the 16.3 ± 4.0 months of follow-up, both early recurrence rate within 3 months after RFCA (P = 0.499) and the clinical recurrence rate (12.0 vs. 16.0%, P = 0.564) were not different between CPVI and catheter Dallas lesion groups. Consistently, Kaplan–Meier analysis showed no significant difference in AF recurrence-free survival between the two ablation strategies (log rank P = 0.642; Figure 4).

Table 2

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Procedural results and clinical outcomes

.	Total (n = 100) .	CPVI (n = 50) .	Catheter Dallas lesion (n = 50) .	P-value .
Total procedure time (min)	175.7 ± 41.6	161.1 ± 30.3	190.3 ± 46.3	<0.001
Ablation time (s)	4693.0 ± 1490.5	4027.2 ± 878.0	5345.4 ± 1676.4	<0.001
Complications	2 (2.0%)	2 (4.0%)a	0 (0%)	0.157
Clinical outcomes
Follow-up (months)	16.34 ± 4.00	16.27 ± 4.50	16.40 ± 3.46	0.872
Early recurrence	27 (27.0%)	12 (24.0%)	15 (30.0%)	0.499
Clinical recurrence	14 (14.0%)	6 (12.0%)	8 (16.0%)	0.564

.	Total (n = 100) .	CPVI (n = 50) .	Catheter Dallas lesion (n = 50) .	P-value .
Total procedure time (min)	175.7 ± 41.6	161.1 ± 30.3	190.3 ± 46.3	<0.001
Ablation time (s)	4693.0 ± 1490.5	4027.2 ± 878.0	5345.4 ± 1676.4	<0.001
Complications	2 (2.0%)	2 (4.0%)a	0 (0%)	0.157
Clinical outcomes
Follow-up (months)	16.34 ± 4.00	16.27 ± 4.50	16.40 ± 3.46	0.872
Early recurrence	27 (27.0%)	12 (24.0%)	15 (30.0%)	0.499
Clinical recurrence	14 (14.0%)	6 (12.0%)	8 (16.0%)	0.564

P-values < 0.05 were marked as bold. CPVI, circumferential pulmonary vein isolation; Catheter Dallas lesion, CPVI with the posterior box lesion and anterior linear ablation.

^aTwo cases of complication; pericardial effusions that did not require pericardiocentesis.

Table 2

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Procedural results and clinical outcomes

.	Total (n = 100) .	CPVI (n = 50) .	Catheter Dallas lesion (n = 50) .	P-value .
Total procedure time (min)	175.7 ± 41.6	161.1 ± 30.3	190.3 ± 46.3	<0.001
Ablation time (s)	4693.0 ± 1490.5	4027.2 ± 878.0	5345.4 ± 1676.4	<0.001
Complications	2 (2.0%)	2 (4.0%)a	0 (0%)	0.157
Clinical outcomes
Follow-up (months)	16.34 ± 4.00	16.27 ± 4.50	16.40 ± 3.46	0.872
Early recurrence	27 (27.0%)	12 (24.0%)	15 (30.0%)	0.499
Clinical recurrence	14 (14.0%)	6 (12.0%)	8 (16.0%)	0.564

.	Total (n = 100) .	CPVI (n = 50) .	Catheter Dallas lesion (n = 50) .	P-value .
Total procedure time (min)	175.7 ± 41.6	161.1 ± 30.3	190.3 ± 46.3	<0.001
Ablation time (s)	4693.0 ± 1490.5	4027.2 ± 878.0	5345.4 ± 1676.4	<0.001
Complications	2 (2.0%)	2 (4.0%)a	0 (0%)	0.157
Clinical outcomes
Follow-up (months)	16.34 ± 4.00	16.27 ± 4.50	16.40 ± 3.46	0.872
Early recurrence	27 (27.0%)	12 (24.0%)	15 (30.0%)	0.499
Clinical recurrence	14 (14.0%)	6 (12.0%)	8 (16.0%)	0.564

P-values < 0.05 were marked as bold. CPVI, circumferential pulmonary vein isolation; Catheter Dallas lesion, CPVI with the posterior box lesion and anterior linear ablation.

^aTwo cases of complication; pericardial effusions that did not require pericardiocentesis.

Figure 4

Kaplan–Meier analysis of AF recurrence-free rate in patients with paroxysmal AF subjected to one of two ablation strategies. There was no significant difference between the two ablation strategies [P = 0.642, log rank (Mantel–Cox) test].

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Complete conduction block after linear ablation and clinical outcomes

We achieved both CPVI and bidirectional blocks of the cavotricuspid isthmus in 100% of patients in both groups. In the catheter Dallas lesion group, bidirectional blocks of the anterior linear ablation and posterior box isolation were achieved in 68.0% (n = 34) and 60.0% (n = 30) of patients, respectively (Table 3). For the posterior box ablation, bidirectional block rates of the roof and posterior inferior lines were 92.0% (n = 46) and 60.0% (n = 30), respectively. The main reasons for failed bidirectional block of the posterior inferior line and anterior line were risks of oesophageal injury and Bachmann's bundle damage during RF energy delivery, respectively.

Overall, 42.0% (n = 21) of the catheter Dallas lesion group achieved a complete bidirectional block with the Dallas lesion set. There were no significant differences in the rates of early recurrence or clinical recurrence among the CPVI group (n = 50), catheter Dallas lesion group with incomplete bidirectional block (n = 29), or catheter Dallas lesion group with complete bidirectional block (n = 21, Table 4). There was no significant difference in terms of clinical outcomes depending on the number of bidirectional blocks after linear ablation (Table 4).

Discussion

In this prospective randomized study for the comparison of two ablation strategies in paroxysmal AF, catheter Dallas lesion did not improve clinical outcome in spite of longer procedure or ablation time compared with CPVI. The clinical recurrence rate was also not significantly different between patients with bidirectional block achievement and those without.

Anti-arrhythmic mechanisms of circumferential pulmonary vein isolation in paroxysmal atrial fibrillation

The main mechanism of paroxysmal AF is regarded as triggered activity, which is initiated by rapid and repetitive discharges originating predominantly in the PV antrum.¹¹ Although non-PV trigger, which is the substantial mechanism in persistent AF, also has been described in paroxysmal AF, it accounts for no more than 10% of AF triggers. In this respect, the purpose of CPVI is blockage of the PV trigger. Moreover, PV antral ablation results in better clinical outcome compared with the segmental ostial ablation approach for PVI. This may be due to the fact that antral CPVI eliminates peri-PV ostial triggers or drivers, affects the ganglionated plexi or cardiac autonomic nerves,¹² and reduces the critical mass of the atrium.¹³ Therefore, permanent and complete CPVI became a cornerstone technique for catheter ablation of paroxysmal AF. In spite of many potential anti-arrhythmic mechanisms of CPVI, the true indication and purpose of CPVI are reduction of AF burden and symptoms. At this time, however, there is no evidence that additional linear ablation or complex fractionated atrial electrogram (CFAE)-guided ablation in addition to CPVI improves clinical outcome of paroxysmal AF ablation.^5,6 We previously proved no additional benefit of roof line and posterior box lesion in patients who underwent CPVI for paroxysmal AF.⁵ In STAR-AF trial, CFAE-guided ablation in addition to CPVI improved clinical outcome of persistent AF ablation, but not in patients with paroxysmal AF.⁶

Catheter Dallas lesion for paroxysmal atrial fibrillation

Although CPVI remarkably reduces the AF burden, the long-term recurrence rate of AF is still 40–50% after CPVI.¹⁴ Moreover, some authors have reported 1-year AF recurrence rate as up to 60%, thus the efficacy of CPVI in real-world practice seems to be less favourable as compared with the results reported in clinical trials.^15,16 For successful catheter ablation of AF, both initiation and perpetuation are important targets for the procedure. While CPVI is more focused on the initiation of AF, linear ablation modifies atrial substrates and compartmentalizes the atrium into smaller regions for prevention of reentry and AF maintenance.⁹ Generally, the clinical outcome of maze surgery is superior to that of catheter ablation,³ despite the lack of direct comparisons of catheter ablation and maze surgery. This clinical difference may be due to critical mass reduction effect of AF surgery or transmurality of linear lesions. Posterior wall isolation also blocks atrial ectopies originating from the posterior venous LA. Therefore, we benchmarked the Dallas lesion set of minimally invasive maze surgery that was initially reported by Edgerton for thoracoscopic AF surgery.⁴ The characteristic lesion of the Dallas lesion is anterior linear ablation, instead of classical left lateral isthmus lesion. This is because left lateral isthmus ablation by epicardial approach carries a risk of cardiac vessel damage. We previously reported on the clinical usefulness and effectiveness of anterior linear ablation in patients with persistent AF who underwent catheter ablation.⁹ Although there were no differences in complications between the CPVI and the catheter Dallas lesion groups, additional catheter ablations for linear lesions are technically challenging to achieve, have a risk of complication, and, if incomplete, may be proarrhythmic.¹⁷ Moreover, CPVI itself has effects on critical mass reduction, and additional linear ablation had no additional benefit in the current study. Therefore, the critical mass of a less remodelled LA in patients with paroxysmal AF may not be large enough to require additional linear ablation after CPVI.¹³

Improving clinical outcomes of paroxysmal atrial fibrillation ablation

Because additional catheter Dallas lesion procedures or complete bidirectional conduction block of linear lesions did not improve clinical outcome, other mechanisms for AF recurrence need to be considered. Although the most common cause of paroxysmal AF recurrence might be PV reconnection,¹⁸ an autonomic neural mechanism or other genetic or biological factors potentially contribute to the clinical recurrence of AF after RFCA.¹² Mother rotor,¹⁹ which is not limited by critical mass, may play a role as a mechanism of AF recurrence. Therefore, the developments of safe and effective energy source for complete and permanent CPVI, fast and sophisticated mapping technique for AF, and strict criteria for appropriate patient selection are warranted to improve the clinical outcome of paroxysmal AF catheter ablation.

Study limitations

This study included a relatively small number of patients from a single centre. Patient characteristics between the two groups were different with regard to CHADS₂ score despite randomization. High CHADS₂ score may affect the clinical outcome of AF catheter ablation associated with advanced remodelling of LA.²⁰ Bidirectional block was achieved only in 42% of patients. Therefore, small number of patients with the complete achievement of bidirectional block may affect the statistical power of the findings. Although we confirmed bidirectional block of linear lesions, some lesions might have recovered conduction, which may have affected the clinical outcome. In this study, we did not exclude potential triggers in the RA. Because current definition of AF recurrence does not consider the reduction of AF burden, the result of this study does not mean no additional benefit of catheter Dallas lesion to reduce AF-related symptom or AF duration. Therefore, the AF ablation strategy should be personalized in a more symptomatic population.

Conclusion

We conducted a prospective randomized study to compare two different ablation strategies for paroxysmal AF and demonstrated that additional linear ablations of the catheter Dallas lesion compared with the CPVI technique did not improve clinical outcome despite longer procedure or ablation times and was independent of bidirectional block achievement.

Conflict of interest: none declared.

Funding

This work was supported by grants from the Korea Health 21 R&D Project, Ministry of Health and Welfare (A085136) and the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (MSIP; 7-2013-0362).

References