Adjunctive interpulmonary isthmus ablation has no added effects on atrial fibrillation recurrence

Introduction

Radiofrequency catheter ablation has currently become the most effective treatment for symptomatic drug-refractory atrial fibrillation (AF).1 2 Pulmonary veins (PVs) are the main trigger source that induce AF.3 In addition, interpulmonary isthmus zone, which is in the carina region, as well as superior vena cava, coronary sinus musculature, Marshall vein, left atrium (LA) posterior wall and left atrial appendage are capable of inducing AF.4

With the development of ablation systems and technology, and devices including catheters, success rates without antiarrhythmic drug use and overall success rates are currently approximately 75% in paroxysmal AF.5 However, the remaining patients are still associated with AF recurrence.

Extensive encircling pulmonary vein isolation (EEPVI) is currently a widely applied treatment method for AF. Previous studies have demonstrated the presence of electrical connections between ipsilateral PVs.6 The interpulmonary isthmus region has also been proven to be a PV trigger origin initiating and perpetuating AF.7 Contribution of the intravenous ridge to PV reconnection has been reported.8 Moreover, the electrical connection between the superior and inferior PVs in patients with paroxysmal AF has been reported.9 10 PV reconnection after EEPVI is observed at a significant rate, and this could cause AF recurrence.

The questions that the present study aimed to resolve are shown in figure 1. Two assumptions can be made. First, block electric current across the interpulmonary isthmus line is presumed to reduce AF recurrence rate when the reconduction site (gap) arises on the EEPVI ablation line associated with the reconnection circuit from the opposite site trigger source, crossing the interpulmonary isthmus line to the reconduction site, as shown in figure 1A,B. Second, in contrast, when gap exists in the EEPVI line and trigger source located on the same site, the reconnection circuit does not cross the isthmus line, resulting in interpulmonary isthmus line ablation not blocking the reconnection circuit (figure 1C,D). The present study intended to clarify which was significant. Furthermore, AF triggers can occur at a significant rate on the interpulmonary isthmus line. A study on double-Lasso technique that compared AF freedom after ablation between pulmonary vein isolation (PVI) and PVI with interpulmonary isthmus ablation reported no statistically significant differences in AF freedom between the two groups.11 The study included a relatively small number of patients and did not confirm bidirectional conduction block between the superior and inferior PVs. Further studies are required to confirm the effects of interpulmonary isthmus ablation on the AF recurrence rate. Consequently, we conducted a single-centre study comparing the AF recurrence rate between EEPVI with and without adjunctive interpulmonary isthmus line.

Methods

We conducted a single-centre, randomised control study at Okayama Heart Clinic. We evaluated consecutive patients with symptomatic paroxysmal AF refractory to medical management who underwent their first ablation therapy. Exclusion criteria were as follows: patients requiring additional region or carina region ablation in addition to EEPVI to achieve PV isolation; patients with individual PV isolation of ipsilateral PVs despite EEPVI and patients with a common PV trunk due to lack of interpulmonary isthmus. Among 230 patients with paroxysmal AF who underwent PVI, 5, 10 and 15 patients requiring carina region ablation, with individual PVI and with a common PV trunk, respectively, were excluded. Consequently, 200 patients (200/230; 87%) met the criteria and were enrolled in the present study. Patients were prospectively randomised to adjunctive interpulmonary isthmus ablation following the completion of EFPVI (group 1; n=100) and EFPVI only (group 2; n=100) between January 2012 and September 2012. The examination procedure complied with the rules of the Declaration of Helsinki, 12 and the study was approved by the Institutional Ethics Committee for Human Research of Okayama Heart Clinic. Written informed consent was obtained from all patients.

AF ablation

Details of the present AF ablation procedure have been published elsewhere.13 Ablation was performed by using the double-Lasso technique.14 In brief, five venous accesses for electrical mapping and ablation were obtained as follows. Two standard electrophysiology catheters were positioned: a 4-F catheter (Japan Lifeline, Tokyo, Japan) at the His bundle region via a femoral vein and a 6-F catheter in the coronary sinus via the right intrajugular vein. Three catheters were introduced in the LA by using the Brockenbrough technique, which requires two decapolar ring catheters (Japan Lifeline) and an open-irrigated, flexible-tip ablation catheter (CoolFlex^TM, St Jude Medical, St Paul, Minnesota).

EEPVI was performed in all patients by using an open-irrigated ablation catheter inserted via the transseptal sheath with an electroanatomical integration mapping system (Ensite-NavX System, St Jude Medical). Irrigated radiofrequency (RF) energy was applied with a target temperature and infusion rate of 43°C and 8–15 mL/min, respectively. RF energy was delivered with a maximal power limit of 35 W and up to 60 s until decrease in the amplitude of the local bipolar atrial electrogram by >80% or <0.1 mV. The temperature of the oesophagus was continuously monitored by using a catheter with a temperature sensor (SensiTherm^TM, St Jude Medical) during ablation.

The EEPVI endpoint was defined as (1) the simultaneous PV potential elimination recorded by the two-ring catheters within the ipsilateral PVs and the lack of LA capture during intra-PV at least 30 min after isolation; and (2) no PV spike recurrence within all the PVs after the intravenous administration of 20–40 mg ATP during sinus rhythm or coronary sinus pacing.

When the PV potential still remained following the one-round, wide-area circumferential ablation around the ipsilateral veins, both PVs were mapped sequentially by the ring catheters to detect the earliest LA–PV conduction sites on the circumferential line and ablated these sites to isolate PV.

RF energy in group 1 patients was supplied on the interpulmonary isthmus line, reaching the anterior and posterior portions of the encircling ablation line (figure 2). The endpoint of the interpulmonary isthmus ablation in group 1 was determined when bidirectional conduction block between the superior and inferior PVs was confirmed by PV pacing using ring catheters placed within the PVs with 20 mg ATP injection (figure 3). After the completion of EEPVI and interpulmonary isthmus ablation in group 1 and EEPVI in group 2, 20 mg ATP was rapidly administered intravenously to evaluate dormant conduction in PVs and interpulmonary isthmus. PVs and interpulmonary isthmus with conduction recovery after adenosine testing were re-ablated. Adenosine testing was repeated until dormant conduction disappeared.

Figure 2

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Comparison of extensive encircling pulmonary vein isolation with and without interpulmonary isthmus ablation on posteroanterior and internal views of the pulmonary veins. White dots represent ablation points. LSPV, left superior pulmonary vein; RSPV, right superior pulmonary vein; RIPV, right inferior pulmonary vein; LIPV, left inferior pulmonary vein; PA, posterior-anterior; PV, pulmonary vein.

Figure 3

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Representation figure of EEPVI with interpulmonary isthmus ablation. (A) Catheter positions during right PV isolation. (B) Intracardiac electrogram of the right superior (RSPV) and inferior (RIPV) pulmonary veins just after EEPVI. No PV potential was observed in both PVs. (C) Pacing at the superior PV by using a ring catheter. A local electrogram of the inferior PV was captured. (D) After interpulmonary isthmus ablation, local electrogram of the inferior PV was not captured despite pacing at the superior PV. (E) Local electrogram of the superior PV was not captured despite pacing at the inferior PV, hence the bidirectional block of the interpulmonary isthmus. AP; anterior-posterior ,EEPVI; extensive encircling pulmonary vein isolation, PV; pulmonary vein.

Results

AF recurrence rate

Group 1 showed 32% (32/100; 95% CI, 23.0% to 42.0%) recurrence rate, which was similar to that of group 2 (33%, 33/100, 95% CI, 23.9% to 43.1%) (table 3). The χ² test demonstrated no significant differences in per cent recurrence rate between the two groups, with probability value of 1.00. Figure 4 shows the AF-free Kaplan-Meier curve. The AF-free curve was not statistically different between the two groups, rather very similar (p=0.450). PV reconnection incidence was observed similarly in both groups during the second session. The reconnection between the superior and inferior PVs, which is the reconnection through the interpulmonary isthmus line, was observed in 22% (6/27) of patients in group 1 who underwent a second session.

Table 3

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AF recurrence electrophysiological results during the second session and PV stenosis

Figure 4

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Cumulative freedom from AF without antiarrhythmic drug after a single procedure in study groups. Group 1: pulmonary vein isolation with interpulmonary isthmus ablation. Group 2: pulmonary vein isolation. AF, atrial fibrillation.

Discussion

The present, prospective randomised, single-centre study revealed that AF recurrence rate was similar between EEPVI with and without adjunctive interpulmonary isthmus ablation, indicating that adjunctive interpulmonary isthmus ablation does not have obvious AF recurrence reduction effect.

The present EEPVI methods used, including electrophysiological monitoring and catheters, were almost identical with well-established methods.14 We applied the double-Lasso technique. The simultaneous records of ipsilateral PVs by two Lasso catheters detect the electrical interactions of the ipsilateral PVs and help identify conduction gaps in the EEPVI line. To make a complete EEPVI in the present study, the double-Lasso technique was suitable, and studies with application of this technique have been reported.14 15 We did not use ablation catheter with contact force sensor (CF catheter). CF catheter has been reported not to improve AF recurrence, although CF catheter avoids both low and high CF.16 17 Another randomised study demonstrated that CF catheter did not improve procedural and fluoroscopy times, or complication rates and 1-year success rates.18 In the present study, the fluoroscopic and procedural times of EEPVI in groups 1 and 2 were comparable or slightly superior to those in recent reports.1 19 20 Interpulmonary isthmus ablation required approximately 10 min. Similar results regarding adjunctive interpulmonary isthmus ablation not lengthening the procedural and fluoroscopic times have been reported.11 Furthermore, all patients reached the endpoint. Thus, application of the double-Lasso technique was appropriate. Furthermore, the use of open-irrigated ablation catheter, not CF catheter, was also satisfactory. Finally, these findings regarding procedural parameters indicated that our methods were reliable, and the results can be analysed.

In patients who underwent the second session in group 1, 88% (21 of 27 patients) did not show electrical reconnection between the superior and inferior PVs, which demonstrated that electrical disconnection through the interpulmonary isthmus was durable. The results indicated that interpulmonary isthmus ablation maintained a non-conducting state in a considerable number of patients in group 1. Thus, the AF recurrence rate must be different between the two groups when conduction block of the interpulmonary isthmus is hypothesised to play a significant role. In contrast to this theory, we found a similar AF recurrence rate. The results indicate that reconnection circuit across the isthmus line is ignorable. The finding proved that the interpulmonary isthmus did not play a significant role in AF recurrence.

We did not find a significant difference in the AF recurrence rate between patients with and without adjunctive interpulmonary isthmus line ablation, although intrapulmonary isthmus ablation was performed in an acceptable short time without significant complications, such as PV stenosis. Letsas et al 11 examined intrapulmonary isthmus ablation after complete PVI by using an ablation method similar to the present study, which is the double-Lasso technique, and did not show a decrease in AF recurrence rate.11 The study did not confirm the bidirectional conduction block between the superior and inferior PVs, whereas we did. In addition, the study examined a small number of patients (76 patients), including patients with chronic AF, and used the CARTO system. The study had lower patients’ age and longer procedural time compared with the present study. The AF recurrence rate in the study seems slightly higher than that in the present study. Although these differences occur between their study and the present study, EEPVI ablation methods and additional interpulmonary isthmus line ablation methods were identical with the present study, and the results were also identical. The present study and the abovementioned study show that no additive effects of adjunctive interpulmonary isthmus line ablation with EEPVI were found on AF recurrence.

Another multicentre study also found no incremental effects of additional intravenous ridge ablation on AF recurrences.21 The ablation methods were different from those of the present study. The study did not use the double-Lasso technique and did not monitor the ipsilateral PV potentials during ablations. The results of the present study, thus, cannot directly compare with the reported results. The study found that PV potential faced the carina zone in 44% (51/117) of patients after circling PVI, and ablation on the carina site was required to eliminate PV potential completely.21 In addition, several studies indicated that interpulmonary isthmus line ablation was required in establishing complete PV isolation.6 22 23 Patients in the present study requiring ablation on the carina site were excluded to avoid interference with the comparison of any ablation on the carina site. Furthermore, the incidence of patients who required ablation on the carina site after EEPVI completion in the present study by using the double-Lasso technique was approximately 1%–2%, which was considerably lower than the reported study.21 The study found a decrease in AF-free rate in patients who required carina site ablation to complete PV electrical isolation. Comparison of the present results with the reported results revealed that EEPVI measuring ipsilateral PV potential simultaneously by using two decapolar ring catheters to achieve complete PV isolation is important with respect to the AF-free rate.

Conclusion

The results of our study showed similar AF recurrence rate between EEPVI with and without adjunctive interpulmonary isthmus ablation, indicating that interpulmonary isthmus ablation does not obviously decrease AF recurrence. This study emphasises the importance of stable and complete PV isolation by EEPVI itself to reduce AF recurrence.