Comparison of Long-Term Clinical Outcomes Between Segmental and Circumferential Pulmonary Vein Isolation in Patients Undergoing Repeat Atrial Fibrillation Ablation

Abstract

Background: Circumferential pulmonary vein isolation (CPVI) has supplanted segmental PVI (SPVI) as standard procedure for atrial fibrillation (AF). However, there is limited evidence examining the efficacy of these strategies in redo ablations. In this study, we investigated the difference in recurrence rates between SPVI and CPVI in redo ablations for PV reconnection.

Methods and Results: This study retrospectively enrolled 543 patients who had undergone AF ablation between 2015 and 2017. Among them, 167 patients (30.8%, including 128 male patients and 100 patients with paroxysmal AF) underwent redo ablation for recurrent AF. Excluding 26 patients without PV reconnection, 141 patients [90 patients of SPVI (Group 1) and 51 patients of CPVI (Group 2)] were included. The AF-free survival rates were 53.3% and 56.9% in Group 1 and Group 2, respectively (P=0.700). The atrial flutter (AFL)-free survival rates were 90% and 100% in Group 1 and Group 2, respectively (P=0.036). The ablation time was similar between groups, and there no major complications were observed.

Conclusions: For redo AF ablation procedures, SPVI and CPVI showed similar outcomes, except for a higher AFL recurrence rate for SPVI after long-term follow-up (>2 years). This may be due to a higher probability of residual PV gaps causing reentrant AFL.

Atrial fibrillation (AF) is the most common arrhythmia in adults and carries considerable morbidity and mortality for patients.¹ According to previous seminal studies, ectopic beats from the pulmonary veins (PV) are crucial in initiating AF,^2,3 and so durable PV isolation (PVI) has become the cornerstone of AF ablation. There were once debates over segmental PVI (SPVI) vs. circumferential PVI (CPVI) for index ablation procedures. Oral et al found CPVI had better outcomes for paroxysmal AF ablation in a 6-month follow-up.⁴ Another 2 studies showed CPVI had similar efficacy as SPVI in AF ablation after 6-month (mainly paroxysmal AF) and 3-year follow-ups (all paroxysmal AF), respectively.^5,6 A later study demonstrated that the wider area of circumferential ipsilateral PV ablation resulted in better sinus rhythm (SR) maintenance than isolation of each individual PV in a mean follow-up >1 year, possibly because CPVI provided additional parasympathetic denervation.⁷ Lo et al also reported similar efficacy between CPVI and SPVI during the index procedure but less left atrial posterior wall ectopy initiating AF during the second procedure when AF recurred.⁸ CPVI using wide antral isolation has subsequently become a standard approach in AF ablation. However, there are limited data comparing the efficacy of these PVI strategies in redo AF ablations, so we investigated the electrophysiologic mechanisms of atrial tachyarrhythmia (ATa) recurrence after SPVI or CPVI in redo AF ablation.

Methods

Study Population and Study Protocol

We retrospectively enrolled patients who underwent redo AF ablation procedures in Taipei Veterans General Hospital and Taichung Veterans General Hospital during 2015–2017. All patients were followed for at least 1 year. Of the AF redo procedures, SPVI or CPVI was performed at operators’ discretion. After re-isolation of the PVs, non-PV trigger ablation was also allowed if clinically indicated (see details below). The baseline characteristics were obtained and analyzed. All procedures performed were in accordance with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was also approved by the Institutional Review Board of Taipei Veteran General Hospital (2023-01-027CC) and Taichung Veteran General Hospital (CE23048C).

Electrophysiological Studies and Ablation Procedures

All patients had undergone prior AF ablations and presented with documented AF recurrence before the redo procedure. Details of the index procedure are given in the Supplementary Table, and the details of the ablation procedures are described in our previous studies.^8–12 Briefly, all patients discontinued antiarrhythmic drugs (AAD; except amiodarone) for at least 5 half-lives and underwent transesophageal echocardiography to exclude left atrial thrombus before the procedure. The electrophysiological studies were performed in a fasting state. Electro-anatomical mapping (EAMs) was guided by the Ensite NavX/Velocity (Abbott, Inc., St. Paul, MN, USA) or CARTO 3 mapping system (CARTO System, Biosense Webster, Inc., Diamond Bar, CA, USA). PVs were mapped with decapolar Spiral catheters (Abbott, Inc., St. Paul, MN, USA), decapolar Lasso catheters (Biosense Webster), or a 20-mm-diameter mapping catheter (Achieve Mapping Catheter, Medtronic Inc., Minneapolis, MN, USA) in cases of cryoballoon ablation. PV reconnection was defined as the presence of PV potentials that were not dissociated or local bipolar voltage >0.5 mV. If PV reconnection was observed, either segmental or circumferential PV ablation was performed to achieve PVI.

CPVI A continuous circumferential ablation was performed 1.5–2 cm outside the PV ostia using an irrigated 3.5-mm tipped ablation catheter (FlexAbility Cardiac Ablation Catheter, Abbott or Thermocool Catheter, Biosense Webster), no matter where the residual gaps were located. A power control mode of 25–30 W, maximal temperature of 40ºC and duration of 40 s were used for each lesion. Successful PVI was defined as the disappearance of all PV potentials in the PV antrum, which was confirmed by circular mapping catheters (entrance block) with no electrical activity inside the PVs or dissociated PVs during SR.

SPVI For SPVI, instead of creating empirical circumferential lines to isolate PVs, the PV potentials were searched along the PV ostium guided by the decapolar ring catheters (as mentioned above). The earliest breakthrough sites from the left atrium (LA) to the PVs were also examined by the coronary sinus (CS) and/or interatrial septum pacing, which were labeled on the EAMs. Ablation was performed segmentally using the same radiofrequency energy as for CPVI. Successful PVI was defined by the same criteria as for CPVI.

Cryoballoon Ablation After a steerable 15-F over-the-wire sheath (FlexCath Advance, Medtronic) was introduced into the LA, a 28-mm 2nd-generation cryoballoon (Arctic Front Advance, Medtronic) was advanced over the Achieve Mapping Catheter to the LA, inflated, and kept in the ostium for each PV. Optimal vessel occlusion was confirmed with contrast injection showing total contrast retention with no backflow to the LA. The cryoballoon applications lasted for 3 min, and an extra freeze following isolation was systematically performed unless phrenic nerve palsy (PNP) occurred. The left superior PV was treated first, followed by the left inferior PV, right inferior PV, and right superior PV. Diaphragmatic stimulation was performed with the quadripolar catheter positioned in the superior vena cava (SVC) by pacing the ipsilateral phrenic nerve with a 1,000-ms cycle and 20-mA output to avoid PNP. Successful PVI was defined by the same criteria as for CPVI.

Additional Ablations Beyond the PVI If paroxysmal AF persisted after successful PVI, electrical cardioversions were performed to restore SR. During SR, any presenting non-PV triggers were searched for and the detailed mapping approach is described in our previous publications.^11,13,14 In brief, the activation sequences of the high right atrium (RA), His bundle area, and CS were compared. The time interval (<0 ms) between the high RA and His bundle area during SR and ectopy can differentiate the site of ectopy as the SVC, upper crista terminalis, or PV. Simultaneous mapping of the SVC and right PV was used to clarify the true ectopy. If the earliest activation site was near the interatrial septum, simultaneous mapping of the right and left septum was done. For non-PV triggers from the LA, the activation time interval between the proximal and distal pairs of the CS catheter during ectopy was evaluated to determine the location of the ectopic foci. If the earliest activation site was in the proximity of the left PV ostium or posterolateral portion of the mitral annulus, potentials from the vein of Marshall (VOM) were identified by differential pacing or epicardial mapping.¹⁵ Isolation of the arrhythmogenic SVC or CS ostium was guided by the circular catheter recordings from the SVC-RA junction. In patients with other non-PV AF ectopies, catheter ablation was performed in the area with the earliest electrical activity or a local unipolar QS pattern of the ectopic beats preceding the AF. The aforementioned open-irrigated 3.5-mm ablation catheter with the power control mode of 25–30 W, maximal temperature of 40ºC and duration of 40 s were used for each lesion. In cases of VOM triggers, we advanced a Swan-Ganz catheter to the proximal CS and contrast agent was injected through the catheter with balloon inflation to reveal the anatomy of the VOM. After removing the Swan-Ganz catheter, an angiographic guiding catheter was inserted to the CS ostium. A 0.014-inch guiding wire (Fielder FC or Sion from Asahi Intecc Corporation, Japan) with an angioplasty balloon (Mini Trek Over The Wire [OTW], 1.20×12 mm, Abbott Vascular, Santa Clara, CA, USA; or Sprinter Legend OTW, 1.25×10 mm, Medtronic) was then delivered to the VOM. After removing the guiding wire and inflating the OTW balloon, contrast was injected into the OTW balloon lumen to ensure its position inside the VOM. Ethanol (98%) was then injected into the VOM (1 mL over the course of 1 min) with occlusive inflation of the OTW balloon; the procedure was performed 2–4 times.¹⁰ The procedural endpoint was disconnection of SVC and RA, CS and RA, and elimination of other non-PV ectopic beats with negative inducibility of a sustained AF.^11,13,14

In cases of non-paroxysmal AF, if AF persisted after successful PVI, complex fractionated atrial electrogram (CFAE) ablation was performed, confined to the maximal CFAEs with a fractionation interval <50 ms. The endpoints of the CFAE ablation were prolongation of the cycle length and elimination of the CFAEs and the local fractionated potentials (bipolar voltage <0.05 mV).^8–11 If AF persisted after CFAE ablation, electrical cardioversion was performed to restore SR. Thereafter, non-PV triggers were searched for by the abovementioned approaches.

If AF changed to organized focal atrial tachycardia (AT) at any time during the procedure, a local activation map was created, and ablation performed accordingly. In cases of macroreentrant atrial flutter (AFL), entrainment maneuvers, post-pacing interval analysis, and local activation mapping were done, and linear ablation or VOM ethanol infusion was performed to terminate the AFL. Of note, in some cases mitral line ablation was empirically performed at the operators’ discretion.

Finally, cavotricuspid isthmus (CTI) ablation was performed with the aforementioned open-irrigated ablation catheters and the same power setting, or an 8-mm-tip EPT ablation catheter (Boston Scientific Corporation) with a maximum power of 60 W, temperature of 60℃, and duration of 120 s if not ablated in the first ablation session or reconnected. Bidirectional conduction block of the CTI was confirmed during SR.

Post-Ablation Follow-up and Evaluation of AF Recurrence

The details of patient follow-up were described in our previous studies.^8–11 In brief, after ablation, AADs were used for 6–8 weeks to prevent an early recurrence of AF. Patients attended clinic follow-up every 1–3 months for at least 1 year. ECG was recorded at every visit, and 24-h Holter recording and/or event recorders were organized every 2 months in the first year after ablation or if any symptoms suggestive of ATa recurrence. After 1 year, patients had periodic follow-up over 6 months, as well as telephone interviews if patients missed regular follow-up visits to determine any ATa recurrence or any redo ablation procedure at other institutes. ATa recurrence was defined as 12-lead ECG-documented AF, Holter ECG or single-lead ECG tracing identifying AF ≥30 s beyond 3 months, or any sustained AFL or AT after the redo ablation procedure.

Statistical Analysis

Continuous parameters were presented as mean±standard deviation, and categorical variables are expressed as number (percentage). Student t-tests were used to compare continuous variables. The Kaplan-Meier method with log-rank test was used to estimate the freedom from AF for the different PVI strategies. Statistical analysis was conducted using IBM SPSS Statistics for Windows, Version 29 (Armonk, NY: IBM Corp.). Statistical significance was set at P<0.05.

Results

Baseline Characteristics

We enrolled 543 patients who underwent index AF ablation procedures (392 paroxysmal, 151 non-paroxysmal AFs). Of them, AF recurrence occurred in 222 (40.9%, 154 paroxysmal, 68 non-paroxysmal AFs) patients after a follow-up of 30.4±7.8 months, and 167 patients underwent redo ablation procedures for recurrent AF (119 paroxysmal, 48 non-paroxysmal AF) after a mean follow-up of 13.9±8.6 months since the index procedure. There were 26 patients who did not have PV reconnection confirmed by EAMs, and only received non-PV ablation for extra-PV trigger elimination or substrate modification in the redo sessions, including LA linear ablation (15 patients), alcohol injection in VOM (4 patients), LA CFAE ablation (11 patients), SVC isolation (8 patients) and RA focal ablation (6 patients).

In the remaining 141 patients who underwent PVI during the redo procedure, 90 had SPVI (Group 1) and 51 had CPVI (Group 2, Figure 1). Of note, there were 8 patients in which cryoballoon ablation was performed to achieve PVI in the redo session and they were classified as Group 2. The detailed baseline characteristics are shown in Table 1. There were no differences in age, sex, echocardiographic parameters, AF type, AAD usage, or underlying comorbidities between the groups, except for a higher prevalence of hypertension in Group 2 (P=0.001).

Figure 1.

Flowchart of study population and grouping. From a cohort of patients with recurrent AF receiving redo ablation (n=167) after index AF ablation during 2015–2017, there were 141 patients with redo PVI, classified as Group 1 (segmental PVI, n=90) and Group 2 (circumferential PVI, n=51). AF, atrial fibrillation; CFAE, complex fractionated atrial electrograms; LA, left atrium; PVI, pulmonary vein isolation; RA, right atrium; SVC, superior vena cava; VOM, vein of Marshall.

Table 1.

Baseline Characteristics of the Study Patients

Variables	All (n=141)	Group 1 (n=90)	Group 2 (n=51)	P value*
Age (years)	56.1±10.7	56.6±10.6	55.4±11.1	0.51
Male sex	108 (76.6%)	71 (78.9%)	37 (72.5%)	0.42
LVEF (%)	58.6±5.2	58.9±5.0	58.1±5.7	0.36
LAD (mm)	39.6±6.6	38.9±6.3	40.9±7.0	0.10
Paroxysmal AF	84 (59.6%)	54 (60%)	30 (58.8%)	0.89
Non-paroxysmal AF	57 (40.4%)	36 (40%)	21 (41.2%)
CAD	18 (12.8%)	12 (13.3%)	6 (11.8%)	0.79
HF	11 (7.8%)	5 (5.6%)	6 (11.8%)	0.19
TIA/stroke	4 (2.8%)	4 (4.4%)	0 (0%)	0.13
Hypertension	69 (48.9%)	35 (38.9%)	34 (66.7%)	0.001
DM	19 (13.5%)	13 (14.4%)	6 (11.8%)	0.65
Class Ic AAD use	95 (67.4%)	60 (66.7%)	35 (68.7%)	0.81
Class III AAD use	106 (75.2%)	69 (76.7%)	37 (72.5%)	0.58

*Comparisons between groups 1 and 2. AAD, antiarrhythmic drug; AF, atrial fibrillation; CAD, coronary artery disease; DM, diabetes mellitus; HF, heart failure; LAD, left atrial diameter; LVEF, left ventricular ejection fraction; TIA, transient ischemic attack.

Redo Ablation Procedures

Table 2 shows the ablation details of the redo procedures. There were similar recurrence rates in each PV between groups. All patients achieved successful PVI after the redo procedure, but 102 patients (72.3% of the entire cohort) received additional extra-PV ablations. There was no significant difference between groups in substrate modification or non-PV trigger ablation, including LA linear ablation, VOM ethanol infusion, LA CFAE ablation, RA focal ablation, SVC isolation and CTI ablation. No patient suffered from post-procedural major complications, including death, stroke or transient ischemic attack, pericardial effusion or cardiac tamponade requiring pericardiocentesis, and atrio-esophageal fistula, except 1 patient in Group 1 had a femoral artery pseudoaneurysm. The procedure times, fluoroscopic time and PVI time were similar between groups, but the number of ablation points required for PVI was higher in the CPVI group than in the SPVI group (40.9±23.2 vs. 68.5±11.3, P=0.03).

Table 2.

Electrophysiologic Findings of Ablation Procedures During Redo Sessions

Ablation procedures	Group 1 (n=90)	Group 2 (n=51)	P value
PVI
PV reconnection
Left superior PV	35 (38.9%)	25 (49.0%)	0.24
Left inferior PV	19 (21.1%)	15 (29.4%)	0.27
Right superior PV	35 (38.9%)	17 (33.3%)	0.51
Right inferior PV	23 (25.6%)	12 (23.5%)	0.79
Complete PVI in redo	90 (100%)	51 (100%)	N/A
Substrate modification
LA CFAE ablation	20 (22.2%)	11(21.6%)	0.93
LA roof line ablation due to roof flutter	18 (20%)	11 (21.6%)	0.82
Mitral line ablation due to mitral flutter	20 (22.2%)	12 (23.5%)	0.86
Empiric mitral line ablation	1 (1.1%)	2 (3.9%)	0.27
Non-PV trigger ablations
VOM ethanol infusion	4 (4.4%)	3 (5.9%)	0.71
Crista terminalis	1 (1.1%)	2 (3.9%)	0.27
RA posterior free wall	1 (1.1%)	0 (0%)	N/A
RA septal wall	1 (1.1%)	0 (0%)	N/A
SVC isolation	19 (21.1%)	5 (5.6%)	0.09
CTI ablation	35 (38.9%)	26 (51%)	0.17
Procedure time (min)	97.3±41.2	93.8±36.0	0.66
Fluoroscopic time (min)	30.8±15.6	25.1±16.9	0.34
PVI time (min)	57.3±22.4	48.6±18.7	0.07
No. of ablation points required for PVI	40.9±23.2	68.5±11.3	0.03

CFAE, complex fractionated atrial electrograms; CTI, cavotricuspid isthmus; LA, left atrium; N/A, not applicable; PV, pulmonary vein; PVI, pulmonary vein isolation; RA, right atrium; SVC, superior vena cava; VOM, vein of Marshall.

Catheter Ablation Outcomes

The ATa-free survival rates of Group 1 and Group 2 were 38.9% and 45.1%, respectively (P=0.553), the AF-free survival rates were 53.3% and 56.9%, respectively (P=0.700), and the AFL-free survival rates were 90% and 100% (P=0.036), respectively. In the 9 patients with AFL recurrence in Group 1, there were 6 who underwent redo procedures, comprising 3 with PV-gap reentrant AFL (50%), 2 with roof-dependent AFL (33%), and 1 (17%) with perimitral AFL. They were all treated with successful ablation. The AT-free survival rates were 100% and 99.3% (P=0.200) between groups, respectively. The Kaplan-Meier survival curves of all arrhythmias are shown in Figure 2. Furthermore, there were 18 patients in the entire cohort (12.8%) who underwent a 3rd ablation procedure due to ATa recurrence (10 of SPVI, 8 of CPVI). PVI was maintained in 5 patients in the SPVI group (50%) and in 6 patients in the CPVI group (75%) (P=0.28).

Figure 2.

Kaplan-Meier curves for ATa-, AF-, AFL- and AT-free survival between groups in the 2-year follow-up. Both groups showed similar overall ATa-free survival rates (A), AF-free survival rates (B) and AT-free survival rates (D). (C) CPVI had a significantly higher AFL-free survival rate than SPVI. AF, atrial fibrillation; AFL, atrial flutter; AT, atrial tachycardia; ATa, atrial tachyarrhythmia; CPVI, circumferential pulmonary vein isolation; SPVI, segmental pulmonary vein isolation.

Discussion

Main Findings

There was a similar recurrence rate of ATa during the AF redo ablation procedure between SPVI and CPVI in during a long-term (>2 years) follow-up. In our subgroup analysis, we observed similar AF and AT recurrence rates between the groups. However, the SPVI group had a higher AFL recurrence rate than the CPVI group, possibly due to reconnected PV gaps during follow-up, which led to macroreentrant AFL.

Impact of Durable PVI on Recurrent AF

Current guidelines recommend PVI as the primary procedure for AF ablation,¹ and it is widely accepted that achieving PVI is crucial in preventing AF recurrence after ablation.^16,17 In the present cohort of patients with recurrent AF, 84.4% (141/167) had at least 1 reconnected PV, which was consistent with a systematic review reporting PV reconnection in 85.5% (324/379) of patients with recurrent AF.¹⁸ Re-isolation of the PVs may further reduce the risk of AF recurrence.^16,19 However, factors such as non-PV triggers and atrial substrate disease may also contribute to AF recurrence.^20–22 Factors such as LA enlargement, non-paroxysmal AF, and atrial fibrosis may strengthen the effect of non-PV ablation and substrate modification, and PVI alone may not be sufficient to reduce AF recurrence in patients with an advanced stage of atrial substrate.^16,23–25 Because we had a balanced distribution of non-PV ablation and substrate modification in both groups, our data support the observation that SPVI had a similar AF/AT recurrence rate but increased AFL recurrence compared with CPVI.

SPVI vs. CPVI in Redo AF Ablation

Previous studies have demonstrated additional benefits of CPVI offered compared with SPVI, including elimination of reentry wavelets near the PV antrum, denervation of ganglionic plexi near the PVs, and encircling the AF triggers and maintenance structure from the LA posterior wall in ablation lesions,^8,16–18 but little data for redo AF ablations. In this study, we found no difference in the ATa recurrence rates between groups, but CPVI had better outcomes regarding the prevention of AFL recurrence during long-term follow-up. Furthermore, of the 6 patients who underwent subsequent ablations for recurrent AFL in Group 1, 3 (50%) had PV-gap reentrant AFL. According to the study by Ouyang et al, durable PVI is difficult to maintain over a long-term follow-up with a single procedure.¹⁹ Another 2 studies that examined the mechanism of LA tachycardia after SPVI in the index ablation procedure reported that focal reentry at the PV ostium played a critical role,^20,21 and similarly it was reported that 90% of recurrent AT/AFL cases after CPVI of AF are due to gap reentry.²² A more recent study, which used a high-resolution mapping system, found that PV gaps resulting from SPVI or CPVI can lead to various patterns of reentry that cause AFL.²³ Therefore, we hypothesize that the different outcomes of AFL recurrence in our groups may be due to increased PV-gap reentry in the SPVI group. Performing CPVI in redo procedures may even improve the durability of PVI. However, redo CPVI requires ablating on previously ablated scars, which can present challenges. Biophysically, scar tissue has a lower baseline impedance, resulting in a larger lesion size and greater current output when using a power-controlled energy source for ablation.²⁴ Theoretically, such a phenomenon could increase the risk of perforation. However, the present study demonstrated comparable safety, and no patients experienced any major complications, but it should be noted that this study was conducted from 2015 to 2017, and all index procedures were performed before the application of the high-power short-duration (HPSD) strategy. As such, we have no evidence that this observation would also apply to HPSD, but because the HPSD strategy produces a lesion with less depth, it may decrease the risk of perforation.²⁵

Clinical Implications

PVI remains the cornerstone of AF ablation and to the best of our knowledge, this study is the first to compare SPVI and CPVI in redo AF ablation. Our study investigated different recurrence modes following AF redo ablation, and found that SPVI was associated with a higher incidence of AFL recurrence during long-term follow-up (>2 years). On the other hand, more reliable PVI by CPVI could ensure better PV trigger elimination. Therefore, we recommend performing CPVI in all cases of recurrent AF. However, if the local impedance is too low on scar tissue, a more cautious energy delivery, or a well-designed lesion line to avoid ablation on the scar tissue, may be needed.

Conclusions

Patients who had previously undergone index AF ablation and presented with recurrent AF due to PV reconnection had similar ATa-free survival over a 2-year follow-up of either SPVI or CPVI. There was no difference in AF recurrence between groups after the redo ablation procedure. However, SPVI had a higher incidence of AFL recurrence than CPVI, possibly due to a higher probability of residual PV gap causing reentrant AFL.

Acknowledgments

The present work was supported by grants from the Taipei Veterans General Hospital (V109-001, V109-005, V110C-024, V110-014, V111C-065, V112C-050, VGHUST111-G1-8-1, VGHUST112-G1-11-1); the Taichung Veterans General Hospital (TCVGH-1113101C, TCVGH-1123101D, TCVGH-1123101C); and the Ministry of Science and Technology (NSTC111-2314-B-A49-009, MOST109-2314-B-075A-011-MY3, MOST110-2314-B-075A-014-MY3, MOST110-2811-B010-511, MOST109-2811-B-010-529, MOST108-2811-B-010-542, MOST108-2314-B-010-051-MY3, MOST 111-2321-B-075-004, MOST 110-2634-F-A49-005, NSTC 111-2634-F-A49-014).

Conflicts of Interest

None.

Data Availability

The data that support the findings of this study are available on request from the corresponding authors.

Supplementary Files

Please find supplementary file(s);

https://doi.org/10.1253/circj.CJ-23-0364

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