Europace Advance Access originally published online on October 8, 2007
Europace 2007 9(12):1129-1133; doi:10.1093/europace/eum219
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ATRIAL FIBRILLATION
Efficacy and late recurrences with wide electrical pulmonary vein isolation for persistent and permanent atrial fibrillation
Department of Cardiology, Westmead Hospital and The University of Sydney, NSW, Australia
Manuscript submitted 22 May 2007. Accepted after revision 3 September 2007.
* Corresponding author: Department of Cardiology, National University Hospital, Level 3 Main Building, 5 Lower Kent Ridge Road, Singapore 119074, Singapore. Tel: +65 67725211; fax: +65 68722998. E-mail address: seow_sc{at}yahoo.com, seowsweechong{at}gmail.com
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Abstract |
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Aims: Early recurrences of atrial arrhythmia after wide electrically isolating ablation for atrial fibrillation (AF) are well described, but the long-term risk of recurrence for patients with persistent and permanent AF has not been studied in detail.
Methods and results: Fifty-six consecutive patients [45 men (80.4%), age 55.9 ± 8.7 years] with persistent [39(69.6%)] or permanent [17(30.4%)] AF were followed for 21.6 ± 8.8 months after ablation. Atrial fibrillation duration prior to ablation was 6.4 ± 5.6 years. Electrically isolating lesions encircling the left and right pulmonary veins (PVs) in pairs were created. After 1.5 ± 0.7 procedures, 48 (85.7%) had sinus rhythm (SR) at 21.6 ± 8.8 months of follow-up: achieved with 1 procedure in 27 (56.3%) and without anti-arrhythmics in 30 (62.5%). Atrial fibrillation recurrence was observed in 69.6% after the first and 46.4% after the last procedure. Of those with late recurrences (>90 days) following the last procedure, most [18 (69.2%)] did not have early recurrences. Pre-procedural AF duration (P = 0.007) and female gender (P = 0.005) were independent predictors of recurrence following the last procedure.
Conclusion: Circumferential PV isolation is effective in most patients with persistent or permanent AF. However, repeat procedures are frequently required. Late recurrences are common and not precluded by the absence of early post-procedural arrhythmias.
Key Words: Atrial fibrillation, Persistent, Ablation, Pulmonary veins, Efficacy, Arrhythmia recurrences
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Introduction |
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Percutaneous techniques for catheter ablation of atrial fibrillation (AF) have evolved rapidly over the last decade. A wide range of techniques have been used to treat a broad range of patients with AF. There is still no consensus on the optimal approach. Good early results have been described for patients with intermittent AF treated with several different ablation techniques.1
–3 Fewer studies have examined the role of catheter ablation for permanent or persistent AF.2,4–6
A common technique for catheter ablation of AF involves wide encirclement of the pulmonary vein (PV) ostia with a ring of radiofrequency (RF) lesions.1,7,8 More recently, this has been combined with electrical isolation of the veins.9 Early recurrences of atrial arrhythmia are well described after wide circumferential PV isolation. However, there are less data on late arrhythmia recurrences and long-term outcomes. The aim of this study was to determine the long-term efficacy and describe the pattern of late post-procedural arrhythmia recurrences in patients with persistent or permanent AF undergoing wide circumferential PV isolation.
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Methods |
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The study population comprised 56 patients (45 males, 80.4%) with symptomatic persistent (39, 69.6%) or permanent (17, 30.4%) AF who had failed anti-arrhythmic drugs (AADs). The mean age of the patients was 55.9 ± 8.7 years. Persistent AF was defined as AF present for more than 7 days. Permanent AF was defined as AF that recurred frequently despite numerous attempts at cardioversion.10
Nine patients (16.1%) had structural heart disease, 2 (3.6%) had coronary artery disease, 4 (10%) had impaired left ventricular systolic function, and 30 (53.6%) had left atrial (LA) size >40 mm. Hypertension was present in 37 (66.1%) patients. Prior to the procedure, the patients had failed 2.0 ± 1.0 AADs. Duration of AF prior to ablation was 6.4 ± 5.6 years. All patients gave written informed consent for the procedure. The study was approved by the institution's Ethics Committee. Following ablation, the patients were followed up for 21.6 ± 8.8 months.
Electrophysiological study
A transoesophageal echocardiogram was performed immediately before the ablation to exclude any intra-atrial thrombus. Anti-arrhythmic medications, except for amiodarone (n = 7), were ceased at least five half-lives before the procedure. Anticoagulation was stopped 3–5 days before. Surface and intracardiac electrograms were continuously monitored and recorded using a computerized amplifier and recording system (Prucka Cardiolab, GE Medical Systems, Milwaukee, WI, USA).
Two trans-septal punctures were performed under fluoroscopic guidance using a modified Brockenbrough technique to gain access to the LA. A long sheath (Preface Multipurpose, Biosense Webster, Diamond Bar, CA, USA) was used to guide a decapolar circular mapping catheter (Lasso, Biosense Webster) in the LA. A 12 F deflectable long sheath (Ultimum Agilis, St Jude Medical, St Paul, MN, USA) was used to manoeuvre the 7 F, 3.5 mm open-irrigated tip ablation catheter (Thermocool Navistar, Biosense Webster). Intravenous unfractionated heparin 100 IU/kg was given following the trans-septal punctures. The activated clotting time was checked every 30 min and subsequent doses of heparin were given to maintain this between 300 and 350 s.
Three-dimensional electroanatomical mapping and irrigated radiofrequency ablation
The CARTO (Biosense Webster) electroanatomical mapping system was used with a merged three-dimensional rendered CT image of the cardiac chambers to guide ablation during AF. Lesions 2–5 mm apart were created using RF energy to form two rings of electrically isolating RF lesions, one around each ipsilateral pair of PVs (Figure 1). Lesions were positioned 
1 cm from the PV ostia and the two rings did not touch posteriorly. Irrigated RF ablation was set at 40 W, temperature 50–53°C, and a flow rate of 17 mL/min. Power was reduced to 30 W over the posterior LA wall and 25 W near the PV ostia. The endpoint of ablation was electrical isolation of all the PVs, defined as the absence of potentials, or dissociated PV potentials with the Lasso mapping catheter positioned at the PV ostia at 30 min after PV isolation. To achieve this endpoint, additional segmental ablation near the ostia of the PV was required in 32 (57.1%) patients. Additional ablation lines were added if sinus rhythm (SR) was not achieved following electrical isolation of the PVs. A roof line between the two superior PVs was created in 32 patients (57.1%) and a mitral isthmus line between the left inferior PV and the mitral annulus (at 4 o'clock position in the left anterior oblique view) was created in 37 patients (66.1%). The cavo-tricuspid isthmus was ablated in 14 (25%). Electrical cardioversion was performed if SR was not attained with the completion of the ablation lines. At the end of the procedure, repeat selective PV angiography was performed.
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Post-procedural care and follow-up
Anticoagulation was omitted for the first 4 h after the procedure to reduce bleeding complications. Thereafter, intravenous unfractionated heparin was used to achieve activated partial thromboplastin time twice the control value till the morning of the following day. Subsequently, subcutaneous injections of low-molecular-weight heparin were administered simultaneously with the recommencement of oral anticoagulation until the INR was greater than 2. Patients were discharged the day after the procedure. All AADs were continued for a month and ceased subsequently if there were no symptoms suggestive of arrhythmia recurrence. Patients who had symptoms suggestive of AF recurrence were investigated with ambulatory electrocardiographic (Holter) monitoring. Documented recurrences lasting 30 s or more were identified. In the case of recurrence, the patient was offered a repeat procedure.
Statistical analysis
Continuous variables are reported as mean ± standard deviation. Comparisons between groups were performed using Student's t-test, in which assumptions of normality were satisfied. Categorical variables are reported as number and percentage, with comparisons made using 
2 analysis or Fisher's exact test. The Kaplan–Meier survival analysis comparing categorical variables using log-rank test was performed. Cox regression was used for continuous variables and multivariate analysis. A probability value of less than 0.05 was considered statistically significant.
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Results |
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Procedural data
Sixteen (28.4%) of the 56 patients had a previous segmental PV isolation. Thirty-nine (69.6%) patients required electrical cardioversion during ablation to restore SR.
In total, the 56 patients underwent 1.5 ± 0.7 procedures [1 procedure in 33 (58.9%) patients, 2 procedures in 16 (28.6%), 3 procedures in 5 (8.9%), and 4 procedures in 1 (1.8%)].
Long-term clinical outcome
After 21.6 ± 8.8 months, 48 patients (85.7%) were in SR at the last follow-up visit. Of these, 30 patients (62.5%) did not require AADs. This was achieved with a single procedure in 27 (56.3%) patients.
Timing of early and late atrial fibrillation recurrences
Early AF recurrence was defined as that occurring within the first 90 days of the procedure. Late recurrence occurred after 90 days. Following the first procedure, early recurrence was seen in 26 (46.4%) subjects. Thirty-nine (69.6%) patients had late recurrences. Half of these occurred by 3.2 months and 90% by 12.1 months (Figure 2). Five (10.4%) patients developed atrial flutter following the initial PV isolation procedure and required further ablation. In total, 23 (41.1%) patients underwent repeat procedures. All patients who underwent repeat procedures had recovered conduction in at least one PV.11–14
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After the final procedure, 13 (23.3%) patients had early recurrences. Late recurrences were seen in 26 (46.4%). Half of the late recurrences occurred by 7.6 months and 90% by 28.6 months following the last procedure (Figure 3). Of those patients with late recurrences, 18 (69.2%) did not have any early recurrence. The incidence of late recurrence at 1-year follow-up was 30.4%. At 2 years, this increased to 41.1%.
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Sinus rhythm maintenance
Forty-eight (85.7%) patients were in SR at the last follow-up visit, of which 30 (62.5%) did not require AADs. Despite late recurrences in 26 (46.4%) patients following the final procedure, 18 (69.2% of 26) were in SR at the last follow-up. Of these patients in SR, 7 (39.9%) were not on AADs.
Predictors of atrial fibrillation recurrence
In univariate analysis, pre-procedural AF duration was longer (8.1 ± 6.2 vs. 4.3 ± 3.9 months, P = 0.011) in patients who experienced AF recurrences following the final procedure. Females were more likely to experience recurrences (P = 0.042). Multivariate analysis using Cox regression showed that female gender [HR 5.76 (1.72–19.29), P = 0.005] and duration of AF prior to ablation [HR 1.12 (1.03–1.22), P = 0.007] were independent predictors of recurrence following the last procedure (Table 1).
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Atrial fibrillation recurrence after the first procedure was predicted by female gender (P = 0.031) and duration of pre-procedural AF (P = 0.025). These two factors were also independent predictors of recurrence on multivariate analysis; HR 3.13 (1.37–7.19), P = 0.007 and HR 1.08 (1.02–1.15), P = 0.007, respectively.
Complications
The complications are summarized in Table 2.
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Discussion |
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The main findings of this study were as follows. (i) Pulmonary vein isolation is effective for persistent or permanent AF; (ii) late recurrences are common and are not precluded by the absence of early post-procedural arrhythmias; (iii) a significant number of late recurrences can manifest more than a year after the procedure; and (iv) despite late recurrences, SR can be maintained in the majority of patients.
Efficacy of wide isolating circumferential ablation in persistent and permanent atrial fibrillation
Pulmonary vein isolation using wide circumferential electrically isolating lesions around the ipsilateral PV pairs is effective in persistent and permanent AF, resulting in maintenance of SR in 85.7% at last follow-up. These outcomes are superior to segmental ostial PV ablation in a similar group of patients previously described by our group15 (SR in 45% after 16.9 ± 9.1 months). This finding is consistent with the results of two previous studies comparing segmental isolation with wider isolating rings of ablation in mixed groups of patients with paroxysmal or persistent AF.16,17
Ouyang et al.6 reported success rates of 62% in 40 patients with persistent AF after one procedure and 95% after repeat ablation in those who had recurrence. The approach used was circumferential ablation of the PVs with electrical isolation as the endpoint, but the follow-up period was only 8 ± 2 months and it is unclear how many required AADs. A higher proportion of the patients experiencing arrhythmia recurrence in the series reported by Ouyang et al. underwent a repeat procedure (93%), compared with the present study (51%).
Previous studies have reported rhythm outcomes after relatively short post-procedural follow-up. In the present study, late recurrences of AF were common, occurring in 69.6% after the first procedure and 46.4% after the last procedure. The absence of early recurrences did not appear to provide any assurance against late post-procedural arrhythmias. In a recent study comparing ostial vs. extraostial PV isolation,16 the recurrence rate following the first procedure was similarly high at 83% in the extraostial group with persistent AF. This improved to 48% after a second procedure with a follow-up of 12 months. However, the majority of patients in that study had intermittent AF. Another study reported by Cheema et al.18 contained a subgroup of 35 patients with persistent and permanent AF. In this subgroup, recurrence was seen in 57.1% following a single procedure and 40% after repeat ablations; after a follow-up of 13 ± 1 months. The 1-year incidence of recurrence following the last procedure in our study was 30.4%. At 2 years, this increased to 41.1%. Thus, although most recurrences presented during the first year, a significant number of recurrences manifested much later.
Predictors of arrhythmia outcomes
Predictors of arrhythmia recurrence may assist in patient selection. We found pre-procedural duration of AF and female gender to be independent predictors of recurrence following the first and final procedures. These relationships have been noted in the previous studies.1,16,18 Previously observed risk factors for arrhythmia recurrence after catheter ablation include the presence of underlying structural heart disease and an enlarged LA. Their relevance to AF recurrence is, however, controversial.1,15,16,18–20 Further studies are required to delineate predictors of arrhythmia outcome after catheter ablation.
Limitations
Our study is limited by its small size and by the fact that we did not routinely monitor patients' rhythm for prolonged periods following the procedure using an event recorder. Patients were investigated only if they had symptoms suggestive of recurrence. It is thus possible that asymptomatic recurrences could have occurred and were not recorded. However, these asymptomatic recurrences are infrequent following PV isolation in patients with previously highly symptomatic arrhythmia in whom anti-arrhythmic and rate controlling medications have been stopped.20
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Conclusion |
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Pulmonary vein isolation is effective for persistent and permanent AF. Late recurrences are common following catheter ablation and are not precluded by the absence of early recurrences. Furthermore, a significant proportion of late recurrences occurs more than a year after the procedure.
Conflict of interest: none declared.
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References |
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