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Alex J.A. McLellan, Sandeep Prabhu, Alex Voskoboinik, Michael C.G. Wong, Tomos E. Walters, Bhupesh Pathik, Gwilym M. Morris, Ashley Nisbet, Geoffrey Lee, Joseph B. Morton, Jonathan M. Kalman, Peter M. Kistler, Isolation of the posterior left atrium for patients with persistent atrial fibrillation: routine adenosine challenge for dormant posterior left atrial conduction improves long-term outcome, EP Europace, Volume 19, Issue 12, December 2017, Pages 1958–1966, https://doi.org/10.1093/europace/euw231
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Abstract
Catheter ablation to achieve posterior left atrial wall (PW) isolation may be performed as an adjunct to pulmonary vein isolation (PVI) in patients with persistent atrial fibrillation (AF). We aimed to determine whether routine adenosine challenge for dormant posterior wall conduction improved long-term outcome.
A total of 161 patients with persistent AF (mean age 59 ± 9 years, AF duration 6 ± 5 years) underwent catheter ablation involving circumferential PVI followed by PW isolation. Posterior left atrial wall isolation was performed with a roof and inferior wall line with the endpoint of bidirectional block. In 54 patients, adenosine 15 mg was sequentially administered to assess reconnection of the pulmonary veins and PW. Sites of transient reconnection were ablated and adenosine was repeated until no further reconnection was present. Holter monitoring was performed at 6 and 12 months to assess for arrhythmia recurrence. Posterior left atrial wall isolation was successfully achieved in 91% of 161 patients (procedure duration 191 ± 49 min, mean RF time 40 ± 19 min). Adenosine-induced reconnection of the PW was demonstrated in 17%. The single procedure freedom from recurrent atrial arrhythmia was superior in the adenosine challenge group (65%) vs. no adenosine challenge (40%, P < 0.01) at a mean follow-up of 19 ± 8 months. After multiple procedures, there was significantly improved freedom from AF between patients with vs. without adenosine PW challenge (85 vs. 65%, P = 0.01).
Posterior left atrial wall isolation in addition to PVI is a readily achievable ablation strategy in patients with persistent AF. Routine adenosine challenge for dormant posterior wall conduction was associated with an improvement in the success of catheter ablation for persistent AF.
What is already known about this subject?
The success of pulmonary vein isolation (PVI) is reduced in patients with persistent compared with paroxysmal atrial fibrillation (AF).
What does this study add?
Although there have been limited small reports of posterior wall isolation, we report the largest series of patients with persistent AF undergoing PVI plus posterior wall isolation. Additionally, there have been no previous reports assessing the role of adenosine to reconnect the isolated posterior wall in a series of patients with persistent AF, which may improve the durability of posterior wall isolation as suggested in PVI procedures.
How might this have impact on clinical practice?
The current study creates a platform for a randomized controlled trial of PVI with or without isolation of posterior left atrial wall in patients with persistent AF. Isolation of the posterior wall including adenosine challenge may change the standard strategies of catheter ablation for persistent AF.
Introduction
Pulmonary vein isolation is less effective in patients with persistent atrial fibrillation (AF). However, a large multicentre international study (STAR AF II) demonstrated that additional linear ablation or targeting of complex atrial activity did not improve procedural outcomes beyond pulmonary vein isolation (PVI) alone.1 Importantly this study did not include electrical isolation of the posterior left atrial wall (PW).2–4 The left atrium (LA) posterior wall may be an important site in the maintenance of atrial fibrillation.5–7 Posterior wall isolation has the potential to improve clinical outcomes in patients with persistent AF through modification of autonomic ganglia, the inclusion of proximal rotors or regions of complex fractionated activity, de-bulking of the atrium, and reinforcement of pulmonary vein isolation.8 The addition of posterior wall isolation was recently shown to improve outcomes in patients with persistent AF undergoing catheter ablation compared with pulmonary vein antral isolation alone.9
Posterior wall isolation may be achieved through a range of ablation strategies including encirclement of the pulmonary veins and posterior wall as a ‘single ring’,10 PVI followed by targeting of all electrical activity on posterior wall11 or as a linear adjunct to PVI.2
Durable pulmonary vein (PV) isolation is the ‘Achilles heel’ of PV isolation for paroxysmal AF with PV reconnection present in the majority of patients with AF recurrence. Similarly reconnection of the posterior wall has been reported in more than 50% of patients when this has been performed.4 Adenosine may unmask dormant pulmonary vein connections through membrane hyperpolarization by activating the IKAdo inward rectifier current.12 Targeting sites of transient PV reconnection following IV adenosine may improve clinical outcomes in patients undergoing PVI;13 however, randomized studies have been conflicting.14,15 To the best of our knowledge, the utility of adenosine to identify reconnection of the posterior left atrium after electrical isolation of the PVs and PW has yet to be determined.
We performed a prospective observational study to determine the acute and long-term effects of adenosine challenge on the posterior left atrium following electrical isolation by catheter ablation.
Methods
Study population
A total of 161 patients with symptomatic persistent atrial fibrillation who had tried at least one antiarrhythmic medication underwent posterior wall isolation. The cohort included all patients with an attempted posterior wall isolation procedure between March 2008 and June 2014. The last 54 patients in this cohort were challenged with adenosine to assess for dormant posterior wall reconnection. The study protocol was approved by the Alfred Hospital and BakerIDI ethics review committee and all patients gave informed consent.
Persistent AF was defined as AF episodes lasting longer than 7 days or AF that was electrically or chemically cardioverted 48 h after symptom onset. Exclusion criteria included paroxysmal AF, age less than 18, and inability to provide informed consent.
Catheter ablation: pulmonary vein isolation
Catheter ablation involved antral circumferential pulmonary vein isolation as described previously.16 All antiarrhythmic medications were stopped 5 half-lives pre-procedure except amiodarone which was ceased 2 weeks prior to the procedure. Warfarin was continued periprocedurally. The procedures were performed under general anaesthetic with an intraoperative trans-oesophageal echocardiogram to rule out intracardiac thrombus. A decapolar catheter was positioned in the coronary sinus and a quadripolar catheter was positioned in the His bundle position via femoral venous access. Two 8 or 8.5 F long sheaths were introduced into the left atrium with transseptal puncture performed with a BRK-1 needle under fluoroscopy and transesophageal echocardiogram (TEE) guidance. A circular mapping catheter was introduced through the SL1 sheath into the left atrium for electrical mapping of the pulmonary veins and patients were given therapeutic heparin to a target ACT >350 s. Ablation was performed with an irrigated ablation catheter (4 mm, DF curve, Thermocool, Navistar SmartTouch, Biosense Webster or Safire Blue, St Jude Medical) with a minimum duration of 30 s at each site or until separation or attenuation of the local electrogram at a maximum power 30 W reduced to 25 W on the posterior wall. Catheter ablation was assisted by 3D mapping with image integration (NavX velocity St Jude Medical in 40% or CARTO3 Biosense Webster in 60%). Pulmonary vein isolation was achieved through ipsilateral circumferential antral ablation and was defined by PV entrance and exit block. Patients with a prior history of atrial flutter underwent cavotricuspid isthmus ablation with bidirectional block confirmed by differential pacing techniques.
Catheter ablation: posterior wall isolation
Following PVI, the circular mapping catheter was placed on the PW to assess PW activity and guide ablation (Figure 1). First a left atrial roof line (25–30 W) at the most cranial aspect of the LA roof was completed. Next a floor line joining the most inferior margin of the inferior PVs was completed. If the PW was not isolated following the floor line, cardioversion was performed to restore sinus rhythm. During CS pacing with the benefit of the posteriorly positioned circular mapping catheter, the original lesion set was mapped to identify gaps. If there were no electrograms along the original lines at the site of earliest activation, then ablation was performed within the posterior ‘box’ immediately adjacent to the earliest site (Figure 1B).
Posterior wall isolation was confirmed with the circular mapping catheter positioned on the posterior wall through the identification of PW entrance and exit block. Exit block was confirmed utilizing the ablator to pace the PW, or documented spontaneous posterior wall potentials through the circular mapping catheter (Figure 2).
Catheter ablation: adenosine challenge
Following PW isolation, intravenous adenosine (12–18 mg) was administered to assess for acute reconnection of the right and left pulmonary veins in all patients, followed by adenosine challenge of the posterior wall in the final 54 patients (Figure 3). All sites of PV adenosine reconnection received consolidation ablation and adenosine testing repeated to confirm no further dormant conduction. Following confirmation of PV isolation, the circular mapping catheter was placed on the PW and a further adenosine challenge was administered to assess for PW reconnection. Any transient or persistent electrical reconnection in response to adenosine was followed by ablation at the site of earliest activity on the original lesion set and adenosine repeated until reconnection was no longer present.
Follow-up
Patients underwent clinical review and 7-day Holter monitoring at 3, 6, and 12 months (unless the patients had documented AF recurrence in the intervening period). Procedural success was defined as freedom from recurrent atrial arrhythmias lasting longer than 30 s after an initial 3-month blanking period. Our standard practice has been to continue anti-arrhythmic medications post ablation unless the patient has medication intolerance, and freedom from AF includes patients on anti-arrhythmic medication. Recurrent arrhythmias were classified as being AF, atrial tachycardia, or both. In patients where redo procedures were performed, reconnection of the pulmonary veins or posterior wall was recorded, and the goal of the redo procedure was re-isolation of pulmonary vein or posterior wall, and additional targeting of clinical atrial tachycardia.
Statistics
Continuous variables are expressed as mean ± SD with comparisons between groups performed with either an unpaired Student's t-test, or where a normal distribution could not be assumed the Mann–Whitney U-test. Categorical variables are expressed as numbers and percentages, and were compared with a χ2 test. Kaplan–Meier analysis was utilized to assess freedom from AF between patients with and without adenosine challenge. All statistical analysis was performed using the SPSS software version 22.0 (SPSS, Chicago, IL, USA).
Results
Baseline characteristics
Baseline characteristics are presented in Table 1. A total of 161 patients were prospectively recruited [age 59 ± 9 years, male 76%, hypertension 53%, LA area 29 ± 6 cm2, left ventricular ejection fraction (LVEF) 55 ± 10%] and underwent PVI followed by PW isolation.
. | Entire cohort (n = 161) . | No adenosine challenge (n = 107) . | Adenosine challenge (n = 54) . | P-value* . |
---|---|---|---|---|
Age (years) | 59 ± 9 | 59 ± 7 | 59 ± 11 | 0.96 |
Gender (male) | 123 (76) | 85 (79) | 38 (70) | 0.20 |
AF history | ||||
AF duration (years from diagnosis) | 6 ± 5 | 7 ± 5 | 5 ± 4 | 0.15 |
Duration persistent AF (years) | 2.7 ± 2.5 | 2.3 ± 2.3 | 3.1 ± 2.7 | 0.16 |
Longstanding persistent AF | 23 (15) | 14 (13) | 9 (17) | 0.56 |
Previous cardioversion | 155 (94) | 104 (94) | 51 (94) | 0.85 |
Number of failed anti-arrhythmic medications | 1.6 ± 0.7 | 1.7 ± 0.7 | 1.4 ± 0.7 | 0.03 |
Comorbidities | ||||
Ischaemic heart disease | 16 (10) | 9 (8) | 7 (13) | 0.29 |
Heart failure | 34 (21) | 21 (20) | 13 (24) | 0.52 |
Hypertension | 85 (53) | 58 (54) | 27 (50) | 0.61 |
Echocardiography | ||||
Left atrial size (cm2) | 29 ± 6 | 28 ± 5 | 31 ± 7 | <0.01 |
LVEF (%) | 55 ± 10 | 56 ± 7 | 53 ± 12 | 0.10 |
. | Entire cohort (n = 161) . | No adenosine challenge (n = 107) . | Adenosine challenge (n = 54) . | P-value* . |
---|---|---|---|---|
Age (years) | 59 ± 9 | 59 ± 7 | 59 ± 11 | 0.96 |
Gender (male) | 123 (76) | 85 (79) | 38 (70) | 0.20 |
AF history | ||||
AF duration (years from diagnosis) | 6 ± 5 | 7 ± 5 | 5 ± 4 | 0.15 |
Duration persistent AF (years) | 2.7 ± 2.5 | 2.3 ± 2.3 | 3.1 ± 2.7 | 0.16 |
Longstanding persistent AF | 23 (15) | 14 (13) | 9 (17) | 0.56 |
Previous cardioversion | 155 (94) | 104 (94) | 51 (94) | 0.85 |
Number of failed anti-arrhythmic medications | 1.6 ± 0.7 | 1.7 ± 0.7 | 1.4 ± 0.7 | 0.03 |
Comorbidities | ||||
Ischaemic heart disease | 16 (10) | 9 (8) | 7 (13) | 0.29 |
Heart failure | 34 (21) | 21 (20) | 13 (24) | 0.52 |
Hypertension | 85 (53) | 58 (54) | 27 (50) | 0.61 |
Echocardiography | ||||
Left atrial size (cm2) | 29 ± 6 | 28 ± 5 | 31 ± 7 | <0.01 |
LVEF (%) | 55 ± 10 | 56 ± 7 | 53 ± 12 | 0.10 |
All values represent mean ± standard deviation or number and (percentage).
*Comparison between patients with or without adenosine PW challenge.
. | Entire cohort (n = 161) . | No adenosine challenge (n = 107) . | Adenosine challenge (n = 54) . | P-value* . |
---|---|---|---|---|
Age (years) | 59 ± 9 | 59 ± 7 | 59 ± 11 | 0.96 |
Gender (male) | 123 (76) | 85 (79) | 38 (70) | 0.20 |
AF history | ||||
AF duration (years from diagnosis) | 6 ± 5 | 7 ± 5 | 5 ± 4 | 0.15 |
Duration persistent AF (years) | 2.7 ± 2.5 | 2.3 ± 2.3 | 3.1 ± 2.7 | 0.16 |
Longstanding persistent AF | 23 (15) | 14 (13) | 9 (17) | 0.56 |
Previous cardioversion | 155 (94) | 104 (94) | 51 (94) | 0.85 |
Number of failed anti-arrhythmic medications | 1.6 ± 0.7 | 1.7 ± 0.7 | 1.4 ± 0.7 | 0.03 |
Comorbidities | ||||
Ischaemic heart disease | 16 (10) | 9 (8) | 7 (13) | 0.29 |
Heart failure | 34 (21) | 21 (20) | 13 (24) | 0.52 |
Hypertension | 85 (53) | 58 (54) | 27 (50) | 0.61 |
Echocardiography | ||||
Left atrial size (cm2) | 29 ± 6 | 28 ± 5 | 31 ± 7 | <0.01 |
LVEF (%) | 55 ± 10 | 56 ± 7 | 53 ± 12 | 0.10 |
. | Entire cohort (n = 161) . | No adenosine challenge (n = 107) . | Adenosine challenge (n = 54) . | P-value* . |
---|---|---|---|---|
Age (years) | 59 ± 9 | 59 ± 7 | 59 ± 11 | 0.96 |
Gender (male) | 123 (76) | 85 (79) | 38 (70) | 0.20 |
AF history | ||||
AF duration (years from diagnosis) | 6 ± 5 | 7 ± 5 | 5 ± 4 | 0.15 |
Duration persistent AF (years) | 2.7 ± 2.5 | 2.3 ± 2.3 | 3.1 ± 2.7 | 0.16 |
Longstanding persistent AF | 23 (15) | 14 (13) | 9 (17) | 0.56 |
Previous cardioversion | 155 (94) | 104 (94) | 51 (94) | 0.85 |
Number of failed anti-arrhythmic medications | 1.6 ± 0.7 | 1.7 ± 0.7 | 1.4 ± 0.7 | 0.03 |
Comorbidities | ||||
Ischaemic heart disease | 16 (10) | 9 (8) | 7 (13) | 0.29 |
Heart failure | 34 (21) | 21 (20) | 13 (24) | 0.52 |
Hypertension | 85 (53) | 58 (54) | 27 (50) | 0.61 |
Echocardiography | ||||
Left atrial size (cm2) | 29 ± 6 | 28 ± 5 | 31 ± 7 | <0.01 |
LVEF (%) | 55 ± 10 | 56 ± 7 | 53 ± 12 | 0.10 |
All values represent mean ± standard deviation or number and (percentage).
*Comparison between patients with or without adenosine PW challenge.
The 54 patients with adenosine PW challenge compared to the 107 patients without adenosine PW challenge were well matched aside from a significantly greater left atrial size (31 ± 7 vs. 28 ± 5 cm2, P < 0.01) (Table 1).
Procedural characteristics
Procedural characteristics are presented in Table 2. Atrial fibrillation was present at the induction of anaesthesia in 122 patients (76%) and a further 19 patients (12%) developed AF during the procedure. Pulmonary vein isolation was achieved in all patients, and posterior wall isolation was achieved in 147 patients (91%). Ablation within the boundaries of the posterior box was required in 41% of patients to achieve posterior wall isolation (Supplementary material online, Figure S1).
. | Entire cohort (n = 161) . | No adenosine challenge (n = 107) . | Adenosine challenge (n = 54) . | P-value* . |
---|---|---|---|---|
Procedure duration (min) | 191 ± 49 | 198 ± 56 | 181 ± 36 | 0.06 |
Radiofrequency ablation time (min) | 40 ± 19 | 40 ± 20 | 42 ± 14 | 0.52 |
Fluoroscopy time (min) | 21 ± 11 | 22 ± 12 | 19 ± 8 | 0.11 |
Contact force catheter | 60 (37) | 41 (38) | 19 (35) | 0.70 |
Deflectable sheath | 10 (6) | 5 (5) | 5 (9) | 0.23 |
Mitral isthmus line | 14 (9) | 12 (11) | 2 (4) | 0.12 |
Cavo-tricuspid isthmus | 24 (15) | 16 (15) | 8 (15) | 0.99 |
CFAE | 19 (12) | 16 (15) | 3 (6) | 0.09 |
Restoration of sinus with ablation | 8 (5) | 4 (4) | 4 (7) | 0.31 |
Procedural cardioversion | 128 (80) | 86 (80) | 42 (78) | 0.54 |
Complications | 6 (4) | 3 (3) | 3 (6) | 0.36 |
. | Entire cohort (n = 161) . | No adenosine challenge (n = 107) . | Adenosine challenge (n = 54) . | P-value* . |
---|---|---|---|---|
Procedure duration (min) | 191 ± 49 | 198 ± 56 | 181 ± 36 | 0.06 |
Radiofrequency ablation time (min) | 40 ± 19 | 40 ± 20 | 42 ± 14 | 0.52 |
Fluoroscopy time (min) | 21 ± 11 | 22 ± 12 | 19 ± 8 | 0.11 |
Contact force catheter | 60 (37) | 41 (38) | 19 (35) | 0.70 |
Deflectable sheath | 10 (6) | 5 (5) | 5 (9) | 0.23 |
Mitral isthmus line | 14 (9) | 12 (11) | 2 (4) | 0.12 |
Cavo-tricuspid isthmus | 24 (15) | 16 (15) | 8 (15) | 0.99 |
CFAE | 19 (12) | 16 (15) | 3 (6) | 0.09 |
Restoration of sinus with ablation | 8 (5) | 4 (4) | 4 (7) | 0.31 |
Procedural cardioversion | 128 (80) | 86 (80) | 42 (78) | 0.54 |
Complications | 6 (4) | 3 (3) | 3 (6) | 0.36 |
All values represent mean ± standard deviation or number and (percentage).
*Comparison between patients with or without adenosine PW challenge.
. | Entire cohort (n = 161) . | No adenosine challenge (n = 107) . | Adenosine challenge (n = 54) . | P-value* . |
---|---|---|---|---|
Procedure duration (min) | 191 ± 49 | 198 ± 56 | 181 ± 36 | 0.06 |
Radiofrequency ablation time (min) | 40 ± 19 | 40 ± 20 | 42 ± 14 | 0.52 |
Fluoroscopy time (min) | 21 ± 11 | 22 ± 12 | 19 ± 8 | 0.11 |
Contact force catheter | 60 (37) | 41 (38) | 19 (35) | 0.70 |
Deflectable sheath | 10 (6) | 5 (5) | 5 (9) | 0.23 |
Mitral isthmus line | 14 (9) | 12 (11) | 2 (4) | 0.12 |
Cavo-tricuspid isthmus | 24 (15) | 16 (15) | 8 (15) | 0.99 |
CFAE | 19 (12) | 16 (15) | 3 (6) | 0.09 |
Restoration of sinus with ablation | 8 (5) | 4 (4) | 4 (7) | 0.31 |
Procedural cardioversion | 128 (80) | 86 (80) | 42 (78) | 0.54 |
Complications | 6 (4) | 3 (3) | 3 (6) | 0.36 |
. | Entire cohort (n = 161) . | No adenosine challenge (n = 107) . | Adenosine challenge (n = 54) . | P-value* . |
---|---|---|---|---|
Procedure duration (min) | 191 ± 49 | 198 ± 56 | 181 ± 36 | 0.06 |
Radiofrequency ablation time (min) | 40 ± 19 | 40 ± 20 | 42 ± 14 | 0.52 |
Fluoroscopy time (min) | 21 ± 11 | 22 ± 12 | 19 ± 8 | 0.11 |
Contact force catheter | 60 (37) | 41 (38) | 19 (35) | 0.70 |
Deflectable sheath | 10 (6) | 5 (5) | 5 (9) | 0.23 |
Mitral isthmus line | 14 (9) | 12 (11) | 2 (4) | 0.12 |
Cavo-tricuspid isthmus | 24 (15) | 16 (15) | 8 (15) | 0.99 |
CFAE | 19 (12) | 16 (15) | 3 (6) | 0.09 |
Restoration of sinus with ablation | 8 (5) | 4 (4) | 4 (7) | 0.31 |
Procedural cardioversion | 128 (80) | 86 (80) | 42 (78) | 0.54 |
Complications | 6 (4) | 3 (3) | 3 (6) | 0.36 |
All values represent mean ± standard deviation or number and (percentage).
*Comparison between patients with or without adenosine PW challenge.
Sinus rhythm was restored during PW isolation in 8 (Figure 4) and following cardioversion in 128 patients (80%).
Additional ablation included cavo-tricuspid isthmus ablation (15%), mitral isthmus line (9%), and complex fractionated atrial electrogram ablation (12%), with no difference in patients with vs. without adenosine PW challenge. There was no difference in the use of a deflectable sheath between groups (Agilis™, SJM) (9% in adenosine challenge vs. 3% in no adenosine challenge, P = 0.13), or contact force catheter (35 vs. 38%, P = 0.70).
The average procedure duration was 191 ± 49 min, mean ablation time 40 ± 19 min, and fluoroscopy time 22 ± 11 min for the total population. There was no significant difference in fluoroscopy time, ablation time, or procedure duration in patients who underwent adenosine challenge compared with those who did not (Table 2).
Adenosine group
Adenosine-induced transient posterior wall reconnection occurred in 9 of 54 (17%) patients. The average duration of adenosine-induced PW reconnection in our study was 30 ± 12 s (range 16–45 s). Adenosine-induced pulmonary vein reconnection was present in 11% of patients. In seven of nine cases of PW reconnection, the site of reconnection was within 1 cm of the initial site of isolation and in two cases the site of reconnection was more remote (Supplementary material online, Figure S1).
Follow-up
After a single procedure, freedom from atrial arrhythmia was significantly greater in the adenosine challenge group (65%) compared with no adenosine challenge (45%, P = 0.03) at a mean follow-up of 19 ± 8 months. Similarly in the 147 (91%) patients where post wall isolation was achieved, single procedure success was significantly higher in patients with (65%) vs. without PW adenosine challenge (40%, P < 0.01, Table 3, Figure 5).
. | Entire cohort (n = 161) . | No adenosine challenge (n = 107) . | Adenosine challenge (n = 54) . | P-value* . |
---|---|---|---|---|
Freedom from atrial arrhythmia | 83 (52) | 48 (45) | 35 (65) | 0.03 |
Mechanism of recurrence | ||||
AF | 56 (35) | 41 (38) | 15 (28) | 0.13 |
Atrial tachycardia | 39 (24) | 27 (25) | 12 (22) | 0.41 |
Redo procedure | 24 (15) | 17 (16) | 7 (13) | 0.62 |
Posterior wall reconnection | 12 (50) | 10 (59) | 2 (29) | 0.18 |
Pulmonary vein reconnection | 18 (75) | 13 (77) | 5 (71) | 0.80 |
Multiple procedure freedom from atrial arrhythmia | 116 (72) | 70 (65) | 46 (85) | 0.01 |
Number of anti-arrhythmic medications | 0.7 ± 0.5 | 0.7 ± 0.5 | 0.7 ± 0.5 | 0.93 |
. | Entire cohort (n = 161) . | No adenosine challenge (n = 107) . | Adenosine challenge (n = 54) . | P-value* . |
---|---|---|---|---|
Freedom from atrial arrhythmia | 83 (52) | 48 (45) | 35 (65) | 0.03 |
Mechanism of recurrence | ||||
AF | 56 (35) | 41 (38) | 15 (28) | 0.13 |
Atrial tachycardia | 39 (24) | 27 (25) | 12 (22) | 0.41 |
Redo procedure | 24 (15) | 17 (16) | 7 (13) | 0.62 |
Posterior wall reconnection | 12 (50) | 10 (59) | 2 (29) | 0.18 |
Pulmonary vein reconnection | 18 (75) | 13 (77) | 5 (71) | 0.80 |
Multiple procedure freedom from atrial arrhythmia | 116 (72) | 70 (65) | 46 (85) | 0.01 |
Number of anti-arrhythmic medications | 0.7 ± 0.5 | 0.7 ± 0.5 | 0.7 ± 0.5 | 0.93 |
All values represent mean ± standard deviation or number and (percentage).
*Comparison between patients with or without adenosine PW challenge.
. | Entire cohort (n = 161) . | No adenosine challenge (n = 107) . | Adenosine challenge (n = 54) . | P-value* . |
---|---|---|---|---|
Freedom from atrial arrhythmia | 83 (52) | 48 (45) | 35 (65) | 0.03 |
Mechanism of recurrence | ||||
AF | 56 (35) | 41 (38) | 15 (28) | 0.13 |
Atrial tachycardia | 39 (24) | 27 (25) | 12 (22) | 0.41 |
Redo procedure | 24 (15) | 17 (16) | 7 (13) | 0.62 |
Posterior wall reconnection | 12 (50) | 10 (59) | 2 (29) | 0.18 |
Pulmonary vein reconnection | 18 (75) | 13 (77) | 5 (71) | 0.80 |
Multiple procedure freedom from atrial arrhythmia | 116 (72) | 70 (65) | 46 (85) | 0.01 |
Number of anti-arrhythmic medications | 0.7 ± 0.5 | 0.7 ± 0.5 | 0.7 ± 0.5 | 0.93 |
. | Entire cohort (n = 161) . | No adenosine challenge (n = 107) . | Adenosine challenge (n = 54) . | P-value* . |
---|---|---|---|---|
Freedom from atrial arrhythmia | 83 (52) | 48 (45) | 35 (65) | 0.03 |
Mechanism of recurrence | ||||
AF | 56 (35) | 41 (38) | 15 (28) | 0.13 |
Atrial tachycardia | 39 (24) | 27 (25) | 12 (22) | 0.41 |
Redo procedure | 24 (15) | 17 (16) | 7 (13) | 0.62 |
Posterior wall reconnection | 12 (50) | 10 (59) | 2 (29) | 0.18 |
Pulmonary vein reconnection | 18 (75) | 13 (77) | 5 (71) | 0.80 |
Multiple procedure freedom from atrial arrhythmia | 116 (72) | 70 (65) | 46 (85) | 0.01 |
Number of anti-arrhythmic medications | 0.7 ± 0.5 | 0.7 ± 0.5 | 0.7 ± 0.5 | 0.93 |
All values represent mean ± standard deviation or number and (percentage).
*Comparison between patients with or without adenosine PW challenge.
Atrial arrhythmias recurred in 80 patients [AF in 56 (35%) and atrial tachycardia in 39 (24%)] including both AT and AF in 15. After a mean of 1.2 ± 0.4 procedures, freedom from atrial arrhythmia remained significantly greater in the adenosine challenge group (85%) compared with no adenosine challenge (65%, P = 0.01). Redo procedures were performed in 24 patients with reconnection of the pulmonary veins present in 18 (75%), and reconnection of the posterior LA wall present in 12 (50%). Only one patient underwent a second redo procedure; in this procedure, the PVs and PW had remained isolated following re-isolation at the time of the first redo procedure, and the patient underwent substrate-guided ablation.
There was no difference in freedom from atrial arrhythmia between patients with vs. without adenosine-induced PW reconnection (67 vs. 64%, P = 0.87).
There was no difference in freedom from AF between patients with (n = 60, freedom from AF 48%) vs. without contact-force sensing catheters (n = 101, freedom from AF 54%, P = 0.23).
Complications
Complications occurred in 6 (3.7%) patients and included one cardiac tamponade requiring pericardiocentesis, a small oesophageal tear related to trans-oesophageal echocardiography which was endoscopically clipped, pneumonia, an acute coronary syndrome requiring intra-procedural coronary stenting, a major groin haematoma and femoral arterio-venous fistula requiring surgical intervention. There were no deaths related to PW isolation in the present cohort.
Discussion
Patients with persistent AF have a significant increase in recurrent AF following pulmonary vein isolation compared with patients with paroxysmal AF. In the present study, we report a significant improvement in the outcomes of PVI followed by LA posterior wall isolation in patients with persistent AF who underwent adenosine challenge of the posterior LA with additional ablation for transient reconnection. The major findings were:
Transient reconnection of the isolated posterior left atrium with adenosine was seen in 17% with additional ablation delivered to consolidate electrical isolation;
Improved single procedure success in patients with adenosine PW challenge (65 vs. 40% in those who did not, P < 0.01) at a mean follow-up of 19 ± 8 months;
Improved multiprocedure success in patients with adenosine PW challenge (85 vs. 65% in those who did not, P = 0.01).
Strategies for catheter ablation of persistent atrial fibrillation
Alternate strategies for ablation of persistent AF beyond pulmonary vein antral isolation (PVAI) and posterior wall isolation include targeting CFAEs, linear ablation, focal impulse and rotor modulation (FIRM) guided ablation, ablation of non-PV triggers, and ganglionic plexi. However, the multicentre international randomized study (STAR AF II) demonstrated no improvement in ablation outcomes for persistent AF with the addition of complex fractionated atrial electrogram (CFAE) or linear ablation compared to PVAI alone.1 Importantly the linear ablation arm of this trial did not incorporate isolation of the entire posterior wall. Several smaller studies have evaluated alternative ablation approaches in persistent AF. Mohanty et al. reported a significant improvement in freedom from AF in persistent AF patients undergoing PVI plus PW isolation and non-PV trigger ablation(76%) compared with FIRM guided(14%) or FIRM plus PVI(52%) at a follow-up of 12 ± 7 months.17 The improved outcome compared with the present study may be explained by the longer duration of follow-up (19 ± 8 months) in the present report and the lack of routine use of isoproterenol for non-PV triggers as commonly identified in persistent AF. Elayi and colleagues demonstrated an improvement in outcomes with PVI and adenosine and isoproterenol challenge compared with PVI alone, with non-PV triggers detected in 61%.18 Katritsis et al. demonstrated an improved outcome for PVI plus GP ablation vs. either strategy alone.19 Mindful of the lessons of STAR AF II further multicentre prospective randomized studies are required before alternate ablation strategies are broadly accepted outside of high-volume academic AF ablation centres.
Previous studies incorporating posterior wall isolation
Experimental studies suggest the posterior LA may play an important role in the initiation and maintenance of AF.7,20–23 Several studies have reported ablation strategies which incorporate posterior left atrial isolation in addition to segmental PV isolation or as part of a ‘single ring’ lesion set with or without the electrophysiological endpoint of electrical isolation.4,10 The ablation strategy in the present study differs from that in earlier reports as antral pulmonary vein isolation was completed first before linear lesions connecting the superior and inferior aspects of the antral rings were completed with confirmation of bidirectional block across all lesion sets.
Bai et al. reported the benefits of more extensive catheter ablation beyond PVAI that included PW electrical isolation with ablation extended inferiorly to the CS and to the left septum.9 Assessment for electrical isolation was performed irrespective of AF recurrence at 3 and 6 months as well as for a matched PVAI only group and additional ablation applied to consolidate isolation. The extensive ablation group demonstrated a significant improvement in freedom from AF (off anti-arrhythmic medication) at 1 year of 65% compared to 20% with PVAI alone. In contrast to the present report where PW isolation was achieved with linear ablation across the roof and inferior wall, Bai et al. performed an intensive debulking strategy extended to the left septum and inferior LA. Reassuringly, with routine oesophageal temperature monitoring, there were no cases of atrio-oesophageal fistula.
A systematic review that pooled 3 small studies of PVI plus posterior wall isolation (10–27 patients) reported 42–50% single procedure and 60% multiple procedure freedom from AF.23 Tamborero et al. performed a randomized study of circumferential PV ablation (CPVA) and posterior wall isolation in 120 patients with predominantly paroxysmal AF (60%) and 9.8 ± 4 months follow-up. Important limitations include a group with predominantly paroxysmal AF, and the absence of a circular mapping catheter to confirm pulmonary vein or posterior wall isolation but rather an abatement of local electrograms or demonstrable exit block.4 Sanders et al. reported 63% freedom from AF after multiple procedures in 27 persistent AF patients who underwent PVI plus LA posterior wall isolation. During follow-up, eight patients required ablation beyond the ‘box’ lesion set due to recurrent arrhythmia in the setting of enduring isolation. Cutler et al. demonstrated that patients with low posterior wall voltage demonstrate significant improvement in freedom from AF if LA posterior wall isolation is added to pulmonary vein isolation.24 The present study includes 161 patients and demonstrated higher procedural success that may be explained by a larger patient cohort, advances in catheter and imaging technologies, and potentially the use of adenosine testing.
Prior studies describing adenosine restoring dormant conduction
The mechanism responsible for transient reconnection of the pulmonary veins was elegantly described by Datino et al.12 Adenosine resulted in hyperpolarization of the resting membrane potential to a greater degree in the PVs with dormant conduction enabling re-excitability. Several non-randomized studies have reported on the utility of adenosine to identify dormant PV conduction in patients undergoing AF ablation translating to a greater freedom from AF,13 and recent randomized controlled trials have reported conflicting results regarding the impact of adenosine challenge for dormant PV conduction on clinical outcomes.14,15 Macle et al. identified dormant PV conduction in 53% of 534 patients with paroxysmal AF, and randomized these patients to further ablation or no further ablation.15 Patients with ablation of adenosine-induced reconnection had improved freedom from AF (69%) compared with patients without ablation of adenosine-induced reconnection (42%), or when compared with patients without dormant conduction (56%).15 In contrast, a randomized controlled trial in patients with paroxysmal, persistent, or longstanding AF performed by Kobori et al. identified no difference in freedom from AF between a strategy of ATP-guided PVI vs. standard PVI.14
To the best of our knowledge, reconnection of the posterior left atrial wall in response to adenosine has yet to be described. In the present study, adenosine induced transient reconnection of the posterior wall in 17% and of the pulmonary veins in 11%. Previous studies have identified transient PV reconnection in 35–59% of patients.13 The lower rate of acute adenosine-induced PV reconnection in our study may be due to the ‘belt and braces’ approach where PW isolation may add to the posterior aspects of PV isolation, and the use of steerable sheathes and contact force sensing catheters.
In 24 patients who underwent redo procedures, posterior wall reconnection was identified in 50%, which is markedly lower than earlier reports of posterior LA reconnection in 67–88% undergoing repeat ablation procedures for recurrent atrial arrhythmias,4,10 and may be explained by the larger cohort with associated procedural learning curve, advances in imaging, catheter technology, and potentially by the use of adenosine challenge of PW dormant conduction.
There are several possible explanations for the improved outcomes in patients with vs. without adenosine PW challenge. Identification of adenosine-induced dormant conduction and ablation at these sites may facilitate enduring PW isolation to improve long-term outcome, supported by the finding of significantly greater enduring PW isolation at redo procedure in patients with (71%) vs. without adenosine PW challenge (41%). Secondly, the additional ablation of adenosine-induced PW reconnection may have incorporated ablation of substrate contributing to AF such as ganglionated plexi, CFAE, and provided an additional posterior barrier to PV reconnection.
Study limitations
The comparison of patients with vs. without adenosine PW challenge generates issues of comparing non-contemporaneous cohorts such as a procedural learning curve effect that may, in part, have contributed to the findings in the present study. However, the findings support the need for a larger randomized controlled trial to determine the role of PW isolation beyond PVAI (with or without adenosine challenge) for catheter ablation of persistent AF. We did not utilize isoproterenol in combination with adenosine to assess for PV or PW reconnection, which may have improved the detection of dormant conduction and increased the likelihood of identifying non-pulmonary vein triggers for AF. Antiarrhythmic medications were not routinely stopped following catheter ablation and as such it is not possible to determine freedom from AF off medication in the present study. Unfortunately contact-force catheters or force-time integral was not used routinely as these technologies only became available later in the study recruitment.
Conclusion
Posterior left atrial wall isolation in addition to PVI is a readily achievable strategy for catheter ablation in patients with persistent AF. Routine adenosine challenge for dormant posterior wall conduction was associated with improved outcomes to catheter ablation in persistent AF.
Supplementary material
Supplementary material is available at Europace online.
Funding
A.J.A.M. and S.P. are supported by co-funded NHMRC/NHF Postgraduate Scholarships and BakerIDI Bright Sparks scholarship. M.C.G.W. is supported by an Australian National Heart Foundation (NHF) Postgraduate Scholarship. T.E.W. and B.P. are supported by NHMRC Postgraduate Research Scholarships. G.L. is supported by an Australian National Health and Medical Research Council (NHMRC) Postdoctoral fellowship. P.M.K. and J.M.K. are supported by practitioner fellowships from the NHMRC. This research is supported in part by the Victorian Government's Operational Infrastructure Funding. All authors have reported no financial relationships to disclose.
Conflict of interest: None declared.