Ablation Strategy for Paroxysmal Atrial Fibrillation
Ablation Strategy for Paroxysmal Atrial Fibrillation
We recruited 234 patients with highly symptomatic paroxysmal atrial fibrillation refractory to medical management to undergo circumferential PVI randomized to a minimal or maximal ablation strategy between January 2010 and August 2013. The study protocol was approved by the Human Research Ethics Committee at each of the participating hospitals and associated research institutions in Australia, New Zealand, and the UK (Clinical trial registration: ACTRN12610000863033).
Paroxysmal AF was defined according to consensus guidelines. Exclusion criteria included non-paroxysmal forms of AF, previous PVI, age <18, and incapacity to provide informed consent. Patients with a long left common PV (>15 mm from common orifice to bifurcation) were excluded due to an inappropriateness of branch isolation if randomized to maximal ablation group. Baseline characteristics and failed anti-arrhythmic drugs were recorded. A pre-procedural transthoracic echocardiogram was routinely performed.
This was a prospective single blind randomized controlled trial. Patients were block randomized (block size, n = 8) using computer random allocation 1 : 1 to a minimal or maximal ablation strategy, with patients blinded to group allocation (electrophysiologists were necessarily aware of group allocation). Assessment of 7-day Holter monitoring for recurrent AF was performed blinded to treatment allocation.
Catheter ablation involved antral circumferential PVI as described previously. All anti-arrhythmic medications except amiodarone were stopped five half-lives before the procedure (amiodarone was ceased 2 weeks before the procedure), and peri-procedural anti-coagulation strategy was at the discretion of the treating electrophysiologist.
The procedures were performed either under general anaesthetic or under conscious sedation as determined by the operator. All patients underwent transoesophageal echocardiography to rule out intra-cardiac 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 (SL1, St. Jude Medical, St. Paul, MN, USA) were introduced into the left atrium with trans-septal puncture performed with a BRK-1 needle (St. Jude Medical) under fluoroscopy and TEE guidance at the operator's discretion. A Lasso circular mapping catheter (Biosense Webster, Diamond Bar, CA, USA) or a Reflexion spiral catheter (St. Jude Medical) was introduced through the SL1 sheath into the left atrium for electrical mapping of the PVs. An irrigated ablation catheter (4 mm, unidirectional or bidirectional, NaviStar® or EZ Steer® Thermocool®, or Thermocool SmartTouch® (target contact-force >10 g), Biosense Webster or Safire™ BLU™, St. Jude Medical) was introduced through the SL1 sheath into the left atrium for ablation (maximum power 30–35 W reduced to 25 W on the posterior wall). Upon completion of the trans-septal puncture, patients received intravenous heparin to maintain an activated clotting time of >350 s.
Left atrial geometry was created using a three-dimensional electroanatomic mapping system (CARTO-CARTO 3, Biosense-Webster or NavX, St. Jude Medical) and fused with pre-procedural CT or MRI. Pre-procedural cardiac anatomy from CT or MRI was used to determine the dimensions of intervenous and left-PV-left atrial appendage ridges, as described previously. Selection of mapping system and irrigated ablation catheters was at the discretion of the operator.
Catheter ablation was delivered at the PV antrum proximal to the PV–LA junction at 30 W reduced to 25 W on the posterior wall and IVR until electrical isolation was achieved. Pulmonary vein isolation (defined by PV entrance and exit block) was confirmed 30 min after initial isolation including two challenges with intravenous adenosine 18 mg to assess for acute reconnection. If transient or persistent reconnection was present further mapping and ablation was applied to re-establish PV isolation and IV adenosine repeated until no reconnection was evident. The point of electrical isolation for each PV was recorded, as were sites of acute reconnection. Procedural duration, ablation times, radiation dose and fluoroscopy times were recorded. Patients remained in hospital for 48 h post-procedure with resumption or continuation of anti-coagulation from 6 h post-procedure.
Minimal Ablation (En Bloc Electrical Isolation of PVs as a Pair). This strategy involves wide encirclement of the PVs in ipsilateral pairs with the endpoint of electrical isolation of all 4 PVs (see Figure 1). Ablation on the IVR was permissible only after the encircling ablation is complete and sequential repositioning of the circular mapping catheter in each vein confirms the site of breakthrough at the IVR (Figure 2).
(Enlarge Image)
Figure 1.
Comparison of minimal and maximal ablation strategy on postero-anterior and internal view of the pulmonary veins. Red dots represent ablation points, blue dots represent isolation points. LSPV, left superior pulmonary vein; LIPV, left inferior pulmonary vein; RSPV, right superior pulmonary vein; RIPV, right inferior pulmonary vein.
(Enlarge Image)
Figure 2.
Representative figure of a minimal patient requiring ablation on the intervenous ridge. Despite a complete antral circumferential ring, the right superior pulmonary vein remains connected (PV 1–2 → PV 19–20) with earliest activation at PV11–12 (adjacent to the intervenous ridge); the ablator signal is earlier still (ABLd) and isolation was achieved at this site.
Maximal Ablation (Electrical Isolation of Individual PVs). This strategy involves antral electrical isolation of the superior vein with linear ablation across the IVR at 25 W until electrical isolation is achieved before ablation is deployed to encircle the inferior vein. This approach ensured electrical isolation of individual veins from each other.
After an initial 3-month blanking period, arrhythmia recurrence was defined as documented atrial arrhythmia (AF or atrial tachycardia) lasting >30 s. Post-procedure patients were followed up in clinic at 1, 3, 6, and 12 months with ongoing review 6 monthly. Patients underwent a 7-day Holter monitor at 6 monthly intervals, with event monitoring performed for patients with recurrent symptoms in the intervening periods. Repeat cardiac computed tomography scan was performed routinely in the first 40 patients at 3 months post-ablation for the presence of PV stenosis. Patients undergoing redo procedures routinely had pulmonary venography for assessment of PV stenosis.
All statistical analysis was performed using SPSS software version 21.0 (SPSS, Chicago, IL, USA) as an intention to treat analysis. A power analysis was performed based on a 20% improvement (60–80%) in 12-month procedural success as clinically relevant, such that a sample of size of 200 patients (100 per arm without drop-out) would be needed using a two-sided P-value of 0.05, and power of 0.80. Continuous variables are expressed as a 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 χ test. Impact of a minimal vs. maximal ablation strategy on freedom from AF was assessed using Kaplan–Meier analysis after single procedure off anti-arrhythmic medications. Multiple procedure freedom from AF at completion of the trial (incorporating patients with freedom from AF after redo procedures) was assessed at the end of the trial as proportions compared with χ analysis. A two-sided P–value of <0.05 was considered statistically significant.
Methods
Study Population
We recruited 234 patients with highly symptomatic paroxysmal atrial fibrillation refractory to medical management to undergo circumferential PVI randomized to a minimal or maximal ablation strategy between January 2010 and August 2013. The study protocol was approved by the Human Research Ethics Committee at each of the participating hospitals and associated research institutions in Australia, New Zealand, and the UK (Clinical trial registration: ACTRN12610000863033).
Paroxysmal AF was defined according to consensus guidelines. Exclusion criteria included non-paroxysmal forms of AF, previous PVI, age <18, and incapacity to provide informed consent. Patients with a long left common PV (>15 mm from common orifice to bifurcation) were excluded due to an inappropriateness of branch isolation if randomized to maximal ablation group. Baseline characteristics and failed anti-arrhythmic drugs were recorded. A pre-procedural transthoracic echocardiogram was routinely performed.
Study Design
This was a prospective single blind randomized controlled trial. Patients were block randomized (block size, n = 8) using computer random allocation 1 : 1 to a minimal or maximal ablation strategy, with patients blinded to group allocation (electrophysiologists were necessarily aware of group allocation). Assessment of 7-day Holter monitoring for recurrent AF was performed blinded to treatment allocation.
Catheter Ablation
Catheter ablation involved antral circumferential PVI as described previously. All anti-arrhythmic medications except amiodarone were stopped five half-lives before the procedure (amiodarone was ceased 2 weeks before the procedure), and peri-procedural anti-coagulation strategy was at the discretion of the treating electrophysiologist.
The procedures were performed either under general anaesthetic or under conscious sedation as determined by the operator. All patients underwent transoesophageal echocardiography to rule out intra-cardiac 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 (SL1, St. Jude Medical, St. Paul, MN, USA) were introduced into the left atrium with trans-septal puncture performed with a BRK-1 needle (St. Jude Medical) under fluoroscopy and TEE guidance at the operator's discretion. A Lasso circular mapping catheter (Biosense Webster, Diamond Bar, CA, USA) or a Reflexion spiral catheter (St. Jude Medical) was introduced through the SL1 sheath into the left atrium for electrical mapping of the PVs. An irrigated ablation catheter (4 mm, unidirectional or bidirectional, NaviStar® or EZ Steer® Thermocool®, or Thermocool SmartTouch® (target contact-force >10 g), Biosense Webster or Safire™ BLU™, St. Jude Medical) was introduced through the SL1 sheath into the left atrium for ablation (maximum power 30–35 W reduced to 25 W on the posterior wall). Upon completion of the trans-septal puncture, patients received intravenous heparin to maintain an activated clotting time of >350 s.
Left atrial geometry was created using a three-dimensional electroanatomic mapping system (CARTO-CARTO 3, Biosense-Webster or NavX, St. Jude Medical) and fused with pre-procedural CT or MRI. Pre-procedural cardiac anatomy from CT or MRI was used to determine the dimensions of intervenous and left-PV-left atrial appendage ridges, as described previously. Selection of mapping system and irrigated ablation catheters was at the discretion of the operator.
Catheter ablation was delivered at the PV antrum proximal to the PV–LA junction at 30 W reduced to 25 W on the posterior wall and IVR until electrical isolation was achieved. Pulmonary vein isolation (defined by PV entrance and exit block) was confirmed 30 min after initial isolation including two challenges with intravenous adenosine 18 mg to assess for acute reconnection. If transient or persistent reconnection was present further mapping and ablation was applied to re-establish PV isolation and IV adenosine repeated until no reconnection was evident. The point of electrical isolation for each PV was recorded, as were sites of acute reconnection. Procedural duration, ablation times, radiation dose and fluoroscopy times were recorded. Patients remained in hospital for 48 h post-procedure with resumption or continuation of anti-coagulation from 6 h post-procedure.
Maximal vs. Minimal Ablation Strategy
Minimal Ablation (En Bloc Electrical Isolation of PVs as a Pair). This strategy involves wide encirclement of the PVs in ipsilateral pairs with the endpoint of electrical isolation of all 4 PVs (see Figure 1). Ablation on the IVR was permissible only after the encircling ablation is complete and sequential repositioning of the circular mapping catheter in each vein confirms the site of breakthrough at the IVR (Figure 2).
(Enlarge Image)
Figure 1.
Comparison of minimal and maximal ablation strategy on postero-anterior and internal view of the pulmonary veins. Red dots represent ablation points, blue dots represent isolation points. LSPV, left superior pulmonary vein; LIPV, left inferior pulmonary vein; RSPV, right superior pulmonary vein; RIPV, right inferior pulmonary vein.
(Enlarge Image)
Figure 2.
Representative figure of a minimal patient requiring ablation on the intervenous ridge. Despite a complete antral circumferential ring, the right superior pulmonary vein remains connected (PV 1–2 → PV 19–20) with earliest activation at PV11–12 (adjacent to the intervenous ridge); the ablator signal is earlier still (ABLd) and isolation was achieved at this site.
Maximal Ablation (Electrical Isolation of Individual PVs). This strategy involves antral electrical isolation of the superior vein with linear ablation across the IVR at 25 W until electrical isolation is achieved before ablation is deployed to encircle the inferior vein. This approach ensured electrical isolation of individual veins from each other.
Follow-up
After an initial 3-month blanking period, arrhythmia recurrence was defined as documented atrial arrhythmia (AF or atrial tachycardia) lasting >30 s. Post-procedure patients were followed up in clinic at 1, 3, 6, and 12 months with ongoing review 6 monthly. Patients underwent a 7-day Holter monitor at 6 monthly intervals, with event monitoring performed for patients with recurrent symptoms in the intervening periods. Repeat cardiac computed tomography scan was performed routinely in the first 40 patients at 3 months post-ablation for the presence of PV stenosis. Patients undergoing redo procedures routinely had pulmonary venography for assessment of PV stenosis.
Statistics
All statistical analysis was performed using SPSS software version 21.0 (SPSS, Chicago, IL, USA) as an intention to treat analysis. A power analysis was performed based on a 20% improvement (60–80%) in 12-month procedural success as clinically relevant, such that a sample of size of 200 patients (100 per arm without drop-out) would be needed using a two-sided P-value of 0.05, and power of 0.80. Continuous variables are expressed as a 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 χ test. Impact of a minimal vs. maximal ablation strategy on freedom from AF was assessed using Kaplan–Meier analysis after single procedure off anti-arrhythmic medications. Multiple procedure freedom from AF at completion of the trial (incorporating patients with freedom from AF after redo procedures) was assessed at the end of the trial as proportions compared with χ analysis. A two-sided P–value of <0.05 was considered statistically significant.
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