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Safety of pulmonary vein isolation and left atrial complex fractionated atrial electrograms ablation for atrial fibrillation with phased radiofrequency energy and multi-electrode catheters

Anton A.W. Mulder, Jippe C. Balt, Maurits C.E.F. Wijffels, Eric F.D. Wever, Lucas V.A. Boersma
DOI: http://dx.doi.org/10.1093/europace/eus086 1433-1440 First published online: 11 April 2012

Abstract

Aims Recently, a multi-electrode catheter system using phased radiofrequency (RF) energy was developed specifically for atrial fibrillation (AF) ablation: the pulmonary vein ablation catheter (PVAC), the multi-array septal catheter (MASC), and the multi-array ablation catheter (MAAC). Initial results of small trials have been promising: shorter procedure times and low adverse event rates. In a large single-centre registry, we evaluated the adverse events associated with multi-electrode ablation catheter procedures with PVAC alone, or combined with MASC and MAAC.

Methods and results In all, 634 consecutive patients with AF had 663 procedures with multi-electrode ablation catheters, 502 patients with the PVAC alone, 128 patients with PVAC/MASC/MAAC, 29 redo procedures with the PVAC or PVAC/MASC/MAAC, and 4 patients had a complicated transseptal puncture. Major and minor adverse events during 6 month follow-up were registered. In 15 cases (2.3%), major adverse events were seen within the first month after the procedure. These included complicated transseptal puncture (4), stroke (2), transient ischaemic attack (5), acute coronary syndrome (2), femoral pseudoaneurysm (1), and arteriovenous fistulae (1). Minor adverse events were seen in 10.7% at 6 months, mostly due to femoral haematoma (3.9%), and non-significant PV stenosis (5.2%). There was no difference in the occurrence of major adverse events between PVAC alone, or PVAC/MASC/MAAC ablation.

Conclusion Ablation with phased RF and multi-electrode catheters is accompanied by a major adverse event rate of 2.3% within 1 month and a minor event rate of 10.7% at 6 months.

  • Arrhythmia
  • Atrial fibrillation
  • Catheter ablation
  • Pulmonary vein isolation
  • Adverse events
  • Safety

Introduction

The incidence of atrial fibrillation (AF) and indication for pulmonary vein isolation (PVI) continues to rise.13 Pulmonary vein isolation is an established therapy for symptomatic patients with AF in whom anti-arrhythmic drugs (AADs) therapy has failed.48 Conventional point-by-point catheter ablation procedures require high operator skill and are often lengthy.4 Moreover, extensive radiofrequency (RF) injury can lead to adverse events such as atrio-oesophageal fistula, PV-stenosis, phrenic nerve palsy, and gastroparesis.1 In a recently updated worldwide survey, major adverse event rate was 4.5%, no minor adverse events were mentioned.9

Recently, a novel technique using anatomically dedicated multi-electrode catheters with duty-cycled phased RF energy was developed. The decapolar circular pulmonary vein ablation catheter (PVAC), multi-array septal catheter (MASC), and multi-array ablation catheter (MAAC) were developed for PVI and additional left atrial (LA) RF-ablation in patients with persistent AF.10 Initial results have been promising with low adverse event rates, shorter procedure time and similar success rates compared with other ablation systems in the literature.10,11 However, studies published so far have all included a limited number of patients and mainly focused on efficacy. The purpose of the present study was to determine the safety of the PVAC and PVAC/MASC/MAAC procedures in a much larger cohort of patients.

Methods

Patients

Consecutive patients with symptomatic paroxysmal AF or [longstanding (>1 year)] persistent AF resistant to one or more AADs, referred to our centre for catheter ablation of AF, were included from July 2006 to August 2010. Patients with paroxysmal or persistent AF were treated with PVAC and patients with longstanding persistent AF were treated with PVAC in combination with MASC and MAAC. All patients underwent pre-procedural screening with echocardiography and cardiac magnetic resonance imaging (MRI) to evaluate cardiac structure and PV anatomy.

Procedure

A detailed description of the catheters and ablation procedure has been given in a previous report by Scharf et al.10 and Boersma et al.11 In patients treated with oral anti-coagulants, the international normalized ratio (INR) on the day of the procedure was managed to be <3.0. A trans-oesophageal echocardiogram to exclude LA thrombus was performed within 1 week before the procedure in patients that only used aspirin. During the procedure, a bolus of heparin of 5.000–10.000 IU was administered intravenously (IV), after transseptal puncture, followed by another 5.000 IU of heparin if LA ablation lasted longer than 60 min. Activated clotting time (ACT) measurements were not performed on a routine basis. A standard deflectable four-polar catheter was introduced in the coronary sinus (CS) for pacing options. Transseptal access was obtained with standard puncture with a Brockenbrough needle. In the first 25 cases a braided non-steerable sheath (Convoy, BScI) with 9.5F Inner lumen diameter was used, while in later cases a braided steerable sheath (Channel, Bard) was used. Briefly, the PVAC catheter (10-polar, electrodes of 3 mm length and spacing, diameter 25 mm, 9.5F) was used for PVI, the MASC (three arms with each four electrodes of 2 mm length and spacing) for septal complex fractionated atrial electrograms (CFAE) ablation, and MAAC catheter (four arms with each two electrodes of 2 mm length and spacing) for CFAE ablation at the LA roof, free wall, mitral isthmus, mitral annulus, and posterior wall. In the rare case when phrenic nerve capture was observed (movement of the right hemi-diaphragm), no ablation was performed at this site, and the catheter was repositioned. After ablation of the PVs and CFAE, sinus rhythm was restored by direct current cardioversion (DCCV) if necessary. The endpoint of PVAC procedures consisted of confirmed absence of local potentials with PVAC and/or Lasso mapping inside the vein, including pacing from the CS and/or the PV to distinguish local potentials from far-field potentials as necessary. The default filter settings of the recording system for multi-electrode ablation were between 100 and 500 kHz to filter far-field activity. The endpoint of MASC and MAAC procedures was achieved when no CFAE was observed anymore at the targeted LA sites. Complex fractionated atrial electrograms were defined visually as local continuous deflections with multiple components crossing the baseline. Cavotricuspid isthmus ablation was never performed in the same procedure.

The same AADs (classes I and III) as before the ablation were continued during the first 3 months after the procedure, with exception of amiodarone which was usually discontinued immediately after the procedure. If patients remained free of AF, their AADs were discontinued.

Oral anti-coagulation (OAC) was (re-)started directly after the procedure, with bridging therapy by weight-based low-molecular-weight heparin (LMWH) until INR was > 2.0. All patients remained on OAC in the first 3 months after ablation, with a target INR between 2 and 3 arranged by the Dutch Thrombosis Service. If patients had an AF recurrence OAC was continued. Based on the CHADS2 score, continuation of aspirin or OAC was recommended at the discretion of the referring cardiologist after the first 3 months up to 1 year.

All patients were on Coumadin therapy with a target INR, arranged by the Dutch Thrombosis Service to be between 2 and 2.5 at the day of the procedure. During the procedure, a bolus of heparin of 10.000 IU was administered IV, after transseptal puncture, followed by another 5.000 IU of heparin if LA ablation lasted longer than 75 min. Oral anti-coagulation was restarted directly after the procedure, and LMWH was given only as bridging therapy until the INR was > 2.5.

Follow-up

Adverse events were scored and categorized according to their occurrence during the procedure, within the first 6 months after the procedure. Data were collected from patients’ charts, and direct communication during consecutive outpatient clinic follow-up. The primary study item was the occurrence of major adverse events that occurred within the first month after an index or repeat ablation procedure. Among the major adverse events scored (Table 1), special attention was given to those commonly attributed to AF ablation. These included vascular access adverse events such as femoral pseudoaneurysm, arteriovenous fistulae, and major bleed requiring blood transfusion and other adverse events such as periprocedural death, complicated transseptal access, tamponade, sepsis, abscesses, endocarditis, pneumothorax, haemothorax, (permanent) diaphragmatic paralysis, atrio-oesophageal fistula or oesophageal injury, valve damage, aortic dissection, haemorrhagic or ischaemic stroke (neurological deficit of cerebrovascular cause that persists beyond 24 h), transient ischaemic attack (TIA) (neurological deficit of cerebrovascular cause that resolves completely within 24 h), acute coronary syndrome (ACS), significant PV stenosis > 70%, and PV stenosis requiring intervention. Death from any cause either during the procedure or the 6 month follow-up was included in the evaluation.

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Table 1

Major adverse events after ablation with a pulmonary vein ablation catheter or a pulmonary vein ablation catheter/multi-array septal catheter/multi-array ablation catheter ≤1 months

Adverse event typeFirst procedure PVAC502First procedure PVAC + MASC/MAAC128Second procedure all29Total659
Major adverse eventsNo. of patientsRate (%)No. of patientsRate (%)No. of patientsRate (%)No. of patientsRate (%)
Vascular access
 Femoral pseudoaneurysm10.2000010.2
 Arteriovenous fistulae10.2000010.2
Other
 Ischaemic stroke10.2000010.2
 Haemorrhagic stroke10.2000010.2
 Transient ischaemic attack51.0000050.8
 Acute coronary syndrome10.210.80020.3
Total102.010.800111.7
  • MAAC, multi-array ablation catheter; MASC, multi-array septal catheter; PVAC, pulmonary vein ablation catheter.

The scoring system used was similar to that described in the worldwide survey to facilitate a comparison with other ablation systems.5 In our study, acute coronary syndrome and minor adverse events were added to the previously reported scoring system as procedural adverse events. In accordance with the recent update of the worldwide survey update, PV stenosis > 70% or requiring treatment was considered a major adverse event.9 The secondary study item was the occurrence of minor adverse events that occurred ≤ 6 month after an index or repeat ablation procedure. Minor adverse events were defined as minor vascular access adverse events such as small groin bleeding (there was a need for compression bandage during hospitalization) and/or groin haematoma not needing transfusion, PV stenosis 50–69%, transient ST-elevation without myocardial infarction (Table 2), and pericarditis. During long-term follow-up, at least 6 months post-procedure, in a selection of patients a repeated cardiac MRI or PV-angiography during a second procedure were available for evaluation of PV stenosis, which was defined as moderate (50–69%) or significant stenosis (≥70%).12

View this table:
Table 2

Minor adverse events after ablation with a pulmonary vein ablation catheter or a pulmonary vein ablation catheter/multi-array septal catheter/multi-array ablation catheter up to 6 months

Adverse event typeFirst procedure PVAC502First procedure PVAC + MASC/MAAC128Second procedure all29Total659
Minor adverse eventsNo. of patientsRate (%)No. of patientsRate (%)No. of patientsRate (%)No. of patientsRate (%)
Vascular access
 Groin bleeding71.40013.481.2
 Groin haematoma224.321.626.9263.9
Other
 PV stenosis >50%a7a7.0a11.9a0a0a8a5.2a
 Pericarditis0010.70010.2
 Transient ST-elevation10.2000010.2
Total3712.944.2310.34410.7
  • a153 patients underwent some form of post-procedure imaging to evaluate the presence of PV stenosis (100 PVAC, 53 PVAC + MASC/MAAC).

  • MAAC, multi-array ablation catheter; MASC, multi-array septal catheter; PV, pulmonary vein; PVAC, pulmonary vein ablation catheter.

Statistical analysis

Patients where the procedure was aborted for any reason, without actually having undergone phased RF with multi-electrode catheter ablation were excluded from the analysis. Categorical variables are presented by number (percentage) and compared between groups by the χ2 test. Numerical variables are expressed as mean, standard deviation (SD), and range. Data analysis was performed using SPSS 17.0.

Results

Patient description

A total of 634 patients (75% male), with a mean age of 59 ± 9 years (range 26–81 years), treated with the multi-electrode catheter ablation at our hospital, were included in this study. In all, 502 patients were treated with the PVAC, 128 patients with PVAC/MASC/MAAC, while the procedure was aborted in 4 patients due to complicated transseptal puncture. On pre-procedure MRI, the majority of patients had four separate PVs, except for 79 (13%) with a common left PV, and 134 (21%) with a separate right middle PV. Most patients had no important valvular disease, preserved cardiac structure and function, with a LA diameter that did not exceed 58 mm (range 29–58 mm).

Procedural data

The average procedural time, in 502 PVAC index procedures, was 86 ± 27 min (range 36–180) from the first femoral puncture to removal of all catheters. Figure 1 shows the average procedural time of consecutive groups of 10 patients and the decrease in procedural times. The average fluoroscopy time was 20 ± 9 min (range 6–55). The average number of applications was 24 ± 7 (range 9–59). The average procedural time, in 10 redo procedures with the PVAC (with a complete follow-up of 6 months), was 68 ± 23 min (range 45–120). The average fluoroscopy time was 13 ± 5 min (range 9–24). The average number of applications was 21 ± 7 (range 7–31). Any repeat procedures with other invasive treatments were not included in this study.

Figure 1

The average procedural time of consecutive groups of 10 patients with a single treatment with pulmonary vein ablation catheter or pulmonary vein ablation catheter/multi-array septal catheter/multi-array ablation catheter and a redo procedure with pulmonary vein ablation catheter or pulmonary vein ablation catheter/multi-array septal catheter/multi-array ablation catheter.

The average procedural time, in 128 index procedures with the PVAC/MASC/MAAC, was 109 ± 29 min (range 75–240). The average fluoroscopy time was 21 ± 8 min (range 10–67). The average number of applications that were needed for a successful procedure was 29 ± 9, 23 ± 7 with PVAC, 7 ± 2 with MASC, and 10 ± 4 with MAAC. The average procedural time, in 19 redo procedures with the PVAC/MASC/MAAC (with a complete follow-up of 6 months), was 115 ± 32 min (range 75–200). The average fluoroscopy time was 22 ± 11 min (range 14–65). The average total number of applications that were given was 32 ± 9, 19 ± 7 with PVAC, 6 ± 2 with MASC, and 9 ± 4 with MAAC.

From the numbers in Figure 1 it can be concluded that the learning curve for using this ablation system shows a rather steep decline, and that repeat procedures in general for the PVAC were shorter than the index procedure. The cohort of patients evaluated in this study, was treated by four different operators, consisting of two fully trained, experienced electro-physiologists (465 cases) and two fellows in training (194 cases, including the first cases together with an experienced electro-physiologists). The PVAC/MASC/MAAC procedure was only performed by the experienced operators. There was no significant relation between adverse events and operator characteristics, except for less PV stenosis after PVAC/MASC/MAAC.

During follow-up, 119 of 630 patients underwent a second treatment at least 6 months after their index procedure. The choice of therapy was left to the discretion of the referring cardiologist/electrophysiologist. Forty-three patients (36%) underwent a second phased RF procedure, being PVAC in 13 patients with paroxysmal AF, and PVAC/MASC/MAAC in 30 patients with non-paroxysmal AF. The remaining 76 patients (64%) had an alternative invasive treatment. These consisted of 43 conventional RF procedures, 28 thoracoscopic surgical ablations, and 5 MAZE-IV cardiac surgeries. Figure 2 shows the incidence of second treatment after PVI with the PVAC by type of AF in consecutive groups of 100 patients.

Figure 2

Second treatment after pulmonary vein isolation with the pulmonary vein ablation catheter in consecutive groups of 100 patients. APR, April; AUG, August; JUN, June; MAR, March; SEP, September; 07, 2007; 08, 2008; 09, 2009; 10, 2010.

Major adverse events

In total, 15 (2.3%) major adverse events were registered within the first month after an index or repeat ablation procedure, of which none occurred during the procedure itself. There were no deaths during the procedure. There were five non-cardiac deaths during 6 months of follow-up, consisting of pancreatic cancer, subarachnoid haemorrhage, and aortic dissection, while two were of unknown origin. These all occurred past the 1-month follow-up, and no link to the procedure or the specific technology could be established. The major adverse event rate was 2.0% with PVAC and a little lower at 0.8% with the more extended PVAC/MASC/MAAC procedure, although not statistically significant (P= 0.47). The procedural time was not related to the major adverse events (P= 0.17). The events were normally distributed over the cases. The major adverse events consisted mainly of five causes; complicated transseptal puncture (four cases), cerebrovascular accident (stroke two cases), TIA (five cases), acute coronary syndrome (two cases), and vascular access problems (two cases) (Table 1). The other major adverse events mentioned in the Methods section were not observed.

In the patients with cerebrovascular accident or TIA, this was almost exclusively of an ischaemic nature. Six of seven occurred during the first 24 h, and one during the first 48 h. The ischaemic strokes were almost all minor, and resolved without any remaining symptoms. Six of the seven patients used anti-coagulation before the procedure, of which three had an INR of < 2.0 during the procedure. Post-procedure anti-coagulation was continued, with additional LMWH if INR was < 2.0. Only one patient used aspirin and had a trans-oesophageal echocardiogram pre-procedure, which showed no LA thrombus. One of the seven patients with a TIA/stroke presented with AF at the electophysiological (EP) study, there was no relation between the presenting rhythm and TIA/Stroke (P= 0.68). Two of the seven patients with a TIA/stroke, including the patient with AF at the start of the procedure, had AF during the procedure, and there was no significant relation to TIA or stroke (P= 0.71). None of the patients with a TIA or stroke had a direct current cardioversion during the procedure. None of the patients who were treated with PVAC/MASC/MAAC had a TIA or stroke in the first month after the procedure. In one patient an intra-cranial haemorrhage occurred within 24 h of the ablation, confirmed by MRI imaging. This patient had an INR of 2.0, had severe peri-procedural hypertension, and was later diagnosed with a major stenosis in the relating cerebral artery.

In two patients, chest pain developed within 24 h after the intervention, which was diagnosed as an acute coronary syndrome, without left ventricular wall motion abnormality. On coronary angiography, both patients showed signs of coronary artery disease, rather than thromboembolism. One patient had a chronic occlusion of a first diagonal branch of the left anterior descending artery, which was probably old and could not be opened; the other had a significant stenosis in the posterolateral circumflex branch (PLCx) remote from the CS which was treated by a percutaneous coronary intervention with stent implantation.

Of the major vascular adverse events, one patient with a pseudo-aneurysm was treated with percutaneous embolization and thrombin injection 2 months after treatment. One other patient developed a small arterio-venous fistulae which did not require any intervention.

In four patients where phased RF ablation was intended but never performed due to problems with transseptal passage that required termination of the procedure. One of these patients needed acute cardiothoracic surgery because of cardiac perforation. Three other patients did not develop tamponade and were treated conservatively.

Late major adverse events

During the follow-up after 1 month up to 6 months three more major adverse events were documented. One patient had a myocardial infarction after 2 months, and another patient had a TIA after 1 month. There was one patient who during the course of 3 months experienced complaints of dyspnoea, due to progressive pericardial effusion (late Dressler syndrome), which eventually was solved by pericardiocentesis. The total major adverse event after an index or repeat ablation procedure up to 6 months is 2.7% (early and late major adverse events).

Minor adverse events

In 10.7% of the procedures a minor adverse event was registered in the first 6 months (Table 2). The length of the procedure time was not related to the minor adverse event (P= 0.88). The events were normally distributed over the cases. Most often, this was due to moderate pulmonary vein stenosis 50–70%, slightly prolonged groin bleeding, or small haematoma. None of the patients with a groin bleeding/haematoma needed specific treatment or transfusion, and hospitalization was not prolonged.

Anti-coagulation strategy before and after the procedure

Oral anti-coagulation was used in 492 cases before procedures (411 acenocoumarol and 81 fenprocoumon), acetylsalicylic acid in 142 cases, and no anti-thrombotic drugs in 25 cases. The mean INR was 2.1 (range 1.0–4.5). The INR was < 2 in 46% of the cases, between 2 and 3 in 49%, and > 3 in 4% before procedure.

No significant difference in major adverse event could be observed between patients who had pre-procedural OAC or not (P= 1.00). Also, no significantly higher rate of major adverse events were seen in patients with an INR >3.0 (P= 0.30).

There was no significant difference between bleeding or haematoma between patients who used OAC or not (P= 0.51). No significantly higher rate of bleeding or haematoma was seen in patients with an INR > 3.0 (P= 0.31). Activated clotting time levels were not routinely measured, and could not be analysed in relation to bleeding.

Pulmonary vein stenosis

Magnetic resonance imaging follow-up was performed in 94 patients and PV angiography during a second procedure was performed in 59 patients (total 153 patients, 24%). In none of the cases was there any evidence for significant PV stenosis (≥70%, major adverse event). There were eight patients with a moderate PV stenosis (50–69%). In these eight patients 10 moderate PV stenosis were found: 6 in the left superior PV, 1 in the left inferior PV, and 3 in the right superior PV. The number of applications was not significantly higher in the group of moderate PV stenosis of the left superior PV or right superior PV compared with the same PV in other patients, respectively, P= 0.43 and 0.25. None of these patients were symptomatic, and none required any intervention. As such, the incidence of moderate PV stenosis is 5.2% of patients in the sub-group of 153 patients with repeated imaging. The incidence of moderate PV stenosis is 1.6% of the total treated PVs (10 of 635).

There were significantly more minor adverse events seen with PVAC compared with PVAC/MASC/MAAC (P< 0.05), primarily due to the higher number of moderate PV stenosis.

Discussion

The multi-electrode catheters PVAC, MASC, and MAAC in combination with phased RF energy were designed with the intention to provide a set of specialized ablation tools using low power, for a relatively fast and safe PVI and CFAE ablation procedure. The present study describes the adverse event rate of treatment with PVAC and/or MASC/MAAC during the procedure, and 6 months of follow-up in a large cohort of patients in a single centre. In 2.3% of the procedures a major adverse event was registered within 1 month and a total of 2.7% at 6 months (including the first month). Minor adverse events were seen in 10.7% at 6 months. In general, it is difficult to directly compare adverse event-rates between studies, because most studies do not work with an internationally acknowledged and well-defined list of adverse events. We used ≤ 1 month for major adverse event in line with literature about percutaneous coronary intervention and coronary artery bypass grafting, because there is no consensus in the literature about electrophysiological investigations.

Pulmonary vein ablation catheter and pulmonary vein ablation catheter/multi-array septal catheter/multi-array ablation catheter

So far, the reported adverse event rates of PVAC procedures in smaller studies, was found to be low (Table 3). Combined, in 4 of a total of 452 patients (0.9%) a major adverse event was registered. Out of seven papers, six papers reported no adverse events and one reported 4 of 75 procedures (5%).10 In this last report, vascular access site adverse events were observed in 2.6% of the procedures.10 The adverse events were cardiac tamponade from the transseptal puncture and a prolonged reversible ischaemic neurologic disorder, and amounted to 2.6%.10 The absence of major adverse events in all but one PVAC-study may be explained by the very small number of patients included (between 21 and 102) combined with a low probability of major adverse events. Overall, the incidence of major adverse events in the present study seems slightly higher than the average of all previously published results. This may in part be due to the fact that the present paper focuses on any adverse event of the procedure, rather than the long-term success rate to cure AF. Since minor adverse events were not reported in the other PVAC studies, comparison with the present study was not feasible.

View this table:
Table 3

Major adverse events after ablation with a pulmonary vein ablation catheter or a pulmonary vein ablation catheter/multi-array septal catheter/multi-array ablation catheter in the literature

ProcedureNo. of patientsStrokeTransient ischaemic attackOther thromboembolic eventsPE/tamponadePhrenic nerve injuryAtrio-oesopageal fistulaFemoral AV fistulaGroin haematomaFemoral artery aneurysmMyocardial infarctionPulmonary vein stenosis*TotalPneumothoraxSepsis, abcess or endocarditis
Boersma et al.11PVAC9800000nsd00nsdnsd0/110/98 (0%)nsdnsd
Scharf et al.10PVAC +MASC/MAAC5010nsd1nsdnsd11nsdnsd0/504/50 (8%)nsdnsd
Fredersdorf et al.13PVAC21nsdnsdnsdNsdnsdnsdnsdnsdnsdnsd0/210/21 (0%)nsdnsd
Wierczorec et al.14PVAC730000000nsdnsdnsd0/60/73 (0%)nsdnsd
Duytschaever et al.15PVAC27000nsd0nsdnsdnsdnsdnsd0/30/27 (0%)nsdnsd
Beukema et al.16PVAC102nsdnsdnsdnsd00nsdnsdnsdnsd0/1020/102 (0%)nsdnsd
Spitzer et al.17PVAC81000000nsdnsd0nsd0/350/81 (0%)nsdnsd
Total4521 (0.2%)0 (0%)0 (0%)1 (0.2%)0 (0%)0 (0%)1 (0.2%)1 (0.2%)0 (0%)0 (0%)0 (0%)4/452 (0,9%)0 (0%)0 (0%)
  • *Only patients in whom imaging was performed (angiography during redo-procedure, cardiac or cardiac MRI > 3 months after the PVAC procedure) are counted.

  • AV, arteriovenous; MAAC, multi-array ablation catheter; MASC, multi-array septal catheter; MRI, magnetic resonance imaging; NSD, not specifically described; PE, pulmonary oedema; PVAC, pulmonary vein ablation catheter. For calculation of the total number of adverse events, if adverse events are not described, and authors state that no other adverse events occurred than specifically described, they are assumed not to have occurred.

From the numbers in Figure 1 it can be concluded that the learning curve for using this ablation system was steep, and that repeat procedures in general for the PVAC were considerably shorter than the index procedure.

The occurrence of acute coronary syndromes < 24 h is not directly explained. A direct effect of ablation on the infarct-related artery was not plausible, since they were not close to the AV-groove. In general, ablation has not been linked to plaque instability, and in none of the patients a pre-procedure coronary angiography was performed to exclude pre-existing stenosis. Although Heparin infusion should have been protective up to hours after the procedure, a thrombo-embolic event cannot be excluded, as we did not routinely measure ACT. It seems advisable to start bridging LMWH as soon as possible to prevent such events in the first 24 h after ablation.

Comparison with conventional catheter ablation

The total incidence of the major adverse events of the present study compares favourably with the data of the worldwide survey of conventional catheter ablation and its recent update.5,9 However, comparison between our prospective, single-centre study and retrospective data collection by questionnaire must be made with caution. Nevertheless, the results are also comparable and a large multi-centre registry from 10 centres, with 1011 consecutive patients, in which the incidence of major adverse events was 3.9%18 and a recent single-centre study of 1295 consecutive patients and 1642 procedures in which a major adverse event occurred in 3.5%.19 With the PVAC treatment, we found a somewhat lower incidence of peripheral vascular adverse events compared with conventional PVI (0.4 vs. 1.2–1.9%). The incidence of pericardial effusion/complicated transseptal puncture or tamponade was lower in our study (0.9 vs. 1.2–1.3). As in the worldwide survey with multiple ablation technologies, we observed a cerebral embolic event rate of 1%, while in the two other large registries with conventional RF this was reported as 0.2 and 0.5%, respectively.18,19 Although we did not observe char formation on the catheters during any of the procedures, this observation warrants close attention in future PVAC studies and registries. As in previous studies, all cerebral embolic events occurred after and not during the procedure, drawing attention to the importance of bridging anti-coagulation until patients have an adequate and stable INR as recommended by the guidelines.1 Whether maintaining ACT levels > 300 during the procedure itself could have lowered the rate of post-procedural thromboembolic events cannot be established from our data.

The number of observed moderate PV stenosis 50–69% also seems somewhat high. In the subgroup of 24% of our population that we evaluated, the incidence was 5.2% of patients, and occurred more so with PVAC alone than in combination with MASC/MAAC. A possible explanation might be that these were performed mostly by the more experienced electrophysiologists, although there was no clear effect of operator with PVAC alone. More importantly, no significant PV stenosis > 70% was observed. Whether these findings can be extrapolated to the whole cohort is unknown. There have been case reports of PV occlusion after PVAC ablation.20 Therefore, the occurrence of PV stenosis should be carefully monitored in future studies.

Obviously, it remains difficult to compare studies and technologies due to differences in definition, and the fact that absolute numbers of observed events are relatively low. Very large randomized trials would be needed to accurately elucidate differences in safety (and efficacy) between ablation strategies. Overall, the major adverse event rate of conventional catheter ablation and multi-electrode catheter ablation does not seem very different.

Asymptomatic cerebral ischaemia

Over the last year, there have been a number of studies reporting on the finding of asymptomatic cerebral ischaemia (ACI) by diffusion weighted MRI (DW-MRI) in patients who have undergone left-sided catheter ablation.2126 Although this is a well-known finding in invasive cardiovascular procedures,27,28 it is a disturbing new phenomenon in AF ablation, of which the exact cause and impact yet remain to be determined. From the published literature it can be derived that the incidence of ACI may vary depending on the technology used. For irrigated-tip RF ablation ACI rates of 8.6–38% have been reported, while for cryo-balloon ablation the incidence was ∼4–10%.22,24,25 For phased RF ablation the ACI rate reported seems to be consistently higher with a rate ∼38%.22 Despite the fact that ACI has been described for decades, no study has been able to identify any effect on long-term neuro-cognitive performance. This could reflect the fact that the mechanism and/or extent of ACI may be different from that of stroke. Recent work from Deneke et al.26 in fact shows that in patients with ACI on DW-MRI directly after an ablation procedure, 94% of these lesions completely disappear without leaving any appreciable scar tissue on a repeat DW-MRI several weeks/months later.

Although the fact that these lesions are asymptomatic, and most seem to completely disappear over time without giving rise to neuro-cognitive impairment, this phenomenon certainly must not be ignored. Further studies should be directed to assess the cause of ACI with phased RF ablation, and apply the appropriate changes to either the procedure or the technology to minimize any potential threat to patients’ well-being.29

Limitations

The present data are from a single centre only. Only a quarter of the patients underwent some form of post-procedure imaging to evaluate the presence of PV stenosis. The small number of events did not allow multivariate analysis, so we could not determine risk factors for the occurrence of adverse events after AF ablation using the PVAC, MASC, or MAAC catheters. Larger multi-centre registries are needed to address this issue. In this study, ACT was not measured on a routine basis, and the INR in the first days after treatment were not investigated. Therefore, it was not possible to study the relationship between ACT and stroke, ACS, or groin bleeding. The occurrence of tamponade was very low, showing that this is uncommon while using phased RF energy with multi-electrode catheters. There were no complications with vascular access in which the procedure was ended. Very recent studies have shown that ablation may be accompanied by (transient) abnormalities on DW-MRI analysis that may relate to silent ischaemia.22 We have no data on this in our patient registry, as this was unknown in the time frame between July 2006 to August 2010.

Conclusion

Ablation with multi-electrode ablation catheters using duty-cycled bipolar and unipolar phased RF energy has a major adverse event rate of 2.3% within the first month after the procedure, comparable with conventional ablation technology.

Conflict of interest: L.V.A.B. is a consultant for Medtronic, and a prior stockholder of Ablation Frontiers. The other authors declare no conflict of interest. The Cardiology Department has received grant support for research from Ablation Frontiers, Inc.

Funding

This work was supported by the Cardiology Department, St Antonius Hospital, Nieuwegein, The Netherlands.

References

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