Europace Advance Access published April 16, 2015
CLINICAL RESEARCH
Europace doi:10.1093/europace/euv046
Safety profile of multielectrode-phased radiofrequency pulmonary vein ablation catheter and irrigated radiofrequency catheter K. Wasmer, P. Foraita, P. Leitz, F. Gu¨ner, C. Pott, P.S. Lange, L. Eckardt, and G. Mo¨nnig* Division of Electrophysiology, Department of Cardiovascular Medicine, University of Muenster, Albert-Schweitzer-Campus 1, Building A1, 48149 Muenster, Germany Received 17 June 2014; accepted after revision 13 February 2015
Silent cerebral lesions with the multielectrode-phased radiofrequency (RF) pulmonary vein ablation catheter (PVACw) have recently been investigated. However, comparative data on safety in relation to irrigated RF ablation are missing. ..................................................................................................................................................................................... Methods One hundred and fifty consecutive patients (58 + 12 years, 56 female) underwent first pulmonary vein isolation (PVI) for atrial fibrillation (61% paroxysmal) using PVACw (PVAC). Procedure data as well as in-hospital complications were and results compared with 300 matched patients who underwent PVI using irrigated RF (iRF). Procedure duration (148 + 63 vs. 208 + 70 min; P , 0.001), RF duration (24 + 10 vs. 49 + 25 min; P , 0.001), and fluoroscopy time (21 + 10 vs. 35 + 13 min; P , 0.001) were significantly shorter using PVAC. Major complication rates [major bleeding, transitoric ischaemic attack (TIA), and pericardial tamponade] were not significantly different between groups (PVAC, n ¼ 3; 2% vs. iRF n ¼ 17; 6%). Overall complication rate, including minor events, was similar in both groups [n ¼ 21 (14%) vs. n ¼ 48 (16%)]. Most of these were bleeding complications due to vascular access [n ¼ 8 (5.3%) vs. n ¼ 22 (7.3%)], which required surgical intervention in five patients [n ¼ 1 (0.7%) vs. n ¼ 4 (1.3%)]. Pericardial effusion [n ¼ 4 (2.7%) vs. n ¼ 19 (6.3%); pericardial tamponade requiring drainage n ¼ 0 vs. n ¼ 6] occurred more frequently using iRF. Two patients in each group developed a TIA (1.3% vs. 0.6%). Of note, four of five thromboembolic events in the PVAC group (two TIAs and three transient ST elevations during ablation) occurred when all 10 electrodes were used for ablation. ..................................................................................................................................................................................... Conclusion Pulmonary vein isolation using PVAC as a ‘one-shot-system’ has a comparable complication rate but a different risk profile. Pericardial effusion and tamponade occurred more frequently using iRF, whereas thromboembolic events were more prevalent using PVAC. Occurrence of clinically relevant thromboembolic events might be reduced by avoidance of electrode 1and 10 interaction and uninterrupted anticoagulation, whereas contact force sensing for iRF might minimize pericardial effusion.
Background
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Atrial fibrillation † Pulmonary vein isolation † Safety † Irrigated radiofrequency ablation † Multielectrode-phased radiofrequency ablation
Introduction Electrical isolation of pulmonary veins is the cornerstone of catheter ablation for patients with symptomatic atrial fibrillation (AF).1 Although the irrigated point-by-point radiofrequency (RF) ablation is the most frequently used technology, various alternative techniques such as the ‘pulmonary vein ablation catheter’ (PVACw, Medtronic
Inc., Minneapolis, MN, USA) have been developed to facilitate pulmonary vein isolation (PVI). This ‘one-shot-system’ achieves comparable clinical outcome but has the advantage of shorter procedure duration as well as lower fluoroscopy time.2 – 5 Concerns have been raised about the safety of this system after detection of increased incidence of silent cerebral embolism using this phased RF ablation device in comparison with irrigated tip RF ablation or
* Corresponding author. Tel: +49 (0)251/8347581; fax: +49 (0)251/8349965, E-mail address: [email protected] Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2015. For permissions please email: [email protected].
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What’s new? † First single-centre direct comparison of PVI using irrigated vs. phased RF ablation with focus on clinical relevant safety endpoints. † We found comparable safety endpoints but different risk profile. † Pericardial effusion and bleeding (groin haematoma) occurred more often using irrigated RF ablation. † New evidence for reducing the increased thromboembolic risk (clinical manifest endpoints rather than silent cerebral lesions) by avoiding electrode 1–10 interaction in phased ablation. † Perspective of possibly lower thromboembolic risk with the new designed phased RF catheter (PVAC Goldw).
cryoablation has been reported.6 – 9 We and other groups have demonstrated that avoidance of an interaction between electrode 1 and 10 can reduce both, silent cerebral microembolism as well as the rate of microembolic signals (MES) detected by transcranial Doppler ultrasound.10 – 12 However, data on safety endpoints and complication rates in direct comparison with the predominant energy source of irrigated RF are still lacking.
Patients and methods Patient cohort We performed a retrospective, single-centre case-control study. Patients who had undergone first PVI without additional linear lesions or ablation of complex fractionated electrograms between 2010 and 2013 with either PVAC or conventional irrigated RF ablation were included in the analysis. All patients had antiarrhythmic drug refractory symptomatic, persistent, or paroxysmal non-valvular AF. Patients with long-standing persistent AF, previous surgical or non-surgical left atrial ablation, including PVI, were not included to achieve a homogenous patient cohort. One hundred and fifty consecutive patients who had undergone multielectrode-phased RF PVI served as study population (PVAC group). These patients were gender- and age-matched in a 1 : 2 manner to 300 patients who had undergone conventional irrigated RF PVI during the same time period (iRF group). The ablation technology was chosen according the operator’s preference. It was not related to specific criteria, namely PV anatomy.
Periprocedural management The study was performed before ablation under uninterrupted vitamin K-antagonist (VKA) was introduced. Accordingly, VKA was discontinued 1 day prior to admission/procedure. In anticoagulated patients with INR value ,2.0 upon admission bridging with weight-adjusted lowmolecular-weight heparin was performed. New oral anticoagulants (Dabigatran, Rivaroxaban) were discontinued 1 day prior to the ablation procedure. A transoesophageal echocardiogram was performed in all patients within 24 h prior to ablation to exclude left atrial thrombus formation. All patients underwent a computed tomography of the heart and the anatomy of the left atrium (LA) and the PVs were reconstructed (EnSite Verismo, St. Jude Medical, St. Paul, MN, USA) to better understand anatomy (PVAC) and to guide catheter ablation (NavX).
K. Wasmer et al.
All patients received oral anticoagulation for 2 months post ablation. Long-term oral anticoagulation was recommended as indicated by current guidelines.1
Ablation procedure Written informed consent was obtained prior to each ablation procedure. All ablation procedures were performed under conscious sedation. Midazolam and piritramide were administered at the discretion of the operator. During the ablation procedure, surface electrocardiograms and bipolar intra-cardiac electrograms were registered using a digital recording system (Axiom Sensis XP, Siemens AG, Erlangen, Germany or a Prucka GE Medical The General Electric Company, Fairfield, CT, USA). Signals were sampled at 1 kHz, filtered at 0.1 – 100 Hz for surface electrocardiograms and at 30 – 250 Hz for intra-cardiac signals. The ablation protocols of our institution for phased and irrigated RF ablation have been described in detail previously.2,11 In brief, ablation was performed as follows.
Phased radiofrequency ablation After gaining femoral venous access, a steerable decapolar catheter (Lifewire, St. Jude Medical, St. Paul, MN, USA) was placed into the coronary sinus. A single transseptal puncture (TSP) was done using a 10-F nonsteerable sheath (Arrive, Medtronic Inc., Minneapolis, MN, USA) under fluoroscopy guidance with continuous pressure monitoring. The long sheath was continuously perfused with heparinized saline solution. Subsequently, a bodyweight-adjusted heparin bolus was applied. The activated clotting time (ACT) was monitored in 30 min intervals with a target ACT between 250 and 350 s. Additional Heparin boli were given if necessary. The ablation procedure was continued irrespective of the ACT value. Selective angiography of the PVs was performed with 50 mL of non-ionic contrast (Ultravist 370, Bayer, Germany). The 10 pole-phased RF catheter (PVACw, Medtronic Inc., Minneapolis, MN, USA) was placed at the ostium of each PV using over-the-wire technique (PV-Tracker, Medtronic Inc., Minneapolis, MN, USA). Ablation was performed exclusively with a 4 : 1 bipolar/unipolar ratio and a maximum power of 8 W for 1 min. In the first 66 patients, all 10 electrodes of the PVACw catheter were activated. After publication of reports finding an association of electrodes 1 and 10 interaction during ablation and increased risk for embolic complications, pair 1 or 5 was deactivated throughout each procedure in the remaining 84 patients. Temperature limit was set to 608C. After each ablation, conduction into the PV was tested and ablation was repeated at sites with remaining conduction. Electrode pairs without tissue contact or positioned at sites without conduction were deactivated at the operators’ discretion. This procedure was repeated until PVI was completed. If AF persisted after ablation, sinus rhythm was restored by electrical cardioversion. Complete isolation of the PVs was then confirmed during sinus rhythm and during coronary sinus and in some cases by left atrial appendage pacing. Protamine was applied once the catheter and sheath had been removed from the LA. Anticoagulation was started/restarted 12 h after ablation. If VKA was used the patient was bridged with Heparin until INR was .2.0.
Irrigated tip radiofrequency ablation In patients undergoing conventional irrigated tip RF ablation, access to the LA was achieved by performing two separate TSPs. A non-steerable sheath (Daig SL1, St. Jude Medical. St. Paul, MN, USA) for the diagnostic circular decapolar catheter (Inquiry Optima, St. Jude Medical, St. Paul, MN, USA), and a deflectable long sheath (Agilis, St. Jude Medical, St. Paul, MN, USA) for the ablation catheter were placed in the LA. Both long sheaths were continuously flushed with heparinized saline
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Safety of PVI using PVAC vs. irrigated RF catheter
solution. Management of anticoagulation including ACT measurements and heparin dosage were identical to the phased RF group. After selective, simultaneous angiography of the ipsilateral PVs and acquisition of the individual 3D anatomy of the LA (Ensite NavX Velocity, St. Jude Medical, St. Paul, MN, USA, with image integration), antral circumferential RF ablation around ipsilateral PVs using a 4-mm open-tipirrigated catheter (IBI Therapy Coolpath Duo, St. Jude Medical) was performed. Maximum power was set to 30 W. Temperature was limited to 438C. Electrical cardioversion was performed if the patient remained in AF after PV isolation and PV isolation was subsequently confirmed during sinus rhythm and pacing as described above. Anticoagulation regime was the same as in phased RF (see above).
Study endpoints and follow-up Major safety endpoints were predefined as major bleeding, transitoric ischaemic attack (TIA), stroke, pericardial tamponade with need for pericardiocentesis, clinically manifest pulmonary stenosis, and death. Overall safety endpoints additionally including minor/minimal bleeding, transient myocardial ischaemia (transient ST-elevation), minor pericardial effusion, and transient fever. Bleeding included minor haematoma at the site of vascular access via femoral vein as well as major bleeding (e.g. haemoglobin fall .20 g/l; haemodynamic instability; need for surgical intervention or for transfusion) as defined by the International Society on Thrombosis and Haemostasis.13 In case of transient fever (body temperature .38.08C), prophylactic antibiotic therapy was given to prevent pulmonary infection. All patients were routinely investigated for these endpoints prior to discharge after PV including an echocardiography. After 3 – 6 months, all patients were scheduled to be seen in our outpatient clinic to re-evaluate the procedural outcome and complications. Patients who missed the follow-up visit were contacted by phone and followed up. Twelve patients were lost to follow-up (2.7%).
Statistics All statistical analyses were performed using SPSS 21.0 (IBM Corporation, Armonk, NY, USA). Continuous variables are presented as mean + SD. Statistical comparison of safety endpoints between the groups as well as between the operators was performed by x2-test. Mann–Whitney U-test was performed for non-parametric data. A P-value of ,0.05 was considered statistically significant.
Results Patient characteristics and procedural data A total number of 450 patients were included into the analysis. There was no significant difference concerning baseline characteristics and cardiovascular risk factors between the PVAC and the iRF group (Table 1). More specifically, the pre-ablation thromboembolic risk determined by CHA2DS2-VASc-Score and also the anticoagulation status were not significantly different between both groups (Table 1). Furthermore, the percentage of patients with PVI under INR .2 was equally distributed between both groups (Table 1). Total procedure duration, fluoroscopy time, and ablation duration were significantly lower in the phased RF group (PVAC) compared with those in the irrigated iRF group (Table 2). The dose of sedation per procedure (midazolam 6.2 + 2.7 vs. 7.0 + 3.2 mg; P ¼ 0.011) and analgesic medication (piritramide 11.3 + 4.7 vs. 13.8 + 6.0 mg; P , 0.001) was slightly but significantly lower in the PVAC group. Activated clotting time .250 s was reached in all patients after the
Table 1 Baseline characteristics of irrigated vs. phased RF ablation groups Irrigated iRF n 5 300
Phased RF Significance (PVAC) n 5 150
................................................................................ Age (mean + SD, years)
59 + 11
59 + 12
Male/female (n)
191/109
94/56
ns
Hypertension (n; %) Diabetes (n; %)
194; 65% 22; 8%
93; 62% 12; 8%
ns ns
Arterial embolism (n)
0
0
ns
Structural heart disease (n; %)
54; 18%
19; 13%
ns
Vascular disease (n; %) CHA2DS2-Vasc (mean)
49; 16% 1.8
27; 18% 2.0
ns ns
AF type (PAF/PersAF)
199/101
Oral anticoagulation (n; %) 188; 62% VKA (n; %) 172; 57% Dabigatran (n; %)
ns
99/51
ns
90; 60% 74; 49%
ns ns
9; 3%
7; 5%
ns
Rivaroxaban (n; %) INR (mean + SD)
7; 2% 1.7 + 0.7
9; 6% 1.6 + 0.6
ns ns
INR . 2 (n; %)
72; 24%
32; 21%
ns
AF, atrial fibrillation; INR, international normalized ratio; ns, non-significant; PAF, paroxysmal atrial fibrillation; PersAF, persistent atrial fibrillation; VKA, vitamin K antagonist.
Table 2 Procedural characteristics of irrigated vs. phased RF ablation groups Irrigated iRF n 5 300
Phased RF (PVAC) n 5 150
Significance
208 + 70
148 + 64
,0.001
Fluoroscopy time (mean, min)
35 + 13
21 + 10
,0.001
Time of energy delivery (mean, min)
49 + 25
24 + 10
,0.001
................................................................................ Total procedure duration (mean, min)
Cardioversion (n; %)
90; 30%
48; 32%
ns
min, minutes; ns, non-significant.
second ACT-check. Length of hospital stay was not different between groups (Figure 1).
Safety endpoints Major safety endpoints were present in 20 patients (4.4%) and more frequent in the iRF group (Table 3 and Figure 1). No death, stroke, or haemorrhagic shock occurred in any of the patients. Overall safety endpoints occurred in 73 patients (Table 3 and Figure 1) and was distributed equally (P ¼ 0.91) between the PVAC [n ¼ 25 (17%)] and the iRF group (n ¼ 48 (16%). There was no significant difference in safety endpoints between operators in univariate
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K. Wasmer et al.
iRF
Table 4 Characteristics of patients with vs. without safety endpoint
8
PVAC
7
7
6
6
5
5
4
4
3
3
2
2
1
1
0
0
Days
Percent
8
Pericardial Bleeding Embolic Fever Major Hospital effusion (total) event complication stay (days) Safety endpoint/hospital stay
Figure 1 Safety endpoints and hospital stay in AF-patients treated with RF (iRF; n ¼ 300) or multipolar-phased RF (PVAC; n ¼ 150). Major complication including major bleeding, TIA, and pericardiocentesis. Embolic event including transient ST elevation and TIA.
Safety endpoint n 5 73
No safety endpoint n 5 377
Significance
Age (mean + SD, years)
63 + 9
57 + 11
ns
Male/female (n)
34/39
251/125
0.001
CHA2DS2-Vasc (mean) AF type (PAF/PersAF)
2.2 62/11
1.8 236/141
ns 0.001
Total procedure duration (mean, min)
187 + 54
188 + 77
ns
Time of energy delivery (mean, min)
39 + 24
41 + 24
ns
INR . 2 (n; %)
16; 22%
88; 23%
ns
3+2
0.001
................................................................................
Hospital stay (mean + SD; 6 + 4 days)
AF, atrial fibrillation; INR, international normalized ratio; ns, non-significant; PAF, paroxysmal atrial fibrillation; PersAF, persistent atrial fibrillation.
Table 3 Adverse events after pulmonary vein isolation using irrigated or phased RF ablation Irrigated iRF n 5 300
Phased RF Significance (PVAC) n 5 150
22; 7%
8; 5%
ns
13; 4% 9; 3%
7; 5% 1; 1%
ns ns
Haemoglobin loss .2 g/dL (n; %)
5; 2%
1; 1%
ns
Surgical intervention (n; %)
4; 1%
1; 1%
ns
TIA (n; %)
2; 1%
2; 1%
ns
Transitoric ST-elevation (n; %)
0
3; 2%
0.04
Pericardial effusion (n; %) 19; 6% Pericardiocentesis (n; %) 6; 2%
4; 3% 0
0.06 0.08
Fever (n; %)
5; 2%
4; 3%
ns
Death (n) Major safety endpoints
0 17; 6%
0 3; 2%
– 0.06
21; 14%
ns
................................................................................ Total bleeding (n; %) Minor bleeding (n; %) Major bleeding (n; %)
Total safety endpoints (n; %) 48; 16%
Adverse events are shown in total number (n) and percentage (%) of the subgroup. Major safety endpoints including major bleeding, TIA, and pericardiocentesis. Exact P-value were given for P , 0.1 (ns, non-significant).
analysis. The most frequent complications were bleeding events due to vascular access [in total n ¼ 30 (6.7%)] or pericardial effusion [in total n ¼ 23 (5.1%)]. Most of the pericardial effusions were detected during routine pre-discharge echocardiography and had no haemodynamic impact (n ¼ 17; 3.8%). Pericardial tamponade requiring emergent pericardiocentesis occurred in six iRF patients (1.33% of all patients; 2% of iRF patients). There was a trend to a higher incidence of major bleedings and pericardial effusion in the iRF group (Table 3 and Figure 1). Transient embolic events defined
as TIA or transient ST elevation without elevated cardiac enzymes [n ¼ 5 (3%) vs. n ¼ 2 (1%), P ¼ 0.044; Table 3 and Figure 1] occurred significantly more often in the PVAC group. Interestingly, four of five embolic events occurred during activation of all 10 electrodes (4/66 ¼ 6% vs. 1/84 ¼ 1%). Nine patients presented with transient fever that occurred 1 day after PVI and was treated with prophylactic antibiotic therapy. This complication was slightly more prevalent in the PVAC group (Table 3 and Figure 1). Overall safety endpoints were not different between patients ablated under INR .2 and interrupted anticoagulation (15% vs. 17%; P ¼ 0.58). Especially, bleeding complications were equally distributed in both groups (0.07%). In univariate analysis, female gender and paroxysmal AF was more frequent in patients with safety endpoints after PVI (Table 4). All other baseline or procedural characteristics were not different. The hospital stay was longer in patients with complications (Table 4). During a mean follow-up of 10.4 months, no late complications occurred. Patients with complications at the time of the procedure were all doing well at follow-up. No symptoms persisted from previous complications. There was no significant impairment due to procedure-related complications at the time of follow-up.
Discussion Uncertainty surrounds the choice of energy source in PVI. While we and other groups have shown that PVAC and iRF have similar outcomes with regard to the maintenance of sinus rhythm,2,3 the safety profile becomes an important criterion to select the right catheter setting in the individual patient. Here, we present data obtained in a single-centre retrospective case–control study. Specifically, we show that PVI using the multipolar PVACatheter is as safe as irrigated iRF PVI in a head-to-head comparison. This is a remarkable observation considering that the catheter setting is different between both groups.
Safety of PVI using PVAC vs. irrigated RF catheter
Deshmukh and co-workers found a correlation of age and gender with the occurrence of any PVI-associated in-hospital complication in 93 801 procedures of the Nationwide Inpatient Sample.14 We could confirm the association of the female gender, but not the age with safety endpoints in our cohort. The longer hospital stay of patients with complications is not surprising and concordant with the analysis of Deshmukh et al. None of the other characteristics were associated with safety endpoints in our study.
Comparing pulmonary vein ablation catheter and irrigated radiofrequency Pulmonary vein ablation catheter requires only one TSP; however, the vascular access at the femoral vein is larger (10 F). In addition, reports of a higher thromboembolic risk using PVAC suggested worse safety profile with this technique.6,7 Irrigated iRF PVI on the other hand requires a longer procedure time compared with PVAC and two TSPs are necessary instead of one as well as two 8 F sheats for venous access. These technical differences could be associated with a different safety profile. However, in the setting of equally experienced investigators and comparable study populations, this study is the first to demonstrate a similar complication rate despite the abovementioned differences. However, there was a different profile of adverse events: while bleeding and pericardial effusion were observed more frequently in the iRF group, embolic events and fever occurred more often in the PVAC group. The need for two venous and TSPs with irrigated iRF may be causing bleeding and pericardial effusion in the iRF group. Use of steerable long sheath with contact force sensing of the ablation catheter may have reduced incidence of pericardial effusions in the iRF group. In animal model using the multipolar PVACatheter, the largest source of gaseous and solid emboli occurred when the distal and proximal electrodes (1 and 10) were in close proximity or overlapping.15 This electrode overlap creates bipolar short circuit resulting in excessive heating of tissue and blood. Therefore, it is not surprising that four of five embolic events occurred during activation of all 10 electrodes. Following deactivation of electrode pair 1 or 5, we observed fewer MES11 and only one additional embolic event (TIA). As the novel catheter design of the PVAC Gold w array might improve safety by reducing embolic events as it prevents electrodes 1–10 interaction and allows for enhanced tissue contact due to the 208 forward tilt we still use both systems (PVAC and irrigated RF) for index PVI. Although no clinical data on this new array are available yet, it appears to be as safe and feasible in our own preliminary experience with the first PVAC Gold w PVIs (n ≈ 50) when compared with the former PVAC array (P. Leitz and G. Mo¨nnig unpublished data). All PV veins were reached by the novel array and no clinical manifest complication occurred so far. Performing PVI on continued VKA with lower INR of 2.0– 2.5 might further reduce the incidence of thromboembolic complications. The overall complication rate of 16% was remarkably highly compared with published data of major complication rates between 4% and 6% in the largest multi-centre registry.16 When taking only the major events into account (10 major bleedings, four TIAs, and six pericardiocentesis; Table 3) complication rate of 4.4% in our cohort is quite in line with the published major complication rate of
Page 5 of 7 4.54%.16 Likewise, the percentage of pericardial tamponade of our group was in line with the reported of the world wide survey by Cappato and co-workers (1.31% vs. 1.33% in our cohort).16 However, no comparable data from this world wide cohort are available for pericardial effusions without haemodynamic impact. Pulmonary vein stenosis has been recognized as a complication of PVI using RF energy and has also been described in patients treated with multipolar PVAC RF catheter.17 In our patient cohort, there was no clinical evidence or significant PV narrowing in 35 PV angiographies after PVAC ablation that were performed during additional ablation procedures due to AF recurrence. No patient reported symptoms of pulmonary vein stenosis (i.e. dyspnoea); however, we did not systematically screen for PV stenosis by routine imaging. Fever after PVI has been described to occur in 10% of patients by Ruby and co-workers.18 They discuss atelectasis, pneumonitis, pericarditis, haematoma at the access site, venous thromboembolism, thrombophlebitis and rarely, oesophageal injury as potential causes. Another reason for elevated body temperature may be nonspecific inflammation after PVI as described by Lim et al. 19 None of our patients had clinical signs of pulmonary oedema as described by Weber and co-workers after extensive ablation.20 As we investigated different ablation approaches, it appears reasonable that particularly the degree of inflammation associated with PVI might differ between PVAC and iRF. While we have screened for elevated body temperature only it is highly speculative to hypothesize an increased inflammation response to PVAC-PVI. Nevertheless, the prophylactic administration of antibiotic therapy to prevent respiratory infection might be questionable.
Safety of pulmonary vein ablation catheter in previous studies Safety and complications using PVAC have been described for AF-ablation in several studies.21 – 24 However, none of these studies report a direct comparison between PVAC and the predominant ablation technique of irrigated RF. The largest study including 502 PVAC index procedures is that of Mulder and co-workers.22 They reported major complications in 2.0% and additional minor complications in 12.9% of the patients. The overall complication rate of that study (15%) is similar to our data. In that study, the procedural time as well as the fluoroscopy time was shorter (86 min and 20 min, respectively). This might point to the importance of a learning curve since these data come from one of the centres with most experience in the PVAC procedure. In a study by Malmborg and co-workers, 110 AF patients were randomized to either Cryo balloon or PVAC.21 In that study, only one periprocedural complication (major groin haematoma) occurred in the PVAC group compared with four in the Cryo group (groin haematoma in two and phrenic nerve paralysis in another two patients). The total procedure time was similar in both groups (165 min) with shorter fluoroscopy time using cryoballon (32 vs. 47 min). We found shorter study duration of 148 min with shorter fluoroscopy time of 21 min in our study. However, overall complication rate was higher compared with the data by Malmborg which may be due to the inclusion of minor complications in our study. A recently published study (TTOP-AF) investigated efficacy and safety of phased RF in patients with persistent AF.23 In that study,
Page 6 of 7 21 acute major adverse events occurred in 17 of 138 patients (12.3%). Stroke occurred in additional four patients (2.9%) and PV stenosis in five (one patient with symptoms). Including these symptomatic patients (n ¼ 22), the overall complication rate (16%) is equal to our data. Another recent study published by De Greef and co-workers compared the long-term outcome of patients undergoing PVI with irrigated RF and phased RF with focus on the long-term outcome.24 In this non-randomized study, there was no difference in outcome or safety between both strategies. There was one major (PV stenosis) and three minor complication (gastroparesis and two groin haematoma) reported in the PVAC group (n ¼ 79; 5.1%) compared with one major (pericardial tamponade) and four minor complications (two patients with pericarditis, groin haematoma, and ‘fluid retention syndrome’) in the iRF group (n ¼ 82; 6.1%). The spectrum of complications might be somewhat different to our observation except the groin haematoma and pericardial tamponade because the focus of that study with smaller groups was on the long-term outcome rather than on the safety aspect of these two strategies. However, the comparable safety between both groups is in good concordance with our finding.
Limitations The descriptive nature of this retrospective analysis is the main limitation that could lead to patient selection bias. We are presenting a retrospective single-centre case–control analysis without a randomized design. Therefore, there is a lack of homogeneity in the anticoagulation strategy around the procedure. Furthermore, the ablation procedures were performed by a constant group of six operators in a single EP lab over the same time period with the same anticoagulation regime between both groups. Even without significantly different safety endpoints for individual operators the influence on complications cannot be fully excluded by this design of study. However, we believe that the conditions of both procedures are very comparable.
Conclusion We found further evidence for shorter procedure duration and lower fluoroscopy time in consecutive index PVI patients using PVACatheter. Of note, complication rate was comparable with irrigated iRF. Safety profile, though was different with more pericardial effusions and bleeding complications in the iRF group while more embolic and infectious events were observed in the PVAC group. Avoidance of electrodes 1– 10 interaction by deactivating electrode pair 1 or 5 seems to reduce clinical relevant thromboembolic events. The novel catheter design (PVAC Gold w) may improve safety by reducing embolic risk, although clinical data are lacking so far. Performing PVI on continued anticoagulation and the use of contact force sensing for iRF might minimize complications irrespective of the technology used. Conflict of interest: K.W., L.E., G.M., and C.P. have received lecture honoraria and travel grants from Astra/Zeneca, Bayer, Biosense Webster, Biotronik, Boehringer Ingelheim, Boston Scientific, Medtronic, Sanofi Aventis, and St. Jude Medical. L.E. has received research grants from Biotronik, St. Jude Medical, Sanofi, and Osypka. C.P. was
K. Wasmer et al.
supported by a grant by the Deutsche Stiftung fu¨r Herzforschung (F 44/12).
References 1. Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Europace 2012;14:1385 –413. 2. Bittner A, Monnig G, Zellerhoff S, Pott C, Kobe J, Dechering D et al. Randomized study comparing duty-cycled bipolar and unipolar radiofrequency with point-bypoint ablation in pulmonary vein isolation. Heart Rhythm 2011;8:1383 –90. 3. Bulava A, Hanis J, Sitek D, Osmera O, Karpianus D, Snorek M et al. Catheter ablation for paroxysmal atrial fibrillation: a randomized comparison between multielectrode catheter and point-by-point ablation. Pacing Clin Electrophysiol 2010; 33:1039 – 46. 4. Scharf C, Ng GA, Wieczorek M, Deneke T, Furniss SS, Murray S et al. European survey on efficacy and safety of duty-cycled radiofrequency ablation for atrial fibrillation. Europace 2012;14:1700 –7. 5. Beukema RP, Beukema WP, Smit JJ, Ramdat Misier AR, Delnoij PP, Wellens H et al. Efficacy of multi-electrode duty-cycled radiofrequency ablation for pulmonary vein disconnection in patients with paroxysmal and persistent atrial fibrillation. Europace 2010;12:502 –7. 6. Gaita F, Leclercq JF, Schumacher B, Scaglione M, Toso E, Halimi F et al. Incidence of silent cerebral thromboembolic lesions after atrial fibrillation ablation may change according to technology used: comparison of irrigated radiofrequency, multipolar nonirrigated catheter and cryoballoon. J Cardiovasc Electrophysiol 2011;22:961 –8. 7. Herrera Siklody C, Deneke T, Hocini M, Lehrmann H, Shin DI, Miyazaki S et al. Incidence of asymptomatic intracranial embolic events after pulmonary vein isolation: comparison of different atrial fibrillation ablation technologies in a multicenter study. J Am Coll Cardiol 2011;58:681–8. 8. McCready J, Chow AW, Lowe MD, Segal OR, Ahsan S, de Bono J et al. Safety and efficacy of multipolar pulmonary vein ablation catheter vs. irrigated radiofrequency ablation for paroxysmal atrial fibrillation: a randomized multicentre trial. Europace 2014;16:1145 –53. 9. Compier MG, Leong DP, Marsan NA, Delgado V, Zeppenfeld K, Schalij MJ et al. Duty-cycled bipolar/unipolar radiofrequency ablation for symptomatic atrial fibrillation induces significant pulmonary vein narrowing at long-term follow-up. Europace 2013;15:690 –6. 10. Verma A, Debruyne P, Nardi S, Deneke T, Degreef Y, Spitzer S et al. Evaluation and reduction of asymptomatic cerebral embolism in ablation of atrial fibrillation, but high prevalence of chronic silent infarction: results of the ERACE trial. Circ Arrhythm Electrophysiol 2013;6:835 –42. 11. Zellerhoff S, Ritter MA, Kochhauser S, Dittrich R, Kobe J, Milberg P et al. Modified phased radiofrequency ablation of atrial fibrillation reduces the number of cerebral microembolic signals. Europace 2014;16:341 –6. 12. Wieczorek M, Hoeltgen R, Brueck M. Does the number of simultaneously activated electrodes during phased RF multielectrode ablation of atrial fibrillation influence the incidence of silent cerebral microembolism? Heart Rhythm 2013;10:953–9. 13. Schulman S, Kearon C. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005;3: 692 –4. 14. Deshmukh A, Patel NJ, Pant S, Shah N, Chothani A, Mehta K et al. In-hospital complications associated with catheter ablation of atrial fibrillation in the United States between 2000 and 2010: analysis of 93 801 procedures. Circulation 2013;128: 2104 –12. 15. Haines DE, Stewart MT, Dahlberg S, Barka ND, Condie C, Fiedler GR et al. Microembolism and catheter ablation I: a comparison of irrigated radiofrequency and multielectrode-phased radiofrequency catheter ablation of pulmonary vein ostia. Circ Arrhythm Electrophysiol 2013;6:16– 22. 16. Cappato R, Calkins H, Chen SA, Davies W, Iesaka Y, Kalman J et al. Updated worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation. Circ Arrhythm Electrophysiol 2010;3:32 –8. 17. von Bary C, Weber S, Dornia C, Eissnert C, Fellner C, Latzin P et al. Evaluation of pulmonary vein stenosis after pulmonary vein isolation using a novel circular mapping and ablation catheter (PVAC). Circ Arrhythm Electrophysiol 2011;4: 630 – 6. 18. Ruby RS, Wells D, Sankaran S, Good E, Jongnarangsin K, Ebinger M et al. Prevalence of fever in patients undergoing left atrial ablation of atrial fibrillation guided by barium esophagraphy. J Cardiovasc Electrophysiol 2009;20:883–7. 19. Lim HS, Schultz C, Dang J, Alasady M, Lau DH, Brooks AG et al. Time course of inflammation, myocardial injury, and prothrombotic response after radiofrequency catheter ablation for atrial fibrillation. Circ Arrhythm Electrophysiol 2014;7:83 –9.
Safety of PVI using PVAC vs. irrigated RF catheter
20. Weber R, Minners J, Restle C, Buerkle G, Neumann FJ, Kalusche D et al. Pulmonary edema after extensive radiofrequency ablation for atrial fibrillation. J Cardiovasc Electrophysiol 2008;19:748 –52. 21. Malmborg H, Lonnerholm S, Blomstrom P, Blomstrom-Lundqvist C. Ablation of atrial fibrillation with cryoballoon or duty-cycled radiofrequency pulmonary vein ablation catheter: a randomized controlled study comparing the clinical outcome and safety; the AF-COR study. Europace 2013;15:1567 –73. 22. Mulder AA, Balt JC, Wijffels MC, Wever EF, Boersma LV. Safety of pulmonary vein isolation and left atrial complex fractionated atrial electrograms ablation for atrial
Page 7 of 7 fibrillation with phased radiofrequency energy and multi-electrode catheters. Europace 2012;14:1433 –40. 23. Hummel J, Michaud G, Hoyt R, Delurgio D, Rasekh A, Kusumoto F et al. Phased RF ablation in persistent atrial fibrillation. Heart Rhythm 2014;11: 202 – 9. 24. De Greef Y, Buysschaert I, Schwagten B, Stockman D, Tavernier R, Duytschaever M. Duty-cycled multi-electrode radiofrequency vs. conventional irrigated point-bypoint radiofrequency ablation for recurrent atrial fibrillation: comparative 3-year data. Europace 2014;16:820 –5.
CLINICAL RESEARCH
Europace doi:10.1093/europace/euv046
Safety profile of multielectrode-phased radiofrequency pulmonary vein ablation catheter and irrigated radiofrequency catheter K. Wasmer, P. Foraita, P. Leitz, F. Gu¨ner, C. Pott, P.S. Lange, L. Eckardt, and G. Mo¨nnig* Division of Electrophysiology, Department of Cardiovascular Medicine, University of Muenster, Albert-Schweitzer-Campus 1, Building A1, 48149 Muenster, Germany Received 17 June 2014; accepted after revision 13 February 2015
Silent cerebral lesions with the multielectrode-phased radiofrequency (RF) pulmonary vein ablation catheter (PVACw) have recently been investigated. However, comparative data on safety in relation to irrigated RF ablation are missing. ..................................................................................................................................................................................... Methods One hundred and fifty consecutive patients (58 + 12 years, 56 female) underwent first pulmonary vein isolation (PVI) for atrial fibrillation (61% paroxysmal) using PVACw (PVAC). Procedure data as well as in-hospital complications were and results compared with 300 matched patients who underwent PVI using irrigated RF (iRF). Procedure duration (148 + 63 vs. 208 + 70 min; P , 0.001), RF duration (24 + 10 vs. 49 + 25 min; P , 0.001), and fluoroscopy time (21 + 10 vs. 35 + 13 min; P , 0.001) were significantly shorter using PVAC. Major complication rates [major bleeding, transitoric ischaemic attack (TIA), and pericardial tamponade] were not significantly different between groups (PVAC, n ¼ 3; 2% vs. iRF n ¼ 17; 6%). Overall complication rate, including minor events, was similar in both groups [n ¼ 21 (14%) vs. n ¼ 48 (16%)]. Most of these were bleeding complications due to vascular access [n ¼ 8 (5.3%) vs. n ¼ 22 (7.3%)], which required surgical intervention in five patients [n ¼ 1 (0.7%) vs. n ¼ 4 (1.3%)]. Pericardial effusion [n ¼ 4 (2.7%) vs. n ¼ 19 (6.3%); pericardial tamponade requiring drainage n ¼ 0 vs. n ¼ 6] occurred more frequently using iRF. Two patients in each group developed a TIA (1.3% vs. 0.6%). Of note, four of five thromboembolic events in the PVAC group (two TIAs and three transient ST elevations during ablation) occurred when all 10 electrodes were used for ablation. ..................................................................................................................................................................................... Conclusion Pulmonary vein isolation using PVAC as a ‘one-shot-system’ has a comparable complication rate but a different risk profile. Pericardial effusion and tamponade occurred more frequently using iRF, whereas thromboembolic events were more prevalent using PVAC. Occurrence of clinically relevant thromboembolic events might be reduced by avoidance of electrode 1and 10 interaction and uninterrupted anticoagulation, whereas contact force sensing for iRF might minimize pericardial effusion.
Background
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Atrial fibrillation † Pulmonary vein isolation † Safety † Irrigated radiofrequency ablation † Multielectrode-phased radiofrequency ablation
Introduction Electrical isolation of pulmonary veins is the cornerstone of catheter ablation for patients with symptomatic atrial fibrillation (AF).1 Although the irrigated point-by-point radiofrequency (RF) ablation is the most frequently used technology, various alternative techniques such as the ‘pulmonary vein ablation catheter’ (PVACw, Medtronic
Inc., Minneapolis, MN, USA) have been developed to facilitate pulmonary vein isolation (PVI). This ‘one-shot-system’ achieves comparable clinical outcome but has the advantage of shorter procedure duration as well as lower fluoroscopy time.2 – 5 Concerns have been raised about the safety of this system after detection of increased incidence of silent cerebral embolism using this phased RF ablation device in comparison with irrigated tip RF ablation or
* Corresponding author. Tel: +49 (0)251/8347581; fax: +49 (0)251/8349965, E-mail address: [email protected] Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2015. For permissions please email: [email protected].
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What’s new? † First single-centre direct comparison of PVI using irrigated vs. phased RF ablation with focus on clinical relevant safety endpoints. † We found comparable safety endpoints but different risk profile. † Pericardial effusion and bleeding (groin haematoma) occurred more often using irrigated RF ablation. † New evidence for reducing the increased thromboembolic risk (clinical manifest endpoints rather than silent cerebral lesions) by avoiding electrode 1–10 interaction in phased ablation. † Perspective of possibly lower thromboembolic risk with the new designed phased RF catheter (PVAC Goldw).
cryoablation has been reported.6 – 9 We and other groups have demonstrated that avoidance of an interaction between electrode 1 and 10 can reduce both, silent cerebral microembolism as well as the rate of microembolic signals (MES) detected by transcranial Doppler ultrasound.10 – 12 However, data on safety endpoints and complication rates in direct comparison with the predominant energy source of irrigated RF are still lacking.
Patients and methods Patient cohort We performed a retrospective, single-centre case-control study. Patients who had undergone first PVI without additional linear lesions or ablation of complex fractionated electrograms between 2010 and 2013 with either PVAC or conventional irrigated RF ablation were included in the analysis. All patients had antiarrhythmic drug refractory symptomatic, persistent, or paroxysmal non-valvular AF. Patients with long-standing persistent AF, previous surgical or non-surgical left atrial ablation, including PVI, were not included to achieve a homogenous patient cohort. One hundred and fifty consecutive patients who had undergone multielectrode-phased RF PVI served as study population (PVAC group). These patients were gender- and age-matched in a 1 : 2 manner to 300 patients who had undergone conventional irrigated RF PVI during the same time period (iRF group). The ablation technology was chosen according the operator’s preference. It was not related to specific criteria, namely PV anatomy.
Periprocedural management The study was performed before ablation under uninterrupted vitamin K-antagonist (VKA) was introduced. Accordingly, VKA was discontinued 1 day prior to admission/procedure. In anticoagulated patients with INR value ,2.0 upon admission bridging with weight-adjusted lowmolecular-weight heparin was performed. New oral anticoagulants (Dabigatran, Rivaroxaban) were discontinued 1 day prior to the ablation procedure. A transoesophageal echocardiogram was performed in all patients within 24 h prior to ablation to exclude left atrial thrombus formation. All patients underwent a computed tomography of the heart and the anatomy of the left atrium (LA) and the PVs were reconstructed (EnSite Verismo, St. Jude Medical, St. Paul, MN, USA) to better understand anatomy (PVAC) and to guide catheter ablation (NavX).
K. Wasmer et al.
All patients received oral anticoagulation for 2 months post ablation. Long-term oral anticoagulation was recommended as indicated by current guidelines.1
Ablation procedure Written informed consent was obtained prior to each ablation procedure. All ablation procedures were performed under conscious sedation. Midazolam and piritramide were administered at the discretion of the operator. During the ablation procedure, surface electrocardiograms and bipolar intra-cardiac electrograms were registered using a digital recording system (Axiom Sensis XP, Siemens AG, Erlangen, Germany or a Prucka GE Medical The General Electric Company, Fairfield, CT, USA). Signals were sampled at 1 kHz, filtered at 0.1 – 100 Hz for surface electrocardiograms and at 30 – 250 Hz for intra-cardiac signals. The ablation protocols of our institution for phased and irrigated RF ablation have been described in detail previously.2,11 In brief, ablation was performed as follows.
Phased radiofrequency ablation After gaining femoral venous access, a steerable decapolar catheter (Lifewire, St. Jude Medical, St. Paul, MN, USA) was placed into the coronary sinus. A single transseptal puncture (TSP) was done using a 10-F nonsteerable sheath (Arrive, Medtronic Inc., Minneapolis, MN, USA) under fluoroscopy guidance with continuous pressure monitoring. The long sheath was continuously perfused with heparinized saline solution. Subsequently, a bodyweight-adjusted heparin bolus was applied. The activated clotting time (ACT) was monitored in 30 min intervals with a target ACT between 250 and 350 s. Additional Heparin boli were given if necessary. The ablation procedure was continued irrespective of the ACT value. Selective angiography of the PVs was performed with 50 mL of non-ionic contrast (Ultravist 370, Bayer, Germany). The 10 pole-phased RF catheter (PVACw, Medtronic Inc., Minneapolis, MN, USA) was placed at the ostium of each PV using over-the-wire technique (PV-Tracker, Medtronic Inc., Minneapolis, MN, USA). Ablation was performed exclusively with a 4 : 1 bipolar/unipolar ratio and a maximum power of 8 W for 1 min. In the first 66 patients, all 10 electrodes of the PVACw catheter were activated. After publication of reports finding an association of electrodes 1 and 10 interaction during ablation and increased risk for embolic complications, pair 1 or 5 was deactivated throughout each procedure in the remaining 84 patients. Temperature limit was set to 608C. After each ablation, conduction into the PV was tested and ablation was repeated at sites with remaining conduction. Electrode pairs without tissue contact or positioned at sites without conduction were deactivated at the operators’ discretion. This procedure was repeated until PVI was completed. If AF persisted after ablation, sinus rhythm was restored by electrical cardioversion. Complete isolation of the PVs was then confirmed during sinus rhythm and during coronary sinus and in some cases by left atrial appendage pacing. Protamine was applied once the catheter and sheath had been removed from the LA. Anticoagulation was started/restarted 12 h after ablation. If VKA was used the patient was bridged with Heparin until INR was .2.0.
Irrigated tip radiofrequency ablation In patients undergoing conventional irrigated tip RF ablation, access to the LA was achieved by performing two separate TSPs. A non-steerable sheath (Daig SL1, St. Jude Medical. St. Paul, MN, USA) for the diagnostic circular decapolar catheter (Inquiry Optima, St. Jude Medical, St. Paul, MN, USA), and a deflectable long sheath (Agilis, St. Jude Medical, St. Paul, MN, USA) for the ablation catheter were placed in the LA. Both long sheaths were continuously flushed with heparinized saline
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Safety of PVI using PVAC vs. irrigated RF catheter
solution. Management of anticoagulation including ACT measurements and heparin dosage were identical to the phased RF group. After selective, simultaneous angiography of the ipsilateral PVs and acquisition of the individual 3D anatomy of the LA (Ensite NavX Velocity, St. Jude Medical, St. Paul, MN, USA, with image integration), antral circumferential RF ablation around ipsilateral PVs using a 4-mm open-tipirrigated catheter (IBI Therapy Coolpath Duo, St. Jude Medical) was performed. Maximum power was set to 30 W. Temperature was limited to 438C. Electrical cardioversion was performed if the patient remained in AF after PV isolation and PV isolation was subsequently confirmed during sinus rhythm and pacing as described above. Anticoagulation regime was the same as in phased RF (see above).
Study endpoints and follow-up Major safety endpoints were predefined as major bleeding, transitoric ischaemic attack (TIA), stroke, pericardial tamponade with need for pericardiocentesis, clinically manifest pulmonary stenosis, and death. Overall safety endpoints additionally including minor/minimal bleeding, transient myocardial ischaemia (transient ST-elevation), minor pericardial effusion, and transient fever. Bleeding included minor haematoma at the site of vascular access via femoral vein as well as major bleeding (e.g. haemoglobin fall .20 g/l; haemodynamic instability; need for surgical intervention or for transfusion) as defined by the International Society on Thrombosis and Haemostasis.13 In case of transient fever (body temperature .38.08C), prophylactic antibiotic therapy was given to prevent pulmonary infection. All patients were routinely investigated for these endpoints prior to discharge after PV including an echocardiography. After 3 – 6 months, all patients were scheduled to be seen in our outpatient clinic to re-evaluate the procedural outcome and complications. Patients who missed the follow-up visit were contacted by phone and followed up. Twelve patients were lost to follow-up (2.7%).
Statistics All statistical analyses were performed using SPSS 21.0 (IBM Corporation, Armonk, NY, USA). Continuous variables are presented as mean + SD. Statistical comparison of safety endpoints between the groups as well as between the operators was performed by x2-test. Mann–Whitney U-test was performed for non-parametric data. A P-value of ,0.05 was considered statistically significant.
Results Patient characteristics and procedural data A total number of 450 patients were included into the analysis. There was no significant difference concerning baseline characteristics and cardiovascular risk factors between the PVAC and the iRF group (Table 1). More specifically, the pre-ablation thromboembolic risk determined by CHA2DS2-VASc-Score and also the anticoagulation status were not significantly different between both groups (Table 1). Furthermore, the percentage of patients with PVI under INR .2 was equally distributed between both groups (Table 1). Total procedure duration, fluoroscopy time, and ablation duration were significantly lower in the phased RF group (PVAC) compared with those in the irrigated iRF group (Table 2). The dose of sedation per procedure (midazolam 6.2 + 2.7 vs. 7.0 + 3.2 mg; P ¼ 0.011) and analgesic medication (piritramide 11.3 + 4.7 vs. 13.8 + 6.0 mg; P , 0.001) was slightly but significantly lower in the PVAC group. Activated clotting time .250 s was reached in all patients after the
Table 1 Baseline characteristics of irrigated vs. phased RF ablation groups Irrigated iRF n 5 300
Phased RF Significance (PVAC) n 5 150
................................................................................ Age (mean + SD, years)
59 + 11
59 + 12
Male/female (n)
191/109
94/56
ns
Hypertension (n; %) Diabetes (n; %)
194; 65% 22; 8%
93; 62% 12; 8%
ns ns
Arterial embolism (n)
0
0
ns
Structural heart disease (n; %)
54; 18%
19; 13%
ns
Vascular disease (n; %) CHA2DS2-Vasc (mean)
49; 16% 1.8
27; 18% 2.0
ns ns
AF type (PAF/PersAF)
199/101
Oral anticoagulation (n; %) 188; 62% VKA (n; %) 172; 57% Dabigatran (n; %)
ns
99/51
ns
90; 60% 74; 49%
ns ns
9; 3%
7; 5%
ns
Rivaroxaban (n; %) INR (mean + SD)
7; 2% 1.7 + 0.7
9; 6% 1.6 + 0.6
ns ns
INR . 2 (n; %)
72; 24%
32; 21%
ns
AF, atrial fibrillation; INR, international normalized ratio; ns, non-significant; PAF, paroxysmal atrial fibrillation; PersAF, persistent atrial fibrillation; VKA, vitamin K antagonist.
Table 2 Procedural characteristics of irrigated vs. phased RF ablation groups Irrigated iRF n 5 300
Phased RF (PVAC) n 5 150
Significance
208 + 70
148 + 64
,0.001
Fluoroscopy time (mean, min)
35 + 13
21 + 10
,0.001
Time of energy delivery (mean, min)
49 + 25
24 + 10
,0.001
................................................................................ Total procedure duration (mean, min)
Cardioversion (n; %)
90; 30%
48; 32%
ns
min, minutes; ns, non-significant.
second ACT-check. Length of hospital stay was not different between groups (Figure 1).
Safety endpoints Major safety endpoints were present in 20 patients (4.4%) and more frequent in the iRF group (Table 3 and Figure 1). No death, stroke, or haemorrhagic shock occurred in any of the patients. Overall safety endpoints occurred in 73 patients (Table 3 and Figure 1) and was distributed equally (P ¼ 0.91) between the PVAC [n ¼ 25 (17%)] and the iRF group (n ¼ 48 (16%). There was no significant difference in safety endpoints between operators in univariate
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K. Wasmer et al.
iRF
Table 4 Characteristics of patients with vs. without safety endpoint
8
PVAC
7
7
6
6
5
5
4
4
3
3
2
2
1
1
0
0
Days
Percent
8
Pericardial Bleeding Embolic Fever Major Hospital effusion (total) event complication stay (days) Safety endpoint/hospital stay
Figure 1 Safety endpoints and hospital stay in AF-patients treated with RF (iRF; n ¼ 300) or multipolar-phased RF (PVAC; n ¼ 150). Major complication including major bleeding, TIA, and pericardiocentesis. Embolic event including transient ST elevation and TIA.
Safety endpoint n 5 73
No safety endpoint n 5 377
Significance
Age (mean + SD, years)
63 + 9
57 + 11
ns
Male/female (n)
34/39
251/125
0.001
CHA2DS2-Vasc (mean) AF type (PAF/PersAF)
2.2 62/11
1.8 236/141
ns 0.001
Total procedure duration (mean, min)
187 + 54
188 + 77
ns
Time of energy delivery (mean, min)
39 + 24
41 + 24
ns
INR . 2 (n; %)
16; 22%
88; 23%
ns
3+2
0.001
................................................................................
Hospital stay (mean + SD; 6 + 4 days)
AF, atrial fibrillation; INR, international normalized ratio; ns, non-significant; PAF, paroxysmal atrial fibrillation; PersAF, persistent atrial fibrillation.
Table 3 Adverse events after pulmonary vein isolation using irrigated or phased RF ablation Irrigated iRF n 5 300
Phased RF Significance (PVAC) n 5 150
22; 7%
8; 5%
ns
13; 4% 9; 3%
7; 5% 1; 1%
ns ns
Haemoglobin loss .2 g/dL (n; %)
5; 2%
1; 1%
ns
Surgical intervention (n; %)
4; 1%
1; 1%
ns
TIA (n; %)
2; 1%
2; 1%
ns
Transitoric ST-elevation (n; %)
0
3; 2%
0.04
Pericardial effusion (n; %) 19; 6% Pericardiocentesis (n; %) 6; 2%
4; 3% 0
0.06 0.08
Fever (n; %)
5; 2%
4; 3%
ns
Death (n) Major safety endpoints
0 17; 6%
0 3; 2%
– 0.06
21; 14%
ns
................................................................................ Total bleeding (n; %) Minor bleeding (n; %) Major bleeding (n; %)
Total safety endpoints (n; %) 48; 16%
Adverse events are shown in total number (n) and percentage (%) of the subgroup. Major safety endpoints including major bleeding, TIA, and pericardiocentesis. Exact P-value were given for P , 0.1 (ns, non-significant).
analysis. The most frequent complications were bleeding events due to vascular access [in total n ¼ 30 (6.7%)] or pericardial effusion [in total n ¼ 23 (5.1%)]. Most of the pericardial effusions were detected during routine pre-discharge echocardiography and had no haemodynamic impact (n ¼ 17; 3.8%). Pericardial tamponade requiring emergent pericardiocentesis occurred in six iRF patients (1.33% of all patients; 2% of iRF patients). There was a trend to a higher incidence of major bleedings and pericardial effusion in the iRF group (Table 3 and Figure 1). Transient embolic events defined
as TIA or transient ST elevation without elevated cardiac enzymes [n ¼ 5 (3%) vs. n ¼ 2 (1%), P ¼ 0.044; Table 3 and Figure 1] occurred significantly more often in the PVAC group. Interestingly, four of five embolic events occurred during activation of all 10 electrodes (4/66 ¼ 6% vs. 1/84 ¼ 1%). Nine patients presented with transient fever that occurred 1 day after PVI and was treated with prophylactic antibiotic therapy. This complication was slightly more prevalent in the PVAC group (Table 3 and Figure 1). Overall safety endpoints were not different between patients ablated under INR .2 and interrupted anticoagulation (15% vs. 17%; P ¼ 0.58). Especially, bleeding complications were equally distributed in both groups (0.07%). In univariate analysis, female gender and paroxysmal AF was more frequent in patients with safety endpoints after PVI (Table 4). All other baseline or procedural characteristics were not different. The hospital stay was longer in patients with complications (Table 4). During a mean follow-up of 10.4 months, no late complications occurred. Patients with complications at the time of the procedure were all doing well at follow-up. No symptoms persisted from previous complications. There was no significant impairment due to procedure-related complications at the time of follow-up.
Discussion Uncertainty surrounds the choice of energy source in PVI. While we and other groups have shown that PVAC and iRF have similar outcomes with regard to the maintenance of sinus rhythm,2,3 the safety profile becomes an important criterion to select the right catheter setting in the individual patient. Here, we present data obtained in a single-centre retrospective case–control study. Specifically, we show that PVI using the multipolar PVACatheter is as safe as irrigated iRF PVI in a head-to-head comparison. This is a remarkable observation considering that the catheter setting is different between both groups.
Safety of PVI using PVAC vs. irrigated RF catheter
Deshmukh and co-workers found a correlation of age and gender with the occurrence of any PVI-associated in-hospital complication in 93 801 procedures of the Nationwide Inpatient Sample.14 We could confirm the association of the female gender, but not the age with safety endpoints in our cohort. The longer hospital stay of patients with complications is not surprising and concordant with the analysis of Deshmukh et al. None of the other characteristics were associated with safety endpoints in our study.
Comparing pulmonary vein ablation catheter and irrigated radiofrequency Pulmonary vein ablation catheter requires only one TSP; however, the vascular access at the femoral vein is larger (10 F). In addition, reports of a higher thromboembolic risk using PVAC suggested worse safety profile with this technique.6,7 Irrigated iRF PVI on the other hand requires a longer procedure time compared with PVAC and two TSPs are necessary instead of one as well as two 8 F sheats for venous access. These technical differences could be associated with a different safety profile. However, in the setting of equally experienced investigators and comparable study populations, this study is the first to demonstrate a similar complication rate despite the abovementioned differences. However, there was a different profile of adverse events: while bleeding and pericardial effusion were observed more frequently in the iRF group, embolic events and fever occurred more often in the PVAC group. The need for two venous and TSPs with irrigated iRF may be causing bleeding and pericardial effusion in the iRF group. Use of steerable long sheath with contact force sensing of the ablation catheter may have reduced incidence of pericardial effusions in the iRF group. In animal model using the multipolar PVACatheter, the largest source of gaseous and solid emboli occurred when the distal and proximal electrodes (1 and 10) were in close proximity or overlapping.15 This electrode overlap creates bipolar short circuit resulting in excessive heating of tissue and blood. Therefore, it is not surprising that four of five embolic events occurred during activation of all 10 electrodes. Following deactivation of electrode pair 1 or 5, we observed fewer MES11 and only one additional embolic event (TIA). As the novel catheter design of the PVAC Gold w array might improve safety by reducing embolic events as it prevents electrodes 1–10 interaction and allows for enhanced tissue contact due to the 208 forward tilt we still use both systems (PVAC and irrigated RF) for index PVI. Although no clinical data on this new array are available yet, it appears to be as safe and feasible in our own preliminary experience with the first PVAC Gold w PVIs (n ≈ 50) when compared with the former PVAC array (P. Leitz and G. Mo¨nnig unpublished data). All PV veins were reached by the novel array and no clinical manifest complication occurred so far. Performing PVI on continued VKA with lower INR of 2.0– 2.5 might further reduce the incidence of thromboembolic complications. The overall complication rate of 16% was remarkably highly compared with published data of major complication rates between 4% and 6% in the largest multi-centre registry.16 When taking only the major events into account (10 major bleedings, four TIAs, and six pericardiocentesis; Table 3) complication rate of 4.4% in our cohort is quite in line with the published major complication rate of
Page 5 of 7 4.54%.16 Likewise, the percentage of pericardial tamponade of our group was in line with the reported of the world wide survey by Cappato and co-workers (1.31% vs. 1.33% in our cohort).16 However, no comparable data from this world wide cohort are available for pericardial effusions without haemodynamic impact. Pulmonary vein stenosis has been recognized as a complication of PVI using RF energy and has also been described in patients treated with multipolar PVAC RF catheter.17 In our patient cohort, there was no clinical evidence or significant PV narrowing in 35 PV angiographies after PVAC ablation that were performed during additional ablation procedures due to AF recurrence. No patient reported symptoms of pulmonary vein stenosis (i.e. dyspnoea); however, we did not systematically screen for PV stenosis by routine imaging. Fever after PVI has been described to occur in 10% of patients by Ruby and co-workers.18 They discuss atelectasis, pneumonitis, pericarditis, haematoma at the access site, venous thromboembolism, thrombophlebitis and rarely, oesophageal injury as potential causes. Another reason for elevated body temperature may be nonspecific inflammation after PVI as described by Lim et al. 19 None of our patients had clinical signs of pulmonary oedema as described by Weber and co-workers after extensive ablation.20 As we investigated different ablation approaches, it appears reasonable that particularly the degree of inflammation associated with PVI might differ between PVAC and iRF. While we have screened for elevated body temperature only it is highly speculative to hypothesize an increased inflammation response to PVAC-PVI. Nevertheless, the prophylactic administration of antibiotic therapy to prevent respiratory infection might be questionable.
Safety of pulmonary vein ablation catheter in previous studies Safety and complications using PVAC have been described for AF-ablation in several studies.21 – 24 However, none of these studies report a direct comparison between PVAC and the predominant ablation technique of irrigated RF. The largest study including 502 PVAC index procedures is that of Mulder and co-workers.22 They reported major complications in 2.0% and additional minor complications in 12.9% of the patients. The overall complication rate of that study (15%) is similar to our data. In that study, the procedural time as well as the fluoroscopy time was shorter (86 min and 20 min, respectively). This might point to the importance of a learning curve since these data come from one of the centres with most experience in the PVAC procedure. In a study by Malmborg and co-workers, 110 AF patients were randomized to either Cryo balloon or PVAC.21 In that study, only one periprocedural complication (major groin haematoma) occurred in the PVAC group compared with four in the Cryo group (groin haematoma in two and phrenic nerve paralysis in another two patients). The total procedure time was similar in both groups (165 min) with shorter fluoroscopy time using cryoballon (32 vs. 47 min). We found shorter study duration of 148 min with shorter fluoroscopy time of 21 min in our study. However, overall complication rate was higher compared with the data by Malmborg which may be due to the inclusion of minor complications in our study. A recently published study (TTOP-AF) investigated efficacy and safety of phased RF in patients with persistent AF.23 In that study,
Page 6 of 7 21 acute major adverse events occurred in 17 of 138 patients (12.3%). Stroke occurred in additional four patients (2.9%) and PV stenosis in five (one patient with symptoms). Including these symptomatic patients (n ¼ 22), the overall complication rate (16%) is equal to our data. Another recent study published by De Greef and co-workers compared the long-term outcome of patients undergoing PVI with irrigated RF and phased RF with focus on the long-term outcome.24 In this non-randomized study, there was no difference in outcome or safety between both strategies. There was one major (PV stenosis) and three minor complication (gastroparesis and two groin haematoma) reported in the PVAC group (n ¼ 79; 5.1%) compared with one major (pericardial tamponade) and four minor complications (two patients with pericarditis, groin haematoma, and ‘fluid retention syndrome’) in the iRF group (n ¼ 82; 6.1%). The spectrum of complications might be somewhat different to our observation except the groin haematoma and pericardial tamponade because the focus of that study with smaller groups was on the long-term outcome rather than on the safety aspect of these two strategies. However, the comparable safety between both groups is in good concordance with our finding.
Limitations The descriptive nature of this retrospective analysis is the main limitation that could lead to patient selection bias. We are presenting a retrospective single-centre case–control analysis without a randomized design. Therefore, there is a lack of homogeneity in the anticoagulation strategy around the procedure. Furthermore, the ablation procedures were performed by a constant group of six operators in a single EP lab over the same time period with the same anticoagulation regime between both groups. Even without significantly different safety endpoints for individual operators the influence on complications cannot be fully excluded by this design of study. However, we believe that the conditions of both procedures are very comparable.
Conclusion We found further evidence for shorter procedure duration and lower fluoroscopy time in consecutive index PVI patients using PVACatheter. Of note, complication rate was comparable with irrigated iRF. Safety profile, though was different with more pericardial effusions and bleeding complications in the iRF group while more embolic and infectious events were observed in the PVAC group. Avoidance of electrodes 1– 10 interaction by deactivating electrode pair 1 or 5 seems to reduce clinical relevant thromboembolic events. The novel catheter design (PVAC Gold w) may improve safety by reducing embolic risk, although clinical data are lacking so far. Performing PVI on continued anticoagulation and the use of contact force sensing for iRF might minimize complications irrespective of the technology used. Conflict of interest: K.W., L.E., G.M., and C.P. have received lecture honoraria and travel grants from Astra/Zeneca, Bayer, Biosense Webster, Biotronik, Boehringer Ingelheim, Boston Scientific, Medtronic, Sanofi Aventis, and St. Jude Medical. L.E. has received research grants from Biotronik, St. Jude Medical, Sanofi, and Osypka. C.P. was
K. Wasmer et al.
supported by a grant by the Deutsche Stiftung fu¨r Herzforschung (F 44/12).
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