Europace Advance Access published April 2, 2015
CLINICAL RESEARCH
Europace doi:10.1093/europace/euv060
Comparison between radiofrequency with contact force-sensing and second-generation cryoballoon for paroxysmal atrial fibrillation catheter ablation: a multicentre European evaluation Fabien Squara1,2*, Alexandre Zhao 2, Eloi Marijon 3,4, Decebal Gabriel Latcu 5, Rui Providencia 3, Giacomo Di Giovanni 6, Gae¨l Jauvert2, Francois Jourda 3, Gian-Battista Chierchia 6, Carlo De Asmundis 6, Giuseppe Ciconte 6, Christine Alonso 2, Caroline Grimard 2, Serge Boveda3, Bruno Cauchemez 2, Nadir Saoudi 5, Pedro Brugada6, Jean-Paul Albenque 3, and Olivier Thomas 2 1 Cardiology Department, Pasteur University Hospital, 30 Voie romaine, 06000 Nice, France; 2Clinique Ambroise Pare´, Neuilly, France; 3Clinique Pasteur, Toulouse, France; 4Cardiology Department, European Georges Pompidou Hospital, Paris, France; 5Service de Cardiologie, Centre Hospitalier Princesse Grace, Monaco; and 6Heart Rhythm Management Centre, UZ Brussel-VUB, Brussels, Belgium
Received 28 November 2014; accepted after revision 10 February 2015
Aims
Whether pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation (PAF) using contact force (CF)-guided radiofrequency (RF) or second-generation cryoballoon (CB) present similar efficacy and safety remains uncertain. ..................................................................................................................................................................................... Methods We performed a multicentre study comparing procedural safety and arrhythmia recurrence after standardized PVI catheter ablation for PAF using CF-guided RF ablation (Thermocoolw SmartTouchTM , Biosense Webster; or TacticathTM , St and results Jude Medical) (CF group) with second-generation CB ablation (Arctic Front AdvanceTM , Medtronic) (CB group). Overall, 376 patients (mean age 59.8 + 10.4 years, 280 males) were enrolled in 4 centres: 198 in CF group and 178 in CB group. Procedure was shorter for CB group than for CF group (109.6 + 40 vs. 122.5 + 40.7 min, P ¼ 0.003), but fluoroscopy duration and X-ray exposure were not statistically different (P ¼ 0.1 and P ¼ 0.22, respectively). Overall complication rate was similar in both groups: 14 (7.1%) in the CF group vs. 13 (7.3%) in the CB group (P ¼ 0.93). However, transient right phrenic nerve palsy occurred only in CB group (10 patients, 5.6%; P ¼ 0.001 vs. CF group) and severe non-lethal complications (embolic event, tamponade, or oesophageal injury) occurred only in CF group (5 patients, 2.5%; P ¼ 0.03 vs. CB group). No periprocedural death occurred in either group. Single-procedure freedom from any atrial arrhythmias at 18 months post-ablation was comparable in CF group and CB group (76 vs. 73.3%, respectively, log rank P ¼ 0.63). ..................................................................................................................................................................................... Conclusion Pulmonary vein isolation using CF-guided RF and second-generation CB leads to comparable single-procedure arrhythmia-free survival at up to 18 months with similar overall complication rate.
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Atrial fibrillation † Ablation † Radiofrequency † Cryoballoon
Introduction Since the seminal observation that pulmonary vein (PV) ectopies can trigger atrial fibrillation (AF), PV isolation (PVI) has become the
cornerstone of AF ablation therapy in paroxysmal AF.1 The selection of the energy—radiofrequency (RF) or cryothermal—for achieving PVI in paroxysmal AF still remains at the discretion of the operator. One study has demonstrated that wide antral PVI using conventional
* Corresponding author. Tel: +33 492038530; fax: +33 492037872, 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? † This multicentre study provides evidence that radiofrequency ablation using contact force-sensing catheters and cryoballoon ablation have comparable efficacy at 18 months after paroxysmal atrial fibrillation ablation, with similar overall complication rate. However, severe non-lethal complications tend to occur more frequently with radiofrequency. † Mean procedure duration is slightly shorter using cryoballoon ablation, but X-ray exposure is equivalent. † Large randomized studies are warranted to confirm these findings.
point-by-point RF had similar single-procedure success rate than PVI using first-generation cryoballoon (CB).2 However, both technologies benefited lately from significant material improvements with the advent of contact force (CF)-sensing RF catheters and secondgeneration CB, both showing improved outcomes compared with the older models.3 – 8 Recently, Jourda et al. 9 have provided preliminary data suggesting that new CF-sensing RF catheters and secondgeneration CB might lead to comparable outcomes at 12 months. In the present multicentre study, we sought to confirm these findings in a large number of patients, comparing safety and efficacy of CF-sensing RF catheters with second-generation CB catheter in the setting of paroxysmal AF catheter ablation.
Methods Study population Consecutive patients undergoing antral PVI for paroxysmal AF ablation using a CF-sensing RF catheter (CF group) or a second-generation CB (CB group) were enrolled in the study. Four different European centres participated in patients’ recruitment (Clinique Ambroise Pare´, Neuilly-sur-Seine, France; Clinique Pasteur, Toulouse, France; UZ Brussel-VUB, Brussels, Belgium; and Centre Hospitalier Princesse Grace, Monaco). This was an ambidirectional cohort study, with patients enrolled either prospectively or retrospectively. Patients were eligible if they presented with paroxysmal AF refractory to antiarrhythmic therapy, and were undergoing a first PVI procedure using either (i) a CF-sensing RF catheter (Thermocoolw SmartTouchTM , Biosense Webster, Inc., Diamond Bar, CA; or TacticathTM , St Jude Medical, Inc., St Paul, MN) or (ii) a second-generation CB (Arctic Front AdvanceTM , Medtronic, Minneapolis, MN). Exclusion criteria were: follow-up of ,6 months at the time of the study, additional linear ablations except for cavo-tricuspid isthmus (CTI) line (i.e. roof line, mitral isthmus line), complex-fractionated electrograms (CFAEs) ablation, repeat AF ablation, and the lack of the use of a three-dimensional (3D) electroanatomic mapping (EAM) system when RF was the selected energy. Importantly, patient selection for one or the other energy group was not made depending on the patient’s characteristics (i.e. PV anatomy) but only on the habits of the electrophysiology physician performing the ablation procedure. Specifically, each electrophysiology physician used always the same ablation energy (either RF or cryothermal) for all his AF ablations, regardless of PV anatomy. All patients provided an informed consent prior to the procedure. The study complied with the Declaration of Helsinki and the research protocol was approved by the local Ethics Committee.
F. Squara et al.
Ablation procedure: common elements between contact force and cryoballoon groups Left atrium (LA) computed tomography scan or magnetic resonance imaging was performed 24 h prior to the procedure, to assess PV anatomy, LA dimensions and to exclude the presence of a potential LA thrombus. Procedures were performed under a mild sedation or under general anaesthesia, depending on the physician performing the procedure. A quadripolar or decapolar catheter was positioned in the coronary sinus, through a transfemoral venous access. A single or double transseptal puncture was performed under fluoroscopic guidance. Depending on the operator, transoesophageal echocardiographic guidance could be used to guide the transseptal puncture. A bolus of unfractionated heparin was administered before the transseptal puncture and infusion was titrated to maintain activated clotting time .300 s for the duration of the procedure. Depending on the referring centre, vitamin-K antagonists (VKAs) were either interrupted before the procedure with periprocedural bridging with subcutaneous heparin, or the procedure was performed without VKA interruption with INR ,3. New oral anticoagulants were interrupted before the procedure in all centres.
Specific procedural details: contact force group In this group, the ablation catheter could be either of the two currently available CF-sensing catheters: (i) Thermocoolw SmartTouchTM that was coupled with the use of the Carto 3 EAM system (Biosense Webster) or (ii) TacticathTM that was coupled with the use of the Ensite Velocity EAM system (St Jude Medical). A circumferential mapping catheter (CMC; LassoTM ; Biosense Webster) was introduced into the LA using an 8.5 Fr long sheath. The ablation catheter was advanced into the LA either sequentially after removing the CMC (in case of single transseptal puncture) or simultaneously with the CMC (in case of double transseptal punctures). The ablation catheter and the CMC were used to collect LA geometry using the EAM system. The ablation strategy consisted of PVI using two wide antral circumferential RF ablations across ipsilateral PVs, without additional adjunctive LA ablation. Carina ablations were performed when PV isolation could not be achieved with antral isolation. Typically carina ablation targeted the earliest potential for both ipsilateral PVs identified at the carina. Powercontrolled RF ablation lesions were delivered with 30 –35 W power; the endpoint was elimination of the local bipolar EGM with 20 – 40 s lesions, or with force-time integral (FTI) .400 g s. A lower power (20 – 30 W) and duration settings were used for ablation on the posterior LA wall close to the oesophagus. Real-time catheter– tissue CF was continuously monitored using either the Carto 3 for the Thermocoolw SmartTouchTM catheter, or using the TactisysTM viewing platform (St Jude Medical) for the TacticathTM catheter. Contact force data were available to the operator throughout the procedure. The aim was to achieve a mean CF of at least 10 g during RF application. The upper limit defined was 50 g force.10 Oesophageal temperature monitoring was performed at the discretion of the operator. When used, the cut-off temperature was 38.58C. At the end of the procedure, a waiting period of at least 20 min was performed, and/or adenosine was administered intravenously (12– 18 mg) to assess for dormant LA– PV connections.11
Specific procedural details: cryoballoon group A 14-Fr deflectable sheath (FlexCathw, Medtronic) was advanced into the LA through the transseptal puncture. Then, the Arctic Front AdvanceTM CB was introduced into the sheath, inflated, and advanced to the ostium of each PV. The procedure was performed using the 28 mm CB in two centres, or with an anatomy-based individualized approach using the 23 or 28 mm CB in the remaining centres.12,13 Before
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Radiofrequency with contact force-sensing vs. second-generation cryoballoon
cryoenergy delivery, the occlusion of each PV was assessed with either a venous angiography or a venous pressure curve,14 at the discretion of the operator. Ablation of PV antra was performed with two applications of 240 s per vein. Continuous monitoring of the phrenic nerve during ablation of the right PVs was systematically performed by pacing the right phrenic nerve with a quadripolar catheter in the superior vena cava. Pulmonary vein isolation was either assessed continuously using the circular Achievew Catheter (Medtronic) during CB freezing or traditionally using a CMC (Lassow, Biosense Webster) after two applications. If the PV remained connected, additional applications were performed using different angulations. No oesophageal monitoring was done during cryoablation procedures. Pulmonary vein isolation was finally checked 20 min after the last CB ablation, and/or an intravenous adenosine challenge (12– 18 mg) was performed.
detailed in Figure 1. Most patients (276/376; 73%) were included prospectively. Within the CF group, 159 patients (80.3%) underwent PVI using the Thermocoolw SmartTouchTM catheter, and 39 patients (19.7%) using the TacticathTM catheter. Within the CB group, 150 patients (84%) underwent PVI using the 28 mm Arctic Front AdvanceTM CB and 28 patients (16%) using the 23 mm CB. Cavotricuspid isthmus ablation was performed in 23 patients (13%) of the CB group and in 46 patients (23%) of the CF group. Table 1 summarizes the characteristics of our study population. No statistical differences were found between CF group and CB group, except for age (61 + 9 years in CF group vs. 58.4 + 11.5 years in CB group, P ¼ 0.02). All the patients were off antiarrhythmic therapy at 3 months post-ablation.
Post-procedure clinical management
Procedural data and safety
A systematic transthoracic echocardiography and 24-h Holter monitoring were performed before hospital discharge. Depending on the referring physician, antiarrhythmic drugs were stopped before hospital discharge or were systematically continued for a period of 1 – 3 months post-ablation. A blanking period of only 1 month has been chosen in this study, since early arrhythmia recurrences at 1 – 3 months have proven to be predictive of late arrhythmia recurrences.15 – 18 Patients with recurrence of AF during the blanking period were cardioverted and antiarrhythmic drugs maintained until 3 months post-ablation. Subjects were then evaluated at 1, 3, 6, 9, 12, and 18 months. Information systematically collected during follow-up included clinical symptoms, a 12-lead electrocardiogram (ECG), and a 24 h-Holter ECG. Additional Holter ECGs were performed in case of symptoms of arrhythmias. Anticoagulation strategy after the first 3 months was based on the CHA2DS2Vasc and HAS-BLED scores.1
Procedural data and complications are detailed in Table 2. All PVs in both groups were successfully isolated during the procedure. Procedure duration was significantly shorter in CB group than in CF group (109.6 + 40 vs. 122.5 + 40.7 min, P ¼ 0.003). Comparison of fluoroscopy duration and X-ray exposure between CF group and CB group did not reach statistical significance (P ¼ 0.10 and P ¼ 0.22, respectively). In CF group, 61/198 (31%) patients underwent oesophageal temperature monitoring. The total number of complications in both groups was similar: 14 (7.1%) in the CF group vs. 13 (7.3%) in the CB group (P ¼ 0.93), including groin haematoma (4.0 vs. 1.7%, P ¼ 0.17). Transient phrenic nerve palsy occurred in 10 patients (5.6%) of the CB group vs. none of the CF group (P ¼ 0.001). No patient died in either group from a procedural complication, but severe complications (embolic event, tamponade, or oesophageal injury) occurred only in CF group (five patients, 2.5%; P ¼ 0.03 vs. CB group). Specifically, two patients (1%) of the CF group had a clot embolic event postablation vs. none of the CB-group patients (P ¼ 0.18). In addition, two patients (1%) of the CF group developed a cardiac tamponade during the procedure (for both patients, PVI was already achieved) vs. none of the CB-group patients (P ¼ 0.18). One patient (0.5%) of the CF group (without oesophageal temperature monitoring) suffered from digestive bleeding after the procedure, leading to oesophageal ulcer diagnosis.
Study endpoints The procedural endpoint was PVI with confirmed entrance and exit blocks. The long-term efficacy endpoint was freedom from any atrial arrhythmia lasting more than 30 s for up to 18 months after a single procedure (median 12 months, interquartile range: 10 – 18 months). The safety endpoint was a comparison of significant adverse events between groups.
Statistical analysis Continuous data are represented as mean SD or median and IQR as appropriate. Comparisons between two groups were made with Student’s t-tests and summarized with means and SDs for independent samples if normally distributed or, if not normally distributed, evaluated with the Mann– Whitney U-test and summarized with medians and quartiles. Nominal values are expressed as n (%) and compared with x 2 tests. Raw event rates were compared with x 2 tests, and event-free survival plots were made by the Kaplan– Meier method and compared with log-rank tests. Sensitivity analysis was performed by comparing long-term efficacy endpoint in patients ablated using the Thermocoolw SmartTouchTM catheter or the 28 mm Arctic Front AdvanceTM CB. A P-value of ≤0.05 was considered statistically significant throughout. SPSS Statistics software version 20 (IBM Corporation, Armonk, NY, USA) was used for descriptive and inferential statistical analysis.
Results Study population Overall, 376 patients were included: 198 in the CF group and 178 in the CB group. The number of patients included in each centre is
Long-term efficacy Patients were followed up for up to 18 months after the procedure. Median follow-up duration was 12 months (interquartile range: 10– 18 months) and the minimum follow-up duration was 6 months. In the CF group, 37 (18.7%) patients suffered from atrial arrhythmia recurrence vs. 34 (19.1%) patients in the CB group (P ¼ 0.92). Using the Kaplan –Meier survival analysis, single-procedure freedom from any atrial arrhythmias at 18 months post-ablation was comparable with CF group and CB group (76 vs. 73.3%, respectively, log rank P ¼ 0.63; Figure 2).
Sensitivity analysis Sensitivity analysis was performed by comparing the long-term efficacy of the ablation using the Thermocoolw SmartTouchTM (ST CF group; n ¼ 159 patients) and using the 28 mm Arctic Front AdvanceTM CB (28 mm CB group; n ¼ 150 patients). Singleprocedure freedom from atrial arrhythmias at 18 months post-ablation
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Cryoablation
Radiofrequency ablation
137 patients 69%
80 patients 45%
50 patients 28%
Neuilly-sur-Seine
48 patients 27%
40 patients 20%
21 patients 11%
Brussels Toulouse Monaco
Figure 1 Number of patients included in each centre, depending on the ablation energy.
Benefit of new radiofrequency and cryoballoon catheters
Table 1 Patient characteristics CF group (n 5 198)
CB group (n 5 178)
P-Value
Age Female gender
61 + 9 45 (12%)
58.4 + 11.5 50 (13.3%)
0.02 0.24
AF duration, months
57.8 + 57.9
46.9 + 53.2
0.08
................................................................................
Hypertension
74 (19.7%)
55 (14.6%)
0.08
Diabetes mellitus Cardiopathy (any) LA area (cm2)
13 (3.5%) 29 (7.7%)
14 (3.7%) 24 (6.4%)
0.76 0.60
21 + 3.9
19.7 + 3.2
0.10
LVEF (%)
55.8 + 9.2
56.6 + 7.7
0.44
CHADS2 score
0.49 + 0.63
0.43 + 0.68
0.42
was comparable with ST CF group and 28 mm CB group (75.5 vs. 73%, respectively, log rank P ¼ 0.8) (Figure 3).
Discussion Main findings In this large multicentre study, we demonstrated that new CF-sensing RF catheters and second-generation CB have similar efficacy in the setting of paroxysmal AF ablation: a comparable proportion of patients in both groups (around 75%) remained free from any atrial arrhythmia at 18 months after a single ablation procedure, free of antiarrhythmic drugs. Also, overall complication rates were equivalent with both technologies, but cryoablation led more frequently to transient phrenic nerve palsy, and RF ablation led more frequently to severe non-lethal complications. Procedure duration was slightly longer (13 min) using RF than using cryoablation; these findings were already reported previously2 and probably account for the time required to create the 3D EAM and to perform the point-by-point isolation of the PVs with the RF ablation catheters.
In experimental studies,10 catheter –tissue contact parameters (CF and FTI) have demonstrated to be tightly correlated with RF lesion size. The rationale for better RF lesions using higher CF is a larger electrode –tissue contact area, allowing improved RF energy delivery to the myocardium. Subsequently, new RF catheters have embedded force-sensing technologies (Thermocoolw SmartTouchTM and TacticathTM ) providing real-time CF monitoring, allowing for electrode–tissue contact optimization. During AF ablation procedures, CF monitoring permitted a reduction of PV chronic reconnection and an improvement of clinical outcomes by targeting a CF of at least 10 g (if possible 20 g) and a FTI .400 g s for each RF application.4,5,19,20 Finally, CF monitoring may increase procedure safety by avoiding high CF values, which are at higher risk of steam pop10 and cardiac perforation.21 On the other hand, AF ablation using cryotherapy has also evolved recently with dramatic CB improvements. Compared with the firstgeneration CB (Arctic FrontTM ), the second-generation CB (Arctic Front AdvanceTM ) has twice as many injection ports (8), and these have been positioned more distally on the catheter’s shaft resulting in a larger and more uniform zone of freezing on the CB surface. This resulted in improved procedural data (procedure duration, fluoroscopy time, time to PVI) compared with the first-generation CB,12,22,23 and in better clinical outcomes.3
Which energy should be used for atrial fibrillation ablation? If the use of CF-sensing RF catheter or second-generation CB catheter should be preferred over older models, the choice of either of the ablation energies (RF or cryothermal) for paroxysmal AF ablation often depends on the operators’ skills and habits, and on available material and associated costs. With the first-generation CB, some PV anatomies (such as left PV common ostium) have been shown to deteriorate procedural outcomes24; however, the new Arctic Front AdvanceTM CB induces a better and more homogeneous cooling at the surface of the balloon, and it remains debated whether PV anatomical variants still play a significant role in PVI success. In our study, patients were not selected for one or the other energy depending on their PV anatomy, but only depending on the electrophysiologist they
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Radiofrequency with contact force-sensing vs. second-generation cryoballoon
Table 2 Procedural data and complications CF group (n 5 198)
CB group (n 5 178)
P-Value
Procedure duration (min) Fluoroscopy duration (min)
122.5 + 40.7 19.3 + 8.2
109.6 + 40 17.6 + 11
0.003 0.10
X-ray exposure (cGy cm2)
4273 + 2934
4853 + 5069
0.22
8 (4%)
3 (1.7%)
0.17
0 (0%)
10 (5.6%)
0.001
............................................................................................................................................................................... Procedural data
Procedural complications Groin haematoma Transient phrenic nerve palsy Severe complications Embolic events
2 (1%)
0 (0%)
0.03 0.18
Tamponade
2 (1%)
0 (0%)
0.18
Oesophageal complication Periprocedural death
1 (0.5%) 0 (0%)
0 (0%) 0 (0%)
0.34 NA
14 (7.1%)
13 (7.3%)
0.93
Total complications
Freedom from atrial arrhythmia recurrence 1.0
Event-free survival
0.8
0.6
0.4 CB group CF group 0.2
Log Rank P = 0.63
0 0
3
6
9
12
15
18
Months post-ablation Proportion of patients free from arrhythmia recurrence 3 months
6 months
9 months
12 months
CF group
97%
88.9%
86%
83.9%
15 months 18 months 80.9%
76%
CB group
97.2%
88.2%
83.6%
82.2%
80.6%
73.3%
CF group
192
176
141
117
73
58
CB group
173
157
126
111
42
27
Number of patients at risk
Figure 2 Cumulative freedom from atrial arrhythmia recurrence after a single ablation procedure, using the Kaplan– Meier survival analysis (blanking period 1 month).
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F. Squara et al.
Freedom from atrial arrhythmia recurrence 1.0
Event-free survival
0.8
0.6
0.4 28 mm CB group ST CF group 0.2
Log Rank P = 0.8
0 0
3
6
9
12
15
18
Months post-ablation Proportion of patients free from arrhythmia recurrence 3 months
6 months
9 months
ST CF group
96.2%
87.4%
84.8%
12 months 15 months 18 months 82.5%
80.4%
75.5%
28 mm CB group
97.3%
88.7%
83.4%
81.9%
80.3%
73%
Number of patients at risk ST CF group
153
139
127
105
72
57
28 mm CB group
146
133
111
108
42
27
Figure 3 Sensitivity analysis: cumulative freedom from atrial arrhythmia recurrence after a single ablation procedure using the Thermocoolw SmartTouchTM catheter (ST CF group), or the 28 mm Arctic Front AdvanceTM CB (28 mm CB group), using the Kaplan –Meier survival analysis (blanking period 1 month).
consulted. Our results suggest that both RF with CF-sensing and cryoenergy lead to comparable outcomes in non-selected patients, with a similar overall complication rate. However, CB ablation led to more transient right phrenic nerve palsies during ablation (5.6% vs. none), and RF ablation led more frequently to severe nonlethal complications (2.5% vs. none). Therefore in case of paroxysmal AF ablation, this study does not provide clues for a clear preference between RF and cryoablation. However, in case of persistent AF or in case of associated atrial flutter, current guidelines recommend RF ablation,1 since additional linear or CFAE ablations are not possible using the CB. Recently, the results of the STAR-AF 2 trial suggest that PVI alone might be a sufficient therapy for persistent AF25: in 589 randomized patients with persistent AF, freedom from AF recurrence at 18 months post-ablation was not significantly different between the three therapy arms (59% for PVI alone, 48% for PVI + CFAE ablation, and 44% for PVI + linear ablations; P ¼ 0.15). These findings might pave the way for cryoablation in the setting of persistent AF ablation.26
Limitations This study has several limitations. First, this is not a randomized trial and inclusion of the patients for one or the other group is potentially subject to significant bias. Secondly, this is an ambidirectional cohort study: some patients were recruited prospectively, and others retrospectively. However, in case of induced bias, the bias would be nondifferential since arrhythmia recurrence rates were comparable with prospective and retrospective inclusions (17 vs. 20%, respectively, P ¼ 0.51). Thirdly, the number of patients in this study provided a power of 70% in order to demonstrate a 10% difference in arrhythmia recurrence rate between both ablation strategies. However, since the difference between recurrence rates was only 2.7% at 18 months, it would be necessary to include more than 6000 patients in order to obtain sufficient study power. Finally, follow-up was performed using systematic 24 h-Holter ECGs, and additional 24 h-Holter ECGs in case of symptoms. This method may underestimate recurrence rates compared with implantable loop recorders.
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Conclusion Our findings suggest that CF-sensing RF catheters and secondgeneration CB lead to very comparable results in the setting of PVI for paroxysmal AF. Very large-scaled randomized studies are warranted to confirm these findings. Conflict of interest: S.B.: Medtronic (consultant); N.S.: Endosense (shares); J.-P.A.: St Jude (consultant), Biosense Webster (consultant).
12.
13.
14.
15.
References 1. Calkins H, Kuck KH, Cappato R, Brugada J, Camm AJ, Chen SA et al. 2012 HRS/ EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design. Europace 2012;14:528–606. 2. Mugnai G, Chierchia GB, de Asmundis C, Sieira-Moret J, Conte G, Capulzini L et al. Comparison of pulmonary vein isolation using cryoballoon versus conventional radiofrequency for paroxysmal atrial fibrillation. Am J Cardiol 2014;113:1509 –13. 3. Di Giovanni G, Wauters K, Chierchia GB, Sieira J, Levinstein M, Conte G et al. One-year follow-up after single procedure cryoballoon ablation: a comparison between the first and second generation balloon. J Cardiovasc Electrophysiol 2014; 25:834 –9. 4. Kimura M, Sasaki S, Owada S, Horiuchi D, Sasaki K, Itoh T et al. Comparison of lesion formation between contact force-guided and non-guided circumferential pulmonary vein isolation: a prospective, randomized study. Heart Rhythm 2014;11:984 –91. 5. Marijon E, Fazaa S, Narayanan K, Guy-Moyat B, Bouzeman A, Providencia R et al. Real-time contact force sensing for pulmonary vein isolation in the setting of paroxysmal atrial fibrillation: procedural and 1-year results. J Cardiovasc Electrophysiol 2014; 25:130 –7. 6. Bordignon S, Fu¨rnkranz A, Perrotta L, Dugo D, Konstantinou A, Nowak B et al. High rate of durable pulmonary vein isolation after second-generation cryoballoon ablation: analysis of repeat procedures. Europace 2015; doi:10.1093/europace/euu331. 7. The authors’ own work: Chierchia GB, Di Giovanni G, Ciconte G, de Asmundis C, Conte G, Sieira-Moret J et al. Second-generation cryoballoon ablation for paroxysmal atrial fibrillation: 1-year follow-up. Europace 2014;16:639 –44. 8. Aytemir K, Gurses KM, Yalcin MU, Kocyigit D, Dural M, Evranos B et al. Safety and efficacy outcomes in patients undergoing pulmonary vein isolation with secondgeneration cryoballoon. Europace 2015;17:379 –87. 9. Jourda F, Providencia R, Marijon E, Bouzeman A, Hireche H, Khoueiry Z et al. Contact-force guided radiofrequency vs. second-generation balloon cryotherapy for pulmonary vein isolation in patients with paroxysmal atrial fibrillation-a prospective evaluation. Europace 2015;17:225 –31. 10. Yokoyama K, Nakagawa H, Shah DC, Lambert H, Leo G, Aeby N et al. Novel contact force sensor incorporated in irrigated radiofrequency ablation catheter predicts lesion size and incidence of steam pop and thrombus. Circ Arrhythm Electrophysiol 2008;1:354 –62. 11. Hachiya H, Hirao K, Takahashi A, Nagata Y, Suzuki K, Maeda S et al. Clinical implications of reconnection between the left atrium and isolated pulmonary veins
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26.
provoked by adenosine triphosphate after extensive encircling pulmonary vein isolation. J Cardiovasc Electrophysiol 2007;18:392 –8. Straube F, Dorwarth U, Schmidt M, Wankerl M, Ebersberger U, Hoffmann E. Comparison of the first and second cryoballoon: high-volume single-center safety and efficacy analysis. Circ Arrhythm Electrophysiol 2014;7:293 –9. Perez-Castellano N, Fernandez-Cavazos R, Moreno J, Canadas V, Conde A, Gonzalez-Ferrer JJ et al. The COR trial: a randomized study with continuous rhythm monitoring to compare the efficacy of cryoenergy and radiofrequency for pulmonary vein isolation. Heart Rhythm 2014;11:8 –14. Siklody CH, Minners J, Allgeier M, Allgeier HJ, Jander N, Keyl C et al. Pressure-guided cryoballoon isolation of the pulmonary veins for the treatment of paroxysmal atrial fibrillation. J Cardiovasc Electrophysiol 2010;21:120 – 5. Lellouche N, Jais P, Nault I, Wright M, Bevilacqua M, Knecht S et al. Early recurrences after atrial fibrillation ablation: prognostic value and effect of early reablation. J Cardiovasc Electrophysiol 2008;19:599 –605. Pokushalov E, Romanov A, Corbucci G, Artyomenko S, Turov A, Shirokova N et al. Use of an implantable monitor to detect arrhythmia recurrences and select patients for early repeat catheter ablation for atrial fibrillation: a pilot study. Circ Arrhythm Electrophysiol 2011;4:823 –31. Pokushalov E, Romanov A, Corbucci G, Bairamova S, Losik D, Turov A et al. Does atrial fibrillation burden measured by continuous monitoring during the blanking period predict the response to ablation at 12-month follow-up? Heart Rhythm 2012;9:1375 – 9. Andrade JG, Khairy P, Macle L, Packer DL, Lehmann JW, Holcomb RG et al. Incidence and significance of early recurrences of atrial fibrillation after cryoballoon ablation: insights from the multicenter Sustained Treatment of Paroxysmal Atrial Fibrillation (STOP AF) Trial. Circ Arrhythm Electrophysiol 2014;7:69 –75. Squara F, Latcu DG, Massaad Y, Mahjoub M, Bun SS, Saoudi N. Contact force and force-time integral in atrial radiofrequency ablation predict transmurality of lesions. Europace 2014;16:660 –7. Reddy VY, Shah D, Kautzner J, Schmidt B, Saoudi N, Herrera C et al. The relationship between contact force and clinical outcome during radiofrequency catheter ablation of atrial fibrillation in the toccata study. Heart Rhythm 2012;9:1789 –95. Shah D, Lambert H, Langenkamp A, Vanenkov Y, Leo G, Gentil-Baron P et al. Catheter tip force required for mechanical perforation of porcine cardiac chambers. Europace 2011;13:277 –83. Furnkranz A, Bordignon S, Dugo D, Perotta L, Gunawardene M, Schulte-Hahn B et al. Improved one-year clinical success rate of pulmonary vein isolation with the secondgeneration cryoballoon in patients with paroxysmal atrial fibrillation. J Cardiovasc Electrophysiol 2014;16:987–93. Straube F, Dorwarth U, Vogt J, Kuniss M, Kuck KH, Tebbenjohanns J et al. Differences of two generations: insights from the prospective multicentre, multinational FREEZE Cohort Substudy. Europace 2014;16:1434 –42. Knecht S, Kuhne M, Altmann D, Ammann P, Schaer B, Osswald S et al. Anatomical predictors for acute and mid-term success of cryoballoon ablation of atrial fibrillation using the 28 mm balloon. J Cardiovasc Electrophysiol 2013;24:132 –8. Verma A, Jiang C-Y, Betts TR, Chen J, Deisenhofer I, Mantovan R et al. Optimal method and outcomes of catheter ablation of persistent atrial fibrillation: Results of the Prospective, Randomized STAR AF 2 trial ESC Congress. 2014. Ciconte G, Baltogiannis G, de Asmundis C, Sieira J, Conte G, Di Giovanni G et al. Circumferential pulmonary vein isolation as index procedure for persistent atrial fibrillation: a comparison between radiofrequency catheter ablation and secondgeneration cryoballoon ablation. Europace 2015; doi:10.1093/europace/euu350.
CLINICAL RESEARCH
Europace doi:10.1093/europace/euv060
Comparison between radiofrequency with contact force-sensing and second-generation cryoballoon for paroxysmal atrial fibrillation catheter ablation: a multicentre European evaluation Fabien Squara1,2*, Alexandre Zhao 2, Eloi Marijon 3,4, Decebal Gabriel Latcu 5, Rui Providencia 3, Giacomo Di Giovanni 6, Gae¨l Jauvert2, Francois Jourda 3, Gian-Battista Chierchia 6, Carlo De Asmundis 6, Giuseppe Ciconte 6, Christine Alonso 2, Caroline Grimard 2, Serge Boveda3, Bruno Cauchemez 2, Nadir Saoudi 5, Pedro Brugada6, Jean-Paul Albenque 3, and Olivier Thomas 2 1 Cardiology Department, Pasteur University Hospital, 30 Voie romaine, 06000 Nice, France; 2Clinique Ambroise Pare´, Neuilly, France; 3Clinique Pasteur, Toulouse, France; 4Cardiology Department, European Georges Pompidou Hospital, Paris, France; 5Service de Cardiologie, Centre Hospitalier Princesse Grace, Monaco; and 6Heart Rhythm Management Centre, UZ Brussel-VUB, Brussels, Belgium
Received 28 November 2014; accepted after revision 10 February 2015
Aims
Whether pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation (PAF) using contact force (CF)-guided radiofrequency (RF) or second-generation cryoballoon (CB) present similar efficacy and safety remains uncertain. ..................................................................................................................................................................................... Methods We performed a multicentre study comparing procedural safety and arrhythmia recurrence after standardized PVI catheter ablation for PAF using CF-guided RF ablation (Thermocoolw SmartTouchTM , Biosense Webster; or TacticathTM , St and results Jude Medical) (CF group) with second-generation CB ablation (Arctic Front AdvanceTM , Medtronic) (CB group). Overall, 376 patients (mean age 59.8 + 10.4 years, 280 males) were enrolled in 4 centres: 198 in CF group and 178 in CB group. Procedure was shorter for CB group than for CF group (109.6 + 40 vs. 122.5 + 40.7 min, P ¼ 0.003), but fluoroscopy duration and X-ray exposure were not statistically different (P ¼ 0.1 and P ¼ 0.22, respectively). Overall complication rate was similar in both groups: 14 (7.1%) in the CF group vs. 13 (7.3%) in the CB group (P ¼ 0.93). However, transient right phrenic nerve palsy occurred only in CB group (10 patients, 5.6%; P ¼ 0.001 vs. CF group) and severe non-lethal complications (embolic event, tamponade, or oesophageal injury) occurred only in CF group (5 patients, 2.5%; P ¼ 0.03 vs. CB group). No periprocedural death occurred in either group. Single-procedure freedom from any atrial arrhythmias at 18 months post-ablation was comparable in CF group and CB group (76 vs. 73.3%, respectively, log rank P ¼ 0.63). ..................................................................................................................................................................................... Conclusion Pulmonary vein isolation using CF-guided RF and second-generation CB leads to comparable single-procedure arrhythmia-free survival at up to 18 months with similar overall complication rate.
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Atrial fibrillation † Ablation † Radiofrequency † Cryoballoon
Introduction Since the seminal observation that pulmonary vein (PV) ectopies can trigger atrial fibrillation (AF), PV isolation (PVI) has become the
cornerstone of AF ablation therapy in paroxysmal AF.1 The selection of the energy—radiofrequency (RF) or cryothermal—for achieving PVI in paroxysmal AF still remains at the discretion of the operator. One study has demonstrated that wide antral PVI using conventional
* Corresponding author. Tel: +33 492038530; fax: +33 492037872, 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? † This multicentre study provides evidence that radiofrequency ablation using contact force-sensing catheters and cryoballoon ablation have comparable efficacy at 18 months after paroxysmal atrial fibrillation ablation, with similar overall complication rate. However, severe non-lethal complications tend to occur more frequently with radiofrequency. † Mean procedure duration is slightly shorter using cryoballoon ablation, but X-ray exposure is equivalent. † Large randomized studies are warranted to confirm these findings.
point-by-point RF had similar single-procedure success rate than PVI using first-generation cryoballoon (CB).2 However, both technologies benefited lately from significant material improvements with the advent of contact force (CF)-sensing RF catheters and secondgeneration CB, both showing improved outcomes compared with the older models.3 – 8 Recently, Jourda et al. 9 have provided preliminary data suggesting that new CF-sensing RF catheters and secondgeneration CB might lead to comparable outcomes at 12 months. In the present multicentre study, we sought to confirm these findings in a large number of patients, comparing safety and efficacy of CF-sensing RF catheters with second-generation CB catheter in the setting of paroxysmal AF catheter ablation.
Methods Study population Consecutive patients undergoing antral PVI for paroxysmal AF ablation using a CF-sensing RF catheter (CF group) or a second-generation CB (CB group) were enrolled in the study. Four different European centres participated in patients’ recruitment (Clinique Ambroise Pare´, Neuilly-sur-Seine, France; Clinique Pasteur, Toulouse, France; UZ Brussel-VUB, Brussels, Belgium; and Centre Hospitalier Princesse Grace, Monaco). This was an ambidirectional cohort study, with patients enrolled either prospectively or retrospectively. Patients were eligible if they presented with paroxysmal AF refractory to antiarrhythmic therapy, and were undergoing a first PVI procedure using either (i) a CF-sensing RF catheter (Thermocoolw SmartTouchTM , Biosense Webster, Inc., Diamond Bar, CA; or TacticathTM , St Jude Medical, Inc., St Paul, MN) or (ii) a second-generation CB (Arctic Front AdvanceTM , Medtronic, Minneapolis, MN). Exclusion criteria were: follow-up of ,6 months at the time of the study, additional linear ablations except for cavo-tricuspid isthmus (CTI) line (i.e. roof line, mitral isthmus line), complex-fractionated electrograms (CFAEs) ablation, repeat AF ablation, and the lack of the use of a three-dimensional (3D) electroanatomic mapping (EAM) system when RF was the selected energy. Importantly, patient selection for one or the other energy group was not made depending on the patient’s characteristics (i.e. PV anatomy) but only on the habits of the electrophysiology physician performing the ablation procedure. Specifically, each electrophysiology physician used always the same ablation energy (either RF or cryothermal) for all his AF ablations, regardless of PV anatomy. All patients provided an informed consent prior to the procedure. The study complied with the Declaration of Helsinki and the research protocol was approved by the local Ethics Committee.
F. Squara et al.
Ablation procedure: common elements between contact force and cryoballoon groups Left atrium (LA) computed tomography scan or magnetic resonance imaging was performed 24 h prior to the procedure, to assess PV anatomy, LA dimensions and to exclude the presence of a potential LA thrombus. Procedures were performed under a mild sedation or under general anaesthesia, depending on the physician performing the procedure. A quadripolar or decapolar catheter was positioned in the coronary sinus, through a transfemoral venous access. A single or double transseptal puncture was performed under fluoroscopic guidance. Depending on the operator, transoesophageal echocardiographic guidance could be used to guide the transseptal puncture. A bolus of unfractionated heparin was administered before the transseptal puncture and infusion was titrated to maintain activated clotting time .300 s for the duration of the procedure. Depending on the referring centre, vitamin-K antagonists (VKAs) were either interrupted before the procedure with periprocedural bridging with subcutaneous heparin, or the procedure was performed without VKA interruption with INR ,3. New oral anticoagulants were interrupted before the procedure in all centres.
Specific procedural details: contact force group In this group, the ablation catheter could be either of the two currently available CF-sensing catheters: (i) Thermocoolw SmartTouchTM that was coupled with the use of the Carto 3 EAM system (Biosense Webster) or (ii) TacticathTM that was coupled with the use of the Ensite Velocity EAM system (St Jude Medical). A circumferential mapping catheter (CMC; LassoTM ; Biosense Webster) was introduced into the LA using an 8.5 Fr long sheath. The ablation catheter was advanced into the LA either sequentially after removing the CMC (in case of single transseptal puncture) or simultaneously with the CMC (in case of double transseptal punctures). The ablation catheter and the CMC were used to collect LA geometry using the EAM system. The ablation strategy consisted of PVI using two wide antral circumferential RF ablations across ipsilateral PVs, without additional adjunctive LA ablation. Carina ablations were performed when PV isolation could not be achieved with antral isolation. Typically carina ablation targeted the earliest potential for both ipsilateral PVs identified at the carina. Powercontrolled RF ablation lesions were delivered with 30 –35 W power; the endpoint was elimination of the local bipolar EGM with 20 – 40 s lesions, or with force-time integral (FTI) .400 g s. A lower power (20 – 30 W) and duration settings were used for ablation on the posterior LA wall close to the oesophagus. Real-time catheter– tissue CF was continuously monitored using either the Carto 3 for the Thermocoolw SmartTouchTM catheter, or using the TactisysTM viewing platform (St Jude Medical) for the TacticathTM catheter. Contact force data were available to the operator throughout the procedure. The aim was to achieve a mean CF of at least 10 g during RF application. The upper limit defined was 50 g force.10 Oesophageal temperature monitoring was performed at the discretion of the operator. When used, the cut-off temperature was 38.58C. At the end of the procedure, a waiting period of at least 20 min was performed, and/or adenosine was administered intravenously (12– 18 mg) to assess for dormant LA– PV connections.11
Specific procedural details: cryoballoon group A 14-Fr deflectable sheath (FlexCathw, Medtronic) was advanced into the LA through the transseptal puncture. Then, the Arctic Front AdvanceTM CB was introduced into the sheath, inflated, and advanced to the ostium of each PV. The procedure was performed using the 28 mm CB in two centres, or with an anatomy-based individualized approach using the 23 or 28 mm CB in the remaining centres.12,13 Before
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Radiofrequency with contact force-sensing vs. second-generation cryoballoon
cryoenergy delivery, the occlusion of each PV was assessed with either a venous angiography or a venous pressure curve,14 at the discretion of the operator. Ablation of PV antra was performed with two applications of 240 s per vein. Continuous monitoring of the phrenic nerve during ablation of the right PVs was systematically performed by pacing the right phrenic nerve with a quadripolar catheter in the superior vena cava. Pulmonary vein isolation was either assessed continuously using the circular Achievew Catheter (Medtronic) during CB freezing or traditionally using a CMC (Lassow, Biosense Webster) after two applications. If the PV remained connected, additional applications were performed using different angulations. No oesophageal monitoring was done during cryoablation procedures. Pulmonary vein isolation was finally checked 20 min after the last CB ablation, and/or an intravenous adenosine challenge (12– 18 mg) was performed.
detailed in Figure 1. Most patients (276/376; 73%) were included prospectively. Within the CF group, 159 patients (80.3%) underwent PVI using the Thermocoolw SmartTouchTM catheter, and 39 patients (19.7%) using the TacticathTM catheter. Within the CB group, 150 patients (84%) underwent PVI using the 28 mm Arctic Front AdvanceTM CB and 28 patients (16%) using the 23 mm CB. Cavotricuspid isthmus ablation was performed in 23 patients (13%) of the CB group and in 46 patients (23%) of the CF group. Table 1 summarizes the characteristics of our study population. No statistical differences were found between CF group and CB group, except for age (61 + 9 years in CF group vs. 58.4 + 11.5 years in CB group, P ¼ 0.02). All the patients were off antiarrhythmic therapy at 3 months post-ablation.
Post-procedure clinical management
Procedural data and safety
A systematic transthoracic echocardiography and 24-h Holter monitoring were performed before hospital discharge. Depending on the referring physician, antiarrhythmic drugs were stopped before hospital discharge or were systematically continued for a period of 1 – 3 months post-ablation. A blanking period of only 1 month has been chosen in this study, since early arrhythmia recurrences at 1 – 3 months have proven to be predictive of late arrhythmia recurrences.15 – 18 Patients with recurrence of AF during the blanking period were cardioverted and antiarrhythmic drugs maintained until 3 months post-ablation. Subjects were then evaluated at 1, 3, 6, 9, 12, and 18 months. Information systematically collected during follow-up included clinical symptoms, a 12-lead electrocardiogram (ECG), and a 24 h-Holter ECG. Additional Holter ECGs were performed in case of symptoms of arrhythmias. Anticoagulation strategy after the first 3 months was based on the CHA2DS2Vasc and HAS-BLED scores.1
Procedural data and complications are detailed in Table 2. All PVs in both groups were successfully isolated during the procedure. Procedure duration was significantly shorter in CB group than in CF group (109.6 + 40 vs. 122.5 + 40.7 min, P ¼ 0.003). Comparison of fluoroscopy duration and X-ray exposure between CF group and CB group did not reach statistical significance (P ¼ 0.10 and P ¼ 0.22, respectively). In CF group, 61/198 (31%) patients underwent oesophageal temperature monitoring. The total number of complications in both groups was similar: 14 (7.1%) in the CF group vs. 13 (7.3%) in the CB group (P ¼ 0.93), including groin haematoma (4.0 vs. 1.7%, P ¼ 0.17). Transient phrenic nerve palsy occurred in 10 patients (5.6%) of the CB group vs. none of the CF group (P ¼ 0.001). No patient died in either group from a procedural complication, but severe complications (embolic event, tamponade, or oesophageal injury) occurred only in CF group (five patients, 2.5%; P ¼ 0.03 vs. CB group). Specifically, two patients (1%) of the CF group had a clot embolic event postablation vs. none of the CB-group patients (P ¼ 0.18). In addition, two patients (1%) of the CF group developed a cardiac tamponade during the procedure (for both patients, PVI was already achieved) vs. none of the CB-group patients (P ¼ 0.18). One patient (0.5%) of the CF group (without oesophageal temperature monitoring) suffered from digestive bleeding after the procedure, leading to oesophageal ulcer diagnosis.
Study endpoints The procedural endpoint was PVI with confirmed entrance and exit blocks. The long-term efficacy endpoint was freedom from any atrial arrhythmia lasting more than 30 s for up to 18 months after a single procedure (median 12 months, interquartile range: 10 – 18 months). The safety endpoint was a comparison of significant adverse events between groups.
Statistical analysis Continuous data are represented as mean SD or median and IQR as appropriate. Comparisons between two groups were made with Student’s t-tests and summarized with means and SDs for independent samples if normally distributed or, if not normally distributed, evaluated with the Mann– Whitney U-test and summarized with medians and quartiles. Nominal values are expressed as n (%) and compared with x 2 tests. Raw event rates were compared with x 2 tests, and event-free survival plots were made by the Kaplan– Meier method and compared with log-rank tests. Sensitivity analysis was performed by comparing long-term efficacy endpoint in patients ablated using the Thermocoolw SmartTouchTM catheter or the 28 mm Arctic Front AdvanceTM CB. A P-value of ≤0.05 was considered statistically significant throughout. SPSS Statistics software version 20 (IBM Corporation, Armonk, NY, USA) was used for descriptive and inferential statistical analysis.
Results Study population Overall, 376 patients were included: 198 in the CF group and 178 in the CB group. The number of patients included in each centre is
Long-term efficacy Patients were followed up for up to 18 months after the procedure. Median follow-up duration was 12 months (interquartile range: 10– 18 months) and the minimum follow-up duration was 6 months. In the CF group, 37 (18.7%) patients suffered from atrial arrhythmia recurrence vs. 34 (19.1%) patients in the CB group (P ¼ 0.92). Using the Kaplan –Meier survival analysis, single-procedure freedom from any atrial arrhythmias at 18 months post-ablation was comparable with CF group and CB group (76 vs. 73.3%, respectively, log rank P ¼ 0.63; Figure 2).
Sensitivity analysis Sensitivity analysis was performed by comparing the long-term efficacy of the ablation using the Thermocoolw SmartTouchTM (ST CF group; n ¼ 159 patients) and using the 28 mm Arctic Front AdvanceTM CB (28 mm CB group; n ¼ 150 patients). Singleprocedure freedom from atrial arrhythmias at 18 months post-ablation
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F. Squara et al.
Cryoablation
Radiofrequency ablation
137 patients 69%
80 patients 45%
50 patients 28%
Neuilly-sur-Seine
48 patients 27%
40 patients 20%
21 patients 11%
Brussels Toulouse Monaco
Figure 1 Number of patients included in each centre, depending on the ablation energy.
Benefit of new radiofrequency and cryoballoon catheters
Table 1 Patient characteristics CF group (n 5 198)
CB group (n 5 178)
P-Value
Age Female gender
61 + 9 45 (12%)
58.4 + 11.5 50 (13.3%)
0.02 0.24
AF duration, months
57.8 + 57.9
46.9 + 53.2
0.08
................................................................................
Hypertension
74 (19.7%)
55 (14.6%)
0.08
Diabetes mellitus Cardiopathy (any) LA area (cm2)
13 (3.5%) 29 (7.7%)
14 (3.7%) 24 (6.4%)
0.76 0.60
21 + 3.9
19.7 + 3.2
0.10
LVEF (%)
55.8 + 9.2
56.6 + 7.7
0.44
CHADS2 score
0.49 + 0.63
0.43 + 0.68
0.42
was comparable with ST CF group and 28 mm CB group (75.5 vs. 73%, respectively, log rank P ¼ 0.8) (Figure 3).
Discussion Main findings In this large multicentre study, we demonstrated that new CF-sensing RF catheters and second-generation CB have similar efficacy in the setting of paroxysmal AF ablation: a comparable proportion of patients in both groups (around 75%) remained free from any atrial arrhythmia at 18 months after a single ablation procedure, free of antiarrhythmic drugs. Also, overall complication rates were equivalent with both technologies, but cryoablation led more frequently to transient phrenic nerve palsy, and RF ablation led more frequently to severe non-lethal complications. Procedure duration was slightly longer (13 min) using RF than using cryoablation; these findings were already reported previously2 and probably account for the time required to create the 3D EAM and to perform the point-by-point isolation of the PVs with the RF ablation catheters.
In experimental studies,10 catheter –tissue contact parameters (CF and FTI) have demonstrated to be tightly correlated with RF lesion size. The rationale for better RF lesions using higher CF is a larger electrode –tissue contact area, allowing improved RF energy delivery to the myocardium. Subsequently, new RF catheters have embedded force-sensing technologies (Thermocoolw SmartTouchTM and TacticathTM ) providing real-time CF monitoring, allowing for electrode–tissue contact optimization. During AF ablation procedures, CF monitoring permitted a reduction of PV chronic reconnection and an improvement of clinical outcomes by targeting a CF of at least 10 g (if possible 20 g) and a FTI .400 g s for each RF application.4,5,19,20 Finally, CF monitoring may increase procedure safety by avoiding high CF values, which are at higher risk of steam pop10 and cardiac perforation.21 On the other hand, AF ablation using cryotherapy has also evolved recently with dramatic CB improvements. Compared with the firstgeneration CB (Arctic FrontTM ), the second-generation CB (Arctic Front AdvanceTM ) has twice as many injection ports (8), and these have been positioned more distally on the catheter’s shaft resulting in a larger and more uniform zone of freezing on the CB surface. This resulted in improved procedural data (procedure duration, fluoroscopy time, time to PVI) compared with the first-generation CB,12,22,23 and in better clinical outcomes.3
Which energy should be used for atrial fibrillation ablation? If the use of CF-sensing RF catheter or second-generation CB catheter should be preferred over older models, the choice of either of the ablation energies (RF or cryothermal) for paroxysmal AF ablation often depends on the operators’ skills and habits, and on available material and associated costs. With the first-generation CB, some PV anatomies (such as left PV common ostium) have been shown to deteriorate procedural outcomes24; however, the new Arctic Front AdvanceTM CB induces a better and more homogeneous cooling at the surface of the balloon, and it remains debated whether PV anatomical variants still play a significant role in PVI success. In our study, patients were not selected for one or the other energy depending on their PV anatomy, but only depending on the electrophysiologist they
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Radiofrequency with contact force-sensing vs. second-generation cryoballoon
Table 2 Procedural data and complications CF group (n 5 198)
CB group (n 5 178)
P-Value
Procedure duration (min) Fluoroscopy duration (min)
122.5 + 40.7 19.3 + 8.2
109.6 + 40 17.6 + 11
0.003 0.10
X-ray exposure (cGy cm2)
4273 + 2934
4853 + 5069
0.22
8 (4%)
3 (1.7%)
0.17
0 (0%)
10 (5.6%)
0.001
............................................................................................................................................................................... Procedural data
Procedural complications Groin haematoma Transient phrenic nerve palsy Severe complications Embolic events
2 (1%)
0 (0%)
0.03 0.18
Tamponade
2 (1%)
0 (0%)
0.18
Oesophageal complication Periprocedural death
1 (0.5%) 0 (0%)
0 (0%) 0 (0%)
0.34 NA
14 (7.1%)
13 (7.3%)
0.93
Total complications
Freedom from atrial arrhythmia recurrence 1.0
Event-free survival
0.8
0.6
0.4 CB group CF group 0.2
Log Rank P = 0.63
0 0
3
6
9
12
15
18
Months post-ablation Proportion of patients free from arrhythmia recurrence 3 months
6 months
9 months
12 months
CF group
97%
88.9%
86%
83.9%
15 months 18 months 80.9%
76%
CB group
97.2%
88.2%
83.6%
82.2%
80.6%
73.3%
CF group
192
176
141
117
73
58
CB group
173
157
126
111
42
27
Number of patients at risk
Figure 2 Cumulative freedom from atrial arrhythmia recurrence after a single ablation procedure, using the Kaplan– Meier survival analysis (blanking period 1 month).
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F. Squara et al.
Freedom from atrial arrhythmia recurrence 1.0
Event-free survival
0.8
0.6
0.4 28 mm CB group ST CF group 0.2
Log Rank P = 0.8
0 0
3
6
9
12
15
18
Months post-ablation Proportion of patients free from arrhythmia recurrence 3 months
6 months
9 months
ST CF group
96.2%
87.4%
84.8%
12 months 15 months 18 months 82.5%
80.4%
75.5%
28 mm CB group
97.3%
88.7%
83.4%
81.9%
80.3%
73%
Number of patients at risk ST CF group
153
139
127
105
72
57
28 mm CB group
146
133
111
108
42
27
Figure 3 Sensitivity analysis: cumulative freedom from atrial arrhythmia recurrence after a single ablation procedure using the Thermocoolw SmartTouchTM catheter (ST CF group), or the 28 mm Arctic Front AdvanceTM CB (28 mm CB group), using the Kaplan –Meier survival analysis (blanking period 1 month).
consulted. Our results suggest that both RF with CF-sensing and cryoenergy lead to comparable outcomes in non-selected patients, with a similar overall complication rate. However, CB ablation led to more transient right phrenic nerve palsies during ablation (5.6% vs. none), and RF ablation led more frequently to severe nonlethal complications (2.5% vs. none). Therefore in case of paroxysmal AF ablation, this study does not provide clues for a clear preference between RF and cryoablation. However, in case of persistent AF or in case of associated atrial flutter, current guidelines recommend RF ablation,1 since additional linear or CFAE ablations are not possible using the CB. Recently, the results of the STAR-AF 2 trial suggest that PVI alone might be a sufficient therapy for persistent AF25: in 589 randomized patients with persistent AF, freedom from AF recurrence at 18 months post-ablation was not significantly different between the three therapy arms (59% for PVI alone, 48% for PVI + CFAE ablation, and 44% for PVI + linear ablations; P ¼ 0.15). These findings might pave the way for cryoablation in the setting of persistent AF ablation.26
Limitations This study has several limitations. First, this is not a randomized trial and inclusion of the patients for one or the other group is potentially subject to significant bias. Secondly, this is an ambidirectional cohort study: some patients were recruited prospectively, and others retrospectively. However, in case of induced bias, the bias would be nondifferential since arrhythmia recurrence rates were comparable with prospective and retrospective inclusions (17 vs. 20%, respectively, P ¼ 0.51). Thirdly, the number of patients in this study provided a power of 70% in order to demonstrate a 10% difference in arrhythmia recurrence rate between both ablation strategies. However, since the difference between recurrence rates was only 2.7% at 18 months, it would be necessary to include more than 6000 patients in order to obtain sufficient study power. Finally, follow-up was performed using systematic 24 h-Holter ECGs, and additional 24 h-Holter ECGs in case of symptoms. This method may underestimate recurrence rates compared with implantable loop recorders.
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Conclusion Our findings suggest that CF-sensing RF catheters and secondgeneration CB lead to very comparable results in the setting of PVI for paroxysmal AF. Very large-scaled randomized studies are warranted to confirm these findings. Conflict of interest: S.B.: Medtronic (consultant); N.S.: Endosense (shares); J.-P.A.: St Jude (consultant), Biosense Webster (consultant).
12.
13.
14.
15.
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