Introduction EHRA SURVEY

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1 Europace (2015) 17, doi: /europace/euv315 EHRA SURVEY Catheter ablation for atrial fibrillation: results from the first European Snapshot Survey on Procedural Routines for Atrial Fibrillation Ablation (ESS-PRAFA) Part II Jian Chen 1,2 *, Nikolaos Dagres 3, Melece Hocini 4, Laurent Fauchier 5, Maria Grazia Bongiorni 6, Pascal Defaye 7, Antonio Hernandez-Madrid 8, Heidi Estner 9, Elena Sciaraffia 10, and Carina Blomström-Lundqvist 10, Conducted by the Scientific Initiatives Committee of the European Heart Rhythm Association (EHRA) 1 Department of Heart Disease, Haukeland University Hospital, N-5021 Bergen, Norway; 2 Department of Clinical Science, University of Bergen, N-5021 Bergen, Norway; 3 Second Cardiology Department, Attikon University Hospital, University of Athens, Athens, Greece; 4 Hôpital Cardiologique du Haut Lévêque Université Victor Segalen Bordeaux II, Bordeaux Pessac, France; 5 Service de Cardiologie, Faculté de Médecine, Centre Hospitalier Universitaire Trousseau, Université François Rabelais, Tours 37044, France; 6 Second Cardiology Department, University Hospital of Pisa, Pisa, Italy; 7 Arrhythmia Department, University Hospital, Grenoble, France; 8 Cardiology Department, Ramon y Cajal Hospital, Alcalá University, Carretera Colmenar Viejo, Madrid, Spain; 9 Department of Cardiology Medizinische Klinik und Poliklinik I, LMU Klinikum der Universität München, Munich, Germany; and 10 Department of Cardiology, Institution of Medical Science, Uppsala University, Uppsala, Sweden Received 1 July 2015; accepted after revision 20 August 2015; online publish-ahead-of-print 13 October 2015 The European Snapshot Survey on Procedural Routines in Atrial Fibrillation Ablation (ESS-PRAFA) is a prospective, multicentre snapshot survey collecting patient-based data on current clinical practices during atrial fibrillation (AF) ablation. The participating centres were asked to prospectively enrol consecutive patients during a 6-week period (from September to October 2014). A web-based case report form was employed to collect information of patients and data of procedures. A total of 455 eligible consecutive patients from 13 countries were enrolled (mean age years, 28.8% women). Distinct strategies and endpoints were collected for AF ablation procedures. Pulmonary vein isolation (PVI) was performed in 96.7% and served as the endpoint in 91.3% of procedures. A total of 52 (11.5%) patients underwent ablation as first-line therapy. The cryoballoon technique was employed in 31.4% of procedures. Procedure, ablation, and fluoroscopy times differed among various types of AF ablation. Divergences in patient selection and complications were observed among low-, medium-, and high-volume centres. Adverse events were observed in 4.6% of AF ablation procedures. In conclusion, PVI was still the main strategy for AF ablation. Procedurerelated complications seemed not to have declined. The centre volume played an important role in patient selection, strategy choice, and had impact on the rate of periprocedural complication Keywords Atrial fibrillation Catheter ablation Strategy Irrigated radiofrequency catheter Cryoballoon Endpoint Complication Survey Introduction Various aspects of atrial fibrillation (AF) ablation procedures have been outlined by contemporary guidelines to improve efficacy and safety and reduce risks of periprocedural complications. 1 4 In the past years, new ablation strategies, techniques, and energy sources have been developed. Indications for AF ablation have been extended from highly symptomatic patients with drug-refractory AF to a first-line treatment for selected patients without previous antiarrhythmic drug therapy. Significant variability has been reported in ablation strategies and periprocedural management in the real world. 5,6 In order to ensure and further improve quality of patient management in this field, it is necessary to understand and analyse changes in the clinical practice of AF ablation. 1 3 Given the diversity of available strategies and techniques for AF ablation, the European Heart Rhythm Association (EHRA) Scientific Initiative Committee designed this European Snapshot Survey on Procedural Routines in Atrial Fibrillation Ablation (ESS-PRAFA) * Corresponding author: Tel: ; fax: address: jian.chen@med.uib.no Published on behalf of the European Society of Cardiology. All rights reserved. & The Author For permissions please journals.permissions@oup.com.

2 1728 J. Chen et al. that collected patient-based data on the routine practices related to AF ablation in the context of the latest AF guidelines. While Part I of ESS-PRAFA focused on the use of antithrombotic therapies, 7 Part II related to the selection of patient, application of strategy, use of catheters, energy, endpoints, and incidence of periprocedural complications. Methods Study design and data collection The design and conduction of the survey were described in Part I of the survey. 7 In brief, ESS-PRAFA is a prospective, multicentre snapshot survey of consecutive patients undergoing AF ablation, conducted over a 6-week period from September to October The ESS-PRAFA survey was approved by the national and/or local Institutional Review Boards, or the need for approval was waived according to the regulations in the respective country. Where requested by the local policy, a signed informed consent was obtained from patients before enrolment. There was no pre-specified protocol or recommendation regarding the patient selection, ablation strategy, technique, and other managements before, during, and after the AF ablation procedure, which were all left to the discretion of the responsible physician. Consecutive patient data were collected using a web-based case report form (CRF) to obtain the following information for each enrolled patient: individual centre statistics (type of hospital and centre volume of AF ablation), patient s baseline characteristics (age, gender, race, height, weight, clinical type of AF, concomitant cardiac or other diseases, and medication), and periprocedural anticoagulant therapy and procedure-related data (type of procedure, ablation strategy, energy source, equipment, technique, endpoints, procedure, ablation and fluoroscopy time, and complications recorded until discharge). First-line therapy was defined as an ablation procedure without prior attempt at antiarrhythmic drug (AAD) treatment, excluding betablockers and calcium-channel antagonists. Owing to the short-term duration of the survey, systematic monitoring of centres was not performed. Participating centres and the national/regional coordinators were the guarantors of the consecutiveness of enrolment, authenticity, accuracy and completeness of data and protection of safety, and rights of subjects. The CRF and the questionnaire served as source documents. Statistical analysis Following a test of statistical normality, continuous variables were presented as mean (+SD). Categorical variables were reported as counts with percentages. Student s t-test and one-way ANOVA were used for comparison of continuous variables with normal distribution. Differences in categorical variables were tested by x 2 test. All statistical analyses were performed using the SPSS 22 software package (SPSS, Inc., Chicago, IL). A two-sided P-value of,0.05 was considered statistically significant. Results Participating countries and patient enrolment In the 6-week survey period, 455 patients [131 (28.8%) women] from 13 countries were enrolled in this survey. Most patients were recruited from university hospitals (n ¼ 385, 84.6%), whereas 35 patients (7.7%) were from non-university hospitals or private hospitals. A total of 267 patients (58.7%) were included from middle-volume centres (performing AF ablations per year), 129 patients (28.4%) from high-volume centres ( 300 AF ablations per year), and 59 patients (12.9%) from low-volume centres (,100 AF ablations annually). Baseline characteristics Most patients were Caucasians (423, 93.0%) and relatively young (mean age: years). The majority 318 patients (69.9%) had a CHA 2 DS 2 -VASc score of 0 1, and only 9 patients (2.0%) had a HASBLED score of 3 (none of the patients had a HASBLED of 4 or more).themeanbodymassindex(bmi)was (range: ). Risk factors for stroke included hypertension in 176 (38.7%), heart failure in 47 (10.3%), diabetes mellitus in 33 (7.3%), prior stroke/transient ischaemic attack in 19 (4.2%), previous myocardial infarction in 31 (6.8%), peripheral artery disease in 7 (1.5%), obesity in 55 (12.1%), and smoking in 18 (4.0%) of the patients, whereas 206 (45.2%) patients had none of the above risk factors. There were 302 (66.5%) patients with paroxysmal, 129 (28.4%) with persistent, and 23 (5.1%) with long-standing persistent AF. The age did not differ among these three groups, but BMI was lower in paroxysmal AF patients than in persistent and long-standing persistent AF groups ( vs and , P, 0.01). A total of 52 (11.5%) patients (33 paroxysmal and 19 persistent AF) underwent ablation as first-line treatment without attempt at AAD therapy, 276 (60.8%) patients underwent ablation after the failure of AAD treatment, and re-do procedure was performed in 126 (27.7%) patients. Patients undergoing ablation as firstline therapy did not differ from other patients with AAD failure regarding age, but their history of chronic heart failure, hypertension, previous myocardial infarction, smoking, and obesity were less frequent. First-line therapy was applied in 10.9% of paroxysmal AF and 14.7% persistent AF patients. Preprocedural management To exclude a thrombus in the left atrial appendage prior to ablation, 201 (44.3%) patients underwent a transoesophageal echocardiographic examination (TOE), 58 (12.8%) had computed tomography (CT), and 145 (31.9%) patients underwent both studies. Fifty patients (11.0%) did not have any of these investigations. Before the ablation procedure, amiodarone (104, 22.9%), flecainide (96, 21.1%), sotalol (22, 4.8%), dronedarone (11, 2.4%), and propafenone (9, 2.0%) have been tried without satisfactory effects. Beta-blockers, calcium-channel blockers, and digitalis were used in 247 (54.3%), 38 (8.4%), and 14 (3.1%) patients, respectively. Periprocedural antithrombotic management was reported previously. 7 Techniques, catheters, energy types, and endpoints Single transseptal puncture was performed in 150 of 201 (74.6%) cases and double punctures in 51 (25.4%) patients. The strategies that were employed for ablation procedures (Table 1) included pulmonary vein isolation (PVI) in 96.7% of procedures, of which 72.9% were stand-alone. Linear ablation in the left atrium (LA) and ablation of areas with complex fractionated atrial electrograms (CFAE) were

3 Catheter ablation for atrial fibrillation 1729 Table 1 Ablation strategies and endpoints in different types of atrial fibrillation ablation procedure Total Type of atrial fibrillation Type of ablation procedure Paroxysmal Persistent Long-standing First-line After AAD Re-do therapy failure... Ablation strategies PVI alone or combined PVI stand-alone Linear lesions in LA CFAE ablation Rotor ablation Ganglionated plexi ablation Cavotricuspid isthmus line Endpoints PVI No re-connection provocated by adenosine Termination of AF Non-inducibility of AF Bi-directional linear block Elimination of CFAE Figures are in percentages unless otherwise stated. ADD, antiarrhythmic drugs; CFAE, complex fractionated atrial electrogram; PVI, pulmonary vein isolation; LA, left atrium. performed in 12.2 and 10.9% patients, respectively, mainly in persistent, long-standing AF and re-do procedures. In only rare cases, linear ablation in LA (0.9%) and CFAE ablation (0.7%) were stand-alone ablation strategies. Rotor ablation was used in 11 (2.4%) patients, as stand-alone in 3 patients with persistent AF. In 5 (1.1%) patients, ganglionated plexi ablation was selected in combination with other methods. Details on procedural endpoints are given in Table 1. In all types of procedures, PVI was the main endpoint. Among the PVI-related procedures, electrical isolation was used as the endpoint in 92.9% of patients, adenosine provocation in 6.9%, termination of AF in 18.6%, and non-inducibility of AF in 7.4% of cases. Bi-directional block was chosen as the endpoint in 65.6% of patients with linear ablation. Elimination or abatement of CFAEs and termination of AF were the procedural endpoint in 55.1 and 59.2% of patients, respectively, in whom CFAE ablation was performed. The most frequently used catheter type was an irrigated radiofrequency ablation catheter (67.4%). A non-irrigated catheter was used in 2 (0.5%) cases and circular radiofrequency ablation catheter in 3 (0.7%) cases with paroxysmal AF. A cryoballoon was employed in 31.4% of procedures including 16.4% of re-do procedures. Most of the patients treated with a cryoballoon technique had paroxysmal AF (76.6%), and only 23.4% had persistent AF. Laser was not applied in any case. A circular mapping catheter was used to confirm PVI in 82.0% of procedures, and a three-dimensional mapping system was employed in 57.6% of the procedures. In 2.9% of cases, a robotic navigation system was applied for mapping and ablation. The procedure time, ablation time, and fluoroscopy time for long-standing AF were significantly longer compared with paroxysmal and persistent AFs (P, 0.01, Table 2). The ablation time for re-do procedure was shorter than that for the first-time procedure, but no significant difference was observed with respect to procedure and fluoroscopy times. Statistically significant differences were found between the procedures performed using the cryoballoon and the irrigated radiofrequency catheter regarding procedure and fluoroscopy times ( vs ; vs , P, 0.01), but not ablation time ( vs , Figure 1). Periprocedural complications A total of 21 adverse events (4.6%) were reported. Pericardial effusion occurred in 11 patients (2.4%), 4 (1.0%) of whom developed tamponade (1 of them died) and 2 (0.4%) late pericardial effusion. One (0.2%) patient suffered an oesophageal lesion, and another patient sustained a stroke. Groin haematoma requiring prolonged hospitalization was reported in 4 patients (0.9%), a bleeding with a drop in haemoglobin for 2 g/dl or requiring transfusion of 2 units of blood occurred in 2 patients (0.4%). Phrenic nerve paralysis occurred in 3 patients in whom cryoballoon technique was applied. No significant difference in complication rates was found between cryoballoon and radiofrequency ablation techniques. Impact of centre volume Data related to the centre volume with respect to AF ablation are given in Table 3. Ablation in patients with persistent AF was more frequently performed in high-volume centres. The rate of periprocedural complication was related to the centre volume (Figure 2). The complication rate was higher in low-volume centres compared with that in high-volume centres (P, 0.05), whereas no statistically

4 1730 J. Chen et al. Table 2 Procedure, ablation, and fluoroscopy times in different types of atrial fibrillation ablation procedures Procedure time (min) Ablation time (min) Fluoroscopy time (min)... Total Type of atrial fibrillation Paroxysmal ** ** ** Persistent ** ** ** Long-standing persistent Type of procedure First time * First-line therapy * * After ADD failure Re-do AAD, antiarrhythmic drug. *P, 0.05 compared with re-do. **P, 0.01 compared with long-standing persistent. 180 Cryoballoon Irrigated radiofrequency ablation Table 3 Comparisons of proportions of ablation procedures in low-, medium-, and high-volume centres Time (min) Procedure time Fluoroscopy time Ablation time Centre volume Low Medium High volume volume volume 300/year <100/year /year (n 5 128) (n 5 59) (n 5 267)... Type of atrial fibrillation Paroxysmal * 65.6* Persistent * 25.0 Long-standing *, ** persistent Type of procedure First-line therapy After ADD failure Re-do Figure 1 Comparison of procedure, fluoroscopy, and ablation times for pulmonary vein isolation between cryoballoon and irrigated radiofrequency ablation catheter. Procedure and fluoroscopy times were shorter in cryoballoon group (P, 0.01), and no difference was observed regarding ablation time. significant difference was observed between medium-volume and low- or high-volume centres (P. 0.05). Discussion This ESS-PRAFA collected consecutive patients data regarding the routine practice of AF ablation in Europe. Patients enrolled in this survey were relatively young, had lower risk (low CHA 2 DS 2 -VASc and HASBLED scores), and relatively few patients had structural heart disease. The findings indicated that the participant centres focused on the patient in whom a higher success rate was expected, and tended to avoid those with increased risk of complications. The age, BMI, and gender distribution in this survey Figures are in percentages unless otherwise stated. AAD, antiarrhythmic drug. *P, 0.05 compared with low-volume centres. **P, 0.01 compared with medium-volume centres. were similar to those in the recently conducted ESC-EURObservational Research Programme, 5 whereas the proportion of hypertension and stroke was lower. The observation of an increased BMI was consistent with previous reports in AF patients. According to the guidelines, catheter ablation is a Class I indication for patients with paroxysmal AF Class IIa for patient with persistent, and Class IIb for those with long-standing persistent AF. 1 3 Most patients (66.5%) undergoing AF ablation had paroxysmal AF, whereas long-standing persistent AF was present in only 5.1% of patients, which was in line with the guidelines. This was probably related to the more complex, time-consuming procedure, and relatively poor clinical results in this patient group. 8,9 Offering ablation as a first-line therapy to patients with AF is supported by the randomized Medical ANtiarrhythmic Treatment or

5 Catheter ablation for atrial fibrillation 1731 Complication rate (%) Low-volume 100/year Medium-volume /year High volume 300/year Figure 2 Complication rates related to centre volume of ablation procedure. Compared with high-volume centres, low-volume centres had higher complication rate (P, 0.05). Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial 10 and the Radiofrequency Ablation vs. Antiarrhythmic drugs as First-line Treatment of paroxysmal atrial fibrillation (RAAFT II), 11 and thereafter recommended by the guidelines for patients with highly symptomatic paroxysmal AF with a low-risk profile. 1,3 This survey showed that ablation had been offered as firstline treatment to a small portion of patients with low risk, which was in adherence to the recommendation. Notably, 14.7% of patients with persistent AF underwent ablation also as first-line treatment, which was not consistent with the guidelines. TOE is recommended as the method of choice to exclude LA thrombosis. 1,2 In our survey, TOE was performed prior to ablation in 76.2% of AF patients and in 91.3% of patients with long-standing persistent AF. This figure is higher than that reported in another European registry, 6 but in congruence with that in a Japanese study 12 and our earlier survey. 13 Isolation of the pulmonary veins or antra is still the cornerstone for AF ablation as 96.7% of the procedures were based on PVI and PVI was the stand-alone strategy in 72.9% of all patients, and in 86.3% of the patients with first-line therapy. The proportion of procedures with additional linear and/or CFAE ablation in LA was lower (12.2 and 10.9%) compared with an earlier survey (19.3 and 17.4%). 5 This indicated that the physicians are now more cautious performing these extensive ablation procedures probably because of their complex techniques, indefinite endpoints, and not least, long procedure times. A recent randomized, multicentre trial showed that no additional benefit was obtained by linear or CFAE ablation adjunctive to PVI, 14 which may have had an important influence on the selection of the ablation strategy. Ablations targeting the ganglionated plexi and AF rotors are still not widely adopted in general and are rarely performed. More extensive ablation was performed in persistent and longstanding persistent AF. Similarly, the strategy was more aggressive in patients after AAD failure than in first-line ablation patients. The irrigated radiofrequency ablation catheter was still the most frequently used catheter for AF ablation, but the usage rate seemed lower than that in previous reports. 1 3 The cryoballoon technique is a relatively new technology and has become more frequently used in clinical practice (31.4% of procedures). This may relate not only to decreased procedure and fluoroscopy times (Figure 1) but also to promising clinical results from the reported long-term followups Meanwhile, PVI is the main endpoint for most procedures. To confirm the complete isolation, the use of a circular mapping catheter was the most common method in Europe, whereas adenosine was only used in a minority of the procedures. Similar complication rates were reported in this survey compared with the European, Asian, and worldwide AF surveys. 5,6,19 Remarkably, the complication rate remains stable over years. Although the rate of acute phrenic nerve paralysis was relatively higher and clearly related to cryoballoon procedures, 20 it was unclear in this survey whether they were transient or long-lasting. Death related to cardiac tamponade was reported in this survey, demonstrating the potential risk of AF ablation. Therefore, careful assessment of the benefit/risk ratio is mandatory in every patient. It has been reported that the complication rate and clinical management of AF ablation were related to the centre volume. 13,21 Our results have confirmed that the experience of centres and operators plays an important role not only in procedure-related complications but also in selection of patients and ablation strategy. It re-emphasizes the importance of a high volume of operations to ensure the safety of AF ablation and also raises other issues of healthcare, such as training, qualification of physicians, and facilities and limitations of centres. Limitations The participation in this survey was voluntary, which might have resulted in selection bias and other limitations associated with this type of studies. Owing to a short duration of the survey, a relatively small number of patients were enrolled, which may limit the data interpretation. Complications may have been underestimated because the data collection was limited to the period until discharge. This may particularly affect delayed complications such as late tamponade and atrioesophageal fistula, which are rare but lifethreatening. In addition, most patients were recruited from the university hospitals, and therefore, this may not fully reflect real-world clinical practice. Conclusion Our survey showed that PVI was still the mainstay of AF ablation procedure. Procedure-related complications seemed to have remained unchanged. The centre volume played an important role in patient selection, strategy choice, and had impact on the rate of periprocedural complication. Acknowledgements The production of this manuscript is under the responsibility of the Scientific Initiative Committee of the EHRA: Carina Blomström- Lundqvist (chairman), Maria Grazia Bongiorni (co-chair), Jian Chen, Nikolaos Dagres, Heidi Estner, Antonio Hernandez-Madrid, Melece Hocini, Torben Bjerregaard Larsen, Laurent Pison, Tatjana Potpara, Alessandro Proclemer, Elena Sciraffia, and Derick Todd. Document reviewer for EP-Europace: Irene Savelieva (St George s

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