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ScienceDirect Journal of Electrocardiology 48 (2015) 729 – 733 www.jecgonline.com
Simultaneous pulmonary vein cryoablation and cavotricuspid isthmus radiofrequency ablation in patients with combined atrial fibrillation and typical atrial flutter☆ Michaël Peyrol, M.D., a,⁎ Pascal Sbragia, M.D., a Thibault Ronchard, M.D., a Jennifer Cautela, M.D., a Chloé Villacampa, M.D., a Marc Laine, M.D., a Laurent Bonello, M.D., a Franck Thuny, M.D., a Franck Paganelli, M.D., a Samuel Lévy, M.D. b a
Service de Cardiologie, Centre Hospitalier Universitaire de Marseille, Hôpital Nord, Aix-Marseille Université, Marseille, France b Aix-Marseille Université, Marseille, France
Abstract
Pulmonary vein isolation (PVI) using cryoballoon (CB) technique and cavotricuspid isthmus (CTI) ablation using radiofrequency (RF) are established interventions for drug-resistant atrial fibrillation (AF) and typical atrial flutter (AFL). Twelve patients with a mean age of 62 ± 12 years underwent simultaneous delivery of RF energy at the CTI during CB applications at the PV ostia. Pulmonary vein isolation was achieved in all PVs and sustained bidirectional CTI conduction block obtained in all patients. The reported ablation protocol of combined paroxysmal AF and typical AFL did not result in prolongation of the procedure duration or in prolonged radiation exposure when compared to CB-PVI alone. No interferences between both ablation energy systems were observed. These preliminary results suggest that combined paroxysmal AF and typical AFL can be successfully and safely ablated using hybrid energy sources with simultaneous CTI ablation using RF during CB applications at the PV ostia. © 2015 Elsevier Inc. All rights reserved.
Keywords:
Atrial fibrillation; Cryoablation; Cryoballoon; Atrial flutter; Radiofrequency ablation
Introduction The common combination of atrial fibrillation (AF) and spontaneous or drug-induced atrial flutter (AFL) has long been reported [1–3]. Both, AF and AFL, are often resistant to antiarrhythmic drug therapy aimed at maintaining sinus rhythm [4]. Consequently, catheter ablation techniques are increasingly offered to drug-resistant patients. On one hand, pulmonary vein isolation (PVI) using either radiofrequency energy (RF) or cryoballoon (CB) techniques has been demonstrated to be safe and effective for the treatment of drug-resistant paroxysmal AF with good short or middle term outcomes [5–9]. On the other hand, cavotricuspid isthmus (CTI) ablation using RF is an established treatment of symptomatic typical AFL, increasingly used as first-line therapy [10–13]. In selected patients with combined AF and AFL, catheter ablation strategy targeting PVI and CTI
conduction block using RF energy has been reported to confer satisfactory outcomes [14,15]. Recently, simultaneous PV and CTI cryoablation, using two cryotherapy generators, were shown to be a safe and effective approach [16]. After the first minute of the 4-minute CB application at the PV, the adherence to the atrial tissue allows the operator to release the grip on the CB catheter. Therefore, the operator has several minutes to perform linear lesions with a focal catheter at the CTI. We hypothesized that simultaneous CTI ablation using RF energy during the 240-second CB applications at the PVs could be an alternative approach for treating patients with combined paroxysmal AF and typical AFL. To our knowledge, such simultaneous hybrid energy source approach has not been reported in these indications.
Patients and methods ☆
Disclosures: Drs Peyrol and Sbragia receive compensation for teaching and proctoring purposes from Medtronic Inc. ⁎ Corresponding author at: Service de Cardiologie, Centre Hospitalier Universitaire de Marseille, Hôpital Nord, Aix-Marseille Université, Marseille, France. E-mail address: [email protected] http://dx.doi.org/10.1016/j.jelectrocard.2015.03.013 0022-0736/© 2015 Elsevier Inc. All rights reserved.
Consecutive patients referred to our institution with combined drug-resistant paroxysmal AF and typical AFL were prospectively included in this study after informed consent obtained. All patients underwent transesophagealechocardiography the day before the procedure mainly to
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M. Peyrol et al. / Journal of Electrocardiology 48 (2015) 729–733
exclude a left atrium (LA) thrombus and to assess LA diameters but also to possibly detect atypical PV anatomy/ early branching. An LA thrombus, an LA anterior-posterior diameter N 50 mm, a moderate to severe mitral insufficiency or stenosis, a severe left ventricular hypertrophy (i.e. septal wall thickness N 15 mm) and a depressed (b 50 %) left ventricular ejection fraction were defined as exclusion criteria. Antithrombotic therapy, either using vitamin K antagonists or direct oral anticoagulant agents (dabigatran or rivaroxaban), was interrupted 2 days before the procedure. Midazolam and nalbuphine were used to obtain conscious sedation and analgesia during the procedure. Our current protocol for PVI procedure using the CB technique has been described elsewhere [17]. Briefly, a single 28-mm CB catheter (Arctic Front Advance™, CryoCath-Medtronic, Quebec, Canada), was advanced into the LA through the 12 French steerable sheath (12French, FlexCath Advance™, Cryocath-Medtronic, Quebec, Canada) via a single transseptal approach. Proper anticoagulation during the procedure was achieved using an intravenous bolus of unfractionated heparin of 100 IU/kg in order to obtain an activated clotting time of 250–300 seconds monitored every 30 minutes thereafter. A 20-mm Achieve™ (Medtronic-CryoCath, Quebec, Canada) endoluminal spiral catheter was inserted into the lumen of the CB both to navigate the CB to the PVs and to allow, when possible, real-time visualization of LA-PV conduction. Four-minute CB applications were initiated at the left-sided PVs. One additional cryoapplication (“bonus”) was delivered after achievement of PVI. During isolation of the right-sided PVs, continuous right phrenic nerve stimulation was performed via a quadripolar catheter positioned in the superior vena cava above the CB in order to detect phrenic nerve palsy. In our ablation protocol, we started with a cryoapplication at the right inferior PV as the risk of phrenic nerve palsy was felt to be lower at this site than with the right superior PV. The endpoint of PV cryoablation was complete PVI. Antithrombotic therapy was resumed the day of the intervention whereas antiarrhythmic drug therapy was discontinued. At time of the beginning of our study, anticoagulant bridging therapy in patients on vitamin K antagonists was still performed in our laboratory (enoxaparin 1.0 mg/kg twice a day starting 2 hours after catheter removal until therapeutic INR was achieved) and was pursued throughout the study. No anticoagulant bridging therapy was used in patients on direct oral anticoagulant therapy. Direct oral anticoagulant therapy was resumed 2 hours after the end of the procedure in the absence of local bleeding. Patients were discharged the day following the procedure in the absence of complications. Radiofrequency delivery at the CTI was performed during cryoapplication at the left-sided PV ostia and at the right inferior PV during second cryoapplication if no phrenic nerve palsy occurred during the first cryoapplication (Fig. 1). A 4-mm open-irrigated tip ablation catheter (Therapy™ Cool Path™, Saint Jude Medical, MN, USA) was advanced to the right atrium via the right femoral vein. Radiofrequency delivery was performed either during atrial flutter or during coronary sinus (CS) pacing at 600 ms via a deflectable quadripolar catheter. The power delivered by the RF generator (IBI-1500T11, Saint Jude Medical, MN, USA)
Fig. 1. Left anterior oblique view of catheters position during simultaneous delivery of radiofrequency energy at the cavotricuspid isthmus via a 4-mm open-irrigated tip catheter and 28-mm cryoballoon application with endoluminal spiral catheter at the left superior pulmonary vein.
was adjusted between 30 and 35 W in order to achieve modification of local electrograms. Cavotricuspid isthmus conduction was tested after completion of CB applications at the right-sided PVs. Bidirectional CTI conduction block was considered achieved if at least one of the following criteria were present: (1) complete descending lateral right atrial activation during pacing through the ablation catheter at the septal end of the CTI and complete descending septal right atrial activation during pacing at the lateral end of the CTI [18] or (2) recording a corridor of parallels double potentials separated (≥ 110 ms) with an isoelectric interval along the CTI ablation line during coronary sinus/low lateral right atrial pacing [19]. The endpoint of the CTI ablation was sustained bidirectional conduction block. For further analysis, we compared procedural characteristics of patients who underwent simultaneous ablation for combined AF and AFL to those of 24 patients, matched for age and LA diameter, who underwent PV cryoablation alone in our institution. Clinical and procedural parameters are given as mean ± standard deviation. Student t-test was used to compare differences between groups. A p value b 0.05 was considered statistically significant. All analyses were performed using GraphPad QuickCalcs (Graphpad, La Jolla, CA, USA).
Results Twelve patients (10 men and 2 women) with a mean age of 62 ± 12 years (range 42–80) were included in this study. History of hypertension was present in 3 patients. The 9 remaining patients had lone AF/AFL. Mean anterior-posterior LA diameter was 41 ± 6 mm. Mean PV diameters were 23 ± 2 mm for the left superior PV, 19 mm ± 3 for the left inferior
M. Peyrol et al. / Journal of Electrocardiology 48 (2015) 729–733
PV, 23 ± 2 mm for the right superior PV and 19 ± 2 mm for the right inferior PV. No atypical PV anatomy was detected during the pre-ablation transesophageal-echocardiography. Clinical and procedural characteristics are presented in Table 1. Simultaneous PVI with the CB technique and RF delivery at the CTI were successfully performed in all patients. Pulmonary vein isolation was achieved in all 48 targeted PVs following CB applications. Real-time PVI was observed in 31/48 treated PVs (64.5%). In “real-time” isolated PVs, mean time to LA-PV disconnection was 64 ± 30 seconds and mean CB temperature at that time was − 38 ± 10 °C. Mean CB temperature reached at the end of the 240 second application was − 51 ± 7 °C. Mean number of cryoapplications per patient was 8.2 ± 0.6 (range 8–10). Radiofrequency CTI ablation was carried out during ongoing AFL in 5 patients and during CS pacing in the remaining 7 patients. Mean procedure duration and radioscopy exposure were 82 ± 29 min (range 60–165 min) and 22 ± 7 min (range 12–31 min) respectively. No RF catheter dislodgment, related to phrenic nerve pacing, was observed during right inferior PV cryoablation. The endpoints of the procedure, complete PVI and bidirectional CTI conduction block, were reached in all patients. All patients presented with bidirectional CTI conduction block after completion of PV cryolesion. Transient right phrenic nerve palsy was observed in 2 patients during CB application at the RSPV. Phrenic nerve function recovered before the end of the procedure in both cases. No other complications including vascular access complications were observed. Of importance, no complications related to the simultaneous use of combined energy sources were recorded. In particular, no electrical interference between the cryoablation system and the RF system was observed during simultaneous delivery of cryoenergy at the PVs and RF energy at the CTI. With a mean follow-up of 12 ± 3 months, atrial arrhythmia recurrence was observed in 3 patients, paroxysmal AF in 2 and paroxysmal atypical AFL in 1 among the group of patients who underwent simultaneous PV cryoablation and CTI RF ablation for combined AF and typical AFL. Procedural characteristics of patients who underwent combined paroxysmal AF and typical AFL were compared to those of 24 patients who underwent PV cryoablation alone
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matched for age and LA diameter (62 ± 12 years vs 61 ± 11 years; p = NS and 41 ± 6 mm vs 40 ± 5 mm; p = NS respectively). Simultaneous PV cryoablation and CTI RF ablation were not associated with significant prolongation of procedure duration or radiation exposure when compared to PV cryoablation alone (82 ± 29 min vs 79 ± 24 min; p = NS and 22 ± 7 min vs 20 ± 10 min; p = NS respectively). Comparison of clinical and procedural data between the two groups of patients is shown in Table 2.
Discussion This study showed that simultaneous PVI using the cryoenergy and CTI ablation using the RF energy can be safely and successfully achieved in patients with combined AF and AFL. No interferences were observed between the two energy sources used simultaneously. The use of two different energy sources simultaneously is made possible after the first minute of the 4-minute CB application at the PV due to the adherence to the atrial tissue allowing the operator to release the grip on the CB catheter. Therefore, in our protocol, the operator had several minutes to achieve CTI conduction block with an RF catheter. Dhillon et al. recently reported that simultaneous PVI with the CB technique and CTI ablation using the 8-mm tip cryocatheter was also feasible and safe [16]. The authors mentioned that, in their experience, RF delivery at the CTI during PV cryoablation systematically triggered a safety cut-off of cryotherapy. Indeed, during RF energy delivery, the security system of the cryoconsole may deliver an alert on fluid detection within the CB. This alert automatically leads to interruption of refrigerant fluid injection and thereafter CB deflation. In our experience with an open irrigated-tip catheter system, such system alert has never been observed. Moreover, no special setup was necessary, neither for cryoenergy system nor for the RF generator. In the present protocol, lesions at the CTI were preferentially created during CB application at the left-sided PVs. Furthermore, if phrenic nerve palsy did not occur during the first CB application at the RIPV, our protocol allowed RF delivery at the CTI during additional cryoapplication at this vein level. Although no RF catheter
Table 1 Clinical and procedural characteristics of patients undergoing simultaneous pulmonary vein cryoablation and cavotricuspid isthmus radiofrequency ablation. Patient
Gender
Age (years)
1 2 3 4 5 6 7 8 9 10 11 12
M M M M M F M F M M M M
44 69 59 54 72 72 55 77 57 42 80 64
Underlying HD HTN
HTN
HTN
LA size (mm)
Procedure duration (min)
Radiation exposure (min)
Nb of CB applications
31 50 36 38 44 40 42 36 50 49 38 39
95 60 70 95 60 165 90 75 75 65 70 65
28 12 12 20 15 31 30 22 27 14 28 24
8 8 8 8 8 10 8 8 9 8 8 8
HD, heart disease; HTN, hypertension; LA, left atrium; CB, cryoballoon; PNP, phrenic nerve palsy; RSPV, right superior pulmonary vein.
PNP
RSPV RSPV
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M. Peyrol et al. / Journal of Electrocardiology 48 (2015) 729–733
Table 2 Comparison between patients undergoing simultaneous pulmonary vein cryoablation and cavotricuspid isthmus radiofrequency ablation and patients undergoing pulmonary vein cryoablation alone. PV-CB ablation/CTI PV-CB p value RF (n=12) ablation (n=24) Age (years) 62 LA diameter (mm) 41 Procedure duration (min) 82 Radiation exposure (min) 22 Nb. of CB applications 8.2
± ± ± ± ±
12 6 29 7 0.6
61 40 79 20 8.4
± ± ± ± ±
11 5 24 10 1.0
0.79 0.94 0.76 0.51 0.65
PV, pulmonary vein; CB, cryoballoon; CTI, cavotricuspid isthmus; RF, radiofrequency; LA, left atrium.
dislodgment due to right phrenic nerve pacing was initially observed, one should acknowledge that catheter instability at the CTI might occur. In this situation, the use of a long dedicated sheath should be of value. The ablation protocol of combined paroxysmal AF using cryoenergy and RF application at the CTI did not result in an increase in procedure time and in radiation exposure as compared to those recorded during PV cryoablation alone. As RF energy is widely available in every electrophysiology laboratory, our technique may be cost-effective compared to approach reported by Dhillon et al. as on one hand, it does not require two cryoenergy generators and on the other hand, the cost of an irrigated tip RF catheter is significantly lower than that of a focal cryocatheter [16]. Since AFL virtually always starts with a run of AF of variable duration (often very short), if one successfully ablates (i.e., prevents) AF, one should thereby also prevent AFL [1,2]. Thus, if cure of AF was both reliable and predictable, it should not be necessary to perform anything more than PVI in population of patients studied. Recently Mohanty et al. reported the results of a large prospective study on different ablation approaches in patients with mixed AF and typical AFL [20]. Three-hundred sixty patients were enrolled and randomized in 2 groups, AF ± AFL ablation (group 1) or AFL ablation only (group 2). As expected, the authors demonstrated that the strategy employed in group 1 was associated with fewer arrhythmia recurrence and better quality of life improvement than in group 2. Otherwise, in group 1, 58/182 patients underwent both AF and AFL ablation if this latter was spontaneous/inducible at time of the procedure. At 21 months of follow-up, Mohanty et al. did not find additional benefit of AFL ablation on recurrence rate compared to AF ablation only (66% vs 64% off-AAD respectively, p = NS). Therefore, PVI might not only be an effective treatment for AF but might also eliminate AFL. However, study from Mohanty et al. was not designed to compare arrhythmia recurrence after AF ablation alone to AF + AFL ablation in patients with mixed AF and AFL and was not powerful enough to demonstrate an eventual difference between these two strategies. Therefore, consensus opinion of Task Force members still recommends CTI ablation in patients with a history of typical AFL or with typical AFL induced during electrophysiology study [21]. On the opposite, prophylactic PVI with the cryoballoon
technique, added to CTI ablation, in patients in whom the only clinical arrhythmia was typical AFL, was associated with a significant reduction of new-onset AF (detected with continuous implantable cardiac monitor) in a prospective randomized study [22]. However, further large-scaled studies are needed to validate this ablation strategy. We acknowledge that the number of patients included in this study is small. However, this study represents our preliminary experience using two different energy sources and the results suggest that this new approach is efficient and safe. Cost effectiveness of our approach should be discussed. As mentioned above, if cure of AF was both reliable and predictable, CTI ablation might be optional. If CTI ablation was planed, one might consider using RF for both PVI and CTI ablation. We thought, but not affirm, that our strategy with hybrid energy sources for simultaneous PVI and CTI ablation might be cost-effective on account of the increment of cost related to electro-anatomical mapping system use for PVI with RF. Otherwise, monitoring of complications in two different areas, i.e. CTI and right phrenic nerve during second cryoapplication at the right inferior PV, could be challenging in some cases. Nevertheless, to the best of our knowledge, occurrence of right PNP at this level after a first uncomplicated cryoapplication has never been reported. Finally, results and conclusions drawn from present study may not be extrapolated to other RF generators and other ablation catheter systems than those used in our study.
Conclusion This study has shown that coexistent paroxysmal AF and typical AFL can be treated using hybrid energy sources strategy with concomitant CTI ablation with RF during the CB applications at the PVs. It suggests that this approach is effective in achieving complete PVI and bidirectional CTI conduction block. The reported ablation protocol of combined paroxysmal AF and typical AFL did not result in prolongation of procedure duration or radiation exposure compared to a group of patients who underwent PV cryoablation alone. Further studies including a larger group of patients are needed in order to validate this approach and to evaluate its potential benefit as compared with a sequential approach. References [1] Waldo AL. Pathogenesis of atrial flutter. J Cardiovasc Electrophysiol 1998;9(8 Suppl):18–25. [2] Waldo AL, Feld GK. Inter-relationships of atrial fibrillation and atrial flutter mechanisms and clinical implications. J Am Coll Cardiol 2008;51(8):779–86. [3] Moreira W, Timmermans C, Wellens HJ, Mizusawa Y, Philippens S, Perez D, et al. Can common-type atrial flutter be a sign of an arrhythmogenic substrate in paroxysmal atrial fibrillation? Clinical and ablative consequences in patients with coexistent paroxysmal atrial fibrillation/atrial flutter. Circulation 2007;116(24):2786–92. [4] Suttorp MJ, Kingma JH, Koomen EM, van't Hof A, Tijssen JG, Lie KI. Recurrence of paroxysmal atrial fibrillation or flutter after successful cardioversion in patients with normal left ventricular function. Am J Cardiol 1993;71(8):710–3.
M. Peyrol et al. / Journal of Electrocardiology 48 (2015) 729–733 [5] Metzner A, Reissmann B, Rausch P, Mathew S, Wohlmuth P, Tilz R, et al. One-year clinical outcome after pulmonary vein isolation using the second-generation 28-mm cryoballoon. Circ Arrhythm Electrophysiol 2014;7(2):288–92. [6] Neumann T, Wójcik M, Berkowitsch A, Erkapic D, Zaltsberg S, Greiss H, et al. Cryoballoon ablation of paroxysmal atrial fibrillation: 5-year outcome after single procedure and predictors of success. Europace 2013;15(8):1143–9. [7] Vogt J, Heintze J, Gutleben KJ, Muntean B, Horstkotte D, Nölker G. Longterm outcomes after cryoballoon pulmonary vein isolation: results from a prospective study in 605 patients. J Am Coll Cardiol 2013;61(16):1707–12. [8] Neumann T, Vogt J, Schumacher B, Dorszewski A, Kuniss M, Neuser H, et al. Circumferential pulmonary vein isolation with the cryoballoon technique results from a prospective 3-center study. J Am Coll Cardiol 2008;52(4):273–8. [9] Packer DL, Kowal RC, Wheelan KR, Irwin JM, Champagne J, Guerra PG, et al. Cryoballoon ablation of pulmonary veins for paroxysmal atrial fibrillation: first results of the North American Arctic Front (STOP AF) Pivotal Trial. J Am Coll Cardiol 2013;61(16):1713–23. [10] Natale A, Newby KH, Pisanó E, Leonelli F, Fanelli R, Potenza D, et al. Prospective randomized comparison of antiarrhythmic therapy versus first-line radiofrequency ablation in patients with atrial flutter. J Am Coll Cardiol 2000;35(7):1898–904. [11] Tai CT, Chen SA. Cavotricuspid isthmus: anatomy, electrophysiology, and long-term outcome of radiofrequency ablation. Pacing Clin Electrophysiol 2009;32(12):1591–5. [12] Da Costa A, Thévenin J, Roche F, Romeyer-Bouchard C, Abdellaoui L, Messier M, et al. Results from the Loire-Ardèche-Drôme-Isère-Puyde-Dôme (LADIP) trial on atrial flutter, a multicentric prospective randomized study comparing amiodarone and radiofrequency ablation after the first episode of symptomatic atrial flutter. Circulation 2006;114(16):1676–81. [13] Pérez FJ, Schubert CM, Parvez B, Pathak V, Ellenbogen KA, Wood MA. Long-term outcomes after catheter ablation of cavo-tricuspid isthmus dependent atrial flutter: a meta-analysis. Circ Arrhythm Electrophysiol 2009;2(4):393–401.
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[14] Kumagai K, Tojo H, Yasuda T, Noguchi H, Matsumoto N, Nakashima H, et al. Treatment of mixed atrial fibrillation and typical atrial flutter by hybrid catheter ablation. Pacing Clin Electrophysiol 2000;23(11 Pt 2):1839–42. [15] Husser D, Bollmann A, Kang S, Girsky MJ, Lerman RD, Cannom DS, et al. Effectiveness of catheter ablation for coexisting atrial fibrillation and atrial flutter. Am J Cardiol 2004;94(5):666–8. [16] Dhillon PS, Domenichini G, Gonna H, Bastiaenen R, Norman M, Gallagher MM, et al. Feasibility and efficacy of simultaneous pulmonary vein isolation and cavotricuspid isthmus ablation using cryotherapy. J Cardiovasc Electrophysiol 2014;25(7):714–8. [17] Peyrol M, Sbragia P, Quatre A, Orabona M, Casalta AC, Boccara G, et al. Reduction of procedure duration and radiation exposure with a dedicated inner lumen mapping catheter during pulmonary vein cryoablation. Pacing Clin Electrophysiol 2013;36(1):24–30. [18] Cauchemez B, Haissaguerre M, Fischer B, Thomas O, Clementy J, Coumel P. Electrophysiological effects of catheter ablation of inferior vena cava-tricuspid annulus isthmus in common atrial flutter. Circulation 1996;93(2):284–94. [19] Tada H, Oral H, Sticherling C, Chough SP, Baker RL, Wasmer K, et al. Double potentials along the ablation line as a guide to radiofrequency ablation of typical atrial flutter. J Am Coll Cardiol 2001;38(3):750–5. [20] Mohanty S, Mohanty P, Di Biase L, Bai R, Santangeli P, Casella M, et al. Results from a single-blind, randomized study comparing the impact of different ablation approaches on long-term procedure outcome in coexistent atrial fibrillation and flutter (APPROVAL). Circulation 2013;127:1853–60. [21] 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(4):528–606. [22] Steinberg JS, Romanov A, Musat D, Preminger M, Bayramova S, Artyomenko S, et al. Prophylactic pulmonary vein isolation during isthmus ablation for atrial flutter: the PReVENT AF Study I. Heart Rhythm 2014;11(9):1567–72.
ScienceDirect Journal of Electrocardiology 48 (2015) 729 – 733 www.jecgonline.com
Simultaneous pulmonary vein cryoablation and cavotricuspid isthmus radiofrequency ablation in patients with combined atrial fibrillation and typical atrial flutter☆ Michaël Peyrol, M.D., a,⁎ Pascal Sbragia, M.D., a Thibault Ronchard, M.D., a Jennifer Cautela, M.D., a Chloé Villacampa, M.D., a Marc Laine, M.D., a Laurent Bonello, M.D., a Franck Thuny, M.D., a Franck Paganelli, M.D., a Samuel Lévy, M.D. b a
Service de Cardiologie, Centre Hospitalier Universitaire de Marseille, Hôpital Nord, Aix-Marseille Université, Marseille, France b Aix-Marseille Université, Marseille, France
Abstract
Pulmonary vein isolation (PVI) using cryoballoon (CB) technique and cavotricuspid isthmus (CTI) ablation using radiofrequency (RF) are established interventions for drug-resistant atrial fibrillation (AF) and typical atrial flutter (AFL). Twelve patients with a mean age of 62 ± 12 years underwent simultaneous delivery of RF energy at the CTI during CB applications at the PV ostia. Pulmonary vein isolation was achieved in all PVs and sustained bidirectional CTI conduction block obtained in all patients. The reported ablation protocol of combined paroxysmal AF and typical AFL did not result in prolongation of the procedure duration or in prolonged radiation exposure when compared to CB-PVI alone. No interferences between both ablation energy systems were observed. These preliminary results suggest that combined paroxysmal AF and typical AFL can be successfully and safely ablated using hybrid energy sources with simultaneous CTI ablation using RF during CB applications at the PV ostia. © 2015 Elsevier Inc. All rights reserved.
Keywords:
Atrial fibrillation; Cryoablation; Cryoballoon; Atrial flutter; Radiofrequency ablation
Introduction The common combination of atrial fibrillation (AF) and spontaneous or drug-induced atrial flutter (AFL) has long been reported [1–3]. Both, AF and AFL, are often resistant to antiarrhythmic drug therapy aimed at maintaining sinus rhythm [4]. Consequently, catheter ablation techniques are increasingly offered to drug-resistant patients. On one hand, pulmonary vein isolation (PVI) using either radiofrequency energy (RF) or cryoballoon (CB) techniques has been demonstrated to be safe and effective for the treatment of drug-resistant paroxysmal AF with good short or middle term outcomes [5–9]. On the other hand, cavotricuspid isthmus (CTI) ablation using RF is an established treatment of symptomatic typical AFL, increasingly used as first-line therapy [10–13]. In selected patients with combined AF and AFL, catheter ablation strategy targeting PVI and CTI
conduction block using RF energy has been reported to confer satisfactory outcomes [14,15]. Recently, simultaneous PV and CTI cryoablation, using two cryotherapy generators, were shown to be a safe and effective approach [16]. After the first minute of the 4-minute CB application at the PV, the adherence to the atrial tissue allows the operator to release the grip on the CB catheter. Therefore, the operator has several minutes to perform linear lesions with a focal catheter at the CTI. We hypothesized that simultaneous CTI ablation using RF energy during the 240-second CB applications at the PVs could be an alternative approach for treating patients with combined paroxysmal AF and typical AFL. To our knowledge, such simultaneous hybrid energy source approach has not been reported in these indications.
Patients and methods ☆
Disclosures: Drs Peyrol and Sbragia receive compensation for teaching and proctoring purposes from Medtronic Inc. ⁎ Corresponding author at: Service de Cardiologie, Centre Hospitalier Universitaire de Marseille, Hôpital Nord, Aix-Marseille Université, Marseille, France. E-mail address: [email protected] http://dx.doi.org/10.1016/j.jelectrocard.2015.03.013 0022-0736/© 2015 Elsevier Inc. All rights reserved.
Consecutive patients referred to our institution with combined drug-resistant paroxysmal AF and typical AFL were prospectively included in this study after informed consent obtained. All patients underwent transesophagealechocardiography the day before the procedure mainly to
730
M. Peyrol et al. / Journal of Electrocardiology 48 (2015) 729–733
exclude a left atrium (LA) thrombus and to assess LA diameters but also to possibly detect atypical PV anatomy/ early branching. An LA thrombus, an LA anterior-posterior diameter N 50 mm, a moderate to severe mitral insufficiency or stenosis, a severe left ventricular hypertrophy (i.e. septal wall thickness N 15 mm) and a depressed (b 50 %) left ventricular ejection fraction were defined as exclusion criteria. Antithrombotic therapy, either using vitamin K antagonists or direct oral anticoagulant agents (dabigatran or rivaroxaban), was interrupted 2 days before the procedure. Midazolam and nalbuphine were used to obtain conscious sedation and analgesia during the procedure. Our current protocol for PVI procedure using the CB technique has been described elsewhere [17]. Briefly, a single 28-mm CB catheter (Arctic Front Advance™, CryoCath-Medtronic, Quebec, Canada), was advanced into the LA through the 12 French steerable sheath (12French, FlexCath Advance™, Cryocath-Medtronic, Quebec, Canada) via a single transseptal approach. Proper anticoagulation during the procedure was achieved using an intravenous bolus of unfractionated heparin of 100 IU/kg in order to obtain an activated clotting time of 250–300 seconds monitored every 30 minutes thereafter. A 20-mm Achieve™ (Medtronic-CryoCath, Quebec, Canada) endoluminal spiral catheter was inserted into the lumen of the CB both to navigate the CB to the PVs and to allow, when possible, real-time visualization of LA-PV conduction. Four-minute CB applications were initiated at the left-sided PVs. One additional cryoapplication (“bonus”) was delivered after achievement of PVI. During isolation of the right-sided PVs, continuous right phrenic nerve stimulation was performed via a quadripolar catheter positioned in the superior vena cava above the CB in order to detect phrenic nerve palsy. In our ablation protocol, we started with a cryoapplication at the right inferior PV as the risk of phrenic nerve palsy was felt to be lower at this site than with the right superior PV. The endpoint of PV cryoablation was complete PVI. Antithrombotic therapy was resumed the day of the intervention whereas antiarrhythmic drug therapy was discontinued. At time of the beginning of our study, anticoagulant bridging therapy in patients on vitamin K antagonists was still performed in our laboratory (enoxaparin 1.0 mg/kg twice a day starting 2 hours after catheter removal until therapeutic INR was achieved) and was pursued throughout the study. No anticoagulant bridging therapy was used in patients on direct oral anticoagulant therapy. Direct oral anticoagulant therapy was resumed 2 hours after the end of the procedure in the absence of local bleeding. Patients were discharged the day following the procedure in the absence of complications. Radiofrequency delivery at the CTI was performed during cryoapplication at the left-sided PV ostia and at the right inferior PV during second cryoapplication if no phrenic nerve palsy occurred during the first cryoapplication (Fig. 1). A 4-mm open-irrigated tip ablation catheter (Therapy™ Cool Path™, Saint Jude Medical, MN, USA) was advanced to the right atrium via the right femoral vein. Radiofrequency delivery was performed either during atrial flutter or during coronary sinus (CS) pacing at 600 ms via a deflectable quadripolar catheter. The power delivered by the RF generator (IBI-1500T11, Saint Jude Medical, MN, USA)
Fig. 1. Left anterior oblique view of catheters position during simultaneous delivery of radiofrequency energy at the cavotricuspid isthmus via a 4-mm open-irrigated tip catheter and 28-mm cryoballoon application with endoluminal spiral catheter at the left superior pulmonary vein.
was adjusted between 30 and 35 W in order to achieve modification of local electrograms. Cavotricuspid isthmus conduction was tested after completion of CB applications at the right-sided PVs. Bidirectional CTI conduction block was considered achieved if at least one of the following criteria were present: (1) complete descending lateral right atrial activation during pacing through the ablation catheter at the septal end of the CTI and complete descending septal right atrial activation during pacing at the lateral end of the CTI [18] or (2) recording a corridor of parallels double potentials separated (≥ 110 ms) with an isoelectric interval along the CTI ablation line during coronary sinus/low lateral right atrial pacing [19]. The endpoint of the CTI ablation was sustained bidirectional conduction block. For further analysis, we compared procedural characteristics of patients who underwent simultaneous ablation for combined AF and AFL to those of 24 patients, matched for age and LA diameter, who underwent PV cryoablation alone in our institution. Clinical and procedural parameters are given as mean ± standard deviation. Student t-test was used to compare differences between groups. A p value b 0.05 was considered statistically significant. All analyses were performed using GraphPad QuickCalcs (Graphpad, La Jolla, CA, USA).
Results Twelve patients (10 men and 2 women) with a mean age of 62 ± 12 years (range 42–80) were included in this study. History of hypertension was present in 3 patients. The 9 remaining patients had lone AF/AFL. Mean anterior-posterior LA diameter was 41 ± 6 mm. Mean PV diameters were 23 ± 2 mm for the left superior PV, 19 mm ± 3 for the left inferior
M. Peyrol et al. / Journal of Electrocardiology 48 (2015) 729–733
PV, 23 ± 2 mm for the right superior PV and 19 ± 2 mm for the right inferior PV. No atypical PV anatomy was detected during the pre-ablation transesophageal-echocardiography. Clinical and procedural characteristics are presented in Table 1. Simultaneous PVI with the CB technique and RF delivery at the CTI were successfully performed in all patients. Pulmonary vein isolation was achieved in all 48 targeted PVs following CB applications. Real-time PVI was observed in 31/48 treated PVs (64.5%). In “real-time” isolated PVs, mean time to LA-PV disconnection was 64 ± 30 seconds and mean CB temperature at that time was − 38 ± 10 °C. Mean CB temperature reached at the end of the 240 second application was − 51 ± 7 °C. Mean number of cryoapplications per patient was 8.2 ± 0.6 (range 8–10). Radiofrequency CTI ablation was carried out during ongoing AFL in 5 patients and during CS pacing in the remaining 7 patients. Mean procedure duration and radioscopy exposure were 82 ± 29 min (range 60–165 min) and 22 ± 7 min (range 12–31 min) respectively. No RF catheter dislodgment, related to phrenic nerve pacing, was observed during right inferior PV cryoablation. The endpoints of the procedure, complete PVI and bidirectional CTI conduction block, were reached in all patients. All patients presented with bidirectional CTI conduction block after completion of PV cryolesion. Transient right phrenic nerve palsy was observed in 2 patients during CB application at the RSPV. Phrenic nerve function recovered before the end of the procedure in both cases. No other complications including vascular access complications were observed. Of importance, no complications related to the simultaneous use of combined energy sources were recorded. In particular, no electrical interference between the cryoablation system and the RF system was observed during simultaneous delivery of cryoenergy at the PVs and RF energy at the CTI. With a mean follow-up of 12 ± 3 months, atrial arrhythmia recurrence was observed in 3 patients, paroxysmal AF in 2 and paroxysmal atypical AFL in 1 among the group of patients who underwent simultaneous PV cryoablation and CTI RF ablation for combined AF and typical AFL. Procedural characteristics of patients who underwent combined paroxysmal AF and typical AFL were compared to those of 24 patients who underwent PV cryoablation alone
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matched for age and LA diameter (62 ± 12 years vs 61 ± 11 years; p = NS and 41 ± 6 mm vs 40 ± 5 mm; p = NS respectively). Simultaneous PV cryoablation and CTI RF ablation were not associated with significant prolongation of procedure duration or radiation exposure when compared to PV cryoablation alone (82 ± 29 min vs 79 ± 24 min; p = NS and 22 ± 7 min vs 20 ± 10 min; p = NS respectively). Comparison of clinical and procedural data between the two groups of patients is shown in Table 2.
Discussion This study showed that simultaneous PVI using the cryoenergy and CTI ablation using the RF energy can be safely and successfully achieved in patients with combined AF and AFL. No interferences were observed between the two energy sources used simultaneously. The use of two different energy sources simultaneously is made possible after the first minute of the 4-minute CB application at the PV due to the adherence to the atrial tissue allowing the operator to release the grip on the CB catheter. Therefore, in our protocol, the operator had several minutes to achieve CTI conduction block with an RF catheter. Dhillon et al. recently reported that simultaneous PVI with the CB technique and CTI ablation using the 8-mm tip cryocatheter was also feasible and safe [16]. The authors mentioned that, in their experience, RF delivery at the CTI during PV cryoablation systematically triggered a safety cut-off of cryotherapy. Indeed, during RF energy delivery, the security system of the cryoconsole may deliver an alert on fluid detection within the CB. This alert automatically leads to interruption of refrigerant fluid injection and thereafter CB deflation. In our experience with an open irrigated-tip catheter system, such system alert has never been observed. Moreover, no special setup was necessary, neither for cryoenergy system nor for the RF generator. In the present protocol, lesions at the CTI were preferentially created during CB application at the left-sided PVs. Furthermore, if phrenic nerve palsy did not occur during the first CB application at the RIPV, our protocol allowed RF delivery at the CTI during additional cryoapplication at this vein level. Although no RF catheter
Table 1 Clinical and procedural characteristics of patients undergoing simultaneous pulmonary vein cryoablation and cavotricuspid isthmus radiofrequency ablation. Patient
Gender
Age (years)
1 2 3 4 5 6 7 8 9 10 11 12
M M M M M F M F M M M M
44 69 59 54 72 72 55 77 57 42 80 64
Underlying HD HTN
HTN
HTN
LA size (mm)
Procedure duration (min)
Radiation exposure (min)
Nb of CB applications
31 50 36 38 44 40 42 36 50 49 38 39
95 60 70 95 60 165 90 75 75 65 70 65
28 12 12 20 15 31 30 22 27 14 28 24
8 8 8 8 8 10 8 8 9 8 8 8
HD, heart disease; HTN, hypertension; LA, left atrium; CB, cryoballoon; PNP, phrenic nerve palsy; RSPV, right superior pulmonary vein.
PNP
RSPV RSPV
732
M. Peyrol et al. / Journal of Electrocardiology 48 (2015) 729–733
Table 2 Comparison between patients undergoing simultaneous pulmonary vein cryoablation and cavotricuspid isthmus radiofrequency ablation and patients undergoing pulmonary vein cryoablation alone. PV-CB ablation/CTI PV-CB p value RF (n=12) ablation (n=24) Age (years) 62 LA diameter (mm) 41 Procedure duration (min) 82 Radiation exposure (min) 22 Nb. of CB applications 8.2
± ± ± ± ±
12 6 29 7 0.6
61 40 79 20 8.4
± ± ± ± ±
11 5 24 10 1.0
0.79 0.94 0.76 0.51 0.65
PV, pulmonary vein; CB, cryoballoon; CTI, cavotricuspid isthmus; RF, radiofrequency; LA, left atrium.
dislodgment due to right phrenic nerve pacing was initially observed, one should acknowledge that catheter instability at the CTI might occur. In this situation, the use of a long dedicated sheath should be of value. The ablation protocol of combined paroxysmal AF using cryoenergy and RF application at the CTI did not result in an increase in procedure time and in radiation exposure as compared to those recorded during PV cryoablation alone. As RF energy is widely available in every electrophysiology laboratory, our technique may be cost-effective compared to approach reported by Dhillon et al. as on one hand, it does not require two cryoenergy generators and on the other hand, the cost of an irrigated tip RF catheter is significantly lower than that of a focal cryocatheter [16]. Since AFL virtually always starts with a run of AF of variable duration (often very short), if one successfully ablates (i.e., prevents) AF, one should thereby also prevent AFL [1,2]. Thus, if cure of AF was both reliable and predictable, it should not be necessary to perform anything more than PVI in population of patients studied. Recently Mohanty et al. reported the results of a large prospective study on different ablation approaches in patients with mixed AF and typical AFL [20]. Three-hundred sixty patients were enrolled and randomized in 2 groups, AF ± AFL ablation (group 1) or AFL ablation only (group 2). As expected, the authors demonstrated that the strategy employed in group 1 was associated with fewer arrhythmia recurrence and better quality of life improvement than in group 2. Otherwise, in group 1, 58/182 patients underwent both AF and AFL ablation if this latter was spontaneous/inducible at time of the procedure. At 21 months of follow-up, Mohanty et al. did not find additional benefit of AFL ablation on recurrence rate compared to AF ablation only (66% vs 64% off-AAD respectively, p = NS). Therefore, PVI might not only be an effective treatment for AF but might also eliminate AFL. However, study from Mohanty et al. was not designed to compare arrhythmia recurrence after AF ablation alone to AF + AFL ablation in patients with mixed AF and AFL and was not powerful enough to demonstrate an eventual difference between these two strategies. Therefore, consensus opinion of Task Force members still recommends CTI ablation in patients with a history of typical AFL or with typical AFL induced during electrophysiology study [21]. On the opposite, prophylactic PVI with the cryoballoon
technique, added to CTI ablation, in patients in whom the only clinical arrhythmia was typical AFL, was associated with a significant reduction of new-onset AF (detected with continuous implantable cardiac monitor) in a prospective randomized study [22]. However, further large-scaled studies are needed to validate this ablation strategy. We acknowledge that the number of patients included in this study is small. However, this study represents our preliminary experience using two different energy sources and the results suggest that this new approach is efficient and safe. Cost effectiveness of our approach should be discussed. As mentioned above, if cure of AF was both reliable and predictable, CTI ablation might be optional. If CTI ablation was planed, one might consider using RF for both PVI and CTI ablation. We thought, but not affirm, that our strategy with hybrid energy sources for simultaneous PVI and CTI ablation might be cost-effective on account of the increment of cost related to electro-anatomical mapping system use for PVI with RF. Otherwise, monitoring of complications in two different areas, i.e. CTI and right phrenic nerve during second cryoapplication at the right inferior PV, could be challenging in some cases. Nevertheless, to the best of our knowledge, occurrence of right PNP at this level after a first uncomplicated cryoapplication has never been reported. Finally, results and conclusions drawn from present study may not be extrapolated to other RF generators and other ablation catheter systems than those used in our study.
Conclusion This study has shown that coexistent paroxysmal AF and typical AFL can be treated using hybrid energy sources strategy with concomitant CTI ablation with RF during the CB applications at the PVs. It suggests that this approach is effective in achieving complete PVI and bidirectional CTI conduction block. The reported ablation protocol of combined paroxysmal AF and typical AFL did not result in prolongation of procedure duration or radiation exposure compared to a group of patients who underwent PV cryoablation alone. Further studies including a larger group of patients are needed in order to validate this approach and to evaluate its potential benefit as compared with a sequential approach. References [1] Waldo AL. Pathogenesis of atrial flutter. J Cardiovasc Electrophysiol 1998;9(8 Suppl):18–25. [2] Waldo AL, Feld GK. Inter-relationships of atrial fibrillation and atrial flutter mechanisms and clinical implications. J Am Coll Cardiol 2008;51(8):779–86. [3] Moreira W, Timmermans C, Wellens HJ, Mizusawa Y, Philippens S, Perez D, et al. Can common-type atrial flutter be a sign of an arrhythmogenic substrate in paroxysmal atrial fibrillation? Clinical and ablative consequences in patients with coexistent paroxysmal atrial fibrillation/atrial flutter. Circulation 2007;116(24):2786–92. [4] Suttorp MJ, Kingma JH, Koomen EM, van't Hof A, Tijssen JG, Lie KI. Recurrence of paroxysmal atrial fibrillation or flutter after successful cardioversion in patients with normal left ventricular function. Am J Cardiol 1993;71(8):710–3.
M. Peyrol et al. / Journal of Electrocardiology 48 (2015) 729–733 [5] Metzner A, Reissmann B, Rausch P, Mathew S, Wohlmuth P, Tilz R, et al. One-year clinical outcome after pulmonary vein isolation using the second-generation 28-mm cryoballoon. Circ Arrhythm Electrophysiol 2014;7(2):288–92. [6] Neumann T, Wójcik M, Berkowitsch A, Erkapic D, Zaltsberg S, Greiss H, et al. Cryoballoon ablation of paroxysmal atrial fibrillation: 5-year outcome after single procedure and predictors of success. Europace 2013;15(8):1143–9. [7] Vogt J, Heintze J, Gutleben KJ, Muntean B, Horstkotte D, Nölker G. Longterm outcomes after cryoballoon pulmonary vein isolation: results from a prospective study in 605 patients. J Am Coll Cardiol 2013;61(16):1707–12. [8] Neumann T, Vogt J, Schumacher B, Dorszewski A, Kuniss M, Neuser H, et al. Circumferential pulmonary vein isolation with the cryoballoon technique results from a prospective 3-center study. J Am Coll Cardiol 2008;52(4):273–8. [9] Packer DL, Kowal RC, Wheelan KR, Irwin JM, Champagne J, Guerra PG, et al. Cryoballoon ablation of pulmonary veins for paroxysmal atrial fibrillation: first results of the North American Arctic Front (STOP AF) Pivotal Trial. J Am Coll Cardiol 2013;61(16):1713–23. [10] Natale A, Newby KH, Pisanó E, Leonelli F, Fanelli R, Potenza D, et al. Prospective randomized comparison of antiarrhythmic therapy versus first-line radiofrequency ablation in patients with atrial flutter. J Am Coll Cardiol 2000;35(7):1898–904. [11] Tai CT, Chen SA. Cavotricuspid isthmus: anatomy, electrophysiology, and long-term outcome of radiofrequency ablation. Pacing Clin Electrophysiol 2009;32(12):1591–5. [12] Da Costa A, Thévenin J, Roche F, Romeyer-Bouchard C, Abdellaoui L, Messier M, et al. Results from the Loire-Ardèche-Drôme-Isère-Puyde-Dôme (LADIP) trial on atrial flutter, a multicentric prospective randomized study comparing amiodarone and radiofrequency ablation after the first episode of symptomatic atrial flutter. Circulation 2006;114(16):1676–81. [13] Pérez FJ, Schubert CM, Parvez B, Pathak V, Ellenbogen KA, Wood MA. Long-term outcomes after catheter ablation of cavo-tricuspid isthmus dependent atrial flutter: a meta-analysis. Circ Arrhythm Electrophysiol 2009;2(4):393–401.
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[14] Kumagai K, Tojo H, Yasuda T, Noguchi H, Matsumoto N, Nakashima H, et al. Treatment of mixed atrial fibrillation and typical atrial flutter by hybrid catheter ablation. Pacing Clin Electrophysiol 2000;23(11 Pt 2):1839–42. [15] Husser D, Bollmann A, Kang S, Girsky MJ, Lerman RD, Cannom DS, et al. Effectiveness of catheter ablation for coexisting atrial fibrillation and atrial flutter. Am J Cardiol 2004;94(5):666–8. [16] Dhillon PS, Domenichini G, Gonna H, Bastiaenen R, Norman M, Gallagher MM, et al. Feasibility and efficacy of simultaneous pulmonary vein isolation and cavotricuspid isthmus ablation using cryotherapy. J Cardiovasc Electrophysiol 2014;25(7):714–8. [17] Peyrol M, Sbragia P, Quatre A, Orabona M, Casalta AC, Boccara G, et al. Reduction of procedure duration and radiation exposure with a dedicated inner lumen mapping catheter during pulmonary vein cryoablation. Pacing Clin Electrophysiol 2013;36(1):24–30. [18] Cauchemez B, Haissaguerre M, Fischer B, Thomas O, Clementy J, Coumel P. Electrophysiological effects of catheter ablation of inferior vena cava-tricuspid annulus isthmus in common atrial flutter. Circulation 1996;93(2):284–94. [19] Tada H, Oral H, Sticherling C, Chough SP, Baker RL, Wasmer K, et al. Double potentials along the ablation line as a guide to radiofrequency ablation of typical atrial flutter. J Am Coll Cardiol 2001;38(3):750–5. [20] Mohanty S, Mohanty P, Di Biase L, Bai R, Santangeli P, Casella M, et al. Results from a single-blind, randomized study comparing the impact of different ablation approaches on long-term procedure outcome in coexistent atrial fibrillation and flutter (APPROVAL). Circulation 2013;127:1853–60. [21] 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(4):528–606. [22] Steinberg JS, Romanov A, Musat D, Preminger M, Bayramova S, Artyomenko S, et al. Prophylactic pulmonary vein isolation during isthmus ablation for atrial flutter: the PReVENT AF Study I. Heart Rhythm 2014;11(9):1567–72.
