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Durability of wide-area left atrial appendage isolation: Results from extensive catheter ablation for treatment of persistent atrial fibrillation
Author’s Accepted Manuscript Durability of Wide-Area Left Atrial Appendage Isolation: Results from Extensive Catheter Ablation for the Treatment of Persistent Atrial Fibrillation Bruno Reissmann, Andreas Rillig, Erik Wissner, Roland Tilz, Michael Schlüter, Christian Sohns, Christian Heeger, Shibu Mathew, Tilman Maurer, Christine Lemes, Thomas Fink, Peter Wohlmuth, Francesco Santoro, Johannes Riedl, Feifan Ouyang, Karl-Heinz Kuck, Andreas Metzner
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To appear in: Heart Rhythm Cite this article as: Bruno Reissmann, Andreas Rillig, Erik Wissner, Roland Tilz, Michael Schlüter, Christian Sohns, Christian Heeger, Shibu Mathew, Tilman Maurer, Christine Lemes, Thomas Fink, Peter Wohlmuth, Francesco Santoro, Johannes Riedl, Feifan Ouyang, Karl-Heinz Kuck and Andreas Metzner, Durability of Wide-Area Left Atrial Appendage Isolation: Results from Extensive Catheter Ablation for the Treatment of Persistent Atrial Fibrillation, Heart Rhythm, http://dx.doi.org/10.1016/j.hrthm.2016.11.009 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Durability of Wide-Area Left Atrial Appendage Isolation: Results from Extensive Catheter Ablation for the Treatment of Persistent Atrial Fibrillation Bruno Reissmann MD¹*; Andreas Rillig MD2*; Erik Wissner MD1; Roland Tilz MD3; Michael Schlüter PhD4; Christian Sohns MD¹; Christian Heeger MD¹; Shibu Mathew MD¹; Tilman Maurer MD¹; Christine Lemes MD¹; Thomas Fink MD¹; Peter Wohlmuth PhD4; Francesco Santoro MD¹; Johannes Riedl MD¹; Feifan Ouyang MD¹; Karl-Heinz Kuck MD¹; Andreas Metzner MD¹ ¹Dept. of Cardiology, Asklepios Klinik St. Georg, Hamburg, Germany; 2Dept. of Cardiology, Campus Benjamin Franklin, Charité Universitätsmedizin Berlin, Germany; 3University Heart Center Lübeck, Medical Clinic II, Lübeck, Germany; 4Asklepios proresearch, Hamburg, Germany.
*Both authors contributed equally to the manuscript
Short title: Durability of left atrial appendage isolation
Conflict of interest disclosures: KHK and AM received speaker´s honoraria from Biosense Webster. Corresponding author: Bruno Reissmann, MD Dept. of Cardiology Asklepios Klinik St. Georg Lohmühlenstr. 5 20099 Hamburg, Germany phone: +4940 181885 2305 fax: +4940 181885 4444 e-mail: [email protected]
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Abstract Background: Extensive ablation strategies are currently performed in addition to pulmonary vein isolation (PVI) to improve the clinical outcome of patients with drug-refractory persistent atrial fibrillation (AF). Ablation of complex fractionated atrial electrograms (CFAE), linear lesions and/or isolation of the left atrial appendage (LAA) are thought to improve arrhythmiafree survival. Objective: This study sought to assess the durability of wide-area LAA isolation (LAAI) achieved by PVI, an anterior line and a mitral isthmus line. Methods: Seventy-one patients with intentional or incidental LAAI during repeat catheter ablation for the treatment of persistent AF were included. The initial ablation strategy was PVI. Additional ablation strategies were only performed if PVI failed to maintain stable sinus rhythm (SR). Durability of LAAI was assessed during a subsequent ablation procedure for arrhythmia recurrences (n=23) or a subsequent percutaneous LAA closure (n=48). Results: LAAI was performed after a mean of 3±1 procedures. Ablation strategies included circumferential PVI in 71 (100%) patients, mitral isthmus line in 64 (90%), anterior line in 60 (85%), CFAE in 27 (38%), and roof line in 13 (18%) patients. LAAI occurred after ablation and bidirectional block of LA linear lesions in 63 (89%) patients and during extensive CFAE ablation in 8 (11%) patients. After a median period of 105 [61;426] days, the LAA remained electrically isolated in 52/71 (73%) patients. Conclusions: Wide-area LAAI following extensive catheter ablation for persistent AF is durable in a majority of patients. The potential clinical benefit of LAAI for maintaining stable SR needs further investigation. Key words: Persistent atrial fibrillation; Catheter ablation; Left atrial appendage isolation; Pulmonary vein isolation; Left atrial linear lesions; Complex fractionated atrial electrograms
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Introduction Pulmonary vein isolation (PVI) is the cornerstone treatment of drug-refractory atrial fibrillation (AF) (1). While the long-term success rate of PVI in patients with paroxysmal atrial fibrillation (PAF) is favorable, clinical outcomes in patients with persistent AF are less beneficial (2-4). To improve the outcome in patients with persistent AF, more extensive ablation strategies in addition to PVI have been proposed (5,6), such as the creation of linear lesions and/or the ablation of complex fractionated atrial electrograms (CFAE) (7-9). Of note, these extensive substrate modifications in the left atrium can result in wide-area left atrial appendage (LAA) isolation (LAAI) (2,10). However, LAAI can improve the outcome in patients with persistent AF (11) but at the same time might increase the risk of LAA thrombus formation despite sufficient oral anticoagulation therapy (OAC) (12). The current study sought to assess the durability of wide-area LAAI following PVI, left atrial (LA) linear ablation, and/or CFAE ablation. Methods Patients Patients with persistent AF and LAAI achieved intentionally or serendipitously in a previous ablation procedure were included into the analysis. All patients were refractory to antiarrhythmic drugs. Transesophageal echocardiography (TEE) was performed prior to the ablation procedure in all patients to assess LA dimensions and to rule out intracardiac thrombi. No additional pre-procedural imaging was performed. The current study is a retrospective analysis based on our institutional database. The study was approved by our institutional review board. Ablation protocol In the initial ablation attempt all patients underwent circumferential PVI applying irrigated radiofrequency current, as previously described (13). The procedural end point was the absence of any pulmonary vein (PV) potential recorded by a spiral mapping catheter (Lasso, 3
Biosense Webster) placed along the ostium of the respective PV following a waiting period of 30 min. If AF did not convert to sinus rhythm (SR) after successful PVI, direct-current cardioversion (DCCV) was performed (Lifepak 12, Medtronic Inc., MN). CFAE ablation was performed if SR could not be achieved by DCCV (2). In cases of extensive CFAE ablation along the anterior LA wall and/or the mitral isthmus area, additional linear lesions were created to prevent atrial tachycardia (AT) recurrences (Figure 1). If AF converted to AT during CFAE ablation, the underlying mechanism was evaluated and linear lesions were created or focal ablation was performed (8,14). Linear lesions included an anterior line (connection between the mitral annulus and the right superior PV), a mitral isthmus line (connection between the mitral annulus and the left-sided PVs), and a roof line (connection between the right superior PV and the left superior PV). Bidirectional block of linear lesions was validated during SR based on established electrophysiological maneuvers (8). During CFAE and/or LA linear ablation, a spiral mapping catheter was positioned in the LAA to continuously record LAA activity. Ablation protocol: Repeat procedures Repeat ablation procedures were performed in patients with recurrence of atrial tachyarrhythmias. In case of PV reconnection, conduction gaps were closed with radiofrequency ablation aiming at PV re-isolation. CFAE ablation was performed if AF could not be converted to SR or AT by re-isolation of the PVs or DCCV (2). In patients presenting with macro-reentrant AT or in cases of conversion to macro-reentrant AT during repeat ablation, linear ablation was performed. Electrical LAAI was defined as follows: 1) demonstration of entrance block (disappearance of all LAA potentials documented with a spiral mapping catheter placed inside the LAA, regardless of the underlying cardiac rhythm) and 2) demonstration of exit block (LAA electric activity dissociated from the LA during LAA ectopy or pacing from inside the LAA) (2,8). In order to detect early reconduction of the LAA, a waiting period of 30 minutes was considered.
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Assessment of Durability of Wide-Area Left Atrial Appendage Isolation All patients included into our analysis underwent a repeat ablation procedure due to arrhythmia recurrence or were scheduled for percutaneous LAA closure. LAAI durability was systematically assessed during these procedures. Therefore, a 15-mm spiral mapping catheter was placed inside the LAA and both entrance and exit block were assessed. Percutaneous LAA closure was performed by implanting either an endocardial or an epicardial LAA closure device, as previously described (15,16). Statistics Continuous data are described as mean and standard deviation (SD) if normally distributed, otherwise the median and interquartile range [IQR] are reported. Categorical data are described with absolute and relative frequencies. Time-to-event curves were generated using Kaplan-Meier analysis. LAAI durability of patients with intentional or incidental LAAI was compared with the use of Pearson’s chi-square test. A probability value of P<0.05 was considered to indicate statistical significance. All calculations were performed using SAS (version 9.3, SAS Institute Inc., Cary, NC, USA). Results Patients During the time of our study (03/2003 to 09/2015) approximately 17,000 patients with a history of AF underwent LA ablation procedures at our institution. Of these patients, intentional LAAI was achieved or incidental LAAI occurred during repeat ablation procedures in a total of 117 patients with persistent AF. Seventy-one [69±7 years, 33 (46%) men, median CHA2DS2-VASc Score 3 (2;3), LA diameter 47±6 mm] of these 117 patients underwent a subsequent procedure affording an opportunity to assess LAAI durability. LAAI was demonstrated during the second ablation procedure in 25/71 (35%) patients, during the third procedure in 27/71 (38%) patients, during the fourth procedure in 13/71 (18%) patients, and
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during the fifth ablation procedure in 6/71 (9%) patients. The patients’ baseline characteristics are shown in Table 1. Procedural characteristics until Left Atrial Appendage Isolation The 71 patients underwent a total of 213 procedures. Overall, the ablation strategies in the 71 patients included circumferential PVI in all patients, creation of a mitral isthmus line in 64 (90%), an anterior line in 60 (85%) and a roof line in 13 (18%) patients, as well as CFAE ablation in 27 patients (38%). LAAI occurred after a mean of 3±1 procedures. The LAA was electrically isolated by linear ablation in the LA in 63 (89%) patients; in these patients, LAAI was the result of achieving bidirectional conduction block along both an anterior and a mitral isthmus line. In the remaining 8 (11%) patients, the LAA was isolated during extensive CFAE ablation. LAAI was intentionally performed in 39 (55%) patients because of localized reentry AT within the LAA. In the other 32 (45%) patients, LAAI occurred during linear ablation for LA tachycardia in 24 (34%), and during extensive CFAE ablation in 8 (11%) patients. Durability of Left Atrial Appendage Isolation At a median of 105 [61;426] days after LAAI, the durability of LAAI was assessed during a repeat ablation procedure necessitated by an arrhythmia recurrence [23 (32%) patients] or during a planned percutaneous LAA closure following LAAI [48 (68%) patients]. At that time, the LAA was found to be electrically isolated in 52/71 (73%) patients (Figure 2). The durability of LAAI did not differ significantly between patients with intentional and incidental LAAI (p=0.57), and there was no significant difference in procedure data and baseline characteristics between patients with persistent LAAI and patients with LAA reconnection (Table 2). At the time of LAAI assessment, 53/71 (75%) patients presented in SR, 10/71 (14%) patients in AT and 8/71 (11%) patients in AF. Of the 53 patients who presented in SR, 7 (13%) patients underwent electrical CV due to AT prior to the re-ablation procedure. 6
Repeat Ablation Procedure following Left Atrial Appendage Isolation A repeat ablation procedure following previously successful LAAI was performed in 23/71 (32%) patients. The LAA remained durably isolated in 11/23 (48%) patients. In these patients the present arrhythmia was a right-sided AT in 6 patients and a focal left-sided AT in 4 patients. In one patient, who presented in SR, the LAA remained durably isolated and no tachycardia could be induced, therefore no ablation was performed. In 8/12 (67%) patients with LAA reconnection, the LAA was identified as the trigger of the current arrhythmia (5 patients with focal AT arising from the LAA, and 3 patients with ectopy from the LAA triggering AF) and was subsequently re-isolated. In the remaining 4/12 (33%) patients with LAA reconnection, but no LAA-dependent tachycardia, no re-isolation of the LAA was performed. Thrombus Formation following Left Atrial Appendage Isolation In 7/71 (10%) patients with previous LAAI who presented for a subsequent procedure, LAA thrombus formation was detected by pre-procedural TEE. Consequently, all 7 patients were treated with phenprocoumon targeting an INR of 2.5 – 3.0, and the procedures were rescheduled. After a median of 64 [57;137] days, the LAA thrombus was no longer detectable, thus allowing for assessment of LAAI durability. LAAI was still present in 6/7 patients; LAA reconduction was demonstrated in the remaining patient. Complications The following complications occurred in 10/213 (4.7%) procedures: arteriovenous fistula or pseudoaneurysm (n=6) and vascular surgery (n=2 of 6), femoral hematoma requiring blood transfusion (n=1), cardiac tamponade requiring pericardiocentesis (n=1), and esophageal thermal lesions (n=2) that recovered under treatment with proton pump inhibitors. The procedural adverse events are shown in Table 2.
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Discussion This study is the first addressing the durability of wide-area LAAI following extensive substrate modification in the LA for the treatment of persistent AF. In the current patient cohort, a high durability of LAAI was observed following PVI, an anterior line and a mitral isthmus line, but also in patients in whom extensive ablation of CFAE was performed with incidental LAAI. PVI is an effective treatment option for patients suffering from PAF and recurrences of AF are the result of electrical reconnections of formerly isolated PVs in the majority of patients (17-21). At the same time, the clinical success of stand-alone PVI for the treatment of persistent AF is limited (2-4). Therefore, additional substrate ablation following durable PVI has become a widely accepted and applied form of therapy (5,6). However, results on the clinical benefit of more extensive ablation strategies are contradictory (22,23). The most commonly used additional ablation strategies are the ablation of CFAE and/or the application of linear lesions (7-9). The LAA is a promising additional target for ablation since it may serve as a potential source for triggering and perpetuating AF. However, to date, clinical data reporting on clinical success after LAAI is limited. Since the LAA can be the source for initiation and maintenance of AF beyond the PVs, electrical isolation of the LAA can significantly improve the outcome in certain patients (11). However, the best strategy to achieve LAAI has not yet been assessed. Segmental and circumferential isolation of the LAA is feasible (11), but is associated with safety concerns while ablating at the ostium of the LAA. In contrast, wide-area isolation of the LAA by aiming for bidirectional block of an anterior line and a mitral isthmus line provides an alternative strategy. The creation of linear lesions might capture additional arrhythmogenic substrate and thereby effectively lower the incidence of macro-reentry ATs that frequently occur after repeat ablation procedures for the treatment of persistent AF (2,24,25).
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However, the key aspect in catheter-based ablation is to create transmural and durable lesions. While acute success is achieved in almost all cases, long-term efficacy is often limited by reconnection of previously blocked lesions (21,26-30). LAAI by creation of linear lesions results in a high rate of durable electrical LAAI and might increase the arrhythmiafree survival in patients with persistent AF. However, the isolation of the LAA is a complex procedure with the potential risk of procedural adverse events and thrombus formation inside or along the isolated LAA despite continuous OAC (12). In our study, transient LAA thrombus formation was detected in a total of 7/71 patients. Therefore, LAAI must be carefully considered and the potential necessity taken into account for a subsequent percutaneous closure of the LAA after electrical isolation. Of note, although a high incidence of LAA thrombus formation following wide-area LAAI has been assessed (12), one report did not find evidence of LAA thrombus after ostial LAAI in 204 patients (11). These data suggest that the impact on LAA contraction and overall flow velocities differs between wide-area LAAI and ostial LAAI. However, before final conclusions can be drawn, more data is required to assess arrhythmia-free survival, safety of the procedure and thrombogenicity inside and along the LAA after electrical isolation. Limitations The current analysis has some limitations. First, no clinical follow-up based on regular HolterECGs is provided. However, the main focus was to assess the durability of wide-area LAAI. Second, LAAI durability was only assessed in patients presenting for a subsequent procedure. Third, LAAI durability was only assessed in patients without LAA thrombus formation as excluded by pre-procedural TEE. Fourth, an esophagogastroduodenoscopy was only performed in symptomatic patients, but not categorically in all patients after the ablation procedures and therefore, asymptomatic esophageal thermal lesions could have been undetected. Finally, this is an observational, non-randomized single-center analysis with a limited number of patients. Further investigations will be required to determine the clinical impact of LAAI and to compare wide-area LAAI versus segmental and circumferential
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LAAI with regard to durability, clinical impact and potential complications such as thromboembolic events. Conclusions Wide-area LAAI following extensive catheter ablation for persistent AF is durable in the majority of patients. The potential clinical benefit of LAAI for maintaining stable SR warrants further investigation.
Acknowledgements: none
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(5) Verma A, Mantovan R, Macle L, De Martino G, Chen J, Morillo CA, Novak P, Calzolari V, Guerra PG, Nair G, Torrecilla EG, Khaykin Y. Substrate and Trigger Ablation for Reduction of Atrial Fibrillation (STAR AF): a randomized, multicentre, international trial. Eur Heart J 2010;31:1344-1356. (6) Verma A. The techniques for catheter ablation of paroxysmal and persistent atrial fibrillation: a systematic review. Curr Opin Cardiol 2011;26:17-24. (7) Fassini G, Riva S, Chiodelli R, Trevisi N, Berti M, Carbucicchio C, Maccabelli G, Giraldi F, Bella PD. Left mitral isthmus ablation associated with PV Isolation: long-term results of a prospective randomized study. J Cardiovasc Electrophysiol 2005;16:1150-1156. (8) Jais P, Hocini M, Hsu LF, et al. Technique and results of linear ablation at the mitral isthmus. Circulation 2004;110:2996-3002. (9) Nademanee K, McKenzie J, Kosar E, Schwab M, Sunsaneewitayakul B, Vasavakul T, Khunnawat C, Ngarmukos T. A new approach for catheter ablation of atrial fibrillation: mapping of the electrophysiologic substrate. J Am Coll Cardiol 2004;43:2044-2053. (10) Park HC, Lee D, Shim J, Choi JI, Kim YH. The clinical efficacy of left atrial appendage isolation caused by extensive left atrial anterior wall ablation in patients with atrial fibrillation. J Interv Card Electrophysiol 2016;46:287-97. (11) Di Biase L, Burkhardt JD, Mohanty P, et al. Left atrial appendage: an underrecognized trigger site of atrial fibrillation. Circulation 2010;122:109-118. (12) Rillig A, Tilz RR, Lin T, et al. Unexpectedly High Incidence of Stroke and Left Atrial Appendage Thrombus Formation After Electrical Isolation of the Left Atrial Appendage for the Treatment of Atrial Tachyarrhythmias. Circ Arrhythm Electrophysiol 2016;9:e003461. (13) Ouyang F, Bansch D, Ernst S, Schaumann A, Hachiya H, Chen M, Chun J, Falk P, Khanedani A, Antz M, Kuck KH. Complete isolation of left atrium surrounding the pulmonary
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veins: new insights from the double-Lasso technique in paroxysmal atrial fibrillation. Circulation 2004;110:2090-2096. (14) Ouyang F, Ernst S, Vogtmann T, Goya M, Volkmer M, Schaumann A, Bänsch D, Antz A, Kuck KH. Characterization of reentrant circuits in left atrial macroreentrant tachycardia: critical isthmus block can prevent atrial tachycardia recurrence. Circulation 2002;105:19341942. (15) Holmes DR, Reddy VY, Turi ZG, Doshi SK, Sievert H, Buchbinder M, Mullin CM, Sick P; Protect AF Investigators. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial. Lancet 2009;374:534-542. (16) Bartus K, Han FT, Bednarek J, Myc J, Kapelak B, Sadowski J, Lelakowski J, Bartus S, Yakubov SJ, LEE RJ. Percutaneous left atrial appendage suture ligation using the LARIAT device in patients with atrial fibrillation: initial clinical experience. J Am Coll Cardiol 2013;62:108-118. (17) Calkins H, Reynolds MR, Spector P, Sondhi M, Xu Y, Martin A, Williams CJ, Sledge I. Treatment of atrial fibrillation with antiarrhythmic drugs or radiofrequency ablation: two systematic literature reviews and meta-analyses. Circ Arrhythm Electrophysiol 2009;2:349361. (18) Verma A, Macle L, Cox J, Skanes AC, CCS Atrial Fibrillation Guidelines Committee. Canadian Cardiovascular Society atrial fibrillation guidelines 2010: catheter ablation for atrial fibrillation/atrial flutter. Can J Cardiol 2011;27:60-66. (19) January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation 2014;130:2071-2104.
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(20) Ouyang F, Antz M, Ernst S, et al. Recovered pulmonary vein conduction as a dominant factor for recurrent atrial tachyarrhythmias after complete circular isolation of the pulmonary veins: lessons from double Lasso technique. Circulation 2005;111:127-135. (21) Ouyang F, Tilz R, Chun J, Schmidt B, Wissner E, Zerm T, Neven K, Köktürk B, Konstantinidou M, Metzner A, Fürnkranz A, Kuck KH. Long-term results of catheter ablation in paroxysmal atrial fibrillation: lessons from a 5-year follow-up. Circulation 2010;122:23682377. (22) Verma A, Jiang CY, Betts TR, et al. Approaches to catheter ablation for persistent atrial fibrillation. N Engl J Med 2015;372:1812-1822. (23) Vogler J, Willems S, Sultan A, Schreiber D, Luker J, Servatius H, Schäffer B, Moser J, Hoffmann BA, Steven D. Pulmonary Vein Isolation Versus Defragmentation: The CHASE-AF Clinical Trial. J Am Coll Cardiol 2015;66:2743-2752. (24) Haissaguerre M, Hocini M, Sanders P, et al. Catheter ablation of long-lasting persistent atrial fibrillation: clinical outcome and mechanisms of subsequent arrhythmias. J Cardiovasc Electrophysiol 2005;16:1138-1147. (25) Schreiber D, Rostock T, Frohlich M, et al. Five-year follow-up after catheter ablation of persistent atrial fibrillation using the stepwise approach and prognostic factors for success. Circ Arrhythm Electrophysiol 2015;8:308-317. (26) Willems S, Steven D, Servatius H, Hoffmann BA, Drewitz I, Mullerleile K, Aydin MA, Wegscheider K, Salukhe TV, Meinertz T, Rostock T. Persistence of pulmonary vein isolation after robotic remote-navigated ablation for atrial fibrillation and its relation to clinical outcome. J Cardiovasc Electrophysiol 2010;21:1079-1084. (27) Nanthakumar K, Plumb VJ, Epstein AE, Veenhuyzen GD, Link D, Kay GN. Resumption of electrical conduction in previously isolated pulmonary veins: rationale for a different strategy? Circulation 2004;109:1226-1229. 13
(28) Weerasooriya R, Khairy P, Litalien J, et al. Catheter ablation for atrial fibrillation: are results maintained at 5 years of follow-up? J Am Coll Cardiol 2011;57:160-166. (29) Verma A, Kilicaslan F, Pisano E, et al. Response of atrial fibrillation to pulmonary vein antrum isolation is directly related to resumption and delay of pulmonary vein conduction. Circulation 2005;112:627-635. (30) Bhargava M, Di Biase L, Mohanty P, et al. Impact of type of atrial fibrillation and repeat catheter ablation on long-term freedom from atrial fibrillation: results from a multicenter study. Heart Rhythm 2009;6:1403-1412. Table 1: Patient Characteristics
All
Durable LAAI
LAA Reconnection
Patients, n
71
52
19
Age, years
69±7
70±8
68±7
33 (46)
22 (31)
11 (15)
LVEF, %
60±7
60±8
60±7
LA diameter, mm
47±6
47±6
46±6
CHA2DS2-VASc score
3 [2;3]
3 [2;3]
2 [1;3]
Number of procedures until LAAI
3±1
3±1
3±1
LAAI during 2nd procedure, n
25 (35)
16 (23)
9 (13)
LAAI during 3rd procedure, n
27 (38)
17 (24)
10 (14)
LAAI during 4th procedure, n
13 (18)
10 (14)
3 (4)
LAAI during 5th procedure, n
6 (9)
5 (7)
1 (1)
Male gender
Values are mean ± SD, median [1st quartile; 3rd quartile], or n (%). LAA = left atrial appendage; LAAI = left atrial appendage isolation; LVEF = left ventricular ejection fraction. 14
Table 2: Procedural Adverse Events
Total, n (%)
10 (4.7)
Hematoma at femoral vascular access site, n (%)
1 (0.5)
Arteriovenous fistula or pseudoaneurysm, n (%)
6 (2.8)
Cardiac tamponade, n (%)
1 (0.5)
Esophageal thermal lesions*, n (%)
2 (0.9)
* An esophagogastroduodenoscopy following the procedures was not categorically performed. Therefore, asymptomatic patients with esophageal thermal lesions remain unreported.
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Figure Legends Figure 1. Wide-area left atrial appendage isolation in a patient presenting with long-standing persistent atrial fibrillation. Panel A. 3D electroanatomic substrate map of the left atrium (LA) in posteroanterior (left-hand panel) and left lateral (right-hand panel) views. White dots mark previously isolated septal and lateral pulmonary veins (PV). A mitral isthmus line (red dots) was created between the left inferior PV (LIPV) and the mitral annulus. Ablation of complex fractionated atrial electrograms (tagged with red dots) was performed below the LIPV during atrial fibrillation. Panel B. 3D electroanatomic substrate map of the LA in anteroposterior (lefthand panel) and right lateral (right-hand panel) views. Additionally an anterior line connecting the mitral annulus and the right superior pulmonary vein was created. AL = Anterior Line; CFAE = Complex Fractionated Atrial Electrograms; LAA = Left Atrial Appendage; LPV = Left Pulmonary Veins; MI = Mitral Isthmus; MV = Mitral Valve; RPV = Right Pulmonary Veins. Figure 2. Kaplan-Meier survival curves demonstrating freedom from left atrial appendage (LAA) reconnection in all patients (n=71, black line), as well as in patients who received an LAA closure device (n=48, red line) or underwent repeat ablation (n=23, blue line). Log-rank p-value indicates lack of statistical difference in event-free survival between the patient subgroups. Kaplan-Meier estimates of event-free survival [with 95% confidence intervals] at 1 and 2 years are given for the total patient cohort.
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Figure 1 A
B
17
Figure 2
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S1547-5271(16)31010-4 http://dx.doi.org/10.1016/j.hrthm.2016.11.009 HRTHM6915
To appear in: Heart Rhythm Cite this article as: Bruno Reissmann, Andreas Rillig, Erik Wissner, Roland Tilz, Michael Schlüter, Christian Sohns, Christian Heeger, Shibu Mathew, Tilman Maurer, Christine Lemes, Thomas Fink, Peter Wohlmuth, Francesco Santoro, Johannes Riedl, Feifan Ouyang, Karl-Heinz Kuck and Andreas Metzner, Durability of Wide-Area Left Atrial Appendage Isolation: Results from Extensive Catheter Ablation for the Treatment of Persistent Atrial Fibrillation, Heart Rhythm, http://dx.doi.org/10.1016/j.hrthm.2016.11.009 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Durability of Wide-Area Left Atrial Appendage Isolation: Results from Extensive Catheter Ablation for the Treatment of Persistent Atrial Fibrillation Bruno Reissmann MD¹*; Andreas Rillig MD2*; Erik Wissner MD1; Roland Tilz MD3; Michael Schlüter PhD4; Christian Sohns MD¹; Christian Heeger MD¹; Shibu Mathew MD¹; Tilman Maurer MD¹; Christine Lemes MD¹; Thomas Fink MD¹; Peter Wohlmuth PhD4; Francesco Santoro MD¹; Johannes Riedl MD¹; Feifan Ouyang MD¹; Karl-Heinz Kuck MD¹; Andreas Metzner MD¹ ¹Dept. of Cardiology, Asklepios Klinik St. Georg, Hamburg, Germany; 2Dept. of Cardiology, Campus Benjamin Franklin, Charité Universitätsmedizin Berlin, Germany; 3University Heart Center Lübeck, Medical Clinic II, Lübeck, Germany; 4Asklepios proresearch, Hamburg, Germany.
*Both authors contributed equally to the manuscript
Short title: Durability of left atrial appendage isolation
Conflict of interest disclosures: KHK and AM received speaker´s honoraria from Biosense Webster. Corresponding author: Bruno Reissmann, MD Dept. of Cardiology Asklepios Klinik St. Georg Lohmühlenstr. 5 20099 Hamburg, Germany phone: +4940 181885 2305 fax: +4940 181885 4444 e-mail: [email protected]
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Abstract Background: Extensive ablation strategies are currently performed in addition to pulmonary vein isolation (PVI) to improve the clinical outcome of patients with drug-refractory persistent atrial fibrillation (AF). Ablation of complex fractionated atrial electrograms (CFAE), linear lesions and/or isolation of the left atrial appendage (LAA) are thought to improve arrhythmiafree survival. Objective: This study sought to assess the durability of wide-area LAA isolation (LAAI) achieved by PVI, an anterior line and a mitral isthmus line. Methods: Seventy-one patients with intentional or incidental LAAI during repeat catheter ablation for the treatment of persistent AF were included. The initial ablation strategy was PVI. Additional ablation strategies were only performed if PVI failed to maintain stable sinus rhythm (SR). Durability of LAAI was assessed during a subsequent ablation procedure for arrhythmia recurrences (n=23) or a subsequent percutaneous LAA closure (n=48). Results: LAAI was performed after a mean of 3±1 procedures. Ablation strategies included circumferential PVI in 71 (100%) patients, mitral isthmus line in 64 (90%), anterior line in 60 (85%), CFAE in 27 (38%), and roof line in 13 (18%) patients. LAAI occurred after ablation and bidirectional block of LA linear lesions in 63 (89%) patients and during extensive CFAE ablation in 8 (11%) patients. After a median period of 105 [61;426] days, the LAA remained electrically isolated in 52/71 (73%) patients. Conclusions: Wide-area LAAI following extensive catheter ablation for persistent AF is durable in a majority of patients. The potential clinical benefit of LAAI for maintaining stable SR needs further investigation. Key words: Persistent atrial fibrillation; Catheter ablation; Left atrial appendage isolation; Pulmonary vein isolation; Left atrial linear lesions; Complex fractionated atrial electrograms
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Introduction Pulmonary vein isolation (PVI) is the cornerstone treatment of drug-refractory atrial fibrillation (AF) (1). While the long-term success rate of PVI in patients with paroxysmal atrial fibrillation (PAF) is favorable, clinical outcomes in patients with persistent AF are less beneficial (2-4). To improve the outcome in patients with persistent AF, more extensive ablation strategies in addition to PVI have been proposed (5,6), such as the creation of linear lesions and/or the ablation of complex fractionated atrial electrograms (CFAE) (7-9). Of note, these extensive substrate modifications in the left atrium can result in wide-area left atrial appendage (LAA) isolation (LAAI) (2,10). However, LAAI can improve the outcome in patients with persistent AF (11) but at the same time might increase the risk of LAA thrombus formation despite sufficient oral anticoagulation therapy (OAC) (12). The current study sought to assess the durability of wide-area LAAI following PVI, left atrial (LA) linear ablation, and/or CFAE ablation. Methods Patients Patients with persistent AF and LAAI achieved intentionally or serendipitously in a previous ablation procedure were included into the analysis. All patients were refractory to antiarrhythmic drugs. Transesophageal echocardiography (TEE) was performed prior to the ablation procedure in all patients to assess LA dimensions and to rule out intracardiac thrombi. No additional pre-procedural imaging was performed. The current study is a retrospective analysis based on our institutional database. The study was approved by our institutional review board. Ablation protocol In the initial ablation attempt all patients underwent circumferential PVI applying irrigated radiofrequency current, as previously described (13). The procedural end point was the absence of any pulmonary vein (PV) potential recorded by a spiral mapping catheter (Lasso, 3
Biosense Webster) placed along the ostium of the respective PV following a waiting period of 30 min. If AF did not convert to sinus rhythm (SR) after successful PVI, direct-current cardioversion (DCCV) was performed (Lifepak 12, Medtronic Inc., MN). CFAE ablation was performed if SR could not be achieved by DCCV (2). In cases of extensive CFAE ablation along the anterior LA wall and/or the mitral isthmus area, additional linear lesions were created to prevent atrial tachycardia (AT) recurrences (Figure 1). If AF converted to AT during CFAE ablation, the underlying mechanism was evaluated and linear lesions were created or focal ablation was performed (8,14). Linear lesions included an anterior line (connection between the mitral annulus and the right superior PV), a mitral isthmus line (connection between the mitral annulus and the left-sided PVs), and a roof line (connection between the right superior PV and the left superior PV). Bidirectional block of linear lesions was validated during SR based on established electrophysiological maneuvers (8). During CFAE and/or LA linear ablation, a spiral mapping catheter was positioned in the LAA to continuously record LAA activity. Ablation protocol: Repeat procedures Repeat ablation procedures were performed in patients with recurrence of atrial tachyarrhythmias. In case of PV reconnection, conduction gaps were closed with radiofrequency ablation aiming at PV re-isolation. CFAE ablation was performed if AF could not be converted to SR or AT by re-isolation of the PVs or DCCV (2). In patients presenting with macro-reentrant AT or in cases of conversion to macro-reentrant AT during repeat ablation, linear ablation was performed. Electrical LAAI was defined as follows: 1) demonstration of entrance block (disappearance of all LAA potentials documented with a spiral mapping catheter placed inside the LAA, regardless of the underlying cardiac rhythm) and 2) demonstration of exit block (LAA electric activity dissociated from the LA during LAA ectopy or pacing from inside the LAA) (2,8). In order to detect early reconduction of the LAA, a waiting period of 30 minutes was considered.
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Assessment of Durability of Wide-Area Left Atrial Appendage Isolation All patients included into our analysis underwent a repeat ablation procedure due to arrhythmia recurrence or were scheduled for percutaneous LAA closure. LAAI durability was systematically assessed during these procedures. Therefore, a 15-mm spiral mapping catheter was placed inside the LAA and both entrance and exit block were assessed. Percutaneous LAA closure was performed by implanting either an endocardial or an epicardial LAA closure device, as previously described (15,16). Statistics Continuous data are described as mean and standard deviation (SD) if normally distributed, otherwise the median and interquartile range [IQR] are reported. Categorical data are described with absolute and relative frequencies. Time-to-event curves were generated using Kaplan-Meier analysis. LAAI durability of patients with intentional or incidental LAAI was compared with the use of Pearson’s chi-square test. A probability value of P<0.05 was considered to indicate statistical significance. All calculations were performed using SAS (version 9.3, SAS Institute Inc., Cary, NC, USA). Results Patients During the time of our study (03/2003 to 09/2015) approximately 17,000 patients with a history of AF underwent LA ablation procedures at our institution. Of these patients, intentional LAAI was achieved or incidental LAAI occurred during repeat ablation procedures in a total of 117 patients with persistent AF. Seventy-one [69±7 years, 33 (46%) men, median CHA2DS2-VASc Score 3 (2;3), LA diameter 47±6 mm] of these 117 patients underwent a subsequent procedure affording an opportunity to assess LAAI durability. LAAI was demonstrated during the second ablation procedure in 25/71 (35%) patients, during the third procedure in 27/71 (38%) patients, during the fourth procedure in 13/71 (18%) patients, and
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during the fifth ablation procedure in 6/71 (9%) patients. The patients’ baseline characteristics are shown in Table 1. Procedural characteristics until Left Atrial Appendage Isolation The 71 patients underwent a total of 213 procedures. Overall, the ablation strategies in the 71 patients included circumferential PVI in all patients, creation of a mitral isthmus line in 64 (90%), an anterior line in 60 (85%) and a roof line in 13 (18%) patients, as well as CFAE ablation in 27 patients (38%). LAAI occurred after a mean of 3±1 procedures. The LAA was electrically isolated by linear ablation in the LA in 63 (89%) patients; in these patients, LAAI was the result of achieving bidirectional conduction block along both an anterior and a mitral isthmus line. In the remaining 8 (11%) patients, the LAA was isolated during extensive CFAE ablation. LAAI was intentionally performed in 39 (55%) patients because of localized reentry AT within the LAA. In the other 32 (45%) patients, LAAI occurred during linear ablation for LA tachycardia in 24 (34%), and during extensive CFAE ablation in 8 (11%) patients. Durability of Left Atrial Appendage Isolation At a median of 105 [61;426] days after LAAI, the durability of LAAI was assessed during a repeat ablation procedure necessitated by an arrhythmia recurrence [23 (32%) patients] or during a planned percutaneous LAA closure following LAAI [48 (68%) patients]. At that time, the LAA was found to be electrically isolated in 52/71 (73%) patients (Figure 2). The durability of LAAI did not differ significantly between patients with intentional and incidental LAAI (p=0.57), and there was no significant difference in procedure data and baseline characteristics between patients with persistent LAAI and patients with LAA reconnection (Table 2). At the time of LAAI assessment, 53/71 (75%) patients presented in SR, 10/71 (14%) patients in AT and 8/71 (11%) patients in AF. Of the 53 patients who presented in SR, 7 (13%) patients underwent electrical CV due to AT prior to the re-ablation procedure. 6
Repeat Ablation Procedure following Left Atrial Appendage Isolation A repeat ablation procedure following previously successful LAAI was performed in 23/71 (32%) patients. The LAA remained durably isolated in 11/23 (48%) patients. In these patients the present arrhythmia was a right-sided AT in 6 patients and a focal left-sided AT in 4 patients. In one patient, who presented in SR, the LAA remained durably isolated and no tachycardia could be induced, therefore no ablation was performed. In 8/12 (67%) patients with LAA reconnection, the LAA was identified as the trigger of the current arrhythmia (5 patients with focal AT arising from the LAA, and 3 patients with ectopy from the LAA triggering AF) and was subsequently re-isolated. In the remaining 4/12 (33%) patients with LAA reconnection, but no LAA-dependent tachycardia, no re-isolation of the LAA was performed. Thrombus Formation following Left Atrial Appendage Isolation In 7/71 (10%) patients with previous LAAI who presented for a subsequent procedure, LAA thrombus formation was detected by pre-procedural TEE. Consequently, all 7 patients were treated with phenprocoumon targeting an INR of 2.5 – 3.0, and the procedures were rescheduled. After a median of 64 [57;137] days, the LAA thrombus was no longer detectable, thus allowing for assessment of LAAI durability. LAAI was still present in 6/7 patients; LAA reconduction was demonstrated in the remaining patient. Complications The following complications occurred in 10/213 (4.7%) procedures: arteriovenous fistula or pseudoaneurysm (n=6) and vascular surgery (n=2 of 6), femoral hematoma requiring blood transfusion (n=1), cardiac tamponade requiring pericardiocentesis (n=1), and esophageal thermal lesions (n=2) that recovered under treatment with proton pump inhibitors. The procedural adverse events are shown in Table 2.
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Discussion This study is the first addressing the durability of wide-area LAAI following extensive substrate modification in the LA for the treatment of persistent AF. In the current patient cohort, a high durability of LAAI was observed following PVI, an anterior line and a mitral isthmus line, but also in patients in whom extensive ablation of CFAE was performed with incidental LAAI. PVI is an effective treatment option for patients suffering from PAF and recurrences of AF are the result of electrical reconnections of formerly isolated PVs in the majority of patients (17-21). At the same time, the clinical success of stand-alone PVI for the treatment of persistent AF is limited (2-4). Therefore, additional substrate ablation following durable PVI has become a widely accepted and applied form of therapy (5,6). However, results on the clinical benefit of more extensive ablation strategies are contradictory (22,23). The most commonly used additional ablation strategies are the ablation of CFAE and/or the application of linear lesions (7-9). The LAA is a promising additional target for ablation since it may serve as a potential source for triggering and perpetuating AF. However, to date, clinical data reporting on clinical success after LAAI is limited. Since the LAA can be the source for initiation and maintenance of AF beyond the PVs, electrical isolation of the LAA can significantly improve the outcome in certain patients (11). However, the best strategy to achieve LAAI has not yet been assessed. Segmental and circumferential isolation of the LAA is feasible (11), but is associated with safety concerns while ablating at the ostium of the LAA. In contrast, wide-area isolation of the LAA by aiming for bidirectional block of an anterior line and a mitral isthmus line provides an alternative strategy. The creation of linear lesions might capture additional arrhythmogenic substrate and thereby effectively lower the incidence of macro-reentry ATs that frequently occur after repeat ablation procedures for the treatment of persistent AF (2,24,25).
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However, the key aspect in catheter-based ablation is to create transmural and durable lesions. While acute success is achieved in almost all cases, long-term efficacy is often limited by reconnection of previously blocked lesions (21,26-30). LAAI by creation of linear lesions results in a high rate of durable electrical LAAI and might increase the arrhythmiafree survival in patients with persistent AF. However, the isolation of the LAA is a complex procedure with the potential risk of procedural adverse events and thrombus formation inside or along the isolated LAA despite continuous OAC (12). In our study, transient LAA thrombus formation was detected in a total of 7/71 patients. Therefore, LAAI must be carefully considered and the potential necessity taken into account for a subsequent percutaneous closure of the LAA after electrical isolation. Of note, although a high incidence of LAA thrombus formation following wide-area LAAI has been assessed (12), one report did not find evidence of LAA thrombus after ostial LAAI in 204 patients (11). These data suggest that the impact on LAA contraction and overall flow velocities differs between wide-area LAAI and ostial LAAI. However, before final conclusions can be drawn, more data is required to assess arrhythmia-free survival, safety of the procedure and thrombogenicity inside and along the LAA after electrical isolation. Limitations The current analysis has some limitations. First, no clinical follow-up based on regular HolterECGs is provided. However, the main focus was to assess the durability of wide-area LAAI. Second, LAAI durability was only assessed in patients presenting for a subsequent procedure. Third, LAAI durability was only assessed in patients without LAA thrombus formation as excluded by pre-procedural TEE. Fourth, an esophagogastroduodenoscopy was only performed in symptomatic patients, but not categorically in all patients after the ablation procedures and therefore, asymptomatic esophageal thermal lesions could have been undetected. Finally, this is an observational, non-randomized single-center analysis with a limited number of patients. Further investigations will be required to determine the clinical impact of LAAI and to compare wide-area LAAI versus segmental and circumferential
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LAAI with regard to durability, clinical impact and potential complications such as thromboembolic events. Conclusions Wide-area LAAI following extensive catheter ablation for persistent AF is durable in the majority of patients. The potential clinical benefit of LAAI for maintaining stable SR warrants further investigation.
Acknowledgements: none
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(5) Verma A, Mantovan R, Macle L, De Martino G, Chen J, Morillo CA, Novak P, Calzolari V, Guerra PG, Nair G, Torrecilla EG, Khaykin Y. Substrate and Trigger Ablation for Reduction of Atrial Fibrillation (STAR AF): a randomized, multicentre, international trial. Eur Heart J 2010;31:1344-1356. (6) Verma A. The techniques for catheter ablation of paroxysmal and persistent atrial fibrillation: a systematic review. Curr Opin Cardiol 2011;26:17-24. (7) Fassini G, Riva S, Chiodelli R, Trevisi N, Berti M, Carbucicchio C, Maccabelli G, Giraldi F, Bella PD. Left mitral isthmus ablation associated with PV Isolation: long-term results of a prospective randomized study. J Cardiovasc Electrophysiol 2005;16:1150-1156. (8) Jais P, Hocini M, Hsu LF, et al. Technique and results of linear ablation at the mitral isthmus. Circulation 2004;110:2996-3002. (9) Nademanee K, McKenzie J, Kosar E, Schwab M, Sunsaneewitayakul B, Vasavakul T, Khunnawat C, Ngarmukos T. A new approach for catheter ablation of atrial fibrillation: mapping of the electrophysiologic substrate. J Am Coll Cardiol 2004;43:2044-2053. (10) Park HC, Lee D, Shim J, Choi JI, Kim YH. The clinical efficacy of left atrial appendage isolation caused by extensive left atrial anterior wall ablation in patients with atrial fibrillation. J Interv Card Electrophysiol 2016;46:287-97. (11) Di Biase L, Burkhardt JD, Mohanty P, et al. Left atrial appendage: an underrecognized trigger site of atrial fibrillation. Circulation 2010;122:109-118. (12) Rillig A, Tilz RR, Lin T, et al. Unexpectedly High Incidence of Stroke and Left Atrial Appendage Thrombus Formation After Electrical Isolation of the Left Atrial Appendage for the Treatment of Atrial Tachyarrhythmias. Circ Arrhythm Electrophysiol 2016;9:e003461. (13) Ouyang F, Bansch D, Ernst S, Schaumann A, Hachiya H, Chen M, Chun J, Falk P, Khanedani A, Antz M, Kuck KH. Complete isolation of left atrium surrounding the pulmonary
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veins: new insights from the double-Lasso technique in paroxysmal atrial fibrillation. Circulation 2004;110:2090-2096. (14) Ouyang F, Ernst S, Vogtmann T, Goya M, Volkmer M, Schaumann A, Bänsch D, Antz A, Kuck KH. Characterization of reentrant circuits in left atrial macroreentrant tachycardia: critical isthmus block can prevent atrial tachycardia recurrence. Circulation 2002;105:19341942. (15) Holmes DR, Reddy VY, Turi ZG, Doshi SK, Sievert H, Buchbinder M, Mullin CM, Sick P; Protect AF Investigators. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial. Lancet 2009;374:534-542. (16) Bartus K, Han FT, Bednarek J, Myc J, Kapelak B, Sadowski J, Lelakowski J, Bartus S, Yakubov SJ, LEE RJ. Percutaneous left atrial appendage suture ligation using the LARIAT device in patients with atrial fibrillation: initial clinical experience. J Am Coll Cardiol 2013;62:108-118. (17) Calkins H, Reynolds MR, Spector P, Sondhi M, Xu Y, Martin A, Williams CJ, Sledge I. Treatment of atrial fibrillation with antiarrhythmic drugs or radiofrequency ablation: two systematic literature reviews and meta-analyses. Circ Arrhythm Electrophysiol 2009;2:349361. (18) Verma A, Macle L, Cox J, Skanes AC, CCS Atrial Fibrillation Guidelines Committee. Canadian Cardiovascular Society atrial fibrillation guidelines 2010: catheter ablation for atrial fibrillation/atrial flutter. Can J Cardiol 2011;27:60-66. (19) January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation 2014;130:2071-2104.
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(20) Ouyang F, Antz M, Ernst S, et al. Recovered pulmonary vein conduction as a dominant factor for recurrent atrial tachyarrhythmias after complete circular isolation of the pulmonary veins: lessons from double Lasso technique. Circulation 2005;111:127-135. (21) Ouyang F, Tilz R, Chun J, Schmidt B, Wissner E, Zerm T, Neven K, Köktürk B, Konstantinidou M, Metzner A, Fürnkranz A, Kuck KH. Long-term results of catheter ablation in paroxysmal atrial fibrillation: lessons from a 5-year follow-up. Circulation 2010;122:23682377. (22) Verma A, Jiang CY, Betts TR, et al. Approaches to catheter ablation for persistent atrial fibrillation. N Engl J Med 2015;372:1812-1822. (23) Vogler J, Willems S, Sultan A, Schreiber D, Luker J, Servatius H, Schäffer B, Moser J, Hoffmann BA, Steven D. Pulmonary Vein Isolation Versus Defragmentation: The CHASE-AF Clinical Trial. J Am Coll Cardiol 2015;66:2743-2752. (24) Haissaguerre M, Hocini M, Sanders P, et al. Catheter ablation of long-lasting persistent atrial fibrillation: clinical outcome and mechanisms of subsequent arrhythmias. J Cardiovasc Electrophysiol 2005;16:1138-1147. (25) Schreiber D, Rostock T, Frohlich M, et al. Five-year follow-up after catheter ablation of persistent atrial fibrillation using the stepwise approach and prognostic factors for success. Circ Arrhythm Electrophysiol 2015;8:308-317. (26) Willems S, Steven D, Servatius H, Hoffmann BA, Drewitz I, Mullerleile K, Aydin MA, Wegscheider K, Salukhe TV, Meinertz T, Rostock T. Persistence of pulmonary vein isolation after robotic remote-navigated ablation for atrial fibrillation and its relation to clinical outcome. J Cardiovasc Electrophysiol 2010;21:1079-1084. (27) Nanthakumar K, Plumb VJ, Epstein AE, Veenhuyzen GD, Link D, Kay GN. Resumption of electrical conduction in previously isolated pulmonary veins: rationale for a different strategy? Circulation 2004;109:1226-1229. 13
(28) Weerasooriya R, Khairy P, Litalien J, et al. Catheter ablation for atrial fibrillation: are results maintained at 5 years of follow-up? J Am Coll Cardiol 2011;57:160-166. (29) Verma A, Kilicaslan F, Pisano E, et al. Response of atrial fibrillation to pulmonary vein antrum isolation is directly related to resumption and delay of pulmonary vein conduction. Circulation 2005;112:627-635. (30) Bhargava M, Di Biase L, Mohanty P, et al. Impact of type of atrial fibrillation and repeat catheter ablation on long-term freedom from atrial fibrillation: results from a multicenter study. Heart Rhythm 2009;6:1403-1412. Table 1: Patient Characteristics
All
Durable LAAI
LAA Reconnection
Patients, n
71
52
19
Age, years
69±7
70±8
68±7
33 (46)
22 (31)
11 (15)
LVEF, %
60±7
60±8
60±7
LA diameter, mm
47±6
47±6
46±6
CHA2DS2-VASc score
3 [2;3]
3 [2;3]
2 [1;3]
Number of procedures until LAAI
3±1
3±1
3±1
LAAI during 2nd procedure, n
25 (35)
16 (23)
9 (13)
LAAI during 3rd procedure, n
27 (38)
17 (24)
10 (14)
LAAI during 4th procedure, n
13 (18)
10 (14)
3 (4)
LAAI during 5th procedure, n
6 (9)
5 (7)
1 (1)
Male gender
Values are mean ± SD, median [1st quartile; 3rd quartile], or n (%). LAA = left atrial appendage; LAAI = left atrial appendage isolation; LVEF = left ventricular ejection fraction. 14
Table 2: Procedural Adverse Events
Total, n (%)
10 (4.7)
Hematoma at femoral vascular access site, n (%)
1 (0.5)
Arteriovenous fistula or pseudoaneurysm, n (%)
6 (2.8)
Cardiac tamponade, n (%)
1 (0.5)
Esophageal thermal lesions*, n (%)
2 (0.9)
* An esophagogastroduodenoscopy following the procedures was not categorically performed. Therefore, asymptomatic patients with esophageal thermal lesions remain unreported.
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Figure Legends Figure 1. Wide-area left atrial appendage isolation in a patient presenting with long-standing persistent atrial fibrillation. Panel A. 3D electroanatomic substrate map of the left atrium (LA) in posteroanterior (left-hand panel) and left lateral (right-hand panel) views. White dots mark previously isolated septal and lateral pulmonary veins (PV). A mitral isthmus line (red dots) was created between the left inferior PV (LIPV) and the mitral annulus. Ablation of complex fractionated atrial electrograms (tagged with red dots) was performed below the LIPV during atrial fibrillation. Panel B. 3D electroanatomic substrate map of the LA in anteroposterior (lefthand panel) and right lateral (right-hand panel) views. Additionally an anterior line connecting the mitral annulus and the right superior pulmonary vein was created. AL = Anterior Line; CFAE = Complex Fractionated Atrial Electrograms; LAA = Left Atrial Appendage; LPV = Left Pulmonary Veins; MI = Mitral Isthmus; MV = Mitral Valve; RPV = Right Pulmonary Veins. Figure 2. Kaplan-Meier survival curves demonstrating freedom from left atrial appendage (LAA) reconnection in all patients (n=71, black line), as well as in patients who received an LAA closure device (n=48, red line) or underwent repeat ablation (n=23, blue line). Log-rank p-value indicates lack of statistical difference in event-free survival between the patient subgroups. Kaplan-Meier estimates of event-free survival [with 95% confidence intervals] at 1 and 2 years are given for the total patient cohort.
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Figure 1 A
B
17
Figure 2
18