Running title: Andrade et al.; Pace-Capture vs. Adenosine Guided PVI. Laurent Macle, MD 1

Transcription

1 Pulmonary Vein Isolation Using a Pace-Capture Guided Versus an Adenosine Guided Approach: The Effect on Dormant Conduction and Long-Term Freedom from Recurrent AF - A Prospective Study Running title: Andrade et al.; Pace-Capture vs. Adenosine Guided PVI Jason G. Andrade, MD 1,2 ; Scott J. Pollak, MD 3 ; George Monir, MD 3 ; Paul Khairy, MD, PhD 1 ; Marc Dubuc, MD 1 ; Denis Roy, MD 1 ; Mario Talajic, MD 1 ; Marc Deyell, MD, MSc 2 ; Léna Rivard, MD 1 ; Bernard Thibault, MD 1 ; Peter G. Guerra, MD 1 ; Stanley Nattel, MD 1 ; Laurent Macle, MD 1 1 Electrophysiology Service at the Montreal Heart Institute, Department of Medicine, Université de Montréal, Montreal, Québec; 2 The University of British ish Columbia, Vancouver, British Columbia, Canada; a a; 3 Arrhythmia rhyt hmia and Ablation Center, Florida Hospital Cardiovascular as Institute, Orlando, FL Correspondence: Jason Andrade, MD Electrophysiology Service Montreal Heart Institute 5000 Belanger St. E. Montreal, QC, H1T 1C8 Canada Tel: Fax: Jason.guy.andrade@umontreal.ca Journal Subject Codes: [5] Arrhythmias, clinical electrophysiology, drugs, [22] Ablation/ICD/surgery, [106] Electrophysiology 1

2 Abstract: Background - Atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) is associated with PV to left atrium re-conduction. We prospectively studied the utility of two procedural techniques designed to facilitate identification of residual gaps within the index ablation line. Methods and Results - Post wide circumferential PVI 40 patients received additional ablation targeted at locations of left atrial capture during high-output pacing (pace-capture group), while 40 patients underwent adenosine testing with targeted ablation at sites of dormant conduction (adenosine group). Patients were followed at 3, 6, and 12 months. Post PVI high output pacecapture was documented in 39 PVs (25%; 50% of patients) in the pace-capture aptu group. Dormant conduction was unmasked in 34 PVs (22%; 53% of patients) in the adenosine e group. A subset of 25 patients in the pace-capture capt group underwent adenosine testing without targeted ablation of dormant conduction. In these patients ts only 10/86 PVs (11.6%; 24% of patients) demonstrated t dormant conduction after the elimination of local pace-capture. capt pture. At a follow-up of 329±124 days the single procedure re off AAD AD freedom from recurrent AF was 67.5% in the adenosine group and 65.0% in the pace-capture aptu group (P=0.814).. Procedure duration and fluoroscopy osco time were e significantly longer in the pace-capture aptu group (P=0.002, 002, and P<0.001), 01 whereas RF time was comparable (P=0.192). Conclusions - The use of high-output pacing post PVI results in a significant reduction in the incidence of dormant conduction with a comparable long-term freedom from recurrent AF (vs. adenosine-guided ablation). The utility of these approaches requires evaluation in a long-term prospective randomized study. Key words: ablation, atrial fibrillation, atrial fibrillation arrhythmia, catheter ablation, pulmonary vein electrophysiology 2

3 Introduction Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia encountered in clinical practice and is associated with reductions in quality of life, functional status, cardiac performance, and overall survival. 1 Radiofrequency catheter ablation (RFCA) centered on electrical isolation of triggering foci within the pulmonary veins through circumferential lesions around PV ostia (PVI) and/or elimination of the arrhythmic substrate, has been shown to be a highly effective option for patients with both paroxysmal and persistent AF. 2 Unfortunately, despite an initial procedural success, up to 20-40% of patients will require a second intervention due to arrhythmia recurrence, which is most often due to recovery of conduction ctio between een PVs and the left atrium (LA) Two procedural techniques aimed at identifying regions of incomplete ablation and/or residual gaps within in the ablation lines have been postulated to reduce PV reconnection. One such technique is the use of intravenous adenosine to differentiate t permanent PV-atrial al block from dormant conduction ction (i.e. viable but latently t non-conducting cting tissue). Thereafter, further ablation targeted to sites of dormant conduction can be performed with the goal of eliminating sites of acute, adenosine-provoked reconnection An alternative strategy is the pace-capture guided approach whereby, after completion of PVI, the antral ablation line encircling the ipsilateral PVs is mapped while pacing from the ablation catheters distal electrode pair. 14, 15 Where local LA capture is identified, additional ablation can be performed with the goal of closure of the residual gaps. The purpose of this study is to validate the use of a pace-capture guided approach, in comparison to adenosine administration for the identification of residual or dormant PV conduction. 3

4 Methods Study population Eighty consecutive patients with highly symptomatic paroxysmal AF refractory to antiarrhythmic drugs referred for catheter ablation between August 2010 and May 2011 were prospectively enrolled in this pragmatic parallel cohort study. All patients had structurally normal hearts as assessed by clinical evaluation and cardiac imaging (echocardiography, computed tomography, and/or magnetic resonance imaging). The study was approved by the local institutional review committees. Written informed consent was obtained from each participant. Pulmonary isolation ion procedure Effective anticoagulation agulation with oral vitamin K antagonists (INR 2-3) or dabigatran for at least one month and/or the exclusion of a LA thrombus by a recent transesophageal soph echocardiogram was realized prior to ablation. Antiarrhythmic rhyt h ic drugs were discontinued i before the procedure, e, allowing a washout period of five half-lives li (except for amiodarone). All patients underwent catheter ablation with an irrigated-tip radiofrequency ablation catheter (RFCA) using standard techniques. Specifically, via central venous access a multipolar catheter was placed in the coronary sinus (CS) to guide electroanatomic mapping, and facilitate left atrial pacing. LA access was obtained via dual trans-septal puncture or patent foramen ovale. After transseptal access, IV heparin was administered as a bolus with continuous infusion to maintain an activated clotting time greater than 300 seconds. Through one transseptal access, a variable decapolar circular mapping catheter (Lasso, Biosense-Webster, Diamond Bar, California) was advanced into the LA for mapping and confirmation of PV isolation. Via the second transseptal access, an irrigated 3.5mm tip mapping and ablation catheter (Thermocool, 4

5 Biosense Webster; or SaphireBlu, St. Jude Medical, Minneapolis, MN.) was advanced into the LA via a long sheath. All procedures were guided by a three-dimensional (3D) electroanatomical mapping system (CARTO, Biosense-Webster, or Ensite NavX, St Jude Medical). Prior to ablation the circular mapping catheter was placed sequentially within each of the four PV antra to record baseline electrical activity (PV potentials or PVPs). The ostia and antra of the PVs were defined through a combination of examination of the 3D electroanatomical shell, pulmonary venography, tactile catheter feedback, catheter impedance changes, signal mapping as the catheter was withdrawn from inside the vein, and when available, intracardiac echocardiography. Targeting ipsilateral PVs in pairs RFCA lesions were placed a minimum mum of 1cm outside of the PV ostia using a standard wide circumferential ial antral isolation on approach. Ablation was allowed within in 1 cm of the ostium of the left superior PV owing to the narrow ridge of tissue between its anterior aspect and the left atrial appendage. pe age. Radiofrequency ency energy was delivered e at a target temperature of 50 C, a power of 30-35W 35W and an irrigation ig i flow rate of ml/min. m On the posterior or wall the RF power was reduced d to 25W with a flow of 17 ml/min. min Patients ts remaining in AF at the end of the procedure were electrically cardioverted back to sinus rhythm. Remapping of all PVs post-cardioversion was performed to confirm PV isolation. Pulmonary vein isolation was considered complete when spontaneous associated PV potentials were no longer recorded by the circular mapping catheter (entrance block), and PV to LA dissociation was noted either spontaneously or with PV pacing (exit block). A waiting time of at least 20 min after index isolation was used for each PV-encircling ablation line to monitor for early PV reconduction; if spontaneous reconnection occurred, reconnected PVs were re-isolated. No induction testing (using burst pacing or isoproterenol infusion), prophylactic linear ablation lesions, or ablation of complex fractionated atrial electrograms (CFAE) were performed. 5

6 Adenosine-Guided Ablation Following confirmation of PV isolation, provocative testing with adenosine was performed to evaluate the presence of dormant conduction in 40 patients from the Montreal Heart Institute (adenosine-guided group Figure 1). Adenosine dosing was titrated to achieve at least one blocked P wave or a sin defined by the reappearance of PV activity recorded on an appropriately positioned circular and supplementary RF energy was delivered at sites of breakthrough until dormant conduction n could no longer be elicited. The process was then repeated for each PV. The procedure endpoint nt was confirmation of bidirectional iona block in all veins despite repeat provocative adenosine. e. Pace-Capture Guided Ablation Following confirmation of PV isolation on high-output pacing from the ablation catheter s ter s distal bipole was performed rmed while slowly ly moving the catheter along the entire circumference of the index ablation line (output t 10 V, 2 msec pulse width; reduced d in regions susceptible sceptible to far-field capture such as near the appendage) in 40 patients from the Florida Hospital Cardiovascular Institute (pace-capture group Figure 2). Pacing was performed on, or as close to the ablation line as possible with careful attention to avoid parallel orientation of the ablation catheter tip to the tissue thus helping to prevent inadvertent capture from the proximal electrode of the distal bipole. The presence or absence of local LA capture on the ablation line was monitored according to the atrial signal of the CS catheter, as well as PV signals on the circular mapping catheter. Lack of local LA capture was considered to represent a site of efficacious ablation. Conversely, the presence of local LA capture was considered indicative of incomplete ablation 6

7 and/or the presence of a residual gap. Additional RF energy was delivered at sites of local LA capture until capture was no longer elicited. The procedure endpoint was confirmation of loss of pace-capture along the entire circumference of the ablation line. In a subset of 25 patients adenosine testing was also undertaken as outlined above after all sites of pace-capture had been eliminated. In this subset of patients sites of dormant conduction were noted, however no further ablation was performed. Post Ablation Follow-up and Outcomes All patients were discharged home within 2 days following the procedure. Post-procedure, re, patients continued anticoagulation with dabigatran or warfarin (to maintain an INR of 2 3) for a minimum of 2 months. Anti-arrhythmic medications (sotalol, propafenone, o e, flecainide, or dofetilide) were continued for a maximum mum 3 months post-ablation on after which they were discontinued. Patients were followed in the outpatient t clinic of their respective institutions itutions with 12-lead ECG and 24h Holter at 3, 6, and 12 months post-ablation. The primary outcome ome was the time to first recurrence rrence of symptomatic ti electrocardiographically-documented all doc ted AF or atrial al flutter/tachycardia in the absence of antiarrhythmic drug therapy. AF or atrial flutter/tachycardia qualified as an arrhythmia recurrence after ablation if it lasted 30 seconds or longer and was documented by 12-lead ECG, surface ECG rhythm strips, 24h Holter or transtelephonic monitor recordings. A blanking period of 3 months after the initial ablation was employed such that recurrences during this time were not counted. No patients were lost to follow-up and all completed the required outpatient visits and monitoring. Statistical Analysis Continuous variables are expressed as the mean ± SD (or median, interquartile range) and were compared Student t-tests or Wilcoxon rank sum tests for continuous variables. Categorical 7

8 variables are expressed as frequency and percentage and were compared by chi-square or Fisher s exact test. All tests were two sided. A P value <0.05 was considered statistically significant. All analyses were performed using STATA 10.1 (Stata-Corp, College Station, Texas). A total of 25 patients per group were required to provide >80% power to detect a 50% difference in the incidence of residual PV conduction unmasked by high-output pacing versus adenosine, assuming an average of 4 PVs per patient and a two-tailed alpha of The authors had full access to and take full responsibility for the integrity of the data. All authors have read and agree on the written manuscript. Results Baseline Parameters am A total of 80 consecutive patients t (59.4± years; 72.5% male) were enrolled led in the study protocol. The mean AF duration prior to enrollment nt was 56.1± months, with patients having failed 1.4± antiarrhythmic ar rhyt hm ic medications io prior to the procedure. e. Overall the mean LA diameter was 39.1±6.0mm, and LV ejection fraction was 61.5±6.6%. Only eight patients (10%) had a CHADS score >1. The baseline characteristics broken down by study group are presented in Table 1. Patients in the adenosine-guided ablation group were more likely to be male, and had a longer duration of AF. Otherwise the groups were comparable. Ablation Procedure The end point of electrical isolation of all PVs (bi-directional entrance and exit block) was achieved in all patients. The mean procedure duration was 201.4±68.2 minutes (venous punctures to groin compression) with mean fluoroscopy duration of 53.2±26.1 minutes and radiofrequency application duration of 60.0±22.7 minutes. 8

9 In the adenosine-guided group dormant conduction was unmasked in 34 of 152 PVs (22.3%) in 21 of 40 patients (52.5%). Of those patients with dormant conduction, an average of 1.38 PVs per patient were affected. PV reconnection was transient in 27 PVs and sustained in 7 PVs. Dormant conduction was documented in 12 RSPVs, 5 RIPVs, 9 LSPVs, and 8 LIPVs. In the pace-capture guided group high output pacing was performed at an average of 20.0±1.8 sites per venous pair (range 14-24). Pace capture was documented in 39 of 156 PVs (25.0%) in 20 of 40 patients (50%). Of those patients with manifest pace-capture, an average of 1.86 PVs per patient were affected. Pace capture was documented in 9 RSPVs, 5 RIPVs, 15 LSPVs, and 6 LIPVs. A subset set of 25 patients underwent adenosine ne testing after targeted t ablation based on locations of local pace-capture. Of these 25 patients dormant conduction was unmasked in 6 patients (10 of 86 PVs). The prevalence of dormant conduction c after pace-capture pture guided ablation was significantly i lower than that observed after PVI alone (P=0.041 per PV, and P=0.032 per patient; t; Figure 3) Procedure duration (223.2±68.0 vs ±61.6 min; p=0.002), and fluoroscopy time (66.6±24.6 vs. 39.9±20.4 min; p<0.001) were significantly longer in the pace-capture group. RF time was comparable among groups (56.0±17.7 vs. 64.1±26.4; p=0.194). Freedom from AF At a mean follow-up of 329.2±124.8 days the single procedure (off AAD) freedom from AF was 65.0% in the pace-capture group and 67.5% in the adenosine-guided group (Figure 4; logrank p=0.378). In exploratory multivariate analyses, there was no significant difference in freedom from recurrent AF with pace-capture versus adenosine-guided ablation [hazard ratio 1.57, 95% confidence interval (0.58, 4.26), P=0.376]. There were no complications in the pace-capture 9

10 group, and one tamponade requiring percutaneous drainage in the adenosine-guided group. Discussion We have demonstrated the following key findings. In patients with a history of drug-refractory paroxysmal atrial fibrillation undergoing PVI: 1. A similar rate of residual PV conduction was unmasked by high-output pacing compared to adenosine provocation; 2. High-output pacing resulted in a significant reduction in the incidence of dormant conduction revealed by adenosine; 3) Exploratory analyses suggest that a high-output pacing approach results in comparable long- term freedom from recurrent AF when compared to adenosine-guided ablation. atio These findings ings have important clinical implications. Although wide circumferential pulmonary vein isolation on is an established treatment tment for patients ts suffering fering from AF, a significant minority (~30%) of patients will require a second intervention en tion due to arrhythmia rhyt hmia recurrence. renc e While the persistence of extra pulmonary triggering ing foci and/or an AF-maintaining i ing re-entrant en substrate have been proposed os as potential etiologic factors, considerable e evidence e has demonstrated that the majority of arrhythmia recurrences reflect recovery of electrical conduction between pulmonary veins and the left atrium after apparently successful initial isolation (i.e., PV-LA reconnection or re-conduction ). In other words, the failure to achieve lasting PV-LA conduction block at the index ablation procedure [due to: 1) intraatrial variability in tissue depth, and/or tissue contact/catheter stability, 2) edema formation, and 3) operator competency] has been etiologically linked to later arrhythmia recurrences. Unfortunately the accepted procedural endpoints of pulmonary vein isolation (i.e. entrance and exit conduction block) do not always represent the index creation of later contiguous transmural scar. Innovative intraprocedural techniques such as the use of adenosine and/or the use of high output pacing along the ablation line, represent means to acutely 10

11 differentiate permanent PV isolation from reversible dormant conduction. 9-12, 14, 15 It is postulated that delivering additional ablation targeting these regions of residual myocardial viability can improve the durability of the index lesion set, an in turn optimize longer-term patient outcomes. In effect this is what we have observed. The addition of pace-capture guided ablation to standard PVI resulted in a significant decrease in the incidence of adenosine provoked dormant conduction with a seemingly comparable longer-term success to that of adenosine-guided ablation (i.e. the identification and targeted ablation of regions of dormant conduction). The evaluation of new approaches to ablation requires a comprehensive appraisal praisal of the risks and complexity of the technique, as well as its potential effect on clinical outcome. While a comparable procedural safety, and longer-term efficacy was observed with both pace-capture and adenosine-guided ed ablation, atio it is important to consider that each technique has its own inherent advantages and disadvantages. Adenosine-guided ided ablation, which is based on the observation that the acute administration atio of IV adenosine results in restored excitability and PV-LA conduction by hyperpolarizing the reversibly injured antral LA cardiomyocytes, is limited by significant cost (requiring a minimum of 4 separate IV challenges), side-effects, contraindications (i.e. those with bronchospastic airway disease), as well as potential complications (prolonged asystole, and/or AF induction) Conversely, pace-capture guided ablation, which is based on the principle that an effective ablation lesion will result in the generation of local non-excitability, by definition necessitates the presence of an organized atrial rhythm. In addition, the effective use of highoutput pacing is dependent on operator experience. For example loss of capture due to inadequate tissue contact during pacing may be misconstrued as an effective ablation site and 11

12 thus compromise procedure efficacy. Conversely, atrial far-field capture may be misinterpreted as an area of vulnerable myocardium leading to unnecessary (and potentially harmful) RF delivery. Specifically, careful attention must be paid to ensure the ablation catheter is oriented as perpendicular as possible in order to prevent inadvertent capture of atrial tissue outside, or adjacent to, the ablation line by the proximal electrode of the distal bipole. Similarly, it is important to limit pacing output in anatomically susceptible locations such as the ridge between the left superior PV and the LA appendage. Moreover, the use of this technique was associated with longer procedure and fluoroscopy durations. Thus, while adenosine-guided ne-guided ablation is feasible (although challenging) in AF, pace-capture guided ablation offers the advantage anta that it can be used to identify ify gaps in not only the PV encircling c ing ablation line, but also other sites of atrial ablation (such as focal- or linear ablation sites). Limitations This report details an observational comparison between two different ent techniques es used to identify regions of myocardial al viability. The major limitations i ti of this study are its nonrandomized design and relatively low number of patients in each group. While the study was specifically designed to compare rates of residual PV conduction, it was adequately powered (>80%) to detect only large differences in clinical recurrences (i.e., hazard ratios >2). Since smaller effect sizes cannot be excluded, these secondary analyses were considered exploratory. Moreover, judgment of the effectiveness of AF ablation techniques is dependent on the quality of clinical follow-up. In our case, we attempted to maximize detection of arrhythmia recurrences through the use of serial 24h Holter monitors. It is possible that the use of longer monitoring durations, and/or loop recorders may have detected more arrhythmia episodes. Lastly, the utility of further ablation geared towards the elimination of residual or dormant PV conduction remains 12

13 unknown. In the case of pace-capture guided ablation both observational studies were lacking comparator groups. In the case of adenosine-guided ablation, while most of the previous observational studies have been positive, not all have been in agreement. 9-11, 13, 19 It is hoped that the results from the international multi-center randomized trial [the Adenosine Following Pulmonary Vein Isolation to Target Dormant Conduction Elimination (ADVICE) trial; ClinicalTrials.gov #NCT ] will answer the question as to whether elimination of dormant conduction unmasked by intravenous adenosine will result in fewer symptomatic AF recurrences compared with standard PVI. 12 Conclusion n A similar incidence of residual PV conduction ction is unmasked by high output pacing and adenosine administration. tion Targeting PV conduction o identified ifie ied by high output pacing results in a significant i reduction in dormant conduction ctio revealed ed by adenosine. e. Exploratory ry analyses suggest that the two approaches aches to unmasking residual PV conduction o yield comparable able long-term freedom edom from recurrent AF. The increased cost associated with adenosine must be weighed against the longer procedure and fluoroscopy time associated with pace-capture. The utility of these approaches needs to be evaluated in a larger-scale prospective randomized trial. Conflict of Interest Disclosures: None References: 1. Wolf PA, Mitchell JB, Baker CS, Kannel WB, D'Agostino RB. Impact of atrial fibrillation on mortality, stroke, and medical costs. Arch Intern Med. 1998;158: Waktare JE, Camm AJ. Acute treatment of atrial fibrillation: Why and when to maintain sinus rhythm. Am J Cardiol. 1998;81:3C-15C. 13

14 3. Verma A, Kilicaslan F, Pisano E, Marrouche NF, Fanelli R, Brachmann J, Geunther J, Potenza D, Martin DO, Cummings J, Burkhardt JD, Saliba W, Schweikert RA, Natale A. Response of atrial fibrillation to pulmonary vein antrum isolation is directly related to resumption and delay of pulmonary vein conduction. Circulation. 2005;112: Ouyang F, Antz M, Ernst S, Hachiya H, Mavrakis H, Deger FT, Schaumann A, Chun J, Falk P, Hennig D, Liu X, Bansch D, Kuck KH. 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: Cappato R, Negroni S, Pecora D, Bentivegna S, Lupo PP, Carolei A, Esposito C, Furlanello F, De Ambroggi L. Prospective assessment of late conduction recurrence across radiofrequency lesions producing electrical disconnection at the pulmonary vein ostium in patients with atrial fibrillation. Circulation. 2003;108: 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 ent strategy? te Circulation. 2004;109: Callans DJ, Gerstenfeld EP, Dixit it S, Zado E, Vanderhoff M, Ren JF, Marchlinski FE. Efficacy of repeat pulmonary vein isolation procedures in patients ts with recurrent ent atrial al fibrillation. i J Cardiovasc Electrophysiol. 2004;15: Cappato R, Calkins H, Chen SA, Davies W, Iesaka Y, Kalman an J, Kim YH, Klein G, Packer D, Skanes A. Worldwide survey on the methods, efficacy, and safety of catheter ter ablation for human atrial fibrillation. lation. Circulation. ion. 2005;111: ;111 11: Miyazaki S, Kuwahara T, Kobori A, Takahashi Y, Takei A, Sato A, Isobe M, Takahashi A. Impact of adenosine-provoked acute dormant pulmonary vein conduction on recurrence of atrial fibrillation. J Cardiovasc Electrophysiol. 2012;23: Matsuo S, Yamane T, Date T, Inada K, Kanzaki Y, Tokuda M, Shibayama K, Miyanaga S, Miyazaki H, Sugimoto K, Mochizuki S. Reduction of af recurrence after pulmonary vein isolation by eliminating atp-induced transient venous re-conduction. J Cardiovasc Electrophysiol. 2007;18: Kumagai K, Muraoka S, Mitsutake C, Takashima H, Nakashima H. A new approach for complete isolation of the posterior left atrium including pulmonary veins for atrial fibrillation. J Cardiovasc Electrophysiol. 2007;18: Macle L, Khairy P, Verma A, Weerasooriya R, Willems S, Arentz T, Novak P, Veenhuyzen G, Scavee C, Skanes A, Puererfellner H, Jais P, Khaykin Y, Rivard L, Guerra PG, Dubuc M, Thibault B, Talajic M, Roy D, Nattel S, Investigators AS. Adenosine following pulmonary vein isolation to target dormant conduction elimination (advice): Methods and rationale. Can J Cardiol. 2012;28:

15 13. Matsuo S, Yamane T, Date T, Lellouche N, Tokutake K, Hioki M, Ito K, Narui R, Tanigawa S, Nakane T, Tokuda M, Yamashita S, Aramaki Y, Inada K, Shibayama K, Miyanaga S, Yoshida H, Miyazaki H, Abe K, Sugimoto K, Taniguchi I, Yoshimura M. Dormant pulmonary vein conduction induced by adenosine in patients with atrial fibrillation who underwent catheter ablation. Am Heart J. 2011;161: Eitel C, Hindricks G, Sommer P, Gaspar T, Kircher S, Wetzel U, Dagres N, Esato M, Bollmann A, Husser D, Hilbert S, Zaker-Shahrak R, Arya A, Piorkowski C. Circumferential pulmonary vein isolation and linear left atrial ablation as a single-catheter technique to achieve bidirectional conduction block: The pace-and-ablate approach. Heart Rhythm. 2010;7: Steven D, Reddy VY, Inada K, Roberts-Thomson KC, Seiler J, Stevenson WG, Michaud GF. Loss of pace capture on the ablation line: A new marker for complete radiofrequency lesions to achieve pulmonary vein isolation. Heart Rhythm. 2010;7: Datino T, Macle L, Chartier D, Comtois P, Khairy P, Guerra PG, Fernandez-Aviles ndez ez-av es F, Nattel S. Differential effectiveness of pharmacological strategies to reveal dormant pulmonary l vein conduction: A clinical-experimental correlation. Heart Rhythm. 2011;8: Datino T, Macle L, Qi XY, Maguy A, Comtois P, Chartier D, Guerra PG, Arenal A, Fernandez-Aviles F, Nattel S. Mechanisms by which adenosine ne restores conduction in dormant canine pulmonary veins. Circulation. ion. 2010;121: Innes JA. Review ew article: Adenosine ne use in the emergency erge department. Emergency medicine Australasia a : EMA. 2008;20: ;2 0: Gula LJ, Massel D, Leong-Sit P, Gray C, Fox DJ, Segal OR, Krahn AD, Yee R, Klein GJ, Skanes AC. Does adenosine response predict clinical recurrence of atrial fibrillation after pulmonary vein isolation? J Cardiovasc Electrophysiol. 2011;22:

16 Table 1: Baseline and Procedural Characteristics. Baseline Parameters Pace-Capture Guided Ablation Adenosine Guided Ablation P Number Age in years mean±sd 60.1± ± Male number (%) 24 (60) 34 (85) <0.001 number (%) 6 (15) 2 (5) AF duration in months mean±sd 40.5± ± Antiarrhythmic drugs failed mean±sd 1.5± ± LV ejection fraction in % mean±sd 63.1± ± Left atrial diameter in mm mean±sd 38.9± ± Procedural Parameters Procedure time in minutes mean±sd 223.2± ± Fluoroscopy time in minutes mean±sd 66.6± ±20.4 <0.001 Ablation time in minutes mean±sd 56.0± ± Follow-up duration in days mean±sd 326.2± ± 331.9± mm: millimeters; met ers; SD standard deviation Figure Legends: Figure 1. Adenosine Guided Ablation. A. This panel illustrates the evaluation of dormant PV conduction. Following pulmonary vein isolation the LSPV is interrogated. On the first beat only atrial (A) and ventricular (V) far-field signals, but no pulmonary vein potentials (P) are observed on the circular mapping catheter (PV; 20 poles). Following the rapid administration of IV adenosine AV block is induced (last two beats) with a coincident recovery of pulmonary vein entrance conduction (P). The pulmonary vein activation sequence demonstrates the earliest 16

17 pulmonary vein activation as occurring at bipoles and The region proximal to this activation was then targeted for further ablation. B. This panel demonstrates the elimination of dormant PV conduction. After further ablation was performed the pulmonary vein was reinterrogated. Following the rapid administration of IV adenosine AV block is again induced (first two beats) although on this occasion there is no further evidence of LA-pulmonary vein conduction (no PVPs are recorded and only atrial far-field signals remain). Figure 2. Pace-capture Guided Ablation. After pulmonary vein isolation on the ablation line is mapped during high output pacing from the distal bipole of the ablation catheter er (MAPd). Panel A - High-output pacing at the location of a small gap demonstrates the presence of left atrial capture (note the change in CS activation). Panel B - After provision of ablation ation at the same site, there is a loss of local high h output pace-capture. e. Top panels - Modified posterior-anterior view of the left atrium. Bottom panels standard surface leads I, II, III and V1, proximal (p) and distal (d) bipoles of the ablation atio (MAP) catheter, t CS coronary sinus, s and Stim pacing stimulus. Figure 3. The Prevalence of Dormant Conduction. A subset of 25 patients in the pace-capture group underwent adenosine testing without targeted ablation of dormant conduction. In these patients only 10/89 PVs (11.2%; 28% of patients) demonstrated dormant conduction after the elimination of local pace-capture. Figure 4. Kaplan-Meier curves depicting time to first recurrence of atrial fibrillation (including a 3-month blanking period) in patients undergoing adenosine-guided and pace-capture guided ablation. 17

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22 Pulmonary Vein Isolation Using a "Pace-Capture Guided" Versus an "Adenosine Guided" Approach: The Effect on Dormant Conduction and Long-Term Freedom from Recurrent AF - A Prospective Study Jason G. Andrade, Scott J. Pollak, George Monir, Paul Khairy, Marc Dubuc, Denis Roy, Mario Talajic, Marc Deyell, Léna Rivard, Bernard Thibault, Peter G. Guerra, Stanley Nattel and Laurent Macle Circ Arrhythm Electrophysiol. published online October 4, 2013; Circulation: Arrhythmia and Electrophysiology is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX Copyright 2013 American Heart Association, Inc. All rights reserved. Print ISSN: Online ISSN: The online version of this article, along with updated information and services, is located on the World Wide Web at: Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation: Arrhythmia and Electrophysiology can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answerdocument. Reprints: Information about reprints can be found online at: Subscriptions: Information about subscribing to Circulation: Arrhythmia and Electrophysiology is online at: