HANDS ON How to perform encircling ablation of the left atrium Carlo Pappone, MD, PhD, Vincenzo Santinelli, MD From the Department of Cardiology, Electrophysiology and Cardiac Pacing Unit, San Raffaele Scientific Institute, Milan, Italy. The purpose of this article is to describe the technique and results of circumferential pulmonary vein ablation (CPVA) in patients with atrial fibrillation (AF) as currently performed in Milan.1–14 Since a significant learning curve still exists with the standard procedure, we have recently developed a new system, called remote magnetic navigation and ablation, which can be performed by less experienced operators while at the same time still reducing complications.13 The results of our standard technique with manually deflectable catheters are based on about 10,000 patients with paroxysmal, persistent, or permanent AF, many of whom have structural heart disease.1–12 At present, remote magnetic navigation and ablation has been performed safely in about 200 patients with paroxysmal, persistent, or permanent AF. Indications for AF ablation Inclusion and exclusion criteria are listed in Table 1. We do not exclude patients with mitral and/or aortic metallic prosthetic valves,6,11 and previous repair of atrial septal defects is not an absolute contraindication for ablation. Preablation preparation All antiarrhythmic drugs are stopped ⬎5 half-lives before ablation (amiodarone for ⬎3 months). Effective anticoagulation is obtained (international normalized ratio [INR] between 2 and 3), and in patients with permanent AF three or more consecutive INR values between 2.5 and 3.5 are documented before ablation. A transesophageal echocardiography (TEE) is performed in all patients. Anticoagulation protocol Three days before the procedure, oral anticoagulant therapy is stopped. The night before the procedure, heparin infusion is started to achieve an activated clotting time (ACT) ranging from 200 to 250 seconds. Heparin is stopped 2 hours before the ablation procedure to safely obtain vascular access and perform the transseptal puncture. After transseptal puncture, heparin is restarted as an initial bolus (5,000 U), followed by infusion or titrated with additional boluses to maintain the target ACT (between 250 and 300 seconds or between 300 and 350 seconds if evidence of smoke and/or decreased velocity is noted at TEE). During the procedure, Address reprint requests and correspondence: Carlo Pappone, M.D., Ph.D., F.A.C.C., Department of Cardiology, San Raffaele University Hospital, Via Olgettina 60, 20132, Milan, Italy. E-mail address: carlo. [email protected]. we monitor the ACT every 20 minutes to the target ACT. At the end of the procedure, protamine (15 mg) is injected to achieve partial reversal of anticoagulation before sheath removal. We remove all venous sheaths when ACT is ⬍200. Heparin is administered intravenously for 24 hours, starting 3 hours after sheath removal at 1,000 U/hour without a bolus. Thereafter, oral anticoagulant therapy is begun and low molecular weight heparin is given for 3 days after discharge. Anticoagulation is discontinued if sinus rhythm (SR) is maintained for ⬎3 months without any episodes of AF. Navigation and mapping systems Different navigation tools, such as an electroanatomic mapping system (CARTO, Biosense-Webster) or the EnSite/NavX system (Endocardial Solution, St. Paul, MN) and more recently a remote navigation system (Niobe II, Stereotaxis, St. Louis) with an integrated CARTO system are used to determine the ablation catheter position relative to the mapping electrodes. These technologies significantly reduce fluoroscopic exposure. Intracardiac echocardiography has been very rarely used. No computer tomographic scan or magnetic resonance imaging is usually performed before ablation. Radiofrequency (RF) ablation targets Currently, we perform circumferential pulmonary vein (PV) lesion lines to perform a point-by-point tailored distal disconnection of all PVs (Figures 1 and 2). Additional lesion lines, including the mitral isthmus line, posterior lines, and cavotricuspid isthmus, are also performed.4 During the procedure, we attempt to perform local vagal denervation by eliciting and eliminating vagal reflexes.5 Inducibility of AF is not routinely assessed.6 Standard circumferential PV ablation At present, we are using an irrigated-tip ablation catheter with a distal 3.5-mm tip (ThermoCool, Biosense-Webster) to ensure lesion transmurality while minimizing risk of perforation, particularly in the posterior lines.6 We still use 8-mm-tip catheters for cavotricuspid-isthmus ablation line. Impedance is monitored continuously as it may increase suddenly if thrombus forms on the catheter tip, and an impedance map is also constructed.14 In our experience, a much more useful indicator of thrombus formation is a 40%–50% reduction in the power delivered to reach target temperature. If thrombus formation is suspected, catheter 1547-5271/$ -see front matter © 2006 Heart Rhythm Society. All rights reserved. doi:10.1016/j.hrthm.2006.03.003 1106 Heart Rhythm, Vol 3, No 9, September 2006 Table 1 Inclusion criteria ● At least one weekly episode of paroxysmal AF ● At least one monthly episode of persistent symptomatic AF ● Permanent AF ● At least one failed antiarrhythmic drug Exclusion criteria ● Age ⬎80 years ● Contraindications to anticoagulation ● Presence of cardiac thrombus ● Left atrial diameter ⱖ65 mm ● Life expectancy ⬍1 year ● Thyroid dysfunction withdrawal from the left atrium (LA) without advancing the transseptal sheath may be necessary to preserve transseptal access. This avoids stripping any thrombus present on the catheter tip as the catheter is withdrawn into the sheath, which can result in systemic embolization. We normally start by determining the location of all four major PVs and the mitral annulus as anatomic landmarks for the EnSite/ NavX system (Figure 3) or the CARTO system and create the map by entering each PV in turn. To locate PVs, we use three criteria based on fluoroscopy, electrical activity, and impedance.14 Entry into the vein is clearly identified as the catheter leaves the cardiac shadow on fluoroscopy, the impedance usually rises above 140 –150 ⍀, and electrical activity disappears. Because of the orientation of some veins and the limitations of catheter shape, it can be difficult to deeply enter some veins, but the impedance still rises when the catheter is in the mouth of the vein. To better differentiate between PVs and LA, we use voltage criteria (fractionation of local bipolar electrogram) and impedance (rise ⬎4 ⍀ above mean LA impedance) to define the PV ostium. Clearly, the anatomic appearance on CARTO acts as added confirmation of catheter entry into the PV ostium. Figure 1 Schematic of CPVA strategy used to distally disconnect PVs using point-by-point tailored lesions with substrate modification inside encircled areas. Figure 2 Panels 1– 4: On tailored ablation lines and within each of the encircled areas, previous electrical activity (yellow arrows) completely disappeared after ablation (blue arrows), which indicates distal electrical disconnection and substrate modification. The mapping and ablation procedures are performed by using the CS atrial signal if the patient is in SR or the right ventricular signal if the patient is in AF; these are the synchronization triggers for CARTO. If spontaneous ventricular rates during AF are too low, we usually pace the right ventricle at higher rates to increase the CARTO system sampling rates. If the patient is in SR, we map during continuous coronary sinus (CS) pacing to increase the refresh rate. The chamber geometry is reconstructed in real time by interpolation of the acquired points. Usually, 100 points are required to create adequate maps of LA and PVs and up to 200 points for accurate mapping of atrial tachycardia (AT). Local activation times can be used to create activation maps, which are extremely important when attempting to ablate focal or macroreentrant ATs.4,6,8 –12 Figure 3 Posterior view of a NavX geometry showing a detailed postablation voltage map using this system (Endocardial Solutions). Tagged ablation points (white circles) around the left- and right-sided PVs are shown; continuous points joining the LSPVs and RSPVs and the LIPVs and RIPVs with a mitral valve to the LIPV line (mitral isthmus line) are depicted. The reference catheter is placed in the CS. Pappone and Santinelli Encircling Ablation of the Left Atrium RF applications and energy setting Once the main PVs and LA have been adequately reconstructed, RF energy is delivered to the atrial endocardium with RF generator settings of 55– 65°C and a power limit of 100 W, but with irrigated catheters much less energy is required (40 W-40°C). This is reduced in the posterior wall to 35 W and 55°C to reduce risk of injury to the surrounding structures.6,7 RF energy is applied continuously on the planned circumferential lines as the catheter is gradually dragged along the line. Continuous catheter movement, often in a to-and-fro movement over a point, helps keep catheter tip temperature down because of passive cooling. Successful lesion creation at each point is considered to have taken place when the local bipolar voltage has decreased by 90% or to ⬍0.05 mV. On average, with irrigated-tip catheters, a total of 15 seconds of RF is required. If the catheter position deviates significantly from the planned line or falls into a PV, RF application is immediately terminated until the catheter is returned to a suitable location. Circumferential ablation lines are usually created starting at the lateral mitral annulus and withdrawing posterior and then anterior to the left-sided PVs, passing between the left superior PV (LSPV) and the LA appendage (LAA) before completing the circumferential line on the posterior wall of the LA. The “ridge” between the LSPV and LAA may be identified by fragmented electrograms from collision of activity from the LAA and LSPV/LA. The appendage is identifiable by a significantly higher impedance (⬎4 ⍀ above LA mean) and a high-voltage local bipolar electrogram, with characteristically organized activity in fibrillating patients. The right PVs are isolated in a similar fashion, and then a posterior line connecting the two circumferential lines is made to reduce the risk of macroreentrant ATs. Gaps are defined as breakthroughs in an ablated area and identified by sites with single potentials and by early local activation. Usually, we do not validate circumferential lesions around PVs by pacing maneuvers. Rather, we accurately validate the bipolar voltage abatement on lesions lines as well as within the encircled areas (Figures 1 and 2) and perform a voltage remap, acquiring new points on the existing geometry to give voltage measurements. This should characteristically show low voltage (red) within the PV encircling lines (Figure 3). Completeness of lesion lines, particularly at the mitral isthmus, is critical in preventing postablation macroreentrant LA tachycardias, which in the majority of cases are mitral-isthmus dependent and incessant.4 The completeness of the mitral isthmus line is demonstrated during CS pacing by endocardial and CS mapping by looking for widely spaced local double potentials across the line of block and is confirmed by differential pacing. In our experience, the minimum double potential interval at the mitral isthmus during CS pacing, after block is achieved, is between 150 and 300 ms, depending on the atrial dimensions and the extent of scarring and lesion creation.4,6 After the planned lines of block have been created, the LA is remapped, and the preablation 1107 and postablation activation maps are compared. Incomplete block is revealed by impulse propagation across the line; in such a case, further RF applications are given to complete the line of block. We observe termination of AF during the procedure in about one-third of patients. If AF does not terminate during RF, then transthoracic cardioversion is performed at the end of the procedure. If AF recurs immediately after cardioversion, then the completeness of the lines is reassessed. Once SR is restored with either RF or cardioversion, attempts to reinduce AF by rapid atrial pacing with and without isoproterenol infusion are only made for investigational purposes in selected patients. We do not isolate the superior vena cava for AF treatment. At present, the CPVA procedure usually lasts approximately 1 hour, including 20 minutes for pre-/postmapping and 40 minutes for ablation. Local vagal denervation A recent target reported for the first time by our group in Milan has been local vagal denervation.5,6 Potential vagal target sites are identified during the procedure in more than one-third of patients. Vagal reflexes are defined as sinus bradycardia (⬍40 beats/min) or asystole, AV block, or hypotension occurring within a few seconds of the onset of RF application. If a reflex is elicited, RF energy is delivered until such reflexes are abolished, or for up to 30 seconds. The endpoint for ablation at these sites is termination of the reflex, followed by sinus tachycardia or AF. Failure to reproduce the reflexes with repeat RF is considered confirmation of denervation. Complete local vagal denervation is defined by the abolition of all vagal reflexes. Complication rates Complications rates with standard CPVA (manually deflectable catheters) are shown in Table 2. Postablation LA tachycardias usually do not require a repeat of procedure, as most resolve spontaneously within 5 months after the index procedure.4,6 Atrio-esophageal fistulas rarely occur but may be dramatic and devastating.6,7 We recommend lower RF energy application when ablating on the LA posterior wall and making the line on the posterior wall near to the roof of the LA, where the LA is not in direct contact with the esophagus.6,7 Table 2 Complications after CPVA % ● ● ● ● ● ● ● ● 0% 0.1% 0.03% 0.2% 0.1% 0.03% 0% 6% Death Pericardial effusion Stroke Transient ischemic attack Tamponade Atrio-esophageal fistula Pulmonary vein stenosis Left atrial tachycardia 1108 Heart Rhythm, Vol 3, No 9, September 2006 Remote circumferential PV ablation We have recently developed a new technique (Niobe II, Stereotaxis) for remote circumferential PV ablation using a soft magnetic catheter.13 The operator is positioned in a separate control room, at a distance from the X-ray beam and the patient’s body. A 4-mm magnetic catheter (NaviStar-RMT, Biosense Webster, Inc.) is integrated with a newly developed electroanatomical mapping system (CARTO-RMT mapping system). Additional magnets in the distal portion of the device can be deflected in any desired direction and steered by the magnetic navigation system. The catheter can be softly advanced or retracted by a mechanical device (Cardiodrive, Stereotaxis). All magnetic field vectors used for each target navigation can be stored and, if necessary, reapplied while the magnetic catheter is navigated automatically. Remote mapping and ablation A transseptal sheath positioned just proximal to the fossa ovalis allows the greatest movement of the magnetic wire catheter. After synchronizing with respiratory and cardiac cycles, such as inspiration and end-diastolic period, a pair of best-matched right anterior oblique/left anterior oblique (RAO/LAO) images are transferred into the Navigant screen as background references for orientation and navigation. Next a PV location is selected by a preset magnetic field vector, and during navigation many points can be simultaneously acquired by the NaviStar-RMT magnetic catheter (Figure 4). Remote CPVA is usually performed with a target temperature of 65°C and a power limit of 50 W. All ablation lines are performed by sequentially navigating to contiguous points with a single 5- to 10-second application of RF current, which is able to achieve a ⬎90% reduction in the bipolar electrogram amplitude (Figure 5). The lesion line can be resent to and recorded on the fluo- Figure 5 Post–remote ablation color-coded voltage remap of the LA is shown. The lesion set includes circumferential lesions (red circles) around the left- and right-sided PVs with additional posterior lines and the mitral isthmus line. roscopic image. Potential vagal target sites are also identified during the procedure as with the manual approach. Sheath insertion and positioning of diagnostic catheters, including the magnetic catheter, requires a few minutes (min-max, 5–12 minutes). After crossing the atrial septum and positioning the transseptal sheath, the operator leaves the interventional room to perform mapping and ablation from the control room. Based on our experience, remote magnetic navigation and ablation to all targeted sites can be safely and successfully achieved in all patients. At the beginning of the learning curve, tip orientation was frequently adjusted as the catheter was retracted and advanced to access all PVs by using this sequence when feasible: LSPV, left inferior PV (LIPV), right superior PV (RSPV), and finally right inferior PV (RIPV). Afterward, the mitral valve annulus and the LAA can be accessed by selecting different field directions on NaviSphere. Finally, we navigate the magnetic catheter in rapid sequence to the posterior wall, roof, septal wall, and anterior wall. Comparison of standard versus remote CPVA Figure 4 Remote magnetic navigation with the Niobe II system (Stereotaxis). The figure shows remote navigation of a soft magnetic catheter on the Navigant screen toward the LSPV (panel 1), LIPV (panel 2), RSPV (panel 3), and RIPV (panel 4). A preset (as a stored vector, LSPV) was selected from the preset list indicated on the right side of each panel and then applied to the desired direction. RAO and LAO appear on the bottom of each panel, and the virtual catheter is marked in yellow. On the top of each panel, two anatomic images of the LA (NaviSphere) are depicted. Initial results indicate that remote navigation and ablation is a simple, safe, and useful system for AF ablation that does not require a substantial learning curve because the endpoint can be successfully reached in almost all patients undergoing such therapy. In the first patients, the procedure and fluoroscopy times were long, which was due to the need to visually confirm catheter location and stability during navigation and RF application. The procedure, which included navigation and ablation, was done from the control room, which reduced fluoroscopic exposure time for the operator. The manual approach is operator-dependent, while the remote one is not, but it is dependent on a well-trained team. Pappone and Santinelli Encircling Ablation of the Left Atrium 1109 This may explain why the overall procedure time can be longer in the remote group than in the control group, while mapping times in both approaches are similar. Ablation time to complete circumferential lesions around right-sided PVs is shorter remotely, which indicates that there are no challenging sites as with standard CPVA, thus avoiding unnecessary RF energy applications. present, then a repeat procedure is scheduled for 6 months after the index procedure. During the repeat ablation procedure, an isthmus line for typical atrial flutter, LA mapping, and ablation of LA flutter or a touchup of the prior ablation lines is performed. A maximum of three separate ablation procedures per patient is allowed. Follow-up and long-term efficacy of standard and remote CPVA 1. Pappone C, Rosanio S, Oreto G, Tocchi M, Gugliotta F, Vicedomini G, Salvati A, Dicandia C, Mazzone P, Santinelli V, Gulletta S, Chierchia S. Circumferential radiofrequency ablation of PV ostia. Circulation 2000;102:2619 –2628. 2. Pappone C, Oreto G, Rosanio S, Vicedomini G, Tocchi M, Gugliotta F, Salvati A, Dicandia C, Calabro MP, Mazzone P, Ficarra E, Di Gioia C, Gulletta S, Nardi S, Santinelli V, Benussi S, Alfieri O. Atrial electroanatomic remodeling after circumferential radiofrequency PV ablation. Efficacy of an anatomic approach in a large cohort of patients with AF. Circulation 2001;103:2539 –2544. 3. Pappone C, Rosanio S, Augello G, Gallus G, Vicedomini G, Mazzone P, Gulletta S, Gugliotta F, Pappone A, Santinelli V, Tortoriello V, Sala S, Zangrillo A, Crescenzi G, Benussi S, Alfieri O. Mortality, morbidity, and quality of life after circumferential pulmonary vein ablation for atrial fibrillation: outcomes from a controlled nonrandomized long-term study. J Am Coll Cardiol 2003;42: 185–197. 4. Pappone C, Manguso F, Vicedomini G, Gugliotta F, Santinelli O, Ferro A, Gulletta S, Sala S, Sora N, Paglino G, Augello G, Agricola E, Zangrillo A, Alfieri O, Santinelli V. Prevention of iatrogenic atrial tachycardia after ablation of atrial fibrillation. A prospective randomized study comparing circumferential pulmonary vein ablation with a modified approach. Circulation 2004;110:3036 – 3042. 5. Pappone C, Santinelli V, Manguso F, Vicedomini G, Gugliotta F, Augello G, Mazzone P, Tortoriello W, Landoni G, Zangrillo A, Lang C, Tomita T, Mesas C, Mastella E, Alfieri O. PV denervation enhances long-term benefit after circumferential ablation for paroxysmal AF. Circulation 2004;109:327–334. 6. Pappone C, Santinelli V. The who, what, why, and how-to guide for circumferential pulmonary vein ablation. J Cardiovasc Electrophysiol 2004;15:1226 – 1230. 7. Pappone C, Oral H, Santinelli V, Vicedomini G, Lang CC, Manguso F, Torracca L, Benussi S, Alfieri O, Hong R, Lau W, Hirata K, Shikuma N, Hall B, Morady F. Atrio-esophageal fistula as a complication of percutaneous transcatheter ablation of AF. Circulation 2004;109:2724 –2726. 8. Pappone C, Santinelli V. Atrial fibrillation ablation: state of the art. Am J Cardiol 2005;96:59L– 64L. 9. Pappone C, Santinelli V. Atrial fibrillation ablation: a realistic alternative to pharmacologic therapy. Nat Clin Pract Cardiovasc Med 2005;2:608 – 609. 10. Pappone C, Santinelli V. Towards a unified strategy for atrial fibrillation ablation? Eur Heart J 2005;26:1687–1688. 11. Lang CC, Santinelli V, Augello G, Ferro A, Gugliotta F, Gulletta S, Vicedomini G, Mesas C, Paglino G, Sala S, Sora N, Mazzone P, Manguso F, Pappone C. Transcatheter radiofrequency ablation of atrial fibrillation in patients with mitral valve prostheses and enlarged atria: safety, feasibility, and efficacy. J Am Coll Cardiol 2005;45:868 – 872. 12. Mesas CE, Pappone C, Lang CC, Gugliotta F, Tomita T, Vicedomini G, Sala S, Paglino G, Gulletta S, Ferro A, Santinelli V. Left atrial tachycardia after circumferential pulmonary vein ablation for atrial fibrillation: electroanatomic characterization and treatment. J Am Coll Cardiol 2004;44:1071–1079. 13. Pappone C, Vicedomini G, Manguso F, Gugliotta F, Mazzone P, Gulletta S, Sora N, Sala S, Marci A, Augello G, Rivolsi L, Santagostino A, Santinelli V. Robotic magnetic navigation for atrial fibrillation ablation. J Am Coll Cardiol 2006;47: 1390 –1400. 14. Lang CC, Gugliotta F, Santinelli V, Mesas C, Tomita T, Vicedomini G, Augello G, Gulletta S, Mazzone P, De Cobelli F, Del Maschio A, Pappone C. Endocardial impedance mapping during circumferential pulmonary vein ablation of atrial fibrillation differentiates between atrial and venous tissue. Heart Rhythm 2006;3:171–178. Patients are supplied with a transtelephonic event recorder for at least 1 year after the ablation and are requested to send recordings weekly, irrespective of the presence or absence of symptoms. We arrange clinical assessment, Transthoracic echocardiography (TTE) and 24-hour ambulatory recordings 1, 3, 6, and 12 months after the procedure. Because a large minority of patients have early recurrence of AF after ablation, many patients are prescribed antiarrhythmic drugs. Long-term efficacy of standard CPVA is ⬎90% for patients with paroxysmal or persistent AF and ⬎80% for permanent AF. In patients with paroxysmal AF and local vagal denervation, the long-term success rate is close to 100%. Early recurrences of AF usually occur within the first 2 months after the index procedure, but in half of cases they are a transient phenomenon that do not require a repeat procedure. After ablation, the follow-up management depends on the clinical and echocardiographic characteristics of the patient population. In patients with LA diameter (LAD) ⬎55 mm and permanent AF, we prescribe oral amiodarone at a total dose of 200 mg, 5 days a week for 30 days, and then 100 mg, 5 days a week for the following 30 days. If TTE performed at 2 months shows a decrease in LAD ⬎35 mm associated with improved atrial transport function and persistent SR documented by daily transtelephonic recordings, amiodarone is replaced by oral sotalol (120 mg daily for 30 days). Usually, sotalol is discontinued after 30 days if SR persists. Angiotensin receptor (ATR) blockers usually are withdrawn 90 days after procedure but are maintained in patients who were undergoing ATR blocker therapy before the procedure. In patients with LAD between 40 and 55 mm and paroxysmal AF, we prescribe sotalol 40 mg twice daily and flecainide 50 mg twice daily for 30 days. If the LAD decreases after this period, the patient continues taking sotalol for another 30 days. In patients with LAD ⬍40 mm and paroxysmal AF, we prescribe sotalol 40 mg daily for 30 days. If recurrence of persistent AF or monthly episodes of symptomatic paroxysmal AF occur beyond the first month after ablation or incessant highly symptomatic left or right atrial flutter is References