Peri-mitral atrial flutter in patients with atrial fibrillation ablation

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1 Peri-mitral atrial flutter in patients with atrial fibrillation ablation Seiichiro Matsuo, MD,* Matthew Wright, MBBS, PhD,* Sébastien Knecht, MD,* Isabelle Nault, MD,* Nicolas Lellouche, MD,* Kang-Teng Lim, MD,* Leonardo Arantes, MD,* Mark D. O Neill, MB, BCh, DPhil,* Mélèze Hocini, MD,* Pierre Jaïs, MD,* Michel Haïssaguerre, MD* From *Hôpital Cardiologique du Haut-Lévêque and Université Victor Segalen Bordeaux II, Bordeaux, France, and Kings College London BHF Centre, Cardiovascular Division, NIHR Biomedical Research Centre at Guy s and St. Thomas NHS Foundation Trust, London, United Kingdom. BACKGROUND Peri-mitral atrial flutter (PMFL) is commonly encountered in patients undergoing atrial fibrillation (AF) ablation. OBJECTIVE The purpose of this study was to determine the electrophysiologic characteristics, procedural success, and medium-term outcomes in patients with PMFL. METHODS The study consisted of 50 consecutive patients (45 men and 5 women, age years) with PMFL following or during AF ablation. Of the 50 PMFLs, 24 occurred during AF ablation (16 at index ablation and 8 at repeat procedure for recurrent AF), and 26 developed during follow-up. Ablation of PMFL was performed by creating a linear lesion joining the mitral annulus to the left inferior pulmonary vein. RESULTS The incidence of PMFL was higher in patients with mitral isthmus (MI) ablation performed during AF ablation, prior to the development of PMFL, than in those in whom MI ablation was not performed (23% vs 8%, P.04). Following the procedure, PMFL was more frequent in patients with prior MI ablation than in those without (41% vs 15%, P.01). Seventy percent (35/50) were terminated by ablation with minutes of radiofrequency application. Among patients in whom PMFL terminated, supplemental ablation was required for bidirectional conduction block in 66% (23/35). MI block was achieved in 92% (46/50) using minutes of ablation. At mean follow-up of 19 4 months, 96% of patients were free from PMFL. CONCLUSION PMFL can be terminated by MI ablation, but the procedure is proarrhythmic. Supplemental ablation is necessary to establish bidirectional block of the line despite termination of PMFL in the majority of patients. KEYWORDS Atrial fibrillation; Catheter ablation; Mitral isthmus; Peri-mitral atrial flutter ABBREVIATIONS AF atrial fibrillation; AT atrial tachycardia; CS coronary sinus; MI mitral isthmus; PMFL peri-mitral atrial flutter; PV pulmonary vein (Heart Rhythm 2010;7:2 8) 2010 Heart Rhythm Society. All rights reserved. Introduction In recent years, catheter ablation has become an accepted treatment of atrial fibrillation (AF) for patients who have not responded to antiarrhythmic drug therapy. 1 4 However, despite the success of catheter ablation in treating AF, recurrent atrial tachycardia (AT) is a major complication of AF ablation. 4 8 These ATs often are more symptomatic than the individual patient s AF and normally are unresponsive to antiarrhythmic drugs. The underlying mechanisms of AT following AF ablation have been described, with peri-mitral atrial flutter (PMFL) being the most common macroreentrant AT in the context of AF ablation. 5 Dr. Wright receives financial support from the Department of Health via the National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre award to Guy s and St. Thomas NHS Foundation Trust in partnership with King s College London and King s College Hospital NHS Foundation Trust. Address reprint requests and correspondence: Dr. Seiichiro Matsuo, Service de Rythmologie, Hôpital Cardiologique du Haut-Lévêque, Avenue de Magellan, Bordeaux- Pessac, France. address: mattsuu@tc4.so-net.ne.jp. (Received August 5, 2009; accepted September 23, 2009.) PMFL is a difficult arrhythmia to treat with antiarrhythmic drugs. A so-called mitral isthmus (MI) line, between the lateral mitral annulus and the isolated left inferior pulmonary vein (PV), is the normal linear lesion created to treat the arrhythmia. However, bidirectional conduction block is difficult to achieve, possibly due to the thickness of the MI and due to the close proximity of the distal coronary sinus (CS), which can act as a heat sink, preventing transmural lesion delivery. 9 Ablation within the CS is not without risk; isolated cases of steam pops and tamponade have been reported. Alternative lesions include an anterior line 10 or a septal MI line 11 ; however, the efficacy of these ablation strategies remains to be determined. The present study investigated the clinical and electrophysiologic characteristics of patients undergoing AF ablation who developed PMFL and their subsequent clinical outcome. Methods Patient population The study consisted of 50 patients from consecutive series who developed PMFL in the context of AF ablation be /$ -see front matter 2010 Heart Rhythm Society. All rights reserved. doi: /j.hrthm

2 Matsuo et al Peri-mitral flutter in atrial fibrillation 3 tween November 2006 and September All patients gave written informed consent. Electrophysiologic study All AF patients had effective anticoagulation therapy (target international normalized ratio 2 3) for more than 1 month and underwent transesophageal echocardiography to exclude atrial thrombus prior to the procedure. All antiarrhythmic drugs, except for amiodarone, were discontinued five half-lives before the procedure. Electrophysiologic study was performed with patients in the fasting state under mild sedation using midazolam and morphine. A steerable decapolar or quadripolar catheter (Xtrem, ELA Medical, Le Plessis-Robinson, France) was placed within the CS at the 4 to 5 o clock position along the mitral annulus in the left anterior oblique projection. A 4-mm externally irrigated-tip ablation catheter (ThermoCool, Biosense Webster, Diamond Bar, CA, USA) was used for mapping and ablation. Following transseptal access, a single bolus of heparin (50 international units per kilogram body weight) was administrated and repeated only for procedures lasting more than 4 hours. Surface and bipolar endocardial electrograms were continuously monitored and recorded for off-line analysis (Bard Electrophysiology, Lowell, MA, USA). Intracardiac electrograms were filtered from 30 to 500 Hz and measured at sweep speed of 100 mm/s. Catheter ablation of AF In patients with persistent AF, a stepwise approach was performed. 12 In patients with paroxysmal AF, stepwise ablation was performed when AF persisted or was induced and sustained ( 10 minutes) by burst atrial pacing following PV isolation. In brief, PV isolation was performed, regardless of ongoing cardiac rhythm. 12 The end-point of this step was elimination or dissociation of PV potentials as determined by a circumferential mapping catheter (Lasso, Biosense Webster) in all PVs. Following PV isolation and cavotricuspid isthmus ablation, electrogram-based ablation in all regions of the left atrium was performed. 12 The endpoint of this step was organization of local activity. Linear ablation in the left atrium was performed as the final step of this sequential ablation technique if patients remained in AF. A roof line ablation joining the superior PVs was performed. If AF continued, then an MI line was performed. The end-point of application during AF was abolition of local electrograms along the linear lesion. After restoration of sinus rhythm, assessment of conduction block across all lines was performed in all patients using conventional techniques, 12 with an end-point of bidirectional conduction block 13 and supplementary ablation as required. The procedural end-point was termination of AF and restoration of sinus rhythm by ablation with confirmed PVisolation and bidirectional conduction block of any linear lesion performed. 12 Mapping and ablation of PMFL PMFL was diagnosed using conventional electrophysiologic techniques without the routine use of three-dimensional navigation systems. If an activation wavefront compatible with PMFL was observed and 90% of the circuit was mapped around the mitral valve annulus, PMFL was suspected. This was confirmed when entrainment mapping at two separate sites of the circuit showed at both sites a corrected postpacing interval (postpacing interval tachycardia cycle length) within 20 ms of the tachycardia cycle length (Figure 1). 5 Ablation of PMFL was performed by creating a line of conduction block between the left inferior PV and the lateral mitral valve annulus. Radiofrequency energy was limited to a maximum power output of 40 W endocardially (usually 35 W), maximum temperature was limited to 50 C, and irrigation rate was titrated to maintain an electrode temperature above 38 C. Epicardial ablation from the CS was attempted when no obvious atrial potential was mapped on the MI line or when a large atrial potential was observed in the CS catheter despite ablation endocardially. Radiofrequency energy was limited to a maximum power output of 25 W endocardially, irrigation rate was 60 ml/s, and temperature was limited to 50 o C. The end-point of MI ablation was establishment of bidirectional conduction block and was assessed using differential pacing analysis after restoration of sinus rhythm. 13,14 In brief, pacing the distal bipole of the CS catheter placed just septal to the linear lesion results in a longer stimulus-to-electrogram timing, measured using the radiofrequency catheter, just lateral to the line, compared to the next more septal bipole of the CS catheter. Pacing lateral to the line via the ablation catheter placed endocardially, a proximal-to-distal activation sequence along the CS septal to the line is seen, confirming bidirectional conduction block. In patients in whom PMFL could not be terminated by ablation, PMFL was terminated by atrial burst pacing (10 patients) and by direct current cardioversion (5 patients) when burst pacing had failed. After termination of PMFL, conduction block through the MI was established by supplemental radiofrequency application as required. Follow-up Patients were hospitalized for 1 day or received periodic follow-up in an outpatient clinic at 1, 3, 6, and 12 months for clinical interview and 24-hour ambulatory monitoring, in addition to routine follow-up by the referring cardiologist. After 1 year from the last procedure, patients were followed every 6 months by the referring cardiologist, who was asked to perform 24-hour ambulatory monitoring within the last 3 months of follow-up. Antiarrhythmic medication was continued for 1 to 3 months following the index procedure for AF, and anticoagulation treatment was continued for at least 6 months. A repeat ablation procedure was performed in the event of recurrence of AF or AT. Statistical analysis Continuous variables are expressed as mean SD or median with interquartile range. Statistical significance was assessed using the unpaired Student s t-test or Mann-Whit-

3 4 Heart Rhythm, Vol 7, No 1, January 2010 Figure 1 Demonstration of peri-mitral atrial flutter (PMFL). A: Electroanatomic mapping in the left oblique view showing macroreentrant atrial tachycardia circulating the mitral annulus in a clockwise direction. B: Entrainment mapping at two separate sites on the mitral annulus. Corrected postpacing interval (PPI) was equal to atrial tachycardia cycle length on the posterior left atrium (i) and 20 ms on the anterior wall (ii). Shown are recordings from surface ECG leads II and V 1 ; mapping catheter (MAP); and distal, middle, and proximal coronary sinus (CSd, CSm, CSp); C: PMFL was terminated during radiofrequency application on the mitral isthmus. ABL ablation catheter; CL cycle length. ney test if necessary. Categorical variables, expressed as numbers or percentages, were analyzed using the Chisquare test or Fisher exact test. All tests were two-tailed, and P.05 was considered significant. Results Patient population Baseline characteristics of the overall study population are given in Table 1. Mean patient age was years, and 90% of patients were male. History (from diagnosis of AF to procedure) and mean duration of persistent AF (from last documentation of sinus rhythm to procedure) were months (median 84 months, interquartile range months) and months (median 12 months, interquartile range 6 28 months), respectively. Evidence of structural heart disease was present in 32% (16/ 50) of patients. Average left atrial diameter was mm from the parasternal view, and average left ventricular ejection fraction was 59.1% 14.6% (Simpson method). All patients were followed up for at least 12 months after the final ablation procedure (mean follow-up months, median 18 months, interquartile range months). Characteristics of PMFL Mean tachycardia cycle length of PMFL was ms. Tachycardia cycle length was significantly longer when PMFL occurred during follow-up than when PMFL oc-

4 Matsuo et al Peri-mitral flutter in atrial fibrillation 5 Table 1 Characteristics of study patients with peri-mitral atrial flutter (n 50) Age (years) Sex (male/female) 45/5 Type of AF (persistent/paroxysmal) 47/3 Structural heart disease 16 Duration of persistent AF (months) Left atrial dimension (mm) Left ventricular ejection fraction (%) No. of antiarrhythmic drugs for AF Amiodarone 14 No. of direct current cardioversions for AF AF atrial fibrillation. curred during the index procedure ( ms vs ms, respectively, P.05; Figure 2). Of the 50 PMFLs, 24 (48%) were clockwise and 26 (52%) were counterclockwise (P NS). Among the 254 patients who underwent AF ablation, 24 (9.4%) developed PMFL during the ablation and 26 developed PMFL after the initial ablation. From among the 254 patients who underwent AF ablation, 48 (20.9%) of 230 ablation patients who did not develop PMFL took amiodarone at the time of procedure, whereas 4 (16.7%) of 24 ablation patients who developed PMFL took amiodarone (P.63). Amiodarone was stopped 1 to 3 months after AF ablation if no arrhythmia recurred. Of the 24 PMFLs that occurred during the AF ablation procedure, 16 developed during the first ablation procedure (14 in patients with persistent AF and 2 in patients with paroxysmal AF) and 8 developed during the repeat AF ablation procedure (Figure 2). PMFL in the context of AF ablation Of the 191 consecutive patients undergoing initial AF ablation (93 with paroxysmal AF and 98 with persistent AF), 47 had an MI line, and bidirectional block was achieved in 89.4% (42/47). Of the 98 consecutive patients with persistent AF, linear ablation of the MI was performed in 44 Figure 2 Characteristics of peri-mitral atrial flutter (PMFL) in the present study. AF atrial fibrillation; ATCL atrial tachycardia cycle length. Figure 3 Incidence of peri-mitral atrial flutter (PMFL). A: PMFL was frequently observed in patients with concurrently performed mitral isthmus (MI) ablation compared to those without. B: Recurrence of PMFL was associated with prior mitral isthmus ablation during the initial ablation procedure for atrial fibrillation. patients, and 14 (14.2%) patients developed PMFL during the first ablation. Of 44 MI ablations, 39 were performed as part of the stepwise approach to achieve procedural termination of AF; the other 5 were performed for PMFL following procedural termination of AF without a previous MI line. Persistent AF was terminated by MI ablation in 59.0% (23/39) of patients but converted directly to PMFL in 61% (14/23) of the patients. The incidence of PMFL during the index ablation was significantly higher in patients who required ablation of the MI as part of the stepwise approach to terminate persistent AF than in those who did not [23% (9/39) vs 8% (5/59), P.04; Figure 3A]. Of the 93 consecutive patients undergoing initial ablation for paroxysmal AF, 2 (2.4%) developed PMFL (P.05 compared to persistent AF). Sustained recurrent PMFL was observed in 29% (26/89) patients who underwent a repeat ablation for recurrent atrial arrhythmia (AF or AT) following AF ablation. PMFL recurred months (median 3 months, interquartile range 3 6 months) after the index procedure, and the ablation procedure for recurrent PMFL was performed months (median 8 months, interquartile range 5 11 months) after the index AF ablation. Fifty-five percent (49/89) of patients had previously undergone ablation of the MI ablation at the index procedure. Prior MI isthmus ablation was more frequent in patients with recurrent PMFL than in those without PMFL [41% (20/49) vs 15% (6/40), P.01; Figure 3B]. Of the 49 patients who had MI ablation during the index procedure, bidirectional conduction block was achieved in 40 (81.6%). There was a trend toward incomplete prior MI conduction block predisposing to recurrent PMFL during follow up [67% (6/9) vs 35% (14/40), P.08]. Termination of PMFL by catheter ablation Mean duration of mapping prior to diagnosis of PMFL was minutes. Thirty-five (70%) of 50 PMFLs were terminated by catheter ablation using minutes of radiofrequency delivery. Of the remaining 15, 1 was termi-

5 6 Heart Rhythm, Vol 7, No 1, January 2010 Table 2 Characteristics of study patients with or without termination of peri-mitral atrial flutter by ablation Termination (n 35) Nontermination (n 15) P value Age (years) Sex (male/female) 31/4 14/1.61 Type of AF (persistent/paroxysmal) 34/1 13/2.15 Structural heart disease Duration of persistent AF (months) Left atrial dimension (mm) Left ventricular ejection fraction (%) No. of antiarrhythmic drugs for AF Amiodarone No. of direct current cardioversions for AF Atrial tachycardia cycle length (ms) Prior mitral isthmus ablation 24 (69%) 2 (13%).0003 Prior mitral isthmus block (yes/no) 21/14 0/ AF atrial fibrillation. nated by performing an anterior linear ablation joining from mitral annulus to right superior PV because of the presence of scar lesion in the anterior wall, 9 by atrial burst pacing, and 5 by direct current cardioversion when burst pacing had failed. Of the 35 patients in whom PMFL was terminated by ablation, 9 (25.7%) were terminated during epicardial ablation within the CS. There were no differences with regard to age, sex, type of AF, structural heart disease, duration of persistent AF, left atrial dimension, left ventricular ejection fraction, number of antiarrhythmic drugs, amiodarone use, number of direct current cardioversions, or tachycardia cycle length between patients with and those without termination of PMFL by ablation (Table 2). However, among patients in whom PMFL was not terminated by ablation, none had previously undergone ablation of the MI, whereas 21 of 35 patients with termination of PMFL had prior MI ablation (0% vs 60.0%, P.0001). Bidirectional MI conduction block Following termination of PMFL, bidirectional conduction block of the MI was achieved in 46 (92%) patients. Supplemental radiofrequency application was required in 23 (66%) patients in whom PMFL had terminated with ablation. Total mean duration of radiofrequency delivery to establish bidirectional conduction block of the MI was minutes (median 13 minutes, interquartile range 8 18 minutes). Mean radiofrequency duration was longer in patients in whom bidirectional block could not be achieved than in those with bidirectional block ( minutes vs minutes, P.04). Mean conduction time from distal CS to left atrial appendage in all patients was ms (median 176 ms, interquartile range ms). Epicardial radiofrequency application was required to establish complete MI block in 76% (35/46) of patients. In 4 patients, bidirectional conduction block was not achieved despite endocardial and epicardial radiofrequency energy delivery. Mean conduction time from distal CS to left atrial appendage was shorter ( ms vs ms, P.02), and mean radiofrequency duration was longer ( minutes vs minutes, P.04) in patients in whom conduction block was not achieved than in those with MI block. At mean follow-up of 19 4 months, 96% of patients were free from recurrence of both PMFL and AF after a mean of procedures. Discussion Main findings The present study investigated the characteristics and ablation results of PMFL occurring in the context of AF. The main findings of this study are as follows. (1) Ablation of the MI promotes PMFL. (2) Bidirectional conduction block results in fewer recurrences of PMFL. (3) PMFL rarely terminates with ablation unless a previous mitral line has been performed. (4) In the majority of cases following termination of PMFL by ablation, additional lesions are required for bidirectional conduction block. PMFL and MI ablation Although lone PMFL is rarely seen, in the context of persistent AF PMFL is the most common macroreentrant tachycardia encountered during stepwise ablation and during medium-term follow-up. This is the first large study to specifically assess the characteristics of PMFL. Ablation of the MI line previously has been demonstrated to improve the outcomes in patients with paroxysmal AF, 14 is required for almost all patients with persistent AF undergoing stepwise ablation, 15 and is part of Cox s original maze procedure and all subsequent modifications. 16 Catheter ablation of the MI is commonly performed by creating a linear lesion from the lateral mitral annulus to the left inferior PV. Due to the difficulty in producing bidirectional block, the MI line is performed as the last step of the stepwise ablation approach in patients with persistent AF. 15 The anatomy of the MI is variable, with thickness along its course ranging between 1 and 8 mm. 9,17 In the present study, the incidence of PMFL during AF ablation was higher in patients who had undergone ablation of the MI before termination of AF than in those who had not required this step. Although bidirectional block resulted in fewer recurrences of PMFL than in those in whom block was not

6 Matsuo et al Peri-mitral flutter in atrial fibrillation 7 achieved, the prevalence of recurrent PMFL following AF ablation was significantly higher in patients with previous ablation of the MI than in those without. Lo et al 18 demonstrated that recurrent conduction through the cavotricuspid isthmus that was performed for typical atrial flutter was observed in 22% of patients following ablation of that line. They reported that conduction through the MI could recur during follow-up despite the establishment of MI block during the index procedure. 15 Chae et al 5 reported that nearly all recurrent ATs that occurred after AF ablation were related to gaps in prior ablation lines. Conduction recovery through the MI resulting gap might be associated with development of PMFL. Although the MI line appears necessary to achieve procedural termination and acceptable medium-term results for patients with persistent AF, 12,15 the results of the present study suggest that MI ablation is the facilitating factor for PMFL. These data suggest that if MI ablation can be avoided, it would be prudent to do so. Performance of MI ablation would be favorable in cases of PMFL development during AF ablation or as the final step in stepwise AF ablation after complete PV isolation and electrogram-based ablation. PV isolation should be evaluated, and all areas in both the left and right atria should be investigated for targets, prior to starting MI ablation. Epicardial ablation within the CS Epicardial ablation was required for bidirectional conduction block in 76% of cases, with termination of PMFL occurring 26% of the time during ablation within the CS. Previous studies demonstrated that the shape and depth of the atrial myocardium vary greatly around the MI, 9,19 and that the depth of the tissue may be the limiting factor in achieving bidirectional block by endocardial ablation alone. In addition, the circumflex coronary artery and the great cardiac vein both pass in close proximity to the MI and may act as a heat sink, preventing adequate tissue heating by radiofrequency delivery. D Avila et al 20 investigated the cooling effect of blood flow in the CS on MI ablation in an animal model. Using an air-filled balloon to occlude the CS, transmural lesions with endocardial ablation alone were achieved in all cases. Jaïs et al 14 reported cardiac tamponade in 4% of patients undergoing MI ablation for AF. In their study, cardiac tamponade occurred exclusively when the delivered power was 50 W endocardially, whereas in the present study the power was limited to 40 W endocardially. In the present study, no incidences of cardiac tamponade occurred and a rate of bidirectional conduction block similar to the earlier study was found, suggesting that the power limits represent a good compromise between safety and efficacy. Whether lower power limits would be as effective is unknown. Termination of PMFL and MI block Thirty-five (70%) of 50 PMFLs were terminated during MI ablation, yet bidirectional block of the MI line was achieved in only 34% (12) of the 35 patients at the time of termination, which is analogous to ablation of cavotricuspid-dependent flutter. 21 A previous study demonstrated that recurrence of typical atrial flutter was observed only in patients in whom bidirectional block was not achieved at the cavotricuspid isthmus following ablation. 21 Another study reported that one of the independent predictors of typical atrial flutter recurrence after cavotricuspid isthmus ablation was lack of bidirectional conduction block of the line. 22 The present study demonstrated that PMFL frequently recurred in patients with incomplete block of the MI. These data suggest that, following termination of PMFL, bidirectional block of the MI should be evaluated, with additional ablation if necessary. Study limitations The present study has a number of limitations. (1) The anatomy of the MI was not evaluated using any imaging modality. Intracardiac echocardiography has been shown to be useful in identifying the thickness of the MI and can show the development of edema during ablation, which may hinder ablation. Preprocedural evaluation of anatomy by echocardiography, computed tomography, or magnetic resonance imaging may help determine the optimal site to ablate or whether an anterior line is preferable. (2) A three-dimensional mapping system was not used, and how much of the MI was ablated during isolation of the left inferior PV and electrogram-based ablation is unknown. (3) Although ablation of the MI and conduction delay across the lesion is the commonly used measure in clinical practice, the circuit around the mitral annulus could include other areas of slow conduction, possibly caused by ablation, that would facilitate PMFL. (4) Sanders et al 26 reported that an anterior linear ablation line from the right superior PV to the mitral annulus was an effective alternative to the conventional MI line; however, this line was performed in only one patient in the present study, and the results cannot be extrapolated to the anterior line. (5) Patients without recurrence of AF or AT were not restudied, so the true incidence of conduction recovery across the mitral line was not assessed. (6) Whether an MI line should be performed in all patients with persistent AF remains unclear. In the stepwise approach, the MI line is performed as the final step, and although procedural termination results in a favorable outcome, the precise benefit of the MI line is not known. A randomized study is required to evaluate the role of MI ablation in patients with persistent AF. (7) Conduction across the MI was checked only at a cycle length of 600 ms. Therefore, it is possible that residual conduction remained across the mitral line at longer base cycle lengths. 27 Conclusion Although MI linear ablation was effective treatment in patients with PMFL, this procedure facilitated the development of PMFL. In the majority of patients, epicardial ablation was necessary to establish MI block. Termination of PMFL occurs commonly while conduction through the MI

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