The Role of Left Atrial Muscular Bundles in Catheter Ablation of Atrial Fibrillation

Transcription

1 Journal of the American College of Cardiology Vol. 50, No. 10, by the American College of Cardiology Foundation ISSN /07/$32.00 Published by Elsevier Inc. doi: /j.jacc Heart Rhythm Disorders The Role of Left Atrial Muscular Bundles in Catheter Ablation of Atrial Fibrillation Shih-Lin Chang, MD,* Ching-Tai Tai, MD,* Yenn-Jiang Lin, MD,* Wanwarang Wongcharoen, MD,* Li-Wei Lo, MD,* Kun-Tai Lee, MD,* Sheng-Hsiung Chang, MD,* Ta-Chuan Tuan, MD,* Yi-Jen Chen, MD, Ming-Hsiung Hsieh, MD, Hsuan-Ming Tsao, MD, Mei-Han Wu, MD, Ming-Huei Sheu, MD, Cheng-Yen Chang, MD, Shih-Ann Chen, MD* Taipei, Taiwan Objectives Background Methods We sought to investigate the imaging of the left atrial (LA) muscular bundle and the relationship between the bundle and inducibility of tachyarrhythmia after pulmonary vein isolation (PVI). Noninducibility is used as a clinical end point of atrial substrate ablation after PVI. However, little is known about the role of the LA muscular bundles in tachyarrhythmia after PVI. Forty-three consecutive patients with paroxysmal atrial fibrillation who underwent catheter ablation were included. Bi-atrial isochronal mapping was performed with the NavX system (St. Jude Medical Inc., St. Paul, Minnesota) during sinus rhythm. After 4 PVI, inducible organized LA flutter with or without transforming to atrial fibrillation (AF) (LA flutter/af) was ablated with additional lines at the roof and/or mitral isthmus. Results The existence of bilateral muscular bundles was an independent predictor of LA flutter/af after PVI (p 0.02). Patients with LA flutter/af after PVI had a greater index of the double potentials ( % vs %, p 0.006) and interpotential interval (33 5 ms vs ms, p 0.02) than without LA flutter/af. The muscular bundles were identified in 28% patients using 16-slice multidetector computed tomography, which were identical to the isochrone map. Patients with noninducible LA flutter/af after PVI plus the additional linear ablation had a lower recurrence rate as compared with the patients without it (19% vs. 75%, p 0.02). Conclusions Left atrial muscular bundles may provide a conduction block line and barrier, which is important for the formation of LA flutter/af after PVI. The noninducibility of LA flutter/af achieved after additional linear ablation may contribute to a better outcome in RF ablation of paroxysmal atrial fibrillation. (J Am Coll Cardiol 2007;50: ) 2007 by the American College of Cardiology Foundation From the *Division of Cardiology and Cardiovascular Research Center, Radiology, National Yang-Ming University, School of Medicine, Taipei, Taiwan; Taipei Veterans General Hospital, Division of Cardiovascular Medicine, Division of Cardiovascular Medicine, Suao Veterans Hospital, Taipei Medical University, Taipei, Taiwan; Wan-Fang Hospital, Taipei, Taiwan; and the Division of Cardiovascular Medicine, I-Lan Hospital, Taipei, Taiwan. Manuscript received February 16, 2007; revised manuscript May 1, 2007, accepted May 21, Papez (1) reported left atrial (LA) muscular bundles, which are large flat external bundles covering the upper and posterior surfaces of the LA between the pulmonary veins (PVs) and encircle the orifices of the PVs. Papez bundle spread out in 6 bands, with conduction occurring along the bundles, and double potentials (DPs) can be recorded along the 2 sides of the bundles. Also, previous studies reported that the muscular bundles play an important role in the pattern of the LA activation (2 4). On the other hand, noninducibility of LA tachyarrhythmia is a clinically useful end point of LA circumferential ablation, and noninducibility of LA tachyarrhythmia achieved by additional LA linear ablation may be associated with a better clinical outcome (5 7). However, the mechanism of inducible LA tachyarrhythmia after PV isolation (PVI) is still unclear. The aim of this study was to investigate the imaging of the LA muscular bundle and the relationship between the LA muscular bundle and inducibility of tachyarrhythmia after isolation of all PVs. Methods Forty-three consecutive patients (age years, 34 men) with paroxysmal atrial fibrillation (AF) and normal structure heart that underwent ablation were included. These patients did not have any prior ablation procedure. The bi-atrial bipolar voltage and total activation time were investigated using a NavX mapping system (St. Jude Medical, Inc., Minnetonka, Minnesota.) during sinus rhythm. The study population underwent a 16-slice multidetector

2 JACC Vol. 50, No. 10, 2007 September 4, 2007: Chang et al. Atrial Fibrillation and Muscular Bundles 965 computed tomography (MDCT) scan 1 to 14 days before the ablation procedure, and informed consent was obtained. Electrophysiological study and electroanatomic mapping. Each patient underwent an electrophysiological study and catheter ablation in the fasting, nonsedative state after written informed consent was obtained. A quadripolar catheter placed in the ascending aorta was selected as the position reference. The electrodes of coronary sinus (CS) catheter were used to provide the timing reference signal during the mapping procedure. The algorithm for the analysis of voltage is shown in Figure 1. After completing an intact right atrial and LA geometry reconstruction, a sequential contact voltage map was constructed in all 43 patients. Bipolar electrograms were filtered between 32 and 300 Hz and recorded digitally. The absolute peak was selected as the detection setting to determine the point of activation in the waveform. A 4-mm tipped ablation catheter (EP Technologies, Boston Scientific, Inc., Boston, Massachusetts) was selected as the roving catheter. The roving signal was used to collect the local activation time (relative to the reference signal) and voltages whereas the roving catheter came in contact with the atrial wall as it was swiped throughout the atrium during sinus rhythm. The signal from the roving catheter was used to build a sequential map. The total activation time was defined as the time interval from the earliest to the latest activation point in the atrium. After completion of the sequential map, the bipolar mapping points were collected and analyzed by the offline software (8,9). The software system determines the voltage contribution to the surface area of each point using the distance to the nearest neighboring point, presenting the weighted voltage ([nearest distance peak to peak Figure 1 3D 3-dimensional. Algorithm for the Analysis of Voltage bipolar voltage]/mean overall nearest distance). An index of heterogeneity of the bipolar voltage amplitude was obtained by calculating the coefficient variation (defined as standard deviation/mean value) of the voltage of all points. The average bipolar mapping sites in the right and left atria were and points for each patient, respectively. A conduction block line was identified as a conduction delay and the occurrence of DPs, associated with the Abbreviations and Acronyms CS coronary sinus CT crista terminalis DP double potential LA left atrial MDCT multidetector computed tomography PV pulmonary vein PVI pulmonary vein isolation RF radiofrequency wavefront turning. The DPs were defined as potentials separated by an isoelectric interval ( 25 ms), with the local activation times of the DP annotated on the largest potential. The peak to peak bipolar voltage and interval between the DPs on the conduction block line were recorded. The DP interval was defined as the interval between the onset of the first and that of the second deflection (10). The index of the DPs was defined as the number of (DPs/total mapping points) 100%. Sinus rhythm DPs were not present at sites other than those included in the anterior and posterior block lines. Because the PV potential on the PV ostium or inside the PV is easily confused with DPs electrogram, the area of PV-atrial junction was excluded for analysis of DP. Catheter ablation. We performed the modified selective PV angiography by positioning the pig-tail catheter in the right and left pulmonary artery level, and took the venous phase of pulmonary angiography with biplane fluoroscopic views (right anterior oblique 30 and left anterior oblique 60 ) in each patient. Provocation of AF was performed in each patient before the catheter ablation procedure. Continuous circumferential lesions were created encircling the right and left PV ostia guided by the NavX system using a 4-mm-tip ablation catheter (EP Technologies, Boston Scientific, Inc.). Radiofrequency (RF) energy was applied continuously while repositioning the catheter tip every 40 s with a target temperature of 50 C to 55 C and maximum power of 50 W in the temperature control mode. Temperature was reduced to 45 C to 50 C when (RF) energy to the posterior wall near the esophagus was necessary. The intention was to place the RF lesions at least 1 to 2 cm away from the angiographically defined ostia. After completion of the circumferential lesion set, ipsilateral superior and inferior PVs were mapped carefully by a circular catheter recording (Spiral, AF Division, St. Jude Medical, Inc.) during sinus rhythm or CS pacing. Supplementary ablations were applied along the circumferential lines close to the earliest ipsilateral PV spikes. Furthermore, ablation of the residual PV potentials was performed from the atrial side of the PV antrum using the electrogram-guided approach (entrance block). After successful isolation of all four PVs, which was confirmed by PV circumferential mapping, high

3 966 Chang et al. JACC Vol. 50, No. 10, 2007 Atrial Fibrillation and Muscular Bundles September 4, 2007: current (3 to 5 times the pacing threshold) and wide (8 ms) pulse duration stimulation from the proximal and distal CS was performed (in 10-ms decrements from 250 to 150 ms, with a duration of each pacing cycle length of 5 to 10 s), and repeated 3 to 5 times. The inducible LA tachyarrhythmia after PVI, termed LA flutter/af, was defined as organized LA flutter with or without transforming to AF. If an induced AF/LA flutter was sustained for 1 min, an additional linear ablation was performed randomly at either the anterior roof or the mitral isthmus, except the re-entry circuit of LA flutter was identified by isochrone mapping, entrainment maneuvers and postpacing interval analysis. Pacing sites with a postpacing interval not exceeding the cycle length by 20 ms were considered to be part of the circuit. Linear ablation was guided by the NavX system with the creation of split potentials or an electrogram voltage reduction of 50% after each application of radiofrequency energy. The end point of the ablation was the disconnection between the PV and LA, and noninducibility of LA flutter/af ( 1 min). If a sustained LA flutter/af was still induced, cardioversion or infusion of amiodarone with 5 mg/kg was performed to restore sinus rhythm. Non-PV AF was also ablated in the same session (11). We attempt to record the spontaneous onset of extra-pv ectopic activity initiating AF before or after isoproterenol loading. Ablation target sites of extra-pv ectopy show the earliest bipolar electrogram deflection or a QS pattern in a unipolar recording from the ectopic foci. We repeat our pacing maneuvers to assess the effects of ablation and search for additional triggers. Computed tomography. Before the ablation procedure, the patients were evaluated with an electrocardiographically gated, 16-slice MDCT scan (Seimens, Sensation 16, Siemens Medical Solutions, Forchheim, Germany). This technique has been established in our laboratory (12). In brief, a nonionic contrast medium, iohexol (350 mg of iodine per milliliter; Omnipaque, Amersham Health, Amersham, United Kingdom), given in a test dose to determine the moment of the peak left atrial filling, and subsequently, 80 ml of a contrast medium chased with 60 ml of saline was administered through the antecubital vein with the use of a power injector at a rate of 3.5 ml/s, after which the scanning was initiated. The image acquisition was performed from the base of the lungs to the apices during a single breath hold. The table speed and pitch were heart rate dependent because the image acquisition was electrocardiographically gated. The acquisition time was 20 to 25 s and the in-plane resolution was 0.6 mm. The endoscopic view. To study the endoscopic views of the LA structures, the image was sent to the workstation (Advantage windows, version 4.0, General Electric Medical Systems, Milwaukee, Wisconsin) and an image analysis was performed with commercially available CT navigator software (Voxtool f, General Electric Medical Systems). The software allowed for voxel elimination on the basis of a user-defined threshold density value, which in the case of the LA usually was between 160 and 300 Housfield units depending on the enhanced density of the contrast. We could choose the intensity level according to the vascular boundaries and adjust the threshold to smooth the endocardial surface. The images were obtained if the LA structures were consistent and showed little change during the fine adjustment of threshold. The ridge was defined as a narrow, raised band above the surface with a width of 5 mm or less. It was possible to examine the area of interest as if the operator had a scope allowing that operator to look inside the LA; the operator could also move freely inside the cardiac cavity and into the PVs. Statistic analysis. The parametric data are reported as the mean SD. Chi-square with the Fisher exact test was used for categorical data. The Mann-Whitney rank-sum test was used for continuous data. Multivariate logistic regression analysis was performed to determine the clinical predictors of LA flutter/af after PVI. Variables selected to be tested in multivariate analysis were those with p 0.2 in the univariate models. A value of p 0.05 was considered to be statistically significant. Results Left atrial activation pattern. Thirty-six of the 43 (84%) patients showed a typical LA activation sequence, which was characterized by the earliest breakthrough site occurring at the high posteroseptum (around right superior PV to Bachmann s bundle) with the wavefront extending to the roof, descending to the posterior wall near the left PV, and finally ending near the mitral isthmus (Fig. 2). Seven of the 43 (16%) patients showed an atypical LA activation pattern. Two of 7 patients with an atypical activation had the earliest activation site at the posterior wall with the wavefront extending to the roof, descending to the anterior and septal wall, and the latest activation site occurred near the mitral isthmus. Four patients with an atypical activation pattern had the earliest activation site at the high posteroseptum with the wavefront extending to the roof, descending to the posterior wall near the left PV, crossing over the lateral mitral isthmus, and ending at the LA appendage (Fig. 3). The remaining patient had the earliest activation site at the high posteroseptum with the wavefront extending to the roof, descending to the posterior wall, crossing over the mitral isthmus, and ending at the low anterior wall near the mitral annulus. Conduction block line during sinus rhythm. Conduction block lines during sinus rhythm were found in 39 (91%) patients, 11 of the 39 (28%) patients had a block line on either the anteroseptal or posterior wall, and the other 28 (72%) patients had block lines on the bilateral (anteroseptal and posterior) walls (Figs. 2 and 4). The electrophysiological findings in the patients with or without a block line are shown in Table 1. In the patients with the bilateral block lines, there was a longer LA total activation time (86 17 ms, 70 9 ms, ms, p 0.009) and greater

4 JACC Vol. 50, No. 10, 2007 September 4, 2007: Chang et al. Atrial Fibrillation and Muscular Bundles 967 Figure 2 Isochrone Map and Local Electrograms During Sinus Rhythm and LA Flutter (A and B) The typical activation pattern in the left atrium (LA). The wavefronts propagating around the gray zone, where isochrone lines crowded together and double potentials were recorded during sinus rhythm in the anteroposterior and left posteromedial view, respectively. (C and D) Activation of a figure-of-eight LA flutter with a cycle length of 199 ms. Arrows indicate circuit loop(s). The brown lesion indicates the pulse of circumferential ablation. One loop rotates around the mitral annulus and the other rotates around the left PVs with a common channel conducted through the mitral isthmus. The re-entrant circuits of atrial flutter were bordered anteriorly and posteriorly by lines of conduction block (gray zone), which were in similar locations during sinus rhythm (A and B). (D) Illustrates the local bipolar electrograms along the circuit of double-loop re-entry. Recording positions are shown in the isochrone map. During LA flutter, clockwise atrial activation around the mitral annulus was manifested by atrial electrograms in the middle posterior wall (site 1), lower posterior wall (site 8), medial mitral isthmus (site 9), and lower anterior wall (site 10), followed by activation in the lateral mitral isthmus (sites 5, 11, and 7). A slow conduction zone with fractionated electrograms was recorded at site 5. Another counterclockwise atrial activation around the left pulmonary vein was manifested by atrial electrograms in the middle posterior wall (site 1), upper posterior wall (site 2), roof (site 3), and upper anterior wall (site 4) followed by activation in the lateral mitral isthmus (sites 5, 6, and 7). Labeled anatomical locations include the mitral valve (MV), right superior pulmonary vein (RSPV), right inferior pulmonary vein (RIPV), left superior pulmonary vein (LSPV), left inferior pulmonary vein (LIPV), and left atrial appendage (LAA). coefficient variation of the voltage ( , , , p 0.01) than in the patients with a block line in only one wall (anteroseptal or posterior wall) or without a block line. There was no difference in the LA activation time between patients with one block line and those with no block line (70 9 ms vs ms, p 0.05). In the patients with the bilateral block lines, the occurrence of LA flutter/af after PVI was higher than that Figure 3 Atypical Activation Pattern in Left Atrium During Sinus Rhythm in Anteroposterior and Left Posteromedial Views, Respectively (A) Anteroposterior view; (B) left posteromedial view. The earliest activation site occurred at the high posteroseptum with the wavefront extending to the roof, descending to the posterior wall near the left pulmonary vein, crossing over the lateral mitral isthmus, and ending at the left atrial appendage. Arrows indicate the activation wavefront.

5 968 Chang et al. JACC Vol. 50, No. 10, 2007 Atrial Fibrillation and Muscular Bundles September 4, 2007: Figure 4 Endoscopic View of MDCT and Isochrone Map During Sinus Rhythm (A and B) Location of a line of conduction block with double potentials (gray zone) marked on a 3-dimensional isochrone map during sinus rhythm in anteroposterior and posteroanterior view, respectively. (C) A 3-dimensional volume rendering technique of left atrial (LA) image, based on multidetector computed tomography (MDCT) in anteroposterior projection, that corresponds to (A). The orientation of the muscular bundles (yellow arrows) corresponds to the line of conduction block (gray zone) in (A). (D and E) Muscular bundles by the endoscopic view of MDCT. (D) The muscular bundles (red arrows) originate in the septum, extend near the fossa ovalis (white arrow), insert upward into the anterior roof, and spread down the posterior wall. In (E), the muscular bundle (red arrows) courses along the septal border of the right superior pulmonary vein (RSPV) ostium to the anterior roof. This location corresponds to the line of conduction block identified during sinus rhythm (A and B). LAA left atrial appendage; other abbreviations as in Figure 2. in the patients with one block line or without a block line (71%, 27%, and 25%, p 0.04) (Table 1). After PVI, 24 patients (56%) had inducible LA flutter/af. The clinical and electrophysiological characteristics in patients with and without LA flutter after PVI are shown in Table 2. There was evidence of a significant conduction delay along the block line in the patients with LA flutter/af after PVI, with a greater index of the DPs ( % vs %, p 0.006) and greater interpotential interval (33 5msvs ms, p 0.02) during sinus rhythm than in the patients without LA flutter/af after PVI. In the patients The and Electrophysiological Without Conduction Block Findings Line During Patients Sinus WithRhythm Table 1 The Electrophysiological Findings in Patients With and Without Conduction Block Line During Sinus Rhythm No BL (n 4) with LA flutter/af after PVI, the mean voltage of the block line was lower ( mv vs mv, p 0.001) than that in the patients without LA flutter/af after PVI (Table 2). Moreover, the patients with LA enlargement (LA diameter 4 cm) had a lower mean voltage ( mv vs mv, p 0.01) and longer interval (36 4 ms vs ms, p 0.001) for the DP line during sinus rhythm than did the patients without LA enlargement. In patients with LA flutter/af after PVI, 16 patients (67%) had an organized LA flutter without transforming to AF after PVI; the other 8 patients (33%) had an BL on 1 Side of the Wall (n 11) BL on 2 Sides of the Wall (n 28) p Value LA voltage (mv) LA AT (ms) * Coefficient variant of the voltage * * Coefficient variant of the AT LA flutter/af after PVI 25% 27%* 71% 0.02 Typical LA activation pattern 75% 100% 79% 0.26 *p 0.05 versus the BL group on 2 sides of the wall. The location of conduction block line was divided into 2 sides: anteroseptum and posterior wall. AF atrial fibrillation; AT activation time; BL block line; LA left atrium; PVI pulmonary vein isolation.

6 JACC Vol. 50, No. 10, 2007 September 4, 2007: Clinical Patients andwith Electrophysiological and Without LA Flutter/AF Characteristics After PVI Table 2 Clinical and Electrophysiological Characteristics in Patients With and Without LA Flutter/AF After PVI Chang et al. Atrial Fibrillation and Muscular Bundles 969 LA Flutter/AF (n 24) No LA Flutter/AF (n 19) p Value Age, yrs Gender, M/F 20/4 14/ Duration of AF, yrs HCVD 54% (13) 26% (5) 0.13 LA diameter, mm LVEF, % BMI, kg/m LA voltage, mv Coefficient variant of the LA voltage LA TAT, ms Coefficient variant of the LA TAT Typical LA activation pattern 79% (19) 90% (17) 0.44 Bilateral block line, n 83% (20) 42% (8) 0.01 Voltage of the DP, mv Interval of the DP, ms Index of the DP, % AF atrial fibrillation; BMI body mass index; DP double potential; EF ejection fraction; HCVD hypertensive cardiovascular disease; LA left atrium; LVEF left ventricular ejection fraction; PVI pulmonary vein isolation; TAT total activation time. organized LA flutter with transforming to AF after PVI. The clinical and electrophysiological characteristics in patients with organized LA flutter with or without transforming to AF after PVI are shown in Table 3. The cycle length of the organized flutter with transition to AF was shorter than those without transition to AF ( ms vs ms, p 0.007). Otherwise, there was no significant difference between the 2 groups. The effect of PVI on the LA substrate. We also investigated LA activation during sinus rhythm before and after PVI in another 25 patients (19 men, age years) with paroxysmal AF. Twenty-three of 25 patients (92%) Clinical of Organized and Electrophysiological Flutter With and Without Characteristics Transforming Patients to AF After PVI Table 3 Clinical and Electrophysiological Characteristics in Patients of Organized Flutter With and Without Transforming to AF After PVI Without Transforming to AF (n 16) had the same LA activation pattern before and after PVI. The remaining 2 patients had the earliest activation site at roof after PVI, which was different from that before PVI (earliest breakthrough at high posteroseptum). There was no difference in the LA total activation time (86 16 ms vs ms, p 0.19), prevalence of DPs ( % vs %, p 0.81), or DP intervals (30 3 ms vs ms, p 0.86) between before and after PVI. LA flutter/af after PVI. An isochrone map of LA flutter was created in 8 patients after PVI (Table 4). Of them, 6 flutter circuits were bounded by the block line located on the bilateral wall (Fig. 2); one was bounded by a block line With Transforming to AF (n 8) p Value Age, yrs Gender, M/F 14/2 6/ Duration of AF, yrs HCVD, n 56% (9) 50% (4) 1.0 LA diameter, mm LVEF, % BMI, kg/m CL of LA flutter/af* LA voltage, mv Coefficient variant of the LA voltage LA TAT, ms Coefficient variant of the LA TAT Typical LA activation pattern, n 88% (14) 63% (5) 0.29 Bilateral block line, n 88% (14) 75% (6) 0.58 Voltage of the DP, mv Interval of the DP, ms Index of the DP, % *CL was measured during the period of stable organized tachycardia. CL cycle length; other abbreviations as in Table 2.

7 970 Chang et al. JACC Vol. 50, No. 10, 2007 Atrial Fibrillation and Muscular Bundles September 4, 2007: Characteristics of LA Flutter After PVI Table 4 Characteristics of LA Flutter After PVI During AFL During SR AS/P Bundle as the Barrier of AFL Circuit Voltage of Re-Entry Barrier (mv) Voltage of Conduction Block Area (mv) Patient # Age (yrs) LAD (mm) Flutter Circuit Flutter CL (ms) Conduction Block Area Peri M LPV 199 AS/P 0.08 AS/P Septal 219 AS 0.09 AS/P Peri RPV 186 AS/P 0.10 AS/P Peri M LPV 205 AS/P 0.28 AS/P Peri M 237 P 0.09 AS/P Peri LPV, septal 208 AS/P 0.21 AS/P Peri M 224 AS/P 0.15 AS/P Peri RPV 188 AS/P 0.27 AS/P 0.32 Mean AFL atrial flutter; AS anteroseptal; CL cycle length; LA left atrial; LAD left atrial diameter; LPV left pulmonary vein; M mitral annulus; P posterior; PVI pulmonary vein isolation; RPV right pulmonary vein; S septal; SR sinus rhythm. located on the septal wall (Fig. 5), the remaining one was bounded by a block line located on the posterior wall. The location of lines of conduction block was similar during sinus rhythm and LA flutter. The mean voltage of block line in flutter circuits was mv, which was lower than the mean voltage of block line during sinus rhythm ( mv, p 0.01). Moreover, all of these patients had the bilateral conduction block lines during sinus rhythm. Patient 2 had a re-entry circuits around a septal muscular bundle (Fig. 5). Left atrial flutter was terminated Figure 5 Endoscopic View of MDCT and Isochrone Map During Left Atrial Flutter (A) Muscular bundles (yellow arrows) by multidetector computed tomography (MDCT) in the endoscopic view. (B) Endoscopic view of a line of conduction block (gray zone), guided by NavX contact mapping, in the same projection as (A). The white arrow indicates the conduction circuit. Double potentials were recorded within the gray zone. The flutter circuit (cycle length, 219 ms) revolves around the muscular bundle, with an anteroseptal central obstacle. The orientation of this muscular bundle, as shown by MDCT endoscopic view, corresponds to the gray zone in the isochrone map. (C) The termination of LA flutter after delivering a line of ablation from the right superior pulmonary vein (RSPV) to the superior aspect of the septal muscular bundle. A circular catheter was placed in the posteroseptal wall. ABL d distal ablation catheter Cir circular catheter; CS-d distal coronary sinus; CS-p proximal coronary; LAA left atrial appendage; other abbreviations as in Figure 2.

8 JACC Vol. 50, No. 10, 2007 September 4, 2007: Chang et al. Atrial Fibrillation and Muscular Bundles 971 after creating an ablation line from the carina of right PVs to the upper part of septal muscular bundle. Image findings. A prominent muscular bundle was identified by the endoscopic view of MDCT in 12 of the 43 (28%) patients in this study. The orientation of the muscular bundles observed in the MDCT originated from the septum, passed near the fossa ovalis, extended upward to the anterior roof, and spread down the posterior wall (Figs. 4 and 5). This location was compatible with the anteroseptal muscular bundle described by previous pathological studies (1,2,4). The ridges identified on the MDCT image were mm in thickness, mm in length, and mm in width. There is no correlation between the morphological measurements of the muscular bundles from the CT (thickness, length, and width) and electrophysiological findings (DP interval and voltage of DP). To compare the orientation of the muscular bundle, which was identified by the endoscopic view of MDCT in 12 patients with their isochrone map, we found the orientation of the muscular bundle and conduction block line were all identical (Figs. 4 and 5). Results of catheter ablation. After PVI, additional LA ablation lines were performed in 24 of the 43 (56%) patients. Of those, 12 patients received 1 additional ablation line, and the other 12 patients received 2 additional ablation lines. After the additional LA ablation, 16 of the 24 (67%) patients did not have any inducible LA flutter/af. In the other 8 (33%) patients, the LA flutter/af was still inducible. At a mean follow-up of 16 4 months, 16 of the 19 (84%) patients without any inducible LA flutter/af after the PVI were free of AF. Thirteen of the 16 (81%) patients without any inducible LA flutter/af after the PVI plus the additional ablation line(s) were free of AF, and 2 of the 8 (25%) patients with inducible LA flutter/af after the PVI plus the additional ablation line(s) were free of AF (p 0.02). Twelve of the 43 (28%) patients had a recurrence of AF, and none of the patient had a recurrence of atrial flutter during follow-up. Predictors of LA flutter/af. The clinical and electrophysiological characteristics in the patients with or without LA flutter/af after PVI were shown in Table 2. In the patients with LA flutter/af after PVI, there was a longer LA total activation time (88 16 ms vs ms, p 0.003), larger LA diameter (38 6 mm vs mm, p 0.04), and greater incidence of bilateral block line (83% vs. 42%, p 0.01) than in the patients without LA flutter/af after PVI. Multivariate analysis revealed that only the existence of bilateral block line in electroanatomical mapping was an independent predictor for the occurrence of LA flutter/af after 4 PVI (p 0.02). Discussion Main findings. The bilateral muscular bundles play an important role in the formation of LA flutter/af after PVI. The electroanatomic and image findings suggested that the muscular bundles are the barriers during LA flutter after PVI. Patients without any inducible LA flutter/af after the PVI or after PVI plus additional ablation lines had an excellent clinical outcome. Left atrial activation during sinus rhythm. Although Lemery et al. (13) reported that LA activation occurred over Bachmann s bundle in all patients, they did not describe the LA activation and the earliest endocardial LA breakthrough in detail. Markides et al. (2) had reported that the earliest endocardial LA breakthrough during sinus rhythm occurred on the posteroseptal wall adjacent to the ostia of the right PVs in 10 patients (53%); Bachmann s bundle in 7 patients (37%); and near the oval fossa in 2 patients (10%). This result is similar to our finding, which indicates that the earliest endocardial LA breakthrough during sinus rhythm varies in study population. Effect of the substrate in the inducible LA flutter/ AF. There is a larger LA diameter in the patients with LA flutter/af after PVI than those without it in our present study. Dilated atria contributes to the change of electroanatomical substrate which is characterized by increased nonuniform anisotropy and macroscopic slowing of conduction, promoting re-entrant circuits in the atria (14,15), which suggests that a remodeling substrate may play an important role in LA flutter/af after PVI. On the other hand, the total activation time of LA was longer in patients with LA flutter/af after PVI compared with those without it, suggesting the potential presence of a conduction delay that may increase the incidence of macro re-entry circuits. Several investigators have reported the prolonged atrial conduction time is the predisposing factor for the development of AF and AFL which is related to fibro-degeneration (16 18). Prolonged intra-atrial conduction may be responsible in part for the increased propensity to atrial arrhythmias (15,19). In addition, there was no difference in the LA total activation time and the prevalence of DPs and DP intervals between before and after PVI, suggests that the PVI may have a less effect in the acute substrate remodeling. Pathologic, electroanatomic, and image findings of the LA muscular bundle. Most of the LA muscular bundles are broad bands with a longitudinal orientation and abrupt change in myocardial fiber orientation that forms the barrier of the muscular bundle (2). The bilaminate structure, a thin layer of muscle sandwiched between the endocardial surfaces of the primary atrial septum, could result in the barrier and maintenance of the LA septal flutter (4). Lines of conduction block, which are observed in the posterior wall, are present during sinus rhythm and CS pacing (3). Left atrial muscular bundle could be identified as a conduction block line in every patient in sinus rhythm, which may be related to the LA re-entry circuit (2,4). The conduction block line was complete in 79% of the patients. In the remaining 21% of the patients, the septal part of the line was incomplete, which shows a considerable anatomic variation in the extent and completeness (2). In the present study, the

9 972 Chang et al. JACC Vol. 50, No. 10, 2007 Atrial Fibrillation and Muscular Bundles September 4, 2007: orientation of the ridge is identical to the LA muscular bundle described by previous pathological studies (1,2,4). In the isochrone map, the location of the conduction block line was found in 91% patients, which were similarly located in each of the patients and compatible with the anatomic orientation of the LA muscular bundle. The location of conduction block lines during LA flutter was similar to those during sinus rhythm, which provides an evidence of functional block across the muscular bundles. Furthermore, the orientation of the muscular bundle in MDCT was identical to the conduction block line in the isochrone map. Both the pathological and image findings suggested that the electroanatomic mapping could identify the muscular bundle. In addition, studies in both atrial and ventricular tissues demonstrated that normal anatomic heterogeneities play an important role in the generation of wave splitting and maintenance of re-entry (20 22). Although conduction block can be found in most of the patients, there were differences in the electrophysiological characteristics between the patients with LA flutter/af and those without it. Only the existence of bilateral block line in electroanatomical mapping was an independent predictor for the occurrence of LA flutter/af after PVI. It suggests that the muscular bundle plays an important role in the formation of LA flutter/af after PVI. On the other hand, some episodes of atrial flutter may degenerate into AF (23,24). A single, stable re-entry circuit with short cycle length could result in fibrillatory conduction (25). Because a re-entry circuit with short cycle length will only activate small portions of the atria in a 1:1 manner, the rest of the atria will be activated irregularly and result in AF (26). Moreover, uneven thickness of the atrial tissue created by pectinate muscle bundles facilitates the development of intra-atrial re-entry, and anchoring of the re-entry to muscle bundles results in a regular tachycardia, whereas detachment of the re-entrant wave front from muscle bundles results in fibrillation-like activity (22,27). In our present study, the cycle length of the organized flutter with transition to AF was shorter than those without it, which may represent the short re-entrant circuit leading to fibrillatory conduction. Role of the DPs in the LA flutter before PVI. Histological finding of the prominent LA muscular bundle confirmed the changes in the fiber orientation and crossover arrangements deeper in the wall (2). The heterogeneous arrangements of the muscular fibers could be represented as a low voltage and conduction block line which provides an electroanatomic barrier for a re-entry circuit. The present study demonstrated a significant conduction delay along the block line with a longer interpotential interval during sinus rhythm in the patients with LA flutter/af after PVI compared with those without it. The area of DP could play a role for the occurrence of LA flutter/af, similar to that of the crista terminalis (CT) during typical atrial flutter (4). Our previous study demonstrated that the maximal DP interval in the CT tended to be longer in patients with clinical atrial flutter than those without atrial flutter (10). Poor transverse conduction property in the CT may be the requisite substrate for the clinical occurrence of atrial flutter (10,28). This result is similar to our present finding that the DP interval in the LA muscular bundle is longer in patients with AFL/AF after PVI than those without it (33 5ms vs ms, p 0.02, 12.1% difference). Furthermore, greater number and longer duration of DPs also may be related to the genesis of atrial arrhythmias (15,19). In the present study, we localized the lines of conduction block with DPs in the anterior septum and posterior wall of the LA, which were compatible with the orientation of the muscular bundles. The existence of bilateral block line was an independent predictor for the occurrence of LA flutter/af after PVI. Therefore, the greater interval of DP may be important in the development of recurrent AFL/ AF. In addition, our present study demonstrated that the LA enlargement contributing to the changes in the electrophysiological properties, including decrease of the voltage and prolongation of the conduction time in the conduction block line. The consistency of electroanatomic remodeling suggests that the muscular bundles have a potential to cause the development of a re-entry circuit in patients with AF (14). Implications for RF ablation of LA flutter/af after PVI. Noninducibility of AF after LA circumferential ablation plus additional ablation lines is the clinically useful end point (5). In our study, the poor outcome in the patients with inducible LA flutter/af after PVI plus additional ablation lines also suggests that the noninducibility is a valuable end point for PVI plus additional ablation lines. Scar zones and DP lines have been documented as anatomic barriers for LA macro re-entrant tachycardia (29). The protected isthmus between 2 anatomical barriers is amenable to RF ablation (30). The present study demonstrates that the muscular bundles with prolonged conduction play an important role in the barrier and maintenance of LA flutter after PVI. Identifying the conduction block line and further creating additional line(s) crossing the isthmus of the re-entry barrier may contribute to a better clinical outcome. Study limitations. First, we did not analyze the electrophysiological characteristics of muscular bundle in normal control patients. Further study with detailed mapping and MDCT image in patients undergoing bypass tract ablation would provide more information to understand the pathophysiology of the muscular bundles. Second, we did not routinely check the complete block by differential pacing or criteria for conduction delay in each patient. However, many laboratories also used the voltage reduction or split potentials along the line as the end point of linear ablation with no attempt to assess the completeness of the line (31 33) because achievement of complete block in the mitral isthmus is sometimes difficult and laborious as a result of the thickness of local atrial tissue and/or to the blood flow of the coronary sinus (34). Finally, a randomized trial with a standardized protocol of linear lesion will draw

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