A Comparative Study With Standard Strategy Targeting the Infarcted Border Zone

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1 Circ J 2017; 81: doi: /circj.CJ ORIGINAL ARTICLE Arrhythmia/Electrophysiology Efficacy of Intensive Radiofrequency Energy Delivery to the Localized Dense Scar Area in Post-Infarction Ventricular Tachycardia Ablation A Comparative Study With Standard Strategy Targeting the Infarcted Border Zone Kenji Kuroki, MD; Akihiko Nogami, MD; Kentaro Yoshida, MD; Masahiko Goya, MD; Masato Fukunaga, MD; Kazuaki Kaitani, MD; Naoaki Onishi, MD; Takanao Mine, MD; Takashi Koyama, MD; Masayuki Igawa, MD; Takeshi Machino, MD; Hiro Yamasaki, MD; Dongzhu Xu, MD; Miyako Igarashi, MD; Nobuyuki Murakoshi, MD; Yukio Sekiguchi, MD; Kazutaka Aonuma, MD Background: Several reports have demonstrated the importance of severely low voltage areas as arrhythmogenic substrates of ventricular tachycardia (VT). However, a comparative study of dense scar-targeted and infarcted border zone-targeted strategies has not been reported. Methods and Results: We divided 109 consecutive patients with VT post-infarction from 6 centers into 2 groups according to the ablation strategy used: dense scar-targeted ablation (DS ablation, 48%) or border zone-targeted ablation (BZ ablation, 52%). During DS ablation, we attempted to identify VT isthmuses in the dense scar areas ( 0.6 mv) using detailed pace mapping, and linear ablation lesions were applied mainly to those areas. During BZ ablation, linear ablation of standard low voltage areas ( mv) was performed along with good pace map sites of the clinical VT. Acute success was defined as complete success (no VTs inducible) or partial success (clinical VT was noninducible). The acute complete success rate was significantly higher for DS ablation than for BZ ablation (62% vs. 42%, P=0.043). During a median follow-up of 37 months, the VT-free survival rate was significantly higher for DS ablation than for BZ ablation (80% vs. 58% at 48 months; log-rank P=0.038). Conclusions: DS ablation may be a more effective therapy for post-infarction VT than BZ ablation in terms of the acute complete success rate and long-term follow-up. Key Words: Catheter ablation; Myocardial infarction; Substrate mapping; Ventricular tachycardia Although several substrate-guided ablation methods for ventricular tachycardia (VT) have been advocated, the long-term outcomes of these methods have been inadequate as a curable therapy. 1 5 Therefore, some extensive ablation strategies targeting late potentials or local abnormal ventricular activities using an epicardial approach have been developed, and relatively good outcomes have been reported. 6,7 However, these strategies often result in extensive ablation from both the endocardial and epicardial sides. Now, electrophysiologists are investigating a new, less invasive ablation strategy in which as good a prognosis as that of whole-scar homogenization can be obtained. Mountantonakis et al showed how to identify channels of relatively higher voltage within the scar by adjusting the voltage limits of bipolar maps. 8 Tung et al demonstrated that targeting relatively earlier late potentials can expedite scar homogenization without the need for extensive ablation of all late potentials. 9 These strategies assess the characteristics within severely low voltage areas. Thus, we hypothesized that an ablation Received March 23, 2017; revised manuscript received April 29, 2017; accepted May 10, 2017; released online June 3, 2017 Time for primary review: 21 days Cardiovascular Division, Faculty of Medicine, University of Tsukuba, Tsukuba (K. Kuroki, A.N., K.Y., T. Machino, H.Y., D.X., M. Igarashi, N.M., Y.S., K.A.); Department of Cardiology, Kokura Memorial Hospital, Kitakyushu (M.G., M.F.); Department of Cardiology, Tenri Hospital, Tenri (K. Kaitani, N.O.); Cardiovascular Division, Hyogo College of Medicine, Nishinomiya (T. Mine); Division of Cardiovascular and Respiratory Medicine, Akita University School of Medicine, Akita (T.K.); and Division of Cardiology, Tsukuba Memorial Hospital, Tsukuba (M. Igawa), Japan Mailing address: Kazutaka Aonuma, MD, Cardiovascular Division, Faculty of Medicine, University of Tsukuba, Tennodai, Tsukuba , Japan. kaonuma@md.tsukuba. ac.jp ISSN All rights are reserved to the Japanese Circulation Society. For permissions, please cj@j-circ.or.jp

2 1604 KUROKI K et al. Figure 1. Dense scar-targeted ablation (DS ablation) of a tolerable ventricular tachycardia (VT) in a patient with previous inferior myocardial infarction. (A) Right posterior oblique (RPO) view of an electroanatomical activation map during VT. The electrophysiologic information is superimposed on the anatomic reconstruction of the left ventricle (red, early activation; purple, late activation). The activation sequence of tachycardia shows a figure of 8 reentry tachycardia (white dotted arrows). The red dot represents the site where the VT was terminated by a radiofrequency energy application. (B) ECG tracing recorded during VT. Surface ECG leads II, III, V1, V2, and V5, and the distal and proximal intracardiac recordings from the ablation catheter (ABL-d and ABL-p) are shown. The ablation catheter is located at the site with the red dot in (A). Presystolic potentials were recorded at this site (arrows). Pacing at that site entrained the tachycardia with concealed fusion. The post-pacing interval was equal to the tachycardia cycle length (470 ms). The stimulus-qrs interval was 80 ms and equal to the presystolic potential-qrs interval, indicating that this site was on the exit site of the critical isthmus. This tachycardia was terminated by a focal ablation in 2 s. (C) RPO view of an electroanatomical substrate mapping with voltage criteria of mv for the low voltage area (LVA). (D) RPO view of substrate mapping with voltage criteria of mv for the LVA. The 5 extremely low voltage islands (*) are depicted in the dense scar area of 0.6 mv. Gray dots, unexcitable scar; red dots, ablation sites. Compared with the activation map during VT, the critical isthmus (CI) was located between the upper (white asterisk) and lower (blue asterisk) extremely low voltage areas. Linear ablation was firstly performed at the exit site of the assumed CI along the border zone of the LVADS (low voltage area in DS ablation, mv) because the VT was terminated by ablation in this area. Secondly, a linear ablation lesion was applied across the CI from the mitral annulus to the unexcitable scar. Finally, the ablation line was extended from the unexcitable scar area to the apical NVADS (normal voltage area in DS ablation, >0.6 mv). Neither clinical VT nor nonclinical VT was induced after ablation. LVABZ, low voltage area in BZ ablation; LVADS, low voltage area in DS ablation; PP-QRS, presystolic potential-qrs; S-QRS, stimulus-qrs. strategy targeting conducting corridors, mainly inside severely low voltage areas ( 0.6 mv; we defined as the dense scar area [DSA]), would be feasible for post-infarction VT, if detailed substrate mapping combined with pace mapping study is performed. In the present study, we verified the acute and long-term efficacy of our hypothesized strategy. Methods Study Population From April 2007 to May 2012, 109 consecutive patients post-infarction (66±11 years, 10 women) underwent VT ablation at 6 different institutions. To be a candidate for VT ablation, patients had to present with repetitive or incessant sustained VT resistant to antiarrhythmic drugs and/or requiring external cardioversion or implantable cardioverter-defibrillator (ICD) therapy. Patients were excluded if the ventricular arrhythmias were attributable to an acute or reversible cause such as an electrolyte abnormality, unstable angina, or myocardial infarction (MI) within the preceding 2 months, or within the preceding 3 weeks in the case of incessant VT. All patients were retrospectively examined and classified into 2 groups according to the 2 different substrate-guided ablation strategies using different voltage criteria for 3D electroanatomical mapping. Border zone-targeted ablation (BZ ablation), which targets the border zone of standard voltage areas ( mv), was performed in 57 patients, whereas dense scar-targeted ablation (DS ablation), which mainly targets the isthmus channels in DSAs ( 0.6 mv), was performed in 52 patients. It was left to the operators at each center to decide which ablation strategy should be used. The study was approved by the local research ethics committees of the participating institutes, and all patients gave their written informed consent. Electrophysiological Study and Ablation After discontinuing all antiarrhythmic drugs, except amiodarone, for at least 5 half-lives, the electrophysiological study and ablation were conducted with conscious sedation

3 Isthmus Channel Mapping-Guided Ablation 1605 Figure 2. DS ablation of the different types of CIs (clitical isthmuses) detected by a pace mapping study. Detailed pace mapping studies were performed inside or around the voltage area of mv. (A) CI between unexcitable scars. [A1] Gray dots, unexcitable scar areas; red dots, ablation points; green dots, points at which the pace map is similar to the clinical VT. The CI is identified as a line from a to d (white dotted arrow) by the pace mapping study. Linear ablation was performed (1) along the CI, (2) between the unexcitable scars (across the CI), (3) along the border zone, and (4) between the unexcitable scars and NVADS (normal voltage areas in DS ablation, >0.6 mv). [A2] The 12-lead ECG morphology of the induced VT and the pace map at each point from a to d in panel A1. Each of the pace maps is similar to the clinical VT. The stimulus-qrs interval gradually shortens from point a to d. (B) The CI between the unexcitable scar and NVADS. The clinical VT activation is assumed to conduct from point a to c. Linear ablation was performed (1) along the CI, (2) between the unexcitable scar to the septal NVADS (across the CI), and (3) from the unexcitable scar to the lateral NVADS. (C) The CI between LVADS and LVADS (low voltage areas in DS ablation, mv). The clinical VT activation is assumed to conduct from point a to d. Linear ablation was performed (1) along the CI, (2) between 2 LVADS (across the CI), and (3) to the mitral annulus. AP, anterior posterior view; LAO, left anterior oblique view; LPO, left posterior oblique view. Other abbreviations as in Figure 1. using dexmedetomidine hydrochloride at 0.4 mcg/kg/hour. Non-invasive or intra-arterial blood pressure monitoring and digital pulse oximetry were performed continuously. ICD therapies were inactivated during the procedure. A quadripolar catheter was placed in the right ventricular apex, and a deflectable, decapolar catheter was placed in the para-hisian area. Further, an octapolar catheter was placed in the coronary sinus. The mapping catheter was advanced into the left ventricle (LV) or right ventricle (RV) using a femoral venous or arterial approach with either a retrograde aortic or transseptal approach. Intravenous heparin boluses were administered to maintain an activated clotting time >250 s during LV mapping and ablation. For DS ablation, only an endocardial approach was used. For BZ ablation, epicardial ablation was performed in 3 patients because clinical VT was persistently inducible after extensive endocardial ablation. All patients underwent substrate mapping during sinus rhythm with a 3D electroanatomical system (CARTO, Biosense Webster, Diamond Bar, CA, USA). For BZ ablation, standard voltage criteria of mv for the LVAs were used. Normal voltage area (NVABZ), low voltage area (LVABZ), and scar area (SABZ) were defined as having electrogram amplitudes of >1.5 mv, >0.5 mv to 1.5 mv, and 0.5 mv, respectively. For DS ablation, we performed electroanatomical substrate mapping using the severely low voltage criteria. 10 Normal voltage area (NVADS), low voltage area (LVADS), and scar area (SADS) were defined as having electrogram amplitudes of >0.6 mv, >0.1 mv to 0.6 mv, and 0.1 mv, respectively. The definition means the DSA ( 0.6 mv) comprised the LVADS and SADS. Sustained VT in the clinical setting or during the procedure was targeted for ablation in both strategies. In the latter 40 cases (21 [37%] underwent BZ ablation and 19 [37%] underwent DS ablation), a 7-Fr, externally irrigated, 3.5-mm tip catheter (Thermocool, Biosense Webster) was used, whereas a 7-Fr, non-irrigated, 4-mm tip catheter (Navistar, Biosense Webster) was used in the former 69 cases. When using the irrigated catheter, radiofrequency (RF) energy with a power of W was delivered for 60 s to the target region until pacing with 5 V and 2 ms stimuli failed to capture. When using the non-irrigated catheter, the RF energy was delivered using the temperature-controlled mode for 60 s at each ablation site with a power of

4 1606 KUROKI K et al. mapping within the SADS (scar area, <0.1 mv), which were depicted as red areas in the DSA. An unexcitable scar was defined as a site without any capture by local bipolar stimulation at an output of 10 V and 2.0 ms pulse width. Further, we performed pace mapping to determine the critical isthmus particularly at sites around unexcitable scar areas. An isthmus of the clinical VT was defined as that with good pace map sites with various stimuli (S)-QRS intervals. If we found a site where the paced QRS morphology was similar to the clinical VT morphology, detailed pace mapping around the site was performed to detect as much of the entire isthmus as possible. We attempted to assume conduction through the isthmus during the clinical VT by measuring the S-QRS intervals of good pace map sites. We found multiple patterns of critical isthmuses: between unexcitable scars (Figure 2A), between an unexcitable scar and NVADS (Figure 2B), and between LVADS (Figure 2C). Figure 3. Border zone-targeted ablation (BZ ablation) of 2 different intolerable VTs in a patient with a previous broad anterior myocardial infarction. (A) LAO view of a substrate map with voltage criteria of mv for the low voltage area (LVABZ). The linear ablation lesion is shown as red dots along the anterolateral area of the border zone of the apical LVABZ. Pace mapping was performed at the sites shown with red and yellow dots. The red dot indicated by a red arrow is the best pace map site. (B) The 12-lead ECGs of the best pace map and one of the clinical VTs (VT1). (C) AP view of the substrate map in the same patient. The linear ablation lesion is shown as red dots along the inferoseptal area of the border zone of the apical LVA. The earliest site of ventricular premature contractions (VPC) with 12-lead ECG morphology similar to another clinical VT (VT2) was located at the red dot indicated by the red arrow. (D) A discrete prepotential preceding the QRS onset by 75 ms was recorded at this site. Surface ECG leads I, II, and V1, and the intracardiac unipolar, and proximal and distal bipolar recordings from the ablation catheter are shown. Abbreviations as in Figures 1, W at a maximal target temperature of 55 C until pacing with 5 V and 2 ms stimuli was unable to be captured. DS Ablation Method Isthmus Identification With Entrainment Mapping: Mappable VT After substrate mapping was completed, VT induction was attempted with programmed ventricular stimulation from 2 RV sites (the apex and outflow tract) at 2 base cycle lengths (400 and 600 ms), with up to 3 extrastimuli decremented to ventricular refractoriness. If hemodynamically stable VT was induced, electroanatomical activation mapping was performed to depict the tachycardia circuit superimposed on the anatomic reconstruction of the ventricle. Figure 1A shows an example of an activation map during VT. The exit or central site of the VT isthmus was identified using entrainment mapping and presystolic or mid-diastolic potentials (Figure 1B). Isthmus Identification With Pace Mapping: Unmappable VT When VT was not inducible or poorly tolerated, mapping within the DSA was performed during sinus rhythm. A substrate map using severely low voltage criteria is shown in Figure 2. We also performed unexcitable scar Ablation When the VT was mappable, after identifying the critical isthmus by maneuvers previously described (entrainment mapping, activation mapping, and/or pace mapping), short linear ablation within the DSA ( 0.6 mv) was performed. 11 After the VT was terminated, detailed substrate mapping using pace mapping was also performed in the DSA, as previously described in the case of unmappable VT. Finally, linear ablation was performed based on information of the substrate map, whether the induced VT was mappable or not. During DS ablation, linear ablation was performed according to the following 4 guiding principles to abolish all possible isthmuses around unexcitable scars in addition to the clinical VT isthmus: (1) lesions must cross the isthmus detected by entrainment mapping and/or pace mapping; (2) lesions must extend between the unexcitable and unexcitable scars; (3) lesions must extend from the unexcitable scar to the NVADS; and/or (4) lesions must extend to the mitral annulus or another LVADS if the NVADS around the LVADS is 2 cm from the mitral annulus or another LVADS. These extra LVADS lesions were extended to the mitral annulus in 36% of the patients with DS ablation (n=20), and to another LVADS in 18% (n=10). Examples of the linear lesion based on isthmus channel mapping inside or around the LVADS are shown in Figure 2. BZ Ablation Method Both mapping and ablation procedures during mappable VT were the same as previously described for the DS ablation method. Substrate-guided ablation was performed after the mappable VT was ablated. Stepwise vector pace mapping and linear ablation along the LVABZ of mv (i.e., the scar border zone) was performed as previously described. 12 The approximated exit of the targeted VT was detected by assessing the 12-lead ECG of the target VT. In the region of interest, stepwise vector mapping along the scar border was performed. Correspondence between the VT electrocardiogram and vector pace mapping was evaluated for each pacing site, and the accurate exit was determined as the best pace map site of all. RF energy was delivered from the accurate exit towards the bilateral directions along the scar border until a discrepancy (change in QRS vector direction) of QRS vectors occurred in 1 lead. In BZ ablation, nonclinical VT was not fundamentally targeted, but if nonclinical VT was induced and sustained, it was treated using activation mapping or substrate mapping. Ablation lesions and the pace map morphology of a

5 Isthmus Channel Mapping-Guided Ablation 1607 Table 1. Baseline Demographic and Clinical Data for Both Groups of Patients Undergoing Post-Infarction VT Ablation Total (n=109) BZ ablation (n=57) DS ablation (n=52) P value Age, years 66±11 68±12 65± Sex, male 99 (91) 51 (89) 48 (92) LVEF, % 35±11 33±9 36± MI site Anterior 53 (49) 24 (42) 29 (56) Inferior 49 (45) 29 (51) 20 (38) Both 7 (6) 4 (7) 3 (6) VT storm 41 (38) 18 (32) 23 (44) Device ICD 74 (68) 36 (63) 38 (73) CRTD 14 (13) 9 (16) 5 (10) None 21 (19) 12 (21) 9 (17) Antiarrhythmic drug Amiodarone 74 (68) 37 (65) 37 (71) Sotalol 14 (13) 5 (9) 9 (17) Follow-up period, months (IQR) 37 (12 60) 37 (11 60) 39 (13 62) Data are presented as mean ± standard deviation or n (%), unless otherwise noted. ACE, angiotensin-converting enzyme inhibitor; ARB, angiotensin-receptor blocker; BZ ablation, border zone-targeted ablation; CRTD, cardiac resynchronization therapy defibrillator; DC ablation, dense scar-targeted ablation; ICD, implantable cardioverterdefibrillator; IQR, interquartile range; LVEF, left ventricular ejection fraction; MI, myocardial infarction; VT, ventricular tachycardia. Table 2. Procedural Parameters for 2 VT Ablation Techniques BZ ablation DS ablation (n=57) (n=52) P value Sustained VT induced 51 (89) 41 (79) No. of VTs induced 2 (1 6) 2 (1 7) Sustained VT cycle length, ms 398±77 408± Nonsustained VT cycle length, ms 310±96 293± Inducible clinical sustained VT 42 (74) 33 (63) Mappable VT 31 (54) 19 (37) Epicardial ablation 3 (5) 0 (0) Mapping point 143±48 369±185 < LVA, cm 2 51±30 34± (Voltage threshold, mv) ( ) ( ) Irrigation catheter use 21 (37) 19 (37) RF time, min 23±15 21± Procedure time, min 198±54 237± Fluoroscopy time, min 34±23 43± Data are presented as mean ± standard deviation, n (%), or median (range), unless otherwise noted. LVA, low voltage area; RF, radiofrequency. Other abbreviations as in Table 1. representative case undergoing BZ ablation are shown in Figure 3. Procedural Endpoint The procedural endpoint was when the monomorphic VT became noninducible or only an unstable VT that was faster than any previous VTs inducible by programmed stimulation with up to 3 extrastimuli in both groups. If a monomorphic VT was induced, the ablation procedure was repeated until no monomorphic VT was inducible. If the same episode of VT was inducible after completing regional linear ablation, ablation was directed towards gaps in the ablation line. If a different VT morphology was induced, a pace mapping study and ablation of the VT were performed until the procedural endpoint could be met. Investigators were allowed to terminate the procedure without further programmed stimulation if the patient s condition was unstable, because numerous patients with a low ejection fraction (EF) were included. The acute result of ablation was defined by the inducibility of any clinical or nonclinical VT. 13 Nonclinical VT was defined as VT presenting with a different morphology from any spontaneous episodes documented by 12-lead ECG monitoring. Preventing the inducibility of any VT was defined as complete success. Elimination of the clinical VT with persistent inducibility of 1 nonclinical sustained VT was defined as

6 1608 KUROKI K et al. Figure 4. Acute success rates of BZ ablation and DS ablation show no significant difference (including complete and partial success) between the treatment strategies. The complete success rate was significantly higher in the DS ablation group than in the BZ ablation group. Complete success=no VT was induced; partial success=clinical VT was not induced; failure=clinical VT was induced. Abbreviations as in Figures 1,3. Figure 5. VT-free survival rate after radiofrequency catheter ablation. Kaplan-Meier curves show a statistically significant difference between BZ ablation and DS ablation. Abbreviations as in Figures 1,3. partial success. The inability to prevent reinduction of 1 clinical VT was considered failure. Follow-up After ablation, all ICDs were programmed to detect VT of at least 20 beats/min slower than the clinical VT. All patients were observed with continuous ECG monitoring until they were discharged from hospital. After discharge, patients were followed at 1, 3, and 6 months at an outpatient clinic. Thereafter, they were followed every 6 months. VT recurrence was evaluated based on ECG monitoring, 24-h ambulatory monitoring, and/or ICD interrogations. VT recurrence was defined as VT lasting >30 s or receiving antitachycardia pacing or a shock, regardless of the morphology or rate. Drug management during follow-up was at the discretion of the investigator. Statistical Analysis Continuous variables are expressed as mean ± standard deviation, and compared using Student s t-test. For nonnormally distributed data, the Mann-Whitney U test or Wilcoxon signed-rank test was used. Categorical variables were compared by chi-square analysis or Fisher s test. The Kaplan-Meier method was used to determine the freedom from any sustained ventricular arrhythmia, and the logrank test was used to compare intergroup differences. A P-value <0.05 was considered statistically significant. Statistical analyses were performed with SPSS 21.0 software (SPSS Inc., Chicago, IL, USA). Results Study Population Baseline characteristics are summarized in Table 1. Patients mean age was 66 years, and 91% were men. Most patients had severe LV dysfunction with a mean LVEF of 35%. Of them, 38% had a VT storm. There were no significant differences in age, sex, LVEF, MI site, or antiarrhythmic use between the BZ and DS ablation groups. Ablation Data The ablation procedural parameters are summarized in Table 2. During the ablation, sustained VT was inducible in 51 patients (89%) in the BZ ablation group and in 41 (79%) in the DS ablation group (P=0.127). Of those, 42 of 51 patients (82%) in the BZ ablation group and 33 of 41 (80%) in the DS ablation group had a sustained clinical VT. In the BZ ablation group, an epicardial ablation was performed in 3 patients (5%) because of inducible VTs after endocardial ablation. Compared with the BZ ablation group, the DS ablation group had significantly more mapping points (P<0.0001) and a longer procedure time (P=0.004). Acute Results of Ablation After the ablation procedure, the VT inducibility was evaluated in all patients. Clinical VT was successfully suppressed in 99 patients (91%). They were all judged as acute success, and included 56 patients (51%) with complete success and 43 (39%) with partial success. Clinical VT was inducible in the remaining 10 patients (9%), who were considered procedural failures. Although no significant difference was found in the overall acute success rate (complete or partial success) between the 2 treatment strategies (P=0.240), the complete success rate was significantly higher in the DS ablation group than in the BZ ablation group (62% vs. 42%, P=0.043, Figure 4). Long-Term Outcomes of Ablation Patients were followed for a median of 37 months (interquartile range (IQR): months) from the ablation procedure. During the follow-up period (median follow-up 37 months [IQR: months] in the BZ ablation group and 39 months [IQR: months] in the DS ablation group, P=0.792), the probability of recurrence-free survival was significantly higher in the DS ablation group than in the BZ ablation group (84% vs. 72% at 24 months, 80% vs. 58% at 48 months, log-rank P=0.038). Kaplan-Meier survival curves are displayed in Figure 5. Adverse Events Major complications potentially related to the ablation procedure occurred in 2 patients (1.8%), including 1 of 57 (1.8%) in the BZ ablation group and 1 of 52 (1.9%) in the DS ablation group. In the BZ ablation group, we observed cerebral infarction in 1 patient 2 days after the ablation

7 Isthmus Channel Mapping-Guided Ablation 1609 References 1. Marchlinski FE, Callans DJ, Gottlieb CD, Zado E. Linear ablation lesions for control of unmappable ventricular tachycardia in patients with ischemic and nonischemic cardiomyopathy. Circuprocedure. In the DS ablation group, we observed pneumothorax requiring drainage in 1 patient. Discussion Major Findings To the best of our knowledge, this is the first study to compare an ablation strategy targeting DSAs of 0.6 mv with another ablation strategy targeting the border zone depicted with standard voltage criteria of mv. The main findings of the present study are as follows. Although more mapping points and a longer procedure time were required in DS ablation, the target area was significantly smaller, and the RF time was the same as in BZ ablation. A higher acute complete success rate and superior longterm prognosis were obtained using DS ablation compared with BZ ablation. Severely Low Voltage Criteria The voltage threshold of DS ablation is reasonable based on the following studies in which a voltage threshold adjustment was conducted. Arenal et al 3 demonstrated there are viable bundles that can function as conduction channels in the non-homogeneous scar tissue by applying a stepwise reduction from mv in defining a scar. They also identified the majority of conducting channels with voltage scar definitions 0.2 mv. Hsia et al 14 analyzed the relationship between conducting channels and the portions of reentry circuits. They demonstrated that most entrance and isthmus sites were located in scar tissue (<0.5 mv), whereas exits were located both in the scar and border zone (from mv). They also identified conducting channels by carefully adjusting the voltage threshold, and showed that the voltage threshold in the conducting channels ranged from 0.1 to 0.7 mv. Tzou et al 15 recently proposed a new strategy isolating core elements of VT circuits. Core isolation was performed by incorporating putative isthmus and early exit site based on standard criteria. If the VT was noninducible, the DSA (<0.5 mv) was isolated. Their study demonstrated that core isolation was achieved in 84% and led to better VTfree survival. Prophylactic Linear Ablation A prospective, randomized study demonstrated that an extensive substrate-based ablation approach that targets all abnormal potentials of the scar is superior to ablation that only targets clinical VTs in patients with ischemic cardiomyopathy (15.5% vs. 48.3%, respectively, of the VT recurrence rate at the 12-month follow-up). 16 Other studies that only targeted clinical VTs showed a similar prognosis. 17,18 On the other hand, DS ablation showed as good prognosis as that of extensive substrate-based ablation 6 (16% and 19%, respectively, of the VT recurrence rate at the 2-year follow-up). DS ablation did not target all abnormal electrographic findings of the scar, but the linear lesion to the critical isthmus was routinely extended to the area, which we considered as not having much arrhythmogenicity (>0.6 mv), and to the mitral annulus or another DSA. This prophylactic linear ablation of nonclinical VTs may have decreased the possibility that a new VT would occur in the chronic phase. Our study at least showed that nonclinical VT was less inducible after DS ablation than after BZ ablation. In core isolation, the target area of <0.5 mv is similar to that in DS ablation, and the VT-free survival rate of the successful core isolation group is also similar. 15 Additional substrate modification was also performed in 61% of cases of core isolation, and this fact suggests that prophylactic ablation in addition to clinical VT is probably necessary to obtain a good VT-free survival rate, even if we target mainly the DSA. Clinical Implications In post-infarction VT, the DS ablation technique demonstrated a favorable prognosis without using an epicardial approach. The recurrence-free survival rate of DS ablation at 2 years (84%) was actually as good as that of endocardial and epicardial homogenization of the scar (81%), 6 although the 2 strategies were not compared directly. Moreover, in DS ablation, the target region for ablation is basically limited to the severely damaged area of 0.6 mv, so it is less likely that DS ablation causes much damage to functioning muscles compared with BZ ablation or other extensive approaches. Therefore, we think it is reasonable to perform DS ablation at least in the first ablation session for ischemic VT. Study Limitations The main limitation is that our study was retrospective and thus subjected to bias. Although the baseline patient characteristics were the same between the 2 ablation groups, it was left to the operators at each center to decide which ablation strategy should be used. Second, no contact forcesensing catheter was used in any case and an irrigation catheter was used in less than 40% of the patients in this study, because it had not yet been introduced in Japan during the study period when the ablation procedures were performed. A recent prospective cohort study reported that a poor contact force may lead to overestimating the LVA and missing of some late potentials. 19 The use of a contact force-sensing catheter may have decreased the low voltage areas and enhanced the quality of the voltage map. Third, a multielectrode mapping catheter was not used for mapping, because it could not be used in Japan during the study period either. This may have affected the size and quality of the LVAs. Our study should be evaluated in a prospective manner with the current ablation system: contact force-sensing catheter and irrigation catheter, and multielectrode mapping catheter. Fourth, DS ablation takes longer than BZ ablation, because it needs many more mapping points, including pacing sites, to detect critical isthmuses or unexcitable scar tissue within the DSA. However, this problem would be reduced by using a multielectrode mapping catheter. Conclusions DS ablation based on detailed mapping in DSAs resulted in a higher complete success rate in the acute phase and a higher recurrence-free survival rate in the chronic phase compared with BZ ablation. These results should be verified in a future prospective, randomized study. Conflict of Interest This study does not have any relationships with an industry.

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