Original Article

Impact of Local Ablation on Interconnected Channels Within Ventricular Scar

Mechanistic Implications for Substrate Modication
Roderick Tung, MD; Nilesh S. Mathuria, MD; Rich Nagel, AS; Ravi Mandapati, MD; Eric F. Buch, MD; Jason S. Bradeld, MD; Marmar Vaseghi, MD, MS; Noel G. Boyle, MD, PhD; Kalyanam Shivkumar, MD, PhD
BackgroundThe extent to which channels within scar are interconnected is not known. The objective of the study was to evaluate the impact of local ablation of late potentials (LPs) on adjacent and remote areas of slow conduction with simultaneous multipolar mapping. Methods and ResultsAnalysis was performed on consecutive patients referred for ablation of scar-mediated ventricular tachycardia with double ventricular access. Ablation was performed targeting the earliest of LPs visualized on the multipolar catheter, and the impact on later LPs was recorded. In 21 patients, a multipolar catheter placed within scar visualized spatially distinct LPs. Among 39 radiofrequency applications, ablation at earlier LPs had an effect on neighboring and remote LPs in 31 (80%), with delay in 8 (21%), partial elimination in 9 (23%), and complete elimination in 14 (36%). The mean distance where an ablation impact was detected was 17.614.7 mm (range, 250 mm). Among all patients, 9.77.8 radiofrequency applications were delivered to homogenize the targeted scar region with a mean number of 2312 LPs targeted. ConclusionsAblation can eliminate neighboring and remote areas of slow conduction, suggesting that channels within scar are frequently interconnected. This is the rst mechanistic demonstration to show that ablation can modify electrical activity in regions of scar outside of the known radius of an radiofrequency lesion. The targeting of relatively earlier LPs can expedite scar homogenization without the need for extensive ablation of all LPs.(Circ Arrhythm Electrophysiol. 2013;6:1131-1138.) Key Words: catheter ablation tachycardia ventricular
low conduction via nonlinear electric impulse activation within complex scar architecture has been implicated in the pathogenesis of fractionated and delayed local electric activity.1 Late potentials (LPs) mapped in sinus rhythm within scar have been shown to have specicity for reentrant isthmuses.24 Although the elimination of LPs has been demonstrated to be effective in preventing recurrent ventricular tachycardia (VT), homogenization of all abnormal local electric activity within scar has been proposed as a more comprehensive end point for substrate-based VT ablation. When compared with inducibility, extensive ablation within scar has been more predictive of clinical success.57

mapping catheter8 and ablation catheter, which has been used for rapid identication of critical isthmuses during VT ablation, can be a useful method to monitor the effect of local ablation on neighboring and remote regions of slow conduction within scar. We hypothesized that (1) areas of LPs are necessarily activated through channels with earlier abnormal activation (Figure1), (2) local ablation frequently impacts neighboring and even remote regions within scar, and (3) ablation in the proximal part of a channel may be a more efcient method to homogenize scar in sinus rhythm.

Clinical Perspective on p 1138

The extent of ablation required to homogenize an entire scar can be variable and result in prolonged procedural times. The impact of radiofrequency (RF) ablation of LPs on other spatially distinct LPs mapped within scar has not been previously quantied or reported. Double ventricular access using a multipolar

Methods
Patient Population
From 2009 to 2013, 128 patients at 2 centers underwent mapping of scar-mediated VT using a multipolar catheter. Among these patients, 21 underwent ablation with double ventricular access using a multipolar catheter to guide and monitor RF ablation. Patients with spatially distinct LPs (>2 mm apart) represented on >1 electrode pair at a stable multipolar catheter position were included for analysis.

Received July 10, 2013; accepted October 3, 2013. From the University of California, Los Angeles Cardiac Arrhythmia Center, University of California, Los Angeles Health System, David Geffen School of Medicine at University of California, Los Angeles (R.T., R.N., R.M., E.F.B., J.S.B., M.V., N.G.B., K.S.); St. Lukes Health System/Texas Heart Institute, Houston (N.S.M.); and University of Texas Health Science Center, Houston (N.S.M.). Correspondence to Roderick Tung, MD, University of California, Los Angeles Cardiac Arrhythmia Center, University of California, Los Angeles Health System, David Geffen School of Medicine at University of California, Los Angeles, 100 UCLA Medical Plaza, Suite 660, Los Angeles, CA 90095-1679. E-mail rtung@mednet.ucla.edu 2013 American Heart Association, Inc. Circ Arrhythm Electrophysiol is available at http://circep.ahajournals.org DOI: 10.1161/CIRCEP.113.000867

1131

1132Circ Arrhythm ElectrophysiolDecember 2013

Figure 1. Schematic of activation within scar demonstrating progressively late activation after the QRS in sinus rhythm. A decapolar catheter oriented along this channel can detect multiple areas with late potential and monitor the impact of ablation. Abl indicates ablation.

The diagnosis of ischemic cardiomyopathy was established by prior history of infarction with Q waves, focal wall motion abnormality, or xed perfusion defect correlated with coronary stenosis or prior coronary intervention. All ablations for scar-mediated VT were performed under general anesthesia. Written informed consent was obtained from all patients. The University of California, Los Angeles Medical Center and University of Texas Health Science institutional review board approved review of this data.

when VT was hemodynamically tolerated. In cases of hemodynamically unstable VT, all LPs sites were tagged and pacemapping was performed. Sites with multiple exit sites and pace-mapped induction were considered isthmus surrogates.9 High-density electroanatomic maps were created in sinus rhythm (intrinsic=13; right ventricular paced=6; biventricular paced=2) using CARTO (Biosense Webster, Diamond Bar, CA) or NAVX (St Jude Medical, Minneapolis, MN) with greater

Electrophysiological Study and Electroanatomic Mapping

The approach and strategy for ablation of scar-mediated VT at our center has been previously reported.9 Entrainment mapping was performed

Table 1. Patient Characteristics

Patient 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Age, y 74 49 59 52 70 63 70 48 80 57 70 69 34 73 60 43 56 71 76 68 51 Sex Male Male Male Male Male Male Male Male Male Male Male Male Male Male Male Male Male Male Male Male Cause ICM ICM ICM ICM ICM ICM NICM ICM ICM ICM ICM Sarcoid ICM Chagas ARVC ICM ICM ICM NICM ICM EF 10 20 35 AAD A A/L S None No A A/S A None A/M A/M S A A/M S A/M/S A A A/M A Prior VT Ablation ICD Storm No No No No Yes No Yes Yes No No No Yes Yes Yes No Yes Yes Yes No Yes No Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes No Yes No No Yes No Yes No Yes No Yes No No No Yes No Yes No No

Male Noncompaction 25 25 25 30 20 35 20 26 35 30 25 55 25 20 30 25 30

35 M/S

Figure 2. Categorization of the impact of local ablation (elimination of distal ablation electrogram) on neighboring and remote late potentials. Local ablation can have no effect, delay, partially eliminate, and completely eliminate spatially distinct areas of late activity. Partial elimination is dened as elimination of the high-frequency component of an electrogram within a far-eld signal. Abl indicates ablation.

21

A indicates amiodarone; AAD, anti arrhythmic drug; ARVC, arrhythmogenic right ventricular dysplasia; EF, ejection fraction; ICD, implantable cardioverterdebrillator; ICM, ischemic cardiomyopathy; M, mexiletine; NICM, nonischemic cardiomyopathy; S, sotalol; and VT, ventricular tachycardia.

Tung et al Effects of Local Ablation 1133

density of sampling in regions of low voltage and border zone tissue (0.51.5 mV). Multipolar mapping was performed using either a duodecapolar catheter (Livewire, 2-2-2 interelectrode spacing, St Jude, Minneapolis, MN), decapolar catheter (DecaNav, 2-8-2 interelectrode spacing, Biosense Webster, Diamond Bar, CA), or a 64-electrode basket catheter (Constellation 60 mm diameter, 5-mm interelectrode spacing, Boston Scientic, Natick, MA) If delay at the remote LPs site was seen before elimination of the local LPs, it was categorized as elimination. RF applications where instability of the multipolar catheter was suspected (change in fareld electrogram of a given bipole pair or variability of electrograms in neighboring electrodes) were excluded. At least 1 multipolar catheter position to evaluate RF delivery was recorded in all patients, and additional monitoring of ablation was left to the discretion of the operator. In addition to analysis of individual RF applications, quantication of the total number of LPs mapped within the scar was performed. These were manually counted for each map and compared with the number of ablation lesions delivered to eliminate or modify the region of substrate targeted, which was veried by remapping after ablation. RF ablation was performed using an open-irrigated catheter (ThermoCool or ThermoCool SF, 3.5 mm, Biosense Webster, Diamond Bar, CA) at 30 to 50 W, temperature limit 45C at 30-mL ow rate or closed-loop irrigated catheter (Chilli, Boston Scientic, Natick, MA) at 30 to 50 W, temperature limit 45C. The temperature limit for epicardial RF applications was 50C. RF energy was applied for 60 seconds for each application. Ablation sites were tagged on the electroanatomic map, and lesions were considered effective if they resulted in 1 of the following: a diminution or elimination of the local

Multipolar Monitoring of LPs Ablation

All LPs (<1.5 mV, with onset after QRS offset or split potential separated by 20 ms isoelectric segment) identied were tagged on electroanatomic mapping, whether detected with the multipolar or ablation catheter. The multipolar catheter was positioned within scar in an orientation that recorded the largest number of LPs with a gradient of earlyto-late activation. Ablation was performed at the earlier electrograms with late activity, and the impact of ablation on neighboring (within 8 mm of RF site) and remote electrodes (>8 mm away from RF site) was classied into 4 responses if the local distal ablation signal was from ablation: (1) no effect, (2) delay in activation, (3) partial elimination of LPs (abolition of sharp, high-frequency component within a far-eld ventricular electrogram),6 or (4) complete elimination of LPs (Figure2).

Table 2. Electroanatomic Mapping and Electrophysiological Findings

Patient 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 EAM CARTO CARTO NAVX NAVX NAVX CARTO CARTO CARTO CARTO CARTO NAVX NAVX CARTO NAVX NAVX CARTO NAVX NAVX CARTO NAVX CARTO Multipolar DD DD DD DD DD DD Deca Basket Basket DD DD DD DD DD DD Deca DD DD DD DD Deca Scar Area, cm2 96 62 57 59 17 88 87 71 64 18 58 83 68 51 22 40 39 70 55 86 127 Scar Location Apical/septal Inferior Apical Epi lateral Anteroseptal Anteroapical Inferior epi Anteroapical Inferoapical Apical Apex Anterior Basal IL epi Epi basal IL Epi inferoapex Epi RVOT Epi IL Endo IL Septal Epi anteroapical Epi inferolateral Mapping Points 861 833 922 531 745 402 721 328 374 399 815 817 522 1157 2890 430 185 417 614 583 1309 MES/PMI No/no No/no No/no No/no Yes/no Yes/yes No/no Yes/no Yes/yes No/no No/no Yes/yes No/no Yes/no No/no Yes/no Yes/yes Yes/yes Yes/no No/no Yes/yes LPs No. Abl No. 11 4 14 33 41 36 10 4 26 11 12 23 30 24 22 32 39 18 37 15 42 4 2 9 25 4 6 3 3 25 1 2 12 10 14 6 11 26 7 16 5 14 Target VT (TCL) RBLS (380) RBLS (355) RBLS (290) RBRS (290) RBRI (320) RBLS (300) RBRS (340) RBRI (360) LBS (360) Non LBI (340) RBLS (440) Non RBRI (530) RBRI (400) LBI (320) RBRI (540) RBRS (585) LBLS (360) RBI (330) RBLI (420) VTs Induced 2 4 3 1 4 1 1 4 4 0 2 4 0 2 3 1 1 3 3 1 3 VT Term Yes Yes No No No Yes No Yes Yes No No No No Yes No Yes Yes Yes Yes No Yes Acute Success Non Flutter Non Non Non Non Partial Non Non Non Non Flutter Non Non Non Non Non No Non Non Failure VT Follow-up, Recurrence mo No No No No No No No Yes No No No No No No No No Yes No No No Yes 6 11 9 13 12 18 21 8 7 17 7 44 11 30 1 1 2 46 2 24 1

Abl indicates ablation; DD, duodecapolar; EAM, electroanatomic mapping; Endo, endocardial; epi, epicardial; IL, inferolateral; LBI, left bundle inferior; LBLS, left bundle left superior; LBS, left bundle superior; LPs, late potentials; MES, multiple exit site; PMI, pace-mapped induction; RBI, right bundle inferior; RBLI, right bundle left inferior; RBLS, right bundle left superior; RBRI, right bundle right inferior; RVOT, right ventricular outow tract; TCL, tachycardia cycle length; and VT, ventricular tachycardia.

1134Circ Arrhythm ElectrophysiolDecember 2013

electrogram, failure to capture at 10 mA at 2-ms pacing, or impedance drop >10 . Distances between LPs were calculated using the uoroscopy, mapping system, and known interelectrode distances. When using a linear catheter, distances are reported as edge-to-edge to the more inner electrode of a pair. For example, the interelectrode distance between bipole 1,2 and bipole 5,6 using a 2-2-2 mm spacing with 1-mm electrode size is 8 mm.

Results
Twenty-one patients (ischemic cardiomyopathy=15; nonischemic cardiomyopathy=2; arrhythmogenic right ventricular dysplasia=1; sarcoid=1; Chagas=1; noncompaction=1) underwent double ventricular access for VT ablation using a multipolar catheter with the intention of monitoring RF application effects within scar. The median age was 63 (5270) years, and all patients were male. The median ejection fraction was 25% (25%30%). Approximately half (48%) of the patients referred had prior ablation, and 90% were on antiarrhythmic medications. Patient characteristics are shown in Table1. Electroanatomic mapping ndings are summarized in Table2. A median of 614 (417833) points were obtained for each map. A multipolar catheter (duodecapolar=16; decapolar=3; basket=2) was placed within scar to visualize spatially distinct LPs at a single stable position. The basket catheter was chosen for patients with apical scar. Nine patients underwent epicardial mapping and ablation, where 2 sheaths were placed into the pericardium using a double-wire technique through a single puncture.10 Each patient had a median of 2 (12.5) RF applications targeted at eliminating multiple potentials visualized on the multipolar

Acute Outcomes and Clinical Follow-up

After ablation was performed in the region of the targeted VT, programmed stimulation was repeated with ventricular extrastimulus testing at drive cycles of 600 and 400 ms, with decrement by 10 ms until refractoriness or 200 ms, up to 4 extrastimuli at a minimum of 2 sites. Acute procedural success was dened as noninducibility after ablation. Partial success was dened as inducibility of only faster nonclinical VTs. Follow-up for VT recurrence and survival data were assessed from outpatient clinic notes, device interrogation, patient charts, and contact with the patients or referring physician by phone.

Statistical Analysis
All continuous data are reported as medians with 25% and 75% percentiles attributable to the small sample size, evidenced by the relatively large standard deviations observed in this cohort.

Figure 3. Placement of a duodecapolar (DD) catheter across a region with multiple late potentials in the apical region of anterior infarction. A single radiofrequency application targeted at the earliest later potential (9,10) eliminates a gradient of late activation down the channel to 19,20, which is 26 mm away. Abl indicates ablation; and AP, anteroposterior.

Tung et al Effects of Local Ablation 1135

catheter. All other RF applications required to complete the ablation were performed without multipolar monitoring. Among 39 RF applications, ablation at earlier abnormal potentials had an effect on neighboring LPs in 31 (80%), with delay in 8 (21%), partial elimination in 9 (23%), and complete elimination in 14 (36%). Figure3 demonstrates ablation within a dense anteroapical infarct with ablation at duodecapolar 9,10 which results in elimination of all LPs to 19,20 (26 mm away). The median delay, when observed, was 26 ms (19 37 ms) on remote LPs. The median distance where an ablation effect was seen remotely was 15 mm (820 mm), with a range from 2 mm to 50 mm from the RF application site. Sixty-one percent (19/31) of the effects were remote (>8 mm from RF site). Figure4 demonstrates delay prior to elimination of a critical remote LPs (mid-diastolic during VT) demonstrated with a basket catheter in a patient with history of a remote stab wound to the chest complicated by cardiac perforation. Among all patients, 7 (414) RF applications were delivered to homogenize the targeted scar region where a median number of 23 (1233) LPs were mapped. Figure5 is an example of ablation along the septal border zone of an anterior infarct, where the latest activity (dark blue and purple on propagation map setting) is seen in sinus rhythm. Only 4 ablations were required to eliminate 41 LPs mapped. Remapping in this region demonstrated elimination of late activity and LPs. A median of 2 (13) VTs were induced with an average cycle length of 360 ms (325410 ms) for the targeted VT. In 5 patients, diastolic activation during VT was recorded on the multipolar catheter at the exact same position that revealed a gradient of LPs in sinus rhythm. In all but 1 patient (Figure3), the diastolic activation sequence during VT was reversed from LPs activation in sinus rhythm. The interval between the earliest and latest LPs was longer during VT compared with sinus rhythm in all patients (136 ms [100171 ms] versus 57 ms [5681 ms]). The latest sinus rhythm LPs in these patients (84 ms [90128 ms] after QRS) was 33% (31%48%) of the tachycardia cycle length during diastole in VT. Concealed entrainment of an isthmus was demonstrated in 2 patients, and the activation of the LPs during entrainment was the same as during VT (Figure6). Multiple exit site pace maps were seen in 52% of patients (11/21), pace-mapped induction was observed in 29% (6/21), and termination of a targeted VT was achieved in 52% (11/31) of cases. Two patients were noninducible throughout the procedure, and the acute end point of noninducibility was obtained in 84% of the remainder (16/19) and a partial success

Figure 4. Placement of basket catheter into trauma-induced (stab wound to chest with cardiac perforation) left ventricular apical aneurysm reveals diastolic activation from spline H1-4 (early diastolic) to G1-4 (presystolic). Ventricular tachycardia was terminated by ablation (Abl) between these 2 splines. After termination, sinus rhythm late potentials (LPs) activation proceeds from G1-4 to H1-4. A single radiofrequency application using retrograde approach magnetic navigation targeted at the earliest LPs at G1-4 delays and eliminates H1-4, which is 15 mm away. LAO indicates left anterior oblique.

1136Circ Arrhythm ElectrophysiolDecember 2013

Figure 5. Late activation map display in sinus rhythm within septal scar. A duodecapolar (DD) catheter was used to map late potentials (LPs; lp tags), and the regions of latest activation are displayed as blue and purple. Four ablation lesions (red) applied within scar eliminates all 41LPs identied, which is conrmed with remapping using the duodecapolar catheter where the latest activation is eliminated postablation.

was seen in 16% (3/19). At a median of 11 (618) months, 86% of patients remained free of recurrent VT.

Discussion
The current study, to our knowledge, is the rst to provide mechanistic evidence of the interconnected nature of channels within scar where (1) RF applications frequently modify regions of late activity within scar outside the known radius of an ablation lesion and (2) the amount of ablation required to eliminate LPs is not as extensive as the number of LPs mapped and identied. The intended elimination of all abnormal electric activity within scar has been shown to improve clinical freedom from recurrent VT compared with more limited strategies.57 These more extensive approaches, however, may prolong procedural time, and the duration of RF application to homogenize scar may be longer. The nature of abnormally fractionated, split, or local electric activity within scar has been attributed to the zigzag propagation of heterogenous conducting channels interspersed and bounded by collagen.1,11 In this construct, every LPs deep within scar is necessarily activated by an earlier later potential. The ablation of a more proximal or entrance site in sinus rhythm is likely to have an effect on more delayed activation downstream in a channel. Jas et al6 demonstrated that epicardial LPs could be abolished during endocardial ablation in 5 patients who underwent combined epi-endo ablation of VT, with the goal of eliminating all local abnormal ventricular activities. However, the local effects of endocardial and epicardial ablation on the same surface have not been systematically studied and quantied. Such an analysis

requires double ventricular access with a stable multipolar catheter to monitor the impact of ablation on spatially adjacent and remote regions of scar. As Jas et al6 classied direct ablation of local abnormal ventricular activities into 4 categories, we similarly classied indirect ablation effects on neighboring and remote ablation into 4 categories only when the local electrogram was eliminated. In this analysis, we also demonstrate that fewer ablation lesions are required to eliminate or modify multiple LPs. Irrigated ablation has been shown to create lesions with a mean diameter of 143 mm and depth of 61 mm on infarcted epicardial tissue in vivo.12 Similar lesion diameters (14 mm) with high power irrigated technology have been shown in ex vivo thigh preparations. Therefore, any effects seen outside of the radius (>8 mm) cannot be attributed to direct resistive or conductive heating. In this study, we observed ablation impact up to the entire length of a duodecapolar catheter which measures 50 mm. The remote effects of ablation are likely to be underestimated with the current methodology when calculating the closest distance between the inner electrodes with edge-to-edge reporting. Theoretically, the maximum distance between a bipole pair 1,2 and 3,4 with 2-mm spacing may be as high as 10 mm. An alternative to displaying scar as gradations of low voltage is displaying activation maps of progressively late electric activity in sinus rhythm (Figure5). This provides more of the functional characteristics of arrhythmogenic scar, which is complementary to structural low-voltage areas. The current ndings suggest that ablation targeted at the border zone of the latest activity region may be a more efcient approach to homogenize scar. This approach

Tung et al Effects of Local Ablation 1137

Figure 6. Evidence of interconnected late potentials (LPs) during sinus rhythm and ventricular tachycardia (VT) in 2 patients. The rst patient (top) had a history of inferolateral myocardial infarction and concealed entrainment is demonstrated from duodecapolar (DD) 3,4, which is latest in sinus and earliest in VT. The interval between the LPs (red arrows) is longer during VT (136 ms) than sinus (104 ms). Activation more distally (DD 912) is the same pattern during entrainment and VT. In the second patient (bottom) with arrhythmogenic right ventricular cardiomyopathy, LPs are seen with a decapolar catheter placed across the epicardial right ventricular outow tract. During induction of VT with programmed stimulation, activation is reversed, and the interval between the LPs (56 ms) is signicantly prolonged during VT (206 ms) with pandiastolic activity recorded. Unidirectional block with emergence of the unopposed orthodromic wavefront is seen with progressive extrastimuli.

would be aimed at eliminating entrances into the latest activity in sinus rhythm, which would represent the exit during VT. As we have previously demonstrated multiple exit site when pacing within scar, it is plausible to expect multiple entrances into a given LPs. Delay of a LPs with ablation of an earlier LPs may be attributable to conduction slowing or alternatively, a shift to a different entrance into channel. Functional conduction slowing during reentry likely accounts for the prolongation in the interval between LPs seen during VT than in sinus rhythm. However, activation of a channel through multiple wavefronts during sinus rhythm, as opposed to a singular wavefront during VT, may also contribute to this phenomenon. Further studies are required to assess the impact of differential pacing from different scar border zones on the identication of LPs because preferential entrance into scar may rely on directionality of the wavefront and anisotropic conduction.

Limitations
The intended purpose of the study is to provide mechanistic insight into the effects of ablation within scar via analysis of individual

RF applications as well as the total extent of ablation required to eliminate the total number of LPs mapped. The objective of the present study is not to propose monitoring of all ablation lesions with a multipolar mapping catheter because this technique can be time consuming. We recognize that only the minority of lesions delivered during the ablation procedure were monitored with the double access setup. This is largely attributable to the fact that these observations require a stable catheter position demonstrating multiple LPs and careful manipulation of the ablation catheter toward the targeted bipole without disturbing the multipolar catheter position or creating intercatheter mechanical artifact. The observed interconnectedness of channels within scar may not be generalizable to all scar substrates because only patients in whom multiple potentials are recorded at a single catheter position were included. Multiple causes of scar were included in this cohort, and the small sample size is inadequate to draw conclusions across all substrates. Only electrograms with a gradient of late activation were chosen, which biases the ablation lesions toward orientation along a channel. However, the absence of remote impact detected

1138Circ Arrhythm ElectrophysiolDecember 2013

during local ablation does not exclude effects on regions that may not contacted by the electrodes on the multipolar catheter. Different multipolar catheters were used within this cohort, and the use of smaller interelectrode spacing may increase the ability to detect ablation impact within scar. Furthermore, remote impact on regions outside of 50 mm may be present but cannot be proven using a single duodecapolar catheter. Distances of remote impact were estimated using eld scaling from known interelectrode size and spacing as well as uoroscopy. The linear catheter is frequently curved to improve mapping contact on the mapping surface contour, and therefore, an overestimation of the distances may result because they are calculated based on a linear orientation. For this reason, we chose to report edge-to-edge distances between the most inner electrodes to avoid overestimation of ablation effects.
2. Arenal A, Glez-Torrecilla E, Ortiz M, Villacastn J, Fdez-Portales J, Sousa E, del Castillo S, Perez de Isla L, Jimenez J, Almendral J. Ablation of electrograms with an isolated, delayed component as treatment of unmappable monomorphic ventricular tachycardias in patients with structural heart disease. J Am Coll Cardiol. 2003;41:8192. 3. Bogun F, Bender B, Li YG, Groenefeld G, Hohnloser SH, Pelosi F, Knight B, Strickberger SA, Morady F. Analysis during sinus rhythm of critical sites in reentry circuits of postinfarction ventricular tachycardia. J Interv Card Electrophysiol. 2002;7:95103. 4. Bogun F, Good E, Reich S, Elmouchi D, Igic P, Lemola K, Tschopp D, Jongnarangsin K, Oral H, Chugh A, Pelosi F, Morady F. Isolated potentials during sinus rhythm and pace-mapping within scars as guides for ablation of post-infarction ventricular tachycardia. J Am Coll Cardiol. 2006;47:20132019. 5. Di Biase L, Santangeli P, Burkhardt DJ, Bai R, Mohanty P, Carbucicchio C, Dello Russo A, Casella M, Mohanty S, Pump A, Hongo R, Beheiry S, Pelargonio G, Santarelli P, Zucchetti M, Horton R, Sanchez JE, Elayi CS, Lakkireddy D, Tondo C, Natale A. Endo-epicardial homogenization of the scar versus limited substrate ablation for the treatment of electrical storms in patients with ischemic cardiomyopathy. J Am Coll Cardiol. 2012;60:132141. 6. Jas P, Maury P, Khairy P, Sacher F, Nault I, Komatsu Y, Hocini M, Forclaz A, Jadidi AS, Weerasooryia R, Shah A, Derval N, Cochet H, Knecht S, Miyazaki S, Linton N, Rivard L, Wright M, Wilton SB, Scherr D, Pascale P, Roten L, Pederson M, Bordachar P, Laurent F, Kim SJ, Ritter P, Clementy J, Hassaguerre M. Elimination of local abnormal ventricular activities: a new end point for substrate modication in patients with scar-related ventricular tachycardia. Circulation. 2012;125:21842196. 7. Vergara P, Trevisi N, Ricco A, Petracca F, Baratto F, Cireddu M, Bisceglia C, Maccabelli G, Della Bella P. Late potentials abolition as an additional technique for reduction of arrhythmia recurrence in scar related ventricular tachycardia ablation. J Cardiovasc Electrophysiol. 2012;23:621627. 8. Tung R, Nakahara S, Maccabelli G, Buch E, Wiener I, Boyle NG, Carbucicchio C, Bella PD, Shivkumar K. Ultra high-density multipolar mapping with double ventricular access: a novel technique for ablation of ventricular tachycardia. J Cardiovasc Electrophysiol. 2011;22:4956. 9. Tung R, Mathuria N, Michowitz Y, Yu R, Buch E, Bradeld J, Mandapati R, Wiener I, Boyle N, Shivkumar K. Functional pace-mapping responses for identication of targets for catheter ablation of scar-mediated ventricular tachycardia. Circ Arrhythm Electrophysiol. 2012;5:264272. 10. Horowitz BN, Vaseghi M, Mahajan A, Cesario DA, Buch E, Valderrbano M, Boyle NG, Ellenbogen KA, Shivkumar K. Percutaneous intrapericardial echocardiography during catheter ablation: a feasibility study. Heart Rhythm. 2006;3:12751282. 11. de Bakker JM, van Capelle FJ, Janse MJ, Tasseron S, Vermeulen JT, de Jonge N, Lahpor JR. Fractionated electrograms in dilated cardiomyopathy: origin and relation to abnormal conduction. J Am Coll Cardiol. 1996;27:10711078. 12. dAvila A, Houghtaling C, Gutierrez P, Vragovic O, Ruskin JN, Josephson ME, Reddy VY. Catheter ablation of ventricular epicardial tissue: a comparison of standard and cooled-tip radiofrequency energy. Circulation. 2004;109:23632369.

Conclusions
Local ablation frequently impacts and eliminates neighboring and spatially remote areas of slow conduction, suggesting that channels within scar are often interconnected. This is the rst mechanistic demonstration to show that ablation can modify electrical activity in regions of scar outside of the known radius of an RF application. The targeting of relatively earlier LPs may expedite a scar homogenization strategy without the need for extensive ablation. Simultaneous multipolar mapping during ablation may be of clinical value.

Acknowledgements
We would like to thank Heather Macken for her helpful review of electroanatomic mapping data.

Sources of Funding
Dr Shivkumar is supported by the National Heart, Lung, and Blood Institute (R01HL084261).

Disclosures
Dr Tung receives research grant from St Jude Medical. The other authors report no conicts.

References
1. de Bakker JM, van Capelle FJ, Janse MJ, Tasseron S, Vermeulen JT, de Jonge N, Lahpor JR. Slow conduction in the infarcted human heart. Zigzag course of activation. Circulation. 1993;88:915926.

CLINICAL PERSPECTIVE
Substrate-based ablation strategies targeting abnormal electrograms have become the mainstay for catheter-based therapy of scar-mediated ventricular tachycardia. Recently, more extensive ablation aimed to homogenize scar by eliminating all late activity within scar has been shown to increase clinical efcacy. However, these proposed strategies can be time consuming with a relatively nonspecic approach. A more elegant and targeted method to eliminate late potentials is feasible if channels within scar are interconnected. As a biologically plausible construct, all regions of late activation necessarily have an earlier region of late activation upstream. By targeting these earlier regions of late activation, slow conduction regions downstream may be eliminated. In this mechanistic report, the vast majority of local ablation lesions within scar demonstrate a remote impact. This is the rst systematic demonstration whereby a single radiofrequency application can modify and eliminate regions of late activity within scar that are well outside of the known radius of an effective lesion. These ndings suggest that an end point equivalent to that of extensive ablation can be achieved with fewer radiofrequency applications attributable to the interconnected nature of channels within scar.