Abstract Aims Ventricular tachycardia (VT) substrate ablation is based on detailed electroanatomical maps (EAM). This study analyses whether high-density multielectrode mapping (MEM) is superior to conventional point-by-point mapping (PPM) in guiding VT substrate ablation procedures. Methods and results This was a randomized controlled study (NCT02083016). Twenty consecutive ischemic patients undergoing VT substrate ablation were randomized to either group A [n = 10; substrate mapping performed first by PPM (Navistar) and secondly by MEM (PentaRay) ablation guided by PPM] or group B [n = 10; substrate mapping performed first by MEM and second by PPM ablation guided by MEM]. Ablation was performed according to the scar-dechanneling technique. Late potential (LP) pairs were defined as a Navistar-LP and a PentaRay-LP located within a three-dimensional distance of ≤ 3 mm. Data obtained from EAM, procedure time, radiofrequency time, and post-ablation VT inducibility were compared between groups. Larger bipolar scar areas were obtained with MEM (55.7±31.7 vs. 50.5±26.6 cm2; P = 0.017). Substrate mapping time was similar with MEM (19.7±7.9 minutes) and PPM (25±9.2 minutes); P = 0.222. No differences were observed in the number of LPs identified within the scar by MEM vs. PPM (73±50 vs. 76±52 LPs per patient, respectively; P = 0.965). A total of 1104 LP pairs were analysed. Using PentaRay, far-field/LP ratio was significantly lower (0.58±0.4 vs. 1.64±1.1; P = 0.01) and radiofrequency time was shorter [median (interquartile range) 12 (7–20) vs. 22 (17–33) minutes; P = 0.023]. No differences were observed in VT inducibility after procedure. Conclusion MEM with PentaRay catheter provided better discrimination of LPs due to a lower sensitivity for far-field signals. Ablation guided by MEM was associated with a shorter radiofrequency time. Multielectrode mapping , PentaRay , Ventricular tachycardia , Substrate ablation What’s new? This is the first randomized clinical study assessing the potential benefits of multielectrode mapping vs. conventional point-by-point mapping for ventricular tachycardia substrate ablation in ischemic patients. Multielectrode mapping with PentaRay catheter provided a lower sensitivity for far-field signals, which allowed better discrimination of local abnormal electrograms and conducting channels. Scar dechanneling guided by MEM was associated with a shorter radiofrequency time. Introduction Current ventricular tachycardia (VT) substrate ablation strategies aim to completely abolish abnormal local electrograms (EGMs) identified within the scar region.1–3 Therefore, substrate-based approaches are highly dependent on accurate delineation of scar architecture and identification of abnormal local EGMs, which are a function of mapping density. Conventional substrate mapping strategies rely on point-by-point electroanatomical mapping (PPM) to identify slow conducting channels (CCs) that are the ablation targets. These CCs can be identified during substrate mapping either by voltage scanning4–6 or by analyzing the activation sequence of the delayed local component of abnormal EGMs identified within the scar region.3,7–9 Both strategies are time consuming and operator dependent, as they require a very detailed and accurate electroanatomical map (EAM). The use of multipolar catheters with smaller electrodes and shorter interelectrode distances may facilitate the detection of such areas of slow conduction, thereby increasing the effectiveness of the ablation procedure. However, to date, no randomized studies comparing multielectrode mapping (MEM) vs. conventional PPM in substrate ablation procedures have been published. The aim of this study was to assess whether MEM improves slow CCs identification in VT substrate ablation procedures, compared to PPM. Methods This is a single-center, randomized controlled pilot study (NCT02083016). Study population Twenty consecutive patients with ischemic heart disease undergoing VT substrate ablation were included from September 2013 to December 2015. Inclusion criteria were age >18 years, the presence of prior myocardial infarction, and a symptomatic episode of sustained monomorphic VT. Patients were randomized (1:1) to group A [n = 10; substrate mapping performed first by PPM (Navistar) and second by MEM (PentaRay), ablation guided by PPM] or group B [n = 10; substrate mapping performed first by MEM and second by PPM, ablation guided by MEM]. All patients provided written informed consent to participate. The Local Ethics Committee approved this study. Pre-procedural evaluation Each patient received a complete clinical evaluation. Before the procedure, all patients underwent transthoracic/transesophageal echocardiogram to rule out atrial or left ventricular (LV) thrombus and to evaluate LV function. Whenever possible, 3-Tesla contrast-enhanced cardiac magnetic resonance (ce-CMR) was acquired to identify the scar presence and obtain its pixel signal intensity (PSI); these results were merged with the EAM images. In the absence of ce-CMR or when epicardial ablation was anticipated, a CT scan was acquired to merge images from coronary arteries. Contrast-enhanced cardiac magnetic resonance processing and integration into navigation system The ce-CMR study was performed, and all (late gadolinium enhancement) LGE-CMR images processed, as previously described.10 Briefly, images were processed with ADAS-VT software (Galgo Medical, Barcelona, Spain). After endocardium and epicardium were delineated semi-automatically, five concentric surface layers were created automatically, from endocardium to epicardium, at 10, 25, 50, 75, and 90%, respectively, of LV wall thickness. A three-dimensional shell was obtained for each layer. Pixel signal intensity maps were obtained from LGE-CMR images, projected to each shell following a trilinear interpolation algorithm, and were color coded. To identify the scar areas, a PSI-based algorithm was applied to characterize the hyperenhanced area as scar core or BZ, using 40 ± 5% and 60 ± 5% of the maximum intensity as thresholds. All shells were exported as VTK files and imported into the navigation system (CARTO; Biosense Webster, Diamond Bar, CA, USA). Ablation procedure The VT ablation procedure used has been previously described.3 Procedures were performed under conscious-sedation (midazolam and fentanyl) or general anesthesia when epicardial access was anticipated. A tetrapolar diagnostic catheter was positioned at the right ventricular (RV) apex. The procedure started with substrate modification as a first step, without baseline VT induction and mapping. Endocardial access to the LV was obtained by single transseptal puncture (BRK needle; Medtronic Inc, Minneapolis, MN, USA). After transseptal access, heparin was intravenously administered to maintain an activated clotting time >300 seconds. A steerable sheath (Agilis St Jude Medical, St Paul, MN) facilitated mapping and ablation through the transseptal access. Epicardial mapping and ablation were performed when pre-procedural ce-CMR showed transmural scar. When ce-CMR was not available, transmurality criteria were analysed using other imaging techniques (CT scan, echocardiography, and SPECT), and when present, a combined endocardial and epicardial access was performed, as previously described.11 Substrate mapping approaches The procedural protocol flowchart is shown in Figure 1. Figure 1 View largeDownload slide Study workflow. Patients were randomized to substrate mapping performed first by point-by-point mapping (Navistar) and secondly by multielectrode mapping (PentaRay), with ablation guided by the PPM (group A) vs. substrate mapping performed first by multielectrode mapping (PentaRay) and secondly by point-by-point mapping (Navistar), with ablation guided by the multielectrode EAM (group B). Figure 1 View largeDownload slide Study workflow. Patients were randomized to substrate mapping performed first by point-by-point mapping (Navistar) and secondly by multielectrode mapping (PentaRay), with ablation guided by the PPM (group A) vs. substrate mapping performed first by multielectrode mapping (PentaRay) and secondly by point-by-point mapping (Navistar), with ablation guided by the multielectrode EAM (group B). Point-by-point mapping Using an open-irrigated 3.5 mm tip ablation catheter (Thermocool, Navistar; Biosense Webster), a high-density substrate voltage map of the LV was obtained during sinus rhythm. Maximum fill thresholds of 10 mm to fill the cavity and 8 mm to fill the low-voltage area were established. Standard voltage cut-off values were used to define normal tissue (>1.5 mV), border zone (BZ) (0.5–1.5 mV), and dense scar (<0.5 mV). Intracavitary points were deleted using an internal point filter software available on the mapping system to limit data acquisition to within 6 mm from the chamber geometry. Multielectrode mapping Multielectrode mapping was performed using a PentaRay catheter (Biosense Webster) with a 2-6-2 mm interelectrode distance. During sinus rhythm, a high-density substrate voltage map of the LV was obtained. At each location, stability and adequate splaying of the PentaRay splines over the LV surface was confirmed fluoroscopically before signal acquisition, and ventricular ectopic beats were excluded. A maximum fill threshold of 10 mm was established to fill the LV cavity, and sufficient sampling of the low-voltage area was performed to obtain a fill threshold <8 mm. Regular voltage thresholds were used to define normal tissue (>1.5 mV), BZ (0.5–1.5 mV), and dense scar (<0.5 mV). In order to avoid internal point acquisition, a filter software available on the mapping system was used to limit point acquisition to within 6 mm from the chamber geometry. Ablation technique The scar dechanneling technique was used in all ablation procedures.3 Conducting channels were identified as either voltage channels4 or late potential (LP) channels.3,7 Voltage CCs were defined as BZ corridors between two areas of dense scar or between a dense scar and the mitral annulus. These voltage CCs were identified through voltage scanning as previously described.7 Electrograms with delayed components (EGM-DC) were tagged and dichotomously classified as entrance or inner CC points, depending on delayed-component precocity during sinus rhythm. Conducting channel entrances were defined as EGM-DC in which fusion between the local potential and the far-field was observed. All CC entrances identified during substrate mapping were targeted for ablation. Backup radiofrequency (RF) applications were delivered inside the scar area when RF lesions at the CC entrance did not eliminate internal EGM-DCs. Radiofrequency (RF) energy was delivered3 using a Navistar catheter (Biosense Webster). Radiofrequency ablation was controlled by a temperature limit of 45°C with a power limit of 50 W at the endocardium and 40–50 W at the epicardium. The catheter irrigation rate during RF application was 26 mL/min in the endocardium and 17 mL/min in the epicardium. A post-ablation remap was always performed to document the elimination of all the CC-EGMs and to eliminate the remaining EGM-DCs by back-up RF applications. Systematic testing of myocardial capture after ablation was not performed. After substrate ablation, programmed RV stimulation with three cycle lengths (600, 500, and 430 ms) and up to three ventricular extrastimuli until refractoriness or 200 ms cycle length was used to induce VT. Clinical and nonclinical VTs induced after scar dechanneling were targeted for ablation. Inducibility was checked after each induced VT was ablated. Acute success was defined as noninducibility of any sustained monomorphic VT at the end of the procedure. All patients were evaluated at 6 and 12 months post ablation. Each visit included implantable cardioverter defibrillator (ICD) interrogation. Any sustained VT, whether or not ICD intervention was required, was considered a VT recurrence. Mapping and ablation data analysis For both mapping approaches (MEM and PPM), substrate mapping times were calculated from the moment the mapping catheter entered the LV to the moment the substrate map was completed. To evaluate mapping density, the fill threshold was lowered to the minimum value that depicted the low-voltage area fully coloured without grey areas, and this value was recorded as the fill threshold. All EGM-DC identified with both mapping approaches were individually analysed, and the amplitude of the bipolar signal of the far-field signal and the local abnormal EGM were defined. The number of CCs identified within the scar region with both mapping approaches was also analysed. Finally, in order to compare the sensitivity of both mapping approaches for the detection of local abnormal EGMs, all EGM-DC, sorted by mapping strategy, were projected to a merged EAM toward the concordant point with the nearest three-dimensional (3D) distance. Once this merged map was obtained, pairs of EGM-DC were identified and these points underwent paired analysis. An EGM-DC pair was defined as a couple of two EGM-DC (one obtained with MEM and one obtained with PPM) with a maximal 3D distance between point pairs of ≤ 3 mm. An experienced electrophysiologist performed this paired analysis of EGM-DC obtained with both mapping systems. Paired analysis for each pair of EGM-DC compared the bipolar EGM of these points. Agreement on EGM-DC was defined as detection of an EGM-DC by both mapping strategies. In case of agreement on the identification of EGM-DC between MEM and PPM, the voltage amplitude of the far-field and local component of these point pairs was manually measured to compare the sensitivity of both mapping approaches to record local and far-field signals. The acute results of the ablation procedure (VT inducibility after ablation) and mid-term outcomes (VT recurrence-free survival at 12 months) were compared between groups. Statistical analysis Continuous variables were expressed as mean ± SD for normally distributed data or median and interquartile range [median (25th–75th percentile)] for non-normal distribution. Categorical data were expressed as counts and percentages and compared between groups using χ2 test. Data were tested for normality by histogram and using the Kolmogorov–Smirnov test. Continuous variables were expressed as mean ± SD, and differences between groups were assessed using paired Student's t-test, or the Wilcoxon signed-rank test when appropriate. All tests with P < 0.05 were considered statistically significant. Statistical analysis was performed using R software for Windows version 3.1.2 (R project for statistical computing; Vienna, Austria) and SPSS version 18.0 (SPSS, Inc., Chicago, IL, USA). Results Study population Twenty patients (95% male, 67.3±10.3 years old) undergoing VT substrate ablation were prospectively included. Baseline clinical characteristics are summarized in Table 1. All patients had ischemic cardiomyopathy. In 11 patients (55%), a pre-procedural ce-CMR was obtained and integrated into the navigation system. Table 1 Baseline clinical characteristics Group A: PPM-guided ablation Group B: MEM-guided ablation P value Age, years 69 ± 11.4 65.6 ± 9.4 0.478 LVEF (%) 34 ± 9 36 ± 8 0.563 Hypertension, n (%) 5 (50) 8 (80) 0.382 Diabetes, n (%) 2 (20) 3 (30) 0.618 NYHA class, n (%) 0.198 I–II 7 (70) 10 (100) III 3 (30) 0 Infarct location, n (%) 0.709 Anteriora 2 (20) 2 (20) Inferiorb 8 (80) 8 (80) Approach, n (%) 0.456 Endocardial 5 (50) 6 (60) Endoepicardial 5 (50) 4 (40) Group A: PPM-guided ablation Group B: MEM-guided ablation P value Age, years 69 ± 11.4 65.6 ± 9.4 0.478 LVEF (%) 34 ± 9 36 ± 8 0.563 Hypertension, n (%) 5 (50) 8 (80) 0.382 Diabetes, n (%) 2 (20) 3 (30) 0.618 NYHA class, n (%) 0.198 I–II 7 (70) 10 (100) III 3 (30) 0 Infarct location, n (%) 0.709 Anteriora 2 (20) 2 (20) Inferiorb 8 (80) 8 (80) Approach, n (%) 0.456 Endocardial 5 (50) 6 (60) Endoepicardial 5 (50) 4 (40) LVEF, left ventricular ejection fraction; NYHA, New York Heart Association. a Anterior location includes anterior, anteroseptal, anterolateral and apical locations of myocardial infarction. b Inferior location includes inferior, inferoseptal and inferolateral locations of myocardial infarction. Substrate mapping A detailed EAM of the LV was obtained during sinus rhythm in all patients. Electroanatomical maps were endocardial only in 11 patients and endo-epicardial in the remaining 9 patients. The mean number of points acquired to build the endocardial (731 ± 274 vs. 294 ± 128; P < 0.001) and epicardial (1137 ± 256 vs. 365 ± 96; P = 0.01) EAMs were higher with MEM than with PPM, respectively. Consequently, the mean number of points acquired within the scar area was also higher with MEM (782 ± 517 vs. 207 ± 100; P < 0.001). However, with both mapping systems, the fill threshold could be lowered to 7 within the scar region in all cases, indicating a similar mapping resolution within the scar region with both mapping approaches. A trend towards shorter mapping times was observed using MEM although no statistically significant differences were observed (24 ± 8 vs. 30 ± 13 minutes; P = 0.209). Both epicardial (66.2 ± 21.6 vs. 39.6 ± 24.4 cm2; P = 0.05) and endocardial (51.3 ± 26 vs. 41.2 cm2; P = 0.017) low-voltage areas were significantly larger using MEM than PPM (Figure 2). However, the overall number of EGM-DCs identified with both mapping approaches was similar (76 ± 52 EGM-DCs per patient using PPM vs. 73 ± 50 using MEM), given the similar mapping density obtained with both catheters. Figure 2 View largeDownload slide Correlation between EAM and ce-CMR. Posterior views of endocardial and epicardial maps from a patient with a transmural inferior infarction. Left column: color-coded ce-CMR derived pixel intensity maps of the endocardial and epicardial layers (red: core, purple: healthy; yellow-green: BZ). Central and right column: bipolar endocardial and epicardial EAMs obtained with Navistar and PentaRay, respectively. Note that the low-voltage areas are much more extensive in the PentaRay map. Figure 2 View largeDownload slide Correlation between EAM and ce-CMR. Posterior views of endocardial and epicardial maps from a patient with a transmural inferior infarction. Left column: color-coded ce-CMR derived pixel intensity maps of the endocardial and epicardial layers (red: core, purple: healthy; yellow-green: BZ). Central and right column: bipolar endocardial and epicardial EAMs obtained with Navistar and PentaRay, respectively. Note that the low-voltage areas are much more extensive in the PentaRay map. No difference was observed in the total number of CCs identified per patient by PPM and MEM (Table 2). A total of 29 CCs were identified using MEM, and 27 using PPM. Good agreement was observed between both mapping approaches in the identification of CCs, as 25 of the 27 (92.5%) CCs identified by PPM were also observed using the PentaRay catheter. On the other hand, 25 of the 29 (86.2%) CCs identified by MEM were also observed using the Navistar catheter. Despite the concordance between MEM and PPM in the identification of CCs, the proportion identified by voltage scanning was higher when using MEM (71.7% vs. 56.3%, respectively; P = 0.024) (see Supplementary material online). Table 2 Substrate mapping data Point-by-point mapping Multielectrode mapping P value No. of points Endocardial 294 ± 128 731 ± 274 <0.001 Epicardial 296 ± 75 1137 ± 256 0.01 Scar area < 1.5 mV (cm2) Total 58.4 ± 41.8 79.6 ± 49.8 0.005 Endocardial 41.2 ± 27.3 51.3 ± 26.5 0.017 Epicardial 39.6 ± 24.4 66.6 ± 21.6 0.05 No. of EGM-DC 76 ± 52 73 ± 50 0.965 No. of CC 1.4 ± 1.1 1.5 ± 1 0.414 Substrate mapping time (min) 29 ± 13 23 ± 9 0.108 Point-by-point mapping Multielectrode mapping P value No. of points Endocardial 294 ± 128 731 ± 274 <0.001 Epicardial 296 ± 75 1137 ± 256 0.01 Scar area < 1.5 mV (cm2) Total 58.4 ± 41.8 79.6 ± 49.8 0.005 Endocardial 41.2 ± 27.3 51.3 ± 26.5 0.017 Epicardial 39.6 ± 24.4 66.6 ± 21.6 0.05 No. of EGM-DC 76 ± 52 73 ± 50 0.965 No. of CC 1.4 ± 1.1 1.5 ± 1 0.414 Substrate mapping time (min) 29 ± 13 23 ± 9 0.108 With respect to the analysis of EGM-DC, a total of 1104 pairs of EGM-DC were identified with a distance ≤3 mm between both points in endocardial and epicardial substrate maps. The amplitude of the far-field and local components was analysed in all EGM-DC pairs. No difference was observed between MEM and PPM in the amplitude of the local delayed potential (0.46 ± 0.28 vs. 0.38 ± 0.33 mV; P = 0.227), although a trend towards detecting higher bipolar voltages of the local LP was observed with MEM. On the other hand, the amplitude of the far-field component was significantly higher using PPM (0.46 ± 0.39 vs. 0.26 ± 0.2 mV; P = 0.044) (Figure 3). Therefore, far-field/LP ratio was significantly higher using conventional PPM than with MEM (1.64±1.1 vs. 0.58±0.4, respectively; P = 0.01). These data demonstrate lower sensitivity for far-field signals with MEM. Figure 3 View largeDownload slide EGM-DC pair analysis in a patient with an anterior myocardial infarction. Right anterior oblique views of the left ventricle are depicted. Substrate maps obtained with multielectrode catheter and conventional catheter were merged and set at 100% transparency (A and B). Electrograms with delayed components identified with PentaRay are tagged in orange and those identified with Navistar in green. A red circle indicates a EGM-DC pair identified with both catheters. (A) The position of Navistar catheter with respect to the EGM-DC pair and the bipolar EGM obtained. (B) The position of Pentaray catheter with respect to the same EGM-pair and the bipolar EGM obtained. Note that the EGM depicted by PentaRay (B) showed a significantly lower amplitude of the far-field component and a significantly higher amplitude of the LP. Figure 3 View largeDownload slide EGM-DC pair analysis in a patient with an anterior myocardial infarction. Right anterior oblique views of the left ventricle are depicted. Substrate maps obtained with multielectrode catheter and conventional catheter were merged and set at 100% transparency (A and B). Electrograms with delayed components identified with PentaRay are tagged in orange and those identified with Navistar in green. A red circle indicates a EGM-DC pair identified with both catheters. (A) The position of Navistar catheter with respect to the EGM-DC pair and the bipolar EGM obtained. (B) The position of Pentaray catheter with respect to the same EGM-pair and the bipolar EGM obtained. Note that the EGM depicted by PentaRay (B) showed a significantly lower amplitude of the far-field component and a significantly higher amplitude of the LP. Correlation between electroanatomical maps and contrast-enhanced cardiac magnetic resonance A total of 11 patients (55%) underwent a pre-procedural ce-CMR. The distribution of the scar assessed by ce-CMR was subendocardial in seven patients and transmural in four patients. All these 11 patients underwent endocardial mapping using PPM and MEM and, additionally, in those with transmural scar (n = 4), an epicardial map was performed with both mapping systems. As previously described,10 PSI maps obtained from ce-CMR revealed a progressive reduction in scar size from endocardium to epicardium [33.5 (15.7–54.7) vs. 4 (1–12.3) cm2, respectively; P = 0.007). At the endocardial level, the correlation between the low-voltage area depicted by the EAM and the scar observed in PSI maps was better when using MEM (r = 0.75; P = 0.021) compared to PPM (r = 0.62; P = 0.05) (Figure 2). In patients with transmural scar undergoing epicardial mapping, median epicardial scar area according to PSI maps was 12.3 (11.9–18.6) cm2. On the other hand, using the standard bipolar voltage threshold values (0.5–1.5 mV), the median of the epicardial low voltage area obtained with PPM [33.2 (31.5–34.4) cm2; P = 0.068] and MEM [48.2 (43.6–52.7) cm2; P = 0.067] were higher (albeit not statistically significant) than the scar depicted by the ce-CMR. Therefore, a trend towards overestimation of epicardial scar area was observed with both mapping systems, probably due to the interposition of epicardial fat. It should be noted that the overestimation was higher when using MEM (Figure 2), suggesting greater voltage attenuation by epicardial fat due to lower sensitivity for far-field signals. However, it should be highlighted that these data are based on maps obtained in only four patients. Thus, it should be confirmed in a larger cohort. Ablation: acute results Complete scar dechanneling (complete elimination of CC-EGMs) was achieved in 17 patients (85%). After VT substrate ablation, two patients (20%) were inducible for VT in group A (ablation guided by PPM) and three patients (30%) in group B (ablation guided by MEM) (P = 0.618). A total of six monomorphic VT were induced in those five patients. All these residual VTs induced after substrate ablation were targeted for ablation. As a result, after residual VT ablation three patients (30%) remained inducible for VT, one in group A and two in group B (P = 0.542). Despite the similar acute results obtained in both groups, guiding scar dechanneling by MEM was associated with a significantly shorter RF time [12 (7–20) vs. 22 (17–33) minutes; P = 0.023], suggesting a better identification of appropriate ablation targets (Figure 4). Figure 4 View largeDownload slide Conducting channel identification. Anterior views of endocardial EAMs obtained with PentaRay (MEM) and Navistar (PPM) in a patient with an anterior infarction (see MRI map in A). A conducting channel is depicted in both EAMs (B and C). Multielectrode mapping (B) allowed a more detailed delineation of the activation sequence (white dotted line). Note that with MEM, the local electrogram has a higher amplitude than the far-field signal. Figure 4 View largeDownload slide Conducting channel identification. Anterior views of endocardial EAMs obtained with PentaRay (MEM) and Navistar (PPM) in a patient with an anterior infarction (see MRI map in A). A conducting channel is depicted in both EAMs (B and C). Multielectrode mapping (B) allowed a more detailed delineation of the activation sequence (white dotted line). Note that with MEM, the local electrogram has a higher amplitude than the far-field signal. Complications and outcomes One patient (5%) had an ischemic stroke within the first week after discharge. In two (10%) patients, MEM had to be interrupted due to ventricular fibrillation induced by multielectrode catheter manipulation. In both cases, ventricular fibrillation occurred after frequent catheter-induced premature beats during mapping close to the posteromedial papillary muscle in patients with an inferior myocardial infarction. At 12 months post procedure, two patients (20%) showed VT recurrence. No difference was observed in VT recurrence rate between group A (n = 1, 10%) and group B (n = 1, 10%). Discussion To our knowledge, this is the first randomized clinical study assessing the potential benefits of MEM vs. conventional PPM for VT substrate ablation in ischemic patients. The main findings are as follows: (i) MEM with PentaRay catheter provided a lower sensitivity for far-field signals and (ii) scar dechanneling guided by MEM was associated with a shorter RF time. Potential advantages of multielectrode catheters Conventional mapping catheters have a 3.5 mm distal tip electrode and a proximal 1 mm electrode, with a center-to-center interelectrode distance of 3.25 mm. It has been estimated that bipolar EGMs obtained by these catheters represent the electrical activity from an underlying tissue area ranging from 1 to 2.4 cm2. This capacity for far-field recording may represent a limitation for accurate identification of slow CC within the scar region because electrogram fractionation observed during substrate mapping is dependent on electrode spatial resolution and can be obscured by the far-field signal.12,13 On the other hand, MEM catheters have smaller electrode size and closer center-to-center interelectrode distance, which is associated with better mapping resolution because each acquired point represents the electric activity from a smaller tissue area.12 The results of this study are consistent with these technical characteristics as the analysis of EGM-DC revealed significantly lower amplitude of the far-field component in those points acquired with MEM. However, whether these potential technical advantages represent a clinical benefit for VT substrate ablation procedures has not been clearly shown. On the other hand, VT substrate mapping with multielectrode catheters such as Pentaray may also have potential disadvantages. First, Pentaray does not have contact force sensing technology, which could result in the acquisition of internal points preventing the appropriate identification of myocardial scar area. However, this can be overcome by the use of a module that selectively uses the points closest to the tissue to generate high-quality 3D maps (Confidence module; Biosense). Second, another potential disadvantage of Pentaray observed in the present study was the mechanical induction of ventricular fibrillation during mapping close to the posteromedial papillary muscle. This suggests that mapping the posteroseptal aspect of the LV with Pentaray could be especially challenging due to the presence of structures (such as papillary muscle, chordae tendinale, or LV septum) that could interfere with the movements of the splines; provoking mechanically induced premature beats that could degenerate into ventricular fibrillation. Impact of multielectrode mapping on ventricular tachycardia substrate ablation Substrate-based VT ablation approaches are highly dependent on accurate delineation of scar architecture and identification of abnormal local EGMs. Therefore, it could be hypothesized that, given its better spatial resolution, MEM could be better than conventional PPM for substrate mapping and, consequently, for guiding VT substrate ablation. Several studies based on animal models have compared MEM vs. PPM for VT substrate ablation. Impact on the identification of the scar area Recently, Tschabrunn et al.14 performed sequential mapping of the LV with PentaRay and Smart-touch in 3 healthy swine and 11 swine with healed myocardial infarction. According to their results, bipolar voltage amplitude in the healthy ventricle was similar between PPM and MEM; however, the mean bipolar voltage amplitude within the low-voltage area was higher with MEM. Interestingly, in the seven swine that showed significant differences in voltage amplitude within scar area between MEM and PPM, a thin layer of surviving myocardium bundle was identified in the subendocardium.14 These data explain the higher voltage observed with MEM and suggest that MEM provides a higher sensitivity for local electrical activity and a lower sensitivity for far-field signals. In the present study, low-voltage areas observed during substrate mapping were larger with MEM than with PPM. Similarly, Berte et al.15 reported an increased bipolar low-voltage area with multielectrode catheters, compared to conventional PPM, in patients with scar-related VTs and in post-infarction sheep. Although it could be argued that the increased low-voltage area depicted by MEM could be due to inadequate tissue contact when mapping with PentaRay, it should be noted that in the present study, the correlation between the endocardial low-voltage area depicted by the EAM and the scar observed in ce-CMR was better when using MEM. The smaller scar area obtained with PPM can be reasonably explained by the effect of the far-field signal of the surrounding healthy tissue. As explained by Andreu et al.,16 this effect is proportionally higher in small and heterogeneous scars. Additionally, although low-voltage areas obtained during substrate mapping were more extensive when using MEM, a higher proportion of CC could be detected by voltage scanning in maps obtained with multielectrode catheter, due to its lower sensitivity for far-field signals (Figures 3 and 4). Therefore, the results of the present study are consistent with those reported by Tschabrunn et al.,14 as they also suggest that MEM is more accurate than PPM to depict the scar architecture. Finally, it should be highlighted that these results refer to endocardial maps. Thereby, data obtained from epicardial maps in this study showed a trend towards overestimation of epicardial scar area with both mapping systems (using standard voltage thresholds), probably due to the interposition of epicardial fat. This overestimation was higher when using MEM, suggesting greater voltage attenuation by epicardial fat due to lower sensitivity for far-field signals. These data should not preclude the use of Pentaray for epicardial substrate mapping; however, they indicate that it is especially important to use strategies to differentiate attenuation by epicardial fat vs. true low-voltage area, such as bipolar EGM analysis (fragmentation, duration) and the use of scar maps derived from the cardiac magnetic resonance and/or epicardial fat segmentation and its integration into the navigation system. Impact on local abnormal electrograms and conducting channel identification Ventricular tachycardia substrate ablation strategies aim to completely eliminate abnormal EGMs and CCs identified within the scar region.1–3,17 Therefore, accurate identification of this arrhythmogenic substrate is the key point of these ablation procedures. Berte et al.15 suggested that, given its capability to perform very high-density maps, MEM may increase local abnormal EGMs and CC identification.15 They also reported that when using a multielectrode catheter, the fill threshold of substrate maps within the scar region could be lowered to 5 mm in 92% of cases, whereas the same was not possible in any case with PPM. As a result, MEM identified a higher number of local abnormal EGMs and CCs than PPM.15 In contrast, in the study by Tschabrunn et al.14 the fill threshold for both types of catheters remained constant at ≤ 5 mm, resulting in the absence of difference between the two mapping approaches in the prevalence of local abnormal EGMs. In the present study, the number of EGM-DCs and CCs identified per patient with MEM and PPM were similar, given the similar mapping density obtained with both catheters (Table 2). Furthermore, a good agreement was observed between both mapping approaches in the identification of CCs. However, although no significant quantitative differences between them were observed in the identification of arrhythmic substrate, ablation guided by MEM was associated with shorter RF time. This suggests that MEM provides a better qualitative assessment of appropriate ablation targets. Multielectrode catheters (such as PentaRay) with smaller electrode size and closer interelectrode distance may provide a better resolution of intracardiac electrograms than conventional mapping catheters,12 allowing more accurate assessment of the activation sequence within the CC and better identification of the CC entrance (Figure 4). Furthermore, the lower sensitivity for far-field signals provided by multielectrode catheters was associated in the present study with a better identification of CCs by voltage scanning (see Supplementary material online). Therefore, the shorter RF time obtained when ablation was guided by MEM could be due to a better identification of appropriate ablation targets (Figure 4). It should be noted that the ablation technique used in this study (scar dechanneling) aims complete arrhythmic substrate elimination by selectively targeting CC entrances. Thus, the appropriate identification of ablation targets becomes a key point when using this ablation approach. Limitations This was a single-center, randomized pilot study. First, the main limitation is the relatively small study cohort. Second, in order to have homogeneous data, only ischemic patients were included and the same ablation strategy was used in all of them. Therefore, it remains unknown whether these results could be reproduced in non-ischemic patients and/or with other ablation approaches. Third, in order to confirm the attenuation of epicardial voltage by the presence of fat, it would have been necessary to use software specifically designed for epicardial fat segmentation and its integration into the CARTO system. Finally, EGM-DC paired analysis was performed manually by an experienced electrophysiologist. Automatic algorithms are required in order to improve the reproducibility and standardization of this analysis. Conclusions Multielectrode mapping with a PentaRay catheter provided better discrimination of local abnormal electrograms and CCs due to lower sensitivity for far-field signals. Scar dechanneling guided by MEM was associated with a shorter RF time. Supplementary material Supplementary material is available at Europace online. Conflict of interest: none declared. Funding This study has been partially funded by Biosense-Webster and by the project PI14/00759, integrated in the Plan Nacional de I + D + I and co-financed by the ‘ISCIII-Subdirección General de Evaluación’ and the ‘Fondo Europeo de Desarrollo Regional (FEDER)’. References 1 Jais P, Maury P, Khairy P, Sacher F, Nault I, Komatsu Y et al. Elimination of local abnormal ventricular activities: a new end point for substrate modification in patients with scar-related ventricular tachycardia. Circulation 2012; 125: 2184– 96. Google Scholar CrossRef Search ADS PubMed 2 Di Biase L, Santangeli P, Burkhardt DJ, Bai R, Mohanty P, Carbucicchio C et al. 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: 132– 41. Google Scholar CrossRef Search ADS PubMed 3 Berruezo A, Fernandez-Armenta J, Andreu D, Penela D, Herczku C, Evertz R et al. Scar dechanneling: a new method for scar-related left ventricular tachycardia substrate ablation. Circ Arrhythm Electrophysiol 2015; 8: 326– 36. Google Scholar CrossRef Search ADS PubMed 4 Arenal A, del Castillo S, Gonzalez-Torrecilla E, Atienza F, Ortiz M, Jimenez J et al. Tachycardia-related channel in the scar tissue in patients with sustained monomorphic ventricular tachycardias: influence of the voltage scar definition. Circulation 2004; 110: 2568– 74. Google Scholar CrossRef Search ADS PubMed 5 Hsia HH, Lin D, Sauer WH, Callans DJ, Marchlinski FE. Anatomic characterization of endocardial substrate for hemodynamically stable reentrant ventricular tachycardia: identification of endocardial conducting channels. Heart Rhythm 2006; 3: 503– 12. Google Scholar CrossRef Search ADS PubMed 6 Andreu D, Ortiz-Pérez JT, Fernández-Armenta J, Guiu E, Acosta J, Prat-Gonzélez S et al. 3D delayed-enhanced magnetic resonance sequences improve conducting channel delineation prior to ventricular tachycardia ablation. Europace 2015; 17: 938– 45. Google Scholar CrossRef Search ADS PubMed 7 Fernández-Armenta J, Andreu D, Penela D, Trucco E, Cipolletta L, Arbelo E et al. Sinus rhythm detection of conducting channels and ventricular tachycardia isthmus in arrhythmogenic right ventricular cardiomyopathy. Heart Rhythm 2014; 11: 747– 54. Google Scholar CrossRef Search ADS PubMed 8 Tung R, Mathuria NS, Nagel R, Mandapati R, Buch EF, Bradfield JS et al. Impact of Local Ablation on interconnected channels within ventricular scar: mechanistic implications for substrate modification. Circ Arrhythm Electrophysiol 2013; 6: 1131– 8. Google Scholar CrossRef Search ADS PubMed 9 Berruezo A, Acosta J, Fernández-Armenta J, Pedrote A, Barrera A, Arana-Rueda E et al. Safety, long-term outcomes and predictors of recurrence after first-line combined endoepicardial ventricular tachycardia substrate ablation in arrhythmogenic cardiomyopathy. Impact of arrhythmic substrate distribution pattern. A prospective multicentre study. Europace 2017; 19: 607– 16. Google Scholar PubMed 10 Fernandez-Armenta J, Berruezo A, Andreu D, Camara O, Silva E, Serra L et al. Three-dimensional architecture of scar and conducting channels based on high resolution ce-CMR: insights for ventricular tachycardia ablation. Circ Arrhythm Electrophysiol 2013; 6: 528– 37. Google Scholar CrossRef Search ADS PubMed 11 Acosta J, Fernandez-Armenta J, Penela D, Andreu D, Borras R, Vassanelli F et al. Infarct transmurality as a criterion for first-line endo-epicardial substrate-guided ventricular tachycardia ablation in ischemic cardiomyopathy. Heart Rhythm 2016; 13: 85– 95. Google Scholar CrossRef Search ADS PubMed 12 Stinnett-Donnelly JM, Thompson N, Habel N, Petrov-Kondratov V, Correa de Sa DD, Bates JH et al. Effects of electrode size and spacing on the resolution of intracardiac electrograms. Coronary Artery Dis 2012; 23: 126– 32. Google Scholar CrossRef Search ADS 13 Correa de Sa DD, Thompson N, Stinnett-Donnelly J, Znojkiewicz P, Habel N, Muller JG et al. Electrogram fractionation: the relationship between spatiotemporal variation of tissue excitation and electrode spatial resolution. Circ Arrhythm Electrophysiol 2011; 4: 909– 16. Google Scholar CrossRef Search ADS PubMed 14 Tschabrunn CM, Roujol S, Dorman NC, Nezafat R, Josephson ME, Anter E. High-resolution mapping of ventricular scar: comparison between single and multielectrode catheters . Circ Arrhythm Electrophysiol 2016; 9. 15 Berte B, Relan J, Sacher F, Pillois X, Appetiti A, Yamashita S et al. . Impact of electrode type on mapping of scar-related VT. J Cardiovasc Electrophysiol 2015; 26: 1213– 1223. Google Scholar CrossRef Search ADS 16 Andreu D, Berruezo A, Ortiz-Perez JT, Silva E, Mont L, Borras R et al. Integration of 3D electroanatomic maps and magnetic resonance scar characterization into the navigation system to guide ventricular tachycardia ablation. Circ Arrhythm Electrophysiol 2011; 4: 674– 83. Google Scholar CrossRef Search ADS PubMed 17 Berruezo A, Fernández-Armenta J. Lines, circles, channels, and clouds: looking for the best design for substrate-guided ablation of ventricular tachycardia. Europace 2014; 16: 943– 5. Google Scholar CrossRef Search ADS PubMed Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: email@example.com.
Europace – Oxford University Press
Published: Mar 1, 2018
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