Dense Scar Research Articles

Anatomy of the isthmus: unraveling tissue composition of ventricular tachycardia diastolic pathway

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Spanish Ministry of Science and Innovation Background Unequal tissue composition of post-myocardial infarction (MI) scar (viable myocardium, fibrosis, fatty infiltration) leads to heterogeneous conduction properties and excitability. The presence of a protected diastolic, slow-conducting pathway (isthmus) is the electrophysiological landmark of post-MI reentrant ventricular tachycardia (VT). Contemporary histological studies evaluating the tissue features needed for slow, protected conduction during VT are lacking. Purpose To characterize tissue composition singularities of confirmed VT isthmuses (VTI) in a chronic MI swine model, and to compare it to non-isthmus scar (NIS). Methods One-month after a non-reperfused anterior MI, 9 Landrace X Large White pigs (4 female; 33.6±2.2 Kg) with inducible VT underwent high-density activation mapping to define the diastolic corridor. VTI was defined as part of the diastolic pathway exhibiting mid-diastolic potentials. Discrete radiofrequency applications were delivered in the vicinity of the VTI and used as tissue landmarks to guide the ex vivo isthmus localization. Tissue transverse samples (5 mm) from the labelled VTI and NIS were obtained for further histological and immunohistochemical analysis. Dense scar and border zones were analyzed. Results Compared to NIS, border zone of VTI showed significantly higher fatty infiltration (p=0.016) and dense scar displayed less Collagen I (p=0.053), Collagen III (p=0.043), and Collagen Volume Fraction (p=0.027), without differences in the overall fibrotic deposition (P=0.119). Immunohistochemical studies revealed greater vascular density (Isolectin B4-positive vessels) at VTI, compared to NIS (p=0.018). Arteries and veins at the VTI were mostly surrounded by preserved cardiomyocytes (figure 1). Viable cardiomyocytes and fibroblasts at VTI displayed higher density of Cx43 and Cx40, respectively, compared to those at NIS (p=0.022 and p=0.004, respectively), despite no differences in cTnI, SERCA2 and Vimentin expression (figure 2). Conclusion The VTI exhibits distinctive tissue features compared to NIS. Unique electrophysiological properties of the VTI may be driven by increased adipocytic deposition, vascular density and Cx43/Cx40 expression, as well as lower presence of Collagen III and Collagen Volume Fraction.

Preinterventional quantification of dense scar or borderline zone in patients undergoing ventricular tachycardia ablation

Abstract Funding Acknowledgements Type of funding sources: None. Introduction This study sought to examine the prognostic role of quantifying areas of interest in preinterventional cardiac magnetic resonance (CMR) in patients with structural heart disease (SHD) referred for ablation of ventricular tachycardia (VT). Background The role of preinterventional CMR for the identification of scar areas, borderline zones and reentry channels in the ventricles has been well established. Whether the burden of dense scar or borderline tissue has a prognostic impact on the acute and the long-term ablation outcome in SHD patients is disputed. Methods and results We investigated 185 patients with SHD undergoing preinterventional CMR prior to VT-ablation. 38 patients were excluded because of poor imaging quality, leaving a cohort of 147 patients with positive late enhancement (LGE) imaging (mean age 62 years, 47% non-ischemic cardiomyopathy, mean left ventricle ejection fraction 38%, 96% with implanted ICD). The cohort was divided in ischemic (ICM) and non-ischemic (NICM) cardiomyopathy group and the results regarding burden of overall scar tissue, dense scar, borderline zone, as well as clinical and procedural characteristics, acute and long-term results of the two groups were compared. The ICM patients had more advanced NYHA stadium (p = 0.046), reduced left ventricular ejection fraction (LV-EF, p <0.001) and higher left ventricular enddiastolic volume (LVEDV, p <0.001). The NICM patients were more often under antiarrhythmic therapy (p = 0.005) and underwent more frequently epicardial ablation (p <0.001). Although the overall scar burden war higher in ICM patients (p <0.001), the groups showed no significant difference in borderline zone burden (p = 0.580). Furthermore, the two groups had similar results in number of inducible VTs (p = 0.054) and VT inducibility at the end of the procedure (p = 0.121). Nevertheless, the NICM group underwent overall more ablation procedures during the 19-month follow up (p = 0.023). Both groups showed similar results regarding assist device implantation, heart transplantation or death until the end of the follow up (p = 0.192). Conclusion While quantification of the scar tissue and the borderline zone is feasible in ICD patients with SHD, the scar or the borderline zone burden were not predictive of the VT ablation outcome.

Microelectrode voltage mapping for substrate assessment in catheter ablation of ventricular tachycardia: a dual-center experience

Abstract Funding Acknowledgements Type of funding sources: None. Background The assessment of the ventricular myocardial substrate critically depends on the size of mapping electrodes, their orientation with respect to wavefront propagation, and interelectrode distance. Objective we conducted a dual-center study to evaluate the impact of microelectrode mapping in patients undergoing catheter ablation (CA) of ventricular tachycardia (VT). Methods We included 21 consecutive patients (median age, 68 [12], 95% male) with structural heart disease undergoing CA for electrical storm (n=14) or recurrent VT (n=7) using the QDOT Micro catheter and a multipolar catheter (PentaRay, n=9). The associations of peak-to-peak maximum standard bipolar (BVc) and minibipolar (PentaRay, BVp) with microbipolar (BVμMax) voltages were respectively tested in sinus rhythm with mixed effect models. Furthermore, we compared the features of standard bipolar (BE) and microbipolar (μBE) electrograms in sinus rhythm at sites of termination with radiofrequency energy. Results BVμMax was moderately associated with both BVc (β=0.85, p<0.01) and BVp (β=0.56, p<0.01). BVμMax was 0.98 (95% CI, 0.93-1.04, p<0.01) mV larger than corresponding BVc, and 0.27 (95% CI, 0.16-0.37, p<0.01) mV larger than matching BVp in sinus rhythm, with higher percentage differences in low voltage regions, leading to smaller endocardial dense scar (2.3 [2.7] vs. 12.1 [17] cm2, p<0.01) and border zone (3.2 [7.4] vs. 4.8 [20.1] cm2, p=0.03) regions in microbipolar maps compared to standard bipolar maps. At sites of VT termination (n=14), μBE were of higher amplitude (0.9 [0.8] mV versus 0.4 [0.2] mV, p<0.01), longer duration (117 [66] ms versus 74 [38] ms, p<0.01), and with greater number of peaks (4 [2] versus 2 [1], p<0.01) in sinus rhythm compared to BE. Conclusions Microelectrode mapping is more sensitive than standard bipolar mapping in the identification of viable myocytes in SR, and may facilitate recognition of targets for catheter ablation.

Arrhythmogenic Right Ventricular Cardiomyopathy With Extensive Abnormal Substrate: Is Isolation Possible?

BackgroundIn arrhythmogenic right ventricular cardiomyopathy (ARVC) patients with extensive right ventricular free wall (RVFW) abnormal substrate, large-area homogenization with combined epicardial and endocardial approach is time consuming and often inadequate for modification. ObjectivesThis study aimed to explore the feasibility and efficacy of RVFW abnormal substrate isolation in such patients to control ventricular tachycardia (VT). MethodsEight consecutive ARVC patients with VT who had extensive abnormal RVFW substrate were included. VT induction was performed before substrate mapping and modification. Detailed voltage mapping was done during sinus rhythm. A circumferential linear lesion was deployed along the border zone of low-voltage area on the RVFW to achieve electrical isolation. Other small areas with fractionated or late potentials were further homogenized. ResultsAll 8 patients had RVFW endocardial low-voltage area. The entire RV low-voltage area was 113.8 ± 84.1 cm2 (49.6% ± 29.8%) and the dense scar was 59.6 ± 39.8 cm2 (25.0% ± 14.1%). Electrical isolation of abnormal substrate was achieved in 5 of 8 (62.5%) patients via endocardial approach alone and 3 of 8 (37.5%) patients via a combination of endocardial and epicardial approach. Electrical isolation was verified by slow automaticity (5 of 8, 62.5%) or RV noncapture (3 of 8, 37.5%) during high-output pacing inside the encircled area. VTs were induced in 6 patients before ablation, and all patients were rendered noninducible after ablation. During a median follow-up of 43 months (range: 24-53 months), 7 of 8 (87.5%) patients remained free of sustained VT. ConclusionsElectrical isolation of RVFW is feasible and can be the option in ARVC patients with extensive abnormal substrate.

Endoscopic laryngotracheoplasty (Maddern procedure) for idiopathic subglottic stenosis

•Endoscopic laryngotracheoplasty (Maddern procedure) is a scarless and durable therapy for iSGS. •Maddern procedure avoids risks associated with cricotracheal resection. •Surgery includes endoscopic scar excision with placement of a split-thickness skin graft and stent. •Exclusion criteria are dense posterior scar, glottic involvement, and long segment stenosis. Endoscopic laryngotracheoplasty, also known as the “Maddern procedure,” is a definitive endoscopic treatment for subglottic stenosis via a scarless approach. This technique focuses on endoscopic resection of the subglottic mucosa and scar without disturbing the cartilaginous framework of the larynx and trachea. A split-thickness skin graft is then used to reline the tracheal lumen, in order to facilitate healing and avoid scar recurrence. The skin graft is held in place by a silastic stent. This article describes the surgical technique of endoscopic laryngotracheoplasty, as well as peri-operative considerations and possible complications. Endoscopic laryngotracheoplasty, also known as the “Maddern procedure,” is a definitive endoscopic treatment for subglottic stenosis via a scarless approach. This technique focuses on endoscopic resection of the subglottic mucosa and scar without disturbing the cartilaginous framework of the larynx and trachea. A split-thickness skin graft is then used to reline the tracheal lumen, in order to facilitate healing and avoid scar recurrence. The skin graft is held in place by a silastic stent. This article describes the surgical technique of endoscopic laryngotracheoplasty, as well as peri-operative considerations and possible complications.

PO-05-069 ASSOCIATION BETWEEN LEFT VENTRICULAR WALL-THICKNESS BY CT AND ENDOCARDIAL VOLTAGE POTENTIALS IN PATIENTS WITH ISCHEMIC CARDIOMYOPATHY UNDERGOING VT ABLATION

Although cardiac magnetic resonance (CMR) is the gold standard for planning ventricular tachycardia (VT) ablation, its accuracy is hindered in patients with implanted cardiac defibrillators (ICD) and resynchronization therapy (CRT). Cardiac computed tomography (CT) has emerged as an alternative for ablation planning in these patients. This pilot study aimed to evaluate the relationship between wall thickness (WT) on CT and voltage of electrical potentials on endocardial electroanatomic mapping (EAM) in patients with ischemic cardiomyopathy. Single centre retrospective study enrolling consecutive patients with ischemic cardiomyopathy referred for endocardial VT ablation that underwent cardiac CT for procedure planning since 2021. Patients were excluded if EAM had < 1000 data points. ADAS 3D® software was used to analyse CT images, automatically segmenting the left ventricle (LV) into the 17 American Heart Association segments and calculating end-diastolic WT for each one. Four standardized views (anterior-posterior, posterior-anterior, superior, and inferior) of the segmented LV on ADAS 3D® were used to aid in manual segmentation of the EAM. The endocardial voltage maps were created using CARTO3® software (Biosense Webster®). For each patient, EAM was interpreted to create 2 different bulls’ eye maps, according to the presence or absence of bipolar potentials < 0.5 (dense scar) or < 1.5mV (low voltage). Only segments with >20% extension of low bipolar voltage were considered as altered. We included a cohort of 8 patients (mean age 67±12 years, 87.5% male, median LVEF of 32% [IQR 25-49]). All but one patient had an implanted cardiac device (6 ICD, 1 CRT-D). Cardiac CT was performed 1 day (IQR 0-2) before the ablation. Overall, 136 segments were analysed, 8 of which did not have voltage information. Of the remaining 128, 51 (39.8%) had dense scar and 57 (41.9%) had low voltage. There was a good correlation between mean WT and the presence or absence of both dense scar (area under de curve (AUC) 0.799, p<0.001) and low voltage (AUC 0.838, p<0.001) in each LV segment. WT measured by CT appears to have a strong correlation with dense scar and low voltage in EAM in patients with ischemic cardiomyopathy undergoing VT ablation. This technique may be useful to plan interventions in patients in whom CMR is not feasible.

PO-05-002 ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY WITH EXTENSIVE ABNORMAL SUBSTRATE: IS ISOLATION POSSIBLE?

In arrhythmogenic right ventricular cardiomyopathy (ARVC) patients with extensive right ventricular free wall (RVFW) abnormal substrate, large area homogenization with combined epicardial and endocardial approach is time consuming and often inadequate for modification. We aim to explore the feasibility and efficacy of RVFW abnormal substrate isolation in such patients to control ventricular tachycardia (VT). Eight consecutive ARVC patients with VT who had extensive abnormal RVFW substrate were included. VT induction was performed before substrate mapping and modification. Detailed voltage mapping was done during sinus rhythm. A circumferential linear lesion was deployed along the border zone of low-voltage-area on the RVFW to achieve electrical isolation. Other small areas with fractionated or late potentials were further homogenized. All eight patients had extensive RV endocardial low-voltage-area (113.8 ± 84.1 cm2, 49.6 ± 29.8%) and dense scar (59.6 ± 39.8 cm2, 25.0 ± 14.1%). Electrical isolation of abnormal substrate was achieved in 5/8 (62.5%) patients via endocardial approach alone and 3/8 (37.5%) patients via a combination of endocardial and epicardial approach. Electrical isolation was verified by slow automaticity (5/8, 62.5%) or RV non-capture (3/8, 37.5%) during high output pacing inside the encircled area. VTs were induced in 6 patients before ablation and all patients rendered non-inducible after ablation. During a median follow-up of 43 months (range 24-53), 7/8 (87. 5%) patients remained free of sustained VT. Electrical isolation of RVFW is feasible and effective in ARVC patients with extensive abnormal substrate and is associated with excellent long-term rhythm control.

PO-01-084 HIDING IN PLAIN SIGHT

Substrate based scar modification requires accurate detection and characterization of myocardial scar in sinus rhythm or using different wavefronts of activation. Mapping during ventricular tachycardia can be performed only in about 30% to 40% cases. We describe a challenging case of scar VT with discrepancy in the delineation of scar between voltage mapping and cardiac MRI and the role of Decremental Evoked Potential Mapping as a guide to a more focussed ablation in such circumstances. N/A N/A 56 year diabetic female status post Coronary artery bypass grafting in 2016 and moderate left ventricular dysfunction with recurrent episodes of hemodynamically unstable ventricular tachycardia and patient's refusal for ICD was evaluated and cardiac MRI revealed subendocardial scar in the anterior wall and patent grafts on coronary angiogram. Patient was taken up for 3D mapping and ablation using 3.5 mm tip non force sensing unidirectional irrigation ablation catheter.In view of hemodynamically unstable VT, activation mapping was not possible, hence substrate mapping was planned. Endocardial bipolar voltage mapping didnot delineate any scar in sinus rhythm and after changing the wavefront of activation to right ventricular paced rhythm. Unipolar voltage map didnot show any scar. While mapping the anterior wall , abnormal local electrograms were seen superimposed into the far field electrograms. To do a foccussed ablation we applied the concept of Decremental Evoked Potential Mapping and identified the slow conduction zone - the most critical component of the scar for initiation and maintainence of re-entry. We identified and ablated only the points with abnormal local electrograms with absolute value of decrement more than 10 ms as part of slow conduction zone. Post ablation, VT was not inducible despite induction protocol using triple extrastimuli from two different sites. Activation mapping is not possible in hemodynamically unstable VT. Substrate based mapping needs accurate delineation of myocardial scar. As the 3D mapping system is an automated system and annotates only the largest amplitude signals for color coded voltage mapping, in cases without dense scar, voltage mapping doesnot reliably identify and delineate the scar when compared to cardiac MRI, particularly with a larger tip diameter ablation catheter. Novel mapping techniques like Decremental Evoked Potential Mapping enable limited ablation in such cases.

PO-04-121 PERSONALIZED VOLTAGE THRESHOLDS IN THE ERA OF HIGH-DENSITY MAPPING AND IMAGING

Substrate-based ventricular tachycardia (VT) methods have been developed to identify ablation target sites during sinus rhythm, especially to guide ablation when VT is non-inducible or hemodynamic non tolerated. Voltage mapping has been one of the main strategies to define the abnormal arrhythmic substrate due to the potential capability of distinguish dense scar, border zone (BZ) and healthy tissue, delimiting the conducting channels potentially responsible for the clinical VT. Thresholds of 0.5-1.5mV using bipolar catheters were proposed initially for ischemic and later for non-ischemic patients being validated in a porcine model with transmural scar. Important limitations have been addressed, including a low correlation between these voltage channels and CMR channels or VT channels. To define new voltage thresholds for high density maps guided by CMR. All consecutive patients with scar-related VT undergoing ablation after CMR (October 2018-December 2020) were included. Voltage maps were compared side by side with CMR. First, the lower threshold was adjusted and after that, the upper threshold was set in order to get a voltage map the most resembling as possible to CMR. The characteristics of the tissue (dense scar, BZ or healthy tissue) of those areas identified as deceleration zones (DZ) in the isochronal late activation maps were recorded. Finally, if VT activation mapping was performed during the case, the concordance between the VT induced circuit and the voltage channels was analyzed. During the study period, 33 patients were included (medium age 66.5±11.1 years; 93.9% male; 78.8% ischemic heart disease, mean ejection fraction of 33.9±7.2). Adjusted cutoff voltages that better match with CMR images were 0.51±0.32 (0.14-1.68) and 1.81±0.71 (0.7-3.21). Overall, 53 DZs were observed, being 75.5% of them identified as BZ using personalized voltage thresholds vs. 44.2% with the standard cutoffs, p=0002. Of the 32 VT isthmus detected during the ablation procedures, 71.9% correlated with a voltage channel using adjusted thresholds vs. 24.4% with the standard ones, p=0.0006. No significant differences were observed between ischemic and non-ischemic patients. Personalized voltage thresholds based in CMR images enable a better identification of the substrate and a higher correlation between voltage channels and VT isthmus.

CE-452773-3 ASSESSMENT OF OPTIMAL VOLTAGE THRESHOLDS FOR VENTRICULAR SCAR SUBSTRATE CHARACTERIZATION

Despite the advancement in technology, historic cut-offs of <0.5mV for dense scar and 0.5-1.5mV for scar borderzone continue to be used in contemporary electrophysiology. Modern multipolar mapping catheters employ smaller electrodes and interelectrode spacing that theoretically allows for mapping with increased resolution and reduced far-field electrogram (EGM) component. We aimed to assess the optimal voltage cut-offs for ventricular scar substrate characterization using HD Grid multipolar mapping catheter against cardiac MRI-derived scar. We compared optimal voltage cut-offs using conventional bipolar sampling,Best Duplicate Algorithm and HD wave solution plus best duplicate algorithm on. A multicenter study of 33 patients with ischaemic heart disease undergoing VT ablation. Substrate mapping was performed using the high-density HD-grid multipolar mapping catheter. Bipolar voltage maps were co-registered with cardiac MRI/CT obtained before the procedure to assess the voltage characteristics of the scar defined by the image. Pre-procedure contrast-enhanced MRI data were analysed using ADAS software (Galgo medical). Data points were collected in regions of scar during (1) HD wave mapping with best duplicate algorithm on(Waveon), (2) Mapping with HD wave off and best duplicate on (Waveoff) and (3) with conventional bipolar mapping (Alloff). 29,633 voltage points were analyzed and compared to their location with the fused MRI voltage map. The median bipolar voltage for regions of dense MRI/CT scar using (Waveon) HD wave solution and best duplicate algorithm was 0.24mV (IQR 0.12 – 0.43). The median voltage with (Waveoff) HD wave off was 0.29mV (0.15 – 0.45). The median voltage with (Alloff) HD wave off and best duplicate off was 0.32mV (0.19 – 0.5). ROC analysis using AUC suggested the optimal cut-off for endocardial dense scar using (Waveon) HD wave mapping and best duplicate algorithm was 0.31mV (sensitivity: 69.6%, specificity: 60.74%) (Figure), (Waveoff) cut-off with the best duplicate and without the HD wave mapping was 0.34mV (sensitivity: 88.0%, specificity: 42.96%) and (Alloff) without wave mapping or best duplication was 0.36mV (sensitivity: 84%, specificity: 52%). Ventricular substrate characterization with newer mapping technology using narrow electrode spacing and smaller electrode sizes suggests that traditional voltage cut-offs may need revision. The optimal cut-off for dense scar delineation with the HD Grid and wave technology is 0.31mV.

PO-04-200 ANALYSIS OF RELATIONSHIP BETWEEN PACING SITE AND EXIT SITE IN REGIONS WITH STIMULUS-QRS DELAY AND IMAGING DEFINED MYOCARDIAL FIBROSIS

Delay between ventricular pacing stimulus and QRS onset (S-QRS delay), often seen in regions of myocardial fibrosis, suggests conduction along a protected channel which often represents substrate for re-entrant arrhythmias. 1. To analyze the relationship between pacing stimulus site and myocardial exit site in regions with stimulus-QRS delay and imaging-defined myocardial fibrosis undergoing VT ablation and 2. To consider conduction time between these two locations. Six patients with structural heart disease who underwent VT catheter ablation with pre-procedural cardiac CT image processing (InHeart Models (Pessac, France)) and evidence of late-iodine enhancement were included. CT images were registered with electroanatomic mapping. At pacing sites with S-QRS delay >40 msec, catheter location was compared to the exit site, predicted using a previously validated algorithm (RAPID-VT). Imputed conduction velocity (CV) between stimulus site and exit site was calculated (stim-QRS time/Euclidian distance). Stimulus to QRS delay in regions of imaging derived fibrosis ranged 40 to 291.4 ms; At 9 pacing sites, multiple QRS morphologies were generated. Imputed CV was reduced in dense scar and borderzone compared to values seen in healthy myocardium and varied between 0.16 and 0.65 m/s. These results may under-estimate true tissue CV given complex routes between pacing and exit sites. In the same region, following delivery of RF, mean imputed CV was reduced, raising the possibility that conduction was altered, potentially diverted along a different path (0.21m/s vs 0.14m/s, p=0.024). Myocardial fibrosis defined on CT may be associated with slowed conduction through protected channels. Delivery of RF increases conduction time and results in different exit sites following pacing, indicating multiple and likely complex routes of conduction in regions of imaging-defined fibrosis. Visualization of predicted exit sites in real time could help focus RF to interrupt these conduction paths.Tabled 1Patient #Stim to QRS onset (ms)Imputed conduction velocity (m/s)166.8±15.20.18±0.09241.0±1.50.65±0.08351.0±9.10.30±0.10460.6±11.50.20±0.105103.7±0.160.16±0.10674.3±13.60.19±0.02 Open table in a new tab

CE-452773-4 ANATOMY OF THE ISTHMUS: UNRAVELING TISSUE COMPOSITION OF VENTRICULAR TACHYCARDIA DIASTOLIC PATHWAY

Unequal tissue composition of post-myocardial infarction (MI) scar (viable myocardium, fibrosis, fatty infiltration) leads to heterogeneous conduction properties and excitability. The presence of a protected diastolic, slow-conducting pathway (isthmus) is the electrophysiological landmark of post-MI reentrant ventricular tachycardia (VT). Contemporary histological studies evaluating the tissue features needed for slow, protected conduction during VT are lacking. To characterize tissue composition singularities of confirmed VT isthmuses (VTI) in a chronic MI swine model, and to compare it to non-isthmus scar (NIS). One-month after a non-reperfused anterior MI, 9 Landrace X Large White pigs (4 female; 33.6±2.2 Kg) with inducible VT underwent high-density activation mapping to define the diastolic corridor. VTI was defined as part of the diastolic pathway exhibiting mid-diastolic potentials. Discrete radiofrequency applications were delivered in the vicinity of the VTI and used as tissue landmarks to guide the ex vivo isthmus localization. Tissue transverse samples (5 mm) from the labelled VTI and NIS were obtained for further histological and immunohistochemical analysis. Dense scar and border zones were analyzed. Compared to NIS, border zone of VTI showed significantly higher fatty infiltration (p=0.016) and dense scar displayed less Collagen I (p=0.053), Collagen III (p=0.043), and Collagen Volume Fraction (p=0.027), without differences in the overall fibrotic deposition (P=0.119). Immunohistochemical studies revealed greater vascular density (Isolectin B4-positive vessels) at VTI, compared to NIS (p=0.018). Arteries and veins at the VTI were mostly surrounded by preserved cardiomyocytes (figure). Viable cardiomyocytes and fibroblasts at VTI displayed higher density of Cx43 and Cx40, respectively, compared to those at NIS (p=0.022 and p=0.004, respectively), despite no differences in cTnI, SERCA2 and Vimentin expression. The VTI exhibits distinctive tissue features compared to NIS. Unique electrophysiological properties of the VTI may be driven by increased adipocytic deposition, vascular density and Cx43/Cx40 expression, as well as lower presence of Collagen III and Collagen Volume Fraction.

PO-04-230 IMPROVED VISUALIZATION OF LOW AMPLITUDE LATE POTENTIALS WITH VT SUBSTRATE MAPPING USING A NOVEL EP RECORDING SYSTEM

Accurate identification of low-voltage electrograms (EGMs) suffer from artifacts that often interfere with physiological signals in the <0.1-0.5mV range. For substrate based ablation of ventricular tachycardia (VT), dense scar is defined as regions of myocardium with EGM amplitudes below 0.5 mV. Within these regions, current EP recording systems can fail at identifying low-voltage late potentials that are effective targets of ablation therapy. More recently, new EP amplifiers designed specifically to reduce the impact of interference on the fidelity of signals have been introduced. This study used a novel EP recording system (ECGenius System, CathVision, Copenhagen, DK) to identify low amplitude (<0.5mV) late potentials in regions of scar, and quantify their characteristics in a head-head comparison to a standard recording system (LabSystem Pro, Boston Scientific, MA). We collected recordings in parallel from four patients (30-250 Hz bipolar recording bandwidth) referred to our center for an EP study and ablation for VT. We performed substrate mapping during sinus rhythm with a standard 4mm irrigated ablation catheter (SmartTouch, Biosense Webster, Diamond Bar, CA) and a multi-spline mapping catheter (PentaRay, Biosense Webster). In regions of dense scar (< 0.5 mV, delineated with 3-D electroanatomical mapping) we identified late potentials that were above the baseline noise level of the CathVision system that were otherwise not clearly visible with the LabSystem Pro system. In four patients we identified fourteen sites with late potentials (110 beats) that were only identified with the CathVision System (see figure). The average amplitude of the late signals was 0.079 +/- 0.063 mV, which was above the baseline mean noise of 0.008 mV (range 0.006 to 0.015 mV). In contrast, the baseline mean noise of the LabSystem Pro was 0.060 mV (range 0.040 to 0.090 mV). The mean delay of the late potentials (after the start of the surface ECG QRS) was 377ms (range 198 to 470ms). Improved visualization of low voltage EGMs and late potentials can improve upon substrate-based ablation of ischemic VT. With a novel, and state-of-the art recording amplifier, we demonstrate an improved ability to detect clinically relevant sites for ablation that were not visible with a standard recording system. This technology could improve upon current ablation strategies, and may be particularly useful in the current era of micro-electrodes and relatively smaller recording voltages.

PO-04-038 ULTRA HIGH DENSITY MAPPING TO IDENTIFY MICRO-REENTRANT LEFT ATRIAL FLUTTER CIRCUITS WITHIN LOW BIPOLAR VOLTAGE REGIONS: A CASE SERIES

Micro-reentrant (MR) atrial flutter (AFL) circuits may not be evident with standard bipolar or multipolar mapping. We report 3 cases of left atrial (LA) AFL where HD Grid + Omnipolar technology (Ensite X, Abbott) revealed MR circuits within an area of scar as noted by standard multipolar mapping. N/A Three patients with prior LA ablation presented with symptomatic AFL. LA mapping was done using the Ensite X system in Voxel mode. Bipolar voltage cutoff was set at 0.3 to 0.05 mV. A 65-year-old presented with AFL CL of 335 ms. Mapping with an Advisor spiral showed a large posterior wall scar and no AFL circuit in LA or RA. Remapping with HD Grid identified a 12 mm MR circuit with entire CL in the low LA posterior wall which showed dense scar by spiral mapping (Figure 1A). A 59-year-old male presented with AFL CL of 340 ms with proximal to distal CS activation. HD grid mapping identified a 21 mm MR circuit in the mid LA posterior with fractionated mid-diastolic electrograms (Figure 1B and 1C). Third patient was a 54-year-old male who had a MR circuit in the posterolateral mitral annulus, otherwise noted as scar by bipolar mapping. Successful ablation sites in all 3 cases did not have an identifiable bipolar electrogram on ablation catheter (<0.05 mV, Figure 1 D). Low voltage cut off during HD mapping was manually adjusted and had to be lowered to 0.04 to identify the circuit in all cases. This case series demonstrates that ultra high-density mapping with HD Grid + Omnipolar technology, with dynamic adjustment of low voltage threshold, enables identification of MR AFL circuits, leading to successful ablation, where critical isthmi were not identified by standard bipolar or multipolar mapping.

Microelectrode voltage mapping for substrate assessment in catheter ablation of ventricular tachycardia: A dual-center experience.

The assessment of the ventricular myocardial substrate critically depends on the size of mapping electrodes, their orientation with respect to wavefront propagation, and interelectrode distance. We conducted a dual-center study to evaluate the impact of microelectrode mapping in patients undergoing catheter ablation (CA) of ventricular tachycardia (VT). We included 21 consecutive patients (median age, 68 [12], 95% male) with structural heart disease undergoing CA for electrical storm (n = 14) or recurrent VT (n = 7) using the QDOT Micro catheter and a multipolar catheter (PentaRay, n = 9). The associations of peak-to-peak maximum standard bipolar (BVc ) and minibipolar (PentaRay, BVp ) with microbipolar (BVμMax ) voltages were respectively tested in sinus rhythm with mixed effect models. Furthermore, we compared the features of standard bipolar (BE) and microbipolar (μBE) electrograms in sinus rhythm at sites of termination with radiofrequency energy. BVμMax was moderately associated with both BVc (β = .85, p < .01) and BVp (β = .56, p < .01). BVμMax was 0.98 (95% CI: 0.93-1.04, p < .01) mV larger than corresponding BVc , and 0.27 (95% CI: 0.16-0.37, p < .01) mV larger than matching BVp in sinus rhythm, with higher percentage differences in low voltage regions, leading to smaller endocardial dense scar (2.3 [2.7] vs. 12.1 [17] cm2 , p < .01) and border zone (3.2 [7.4] vs. 4.8 [20.1] cm2 , p = .03) regions in microbipolar maps compared to standard bipolar maps. Late potentials areas were nonsignificantly greater in microelectrode maps, compared to standard electrode maps. At sites of VT termination (n = 14), μBE were of higher amplitude (0.9 [0.8] vs. 0.4 [0.2] mV, p < .01), longer duration (117 [66] vs. 74 [38] ms, p < .01), and with greater number of peaks (4 [2] vs. 2 [1], p < .01) in sinus rhythm compared to BE. microelectrode mapping is more sensitive than standard bipolar mapping in the identification of viable myocytes in SR, and may facilitate recognition of targets for CA.

Myoscaffolds reveal laminin scarring is detrimental for stem cell function while sarcospan induces compensatory fibrosis

We developed an on-slide decellularization approach to generate acellular extracellular matrix (ECM) myoscaffolds that can be repopulated with various cell types to interrogate cell-ECM interactions. Using this platform, we investigated whether fibrotic ECM scarring affected human skeletal muscle progenitor cell (SMPC) functions that are essential for myoregeneration. SMPCs exhibited robust adhesion, motility, and differentiation on healthy muscle-derived myoscaffolds. All SPMC interactions with fibrotic myoscaffolds from dystrophic muscle were severely blunted including reduced motility rate and migration. Furthermore, SMPCs were unable to remodel laminin dense fibrotic scars within diseased myoscaffolds. Proteomics and structural analysis revealed that excessive collagen deposition alone is not pathological, and can be compensatory, as revealed by overexpression of sarcospan and its associated ECM receptors in dystrophic muscle. Our in vivo data also supported that ECM remodeling is important for SMPC engraftment and that fibrotic scars may represent one barrier to efficient cell therapy.

In vivo pulsed-field ablation in healthy vs. chronically infarcted ventricular myocardium: biophysical and histologic characterization.

Data on ventricular pulsed-field ablation (PFA) are sparse in the setting of chronic myocardial infarction (MI). The objective of this study was to compare the biophysical and histopathologic characteristics of PFA in healthy and MI swine ventricular myocardium. Myocardial infarction swine (n = 8) underwent coronary balloon occlusion and survived for 30 days. We then performed endocardial unipolar, biphasic PFA of the MI border zone and a dense scar with electroanatomic mapping and using an irrigated contact force (CF)-sensing catheter with the CENTAURI System (Galaxy Medical). Lesion and biophysical characteristics were compared with three controls: MI swine undergoing thermal ablation, MI swine undergoing no ablation, and healthy swine undergoing similar PFA applications that included linear lesion sets. Tissues were systematically assessed by gross pathology utilizing 2,3,5-triphenyl-2H-tetrazolium chloride staining and histologically with haematoxylin and eosin and trichrome. Pulsed-field ablation in healthy myocardium generated well-demarcated ellipsoid lesions (7.2 ± 2.1 mm depth) with contraction band necrosis and myocytolysis. Pulsed-field ablation in MI demonstrated slightly smaller lesions (depth 5.3 ± 1.9 mm, P = 0.0002), and lesions infiltrated into the irregular scar border, resulting in contraction band necrosis and myocytolysis of surviving myocytes and extending to the epicardial border of the scar. Coagulative necrosis was present in 75% of thermal ablation controls but only in 16% of PFA lesions. Linear PFA resulted in contiguous linear lesions with no gaps in gross pathology. Neither CF nor local R-wave amplitude reduction correlated with lesion size. Pulsed-field ablation of a heterogeneous chronic MI scar effectively ablates surviving myocytes within and beyond the scar, demonstrating promise for the clinical ablation of scar-mediated ventricular arrhythmias.

MiR-155-5p Aggravated Astrocyte Activation and Glial Scarring in a Spinal Cord Injury Model by Inhibiting Ndfip1 Expression and PTEN Nuclear Translocation

Central nervous injury and regeneration repair have always been a hot and difficult scientific questions in neuroscience, such as spinal cord injury (SCI) caused by a traffic accident, fall injury, and war. After SCI, astrocytes further migrate to the injured area and form dense glial scar through proliferation, which not only limits the infiltration of inflammatory cells but also affects axon regeneration. We aim to explore the effect and underlying mechanism of miR-155-5p overexpression promoted astrocyte activation and glial scarring in an SCI model. MiR-155-5p mimic (50 or 100 nm) was used to transfect CTX-TNA2 rat brain primary astrocyte cell line. MiR-155-5p antagonist and miR-155-5p agomir were performed to treat SCI rats. MiR-155-5p mimic dose-dependently promoted astrocyte proliferation, and inhibited cell apoptosis. MiR-155-5p overexpression inhibited nuclear PTEN expression by targeting Nedd4 family interacting protein 1 (Ndfip1). Ndfip1 overexpression reversed astrocyte activation which was induced by miR-155-5p mimic. Meanwhile, Ndfip1 overexpression abolished the inhibition effect of miR-155-5p mimic on PTEN nuclear translocation. In vivo, miR-155-5p silencing improved SCI rat locomotor function and promoted astrocyte activation and glial scar formation. And miR-155-5p overexpression showed the opposite results. MiR-155-5p aggravated astrocyte activation and glial scarring in a SCI model by targeting Ndfip1 expression and inhibiting PTEN nuclear translocation. These findings have ramifications for the development of miRNAs as SCI therapeutics.

Ureteral Complications during Surgery

Historically, ureteral complications during surgery have been occurring since the earliest performances of major abdominal or pelvic surgery. In the early 1960s, few diagnostic techniques were available to diagnose ureteral injury and determine the subsequent timely treatment required. Illustrations from two different time periods of possible operative ureteral injury, ligation, or transection following major complicated surgical procedures are presented, along with the diagnostic and therapeutic approach currently followed. The first individual had apparently sustained a ureteral injury during a prior surgical procedure, which, with limited diagnostic options, was not recognized until she visited us years later—as was the case for many early ureteral injuries. Major abdominal or pelvic surgery may be extensive and complicated, especially when dense fibrosis, scarring, and benign or malignant mass formation are present. Unfortunately, surgical complications, including bleeding and ureteral concerns, may develop during these extensive procedures. A more recent patient underwent major, life-threatening retroperitoneal surgery due to a chronic aortoenteric fistula (17 months total preoperative hospitalization elsewhere), during which the left ureter was transected. In our second patient, recognition and correction of the ureteral transection during the aortic surgery, upon completion of the aortic repair, prevented a potential major renal complication. The timely diagnosis of the operative ureteral injury and the repair prior to wound closure prevented major postoperative complications. As some physicians believe that surgically induced ureteral injuries are increasing in frequency, we present this report to enhance awareness of the possibility of injury and the potential value of recognition prior to abdominal closure. In addition, current operative and postoperative strategies available to identify and reduce potential ureteral injury complications when they occur are discussed.

Man with chest tightness and diaphoresis.

A 67-year-old male patient with chest tightness and diaphoresis presented to the emergency department 1 hour before admission. The patient had a myocardial infarction with stent implantation history for the left circumflex and right coronary arteries 1 month ago. On arrival, his blood pressure was 85/52 mmHg; pulse rate was 166 bpm, and temperature was 35.6°C. A 12-lead electrocardiogram (ECG) was performed immediately (Figure 1). The emergency physician also performed echocardiography (Figure 2) (Videos 1 and 2). Ventricular tachycardia secondary to a postinfarction left ventricular aneurysm. The patient underwent a 100J synchronized cardioversion and the electrocardiogram returned to sinus rhythm (Figure 3). Continuous intravenous amiodarone was administered. He was admitted to the intensive care unit (ICU), where a cardiologist performed successful radiofrequency catheter ablation. Coronary artery disease is the most common cause of left ventricular aneurysms. Echocardiography is the preferred diagnostic method for left ventricular aneurysms after cardiac events.1 The aneurysm's thin-walled dyskinetic or akinetic segments may be composed of dense scars with viable myocardium channels. It may be the site of origin for ventricular tachycardia.2 Antiarrhythmic drugs and radiofrequency catheter ablation are frequently used to reduce ventricular tachycardia frequency and shocks in patients with implantable cardioverter-defibrillators.3