Scar Region Research Articles

UltraSOUND-based characterization of ventricular tachycardia SCAR and arrhythmogenic substrate: The SOUNDSCAR study

BackgroundIntracardiac echocardiography (ICE) represents a valuable image integration technique, with the unique advantage of dynamic real-time scar characterization. ObjectivesThe goals of this study were to assess the correlation between ICE-defined and electroanatomic mapping (EAM)–defined scar in patients with ischemic cardiomyopathy and to define the outcomes of ICE-guided ventricular tachycardia (VT) ablation. MethodsThirty-eight patients with ischemic cardiomyopathy (SOUNDSCAR cohort) underwent full left ventricular (LV) ICE imaging and EAM. ICE-defined scar parameters (end-diastolic and end-systolic wall diameter [EDWD and ESWD], end-systolic wall thickening [percentage difference between EDWD and ESWD with respect to EDWD], slope [end-diastole to end-systole wall thickening], and American Heart Association wall motion scoring) were correlated with EAM-defined scar (voltage <1.5 mV). In a separate cohort (n = 21), outcomes of an ICE-guided VT ablation approach (EAM focused to ICE-defined scar regions) were compared with those of conventional ablation (full left ventricular mapping with EAM only; n = 21). ResultsIn the 38 SOUNDSCAR patients (mean age 67 ± 11 years; 35 male [92%]; left ventricular ejection fraction 31% ± 10%; 2474 ICE segments; 524 ICE sectors), all ICE-defined parameters strongly predicted EAM-defined scar (area under the curve: American Heart Association score 0.873; ESWD 0.880; EDWD 0.827; slope 0.855; percentage difference between EDWD and ESWD with respect to EDWD, 0.851). All ICE-defined parameters had large effect sizes for predicting EAM-defined scar (logistic regression, P < .001). A detailed topographical comparison of ICE-defined (slope) and EAM-defined scar was possible in 25 patients and demonstrated 88% ± 10% overlap. Compared with conventional VT ablation, ICE-guided ablation was associated with shorter procedure times and comparable VT-free survival (ICE-guided vs conventional: procedure time 240 ± 20 minutes vs 298 ± 39 minutes; P < .001; VT recurrence 3 [14%] vs 7 [31%]; P = .19). ConclusionICE-defined scar demonstrates a strong correlation with EAM-defined scar. ICE-guided VT ablation is associated with enhanced procedural efficiency.

Automated spatially targeted optical micro proteomics identifies fibroblast- and macrophage-specific regulation of myocardial infarction scar maturation in rats

Myocardial infarction (MI) results from occlusion of blood supply to the heart muscle causing death of cardiac muscle cells. Following myocardial infarction (MI), extracellular matrix deposition and scar formation mechanically stabilize the injured heart as damaged myocytes undergo necrosis and removal. Fibroblasts and macrophages are key drivers of post-MI scar formation, maturation, and ongoing long-term remodelling; however, their individual contributions are difficult to assess from bulk analyses of infarct scar. Here, we employ state-of-the-art automated spatially targeted optical micro proteomics (autoSTOMP) to photochemically tag and isolate proteomes associated with subpopulations of fibroblasts (SMA+) and macrophages (CD68+) in the context of the native, MI tissue environment. Over a time course of 6-weeks post-MI, we captured dynamic changes in the whole-infarct proteome and determined that some of these protein composition signatures were differentially localized near SMA+ fibroblasts or CD68+ macrophages within the scar region. These results link specific cell populations to within-infarct protein remodelling and illustrate the distinct metabolic and structural processes underlying the observed physiology of each cell type.

The Influence of Scar Patterns After Reduction Mammoplasty on Eye Movement and Gaze Pattern: An Eye-Tracking Investigation

BackgroundGiven that scars are acknowledged as the primary cause of postoperative dissatisfaction following reduction mammoplasty, it is imperative to comprehend the patient’s visual perception of different scar patterns in order to enhance patient satisfaction. To achieve this, eye-tracking technology provides an unbiased method of evaluating how observers assess breast scars.Methods58 participants (32 females and 26 males) between the ages of 19 and 82 years (mean age of 29.47 ± 10.98 years) were shown 18 color photographs, taken at 3 viewing angles (right 45° oblique, frontal and frontal view with arms raised), from 6 patients undergone reduction mammoplasty with the inverted T-scar technique (3 patients) or no-vertical-scar technique (3 patients). The images were presented to every participant for a fixed duration of 5 s each. Eye-tracking device was used to collect and analyze the gaze data of viewers.ResultsThe nipple-areola complex (NAC) and the periareolar scar captured observers’ gaze faster, had longer duration and more count of eye fixation than all other parts of breast scars, regardless of the viewing angle and scar pattern. Moreover, the scar region in the inverted T-scar pattern received greater and faster visual attraction of observer’s gaze than the no-vertical-scar pattern.ConclusionThe NAC and the periareolar scar seem to be perceived as the most important regions for breast aesthetics. The findings can be helpful to assist plastic surgeons in determining the most appropriate technique for reduction mammoplasty, meanwhile underlining the importance of a fine periareolar scar and symmetric NAC for excellent aesthetic outcomes.This is to our best knowledge the first study using eye-tracking technology in evaluating reduction mammoplasty outcomes.This study explored the influence of different scar patterns after reduction mammoplasty on eye movements and gaze patterns among observers.The study have validated the significance of the NAC and the periareolar scar for breast aesthetics and revealed that the scar region in the inverted T-scar pattern may be judged less visually attractive than the no-vertical-scar pattern.Level of Evidence VThis journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Impact of noise on the instability of spiral waves in stochastic 2D mathematical models of human atrial fibrillation.

Sustained spiral waves, also known as rotors, are pivotal mechanisms in persistent atrial fibrillation (AF). Stochasticity is inevitable in nonlinear biological systems such as the heart; however, it is unclear how noise affects the instability of spiral waves in human AF. This study presents a stochastic two-dimensional mathematical model of human AF and explores how Gaussian white noise affects the instability of spiral waves. In homogeneous tissue models, Gaussian white noise may lead to spiral-wave meandering and wavefront break-up. As the noise intensity increases, the spatial dispersion of phase singularity (PS) points increases. This finding indicates the potential AF-protective effects of cardiac system stochasticity by destabilizing the rotors. By contrast, Gaussian white noise is unlikely to affect the spiral-wave instability in the presence of localized scar or fibrosis regions. The PS points are located at the boundary or inside the scar/fibrosis regions. Localized scar or fibrosis may play a pivotal role in stabilizing spiral waves regardless of the presence of noise. This study suggests that fibrosis and scars are essential for stabilizing the rotors in stochastic mathematical models of AF. Further patient-derived realistic modeling studies are required to confirm the role of scar/fibrosis in AF pathophysiology.

A Phase II, Randomized, Double Blind, Placebo Controlled Study of the Safety and Efficacy of a Caffeine-Based Antifibrosis Cream in Patients with Breast Cancer Undergoing Radiation Therapy

Radiation induced fibrosis (RIF) is a common long term adverse event in patients undergoing post-mastectomy radiation therapy (PMRT) which can cause capsular contracture, implant loss, and reconstruction complications in women with implant-based breast reconstruction. At a molecular level, adenosine is a driver of RIF. Preclinical data have shown that pharmacologic blockade of the adenosine A2A Receptor (A2AR) in mice as well as an A2AR knockout mouse model prevented skin fibrosis associated with radiation injury. Caffeine is an A2AR antagonist which has been shown to block the development of hepatic fibrosis in liver disease patients. We present a phase II placebo controlled clinical trial to evaluate whether a caffeine-based cream can prevent RIF and thus reduce the rates of reconstructive complications in patients with tissue expander-based reconstruction requiring PMRT. Women ≥ 18 years old with breast carcinoma stage 0-III status post mastectomy with tissue expander-based reconstruction who require PMRT to the chest wall +/- the regional nodes are being enrolled. The target accrual is 60 patients. Boost field to the chest wall, scar and/or nodal region is allowed. Patients with inflammatory breast cancer or those requiring skin bolus are excluded. Prior to starting radiation, patients will be randomized to placebo vs. caffeine cream and they will be instructed to apply the cream twice a day starting on the first day of radiation treatment and continuing daily for the duration of radiation until the removal of tissue expanders. The primary study endpoint is reconstructive complications requiring rehospitalization or reoperation by 2 years post radiation including reconstructive failure with or without reconstruction. A safety endpoint of grade ≥ 2 acute radiation dermatitis will also serve as a co-primary endpoint. Secondary endpoints are wound infection/cellulitis, hematoma, seroma, threatened exposure, wound dehiscence, implant leakage, rupture, and or deflation, and capsular contracture that do not meet criteria for the primary endpoint. Clinician rated cosmesis, local recurrence, regional recurrence, distant metastasis and survival up to 4 years are additional secondary endpoints. Exploratory endpoint includes the use of shear wave elastography (SWE) as a potential tool to quantitatively measure post irradiation fibrosis. Correlative aims include assessing epidermal thickness and fat layer thickness from tissue obtained at time of implant exchange for association with the development of fibrosis. The primary efficacy endpoint will be estimated using Kaplan Meier methods from date of randomization. Treatment comparisons will be based on a 2-sided log rank chi-square test and the hazard ratio will be estimated with 95% confidence intervals. The study started accruing in 12/2019 and is estimated to end by 04/2024. As of January 2023, 67% (40/60 patients) of the planned patients have been enrolled. To be determined. To be determined.

One Year Follow-up and Toxicity Review in a Series of 6 Patients Receiving Stereotactic Arrhythmia Radioablation for Ventricular Tachycardia

Stereotactic body radiation therapy (SBRT) to arrhythmogenic scar regions defined by noninvasive cardiac mapping has recently been described for patients with treatment refractory ventricular tachycardia (VT). Long-term outcomes and both intra- and extra-cardiac toxicities are not well described in this patient population. We report the outcomes following at least 1-year post-treatment along with toxicity for 6 patients treated with this technique in our institution. A total of 6 patients treated between 2019 and 2022 with refractory VT with previously failed ablations and at least one anti-arrhythmic drug was treated at our institution. All were treated with 25 Gy in a single fraction to the suspected arrhythmogenic scar. Cardiac microstructure contouring was done following the atlas by Duane et al. 2017. Implantable cardioverter defibrillator (ICD) interrogation was performed regularly by the treating cardiologist to assess the number of VT and ICD events, and, patients were seen immediately following SBRT, and at 3, 6, and 12 months respectively. Computed tomography of the chest was done at 3 months to assess for radiation induced pneumonitis and transthoracic echocardiograms were done as per the cardiologist's discretion. Radiation toxicity was evaluated using CTCAE v5.0. The median follow-up time for the 6 evaluated patients is 24 months. Three patients (50%) remained VT free during the one-year period post SBRT. Two of these patients remain VT free and are either on reduced or discontinued anti-arrhythmic drugs, while another failed at 24 months in an area of the arrhythmogenic substrate that was intentionally not irradiated due to organ at risk safety concerns. Among those that failed, the median time to failure was 4 months (range 3-5 months). All 6 patients tolerated treatment with no immediate acute side effects. Three (50%) of patients had no acute clinical or radiographic side effects. Grade 1 esophagitis, grade 1 fatigue, and grade 1 cough was reported in 1 (17%) patient each (all different patients), and 1 patient required hospitalization 4 months after SBRT for a heart failure exacerbation (potentially SBRT related). One patient (17%) died within 3 months following treatment but their death was not attributed to radiation treatment. No cardiac microstructure toxicity has been reported to date. Despite increasing reports in the literature, there are no established criteria to predict success for SBRT in the context of treatment-refractory VT, or the optimal treatment dose for success, making it difficult to identify optimal patients. Current limited evidence suggests that this technique may be a relatively safe approach to provide an acute reduction in VT burden for those refractory to standard of care and has an acceptable acute toxicity profile however longer term follow-up is required. Long term toxicity, specifically to cardiac microstructures, and dose optimization is currently are the focus of ongoing study.

Assessment of resting myocardial blood flow in regions of known transmural scar to confirm accuracy and precision of 3D cardiac positron emission tomography

BackgroundComposite invasive and non-invasive data consistently demonstrate that resting myocardial blood flow (rMBF) in regions of known transmural myocardial scar (TMS) converge on a value of ~ 0.30 mL/min/g or lower. This value has been confirmed using the 3 most common myocardial perfusion agents (13N, 15O-H2O and 82Rb) incorporating various kinetic models on older 2D positron emission tomography (PET) systems. Thus, rMBF in regions of TMS can serve as a reference “truth” to evaluate low-end accuracy of various PET systems and software packages (SWPs). Using 82Rb on a contemporary 3D-PET-CT system, we sought to determine whether currently available SWP can accurately and precisely measure rMBF in regions of known TMS.ResultsMedian rMBF (in mL/min/g) and COV in regions of TMS were 0.71 [IQR 0.52–1.02] and 0.16 with 4DM; 0.41 [0.34–0.54] and 0.10 with 4DM-FVD; 0.66 [0.51–0.85] and 0.11 with Cedars; 0.51 [0.43–0.61] and 0.08 with Emory-Votaw; 0.37 [0.30–0.42], 0.07 with Emory-Ottawa, and 0.26 [0.23–0.32], COV 0.07 with HeartSee.ConclusionsSWPs varied widely in low end accuracy based on measurement of rMBF in regions of known TMS. 3D PET using 82Rb and HeartSee software accurately (0.26 mL/min/g, consistent with established values) and precisely (COV = 0.07) quantified rMBF in regions of TMS. The Emory-Ottawa software yielded the next-best accuracy (0.37 mL/min/g), though rMBF was higher than established gold-standard values in ~ 5% of the resting scans. 4DM, 4DM-FDV, Cedars and Emory-Votaw SWP consistently resulted values higher than the established gold standard (0.71, 0.41, 0.66, 0.51 mL/min/g, respectively), with higher interscan variability (0.16, 0.11, 0.11, and 0.09, respectively).Trial registration: clinicaltrial.gov, NCT05286593, Registered December 28, 2021, https://clinicaltrials.gov/ct2/show/NCT05286593.

On the Issue of Optimizing Surgical Tactics and Blood-Saving Techniques in Case of Placenta Ingrowth Into the Uterine Scar

AIM OF STUDY The study of the results of delivery of pregnant women with placenta ingrowth in the uterine scar depending on the clinical status and the methods of blood saving.MATERIAL AND METHODS The design of a selective retrospective study included 54 pregnant women with central placenta previa and uterine scar after caesarean section (CS), with histologically confirmed results of placenta accreta. Among blood-saving methods we used: ligation of three pairs of main vessels of the uterus, ligation of the internal iliac arteries, complex compression hemostasis according to R.G. Shmakov, temporary clamping of the common iliac arteries.RESULTS CS with fundal incision was performed in 47 women (87.0%) out of 54. Hysterectomy was performed in 17 women (31.5%) out of 54. In the remaining 37 cases (68.5%), metroplasty and organ preservation were performed. There was no relaparotomy; there was no maternal mortality; perinatal mortality was 4 (7.4%); forced opening, bladder resection were performed in 7 (13.0%) cases; opening of the bladder without wall resection — in 2 (3.7%); 2 near miss cases; there were no complications associated with temporary clamping of the common iliac arteries; endometritis (recovery after conservative treatment) was revealed in 2 women (3.7%). Histologic examination results: 15 (27.8%) of placenta accreta, 30 (55.6%) of placenta increta, 8 (14.8%) of placenta percreta. In 8 cases, there was a combination of placenta increta into the uterine scar region of different depths, and in 2 (3.7%) cases, a combined deeply invasive lesion of the posterior wall of the lower segment and the body of the uterus.CONCLUSION Complex compression hemostasis according to R.G. Shmakov is the most rational and promising method of blood saving, acceptable among the majority of patients with placenta accreta spectrum. Temporary clamping of the common iliac arteries is advisable in case of damage to the posterior wall of the bladder. Preservation of the uterus: in case of a deeply invasive lesion, including cases of combined damage to the posterior wall of the lower segment of the uterus or the body of the uterus, significant blood loss before the woman enters the hospital, it is not an imperative of surgical tactics.

Recurrence quantification analysis for fine-scale characterisation of arrhythmic patterns in cardiac tissue

This paper uses recurrence quantification analysis (RQA) combined with entropy measures and organization indices to characterize arrhythmic patterns and dynamics in computer simulations of cardiac tissue. We performed different simulations of cardiac tissues of sizes comparable to the human heart atrium. In these simulations, we observed four classic arrhythmic patterns: a spiral wave anchored to a highly fibrotic region resulting in sustained re-entry, a meandering spiral wave, fibrillation, and a spiral wave anchored to a scar region that breaks up into wavelets away from the main rotor. A detailed analysis revealed that, within the same simulation, maps of RQA metrics could differentiate regions with regular AP propagation from ones with chaotic activity. In particular, the combination of two RQA metrics, the length of the longest diagonal string of recurrence points and the mean length of diagonal lines, was able to identify the location of rotor tips, which are the active elements that maintain spiral waves and fibrillation. By proposing low-dimensional models based on the mean value and spatial correlation of metrics calculated from membrane potential time series, we identify RQA-based metrics that successfully separate the four different types of cardiac arrhythmia into distinct regions of the feature space, and thus might be used for automatic classification, in particular distinguishing between fibrillation driven by self-sustaining chaos and that created by a persistent rotor and wavebreak. We also discuss the practical applicability of such an approach.

Assessment of Risk for Ventricular Tachycardia based on Extensive Electrophysiology Simulations.

Patients that have suffered a myocardial infarction are at high risk of developing ventricular tachycardia. Patient stratification is often determined by characterization of the underlying myocardial substrate by cardiac imaging methods. In this study, we show that computer modeling of cardiac electrophysiology based on personalized fast 3D simulations can help to assess patient risk to arrhythmia. We perform a large simulation study on 21 patient digital twins and reproduce successfully the clinical outcomes. In addition, we provide the sites which are prone to sustain ventricular tachycardias, i.e, onset sites around the scar region, and validate if they colocalize with exit sites from slow conduction channels.Clinical relevance- Fast electrophysiological simulations can provide advanced patient stratification indices and predict arrhythmic susceptibility to suffer from ventricular tachycardia in patients that have suffered a myocardial infarction.

A deep learning approach to predict myocardial fibrosis in early contrast-enhanced CCT images

Abstract Funding Acknowledgements Type of funding sources: None. Background Late gadolinium enhancement (LGE) derived from cardiac magnetic resonance (CMR) has become a method of choice for the evaluation of myocardial tissue composition and detection of myocardial fibrosis. Advances in cardiac computed tomography (CCT) imaging have led to its growing role as possible alternative to CMR, because of its wider availability and suitability for patients with contraindication. Purpose To develop a myocardial fibrosis detection method from early contrast-enhanced CCT (CE-CCT) imaging using a deep learning (DL) approach. Methods Fifty consecutive patients (age: 62±10 y, male 84%) with known left ventricular dysfunction were enrolled. All patients underwent both LGE-CMR and early and delayed CE-CCT. According to the LGE-CMR patterns, patients were classified as ischemic (n=15, 30%) or non-ischemic (n=35, 70%). Scar regions were manually traced on delayed CE-CCT using LGE-CMR as reference. On early CE-CCT images, segments were extracted according to American Heart Association (AHA) 16-segment model and labeled (scar/no scar) based on the delayed CE-CCT manual tracing. A DL model was developed for automatic segmental classification. Results Based on 44187 segments analyzed, 71% of accuracy (ischemic: 66%; non-ischemic: 74%) for detecting scar on early CE-CCT images was achieved (Picture 1). In a per-segment analysis of the 16-segment AHA model, an accuracy of 91% (ischemic: 87%; non-ischemic: 93%) was obtained from early CE-CCT compared to the LGE-CMR. Conclusions DL on early CE-CCT acquisition may allow the detection of myocardial fibrosis without additional contrast-agent administration or radiation exposure, thus reducing the user interaction and visual inspection with benefit in both efforts and time.

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&amp;lt;0.01) and BVp (β=0.56, p&amp;lt;0.01). BVμMax was 0.98 (95% CI, 0.93-1.04, p&amp;lt;0.01) mV larger than corresponding BVc, and 0.27 (95% CI, 0.16-0.37, p&amp;lt;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&amp;lt;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&amp;lt;0.01), longer duration (117 [66] ms versus 74 [38] ms, p&amp;lt;0.01), and with greater number of peaks (4 [2] versus 2 [1], p&amp;lt;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.

P153 A DEEP–LEARNING APPROACH FOR SCAR DETECTION IN EARLY CONTRAST–ENHANCED CARDIAC COMPUTED TOMOGRAPHY IMAGES

Abstract Diagnosis of myocardial fibrosis has a relevant prognostic and therapeutic role. Scar–tissue analysis is commonly performed with late gadolinium contrast–enhanced (CE) cardiac magnetic resonance (CMR). However, CMR might be contraindicated or unavailable. Coronary computed tomography (CCT), which is the technique of choice for many routine assessments, is emerging as an alternative to CMR. The objective of this study is to evaluate whether artificial intelligence (AI) could allow identification of myocardial fibrosis from routine early CE–CCT images. Fifty consecutive patients with left ventricular dysfunction (LVD), who underwent both CE–CMR and (early and late) CE–CCT were retrospectively selected. According to the late enhancement CMR patterns, patients were classified as with ischemic (n=15, 30%) or non–ischemic (n=25, 70%) LVD. Scar regions were manually traced on late CE–CCT using CE–CMR as ground–truth. On early CE–CCT images, the myocardial sectors were extracted according to AHA 16–segment model and labeled as with scar or not based on the late CE–CCT manual tracing. A deep–learning model was developed to classify each sector (Picture 1). Of the initial 44187 sectors computed out of the 8285 slices available from the early CE–CCT images, 4594 sectors (10%) presented scar. The CNN approach on the early CE–CCT images yielded a classification accuracy for all sectors of 71% (95% confidence interval (CI): 63%–79%) obtained through 5–fold cross validation. The mean sensitivity, positive predictive value (PPV) and negative predictive value (NPV) for the testing fold resulted in 73% (95% CI: 66%–79%), 56% (95% CI: 48%–65%) and 85% (95% CI: 82%– 88%), respectively. The mean AUC across the five folds was 76% (95% CI: 72%–81%). In a per–segment analysis of the 16–segment AHA model the bull’s eye segmental comparison of CE–CMR and respective early CE–CCT findings an 91% agreement was achieved (Picture 2). Artificial intelligence can detect both ischemic and non–ischemic myocardial fibrosis from routine noninvasive coronary scans, without additional contrast–agent administration or radiational dose, thus assisting diagnosis and management of patients with LV dysfunction and coronary artery disease.

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.

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-05-086 HYDROGEL ELECTRODE SUB-ACUTE SAFETY IN A PORCINE MODEL

Our lab has developed a biostable, in-situ curing hydrogel with conductive properties enabling its use in electrotherapies. This hydrogel is formed by the reaction between two precursor solutions, enabling intravascular delivery via a catheter system. By virtue of its fluid nature prior to curing, this "liquid wire” can fill mid-myocardial venous tributaries, presenting significant advantages over standard pacing systems. The length of the liquid wire enables synchronization of pacing across scar regions. For this technology to be further developed, it must first demonstrate long-term safety as a chronic implant. Determine the initial safety of the hydrogel electrode in the anterior intraventricular vein (AIV) over four weeks and the middle cardiac vein (MCV) over two weeks. The hydrogel electrode was delivered into the AIV using a dual barrel syringe via an open chest procedure in 3 pigs. The pigs were recovered and observed for four weeks with weekly blood draws to assess troponins. A similar procedure was performed for the MCV in one pig and the animal was recovered and observed for two weeks. ECG tracings were recorded before injection and immediately before termination. Echocardiography was performed to assess EF. The lungs, liver, and brain were collected for gross examination for hydrogel particulates. The hearts were collected, fixed, and stained (Mason’s trichrome, hematoxylin, and eosin) to assess foreign body response and remodeling. Little change was observed in ECG tracings for all animals (Fig 1A). Troponins were high immediately after the procedure, likely due to the invasive surgery, but these values trended down towards normal levels (45-54 ng/L, Fig 1B). EF values remained in normal ranges (65-69%). Histological analysis (Fig 1C) shows a giant foreign body cell reaction immediately surrounding the vessel, along with some replacement fibrosis, likely due to the vessel dilation. The surrounding myocardium remains well preserved. The subacute implantation of the hydrogel electrode into cardiac veins has no deleterious effect on overall cardiac function. Future studies will explore the hydrogel electrode function and safety in diseased porcine hearts as well as the testing of the total endovascular delivery system that could potentially limit the dilation of the vessel.

PO-04-137 SCAR TRANSMURALITY IN VENTRICULAR ENDOCARDIAL UNIPOLAR ELECTROGRAMS IS RELATED TO POWER OF PATIENT-SPECIFIC FREQUENCY BANDS

Characteristic endocardial electrogram (EGM) features such as fractionation and late potentials have been associated with ventricular tachycardia (VT) substrate. Our prior analyses show that EGM frequency content allows for more accurate identification of mid-myocardial fibrosis within a given patient, compared to traditional bipolar or unipolar voltage thresholds. A relationship between frequency information and endocardial scar transmurality has not been described. To explore the relationship of frequency spectra to ventricular scar transmurality in patients undergoing VT catheter ablation. Thirteen patients with non-ischemic cardiomyopathy (NICM) undergoing VT ablation with pre-procedural tissue characterization using cardiac computed tomography (CCT) imaging with late-iodine enhancement were assessed. From the CCT data, scar transmurality was calculated for every EGM recording location. With multitaper spectral estimation, average normalized frequency content was calculated for regions with different levels of scar transmurality and compared to average frequency content from tissue locations with no scar. K-nearest neighbors classifiers were trained within patients to predict scar transmurality, assuming presence of scar is known. Frequency content of regions without scar is similar among patients. A comparison of the average normalized frequency spectra of the non-fibrotic endocardial tissue for each patient is presented. Differences in scar transmurality led to changes in strength of certain frequency bands, which varied between patients. Observed responses included a peak at 10-15 Hz whose magnitude increased with scar transmurality (panel B) and a peak at 35-40 Hz in regions with higher scar transmurality. Normalized frequency content predicted transmural scar above chance with at least p < .05 for all 13 patients. Frequency content of endocardial unipolar EGMs is related to scar transmurality in those regions. This relationship changes patient to patient, potentially due to differences in morphology of fibrotic tissue. Deviation from the consistent spectra seen in non-fibrotic tissue may be a strategy to identify fibrosis and these insights can inform development of physiological models of VT. Because of low EGM sample sizes in higher scar transmurality regions, more data should be collected to further support this claim.

PO-02-216 SEGMENTAL INCREASE IN HETEROGENEITY OF REPOLARIZATION CORRESPONDS TO REGIONS OF DECREASED INNERVATION AFTER MYOCARDIAL INFARCTION

Myocardial infarction (MI) results in a dense scar region surrounded by a heterogeneous remodeled border zone. In this region denervation and nerve regeneration during healing could be region dependent and contribute to segmental differences in the functional substrate for arrhythmias. To examine regional electrophysiological remodeling in relation to perfusion and innervation changes after myocardial infarction. Anterio-septal MI was induced in 6 domestic pigs by a 120-minute occlusion of the left anterior descending artery (LAD) followed by reperfusion. After one month, PET-MR imaging was performed to evaluate myocardial perfusion (13N-ammonia) and innervation (11C-epinephrine), together with late gadolinium enhanced MR imaging for scar quantification. The next day electro-anatomical mapping was performed. The BZ was defined using contact mapping as the region with bipolar voltage between 0.5 and 1.5 mV. A non-contact recording of a 64-electrode array was translated to 2048 non-contact electrograms distributed over the LV (EnSite PrecisionTM, St. Jude/Abbott Medical). In each of the 2048 points non-contact electrograms over 25 consecutive beats were processed to determine the beat-to-beat variability of repolarization (BVR). Spatial heterogeneity of repolarization was quantified in each point as the repolarization time variability within a 1cm radius neighborhood. MI size was 14.2±3.2% of the left ventricle on gadolinium enhanced MR imaging. The perfusion and innervation defects were significantly larger (22.3±3.2%, P<0.01 and 28.1±4.3%, P<0.01 respectively). The innervation defect was also significantly larger than the perfusion defect (P=0.03). Regional analysis revealed less innervation in the anterior versus the septal border zone (14.2±2.9 %/min vs 18.6+3.1 %/min, P<0.01). In one animal the electrophysiology study was unsuccessful due to a high baseline heart rate (>120 BPM). In the remaining animals, the average spatial heterogeneity was higher in the anterior than septal border zone (5.8±3.0 ms vs 3.8±2.6 ms, P<0.01). Additionally, the maximum BVR tended to be higher in the anterior than septal border zone (2.6±1.3 ms vs 2.02±0.77 ms, P=0.08). MI resulting from LAD occlusion/reperfusion leads to increased denervation on the anterior side of the infarct, correlating with increased repolarization heterogeneity in this region.

PO-05-037 EFFICACY AND CLINICAL CHARACTERISTICS OF AVERT-VT: ABLATION AT VIRTUAL-HEART PREDICTED VT

We have previously demonstrated the feasibility of virtual-heart simulations in determining noninvasively the optimal infarct-related ventricular tachycardia (VT) ablation targets and guiding the clinical ablation. We are now proceeding with AVERT-VT, an FDA-approved study for ten prospective patients. To develop the end-to-end personalized computational modeling prediction pipeline enabling AVERT-VT and to assess the corresponding clinical characteristics of the predicted virtual-heart ablation targets. We developed a comprehensive end-to-end computational pipeline enabling AVERT-VT (Fig). 3D LGE-MRI scans with 1.5x1.5mm in-plane spatial resolution and slice thickness <2mm were used to reconstruct the 3D left ventricular (LV) model incorporating deep scar, border (gray) zone, and non-infarcted tissue. In silico rapid pacing from 7 LV regions were performed to induce VTs. The optimal ablation targets were determined by thorough analyses of the wavefront propagation of the induced in silico VTs. A linear ablation connecting a VT ablation target to a transmural deep scar region, the basal region, or the other VT target was performed to eliminate the potential VT pathway formed by the target ablation. Potential emergent VTs in the post-ablation substrate were investigated by repeating the VT induction pacing protocol. This process was iterated until complete VT non-inducibility was achieved. The initial and repeat ablation targets, linear ablations, as well as the LV, right ventricle, infarct area, aortic arch, and left and right coronary cusp geometries, were exported as an ablation strategy plan compatible with the clinical mapping system. The figure presents results from one patient in the clinical study. The ablation plan was successfully imported and co-registered to the patient’s heart. The extent of the model infarct corresponded to the bipolar low-voltage regions. Abnormal electrograms were observed at the proposed targets. 2 VTs were observed during the procedure. Areas of latest activation in sinus rhythm and best pace maps, with a long stimulus to QRS, were found at 2 of the proposed targets. One of the seven proposed targets was not ablated due to the proximity to the left sided His potential. The patient was not inducible of any VT at the end of the procedure. AVERT-VT proposed targets corresponded to abnormal electrograms, and ablating at the targets led to VT non-inducibility.

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.