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Background: The presence of dynamic substrate changes may facilitate functional block and reentry in ventricular tachycardia (VT). Objective: We aimed to study dynamic ventricular repolarization changes in critical regions of the VT circuit during sensed single extrastimulus pacing known as the Sense Protocol (SP). Methods: Twenty patients (aged 67 ± 9 years, 17 male) underwent VT ablation. A bipolar voltage map was obtained during sinus rhythm (SR) and right ventricular SP pacing at 20 ms above ventricular effective refractory period. Ventricular repolarization maps were constructed. Ventricular repolarization time (RT) was calculated from unipolar electrogram T waves, using the Wyatt method, as the dV/dtmax of the unipolar T wave. Entrainment or pace mapping confirmed critical sites for ablation. Results: The median global repolarization range (max-min RT per patient) was 166 ms (interquartile range [IQR] 143–181 ms) during SR mapping vs 208 ms (IQR 182–234) during SP mapping (P = .0003 vs intrinsic rhythm). Regions of late potentials (LP) had a longer RT during SP mapping compared to regions without LP (mean 394 ± 40 ms vs 342 ± 25 ms, P < .001). In paired regions of normal myocardium there was no significant spatial dispersion of repolarization (SDR)/10 mm2 during SP mapping vs SR mapping (SDR 11 ± 6 ms vs 10 ± 6 ms, P = .54). SDR/10 mm2 was greater in critical areas of the VT circuit during SP mapping 63 ± 29 ms vs SR mapping 16 ± 9 ms (P < .001). Conclusion: Ventricular repolarization is prolonged in regions of LP and increases dynamically, resulting in dynamic SDR in critical areas of the VT circuit. These dynamic substrate changes may be an important factor that facilitates VT circuits.

Background: Established electroanatomic mapping techniques for substrate mapping for ventricular tachycardia (VT) ablation includes voltage mapping, isochronal late activation mapping (ILAM), and fractionation mapping. Omnipolar mapping (Abbott Medical, Inc.) is a novel optimized bipolar electrogram creation technique with integrated local conduction velocity annotation. The relative utilities of these mapping techniques are unknown., Objective: The purpose of this study was to evaluate the relative utility of various substrate mapping techniques for the identification of critical sites for VT ablation., Methods: Electroanatomic substrate maps were created and retrospectively analyzed in 27 patients in whom 33 VT critical sites were identified., Results: Both abnormal bipolar voltage and omnipolar voltage encompassed all critical sites and were observed over a median of 66 cm 2 (interquartile range [IQR] 41.3-86 cm 2 ) and 52 cm 2 (IQR 37.7-65.5 cm 2 ), respectively. ILAM deceleration zones were observed over a median of 9 cm 2 (IQR 5.0-11.1 cm 2 ) and encompassed 22 critical sites (67%), while abnormal omnipolar conduction velocity (CV <1 mm/ms) was observed over 10 cm 2 (IQR 5.3-16.6 cm 2 ) and identified 22 critical sites (67%), and fractionation mapping was observed over a median of 4 cm 2 (IQR 1.5-7.6 cm 2 ) and encompassed 20 critical sites (61%). The mapping yield was the highest for fractionation + CV (2.1 critical sites/cm 2 ) and least for bipolar voltage mapping (0.5 critical sites/cm 2 ). CV identified 100% of critical sites in areas with a local point density of >50 points/cm 2 ., Conclusion: ILAM, fractionation, and CV mapping each identified distinct critical sites and provided a smaller area of interest than did voltage mapping alone. The sensitivity of novel mapping modalities improved with greater local point density., (Copyright © 2023 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Right bundle branch block (RBBB) ventricular tachycardia (VT) morphology is a criterion for left ventricular (LV) involvement in arrhythmogenic right ventricular cardiomyopathy (ARVC)., Objective: The purpose of this study was to determine the frequency and chamber of origin of RBBB VT in patients with ARVC and VT., Methods: We studied 110 consecutive patients with VT who met the diagnostic International Task Force criteria for ARVC and underwent VT mapping/ablation. Patients with ≥1 RBBB VT were identified. Right ventricular (RV) origin of the RBBB VT was determined based on standard mapping criteria and elimination with ablation., Results: Nineteen patients (17%) had 26 RBBB VTs. Eleven of these 19 patients (58%) had 16 RBBB VTs from the RV, and 9 patients (47%) had 10 RBBB VTs originating from the LV, with 1 patient demonstrating both. RBBB VT from RV most commonly (13/16 RBBB VTs) had an early precordial QRS transition (V 2 or V 3 ), with superiorly and typically leftward directed frontal plane axis, consistent with exit from dilated RV adjacent to inferior LV septum, whereas all 10 VTs from LV had RBBB morphology with positive R waves to V 5 or V 6 and rightward axis in 6 VTs characteristic of basal lateral origin., Conclusion: In patients with ARVC and VT presenting for VT ablation, RBBB VT occurs in 17% of cases, with most RBBB VTs (62%) originating from the RV and not indicative of LV origin. Precordial R-wave transition and frontal plane axis can be used to identify the anticipated chamber of origin of RBBB VT., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Coumarins represent well-established structures to introduce fluorescence into tool compounds for biochemical investigations. They are valued for their small size, chemical stability and accessibility as well as their tunable photochemical properties. As components of fluorophore/quencher pairs or FRET donor/acceptor pairs, coumarins have frequently been applied in substrate mapping approaches for serine and cysteine proteases. This review also focuses on the incorporation of coumarins into the side chain of amino acids and the exploitation of the resulting fluorescent amino acids for the positional profiling of protease substrates. The protease-inhibiting properties of certain coumarin derivatives and the utilization of coumarin moieties to assemble activity-based probes for serine and cysteine proteases are discussed as well., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The amplitude of bipolar electrograms (EGMs) is directionally sensitive, decreasing when measured from electrode pairs oriented oblique to a propagating wavefront., Objective: The purpose of this study was to use a computational model and clinical data to establish the mechanism and magnitude of directional sensitivity., Methods: Simulated EGMs were created using a computational model with electrode pairs rotated relative to a passing wavefront. A clinical database of 18,740 EGMs with varying electrode separation and orientations was recorded from the left atrium of 10 patients with atrial fibrillation during pacing. For each EGM, the angle of incidence between the electrodes and the wavefront was measured using local conduction velocity (CV) mapping., Results: A theoretical model was derived describing the effect of the changing angle of incidence, electrode spacing, and CV on the local activation time difference between a pair of electrodes. Model predictions were validated using simulated and clinical EGMs. Bipolar amplitude measured by an electrode pair is decreased (directionally sensitive) at angles of incidence resulting in local activation time differences shorter than unipolar downstroke duration. Directional sensitivity increases with closer electrode spacing, faster CV, and longer unipolar EGM duration. For narrowly spaced electrode pairs (<5 mm), it is predicted at all orientations., Conclusion: Directional sensitivity occurs because bipolar amplitude is reduced when the component unipolar EGMs overlap, such that neither electrode is "indifferent." At the electrode spacing of clinical catheters, this is predicted to occur regardless of catheter orientation. This suggests that bipolar directional sensitivity can be lessened but not overcome by recently introduced catheters with additional rotated electrode pairs., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Identifying arrhythmogenic sites to improve ventricular tachycardia (VT) ablation outcomes remains unresolved. The reentry vulnerability index (RVI) combines activation and repolarization timings to identify sites critical for reentrant arrhythmia initiation without inducing VT., Objective: The purpose of this study was to provide the first assessment of RVI's capability to identify VT sites of origin using high-density contact mapping and comparison with other activation-repolarization markers of functional substrate., Methods: Eighteen VT ablation patients (16 male; 72% ischemic) were studied. Unipolar electrograms were recorded during ventricular pacing and analyzed offline. Activation time (AT), activation-recovery interval (ARI), and repolarization time (RT) were measured. Vulnerability to reentry was mapped based on RVI and spatial distribution of AT, ARI, and RT. The distance from sites identified as vulnerable to reentry to the VT site of origin was measured, with distances <10 mm and >20 mm indicating accurate and inaccurate localization, respectively., Results: The origins of 18 VTs (6 entrainment, 12 pace-mapping) were identified. RVI maps included 1012 (408-2098) (median, 1st-3rd quartiles) points per patient. RVI accurately localized 72.2% VT sites of origin, with median distance of 5.1 (3.2-10.1) mm. Inaccurate localization was significantly less frequent for RVI than AT (5.6% vs 33.3%; odds ratio 0.12; P = .035). Compared to RVI, distance to VT sites of origin was significantly larger for sites showing prolonged RT and ARI and were nonsignificantly larger for sites showing highest AT and ARI gradients., Conclusion: RVI identifies vulnerable regions closest to VT sites of origin. Activation-repolarization metrics may improve VT substrate delineation and inform novel ablation strategies., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

The primary goal of catheter ablation of scar-related ventricular tachycardia (VT) is the interruption of critical areas of slow conduction responsible for the development and maintenance of the reentrant VT circuit. Most patients with scar-related VT present with unstable arrhythmias that are not amenable to interrogation from multiple sites to define the VT circuit based on the intracardiac activation sequence and the response to entrainment mapping. In order to effectively target unstable VTs, a number of ablation approaches have been described with the aim of targeting the abnormal substrate defined with mapping in sinus or paced rhythm. Some of these strategies (eg, late potential and local abnormal ventricular activity ablation or scar homogenization) target the entire abnormal substrate harboring abnormal electrograms, defined with a variety of different criteria. Scar dechanneling, linear ablation through sites matching VT with pacing, and the core isolation approach focus on more discrete regions within the abnormal substrate that have been proven relevant to the clinical and/or inducible arrhythmias by means of physiologic maneuvers, although this does not necessarily translate to fewer radiofrequency lesions to achieve the procedural end-point. Observational studies evaluating different substrate-based ablation techniques have reported fairly uniform arrhythmia-free survivals at short- and mid-term follow-up, although direct comparisons between different techniques are lacking. In this article, we summarize the different state-of-the-art substrate mapping and ablation approaches for targeting unstable VT, with a particular focus on the relative merits and limitations of the described techniques., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)