Search

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. 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. Electroanatomic substrate maps were created and retrospectively analyzed in 27 patients in whom 33 VT critical sites were identified. Both abnormal bipolar voltage and omnipolar voltage encompassed all critical sites and were observed over a median of 66 cm2 (interquartile range [IQR] 41.3–86 cm2) and 52 cm2 (IQR 37.7–65.5 cm2), respectively. ILAM deceleration zones were observed over a median of 9 cm2 (IQR 5.0–11.1 cm2) and encompassed 22 critical sites (67%), while abnormal omnipolar conduction velocity (CV <1 mm/ms) was observed over 10 cm2 (IQR 5.3–16.6 cm2) and identified 22 critical sites (67%), and fractionation mapping was observed over a median of 4 cm2 (IQR 1.5–7.6 cm2) and encompassed 20 critical sites (61%). The mapping yield was the highest for fractionation + CV (2.1 critical sites/cm2) and least for bipolar voltage mapping (0.5 critical sites/cm2). CV identified 100% of critical sites in areas with a local point density of >50 points/cm2. 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. [ABSTRACT FROM AUTHOR]

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 (V2 or V3), 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 V5 or V6 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: SufA, which belongs to the subtilisin-like serine protease family, contains a non-canonical Asp-His-Ser catalytic triad. Under in vitro conditions, SufA is capable of human fibrinogen hydrolysis leading to inhibition of fibrin network formation, thus suggesting its important role in the development and progression of Finegoldia magna infections. In addition, it has been demonstrated that SufA can hydrolyze antibacterial peptides such as LL-37 and the chemokine MIG/CXCL 9, hence evading host defence mechanisms. Although the SufA protease from F. magna was discovered several years ago, its optimal substrate preference has not yet been identified. Considering the role of SufA, we have focused on the profiling of its substrate sequence preference spanning S1–S3 binding pockets using the FRET (fluorescence resonance energy transfer) approach. Next, based on the structure of the P1 residue of the developed substrate, we narrowed the inhibitor screening to the phosphonic analogues of amino acids containing an arginine-like side chain. Among all the compounds tested, only Cbz-6-AmNphthP(OPh)2 showed any inhibitory activity against SufA displaying k 2/K i value of 10 800 M−1 s−1. In addition, it prevented SufA-mediated human fibrinogen hydrolysis in vitro and exhibited potent antibacterial activity against F. magna, Staphylococcus aureus and Escherichia coli. Herein, we report on the substrate specificity, synthesis and kinetic evaluation of phosphonic inhibitors of SufA protease from F. magna which could help to establish its function in pathogenesis development and may lead to the elaboration of new antibacterial drugs. [Copyright &y& Elsevier]

Abstract: In recent years, low cost and highly accurate underwater remote sensing instruments and technologies have advanced at an astonishing rate. Intense competition among manufacturers, coupled with advances in digital signal processing has brought about these breakthroughs, all to the benefit of the scientific community. Commercial Off the Shelf Technology (COST) is now available and incorporated into current acoustic sensors, with quality and resolution that was previously reserved for only large-scale ocean exploration. The corollary to this observation is that the entire field of acoustic remote sensing of the aquatic environment is rapidly evolving and is likely to continue to do so over the next decade. Acoustic bottom mapping, Doppler sensing and remote and autonomous vehicle imaging systems are now becoming commonplace for large lake science and are approaching maturity. Given this evolution, this summary reviews two major categories of underwater, acoustic remote sensing technologies; bottom mapping systems and Doppler sensing systems. Bottom mapping systems are primarily used to determine the presence of the bottom, map its features and classify its composition. Doppler systems make use of target motion to deduce the velocity of the target, in up to three spatial dimensions. For each category of acoustic remote sensing a brief description of the theory of operation is provided, followed by examples of the types of data produced by the technology. When possible, estimates of range and accuracy of typical units in each class is provided. Finally, examples of new utilizations of combined remote sensing technologies are discussed. [Copyright &y& Elsevier]

Background: The biatrial substrate properties in patients with paroxysmal atrial fibrillation (AF) originating from the pulmonary veins (PVs) and superior vena cava (SVC) are not available. Objective: The purpose of this study is to characterize the differences of biatrial substrate properties in patients with different types of AF. Methods: A total of 36 patients with paroxysmal AF originating from the PV (PV-AF) and 9 patients with paroxysmal AF initiating from the SVC (SVC-AF) were included. Regional electrogram voltage, conduction velocity (CV), and spectral analysis to identify the AF nest were performed to characterize the biatrial, PVs, and SVC substrate. Results: In the left atrial (LA) body, the bipolar voltage, total activation time, CV, and dominant frequency (DF) were similar between the PV-AF and SVC-AF. However, in the PV regions, the electrogram voltage, CV, and DF were decreased in the PV-AF. The proportions of AF nest in the LA body (72.2% vs. 22.2%, P = .008) and PV regions (100% vs. 22.2%, P <.001) were higher in PV-AF compared with SVC-AF, respectively. On the other hand, lower bipolar voltage, longer total activation time, and slower CV of RA body were recognized in the SVC-AF as compared with the PV-AF. In the SVC, lower bipolar voltage, slower CV, higher DF, and higher proportions of AF nest in SVC (16.7% vs. 66.7%, P = .002) were identified in SVC-AF. Conclusion: These most-remodeled substrates in different types of paroxysmal AF indicated the importance of the atrial substrate in the vicinity of the arrhythmogenic thoracic veins. [ABSTRACT FROM AUTHOR]

Abstract: The sunflower seed (Helianthus annuus L.) major aminopeptidase primary specificity has been assessed with a number of specially designed amino acid amides and alkyl esters. Studies with amino acid 4-nitroanilides with straight alkyl side chains suggest the enzyme possesses an S1 hydrophobic binding site of limited size and effects of substrate sorption are present in both its binding and turnover. The enzyme S1′-subsite is able to accommodate a number of different leaving groups—primary amide, one- and two-ring condensed aromatic structures, amino acid residues and alkyl ester moieties. The hydrolysis of amide substrates is affected by both their P1 and the P1′ part. The replacement of the amide leaving group with an ester one tents to minimize the P1-part effect. The enzyme''s high enantioselectivity towards the configuration of the substrate P1-part has been successfully utilized for resolution of racemic amino acid amides. [Copyright &y& Elsevier]

Background: Complex fractionated atrial electrograms are used as potential targets for catheter ablation therapy of atrial fibrillation. Although fibrosis has been associated with the presence of fractionated electrograms, characterizing the substrate through the inspection of electrograms is challenging. Objective: This study sought to determine how progression of microfibrosis and slow conduction affect electrogram morphology. Methods: A microstructure computer model representing a monolayer of cardiac cells was developed. Slow conduction was induced by: (1) sodium channel blockade, (2) uniform reduction in cell-to-cell coupling, and (3) microfibrosis incorporated as a set of collagenous septa disconnecting transverse coupling. The density (0 to 30%) and length (30 to 945 μm) of these collagenous septa were varied. Unipolar and bipolar electrograms were computed during paced rhythm for a set of electrodes with different tip sizes. Results: The analysis of unipolar electrograms with realistic temporal and spatial filtering showed that increasing the density and length of collagenous septa decreased conduction velocity by up to 75% and increased the amount of fractionation (up to 14 deflections) and asymmetry of the electrograms. In contrast, slow conduction induced by sodium channel blockade or uniformly reduced coupling did not result in electrogram fractionation. When a larger electrode was used, electrogram amplitude was smaller and fractionation increased in a substrate-dependent way. Conclusion: Microscale obstacles cause significant changes to electrogram waveforms. Conduction velocity and electrogram amplitude and degree of fractionation can be used to discriminate the nature of the substrate and characteristics of fibrosis, giving rise to slow conduction. [Copyright &y& Elsevier]

A multi-disciplinary, multi-institutional research team evaluated a broad range of physical and biological characteristics at six Great Lakes nearshore sites in order to develop and test a conceptual modeling framework to assess linkages between bluff erosion, sediment supply, coastal processes, and biological utilization of nearshore and coastal habitats. The sites were chosen to represent a broad range of hydrogeomorphic conditions, with the objective of assessing the response of these nearshore systems to anthropogenic modifications and coastal change. As a result of this 2-year field effort, new methods and integrated approaches were developed to characterize, map, and assess the dynamic nature of the nearshore zone (area generally less than 10 m water depth). Thus, these data provide an initial quantitative assessment of nearshore change. In addition, our data indicate that shoreline modifications have led to cumulative impacts that have irreversibly modified Great Lakes nearshore coastal habitats and the processes that create and maintain them. Of special note is our observation that altered nearshore substrate dynamics resulting from shoreline modifications may enhance the colonization success of lithophilic aquatic invasive species in nearshore areas of the Great Lakes. Continued development of the shoreline may exacerbate changes in Great Lakes nearshore food-web structures and ecosystem services. Further study and monitoring of these phenomena are needed, and our work suggests that a holistic, multidisciplinary approach is necessary to develop effective management strategies to address these and other issues affecting nearshore areas of the Great Lakes. [ABSTRACT FROM AUTHOR]

Nearshore substrate characteristics such as texture (grain size) and composition, available surface area, pattern, distribution, and relative stability are critical parameters that determine how biological organisms (and communities) utilize those substrates during different life stages. Geo-referenced sidescan-sonar data are used in combination with traditional sampling techniques and Geographic information System (GIS) technologies to map substrate contacts and aquatic habitat distributions within Great Lakes nearshore areas. New methods are developed that includes area change analysis and centroid analysis to quantitatively assess net change in substrate area and evaluate relative substrate stability. An Area Change Ratio (ACR) can be calculated for individual substrate polygons (patch analysis) or groups of substrate polygons (area analysis) of the same substrate type. Areas of relative stability are represented by ACR values near zero. Areas of moderate stability are represented by values ranging between 0.2 and 0.5 and highly unstable areas are represented by values of 0.5 or greater. Substrate centroids or "centers of mass" are also calculated and can be used to quantitatively integrate change in substrate area and the location of individual substrate polygons or groups of polygons within a survey area. Comparison of centroid movement provides a quantitative measure of the magnitude and direction of change in substrate area through time. These techniques address many of the spatial and temporal limitations associated with more traditional approaches, e.g., shore-normal profiling, detailed bathymetric surveys, and repetitive sampling of bottom materials, and yet can be combined with these traditional approaches to develop a more detailed understanding of nearshore habitat distribution and stability. [ABSTRACT FROM AUTHOR]

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. • 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. • Coumarins are components of fluorophore/quencher pairs or FRET donor/acceptor pairs in substrate mapping of proteases. • Coumarins have been incorporated into amino acids side chains to be used for the positional profiling of protease substrates. • Coumarins have protease-inhibiting properties and are used for activity-based probes for serine and cysteine proteases. [ABSTRACT FROM AUTHOR]