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Introduction: Over the past years, mapping and ablation techniques for the treatment of ventricular tachycardia (VT) have evolved rapidly. High Density (HD) substrate mapping is now routine and pre‐procedural imaging is increasingly used. The additional value of these techniques for long‐term VT‐free survival is not clear. Methods: We compared baseline and procedural characteristics, procedural success, safety and outcome of mapping and ablation of ventricular tachycardia in patients with ischemic heart disease between two groups. (1) Low Density (LD) group: VT mapping and ablation with a 4 mm single tip catheter (2) HD group: HD substrate mapping with the Pentaray (Biosense Webster, USA) or HD Grid (Abbott, USA) catheter and ablation with a 4 mm single tip catheter. Results: VT ablation was performed in 133 patients (71 patients in LD group and 62 patients in HD group). The median follow‐up was 5.0 years in LD group and 2.0 years in HD group. One‐, two‐, and five‐year VT recurrence rates were 47%, 56%, and 65% in the LD group versus 39%, 50%, and 55% in the HD group (log‐rank test for VT recurrence p =.70). One‐, two‐, and five‐year ICD shock recurrence rates were 14%, 18%, and 24% in the LD group versus 8%, 15%, and 19% in the HD group (log‐rank test for ICD‐shock p =.79). All‐cause mortality, cardiac (non‐arrhythmic), and arrhythmic death, were similar in both groups. Severe procedural complications (tamponade, stroke, or procedural death) occurred in four patients (5%, 1 vascular, 3 tamponade) in the LD group versus two patients (3%, both tamponade) in the HD group (NS). In univariate and multivariable analysis, only a higher LVEF was significantly associated with VT‐free survival. HD mapping was not significantly associated with VT‐free survival. Anterior infarct location and age were significantly associated with ICD recurrent shock in both univariate and multivariable analyses. Conclusions: In patients with ischemic cardiomyopathy, a HD substrate mapping, and ablation strategy did not lead to higher VT‐free survival and shock‐free survival compared to a single tip mapping and ablation strategy. In this study, only LVF is an independent predictor for VT recurrence. Anterior infarct location and age predict recurrent ICD shocks. [ABSTRACT FROM AUTHOR]

Introduction: 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). 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 =.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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

The treatment of ventricular tachycardia caused by nonischemic cardiomyopathy (NICM-VT) is challenging in clinical practice, however, the related clinical data of catheter ablation for NICM-VT are limited. This paper reviews the progress of catheter ablation for NICM-VT from three aspects: clinical efficacy, mapping strategy, and future prospect. [ABSTRACT FROM AUTHOR]

The characterization of benthic habitats is essential for aquatic ecosystem science and management, but is frequently limited by waterbody visibility and depth. Recreation‐grade side‐scan sonar systems are increasingly used to aid scientific inquiries in aquatic environments due to their relative low‐cost, ease of operation, low‐weight, and ease of mounting on a variety of vessels. However, existing procedures and software for post‐processing these data are either limited, closed source, or fail on data from new sonar models, limiting the development of reproducible workflows. Here, we present PING‐Mapper, an open‐source and freely available side‐scan sonar post‐processing toolset for processing and mapping sonar recordings from popular Humminbird instruments. The modular software automatically: (a) decodes sonar recordings from any Humminbird system, (b) exports ping attributes from every sonar channel, (c) uses sonar sensor depth for water column removal, and (d) exports sonogram tiles and georectified mosaics. Sonar channels are processed in parallel for quick decoding and metadata extraction. Major processing wokflows, including georectification and image export, are optimized to scale with computing resources. The software has been extensively tested using data from several rivers of varying character and distribution of depths, but could also be used in estuarine and lacustrine environments. Usage of PING‐Mapper is illustrated in three case studies focused on mapping large woody debris, bathymetric mapping, and visual interpretation and mapping of substrates for selected reaches of the Pearl and Pascagoula river systems in Mississippi. Plain Language Summary: Side‐scan sonar instruments provide a way to survey and visualize the bottom of rivers, lakes, or oceans. Since the early 2000s, companies catering predominantly to anglers have manufactured recreation‐grade side‐scan sonar systems to aid fishermen in locating fish and identifying potential hazards. Scientists seeking to understand and manage aquatic habitats used these systems to create grayscale images of water bottoms because they are inexpensive, easy to operate, and require minimal mounting equipment on the boat. Software has been created by companies to process these data, but the underlying processing workflow and computer code are not publicly available, making it difficult to reproduce and compare results across studies. Other publicly available approaches and software are either outdated, not maintained, or not free. That is why we made PING‐Mapper, a freely available software developed in an increasingly popular programming language called Python. We designed the software to work on any computer to export the data sets quickly and efficiently. The scientific use of exported data sets is demonstrated with three case studies focused on locating and mapping targets (specifically large trees and branches), creating depth maps, and visually discerning the distributions of common substrates, such as sand and cobble. Key Points: We developed an open‐source software for exporting benthic data sets and georeferenced imagery from Humminbird side‐scan sonar systemsSoftware provides an automated and reproducible approach to processing sonar data with minimal interaction from the userThree case studies are presented to highlight use cases of processed benthic data sets [ABSTRACT FROM AUTHOR]

Introduction: An important substrate for atrial fibrillation (AF) is fibrotic atrial myopathy. Identifying low voltage, myopathic regions during AF using traditional bipolar voltage mapping is limited by the directional dependency of wave propagation. Our objective was to evaluate directionally independent unipolar voltage mapping, but with far‐field cancellation, to identify low‐voltage regions during AF. Methods: In 12 patients undergoing pulmonary vein isolation for AF, high‐resolution voltage mapping was performed in the left atrium during sinus rhythm and AF using a roving 20‐pole circular catheter. Bipolar electrograms (EGMs) (Bi) < 0.5 mV in sinus rhythm identified low‐voltage regions. During AF, bipolar voltage and unipolar voltage maps were created, the latter with (uni‐res) and without (uni‐orig) far‐field cancellation using a novel, validated least‐squares algorithm. Results: Uni‐res voltage was ~25% lower than uni‐orig for both low voltage and normal atrial regions. Far‐field EGM had a dominant frequency (DF) of 4.5–6.0 Hz, and its removal resulted in a lower DF for uni‐orig compared with uni‐res (5.1 ± 1.5 vs. 4.8 ± 1.5 Hz; p <.001). Compared with Bi, uni‐res had a significantly greater area under the receiver operator curve (0.80 vs. 0.77; p <.05), specificity (86% vs. 76%; p <.001), and positive predictive value (43% vs. 30%; p <.001) for detecting low‐voltage during AF. Similar improvements in specificity and positive predictive value were evident for uni‐res versus uni‐orig. Conclusion: Far‐field EGM can be reliably removed from uni‐orig using our novel, least‐squares algorithm. Compared with Bi and uni‐orig, uni‐res is more accurate in detecting low‐voltage regions during AF. This approach may improve substrate mapping and ablation during AF, and merits further study. [ABSTRACT FROM AUTHOR]

Introduction: Stand‐alone substrate ablation has become a standard ventricular tachycardia (VT) ablation strategy. We sought to evaluate the influence of baseline VT inducibility and activation mapping on ablation outcomes in patients with structural heart disease (SHD) undergoing VT ablation. Methods: Single center, observational and retrospective study including consecutive patients with SHD and documented VT undergoing ablation. Baseline VT induction was attempted before ablation in all patients and VT activation mapping performed when possible. Ablation was guided by activation mapping for mappable VTs plus substrate ablation for all patients. Ablation outcomes and complications were evaluated. Results: One hundred and sixty patients were included and were classified in three groups according to baseline VT inducibility:group 1 (non inducible, n = 18), group 2 (1 VT morphology induced, n = 53), and group 3 (>1 VT morphology induced, n = 89). VT activation mapping was possible in 35%. After a median follow‐up of 38.5 months, baseline inducibility of greater than 1 VT morphology was associated with a significant incidence of VT recurrence (42% for group 3 vs. 15.1% for group 2% and 5.6% for group 1, Log‐rank p <.0001) and activation mapping with a lower rate of VT recurrence (24% vs. 36.3%, Log‐rank p =.035). Baseline inducibility of greater than 1 VT morphology (hazards ratio [HR]: 12.05, 95% confidence interval [CI]: 1.60–90.79, p =.016) was an independent predictor of VT recurrence while left ventricular ejection fraction less than 30% (HR: 1.93, 95% CI: 1.13–3.25, p =.014) and advanced heart failure (HR: 4.69, 95% CI: 2.75–8.01, p <.0001) were predictors of mortality or heart transplantation. Complications occurred in 11.2% (5.6% hemodynamic decompensation). Conclusion: Baseline VT inducibility and activation mapping may add significant prognostic information during VT ablation procedures. [ABSTRACT FROM AUTHOR]

Introduction: The voltage map during sinus rhythm (SR) is a cornerstone of substrate mapping (SM) in scar‐related ventricular tachycardia (VT) and frequently used with pace mapping (PM). Where to conduct PM is unclear in cases of an extensive or unidentified substrate. Conduction properties are another aspect incorporated by SM, and conduction slowing has gained interest as being related to successful ablation, although its mechanism has not been elucidated. We aimed to investigate the relationship between SR conduction properties and VT isthmuses. Methods: Nineteen patients (mean age, 62 years) who underwent VT ablation with voltage mapping and PM were reviewed. Isochronal late activation maps (ILAMs) with eight zones were reconstructed and sequentially named from one to eight according to the SR propagation. Good PM sites were superimposed on ILAMs, and the isthmus was defined using different pacing latencies. ILAM properties harboring isthmuses were investigated. Results: Twenty‐eight ILAMs (13 epicardium, 1 right ventricular [RV], and 14 left ventricular [LV] endocardium) were reviewed. Eighteen isthmuses of 24 target VTs were identified, in which the proximal ends were in a later zone than the distal ends (zone 6 vs 4; P <.001), suggesting a reverse isthmus vector to the SR. The conduction velocity of the zone involving the distal isthmus was significantly lower than that of the SR preceding zone (0.40 vs 1.30 m/s; P <.001). SR conduction velocity decelerated by 69.5% (range 59.7%‐74.5%) before propagating into the isthmus area. Conclusion: Conduction slowing area during SR were related with the exit portion of the VT isthmuses. [ABSTRACT FROM AUTHOR]

There is no known strategy to differentiate which multicomponent electrograms in sinus rhythm maintain reentrant ventricular tachycardia (VT). Low entropy in the voltage breakdown of a multicomponent electrogram can localize conditions suitable for reentry but has not been validated against the classic VT activation mapping. We examined whether low entropy in a late and diversely activated ventricular scar region characterizes and differentiates the diastolic path of VT and represents protected tissue channels devoid of side branches. Intraoperative bipolar electrogram (BiEGM) activation and entropy maps were obtained during sinus rhythm in 17 patients with ischemic cardiomyopathy and compared with diastolic activation paths of VT (total of 39 VTs). Mathematical modeling of a zigzag main channel with side branches was also used to further validate structural representation of low entropy in the ventricular scar. A median of one region per patient (range: 1-2 regions) was identified in sinus rhythm, in which BiEGM with the latest mean activation time and adjacent minimum entropy were assembled together in a high-activation dispersion region. These regions accurately recognized diastolic paths of 34 VTs, often to multiple inducible VTs within a single individual arrhythmogenic region. In mathematical modeling, side branching from the main channel had a strong influence on the BiEGM composition along the main channel. The BiEGM obtained from a long unbranched channel had the lowest entropy compared with those with multiple side branches. In conclusion, among a population of multicomponent sinus electrograms, those that demonstrate low entropy and are delayed colocalize to critical long-protected channels of VT. This information is pertinent for planning VT ablation in sinus rhythm. [ABSTRACT FROM AUTHOR]

Background Left ventricular aneurysm (LVA) might be an arrhythmogenic substrate. Endocardiectomy and cryoablation for ventricular tachycardia (VT) with LVA can cause extensive myocardial damage. We aimed to evaluate the feasibility of surgical radial linear ablation for VT with LVA guided by electrophysiological mapping. Materials and methods Porcine models of VT with LVA were developed. Endocardial and epicardial substrate mapping during sinus rhythm were performed under thoracotomy. Surgical radial linear ablation was achieved by a bipolar radiofrequency ablation device. Outcomes, including procedural success and acute freedom of VT, were analyzed. Results Fifteen of 20 pigs developed LVA in a 6-wk survival period. A total of 28 sustained monomorphic VTs were initiated in 13 of 15 pigs (86.67%). The number of potential points captured from the endocardium and epicardium were 319 ± 45 and 358 ± 52 per animal, respectively. The ablative targets containing abnormal potentials were located largely on the border zone of LVA. Eight linear lesions from core to border zone of LVA were achieved per animal in a radial and even manner continuously, and ablation was repeated three times to transect border zone. The acute freedom of VT was 84.62%, P < 0.05. Conclusions Surgical linear endo-epicardial ablation seemed to be feasible in a porcine model with VT and LVA. [ABSTRACT FROM AUTHOR]

Substrate vs. Activation/Entrainment Guided VT Ablation Introduction Substrate-based ablation for scar-related ventricular tachycardia (VT) has gained prominence: however, there is limited data comparing it to ablation guided predominantly by activation and entrainment mapping of inducible and hemodynamically tolerated VTs. We compared the acute procedural efficacy and outcomes of predominantly substrate-based ablation versus ablation guided predominantly by activation and entrainment mapping. Methods and Results Database searches through April 2016 identified 6 eligible studies (enrolling 403 patients, with 1 randomized study) comparing the 2 strategies. The relative risk of VT recurrence at follow-up was assessed as the primary outcome using a random-effects meta-analysis. Secondary endpoints of acute success (based on noninducibility of VT), procedural complications, and mortality were assessed using weighted mean difference with the random effects model. At a median follow-up of 18 months, the relative risk (RR) of VT recurrence was not significantly different with substrate-based versus activation/entrainment guided VT ablation (0.72, 95% confidence interval [CI] 0.44-1.18), P = 0.2). Acute success (RR 1.02, 95% CI 0.95-1.1, P = 0.6), procedural complications (RR 0.8, 95% CI 0.35-1.82, P = 0.5) cardiovascular mortality and total mortality did not differ significantly (RR 0.83, 95% CI 0.38-1.79, P = 0.6 and RR 0.76, 95% CI 0.36-1.59, P = 0.5, respectively). Conclusions This meta-analysis demonstrates similar acute procedural efficacy, and complications, VT recurrence and mortality rates when comparing a predominantly substrate-based ablation strategy to a strategy guided predominantly by activation and entrainment mapping of inducible and hemodynamically tolerated VTs. [ABSTRACT FROM AUTHOR]

Zika virus ( ZIKV), isolated from macaques in Uganda in 1947, was not considered to be a dangerous human pathogen. However, this view has recently changed as ZIKV infections are now associated with serious pathological disorders including microcephaly and Guillain-Barré syndrome. Similar to other viruses in the Flaviviridae family, ZIKV expresses the serine protease NS3 which is responsible for viral protein processing and replication. Herein, we report the expression of an active NS3pro domain fused with the NS2B cofactor ( NS2 BLNNS3pro) in a prokaryotic expression system and profile its specificity for synthesized FRET-type substrate libraries. Our findings pave way for screening potential intracellular substrates of NS3 and for developing specific inhibitors of this ZIKV protease. [ABSTRACT FROM AUTHOR]

Tachycardias after atrial incisions represent frequent and serious problem. The majority of them are based on a re-entry electrical activation around a combination of anatomic and surgically created obstacles. Considering significant progress of cardiovascular surgery during the last decade along with potential large amount of open-heart procedures in the near future the number of incisional tachycardias has a tendency to increase. The aim of this work was to quantify the magnitude of the problem, characterize the tachycardias after different surgical operations and to analyze possible interventional treatment strategies. Nowadays evolution of mapping and ablation technologies may contribute to radically treatment of this type of arrhythmias while there are still a lot of issues that should be solved to improve the results of interventional treatment of incisional tachycardias. [ABSTRACT FROM AUTHOR]

Low Voltage-Based Ablation for Atrial Fibrillation Background Low-voltage zones (LVZs) represent fibrotic tissue and are substrates for atrial fibrillation (AF). We hypothesized that LVZ-based substrate modification along with pulmonary vein isolation (PVI) would improve outcomes in persistent AF (PeAF) patients with LVZs, whereas PVI alone would work in patients without LVZs. Methods and Results Voltage mapping of the left atrium (LA) was performed during sinus rhythm in 101 PeAF patients in whom LVZ was defined as an area with bipolar electrograms <0.5 mV. Thirty-nine patients had LVZs and underwent ablation of the entire LVZ area after PVI (LVZabl group). In the remaining 62 patients without LVZs, PVI alone was performed with no further substrate modifications (PVI group). An additional group of 16 consecutive PeAF patients with LVZ did not undergo any substrate modification after PVI and were used as a comparison group (LVZnon-abl group) despite having similar size of LVZs to that in the LVZabl group. After a single session, 28 (72%) patients in the LVZabl group had no recurrence, whereas 49 (79%) patients in the PVI group had no recurrence during 18 ± 7 months of follow-up (log-rank, P = 0.400). In the LVZnon-abl group, only 6 patients (38%) had no recurrence during 32 ± 7 months of follow-up, even after a mean number of sessions of 1.8 (log-rank, P < 0.001, compared with the LVZabl group). Conclusions Additional LVZ-based substrate modification after PVI improved the outcome in PeAF patients with LVZs, whereas PVI alone worked in patients without LVZs, even in those with PeAF. [ABSTRACT FROM AUTHOR]

Voltage-Guided Ablation for Persistent Afib Background Fibrosis as a substrate for atrial fibrillation (AF) has been shown in numerous preclinical models. Voltage mapping enables in vivo assessment of scar in the left atrium (LA), which can be targeted with catheter ablation. Objective We hypothesized that using the presence or absence of low voltage to guide ablation beyond pulmonary vein antral isolation (PVAI) will improve atrial arrhythmia (AF/AT)-free survival in persistent AF. Methods and Results Single-center retrospective analysis of 2 AF ablation strategies: (1) standard ablation (SA) versus (2) voltage-guided ablation (VGA). PVAI was performed in both groups. With SA, additional lesions beyond PVAI were performed at the discretion of the operator. With VGA, additional lesions to isolate the LA posterior wall were performed if voltage mapping of this region in sinus rhythm showed scar (LA voltage < 0.5 mV). AF-/AT-free endpoint was defined as no sustained AF/AT seen off antiarrhythmic medications after a 2-month postablation blanking period. Seventy-six patients underwent SA and 65 underwent VGA. Patients were well matched for comorbidities, LVEF, and left atrial size. Posterior wall ablation was performed in 57% of patient with SA compared to 42% with VGA. VGA ablation increased 1-year AF-/AT-free survival in patients when compared to SA (80% vs. 57%; P = 0.005). In a multivariate analysis, VGA was the only independent predictor of AF-/AT-free survival (hazard ratio of 0.30; P = 0.002). Conclusions The presence of LA posterior wall scar may be an important ablation target in persistent AF. A prospective randomized trial is needed to confirm these data. [ABSTRACT FROM AUTHOR]

Mapping of Scar-Related VT Background Substrate-based VT ablation is mostly based on maps acquired with ablation catheters. We hypothesized that multipolar mapping catheters are more effective for identification of scar and local abnormal ventricular activity (LAVA). Methods and results Phase1: In a sheep infarction model (2 months postinfarction), substrate mapping and LAVA tagging (CARTO®3) was performed, using a Navistar (NAV) versus a PentaRay (PR) catheter (Biosense Webster). Phase2: Consecutive VT ablation patients from a single center underwent NAV versus PR mapping. Point pairs were defined as a PR and a NAV point located within a 3D-distance of ≤3 mm. Agreement was defined as both points in a pair being manually tagged as normal or LAVA. Four sheep (4 years, 50 ± 4.8 kg) and 9 patients were included (53 ± 14 years, 8 male, 6 ischemic cardiomyopathy). Mapping density was higher within the scar with PR versus NAV (3.2 vs. 0.7 points/cm2, P = 0.001) with larger bipolar scar area (68 ± 55 cm2 vs. 58 ± 48 cm2, P = 0.001). In total, 818 point pairs were analyzed. Using PR, far-field voltages were smaller (PR vs. NAV; bipolar: 1.43 ± 1.84 mV vs. 1.64 ± 2.04 mV, P = 0.001; unipolar; 4.28 ± 3.02 mV vs. 4.59 ± 3.67 mV, P < 0.001). More LAVA were also detected with PR (PR vs. NAV; 126 ± 113 vs. 36 ± 29, P = 0.001). When agreement on LAVA was reached (overall: 72%; both LAVA, 40%; both normal, 82%) higher LAVA voltages were recorded on PR (0.48 ± 0.33 mV vs. 0.31 ± 0.21 mV, P = 0.0001). Conclusion Multipolar mapping catheters with small electrodes provide more accurate and higher density maps, with a higher sensitivity to near-field signals. Agreement between PR and NAV is low. [ABSTRACT FROM AUTHOR]

The fine characterization of the substrate is a baseline to thoroughly investigate the relations between organisms and their biotopes. Cutting edge spatial technologies now provide access to accurate information on biotopes and biocenoses both in terrestrial and in marine environments. Photogrammetry is one of them and has recently been applied in submarine environments especially in shallow clear water. In this study, we investigated the potential of photogrammetry to characterise benthic habitats in turbid environments. Although more challenging, turbid environments are more frequent in temperate marine coastal areas. We selected two rocky sites in the bay of Saint-Malo (Brittany, France), differentiated by their level of turbidity, one being a marine site exposed to natural tides (Buharats), while the other (Bizeux) is subjected to both natural tides and artificial currents created by the functioning of a hydroelectric dam. The different substrates observed were classified into eight classes at a centimetre resolution using photogrammetry-based spatial and multispectral predictors. The spatial benthic terrain predictors were derived from a digital surface model (DSM) at various spatial scales, and the multispectral predictors were retrieved from the red-green-blue (RGB, natural colours) orthomosaic imagery. An overall classification was computed for Buharats and Bizeux, with accuracies of 84.76% and 79.54% respectively, revealing a good quality of the substrate classification. The combination of RGB, DSM, and several spatial benthic terrain variables, with a pixel resolution of 5 and 10 mm, and a kernel size of 30, 60 and 90 pixels leads to the best benthic substrate classification (highest overall accuracy). At the class scale, producer's (PA) and user's (UA) accuracy showed that big boulders and field material were correctly distinguished. Small boulders and cobbles, having similar sizes, showed the lowest classification performances. This classification methodology provides new perspectives for mesoscale (100 m2 to 1 km2) semi-automatic mapping of the fine resolution (1 cm) relationship between benthic organisms and their substrate. • Photogrammetry is applicable for high resolution (∼1 cm) mesoscale (∼100 m2) reef characterization in turbid coastal waters. • Supervised classification provides good performance for benthic substrate mapping at a centimetre resolution. • Resulting maps enable detection of landscape variability within and between sites. [ABSTRACT FROM AUTHOR]

The author discusses the reliability of substrate ablation in treating atrial fibrillation. Topics discussed include the key parts of the cardiovascular system targeted by ablation including pulmonary vein potential and pulmonary vein tachycardia, the evaluated ablation method using an irrigated tip ablation catheter, and the potential of targeting low voltage areas in the atrium of the heart in boosting treatment efficiency of substrate ablation.

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]

We report a patient with non-ischemic dilated cardiomyopathy presenting with an electrical storm because of a poorly tolerated monomorphic ventricular tachycardia. Electroanatomical mapping revealed a scar restricted to the epicardium, whereas the endocardial voltage map was completely normal. Epicardial catheter ablation based on substrate mapping and limited pace and entrainment mapping eliminated the tachycardia. [ABSTRACT FROM AUTHOR]

Introduction: Animal studies show that atrial fibrillation (AF) may emanate from sites of high rate and regularity, with fibrillatory conduction to adjacent areas. We used simultaneous mapping to find evidence for potential drivers in human AF defined as sites with higher rate and regularity than surrounding tissue. Materials and Methods: In 24 patients (age 61 ± 10 years; 12 persistent), we recorded AF simultaneously from 32 left atrial bipolar basket electrodes in addition to pulmonary veins (PV), coronary sinus, and right atrial electrodes. We measured AF cycle length (CL) by Fourier transform and electrogram regularity at each electrode, referenced to patient-specific atrial anatomy. Results: We analyzed 10,298 electrode-periods. Evidence for potential AF drivers was found in 11 patients (five persistent). In persistent AF, these sites lay at the coronary sinus and left atrial roof but not PVs, while in paroxysmal AF six of nine sites lay at PVs (P < 0.05). During ablation, a subset of patients experienced AF CL prolongation or termination with a focal lesion; in each case this lesion mapped to potential driver sites on blinded analysis. Conversely, sequential mapping failed to reveal these sites, possibly due to fluctuations in dominant frequency at driver locations in the context of migratory AF. Conclusions: Simultaneous multisite recordings in human AF reveal evidence for drivers that lie near PVs in paroxysmal but not persistent AF, and were sites where ablation slowed or terminated AF in a subset of patients. The future work should determine if real-time ablation of AF-maintaining regions defined in this fashion eliminates AF. [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]

Objective: To study fluctuations in intracardiac atrial fibrillation (AF) cycle length (CL). Background: Sites of short AF CL may be good ablation targets, and cycle lengthening predicts ablation success. However, the optimum method for measuring AF CL, and its stability, are unclear. We hypothesized that autocorrelation better estimates AF CL than spectral dominant frequency (DF), which is susceptible to double counting, using monophasic action potentials (MAPs) to separate atrial activation from artifact. Methods: In 28 patients with paroxysmal or persistent AF, we analyzed 49 AF epochs using MAPs at the high (HRA) and low (LRA) right atrium. We estimated AF CL over 2 seconds, 10 seconds, and 2 minutes using spectral DF and autocorrelation in MAPs and filtered bipoles. Results: In the HRA, manually measured CL was 167 ± 25 ms. Spectral DF poorly estimated AF CL in bipolar signals (R = 0.31; P = NS), due to double counting, but accurately estimated MAP CL (R = 0.73, P < 0.001). Autocorrelation estimated MAP (R = 0.92; P < 0.001) and bipolar (R = 0.83; P < 0.001) CL, with lower errors than spectral DF (P < 0.0001). Over time, changes in DF consistently preceded reciprocal changes in organization (P < 0.001). Finally, excluding inaccurate spectra, DF and AF organization differed between HRA and LRA over 2 seconds, but correlated over 10 seconds and 2 minutes (P < 0.05). Conclusions: AF CL is better estimated by autocorrelation than spectral DF, particularly for bipoles, and stable when measured for >10 seconds. Notably, changes in AF CL preceded reciprocal changes in organization, yet changes in organization did not precede changes in AF CL. These results may help to interpret AF CL fluctuations. [ABSTRACT FROM AUTHOR]

Substrate Mapping in a Porcine Model of Chronic MI. Introduction: Substrate-based catheter ablation of postmyocardial infarction (post-MI) ventricular tachycardia necessitates electroanatomic definition of the scarred endocardium. We sought to determine whether electrogram criteria during sinus rhythm could identify the location and extent of the myocardial scar by electroanatomic mapping. Methods and Results: A porcine model of healed MI was generated by injecting agarose microspheres into the mid left anterior descending coronary artery. At least 4 weeks post-MI, the animals (n = 24) underwent detailed left ventricular endocardial electroanatomic mapping using a 4-mm-tip catheter (BioSense-Webster, Inc.). Based upon mapping data in normal animals, infarcted tissue was defined as bipolar electrogram amplitude <1.5 mV and electrogram duration ≥50 msec. Radiofrequency ablation lesions (2–10 per animal) were placed to tag the endocardial borders of the electroanatomic mapping-defined scar. The area of the scar defined by abnormal voltage amplitude was 25.9 ± 15.4 cm[sup 2] (range 6.9–60.5). This area correlated well with that defined as scar by the electrogram duration criteria (26.4 ± 16 cm[sup 2]) . Of those points remote from the infarct with falsely low voltage amplitude resulting from presumed poor catheter-tissue contact, 94% were correctly identified as normal when using the electrogram duration criteria. Late potentials were observed predominantly along the borders of the infarcted myocardium. The radiofrequency lesions placed to tag the scar borders were located along the scar periphery during gross pathologic examination. Conclusion: During normal sinus rhythm, both bipolar electrogram voltage amplitude and electrogram duration criteria are able to help differentiate normal from scarred myocardial tissue. Using these criteria, a detailed reconstruction of the endocardial scar can be rendered by electroanatomic mapping of the heart.(J Cardiovasc Electrophysiol, Vol. 14, pp. 524-529, May 2003). [ABSTRACT FROM AUTHOR]

Myocardial Scar Characterization with CT Scar delineation with late gadolinium-enhanced MRI can direct VT substrate mapping and ablation, but imaging is poor and relatively contraindicated in the majority of patients with ICDs. We present a case of scar definition using late iodine-enhanced multidetector CT in a patient with ischemic cardiomyopathy and multiple ICD shocks for VT. CT images were acquired using a novel intracoronary contrast delivery protocol which provided high-resolution subendocardial scar visualization. The segmented scar images were subsequently imported into an electroanatomic mapping platform to guide successful VT ablation. [ABSTRACT FROM AUTHOR]

The authors reflect on the use of ventricular tachycardia substrate mapping in catheter ablation for scar-related ventricular tachycardia (VT). In the article the authors discuss research which has investigated ablation and mapping and offer their opinions on several points raised in the article "Integration of Merged Delayed-Enhanced Magnetic Resonance Imaging and Multi-Detector Computed Tomography for the Guidance of Ventricular Tachycardia Ablation:A Pilot Study" by H. Cochet et al.

A positive endomyocardial biopsy (EMB) is a major diagnostic criterion for arrhythmogenic right ventricular cardiomyopathy (ARVC). Nevertheless, its sensitivity is low due to the focal nature of the disease. Moreover, myocardial samples are usually taken from the uncommonly involved interventricular septum to minimize the risk of perforation. In this report, we describe a novel bioptical approach for ARVC diagnosis guided by the identification of right ventricle (RV) affected regions by means of electroanatomical voltage mapping. [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]