Non-invasive detection of slow conduction with cardiac magnetic resonance imaging for ventricular tachycardia ablation.

AIMS: Non-invasive myocardial scar characterization with cardiac magnetic resonance (CMR) has been shown to accurately identify conduction channels and can be an important aid for ventricular tachycardia (VT) ablation. A new mapping method based on targeting deceleration zones (DZs) has become one of the most commonly used strategies for VT ablation procedures. The aim of the study was to analyse the capability of CMR to identify DZs and to find predictors of arrhythmogenicity in CMR channels. METHODS AND RESULTS: Forty-four consecutive patients with structural heart disease and VT undergoing ablation after CMR at a single centre (October 2018 to July 2021) were included (mean age, 64.8 ± 11.6 years; 95.5% male; 70.5% with ischaemic heart disease; a mean ejection fraction of 32.3 ± 7.8%). The characteristics of CMR channels were analysed, and correlations with DZs detected during isochronal late activation mapping in both baseline maps and remaps were determined. Overall, 109 automatically detected CMR channels were analysed (2.48 ± 1.15 per patient; length, 57.91 ± 63.07 mm; conducting channel mass, 2.06 ± 2.67 g; protectedness, 21.44 ± 25.39 mm). Overall, 76.1% of CMR channels were associated with a DZ. A univariate analysis showed that channels associated with DZs were longer [67.81 ± 68.45 vs. 26.31 ± 21.25 mm, odds ratio (OR) 1.03, P = 0.010], with a higher border zone (BZ) mass (2.41 ± 2.91 vs. 0.87 ± 0.86 g, OR 2.46, P = 0.011) and greater protectedness (24.97 ± 27.72 vs. 10.19 ± 9.52 mm, OR 1.08, P = 0.021). CONCLUSION: Non-invasive detection of targets for VT ablation is possible with CMR. Deceleration zones found during electroanatomical mapping accurately correlate with CMR channels, especially those with increased length, BZ mass, and protectedness.

Arrhythmogenic substrate detection in chronic ischaemic patients undergoing ventricular tachycardia ablation using multidetector cardiac computed tomography: compared evaluation with cardiac magnetic resonance.

AIMS: Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) permits characterizing ischaemic scars, detecting heterogeneous tissue channels (HTCs) which constitute the arrhythmogenic substrate (AS). Late gadolinium enhancement cardiac magnetic resonance also improves the arrhythmia-free survival when used to guide ventricular tachycardia (VT) substrate ablation. However, its availability may be limited. We sought to evaluate the performance of multidetector cardiac computed tomography (MDCT) imaging in identifying HTCs detected by LGE-CMR in ischaemic patients undergoing VT substrate ablation. METHODS AND RESULTS: Thirty ischaemic patients undergoing both LGE-CMR and MDCT before VT substrate ablation were included. Using a dedicated post-processing software, two blinded operators, assigned either to LGE-CMR or MDCT analysis, characterized the presence of CMR and computed tomography (CT) channels, respectively. Cardiac magnetic resonance channels were classified as endocardial (layers < 50%), epicardial (layers ≥ 50%), or transmural. Cardiac magnetic resonance- vs. CT-channel concordance was considered when showing the same orientation and American Heart Association (AHA) segment. Mean age was 69 ± 10 years; 90% were male. Mean left ventricular ejection fraction was 35 ± 10%. All patients had CMR channels (n = 76), whereas only 26/30 (86.7%) had CT channels (n = 91). Global sensitivity (Se) and positive predictive values for detecting CMR channels were 61.8% and 51.6%, respectively. MDCT performance improved in patients with epicardial CMR channels (Se 80.5%) and transmural scars (Se 72.2%). In 4/11 (36%) patients with subendocardial myocardial infarction (MI), MDCT was unable to identify the AS. CONCLUSIONS: Compared to LGE-CMR, myocardial wall thickness assessment using MDCT fails to detect the presence of AS in 36% of patients with subendocardial MI, showing modest sensitivity identifying HTCs but a better performance in patients with transmural scars.

Topography of the TH5 Segment in the Diphtheria Toxin T-Domain Channel.

The translocation domain (T-domain) of diphtheria toxin contains 10 α helices in the aqueous crystal structure. Upon exposure to a planar lipid bilayer under acidic conditions, it inserts to form a channel and transport the attached amino-terminal catalytic domain across the membrane. The TH5, TH8, and TH9 helices form transmembrane segments in the open-channel state, with TH1-TH4 translocated across the membrane. The TH6-TH7 segment also inserts to form a constriction that occupies only a small portion of the total channel length. Here, we have examined the TH5 segment in more detail, using the substituted-cysteine accessibility method. We constructed a series of 23 mutant T-domains with single cysteine residues at positions in and near TH5, monitored their channel formation in planar lipid bilayers, and probed for an effect of thiol-specific reagents added to the solutions on either side of the membrane. For 15 of the mutants, the reagent caused a decrease in single-channel conductance, indicating that the introduced cysteine residue was exposed within the channel lumen. We also found that reaction caused large changes in ionic selectivity for some mutant channels. We determined whether reaction occurred in the open state or in the brief flicker-closed state of the channel. Finally, we compared the reaction rates from either side of the membrane. Our experiments are consistent with the hypotheses that the TH5 helix has a transmembrane orientation and remains helical in the open-channel state; they also indicate that the middle of the helix is aligned with the constriction in the channel.

3D delayed-enhanced magnetic resonance sequences improve conducting channel delineation prior to ventricular tachycardia ablation.

AIMS: Non-invasive depiction of conducting channels (CCs) is gaining interest for its usefulness in ventricular tachycardia (VT) ablation. The best imaging approach has not been determined. We compared characterization of myocardial scar with late-gadolinium enhancement cardiac magnetic resonance using a navigator-gated 3D sequence (3D-GRE) and conventional 2D imaging using either a single shot inversion recovery steady-state-free-precession (2D-SSFP) or inversion-recovery gradient echo (2D-GRE) sequence. METHODS AND RESULTS: We included 30 consecutive patients with structural heart disease referred for VT ablation. Preprocedural myocardial characterization was conducted in a 3 T-scanner using 2D-GRE, 2D-SSFP and 3D-GRE sequences, yielding a spatial resolution of 1.4 × 1.4 × 5 mm, 2 × 2 × 5 mm, and 1.4 × 1.4 × 1.4 mm, respectively. The core and border zone (BZ) scar components were quantified using the 60% and 40% threshold of maximum pixel intensity, respectively. A 3D scar reconstruction was obtained for each sequence. An electrophysiologist identified potential CC and compared them with results obtained with the electroanatomic map (EAM). We found no significant differences in the scar core mass between the 2D-GRE, 2D-SSFP, and 3D-GRE sequences (mean 7.48 ± 6.68 vs. 8.26 ± 5.69 and 6.26 ± 4.37 g, respectively, P = 0.084). However, the BZ mass was smaller in the 2D-GRE and 2D-SSFP than in the 3D-GRE sequence (9.22 ± 5.97 and 9.39 ± 6.33 vs. 10.92 ± 5.98 g, respectively; P = 0.042). The matching between the CC observed in the EAM and in 3D-GRE was 79.2%; when comparing the EAM and the 2D-GRE and the 2D-SSFP sequence, the matching decreased to 61.8% and 37.7%, respectively. CONCLUSION: 3D scar reconstruction using images from 3D-GRE sequence improves the overall delineation of CC prior to VT ablation.

Preparation of High Conductive Medium and Establishment of Laege Capacity Conductive Channel.

The preparation of highly conductive media and the construction of conducting channels play a crucial role in improving the electrical conductivity of electrically conductive adhesives. Therefore, a new MXene structure is reported in this paper, and the improved structure is rationally designed by computational modeling, which greatly prevents the buildup of MXene nanosheets, improves the stability of the structure, and creates a wide electron transfer channel, and the capacitance contribution of this structure is up to 86.3%. By mixing MXene modified with Ag-plated copper powder in a quantitative relationship to form high conductive media, the electrical conductivity is largely improved and the defect of low electron transfer rate of conventional conductive fillers is broken. The potential value of high conductive media is largely exploited using high throughput and machine learning methods, and here we show that the resistivity has reached 9.668 × 10-7 Ω m. The first principles investigate the conductive channels and electron transfer pathways of high-conductive media at the atomic level, further revealing the mechanism of action of high-conductive media. This study is also the first report on the application of MXene to high-conductive media.

The C-terminal domain of Bacillus cereus hemolysin II oligomerizes by itself in the presence of cell membranes to form ion channels.

Bacillus cereus hemolysin II, a pore-forming ß-barrel toxin (HlyII), has a C-terminal extension of 94 amino acid residues, designated as the C-terminal domain of HlyII (HlyIICTD). HlyIICTD is capable of forming oligomers in aqueous solutions. Oligomerization of HlyIICTD significantly increased in the presence of erythrocytes and liposomes. Its affinity for erythrocytes of various origins differed insignificantly but was noticeably higher for T-cells. HlyIICTD destroyed THP-1 monocytes and J774 macrophages, acted most effectively on Jurkat T-lymphocytes and had virtually no impact on B-cell lines. HlyIICTD was able to form ion-conducting channels on an artificial bilayer membrane.

The Ionic Selectivity of Lysenin Channels in Open and Sub-Conducting States.

The electrochemical gradients established across cell membranes are paramount for the execution of biological functions. Besides ion channels, other transporters, such as exogenous pore-forming toxins, may present ionic selectivity upon reconstitution in natural and artificial lipid membranes and contribute to the electrochemical gradients. In this context, we utilized electrophysiology approaches to assess the ionic selectivity of the pore-forming toxin lysenin reconstituted in planar bilayer lipid membranes. The membrane voltages were determined from the reversal potentials recorded upon channel exposure to asymmetrical ionic conditions, and the permeability ratios were calculated from the fit with the Goldman-Hodgkin-Katz equation. Our work shows that lysenin channels are ion-selective and the determined permeability coefficients are cation and anion-species dependent. We also exploited the unique property of lysenin channels to transition to a stable sub-conducting state upon exposure to calcium ions and assessed their subsequent change in ionic selectivity. The observed loss of selectivity was implemented in an electrical model describing the dependency of reversal potentials on calcium concentration. In conclusion, our work demonstrates that this pore-forming toxin presents ionic selectivity but this is adjusted by the particular conduction state of the channels.

Scar channels in cardiac magnetic resonance to predict appropriate therapies in primary prevention.

BACKGROUND: Scar characteristics analyzed by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) are related with ventricular arrhythmias. Current guidelines are based only on the left ventricular ejection fraction to recommend an implantable cardioverter-defibrillator (ICD) in primary prevention. OBJECTIVES: Our study aims to analyze the role of imaging to stratify arrhythmogenic risk in patients with ICD for primary prevention. METHODS: From 2006 to 2017, we included 200 patients with LGE-CMR before ICD implantation for primary prevention. The scar, border zone, core, and conducting channels (CCs) were automatically measured by a dedicated software. RESULTS: The mean age was 60.9 ± 10.9 years; 81.5% (163) were men; 52% (104) had ischemic cardiomyopathy. The mean left ventricular ejection fraction was 29% ± 10.1%. After a follow-up of 4.6 ± 2 years, 46 patients (22%) reached the primary end point (appropriate ICD therapy). Scar mass (36.2 ± 19 g vs 21.7 ± 10 g; P < .001), border zone mass (26.4 ± 12.5 g vs 16.0 ± 9.5 g; P < .001), core mass (9.9 ± 8.6 g vs 5.5 ± 5.7 g; P < .001), and CC mass (3.0 ± 2.6 g vs 1.6 ± 2.3 g; P < .001) were associated with appropriate therapies. Scar mass > 10 g (25.31% vs 5.26%; hazard ratio 4.74; P = .034) and the presence of CCs (34.75% vs 8.93%; hazard ratio 4.07; P = .003) were also strongly associated with the primary end point. However, patients without channels and with scar mass < 10 g had a very low rate of appropriate therapies (2.8%). CONCLUSION: Scar characteristics analyzed by LGE-CMR are strong predictors of appropriate therapies in patients with ICD in primary prevention. The absence of channels and scar mass < 10 g can identify patients at a very low risk of ventricular arrhythmias in this population.

Cardiac Magnetic Resonance-Guided Ventricular Tachycardia Substrate Ablation.

OBJECTIVES: This study assessed the feasibility and potential benefit of performing ventricular tachycardia (VT) substrate ablation procedures guided by cardiac magnetic resonance (CMR)-derived pixel signal intensity (PSI) maps. BACKGROUND: CMR-aided VT ablation using PSI maps from late gadolinium enhancement-CMR (LGE-CMR), together with electroanatomical map (EAM) information, has been shown to improve outcomes of VT substrate ablation. METHODS: Eighty-four patients with scar-dependent monomorphic VT who underwent substrate ablation were included in the study. In the last 28 (33%) consecutive patients, the procedure was guided by CMR. Procedural data, as well as acute and follow-up outcomes, were compared between patients who underwent guided CMR and 2 control groups: 1) patients who had PSI maps were available but the EAM was acquired and used to select the ablation targets (CMR aided); and 2) patients with no CMR-derived PSI maps available (no CMR). RESULTS: Mean procedure duration was lower in CMR-guided substrate ablation compared with CMR-aided and no CMR (107 ± 59 min vs. 203 ± 68 min and 227 ± 52 min; p < 0.001 for both comparisons). CMR-guided ablation required less fluoroscopy time than CMR-aided ablation and no CMR (10 ± 4 min vs. 23 ± 11 min and 20 ± 9 min, respectively; p < 0.001 for both comparisons) and less radiofrequency time (15 ± 8 min vs. 20 ± 15 min and 26 ± 10 min; p = 0.16 and p < 0.001, respectively). After substrate ablation, VT inducibility was lower in CMR-guided ablation compared with CMR-aided ablation and no CMR (18% vs. 32% and 46%; p = 0.35 and p = 0.04, respectively), without significant differences in complications. After 12 months, VT recurrence was lower in those who underwent CMR-guided ablation compared with no CMR (log-rank: 0.019), with no differences with CMR-aided ablation. CONCLUSIONS: CMR-guided VT ablation is feasible and safe, significantly reduces the procedural, fluoroscopy, and radiofrequency times, and is associated with a higher noninducibility rate and lower VT recurrence after substrate ablation.

Analysis of Three-Dimensional Scar Architecture and Conducting Channels by High-Resolution Contrast-Enhanced Cardiac Magnetic Resonance Imaging in Chagas Heart Disease

ABSTRACT Background: We aimed to describe the morphology of the border zone of viable myocardium surrounded by scarring in patients with Chagas heart disease and study their association with clinical events. Methods: Adult patients with Chagas heart disease (n=22; 55% females; 65.5 years, SD 10.1) were included. Patients underwent high-resolution contrast-enhanced cardiac magnetic resonance using myocardial delayed enhancement with postprocessing analysis to identify the core scar area and border zone channels number, mass, and length. The association between border zone channel parameters and the combined end-point (cardiovascular mortality or internal cardiac defibrillator implantation) was tested by multivariable Cox proportional hazard regression analyses. The significance level was set at 0.05. Data are presented as the mean (standard deviation [SD]) or median (interquartile range). Results: A total of 44 border zone channels (1[1-3] per patient) were identified. The border zone channel mass per patient was 1.25 (0.48-4.39) g, and the extension in layers of the border zone channels per patient was 2.4 (1.0-4.25). Most border zone channels were identified in the midwall location. Six patients presented the studied end-point during a mean follow-up of 4.9 years (SD 1.6). Border zone channel extension in layers was associated with the studied end-point independent from left ventricular ejection fraction or fibrosis mass (HR=2.03; 95% CI 1.15-3.60). Conclusions: High-resolution contrast-enhanced cardiac magnetic resonance can identify border zone channels in patients with Chagas heart disease. Moreover, border zone channel extension was independently associated with clinical events.

Ion conductance of the stem of the anthrax toxin channel during lethal factor translocation.

The tripartite anthrax toxin consists of protective antigen, lethal factor (LF), and edema factor. PA63 (the 63-kDa, C-terminal part of protective antigen) forms heptameric channels in cell membranes that allow for the transport of LF and edema factor into the cytosol. These channels are mushroom shaped, with a ring of seven phenylalanine residues (known as the phenylalanine clamp) lining the junction between the cap and the stem. It is known that when LF is translocated through the channel, the phenylalanine clamp creates a seal that causes an essentially complete block of conduction. In order to examine ion conductance in the stem of the channel, we used Venus yellow fluorescent protein as a molecular stopper to trap LFN (the 30-kDa, 263-residue N-terminal segment of LF), as well as various truncated constructs of LFN, in mutant channels in which the phenylalanine clamp residues were mutated to alanines. Here we present evidence that ion movement occurs within the channel stem (but is stopped, of course, at the phenylalanine clamp) during protein translocation. Furthermore, we also propose that the lower region of the stem plays an important role in securing peptide chains during translocation.

Current Distributions in Quantum Hall Effect Devices.

This paper addresses the question of how current is distributed within quantum Hall effect devices. Three types of flow patterns most often mentioned in the literature are considered. They are: (1) skipping orbits along the device periphery (which arise from elastic collisions off hard-walled potentials); (2) narrow conducting channels along the device sides (which are presumed to be generated from confining potentials); and (3) currents distributed throughout the device (which are assumed to arise from a combination of confining and charge-redistribution potentials). The major conclusions are that skipping orbits do not occur in quantum Hall effect devices, and that nearly all of the externally applied current is located within the device interior rather than along the device edges.

Sinus rhythm detection of conducting channels and ventricular tachycardia isthmus in arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: The identification of conducting channels (CCs) based on its relative high voltage or the presence of electrograms with delayed components has been proposed for substrate-guided scar-related ventricular tachycardia (VT) ablation. The relationship of these channels with the VT isthmuses remains unclear. OBJECTIVE: To assess the link between CCs identified during sinus rhythm (SR) and VT isthmuses in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). METHODS: Twenty-two consecutive patients with ARVC undergoing substrate-guided VT ablation (scar dechanneling technique) were analyzed. High-density endocardial and epicardial electroanatomic maps were obtained during SR. Standard bipolar cutoff values (0.5-1.5 and <0.5 mV) were used to define border zone and dense scar. The CCs were identified by voltage threshold adjustment (voltage channels) or by tagging the electrograms with delayed components that are sequentially activated (late potential channels). RESULTS: A total of 87 CCs were identified; 65 (74.7%) of them on the epicardial surface. Twenty-four (27.6%) CCs were voltage channels, and compared with late potential CCs, these had a higher bipolar voltage (0.96 [0.48-1.29] mV vs 0.39 [0.26-0.50] mV; P < .001] and required more radiofrequency applications (5 [4-7] vs 3 [2-5]; P = .048]. Eighteen (90%) of 20 identified VT isthmuses were located on the epicardium. Only 8 (40%) VT isthmuses were related to a voltage CC. The remaining 12 (60%) VT isthmuses were linked to a late potential CC. CONCLUSION: Late potential CCs more frequently act as the VT substrate in ARVC and therefore should also be considered to guide SR substrate-guided ablation.

Three-dimensional architecture of scar and conducting channels based on high resolution ce-CMR: insights for ventricular tachycardia ablation.

BACKGROUND: Conducting channels are the target for ventricular tachycardia (VT) ablation. Conducting channels could be identified with contrast enhanced-cardiac magnetic resonance (ce-CMR) as border zone (BZ) corridors. A 3-dimensional (3D) reconstruction of the ce-CMR could allow visualization of the 3D structure of these BZ channels. METHODS AND RESULTS: We included 21 patients with healed myocardial infarction and VT. A 3D high-resolution 3T ce-CMR was performed before CARTO-guided VT ablation. The left ventricular wall was segmented and characterized using a pixel signal intensity algorithm at 5 layers (endocardium, 25%, 50%, 75%, epicardium). A 3D color-coded shell map was obtained for each layer to depict the scar core and BZ distribution. The presence/characteristics of BZ channels were registered for each layer. Scar area decreased progressively from endocardium to epicardium (scar area/left ventricular area: 34.0±17.4% at endocardium, 24.1±14.7% at 25%, 16.3±12.1% at 50%, 13.1±10.4 at 75%, 12.1±9.3% at epicardium; P<0.01). Forty-five BZ channels (2.1±1.0 per patient, 23.7±12.0 mm length, mean minimum width 2.5±1.5 mm) were identified, 85% between the endocardium and 50% shell and 76% present in ≥1 layer. The ce-CMR-defined BZ channels identified 74% of the critical isthmus of clinical VTs and 50% of all the conducting channels identified in electroanatomic maps. CONCLUSIONS: Scar area in patients with healed myocardial infarction decreases from the endocardium to the epicardium. BZ channels, more commonly seen in the endocardium, display a 3D structure within the myocardial wall that can be depicted with ce-CMR. The use of ce-CMR-derived maps to guide VT ablation warrants further investigation.