Reentrant Pathway Research Articles

The characterization of functional conduction block in patients with multiple types of atrial tachycardia- A discussion on the mechanism of multiple atrial tachycardia

BackgroundHigh-resolution mapping offers superior accuracy in delineating conduction features; however, certain characteristics are still linked to elevated recurrence rates of atrial tachycardia (AT), suggesting the influence of additional mechanisms. This study systematically assessed the substrate of functional conduction block (FCB) regions in relation to the mechanisms of multiple ATs.MethodsIn this study, the Carto system facilitated the mapping of ATs in 13 patients undergoing ablation, each presenting with more than two AT variants. FCB regions were marked and further analyzed.ResultsA total of 33 sustained ATs were mapped across the patient cohort. FCB regions showed convertibility in 7 of 13 patients (54%). Three kinds of presentations can be summarized by the FCB region: Firstly, the FCB region could act as the main obstacle sustaining the localized reentrant pathway, for which rounding obviously has a direct correlation with the mechanism of the AT (27%). Secondly, the FCB regions could act as obstacle lines to reorganize the propagation of the reentry in localized AT and macroreentrant AT (55%). Lastly, the FCB region could act as a bystander and may not be related to the mechanism of the ATs (18%). The potentials in FCB regions mostly performed low voltages or fragmented potentials (FPs) in the ATs which they did not perform the conduction block (90%).ConclusionIn multiple ATs, FCB regions may not be uncommon. The participation of FCB regions in the mechanism of ATs showed three different kinds of performance. The dynamic nature of this substrate may provide insight into the reasons for the high recurrence of related ATs.

Predicting postinfarct ventricular tachycardia by integrating cardiac MRI and advanced computational reentrant pathway analysis

BackgroundImplantable cardiac defibrillator (ICD) implantation can protect against sudden cardiac death after myocardial infarction. However, improved risk stratification for device requirement is still needed. ObjectiveThe purpose of this study was to improve assessment of postinfarct ventricular electropathology and prediction of appropriate ICD therapy by combining late gadolinium enhancement (LGE) and advanced computational modeling. MethodsADAS 3D LV (ADAS LV Medical, Barcelona, Spain) and custom-made software were used to generate 3-dimensional patient-specific ventricular models in a prospective cohort of patients with a myocardial infarction (N = 40) having undergone LGE imaging before ICD implantation. Corridor metrics and 3-dimensional surface features were computed from LGE images. The Virtual Induction and Treatment of Arrhythmias (VITA) framework was applied to patient-specific models to comprehensively probe the vulnerability of the scar substrate to sustaining reentrant circuits. Imaging and VITA metrics, related to the numbers of induced ventricular tachycardias and their corresponding round trip times (RTTs), were compared with ICD therapy during follow-up. ResultsPatients with an event (n = 17) had a larger interface between healthy myocardium and scar and higher VITA metrics. Cox regression analysis demonstrated a significant independent association with an event: interface (hazard ratio [HR] 2.79; 95% confidence interval [CI] 1.44–5.44; P < .01), unique ventricular tachycardias (HR 1.67; 95% CI 1.04–2.68; P = .03), mean RTT (HR 2.14; 95% CI 1.11–4.12; P = .02), and maximum RTT (HR 2.13; 95% CI 1.19–3.81; P = .01). ConclusionA detailed quantitative analysis of LGE-based scar maps, combined with advanced computational modeling, can accurately predict ICD therapy and could facilitate the early identification of high-risk patients in addition to left ventricular ejection fraction.

Arrhythmogenic Vulnerability of Reentrant Pathways in Post-Infarct Ventricular Tachycardia Assessed by Advanced Computational Modelling.

Arrhythmogenic Vulnerability of Reentrant Pathways in Post-Infarct Ventricular Tachycardia Assessed by Advanced Computational Modelling.

Arrhythmogenic vulnerability of re-entrant pathways in post-infarct ventricular tachycardia assessed by advanced computational modelling.

Substrate assessment of scar-mediated ventricular tachycardia (VT) is frequently performed using late gadolinium enhancement (LGE) images. Although this provides structural information about critical pathways through the scar, assessing the vulnerability of these pathways for sustaining VT is not possible with imaging alone.This study evaluated the performance of a novel automated re-entrant pathway finding algorithm to non-invasively predict VT circuit and inducibility. Twenty post-infarct VT-ablation patients were included for retrospective analysis. Commercially available software (ADAS3D left ventricular) was used to generate scar maps from 2D-LGE images using the default 40-60 pixel-signal-intensity (PSI) threshold. In addition, algorithm sensitivity for altered thresholds was explored using PSI 45-55, 35-65, and 30-70. Simulations were performed on the Virtual Induction and Treatment of Arrhythmias (VITA) framework to identify potential sites of block and assess their vulnerability depending on the automatically computed round-trip-time (RTT). Metrics, indicative of substrate complexity, were correlated with VT-recurrence during follow-up. Total VTs (85 ± 43 vs. 42 ± 27) and unique VTs (9 ± 4 vs. 5 ± 4) were significantly higher in patients with- compared to patients without recurrence, and were predictive of recurrence with area under the curve of 0.820 and 0.770, respectively. VITA was robust to scar threshold variations with no significant impact on total and unique VTs, and mean RTT between the four models. Simulation metrics derived from PSI 45-55 model had the highest number of parameters predictive for post-ablation VT-recurrence. Advanced computational metrics can non-invasively and robustly assess VT substrate complexity, which may aid personalized clinical planning and decision-making in the treatment of post-infarction VT.

Site-specific prolongation of repolarization prevents postmyocardial infarction tachycardia.

Site-specific prolongation of repolarization prevents postmyocardial infarction tachycardia.

Predicting ICD therapy and post-ablation ventricular tachycardia recurrence using cardiac MRI-based advanced computational reentrant pathway analysis

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): EACVI, Netherlands Heart Institute. Background MRI late gadolinium enhancement (LGE) images can provide novel insights about critical pathways through scar but does not assess the vulnerability of these pathways for sustaining scar-mediated ventricular tachycardia (VT). Computational modelling can augment the insights from imaging derived metrics by providing the functional implications of structural anatomy of the substrate. However, current (monodomain) approaches are computationally expensive and may not, by design, extract all critical pathways. Aim This study evaluated the performance of a novel, reaction-Eikonal based, automated reentrant pathway finding algorithm (VITA) to assess the functional viability of critical circuits identified on LGE and non-invasively predict arrhythmic risk in both an ICD and post-ablation cohort recurrence. Methods ADAS LV and custom-made software was used to generate 3D patient-specific ventricular models in a prospective cohort of post-infarct ICD patients (cohort 1, n=40) and a retrospective cohort of 20 post-infarct VT-ablation patients (cohort 2). Our Virtual Induction and Treatment of Arrhythmias (VITA) framework was then applied to comprehensively probe the viability of the scar substrate to sustaining reentrant circuits. VITA metrics, related to the numbers of induced VTs and their corresponding round trip times (RTTs), were compared with appropriate ICD therapy (cohort 1) and VT-recurrence (cohort 2) during follow-up. Results Patients in both cohorts with an event had higher VITA metrics. In cohort 1 (ICD), VITA demonstrated significantly more inducible VTs (6.6±4.2 vs. 4.1±3.4, p = .044), longer mean RTT (116.2±50.9 ms vs. 76.9±42.6 ms, p = .012) and max RTT (194.4±105.1 ms vs. 109.6±78.7, p =.009) in the event group. In addition, Cox-regression demonstrated a significant independent association with an event: induced VTs (HR 1.67; CI 1.04–2.68, p = .03), mean RTT (HR 2.14; CI 1.11–4.12, p = .02), maximum RTT (HR 2.13; CI 1.19–3.81, p = .01). In cohort 2 (VT-ablation), total induced VTs (85±43 vs. 42±27, p = .01) and unique VTs (9±4 vs. 5±4, p = .04) were significantly higher in patients with- compared to patients without recurrence, and were predictive of recurrence with AUC of .820 and .770, respectively. Max RTT demonstrated a trend towards significance 293 ± 90 ms vs. 200 ± 114 ms (p = .06) for recurrence and non-recurrence, respectively. No differences were observed in mean RTT between the two groups. Conclusion VITA enabled quantitative assessment of pro-arrhythmic vulnerability of the substrate which related directly to patient outcomes. The number of induced VTs were the most robust measure of appropriate ICD therapy and post-ablation arrhythmia recurrence. The RTT metrics, related to viable circuit lengths through scar, demonstrated a significant independent association with appropriate ICD therapy. Future studies should investigate the clinical utility of a VITA-guided selection and treatment approach.

Predicting ICD therapy and post-ablation ventricular tachycardia recurrence using cardiac MRI-based advanced computational reentrant pathway analysis

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Netherlands Heart Institute Fellowship, CVON PREDICT2 Young Talent Program Background MRI late gadolinium enhancement (LGE) images can provide novel insights about critical pathways through scar but does not assess the vulnerability of these pathways for sustaining scar-mediated ventricular tachycardia (VT). Computational modelling can augment the insights from imaging derived metrics by providing the functional implications of structural anatomy of the substrate. However, current (monodomain) approaches are computationally expensive and may not, by design, extract all critical pathways. Aim This study evaluated the performance of a novel, reaction-Eikonal based, automated reentrant pathway finding algorithm (VITA) to assess the functional viability of critical circuits identified on LGE and non-invasively predict arrhythmic risk in both an ICD and post-ablation cohort recurrence. Methods ADAS LV and custom-made software was used to generate 3D patient-specific ventricular models in a prospective cohort of post-infarct ICD patients (cohort 1, n=40) and a retrospective cohort of 20 post-infarct VT-ablation patients (cohort 2). Our Virtual Induction and Treatment of Arrhythmias (VITA) framework was then applied to comprehensively probe the viability of the scar substrate to sustaining reentrant circuits. VITA metrics, related to the numbers of induced VTs and their corresponding round trip times (RTTs), were compared with appropriate ICD therapy (cohort 1) and VT-recurrence (cohort 2) during follow-up. Results Patients in both cohorts with an event had higher VITA metrics. In cohort 1 (ICD), VITA demonstrated significantly more inducible VTs (6.6±4.2 vs. 4.1±3.4, p = .044), longer mean RTT (116.2±50.9 ms vs. 76.9±42.6 ms, p=.012) and max RTT (194.4±105.1 ms vs. 109.6±78.7, p =.009) in the event group. In addition, Cox-regression demonstrated a significant independent association with an event: induced VTs (HR 1.67; CI 1.04–2.68, p = .03), mean RTT (HR 2.14; CI 1.11–4.12, p = .02), maximum RTT (HR 2.13; CI 1.19–3.81, p = .01). In cohort 2 (VT-ablation), total induced VTs (85±43 vs. 42±27, p = .01) and unique VTs (9±4 vs. 5±4, p = .04) were significantly higher in patients with- compared to patients without recurrence, and were predictive of recurrence with AUC of .820 and .770, respectively. Max RTT demonstrated a trend towards significance 293 ± 90 ms vs. 200 ± 114 ms (p = .06) for recurrence and non-recurrence, respectively. No differences were observed in mean RTT between the two groups. Conclusion VITA enabled quantitative assessment of pro-arrhythmic vulnerability of the substrate which related directly to patient outcomes. The number of induced VTs were the most robust measure of appropriate ICD therapy and post-ablation arrhythmia recurrence. The RTT metrics, related to viable circuit lengths through scar, demonstrated a significant independent association with appropriate ICD therapy. Future studies should investigate the clinical utility of a VITA-guided selection and treatment approach.

Subthreshold delayed afterdepolarizations provide an important arrhythmogenic substrate in the border zone of infarcted hearts

Sudden cardiac arrest resulting from myocardial infarction (MI) is most often due to ventricular tachycardia (VT). In the infarcted heart, VT has been shown to originate at the periphery of the scar1. Such tissue is often termed the infarct border zone (BZ) and is comprised of a heterogeneous admixture of fibrosis and surviving cardiomyocytes2. Extended regions of BZ tissue that penetrate through non-conducting necrotic core scar can give rise to anatomical isthmuses which provide slow conducting re-entrant pathways that can help sustain VT circuits3.

Optimization of anti-tachycardia pacing efficacy through scar-specific delivery and minimization of re-initiation: a virtual study on a cohort of infarcted porcine hearts.

Anti-tachycardia pacing (ATP) is a reliable electrotherapy to painlessly terminate ventricular tachycardia (VT). However, ATP is often ineffective, particularly for fast VTs. The efficacy may be enhanced by optimized delivery closer to the re-entrant circuit driving the VT. This study aims to compare ATP efficacy for different delivery locations with respect to the re-entrant circuit, and further optimize ATP by minimizing failure through re-initiation. Seventy-three sustained VTs were induced in a cohort of seven infarcted porcine ventricular computational models, largely dominated by a single re-entrant pathway. The efficacy of burst ATP delivered from three locations proximal to the re-entrant circuit (septum) and three distal locations (lateral/posterior left ventricle) was compared. Re-initiation episodes were used to develop an algorithm utilizing correlations between successive sensed electrogram morphologies to automatically truncate ATP pulse delivery. Anti-tachycardia pacing was more efficacious at terminating slow compared with fast VTs (65 vs. 46%, P = 0.000039). A separate analysis of slow VTs showed that the efficacy was significantly higher when delivered from distal compared with proximal locations (distal 72%, proximal 59%), being reversed for fast VTs (distal 41%, proximal 51%). Application of our early termination detection algorithm (ETDA) accurately detected VT termination in 79% of re-initiated cases, improving the overall efficacy for proximal delivery with delivery inside the critical isthmus (CI) itself being overall most effective. Anti-tachycardia pacing delivery proximal to the re-entrant circuit is more effective at terminating fast VTs, but less so slow VTs, due to frequent re-initiation. Attenuating re-initiation, through ETDA, increases the efficacy of delivery within the CI for all VTs.

Virtual induction and treatment of arrhythmias (VITA): a fast automated computational tool to induce scar-related tachycardia and identify ablation targets

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): British Heart Foundation, Wellcome Trust Background Catheter ablation therapy of post-infarction ventricular tachycardia (VT) is often a lengthy procedure, with a high risk profile, and VT recurrence remains common. While computational modeling may aid pre-procedure planning and target identification, state-of-the-art reaction diffusion (R-D) simulations require access to high performance computing facilities, making them incompatible with clinical workflows. Purpose To present the Virtual Induction and Treatment of Arrhythmias (VITA), a novel, fast and fully automated computational tool to induce VT and identify subsequent ablation targets. Methods VITA employs multisite pacing to automatically find split activation wavefronts associated with the presence of channel isthmuses of viable myocytes within the inexcitable scar. The algorithm probes for all possible associated reentrant pathways and refines these to obtain a set of unique circuits sustaining potential clinical VTs. VT sustenance is assessed by comparing the electrical wavelength with the anatomical circuit path length. Corresponding exit sites of susceptible circuits are automatically identified, and a minimal lesion set constructed for ablation targeting. VITA also allows for rapid simulation of ECGs for clinical comparison. A summary of the VITA is shown in the Figure. VITA was tested on a virtual cohort of 7 post-infarcted porcine hearts and results compared to R-D simulations. Results Using only a desktop computer, VITA successfully identified all possible scar-related VT circuits and optimal ablation targets in just 48mins (per model), compared to 68.5hrs using a high-performance computer required by the R-D approach. Furthermore, VITA consistently identified more VTs associated with intra-scar circuits than R-D (Figure C). Conclusion VITA provides the first near real-time computational tool to aid treatment of post-infarction VTs.

PO-694-07 COMPARISON OF INTRACARDIAC ECHOCARDIOGRAPHY VERSUS CONVENTIONAL 3-DIMENSIONAL ELECTROANATOMIC MAPPING GUIDED TYPICAL CAVOTRICUSPID ISTHMUS ATRIAL FLUTTER ABLATIONS: INSIGHTS FROM THE ICE FLUTTER STUDY

Cavotricuspid isthmus (CTI) radiofrequency ablations (RFA) remain a common intervention for typical re-entrant pathway atrial flutter (AFL). 3-D electroanatomic mapping has been the cornerstone of CTI ablation, however further visualization with intracardiac echocardiography (ICE) provides an additional technique to ensure a more accurate and complete CTI full thickness ablation.

Analyzing the Role of Repolarization Gradients in Post-infarct Ventricular Tachycardia Dynamics Using Patient-Specific Computational Heart Models.

Aims: Disease-induced repolarization heterogeneity in infarcted myocardium contributes to VT arrhythmogenesis but how apicobasal and transmural (AB-TM) repolarization gradients additionally affect post-infarct VT dynamics is unknown. The goal of this study is to assess how AB-TM repolarization gradients impact post-infarct VT dynamics using patient-specific heart models.Method: 3D late gadolinium-enhanced cardiac magnetic resonance images were acquired from seven post-infarct patients. Models representing the patient-specific scar and infarct border zone distributions were reconstructed without (baseline) and with repolarization gradients along both the AB-TM axes. AB only and TM only models were created to assess the effects of each ventricular gradient on VT dynamics. VTs were induced in all models via rapid pacing.Results: Ten baseline VTs were induced. VT inducibility in AB-TM models was not significantly different from baseline (p>0.05). Reentry pathways in AB-TM models were different than baseline pathways due to alterations in the location of conduction block (p<0.05). VT exit sites in AB-TM models were different than baseline VT exit sites (p<0.05). VT inducibility of AB only and TM only models were not significantly different than that of baseline (p>0.05) or AB-TM models (p>0.05). Reentry pathways and VT exit sites in AB only and TM only models were different than in baseline (p<0.05). Lastly, repolarization gradients uncovered multiple VT morphologies with different reentrant pathways and exit sites within the same structural, conducting channels.Conclusion: VT inducibility was not impacted by the addition of AB-TM repolarization gradients, but the VT reentrant pathway and exit sites were greatly affected due to modulation of conduction block. Thus, during ablation procedures, physiological and pharmacological factors that impact the ventricular repolarization gradient might need to be considered when targeting the VTs.

Ambulatory continuous peripheral nerve blocks to treat postamputation phantom limb pain: a multicenter, randomized, quadruple-masked, placebo-controlled clinical trial.

Phantom limb pain is thought to be sustained by reentrant neural pathways, which provoke dysfunctional reorganization in the somatosensory cortex. We hypothesized that disrupting reentrant pathways with a 6-day-long continuous peripheral nerve block reduces phantom pain 4 weeks after treatment. We enrolled patients who had an upper- or lower-limb amputation and established phantom pain. Each was randomized to receive a 6-day perineural infusion of either ropivacaine or normal saline. The primary outcome was the average phantom pain severity as measured with a Numeric Rating Scale (0-10) at 4 weeks, after which an optional crossover treatment was offered within the following 0 to 12 weeks. Pretreatment pain scores were similar in both groups, with a median (interquartile range) of 5.0 (4.0, 7.0) for each. After 4 weeks, average phantom limb pain intensity was a mean (SD) of 3.0 (2.9) in patients given local anesthetic vs 4.5 (2.6) in those given placebo (difference [95% confidence interval] 1.3 [0.4, 2.2], P = 0.003). Patients given local anesthetic had improved global impression of change and less pain-induced physical and emotional dysfunction, but did not differ on depression scores. For subjects who received only the first infusion (no self-selected crossover), the median decrease in phantom limb pain at 6 months for treated subjects was 3.0 (0, 5.0) vs 1.5 (0, 5.0) for the placebo group; there seemed to be little residual benefit at 12 months. We conclude that a 6-day continuous peripheral nerve block reduces phantom limb pain as well as physical and emotional dysfunction for at least 1 month.

Role of infarct scar dimensions, border zone repolarization properties and anisotropy in the origin and maintenance of cardiac reentry

Cardiac ventricular tachycardia (VT) is a life-threatening arrhythmia consisting of a well organized structure of reentrant electrical excitation pathways. Understanding the generation and maintenance of the reentrant mechanisms, which lead to the onset of VT induced by premature beats in presence of infarct scar, is one of the most important issues in current electrocardiology. We investigate, by means of numerical simulations, the role of infarct scar dimension, repolarization properties and anisotropic fiber structure of scar tissue border zone (BZ) in the genesis of VT. The simulations are based on the Bidomain model, a reaction-diffusion system of Partial Differential Equations, discretized by finite elements in space and implicit-explicit finite differences in time. The computational domain adopted is an idealized left ventricle affected by an infarct scar extending transmurally. We consider two different scenarios: i) the scar region extends along the entire transmural wall thickness, from endocardium to epicardium, with the exception of a BZ region shaped as a central sub-epicardial channel (CBZ); ii) the scar region extends transmurally along the ventricular wall, from endocardium to a sub-epicardial surface, and is surrounded by a BZ region (EBZ). In CBZ simulations, the results have shown that: i) the scar extent is a crucial element for the genesis of reentry; ii) the repolarization properties of the CBZ, in particular the reduction of IKs and IKr currents, play an important role in the genesis of reentrant VT. In EBZ simulations, since the possible reentrant pathway is not assigned a-priori, we investigate in depth where the entry and exit sites of the cycle of reentry are located and how the functional channel of reentry develops. The results have shown that: i) the interplay between the epicardial anisotropic fiber structure and the EBZ shape strongly affects the propensity that an endocardial premature stimulus generates a cycle of reentry; ii) reentrant pathways always develop along the epicardial fiber direction; iii) very thin EBZs rather than thick EBZs facilitate the onset of cycles of reentry; iv) the sustainability of cycles of reentry depends on the endocardial stimulation site and on the interplay between the epicardial breakthrough site, local fiber direction and BZ rim.

Role of 3-Dimensional Architecture of Scar and Surviving Tissue in Ventricular Tachycardia: Insights From High-Resolution Ex Vivo Porcine Models.

An improved knowledge of the spatial organization of infarct structure and its contribution to ventricular tachycardia (VT) is important for designing optimal treatments. This study explores the relationship between the 3-dimensional structure of the healed infarct and the VT reentrant pathways in high-resolution models of infarcted porcine hearts. Structurally detailed models of infarcted ventricles were reconstructed from ex vivo late gadolinium enhancement and diffusion tensor magnetic resonance imaging data of 8 chronically infarcted porcine hearts at submillimeter resolution (0.25×0.25×0.5 mm3). To characterize the 3-dimensional structure of surviving tissue in the zone of infarct, a novel scar-mapped thickness metric was introduced. Further, using the ventricular models, electrophysiological simulations were conducted to determine and analyze the 3-dimensional VT pathways that were established in each of the complex infarct morphologies. The scar-mapped thickness metric revealed the heterogeneous organization of infarct and enabled us to systematically characterize the distribution of surviving tissue thickness in 8 hearts. Simulation results demonstrated the involvement of a subendocardial tissue layer of varying thickness in the majority of VT pathways. Importantly, they revealed that VT pathways are most frequently established within thin surviving tissue structures of thickness ≤2.2 mm (90th percentile) surrounding the scar. The combination of high-resolution imaging data and ventricular simulations revealed the 3-dimensional distribution of surviving tissue surrounding the scar and demonstrated its involvement in VT pathways. The new knowledge obtained in this study contributes toward a better understanding of infarct-related VT.

Optogenetic manipulation of anatomical re-entry by light-guided generation of a reversible local conduction block.

Anatomical re-entry is an important mechanism of ventricular tachycardia, characterized by circular electrical propagation in a fixed pathway. It's current investigative and therapeutic approaches are non-biological, rather unspecific (drugs), traumatizing (electrical shocks), or irreversible (ablation). Optogenetics is a new biological technique that allows reversible modulation of electrical function with unmatched spatiotemporal precision using light-gated ion channels. We therefore investigated optogenetic manipulation of anatomical re-entry in ventricular cardiac tissue. Transverse, 150-μm-thick ventricular slices, obtained from neonatal rat hearts, were genetically modified with lentiviral vectors encoding Ca2+-translocating channelrhodopsin (CatCh), a light-gated depolarizing ion channel, or enhanced yellow fluorescent protein (eYFP) as control. Stable anatomical re-entry was induced in both experimental groups. Activation of CatCh was precisely controlled by 470-nm patterned illumination, while the effects on anatomical re-entry were studied by optical voltage mapping. Regional illumination in the pathway of anatomical re-entry resulted in termination of arrhythmic activity only in CatCh-expressing slices by establishing a local and reversible, depolarization-induced conduction block in the illuminated area. Systematic adjustment of the size of the light-exposed area in the re-entrant pathway revealed that re-entry could be terminated by either wave collision or extinction, depending on the depth (transmurality) of illumination. In silico studies implicated source-sink mismatches at the site of subtransmural conduction block as an important factor in re-entry termination. Anatomical re-entry in ventricular tissue can be manipulated by optogenetic induction of a local and reversible conduction block in the re-entrant pathway, allowing effective re-entry termination. These results provide distinctively new mechanistic insight into re-entry termination and a novel perspective for cardiac arrhythmia management.

Investigating a Novel Activation-Repolarisation Time Metric to Predict Localised Vulnerability to Reentry Using Computational Modelling

Exit sites associated with scar-related reentrant arrhythmias represent important targets for catheter ablation therapy. However, their accurate location in a safe and robust manner remains a significant clinical challenge. We recently proposed a novel quantitative metric (termed the Reentry Vulnerability Index, RVI) to determine the difference between activation and repolarisation intervals measured from pairs of spatial locations during premature stimulation to accurately locate the critical site of reentry formation. In the clinic, the method showed potential to identify regions of low RVI corresponding to areas vulnerable to reentry, subsequently identified as ventricular tachycardia (VT) circuit exit sites. Here, we perform an in silico investigation of the RVI metric in order to aid the acquisition and interpretation of RVI maps and optimise its future usage within the clinic. Within idealised 2D sheet models we show that the RVI produces lower values under correspondingly more arrhythmogenic conditions, with even low resolution (8 mm electrode separation) recordings still able to locate vulnerable regions. When applied to models of infarct scars, the surface RVI maps successfully identified exit sites of the reentrant circuit, even in scenarios where the scar was wholly intramural. Within highly complex infarct scar anatomies with multiple reentrant pathways, the identified exit sites were dependent upon the specific pacing location used to compute the endocardial RVI maps. However, simulated ablation of these sites successfully prevented the reentry re-initiation. We conclude that endocardial surface RVI maps are able to successfully locate regions vulnerable to reentry corresponding to critical exit sites during sustained scar-related VT. The method is robust against highly complex and intramural scar anatomies and low resolution clinical data acquisition. Optimal location of all relevant sites requires RVI maps to be computed from multiple pacing locations.

Accuracy of prediction of infarct-related arrhythmic circuits from image-based models reconstructed from low and high resolution MRI.

Identification of optimal ablation sites in hearts with infarct-related ventricular tachycardia (VT) remains difficult to achieve with the current catheter-based mapping techniques. Limitations arise from the ambiguities in determining the reentrant pathways location(s). The goal of this study was to develop experimentally validated, individualized computer models of infarcted swine hearts, reconstructed from high-resolution ex-vivo MRI and to examine the accuracy of the reentrant circuit location prediction when models of the same hearts are instead reconstructed from low clinical-resolution MRI scans. To achieve this goal, we utilized retrospective data obtained from four pigs ~10 weeks post infarction that underwent VT induction via programmed stimulation and epicardial activation mapping via a multielectrode epicardial sock. After the experiment, high-resolution ex-vivo MRI with late gadolinium enhancement was acquired. The Hi-res images were downsampled into two lower resolutions (Med-res and Low-res) in order to replicate image quality obtainable in the clinic. The images were segmented and models were reconstructed from the three image stacks for each pig heart. VT induction similar to what was performed in the experiment was simulated. Results of the reconstructions showed that the geometry of the ventricles including the infarct could be accurately obtained from Med-res and Low-res images. Simulation results demonstrated that induced VTs in the Med-res and Low-res models were located close to those in Hi-res models. Importantly, all models, regardless of image resolution, accurately predicted the VT morphology and circuit location induced in the experiment. These results demonstrate that MRI-based computer models of hearts with ischemic cardiomyopathy could provide a unique opportunity to predict and analyze VT resulting for from specific infarct architecture, and thus may assist in clinical decisions to identify and ablate the reentrant circuit(s).

Arrhythmia in stem cell transplantation.

Stem cell regenerative therapies hold promise for treating diseases across the spectrum of medicine. While significant progress has been made in the preclinical stages, the clinical application of cardiac cell therapy is limited by technical challenges. Certain methods of cell delivery, such as intramyocardial injection, carry a higher rate of arrhythmias. Other potential contributors to the arrhythmogenicity of cell transplantation include reentrant pathways caused by heterogeneity in conduction velocities between graft and host as well as graft automaticity. In this article, the arrhythmogenic potential of cell delivery to the heart is discussed.

A theoretical study of the initiation, maintenance and termination of gastric slow wave re-entry.

Gastric slow wave dysrhythmias are associated with motility disorders. Periods of tachygastria associated with slow wave re-entry were recently recognized as one important dysrhythmia mechanism, but factors promoting and sustaining gastric re-entry are currently unknown. This study reports two experimental forms of gastric re-entry and presents a series of multi-scale models that define criteria for slow wave re-entry initiation, maintenance and termination. High-resolution electrical mapping was conducted in porcine and canine models and two spatiotemporal patterns of re-entrant activities were captured: single-loop rotor and double-loop figure-of-eight. Two separate multi-scale mathematical models were developed to reproduce the velocity and entrainment frequency of these experimental recordings. A single-pulse stimulus was used to invoke a rotor re-entry in the porcine model and a figure-of-eight re-entry in the canine model. In both cases, the simulated re-entrant activities were found to be perpetuated by tachygastria that was accompanied by a reduction in the propagation velocity in the re-entrant pathways. The simulated re-entrant activities were terminated by a single-pulse stimulus targeted at the tip of re-entrant wave, after which normal antegrade propagation was restored by the underlying intrinsic frequency gradient. (i) the stability of re-entry is regulated by stimulus timing, intrinsic frequency gradient and conductivity; (ii) tachygastria due to re-entry increases the frequency gradient while showing decreased propagation velocity; (iii) re-entry may be effectively terminated by a targeted stimulus at the core, allowing the intrinsic slow wave conduction system to re-establish itself.