| 1. |
- Hill, Y.R., et al.
(författare)
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Investigating a novel activation-repolarisation time metric to predict localised Vulnerability to reentry using computational modelling
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- © 2016 Hill et al. 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. Copyright:
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| 2. |
- Wallman, Mikael, 1979, et al.
(författare)
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A Spatially Extended Model of the Human Atrioventricular Node
- 2017
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Ingår i: 2017 COMPUTING IN CARDIOLOGY (CINC). - 0276-6574. ; 44
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Konferensbidrag (refereegranskat)abstract
- The atrioventricular (AV) node plays a crucial role during many supraventricular tachycardias (SVT). To better understand its function under these complex conditions, mathematical modelling has emerged as a valuable tool. The model presented here builds on a recently published 1D model of the human AV-node, consisting of a series of interacting nodes, each with separate dynamics in refractory time and conduction delay. Here, we extend the formulation to 2D and demonstrate its ability to reproduce clinical data. Subsequently, we use it to study how AV-nodal properties for clinically assessed single and dual AV-node physiology affect activation for regular and stochastic input. In particular we study the effect of functional gradients within the AV node on ventricular response during atrial pacing and atrial fibrillation. Simulation results display important emergent features such as pathway switching and concealed conduction, and show differences in AF response that are not present in response to pacing. Simulation of a single impulse takes around 30 ms, admitting interactive use on clinical time scales as well as parameter estimation and uncertainty quantification. To our knowledge, the presented model is the first spatially extended human AV-node model, and as such represents a novel tool for understanding the human AV-nodal function in both healthy and diseased individuals, thereby paving the way for improved SVT diagnosis and therapy.
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| 3. |
- Wallman, Mikael, 1979, et al.
(författare)
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Assessment of cardiotoxic effects from ion channel assay data
- 2017
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Ingår i: Proceedings of Advances in Cell Based Screening 2017.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Drug-induced cardiotoxicity or torsades de pointes (TdP), a potentially lethal cardiac ventricular arrhythmia, is an adverse effect that has long been a leading cause of attrition during drug development.Minimizing the risk of this cardiotoxic effect is thus an important task during the drug development process and regulatory guidelines require new drugs to be evaluated for pro-arrhytmic risk before entering clinical testing. At present, block of the cardiac potassium channel hERG and human QT intervals are assessed as part of the current safety guidelines. Although a block of the cardiac potassium channel hERG and subsequent prolongation of the cardiac QT interval are common features of cardiotoxic drugs, there is no simple one-to-one correlation. TdP involves changes in cardiac cell repolarisation, which is dependent on the concerted activity of several ion channels including hERG, Na-, and Ca-channels. Too much emphasis on hERG as a marker has most likely hampered the development of new drugs by premature discontinuation from development.We aim to directly assess the primary clinical endpoint, namely ventricular proarrhythmia (i.e., cardiotoxicity). To achieve this, we use a data driven approach based on published data to train a neural network architecture.The technology is made easily accessible to potential users via a web based demonstrator.
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