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Article ; Online: Interactions between calcium-induced arrhythmia triggers and the electrophysiological-anatomical substrate underlying the induction of atrial fibrillation.

Colman, Michael A / Varela, Marta / MacLeod, Rob S / Hancox, Jules C / Aslanidi, Oleg V

2024 Volume 602, Issue 5, Page(s) 835–853

Abstract: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is sustained by spontaneous focal excitations and re-entry. Spontaneous electrical firing in the pulmonary vein (PV) sleeves is implicated in AF generation. The aim of this simulation ... ...

Abstract	Atrial fibrillation (AF) is the most common cardiac arrhythmia and is sustained by spontaneous focal excitations and re-entry. Spontaneous electrical firing in the pulmonary vein (PV) sleeves is implicated in AF generation. The aim of this simulation study was to identify the mechanisms determining the localisation of AF triggers in the PVs and their contribution to the genesis of AF. A novel biophysical model of the canine atria was used that integrates stochastic, spontaneous subcellular Ca
MeSH term(s)	Animals ; Dogs ; Atrial Fibrillation/etiology ; Calcium ; Heart Atria ; Calcium, Dietary ; Action Potentials ; Fibrosis ; Potassium ; Pulmonary Veins
Chemical Substances	Calcium (SY7Q814VUP) ; Calcium, Dietary ; Potassium (RWP5GA015D)
Language	English
Publishing date	2024-02-19
Publishing country	England
Document type	Journal Article
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/JP285740
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Article: Patchy fibrosis promotes trigger-substrate interactions that both generate and maintain atrial fibrillation.

Colman, Michael A / Sharma, Roshan / Aslanidi, Oleg V / Zhao, Jichao

Interface focus

2023 Volume 13, Issue 6, Page(s) 20230041

Abstract: Fibrosis has been mechanistically linked to arrhythmogenesis in multiple cardiovascular conditions, including atrial fibrillation (AF). Previous studies have demonstrated that fibrosis can create functional barriers to conduction which may promote ... ...

Abstract	Fibrosis has been mechanistically linked to arrhythmogenesis in multiple cardiovascular conditions, including atrial fibrillation (AF). Previous studies have demonstrated that fibrosis can create functional barriers to conduction which may promote excitation wavebreak and the generation of re-entry, while also acting to pin re-entrant excitation in stable rotors during AF. However, few studies have investigated the role of fibrosis in the generation of AF triggers in detail. We apply our in-house computational framework to study the impact of fibrosis on the generation of AF triggers and trigger-substrate interactions in two- and three-dimensional atrial tissue models. Our models include a reduced and efficient description of stochastic, spontaneous cellular triggers as well as a simple model of heterogeneous inter-cellular coupling. Our results demonstrate that fibrosis promotes the emergence of focal excitations, primarily through reducing the electrotonic load on individual fibre strands. This enables excitation to robustly initiate within these single strands before spreading to neighbouring strands and inducing a full tissue focal excitation. Enhanced conduction block can allow trigger-substrate interactions that result in the emergence of complex, re-entrant excitation patterns. This study provides new insight into the mechanisms by which fibrosis promotes the triggers and substrate necessary to induce and sustain arrhythmia.
Language	English
Publishing date	2023-12-15
Publishing country	England
Document type	Journal Article
ISSN	2042-8898
ISSN	2042-8898
DOI	10.1098/rsfs.2023.0041
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Role of atrial tissue substrate and electrical activation pattern in fractionation of atrial electrograms: a computational study.

Varela, Marta / Aslanidi, Oleg V

Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference

2015 Volume 2014, Page(s) 1587–1590

Abstract: Complex fractionated atrial electrograms (CFAEs) are often used as a clinical marker for re-entrant drivers of atrial fibrillation. However, outcomes of clinical ablation procedures based on CFAEs are controversial and the mechanistic links between ... ...

Abstract	Complex fractionated atrial electrograms (CFAEs) are often used as a clinical marker for re-entrant drivers of atrial fibrillation. However, outcomes of clinical ablation procedures based on CFAEs are controversial and the mechanistic links between fractionation, re-entrant activity and the characteristics of the atrial substrate are not completely understood. We explore such links by simulating electrograms arising from both normal and re-entrant electrical activity in atrial tissue models. 2D and 3D tissue geometries with a range of conditions for intracellular coupling and myofiber orientation fields were studied. Electrograms were fractionated in the presence of complex atrial fiber fields and in 3D irregular geometries, due to far-field excitations. The complexity of the local electrical activity was not a strong determinant of the degree of fractionation. These results suggest that electrogram fractionation is more strongly linked to atrial substrate characteristics (including tissue geometry, fiber orientation and degree of intercelullar coupling) than to the electrical activation pattern sustaining atrial fibrillation.
MeSH term(s)	Computer Simulation ; Electrophysiologic Techniques, Cardiac/methods ; Heart Atria/physiopathology ; Humans ; Signal Processing, Computer-Assisted
Language	English
Publishing date	2015-01-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2694-0604
ISSN (online)	2694-0604
DOI	10.1109/EMBC.2014.6943907
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Initiation and sustenance of reentry are promoted by two different mechanisms.

Aslanidi, Oleg V / Hancox, Jules C

Heart rhythm

2014 Volume 12, Issue 1, Page(s) e2

MeSH term(s)	Animals ; Arrhythmias, Cardiac/physiopathology ; Heart Atria/physiopathology ; Male ; Small-Conductance Calcium-Activated Potassium Channels/drug effects ; Voltage-Sensitive Dye Imaging
Chemical Substances	Small-Conductance Calcium-Activated Potassium Channels
Language	English
Publishing date	2014-10-08
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	2229357-7
ISSN	1556-3871 ; 1547-5271
ISSN (online)	1556-3871
ISSN	1547-5271
DOI	10.1016/j.hrthm.2014.10.012
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Article ; Online: Towards patient-specific modelling of lesion formation during radiofrequency catheter ablation for atrial fibrillation.

Soor, Navjeevan / Morgan, Ross / Varela, Marta / Aslanidi, Oleg V

Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference

2016 Volume 2016, Page(s) 489–492

Abstract: Radiofrequency catheter ablation procedures are a first-line method of clinical treatment for atrial fibrillation. However, they suffer from suboptimal success rates and are also prone to potentially serious adverse effects. These limitations can be at ... ...

Abstract	Radiofrequency catheter ablation procedures are a first-line method of clinical treatment for atrial fibrillation. However, they suffer from suboptimal success rates and are also prone to potentially serious adverse effects. These limitations can be at least partially attributed to the inter- and intra- patient variations in atrial wall thickness, and could be mitigated by patient-specific approaches to the procedure. In this study, a modelling approach to optimising ablation procedures in subject-specific 3D atrial geometries was applied. The approach enabled the evaluation of optimal ablation times to create lesions for a given wall thickness measured from MRI. A nonliner relationship was revealed between the thickness and catheter contact time required for fully transmural lesions. Hence, our approach based on MRI reconstruction of the atrial wall combined with subject-specific modelling of ablation can provide useful information for improving clinical procedures.
MeSH term(s)	Atrial Fibrillation/diagnostic imaging ; Atrial Fibrillation/surgery ; Catheter Ablation/adverse effects ; Humans ; Image Processing, Computer-Assisted ; Magnetic Resonance Imaging ; Patient-Specific Modeling ; Treatment Outcome
Language	English
Publishing date	2016-04-15
Publishing country	United States
Document type	Journal Article
ISSN	2694-0604
ISSN (online)	2694-0604
DOI	10.1109/EMBC.2016.7590746
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Atrial Heterogeneity Generates Re-entrant Substrate during Atrial Fibrillation and Anti-arrhythmic Drug Action: Mechanistic Insights from Canine Atrial Models.

Varela, Marta / Colman, Michael A / Hancox, Jules C / Aslanidi, Oleg V

PLoS computational biology

2016 Volume 12, Issue 12, Page(s) e1005245

Abstract: Anti-arrhythmic drug therapy is a frontline treatment for atrial fibrillation (AF), but its success rates are highly variable. This is due to incomplete understanding of the mechanisms of action of specific drugs on the atrial substrate at different ... ...

Abstract	Anti-arrhythmic drug therapy is a frontline treatment for atrial fibrillation (AF), but its success rates are highly variable. This is due to incomplete understanding of the mechanisms of action of specific drugs on the atrial substrate at different stages of AF progression. We aimed to elucidate the role of cellular, tissue and organ level atrial heterogeneities in the generation of a re-entrant substrate during AF progression, and their modulation by the acute action of selected anti-arrhythmic drugs. To explore the complex cell-to-organ mechanisms, a detailed biophysical models of the entire 3D canine atria was developed. The model incorporated atrial geometry and fibre orientation from high-resolution micro-computed tomography, region-specific atrial cell electrophysiology and the effects of progressive AF-induced remodelling. The actions of multi-channel class III anti-arrhythmic agents vernakalant and amiodarone were introduced in the model by inhibiting appropriate ionic channel currents according to experimentally reported concentration-response relationships. AF was initiated by applied ectopic pacing in the pulmonary veins, which led to the generation of localized sustained re-entrant waves (rotors), followed by progressive wave breakdown and rotor multiplication in both atria. The simulated AF scenarios were in agreement with observations in canine models and patients. The 3D atrial simulations revealed that a re-entrant substrate was typically provided by tissue regions of high heterogeneity of action potential duration (APD). Amiodarone increased atrial APD and reduced APD heterogeneity and was more effective in terminating AF than vernakalant, which increased both APD and APD dispersion. In summary, the initiation and sustenance of rotors in AF is linked to atrial APD heterogeneity and APD reduction due to progressive remodelling. Our results suggest that anti-arrhythmic strategies that increase atrial APD without increasing its dispersion are effective in terminating AF.
MeSH term(s)	Animals ; Anti-Arrhythmia Agents/pharmacology ; Arrhythmias, Cardiac/physiopathology ; Biomechanical Phenomena ; Dogs ; Heart Atria/cytology ; Heart Atria/drug effects ; Models, Cardiovascular ; Reproducibility of Results ; Single-Cell Analysis
Chemical Substances	Anti-Arrhythmia Agents
Language	English
Publishing date	2016-12-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2193340-6
ISSN	1553-7358 ; 1553-734X
ISSN (online)	1553-7358
ISSN	1553-734X
DOI	10.1371/journal.pcbi.1005245
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Slow Conduction in the Border Zones of Patchy Fibrosis Stabilizes the Drivers for Atrial Fibrillation: Insights from Multi-Scale Human Atrial Modeling.

Morgan, Ross / Colman, Michael A / Chubb, Henry / Seemann, Gunnar / Aslanidi, Oleg V

Frontiers in physiology

2016 Volume 7, Page(s) 474

Abstract: Introduction: ...

Abstract	Introduction:
Language	English
Publishing date	2016-10-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2016.00474
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Article: Novel Computational Analysis of Left Atrial Anatomy Improves Prediction of Atrial Fibrillation Recurrence after Ablation.

Varela, Marta / Bisbal, Felipe / Zacur, Ernesto / Berruezo, Antonio / Aslanidi, Oleg V / Mont, Lluis / Lamata, Pablo

Frontiers in physiology

2017 Volume 8, Page(s) 68

Abstract: The left atrium (LA) can change in size and shape due to atrial fibrillation (AF)-induced remodeling. These alterations can be linked to poorer outcomes of AF ablation. In this study, we propose a novel comprehensive computational analysis of LA anatomy ... ...

Abstract	The left atrium (LA) can change in size and shape due to atrial fibrillation (AF)-induced remodeling. These alterations can be linked to poorer outcomes of AF ablation. In this study, we propose a novel comprehensive computational analysis of LA anatomy to identify what features of LA shape can optimally predict post-ablation AF recurrence. To this end, we construct smooth 3D geometrical models from the segmentation of the LA blood pool captured in pre-procedural MR images. We first apply this methodology to characterize the LA anatomy of 144 AF patients and build a statistical shape model that includes the most salient variations in shape across this cohort. We then perform a discriminant analysis to optimally distinguish between recurrent and non-recurrent patients. From this analysis, we propose a new shape metric called vertical asymmetry, which measures the imbalance of size along the anterior to posterior direction between the superior and inferior left atrial hemispheres. Vertical asymmetry was found, in combination with LA sphericity, to be the best predictor of post-ablation recurrence at both 12 and 24 months (area under the ROC curve: 0.71 and 0.68, respectively) outperforming other shape markers and any of their combinations. We also found that model-derived shape metrics, such as the anterior-posterior radius, were better predictors than equivalent metrics taken directly from MRI or echocardiography, suggesting that the proposed approach leads to a reduction of the impact of data artifacts and noise. This novel methodology contributes to an improved characterization of LA organ remodeling and the reported findings have the potential to improve patient selection and risk stratification for catheter ablations in AF.
Language	English
Publishing date	2017-02-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2017.00068
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Article ; Online: Atrial Heterogeneity Generates Re-entrant Substrate during Atrial Fibrillation and Anti-arrhythmic Drug Action

Marta Varela / Michael A Colman / Jules C Hancox / Oleg V Aslanidi

PLoS Computational Biology, Vol 12, Iss 12, p e

Mechanistic Insights from Canine Atrial Models.

2016 Volume 1005245

Abstract	Anti-arrhythmic drug therapy is a frontline treatment for atrial fibrillation (AF), but its success rates are highly variable. This is due to incomplete understanding of the mechanisms of action of specific drugs on the atrial substrate at different stages of AF progression. We aimed to elucidate the role of cellular, tissue and organ level atrial heterogeneities in the generation of a re-entrant substrate during AF progression, and their modulation by the acute action of selected anti-arrhythmic drugs. To explore the complex cell-to-organ mechanisms, a detailed biophysical models of the entire 3D canine atria was developed. The model incorporated atrial geometry and fibre orientation from high-resolution micro-computed tomography, region-specific atrial cell electrophysiology and the effects of progressive AF-induced remodelling. The actions of multi-channel class III anti-arrhythmic agents vernakalant and amiodarone were introduced in the model by inhibiting appropriate ionic channel currents according to experimentally reported concentration-response relationships. AF was initiated by applied ectopic pacing in the pulmonary veins, which led to the generation of localized sustained re-entrant waves (rotors), followed by progressive wave breakdown and rotor multiplication in both atria. The simulated AF scenarios were in agreement with observations in canine models and patients. The 3D atrial simulations revealed that a re-entrant substrate was typically provided by tissue regions of high heterogeneity of action potential duration (APD). Amiodarone increased atrial APD and reduced APD heterogeneity and was more effective in terminating AF than vernakalant, which increased both APD and APD dispersion. In summary, the initiation and sustenance of rotors in AF is linked to atrial APD heterogeneity and APD reduction due to progressive remodelling. Our results suggest that anti-arrhythmic strategies that increase atrial APD without increasing its dispersion are effective in terminating AF.
Keywords	Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2016-12-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: A novel computational sheep atria model for the study of atrial fibrillation.

Butters, Timothy D / Aslanidi, Oleg V / Zhao, Jichao / Smaill, Bruce / Zhang, Henggui

Interface focus

2014 Volume 3, Issue 2, Page(s) 20120067

Abstract: Sheep are often used as animal models for experimental studies into the underlying mechanisms of cardiac arrhythmias. Previous studies have shown that biophysically detailed computer models of the heart provide a powerful alternative to experimental ... ...

Abstract	Sheep are often used as animal models for experimental studies into the underlying mechanisms of cardiac arrhythmias. Previous studies have shown that biophysically detailed computer models of the heart provide a powerful alternative to experimental animal models for underpinning such mechanisms. In this study, we have developed a family of mathematical models for the electrical action potentials of various sheep atrial cell types. The developed cell models were then incorporated into a three-dimensional anatomical model of the sheep atria, which was recently reconstructed and segmented based on anatomical features within different regions. This created a novel biophysically detailed computational model of the three-dimensional sheep atria. Using the model, we then investigated the mechanisms by which paroxysmal rapid focal activity in the pulmonary veins can transit to sustained atrial fibrillation. It was found that the anisotropic property of the atria arising from the fibre structure plays an important role in facilitating the development of fibrillatory atrial excitation waves, and the electrical heterogeneity plays an important role in its initiation.
Language	English
Publishing date	2014-01-10
Publishing country	England
Document type	Journal Article
ISSN	2042-8898
ISSN	2042-8898
DOI	10.1098/rsfs.2012.0067
Database	MEDical Literature Analysis and Retrieval System OnLINE

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