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University of Auckland

Country: New Zealand

University of Auckland

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42 Projects, page 1 of 9
  • Funder: UKRI Project Code: EP/P008690/1
    Funder Contribution: 12,814 GBP

    Despite over a century's study, the mechanisms of cardiac arrhythmias are poorly understood. Even modern experimental methods do not provide sufficient temporal and spacial resolution to trace down fine details of fibrillation development in samples of cardiac tissue, not to mention the heart in vivo. Advances in human genetics provide information on the impact of certain genes on cellular activity, but do not explain the resultant mechanisms by which fibrillation arises. Thus, for some genetic cardiac diseases, the first presenting symptom is death. Combination of mathematical modelling and the latest realistic computer simulations of electrical activity in the heart have much advanced our understanding of heart fibrillation and sudden cardiac death, and the impact of in-silico modelling, or indeed in-silico "testing", is expected to increase significantly as we approach the ultimate goal of the whole-heart modelling. Biophysically and anatomically realistic simulation of cardiac action potential propagation through the heart is computationally expensive due to the huge number of equations per cell and the vast spacial and temporal scales required. Therefore any insights that can be obtained through generic mathematical model analysis is very valuable, as it tends to reveal generic mechanisms, unlike direct computer simulations, which provide answers valid only for a specific choice of parameters and initial conditions and depend on the computer model accuracy. Note that despite of the decades of steady progress, computer models still have qualitative rather than quantitative predictive power on the macroscopic scale, e.g. where whole heart or a whole chamber of the heart are concerned. Our recent progress in asymptotic analysis of dissipative vortices dynamics has revealed a new phenomenon of the vortices interaction with sharp variations of thickness in excitable layer. Such interaction of cardiac re-entry with sharp anatomical features, as e.g. pectinate muscles and terminal crest in atria, can cause considerable displacement of established localisation of re-entry compared to where it was first localised. The asymptotic theory prediction of the vortices drift caused by interaction with sharp thickness variations in a layer has been confirmed in experiments with Belousov-Zhabotinski reaction, and verified in computer simulations with a variety of cell excitation models, from extremely simplified "conceptual" models to realistic ionic kinetics models, and for tissue geometries from artificial idealised geometries to a realistic anatomy of human atria. A better underestanding of this phenomenon may have significant implications in clinics, say for chosing an individual ablation strategy for treatment of atrial fibrillation. Validation of the identified new phenomenon has so far been done only on a single model of human atrium, and understanding of to what extent the effect is universal requires extensive testing on a wide variety of cardiac MRI anatomy models, before experimental testing and clinical implications can be considered. The aim of the proposed project is to visit the Auckland Bioengineering Institute (ABI), New Zealand, which is an international leader in the heart and cardiovascular system research that combines instrumentation development, experimental measurements and modelling. ABI cardiovascular magnetic resonance (CMR) imaging group obtains most detail models of heart geometry and tissue microstructure. This visit will forge a closer collaboration than it is feasible from a distance, and provide a possibility of exhaustive testing of the new phenomenon in the most up-to-date anatomically and biophysically realistic models. An extra benefit will be provided by the applicant's participation in Cardiac Physiome Workshop (23 August 2016, Seoul, Korea), which will be a unique opportunity to discuss our recent findings and future directions of research with the world leaders in the field.

  • Funder: EC Project Code: 339993
  • Funder: EC Project Code: 617060
  • Funder: UKRI Project Code: BB/S020616/1
    Funder Contribution: 30,612 GBP

    Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

  • Funder: UKRI Project Code: EP/K034367/1
    Funder Contribution: 99,016 GBP

    Although an increasing number of people survive heart attacks, the scar left in their heart muscle leaves them at an increased risk of developing lethal cardiac 'arrhythmias' (abnormal beating of the heart) following the initial attack. Little is known about the underlying processes linking the presence of scars to increased death from cardiac arrhythmias. Specifically, it is not well understood whether the scar is involved in the actual generation of the arrhythmia, or whether it just helps to stabilise an arrhythmic episode generated by another mechanism, unrelated to the scar itself. As a result, diagnosis and therapy planning is non-optimal for these patients, and the rate of sudden death due to arrhythmic events is still high within this population. Current clinical tools can provide useful information regarding scars within patients who have suffered prior heart attacks. Clinical magnetic resonance (MR) imaging gives an important non-invasive means of analysing the location and shape of scars in patients. In addition, analysis of clinical electrocardiogram (ECG) recordings during arrhythmia can suggest not only the type of arrhythmia, but also the role the scar may play in such episodes. In particular, careful analysis of the shape of the ECG trace in the first few arrhythmic beats has suggested that, in many cases, the scar itself is highly likely to be the actual source of the ectopic activity responsible for generating the arrhythmia. Basic science investigations have shown that the structure of the tissue in and around the scar is highly diverse, and that the functional electrical properties are also changed from that of the normal, healthy cardiac tissue. As such, how the scar may act to generate lethal arrhythmia is thought to involve highly complex processes, which are not yet well understood. Our goal is to use computer modelling alongside high-resolution animal and clinical images to gain an in-depth understanding of the underlying processes involved in the generation of lethal arrhythmias directly from within cardiac scars. By using high-resolution animal images of scars, we will generate exceptionally-detailed computational models to investigate how the interaction between structural and functional diversity within a scar may encourage the generation of arrhythmia. This will allow us to understand how the fine-scaled properties of the scar and surrounding tissue make it susceptible to arrhythmias, identifying key 'hot spot' regions which represent the most dangerous potential sources of arrhythmic activity. We will then use this knowledge in comparison with patient MR and arrhythmia incidence data to make an important step towards translating these findings into the clinic, helping provide a mechanistic explanation of the underlying observed relationships uncovered in the clinical data. Overall, the findings from this research will pave the way for improved of risk stratification in patients with cardiac scars, and the development of novel clinically-useful therapies targeting the scar as a source of arrhythmia generation. The potential beneficiaries from this research will be extensive due to the high incidence of heart attacks annually in the UK (124,000), and the significant risk posed by arrhythmia to individuals following a heart attack. Consequently, this work also has the potential to reduce the health and economic costs of associated death and illness.

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