BeatBox - HPC Environment for Biophysically and Anatomically Realistic Cardiac Simulations

Despite over a century's study, the trigger mechanisms of cardiac arrhythmias are poorly understood. Even modern experimental methods do not provide sufficient temporal and spacial resolution to trace the development of fibrillation 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.Computer simulations of electrical activity in cardiac tissue have already led to developments in our understanding of heart fibrillation and sudden cardiac death and their impact is expected to increase significantly as we approach the ultimate goal of whole-heart modelling. Modelling the propagation of Action Potential through cardiac tissue is computationally expensive due to the huge number of equations per cell and the vast spacial and temporal scales required. The complexity of the problem encompasses the description of ionic currents underlying excitation of a single cell through the inhomogeneity of the tissue to the complex geometry of the whole heart. The timely running of computational models of cardiac tissue is increasingly dependent on the effective use of High Performance Computing (HPC). Current state of the art cardiac simulation tools are limited either by the availability of modern, detailed models, or by their ease of use. The miscellany of current model implementations leads many researchers to develop their own ad-hoc software, preventing them from both utilising the power of HPC effectively, and from collaborating fluidly. It is, therefore, impeding scientific progress.The aim of this project is to develop an HPC environment for biophysically and anatomically realistic simualtion of cardiac activity, an adaptable and extensible framework with which High Performance Computing may be harnessed by researchers.

The proposed project is fundamental research, and it is expected that its economic and public health impact will be not immediate, but via subsequent research, so immediate beneficiaries are most likely to be academic. The impact on wellbeing and economy of the UK will depend on the results that are yet to be obtained, both within this project and by subsequent research, and therefore by necessity are highly speculative. I. Specifically, we identify the following groups of immediate potential beneficiaries: - Researchers working in mathematical modelling of cardiac arrhythmias. Benefits: the new research software tool that we develop, which will complement the existing software; our results obtained with this software which will stimulate further research. - Cardiac electrophysiology: experimentalists studying re-entrant arrhythmia in cell cultures, tissues and animals. Benefits: predictions obtained by mathematical modelling using the software we develop, both by ourselves and by other researchers, which are testable experimentally and which are potentially relevant for biomedical applications. - Nonlinear science: researchers working in the theory and applications of excitable media and in the theory of other nonlinear self-organized dissipative structures. For this group, the benefits will be of a similar kind to the first group above. Excitable media in general, and spiral and scroll waves in particular, have been predicted and observed in a wide variety of spatially extended thermodynamically non-equilibrium systems of various physical, chemical and biological origin. The software we develop will be easily adaptable to those kinds of models, and most advantages provided by it will be relevant in those applications, too. - Applied mathematicians and software developers. This group are also likely beneficiaries, as the practical solutions we will develop may be applicable in other areas. For the groups above, the ways to ensure the delivery of benefits will be traditional, via providing free access to the software, advice on its use, and publishing research journals and relevant conferences. The associated time scales are minimal, as the benefits will start immediately upon publication and we choose journals that publish quickly. II. The impact on public health and wealth creation will be through long-term potential beneficiaries. Speculatively, if our study will lead to the expected improvements in efficiency of the resonant pacing as a tool for low-voltage defibrillation, or deeper understanding of the Sick Sinus Syndrome, such long-term beneficiaries would be: - companies that manufacture pacemakers, operating theatre and implantable defibrillators, who will be able to get new pacing protocols to improve efficiency or decrease harmful side-effects of the devices and widen their use; - pharmaceutical companies that manufature antiarrhythmic drugs, who will develop new classes of drugs based on the new understanding of the dynamics of cardiac arrhythmia; - clinicians and the NHS, who will have new more efficients methods of treatment of cardiac arrhythmia at their disposal, with fewer harmful side-effects, and lower treatmeant and care costs. - cardiac patients, whose life expectancy and quality of life will improve, - general public, through tax revenue of the industries involved, lower burden on NHS and prolongation of the active life of the ageing population. These benefits will be delivered indirectly via subsequent, more applicable research projects, both by other researchers and by ourselves, that will utilize the results of this project. The timescales here are hardly predictable but in any case it will be many years, as is usually the case with new medical treatments. There is a possibility that some of the results obtained with this project will be directly exploitable. In such cases, we will contact relevant University offices.