Participation in the Cardiac Dynamics research program organised by Kavli Iinstitute for Theoretical Physics, summer 2006.

Lead Research Organisation: University of Liverpool
Department Name: Computer Science

Abstract

Cardiac disease is a major cause of premature death. More than half ofcardiac disease deaths are sudden and result from a spatiotemporalchaotic wave activity that prevents the main chambers of the heartfrom pumping blood normally (ventricular fibrillation). Developing afundamental understanding of the mechanisms that trigger and maintainlife-threatening cardiac arrhythmias is crucially important fordesigning antiarrhythmic therapies to reduce mortality.Kavli Institute for Theoretical Physics, University of California inSanta Barbara, runs Cardiac Dynamics ``miniprogram'' in the summer 2006. The goal of the program is to bring together aninterdisciplinary group of theorists, experimentalists and clinicianswith common interests in arrhythmogenesis. The program is expected toprovide a unique forum to foster collaborations that will lead to theintegration of new knowledge of biology and nonlinear dynamics inextended media and to the application of this knowledge to controlcardiac arrhythmias and to prevent sudden cardiac death in a clinicalsetting.I am one of 35 participants of the program confirmed to date, and of only 18invited to stay for its full duration. The topics to be covered by theprogram are highly relevant to the above mentioned my two currentlyactive EPSRC projects, GR/D500338/01``Feedback control of resonant drift as a tool for low voltage defibrillation''andEP/D0747891/1 ``Response functions for drift of spiral and scroll waves''.Both of the projects are to bringthe mathematical theory of re-entrant tachycardiacloser to real physiology and clinical applications. The KITP ``Cardiac Dynamics'' research program provides a unique opportunity to meet in a creative environment with world leading experimentalists, informally present and discuss key directions in the area, and formulate interesting problems for further research. The attached invitation from KITP promises to cover part ofmy local expenses, and not any travel expenses. As the invitation came after my most recent grant, EP/D0747891/1, applicationhad been submitted, expenses for the KITP program were notanticipated in either of the existing grant budgets, hence this application.

Publications

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Dierckx H (2017) Filament Tension and Phase Locking of Meandering Scroll Waves. in Physical review letters

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Kharche S. (2012) Cardioversion using feedback stimuli in human atria in Computing in Cardiology

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Kharche SR (2013) Simulating the role of anisotropy in human atrial cardioversion. in Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference

 
Description Localisation of cardiac re-entry sensitivity to small external perturbations and mechanisms of cardiac
arrhythmias self-termination are among my main research interests. The first is important for effective control
and elimination of stable re-entry (aka mother-rotor) underlying tachycardia and (multiple re-entry) fibrillation, while the mechanisms of cardiac arrhythmias self-termination provide clues on what might be wrong
when the self-termination fails. Participation in the miniprogram was most useful for my research. The utmost informative presentations and opportunity of informal discussion with the leading theoreticians and
experimentalists in the area can not be overvalued.

The mainstream focus in the area is on cardiac arrhythmias origin not on mechanisms of self-termination, thus very limited indirect experimental
data. It seems that the approach must be rather computer and mathematical modelling first to stimulate further experimental testing. Collaboration with E.Cherry and F.Fenton providing their expertise in the detailed ionic models is of a particular interest with regard to
this direction.

A lot of attention has been on the ``APD restitution slope'' theory (A.Karma, E.Cherry, F.Fenton) and spatially discordant alternans(SDA). The SAD have been demonstrated by many experimentalists (E.Entcheva, Kyoung Lee, J.Weiss, D.Rosenbaum, A.Pertsov) in cardiac
cell and tissue cultures. It will be most interesting to reproduce their results in biophysically realistic computer simulation to identify role of individual ionic currents in the development of SDA. I think, this might be closely connected to the problem of evolution of cardiac fibrillation and the ultimate question ``How many different fibrillations are there?'' (A.Zaitsev, J.Weiss).

The experimental results presented by R.Abraham addressed questions arising from modern clinical treatment of arrhythmias, e.g. low-voltage defibrillation and stem cells transplantation. I think there might be a number of interesting theoretical issues to comprehend and try to model based on these experiments.

The miniprogram has been the most interesting and stimulating meeting of the leading specialists in cardiac dynamics. It has advanced existing and fostered new collaborations leading to development of new approaches and ideas.

I thank KITP and the ``Cardiac Dynamics'' miniprogram organisers, Professors E.Bodenschatz, E.Entcheva, R.Gilmour, A.Karma, and V.Krinsky for the great
opportunity to participate in the milestone event in cardiac arrhythmias research.
Exploitation Route Collaborative Advanced multidisciplinary research into mechanisms of cardiac arrhythmias and fibrillation, supported by the recent developments in experiment (DT-MRI, latest bio-fysically realistic cell models, genetic profiling, etc.) and further development of the asymptotic theory of the spiral waves drift combined with HPC anatomically and biophysically realistic simulations.
Sectors Digital/Communication/Information Technologies (including Software),Education,Electronics,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description The research contacts established during the visit to Kavli Institute for the Cardiac Dynamics mini program, 10th July - 4th August, 2006, resulted in further, and still active collaboration with Professors E.Cherry (Rochester Institute of Technology, USA), F.Fenton (the Georgia Institute of Technology, USA), E.Entcheva (Stony Brook University, USA), E.Bodenschatz and V.Krinsky (MPI for Dynamics and Self-Organization, Germany), with subsequent mutual visits, conference organisation, and applications for the research funding.
First Year Of Impact 2006
Sector Digital/Communication/Information Technologies (including Software),Education,Healthcare,Other
Impact Types Cultural

 
Description Georgia Tech 
Organisation Georgia Institute of Technology
Country United States 
Sector Academic/University 
PI Contribution Joint research, participation in and organisation of mini symposia,
Collaborator Contribution Joint research, participation in and organisation of mini symposia, provision of computer models of heart anatomy
Impact Conference/Minisymposium 1. Kavli Institute "Cardiac Dynamics" mini program, 2006, University of Santa Barbara, USA. Software 1. BeatBox - HPC Environment for Biophysically and Anatomically Realistic Cardiac Simulations
Start Year 2006
 
Description MPI for Dynamics and Self-Organization 
Organisation Max Planck Society
Department Max Planck Institute for Dynamics and Self-Organization
Country Germany 
Sector Public 
PI Contribution joint research, participation in and organisation of mini symposia, joint funding application
Collaborator Contribution joint research, participation in and organisation of mini symposia, joint funding application
Impact 1. EPSRC Grant application EP/L005387/1 "Meander and drift of spiral and scroll waves", 2013. 2. Kavli Institute "Cardiac Dynamics" mini program, 2006, University of Santa Barbara, USA. 3. Mini symposium "Dynamics of Spiral Waves - Parts I and II", SIAM CONFERENCE ON APPLICATIONS OF DYNAMICAL SYSTEMS 2013 (DS13), Snow Bird, Utah, USA.
Start Year 2006
 
Description RIT 
Organisation Rochester Institute of Technology
Country United States 
Sector Academic/University 
PI Contribution Joint research, participation in and organisation of mini symposia,
Collaborator Contribution Joint research, participation in and organisation of mini symposia, provision of computer models of heart anatomy
Impact Conference/Minisymposium 1. Kavli Institute "Cardiac Dynamics" mini program, 2006, University of Santa Barbara, USA. Software 1. BeatBox - HPC Environment for Biophysically and Anatomically Realistic Cardiac Simulations
Start Year 2006
 
Description Stony Brook 
Organisation Stony Brook University
Country United States 
Sector Academic/University 
PI Contribution joint research, participation in and organisation of mini symposia
Collaborator Contribution joint research, participation in and organisation of mini symposia
Impact 1. Kavli Institute "Cardiac Dynamics" mini program, 2006, University of Santa Barbara, USA. 2. Minisymposium "Dynamics of Spiral and Scroll Waves in Cardiac Tissue", SIAM CONFERENCE ON Nonlinear Waves and Coherent Structures 2014 (DS14), Cambridge, UK.
Start Year 2006
 
Description The George Washington University 
Organisation George Washington University
Country United States 
Sector Academic/University 
PI Contribution Joint research and joint research output
Collaborator Contribution Joint research and joint research output
Impact 1. I.V. Biktasheva, N A. Sarvazyan, and V.N. Biktashev, "Dynamics of Scroll Waves of Excitation in a Mathematical Model of Ischaemic Border Zone" , COMPUTING IN CARDIOLOGY, 39:445-448, 2012. 2. V.N. Biktashev, I.V. Biktasheva and N A. Sarvazyan, "Evolution of spiral and scroll waves of excitation in a mathematical model of ischaemic border zone", PLoS ONE 6(9): e24388, 2011. doi:10.1371/journal.pone.0024388
Start Year 2011
 
Description University of California Santa Barbara 
Organisation University of California, Santa Barbara
Country United States 
Sector Academic/University 
Start Year 2006