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A universal framework to quantify rotor formation and destruction in atrial fibrillation
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A universal framework to quantify rotor formation and destruction in atrial fibrillation

Associate Professor Anand Ganesan, Institution: Flinders University

2019 Vanguard Grant

Years funded: 2020-2021


Atrial fibrillation (AF) is the most common cardiac arrhythmia, and the leading cause of cardiac hospitalisation in Australia. For over 100 years, it has been recognised that a key feature of cardiac fibrillation is the presence of unstable functional re-entrant circuits known as rotors, which have been postulated as the drivers of AF. Rotors are like mini vortices of electricity that perpetually form and annihilate during both forms of cardiac fibrillation. In NHMRC Project grant (1063754, CIA Ganesan) and NHF FLF (101188, CIA Ganesan) we developed a universal renewal-theory based quantitative framework to measure for the first time the rates at which rotors form and die during fibrillation.

We validated this approach in 6 systems including human and experimental AF and VF. Here, we conduct an integrated bench-to-bedside investigation of renewal processes of rotor formation and destruction using computational simulation, experimental models and human studies.

The application will determine:
  1. The ion channel and substrate determinants of these rate constants, and their association with AF termination in pre-clinical computational and experimental studies;
  2. The clinical correlates of the rate constants of rotor formation and destruction in human AF patients undergoing ablation, with the long-term objective of developing the rate constants of rotor formation and destruction as a new marker of AF prognosis, and potential targets for therapeutic modulation.

The team combines cross-disciplinary technical expertise in clinical and experimental arrhythmia science, along with mathematics. The project will deliver not only fundamental new mechanistic knowledge of profound interest to basic arrhythmia research but defines the properties of a powerful new paradigm that has the potential to transform the clinical care of atrial fibrillation patients.

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