Creating an Interactive Computer Model of Left Atrium Electrophysiology to Study the Underlying Mechanisms Leading to Atrial Fibrillation

About This Grant

Project Summary/Abstract Heart disease and strokes are the leading causes of death worldwide. Atrial arrhythmias are significant contributors to strokes, heart failure, and, in some cases, acute myocardial infarction. Atrial fibrillation (AF), the most prevalent but least understood atrial arrhythmia, is associated with a five-fold increased risk of stroke for patients. Therefore, it is imperative that, in our pursuit of building healthier lives free of cardiovascular diseases and strokes, we focus on reducing the occurrence of atrial arrhythmias, especially AF. The left atrium (LA) is the most complex of the heart's four chambers, and it is where most complex arrhythmias arise. AF exhibits many characteristics of chaos. If AF is truly chaotic, it cannot be studied analytically; rather, it must be examined through computational mathematics and simulations. While our digital twin of the LA has been utilized to simulate and study many textbook atrial arrhythmias, it lacks the complexity necessary to investigate the underlying mechanisms of AF. True chaos can only manifest on high-dimensional landscapes and must be driven by nonlinear functions. The primary objective of this work will be to introduce the requisite complexity to the model to enable the study of the underlying mechanisms responsible for AF. This will be accomplished through two specific aims. Aim 1: Utilize computed tomography angiography (CTA) images to construct an anatomically accurate three- dimensional lattice of the LA. This approach will facilitate the creation of a high-dimensional landscape where chaos can emerge. Aim 2: Incorporate electrochemical and stochastic processes into the model, and enhance the representation of Bachmann's Bundle from a single pulse node to a branching tree of specialized myocytes. This will generate a nonlinear, dynamically evolving landscape conducive to chaos. After achieving each aim, the improved model will undergo testing against textbook arrhythmias. If the enhancement is deemed to contribute to the understanding of the underlying mechanisms behind left atrium arrhythmias, it will be integrated into the model. Otherwise, it will not be included. The objective is to refrain from adding complexity that does not enhance utility, and the failure of one aim should not hinder the implementation of others. The ultimate goal is to employ the final model to investigate the root causes of atrial fibrillation and develop strategies for its elimination to save lives.