Myocardial Substrate Driven Mechanistic Insights Into Atrial Fibrillation

University Of Utah, Salt Lake City UT

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Abstract

? DESCRIPTION (provided by applicant): Atrial fibrillation (AF) affects 3-5 million people in the US alone. Although catheter-based radiofrequency ablation is routinely used today in treating AF, the high recurrence rate of up to 60 % continues to be a challenge. Over the years it has been shown that the atrial myocardium undergoes significant remodeling including fibrosis and this substrate is thought to play a major role in sustaining atrial fibrillation. Yet, the goal formost ablation procedures is to electrically isolate the pulmonary veins and this anatomical approach is based on the assumption that the pulmonary veins are the foci for ectopic activity driving atria fibrillation. More mechanistic approaches based on targeting diseased areas beyond the pulmonary veins have yielded varying results. This is mostly because there is no good way to identify these diseased areas. More recently, there have been some reports of rotors driving the AF. These rotors are based on high- density atrial electrical mapping. Targeting these rotors has shown some promising early results. The structural basis of these rotors and its anchor sites are still unknown. At the University of Utah we have pioneered using MRI to detect atrial wall remodeling in atrial fibrillation. Most of the MRI used for this purpose has been a gadolinium contrast imaging technique, which is good at detecting focal scar areas but not as good for detecting diffuse remodeling commonly seen in AF. To overcome this, a T1 based MRI mapping technique has been developed to quantify the extracellular space in the myocardium as a measure of the degree of atrial remodeling. We have also developed a chronic rapidly atrial paced large animal model of persistent atrial fibrillation. We hypothesize that developing a more mechanistic approach to ablation that includes the structural remodeling information of the atrial wall along with high density electrical mapping will lead to significant improvement in ablation outcomes. Based on serial high density electrical recording of electrograms processed in both time and frequency domains and MRI done at different time points in the progression of AF we will develop a detailed mechanistic understanding of AF. With the incorporation of structural remodeling information we will have a much better understanding of the drivers and anchor sites of these rotors. The structural remodeling can also form the basis of ablation. To test this hypothesis, we will make use of unique experimental, clinical, and animal model facilities as well as the extensive expertise in MRI acquisition and image analysis available at University of Utah. The clinical consequence will be reduced number of repeat procedures that are currently done due to arrhythmia recurrence at a significant cost and risk to patients.