# Myocardial Substrate Driven Mechanistic Insights into Atrial Fibrillation

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $599,031

## Abstract

Project Summary/Abstract
Atrial fibrillation (AF) affects 3-5 million people in the US alone. Although catheter-based procedure is routinely
used 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 in AF is associated with fibrosis and this fibrotic substrate is thought to
play a major role in sustaining AF. Yet, the goal for most ablation procedures is to electrically isolate the
pulmonary veins. This anatomical approach to ablation is based on the assumption that the pulmonary veins
are the foci for ectopic activity driving atrial fibrillation shown in paroxysmal AF. More mechanistic approaches
based on targeting “diseased” areas beyond the pulmonary veins, specially, for persistent AF has yielded
varying results. This is mostly because (i) there is no good way to identify these diseased areas and (ii) there is
no mechanistic understanding of the role played by these fibrotic areas in sustaining AF. More recently, there
have been some reports of rotors driving AF. Targeting these rotors has shown some promising early results.
The structural basis of these rotors and the mechanism anchoring these to stable sites are still unknown. At the
University of Utah we have developed a chronic large animal model of persistent atrial fibrillation. We have
also pioneered using MRI to detect atrial wall remodeling in atrial fibrillation but it lacks rigorous histological
validation. Using a combination of serial electrical mapping at different resolutions and high resolution
in-vivo and ex-vivo MRI proposed here we will develop a more mechanistic approach to catheter-based
ablation leading to significant improvement in procedural outcomes. Based on serial high density
electrical recording of electrograms processed in both time and frequency domains at different time points in
the progression of AF we will develop a detailed mechanistic understanding of AF. These translation studies
will show if there are stable drivers of AF and the mechanistic basis for their stability at various locations.
These areas of fibrosis that provide stability to AF drivers can be the basis of catheter ablation resulting in an
improved outcome. To test this hypothesis, we will make use of unique experimental, clinical and animal model
facilities as well as the extensive expertise in electrical mapping, computational modeling and imaging
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.

## Key facts

- **NIH application ID:** 9997988
- **Project number:** 5R01HL142913-03
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Ravi Ranjan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $599,031
- **Award type:** 5
- **Project period:** 2018-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9997988

## Citation

> US National Institutes of Health, RePORTER application 9997988, Myocardial Substrate Driven Mechanistic Insights into Atrial Fibrillation (5R01HL142913-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9997988. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*