# Surgical Treatment of Cardiac Arrhythmias

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $412,795

## Abstract

Project Summary
 Our goal is to elucidate the mechanisms by which mitral regurgitation (MR) creates substrates for arrhythmias,
both atrial and ventricular, and to identify targeted interventions. Valvular heart disease is the most common
etiology of chronic atrial fibrillation (AF). Prospective, randomized trials have shown that surgical ablation is
highly effective in restoring normal sinus rhythm in patients with mitral valve disease and there is clear evidence
that it provides a survival benefit. Newer studies have shown that ventricular remodeling and arrhythmias
following MR increase the risk of sudden cardiac death, especially in young women.
 In the previous cycle of the grant, we refined a canine open chest model of MR via chordae avulsion previously
developed in our laboratory into a minimally invasive model that better mirrors the clinical picture. In our clinical
practice, we treat MR patient with and without AF, and are able to characterize their cardiac anatomy and
electrophysiology with delayed-enhancement MRI (DE-MRI) and electrocardiographic imaging (ECGI),
respectively
 We propose to characterize the remodeling of the atria and ventricles following MR in our canine chordae
avulsion model and in patients. As our preliminary data suggest an inflammatory-mediated mechanism, we will
identify patterns of immune cell infiltration that correspond to anatomical and electrophysiological changes to
facilitate the development of novel therapeutic strategies. We propose the following specific aims:
 Specific Aim 1. Define the anatomical and electrical substrates for AF and ventricular arrhythmias in a chronic
canine model of MR. The anatomical substrate will be characterized using echocardiography and DE-MRI, the
electrical substrate using in-vivo plaque mapping, optical mapping, and ECGI. We will obtain activation maps of
the heart, including the most arrhythmogenic parts of the atria (the LAPW) and the ventricles (periannular region
and papillary muscles) and correlate them with fibrosis as defined by DE-MRI. Specific Aim 2. In our canine MR
model, we will determine if inflammatory leukocyte infiltration precedes remodeling following MR induction and
whether its presence corresponds to changes in electrophysiology. We will perform single nuclear RNA (snRNA)
analysis of the LAPW and correlate it with LAPW electrophysiology characterized in thin slices at baseline, 4
weeks, and 6 months after MR induction. In the ventricle, snRNA analysis of the mitral periannular region and
papillary muscles at the same time points will be correlated with local electrophysiology. Specific Aim 3. Define
the atrial and ventricular electrophysiological remodeling in MR patients with and without AF referred for surgery.
ECGI will be used to detect changes in the atrial and ventricular activation sequences and to detect premature
ventricular contractions. Electrical remodeling will be correlated with fibrosis and fiber orientation as well as atrial
and ventricu...

## Key facts

- **NIH application ID:** 10898622
- **Project number:** 5R01HL032257-39
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** RALPH J DAMIANO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $412,795
- **Award type:** 5
- **Project period:** 1983-08-08 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10898622

## Citation

> US National Institutes of Health, RePORTER application 10898622, Surgical Treatment of Cardiac Arrhythmias (5R01HL032257-39). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10898622. Licensed CC0.

---

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