# Determining the Mechanisms of Radiation Biomodulation of the Ventricular Tachycardia Arrhythmogenic Substate

> **NIH NIH R56** · UNIVERSITY OF PENNSYLVANIA · 2024 · $812,403

## Abstract

Project Summary
Cardiovascular disease is the leading cause of death in the United States and accounts for 1 in every 5 deaths.
Sudden cardiac death is responsible for nearly half of all heart disease related mortality and is often attributed
to the occurrence of lethal ventricular arrhythmias. Ventricular arrhythmias also are a major source of morbidity
and mortality in patients with structural heart disease. Antiarrhythmic drug therapy provides only limited efficacy
in preventing ventricular arrhythmias and while implantable cardioverter defibrillators provide life-saving therapy
to terminate the arrhythmia once it has occurred, they do not prevent them from occurring. For these reasons,
catheter ablation of ventricular arrhythmias has emerged as an additional therapy for many patients with
refractory ventricular tachycardia (VT). However, VT ablation procedures are complex and multiple procedures
are often required to achieve modest long-term success. Therefore, there is a critical need for additional VT
therapies. Cardiac stereotactic body radiation therapy (cSBRT) has emerged as an adjunctive noninvasive
approach that can be utilized to treat patients with VT that is refractory to standard antiarrhythmic drug therapy
and catheter ablation with clinical efficacy observed in some very complex patients. However, the clinical
response following cSBRT has been highly variable and the electrophysiologic mechanism is unclear. We
believe that better understanding the mechanisms of cSBRT will help refine and guide clinical cSBRT paradigms,
optimize patient selection, and better define the appropriate role this therapy should have in clinical practice. We
propose a series of experiments to investigate the association between cSBRT dose and structural and
electrophysiologic changes using longitudinal cardiac magnetic resonance (CMR) imaging and high-resolution
electroanatomic mapping in a large animal model of chronic myocardial infarction and reentrant VT. In Aim 1,
we will investigate the impact of cSBRT dose (15Gy, 25Gy, and 35Gy) at short and intermediate follow-up
timepoints. We will also investigate the long-term impact of cSBRT delivered at the dose currently used clinically
(25Gy) out to 1 year. In Aim 2, we will similarly investigate structural and electrophysiologic changes that occur
in patients undergoing clinically indicated cSBRT compared to catheter ablation. This study will give a new
understanding of the dose and time relationship of cSBRT on the heart that will be essential in moving this field
forward.

## Key facts

- **NIH application ID:** 11192963
- **Project number:** 1R56HL174836-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Cory Michael Tschabrunn
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $812,403
- **Award type:** 1
- **Project period:** 2024-09-24 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11192963

## Citation

> US National Institutes of Health, RePORTER application 11192963, Determining the Mechanisms of Radiation Biomodulation of the Ventricular Tachycardia Arrhythmogenic Substate (1R56HL174836-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11192963. Licensed CC0.

---

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