# Mechanistic Basis of Cardiac Irradiation as a Therapy for Ventricular Tachycardia

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2022 · $787,498

## Abstract

Project Summary
Ventricular tachycardia (VT) is a dangerous arrhythmia that leads to sudden cardiac arrest if left untreated. VT
most often involves regions of the heart that are structurally and/or electrically heterogeneous which provide a
substrate for reentry. Currently available antiarrhythmic and catheter ablation therapies are limited in both safety
and efficacy. In patients with VT that is refractory to conventional therapy, stereotactic body radiation therapy
(RT) has emerged as a promising new treatment. An initial clinical trial showed that a single fraction of 25 Gy
ionizing radiation to the heart was associated with greater than 99.9% reduction of VT burden, and this VT
reduction persisted for at least 12 months. Importantly, studies at several independent academic hospitals have
now demonstrated the efficacy of RT for the treatment of ventricular tachycardia. Despite these promising results,
the precise mechanisms by which high-dose radiation reduces VT is unknown. It has been hypothesized that 25
Gray radiation to arrhythmogenic regions of the heart causes late-stage fibrosis thereby preventing re-entry,
analogous to scar created by thermal catheter ablation. However, histologic data from explanted hearts of SBRT-
treated patients suggests that fibrosis alone cannot account for the magnitude of the observed clinical effect
(unpublished). Instead, our preliminary data suggest that radiation to the heart causes functional changes in the
electrical substrate that may prevent reentry and reduce VT. We hypothesize that ionizing radiation to the heart
leads to changes in cardiac gene expression and electrophysiology. The proposed studies will characterize key
molecular and cell-signaling mechanisms by which ionizing radiation influences cardiac conduction. The
following specific aims will (1) determine the cellular mechanisms by which ionizing radiation influences cardiac
electrophysiology, (2) determine the minimal dose response in a porcine model, and (3) translate biological
insights from animal models into humans through analysis of serum-derived biomarkers from RT-treated
patients. Defining the acute effects of irradiation on the electrical substrate is expected to facilitate clinical
implementation of this promising new anti-arrhythmic therapy and advance the field of cardiac radiation biology.

## Key facts

- **NIH application ID:** 10422204
- **Project number:** 1R01HL163274-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** STACEY Lynn RENTSCHLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $787,498
- **Award type:** 1
- **Project period:** 2022-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10422204

## Citation

> US National Institutes of Health, RePORTER application 10422204, Mechanistic Basis of Cardiac Irradiation as a Therapy for Ventricular Tachycardia (1R01HL163274-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10422204. Licensed CC0.

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