# Pathological findings of stereotactic cardiac radiotherapy for the treatment of ventricular tachycardia in patients with Chagas disease: case series

## TL;DR

This study examines the heart tissue changes in Chagas disease patients after a new non-invasive treatment for arrhythmia called STAR.

## Contribution

The study provides the first pathological characterization of STAR effects in Chagas disease patients.

## Key findings

- STAR caused acute cellular injury and fibrosis in treated heart areas.
- Apoptotic activity was not detected in the analyzed tissue samples.
- Fibrosis was also observed in non-irradiated areas, likely due to underlying Chagas disease.

## Abstract

Stereotactic arrhythmia radiotherapy (STAR) is a novel, non-invasive therapeutic option for managing ventricular tachycardia (VT), including in patients with chronic Chagas cardiomyopathy (CCC). However, the histopathological substrate underlying its antiarrhythmic effect remains poorly defined, particularly in the Chagas population. This study aims to characterize the myocardial tissue changes following STAR in two CCC patients, evaluated at different time points after treatment.

Two CCC patients with recurrent VT underwent STAR as part of a multidisciplinary treatment protocol. One patient died 50 days post-STAR, and the other underwent heart transplantation 702 days after the procedure. Myocardial tissue was collected from irradiated and non-irradiated regions. Gross pathology, histological staining (haematoxylin–eosin and Masson’s trichrome), and immunohistochemistry for apoptosis markers (p53, Bcl-2, and caspase-3) were performed and analysed by a cardiac pathologist. Macroscopic analysis showed fibrosis in the STAR-targeted areas. Histological evaluation revealed varying degrees of myocyte damage, including cytoplasmic vacuolization and myocytolysis, more pronounced in the early post-STAR case. Extensive fibrosis was present in both cases, but also observed in non-irradiated areas, reflecting underlying CCC pathology. Immunohistochemistry for apoptosis markers was negative in both patients.

Stereotactic arrhythmia radiotherapy areas present myocardial changes consistent with acute cellular injury and fibrosis in CCC patients treated for VT. However, apoptotic activity was not detected within the analysed timeframe. Fibrosis was found in both irradiated and non-irradiated areas, and differentiating STAR-induced fibrosis from baseline Chagas-related remodelling remains challenging.