Feasibility Study on Stereotactic Radiotherapy for Total Pulmonary Vein Isolation in A Canine Model

Abstract

We tested the feasibility of pulmonary vein (PV) and left atrial (LA) posterior wall isolation using non-invasive stereotactic ablative body radiotherapy (SABR) and investigated pathological changes in irradiated lesions in a canine model. Seven male Mongrel dogs received single-fraction 33-Gy SABR. We designed the en-bloc circular target of total PVs and LA posterior wall to avoid the esophagus. The circular box lesion included the LA roof and ridge, low posterior wall, and posterior interatrial septum. At 6 weeks or 4 months post-SABR, electrical isolation of the SABR lesion was confirmed using LA posterior wall pacing, and histopathological review was performed. Electrical isolation of all PVs and the LA posterior wall was achieved in three of five dogs in the 4-month group. There was one target failure and one sudden death at 15 weeks. Although two dogs in the 6-week group failed to achieve electrical lesion isolation, the irradiated atrial myocardium showed diffuse hemorrhage with inflammatory cell infiltration. In successfully isolated 4-month model dogs, we observed transmural necrotic scarring with extensive fibrosis on irradiated atrial tissue. The findings suggest that this novel circular box-design radiotherapy technique using SABR could be applied to humans after further studies are conducted to confirm safety.

Leveraging Radiobiology for Arrhythmia Management: A New Treatment Paradigm?

“…The observed effect of conduction protein upregulation on reducing ventricular tachycardia inducibility is supported by previous studies that showed an anti-arrhythmic effect after cell-or adenoviralmediated overexpression of cardiac conduction proteins, including Cx43, in several animal models [101,102,119]. However, higher-dose proton and carbon ion studies (25e35 GyE) have shown decreases in relative Cx43 expression after radiation [40,94], although these effects may occur secondary to observed increases in fibrosis and decreases in cardiomyocytes [40,94]. The potential pro-conductive effects of radiation therapy, in the absence of observed functional conduction block and prior to an expected fibrosis response, may explain mechanisms of both acute and persistent antiarrhythmic benefits conferred to refractory ventricular tachycardia patients after treatment with doses in the range of 25 Gy after gamma radiation.…”