Safety and efficacy of stereotactic radioablation targeting pulmonary vein tissues in an experimental model

Abstract

Stereotactic radioablation (SR), a commonly used therapy to treat malignant tumors, has been used to treat refractory ventricular tachycardia, but the feasibility of treating atrial fibrillation with SR is unknown. We evaluated the safety and efficacy of SR targeting pulmonary vein (PV) antral tissues as a potential therapy for atrial fibrillation. Seventeen adult canines and 2 adult swine underwent surgical fiducial marker placement, 3-dimensional anatomic rendering computed tomography angiogram of the left atrium, and creation of a treatment plan targeting the right superior PVs. Four treatment doses (15, 20, 25, and 35 Gy) were administered to 4 cohorts. Subjects were monitored for 3-6 months, followed by electrophysiological testing, gross pathological examination, and histopathology in 2 subjects. All subjects received SR treatment without complication. Electrophysiology study and gross pathological analysis demonstrated treatment effect in all treated PVs at 35 Gy and 25 Gy (n= 11 of 11 [100%]), with a partial effect at 20 Gy (n = 4 of 5 [80%]; 1 did not undergo repeat electrophysiology study) and 15 Gy (n = 1 of 2 [50%]). No evidence of collateral injury was found in tissues directly adjacent to the treated PVs. In 2 subjects, detailed histopathology demonstrated evidence of circumferential, transmural scar at the PV ablation sites, with sparing of the surrounding structures. SR is safe and effective for creating precise circumferential scar and electrical isolation of the right superior PV in an experimental model, with dose dependence between delivered radioablative energy and observed electrical effects.