Cardiac Radiosurgery (CyberHeart™) for Treatment of Arrhythmia: Physiologic and Histopathologic Correlation in the Porcine Model

Abstract

Objectives: This porcine pre-clinical investigation sought to demonstrate a new and novel application for radiosurgery, the ablation of cardiac arrhythmias. Pre-clinical studies in the porcine animal model were used to investigate the accuracy with which the pathological region in the heart that is routinely treated for atrial fibrillation could be targeted with radiosurgery. Pathologic and electrophysiologic (EP) changes resulting from radiosurgical ablation were used as primary study endpoints.Methods: Two Hanford mini-swine (approximately 35 kg) were studied. A cardiac-gated CT study was performed. Isocentric treatments were delivered with the CyberKnife® (Accuray Inc, Sunnyvale, CA) in a single fraction at prescribed doses of 25 Gy (N=1) and 35 Gy (N=1). The treatment volume was selected to create electrical isolation of two pulmonary veins (the source of atrial aberrant tachycardias, such as atrial fibrillation) from the body (antrum) of the left atrium, as has been proven successful with thermal catheter ablation procedures. Animals were followed for six months, and then underwent electrophysiologic (EP) testing in the cardiac catheterization lab to test for electrical isolation of the pulmonary veins. Trans esophageal echocardiography was carried out to examine cardiac function post-radiosurgery. Finally, the hearts of the treated animals were submitted for pathologic analysis.

Radiosurgery for ventricular tachycardia: preclinical and clinical evidence and study design for a German multi-center multi-platform feasibility trial (RAVENTA)

“…Although the authors claimed that both 25 Gy and 35 Gy in a single fraction can lead to electrical block and transmural fibrosis, only data for the 35 Gy treatment were shown. A third publication by Zei et al [37] presented the same data as in Maguire et al [32] with the additional data of RA/CRS targeted to the pulmonary veins in 17 canines. The authors found treatment effects for doses between 15 and 35 Gy during electrophysiology studies and gross pathological analysis [37].…”

“…Finally, we added initial technical, pre-clinical, and clinical manuscripts not covered by the search based on our own experience in cardiac radiosurgery in the past 12 years. Evidence was finally extracted from the remaining 42 manuscripts, which include reports on two clinical trials [22,23], two clinical case series [24,25], eight case reports [19,20,[26][27][28][29][30][31], eight preclinical studies [18,[32][33][34][35][36][37][38][39], fourteen technical studies [40][41][42][43][44][45][46][47][48][49][50][51][52][53], and eight reviews or opinions [7,[54][55][56][57][58][59][60].…”

“…The first preclinical studies for RA/CRS were the studies from CyberHeart Inc. [18,32], the company that owned several patents for performing cardiac radiosurgery until 2018 ( [17], among others). The first study published by Sharma et al was mainly exploratory; the authors reported on irradiation of different locations in the hearts of 16 Hanford-Sinclair mini swine with various doses [18].…”

“…The studies showed that cardiac radiosurgery can produce cavotricuspid isthmus block, AV nodal block, and decreased voltage at the pulmonary vein-left atrial junction with single fraction treatment. A second publication by Maguire et al revealed more details in terms of electrophysiology and pathology correlations of focused PA/CRS to the pulmonary veins in the same animal model to treat AF [32]. Although the authors claimed that both 25 Gy and 35 Gy in a single fraction can lead to electrical block and transmural fibrosis, only data for the 35 Gy treatment were shown.…”

Radiotherapy beyond cancer: Target localization in real‐time MRI and treatment planning for cardiac radiosurgery

“…The two reported human phase I studies have prescribed a potentially safe 25 Gy for cardiac ablation of ventricular tachycardia, 8,9 while the most recent animal studies for AF suggested that doses over 30-32.5 Gy might be needed for the treatment to be effective. 5,7 The transferability of the animal results to human treatment, however, remains unclear.…”