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

Abstract

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 6 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. Results: Long term follow-up after left atrial radiosurgery demonstrated transmural, circumferential fibrosis that correlated to electrical isolation, similar to that found in catheter ablation. The EP study documented intended pulmonary vein isolation (electrical block), using a decapolar Lasso catheter (Biosense Webster, Diamond Bar, CA). Histologic analysis showed transmural fibrosis and contiguity (desired) of the ablation scar within the target. Echocardiographic monitoring of atrial and ventricular function six months post radiosurgery demonstrated normal cardiac function. Both animals met the survival endpoint with no adverse events. Conclusions: Cardiac radiosurgery for the treatment of atrial fibrillation can be safely performed in the porcine animal model using appropriate treatment planning, taking into account cardiac anatomy, motion and targeting concerns. Electrophysiologic and pathologic assessment correlated radiation induced tissue effect to the target tissue. Proof of concept is therefore confirmed. This technique has the potential to provide a significant advancement in the treatment of atrial fibrillation and other cardiac arrhythmias, especially for those patients who have failed drug therapy and are not candidates for intra-cardiac catheter ablation. Clinical studies are needed to prove safety and efficacy.