Catheter-free Arrhythmia Ablation using Scanned Proton Beams: Electrophysiologic Outcomes, Biophysics and Characterization of Lesion Formation in a Porcine Model

Background - Proton beam therapy offers radiophysical properties that are appealing for noninvasive arrhythmia elimination. This study was conducted to use scanned proton beams for ablation of cardiac tissue, investigate electrophysiologic outcomes, and characterize the process of lesion formation in a porcine model using particle therapy. Methods - Twenty-five animals received scanned proton beam irradiation. ECG-gated CT scans were acquired at end-expiration breath hold. Structures (atrioventricular junction [AVJ] or left ventricular myocardium [LV]) and organs at risk were contoured. Doses of 30, 40, and 55Gy were delivered during expiration to the AVJ (AVJ; n=5) and LV myocardium (LV; n=20) of intact animals. Results - In this study, procedural success was tracked by pacemaker interrogation in the AVJ group, time-course magnetic resonance imaging (MR) in the LV group, and correlation of lesion outcomes displayed in gross and microscopic pathology. Protein extraction (active caspase-3) was performed to investigate tissue apoptosis. Doses of 40 and 55Gy caused slowing and interruption of cardiac impulse propagation at the AVJ. In 40 LV irradiated targets, all lesions were identified on MR after twelve weeks, being consistent with outcomes from gross pathology. In the majority of cases, lesion size plateaued between 12 and 16 weeks. Active caspase-3 was seen in lesions 12 and 16 weeks after irradiation, but not after 20 weeks. Conclusions - Scanned proton beams can be used as a tool for catheter-free ablation, and time-course of tissue apoptosis was consistent with lesion maturation.