Catheter-free ablation of infarct scar through proton beam therapy: Tissue effects in a porcine model

Background: Scar-related ventricular arrhythmias are common after myocardial infarction. Catheter ablation can improve prognosis, but the procedure is invasive and results are not always satisfactory. Noninvasive, catheter-free ablation using ionizing radiation has recently gained interest among electrophysiologists, but the tissue effects and physiological outcome have not been fully characterized. Objective: The purpose of this study was to investigate the structural effects of cardiac scanned pencil beam proton therapy on infarct scar, the time course of imaging biomarkers, arrhythmias, and cardiac function in a porcine model. Methods: Fourteen infarcted swine underwent proton beam treatment of the scar (40 or 30 Gy) and were followed for up to 30 weeks. Magnetic resonance imaging was performed every 4 weeks. Results: Treated scar areas showed a significantly lower fraction of surviving myocytes at 30 weeks compared to untreated scar (30.1% ± 18.5% and 59.9% ± 10.1% in treated and untreated infarct, respectively), indicating scar homogenization. Four animals died suddenly during follow-up, all from documented monomorphic ventricular tachycardia. Cardiac function remained stable over the course of the study. Distinct imaging morphologies corresponded to certain tissue dose ranges and time points. Conclusion: Radioablation of cardiac infarct scar leads to significant homogenization of the scar, replicating the histologic effects of radiofrequency ablation. These changes correspond to distinct imaging morphologies on delayed contrast-enhanced cardiac magnetic resonance imaging, enabling noninvasive confirmation of tissue ablation effects The present study is the first to thoroughly investigate the structural effects of cardiac proton beam therapy in infarcted myocardium.