Histopathologic and Ultrastructural Findings in Human Myocardium After Stereotactic Body Radiation Therapy for Recalcitrant Ventricular Tachycardia

Abstract

Background: Stereotactic body radiation therapy (SBRT) is a novel treatment for refractory ventricular tachycardia (VT). While outcomes have been described in small studies, histological findings after SBRT for VT are unknown. Methods: We identified 4 explanted hearts in the context of transplant that received prior SBRT as part of an 11-patient compassionate use series at our institution. Clinical VTs and computed tomography–defined target volume areas of SBRT were correlated to the anatomic specimens. Gross pathological, histological, and ultrastructural examination of tissue in the target area of SBRT was performed. Results: All 4 patients had nonischemic cardiomyopathy, and 3 had left ventricular assist devices. In all cases, patients had recurrent sustained VT and had failed multiple antiarrhythmics and radiofrequency ablations. Four patients underwent 5 total SBRT therapy sessions with 25-Gy single-fraction dose delivered to the area of culprit scar. The time from SBRT to explant ranged from 12 to 250 days. Histopathologic features following radiation were comparable in all patients and were characterized by areas of subendocardial necrosis surrounded by a rim of fibrosis. In 1 patient, the surrounding myocardium showed cytoplasmic vacuolization in myocytes and in another patchy interstitial fibrosis. Vascular changes consisted of myointimal thickening with prominence of endothelial cells. Electron microscopy of myocardium showed irregular, convoluted intercalated disc regions, loss of contractile elements with disrupted and haphazardly arranged myofibrils, and edematous mitochondria with loss of cisternae. Conclusions: Here, we report the first series of findings in human tissue in 4 patients after SBRT. Histopathologic features were consistent across all 4 patients and were indicative of cell injury, death, and to a lesser extent, fibrosis. Electron microscopy demonstrated features consistent with acute injury. These specimens provide radiobiological mechanisms of acute cellular injury during SBRT for VT, which may have an antiarrhythmic effect before the onset of fibrosis.