CA-533-02 STANDARD CARDIAC RADIOABLATION DOSE (25 GRAY) DOES NOT CAUSE MYOCYTE INJURY OR NEW FIBROSIS

Abstract

Noninvasive cardiac radioablation (CRA) is an emerging therapy for refractory ventricular tachycardia (VT). Focused radiation to the heart is expected to cause local myocardial destruction with replacement fibrosis (ablation effect). The extent this effect in humans is unknown. To measure the CRA ablation effect with serial serum biomarkers and late gadolinium enhanced cardiac MRI (LGE-CMR). Single-center, IRB-approved case series of patients with refractory VT (ENCORE-VT NCT02919618). Patients without contraindication underwent LGE-CMR and blood draws at three timepoints: before treatment, 3 days, and 3 months after treatment. Left ventricle (LV) scar burden was assessed using semi-automatic contouring (Medis, Netherlands), blinded to location of radioablation. Global and segmental scar burden (%) was compared across timepoints. Segments targeted for radioablation (25 Gray) were compared to surrounding and off-target segments. Blood samples were analyzed for high-sensitivity troponin-I (Tn-I, marker of myocyte injury) and galectin-3 (Gal3, marker of fibroblast activation and fibrosis). 7 patients were included for analysis: mean age 64 years, 14% female, 57% nonischemic cardiomyopathy, 86% with history of VT storm, mean LVEF 32% (range 19-58%). Mean number of cardiac segments targeted for radioablation was 4 (range 3-8), resulting in mean cardiac treatment volume (CTV) 29 cm3 and planning treatment volume (PTV) 114 cm3. Mean scar burden at baseline was 49% (range 29-68%). Changes in scar burden at 3 days and 3 months were -0.4% (IQR = 5.5%) and 3.3% (IQR = 3%). Segment-by-segment analysis (Figure 1) showed no significant scar progression in segments targeted for radioablation (mean 68% to 68% to 71%), segments surrounding the target (43% to 44% to 47%), or off-target segments (44% to 42% to 46%). Serum Tn-I and Gal3 were not significantly changed (Figure 2). Compared to VT burden before treatment, all 7 patients had substantial reduction 6 months after treatment (4 had > 95% burden reduction, 1 had resolution of incessant slow VT). Despite improvement in VT burden, there was no appreciable cardiac injury or replacement fibrosis after CRA with 25 Gray. The mechanism of early VT control with cardiac radioablation is not myocyte injury or fibrosis.View Large Image Figure ViewerDownload Hi-res image Download (PPT)