Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Winkelman family research fund. Background. The arrhythmogenic substrate in nonischemic cardiomyopathy (NICM) characteristically consists of fibrosis with surviving myocytes. We hypothesized that the substrate may be reflected on the 12-lead ECG as depolarization abnormalities (QRS fragmentation [QRSf] and J waves) during sinus rhythm in patients with VT. Methods. Phase I subjects included a retrospective cohort with NICM and VT referred for VT ablation between 2007 and 2020 who had detailed substrate mapping. Phase II subjects included a prospective reference cohort with NICM and No VT referred for primary prevention ICD between 2017 and 2019. All patients had supraventricular rhythm. 12-lead ECGs voltage and presence of QRSf/J waves were compared between phase I and phase II patients. Results. Forty-five (59.2%) patients had epicardial (EPI) VT circuits and EPI LV low voltage. Thirty-one (40.8%) had endocardial (ENDO) VT circuits and Endo LV low voltage. All 38 Phase II subjects had cardiac magnetic resonance imaging (cMRI) with 26 (68.4%) patients demonstrating late gadolinium enhancement (LGE). Lower voltage in the limb leads was present in Phase I (NICM/VT) [DI (0.63 ± 0.33 vs 0.87 ± 0.4, p = 0.002), DII (0.6 ± 0.27 vs 0.85 ± 0.36, p < 0.001), DIII (0.59 ± 0.35 vs 0.74 ± 0.33, p = 0.03), AVR (0.53 ± 0.24 vs 0.75 ± 0.32, p < 0.001) and AVF (0.50 ± 0.26 vs 0.70 ± 0.28, p < 0.001)] than phase II (NICM/No VT) patients. A high prevalence of QRSf was observed in patients who had indices of LV scar with abnormal bipolar map or LGE on cMRI (ENDO 74.1% vs EPI 77.7%, p = 0.71 and LGE 73% vs No LGE 41.7%, p = 0.06). QRSf were noted in order of prevalence, in the inferior leads (ENDO 67.7% vs EPI 66.6%, p = 0.92), lateral leads (ENDO 35.5% vs EPI 48.9%, p = 0.24) and anterior leads (ENDO 22.6% vs EPI 22.2%, p = 0.97). The positive predictive value of inferior, lateral or anterior ≥2 QRSf leads as a predictor of regional scar among sustained VT patients was 92%, 97% and 88%, respectively. The presence of J waves was more frequently in patients with EPI substrate vs ENDO substrate (57.7% vs 9.6%, p < 0.001), and mainly noted in lateral and inferior leads. Conclusions. In patients with NICM and VT the presence and location of LV scarring can be predicted by depolarization abnormalities on 12-lead ECG. ECG characteristics NICM VT and EPI substrate(n = 45) NICM VT and ENDO substrate(n = 31) p value NICM No VT and LGE(n = 26) NICM No VT and No LGE(n = 12) p value QRSf in 2 contiguous leads 35 (77.7%) 23 (74.1%) p = 0.71 19 (73%) 5 (41.7%) p = 0.06 QRSf in lead DII, DIII, AVF 30 (66.6%) 21 (67.7%) p = 0.92 17 (65.4%) 5 (41.7%) p = 0.16 QRSf in lead DI, AVL, V5, V6 22 (48.9%) 11 (35.5%) p = 0.24 10 (38.5%) 3 (25%) p = 0.41 QRSf in lead V1, V2, V3, V4 10 (22.2%) 7 (22.6%) p = 0.97 9 (34.6%) 2 (16.7%) p = 0.25