Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): a grant [2022R1I1A1A0106342211] from the Basic Science Research Program run by the National Research Foundation of Korea (NRF) which is funded by the Ministry of Science, ICT & Future Planning (MSIP) Background It has been suggested that the high dominant frequency (DF) site plays an atrial fibrillation (AF) driver, but its relationship with the atrial substrate voltage map (Vm) in the entire chamber AF map has yet to be studied. We explored the relationship between the DF site during AF and Vm in the entire chamber maps by applying the human left atrial (LA) electroanatomical map (EAM) to the digital twin AF map. Methods We acquired LA substrate Vm (at sinus rhythm, >800 points bipolar electrograms) of 110 patients with persistent AF (male 72.7%, 58.7±9.8 years old) who underwent AF catheter ablation. We applied EAM to digital twins (0.4 million nodes), reflecting anatomy, histology, and electrophysiology. We evaluated the highest 10% DF areas for 6 sec after inducing virtual AF. The correlation between the highest 10% DF and the low Vm areas (<0.2mV) was evaluated in the LA region of 10 segments. Results The mean voltage of the entire LA area was 1.96±0.85 mV (2.19±0.82 mV extra-PV area, 1.33±0.93 mV PV area) in 110 patients. The correlation between low Vm and high DF areas was not significant in the entire LA (r=0.106, p<0.001), extra-PV (r=0.157, p<0.001), and PV (r=0.079, p=0.097) areas. In the LA 10 segment regional analysis, 72 patients (65.5%) showed the co-localization of the highest DF in the region with the lowest Vm, and 14 patients (12.7%) had the lowest Vm segment in the region with the highest DF. The mean voltage where high DF appeared was 0.69±1.35 mV, and the mean voltage of the region where high DF did not appear was 0.59±1.15 mV (p=0.171). Conclusion High DF site, a parameter representing a localized focal source, had statistically significant but very poor correlations with LA extra-PV voltage substrate in patients with persistent AF.