Abstract Body: In this study, we investigated the relationship between plasma vascular endothelial growth factor A (VEGFA) levels and the phenotypic differentiation of the collateral circulation in patients with chronic total occlusion (CTO) of coronary arteries, with a focus on comparing the differences between predominantly septal and predominantly epicardial collateral branches. The study included 149 patients with CTO, who were evaluated for side branch type by coronary angiography and plasma VEGFA levels were measured by ELISA. The results showed that VEGFA levels were significantly higher in the septal branch group (n=77) than in the epicardial group (n=72) (130.96±125.34 vs. 66.20±69.84 pg/mL, P<0.001).Logistic regression analysis showed that elevated VEGFA was an independent predictor of septal branch side branch formation (OR=1.006, 95% CI: 1.001-1.010, P=0.009) with an area under the ROC curve (AUC) of 0.82 (sensitivity 78%, specificity 75%, critical value 98.4 pg/mL). There were no significant differences between the two groups in demographic and conventional clinical indicators (e.g., hypertension, diabetes, etc.). The study suggests that the formation of septal branch side branches may be more dependent on VEGFA-mediated angiogenesis, whereas epicardial side branches may be regulated by arteriogenesis mechanisms such as shear force. The present study provides a new biological marker and theoretical basis for the evaluation of collateral circulation and optimization of therapeutic strategies in CTO patients, and the specific mechanism of VEGFA and its potential for clinical translation should be further explored in the future.