Aim To detect the changes of serum cardiotrophin-1 (CT-1) and angiopoietin-like protein 3 (ANGPTL3) levels in patients with coronary heart disease (CHD) complicated with heart failure (HF) after percutaneous coronary intervention (PCI), and analyze their relationship with prognosis. Methods 199 patients with CHD complicated with HF who underwent PCI in the Second Affiliated Hospital of Zhengzhou University from March 2022 to March 2023 were selected. The serum CT-1 and ANGPTL3 levels of patients with different New York Heart Association (NYHA) cardiac function grades were compared before surgery. The prognosis was followed up after PCI, and the patients who had major adverse cardiovascular event (MACE) were included in the poor prognosis group, and the rest were included in the good prognosis group. The general data and serum CT-1 and ANGPTL3 levels were compared between the poor prognosis group and the good prognosis group. Logistic regression model was used to analyze the influencing factors of poor prognosis after surgery in patients with CHD and HF. The predictive value of serum CT-1 and ANGPTL3 alone and in combination were analyzed. Results Compared with the patients with cardiac function grade Ⅰ, the serum CT-1 and ANGPTL3 levels of the patients with cardiac function grade Ⅱ, Ⅲ and Ⅳ were increased (P＜0.05). Compared with the patients with cardiac function grade Ⅱ, the serum CT-1 and ANGPTL3 levels of the patients with cardiac function grade Ⅲ and Ⅳ were increased (P＜0.05). Compared with the patients with cardiac function grade Ⅲ, the serum CT-1 and ANGPTL3 levels of the patients with acrdiac function grade Ⅳ were increased (P＜0.05). Spearman correlation analysis showed that the serum CT-1 and ANGPTL3 levels were positively correlated with NYHA cardiac function grade (r＝0.8,5%CI:0.408~0.613, P＜0.001, r＝0.7,5%CI:0.666~0.794, P＜0.001). The poor prognosis rate of patients was 17.93%. Compared with the good prognosis group, the serum CT-1 and ANGPTL3 levels of the poor prognosis group were increased (P＜0.05). Logistic regression model analysis showed that smoking, diabetes, lesion vessel number≥3, irregular medication outside the hospital, serum CT-1 and ANGPTL3 levels were the influencing factors of poor prognosis in patients with CHD complicated with HF (P＜0.05). ROC curve analysis showed that the sensitivity and area under the curve (AUC) of combined serum CT-1 and ANGPTL3 levels for predicting poor prognosis of patients with CHD complicated with HF were higher than those of either marker alone, while the specificity was basically similar to that of single-marker prediction. Conclusion Serum CT-1 and ANGPTL3 levels are abnormally elevated in patients with CHD complicated with HF after PCI, and are closely related to the cardiac function and prognosis.