This is a retrospective cohort study conducted at the People's Hospital of Liaoning Province between February 2021 and September 2023. The inclusion criteria were as follows: (1) aged ≥18 years, (2) diagnosed with CTO, (3) without a history of PCI or coronary artery bypass grafting (CABG), and (4) with complete clinical data. Patients were excluded based on at least one of the following conditions: (1) contraindications for PCI or contrast agent injection; (2) concurrent cardiac diseases like heart failure or pulmonary heart disease; (3) severely impaired liver or kidney functions; and (4) malignant tumors or immune system diseases.

CTO was defined as arteries occluded for a documented duration of occlusion ≥3 months with absolutely antegrade flow through the lesion [thrombolysis in myocardial infarction (TIMI) grade 0 flow] (13). The Syntax score served as a reproducible angiographic tool to quantify the extent of coronary artery disease. MetS was determined based on the criteria of the International Diabetes Federation (14). Participants were required to have a waist circumference of ≥94 cm (men) or ≥80 cm (women). Meanwhile, participants needed to meet at least two of the following criteria: (1) glucose levels ≥5.6 mmol/L or diagnosed diabetes; (2) low high-density lipoprotein cholesterol (HDL-C) levels <1.0 mmol/L (men), <1.3 mmol/L (women), or receiving drug treatment for low HDL-C; (3) triglyceride (TG) levels ≥1.7 mmol/L or receiving drug treatment for high TG; (4) blood pressure ≥130/85 mmHg or receiving drug treatment for hypertension. The study protocol was reviewed and approved by the Ethics Committee of the People's Hospital of Liaoning Province (Approval No. 2023-K063). All participants signed written informed consent.

Trained physicians or nurses collected the following information about patients: demographic data, disease characteristics, treatment-related data, and occurrences of MACCEs. Demographic data included age, gender, height, weight, smoking and drinking habits, family history of CAD, history of myocardial infarction (MI), cerebral infarction, diabetes mellitus (DM), and MetS. Before the coronary interventions were performed, information on the characteristics of the disease was collected, including the number of occluded vessels, location of the CTO lesion, left ventricular ejection fraction, number of recanalized vessels in the CTO lesion, complete revascularization, and number of implanted stents. Treatment-related data included the type of therapeutic drugs, such as angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), β-blockers, statins, and hypoglycemic drugs.

The Rentrop scoring system was used to evaluate the grading of coronary collateralization: grade 0 indicates no visible filling of any collateral vessel, grade 1 indicates filling of the side branches by collateral vessels without filling of the epicardial arteries, grade 2 indicates partial filling of the epicardial artery by collateral vessels, and grade 3 indicates complete filling of the epicardial artery by collateral vessels (15). The Rentrop classification, categorized as grade 0 or 1, was defined as a poor coronary collateralization group, and grade 2 or 3 was considered a good group.

The outcome was MACCEs, consisting of all-cause death, cardiac death, non-fatal MI, target vessel revascularization (TVR), and non-fatal stroke (15). Cardiac death was defined as any death for which a definite non-cardiac cause could not be determined. MI was defined as participants with typical chest pain, ST-segment deviation, T wave changes, and creatine kinase-myocardial band levels at least three times the upper limit of normal (16). TVR, which included interventions on the target and non-target vessels by PCI or CABG, was performed in patients with severe in-stent restenosis or newly emerged coronary lesions (70% luminal diameter stenosis) (15). The study population was followed up at 3, 6, 9, and 12 months after discharge through office interviews, outpatient visits, telephone consultations, and a review of medical records.

The normality of continuous variables was tested by skewness and kurtosis, while homogeneity was detected by the Levene test. Continuous variables with a normal distribution were described by the mean ± SD (standard deviation), while variables without a normal distribution were described by the median (interquartile range). Categorical variables were expressed as numbers and percentages. Student's t-test was used to compare group differences for continuous variables satisfying normal distribution and homogeneity of variance. A Satterthwaite t-test was used for continuous variables exhibiting normal distribution but lacking homogeneity of variance. For continuous variables that did not exhibit a normal distribution or homogeneity of variance, the Wilcoxon rank-sum test was used to evaluate differences between the two groups. The chi-squared test and Fisher's exact test were conducted to assess categorical variables between different groups, while the Wilcoxon rank-sum test was used for rank data. Covariates with P < 0.05 on univariate logistic analysis were considered potential confounders. Multivariable logistic regression analyses were conducted to investigate the relationship between the status of CCC and MACCEs. The results were presented as odds ratios (ORs) with their corresponding 95% confidence intervals (CIs). Survival curves were plotted for the two groups using the Kaplan–Meier method. Subgroup analyses stratified by MetS were also performed to explore the association between CCC and MACCEs. Model 1 was the crude model. Model 2 was adjusted for history of MI, number of occluded vessels, ACEI or ARB, and statins. The association of CCC with MACCEs was also explored in different DM and Syntax score subgroups. A two-sided P < 0.05 was used to indicate statistical significance. All analyses were performed using R version 4.2.3 (2023-03-15 ucrt).

A total of 342 CTO patients undergoing PCI were enrolled, with an average age of 61.43 years. Among them, 151 patients were classified as having a good CCC. There was statistical significance between the two groups in terms of smoking (P < 0.05). The demographic, clinical, and treatment information is presented in Table 1. Figure 1 illustrates the participants selection process.

Table 2 presents the clinical outcomes of CTO patients with good or poor CCC. During the 1-year follow-up period, 99 CTO patients experienced MACCEs. In total, 18 CTO patients succumbed to all-cause death, with 17 of them being attributed to cardiac death. In addition, 78 CTO patients experienced non-fatal MI, while 15 CTO patients suffered a non-fatal stroke. The survival curve of the MetS group was significantly lower than that of the non-MetS group (Figure 2). All participants received coronary angiography during follow-up, with 77 of them undergoing repeat revascularization. Overall, the rate of MACCEs and their components was higher in patients with poor CCC compared to those with good CCC.

In model 2, confounders were adjusted, including history of MI, number of occluded vessels, ACEI or ARB, and statin use. Poor CCC was related to a higher incidence of MACCEs (OR = 3.33, 95% CI: 1.93–5.72), non-fatal MI (OR = 3.11, 95% CI: 1.73–5.58), TVR (OR = 3.06, 95% CI: 1.70–5.53), and stent thrombosis (OR = 6.14, 95% CI: 2.76–13.65) (Table 3).

The relationship of CCC status with MACCEs was further assessed in CTO patients with or without MetS. Poor CCC in patients with MetS was associated with higher odds of MACCEs (OR = 4.21, 95% CI: 2.05–8.65), non-fatal MI (OR = 4.44, 95% CI: 2.01–9.83), TVR (OR = 3.28, 95% CI: 1.51–7.11), and stent thrombosis (OR = 10.80, 95% CI: 3.11–37.54) (Table 4).

Table 5 illustrates the relationship between CCC and MACCEs in different DM and Syntax score subgroups. In DM patients, poor CCC was related to higher odds of MACCEs (OR = 4.42, 95% CI: 1.96–10.97), non-fatal MI (OR = 4.12, 95% CI: 1.70–11.39), TVR (OR = 3.09, 95% CI: 1.34–7.83), and stent thrombosis (OR = 10.98, 95% CI: 2.97–71.98). In CTO patients with Syntax score ≥23, poor CCC was associated with a higher incidence of MACCEs (OR = 3.83, 95% CI: 1.43–11.72), non-fatal MI (OR = 5.89, 95% CI: 1.77–27.28), TVR (OR = 3.45, 95% CI: 1.19–11.89), and stent thrombosis (OR = 11.49, 95% CI: 2.64–89.60).