This retrospective study was conducted on consecutive patients with NSTEMI who were admitted to our emergency room between 1 January 2016 and 1 August 2022. The inclusion criteria were as follows: established diagnosis of NSTEMI and a need for interventional treatment within 72 h of admission, as recommended by the relevant guidelines. Exclusion criteria were as follows: previous myocardial infarction, coronary artery bypass grafting, or percutaneous coronary intervention (PCI). This study was approved by the Institutional Ethics Committee of the Sir Run Run Shaw Hospital. Informed consent was obtained from all patients enrolled in this study.

The demographic features of all patients, such as age, gender, body mass index (BMI), history of hypertension or diabetes, smoking, and family history of coronary artery disease (CAD), were obtained from electronic medical records. Blood samples were drawn from the patients upon their arrival at the emergency department via a peripheral venous line and processed immediately. ECG data on ST-segment depression, flat T waves or T-wave inversion, and pathological Q wave and echocardiographic data consisting of ejection fraction (EF), regional wall motion abnormalities (RWMAs), and left ventricular end-diastolic dimension (LVEDD) were extracted. Moreover, the TIMI (http://www.timi.org/index.php?page=calculators) and GRACE scores (https://www.outcomes-umassmed.org/grace/acs_risk/) were calculated separately for all patients.

Two experienced interventional cardiologists identified the culprit vessel using coronary angiography, ECG, and echocardiogram. TO was defined as a culprit vessel with a TIMI flow of 0–1, indicating no dye penetration or minimal dye penetration without complete vessel opacification. MVD was defined as significant stenosis (>70%) in two or more major coronary arteries of 2.5 mm diameter or more. NSTEMI was defined as elevated troponin levels and the absence of ST elevation at the time of diagnosis according to 2014 NSTEMI guidelines (3). According to the guidelines of the American Society of Echocardiography (9), longitudinal shortening or radial thickening of the myocardium after aortic valve closure (postsystolic shortening or thickening, sometimes referred to as tardokinesis) of >20% of the total deformation during the cardiac cycle is a consistent sign of regional functional inhomogeneity. And also, RWMAs were defined as the occurrence of hypokinetic (reduced thickening), akinetic (absent or negligible thickening), and dyskinetic (systolic thinning or stretching) which were detected by experienced sonographers and confirmed by trained cardiologists. According to the severity of RWMAs, we defined the RWMA score as normal = 1, hypokinetic = 2, akinetic = 3, and dyskinetic = 4.

Detailed in-hospital and follow-up data were recorded and entered into a database. Patients were followed up through clinical visits or telephone calls to the referring physician. The clinical endpoint was cardiac death, which included death due to myocardial infarction, ventricular tachycardia/ventricular fibrillation, sudden cardiac arrest, or heart failure.

Categorical variables were expressed as percentages and compared using the chi-square test. Continuous variables were expressed as a mean ± SD or median with interquartile ranges and were compared using Student's t-test or the Wilcoxon rank-sum test as appropriate. The independent predictors of acute TO and MVD were confirmed by using the multivariate logistic regression model after adjusting for the potentially related variables (P < 0.2 and P < 0.05, respectively) identified in the univariate analysis. Kaplan–Meier survival curves were compared using the log-rank test. SPSS V.26.0 was used for all analyses, and a value of P < 0.05 was considered statistically significant.

The study population comprised 835 patients with NSTEMI: 349 (41.8%) presented with a TO culprit vessel and 486 (58.2%) had a patent culprit vessel. Baseline characteristics according to the patency of the culprit artery are listed in Table 1. The two groups showed similarities with respect to demographic characteristics and clinical data, and there were no significant differences between them, although differences were noticed with regard to BMI, white blood cell (WBC) count, neutrophil count, low-density lipoprotein cholesterol (LDL-C) level, high-sensitivity C-reactive protein (hs-CRP) level, heart rate (HR), and RWMAs, which were all higher or more commonly detected in patients with TO. TIMI and GRACE risk stratification were similar in both groups (P = 0.712 and 0.991, respectively). The proportion of patients with a TO of the culprit artery divided by different types of risk stratification is shown in Figures 1A,B.

The angiographic characteristics of the patient groups are presented in Table 1. TO was more commonly observed in the left circumflex artery (LCX). Patients with a TO of the culprit artery had a higher incidence of MVD (P = 0.004), a greater number of thrombotic culprit lesions (P < 0.001), high levels of collateral circulation (P < 0.001), and fewer calcified lesions (P = 0.008). In the TO group, glycoprotein IIb/IIIa inhibitors were used more frequently.

Univariate and multivariate linear regression analyses were performed to evaluate the role of variables in NSTEMI patients with a TO of the culprit artery. RWMA [odds ratio (OR) = 4.022, confidence interval (CI): 2.782–5.813; P < 0.001] was significantly associated with TO after adjusting for potentially related variables (Table 2). We also examined the variables through univariate and multivariate regression analyses and found that age (OR = 1.032, CI: 1.018–1.047; P < 0.001), hypertension (OR = 1.499, CI: 1.048–2.144; P = 0.027), and diabetes mellitus (OR = 3.007, CI: 1.764–5.125; P < 0.001) were independent predictors of MVD in patients with NSTEMI (Table 3). An assessment of the predictive value of MVD by risk stratification revealed that the TIMI and GRACE risk scores were associated with the prevalence of MVD in the multivariate logistic regression model (Table 4).

The outcomes of the 2-year follow-up period were compared between the TO and the non-TO groups of patients. A Kaplan–Meier analysis showed similar rates of in-hospital, 6-month out-of-hospital, and 1-year out-of-hospital cardiac deaths within the two groups (P = 0.727, 0.393, and 0.407, Figures 2A–C). However, patients with a TO culprit vessel had a higher rate of out-of-hospital cardiac death after the 2-year follow-up compared with those without a TO culprit vessel (P = 0.022, Figure 2D).

The principal findings of this study are as follows: (1) the rate of prevalence of acute TO in patients with NSTEMI was 41.8%; (2) the LCX culprit vessel had the highest likelihood of TO in the setting of NSTEMI; (3) TIMI and GRACE risk stratification did not correlate with a TO of the culprit vessel but correlated with the prevalence of MVD; (4) RWMA was an independent predictor of TO in patients with NSTEMI; (5) patients with a TO of the culprit vessel had worse clinical outcomes at the mid-term follow-up compared with those without a TO of the culprit vessel.

The reported rates of prevalence of acute TO in patients with NSTEMI ranged from 24.0% to 37.2% (4, 10–12). In our study, the frequency was higher than that reported in previous studies, which may be explained by the differences in patient selection and variation in the risk stratification of the patients. Our study found that the vessel most likely occluded in NSTEMI is the LCX, which is consistent with the results of previous trials (13, 14). This finding is perhaps attributed to the fact ischemia in the LCX territory is difficult to detect since 38%–47% of patients do not show ST-segment shifts in any standard ECG lead (15). At our center, we routinely obtained an 18-lead electrocardiogram for patients presenting to the emergency department with ACS. STEMI due to occlusion of the LCX was typically manifested on ECG as ST-segment elevations in lateral, inferior, and posterior leads, while NSTEMI due to occlusion of the LCX was defined as elevated troponin levels and the absence of ST-segment elevations in any standard ECG lead at the time of diagnosis.

In patients with NSTEMI, a quantitative assessment of ischemic risk employing scores such as the GRACE risk score and TIMI risk stratification proved to be superior to clinical assessment alone. Current clinical practice guidelines for non-ST-segment-elevation acute coronary syndrome (NSTE-ACS) recommend different treatment strategies and timings for intervention according to the initial risk stratification (16). However, we demonstrated that the proportion of TO in different risk stratifications of TIMI and GRACE was similar, which accounted for the inability of the TIMI and GRACE risk scores to indicate whether the culprit vessel was totally occluded. This may result in delayed revascularization in non-high-risk patients. Prior studies have shown that the outcomes for NSTEMI patients with TO who do not receive timely revascularization are poorer than those for STEMI patients (17, 18). Moreover, a meta-analysis suggested that NSTEMI patients with totally occluded culprit vessels on coronary angiography were at a higher risk of mortality and major adverse cardiac events (19). Our findings were comparable but not identical to those of previous studies regarding the outcomes for patients with a TO culprit vessel. Patients with a TO culprit vessel had a similar rate of cardiac death in the hospital and at the short-term follow-up, while these patients had a higher risk of mortality in the mid-term follow-up compared with those without a TO culprit vessel. This could be attributed to the following: (1) all patients with NSTEMI received timely revascularization and proper medication in our center, contributing to a reduction in mortality after PCI and at the short-term follow-up. (2) Patients with a TO culprit vessel usually suffered a complete infarction of a part of the myocardium, requiring better treatment for myocardial remodeling. Some patients had a higher mortality rate due to poor drug adherence at the mid-term follow-up. Hence, finding reliable predictors of TO in patients with NSTEMI is of great significance.

Echocardiography is a feasible tool for TO detection. Eek et al. (20) found that detection of contractile abnormalities by strain or conventional echocardiography might be a very useful method to identify acute TO in NSTEMI. In our study, RWMA was also shown to be an effective predictor of acute TO in patients with NSTEMI. The possible mechanism is that acute persistent coronary occlusion can cause more severe ischemia and impaired systolic function in large regions of the myocardium.

The prognosis of NSTEMI in the presence of MVD is poor (3). Although risk factors for coronary heart disease are included in risk stratification, the association between the above-mentioned risk scores and coronary severity in NSTEMI has rarely been studied. A few studies have reported on the relationship between risk stratification and the extent of disease (21–25). Our study further evaluated the novel role of existing risk stratification. Identifying the predictors of severe NSTEMI is necessary for preoperative evaluation and developing postoperative preventive strategies based on risk factors.

Our study had some limitations. First, this was a retrospective, single-center study; therefore, a larger sample size with cross-center comparisons is required to validate the results further. Second, the outcome of the patients stratified into two groups in our study was recorded only in terms of cardiac death; it was not recorded by also taking into account other major adverse cardiac and cerebrovascular events, such as recurrent angina, heart failure, and stroke. Detailed records of the causes of adverse events can help make better decisions.