The key findings of this study can be summarized as follows: (1) Approximately 49.5% of NSTEMI patients had complete occlusive lesions in their IRAs. (2) the LCX served as the primary IRA in the TO group, whereas in the non-TO group, the LAD was more frequently identified as the IRA. (3) In this study, over a third of the patients diagnosed with NSTEMI showed the presence of red thrombus/mixed thrombus in their IRAs. Furthermore, this type of thrombus was observed more frequently in NSTEMI patients with TO in the IRA. (4) STDMI and STUMI were identified as two distinct ECG patterns in NSTEMI patients, with the TO group primarily showing STUMI and the non-TO group mainly exhibiting STDMI. (5) NSTEMI patients with red thrombus/mixed thrombus in their IRAs typically displayed STUMI on ECG, whereas those with STDMI predominantly had white thrombus in the IRA.

Our study involved a comparison of the baseline characteristics, angiographic findings, and OCT results between the TO and Non-TO groups. The TO group displayed a younger demographic with a higher frequency of smoking and a lower prevalence of cardiovascular risk factors such as hypertension and diabetes. These findings align with the literature, as reported by Jarosław Karwowski et al. [12]. A study by Wang and colleagues found that 27% of patients diagnosed with non-ST segment elevation acute coronary syndrome (NSTE-ACS) had an occluded infarct artery. Additionally, it was found that these patients exhibited larger infarct sizes and had a higher risk-adjusted 6-month mortality rate [15]. Consistent with these findings, our study revealed a higher proportion of Killip grade ≥ 2, more abnormal left wall motion, and higher peak values of CK and CKMB in the group with TO. Additionally, our literature review revealed that occluded arteries were more prevalent in NSTEMI patients about the LCX. This finding aligned with conventional wisdom, emphasizing that complete occlusion without ST-segment elevation primarily occurs in the LCX. Furthermore, our study observed a higher prevalence of Rentrop grade 1–3 in the TO group. Based on the previous literatures and the experience of our research group, the main reason for acute coronary artery occlusion without ST segment elevation is that the infarcted myocardium has well-developed collateral circulation. This intricate network of blood vessels enables the myocardium affected by ischemia to receive blood supply in a reverse direction, effectively mitigating the impact of the occlusion. Furthermore, the absence of ST-segment elevation in patients with occlusion of the distal end of the LCX can be attributed to the fact that the location of the lower posterior wall of the heart is a blind spot detected by a 12-lead or even 18-lead ECG [16,17,18].

The current guidelines for managing acute coronary syndrome (ACS) emphasize the emergency revascularization of IRA for patients who present with STEMI [19]. However, in cases with no typical ECG indications, there is a potential risk of underestimating the severity of certain NSTEMI patients with total occlusion of the infarct-related artery (TO of IRA). Consequently, the delay or even exclusion of revascularization procedures may occur. A study conducted by Abdul R et al. (2017) demonstrated that patients diagnosed with NSTEMI who experienced total occlusion of the IRA, as observed during coronary angiography, were associated with a significantly higher mortality risk and major adverse cardiac events. Early vascular reconstruction could potentially enhance the prognosis [2]. In 2016, Jaroslaw Karwowski et al. conducted a study on a cohort of 2767 NSTEMI patients in Poland who had been registered for ACS. The researchers discovered that 26.3% of the patients had TIMI flow grade 0, while the remaining 73.7% had TIMI flow grade 1–3 [12]. In a more recent study conducted in 2021, Irmina Morawska et al. included 399 NSTEMI patients in their research, according to the findings, 138 were classified as having preoperative TIMI flow grade 0 (TO group), while 261 patients fell into the preoperative TIMI flow grade 1–3 category (Non-TO group) [20]. There is a rising trend of individuals with NSTEMI who experience TO of the culprit artery. Our study revealed that almost half (49.5%) of NSTEMI patients had TO of the culprit artery, a considerably higher proportion than previous literature. Hence, it is crucial to recognize and prioritize the NSTEMI population presenting with TO of the culprit artery, and further research is necessary to enhance the identification of this particular group.

According to traditional theory, STEMI is commonly caused by a single vessel occlusive lesion, characterized by red blood cells and fibrinogen as the primary components of the thrombus. The treatment approach for STEMI focuses on wholly and promptly opening the IRA while simultaneously implementing intensified antithrombotic and anti-ischemic measures. Thrombolysis or emergency intervention may also be viable treatment options. In contrast, NSTEMI typically presents as a non-occlusive lesion involving multiple blood vessels, with platelet representing the major thrombus component. The recommended treatment approach for NSTEMI involves enhancing antithrombotic and anti-ischemic measures, and if necessary, emergency intervention can be considered. However, thrombolysis is contraindicated for NSTEMI. In 2012, Quadros et al. performed a pathological examination on thrombi obtained from the affected blood vessels of 113 patients diagnosed with STEMI. Their study revealed that approximately one-third (31%) of the thrombi observed in STEMI patients appeared as white thrombi [21]. In 2011, Yasushi et al. employed OCT technology to investigate thrombus formation in the IRA of 89 patients diagnosed with ACS. The study population comprised 40 cases of STEMI and 49 cases of NSTE-ACS. Their study revealed that in STEMI patients, 78% had red thrombus in the IRA, whereas 22% had white thrombus in the IRA. Additionally, among NSTE-ACS patients, 39% had white thrombus, and 27% had red thrombus in the IRA [6]. These findings suggest that red thrombus is more prevalent in STEMI cases, while white thrombus is more common in NSTE-ACS. Consistent with prior literature, the NSTEMI population in which the IRA primarily consists of white thrombus was examined. Within our study, encompassing 202 NSTEMI patients, we uncovered 132 white thrombus and 70 cases of red thrombus. Among the 70 cases of red thrombus, occlusive lesions were present in 48 cases (68.6%), and non-occlusive lesions were present in 22 cases (31.4%) in the IRA. Our research reveals that red thrombus predominantly occurs in the group with TO of the IRA, whereas white thrombus exists primarily in the group without total occlusion (Non-TO) of the IRA. Based on these findings, we hypothesize that blood flow is a crucial factor influencing the type of thrombus and that the type of thrombus is correlated with the TIMI flow of the IRA. The association between ST-segment elevation and thrombotic composition is correlative rather than causal. Hence, the understanding that “ST segment elevation indicates red thrombus” and “ST segment non-elevation indicates white thrombus” lacks rigor. Consequently, adopting a “one-size-fits-all” treatment approach for AMI patients is not justifiable solely based on ECG manifestations. Based on the study’s findings, a hypothesis suggests a significant correlation between the type of thrombus and the occurrence of coronary artery occlusion. The study reveals that patients with primarily red thrombus in the IRA tend to have occlusive lesions, while those with primarily white thrombus in the IRA tend to have non-occlusive lesions. We innovatively used OCT technology to observe coronary thrombus in NSTEMI patients, Luis Augusto Palma Dallan et al. found that OCT-proven images completely changed the treatment of patients, mainly manifested by further improvement of treatment plans, including adequate pre-dilation and ideal stent size with good treatment outcomes [22]. If the IRA shown by our OCT are red thrombus/mixed thrombus, whether the one-size-fits-all treatment strategy can be interrupted to perform thrombolytic therapy for these NSTEMI patients is a question worth exploring.

The ST segment of the ECG in patients with NSTEMI comprises two distinct characteristics: depression and unoffset. Are there any similarities or differences between these characteristics, similar to the distinctions between NSTEMI and STEMI? In a 2021 study by Shujuan Dong et al., a group of individuals diagnosed with occlusion of the IRA were analyzed and divided into three distinct categories according to their ST segment characteristics: ST-segment elevation, normal ST segment, and ST segment depression. The study findings suggested that patients with myocardial infarction characterized by ST-segment elevation or a normal ST segment frequently exhibited more occlusive lesions [23]. Consistent with our study, we observed that NSTEMI patients with STUMI (normal ST segment) showed a higher occurrence of occlusive lesions than those with STDMI (ST segment depression). Furthermore, our investigation revealed discrepancies in the thrombotic types between STUMI and STDMI as observed by OCT. Patients with red thrombus/mixed thrombus in their IRA typically displayed STUMI on ECG, whereas patients with STDMI predominantly displayed white thrombus in the IRA. In the case of NSTEMI, some patients may benefit from thrombolysis treatment. It is arbitrary to assess the suitability of ST segment elevation for thrombolysis in a biased manner.

The findings of this study subdivided NSTEMI into STUMI and STDMI, deepening the cognitive theory of NSTEMI. Additionally, our study demonstrated the presence of a substantial number of red thrombi in the IRA of NSTEMI patients, with a majority observed in TO of the IRA. These findings provide a valuable research foundation for further refinement of NSTEMI treatment strategies. (clinical implication).

This study is limited in a few ways. Firstly, it is a retrospective analysis conducted at a single center, which might restrict the generalizability of the findings. Additionally, the sample size in this study is relatively small, which could reduce the statistical power and limit the generalizability of the results. To address these limitations, future studies should consider conducting prospective multi-center trials with larger sample sizes to enhance the validity and generalizability of the findings. Secondly, a few NSTEMI patients were excluded during the study period, including those with restenosis within the stent. The presence of the steel beam in the stent may have impacted the evaluation of plaque and thrombus characteristics using OCT. Additionally, some patients did not find thrombus through OCT, which might have introduced selection bias that could have influenced the results. Thirdly, in NSTEMI patients with TIMI grade less than 2, it is imperative to conduct a small balloon pre-dilation before OCT to ensure adequate blood perfusion. This pre-dilation process, however, carries the risk of potential mechanical damage, which in turn could lead to alterations in the morphological features of potential plaques in these patients. Lastly, it is essential to validate the findings of this study through large-scale, multicenter clinical investigations.