Cardiovascular diseases pose a major threat to humans (1, 2). Acute coronary artery disease manifests as an ST-segment elevation myocardial infarction (STEMI). Patients with STEMI continue to experience significant rates of impairment and mortality, even with ongoing optimization of treatment strategies (2). Irreversible myocardial necrosis and its related consequences are among the possible causes. Following STEMI, up to 12% of patients may develop left ventricular thrombus (LVT) (3). Mechanistically, LVT is caused by endothelial damage because of inflammatory responses, blood stasis from abnormal wall motion following STEMI, and a hypercoagulable state (4). LVT is associated with major adverse cardiac events and poor prognosis in patients (5–7). Therefore, identifying additional risk factors for LVT will help identify high-risk patients early, allowing for timely intervention and improved prognosis in patients with STEMI.

Commonly used diagnostic methods for LVT include transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) imaging, among which CMR is the most accurate imaging modality for detecting LVT (8). CMR outperforms TTE in detecting smaller, layered LVTs (9). A recent meta-analysis of 2,072 patients with STEMI reported that among 431 patients with both CMR and TTE data, the sensitivity of TTE was only 29%, possibly because of poor visualization of the apical region, limiting its diagnostic utility for LVT (9–11). PInflammatory markers, such as high-sensitivity C-reactive protein (CRP), interleukin-6, fibrinogen, and the systemic inflammation index can predict LVT (5, 12). Recently, the lymphocyte-to-CRP ratio (LCR), a new and valuable inflammatory biomarker, has emerged as a useful tool for predicting outcomes and guiding treatment decisions in various diseases, including cancer (7, 13–16), the severity of myocardial injury, and the progression of COVID-19 (17). A previous study showed that LCR is an independent predictor of short- and long-term major adverse cardiac events after acute myocardial infarction (18). In addition, LCR has been associated with new-onset atrial fibrillation in patients with STEMI undergoing primary percutaneous coronary intervention (pPCI) (19). However, the relation between LCR and LVT in patients with STEMI remains unclear. This study aimed to investigate the predictive value of LCR for LVT after pPCI in patients with STEMI.

To the best of our knowledge, this is the first study to examine the relation between LCR and LVT in patients with STEMI. The main findings of this study are as follows: First, LCR was significantly associated with LVT in patients with STEMI. Second, lower ventricular volume was an independent risk factor for LVT in STEMI. Third, integrating LCR into risk models significantly improved LVT prediction.

STEMI is a leading cause of death globally (1, 2). Despite significant improvements in STEMI prognosis owing to the widespread use of early pPCI in recent decades, LVT remains a common complication. Previous studies have identified LVT as an independent risk factor for major adverse cardiovascular and cerebrovascular events (11). Although various clinical diagnostic tools exist for LVT, the risk of missed diagnoses remains. Therefore, identifying a reliable biomarker is crucial for early risk stratification of LVT.

Currently, LVT diagnosis primarily relies on imaging techniques, such as TTE, TTE with an ultrasound-enhancing agent, and CMR. TTE primarily detects LVT based on cardiac structure. However, small adherent LVTs, apically located LVTs, and cases with poor image quality may be missed. Although TTE has a high specificity (91%), its sensitivity is low (33%) (9, 11, 22, 23). TTTE with ultrasound-enhancing agent improves sensitivity to 60%, but over one-third of LVTs may still go undetected (24). RRecently, CMR, which detects thrombi based on histological characteristics, has become the gold standard for diagnosing LVT, with a sensitivity of 88% and specificity of 99% (10). In a study involving 265 patients with STEMI who underwent CMR within 3 weeks of onset, the incidence of LVT was 12.8% (25). Similarly, in this study, the incidence of LVT was 10.1% when CMR imaging was performed within a median of 5 d (4–6 d) of STEMI onset. However, studies have reported an overall LVT incidence rate of 2.7%–6.3% in patients with STEMI, likely due to the low sensitivity of TTE, which may lead to underdiagnosis (9, 22).

The correlation between inflammation and LVT has been confirmed by numerous studies (5, 6, 26). Recently, the LCR has been demonstrated to be a convenient and readily accessible inflammatory marker associated with the development and prognosis of various diseases (7, 13–17). IIt plays a crucial role in both the prognosis and diagnosis of cardiovascular diseases (19). In this study, we found that LCR was an independent risk marker for LVT after pPCI in patients with STEMI. Although the exact mechanism remains unclear, it may be related to several factors. Virchow's triad, which includes blood stasis, endothelial injury, and a hypercoagulable state, is the core mechanism underlying LVT after STEMI. Inflammatory factors are involved in Virchow's triad (27). Inflammatory responses play a crucial role in blood stasis during STEMI (28). During myocardial infarction-induced hypoxia, inflammatory cells are activated, producing large amounts of inflammatory factors that attach to endothelial cells, increasing blood flow resistance and contributing to blood stasis (5, 6, 22, 28). Simultaneously, the inflammatory cascade leads to endothelial injury after myocardial infarction, exposing the subendothelial tissue and collagen, which perpetuates inflammation and promotes a hypercoagulable state (22, 29). This may partially explain the results of this study. Furthermore, lymphocytes play a vital role in myocardial ischemia-reperfusion injury (29, 30). After reperfusion, lymphocytes rapidly accumulate at the site of injury, releasing cytokines and chemokines that attract other immune cells, such as neutrophils and monocytes, thereby exacerbating the inflammatory response (30). A previous study showed that a high neutrophil-to-lymphocyte ratio is associated with post-PCI hyperthrombosis in patients with STEMI; therefore, higher neutrophil counts or lower lymphocyte counts contribute to a higher incidence of high thrombotic load after PCI (31). CRP stimulates monocytes, endothelial cells, and smooth muscle cells to release tissue factors while inhibiting the release of tissue factor pathway inhibitors—a natural anticoagulant—by human endothelial cells, suggesting that CRP may have a prothrombotic effect. CRP may also increase LOX-1 expression, which plays a key role in the deleterious effects of oxidized LDL on endothelial function. Additionally, CRP enhances the proinflammatory effect induced by angiotensin II, further promoting thrombosis (32). Although this inflammatory response aids in clearing necrotic cells and tissues during the early stages, excessive inflammation can exacerbate myocardial damage and impair cardiac function recovery, thus significantly influencing the long-term prognosis of patients with STEMI (3, 29). CRP level is a powerful predictor of LVT after pPCI in acute anterior myocardial infarction (5, 6). ResultsIn a study of patients admitted to a cardiac intensive care unit, Litmanowicz et al. demonstrated that peak CRP levels predict ventricular thrombus formation (33). Additionally, Li et al. investigated infarct-related arterial thrombosis in patients with acute myocardial infarction and found that higher CRP levels were predictive of thrombus formation (34). As a combination of lymphocyte and CRP levels, LCR provides a more comprehensive reflection of the inflammatory state following STEMI. In this study, LCR correlated with peak high-sensitivity troponin T, peak N-terminal pro-B-type natriuretic peptide, late gadolinium enhancement percentage (LGE%), left ventricular ejection fraction, and microvascular obstruction percentage, all known risk markers for LVT (2, 35–37).This supports the findings of the present study from a different perspective. Although the correlation between LVT and other cardiovascular markers was not strong, a significant relation was observed.The relatively weak correlation could be because of the study's limited sample size or underlying mechanistic differences.

In previous studies, LGE% and infarct-related artery in the left anterior descending artery (IRA-LAD) were identified as LVT-related factors (36, 38). This study consistently found that LGE% and IRA-LAD were independent risk factors for LVT. Subsequently, a traditional risk model incorporating LGE% and IRA-LAD was established. Receiver operating characteristic analysis demonstrated that integrating LCR significantly improved the model's discriminatory ability for LVT (AUC = 0.732). When LCR was incorporated into the traditional model, discrimination and reclassification accuracy for LVT improved significantly (NRI = 0.517, IDI = 0.030, p < 0.001). This study demonstrates that LCR, as a simple and easily accessible clinical indicator, can predict LVT after myocardial infarction and enhance risk stratification. Therefore, LCR may serve as a valuable marker for identifying LVT in patients with STEMI undergoing pPCI.

We found that a lower LCR was independently associated with an increased risk of LVT in patients with STEMI after pPCI. Integrating LCR into the LVT risk model significantly improved its predictive accuracy.