Using a multi-center, observational cohort of 5208 individuals suffering from AMI, we observed an apparently higher TyG level in AMI populations developing CS than in those without CS. The TyG index exhibited a moderate ability to discriminate individuals occurring CS from the general AMI populations. Moreover, elevated TyG levels were strongly associated with heightened risks regarding both in-hospital and ICU mortality among those who had AMICS, even following controlling for potential confounders and employing several statistical approaches. Collectively, our findings illustrate the previously unacknowledged significance of TyG index for AMICS, thereby improving the comprehension of its involvement in cardiovascular conditions.

The TyG index has gained considerable attention regarding the cardiovascular field in recent years due to its easily obtainable and reliable reflection of IR, compared to classical testing methods such as euglycemic hyper-insulinemic clamp and homeostasis model assessment of IR [23]. As previously meta-analyzed, the TyG index served as a dependable indicator for the occurrence and severity of atherosclerotic disorders in the general population [24, 25], as well as a reliable predictor for poor outcomes in individuals with coronary artery disease [26]. Moreover, associations of TyG index with other cardiovascular diseases, including but not limited to chronic heart failure [27], AMI [28], hypertension [29], coronary artery calcification [29] and atrial fibrillation have already been identified [30]. From a pathological perspective, IR can disrupt myocardial metabolism during ischemia, exacerbate endothelial dysfunction, and disturb cardiac autonomic system function [31,32,33]. Therefore, it is reasonable to conclude that the TyG index holds predictive value for multiple cardiovascular disorders, including its potential predictive role in AMICS as investigated in our study. Notably, elevated levels of TyG have been shown to be linked with adverse outcomes in ICU cohorts [34], who often shared partial overlap with the AMICS populations targeted by our study.

The AMICS consistently demonstrated high mortality rates, with a 30-day mortality rate of nearly 40% and a one-year mortality rate of approximately 50% [2]. Despite the proven benefits of prompt revascularization in improving prognosis, there has been no observed change in AMICS-related mortality over the past decades. In the present study, we observed apparently higher in-hospital (26.9% vs. 5.7%) and ICU mortality (22.7% vs. 3.5%) among those with AMICS. CS complicates 3–13% of cases following AMI [2,3,4], often presenting as a sudden manifestation following AMI, posing a life-threatening yet unpredictable situation. Established risk indicators for CS after AMI, such as advanced age, male gender, and larger infarct size have limited clinical utility due to their unmodifiable nature [2, 35]. Our findings demonstrated a significant elevation in TyG index among patients who developed CS following AMI compared to those who did not experience this complication. More notably, the TyG index demonstrated superior discriminatory ability in identifying patients at risk for developing AMICS within the overall population with AMI when compared to age, gender, BMI, CK-MB, NT-pro BNP, and certain serum lipid levels.

Massive myocardial infarction and malignant arrhythmia are significant risk factors for CS following AMI [2], contributing not only to permanent infarction but also to temporary myocardial dysfunction. Interestingly, an elevated TyG level is greatly correlated with larger infarct size and various arrhythmia including not only ventricular fibrillation examined in our study (adjusted OR: 1.331 of AMI population and 1.824 of AMICS population, Table S10) but also QT interval prolongation and atrial fibrillation as previously documented [22, 36, 37], which partially explain the relationship of TyG levels with the occurrence and outcomes of AMICS. Myocardial stunning is characterized by temporary cardiomyocyte dysfunction without necrosis, and it has been demonstrated to play a role in the advancement of AMICS [38]. This dysfunction can be alleviated after euglycemic insulin clamp [39], suggesting a potential link between elevated TyG index and AMICS might be partially established via the exacerbation of myocardial stunning. Additionally, researchers have identified a significant correlation between elevated TyG index and coronary slow flow that has been linked to increased risk of major cardiovascular adverse events post-AMI [40,41,42], potentially due to diminished coronary flow reserve and endothelial dysfunction [43, 44]. These findings indicate that patients with a higher TyG index who have suffered from AMI may be at a hazardous and susceptible status for developing CS, whereas further validation is required in prospective cohorts or randomized controlled trials. Established scoring systems for assessing the severity of illness in the ICU, for instance, APACHE II score, have been proved to be an effective stratification tool for the AMICS population [45, 46]. Nevertheless, implementing these scoring systems practically remains challenging due to the need for collecting multiple physiological measures [47]. Surprisingly, we found an apparent association of TyG levels with APS scores in the AMICS population, which is a component of APACHE II focusing on acute physiological abnormalities assessment. Given these findings, it can be inferred that individuals with higher TyG index face more serious conditions in AMICS. Additionally, although there was a noticeable trend of increased LOS-ICU with higher TyG index levels, no consistent conclusions regarding this association were found in further adjusted cohort. Herein, we do not consider so yet that the TyG index was linked with the LOS-H nor LOS-ICU in patients with AMICS.

Disturbance of glucose metabolism is commonly seen in critically illness patients [48, 49]. Numerous reports from ICU cohorts have independently demonstrated poor outcomes relevant to glucose disorders [50,51,52]. For the past few years, scholars have established some scores to assess the severity and clinical outcomes of AMICS population such as IABP-Shock II score [35], Card Shock score [2], and residual SYNTAX score [53]. These scoring systems incorporate variables related to glucose metabolism such as FBG, and have shown strong predictive capability by combining risk indicators, including age, gender, stroke, Cr, LAC, MAP, etc. In addition, the use of vasoactive agents, the use of mechanical circulatory support, number of diseased vessels, and TIMI after PCI were also employed as predictors for adverse prognosis in patients with AMICS. In this regard, it was not unexpected, because former studies have previously pointed the correlation of admission hyperglycemia with adverse outcomes in patients undergoing extracorporeal membrane oxygenation for AMICS [10], while this elevated glucose level was very likely to appear as a presentation of IR [54]. In the present work, we carefully considered confounding factors to maximize the reliability of our findings.

To the best of our knowledge, this study represents the first attempt to assess the correlation of the TyG index with the incidence and prognosis of CS in patients with AMI. It amalgamates data from two large cohorts, encompassing records from 209 medical centers, offering a novel perspective on the relevance of TyG index to cardiovascular disorders. As an easily and inexpensively available indicator calculated from routine tests, the TyG index is readily obtainable for the majority of AMI patients. Given the explored significant association between the TyG index and AMICS, healthcare professionals can widely and promptly utilize this index to monitor the metabolic status of patients with AMI/AMICS in various clinical settings, allowing for duly implementation of lifestyle interventions or adjustment of therapy strategies to reduce its level, thereby contributing to minimizing the occurrence of CS following AMI and maximizing the benefits for patients with AMICS. Additionally, incorporating the TyG index into future scoring systems for AMICS to measure the risk of glucolipid metabolism has the potential to enhance the overall cardiovascular risk assessment capacity for these populations. However, further explorations are needed to illustrate the causal association between the two.

There were some limitations that need to be acknowledged. Firstly, the retrospective design of this study limits control over the temporal sequence of events, thereby precluding the establishment of a definitive causal relationship between the TyG index and the occurrence and prognosis of AMICS. Thus, further prospective research and randomized controlled trials are required to probe the causality of an elevation of TyG in the AMI population with increased risk and worse prognosis of CS; Secondly, despite we have controlled for confounders as much as possible, there are still certain variables that were not included in this study, such as no-reflow events, door-to-balloon time, AMI location, and so on, which have been identified as significant risk factors for the prognosis of AMICS patients [53]. Thus, there might be potential selection biases in our study, and future studies with access to more detailed clinical data are essential; Thirdly, this study is primarily grounded in historical data and may exhibit slight variations from current clinical practices and disease development trends; Fourthly, given that surrogate of IR is considered a general marker of poor prognosis for multiple disorders, the TyG index thus demonstrates diminished precise diagnostic value for a specific and well-defined pathological setting. Therefore, despite the TyG index serving as a dependable screening tool for AMICS, the relatively low diagnostic specificity value of this index should be likewise acknowledged; Furthermore, an elevated TyG has been recognized as an independent risk indicator for adverse long-term cardiovascular outcomes following AMI [55]. Hence, as a substage of AMI, additional longer follow-up studies regarding AMICS is indispensable, which will be pivotal in delving into the correlation between the TyG index and the long-term prognosis among the AMICS population.