Design and rationale of the ATTRACTIVE trial: a randomised trial of intrAThrombus Thrombolysis versus aspiRAtion thrombeCTomy during prImary percutaneous coronary interVEntion in ST-segment elevation myocardial infarction patients with high thrombus burden.

INTRODUCTION: ST-segment elevation myocardial infarction (STEMI) with high thrombus burden is associated with a poor prognosis. Manual aspiration thrombectomy reduces coronary vessel distal embolisation, improves microvascular perfusion and reduces cardiovascular deaths, but it promotes more strokes and transient ischaemic attacks in the subgroup with high thrombus burden. Intrathrombus thrombolysis (ie, the local delivery of thrombolytics into the coronary thrombus) is a recently proposed treatment approach that theoretically reduces thrombus volume and the risk of microvascular dysfunction. However, the safety and efficacy of intrathrombus thrombolysis lack sufficient clinical evidence. METHODS AND ANALYSIS: The intrAThrombus Thrombolysis versus aspiRAtion thrombeCTomy during prImary percutaneous coronary interVEntion trial is a multicentre, prospective, open-label, randomised controlled trial with the blinded assessment of outcomes. A total of 2500 STEMI patients with high thrombus burden who undergo primary percutaneous coronary intervention will be randomised 1:1 to intrathrombus thrombolysis with a pierced balloon or upfront routine manual aspiration thrombectomy. The primary outcome will be the composite of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, heart failure readmission, stent thrombosis and target-vessel revascularisation up to 180 days. ETHICS AND DISSEMINATION: The trial was approved by Ethics Committees of China-Japan Friendship Hospital (2022-KY-013) and all other participating study centres. The results of this trial will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05554588.

Effect of Triglyceride-Glucose Indices and Circulating PCSK9-Associated Cardiovascular Risk in STEMI Patients with Primary Percutaneous Coronary Artery Disease: A Prospective Cohort Study.

Background and Aims: This study aimed to determine whether convertase subtilisin/kexin type 9 (PCSK9)-associated cardiovascular risk is modulated by triglyceride-glucose (TyG) in ST-segment elevation myocardial infarction (STEMI) patients with primary percutaneous coronary disease (PCI). Methods: A total of 1541 patients with STEMI (aged ≥18 years) undergoing primary PCI were consecutively enrolled between March 2017 and March 2019. Outcomes: When stratifying the overall population according to TyG indices less than or greater than the median (TyG median = 9.07) as well as according to quartiles of PCSK9 levels, higher TyG index levels were significantly associated with all-cause mortality only when TyG levels were 9.07 or higher (ie, relative to quartile 1 [Q1], the adjusted HR for all-cause mortality was 3.20 [95% CI, 0.54-18.80] for Q2, p = 0.199; 7.89 [95% CI, 1.56-40.89] for Q3, p = 0.013; and 5.61 [95% CI, 1.04-30.30] for Q4, p = 0.045. During a median follow-up period of 1.96 years, the HR for all-cause mortality was higher in the subset of patients with TyG ≥median and PCSK9 ≥median (p for trend = 0.023) among those with type 2 diabetes mellitus (T2DM). However, there were no statistically significant differences among the subgroups. Among T2DM patients with a TyG index greater than the median, the Kaplan-Meier curve showed that patients with the highest PCSK9 levels had an increased risk of all-cause mortality (log-rank p = 0.017) and cardiac-cause mortality (log-rank p = 0.037) compared with lower PCSK9 quartile levels. Conclusion: Elevated PCSK9 levels are related to all-cause mortality and cardiac-related mortality when TyG levels are greater than the median, but not when levels are less than the median. This suggests a potential benefit of lowering circulating PCSK9 levels in STEMI patients with insulin resistance.

Associations Between Resolvin D1 and Culprit Plaque Morphologies: An Optical Coherence Tomography Study in Patients with ST-Segment Elevation Myocardial Infarction.

Background: As a specialized pro-resolving lipid mediator, resolvin D1 (RvD1) inhibits atherosclerosis progression in vivo by reducing regional oxidative stress and chronic inflammation. However, it is unclear how RvD1 is involved in human coronary artery disease. This study aims to investigate the association between plasma levels of RvD1 and culprit-plaque characteristics in patients with ST-segment elevation myocardial infarction (STEMI). Methods: A total of 240 STEMI patients undergoing optical coherence tomography (OCT) examination were analyzed. RvD1 levels were measured in patient plasma samples using an enzyme-linked immunosorbent assay. Logistic regression was performed to assess the association between RvD1 levels and various culprit plaque morphologies, and the receiver operating curve was used to search for an optimal cutoff threshold to predict certain pathological features. Results: The median RvD1 level was 129.7 (56.6-297.8) pg/mL. According to multivariable logistic regression, high RvD1 was associated with plaque rupture (≥111.5 pg/mL, odds ratio [OR]: 2.09, 95% confidence interval [CI]: 1.20-3.66, P = 0.010), healed plaques (≥246.4 pg/mL, OR: 2.17, 95% CI: 1.11-4.24, P = 0.023), and calcification (≥293.38 pg/mL, OR: 2.10, 95% CI: 1.21-3.66, P = 0.008) at culprit lesions. Conclusion: Increased levels of RvD1 were associated with higher instability of coronary atherosclerotic plaques in STEMI patients.

Development and Validation of a Prediction Rule for Major Adverse Cardiac and Cerebrovascular Events in High-Risk Myocardial Infarction Patients After Primary Percutaneous Coronary Intervention.

Background and Aims: We aimed to develop a clinical prediction tool to improve the prognosis of major adverse cardiac and cerebrovascular events (MACCE) among high-risk myocardial infarction (MI) patients undergoing primary percutaneous coronary intervention (PCI). Methods: The present study was a prospective and observational study. A total of 4151 consecutive MI patients who underwent primary PCI at Fuwai Hospital in Beijing, China (January 2010 and June 2017) were enrolled. Forty-eight patients without follow-up data were excluded from the study. The pre-specified criteria (Supplementary Information 1) were chosen to enroll MI patients at high risk for MACCE complications after PCI. Results: The full model included seven variables, with a risk score of 160 points. Derivation and validation cohort models predicting MACCE had C-statistics of 0.695 and 0.673. The area under the curve (AUC) of the survival receiver operating characteristic curve (ROC) for predicting MACCE was 0.991 and 0.883 in the derivation and validation cohorts, respectively. Conclusion: The predicted model was internally validated and calibrated in large cohorts of patients with high-risk MI receiving primary PCI to predict MACCE and showed modest accuracy in the derivation and validation cohorts.

High-Risk Culprit Plaque Predicts Cardiovascular Outcomes Independently of Plaque Rupture in ST-Segment Elevation Myocardial Infarction: Insight From Optical Coherence Tomography.

The present study explored the predictive value of culprit high-risk plaque (HRP) detected by optical coherence tomography (OCT) for predicting major adverse cardiovascular events (MACEs) in patients with ST-segment elevation myocardial infarction (STEMI). HRP was defined as the simultaneous presence of four criteria: minimum lumen area <3.5 mm2, fibrous cap thickness <75 µm, lipid plaque with lipid arc extension >180°, and presence of macrophages. Patients (n = 274) were divided into non-HRP group (n = 206) and HRP group (n = 68). MACEs were defined as a composite of all-cause death, myocardial infarction, stroke, and revascularization. During a mean follow-up of 2.2 years, 47 (17.5%) MACEs were observed: 28 (13.6%) in the non-HRP group and 19 (27.9%) in the HRP group (log-rank P = .005). Patients with HRP were 2.05 times more likely to suffer from a MACE than those without HRP (hazards ratio: 2.05, 95% confidence interval: 1.04-4.02, P = .038); MACE risk was comparable between plaque rupture and plaque erosion. In conclusion, HRP was present in 24.8% of STEMI patients and associated with higher cardiovascular risk independent of plaque rupture, suggesting that HRP detected by OCT may help identify patients at high risk of future cardiac events.

High Human Antimicrobial Peptide LL-37 Level Predicts Lower Major Adverse Cardiovascular Events after an Acute ST-Segment Elevation Myocardial Infarction.

AIMS: We previously associated acute ST-elevation myocardial infarction (STEMI) with decreased plasma LL-37 levels. Therefore, this study investigated whether plasma LL-37 levels could predict ischemic cardiovascular events in patients after STEMI. METHODS: We prospectively collected peripheral plasma samples and clinical and laboratory data from consecutive patients who presented with STEMI and underwent primary percutaneous coronary intervention at Fuwai Hospital between April and November 2017. Enzyme-linked immunosorbent assay measured plasma LL-37 levels, and we followed the patients for 3 years. Major adverse cardiovascular events (MACEs) were a composite of all-cause mortality, reinfarction, unscheduled revascularization, or ischemic stroke. RESULTS: The study included 302 patients divided into high (≥ median) and low LL-37 level (＜median) groups. The cumulative incidence of MACE (29.1% vs. 12.6%, p=0.0003), all-cause death (12.6% vs. 3.3%, p=0.003), reinfarction (7.1% vs. 2.0%, p=0.04), and unscheduled revascularization (13.0% vs. 5.4%, p=0.04) were higher in the low than those in the high LL-37 level group. Multivariable Cox regression analysis showed that higher LL-37 level independently predicted lower risks of MACE (hazard ratio [HR] 0.390; 95% confidence interval [CI] 0.227-0.669; p＜0.001), all-cause death (HR 0.324; 95%CI 0.119-0.879; p=0.027), and unscheduled revascularization (HR 0.391; 95%CI 0.171-0.907; p=0.027). CONCLUSIONS: High basal plasma level of human LL-37 may predict lower 3-year risks of ischemic cardiovascular events in patients after STEMI.

Culprit-Plaque Morphology and Residual SYNTAX Score Predict Cardiovascular Risk in Acute Myocardial Infarction: An Optical Coherence Tomography Study.

AIMS: Culprit-plaque morphology [plaque rupture (PR) and plaque erosion (PE)] and high-risk plaques (HRP) identified by optical coherence tomography (OCT) and residual SYNTAX score (rSS) have been reported to influence clinical outcomes. Thus, in this study, we aimed to investigate the prognostic implication of culprit-plaque morphology and rSS for major adverse cardiovascular events (MACE) in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: Based on plaque morphology and rSS, 274 STEMI patients were divided into 4 groups: PE/low-rSS (n=61), PE/high-rSS (n=58), PR/low-rSS (n=55), and PR/high-rSS (n=100). According to HRP and rSS, patients were stratified to non-HRP/low-rSS (n=97), non-HRP/high-rSS (n=109), HRP/low-rSS (n=19), and HRP/high-rSS (n=49). MACE was defined as the composite of all-cause death, recurrence of myocardial infarction, stroke, and unplanned revascularization of any coronary artery. RESULTS: During the follow-up of 2.2 years, 47 (17.2%) MACE were observed. Patients with PR/high-rSS and HRP/high-rSS presented lower survival probability on revascularization and MACE. In fully adjusted analyses, PR/high-rSS group presented higher MACE risk than PE/low-rSS (HR: 4.80, 95% CI: 1.43-16.11, P=0.025). Patients with non-HRP/high-rSS (HR: 2.90, 95% CI: 1.01-8.38, P=0.049) and HRP/high-rSS (HR: 8.67, 95% CI: 2.67-28.21, P＜0.001) presented higher risk of cardiac events than non-HRP/low-rSS. Adding rSS and HRP to the risk prediction model increased the C-statistic to 0.797 (95% CI: 0.737-0.857), with ΔC-statistic of 0.066 (P=0.002) and the NRI (46.0%, 95% CI: 20.5-56.8%, P＜0.001) and IDI (8.7%, 95% CI: 3.6-18.2%, P＜0.001). CONCLUSION: High-risk plaques in combination with rSS enhanced the predictive ability for MACE, indicating culprit-plaque features and residual atherosclerosis burden should be taken into account in risk stratification of STEMI patients.

Residual SYNTAX Score in Relation to Coronary Culprit Plaque Characteristics and Cardiovascular Risk in ST Segment Elevation Myocardial Infarction: an Intravascular Optical Coherence Tomography Study.

This study aimed to investigate the association of high-risk culprit plaque features by optical coherence tomography (OCT) with residual SYNTAX score (rSS) and the predictive value of rSS for major adverse cardiac events (MACE) in patients with ST segment elevation myocardial infarction (STEMI). We included 274 patients and divided them into 3 groups - rSS=0 (n=72), 08 (n=68). There were significant differences in plaque characteristics among three groups (plaque rupture: 44.4% versus 59.0% versus 64.7%, lowest to highest rSS, p=0.040; OCT-defined high-risk plaques: 16.7% versus 23.9% versus 35.3%, lowest to highest rSS, p=0.036; calcification: 38.9% versus 52.5% versus 61.8%, lowest to highest rSS, p=0.024). During a mean follow-up of 2.2 years, MACE occurred in 47 (17.2%) patients; rSS >8 group had higher MACE risk compared to rSS=0 (HR: 2.68, 95%CI: 1.11-6.5, P=0.029). In conclusion, culprit plaque morphology was significantly correlated with rSS, and elevated rSS was associated with higher cardiovascular risk in STEMI patients. ClinicalTrials.gov : NCT03593928.

Risk prediction score for the incidence of long-term cerebrovascular events among patients undergoing primary percutaneous coronary intervention: a retrospective real-world study.

INTRODUCTION: Although the rates of long­term outcome events are low, stroke is associated with high short- and long­term mortality and adversely affects the quality of life of patients with a history of primary percutaneous coronary intervention (PCI). OBJECTIVES: We sought to develop and validate a novel marker­based risk score to improve stroke prognostication in patients with myocardial infarction (MI) undergoing primary PCI. PATIENTS AND METHODS: A retrospective study was conducted to internally validate a new biomarker­based risk score for the incidence of stroke in 4103 patients with MI undergoing primary PCI who were randomized into derivation and validation cohorts. RESULTS: Significant predictors of cerebrovascular events included age, history of atrial fibrillation, history of hypertension, and the target lesion involving branches. The models had good calibration and discrimination in both derivation and internal validation. The areas under the receiver operating characteristic curve for predicting cerebrovascular events were 0.826 (sensitivity, 84.78%; specificity, 65.18%) and 0.846 (sensitivity, 71.43%; specificity, 90.29%) for the derivation and validation cohorts, respectively, at the 5­year follow­up. We calculated the total risk score for each participant, and divided them into low- and high­risk groups according to the median of the total risk score. A Kaplan-Meier survival analysis for the cohort showed significant differences in the total cohort (P <0.001) and derivation cohorts (P = 0.001). CONCLUSIONS: The prediction model was internally validated and calibrated in large cohorts of patients with MI receiving primary PCI therapy. This risk score allows re­evaluation of the risk of cerebrovascular events in patients after primary PCI.

Prognostic value of characteristics of plaque combined with residual syntax score among patients with STEMI undergoing primary PCI: an intravascular optical coherence tomography study.

AIM: The present study aimed to explore these characteristics, particularly thin-cap fibroatheroma (TCFA), in relation to residual syntax score (rSS) in patients who presented with acute MI. METHODS AND OUTCOMES: A total of 434 consecutive patients with MI aged ≥18 years who had STEMI underwent primary PCI. Notably, compared with other subgroups, the presence of TCFA in culprit lesions and a higher level of rSS, were significantly associated with MACE. When rSS was divided into three groups, high rSS levels were associated with a higher incidence of MACE, in the subgroups of without TCFA (P = 0.005), plaque erosion (P = 0.045), macrophage infiltration (P = 0.026), and calcification (P = 0.002). AUC of ROC curve was 0.794 and 0.816, whereas the AUC of the survival ROC was 0.798 and 0.846. CONCLUSION: The results of this study could be used in clinical practice to support risk stratification. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov as NCT03593928 .

Proprotein Convertase Subtilisin/Kexin Type 9 and Systemic Inflammatory Biomarker Pentraxin 3 for Risk Stratification Among STEMI Patients Undergoing Primary PCI.

BACKGROUND AND AIM: The aim of prospective study was to determine the prognostic value of combined measures of plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) and pentraxin 3 (PTX3) according to the culprit-plaque morphology (plaque rupture versus plaque erosion) in relation to the in patients with acute ST-elevated myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention. METHODS: A total of 434 patients with STEMI aged ≥18 years who underwent pre-intervention OCT imaging of culprit lesions between March 2017 and March 2019 were enrolled. Finally, 235 patients who meet the inclusion criteria were enrolled and the cohort was divided into 3 groups according to PCSK9 and PTX3 levels: group A: PCSK9 < median and Pentraxin 3 (N = 72/30.6%); group B: PCSK9 ≥ median or Pentraxin 3≥ median (N = 91/38.7%); group C: PCSK9 ≥ median and Pentraxin 3≥ median (N = 72/30.6%). MACEs were defined as a composite of all-cause death, myocardial infarction (MI) recurrence, and ischemic stroke, revascularization and heart failure. OUTCOMES: During a median follow-up of 2.01 years, 50 patients has occurred MACE. Two-year MACE was higher in group C (23/31.9%) than in group B (16/17.6%) and group A (11/15.3%) (p = 0.028). There was a correlation between PCSK9 and PTX3 (r = 0.302, p < 0.003). In multivariable analysis adjusted for age, gender, risk factors, and serum indexes, being in group C remained independently associated with an increased risk of MACE (hazard ratio [HR]: 2.90; p = 0.010), and group B tended to have higher MACE (HR: 1.76; p = 0.172) compared with group A. Among patients with plaque erosion by OCT, group C was independently associated with an increased risk of MACE (HR: 9.04; p = 0.048) after fully adjustment. However, the significant association was absence among patients with plaque rupture. CONCLUSION AND RELEVANCE: This study demonstrated the usefulness of combined measures of PCSK9 and PTX3 to enhance risk stratification in patients with STEMI especially among patients with plaque erosion. Patients with elevation of both PCSK9 and PTX3 had a markedly increased risk of MACE.

Plasma Pentraxin-3 Combined with Plaque Characteristics Predict Cardiovascular Risk in ST-Segment Elevated Myocardial Infarction: An Optical Coherence Tomography Study.

BACKGROUND: Culprit­plaque morphology [plaque rupture (PR) and plaque erosion (PE) identified by optical coherence tomography (OCT)] and biomarker of vascular inflammation, pentraxin-3 (PTX3), have been reported to influence clinical outcomes in coronary diseases. We aimed to investigate the prognostic implication of culprit-plaque morphology and plasma PTX3 for major adverse cardiovascular events (MACE) in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: A total of 236 patients were enrolled and divided into four groups: PE/low-PTX3 (n = 57), PE/high-PTX3 (n = 47), PR/low-PTX3 (n = 78) and PR/high-PTX3 (n = 54). MACE was defined as the composite of all-cause death, recurrence of myocardial infarction, stroke and unplanned revascularization of any coronary artery. RESULTS: During the follow-up of 1.9 years, a total of 40 (16.9%) MACE were observed: 5.3% (3 patients) among patients with PE/low-PTX3, 21.3% (10 patients) among patients with PE/high-PTX3, 17.9% (14 patients) among patients with PR/low-PTX3 and 24.1% (13 patients) among patients with PR/high-PTX3 (Log rank P = 0.013). In fully adjusted analyses, patients with high-PTX3 were associated with higher MACE risk (HR: 2.40, 95% CI: 1.26-4.57, P = 0.008). Patients with PR/high-PTX3 (HR: 5.63, 95% CI: 1.57-20.16, P = 0.008) and PE/high-PTX3 (HR: 5.44, 95% CI: 1.46-20.29, P = 0.012) presented higher MACE risk than those with PE/low-PTX3. Adding plasma PTX3 levels and PR to the risk prediction model increased the area under curves to 76.1% (95% CI: 67.6-84.5%) and the NRI (28.1%, 95% CI: 0.3-48.3%, P=0.040) and IDI (2.4%, 95% CI: 0.1-12.9%, P = 0.040). CONCLUSION: Patients with PR/high-PTX3 and PE/high-PTX3 presented a poorer prognosis than those with PE/low-PTX3. Combining the culprit-plaque morphology with PTX3 enhanced the predictive ability for MACE and contributed to better identification of high-risk patients. TRIAL REGISTRATION NUMBER: This study is registered at clinical trials.gov as NCT03593928.

Impact of residual thrombus burden on ventricular deformation after acute myocardial infarction: A sub-analysis from an intravascular optical coherence tomography study.

BACKGROUND: Coronary residual thrombus before stenting in ST-segment elevation myocardial infarction (STEMI) has been linked to microvascular injury but its impact on ventricular deformation and cardiac dysfunction in longer term remains unclear. METHODS: This was a post-hoc sub-analysis from an optical coherence tomography registry. Residual thrombus before stenting was measured geometrically and maximal thrombus-to-lumen area ratio (MTR) was reported. Cardiovascular magnetic resonance (CMR) follow-ups were performed at 30 days post STEMI. The primary outcomes were CMR-derived parameters including left ventricular ejection fraction (LVEF), infarct size, microvascular obstruction (MVO), and left ventricular global strains in radial (GRS), circumferential (GCS), longitudinal (GLS) directions. FINDINGS: From March 2017 to March 2019, forty-two patients with first-ever anterior STEMI were included. Average CMR follow-up time was 33 (IQR 30-37) days. In multivariable analysis, MTR was significantly associated with LVEF (per 10%, adjusted ß = -1·96, 95%CI -3·66 to -0·26), MVO (per 10%, adjusted ß = 0·07, 95%CI 0·01 to 0·13), GRS (per 10%, adjusted ß = -1·26, 95%CI -2·28 to -0·23), and GCS (per 10%, adjusted ß = 0·53, 95%CI 0·01 to 1·06). However, it was not related to GLS (per 10%, adjusted ß = 0·29, 95%CI -0·85 to 1·43) or infarct size (per 10%, adjusted ß = 0·07, 95%CI -0·40 to 0·55). INTERPRETATION: Larger residual thrombus burden was associated with worse GRS and GCS but not GLS after a first anterior myocardial infarction. FUNDING: This work was supported by Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2016-I2M-1-009), National Natural Science Foundation of China (81,970,308, 81,930,044, and 81,620,108,015), Sanming Project of Medicine in Shenzhen (SZSM201911017), and Shenzhen Key Medical Discipline Construction Fund (No. SZXK001).

Primary Percutaneous Coronary Intervention in Patients With Type 2 Diabetes With Late/Very Late Stent Thrombosis and de novo Lesions: A Single-Center Observational Cohort Study of Clinical Outcomes and Influencing Factors.

Background: This study compared differences in the risk factors and clinical outcomes of primary percutaneous coronary intervention (PCI) in type 2 diabetes mellitus (DM) and non-DM patients with de novo lesions (DNLs) and late or very late stent thrombosis (LST/VLST). Methods: We used angiography to screen 4,151 patients with acute coronary syndrome for DNL and LST/VLST lesions. Overall, 3,941 patients were included in the analysis and were allocated to the DM (n = 1,286) or non-DM (n = 2,665) group at admission. The primary endpoint was a composite of major adverse cardiovascular events (MACEs), defined as death, myocardial infarction, revascularization, and ischemic stroke, within a median follow-up period of 698 days. Results: In the group with a total white blood cell count >10 × 109/L (P = 0.004), a neutral granular cell count >7 × 109/L (P = 0.030), and neutrophil-lymphocyte ratio >1.5 (P = 0.041), revascularization was better for DNL than for LST/VLST lesions. Among DM patients with DNLs, each unit increase in age was associated with a 53.6% increase in the risk of MACEs [hazard ratio (HR): 1.536, 95% confidence interval (CI), 1.300-1.815, P < 0.0001]. Older age (≥65 years) was associated with a significantly greater risk of MACEs (P < 0.0001). Furthermore, each standard deviation (SD) increase in the level of peak white blood cell counts was associated with a 50.1% increase in the risk of MACEs (HR, 1.501; 95% CI, 1.208-1.864; P = 0.0002). When stratifying the DM population with DNLs according to the D-dimer baseline and peak levels <0.5 vs. ≥0.5 mg/L, the high D-dimer group at baseline had a 2.066-fold higher risk of MACEs (P < 0.0001), and the high peak level D-dimer group had a 1.877-fold higher risk of MACEs (P = 0.001) compared to the low-level groups. Among DM patients with LST/VLST, each unit increase in age was associated with a 75.9% increase in the risk of MACEs (HR: 1.759, 95% CI, 1.052-2.940, P = 0.032). Furthermore, for each SD increase in the peak D-dimer level, the risk of MACEs increased by 59.7% (HR, 1.597; 95% CI, 1.110-2.295; P = 0.041). Conclusion: Following successful primary PCI, the measurement of baseline and peak D-dimer values may help identify individuals at high cardiovascular risk. This suggests a potential benefit of lowering D-dimer levels among T2DM patients with DNL. Furthermore, age and the peak D-dimer values may facilitate the risk stratification of T2DM patients with LST/VLST.

Triglyceride glucose index combined with plaque characteristics as a novel biomarker for cardiovascular outcomes after percutaneous coronary intervention in ST-elevated myocardial infarction patients: an intravascular optical coherence tomography study.

BACKGROUND AND AIM: This prospective study explored plaque morphology according to the underlying culprit lesion pathology (rupture versus erosion) in relation to the triglyceride glucose (TyG) index in patients with acute ST-elevated myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention and optical coherence tomography (OCT) for culprit lesions to elucidate the effects of the TyG index and type of plaque on the incidence of major adverse cardiovascular events (MACEs). METHODS AND OUTCOMES: A total of 274 patients with STEMI aged ≥ 18 years who underwent pre-intervention OCT imaging of culprit lesions between March 2017 and March 2019 were enrolled. The TyG index was calculated using the formula ln[fasting TG (mg/dL) × fasting glucose (mg/dL)/2]. Patients with plaque rupture (PR) and plaque erosion (PE) were divided into three groups across the TyG tertiles. MACEs were defined as a composite of all-cause death, myocardial infarction (MI) recurrence, and ischaemic stroke. In fully adjusted analyses, the middle tertile of TyG was significantly associated with greater rates of MACEs in patients with PR but not in those with PE (relative to the low tertile, HR [hazard ratio], 6.01; 95% confidence interval [CI], 1.25-28.88; P = 0.025). Cox regression models indicated a significantly higher HR for MACEs in patients in the middle tertile of TyG than in those in the low tertile of TyG after full additional adjustment (HR, 5.45; 95% CI, 1.10-27.09; P = 0.038). However, being in the high tertile of TyG independently and significantly increased the risk of major bleeding events among patients with PE (HR, 2.50; 95% CI, 1.11-5.65; P = 0.028). The area under the receiver operating characteristic curve for predicting MACEs to evaluate the diagnostic value of the TyG index combined with the morphological characteristics of plaque after full adjustment was 0.881 (sensitivity = 94.74%, specificity = 78.04%, cut-off level = 0.73). Kaplan-Meier curves were generated for the cumulative incidence of MACEs for up to a median of 1.98 years stratified by tertiles of TyG among the PR and PE subgroups. Among patients with PR, there were significant differences among the tertiles of TyG (p = 0.030). CONCLUSION AND RELEVANCE: Microstructural OCT features of culprit lesions in combination with the TyG index, a surrogate estimate of insulin resistance, can be used in clinical practice to support risk stratification and predict adverse events in patients with STEMI.

Prognostic Value of D-dimer in patients with acute coronary syndrome treated by percutaneous coronary intervention: a retrospective cohort study.

BACKGROUND: Associations between D-dimer and outcomes of patients with acute coronary syndromes (ACS) remain controversial. This study aimed to investigate the prognostic value of D-dimer in ACS patients treated by percutaneous coronary intervention (PCI). METHODS: In this observational study, 3972 consecutive patients with ACS treated by PCI were retrospectively recruited. The X-tile program was used to determine the optimal D-dimer thresholds for risk stratifications. Cox regression with multiple adjustments was used for outcome analysis. Restricted cubic spline (RCS) analysis was performed to assess the dose-response association between D-dimer and outcomes. The C-index was calculated to evaluate the additional prognostic value of D-dimer when added to clinical risk factors and commonly used clinical risk scores, with internal validations using bootstrapping methods. The primary outcome was all-cause death. RESULTS: During a median follow-up of 720 days, 225 deaths occurred. Based on the thresholds generated by X-tile, ACS-PCI patients with median (420-1150 ng/mL, hazard ratio [HR]: 1.58, 95 % confidence interval [CI]: 1.14-2.20, P = 0.007) and high (≥ 1150 ng/mL, HR: 1.98, 95 % CI: 1.36-2.89, P < 0.001) levels of D-dimer showed substantially higher risk of death compared to those with low D-dimer (< 420 ng/mL). RCS analysis depicted a constant relation between D-dimer and various outcomes. The addition of D-dimer levels significantly improved risk predictions for all-cause death when combined with the fully adjusted models (C-index: 0.853 vs. 0.845, P difference = 0.021), the GRACE score (C-index: 0.826 vs. 0.814, P difference = 0.027), and the TIMI score (C-index: 0.804 vs. 0.776, P difference < 0.001). The predicted mortality at the median follow-up (two years) was 1.7 %, 5.2 %, and 10.9 % for patients with low, median, and high D-dimer, respectively, which was well matched with the observed mortality (low D-dimer group: 1.2 %, median D-dimer group: 5.2 %, and high D-dimer group: 12.6 %). CONCLUSIONS: For ACS patients treated by PCI, D-dimer level was an independent predictor for adverse outcomes, and provided additional prognostic value when combined with clinical risk factors and risk scores. Risk stratifications based on D-dimer was plausible to differentiate ACS-PCI patients with higher risk of death.

Impact of Postprocedural High-Sensitivity C-Reactive Protein on Lipoprotein(a)-Associated Cardiovascular Risk with ST-Segment Elevation Myocardial Infarction With Percutaneous Coronary Intervention.

This study aimed to investigate the impact of high-sensitivity C-reactive protein (hsCRP) on Lipoprotein(a) [Lp(a)] associated cardiovascular risk in patients with ST-segment elevation myocardial infarction (STEMI) underwent percutaneous coronary intervention (PCI). A total of 2318 STEMI-PCI patients were retrospectively recruited, and further stratified based on postprocedural hsCRP levels (≥ 2 vs < 2 mg/L). Major adverse cardiac events (MACE) were defined as all-cause death, myocardial infarction and stroke. During a mean follow-up of 2.5 years, MACE occurred in 159 (6.9%) patients. In the setting of hsCRP ≥ 2mg/L, per unit increase of Lp(a) was associated with a 28% increase of MACE risk (HR: 1.28, 95% CI: 1.09 to 1.49, p = 0.002; p = 0.031 for interaction); increasing tertiles of Lp(a) were significantly related to greater rates of MACE (p = 0.011 for interaction; p = 0.005 for trend across tertiles). Patients with upper tertile of Lp(a) had a significant lower event-free survival (p = 0.034) when hsCRP ≥ 2mg/L. No similar association between Lp(a) and MACE was noted when hsCRP < 2mg/L. In conclusion, high Lp(a) levels were associated with poor prognosis when hsCRP ≥ 2mg/L, implying systemic inflammation can modulate Lp(a)-associated MACE risk in STEMI-PCI patients. Measurement of Lp(a) in patients with high inflammation risk may identify individuals at high cardiovascular risk.

Mean Platelet Volume/Platelet Count Ratio and Culprit Plaque Morphologies: An Optical Coherence Tomography Study in Patients with ST Segment Elevation Myocardial Infarction.

This study aimed to investigate the predictive value of mean platelet volume/platelet count ratio (MPR) for coronary plaque features in patients with ST segment elevation myocardial infarction (STEMI). A total of 275 STEMI patients undergoing preintervention optical coherence tomography examination were included, with 142 categorized as plaque rupture (PR) and 133 as plaque erosion (PE). Multivariable logistic regression showed higher MPR was an independent predictor of PR (tertile 3 vs tertile 1, odds ratio: 6.257, 95% confidence interval: 1.586-24.686, P = 0.009). MPR showed better diagnostic performance than other platelet indices. The optimal MPR threshold for diagnosing PR was 0.0473 (sensitivity: 0.721, specificity: 0.647). When added to models of established risk factors, MPR significantly improved the predictive accuracy of PR (area under the curve: 0.767 vs 0.722, P difference = 0.004). In conclusion, for STEMI patients, MPR was an independent predictor of PR and improved diagnostic performance for PR.

The Association Between Plasma Hyaluronan Level and Plaque Types in ST-Segment-Elevation Myocardial Infarction Patients.

Background: The metabolism of hyaluronan (HA) is widely known to be involved in the process of acute coronary syndrome, but it is unknown how circulating HA levels change in ST-Segment-Elevation Myocardial Infarction (STEMI) patients and whether HA is associated with plaque morphology, including rupture and erosion. Objectives: This study focused on the changes in the plasma levels of high molecular weight (HMW) HA (>35 kDa) and CD44 in STEMI patients and their relationship with plaque morphology evaluated by optical coherence tomography (OCT). Methods: We prospectively enrolled 3 cohorts in this study, including 162 patients with STEMI, 34 patients with stable coronary artery disease (S-CAD) and 50 healthy controls. Plaque morphology was detected by OCT analysis, and the plasma levels of HMW HA and CD44 were examined by enzyme-linked immunosorbent assay (ELISA). We compared plasma level of HMW HA and CD44 among STEMI patients, S-CAD patients and healthy controls, as well as in plaque rupture and plaque erosion. Results: The plasma levels of HMW HA and CD44 were significantly lower in STEMI patients than in healthy controls (p = 0.009 and p < 0.001, respectively). In addition, plasma level of HMW HA in plaque erosion was significantly lower than that in plaque rupture (p = 0.021), whereas no differences were found in plasma level of soluble CD44 between plaque rupture and erosion. Conclusions: Low levels of circulating HMW HA and CD44 were independently correlated with STEMI, and low levels of HMW HA were associated with plaque erosion compared with rupture. Moreover, plasma HMW HA might be a useful biomarker for identifying plaque erosion to improve the risk stratification and management of STEMI patients.

Association of plasma trimethylamine N-Oxide level with healed culprit plaques examined by optical coherence tomography in patients with ST-Segment elevation myocardial infarction.

BACKGROUND AND AIMS: Healed plaque is a hallmark of previous regional plaque rupture or erosion. We hypothesized that the plasma level of trimethylamine N-oxide (TMAO) is related to healed culprit plaque in ST-segment elevation myocardial infarction (STEMI) patients. METHODS AND RESULTS: A prospective cohort of 206 patients with STEMI, who were examined by optical coherence tomography (OCT) was enrolled in our study. After exclusion, 156 patients were categorized into healed plaque (n = 54) and nonhealed plaque (n = 102) groups. Plasma TMAO levels were detected by stable isotope dilution liquid chromatography tandem mass spectrometry in these two groups. Increased age and low BMI were more common in patients with healed plaques than in those without healed plaques. Through OCT observation, plaque rupture (81.5% vs. 45.1%, p < 0.001), thin cap fibroatheroma (TCFA) and macrophages (42.6% vs. 20.6%, p = 0.004, 70.4% vs. 26.5%, p < 0.001, respectively) were more frequently seen in patients with healed plaques than in those without healed plaques. The TMAO level in patients with healed plaques was significantly higher than that in patients with nonhealed plaques (3.9 µM [2.6-5.1] vs. 1.8 µM [1.0-2.7], p < 0.001). Furthermore, the receiver operating characteristic curve showed that TMAO can be used as a potential biomarker to predict healed plaque presence with a cutoff value of 2.9 µM (AUC = 0.810, sensitivity: 72.2%, specificity: 81.4%). CONCLUSIONS: Healed plaque in STEMI patients is associated with a high level of plaque vulnerability and inflammation. A high level of plasma TMAO can be a useful biomarker to differentiate STEMI patients with healed culprit plaques.