Sirolimus-eluting iron bioresorbable scaffold versus cobalt-chromium everolimus-eluting stents in patients with coronary artery disease: Rationale and design of the IRONMAN-II trial.

BACKGROUND: The previous first-in-human study established the preliminary safety and effectiveness of the novel thin-strut iron bioresorbable scaffold (IBS). The current study aims to directly compare the imaging and physiological efficacy, and clinical outcomes of IBS with contemporary metallic drug-eluting stents (DES). METHODS: A total of 518 patients were randomly allocated to treatment with IBS (257 patients) or metallic DES (261 patients) from 36 centers in China. The study is powered to test noninferiority of the IBS compared with the metallic everolimus-eluting stent in terms of the primary endpoint of in-segment late lumen loss at 2 years, and major secondary endpoints including 2-year quantitative flow ratio and cross-sectional mean flow area measured by optical coherence tomography (OCT) (limited to the OCT subgroup, 25 patients in each group). CONCLUSION: This will be the first powered randomized trial investigating the safety and efficacy of the novel thin-strut IBS compared to a contemporary metallic DES. The findings will provide valuable evidence for future research of this kind and the application of metallic bioresorbable scaffolds.

Integrin ß5 subunit regulates hyperglycemia-induced vascular endothelial cell apoptosis through FoxO1-mediated macroautophagy.

BACKGROUND: Hyperglycemia frequently induces apoptosis in endothelial cells and ultimately contributes to microvascular dysfunction in patients with diabetes mellitus (DM). Previous research reported that the expression of integrins as well as their ligands was elevated in the diseased vessels of DM patients. However, the association between integrins and hyperglycemia-induced cell death is still unclear. This research was designed to investigate the role played by integrin subunit ß5 (ITGB5) in hyperglycemia-induced endothelial cell apoptosis. METHODS: We used leptin receptor knockout (Lepr-KO) ( db / db ) mice as spontaneous diabetes animal model. Selective deletion of ITGB5 in endothelial cell was achieved by injecting vascular targeted adeno-associated virus via tail vein. Besides, we also applied small interfering RNA in vitro to study the mechanism of ITGB5 in regulating high glucose-induced cell apoptosis. RESULTS: ITGB5 and its ligand, fibronectin, were both upregulated after exposure to high glucose in vivo and in vitro . ITGB5 knockdown alleviated hyperglycemia-induced vascular endothelial cell apoptosis and microvascular rarefaction in vivo.In vitro analysis revealed that knockdown of either ITGB5 or fibronectin ameliorated high glucose-induced apoptosis in human umbilical vascular endothelial cells (HUVECs). In addition, knockdown of ITGB5 inhibited fibronectin-induced HUVEC apoptosis, which indicated that the fibronectin-ITGB5 interaction participated in high glucose-induced endothelial cell apoptosis. By using RNA-sequencing technology and bioinformatic analysis, we identified Forkhead Box Protein O1 (FoxO1) as an important downstream target regulated by ITGB5. Moreover, we demonstrated that the excessive macroautophagy induced by high glucose can contribute to HUVEC apoptosis, which was regulated by the ITGB5-FoxO1 axis. CONCLUSION: The study revealed that high glucose-induced endothelial cell apoptosis was positively regulated by ITGB5, which suggested that ITGB5 could potentially be used to predict and treat DM-related vascular complications.

Additive Strategy Enhancing In Situ Polymerization Uniformity for High-Voltage Sodium Metal Batteries.

In situ polymerization to prepare quasi-solid electrolyte has attracted wide attentions for its advantage in achieving intimate electrode-electrolyte contact and the high process compatibility with current liquid batteries; however, gases can be generated during polymerization process and remained in the final electrolyte, severely impairing the electrolyte uniformity and electrochemical performance. In this work, an in situ polymerized poly(vinylene carbonate)-based quasi-solid electrolyte for high-voltage sodium metal batteries (SMBs) is demonstrated, which contains a novel multifunctional additive N-methyl-N-(trimethylsilyl)trifluoroacetamide (MSTFA). MSTFA as high-efficient plasticizer diminishes residual gases in electrolyte after polymerization; the softer and homogeneous electrolyte enables much faster ionic conduction. The HF/H2 O scavenge effect of MSTFA mitigates the corrosion of free acid to cathode and interfacial passivating layers, enhancing the cycle stability under high voltage. As a result, the 4.4 V Na||Na3 V2 (PO4 )2 F3 cell employing the optimized electrolyte possesses an initial discharge capacity of 112.0 mAh g-1 and a capacity retention of 91.3% after 100 cycles at 0.5C, obviously better than those of its counterparts without MSTFA addition. This work gives a pioneering study on the gas residue phenomenon in in situ polymerized electrolytes, and introduces a novel multifunctional silane additive that effectively enhances electrochemical performance in high-voltage SMBs, showing practical application significance.

Chinese expert consensus on the diagnosis and treatment of coronary microvascular diseases (2023 Edition).

Since the four working groups of the Chinese Society of Cardiology issued first expert consensus on coronary microvascular diseases (CMVD) in 2017, international consensus documents on CMVD have increased rapidly. Although some of these documents made preliminary recommendations for the diagnosis and treatment of CMVD, they did not provide classification of recommendations and levels of evidence. In order to summarize recent progress in the field of CMVD, standardize the methods and procedures of diagnosis and treatment, and identify the scientific questions for future research, the four working groups of the Chinese Society of Cardiology updated the 2017 version of the Chinese expert consensus on CMVD and adopted a series of measures to ensure the quality of this document. The current consensus has raised a new classification of CMVD, summarized new epidemiological findings for different types of CMVD, analyzed key pathological and molecular mechanisms, evaluated classical and novel diagnostic technologies, recommended diagnostic pathways and criteria, and therapeutic strategies and medications, for patients with CMVD. In view of the current progress and knowledge gaps of CMVD, future directions were proposed. It is hoped that this expert consensus will further expedite the research progress of CMVD in both basic and clinical scenarios.

Prognostic implications of stress hyperglycemia ratio in patients with myocardial infarction with nonobstructive coronary arteries.

BACKGROUND: The role of stress hyperglycemia in acute myocardial infarction (AMI) has long been emphasized. Recently, the stress hyperglycemia ratio (SHR), a novel index reflecting an acute glycemia rise, has shown a good predictive value in AMI. However, its prognostic power in myocardial infarction with nonobstructive coronary arteries (MINOCA) remains unclear. METHODS: In a prospective cohort of 1179 patients with MINOCA, relationships between SHR levels and outcomes were analyzed. SHR was defined as acute-to-chronic glycemic ratio using admission blood glucose (ABG) and glycated hemoglobin. The primary endpoint was defined as major adverse cardiovascular events (MACE), including all-cause death, nonfatal MI, stroke, revascularization, and hospitalization for unstable angina or heart failure. Survival analyses and receiver-operating characteristic (ROC) curve analyses were performed. RESULTS: Over the median follow-up of 3.5 years, the incidence of MACE markedly increased with higher SHR tertile levels (8.1%, 14.0%, 20.5%; p < 0.001). At multivariable Cox analysis, elevated SHR was independently associated with an increased risk of MACE (HR 2.30, 95% CI: 1.21-4.38, p = 0.011). Patients with rising tertiles of SHR also had a significantly higher risk of MACE (tertile 1 as reference; tertile 2: HR 1.77, 95% CI: 1.14-2.73, p = 0.010; tertile 3: HR 2.64, 95% CI: 1.75-3.98, p < 0.001). SHR remained a robust predictor of MACE in patients with and without diabetes; whereas ABG was no longer associated with the MACE risk in diabetic patients. SHR showed an area under the curve of 0.63 for MACE prediction. By incorporating SHR to TIMI risk score, the combined model further improved the discrimination for MACE. CONCLUSIONS: The SHR independently confers the cardiovascular risk after MINOCA, and may serve as a better predictor than glycemia at admission alone, particularly in those with diabetes.KEY MESSAGESStress hyperglycemia ratio (SHR) is independently associated with the prognosis in a distinct population with myocardial infarction with nonobstructive coronary arteries (MINOCA).SHR is a better predictor of prognosis than admission glycemia alone, especially in diabetic patients with MINOCA.SHR may serve as a prognostic marker for risk stratification as well as a potential target for tailored glucose-lowering treatment in MINOCA.

A First-in-Human Study of the Bioheart Sirolimus-Eluting Bioresorbable Vascular Scaffold in Patients with Coronary Artery Disease: Two-Year Clinical and Imaging Outcomes.

INTRODUCTION: Newer generation bioresorbable scaffolds (BRSs) with thinner struts and improved deliverability are expected to enhance safety and efficacy profiles. Bioheart (Bio-Heart, Shanghai, China) BRS is constructed from a PLLA (poly-l-lactic acid) backbone coated with a PDLLA (poly D-l-lactic acid) layer eluting sirolimus. We report 2-year serial intracoronary imaging findings. METHODS: In this first-in-human study, 46 patients with single de novo lesions in native coronary vessels (vessel size 3.0-3.75 mm, lesion length ≤ 25 mm) were enrolled at a single institution. Baseline intravascular ultrasound (IVUS) and post-implantation IVUS and optical coherence tomography (OCT) examinations were mandatory. After successful implantations of BRS, the 46 patients were randomized to two different follow-up cohorts in a 2:1 ratio. Thirty patients in cohort 1 had to undergo angiography, IVUS, and OCT follow-ups at 6 and 24 months, respectively. The 16 patients in cohort 2 underwent the same types of imaging follow-ups at 12 and 36 months, respectively. Clinical follow-ups were scheduled uniformly in both cohorts at 1, 6, and 12 months and annually up to 5 years for all patients. RESULTS: Between August and November 2016, a total of 54 patients were assessed. However, 8 patients could not meet all the inclusion criteria; thus, the remaining 46 patients (age 57.5 ± 8.7 years, 34.8% female, 50.0% with unstable angina, 26.1% diabetics) with 46 target lesions were enrolled in this study. All patients in both cohorts were required to complete clinical follow-up uniformly and regularly. In cohort 1, one patient had definite scaffold thrombosis within 6 months of follow-up; thus, after 6 months, cohort 1 had 96.7% patients . Imaging follow-up was available in 24 patients, and in-scaffold late loss was 0.44 ± 0.47 mm; intracoronary imaging confirmed the late loss was mainly due to to neointimal hyperplasia, but not scaffold recoil. CONCLUSIONS: Serial 2-year clinical and imaging follow-up results confirmed the preliminary safety and efficacy of Bioheart BRS for treatment of simple coronary lesions.

Remnant Cholesterol Predicts Risk of Cardiovascular Events in Patients With Myocardial Infarction With Nonobstructive Coronary Arteries.

Background Remnant cholesterol (RC) has been reported to promote atherosclerotic cardiovascular disease. Yet little is known regarding the RC-related residual risk in patients with myocardial infarction (MI) with nonobstructive coronary arteries. Methods and Results A total of 1179 patients with MI with nonobstructive coronary arteries were enrolled and divided according to median level of RC calculated as non-high-density lipoprotein cholesterol minus low-density lipoprotein cholesterol. The primary end point was a composite of major adverse cardiovascular events (MACEs), including all-cause death, nonfatal MI, stroke, revascularization, and hospitalization for unstable angina or heart failure. Kaplan-Meier, Cox regression, and receiver-operating characteristic analyses were used. Patients with higher median level of RC had a significantly higher incidence of MACEs (16.9% versus 11.5%; P=0.009) over the median follow-up of 41.7 months. High RC levels were significantly associated with an increased risk of MACEs after adjustment for multiple clinically relevant variables (per 1 SD increase, hazard ratio, 0.61; 95% CI, 1.12-2.31; P=0.009). Elevated RC also contributed to residual risk beyond conventional lipid parameters. Moreover, RC had an area under the curve of 0.61 for MACE prediction. When adding RC to the Thrombolysis in Myocardial Infarction risk score, the combined model yielded a significant improvement in discrimination for MACEs. Conclusions Elevated RC was closely associated with poor outcomes after MI with nonobstructive coronary arteries independent of traditional risk factors, indicating the utility of RC for risk stratification and a rationale for targeted RC-lowering trials in patients with MI with nonobstructive coronary arteries.

Hyperuricemia as a prognostic marker for long-term outcomes in patients with myocardial infarction with nonobstructive coronary arteries.

BACKGROUND: Hyperuricemia (HUA) has been proved as a predictor of worse outcomes in patients with coronary artery disease. Here, we investigated the prognostic value of HUA in a distinct population with myocardial infarction with nonobstructive coronary arteries (MINOCA). METHODS: A total of 1179 MINOCA patients were enrolled and divided into HUA and non-HUA groups. HUA was defined as a serum uric acid level ≥ 420 µmol/L in men or ≥ 357 µmol/L in women. The primary study endpoint was a composite of major adverse cardiovascular events (MACE), including all-cause death, nonfatal MI, nonfatal stroke, revascularization, and hospitalization for unstable angina or heart failure. Kaplan-Meier, Cox regression, and receiver-operating characteristic analyses were performed. RESULTS: Patients with HUA (prevalence of 23.5%) had a significantly higher incidence of MACE (18.7% vs. 12.8%; p = 0.015) than patients without during the median follow-up of 41.7 months. HUA was closely associated with an increased risk of MACE even after multivariable adjustment (hazard ratio 1.498, 95% confidence interval: 1.080 to 2.077; p = 0.016). HUA remained a robust risk factor of MACE after propensity score matching analysis. Moreover, HUA showed an area under the curve (AUC) of 0.59 for predicting MACE. Incorporation of HUA to the thrombolysis in myocardial infarction (TIMI) score yielded a significant improvement in discrimination for MACE. CONCLUSIONS: HUA was independently associated with poor prognosis after MINOCA. Routine assessment of HUA may facilitate risk stratification in this specific population.

Omentin-1 Modulates Macrophage Function via Integrin Receptors αvß3 and αvß5 and Reverses Plaque Vulnerability in Animal Models of Atherosclerosis.

Backgrounds: Omentin-1 is a novel cytokine that is primarily released by the epicardial adipose tissue. Molecular structure analysis revealed that it contained a fibrinogen-like domain. Clinical studies have demonstrated that the expression of omentin-1 is tightly associated with the development of cardiovascular diseases, but the receptor by which omentin-1 modulates macrophage function has not been identified yet. Objective: This study sought to investigate the effect of omentin-1 on already-established atherosclerosis (AS) lesions in both ApoE-/- and Ldlr-/- mice and further, study its underlying mechanisms. Methods and Results: We investigated the effect of omentin-1 on the plaque phenotype by implanting a minipump in ApoE-/- and Ldlr-/- mice. In vivo studies showed that the infusion of omentin-1 increased the collagen content and mitigated the formation of the necrotic core in both animal models. Immunohistochemistry and immunofluorescence analysis revealed that omentin-1 suppressed inflammatory cytokines expression, macrophage infiltration, and apoptosis within the plaque. An immunoprecipitation experiment and confocal microscopy analysis confirmed the binding of omentin-1 to the integrin receptors αvß3 and αvß5. The cell studies demonstrated that omentin-1 suppressed the apoptosis and inflammatory cytokines expression induced by the oxidized low-density lipoprotein in the macrophage. In addition, omentin-1 promoted the phosphorylation of the integrin-relevant signaling pathway as well as the Akt and AMPK in the macrophage. The addition of the inhibitor of the integrin receptor or interfering with the expression of the integrin subunit αv (ITGAV) both significantly abrogated the bioeffects induced by omentin-1. A flow cytometry analysis indicated that the antibodies against αvß3 and αvß5 had a competitive effect on the omentin-1 binding to the cell membrane. Conclusions: The administration of adipokine omentin-1 can inhibit the necrotic cores formation and pro-inflammatory cytokines expression within the AS lesion. The mechanisms may include the suppression of apoptosis and pro-inflammatory cytokines expression in the macrophage by binding to the integrin receptors αvß3 and αvß5.

The Clinical Impact of Proton Pump Inhibitors When Co-Administered With Dual Antiplatelet Therapy in Patients Having Acute Myocardial Infarction With Low Risk of Gastrointestinal Bleeding: Insights From the China Acute Myocardial Infarction Registry.

Background: The latest guidelines recommend the use of proton pump inhibitors (PPIs) to minimize gastrointestinal bleeding (GIB) in patients receiving dual antiplatelet therapy (DAPT), even though this co-administration may increase the risk of ischemia due to drug interactions. We have noticed that there are few studies conducted on patients with a lower risk of GIB. Therefore, we investigated the clinical effect of co-administration of PPI on DAPT patients with low GIB risk. Methods and Results: From January 2013 to September 2014, a total of 17,274 consecutive patients on DAPT from 108 hospitals with low risk for GIB in the China Acute Myocardial Infarction (CAMI) registry were analyzed. The primary endpoints were GIB and major adverse cardiovascular and cerebrovascular events (MACCE). Multivariate logistic regression analysis and Cox proportional hazard models were used to assess the effect of PPIs use. Of the analyzed patients, 66.6% (n = 11,487) were treated with PPIs. PPI use did not show an extra gastrointestinal protective effect in patients with low risk for GIB who were hospitalized and on follow-up after 2 years. Moreover, it was associated with an increased risk of stroke during the 2-year follow-up [hazard ratio (HR) 2.072, 95% confidence interval (CI) 1.388-3.091, p = 0.0003] and an increased risk of MI after 6 months (HR 1.580, 95% CI 1.102-2.265, p = 0.0119). We found the same results after propensity score matching. Conclusion: PPI use is prevalent in DAPT patients with low GIB risk. PPIs did not show an extra gastrointestinal protective effect, while an increased risk of stroke was observed during the 2-year follow-up. Clinical Trial Registration:www.clinicaltrials.gov, identifier NCT01874691.

Impact of triglyceride-glucose index on long-term cardiovascular outcomes in patients with myocardial infarction with nonobstructive coronary arteries.

BACKGROUND AND AIMS: Triglyceride-glucose (TyG) index has been reported as a novel surrogate marker of insulin resistance and a risk factor in patients with coronary artery disease. We aimed to investigate the prognostic value of TyG index in a distinct entity with myocardial infarction with nonobstructive coronary arteries (MINOCA). METHODS AND RESULTS: A total of 1179 MINOCA patients were recruited and divided according to tertile levels of TyG index. The primary endpoint was a composite of major adverse cardiovascular events (MACE), including all-cause death, reinfarction, stroke, revascularization and hospitalization for unstable angina or heart failure. Kaplan-Meier, Cox regression and receiver-operating characteristic analyses were performed. Patients with higher tertiles of TyG index had a significantly higher incidence of MACE (9.6%, 14.9%, 18.0%; p = 0.003) over the median follow-up of 41.7 months. After multivariate adjustment, elevated TyG index was significantly associated with an increased risk of MACE (HR 1.33, 95% CI: 1.04-1.69, p = 0.020). The adjusted risk of MACE also increased with rising tertiles of TyG index (tertile 1 as reference; tertile 2: HR 1.64, 95% CI: 1.06-2.53, p = 0.025; tertile 3: HR 1.85, 95% CI: 1.17-2.93, p = 0.008). The TyG index remained a robust risk factor in overall and subgroups of MINOCA patients (all p < 0.05). Moreover, the TyG index yielded a moderate predictive value of MACE (area under the curve 0.66, 95% CI:0.61-0.71, p < 0.001). CONCLUSION: Elevated TyG index was independently associated with a poor prognosis after MINOCA. Routine assessment of TyG index may improve risk stratification and facilitate decision making in MINOCA patients.

Impact of prediabetes on long-term cardiovascular outcomes in patients with myocardial infarction with nonobstructive coronary arteries.

BACKGROUND: Abnormal glucose metabolism including diabetes (DM) and prediabetes (pre-DM) have been reported as predictors of poorer outcomes after acute myocardial infarction (AMI). However, the prognostic value of pre-DM in patients with myocardial infarction with nonobstructive coronary arteries (MINOCA) remains unclear. METHODS: A total of 1179 MINOCA patients were prospectively recruited and divided into normoglycemia (NG), pre-DM, and DM groups according to glycated hemoglobin (HbA1c) levels or past history. The primary endpoint was a composite of major adverse cardiovascular events (MACE), including all-cause death, nonfatal MI, nonfatal stroke, revascularization and hospitalization for unstable angina or heart failure. Kaplan-Meier and Cox regression analyses were performed. RESULTS: Patients with pre-DM and DM had a significantly higher incidence of MACE compared with NG group (10.8%, 16.1%, 19.4%; p = 0.003) over the median follow-up of 41.7 months. After multivariate adjustment, both pre-DM and DM were significantly associated with an increased risk of MACE (NG as reference; pre-DM: 1.45, 95% CI 1.03-2.09, p = 0.042; DM: HR 1.79, 95% CI 1.20-2.66, p = 0.005). At subgroup analysis, pre-DM remained a robust risk factor of MACE compared to NG. In addition, pre-DM had a similar impact as DM on long-term prognosis in patients with MINOCA. CONCLUSIONS: Pre-DM defined as raised HbA1c was associated with a poor prognosis in patients with MINOCA. Routine assessment of HbA1c enables an early recognition of pre-DM and thus may facilitate risk stratification in this specific population.

In-hospital gastrointestinal bleeding in patients with acute myocardial infarction: incidence, outcomes and risk factors analysis from China Acute Myocardial Infarction Registry.

OBJECTIVE: To investigate the incidence of gastrointestinal bleeding (GIB) in patients with acute myocardial infarction (AMI), clarify the association between adverse clinical outcomes and GIB and identify risk factors for in-hospital GIB after AMI. DESIGN: Retrospective cohort study. SETTING: 108 hospitals across three levels in China. PARTICIPANTS: From 1 January 2013 to 31 August 2014, after excluding 2659 patients because of incorrect age and missing GIB data, 23 794 patients with AMI from 108 hospitals enrolled in the China Acute Myocardial Infarction Registry were divided into GIB-positive (n=282) and GIB-negative (n=23 512) groups and were compared. PRIMARY AND SECONDARY OUTCOME MEASURES: Major adverse cardiovascular and cerebrovascular events (MACCEs) are a composite of all-cause death, reinfarction and stroke. The association between GIB and endpoints was examined using multivariate logistic regression and Cox proportional hazards models. Independent risk factors associated with GIB were identified using multivariate logistic regression analysis. RESULTS: The incidence of in-hospital GIB in patients with AMI was 1.19%. GIB was significantly associated with an increased risk of MACCEs both in-hospital (OR 2.314; p<0.001) and at 2-year follow-up (HR 1.407; p=0.0008). Glycoprotein IIb/IIIa (GPIIb/IIIa) receptor inhibitor, percutaneous coronary intervention (PCI) and thrombolysis were novel independent risk factors for GIB identified in the Chinese AMI population (p<0.05). CONCLUSIONS: GIB is associated with both in-hospital and follow-up MACCEs. Gastrointestinal prophylactic treatment should be administered to patients with AMI who receive primary PCI, thrombolytic therapy or GPIIb/IIIa receptor inhibitor. TRIAL REGISTRATION NUMBER: NCT01874691.

Predictive Value of Free Triiodothyronine to Free Thyroxine Ratio in Euthyroid Patients With Myocardial Infarction With Nonobstructive Coronary Arteries.

Background: Thyroid function is closely involved in cardiovascular diseases. The free triiodothyronine (fT3) to free thyroxine (fT4) ratio has been reported as a risk factor for coronary artery disease, but its prognostic value in euthyroid patients with myocardial infarction with nonobstructive coronary arteries (MINOCA) remains unclear. Methods: A total of 1162 euthyroid patients with MINOCA were enrolled and divided according to decreased tertiles of fT3/fT4 ratio. The study endpoint was major adverse cardiovascular events (MACE), including all-cause death, nonfatal MI, nonfatal stroke, revascularization, and hospitalization for unstable angina or heart failure. Kaplan-Meier, Cox regression, and receiver-operating characteristic analyses were performed. Results: Patients with lower fT3/fT4 tertile levels had a significantly higher incidence of MACE (10.0%, 13.9%, 18.2%; p=0.005) over the median follow-up of 41.7 months. The risk of MACE increased with the decreasing fT3/fT4 tertiles even after multivariate adjustment (tertile1 as reference, tertile2: HR 1.58, 95% CI: 1.05-2.39, p=0.030; tertile3: HR 2.06, 95% CI: 1.17-3.11, p=0.006). Lower level of fT3/fT4 ratio remained a robust predictor of MACE in overall (HR 1.64, 95% CI: 1.18-2.29, p=0.003) and in subgroups. When adding fT3/fT4 ratio [area under the curve (AUC) 0.61] into the thrombolysis in myocardial infarction (TIMI) risk score (AUC 0.69), the combined model (AUC 0.74) yielded a significant improvement in discrimination for MACE (ΔAUC 0.05, p=0.023). Conclusions: Low level of fT3/fT4 ratio was strongly associated with a poor prognosis in euthyroid patients with MINOCA. Routine assessment of fT3/fT4 ratio may facilitate risk stratification in this specific population.

Identification of Key Genes and Underlying Mechanisms in Acute Kawasaki Disease Based on Bioinformatics Analysis.

BACKGROUND Kawasaki disease (KD) is a systemic vasculitis that predominantly occurs in children, but the pathogenesis of KD remains unclear. Here, we explored key genes and underlying mechanisms potentially involved in KD using bioinformatic analyses. MATERIAL AND METHODS The shared differentially expressed genes (DEGs) in KD compared to control samples were identified using the microarray data from the Gene Expression Omnibus Series (GSE) 18606, GSE68004, and GSE73461. Analyses of the functional annotation, protein-protein interaction (PPI) network, microRNA-target DEGs regulatory network, and immune cell infiltration were performed. The expression of hub genes before and after intravenous immunoglobulin (IVIG) treatment in KD was further verified using GSE16797. RESULTS A total of 195 shared DEGs (164 upregulated and 31 downregulated genes) were identified between KD and healthy controls. These shared DEGs were mainly enriched in immune and inflammatory responses. Ten upregulated hub genes (ITGAX, SPI1, LILRB2, MMP9, S100A12, C3AR1, RETN, MAPK14, TLR5, MYD88) and the most significant module were identified in the PPI network. There were 309 regulatory relationships detected within 70 predicted microRNAs and 193 target DEGs. The immune cell infiltration analysis showed that monocytes, neutrophils, activated mast cells, and activated natural killer cells had relatively high proportions and were significantly more infiltrated in KD samples. Six hub genes of ITGAX, LILRB2, C3AR1, MAPK14, TLR5, and MYD88 were markedly downregulated after IVIG treatment for KD. CONCLUSIONS Our study identified the candidate genes and associated molecules that may be related to the KD process, and provided new insights into potential mechanisms and therapeutic targets for KD.

Off-hours admission does not impact outcomes in patients undergoing primary percutaneous coronary intervention and with a first medical contact-to-device time within 90 min.

BACKGROUND: It remains unclear whether the outcomes of ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PPCI) during off-hours are as favorable as those treated during on-hours, especially those with a first medical contact-to-device (FMC-to-device) time within 90 min. We aimed to determine whether off-hours admission impacted late outcomes in patients undergoing PPCI and with an FMC-to-device time ≤90 min. METHODS: This multicenter retrospective study included 670 STEMI patients who underwent successful PPCI and had an FMC-to-device time ≤90 min from 19 chest pain centers in Beijing from January 2018 to December 2018. Patients were divided into on-hours group and off-hours group based on their arrival time. Baseline characteristics, clinical data, and key time intervals during treatment were collected from the Quality Control & Improvement Center of Cardiovascular Intervention of Beijing by the "Heart and Brain Green Channel" app. RESULTS: Overall, the median age of the patients was 58.8 years and 19.9% (133/670) were female. Of these, 296 (44.2%) patients underwent PPCI during on-hours and 374 (55.8%) patients underwent PPCI during off-hours. Compared with the on-hours group, the off-hours group had a longer FMC-to-device time and fewer patients with FMC-to-device time ≤60 min (P < 0.05). During the mean follow-up period of 24 months, a total of 64 (9.6%) participants experienced a major adverse cardiovascular event (MACE), with 28 (9.1%) in the on-hours group and 36 (9.6%) in the off-hours group (P > 0.05). According to the Cox regression analyses, off-hours admission was not a predictor of 2-year MACEs (P = 0.788). Similarly, the Kaplan-Meier curves showed that the risks of a MACE, all-cause death, reinfarction, and target vessel revascularization were not significantly different between the two groups (P > 0.05). CONCLUSIONS: This real-world, multicenter retrospective study demonstrated that for STEMI patients who underwent PPCI within 90 min, off-hours admission was safe, with no difference in the risk of 2-year MACEs compared with those with on-hours admission.

Sex-Specific Clinical Characteristics and Long-Term Outcomes in Patients With Myocardial Infarction With Non-obstructive Coronary Arteries.

Background: Sex differences in clinical profiles and prognosis after acute myocardial infarction have been addressed for decades. However, the sex-based disparities among patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) remain largely unreported. Here, we investigated sex-specific characteristics and long-term outcomes in MINOCA population. Methods: A total of 1,179 MINOCA patients were enrolled, including 867 men and 312 women. The mean follow-up was 41.7 months. The primary endpoint was a composite of major adverse cardiovascular events (MACE), including all-cause death, non-fatal reinfarction, revascularization, non-fatal stroke, and hospitalization for unstable angina or heart failure. Baseline data and outcomes were compared. Kaplan-Meier curves and Cox regression analyses were used to identify association between sex and prognosis. Results: Female patients with MINOCA had more risk profiles with regard to older age and higher prevalence of hypertension and diabetes compared with men. The evidence-based medical treatment was similar in men and women. The incidence of MACE (men vs. women: 13.8 vs. 15.3%, p = 0.504) did not differ significantly between the sexes. The Kaplan-Meier analysis also indicated that women had a similar incidence of MACE compared to men (log rank p = 0.385). After multivariate adjustment, female sex was not associated with the risk of MACE in overall (adjusted hazard ratio 1.02, 95% confidence interval: 0.72-1.44, p = 0.916) and in subgroups of MINOCA patients. Conclusion: The long-term outcomes were similar for men and women presenting with MINOCA despite older age and more comorbidities in women. Future research should aim to improve in-hospital and post-discharge care for both sexes with MINOCA.

Predictive value of the age, creatinine, and ejection fraction score in patients with myocardial infarction with nonobstructive coronary arteries.

BACKGROUND: Little is known about risk stratification in patients with myocardial infarction with nonobstructive coronary arteries (MINOCA). We investigated whether the age, creatinine, and ejection fraction (ACEF) score (age [years]/ejection fraction [%] + 1 [if creatinine >176 µmol/L]) might predict long-term outcomes after MINOCA. HYPOTHESIS: The ACEF score enables accurate risk prediction in patients with MINOCA. METHODS: A total of 1179 patients with MINOCA were enrolled and divided based on their ACEF score tertile levels. The primary endpoint was a composite of major adverse cardiovascular events (MACE), including all-cause death, nonfatal MI, nonfatal stroke, revascularization, and hospitalization for unstable angina or heart failure. Kaplan-Meier and Cox regression analyses were performed. Discrimination was defined as the area under the curve (AUC) using receiver operating characteristic analysis. RESULTS: During the median follow-up of 41.7 months, patients with MINOCA with higher ACEF score tertiles had a significantly higher incidence of MACE (6.3%, 12.5%, and 23.8%, respectively; p < .001). The adjusted risk of MACE increased with the rising ACEF score tertiles (1st tertile as reference; 2nd tertile: HR 2.70, 95% CI: 1.38-5.29, p = .004; and 3rd tertile: HR 5.35, 95% CI: 2.72-10.51, p < .001). Moreover, an elevated ACEF score was closely associated with an increased risk of MACE overall (HR 4.23, 95% CI: 3.37-5.30, p < .001) and in subgroups (all p < .05). The ACEF score also yielded a good predictive value (AUC 0.79) for MACE. CONCLUSION: Elevated ACEF scores were strongly associated with a poor prognosis after MINOCA. This simple and valid risk score may facilitate risk stratification and decision making in the population with MINOCA.

Effect of Lipoprotein (a) Levels on Long-term Cardiovascular Outcomes in Patients with Myocardial Infarction with Nonobstructive Coronary Arteries.

The association between elevated lipoprotein(a) [Lp(a)] and poor outcomes in coronary artery disease (CAD) has been addressed for decades. However, little is known about the prognostic value of Lp(a) in patients with myocardial infarction with nonobstructive coronary arteries (MINOCA). A total of 1179 patients with MINOCA were enrolled and divided into low, medium, and high Lp(a) groups based on the cut-off value of 10 and 30mg/dL. The primary endpoint was major adverse cardiovascular events (MACE), a composite of all-cause death, nonfatal MI, nonfatal stroke, revascularization, and hospitalization for unstable angina or heart failure. Kaplan-Meier and Cox regression analyses were performed. Accuracy was defined as area under the curve (AUC) using a receiver-operating characteristic analysis. Patients with higher Lp(a) levels had a significantly higher incidence of MACE (9.5%, 14.6%, 18.5%; p = 0.002) during the median follow-up of 41.7 months. The risk of MACE also increased with the rising Lp(a) levels even after multivariate adjustment [low Lp(a) group as reference, medium group: hazard ratio (HR) 1.55, 95% confidence interval (CI): 1.02-2.40, p = 0.047; high group: HR 2.07, 95% CI: 1.32-3.25, p = 0.001]. Further, clinically elevated Lp(a) defined as Lp(a) ≥30 mg/dL was closely associated with an increased risk of MACE in overall and in subgroups (all p <0.05). When adding Lp(a) (AUC 0.61) into the Thrombolysis in Myocardial Infarction (TIMI) score (AUC 0.68), the combined model (AUC 0.73) yielded a significant improvement in discrimination for MACE (ΔAUC 0.05, p = 0.032). In conclusion, elevated Lp(a) was strongly associated with a poor prognosis in patients with MINOCA. Adding Lp(a) to traditional risk score further improved risk prediction. Our data, for the first time, confirmed the Lp(a) as a residual risk factor for MINOCA.

Impact of low triiodothyronine syndrome on long-term outcomes in patients with myocardial infarction with nonobstructive coronary arteries.

BACKGROUND: Low triiodothyronine syndrome (LT3S), frequently seen in patients with acute myocardial infarction (AMI), has been regarded as a predictor of poor outcomes after AMI. However, little is known about the prognostic value of LT3S in euthyroid patients with myocardial infarction with nonobstructive coronary arteries (MINOCA). METHODS: A total of 1162 MINOCA patients were enrolled and divided into LT3S and no-LT3S groups. LT3S was defined as decreased free T3 (fT3 < 2.36 pg/mL) with normal values of thyroid-stimulating hormone. The primary endpoint was a composite of major adverse cardiovascular events (MACE), including all-cause death, nonfatal MI, stroke, revascularization, and hospitalization for unstable angina or heart failure. Kaplan-Meier, Cox regression, propensity score matching (PSM), and receiver-operating characteristic analyses were performed. RESULTS: Patients with LT3S (prevalence of 17.5%) had a significantly higher incidence of MACE (19.6% vs. 12.9%; p = .013) than patients without during the median follow-up of 41.7 months. LT3S was closely associated with an increased risk of MACE even after multivariable adjustment (HR 1.50, 95% CI: 1.03-2.18, p = .037). After PSM, 197 pairs of patients with or without LT3S were identified, and LT3S remained a robust risk factor of worse outcomes (HR 1.53, 95% CI: 1.02-2.65, p = .042). Moreover, LT3S had an area under the curve (AUC) of 0.60 for predicting MACE. When adding LT3S to the thrombolysis in myocardial infarction (TIMI) risk score, the combined model yielded a significant improvement in discrimination for MACE. CONCLUSIONS: LT3S was independently associated with poor outcomes after MINOCA. Routine assessment of LT3S may provide valuable prognostic information in this specific population.