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Introduction: Acute myocardial infarction (AMI) accounts for the majority of deaths caused by coronary artery disease (CAD). Early warning of AMI, especially for patients with stable coronary artery disease (sCAD), is urgently needed. Our previous study showed that alterations in the gut microbiota were correlated with CAD severity., Objectives: Herein, we tried to discover accurate and convenient biomarkers for AMI by combination of gut microbiota and fecal/blood/urinary metabolomics., Methods: We recruited 190 volunteers including 93 sCAD patients, 49 AMI patients, and 48 subjects with normal coronary artery (NCA), and measured their blood biochemical parameters, 16S rRNA-based gut microbiota and NMR-based fecal/blood/urinary metabolites. We further selected 20 subjects from each group and analyzed their gut microbiota by whole-metagenome shotgun sequencing., Results: Multi-omic analyses revealed that AMI patients exhibited specific changes in gut microbiota and serum/urinary/fecal metabolites as compared to subjects with sCAD or NCA. Fourteen bacterial genera and 30 metabolites (11 in feces, 10 in blood, 9 in urine) were closely related to AMI phenotypes and could accurately distinguish AMI patients from sCAD patients. Some species belonging to Alistipes, Streptococcus, Ruminococcus, Lactobacillus and Faecalibacterium were effective to distinguish AMI from sCAD and their predictive ability was confirmed in an independent cohort of CAD patients. We further selected nine indicators including 4 bacterial genera, 3 fecal and 2 urinary metabolites as a noninvasive biomarker set which can distinguish AMI from sCAD with an AUC of 0.932., Conclusion: Combination of gut microbiota and fecal/urinary metabolites provided a set of potential useful and noninvasive predictive biomarker for AMI from sCAD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Production and hosting by Elsevier B.V.)

Background: Coronary artery involvement is a severe but uncommon manifestation of polyarteritis nodosa (PAN), so clinicians have little knowledge of it. Our aim was to investigate the clinical characteristics, risk factors and outcomes of patients with PAN complicated with coronary artery lesions., Methods: Data from 145 patients with PAN who were admitted to Peking Union Medical College Hospital from January 2000 to September 2019 were retrospectively collected., Results: Nineteen patients (13.1%) had coronary artery lesions due to PAN. The age at the onset of PAN was 32.3 ± 11.8 years. There were no significant differences in common risk factors for coronary arterial atherosclerosis between the patients with coronary artery involvement and those without. Affected branches of the coronary arteries were left anterior descending branch (15 patients), right coronary artery (14 patients), and left circumflex branch (9 patients). Eleven of the 19 patients exhibited multivessel lesions. Multivariate logistic regression analysis showed that celiac artery involvement (odds ratio [OR] 3.722, 95% confidence interval [CI] 1.115-12.427; P = 0.033) and new-onset hypertension (OR 6.668, 95% CI 1.936-22.961; P = 0.003) were risk factors for coronary artery involvement in patients with PAN. Stent placement was performed for 2 patients, and in-stent restenosis occurred in 1 of those patients a year later., Conclusions: PAN with coronary artery involvement exhibits more combined involvement of arteries of other organs and more severe diseases. PAN should be considered when treating young adults with an unknown origin of coronary artery lesions. In addition to systemic immunosuppressive treatment, other measures including antiplatelet and anticoagulation therapy should be initiated; however, determining the optimal time to perform procedures such as intervention or surgery is still challenging., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Host-microbiota interactions involving metabolic pathways have been linked to the pathogenesis of atherosclerotic disease and type 2 diabetes. As stable coronary artery disease (SCAD) patients combined with type 2 diabetes have significantly increased risk for cardiac event, we focused on elucidating the role of microbiota affecting cardiometabolic disease development., Methods and Results: We used multi-omics analyses (metagenomics and metabolomics) of fecal and serum samples from a prospective cohort including stable coronary artery disease combined with diabetes mellitus (SCAD + T2DM, n = 38), SCAD (n = 71), and healthy control (HC, n = 55). We linked microbiome features to disease severity in a three-pronged association analysis and identified prognostic bacterial biomarkers. We identified that bacterial and metabolic signatures varied significantly between SCAD and SCAD + T2DM groups. SCAD + T2DM individuals were characterized by increased levels of aromatic amino acids and carbohydrates, which correlate with a gut microbiome with enriched biosynthetic potential. Our study also addressed how metformin may confound gut dysbiosis and increase the potential for nitrogen metabolism. In addition, we found that specific bacterial taxa Ruminococcus torques [HR: 2.363 (08-4.56), P = 0.03] was predictive of cardiac survival outcomes., Conclusion: Overall, our study identified relationships between features of the gut microbiota (GM) and circulating metabolites, providing a new direction for future studies aiming to understand the host-GM interplay in atherosclerotic cardiovascular pathogenesis., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: The gut microbiota was shown to play a crucial role in the development of vascular dysfunction, and the bacterial composition differed between healthy controls and coronary artery disease patients. The goal of this study was to investigate how the gut microbiota affects host metabolic homeostasis at the organism scale., Methods: We colonized germ-free C57BL/6 J mice with faeces from healthy control donors (Con) and coronary artery disease (CAD) patients and fed both groups a high fat diet for 12 weeks. We monitored cholesterol and vascular function in the transplanted mice. We analysed bile acids profiles and gut microbiota composition. Transcriptome sequencing and flow cytometry were performed to evaluate inflammatory and immune response., Results: CAD mice showed increased reactive oxygen species generation and intensive arterial stiffness. Microbiota profiles in recipient mice clustered according to the microbiota structure of the human donors. Clostridium symbiosum and Eggerthella colonization from CAD patients modulated the secondary bile acids pool, leading to an increase in lithocholic acid and keto-derivatives. Subsequently, bile acids imbalance in the CAD mice inhibited hepatic bile acids synthesis and resulted in elevated circulatory cholesterol. Moreover, the faecal microbiota from the CAD patients caused a significant induction of abnormal immune responses at both the transcriptome level and through the enhanced secretion of cytokines. In addition, microbes belonging to CAD promoted intestinal inflammation by contributing to lamina propria Th17/Treg imbalance and worsened gut barrier permeability., Conclusions: In summary, our findings elucidated that the gut microbiota impacts cholesterol homeostasis by modulating bile acids. In addition, the CAD-associated bacterial community was shown to function as an important regulator of systemic inflammation and to influence arterial stiffness.

Competing Interests: Declaration of Competing Interest The authors declare there is no conflict of interest.

Background: The long-term outcomes and optimal treatment strategy for patients with Takayasu arteritis (TA) and significant coronary stenosis remain unclear. We aim to investigate the prognosis of these patients according to the initial management strategy., Methods: A total of 57 consecutive patients with TA and significant coronary stenosis were included between 2002 and 2018. The cohort was divided into the percutaneous coronary intervention (PCI) group (n = 18), coronary artery bypass graft (CABG) group (n = 10), and medical-therapy group (n = 29). The primary outcome was major adverse cardiac events (MACEs) defined as a composite of cardiac death, myocardial infarction, and coronary revascularization., Results: Over a median follow-up of 4.5 (IQR 3.5-8.0) years, 24 (42.1%) patients experienced at least one MACE. The long-term rates of MACEs and re-revascularization were significantly higher in the PCI group than in the other 2 groups (HR 5.306, 95% CI 2.160-13.036, p < 0.001; HR 12.286, 95% CI 3.257-46.343, p < 0.001, respectively). The cumulative incidences of MACEs and subsequent revascularization were similar between the CABG and medical-therapy group. Active disease at baseline and PCI were independent predictors of MACEs (HR, 7.039, 95% CI 2.031-24.396; p = 0.002; HR, 4.400; 95% CI 1.804-10.727; p = 0.001, respectively) and revascularization (HR 4.632, 95% CI 1.010-21.235, p = 0.048; HR 9.820, 95% CI 2.641-36.514, p = 0.001, respectively)., Conclusions: The initial baseline active disease is an important predictor of long-term outcome and subsequent revascularization in patients with TA and significant coronary artery stenosis. Also, PCI is independently associated with higher risk of MACEs and re-revascularization., Competing Interests: Declaration of competing interest The authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: This study investigated neutrophil activation and neutrophil-derived extracellular traps formation in coronary artery ectasia., Methods: We enrolled 90 patients who underwent coronary angiography, and included 30 patients with coronary artery ectasia (CAE), 30 patients with obstructive coronary artery disease (CAD) and 30 patients with normal coronary arteries (CON). Intra-neutrophil mean myeloperoxidase index (MPXI) was determined using an automated blood cell counter (ADVIA2120 Hematology System). Serum concentrations of plasma adhesion molecules, cytokines, and neutrophil-derived extracellular traps were quantified., Results: The intra-neutrophil mean myeloperoxidase index was reduced in CAE patients compared to CAD and CON patients (1.02 ± 3.01, 3.22 ± 3.03, 3.52 ± 4.25, respectively; CAE vs CAD, p = 0.016 and CAE vs CON, p = 0.007). Multiple logistic regression analysis showed that MPXI and dsDNA were independent factors that predicted the presence of CAE. CAE patients had higher levels of plasma adhesion molecules (P-selectin glycoprotein ligand-1, E-selectin, L-selectin) and interleukin 1 beta levels. Neutrophil extracellular trap concentrations were significantly higher in the CAE group compared to CAD and CON patients (284.31(258.33-449.91) ng/mL, 225.12(203.34-257.13) ng/mL, and 247.37(231.04-273.01) ng/mL, respectively; CAE vs CAD, p = 0.000 and CAE vs CON, p = 0.001)., Conclusions: Peripheral neutrophils from CAE patients were activated and neutrophil extracellular traps were elevated in the plasma. IL-1β and soluble adhesion molecules may be the causal factors for neutrophil activation.

Coronary artery disease (CAD) is a major threat to human health. In clinical practice, X-ray coronary angiography remains the gold standard for CAD diagnosis, where the detection of stenosis is a crucial step. However, detection is challenging due to the low contrast between vessels and surrounding tissues as well as the complex overlap of background structures with inhomogeneous intensities. To achieve automatic and accurate stenosis detection, we propose a convolutional neural network-based method with a novel temporal constraint across X-ray angiographic sequences. Specifically, we develop a deconvolutional single-shot multibox detector for candidate detection on contrast-filled X-ray frames selected by U-Net. Based on these static frames, the detector demonstrates high sensitivity for stenoses yet unacceptable false positives still exist. To solve this problem, we propose a customized seq-fps module that exploits the temporal consistency of consecutive frames to reduce the number of false positives. Experiments are conducted with 148 X-ray angiographic sequences. The results show that the proposed method outperforms existing stenosis detection methods, achieving the highest sensitivity of 87.2% and positive predictive value of 79.5%. Furthermore, this study provides a promising tool to improve CAD diagnosis in clinical practice., Competing Interests: Declaration of competing interest The authors declares that they have no conflict of interest., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Coronary artery disease (CAD) is associated with gut microbiota alterations in different populations. Gut microbe-derived metabolites have been proposed as markers of major adverse cardiac events. However, the relationship between the gut microbiome and the different stages of CAD pathophysiology remains to be established by a systematic study., Results: Based on multi-omic analyses (sequencing of the V3-V4 regions of the 16S rRNA gene and metabolomics) of 161 CAD patients and 40 healthy controls, we found that the composition of both the gut microbiota and metabolites changed significantly with CAD severity. We identified 29 metabolite modules that were separately classified as being positively or negatively correlated with CAD phenotypes, and the bacterial co-abundance group (CAG) with characteristic changes at different stages of CAD was represented by Roseburia, Klebsiella, Clostridium IV and Ruminococcaceae. The result revealed that certain bacteria might affect atherosclerosis by modulating the metabolic pathways of the host, such as taurine, sphingolipid and ceramide, and benzene metabolism. Moreover, a disease classifier based on differential levels of microbes and metabolites was constructed to discriminate cases from controls and was even able to distinguish stable coronary artery disease from acute coronary syndrome accurately., Conclusion: Overall, the composition and functions of the gut microbial community differed from healthy controls to diverse coronary artery disease subtypes. Our study identified the relationships between the features of the gut microbiota and circulating metabolites, providing a new direction for future studies aiming to understand the host-gut microbiota interplay in atherosclerotic pathogenesis.

Background: The precise relationship between increased thrombolysis in myocardial infarction (TIMI) frame counts and the topographical extent of isolated coronary artery ectasia (CAE) has not been fully explained. New parameters of linear dimension (LD) and the estimated ectatic area (EEA) together with the diameter and ectasia ratio may be associated with the corrected TIMI frame count (CTFC) in isolated CAE patients., Methods: The topographical parameters of ectatic coronary arteries and/or segments of 77 isolated CAE patients were consecutively studied. The CTFC for each coronary artery was determined by angiographic frame count., Results: Right coronary artery (RCA) was the most frequently affected. The RCA and left circumflex (LCX) had significantly longer LD (p < 0.001 for both), and greater EEA (p < 0.001 for both) than those of left anterior descending artery (LAD). Similarly, the RCA and LCX have higher CTFCs (p = 0.001 and p = 0.008, respectively) than LAD. All topographic parameters and CTFCs were positively correlated with Markis classification. Linear regression analyses revealed that CTFCs were strongly correlated with diameter, LD, ectasia ratio and EEA, while EEA was the best predictor for the CTFC. Among multiple linear and nonlinear regression models, the cubic model between the CTFC and EEA exhibits the best Goodness-of-Fit., Conclusion: The severity of the topographical extent of CAE was significantly correlated with increased CTFCs. Both the linear dimension and ectatic diameter (combined as EEA) were important for evaluating decreased coronary flow in isolated CAE patients.

Background: In the present study we investigated the effects of genetic variations in the C-C motif chemokine ligand 17 (CCL17) gene on serum CCL17 levels and risk of coronary artery disease (CAD).Methods and Results:A case-control study was conducted to determine causal inferences amongCCL17single-nucleotide polymorphisms (SNPs), serum CCL17 levels, and risk of CAD. Luciferase assays, electrophoretic mobility shift assays (EMSA), and allele-specific quantitative chromatin immunoprecipitation (ChIP) assays were used to assess the function of the SNPs. In all, 947 participants (794 with CAD, 153 without CAD) were included in the study. The T allele in rs223828, located in intron of theCCL17gene, was associated with increased serum CCL17 levels as well as increased CAD risk. A causal inference test using mediation analysis suggested that rs223828 had a significant indirect casual effect on the increased risk of CAD mediated via serum CCL17 levels. Luciferase assays confirmed that the rs223828T allele enhancesCCL17promoter activity. Protein-DNA binding studies using EMSA and allele-specific quantitative ChIP assays indicated preferential activator protein-1 (AP-1) complex formation and recruitment with the rs223828 T allele compared with the C allele., Conclusions: We propose that theCCL17SNP rs223828 is associated with increased risk of CAD, and that this site may be a potential AP-1 binding site.

Background: Several updated meta-analyses comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) for left main coronary artery disease (LM CAD) have been published recently. However, the risk of false-positive results could be high in conventional updated meta-analyses due to repetitive testing of accumulating data. Therefore, we compared these treatment approaches via trial sequential analysis (TSA)., Methods: The MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases were searched for published randomized controlled trials (RCTs) or subgroups of RCTs comparing PCI and CABG in patients with LM CAD. The primary outcome was major cardiac and cerebrovascular adverse events (MACCE). TSA was used to confirm the conclusions derived from conventional meta-analysis., Results: Six RCTs with 4700 patients were included. PCI was associated with a greater risk of MACCE compared with CABG (pooled relative risk [RR] 1.21, 95% confidence interval [CI]: 1.05-1.40, P = .008). In addition, PCI resulted in a significantly higher risk of revascularization than CABG (pooled RR 1.61, 95% CI: 1.33-1.95, P < .0001). TSA provided firm evidence for the reduction of MACCE and revascularization with CABG compared with PCI (cumulative z-curve crossed the monitoring boundary). In the subgroup analysis, CABG was better than PCI in patients with SYNTAX score >32 (pooled RR 1.41, 95% CI: 1.12-1.76, P = .003), which was confirmed by the TSA. There was no difference in patients with a SYNTAX score from 0 to 32., Conclusions: In patients with LM CAD, CABG may be better than PCI for reducing MACCE due to a reduced risk of revascularization. CABG remains the first choice for LM CAD patients with high anatomic complexity, while PCI could be an alternative for those with low-to-moderate anatomic complexity.

Objective We aimed to determine the capacity of drug-eluting stent (DES) over-expansion in left main coronary artery disease. Methods Left main interventions with the largest available DES platforms (4.0 mm) and post-dilation performed with large non-compliant balloons (≥ 4.5 mm) were included. Maximal stent diameter (mm) and area (mm 2 ) were measured using post-intervention intravascular ultrasound (IVUS). Stent diameter and area were calculated with the balloon diameter and inflation pressure. The diameter and area expansion indices were defined as follows: maximal/calculated stent diameter and maximal/calculated stent area, respectively. Results Twenty-three consecutive patients were included. The maximal stent diameter was 4.40 mm (4.30-4.80 mm), and 22 of 23 patients showed a diameter expansion index greater than 0.90. The area expansion index was 0.862. The expansion index < 0.85 group had a significantly higher percentage of calcification ≥ 90° on IVUS than did the expansion index ≥ 0.85 group (72.7% versus 16.7%, P = 0.007). One stent fracture occurred during over-expansion and one ischemic event occurred during follow-up. Conclusions DESs with a nominal diameter of 4.0 mm can be effectively over-expanded in left main coronary artery disease. Achievement of predicted stent area can be affected by calcification.

This meta-analysis compared IVUS-guided with angiography-guided PCI to determine the effect of IVUS on the mortality in patients with LM CAD. Current guidelines recommend intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) in patients with left main coronary artery disease (LM CAD; Class IIa, level of evidence B). A systematic search of the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases was conducted to identify randomized or non-randomized studies comparing IVUS-guided PCI with angiography-guided PCI in LM CAD. Ten studies (9 non-randomized and 1 randomized) with 6,480 patients were included. The primary outcome was mortality including all-cause death and cardiac death. Compared with angiography-guide PCI, IVUS-guided PCI was associated with significantly lower risks of all-cause death (risk ratio [RR] 0.60, 95% confidence interval [CI] 0.47-0.75, p<0.001), cardiac death (RR 0.47, 95% CI 0.33-0.66, p<0.001), target lesion revascularization (RR 0.43, 95% CI 0.25-0.73, p = 0.002), and in-stent thrombosis (RR 0.28, 95% CI 0.12-0.67, p = 0.004). Subgroup analyses indicated the beneficial effect of IVUS-guide PCI was consistent across different types of studies (unadjusted non-randomized studies, propensity score-matched non-randomized studies, or randomized trial), study populations (Asian versus non-Asian), and lengths of follow-up (<3 years versus ≥3 years). IVUS-guided PCI in LM CAD significantly reduced the risks of all-cause death by ~40% compared with conventional angiography-guided PCI. PROSPERO registration number: CRD 42017055134.

The plasma levels of asymmetric dimethylarginine (ADMA) had been proved to be an independent cardiovascular risk factor. Few studies involved the entire arginine methylation dysfunction. This study was designed to investigate whether arginine methylation dysfunction is associated with acute coronary syndrome risk in coronary artery disease population.In total 298 patients undergoing coronary angiography because of chest pain with the diagnosis of stable angina pectoris or acute coronary syndrome from February 2013 to June 2014 were included. Plasma levels of free arginine, citrulline, ornithine, and the methylated form of arginine, ADMA, and symmetric dimethylarginine (SDMA) were measured with high-performance liquid chromatography coupled with tandem mass spectrometry. We examined the relationship between arginine metabolism-related amino acids or arginine methylation index (AMI, defined as ratio of [arginine + citrulline + ornithine]/[ADMA + SDMA]) and acute coronary events.We found that plasma ADMA levels were similar in the stable angina pectoris group and the acute coronary syndrome group (P = 0.88); the AMI differed significantly between 2 groups (P < 0.001). Multivariate logistic regression demonstrated that AMI was an independent risk factor of acute coronary events in patients with coronary artery disease (OR = 0.975, 95% confidence interval 0.956-0.993; P = 0.008).Our study suggested that ADMA levels were very similar in the stable angina and acute coronary syndrome patients; AMI might be an independent risk factor of acute coronary events in coronary artery disease population.

Background and Aims: Immunoglobulin E (IgE), a key element of allergic reactions, was considered to be involved in the development of atherosclerosis and the pathogenesis of myocardial ischemia. This study was designed to test whether total serum IgE levels were associated with the atherosclerosis severity of coronary artery disease (CAD)., Methods: Total serum IgE concentrations were measured in 708 consecutive patients who were presented to our center for coronary angiography. Atherosclerosis severity of CAD was assessed by the number of diseased vessels showing ≥50% diameter stenosis and quantified by Gensini score., Results: Patients with CAD (N = 562) had higher serum IgE levels than those without CAD (N = 146) [55.90 (19.10-156.00) vs. 26.90 (11.80-62.10) KU/L, p = 0.003]. Furthermore, the serum IgE levels were significantly increased in patients with multivessel disease (MVD) compared to those with single-vessel disease [61.80 (23.20-159.00) vs. 32.45(14.15-94.38) KU/L, p = 0.003]. After adjustment for traditional cardiovascular risk factors, a high serum IgE level was an independent predictor for an increased risk of MVD (OR 1.003; 95% CI 1.001-1.004; p = 0.041). Receiver-operating characteristic curve analysis demonstrated that serum IgE levels improved the predictive capability of traditional risk factors for MVD (area under the curve with and without IgE: 0.734 and 0.713, respectively, p < 0.001). Meanwhile, there was a significant linear relationship between Gensini score and the serum IgE level quartiles (p for linear trend <0.001)., Conclusions: Increased total serum IgE levels are associated with MVD and contribute to discriminating CAD severity independently of traditional cardiovascular risk factors., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: Proteolytic enzymes might contribute to coronary artery ectasia (CAE) through the destruction of extracellular matrix (ECM) vessel components. This study aimed to find out if peripheral blood mononuclear cells (PBMCs) served as a source of those proteinases and their regulators., Method: In this study, transcriptional expression profiles of the main proteinases and their regulators were detected in the PBMCs of CAE patients as follows: (1) matrix metalloproteinases (MMP) 1, 2, 3, 8, 9, 10, 12 and 13; (2) the serine proteinases elastase: cathepsin G and proteinases 3; (3) the cysteine proteinases: cathepsin L and cathepsin S; (4) the main endogenous inhibitors for the above proteinases: tissue inhibitors of metalloproteinase (TIMP) 1 and 2, α1-antitrypsin (α1-PI) and α2-macroglobulin (A2M); (5) twelve cytokines that could regulate the above proteinases., Result: The characteristic changes in CAE were: (1) MMP1 and MMP9 increased while the serine and cysteine families did not change; (2) the four proteinase inhibitors did not change in the CAE group; (3) among the 12 cytokines, interleukin-1 alpha (IL1A), platelet-derived growth factor (PDGF), interferon gamma (IFNγ) and growth differentiation factor 15 (GDF15) were elevated. Partial correlation analysis showed that MMP1 significantly correlated with IL1A and with IFNγ, and MMP9 correlated with IFNγ and with GDF 15., Conclusion: PBMCs might participate in the pathological process of CAE by the increased expression of MMP1, MMP9, IL1A, IFNγ and GDF15.

Dysregulation of the metabolism of the extracellular matrix (ECM) may contribute to coronary artery ectasia (CAE). This study evaluated the turnover of main ECM components and related proteolytic enzymes activities. In this study, thirty patients with CAE, 30 patients with coronary artery disease (CAD) and 30 subjects with normal coronary arteries (Control) were selected. The following circulating ECM metabolism markers were measured: soluble elastin (sElastin), collagen type I cross-linked telopeptides (ICTP), procollagen type I carboxy terminal peptide (PICP), protocollagen III N-terminal propeptide (PIIINP), and procollagen a1(III) C-terminal propeptide (PIIICP). Serum total elastase activity and total matrix metalloproteinase (MMP) activity were also determined. The level of sElastin was higher in the CAE group than in the CAD and Control groups (P1 = 0.009, P2 = 0.000). There was no difference in ICTP (P = 0.168) or PIIICP (P = 0.079) among the three groups. PICP was significantly elevated in CAE (P1 = 0.001, P2 = 0.002). PIIINP was also significantly increased in CAE (P1 = 0.002, P2 = 0.007). Total elastase activity was higher in the CAE group than in the other two groups (P1 = 0.006, P2 = 0.022). Total MMP activity was significantly higher in the CAE group than the Control group (P2 = 0.013) but not higher than the CAD group (P1 = 0.477). In conclusion, within CAE patients the main changes in ECM metabolism were increased degradation of elastin fibres and the transition of collagen from type III to type I. Elastase and MMPs appear to be associated with this kind of ECM turnover.

Thrombus formation and myocardial infarction are not uncommon in patients with coronary artery ectasia (CAE). In light of this, the present study aims to systemically evaluate the blood coagulation and fibrinolytic systems in CAE patients. In this study, we enrolled 30 patients with CAE, 30 patients with coronary atherosclerosis disease (CAD), and 29 subjects with normal coronary arteries (control). The coagulation system was evaluated using a routine coagulation function test performed in the hospital laboratory before coronary angiography, and measurements included prothrombin time, international normalized ratio, activated partial thromboplastin time, fibrinogen time, and thrombin time. The evaluation of the fibrinolytic system included measurements of D-dimer, euglobulin lysis time, plasminogen activator inhibitor 1, plasminogen, plasminogen activity assay, α1-antitrypsin (α1-AT), α2 plasmin inhibitor (α2-PI), and α2-macroglobulin (α2-MG). Alpha1-AT, α2-PI, and α2-MG also inhibit activities of 3 neutrophil serine proteases, namely human neutrophil elastase (HNE), cathepsin G (CG), and proteinase 3 (PR3); therefore, the plasma levels of these 3 proteinases were also evaluated.In CAE patients, the circulating coagulation system was normal. For the fibrinolytic system, a decrease of plasminogen activity was observed (P = 0.029) when compared with CAD patients, and the concentrations of α1-AT (both P < 0.001), α2-PI (P = 0.002 and P = 0.025), and α2-MG (P = 0.034 and P < 0.001) were significantly elevated when compared with CAD patients and normal controls. Moreover, the plasma levels of HNE (both P < 0.001) and CG (P = 0.027 and 0.016) in CAE patients were also significantly higher than those of the CAD and control groups. There was no difference in plasma PR3 concentration among these 3 groups.Disequilibrium of the coagulation/fibrinolytic system may contribute to thrombus formation and clinical coronary events in patients with CAE. The increased plasma concentrations of α1-AT, α2-PI, and α2-MG might provide beneficial effects by inhibiting the proteinases and restraining the ectatic process; on other hand, they led to unfavorable results by inhibiting plasmin and decreasing thrombus degradation in CAE patients.

Objective: Proteolytic enzymes possibly contribute to coronary artery ectasia (CAE). This study aimed to determine whether neutrophils, neutrophil serine proteases (NSPs), and their endogenous inhibitors participated in the pathological process of CAE., Methods: The study consisted of 30 patients with CAE, 30 patients with coronary artery disease (CAD), and 29 subjects with normal coronary arteries (Control). The following circulating items were measured: the main NSPs, including human neutrophil elastase (HNE), cathepsin G (CG), and proteinase 3 (PR3); soluble elastin (sElastin), which was a degradation product of elastin fibres; NSP inhibitors such as α1-protease inhibitor (α1-PI), α2-macroglobulin (α2-MG), secretory leucoprotease inhibitor (SLPI), and elafin; as well as two neutrophil activation markers (myeloperoxidase and lactoferrin) and three classic neutrophil activators [tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), and bacterial endotoxin]., Results: The levels of HNE, CG, and sElastin were elevated in the CAE group. The levels of α1-PI and α2-MG were also significantly increased in the CAE group. The levels of myeloperoxidase and lactoferrin were higher in the CAE group. The levels of TNF-α, IL-8, and endotoxin were unchanged in the CAE group compared with those in the CAD group., Conclusion: Neutrophils may participate in the process of vessel extracellular matrix destruction and coronary ectasia by releasing NSPs in a non-classical manner.

Objective: It was recently reported that chemokine CC-motif ligand 17 (CCL17)-expressing dendritic cells drove atherosclerosis by restraining regulatory T cell homeostasis in an animal model. Our preliminary study has shown that serum CCL17 levels may be associated with coronary artery disease (CAD). The aim of this study was to confirm the relationship between serum CCL17 levels and CAD., Methods: Patients presenting to our center for coronary angiography between January 2013 and December 2013 were recruited for the study. Serum CCL17 levels were determined by enzyme-linked immunosorbent assay. Atherosclerosis severity was assessed in each patient according to the Gensini score., Results: In total, 971 consecutive patients were enrolled in this study, including 158 non-CAD patients and 813 CAD patients (238 with stable angina pectoris, 321 with unstable angina, 128 with non-ST elevation myocardial infarction, and 126 with ST elevation myocardial infarction). CAD patients had higher serum CCL17 levels compared to patients without CAD [265.90 (170.80-376.65) pg/mL versus 218.35 (142.83-293.45) pg/mL, p < 0.001]. After adjusting for traditional risk factors, serum CCL17 levels remained associated with CAD. Meanwhile, there was a significant linear trend between serum CCL17 levels and the different CAD subtypes (p for linear trend = 0.002). Finally, serum CCL17 levels (per 100 pg/mL) were positively associated with the Gensini score (B 2.310; 95% CI 0.503-4.118; p = 0.012) even after adjusting for confounding factors., Conclusion: Serum CCL17 levels are associated with CAD and atherosclerosis severity independently of traditional cardiovascular risk factors., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Aims: To assess the relationship between mutations of the myocyte enhancer factor 2A (MEF2A) and premature coronary artery disease (PCAD) in a Chinese population., Methods and Results: The mutations in the exons 8 and 12 of the MEF2A gene were analyzed in both PCAD families and sporadic cases using direct sequencing of polymerase chain reaction products. In one PCAD family, seven members of the third generation were all diagnosed with CAD, and five of them had PCAD. All five members with PCAD displayed a mutation of the TT genotype in the site of 1353 G/T. Moreover, three of them (3/5) had a mutation of the DW genotype in the site of 1291-1293 CCG W/D. In sporadic cases, we also found that the haplotype of 1291-1293 CCG D+1305 G+1353 T was significantly associated with PCAD., Conclusions: The mutations of MEF2A exon 12 are implicated in PCAD, suggesting a strong genetic component in the pathogenesis of PCAD in the Chinese population.

Percutaneous coronary intervention is widely applied for the treatment of coronary artery disease under the guidance of X-ray coronary angiography (XCA) image. However, the projective nature of XCA causes the loss of 3D structural information, which hinders the intervention. This issue can be addressed by the deformable 3D/2D coronary artery registration technique, which fuses the pre-operative computed tomography angiography volume with the intra-operative XCA image. In this study, we propose a deep learning-based neural network for this task. The registration is conducted in a segment-by-segment manner. For each vessel segment pair, the centerlines that preserve topological information are decomposed into an origin tensor and a spherical coordinate shape tensor as network input through independent branches. Features of different modalities are fused and processed for predicting angular deflections, which is a special type of deformation field implying motion and length preservation constraints for vessel segments. The proposed method achieves an average error of 1.13 mm on the clinical dataset, which shows the potential to be applied in clinical practice. [ABSTRACT FROM AUTHOR]

Objective: We performed a network meta-analysis to investigate the optimal antithrombotic regime by indirectly comparing new antithrombotic regimes (new P2Y12 inhibitors plus aspirin or novel oral anticoagulants on top of traditional dual antiplatelet therapy [DAPT]) in patients with acute coronary syndrome (ACS). Methods: A systematic search of MEDLINE, EMBASE, and the Cochrane databases was performed to identify all phase 3 randomized controlled trials (RCTs) involving novel oral anticoagulants or oral P2Y12 inhibitors in patients with ACS. Major adverse cardiac events (MACE) were regarded as the efficacy endpoint, and thrombolysis in myocardial infarction (TIMI) major bleeding events were used as the safety endpoint. The net clinical benefit was calculated as the sum of MACE and TIMI major bleeding events. Results: Five phase 3 RCTs with 64,476 ACS patients were included. Although there were no significant differences among new antithrombotic regimes, rivaroxaban 5 mg twice daily plus traditional DAPT might be the most effective in reducing the incidence of MACE, accompanying the highest risk of TIMI major bleeding. Ticagrelor plus aspirin presented slight advantage on the net clinical benefit over other new antithrombotic regimes, with the highest probability of being the best regimes for net clinical benefit (35.0%), followed by prasugrel plus aspirin (28.0%), and rivaroxaban 2.5 mg twice daily plus traditional DAPT (19.5%). Conclusion: Novel antithrombotic regime with ticagrelor plus aspirin brings a larger clinical benefit in comparison with other regimes, suggesting that it may be the optimal antithrombotic regime for patients with ACS. [ABSTRACT FROM AUTHOR]