Correlation Between Serum Uric Acid Levels and Coronary Plaque Characteristics on Optical Coherence Tomography.

Elevated serum uric acid (sUA) is associated with increasing risk of coronary heart disease (CHD). However, existing research is limited by potential confounders. Herein, our study aims to probe the association between sUA levels and the morphological characteristics of coronary plaque by a propensity score matching (PSM) analysis.All 420 patients with CHD who had undergone optical coherence tomography of culprit lesions were included. Eligible patients were assigned into 2 groups according to sUA level: high-sUA group (sUA ≥ 6.0 mg/dL) and low-sUA group (sUA < 6.0 mg/dL). PSM was applied to control the balance of baseline characteristics.After PSM, a total of 112 patients were included in our study (56 in each group). The high-sUA group showed a higher prevalence of TCFA (35.7% versus 16.1%, P = 0.03) and macrophage infiltration (33.9% versus 14.3%, P = 0.026) compared with the low-sUA group. Plaques in the high-sUA group had a wider maximum lipid arc (166.51° (115.77°, 224.14°) versus 142.29° (93.95°, 169.06°), P = 0.048), longer calcification length (6.77 (3.90, 20.55) mm versus 4.20 (1.95, 7.45) mm, P = 0.040), and thinner minimum fibrous cap thickness (43.81 (28.17, 62.26) µm versus 92.57 (46.25, 135.37) µm, P = 0.003). Correlation analysis indicated that the sUA value was inversely associated with the minimum fibrous cap thickness (r = -0.332, P = 0.015) and positively associated with the maximum lipid arc (r = 0.399, P = 0.003), average lipid arc (r = 0.347, P = 0.011), and calcification length (r = 0.386, P = 0.006).The relationship between high-sUA levels and typical vulnerable features of plaques persisted after balancing the traditional risk factors.

Morphological and Physiological Characteristics of Ruptured Plaques in Native Arteries and Neoatherosclerotic Segments: An OCT-Based and Computational Fluid Dynamics Study.

Background: Intravascular imaging has been used to assess the morphology of lesions causing an acute coronary syndrome (ACS) in native vessels (NV) and identify differences between plaques that ruptured (PR) and caused an event and those that ruptured without clinical manifestations. However, there is no data about the morphological and physiological characteristics of neoatherosclerotic plaques that ruptured (PR-NA) which constitute a common cause of stent failure. Methods: We retrospectively analyzed data from patients admitted with an acute myocardial infarction that had optical coherence tomography (OCT) imaging of the culprit vessel before balloon pre-dilation. OCT pullbacks showing PR were segmented at every 0.4 mm. The extent of the formed cavity, lipid and calcific tissue, thrombus, and macrophages were measured, and the fibrous cap thickness (FCT) and the incidence of micro-channels and cholesterol crystals were reported. These data were used to reconstruct a representative model of the native and neoatherosclerotic lesion geometry that was processed with computational fluid dynamics (CFD) techniques to estimate the distribution of the endothelial shear stress and plaque structural stress. Result: Eighty patients were included in the present analysis: 56 had PR in NV (PR-NV group) and 24 in NA segments (PR-NA group). The PR-NV group had a larger minimum lumen area (2.93 ± 2.03 vs. 2.00 ± 1.26 mm2, p = 0.015) but similar lesion length and area stenosis compared to PR-NA group. The mean FCT (186 ± 65 vs. 232 ± 80 µm, p = 0.009) and the lipid index was smaller (16.7 ± 13.8 vs. 25.9 ± 14.1, p = 0.008) while the of calcific index (8.3 ± 9.5 vs. 2.2 ± 1.6%, p = 0.002) and the incidence of micro-channels (41.4 vs. 12.5%, p = 0.013) was higher in the PR-NV group. Conversely, there was no difference in the incidence of cholesterol crystals, thrombus burden or the location of the rupture site between groups. CFD analysis revealed higher maximum endothelial shear stress (19.1 vs. 11.0 Pa) and lower maximum plaque structural stress (38.8 vs. 95.1 kPa) in the PR-NA compared to the PR-NV model. Conclusion: We reported significant morphological and physiological differences between culprit ruptured plaques in native and stented segments. Further research is needed to better understand the causes of these differences and the mechanisms regulating neoatherosclerotic lesion destabilization.

Comparison of diagnostic accuracy of immediate angiography derived residual quantitative flow ratio after bioresorbable scaffold and drug eluting stent implantation.

BACKGROUND: Quantitative flow ratio (QFR) is a novel angiography derived fractional flow reserve (FFR) technique. However, its diagnostic accuracy has only be validated in native coronary lesions but not in vessels after bioresorbable scaffold (BRS) implantation. This study aims to evaluate the diagnostic accuracy of residual QFR in coronary vessels immediately post-BRS implantation. METHODS: This is a retrospective, two center, validation cohort study. 73 stable angina patients who received at least one de novo lesion of an everolimus eluting stent (EES)/BRS implantation with subsequent residual FFR assessment were screened. Patients with aorta-ostial stenoses, bridge vessels at the distal segment of targeted vessels, acute coronary syndrome, previous coronary artery bypass grafting, age <18 years, lack of ≥2 final angiographic projections were excluded. Contrast QFR assessment was performed blinded to FFR assessment. RESULTS: A good correlation (r = 0.680, p < 0.001) was found between residual QFR and FFR. In the EES implantation cohort, a good correlation (r = 0.769, p < 0.001) was found between residual QFR and FFR, and a moderate correlation (r = 0.446, p = 0.038) in the BRS cohort. The area under the Receiver operator characteristic (ROC) curve for detecting FFR ≤0.86 was 0.883 for all patients. CONCLUSION: Residual QFR assessment after BRS implantation is feasible, and has a moderate correlation and agreement with residual FFR. QFR may be a promising tool similar to FFR to evaluate post-BRS effect.

Effects of Metoprolol on Periprocedural Myocardial Infarction After Percutaneous Coronary Intervention (Type 4a MI): An Inverse Probability of Treatment Weighting Analysis.

Background: Metoprolol is the most used cardiac selective ß-blocker and has been recommended as a mainstay drug in the management of acute myocardial infarction (AMI). However, the evidence supporting this regimen in periprocedural myocardial infarction (PMI) is limited. Methods: This study identified 860 individuals who suffered PMI following percutaneous coronary intervention (PCI) procedure and median followed up for 3.2 years. Subjects were dichotomized according to whether they received chronic oral sustained-release metoprolol succinate following PMI. After inverse probability of treatment weighting (IPTW) adjustment, logistic regression analysis, Kaplan-Meier curve, and Cox regression analysis were performed to estimate the effects of metoprolol on major adverse cardiovascular events (MACEs) which composed of cardiac death, myocardial infarction (MI), stroke, and revascularization. Moreover, an exploratory analysis was performed according to hypertension, cardiac troponin I (cTnI) elevation, and cardiac function. A double robust adjustment was used for sensitivity analysis. Results: Among enrolled PMI subjects, 456 (53%) patients received metoprolol treatment and 404 (47%) patients received observation. After IPTW adjustment, receiving metoprolol was found to reduce the subsequent 3-year risk of MACEs by nearly 7.1% [15 vs. 22.1%, absolute risk difference (ARD) = 0.07, number needed to treat (NNT) = 14, relative risk (RR) = 0.682]. In IPTW-adjusted Cox regression analyses, receiving metoprolol was related to a reduced risk of MACEs (hazard ratio [HR] = 0.588, 95%CI [0.385-0.898], P = 0.014) and revascularization (HR = 0.538, 95%CI [0.326-0.89], P = 0.016). Additionally, IPTW-adjusted logistic regression analysis showed that receiving metoprolol reduced the risk of MI at the third year (odds ratio [OR] = 0.972, 95% CI [0.948-997], P = 0.029). Exploratory analysis showed that the protective effect of metoprolol was more pronounced in subgroups of hypertension and cTnI elevation ≥1,000%, and was remained in patients without cardiac dysfunction. The benefits above were consistent when double robust adjustments were performed. Conclusion: In the real-world setting, receiving metoprolol treatment following PCI-related PMI has decreased the subsequent risk of MACEs, particularly the risk of recurrent MI and revascularization.

Diagnostic accuracy of quantitative flow ratio (QFR) and vessel fractional flow reserve (vFFR) estimated retrospectively by conventional radiation saving X-ray angiography.

BACKGROUND: Angiography derived FFR reveals good performance in assessing intermediate coronary stenosis. However, its performance under contemporary low X-ray frame and pulse rate settings is unknown. We aim to validate the feasibility and performance of quantitative flow ratio (QFR) and vessel fractional flow reserve (vFFR) under such angiograms. METHODS: This was an observational, retrospective, single center cohort study. 134 vessels in 102 patients, with angiograms acquired under 7.5fps and 7pps mode, were enrolled. QFR (fQFR and cQFR) and vFFR were validated with FFR as the gold standard. A conventional manual and a newly developed algorithmic exclusion method (M and A group) were both evaluated for identification of poor-quality angiograms. RESULTS: Good agreement between QFR/vFFR and FFR were observed in both M and A group, except for vFFR in the M group. The correlation coefficients between fQFR/cQFR/vFFR and FFR were 0.6242, 0.5888, 0.4089 in the M group, with rvFFR significantly lower than rfQFR (p = 0.0303), and 0.7055, 0.6793, 0.5664 in the A group, respectively. AUCs of detecting lesions with FFR ≤ 0.80 were 0.852 (95% CI 0.722-0.913), 0.858 (95% CI 0.778-0.917), 0.682 (95% CI 0.586-0.768), for fQFR/cQFR/vFFR in the M group, while vFFR performed poorer than fQFR (p = 0.0063) and cQFR (p = 0.0054). AUCs were 0.898 (95% CI 0.811-0.945), 0.892 (95% CI 0.803-0.949), 0.843 (95% CI 0.746-0.914) for fQFR/cQFR/vFFR in the A group. AUCvFFR was significantly higher in the A group than that in the M group (p = 0.0399). CONCLUSIONS: QFR/vFFR assessment is feasible under 7.5fps and 7pps angiography, where cQFR showed no advantage compared to fQFR. Our newly developed algorithmic exclusion method could be a better method of selecting angiograms with adequate quality for angiography derived FFR assessment.

Effect of Shexiang Tongxin dropping pill on stable coronary artery disease patients with normal fractional flow reserve and coronary microvascular disease: A study protocol.

INTRODUCTION: Coronary microvascular disease (CMVD) can affect the structure, function, and metabolism of the heart, and has an important impact on the occurrence, development and prognosis of coronary artery disease (CAD). Shexiang Tongxin dropping pill (STDP) can dilate blood vessels, alleviate inflammation, reduce endothelial damage, and improve coronary microvascular function in mice with myocardial infarction. This study aims to assess the impact of STDP on stable coronary artery disease (SCAD) patients with normal FFR and CMVD. METHODS AND ANALYSIS: This is a single-center, prospective randomized trial that will enroll 64 SCAD patients, CAD with normal FFR and CMVD. Patients will be randomly divided into study group and control group in a 1:1 fashion. On the basis of conventional drug treatment, the former will receive STDP while the latter will not. The follow-up period of the subjects is 12 months, and clinical follow-up will be conducted before discharge, 30 days, 3 months, 6 months, and 12 months after procedure to complete the detection of relevant indicators. The primary endpoint is the change of index of microcirculatory resistance (ΔIMR) at 12-month follow-up. DISCUSSION: The present study will be the first randomized control study to evaluate the efficacy and safety of STDP on SCAD patients, CAD with normal FFR and CMVD, which will provide a broader idea and more experimental basis for improving the treatment of CMVD. TRIAL REGISTRATION: This is a protocol for the randomized clinical trial which has been registered in the Chinese clinical Trial Registry with an identifier: ChiCTR2000032429.

Effects of trimetazidine on ventricular remodeling in coronary artery disease patients with left ventricular hypertrophy: the rationale and design of a randomized controlled trial.

BACKGROUND: Trimetazidine is a metabolic anti-ischemic agent, which increases the tolerance of cardiomyocytes to ischemia. However, few studies have explored the effect of trimetazidine on ventricular remodeling in coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI) with left ventricular hypertrophy (LVH). METHODS: It is a randomized, placebo-controlled trial, and we propose to recruit one hundred and twenty-four CAD patients undergoing PCI with LVH during a 12-month period. They will be randomized to receive either trimetazidine (35 mg twice a day) or placebo in the following 12 months after PCI. Blood tests, echocardiography, symptom of angina and major adverse cardiovascular events (MACEs) will be collected at follow-up visit at 3 and 12 months. The primary end point will be the left ventricular remodeling measured by left ventricular mass index (LVMI) at 3- and 12-month follow-up compared with the baseline. The secondary end points will be the symptom of angina assessed by Seattle Angina Questionnaire, myocardial ischemia measured by 6-min walk test and exercise electrocardiography test, as well as MACEs (defined as a composite of death, myocardial infarction, stroke, recurrent angina, re-hospitalization, change of viable myocardium). DISCUSSION: This study aims to demonstrate the effect of trimetazidine on left ventricular remodeling and myocardial ischemia in CAD patients undergoing PCI with LVH. Trimetazidine treatment is likely to improve the left ventricular remodeling, symptoms of angina and myocardial ischemia. It might also reduce the risk of MACEs in CAD patients undergoing PCI with LVH. TRIAL REGISTRATION: http://www.chictr.org.cn, Chinese Clinical Trial Registry (ChiCTR1800017876). Registered on 19 Aug 2018.

Computerised Methodologies for Non-Invasive Angiography-Derived Fractional Flow Reserve Assessment: A Critical Review.

Fractional flow reserve is the gold standard for assessing the haemodynamic significance of intermediate coronary artery stenoses. Cumulative evidence has shown that FFR-guided revascularisation reduces stent implantations and improves patient outcomes. However, despite the wealth of evidence and guideline recommendations, its use in clinical practice remains minimal. Patient and technical limitations of FFR as well as the need for intracoronary instrumentation, use of adenosine, and increased costs have limited FFR's applicability in clinical practice. Over the last decade, several angiography-derived FFR software packages have been developed which do not require intracoronary pressure assessment with a guidewire or need for administration of hyperaemic agents. At present, there are 3 commercially available software packages and several other non-commercial technologies that have been described in the literature. These technologies have been validated against invasive FFR showing good accuracy and correlation. However, the methodology behind these solutions is different-some algorithms are based on solving the governing equations of fluid dynamics such as the Navier-Stokes equation while others have opted for a more simplified mathematical formula approach. The aim of this review is to critically appraise the methodology behind all the known angiography-derived FFR technologies highlighting the key differences and limitations.

Predictive value of the QFR in detecting vulnerable plaques in non-flow limiting lesions: a combined analysis of the PROSPECT and IBIS-4 study.

Studies have shown that the quantitative flow ratio (QFR), recently introduced to assess lesion severity from coronary angiography, provides useful prognostic information; however the additive value of this technique over intravascular imaging in detecting lesions that are likely to cause events is yet unclear. We analysed data acquired in the PROSPECT and IBIS-4 studies, in particular the baseline virtual histology-intravascular ultrasound (VH-IVUS) and angiographic data from 17 non-culprit lesions with a presumable vulnerable phenotype (i.e., thin or thick cap fibroatheroma) that caused major adverse cardiac events or required revascularization (MACE) at 5-year follow-up and from a group of 78 vulnerable plaques that remained quiescent. The segments studied by VH-IVUS were identified in coronary angiography and the QFR was estimated. The additive value of 3-dimensional quantitative coronary angiography (3D-QCA) and of the QFR in predicting MACE at 5 year follow-up beyond plaque characteristics was examined. It was found that MACE lesions had a greater plaque burden (PB) and smaller minimum lumen area (MLA) on VH-IVUS, a longer length and a smaller minimum lumen diameter (MLD) on 3D-QCA and a lower QFR compared with lesions that remained quiescent. By univariate analysis MLA, PB, MLD, lesion length on 3D-QCA and QFR were predictors of MACE. In multivariate analysis a low but normal QFR (> 0.80 to < 0.97) was the only independent prediction of MACE (HR 3.53, 95% CI 1.16-10.75; P = 0.027). In non-flow limiting lesions with a vulnerable phenotype, QFR may provide additional prognostic information beyond plaque morphology for predicting MACE throughout 5 years.

Identification of differentially expressed genes in the endothelial precursor cells of patients with type 2 diabetes mellitus by bioinformatics analysis.

Type 2 diabetes mellitus (DM) is a metabolic disease with worldwide prevalence that is associated with a decrease in the number and function of endothelial progenitor cells (EPCs). The aim of the present study was to explore the potential hub genes of EPCs in patients with type 2 DM. Differentially expressed genes (DEGs) were screened from a public microarray dataset (accession no. GSE43950). Pathway and functional enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery. The protein-protein interaction (PPI) network was visualized. The most significantly clustered modules and hub genes were identified using Cytoscape. Furthermore, hub genes were validated by quantitative PCR analysis of EPCs isolated from diabetic and normal subjects. Subsequently, weighted gene co-expression network analysis (WGCNA) was performed to identify the modules incorporating the genes exhibiting the most significant variance. A total of 970 DEGs were obtained and they were mainly accumulated in inflammation-associated pathways. A total of 9 hub genes were extracted from the PPI network and the highest differential expression was determined for the interleukin 8 (IL8) and CXC chemokine ligand 1 (CXCL1) genes. In the WGCNA performed to determine the modules associated with type 2 DM, one module incorporated IL8 and CXCL1. Finally, pathway enrichment of 10% genes in the pink module ordered by intramodular connectivity (IC) was associated with the IL17 and the chemokine signaling pathways. The present results revealed that the expression of IL8 and CXCL1 may serve important roles in the pathophysiology of EPCs during type 2 DM and inflammatory response may be critical for the reduced number and hypofunction of EPCs isolated from patients with diabetes.

Optical coherence tomography enables more accurate detection of functionally significant intermediate non-left main coronary artery stenoses than intravascular ultrasound: A meta-analysis of 6919 patients and 7537 lesions.

OBJECTIVE: Fractional flow reserve (FFR) is regarded as the gold standard for the physiological assessment of intermediate coronary artery stenoses. However, FFR does not allow assessment of plaque morphology and lesion geometry. Intracoronary imaging techniques such as intravascular ultrasound (IVUS) and optical coherence tomography (OCT) can help treatment planning by optimising stent implantation, which can improve patient outcomes. The aim of this meta-analysis is to compare the efficacy of IVUS and OCT-derived metrics in detecting flow limiting stenoses in non-left main stem lesions. METHODS: A systematic review of PubMed, Medline, and Cochrane databases was performed and identified studies examining the diagnostic accuracy of IVUS and OCT in detecting significant stenoses when compared to FFR. RESULTS: A total of 33 (7537 lesions) studies (24 IVUS, 7 OCT and 2 IVUS & OCT studies) were included in the meta-analysis. Pooled analysis showed that IVUS- and OCT-derived minimum lumen area (MLA) had a similar sensitivity in predicting haemodynamically significant lesions (IVUS-MLA: 0.747 vs OCT-MLA 0.732, p = 0.519). However, OCT-MLA had a higher specificity (0.763 vs 0.665, p < 0.001) and diagnostic accuracy in detecting flow-limiting stenoses than IVUS-MLA (AUC 0.810 vs 0.754, p = 0.045). Sub-analysis of the studies with the clinically significant FFR cut-off value of 0.80 yielded similar results demonstrating that OCT-MLA has a better accuracy than IVUS-MLA in detecting haemodynamically significant stenoses (AUC 0.809 vs 0.750, p = 0.034). CONCLUSIONS: OCT with its superior image resolution appears to be the preferable intravascular imaging modality for the detection of haemodynamically significant stenoses in non-left main stem lesions.

Efficacy and Reproducibility of Attenuation-Compensated Optical Coherence Tomography for Assessing External Elastic Membrane Border and Plaque Composition in Native and Stented Segments　- An In Vivo and Histology-Based Study.

BACKGROUND: Attenuation-compensated (AC) technique was recently introduced to improve the plaque characterization of optical coherence tomography (OCT). Histological validation demonstrated promising results but the efficacy and reproducibility of this technique for assessing in-vivo tissue composition remains unclear.Methods and Results:OCT images portraying native (n=200) and stented (n=200) segments and 31 histological cross-sections were analyzed. AC-OCT appeared superior to conventional (C)-OCT in detecting the external elastic lamina (EEM) borders (76% vs. 65.5%); AC-OCT enabled larger EEM arc detection compared with C-OCT (174.2±58.7° vs. 137.5±57.9°; P<0.001). There was poor agreement between the 2 techniques for detection of lipid in native and lipid and calcific tissue in stented segments (κ range: 0.164-0.466) but the agreement of C-OCT and AC-OCT was high for calcific tissue in native segments (κ=0.825). Intra and interobserver agreement of the 2 analysts was moderate to excellent with C-OCT (κ range: 0.681-0.979) and AC-OCT (κ range: 0.733-0.892) for all tissue types in both native and stented segments. Ex-vivoanalysis demonstrated that C-OCT was superior to AC-OCT (κ=0.545 vs. κ=0.296) for the detection of the lipid component in native segments. CONCLUSIONS: The AC technique allows better delineation of the EEM but it remains inferior for lipid pool detection and neointima characterization. Combined AC- and C-OCT imaging may provide additional value for complete assessment of plaque and neointima characteristics.

Theaflavin 3,3'-digallate reverses the downregulation of connexin 43 and autophagy induced by high glucose via AMPK activation in cardiomyocytes.

Theaflavin 3,3'-digallate (TF3), is reported to protect cardiomyocytes from lipotoxicity and reperfusion injury. However, the role of TF3 in the protection of high-glucose injury is still poorly understood. This study investigated the protective effects of TF3 on gap junctions and autophagy in neonatal cardiomyocytes (NRCMs). NRCMs preincubated with high glucose were coincubated with TF3. The expression of connexins and autophagy-related proteins was determined. The functioning of gap-junctional intercellular communication (GJIC) was measured by a dye transfer assay. Adenosine monophosphate-activated protein kinase (AMPK) activity was determined by western blot. Moreover, AMPK was activated with aminoimidazole-4-carboxamide-1-ß-d-ribofuranoside (AICAR) or inhibited by AMPKα small interfering RNA (siRNA) to explore the role of AMPK in the modulation of connexin 43 (Cx43) and autophagy. Meanwhile, autophagy was activated or blocked to observe the change in Cx43 expression. It was found that the protein expression of Cx43 and autophagy-related proteins was increased in a TF3 dose- and time-dependent manner under high glucose. TF3 also recovered the reduced GJIC function induced by high glucose concentrations. TF3 activated phosphorylated AMPK in a time-dependent way. AMPKα siRNA abrogated the protection of TF3, while AICAR showed similar results compared to the TF3 treatment. Meanwhile, autophagy activation caused decreased Cx43, while cotreatment with baf A1 enhanced Cx43 expression further compared with the TF3 treatment alone under high glucose. We concluded that TF3 partly reversed the inhibition of Cx43 expression and autophagy induced by high glucose in NRCMs, partly by restoring AMPK activity. Inhibition of autophagy might be protective by preserving Cx43 expression in NRCMs stimulated by high glucose.

Green Tea Polyphenol Epigallocatechin-3-Gallate Promotes Reendothelialization in Carotid Artery of Diabetic Rabbits by Reactivating Akt/eNOS Pathway.

Background: Epigallocatechin gallate (EGCG) is the most abundant catechin in green tea and has proven benefits on endothelial cells in diabetes. However, it remains unclear whether EGCG could improve function of late endothelial progenitor cells (L-EPCs) in diabetes. Methods: Thirty-six rabbits were randomized into six groups. Thirty diabetic rabbits were induced by a single dose of alloxan (100 mg/kg injection intraperitoneally). All of them were given intragastrically EGCG (50 mg/kg/day) or saline for 7 days after carotid injury. In autotransfusion experiment, L-EPCs were cultured with pre-treated EGCG (40 µM for 72 h) and then were injected into the site of injured vascular. Proliferation and migration of EGCG pre-treated L-EPCs in high glucose condition were assessed by EDU incorporation assay and modified Boyden chamber assay, respectively. The mRNA and protein expression of Akt-eNOS pathway were detected by real-time PCR and western blot. Results: Reendothelialization rate in injured carotid artery of diabetic rabbits was augmented in the EGCG group (50 mg/kg/d for 7 days) compared with the non-EGCG group (74.2 ± 4.6% vs. 25.6 ± 5.9%, P < 0.001). EGCG pre-treated L-EPCs autologous transfusion also accelerated the diabetic rabbits' carotid reendothelialization compared with the diabetic sham-operated group (65.6 ± 8.5% vs. 32.9 ± 5.0%, P = 0.011). In vitro studies showed, 40 µM EGCG treatment for 72 h recovered L-EPCs' proliferation and migration, as well as restored the phosphorylation level of Akt and eNOS blocked by high glucose condition. Conclusion: EGCG accelerated reendothelialization in diabetic rabbits after carotid injury in part by reactivating the Akt/eNOS pathway, which might contribute to recovering proliferation and migration of L-EPCs impaired by high glucose.

Effect of Breviscapine on Recovery of Viable Myocardium and Left Ventricular Remodeling in Chronic Total Occlusion Patients After Revascularization: Rationale and Design for a Randomized Controlled Trial.

BACKGROUND How to speed the recovery of viable myocardium in chronic total occlusion (CTO) patients after revascularization is still an unsolved problem. Breviscapine is widely used in cardiovascular diseases. However, there has been no study focused on the effect of breviscapine on viable myocardium recovery and left ventricular remodeling after CTO revascularization. MATERIAL AND METHODS We propose to recruit 78 consecutive coronary artery disease (CAD) patients with CTO during a period of 12 months. They will be randomly assigned to receive either breviscapine (40 mg) or placebo in the following 12 months. Blood tests, electrocardiogram, and Major Adverse Cardiac Events (MACE) will be collected at baseline and the follow-up visits at 1, 3, 6, 9, and 12 months. Low-dose dobutamine MRI will be applied for the assessment of viable myocardium, microcirculation perfusion, and left ventricular remodeling, and the concentrations of angiogenic cytokine, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) will be investigated at baseline and at 1- and 12-month follow-up. The recovery of viable myocardium after revascularization in CTO patients was the primary endpoint. Improvement of microcirculation perfusion, left ventricular remodeling, peripheral concentrations of VEGF and bFGF as well as MACE will be the secondary endpoints. RESULTS Breviscapine treatment obviously improve the recovery of viable myocardium, myocardial microcirculation perfusion, and left ventricular remodeling after revascularization in CTO patients, and reduce the occurrence of MACE. We also will determine if breviscapine increases the peripheral blood angiogenic cytokine concentrations of VEGF and bFGF. CONCLUSIONS This study will aim to demonstrate the effect of breviscapine on the recovery of viable myocardium and left ventricular remodeling in CTO patients after revascularization.

A Randomized Trial Comparing the NeoVas Sirolimus-Eluting Bioresorbable Scaffold and Metallic Everolimus-Eluting Stents.

OBJECTIVES: The authors sought to evaluate the safety and effectiveness of the NeoVas bioresorbable scaffold (BRS) compared with metallic drug-eluting stents. BACKGROUND: BRS have the potential to improve very late outcomes compared with metallic drug-eluting stents, but some BRS have been associated with increased rates of device thrombosis before complete bioresorption. NeoVas is a new poly-l-lactic acid BRS that elutes sirolimus from a poly-D, l-lactide coating. METHODS: Eligible patients with a single de novo native coronary artery lesion with a reference vessel diameter 2.5 to 3.75 mm and a lesion length ≤20 mm were randomized 1:1 to NeoVas BRS versus cobalt-chromium everolimus-eluting stents (CoCr-EES). Angiographic follow-up was performed in all patients at 1 year. The primary endpoint was angiographic in-segment late loss (LL), and the major secondary endpoint was the rate of angina. Baseline and follow-up optical coherence tomography and fractional flow reserve were performed in a pre-specified subgroup of patients. RESULTS: The authors randomized 560 patients at 32 centers to treatment with NeoVas (n = 278) versus CoCr-EES (n = 282). One-year in-segment LL with NeoVas and CoCr-EES were 0.14 ± 0.36 mm versus 0.11 ± 0.34 mm (difference 0.03 mm; upper 1-sided 97.5% confidence interval 0.09 mm; pnoninferiority < 0.0001; psuperiority = 0.36). Clinical outcomes at 1 year were similar in the 2 groups, as were the rates of recurrent angina (27.9% vs. 32.1%; p = 0.26). Optical coherence tomography at 1 year demonstrated a higher proportion of covered struts (98.7% vs. 96.2%; p < 0.001), less strut malapposition (0% vs. 0.6%; p <0.001), and a smaller minimal lumen area (4.71 ± 1.64 vs. 6.00 ± 2.15 mm2; p < 0.001) with NeoVas compared with CoCr-EES respectively, with nonsignificant differences in fractional flow reserve (0.89 ± 0.08 vs. 0.91 ± 0.06; p = 0.07). CONCLUSIONS: The NeoVas BRS was noninferior to CoCr-EES for the primary endpoint of 1-year angiographic in-segment LL, and resulted in comparable 1-year clinical outcomes, including recurrent angina. (NeoVas Bioresorbable Coronary Scaffold Randomized Controlled Trial; NCT02305485).

PKC/NADPH oxidase are involved in the protective effect of pioglitazone in high homocysteine-induced paracrine dyfunction in endothelial progenitor cells.

Increasing evidence suggests that EPCs improve neovascularization and endothelial regeneration via the production of paracrine factors. VEGF and IL-8 are major cytokines involved in EPC-mediated angiogenesis and re-endothelialization. In our previous studies, Hcy impaired EPC migratory and adhesive activities. We devised this study to determine whether Hcy could affect the expression and secretion of VEGF and IL-8 from EPCs. We found that high levels of Hcy (100-500 µM) decreased the EPC-mediated protein secretion and mRNA expression of VEGF and IL-8. Moreover, PIO, a PPARγ agonist, has been suggested to regulate EPC adhesion, migration, survival. In this study, PIO normalized the production of these cytokines by EPCs stimulated with Hcy. These effects of Hcy and PIO were primarily mediated by PKC and ROS via NADPH oxidase. We further confirmed this mechanism via knockdown of the NADPH oxidase subunits p67phox and Nox2. Furthermore, the PPARγ inhibitor GW9662 was not observed to abrogate the beneficial effect of PIO, indicating that PIO protected EPC paracrine function against Hcy in a PPARγ-independent manner.

Clinical and multimodality imaging results at 6 months of a bioresorbable sirolimus-eluting scaffold for patients with single de novo coronary artery lesions: the NeoVas first-in-man trial.

AIMS: The study sought to investigate clinical and multimodality imaging assessment of a bioresorbable sirolimus-eluting scaffold (NeoVas, Lepu Medical, Beijing, China) for patients with single de novo coronary artery lesions. METHODS AND RESULTS: The NeoVas first-in-man study was a prospective, open-label study which enrolled 31 patients with single de novo lesions treated with a bioresorbable sirolimus-eluting scaffold. The primary endpoint was target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction and clinically indicated target lesion revascularisation (TLR). Angiography, intravascular ultrasound (IVUS) and optical coherence tomography (OCT) imaging were performed at baseline and six months. Procedural success and device success were 100% (31/31 patients). At six months, the rate of TLF was 3.2%, with only one patient having clinically indicated TLR. No scaffold thrombosis was observed. The angiographic six-month in-scaffold late loss was 0.26±0.32 mm. The minimal scaffold area decreased from 7.11±1.56 mm2 post procedure to 6.74±1.38 mm2 at six months, as measured by IVUS. The OCT results showed that the neointimal hyperplasia area was low (1.56±0.46 mm2), with a high proportion of scaffold strut coverage (95.7%). CONCLUSIONS: This first-in-man study shows feasibility, promising clinical and multimodality imaging results up to six months for the NeoVas bioresorbable sirolimus-eluting scaffold in the treatment of patients with simple de novo lesions, with an acceptable in-scaffold late loss, low neointimal hyperplasia, and a high percentage of scaffold strut coverage.

The Impact of Rosuvastatin on the Density Score of Coronary Artery Calcification in Coronary Artery Disease Patients with Type 2 Diabetes Mellitus: Rationale and Design of RosCal Study.

INTRODUCTION: More and more evidence suggests that the density of calcification plays an important role in the plaque stability. However, few studies have investigated the statin treatment on the density of plaque calcification in patients with both coronary artery disease (CAD) and type 2 diabetes mellitus. METHODS: One hundred and twenty-two CAD patients with type 2 diabetes with confirmed coronary artery calcification (CAC) will be recruited consecutively in a 12-month period. These patients will receive rosuvastatin (20 mg/day) therapy in the next 24 months. Blood tests and adverse events will be collected at routine follow-up of 1, 3, 6, 12, 18 and 24 months. The primary endpoint will be the change of CAC density score measured by coronary CT angiography after 24 months' treatment of rosuvastatin (20 mg/day) compared with baseline. The secondary endpoints will be the change of serum sclerostin and the effect on the volume score of CAC in those patients. RESULTS: We expect that rosuvastatin could both increase the density of CAC to improve plaque stability and up-regulate serum sclerostin, which would suggest the underlying mechanism of the plaque stabilization by a statin. CONCLUSION: This study would be the first to demonstrate the impact of rosuvastatin on the density score of coronary artery calcification in CAD patients with type 2 diabetes. This study has been registered in ClinicalTrials.gov (NCT02418884).