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.

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.

Predictive value of stress hyperglycemia ratio for the occurrence of acute kidney injury in acute myocardial infarction patients with diabetes.

BACKGROUND: Acute hyperglycemia has been recognized as a robust predictor for occurrence of acute kidney injury (AKI) in nondiabetic patients with acute myocardial infarction (AMI), however, its discriminatory ability for AKI is unclear in diabetic patients after an AMI. Here, we investigated whether stress hyperglycemia ratio (SHR), a novel index with the combined evaluation of acute and chronic glycemic levels, may have a better predictive value of AKI as compared with admission glycemia alone in diabetic patients following AMI. METHODS: SHR was calculated with admission blood glucose (ABG) divided by the glycated hemoglobin-derived estimated average glucose. A total of 1215 diabetic patients with AMI were enrolled and divided according to SHR tertiles. Baseline characteristics and outcomes were compared. The primary endpoint was AKI and secondary endpoints included all-cause death and cardiogenic shock during hospitalization. The logistic regression analysis was performed to identify potential risk factors. Accuracy was defined with area under the curve (AUC) by a receiver-operating characteristic (ROC) curve analysis. RESULTS: In AMI patients with diabetes, the incidence of AKI (4.4%, 7.8%, 13.0%; p < 0.001), all-cause death (2.7%, 3.6%, 6.4%; p = 0.027) and cardiogenic shock (4.9%, 7.6%, 11.6%; p = 0.002) all increased with the rising tertile levels of SHR. After multivariate adjustment, elevated SHR was significantly associated with an increased risk of AKI (odds ratio 3.18, 95% confidence interval: 1.99-5.09, p < 0.001) while ABG was no longer a risk factor of AKI. The SHR was also strongly related to the AKI risk in subgroups of patients. At ROC analysis, SHR accurately predicted AKI in overall (AUC 0.64) and a risk model consisted of SHR, left ventricular ejection fraction, N-terminal B-type natriuretic peptide, and estimated glomerular filtration rate (eGFR) yielded a superior predictive value (AUC 0.83) for AKI. CONCLUSION: The novel index SHR is a better predictor of AKI and in-hospital mortality and morbidity than admission glycemia in AMI patients with diabetes.

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.

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.

Multicentre, randomized comparison of two-stent and provisional stenting techniques in patients with complex coronary bifurcation lesions: the DEFINITION II trial.

AIM: The present study aimed to assess the benefits of two-stent techniques for patients with DEFINITION criteria-defined complex coronary bifurcation lesions. METHODS AND RESULTS: In total, 653 patients with complex bifurcation lesions at 49 international centres were randomly assigned to undergo the systematic two-stent technique (two-stent group) or provisional stenting (provisional group). The primary endpoint was the composite of target lesion failure (TLF) at the 1-year follow-up, including cardiac death, target vessel myocardial infarction (TVMI), and clinically driven target lesion revascularization (TLR). The safety endpoint was definite or probable stent thrombosis. At the 1-year follow-up, TLF occurred in 37 (11.4%) and 20 (6.1%) patients in the provisional and two-stent groups, respectively [77.8%: double-kissing crush; hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.30-0.90; P = 0.019], largely driven by increased TVMI (7.1%, HR 0.43, 95% CI 0.20-0.90; P = 0.025) and clinically driven TLR (5.5%, HR 0.43, 95% CI 0.19-1.00; P = 0.049) in the provisional group. At the 1 year after indexed procedures, the incidence of cardiac death was 2.5% in the provisional group, non-significant to 2.1% in the two-stent group (HR 0.86, 95% CI 0.31-2.37; P = 0.772). CONCLUSION: For DEFINITION criteria-defined complex coronary bifurcation lesions, the systematic two-stent approach was associated with a significant improvement in clinical outcomes compared with the provisional stenting approach. Further study is urgently warranted to identify the mechanisms contributing to the increased rate of TVMI after provisional stenting. STUDY REGISTRATION: http://www.clinicaltrials.com; Identifier: NCT02284750.

First-in-man study of a thinner-strut sirolimus-eluting bioresorbable scaffold (FUTURE-I): Three-year clinical and imaging outcomes.

OBJECTIVES: The FUTURE-I study aimed to assess preliminary safety and effectiveness with the long-term clinical and imaging follow-up for the Firesorb (MicroPort, Shanghai, China), a thinner-strut sirolimus-eluting bioresorbable scaffold (BRS). BACKGROUND: First-generation BRS has been associated with unexpected device-related adverse outcomes at long-term follow-up. METHODS: In this prospective, open-label, first-in-man study, patients with single de novo lesions in native coronary arteries were randomized 2:1 into two cohorts after successful Firesorb implantation: cohort 1 (n = 30) underwent multimodality imaging assessment at 6 and 24 months; and cohort 2 (n = 15) at 12 and 36 months. All patients underwent clinical follow-up at 1, 6, and 12 months and annually up to 5 years. RESULTS: Between January and March 2016, 45 patients were enrolled. At 3-year follow-up, one patient had experienced target lesion failure and none scaffold thrombosis. In-scaffold minimal lumen diameter decreased significantly from 6-month to 2-year (2.53 ± 0.24 mm vs. 2.27 ± 0.37 mm, p = .0003), and only numerically from 1-year to 3-year follow-up (2.48 ± 0.28 mm vs. 2.22 ± 0.13 mm, p = .08). By optical coherence tomography, neointimal strut coverage at 3-year follow-up was 99.8%, and very low rate of late scaffold discontinuity was observed, only in one patient on two cross sections with three malapposed struts. CONCLUSIONS: At 3-year follow-up of the FUTURE-I study, implantation of the thinner-strut Firesorb BRS appeared preliminary feasible and effective in the treatment of patients with noncomplex coronary lesions.

[Related factors of optical coherence tomography detected in-stent heterogonous neointima].

OBJECTIVE: To explore the related factors of optical coherence tomography (OCT) detected in-stent heterogeneous neointimal in coronary stents. METHODS: A total of 143 cases of coronary heart disease patients with OCT detected in-stent neointimal hyperplasia in Fuwai hospital from September 2009 to April 2012 were included in this study and patients data were retrospectively analyzed. Patients were divided into heterogeneous intima group(26 cases) and homogeneous intima group(117 cases)according to neointimal characteristics. Clinical features and OCT characteristics of the 2 groups were compared and binary logistic regression analysis was performed to analyze the risk factors of in-stent heterogonous neointimal hyperplasia. RESULTS: Compared to homogeneous intima group, patients in heterogeneous intima group had significantly higher cholesterol level ((5.31±1.11)mmol/L vs.(4.70±0.94)mmol/L, P=0.005), low-density lipoprotein cholesterol level ((2.57±0.87)mmol/L vs.(2.29±0.46)mmol/L, P=0.021) and triglyceride level (2.12(1.82-2.87)mmol/L vs. 1.90(1.73-2.11)mmol/L, P=0.015). Moreover, the percent of percutaneous coronary intervention (PCI) because of acute coronary syndrome (23.1%(6/26) vs. 6.8%(8/117), P=0.022) and the thin cap neoatheroma (5.8%(28/481)vs. 3.9%(89/2 276), P=0.043) were also significantly higher in heterogeneous intima group than in homogeneous intima group. Binary logistic regression analysis showed that low-density lipoprotein cholesterol (OR=2.74, 95%CI 1.04-7.24, P=0.042), triglyceride (OR=2.88, 95%CI 1.05-7.89, P=0.040), PCI for acute coronary syndrome (OR=12.74, 95%CI 2.69-60.49, P=0.001), and cerebrovascular disease (OR=13.09, 95%CI 2.16-79.53, P=0.005) were risk factors for in-stent heterogenous intima. Time post stent implantation was protective factor for in-stent heterogenous intima (OR=0.63, 95%CI 0.42-0.96, P=0.033). CONCLUSION: OCT detected heterogeneous intima is correlated with level of blood lipid, PCI for acute coronary syndrome and history of cerebrovascular disease, and it may lead to unstable intima.

First report of a novel polymer-free dual-drug eluting stent in de novo coronary artery disease: results of the first in human BICARE trial.

BACKGROUND: Persistence of stent polymer coating has been associated with incomplete endothelialization, expansive vessel remodeling, neoatherosclerosis, and delayed healing associated with inflammation that may contribute to late adverse events. METHODS: The BICARE (Lepu Medical, Beijing, China) stent is a novel polymer-free, nanotechnology-based stent eluting sirolimus and probucol. As a first in human feasibility study, patients with a single de novo native coronary stenosis <30 mm in length and with reference vessel diameter from 2.5 to 4.0 mm underwent revascularization with the BICARE stent. The primary endpoint of target lesion failure (TLF) was assessed at 30 days. Secondary endpoints included in-stent late lumen loss and proportion of uncovered or malapposed stent struts by optical coherence tomography at 4-month angiographic surveillance. RESULTS: Among 32 consecutive patients (age, 55.7 ± 8.7 years; men, 62.5%; diabetes, 18.8%), the average baseline reference vessel diameter and lesion length were 2.85 ± 0.48 mm and 15.0 ± 5.6 mm, respectively. At 30 days there was no occurrence of TLF. At 4 months (angiographic follow-up, N=32), angiographic in-stent late loss was 0.14 ± 0.19 mm, and the in-stent binary restenosis rate was 3.1%. Complete strut coverage was 98.2% with 0.2% malapposition among 16,751 analyzed struts. At 18 months, TLF occurred in 3 (9.4%) patients related to repeat revascularization with no adverse safety events identified. CONCLUSIONS: The preliminary feasibility and safety of a polymer-free, dual-drug eluting stent are demonstrated by absence of early adverse safety events and favorable angiographic suppression of neointimal hyperplasia. Stent imaging suggests favorable healing with extensive stent strut coverage and very low malapposition. These findings further inform comparison with biopermanent polymer DES.

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.

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.

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.

Transient expression of cellular retinol-binding protein-1 during cardiac repair after myocardial infarction.

Retinoic acid (RA) is a vitamin A derivative that exerts pleiotropic biological effects. Intracellular transport and metabolism of RA are regulated by cellular retinol-binding proteins (CRBP). CRBP-1 is transiently expressed in granulation tissue fibroblasts during wound healing; however, its role in cardiac remodeling remains unknown. A rat myocardial infarction (MI) model was established by ligation of the left coronary artery, and hearts were obtained at 3, 6, 15, 30 and 45 days after operation. Heart sections were examined immunohistochemically using anti-vimentin, anti-α-smooth muscle actin (α-SMA), anti-matrix metalloproteinase (MMP)-2, anti-MMP-9 and anti-CRBP-1 antibodies. Infarction involved 48.8 ± 3.6% of the left ventricle and was followed by an important cardiac remodeling. Vimentin-positive fibroblastic cells including α-SMA-positive myofibroblasts expressed CRBP-1 at 3-, 6-, and 15-days after MI. Expression of CRBP-1 reached a maximum at 6-days after infarction. Thereafter, CRBP-1 expression was dramatically decreased, showing a similar tendency to MMP expression. Human heart specimens of individuals with a recent myocardial infarction demonstrated presence of CRBP-1-positive fibroblasts by immunohistochemistry. We have demonstrated that CRBP-1 is transiently expressed by fibroblasts during cardiac remodeling. Our results suggest that CRBP-1 plays a role in ventricular remodeling after MI allegedly through its RA binding activity.

[The role of cellular retinol-binding protein-1 on pulmonary structural remodeling after rat myocardial infarction].

OBJECTIVES: To observe the expression of cellular retinol-binding protein-1 (CRBP-1) in pulmonary tissues after rat myocardial infarction (MI) and uncover the role of CRBP-1 on the pulmonary structural remodeling. METHODS: MI was produced in male Wistar rats by left coronary ligation. Rats were sacrificed to obtain the lung at the 3(rd), 6(th), 15(th), 30(th), and 45(th) day after operation. After weighted, the rat lungs were fixed in 4% formalin and embedded in paraffin. Sections were cut and stained with hematoxylin and eosin (HE), Masson's trichrome (MT), rabbit anti-CRBP-1 antibody. RESULTS: Thirty-nine Wistar rats survived and developed MI. Pulmonary tissue sections with HE and MT staining showed a remarkable lung structural remodeling. The content of pulmonary tissue collagen at the 30(rd) was higher than in the sham group (8.4% ± 3.6 vs 4.5% ± 2.6, P < 0.001). CRBP-1 expression was detected on the alveolar septa at the 3(rd) day after operation, and peaked at the 15(th) day (43.8 ± 7.4). Then the CRBP-1 expression decreased, and arrived at the level of the 3(rd) day. CONCLUSIONS: We demonstrate that CRBP-1 is expressed temporal on the alveolar septa after rat MI. It indicates a potential relationship between CRBP-1 and lung structure remodeling process after MI.

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.

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.

Ethnic variance on long term clinical outcomes of concomitant use of proton pump inhibitors and clopidogrel in patients with stent implantation: A PRISMA-complaint systematic review with meta-analysis.

BACKGROUND: Pharmacokinetic and pharmacodynamic study showed a lower clopidogrel response when coprescribed with proton pump inhibitors (PPIs). Despite this, PPIs is necessary for patients treated with long term dual antiplatelet therapy (DAPT). Ethnic variance also played a different effect on clopidogrel response. Our study evaluated the effect of concomitant use of DAPT and PPIs and assessed whether ethnic variance exert different effect on clinical outcomes. METHODS: We carefully searched EMBASE, PubMed/Medline databases, and the Cochrane library in April 2019. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE) and individual endpoints reported. We also focused on bleeding events. Studies were excluded if the follow-up were <12 months and patients were not treated with clopidogrel after stent implantation. RESULTS: A total of 18 studies were included in the systematic review (involving 79,670 patients). No randomized controlled trials (RCTs) were included. PPIs comedication were associated with increased MACCE (odds ratio [OR] = 1.38; 95% confidence interval [CI] = 1.28-1.49) while not associated with decreased bleeding risks, such as gastrointestinal bleeding (OR = 1.05; 95% CI = 0.53-2.11). PPIs comedication were associated with increased risk for all endpoints among Caucasian population while not with increased risk for MACE (OR = 1.20; 95% CI = 0.99-1.39), all-cause death (OR = 1.24; 95% CI = 0.74-2.06), cardiac-death (OR = 1.29; 95% CI = 0.64-2.57) among Asian population. CONCLUSION: PPIs comedication were associated with adverse clinical outcomes, and ethnic variance may exert different effect on clinical outcomes. Subgroup analysis indicated that concomitant use of PPI might be suitable for Asian patients after stent implantation.

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.

Real-World Use of Clopidogrel and Ticagrelor in Patients With Myocardial Infarction With Nonobstructive Coronary Arteries: Patient Characteristics and Long-Term Outcomes.

Background: Current guidelines recommend ticagrelor as the preferred P2Y12 inhibitor on top of aspirin in patients after an acute coronary syndrome. Yet, the efficacy and safety of ticagrelor vs. clopidogrel in patients with myocardial infarction with nonobstructive coronary arteries (MINOCA) remain uncertain. Methods: A total of 1,091 patients with MINOCA who received dual antiplatelet therapy were enrolled and divided into the clopidogrel (n = 878) and ticagrelor (n = 213) groups. The primary efficacy 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. The safety endpoint referred to bleeding events. The Kaplan-Meier, propensity score matching (PSM), and Cox regression analyses were performed. Results: The incidence of MACE was similar for clopidogrel- and ticagrelor-treated patients over the median follow-up of 41.7 months (14.3 vs. 15.0%; p = 0.802). The use of ticagrelor was not associated with a reduced risk of MACE compared with clopidogrel after multivariable adjustment in overall (HR = 1.25, 95% CI: 0.84-1.86, p = 0.262) and in subgroups of MINOCA patients. Further, there was no significant difference in the risk of bleeding between two groups (HR = 1.67, 95% CI: 0.83-3.36, p = 0.149). After PSM, 206 matched pairs were identified, and the differences between clopidogrel and ticagrelor for ischemic endpoints and bleeding events remained nonsignificant (all p > 0.05). Conclusions: In this observational analysis of MINOCA patients, ticagrelor was not superior to clopidogrel in reducing ischemic events and did not cause a significant increase in bleeding, indicating a similar efficacy and safety between clopidogrel and ticagrelor. A randomized study of ticagrelor vs. clopidogrel in this specific population is needed.

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.