Inhibition of myocardial remodeling through miR-150/TET3 axis after AMI.

BACKGROUND: Current studies have suggested that miRNA is beneficial in inhibiting myocardial remodeling after myocardial infarction (AMI), however, its underlying mechanism is unclear. OBJECTIVES: We aimed to investigate whether miR-150 can inhibit myocardial remodeling after myocardial infarction and whether this process is regulated by the miR-150/TET3 pathway. METHODS: On the first day, C57BL/6 AMI mice(n = 15) were administrated with miR-150, and another 15 AMI mice were administrated with the same volume of control Agomir. Left ventricular ejection fraction (LVEF%) and myocardial remodeling were compared after one week; TET3 (ten-eleven translocation 3) and VEGF-α (vascular endothelial growth factor-α) were also determined in the infracted heart simultaneously. The neovascularization in the infarcted area at day 21 was compared through CD31 using fluorescence microscopy; Activated monocytes stimulated with LPS were transfected with miR-150. Laser scanning confocal microscopy was used to detect the intracytoplasmic imaging of miR-150 in Ly6Chigh monocytes. Expression of the miR-150 in the monocytes was measured using Q-PCR. After 48 h, the proportion of Ly6Chigh/low monocytes was determined using flow cytometry. Expression of TET3 in Ly6Chigh/low monocytes was measured using Q-PCR and Western blot. After the downregulation of TET3 specifically, the levels of Ly6Chigh/low monocytes were further determined. RESULTS: We first observed an increased trend of mice survival rate in the miR-150 injection group, but it didn't reach a statistical difference (66.7% vs. 40.0%, p = 0.272). However, AMI mice administrated with miR-150 displayed better LVEF% (51.78%±2.90% vs. 40.28%±4.20%, p<0.001) and decreased infarct size% (25.47 ± 7.75 vs. 50.39 ± 16.91, p = 0.002). After miR-150 was transfected into monocytes, the percentage of Ly6Clow monocytes increased significantly after 48 h (48.5%±10.1% vs. 42.5%±8.3%, p < 0.001). Finally, Western blot analysis (0.56 ± 0.10/ß-actin vs. 0.99 ± 0.12/ß-actin, p < 0.001) and real-time PCR (1.09 ± 0.09/GAPDH vs. 2.53 ± 0.15/GAPDH, p < 0.001, p < 0.001) both confirmed decreased expression of TET3 in monocytes after transfection with miR-150. After the downregulation of TET3 specifically, Ly6Clow monocytes showed a significant increase (16.73%±6.45% vs. 6.94%±2.99%, p<0.001, p < 0.001). CONCLUSIONS: miR-150 alleviated myocardial remodeling after AMI. Possible mechanisms are ascribed to the regulating of TET3 and VEGF-α in inflammatory monocytes.

Very high HDL-C (high-density lipoprotein cholesterol) is associated with increased cardiovascular risk in patients with NSTEMI (non-ST-segment elevation myocardial infarction) undergoing PCI (percutaneous coronary intervention).

BACKGROUND: Studies in populations with or without cardiovascular disease have shown that very high HDL-C levels are associated with an increased risk of cardiovascular events. However, the exact relationship between HDL-C levels and long-term prognosis remains unknown in patients with myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI). METHODS: This was a post hoc secondary analysis of long-term follow-up results in patients undergoing PCI open-label, observational cohort study. Patients with MI who had undergone PCI were enrolled. Restricted cubic spline (RCS) analysis and logistic regression analysis were performed to assess the relationship between HDL-C levels and the risk of cardiovascular events. RESULTS: A total of 1934 patients with MI undergoing PCI were enrolled in our analysis and our population was divided in 3 groups according to the HDL-C plasma levels: HDL-C < 40 mg/dL (low HDL-C); HDL-C between 40 and 80 mg/ dL (medium HDL-C); and HDL-C > 80 mg/dL (high HDL-C). RCS analysis showed a nonlinear U-shaped association between HDL-C levels and major adverse cardiac and cerebrovascular events (MACCE) in patients with NSTEMI with adjusted variables. After adjusting for potential confounders, the follow-up analysis indicated that high risk group had elevated occurrence of MACCE than low risk group (HDL-C 35 and 55 mg/dL) (OR:1.645, P = 0.006). CONCLUSIONS: Our analysis demonstrated that there is a U-shaped association between HDL-C and MACCE in patients with NSTEMI undergoing PCI.

Upregulation of Biomarker Limd1 Was Correlated with Immune Infiltration in Doxorubicin-Related Cardiotoxicity.

Doxorubicin is one of the most common antitumor drugs. However, cardiotoxicity's side effect limits its clinical applicability. In the present study, Gene Expression Omnibus (GEO) datasets were applied to reanalyze differentially expressed genes (DEGs) and construct weighted correlation network analysis (WGCNA) modules of doxorubicin-induced cardiotoxicity in wild-type mice. Several other bioinformatics analyses were performed to pick out the hub gene, and then the correlation between the hub gene and immune infiltration was evaluated. In total, 120 DEGs were discovered in a mouse model of doxorubicin-induced cardiotoxicity, and PF-04217903, propranolol, azithromycin, etc. were found to be potential drugs against this pathological condition. Among all the DEGs, 14 were further screened out by WGCNA modules, of which Limd1 was upregulated and finally regarded as the hub gene after being validated in other GEO datasets. Limd1 was upregulated in the peripheral blood mononuclear cell (PBMC) of the rat model, and the area under curve (AUC) of the receiver operating characteristic curve (ROC) in diagnosing cardiotoxicity was 0.847. The GSEA and PPI networks revealed a potential immunocyte regulatory role of Limd1 in cardiotoxicity. The proportion of "dendritic cells activated" in the heart was significantly elevated, while "macrophage M1" and "monocytes" declined after in vivo doxorubicin application. Finally, Limd1 expression was significantly positively correlated with "dendritic cells activation' and negatively correlated with "monocytes" and "macrophages M1'. In summary, our results suggested that limd1 is a valuable biomarker and a potential inflammation regulator in doxorubicin-induced cardiotoxicity.

METTL3 mediates Ang-II-induced cardiac hypertrophy through accelerating pri-miR-221/222 maturation in an m6A-dependent manner.

BACKGROUND: METTL3 is the core catalytic enzyme in m6A and is involved in a variety of cardiovascular diseases. However, whether and how METTL3 plays a role during angiotensin II (Ang-II)-induced myocardial hypertrophy is still unknown. METHODS: Neonatal rat cardiomyocytes (NRCMs) and C57BL/6J mice were treated with Ang-II to induce myocardial hypertrophy. qRT-PCR and western blots were used to detect the expression of RNAs and proteins. Gene function was verified by knockdown and/or overexpression, respectively. Luciferase and RNA immunoprecipitation (RIP) assays were used to verify interactions among multiple genes. Wheat germ agglutinin (WGA), hematoxylin and eosin (H&E), and immunofluorescence were used to examine myocardial size. m6A methylation was detected by a colorimetric kit. RESULTS: METTL3 and miR-221/222 expression and m6A levels were significantly increased in response to Ang-II stimulation. Knockdown of METTL3 or miR-221/222 could completely abolish the ability of NRCMs to undergo hypertrophy. The expression of miR-221/222 was positively regulated by METTL3, and the levels of pri-miR-221/222 that bind to DGCR8 or form m6A methylation were promoted by METTL3 in NRCMs. The effect of METTL3 knockdown on hypertrophy was antagonized by miR-221/222 overexpression. Mechanically, Wnt/ß-catenin signaling was activated during hypertrophy and restrained by METTL3 or miR-221/222 inhibition. The Wnt/ß-catenin antagonist DKK2 was directly targeted by miR-221/222, and the effect of miR-221/222 inhibitor on Wnt/ß-catenin was abolished after inhibition of DKK2. Finally, AAV9-mediated cardiac METTL3 knockdown was able to attenuate Ang-II-induced cardiac hypertrophy in mouse model. CONCLUSIONS: Our findings suggest that METTL3 positively modulates the pri-miR221/222 maturation process in an m6A-dependent manner and subsequently activates Wnt/ß-catenin signaling by inhibiting DKK2, thus promoting Ang-II-induced cardiac hypertrophy. AAV9-mediated cardiac METTL3 knockdown could be a therapeutic for pathological myocardial hypertrophy.

Donor-Acceptor 1,2,4,5-Tetrazines Prepared by the Buchwald-Hartwig Cross-Coupling Reaction and Their Photoluminescence Turn-On Property by Inverse Electron Demand Diels-Alder Reaction.

A facile efficient synthetic tool, Buchwald-Hartwig cross-coupling reaction, for the functionalization of 1,2,4,5-tetrazines is presented. Important factors affecting the Buchwald-Hartwig cross-coupling reaction have been optimized. Seven new donor-acceptor tetrazine molecules (TA1-TA7) were conveniently prepared in good to high yields (61-72%). They have been subsequently engaged in the inverse electron demand Diels-Alder (iEDDA) reaction with cyclooctyne. The photophysical and electrochemical properties of the new pyridazines have been studied. Some are fluorescent acting as turn-on probes. More importantly, two pyridazines (DA3 and DA6) exhibit room-temperature phosphorescence (RTP) properties.

N6-methyladenosine methyltransferase plays a role in hypoxic preconditioning partially through the interaction with lncRNA H19.

N6-methyladenosine (m6A), a methylation in the N6 position of adenosine especially in the mRNA, exerts diverse physiological and pathological functions. However, the precise role of m6A methylation in hypoxic preconditioning (HPC) is still unknown. Here, we observed that HPC treatment protected H9c2 cells against H2O2-induced injury, upregulated the m6A level in the total RNA and the expression of methyltransferase like 3 (METTL3), methyltransferase like 14 (METTL14), and long noncoding RNA (lncRNA) H19. Either knockdown of METTL3 or METTL14 notably reversed the HPC-induced enhancement of cell viability, anti-apoptosis ability, and H19 expression. Methylated RNA immunoprecipitation (IP) indicated that knockdown of METTL3 or METTL14 decreased m6A level in the lncRNA H19. Gain-of-function assay demonstrated that H19 overexpression could partially rescue the decreased protection mediated by METTL3 or METTL14 knockdown in HPC-treated H9c2 cells. RNA binding protein immunoprecipitation (RIP) assay showed that METTL3 and METTL14 could directly bind with H19. Our study identified a novel pattern of posttranscriptional regulation in HPC treatment. Since METTL3, METTL14, and lncRNA H19 were involved in HPC protection, they could be considered as potential biomarkers and therapeutic targets in HPC-derived cardiac rehabilitation and therapeutic approaches.

Convenient One-Pot Synthesis of 1,2,3,4-Thiatriazoles Towards a Novel Electron Acceptor for Highly-Efficient Thermally-Activated Delayed-Fluorescence Emitters.

A novel and unexpected convenient one-pot synthesis of 1,2,3,4-thiatriazoles has been discovered while investigating the classical tetrazine "Pinner synthesis". The synthetic route starts from commercially-available nitrile derivatives and gives good to high yields (51-80 %) with no need to isolate any thioacylating agents. The crucial impact of the solvent on the outcome of the modified "Pinner synthesis" is moreover examined and discussed. Using this new synthetic route, a novel donor-acceptor thiatriazole derivative has been prepared, which exhibits prominent thermally-activated delayed fluorescence (TADF) in both solution and film. The photoluminescence quantum yield (PLQY) in methylcyclohexane (MCH) and Zeonex (a cyclo olefin polymer) in oxygen-free conditions were determined to be 76 and 99 %, respectively. This work provides an efficient and practical synthetic approach to functionalized 1,2,3,4-thiatriazole derivatives, and will noticeably facilitate the application of 1,2,3,4-thiatriazole as an electron acceptor in organic electronics.

Metal-Free Synthetic Approach to 3-Monosubstituted Unsymmetrical 1,2,4,5-Tetrazines Useful for Bioorthogonal Reactions.

A facile, efficient and metal-free synthetic approach to 3-monosubstituted unsymmetrical 1,2,4,5-tetrazines is presented. Dichloromethane (DCM) is for the first time recognized as a novel reagent in the synthetic chemistry of tetrazines. Using this novel approach 11 3-aryl/alkyl 1,2,4,5-tetrazines were prepared in excellent yields (up to 75 %). The mechanism of this new reaction, including the role of DCM in the tetrazine ring formation, has been investigated by 13 C labeling of DCM, and is also presented and discussed as well as the photophysical and electrochemical properties.

Quantum dots increased fat storage in intestine of Caenorhabditis elegans by influencing molecular basis for fatty acid metabolism.

Caenorhabditis elegans is a useful model animal for fat storage study. In nematodes, CdTe quantum dots (QDs) induced an increase in fat storage in intestine that is partially due to prolonged defecation cycle length, and not attributed to altered feeding or cadmium ion released from CdTe QDs. Moreover, CdTe QDs altered the molecular basis of both synthesis and degradation of fatty acid; however, CdTe QDs did not influence that of degradation of phospholipids. CdTe QDs increased expression of fasn-1 and pod-2 genes encoding enzymes required for fatty acid synthesis, and decreased expression of acs-2 and ech-1 genes encoding enzymes required for fatty acid ß-oxidation. The altered molecular basis of fatty acid synthesis or degradation by CdTe QDs acted in intestine to regulate fat storage. Our study highlights the potential of CdTe QDs in influencing lipid metabolism in certain organs or tissues in animals.

A novel cartilage-targeting MOF-HMME-RGD sonosensitizer combined with sonodynamic therapy to enhance chondrogenesis and cartilage regeneration.

Articular cartilage regeneration is still a difficult task due to the cartilage's weak capacity for self-healing and the effectiveness of the available therapies. The engineering of cartilage tissue has seen widespread use of stem cell-based therapies. However, efficient orientation of line-specific bone marrow mesenchymal stem cells (BMSCs) to chondrogenesis and maintenance of chondrogenic differentiation challenged stem cell-based therapy. Herein, we developed a Fe-based metal-organic framework (MOF) loaded with hematoporphyrin monomethyl ether (HMME) and cartilage-targeting arginine-aspartate-glycine (RGD) peptide to form MOF-HMME-RGD sonosensitizer to regulate BMSCs chondrogenic differentiation for cartilage regeneration via the modulation of reactive oxygen species (ROS). By using sonodynamic therapy (SDT), the MOF-HMME-RGD demonstrated favorable biocompatibility, could generate a modest amount of ROS, and enhanced BMSCs chondrogenic differentiation through increased accumulation of glycosaminoglycan, an ECM component specific to cartilage, and upregulated expression of key chondrogenic genes (ACAN, SOX9, and Col2a1). Further, transplanted BMSCs loading MOF-HMME-RGD combined with SDT enhanced cartilage regeneration for cartilage defect repair after 8 weeks into treatment. This synergistic strategy based on MOF nanoparticles provides an instructive approach to developing alternative sonosensitizers for cartilage regeneration combined with SDT.

[Oxidative stress and calcium/calmodulin-dependent protein kinase II contribute to the development of sustained ß adrenergic receptor-stimulated cardiac hypertrophy in rats].

Sustained activation of ß adrenergic receptor (ßAR) leads to pathologic cardiac hypertrophy. However, the related mechanisms still remain unclear. In this study, we observe how N-acetylcysteine (NAC) affects the oxidative stress and calcium/calmodulin-dependent protein kinase II (CaMKII) expression in heart of isoproterenol (ISO)-stimulated rats, and investigate whether oxidative stress and CaMKII contribute to the development of sustained ßAR-stimulated cardiac hypertrophy. Healthy male Wistar rats were randomly separated into 4 groups: control (CTRL), ISO-treated (ISO), control with NAC supplement (CTRL+NAC) and ISO-treated with NAC supplement (ISO+NAC) groups (6 rats in each group). Systolic blood pressure (SBP) was measured in awake rats with the tail-cuff method every week for two weeks. Heart weight/body weight ratio (HW/BW) and HE staining were used for the detection of myocardial hypertrophy. Myocardial mitochondrial reactive oxygen species (ROS) levels were measured by DCF fluorometry. The expressions of activated-CaMKII (p-CaMKII/CaMKII) and NADPH oxidase 4 (NOX(4)) were determined by Western blot analysis. The results showed that ISO-treated (i.p., daily 3 mg/kg, 2 weeks) rats developed an obvious cardiac hypertrophy as expressed by increases of HW/BW and myocyte cross-section area. Cardiac mitochondrial ROS level was significantly enhanced in ISO group as compared to CTRL group (P < 0.05). The expressions of NOX(4) and p-CaMKII in ISO group were also up-regulated as compared to CTRL group (1.4 and 1.6 times of CTRL, respectively, P < 0.05). NAC supplement significantly suppressed the hypertrophic development of heart in ISO-stimulated rats. The cardiac mitochondrial ROS level showed a significant decrease in rats of ISO+NAC group (P < 0.05 vs ISO). In accordance with this, ISO+NAC group rats also showed marked reductions in the expressions of NOX(4) and p-CaMKII/CaMKII compared to ISO group rats (P < 0.05). There were no significant differences of the detected indices between the rats from CTRL+NAC and CTRL groups. SBP showed no differences among four groups. These results suggest that both oxidative stress and CaMKII play important roles in sustained ßAR-stimulated cardiac hypertrophy. NAC may suppress ISO-induced cardiac hypertrophy by down-regulating the expression of activated-CaMKII, and by reducing the level of oxidative stress originated from mitochondria and NADPH oxidase pathways.

Photocrosslinkable, Injectable Locust Bean Gum Hydrogel Induces Chondrogenic Differentiation of Stem Cells for Cartilage Regeneration.

Due to the limited therapeutic efficacy of current treatments, articular cartilage regeneration is still challenging work. Scaffold-based tissue engineering provides a promising strategy for cartilage regeneration, but most scaffolds are limited by poor mechanical properties or unfavorable biocompatibility. Here, a novel photocrosslinkable, injectable locust bean gum (LBG)-methacrylate (MA) hydrogel is reported as a biomimetic extracellular matrix (ECM) for cartilage repair with minimal invasive operation. LBG-MA hydrogels show controllable degradation rate and improve mechanical properties and excellent biocompatibility. More importantly, LBG-MA hydrogel significantly induces bone mesenchymal stem cells to chondrogenic differentiation in vitro, as evidenced by high accumulation of cartilage-specific ECM components glycosaminoglycan and upregulated expression of key chondrogenic genes (collagen type II, aggrecan, and sex determining region Y-box9). Besides, the hydrogel is injectable, which can be in situ crosslinked via UV irradiation. Further, the photocrosslinkable hydrogels accelerate cartilage healing in vivo after 8 weeks of therapy. A strategy is provided here for photocrosslinkable, injectable, biodegradable scaffold fabrication based on native polysaccharide polymer for minimal invasive cartilage repair.

Inhibition of miR-195-3p protects against cardiac dysfunction and fibrosis after myocardial infarction.

Cardiac fibrosis following myocardial infarction is a major risk factor for heart failure. Recent evidence suggests that miR-195-3p is up-regulated in fibrotic diseases, including kidney and liver fibrosis. However, its function and underlying mechanisms in cardiac fibrosis after MI remain unknown. To investigate the role of miR-195-3p in MI-induced cardiac fibrosis, we established acute MI models by ligating adult C57B/L6 mice LAD coronary artery while sham-operated mice were used as controls. In vivo inhibition of miR-195-3p was conducted by intramyocardial injection of AAV9-anti-miR-195-3p. In vitro overexpression and inhibition of miR-195-3p were performed by transfecting cultured Cardiac Fibroblasts (CFs) with synthetic miRNA mimic and inhibitor. Our results showed that MI induced the expression of miR-195-3p and that inhibition of miR-195-3p reduced myofibroblast differentiation and collagen deposition and protected cardiac function. In vitro stimulation of CFs with TGF-ß1 resulted in a significant increase in miR-195-3p expression. Inhibition of miR-195-3p attenuated the TGF-ß1-induced expression of ECM proteins, migration, and proliferation. PTEN expression was significantly reduced in the hearts of MI mice, in activated CFs, and in CFs transfected with miR-195-3p mimic. Inhibition of miR-195-3p markedly restored PTEN expression in MI mice and TGF-ß1-treated CFs. In conclusion, this study highlights the crucial role of miR-195-3p in promoting cardiac fibrosis and dysfunction after MI. Inhibiting miR-195-3p could be a promising therapeutic strategy for preventing cardiac fibrosis and preserving cardiac function after MI. Additionally, the study sheds light on the mechanisms underlying the effects of miR-195-3p on fibrosis, including its regulation of PTEN/AKT pathway.

Quantification of patient-specific coronary material properties and their correlations with plaque morphological characteristics: An in vivo IVUS study.

BACKGROUND: A method using in vivo Cine IVUS and VH-IVUS data has been proposed to quantify material properties of coronary plaques. However, correlations between plaque morphological characteristics and mechanical properties have not been studied in vivo. METHOD: In vivo Cine IVUS and VH-IVUS data were acquired at 32 plaque cross-sections from 19 patients. Six morphological factors were extracted for each plaque. These samples were categorized into healthy vessel, fibrous plaque, lipid-rich plaque and calcified plaque for comparisons. Three-dimensional thin-slice models were constructed using VH-IVUS data to quantify in vivo plaque material properties following a finite element updating approach by matching Cine IVUS data. Effective Young's moduli were calculated to represent plaque stiffness for easy comparison. Spearman's rank correlation analysis was performed to identify correlations between plaque stiffness and morphological factor. Kruskal-Wallis test with Bonferroni correction was used to determine whether significant differences in plaque stiffness exist among four plaque groups. RESULT: Our results show that lumen circumference change has a significantly negative correlation with plaque stiffness (r = -0.7807, p = 0.0001). Plaque burden and calcification percent also had significant positive correlations with plaque stiffness (r = 0.5105, p < 0.0272 and r = 0.5312, p < 0.0193) respectively. Among the four categorized groups, calcified plaques had highest stiffness while healthy segments had the lowest. CONCLUSION: There is a close link between plaque morphological characteristics and mechanical properties in vivo. Plaque stiffness tends to be higher as coronary atherosclerosis advances, indicating the potential to assess plaque mechanical properties in vivo based on plaque compositions.

Inflammatory activation and immune cell infiltration are main biological characteristics of SARS-CoV-2 infected myocardium.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can target cardiomyocytes (CMs) to directly invade the heart resulting in high mortality. This study aims to explore the biological characteristics of SARS-CoV-2 infected myocardium based on omics by collecting transcriptome data and analyzing them with a series of bioinformatics tools. Totally, 86 differentially expressed genes (DEGs) were discovered in SARS-CoV-2 infected CMs, and 15 miRNAs were discovered to target 60 genes. Functional enrichment analysis indicated that these DEGs were mainly enriched in the inflammatory signaling pathway. After the protein-protein interaction (PPI) network was constructed, several genes including CCL2 and CXCL8 were regarded as the hub genes. SRC inhibitor saracatinib was predicted to potentially act against the cardiac dysfunction induced by SARS-CoV-2. Among the 86 DEGs, 28 were validated to be dysregulated in SARS-CoV-2 infected hearts. Gene Set Enrichment Analysis (GSEA) analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) showed that malaria, IL-17 signaling pathway, and complement and coagulation cascades were significantly enriched. Immune infiltration analysis indicated that 'naive B cells' was significantly increased in the SARS-CoV-2 infected heart. The above results may help to improve the prognosis of patients with COVID-19.

Novel Easy to Synthesize Benzonitrile Compounds with Mixed Carbazole and Phenoxazine Substituents Exhibiting Dual Emission and TADF Properties.

The photophysical and electrochemical properties of a new class of fluorinated benzonitrile compounds substituted with mixed phenoxazine and carbazole units have been investigated. When absorbing in a large range of the UV-vis spectrum due to both localized and charge-transfer absorptions, these compounds show dual broad emission in solution and intense emission in PMMA films, with photoluminescence quantum yields changing from a few percent in solution to 18% in a more rigid environment. The compounds also exhibit thermally activated delayed fluorescence demonstrated by the role of oxygen in the quenching of delayed fluorescence and by time-resolved luminescence studies, with an efficiency directly related to the number of phenoxazine substituents. Electrochemistry reveals dramatic changes in the reduction mechanisms according to the number of remaining fluorine atoms on the benzonitrile core. All these results demonstrate how it is possible to tune the photophysical and electrochemical properties of easily synthesizable derivatives by controlling the nature and relative number of the substituents on a simple aromatic platform.

High-density lipoprotein cholesterol to apolipoprotein A-1 ratio is an important indicator predicting in-hospital death in patients with acute coronary syndrome.

BACKGROUND: Dyslipidemia plays a pivotal role in the pathogenesis of acute coronary syndrome (ACS). This study aims to investigate the value of two indices associated with lipid metabolism, low-density lipoprotein cholesterol to apolipoprotein B ratio (LBR) and high-density lipoprotein cholesterol to apolipoprotein A-1 ratio (HAR), to predict in-hospital death in patients with ACS. METHODS: This single-center, retrospective, observational study included 3,366 consecutive ACS patients in Zhongda Hospital, Southeast University from July 2013 to January 2018. The clinical and laboratory data were extracted, and the in-hospital death and hospitalization days were also recorded. RESULTS: All patients were equally divided into four groups according to quartiles of HAR: Q1 (HAR < 1.0283), Q2 (1.0283 ≤ HAR < 1.0860), Q3 (1.0860 ≤ HAR < 1.1798), and Q4 (HAR ≥ 1.1798). Overall, HAR was positively associated with the counts of neutrophils and monocytes, whereas negatively correlated to lymphocyte counts. HAR was negatively correlated to left ventricular ejection fraction (LVEF). Compared to other three groups, in-hospital mortality (vs. Q1, Q2, and Q3, p < 0.001) and hospitalization length (vs. Q1, Q2, and Q3, p < 0.001) were significantly higher in the Q4 group. When grouped by LBR, however, there was no significant difference in LVEF, in-hospital mortality, and hospitalization length among groups. After adjusting potential impact from age, systolic blood pressure, creatine, lactate dehydrogenase, albumin, glucose, and uric acid, multivariate analysis indicated that HAR was an independent factor predicting in-hospital death among ACS patients. CONCLUSIONS: HAR had good predictive value for patients' in-hospital death after the occurrence of acute coronary events, but LBR was not related to in-hospital adverse events.

Age-Related Utilization of Thrombus Aspiration in Patients With ST-Segment Elevation Myocardial Infarction: Findings From the Improving Care for Cardiovascular Disease in China Project.

Background: There are some controversies on the utilization and benefits of thrombus aspiration in patients with ST-segment elevation myocardial infarction (STEMI). However, a few studies investigated this issue and the age-associated effects among the large population in China. Hence, we aimed to figure out the age-associated utilization and in-hospital outcomes of thrombus aspiration to improve therapeutic decisions in clinical routine. Methods: We retrospectively recruited 13,655 eligible STEMI patients from the database of the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project. These subjects were allocated into primary percutaneous coronary intervention (PPCI)-only group and thrombus aspiration group after being subdivided into three age groups (G21-50, G51-75, and G76-95). After 1:1 propensity score matching for PPCI-only and thrombus aspiration groups, a total of 8,815 matched patients were enrolled for the subsequent analysis. The primary outcome was in-hospital cardiovascular death, and the key safety outcome was in-hospital stroke. Results: We observed that the ratio of STEMI patients undergoing thrombus aspiration to PPCI-only reduced with aging. For patients ≤ 75 years, the culprit lesion suffered from thrombus aspiration was mainly located in the left anterior descending branch, and left-ventricular ejection fraction (LVEF) was lower (G21-50: 54.9 ± 8.9 vs. 56.0 ± 8.7%, P = 0.01; G51-75: 53.9 ± 9.6 vs. 54.8 ± 9.0%, P = 0.001) and the rate of regional wall motion abnormality was higher (G21-50: 75.7 vs. 66.5%, P < 0.001; G51-75: 75.4 vs. 69.1%, P < 0.001) in the thrombus aspiration group. By contrast, for patients > 75 years, the right coronary artery was the predominant culprit lesion undergoing thrombus aspiration, LVEF (63.1 ± 10.5 vs. 53.1 ± 9.5%, P = 0.985) and the regional wall motion abnormality (79.2 vs. 74.2%, P = 0.089) were comparable between the two treatment groups. Thrombus aspiration neither reduced the in-hospital risk of cardiovascular death, all-cause death, recurrent myocardial infarction, acute stent thrombosis, heart failure, cardiogenic shock, and sudden cardiac arrest nor increased stroke risk compared with the PPCI-only group. However, after adjustment for age, thrombus aspiration presented the tendency to reduce the incidence of sudden cardiac arrest (4.9 vs. 2.5%, P = 0.06) and in-hospital cardiovascular death at 3 days (hazard ratio 0.46; 95% CI, 0.20-1.06; log-rank P = 0.08) in G76-95 group and tended to increase the incidence of heart failure in G51-75 (5.7 vs. 6.9%, P = 0.07). Conclusion: The thrombus aspiration neither significantly reduced the in-hospital incidence of major adverse cardiac events nor increased stroke risk. However, it might play a protective role in reducing in-hospital sudden cardiac arrest and increasing survival from cardiovascular death at 3 days for the elderly.

Quantitative Assessment of Left and Right Atrial Strains Using Cardiovascular Magnetic Resonance Based Tissue Tracking.

Background: Left and right atrium (LA and RA) exert an essential and dynamic role in ventricular filling and hence affect heart performance. Strain quantification has been reported as a novel parameter to assess function. However, the assessment of bi-atrial strains with cardiovascular magnetic resonance (CMR) based techniques is still limited and gender- and age-specific normal values in a healthy population are missing. Methods: One hundred and fifty healthy volunteers (49.8 ± 17.3 years, 75 males) undergoing 1.5 Tesla CMR examination were retrospectively and consecutively recruited. LA and RA free wall (RAFW) radial and longitudinal strains (RS and LS) associated with atrial reservoir, conduit and booster pump functions were evaluated with CMR based tissue tracking (CMR-TT) technique. Results: The reservoir, conduit and pump LS resulted as 30.7 ± 10.2%, 19.5 ± 8.2%, 10.9 ± 3.7% for LA, and 52.2 ± 17.6%, 33.3 ± 14.2%, 19.1 ± 8.5% for RAFW, respectively. The amplitude of RA strains was significantly larger than that of LA strains, except for conduit RS. With the increase of age, the decrement of majority of reservoir and conduit strains were observed, while pump strains remained unaffected. Females presented with significantly larger RAFW strains compared with males, especially in the elderly. In addition to the positive correlation between atrial strains and emptying fraction, the negative correlation between atrial strains and volume index was also confirmed. Intra-observer reproducibility of LA strains was superior to RAFW strains (coefficient of variation: 10.12-17.04% vs. 10.80-27.36%, respectively), and the measurement of reservoir and conduit strains was more reproducible in comparison with pump strain. Conclusion: CMR-TT is a feasible and reproducible technique to quantify LA and RA strains and determine atrial phasic functions. The existence of age- and gender-related difference of strains suggests the necessity to establish specific normal values for individual populations.

Impact of diabetes mellitus on the relationship between a Poiseuille-based index and fractional flow reserve in intermediate coronary lesions.

BACKGROUND: The ratio of lesion length (LL) to the fourth power of minimal lumen diameter (MLD) (LL/MLD4) is a Poiseuille-based index with good diagnostic accuracy for the detection of coronary lesions with abnormal fractional flow reserve (FFR). We aimed to evaluate the impact of diabetes mellitus (DM) on its performance in intermediate coronary stenoses. METHODS: We performed quantitative coronary angiography and simultaneous FFR measurement in 324 patients (234 non-DM and 90 DM) with 335 coronary lesions. The area under the receiver-operating characteristic curve (AUC) for angiographic parameters was determined, using an FFR value ≤0.80 to indicate the physiological significance of coronary stenoses. RESULTS: In the non-DM group, FFR was significantly related to percent diameter stenosis (%DS) (R = -0.238) and LL/MLD4 ratio (R = -0.301; P < 0.001 for both). In the DM group, there was no correlation between %DS and FFR, whereas a close-to-threshold correlation was observed for the LL/MLD4 ratio (R = -0.205; P = 0.048). The AUC of LL/MLD4 ratio was significantly different between non-diabetic and diabetic subjects (0.738 vs. 0.540; P = 0.024). Moreover, the LL/MLD4 ratio showed higher AUCs than %DS (0.738 vs. 0.635; P = 0.017) and LL (0.738 vs. 0.634; P = 0.024) in non-diabetic population but this superiority did not exist in diabetic population. CONCLUSION: We showed good diagnostic accuracy of LL/MLD4 ratio for identifying ischemic lesions in patients without DM. However, there was an impaired performance in diabetic patients and thus FFR measurement is essential to determine their hemodynamic status.