Impact of plaque characteristics on percutaneous coronary intervention-related microvascular dysfunction: insights from angiographic microvascular resistance and intravascular ultrasound.

Background: The correlation between percutaneous coronary intervention (PCI)-related microvascular dysfunction (MVD) and plaque characteristics remains unclear. To investigate this correlation and its prognosis, we assessed changes in MVD by angiographic microvascular resistance (AMR) and intracoronary ultrasound scans after PCI. Methods: We conducted a retrospective study that enrolled 250 patients with coronary artery disease between July 2016 and December 2018. We collected demographic characteristics, laboratory tests, coronary angiography (CAG) and intracoronary ultrasound findings. We calculated quantitative flow ratio (QFR) and AMR by CAG. The endpoint was vessel-oriented composite outcomes (VOCOs). Results: After 47 exclusions, we divided 203 cases into a deteriorated group (n=139) and an improved group (n=64) based on AMR change after PCI. Compared with the improved group, the deteriorated group had smaller lumen area [3.03 (interquartile range, 2.20-3.91) vs. 3.55 mm2 (interquartile range, 2.45-4.57), P=0.033], higher plaque burden [78.92% (interquartile range, 73.95-82.61%) vs. 71.93% (interquartile range, 62.70-77.51%), P<0.001], and higher proportion of lipidic components (13.86%±4.67% vs. 11.78%±4.41%, P=0.024). Of 186 patients who completed 4.81±1.55 years follow-up, 56 developed VOCOs. Receiver-operating characteristic (ROC) curve analysis showed post-PCI AMR and VOCOs correlation (area under the curve: 0.729, P<0.001). Multivariate regression analysis showed post-PCI AMR >285 mmHg·s/m correlated with adverse outcome (hazard ratio =4.350; 95% confidence interval: 1.95-9.703; P<0.001). Conclusions: Intravascular ultrasound (IVUS) imaging and AMR revealed an association of post-PCI MVD with a smaller lumen area, more severe plaque burden, and a higher percentage of lipidic components. Post-PCI MVD was an independent risk factor for poor prognosis.

Paeonol Pretreatment Attenuates Anoxia-Reoxygenation Induced Injury in Cardiac Myocytes via a BRCA1 Dependent Pathway.

Breast cancer type 1 sensitive protein (BRCA1) is a well-known tumor suppressor and its role in oxidative stress has been confirmed. The purpose of this study is to evaluate whether paeonol has a protective effect on myocardial hypoxia-reoxygenation (A/R) injury, and to explore H9C2 cells through a mechanism-dependent pathway mediated by BRCA1. H9C2 cells were pretreated with paeonol (10 µM) for 18 h before hypoxia was induced to establish a cell model of myocardial ischemia/reperfusion (I/R) injury. Use commercial kits to detect antioxidant indicators, including relative oxygen content (ROS) levels, total antioxidant capacity (T-AOC), superoxide dismutase (SOD), lactate dehydrogenase (LDH) activity, and creatine kinase (CK-MB) and nuclear factor-kappaB (NF-κB) activity. The cell viability was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction method. Real-time fluorescent quantitative PCR was used to detect BRCA1 mRNA and protein levels. The expression levels of BRCA1, NLRP3 and ACS were determined by Western blotting. In addition, the release of interleukin (IL)-1ß (IL-1ß), IL-6 and tumor necrosis factor-α (TNF-α) was also evaluated by an enzyme-linked immunosorbent assay (ELISA) kit. The results showed that paeonol (10 µM) can significantly improve the hypoxic A/R damage of H9C2 cells, and the BRCA1 expression of H9C2 cells pretreated with paeonol was significantly increased before A/R damage was induced. BRCA1 is widely known in breast and ovarian cancer. Our data proves that the down-regulation of BRCA1 participates in the decrease of cell viability and the decrease of CK-MB and LDH activities, and protects cells by inhibiting the production of ROS and the activation of Nod-like receptor protein 3 (NLRP3) inflammasomes and NF-κB. In conclusion, paeonol significantly improved the A/R damage of H9C2 cells induced by hypoxia through the BRCA1/ROS-regulated NLRP3 inflammasome/IL-1ß and NF-κB/TNF-α/IL-6 pathways. It may be a potential drug against myocardial I/R injury.

Coronary plaque tissue characterization in patients with premature coronary artery disease.

Premature coronary artery disease (CAD) studies rarely involve coronary plaque characterization. We characterize coronary plaque tissue by radiofrequency intravascular ultrasound (IVUS) in patients with premature CAD. From July 2015 to December 2017, 220 patients from the Department of Cardiology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine with first occurrence of angina or myocardial infarction within 3 months were enrolled. Patients with premature CAD (n = 47, males aged < 55 years, and females aged < 65 years) or later CAD (n = 155) were retrospectively compared for cardiovascular risk factors, laboratory examination findings, coronary angiography data, gray-scale IVUS, and iMap-IVUS. The mean age was 53.53 ± 7.24 vs. 70.48 ± 8.74 years (p < 0.001). The groups were similar for traditional coronary risk factors except homocysteine (18.60 ± 5.15 vs. 17.08 ± 4.27 µmol/L, p = 0.043). After matching for baseline characteristics, LDL cholesterol (LDL-C) was higher for premature CAD than later CAD (2.50 ± 0.96 vs. 2.17 ± 0.80 mmol/L, p = 0.019). Before the matching procedure, the premature CAD group had shorter target lesion length [18.50 (12.60-32.00) vs. 27.90 (18.70-37.40) mm, p = 0.002], less plaque volume [175.59 (96.60-240.50) vs. 214.73 (139.74-330.00) mm3, p = 0.013] than the later CAD group. After the matching procedure, the premature CAD group appeared to be less plaque burden (72.69 ± 9.99 vs. 74.85 ± 9.80%, p = 0.005), and positive remodeling (1.03 ± 0.12 vs. 0.94 ± 0.18, p = 0.034), and lower high risk feature incidence (p = 0.006) than the later CAD group. At the plaque's minimum lumen, premature CAD had more fibrotic (p < 0.001), less necrotic (p = 0.001) and less calcified areas (p = 0.012). Coronary plaque tissue was more fibrotic with less necrotic and calcified components in premature than in later CAD, and the range and degree of atherosclerosis were significantly lower.

Acute Hemodynamic Effects of Remote Ischemic Preconditioning on Coronary Perfusion Pressure and Coronary Collateral Blood Flow in Coronary Heart Disease.

BACKGROUND: The aim of this study was to assess the acute hemodynamic effects of remote ischemic preconditioning (RIPC) on coronary perfusion pressure and coronary collateral blood flow. METHODS: A total of 17 patients with coronary heart disease with severe (70%-85%) stenosis in one or two vessels confirmed by angiography were enrolled into this study. They were randomly divided into the RIPC group (9 patients) and the control group (8 patients). Distal pressure of coronary artery stenosis before balloon dilation (non-occlusive pressure, Pn-occl) and distal coronary artery occlusive pressure (Poccl) during balloon dilation occlusion were measured in all patients. The patients in the RIPC group received three cycles of lower limb ischemia-reperfusion preconditioning (5 minutes inflation of a blood pressure cuff, followed by 5 minutes reperfusion). For controls, the cuff was not inflated. After this process, Pn-occl and Poccl were measured again in each patient. RESULTS: There were no significant differences in angiographic characteristics between the two groups (all p > 0.05). Troponin I (TNI) levels after percutaneous coronary intervention (PCI) were lower in the RIPC group than in the control group (p = 0.004). In the RIPC group, mean Pn-occl and Poccl were significantly increased after RIPC compared to before RIPC [(72.78 ± 10.10) mmHg vs. (79.67 ± 9.79) mmHg, p = 0.002, (20.89 ± 8.61) mmHg vs. (26.78 ± 10.73) mmHg, p = 0.001, respectively]. CONCLUSIONS: RIPC can improve distal coronary perfusion pressure and rapidly increase distal coronary occlusive pressure thereby improving coronary collateral blood flow.

Transplantation of Endothelial Progenitor Cells Overexpressing miR-126-3p Improves Heart Function in Ischemic Cardiomyopathy.

BACKGROUND: In a previous study, a low level of miR-126-3p in endothelial progenitor cells (EPCs) was linked to the outcome of ischemic cardiomyopathy (ICM) patients. However, it remains unclear whether transplantation with miR-126-3p-overexpressing EPCs (MO-EPCs) can improve the cardiac function of ICM animal models. Methods and Results: miR-126-3p overexpression by lentiviral vector significantly increased migration and tube-like structures of EPCs from ICM patients. MO-EPCs or non-modified EPCs (NM-EPCs) were transplanted into nude rats with ICM induced by coronary artery ligation. MO-EPC transplantation increased capillary density and EPC survival rate in myocardial tissues of nude rats. Cytokines were also assessed by antibody array and real-time RT-PCR. G-CSF, VEGF-A, IL-3, IL-10, IGF-1, angiogenin, HGF, TIMP-1 and TIMP-2 were upregulated, and IL-8, MCP-1, MCP-2, TNF-α, TNF-ß and MIP-1ß were downregulated after miR-126-3p overexpression in EPCs. The same results were obtained in infarction tissues of nude rats after MO-EPC transplantation. Eight weeks after MO-EPC transplantation, left ventricular function improved significantly with clearly decreased infarction size, increased anterior wall thickness, and inhibition of inflammation compared with the results for NM-EPC transplantation. However, MO-EPC transplantation showed no increase in survival time of nude rats with ICM during 8 weeks of observation. CONCLUSIONS: miR-126-3p can restore the biology of EPCs from ICM patients. Moreover, MO-EPC transplantation improves cardiac function effectively, representing a promising future treatment for ICM.

Occurrence of composite cardiac endpoints with change in resting heart rate among Chinese patients with coronary artery disease: Chinese cohort from the real-world BISO-CAD study.

OBJECTIVE: We evaluated change in resting heart rate (RHR) and its impact on prognosis in Chinese coronary artery disease (CAD) patients treated with bisoprolol, and also assessed drug safety and tolerability. METHODS: This phase IV, single arm observational study was a sub-study of the BISO-CAD study conducted across 20 hospitals in China between October 2011 and July 2015 with follow-up at 6, 12 and 18 months after baseline. The primary endpoint was occurrence of composite cardiac events. RESULTS: A total of 663 CAD patients (baseline RHR 75.47 ± 6.62 bpm) were enrolled in the intent-to-treat (ITT) set, and 513 patients were included in the efficacy analysis (EA) set. In the ITT set, the risk and the number of composite cardiac events in patients with mean RHR 69-74 bpm were significantly higher than in the <65 bpm group (ITT: estimate 1.03 ± 0.47, p = .029). The incidence of the composite cardiac endpoint was not affected by continuous mean RHR (p = .5070). RHR significantly decreased from baseline to 18 months, most obviously in the first 6 months (p < .0001). Ejection fraction and fractional shortening significantly improved in both the ITT and EA sets. An average RHR of 69-74 bpm had a significant effect on admission to hospital for acute coronary syndrome in the ITT (estimate 1.10, HR 3.004, p = .0196) and EA (estimate 1.26, HR 3.526, p = .0132) groups. Seven (1.1%) patients reported drug related adverse events. CONCLUSION: Reduction in RHR with bisoprolol lowered the incidence of composite cardiac events along with an acceptable safety and tolerability profile.

SOCS1 gene promoter methylation status is associated with in-stent restenosis after percutaneous coronary intervention.

BACKGROUND: Inflammation is involved in the development of In-stent restenosis (ISR) after percutaneous coronary intervention. We aimed to investigate the association between of suppressor of cytokine signaling-1 (SOCS1), a major negative regulator for inflammation, and the occurrence of ISR in Chinese patients. METHODS: We enrolled patients with coronary artery disease who underwent PCI with stenting. PCI procedures were performed successfully and a follow-up angiography was repeated 1 year later to determine ISR presence. Real-time quantitative reverse transcription polymerase chain reaction and methylation-specific polymerase chain reaction (MSP) was used for SOCS1 methylation status determination. RESULTS: There are a total of 187 patients had SOCS1 methylation while there are 275 had no methylated SOCS1. Patients with SOCS1 methylation have a higher inflammatory status. Of note, patients with SOCS1 methylation had a significantly lower SOCS1 mRNA levels compared to those without. Patients with ISR tend to have a significantly higher percentage of SOCS1 gene methylation (P<0.001). We next conducted the Binary logistic regression analyses to determine the correlation of SOCS1 with ISR, using demographic and clinical characteristics. Our data show that SOCS1 methylation is the only factors which are closely associated with ISR incidence. Patients with SOCS1 methylation are 5 times more likely to have ISR after successful PCI as opposed to those without SOCS1 methylation (P<0.001). CONCLUSION: Our data suggest that blood SOCS1 gene promoter methylation status is closely associated with ISR occurrence, thus may be used as a marker to predict ISR.

MiRNA-30e mediated cardioprotection of ACE2 in rats with Doxorubicin-induced heart failure through inhibiting cardiomyocytes autophagy.

OBJECTIVE: miRNAs are a class of small non-coding RNAs that has been proved to be involved in cardioprotection. The present study was to detect role of miR-30e in cardiac-protective action of ACE2 (angiotensin-converting enzyme 2). METHODS: Sprague Dawley rats were divided into 3 groups and received treatment for a total of 6weeks: group1, normal rats; group2, Doxorubicin-induced heart cardiomyopathy (DHC) rats; and group3, rhACE2 (recombinant human ACE2) treated DHC rats. Doxorubicin was discontinuously administered via intraperitoneal injection. Primary cardiomyocytes and H9C2 cell line were used for in vitro experiments. MiR-30a, miR-30c and miR-30e expression were determined using qRT-PCR. Expression of autophagy associated gene expression including Beclin-1 and LC3 II/I were determined using western blot. Cell apoptosis was evaluated using TUNEL assay. RESULTS: Administration of ACE2 suppressed harmful action of Doxorubicin and caused a significant improvement of left ventricular contractility function, upregulation in miR-30 (a, c and e) expression, and inhibition in Beclin-1 expression and LC3-II/I ratio. This was supported by results of Ad-ACE2-incubated primary cardiomyocytes. By manipulating miR-30e expression in H9C2 cells, we observed that miR-30e regulated Beclin-1 expression via inhibiting its 3'UTR activity. MiR-30e mimic treatment resulted in downregulation of Beclin-1 and protected primary cardiomyocytes against apoptosis. Moreover, silencing miR-30e induced cardiomyocytes apoptosis was abrogated by ACE2 overexpresssion. This was further confirmed by in vivo DHC rat experiments that showed that co-injected ACE2 and miR-30 inhibitor reduced cardiac function. CONCLUSION: In summary, administration of ACE2 attenuates Doxorubicin-induced cardiac dysfunction via preservation of cardiomyocytes autophagy in a miR-30e/beclin-1 signal pathway.

The relationship between serum levels of total bilirubin and coronary plaque vulnerability.

OBJECTIVES: Previous studies have reported that serum total bilirubin provides some protection against coronary artery disease (CAD); however, the relationship between serum levels of total bilirubin and culprit/target plaque vulnerability in patients with CAD remains unclear. In this study, we investigated the association between total bilirubin and tissue characterization of coronary plaque in patients with CAD. METHODS: We enrolled 85 consecutive patients with CAD who underwent coronary angiography and intravascular ultrasound analyses [45 with acute coronary syndrome (ACS); 40 with stable angina pectoris (SAP)], and 45 age-matched participants served as the control group. Serum levels of total bilirubin in all participants were measured. The stability of the coronary plaque was compared between the ACS group and the SAP group, and the relationship between serum levels of total bilirubin and the features of coronary plaque was analyzed. RESULTS: Serum levels of total bilirubin in the ACS group were significantly lower than those in the SAP and control groups (P<0.01). Serum levels of total bilirubin were positively associated with fibrous plaques (r=0.386, P<0.001), whereas they were negatively associated with plaque burden (r=-0.413, P<0.001), lipid plaque (r=-0.419, P<0.001), and remodeling index (r=-0.275, P<0.05). Furthermore, an independent association between serum levels of total bilirubin and lipid-rich plaques (odds ratio, 0.78; 95% confidence interval, 0.64-0.95) was observed. CONCLUSION: Serum total bilirubin levels were found to be inversely associated with coronary plaque vulnerability, and decreased serum levels of total bilirubin may be an important factor for coronary lipid plaque formation, which contributes to the pathogenesis of CAD.

National prevalence of coronary heart disease and its relationship with human development index: A systematic review.

BACKGROUND: Coronary heart disease has become a major health concern over the past several decades. Several reviews have assessed the effects of socioeconomic status on the coronary heart disease epidemic in communities and countries, but only a few reviews have been performed at a global level. This study was to explore the relationship between the prevalence of coronary heart disease and socioeconomic development worldwide using the Human Development Index. DESIGN: Systematic review. METHODS: The data in this study were collected from the MEDLINE database. Cross-sectional studies reporting the prevalence of coronary heart disease until November 2014 were collected. The Human Development Index was sourced from the United Nations Development Programme Database and was used to measure the socioeconomic achievements of countries. Each country was classified as a developing or developed country based on its level of development according to the Human Development Index value. RESULTS: Based on the data analysis on the global level, coronary heart disease prevalence had no association with the national Human Development Index (rho = 0.07). However, there was a positive association between coronary heart disease prevalence and the national Human Development Index in developing countries, although a negative association existed in developed countries (rho = 0.47 and -0.34, respectively). In addition, the past decades have witnessed a growing coronary heart disease epidemic in developing countries, with reverse trends observed in developed countries (P = 0.021 and 0.002, respectively). CONCLUSIONS: With the development of socioeconomic status, as measured by the Human Development Index, the prevalence of coronary heart disease is growing in developing countries, while declining in developed countries. Future research needs to pay more attention to the reasonable allocation of medical resources and control of coronary heart disease risk factors.

The Combined Effect of Ear Lobe Crease and Conventional Risk Factor in the Diagnosis of Angiographically Diagnosed Coronary Artery Disease and the Short-Term Prognosis in Patients Who Underwent Coronary Stents.

The role of diagonal ear lobe crease (DELC) in coronary artery disease (CAD) diagnosis and prognosis remains controversial. In this study, we aimed to assess the combined effect of DELC with other conventional risk factors in the diagnosis and prognosis of CAD in Chinese patients who underwent angiography and coronary stent implantation.The study consisted of 956 consecutive patients who underwent angiography. The DELC was identified as no DELC, unilateral, and bilateral DELC. The conventional risk factors for CAD were recorded.Our dada showed that the overall presence of DELC is associated with CAD risk. Stratification analyses revealed that the diagnostic value of DELC was mostly significant in those with >4 risk factors. Also in patients with >4 risk factors, the presence of bilateral DELC remains to be associated with higher hs-CRP level, higher severity of CAD, and higher possibility of developing major adverse cardiac events after successful percutaneous coronary intervention (PCI).Our study confirmed the relation of DELC with CAD in Chinese patients; more importantly, our data suggest the combination of DELC and CAD risk factors will help to predict the incidence of CAD and may predict the prognosis after successfully PCI.

WITHDRAWN: Traditional acupuncture and myocardial ischemia.

The Publisher regrets that this article is an accidental duplication of an article that has already been published in Int. J. Cardiol. 189 (2015) 281, http://dx.doi.org/10.1016/j.ijcard.2014.11.202. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

Myocardial protection of early extracorporeal membrane oxygenation (ECMO) support for acute myocardial infarction with cardiogenic shock in pigs.

The aim of this study was to explore myocardial protection of early extracorporeal membrane oxygenation (ECMO) support for acute myocardial infarction with cardiogenic shock in pigs. 24 male pigs (34.6 ± 1.3 kg) were randomly divided into three groups-control group, drug therapy group, and ECMO group. Myocardial infarction model was created in drug therapy group and ECMO group by ligating coronary artery. When cardiogenic shock occurred, drugs were given in drug therapy group and ECMO began to work in ECMO group. The pigs were killed 24 h after cardiogenic shock. Compared with in drug therapy group, left ventricular end-diastolic pressure in ECMO group decreased significantly 6 h after ligation (P < 0.05). At the end of the experiments, LV - dp/dt among three groups was significantly different, drug therapy group < ECMO group < control group. There was no difference in LV + dp/dt between drug therapy group and ECMO group. Compared with drug group, myocardial infarct size of ECMO group did not reduce significantly, but myocardial enzyme and troponin-I decreased significantly. Compared with drug therapy, ECMO improves left ventricular diastolic function, and may improve systolic function. ECMO cannot reduce myocardial infarct size without revascularization, but may have positive effects on ischemic areas by avoiding further injuring.

Impact of guidewire selection and operator expertise on radiation exposure in transradial angiography.

BACKGROUND: Several studies have implied that the time of radiation exposure for patients and operators during the transradial approach for coronary angiography (TRA) is associated with the use of different guidewire or catheter and operator's finesse. This study aimed to assess the effects of non-hydrophilic or hydrophilic guidewire and operator expertise on fluoroscopy time and procedure time of TRA and further effects on the procedure safety. METHODS: A total of 1035 consecutive patients undergoing TRA were recruited prospectively and respectively divided into non-hydrophilic guidewire and hydrophilic guidewire group, or well-experienced group and less-experienced group. The primary endpoints were fluoroscopy time and procedure time. Secondary endpoints included contrast volume, cost, guidewire exchange, switchover and complications . RESULTS: TRA by non-hydrophilic guidewire group showed shorter fluoroscopy time and procedure time compared with hydrophilic guidewire group, similar results were found between well-experienced group and less-experienced group. Moreover, using of non-hydrophilic guidewire significantly reduced the incidence of hematoma and abnormal guidewie advancement, well-experienced group showed less dosage of contrast volume, lower incidence of radial artery spasm and frequency of guidewire exchange. CONCLUSIONS: TRA by non-hydrophilic guidewire and well-experienced operator can decrease radiation exposure of patients and operators through reducing the fluoroscopy time and procedure time and further increase procedure safety. These will contribute to the optimization of TRA procedure and promote its widely application.

Role of stromal cell-derived factor-1 in patients with non-ST elevation acute coronary syndrome.

The predictive value of stromal cell-derived factor-1 (SDF-1) has not been established in patients with non-ST elevation acute coronary syndrome (non-STEACS). A total of 678 consecutive patients with non-STEACS and moderate to high TIMI (Thrombolysis In Myocardial Infarction) risk scores were recruited. All patients underwent an early invasive strategy and then were followed-up for 18 months for clinical events. Left ventricular remodeling was assessed by echocardiography. Plasma concentrations of SDF-1 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were analyzed. SDF-1 level was an independent predictor of left ventricular remodeling (OR = 2.95, 95% CI = 2.02-4.30, P < 0.001). Cox regression analysis demonstrated that both SDF-1 and NT-proBNP levels were significant independent predictors of death, myocardial infarction, or heart failure (HR = 2.45, 95% CI = 1.71-3.50, P < 0.001; HR = 3.71, 95% CI = 2.41-5.70, P < 0.001, respectively). The area under the ROC curves for SDF-1 (0.776) and NT-proBNP (0.817) were similar. The logistic model with both markers yielded a larger area under the ROC curve (0.862) than that of SDF-1 (P < 0.001) or NT-proBNP (P = 0.0001) alone. In patients stratified by NT-proBNP (above 615.4 pmol/L), SDF-1 (above 2175.1 pg/mL) was associated with poorer outcome (P < 0.001). Findings were similar for death and heart failure as individual endpoints. In non-STEACS, higher SDF-1 levels were a significant predictor of death, myocardial infarction, or heart failure independently of baseline clinical characteristics and NT-proBNP, and the combination of SDF-1 and NTproBNP significantly improved risk stratification. These data highlight the prognostic value of multiple, complementary biomarkers in non-ST elevation acute coronary syndrome.