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Aims  Many patients with angina, especially women, do not have obstructive coronary artery disease (CAD) yet have impaired prognosis. We investigated whether routine assessment of coronary microvascular dysfunction (CMD) is feasible and predicts adverse outcome in women with angina and no obstructive CAD. Methods and results  After screening 7253, we included 1853 women with angina and no obstructive CAD on angiogram who were free of previous CAD, heart failure, or valvular heart disease in the prospective iPOWER (Improving Diagnosis and Treatment of Women with Angina Pectoris and Microvascular Disease) study. CMD was assessed by Doppler echocardiography in the left anterior descending artery as coronary flow velocity reserve (CFVR). Patients were followed for a composite outcome of cardiovascular death, myocardial infarction (MI), heart failure, stroke, and coronary revascularization. CFVR was obtained in 1681 patients (91%) and the median CFVR was 2.33 (quartiles 1–3: 2.00–2.74). During a median follow-up of 4.5 years, 96 events occurred. In univariate Cox regression, CFVR was associated with the composite outcome {hazard ratio (HR) 1.07 [95% confidence interval (CI) 1.03–1.11] per 0.1 unit decrease in CFVR; P  < 0.001}, primarily driven by an increased risk of MI and heart failure. Results remained significant in multivariate analysis [HR 1.05 (95% CI 1.01–1.09) per 0.1 unit decrease in CFVR; P  = 0.01]. In exploratory analyses, CFVR was also associated with the risk of repeated hospital admission for angina and all-cause mortality. Conclusion  Assessment of CFVR by echocardiography is feasible and predictive of adverse outcome in women with angina and no obstructive CAD. Results support a more aggressive preventive management of these patients and underline the need for trials targeting CMD. Open in new tab Download slide Open in new tab Download slide [ABSTRACT FROM AUTHOR]

Background: Pregnant women are at increased risk of thrombotic adverse events. Plasma derived immune globulin (IG) products, which are used in pregnancy for various indications, may contain procoagulant impurity activated coagulation factor XI (FXIa). Procoagulant IG products have been associated with increased thrombogenicity but their effect in pregnancy is unknown. Methods: Late pregnant (gestation days 17–20) or early lactation (days 1–3) and control female mice were treated with IGs supplemented with human FXIa then subjected to ferric chloride (FeCl3) vessel injury. Occlusion of blood vessel was assessed by recording blood velocity in the femoral vein for 20 min using doppler ultrasound laser imaging. FXIa dose was selected by the ability to increase thrombin generation in mouse plasma in vitro. Results: FXIa produced robust thrombin generation in mouse plasma ex vivo. Following FeCl3 injury, pregnant and non-pregnant mice receiving IG + FXIa exhibited faster reduction of blood velocity in femoral vein compared to IG alone or untreated controls. In vitro, thrombin generation in plasma samples collected after thrombosis in FXIa-treated animals was elevated and could be reduced by anti-FXI antibody. Conclusions: Our results suggest that intravenously-administered FXIa may contribute to thrombosis at the site of vascular injury in both pregnant and non-pregnant animals. [ABSTRACT FROM AUTHOR]

Coronary artery lesion (CAL) caused by Kawasaki disease (KD) is currently the most common acquired heart disease in children in many countries. Nevertheless, there is no single useful marker existing for predicting CAL of KD. Recently, many reports have noted that N-terminal pro-brain natriuretic peptide (NT-proBNP) can be utilized as a biomarker to predict CAL. Thus, we perform a meta-analysis to ascertain the diagnostic value of NT-proBNP in detecting CAL of KD in the acute phase. PubMed, the Cochrane Central Register of Controlled Trials, EMBASE, and China National Knowledge Infrastructure were searched to detect relevant publications. Finally, eight eligible studies were included. The overall diagnostic sensitivity and specificity were 0.84 (95% confidence interval [CI]: 0.78–0.89) and 0.71 (95% CI: 0.68–0.75), respectively. The area under the summary receiver operating characteristic curves value (SROC) curve was 0.8582 ± 0.0531. Moreover, the overall sensitivity and specificity across five studies adopted the threshold of approximately 900 ng/L were 0.82 (95% CI: 0.73–0.89) and 0.72 (95% CI: 0.68–0.76), respectively. SROC was 0.8868 ± 0.0486. This meta-analysis would be the first one to describe the role of NT-proBNP in detecting CAL of KD. We register this study with PROSPERO (CRD42019130083). [ABSTRACT FROM AUTHOR]

The present study aimed to analyze the effects of reperfusion of a distant coronary artery on cardiac function, the ultrastructure, and the molecular environment of the remote myocardium immediately after the completion of myocardial regional necrosis: delayed reperfusion (DR). Additionally, the effects of prior exercise on the outcomes of DR were investigated. Female rats with permanent occlusion or delayed reperfusion were randomly assigned to an exercise (swimming, 1 h/day, 5 days/week for 8 weeks) or sedentary protocol. Thus, the study included the following four groups: sedentary permanent occlusion, exercise permanent occlusion, sedentary delayed reperfusion, and exercise delayed reperfusion. The descending coronary artery was occluded for 1 h. Reperfusion was confirmed by contrast echocardiography, and the rats were observed for 4 weeks. Permanent occlusion and DR caused similar myocardial infarction sizes among the four groups. Interestingly, exercise significantly decreased the mortality rate. Delayed reperfusion resulted in significant benefits, including enhanced hemodynamics and papillary muscle contraction, as well as reduced apoptosis and collagen content. Protein calcium kinetics did not change. Meanwhile, developed tension and the Frank–Starling mechanism were enhanced, suggesting that calcium sensitivity was intensified in myofilaments. Remarkable remote myocardial benefits occurred after distant DR, and prior exercise intensified cardiac recovery. Our findings provide valuable information about DR. Our data might explain the better clinical outcomes in recent studies showing that late reperfusion could improve heart failure in patients with myocardial infarction. In conclusion, DR has remote myocardial benefits, including inotropism enhancement, pulmonary congestion reduction, and collagen and apoptosis attenuation, which are enhanced by prior exercise. [ABSTRACT FROM AUTHOR]

Background: The second generation STENTYS Xposition S self-expanding stent with a novel balloon delivery system was launched in May 2015. The stents unique properties are well suited for the treatment of left main stem disease where large diameters, coverage of diameter differences and precise positioning are required. We report the first consecutive experience of using this device in the treatment of left main stem lesions. Methods: 20 consecutive patients with a mean age of 73.9±10.1 years were treated over a period of 8 months at our institution and were assessed on the parameters of technical, angiographic and procedural success. Results: Technical success was achieved in 95% of cases and angiographic success in 80% of cases. There was no incidence of geographical miss. Side branch access was straightforward, with no failure to recross stent struts, dilate or deploy a second stent if required. In this unselected clinical cohort, 2 critically ill patients with cardiogenic shock on presentation died despite successful revascularisation. There was no incidence of early stent related complications up to 30-day follow up. Conclusion: This first consecutive series of left main lesions treated with STENTYS Xposition S documents high acute technical and procedural success rates. [ABSTRACT FROM AUTHOR]

Aims: To assess the serial changes of de novo coronary lesions treated with paclitaxel-coated balloon (PCB) using intravascular ultrasound virtual histology (IVUS-VH) and fractional flow reserve (FFR). Method and Results: This prospective observational study enrolled 27 patients with coronary artery disease treated with PCB who underwent coronary angiography, IVUS-VH and FFR before, immediately after intervention and at 9 months. 28 de novo lesions were successfully treated with PCB. Angiographic late luminal loss was 0.02 ± 0.27mm. Mean vessel and lumen areas showed increase at 9 months (12.0 ± 3.5mm2 to 13.2 ± 3.9mm2, p <0.001; and 5.4 ± 1.2mm2 to 6.5 ± 1.8mm2, p <0.001, respectively). Although mean plaque area was unchanged (6.6 ± 2.6mm2 to 6.6 ± 2.4mm2, p = 0.269), percent atheroma volume decreased significantly (53.4 ± 7.9% to 49.5 ± 6.4%, p = 0.002). The proportion of plaque compositions including fibrous, fibrofatty, dense calcium and necrotic core by IVUS-VH was unchanged at 9 months. The FFR of the treated lesion was 0.71 ± 0.13 pre-procedure, 0.87 ± 0.06 post-procedure and 0.84 ± 0.06 at follow-up. Conclusions: De novo coronary lesions treated with PCB showed persistent anatomical and physiological patency with plaque redistribution and vessel remodeling without chronic elastic recoil or plaque compositional change during follow-up. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) is a systemic vasculitis primarily affecting children < 5 years old. Genes significantly associated with KD mostly involve cardiovascular, immune, and inflammatory responses. Recent studies have observed stronger associations for KD risk with multiple genes compared to individual genes. Therefore, we investigated whether gene combinations influenced KD susceptibility or coronary artery lesion (CAL) formation. We examined 384 single-nucleotide polymorphisms (SNPs) for 159 immune-related candidate genes in DNA samples from KD patients with CAL (n = 73), KD patients without CAL (n = 153), and cohort controls (n = 575). Individual SNPs were first assessed by univariate analysis (UVA) and multivariate analysis (MVA). We used multifactor dimensionality reduction (MDR) to examine individual SNPs in one-, two-, and three-locus best fit models. UVA identified 53 individual SNPs that were significantly associated with KD risk or CAL formation (p < 0.10), while 35 individual SNPs were significantly associated using MVA (p ≤ 0.05). Significant associations in MDR analysis were only observed for the two-locus models after permutation testing (p ≤ 0.05). In logistic regression, combined possession of PDE2A (rs341058) and CYFIP2 (rs767007) significantly increased KD susceptibility (OR = 3.54; p = 4.14 x 10−7), while combinations of LOC100133214 (rs2517892) and IL2RA (rs3118470) significantly increased the risk of CAL in KD patients (OR = 5.35; p = 7.46 x 10−5). Our results suggest varying gene-gene associations respectively predispose individuals to KD risk or its complications of CAL. [ABSTRACT FROM AUTHOR]

Introduction. Spontaneous coronary artery dissection (SCAD) is a rare but important cause of acute coronary syndrome with a spectrum of disease that can include unstable angina, acute myocardial infarction, or sudden cardiac death. It has also been found in case reports to be caused by shear stress from physical exertion. We present a rare cycling induced SCAD that occurred in our institution in an otherwise healthy male with no cardiac risk factors. Case Presentation. A 36-year-old male presented to the emergency department with complaints of lightheadedness and diaphoresis after a bicycle fall. In the emergency department, he complained of feeling lightheaded and diaphoretic and having mid back pain. Patient had an ECG performed which showed lateral ST segment elevation and troponin I that was positive. A coronary angiography was subsequently performed demonstrating a spontaneous coronary artery dissection of left anterior descending coronary artery. Conclusion. SCAD is a rare cause of myocardial infarction, occurring in healthy individuals, which is rarely reported in the literature. Nearly 70% are diagnosed in postmortem studies after sudden cardiac death. Only 12 cases have been reported from activities involving physical exertion and no studies to our knowledge demonstrate this. [ABSTRACT FROM AUTHOR]

Neointimal formation and cell proliferation resulting into in-stent restenosis is a major pathophysiological event following the deployment of stents in the coronary arteries. In this study, we assessed the degree of injury, based on damage to internal elastic lamina, media, external elastic lamina, and adventitia following the intravascular stenting, and its relationship with the degree of smooth muscle cell proliferation. We examined the smooth muscle cell proliferation and their phenotype at different levels of stent injury in the coronary arteries of domestic swine fed a normal swine diet. Five weeks after stent implantation, swine with and without stents were euthanized and coronaries were excised. Arteries were embedded in methyl methacrylate and sections were stained with H&E, trichrome, and Movat’s pentachrome. The expression of Ki67, α-smooth muscle actin (SMA), vimentin, and HMGB1 was evaluated by immunofluorescence. There was a positive correlation between percent area stenosis and injury score. The distribution of SMA and vimentin was correlated with the degree of arterial injury such that arteries that had an injury score >2 did not have immunoreactivity to SMA in the neointimal cells near the stent struts, but these neointimal cells were positive for vimentin, suggesting a change in the smooth muscle cell phenotype. The Ki67 and HMGB1 immunoreactivity was highly correlated with the fragmentation of the IEL and injury in the tunica media. Thus, the extent of coronary arterial injury during interventional procedure will dictate the degree of neointimal hyperplasia, in-stent restenosis, and smooth muscle cell phenotype. [ABSTRACT FROM AUTHOR]

Objectives: Glycated hemoglobin (HbA1c) is associated with an increased risk of cardiovascular disease. The aim of this study was to examine the relationship between HbA1c levels and the complexity of coronary artery lesions among the older patients with diabetes mellitus (DM). Methods: This retrospective study enrolled a total of 3805 consecutive type 2 DM patients aged 60 years and older who underwent their first elective coronary angiography and had their HbA1c levels measured at the Chinese PLA General Hospital between December 2005 and December 2012.The complexity of the coronary artery lesions was evaluated using the Syntax score, and the subjects were divided into three groups according to their HbA1c levels. Logistic regression and Pearson correlation were used to analyze the association between the measured HbA1c levels and Syntax score. Results: The mean age was 72.3±10.6 years. The higher HbA1c levels were significantly associated with higher Syntax score (p<0.001). The unadjusted correlation coefficient of HbA1c levels and the Syntax score was 0. 371 (p<0.001). In addition, the higher HbA1c categories were able to independently predict patients with intermediate or high Syntax score (Syntax score ≥23) after adjustment for age, sex, hypertension, smoking, dyslipidemia and creatinine levels in the logistic regression analysis. Conclusion: HbA1c is significantly associated with the complexity of coronary lesions among older patients with DM. A higher HbA1c value is an independent predictor of the prevalence of complex coronary lesions. Further prospective multi-centre studies are needed to confirm this finding. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) is a multi-systemic vasculitis that preferentially affects children. A single nucleotide polymorphism (SNP) in inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) has been identified to be an important polymorphism in the risk of KD. This study was conducted to comprehensively investigate the associations between all tagging SNPs of ITPKC in the risk of KD in a Taiwanese population. A total of 950 subjects (381 KD patients and 569 controls) were recruited. Seven tagging SNPs (rs11673492, rs7257602, rs7251246, rs890934, rs10420685, rs2607420, rs2290692) were selected for TaqMan allelic discrimination assay. Clinical data of coronary artery lesions (CAL) and aneurysms were collected for analysis. A significant association was found between rs7251246 in ITPKC and CAL formation. Haplotype analysis for ITPKC polymorphisms also confirmed this association in the patients with CAL and aneurysm formation. This is the first study to identify that SNP rs7251246 in ITPKC is associated with the severity of KD. [ABSTRACT FROM AUTHOR]

Coronary artery perforation is an uncommon complication in patients with coronary heart disease undergoing percutaneous coronary intervention. However, pericardial tamponade following coronary artery perforation may be lethal, and prompt treatment is crucial in managing such patients. Balloon occlusion and the reversal of anticoagulant activity are the common methods used to prevent cardiac tamponade by reducing the amount of bleeding. Herein, we discuss the pros and cons of currently used occlusion types for coronary perforation. Optimal balloon occlusion methods should reduce the amount of bleeding and ameliorate subsequent myocardial ischemia injury, even during cardiac surgery. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) usually affects the children younger than 5 years of age and subsequently causes coronary artery lesions (CALs) without timely identification and treatment. Developing a robust and fast prediction method may facilitate the timely diagnosis of KD, significantly reducing the risk of CALs in KD patients. The levels of inflammatory serum proteins dramatically vary during the onsets of many immune diseases, including in KD. However, our understanding of their pathogenic roles in KD is behind satisfaction. The purpose of this study was to evaluate candidate diagnostic serum proteins and the potential mechanism in KD using iTRAQ gel-free proteomics. We enrolled subjects and conducted iTRAQ gel-free proteomics to globally screen serum proteins followed by specific validation with ELISA. Further in vitro leukocyte trans-endothelial model was also applied to investigate the pathogenesis roles of inflammatory serum proteins. We identified six KD protein biomarkers, including Protein S100-A8 (S100A8), Protein S100-A9 (S100A9), Protein S100-A12 (S100A12), Peroxiredoxin-2 (PRDX2), Neutrophil defensin 1 (DEFA1) and Alpha-1-acid glycoprotein 1 (ORM1). They enabled us to develop a high-performance KD prediction model with an auROC value of 0.94, facilitating the timely identification of KD. Further assays concluded that recombinant S100A12 protein treatment activated neutrophil surface adhesion molecules responsible for adhesion to endothelial cells. Therefore, S100A12 promoted both freshly clinically isolated neutrophils and neutrophil-like cells to infiltrate through the endothelial layer in vitro. Finally, the antibody against S100A12 may attenuate the infiltration promoted by S100A12. Our result demonstrated that evaluating S100A8, S100A9, S100A12, PRDX2, DEFA1 and ORM1 levels may be a good diagnostic tool of KD. Further in vitro study implied that S100A12 could be a potential therapeutic target for KD. [ABSTRACT FROM AUTHOR]