Plaque burden is associated with minimal intimal coverage following drug-eluting stent implantation in an adult familial hypercholesterolemia swine model

Abstract Safety and efficacy of coronary drug-eluting stents (DES) are often preclinically tested using healthy or minimally diseased swine. These generally show significant fibrotic neointima at follow-up, while in patients, incomplete healing is often observed. The aim of this study was to investigate neointima responses to DES in swine with significant coronary atherosclerosis. Adult familial hypercholesterolemic swine (n = 6) received a high fat diet to develop atherosclerosis. Serial OCT was performed before, directly after, and 28 days after DES implantation (n = 14 stents). Lumen, stent and plaque area, uncovered struts, neointima thickness and neointima type were analyzed for each frame and averaged per stent. Histology was performed to show differences in coronary atherosclerosis. A range of plaque size and severity was found, from healthy segments to lipid-rich plaques. Accordingly, neointima responses ranged from uncovered struts, to minimal neointima, to fibrotic neointima. Lower plaque burden resulted in a fibrotic neointima at follow-up, reminiscent of minimally diseased swine coronary models. In contrast, higher plaque burden resulted in minimal neointima and more uncovered struts at follow-up, similarly to patients’ responses. The presence of lipid-rich plaques resulted in more uncovered struts, which underscores the importance of advanced disease when performing safety and efficacy testing of DES

SYNTAX score II predicts long-term mortality in patients with one- or two-vessel disease

Objective SYNTAX score II (SSII) is a long-term mortality prediction model to guide the decision making of the heart-team between coronary artery bypass grafting or percutaneous coronary intervention (PCI) in patients with left main or three-vessel coronary artery disease. This study aims to investigate the long-term predictive value of SSII for all-cause mortality in patients with one- or two-vessel disease undergoing PCI. Methods A total of 628 patients (76% men, mean age: 61±10 years) undergoing PCI due to stable angina pectoris (43%) or acute coronary syndrome (57%), included between January 2008 and June 2013, were eligible for the current study. SSII was calculated using the original SYNTAX score website (www.syntaxscore.com). Cox regression analysis was used to assess the association between continuous SSII and long-term all-cause mortality. The area under the receiver-operating characteristic curve was used to assess the performance of SSII. Results SSII ranged from 6.6 to 58.2 (median: 20.4, interquartile range: 16.1–26.8). In multivariable analysis, SSII proved to be an independent significant predictor for 4.5-year mortality (hazard ratio per point increase: 1.10; 95% confidence interval: 1.07–1.13; p<0.001). In terms of discrimination, SSII had a concordance index of 0.77. Conclusion In addition to its established value in patients with left main and three-vessel disease, SSII may also predict long-term mortality in PCI-treated patients with one- or two-vessel disease

Serial Coronary Imaging of Early Atherosclerosis Development in Fast-Food-Fed Diabetic and Nondiabetic Swine

Patients with diabetes mellitus (DM) are at increased risk for atherosclerosis-related events compared to non-DM (NDM) patients. With an expected worldwide epidemic of DM, early detection of anatomic and functional coronary atherosclerotic changes is gaining attention. To improve our understanding of early atherosclerosis development, we studied a swine model that gradually developed coronary atherosclerosis. Interestingly, optical coherence tomography, near-infrared spectroscopy (NIRS), vascular function, and histology demonstrated no differences between development of early atherosclerosis in fast-food-fed (FF) DM swine and that in FF-NDM swine. Coronary computed tomography angiography did not detect early atherosclerosis, but optical coherence tomography and near-infrared spectroscopy demonstrated coronary atherosclerosis development in FF-DM and FF-NDM swine

Neoatherosclerosis development following bioresorbable vascular scaffold implantation in diabetic and non-diabetic swine

Background: DM remains a risk factor for poor outcome after stent-implantation, but little is known if and how DM affects the vascular response to BVS. Aim: The aim of our study was to examine coronary responses to bioresorbable vascular scaffolds (BVS) in swine with and without diabetes mellitus fed a ‘fast-food’ diet (FF-DM and FF-NDM, respectively) by sequential optical coherence tomography (OCT)-imaging and histology. Methods: Fifteen male swine were evaluated. Eight received streptozotocin-injection to induce DM. After 9 months (M), 32 single BVS were implanted in epicardial arteries with a stent to artery (S/A)-ratio of 1.1:1 under quantitative coronary angiography (QCA) and OCT guidance. Lumen, scaffold, neointimal coverage and composition were assessed by QCA, OCT and near-infrared spectroscopy (NIRS) pre- and/or post-procedure, at 3M and 6M. Additionally, polarization-sensitive (PS)-OCT was performed in 7 swine at 6M. After sacrifice at 3M and 6M, histology and polymer degradation analysis were performed. Results: Late lumen loss was high (~60%) within the first 3M after BVS-implantation (P0.20). Neointimal coverage was highly heterogeneous in all swine (DM vs. NDM P>0.05), with focal lipid accumulation, irregular collagen distribution and neointimal calcification. Likewise, polymer mass loss was low (~2% at 3M, ~5% at 6M;P>0.20) and not associated with DM or inflammation. Conclusion: Scaffold coverage showed signs of neo-atherosclerosis in all FF-DM and FF-NDM swine, scaffold polymer was preserved and the vascular response to BVS was not influenced by diabetes

Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease

BACKGROUND: DNA methylation is implicated in coronary heart disease (CHD), but current evidence is based on small, cross-sectional studies. We examined blood DNA methylation in relation to incident CHD across multiple prospective cohorts. METHODS: Nine population-based cohorts from the United States and Europe profiled epigenome-wide blood leukocyte DNA methylation using the Illumina Infinium 450k microarray, and prospectively ascertained CHD events including coronary insufficiency/unstable angina, recognized myocardial infarction, coronary revascularization, and coronary death. Cohorts conducted race-specific analyses adjusted for age, sex, smoking, education, body mass index, blood cell type proportions, and technical variables. We conducted fixed-effect meta-analyses across cohorts. RESULTS: Among 11 461 individuals (mean age 64 years, 67% women, 35% African American) free of CHD at baseline, 1895 developed CHD during a mean follow-up of 11.2 years. Methylation levels at 52 CpG (cytosine-phosphate-guanine) sites were associated with incident CHD or myocardial infarction (false discovery rate<0.05). These CpGs map to genes with key roles in calcium regulation (ATP2B2, CASR, GUCA1B, HPCAL1), and genes identified in genome- and epigenome-wide studies of serum calcium (CASR), serum calcium-related risk of CHD (CASR), coronary artery calcified plaque (PTPRN2), and kidney function (CDH23, HPCAL1), among others. Mendelian randomization analyses supported a causal effect of DNA methylation on incident CHD; these CpGs map to active regulatory regions proximal to long non-coding RNA transcripts. CONCLUSION: Methylation of blood-derived DNA is associated with risk of future CHD across diverse populations and may serve as an informative tool for gaining further insight on the development of CHD

Analysis of shared heritability in common disorders of the brain

Paroxysmal Cerebral Disorder

Design-for-testability of PLA's using statistical cooling

A method for designing easily testable PLA's with low overhead is presented. The method is based on a reduction of product lines and the addition of a small number of inputs. The required additional hardware is calculated using a statistical cooling algorithm. The presented design-for-testability method guarantees a 100 percent fault coverage with respect to multiple stuck-at faults and multiple missing/extra crosspoint faults

Invasive imaging of bioresorbable coronary scaffolds - A review

Various fully bioresorbable stents (BRS) have been recently developed, allowing for temporary scaffolding of the vessel wall. The potentially unique advantage of BRS to temporary scaffold the vessel could reduce the risk of adverse clinical outcomes caused by acute vessel geometry changes, late malapposition, jailed side branches or inflexibility of permanent stents. The design of BRS is, however, not similar for all stents, resulting in differences in degradation and behaviour. To assess the performance of BRS, the effect of degradation and behaviour on the vessel wall should be accurately evaluated. Intracoronary imaging techniques such as intravascular ultrasound (IVUS), optical coherence tomography (OCT) and near-infrared spectroscopy (NIRS) allow for detailed longitudinal evaluation of the stent and the vessel wall and might therefore aid in improving design and behaviour of BRS