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Background: We studied the effect of bioresorbable vascular scaffold (BVS) implantation on distal coronary endothelial function, in swine on a high fat diet without (HFD) or with diabetes (DM + HFD). Methods: Five DM + HFD and five HFD swine underwent BVS implantation on top of coronary plaques, and were studied six months later. Conduit artery segments >5 mm proximal and distal to the scaffold and corresponding segments of non-scaffolded coronary arteries, and segments of small arteries within the flow-territory of scaffolded and non-scaffolded arteries were harvested for in vitro vasoreactivity studies. Results: Conduit segments proximal and distal of the BVS edges showed reduced endothelium-dependent vasodilation as compared to control vessels (p ≤ 0.01), with distal segments being most prominently affected (p ≤ 0.01). Endothelial dysfunction was only observed in DM ± HFD swine and was principally due to a loss of NO. Endothelium-independent vasodilation and vasoconstriction were unaffected. Surprisingly, segments from the microcirculation distal to the BVS showed enhanced endothelium-dependent vasodilation (p < 0.01), whereas endothelium-independent vasodilation and vasoconstriction were unaltered. This enhanced vasorelaxation was only observed in DM + HFD swine, and did not appear to be either NO- or EDHF-mediated. Conclusions: Six months of BVS implantation in DM + HFD swine causes NO-mediated endothelial dysfunction in nearby coronary segments, which is accompanied by a, possibly compensatory, increase in endothelial function of the distal microcirculation. Endothelial dysfunction extending into coronary conduit segments beyond the implantation-site, is in agreement with recent reports expressing concern for late scaffold thrombosis and of early BVS failure in diabetic patients.

BACKGROUND: Diabetes mellitus (DM) is associated with a range of microvascular complications including diabetic nephropathy (DN). Microvascular abnormalities in the kidneys are common histopathologic findings in DN, which represent one manifestation of ongoing systemic microvascular damage. Recently, sidestream dark-field (SDF) imaging has emerged as a noninvasive tool that enables one to visualize the microcirculation. In this study, we investigated whether changes in the systemic microvasculature induced by DM and an atherogenic diet correlated spatiotemporally with renal damage.METHODS: Atherosclerotic lesion development was triggered in streptozotocin-induced DM pigs (140 mg/kg body weight) by administering an atherogenic diet for approximately 11 months. Fifteen months following induction of DM, microvascular morphology was visualized in control pigs (n = 7), non-diabetic pigs fed an atherogenic diet (ATH, n = 5), and DM pigs fed an atherogenic diet (DM+ATH, n = 5) using SDF imaging of oral mucosal tissue. Subsequently, kidneys were harvested from anethesized pigs and the expression levels of well-established markers for microvascular integrity, such as Angiopoietin-1 (Angpt1) and Angiopoietin-2 (Angpt2) were determined immunohistochemically, while endothelial cell (EC) abundance was determined by immunostaining for von Willebrand factor (vWF).RESULTS: Our study revealed an increase in the capillary tortuosity index in DM+ATH pigs (2.31±0.17) as compared to the control groups (Controls 0.89±0.08 and ATH 1.55±0.11; p<0.05). Kidney biopsies showed marked glomerular lesions consisting of mesangial expansion and podocyte lesions. Furthermore, we observed a disturbed Angpt2/Angpt1 balance in the cortex of the kidney, as evidenced by increased expression of Angpt2 in DM+ATH pigs as compared to Control pigs (p<0.05).CONCLUSION: In the setting of DM, atherogenesis leads to the augmentation of mucosal capillary tortuosity, indicative of sys

Background-As bioresorbable vascular scaffolds (BVSs) are being increasingly used in complex real-world lesions and populations, BVS thrombosis cases have been reported. We present angiographic and optical coherence tomography (OCT) findings in a series of patients treated in our center for definite bioresorbable scaffold thrombosis. Methods and Results-Up to June 2014, 14 patients presented with definite BVS thrombosis in our center. OCT was performed in 9 patients at the operator's discretion. Angiographic and OCT findings were compared with a control group comprising 15 patients with definite metallic stent thrombosis. In the BVS group, time interval from index procedure to scaffold thrombosis ranged from 0 to 675 days. Incomplete lesion coverage by angiography was identified in 4 of 14 cases, malapposition by OCT in 5 of 9 cases, strut discontinuity in 2 of 9 cases, and underexpansion in 2 of 9 cases. Five patients had discontinued dual antiplatelet therapy, and in 3 of them discontinued dual antiplatelet therapy discontinuation had occurred the week preceding the event. There were no significant differences in angiographic or OCT findings between BVS and metallic stent thrombosis. Conclusions-Suboptimal implantation with incomplete lesion coverage, underexpansion, and malapposition comprises the main pathomechanism for both early and late BVS thrombosis, similar to metallic stent thrombosis. Dual antiplatelet therapy discontinuation seems to also be a secondary contributor in several late events. Our observations suggest that several potential triggers for BVS thrombosis could be avoided.

Introduction Wall shear stress (WSS) plays a key role in the onset and progression of atherosclerosis in human coronary arteries. Especially sites with low and oscillating WSS near bifurcations have a higher propensity to develop atherosclerosis. WSS computations in coronary bifurcations can be performed in angiography-based 3D reconstructions. It is essential to evaluate how reconstruction errors influence WSS computations in mildly-diseased coronary bifurcations. In mildly-diseased lesions WSS could potentially provide more insight in plaque progression. Materials Methods Four Plexiglas phantom models of coronary bifurcations were imaged with bi-plane angiography. The lumens were segmented by two clinically experienced readers. Based on the segmentations 3D models were generated. This resulted in three models per phantom: one gold-standard from the phantom model itself, and one from each reader. Steady-state and transient simulations were performed with computational fluid dynamics to compute the WSS. A similarity index and a noninferiority test were used to compare the WSS in the phantoms and their reconstructions. The margin for this test was based on the resolution constraints of angiography. Results The reconstruction errors were similar to previously reported data; in seven out of eight reconstructions less than 0.10 mm. WSS in the regions proximal and far distal of the stenosis showed a good agreement. However, the low WSS areas directly distal of the stenosis showed some disagreement between the phantoms and the readers. This was due to small deviations in the reconstruction of the stenosis that caused differences in the resulting jet, and consequently the size and location of the low WSS area. Discussion This study showed that WSS can accurately be computed within angiography-based 3D reconstructions of coronary arteries with early stage atherosclerosis. Qualitatively, there was a good agreement between the phantoms and the readers. Quantitatively, the low

BACKGROUND Although recent observations suggest a favorable initial healing process of the everolimus-eluting bioresorbable vascular scaffold (BVS), little is known regarding long-term healing response. OBJECTIVES This study assessed the in vivo vascular healing response using optical coherence tomography (OCT) 5 years after elective first-in-man BVS implantation. METHODS Of the 14 living patients enrolled in the Thoraxcenter Rotterdam cohort of the ABSORB A study, 8 patients underwent invasive follow-up, including OCT, 5 years after implantation. Advanced OCT image analysis included luminal morphometry, assessment of the adluminal signal-rich layer separating the lumen from other plaque components, visual and quantitative tissue characterization, and assessment of side-branch ostia "jailed" at baseline. RESULTS In all patients, BVS struts were integrated in the vessel and were not discernible. Both minimum and mean luminal area increased from 2 to 5 years, whereas lumen eccentricity decreased over time. In most patients, plaques were covered by a signal-rich, low-attenuating layer. Minimum cap thickness over necrotic core was 155 +/- 90 mu m. One patient showed plaque progression and discontinuity of this layer. Side-branch ostia were preserved with tissue bridge thinning that had developed in the place of side-branch struts, creating a neo-carina. CONCLUSIONS At long-term BVS follow-up, we observed a favorable tissue response, with late luminal enlargement, side-branch patency, and development of a signal-rich, low-attenuating tissue layer that covered thrombogenic plaque components. The small size of the study and the observation of a different tissue response in 1 patient warrant judicious interpretation of our results and confirmation in larger studies. (C) 2014 by the American College of Cardiology Foundation.

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.