Nienke S. van Ditzhuijzen

Angiographic and Optical Coherence Tomography Insights Into Bioresorbable Scaffold Thrombosis Single-Center Experience

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.

Assessment of coronary atherosclerosis progression and regression at bifurcations using combined IVUS and OCT.

OBJECTIVES The aim of this study was to evaluate the progression of atherosclerotic coronary plaques at bifurcations, using combined intravascular ultrasound-virtual histology (IVUS-VH) and optical coherence tomography (OCT). BACKGROUND Pathological findings reveal that atherosclerotic plaques characterized by the presence of large necrotic cores (NCs) with fibrous cap thicknesses < 65 μm are more prone to rupture. Accuracy in the detection of high-risk plaques could be improved by the combined use of IVUS-VH and OCT. METHODS IVUS-VH and OCT are 2 imaging modalities with different lateral resolutions and different depths of penetration. To provide a precise matching of the images, bifurcations were used as landmarks. IVUS-VH and OCT were performed in 56 bifurcations from 24 patients at baseline and at 6-month follow-up. All patients were treated with standard medical therapy. Bifurcations were studied at the proximal, in-bifurcation, and distal regions. Plaques were classified according to their composition as assessed by IVUS-VH and fibrous cap thickness as quantified by OCT. RESULTS At baseline, 27 NC-rich plaques were found. At 6-month follow-up, 22 (81%) did not show any significant change. Four new NC-rich lesions developed. At both time points, percent NC was higher and the fibrous cap was thinner at the proximal bifurcation rim compared with the distal. There were no significant changes in percent NC and fibrous cap thickness in the 3 bifurcation regions between baseline and follow-up examinations. No major cardiovascular events due to bifurcation lesion progression were observed. CONCLUSIONS The combined use of IVUS-VH and OCT is a reliable tool to serially assess plaque progression and regression, and in the present study it was demonstrated to be safe and feasible. At 6-month follow-up, in this post-percutaneous coronary intervention patient population, most high-risk plaques remained unchanged, retaining their imaging classifications, nevertheless appearing to have remained clinically silent.

A novel method to assess coronary artery bifurcations by OCT: cut-plane analysis for side-branch ostial assessment from a main-vessel pullback.

AIMS In coronary bifurcations assessment, evaluation of side-branch (SB) ostia by an optical coherence tomography (OCT) pullback performed in the main branch (MB) could speed up lesion evaluation and minimize contrast volume. Dedicated software that reconstructs the cross-sections perpendicular to the SB centreline could improve this assessment. We aimed to validate a new method for assessing the SB ostium from an OCT pullback performed in the MB. METHODS AND RESULTS Thirty-one sets of frequency-domain OCT pullbacks from 28 patients, both from the MB and the SB of a coronary artery bifurcation were analysed. Measurements of the SB ostium from the SB pullback were used as a reference. Measurements of the SB ostium from the MB pullback were then performed in a laboratory setting by (i) conventional analysis and (ii) cut-plane analysis, and the measurement error for each analysis was estimated. Correlations of SB ostium measurements acquired from the MB pullback in comparison with reference measurements acquired from the SB pullback were higher with cut-plane analysis compared with conventional analysis, albeit not reaching statistical significance (area: rcut-plane = 0.927 vs. rconventional = 0.870, P = 0.256; mean diameter: rcut-plane = 0.918 vs. rconventional = 0.788, P = 0.056; minimum diameter: rcut-plane = 0.841 vs. rconventional = 0.812, P = 0.734; maximum diameter: rcut-plane = 0.770 vs. rconventional = 0.635, P = 0.316). Cut-plane analysis was associated with lower absolute error than conventional analysis (area: 0.56 ± 0.45, vs. 1.50 ± 1.31 mm(2), P < 0.001; mean diameter: 0.18 ± 0.14 vs. 0.44 ± 0.30 mm, P < 0.001). CONCLUSION Measurements of SB ostium performed in a laboratory setting by cut-plane analysis of an OCT pullback of the main branch have high correlation with reference measurements performed in a SB OCT pullback and lower error compared with conventional analysis.

Safety of optical coherence tomography in daily practice: A comparison with intravascular ultrasound

Aims Previous studies have reported the safety and feasibility of both time-domain optical coherence tomography (TD-OCT) and Fourier-domain OCT (FD-OCT) in highly selected patients and clinical settings. However, the generalizability of these data is limited, and data in unselected patient populations reflecting a routine cathlab practice are lacking. We compared safety of intracoronary FD-OCT imaging to intravascular ultrasound (IVUS) imaging in a large real-world series of consecutive patients who underwent invasive imaging during coronary catheterization in our centre. Methods and results This is a prospective, single-centre registry of patients scheduled for coronary angiography or intervention undergoing intracoronary imaging with FD-OCT or IVUS between April 2008 and December 2013. Intra-procedural and major in-hospital adverse events that could be possibly related to invasive imaging were registered routinely by the operator as part of our clinical report and prospectively recorded in our database. These events were retrospectively individually adjudicated by an independent safety committee. Between April 2008 and December 2013, 13 418 diagnostic or interventional coronary catheterization procedures were performed. Of these, 1142 procedures used OCT and 2476 procedures used IVUS. Invasive imaging-related complications were rare, did not differ between the two imaging methods (OCT: n = 7, 0.6%; IVUS: n = 12, 0.5%; P = 0.6), and were self-limiting after retrieval of the imaging catheter or easily treatable in the catheterization laboratory. No major adverse events, prolongation of hospital stay, or permanent patient harm was observed. Conclusion FD-OCT is safe in an unselected and heterogeneous group of patients with varying clinical settings.

Early Systemic Microvascular Damage in Pigs with Atherogenic Diabetes Mellitus Coincides with Renal Angiopoietin Dysbalance

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/ Angpt1balance 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 systemic microvascular damage. Concomitantly, a dysbalance in renal angiopoietins was correlated with the development of diabetic nephropathy. As such, our studies strongly suggest that defects in the systemic microvasculature mirror the accumulation of microvascular damage in the kidney.

Coronary microvascular dysfunction after long-term diabetes and hypercholesterolemia

Coronary microvascular dysfunction (CMD) has been proposed as an important component of diabetes mellitus (DM)- and hypercholesterolemia-associated coronary artery disease (CAD). Previously we observed that 2.5 mo of DM and high-fat diet (HFD) in swine blunted bradykinin (BK)-induced vasodilation and attenuated endothelin (ET)-1-mediated vasoconstriction. Here we studied the progression of CMD after 15 mo in the same animal model of CAD. Ten male swine were fed a HFD in the absence (HFD, n = 5) or presence of streptozotocin-induced DM (DM + HFD, n = 5). Responses of small (∼300-μm-diameter) coronary arteries to BK, ET-1, and the nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine were examined in vitro and compared with those of healthy (Normal) swine (n = 12). Blood glucose was elevated in DM + HFD (17.6 ± 4.5 mmol/l) compared with HFD (5.1 ± 0.4 mmol/l) and Normal (5.8 ± 0.6 mmol/l) swine, while cholesterol was markedly elevated in DM + HFD (16.8 ± 1.7 mmol/l) and HFD (18.1 ± 2.6 mmol/l) compared with Normal (2.1 ± 0.2 mmol/l) swine (all P < 0.05). Small coronary arteries showed early atherosclerotic plaques in HFD and DM + HFD swine. Surprisingly, DM + HFD and HFD swine maintained BK responsiveness compared with Normal swine due to an increase in NO availability relative to endothelium-derived hyperpolarizing factors. However, ET-1 responsiveness was greater in HFD and DM + HFD than Normal swine (both P < 0.05), resulting mainly from ETB receptor-mediated vasoconstriction. Moreover, the calculated vascular stiffness coefficient was higher in DM + HFD and HFD than Normal swine (both P < 0.05). In conclusion, 15 mo of DM + HFD, as well as HFD alone, resulted in CMD. Although the overall vasodilation to BK was unperturbed, the relative contributions of NO and endothelium-derived hyperpolarizing factor pathways were altered. Moreover, the vasoconstrictor response to ET-1 was enhanced, involving the ETB receptors. In conjunction with our previous study, these findings highlight the time dependence of the phenotype of CMD.

Influence of the accuracy of angiography-based reconstructions on velocity and wall shear stress computations in coronary bifurcations: A phantom study

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 WSS regions directly distal to the stenosis were sensitive to small reconstruction errors.

Automated characterisation of lipid core plaques in vivo by quantitative optical coherence tomography tissue type imaging

AIMS Qualitative criteria for plaque tissue characterisation by OCT are well established, but quantitative methods lack systematic validation in vivo. High optical attenuation coefficient µt has been associated with unstable plaque features, such as lipid core. The purpose of this study was to validate optical coherence tomography (OCT) attenuation imaging for tissue characterisation in vivo, specifically to detect lipid core in coronary atherosclerotic plaques, and to evaluate quantitatively the ability of OCT attenuation imaging to differentiate thin-cap (TCFA) and thick-cap fibroatheroma (FA). METHODS AND RESULTS We prospectively enrolled 85 patients undergoing imaging of a native coronary segment by both OCT and near-infrared spectroscopy and intravascular ultrasound (NIRS-IVUS). Ninety-eight NIRS-positive 4 mm plaque segments were selected and matched to the OCT data. Two experienced OCT readers classified the plaque type using OCT criteria. A cap thickness of 65 μm was used to differentiate TCFA and FA. We computed an index of plaque attenuation (IPA) in the 4 mm blocks, and assessed the association of this index with plaque type. IPA differentiated between TCFA and FA (AUC=0.82 in ROC analysis; p<0.0001). LCBI was numerically, but not significantly, higher in TCFA compared to FA (p=0.097). CONCLUSIONS IPA is an unbiased reproducible measure of tissue optical properties. The fraction of pixels with attenuation coefficient ≥11 mm-1 can identify TCFA.

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 (P<0.01 FF-DM vs. FF-NDM) and stabilized between 3M and 6M (<5% change in FF-DM, ~10% in FF-NDM; P>0.20). 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.

Expanded clinical use of everolimus eluting bioresorbable vascular scaffolds for treatment of coronary artery disease

Limited data are currently available on the performance of everolimus eluting bioresorbable vascular scaffold (BVS) for treatment of complex coronary lesions representative of daily practice.