Kojiro Miki

Multiple complex coronary atherosclerosis in diabetic patients with acute myocardial infarction: a three-vessel optical coherence tomography study

AIMS The main cause of acute myocardial infarction (AMI) is the disruption of a thin-cap fibroatheroma (TCFA) and subsequent thrombosis. Mortality increases in diabetic patients due to cardiovascular events; there may be differences in the vulnerable plaques between diabetic and non-diabetic patients. We used optical coherence tomography (OCT) to assess the incidence of vulnerable plaques in diabetic patients with AMI. METHODS AND RESULTS OCT was performed in all three major coronary arteries of 70 AMI patients: 48 non-diabetic and 22 diabetic patients. The OCT criterion for TCFA was the presence of both a lipid-rich plaque composition and a fibrotic cap thickness of <65 µm. A ruptured plaque contains a cavity in contact with a lumen and a residual fibrous cap. OCT identified 68 plaque ruptures (1.0 per patient; range, 0-3) and 162 TCFAs (2.3 per patient; range, 0-5). The incidences of plaque rupture and TCFA at culprit lesions were similar. However, non-culprit-lesion TCFAs were observed more frequently in diabetic patients than in non-diabetic patients. CONCLUSIONS Although the prevalence of vulnerable plaque in culprit lesions was similar between diabetic and non-diabetic patients, vulnerable plaques were observed in non-culprit lesions more in diabetic patients than in non-diabetic patients.

Ex vivo assessment of neointimal characteristics after drug-eluting stent implantation: Optical coherence tomography and histopathology validation study.

BACKGROUND Optical coherence tomography (OCT) is one of the tools trying to distinguish neoatherosclerosis from other neointimal tissue but its role has to be still validated. This study evaluated the diagnostic accuracy of OCT for characterization of lipid-atherosclerotic neointima following drug-eluting stent (DES) implantation. METHODS Twelve stented coronary arteries from the 7 autopsy hearts were imaged by OCT. These OCT images were compared with histology. By OCT, the morphological appearances of neointima were classified into three patterns: homogeneous pattern, heterogeneous pattern with visible strut, or heterogeneous pattern with invisible strut. RESULTS Of 21 histological cross-sections, 6 were categorized as homogeneous patterns (29%), 11 as heterogeneous patterns with visible stent strut (52%), and 4 as heterogeneous patterns with invisible stent strut (19%). All homogeneous patterns were composed of smooth muscle cells with collagen fibers. The heterogeneous patterns with visible stent strut included proteoglycan-rich myxomatous matrix and calcium deposition. On the other hand, the heterogeneous patterns with invisible stent strut comprised atheromatous tissue, including a large amount of foam cell accumulation (25%) or large fibroatheroma/necrotic core (75%) inside the stent struts within neointima. The optical attenuation coefficient was highest in the heterogeneous pattern with invisible stent strut due to scattering of light by atheromatous tissue. CONCLUSION The heterogeneous patterns with invisible stent strut on OCT imaging identify the presence of lipid-atherosclerotic tissue within neointima after DES. This may suggest the potential capability of OCT based on visualization of stent struts for discriminating atheromatous formation within neointima from other neointimal tissue.

Intravascular Ultrasound-Derived Stent Dimensions as Predictors of Angiographic Restenosis Following Nitinol Stent Implantation in the Superficial Femoral Artery.

Purpose: To identify intravascular ultrasound (IVUS) measurements that can predict angiographic in-stent restenosis (ISR) following nitinol stent implantation in superficial femoral artery (SFA) lesions. Methods: A retrospective review was conducted of 97 patients (mean age 72.9±8.9 years; 63 men) who underwent IVUS examination during endovascular treatment of 112 de novo SFA lesions between July 2012 and December 2014. Self-expanding bare stents were implanted in 46 lesions and paclitaxel-eluting stents in 39 lesions. Six months after stenting, follow-up angiography was conducted to assess stent patency. The primary endpoint was angiographic ISR determined by quantitative vascular angiography analysis at the 6-month follow-up. Variables associated with restenosis were sought in multivariate analysis; the results are presented as the odds ratio (OR) and 95% confidence interval (CI). Results: At follow-up, 27 (31.8%) angiographic ISR lesions were recorded. The lesions treated with uncoated stents were more prevalent in the ISR group compared with the no restenosis group (74.1% vs 44.8%, p=0.02). Lesion length was longer (154.4±79.5 vs 109.0±89.3 mm, p=0.03) and postprocedure minimum stent area (MSA) measured by IVUS was smaller (13.9±2.8 vs 16.3±1.6 mm2, p<0.001) in the ISR group. Multivariate analysis revealed that bare stent use (OR 7.11, 95% CI 1.70 to 29.80, p<0.01) and longer lesion length (OR 1.08, 95% CI 1.01 to 1.16, p=0.04) were predictors of ISR, while increasing postprocedure MSA (OR 0.58, 95% CI 0.41 to 0.82, p<0.01) was associated with lower risk of ISR. Receiver operating characteristic analysis identified a MSA of 15.5 mm2 as the optimal cutpoint below which the incidence of restenosis increased (area under the curve 0.769). Conclusion: Postprocedure MSA can predict ISR in SFA lesions, which suggests that adequate stent enlargement during angioplasty might be required for superior patency.

Histopathological validation of optical frequency domain imaging to quantify various types of coronary calcifications.

Aims This study evaluated whether optical frequency domain imaging (OFDI) could identify various coronary calcifications and accurately measure calcification thickness in comparison with histopathology. Methods and results A total of 902 pathological cross‐sections from 44 coronary artery specimens of human cadavers were examined to compare OFDI and histological images. Histological coronary calcification was classified into four different types: (i) superficial dense calcified plates, (ii) deep intimal calcification, (iii) scattered microcalcification, and (iv) calcified nodule. The thickness of calcification was measured when both the leading and trailing edges of calcification were visible on OFDI. Of the 902 histological cross‐sections, 158 (18%) had calcification: 105 (66%) were classified as superficial dense calcified plates, 20 (13%) as deep intimal calcifications, 30 (19%) as scattered microcalcifications, and 3 (2%) as calcified nodules. Superficial dense calcified plates appeared as well‐delineated heterogeneous signal‐poor regions with sharp borders on OFDI. Deep intimal calcifications could not be identified on OFDI. Scattered microcalcification appeared as homogeneous low intensity areas with indiscriminant borders. Calcified nodule, a high‐backscattering protruding mass with an irregular surface, also appeared as a low intensity area with a diffuse border. The ROC analysis identified calcium thicknesses <893 µm as cut points for the prediction of measurable calcification (72% sensitivity and 91% specificity, area under the curve = 0.893, P < 0.001). Conclusion Our study demonstrated the potential capability of OFDI to characterize various types of coronary calcifications, which may contribute to the understanding of the pathogenesis of coronary atherosclerosis.

Tissue Characterization of In-Stent Neointima Using Optical Coherence Tomography in the Late Phase After Bare-Metal Stent Implantation – An Ex Vivo Validation Study –

BACKGROUND We performed an ex vivo study to investigate optical coherence tomography (OCT) imaging for differentiating several types of neointimal tissue during the later phases after bare-metal stent (BMS) implantation as compared with histologic results. METHODSANDRESULTS OCT imaging was performed in 6 autopsy hearts for 10 BMS with implant duration >4 years. OCT qualitative neointimal tissue characterization was based on tissue structure and classified as homogeneous pattern, heterogeneous pattern with visible struts, or heterogeneous pattern with invisible struts. Corresponding histological analyses of each 2-mm cross-section of the entire BMS were performed. Of 81 cross-sections, histological analysis revealed that the homogeneous pattern of neointima on OCT (n=39) contained smooth muscle cells with collagen, indicating high neointimal maturity. The heterogeneous patterns with visible struts (n=35) contained different tissues, including a proteoglycan-rich myxomatous matrix or dense calcified plate deposition. The heterogeneous patterns with invisible struts (n=7) included neointimal lipid/necrotic core formation, accumulation of foam cells, or microcalcification scattering. Of the 66 cross-sections containing large microvessels within the neointima on histology, only 6 (9%) were visualized by OCT. CONCLUSIONS The present study confirmed the potential use of OCT in differentiating several types of neointima after BMS implantation. The image interpretation of OCT, based on visualization of stent struts, enables identification of several types of neointimal tissues, including in-stent fibroatheroma formation, more accurately.

Natural history of low-intensity neointimal tissue after an everolimus-eluting stent implantation: a serial observation with optical coherence tomography

Although previous optical coherence tomography (OCT) studies reported that restenosis tissue after implantation of a drug-eluting stent (DES) was composed of a variety of cells, the clinical significance of morphologic characteristics for in-stent neointimal tissue as assessed by OCT has not been clarified. We experienced a patient with stable angina who underwent percutaneous coronary intervention with a 2.5 × 18-mm DES implantation 6 months before the OCT examination. OCT imaging showed a mild intimal hyperplasia (39 % neointimal hyperplasia) with eccentric, heterogeneous tissue, predominantly of low signal intensity. Seventeen months after the initial procedure, OCT revealed a significant increase in percent neointimal hyperplasia of 58 %, with morphologically different intimal tissue of concentric homogeneous high intensity in the stented segments. This finding suggests that low-intensity intimal tissue morphology detected by OCT could be a morphometric predictor of late neointimal tissue growth after DES implantation.

Expression of interleukin-33 and ST2 in nonrheumatic aortic valve stenosis

Thenumberof patientswithnonrheumatic aortic valve stenosis (NRAS) is increasing in recent years. NR-AS generally progresses without symptoms, and severe NR-AS is related to increased morbidity and mortality. The effective treatment for severe NR-AS is aortic valve replacement [1]. Many clinical trials of medical therapy have been carried out to prevent the progression of NR-AS; however, there is still a controversy in terms of an effective medical strategy to retard the progression of NR-AS. Thus, it is extremely important to elucidate the molecular pathophysiology of NR-AS to find the prevention strategies of NR-AS. Interleukin (IL)-33 is a recently identified cytokine of the IL-1 family and a ligand for ST2 [2]. IL-33 has immunomodulatory functions. A recent study has shown that IL-33 and ST2 are crucial systems that control atherosclerosis through the inhibition of inflammatory response [3]. Although inflammationplays a pivotal role in thepathophysiologyof NR-AS, the role of IL-33 and ST2 inNR-AS has not been investigated.We, therefore, hypothesized that IL-33 and ST2 systemsmight be associated with the pathophysiology of NR-AS. In the present study, we investigated the expression and cellular localization of IL-33 and ST2 in human NR-AS and aortic regurgitation (AR) valves. Aortic valve samples were collected from 67 patients undergoing valve replacement surgery (40 NR-AS and 27 AR). Patients with significant diseases such as autoimmune diseases, infections, cancer, or renal failure were excluded. All of our protocols were approved by the ethics committee of Hyogo College of Medicine. Aortic valve tissues were collected at the time of surgical valve replacement. They were immediately fixed with 4% paraformaldehyde for paraffin embedding. In addition, aortic valve tissues were frozen in liquid nitrogen and stored at −80 °C for Western blot analysis. Sections measuring 4 μm from paraffin-embedded samples were stained with hematoxylin–eosin and were incubated with either a primary antihuman IL-33 antibody (R&D, dilution 1:1000), a primary anti-human ST2 antibody (R&D, dilution 1:1000), a primary anti-human CD68 antibody (Dako, dilution1:200) formacrophages, a primaryanti-human α-smooth muscle actin (SMA) antibody (Dako, dilution 1:200) for smooth muscle cells or myofibroblasts, and a primary anti-human von Willebrand factor (vWF) antibody (Dako, dilution 1:1000) for endothelial cells. Immunostainswere visualizedwith the use of an avidin–biotin peroxidase conjugate and 3,3′-diaminobenzidine substrate. Every section was counterstained with hematoxylin. Aortic valve tissues were homogenizedwith ice-cold lysis buffer as previously described [4]. Protein extracts from aortic valves were separated by SDS-PAGE and transferred onto PVDF membranes. The expression levels of molecules were detected by an enhanced chemiluminescence kit (Thermo Scientific). The antibodies used were against anti-human IL-33 (R&D, dilution 1:1000), anti-human ST2 (R&D, dilution 1:1000), and antihuman glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (Cell Signaling, dilution 1:1000). Values are reported as means±SD. Statistical analysis was performed using Mann–Whitney U test. Categorical variables were compared using chi-square statistics. Differences were considered significant at pb0.05. The clinical characteristics of patientswith NR-AS and ARwere shown in Table 1. There was no significant difference in any parameters between NR-AS andAR valves. Initially,we investigated IL-33 and ST2 expression in aortic valves byWestern blot analysis. IL-33 was expressed in both NR-AS and AR valves, and the expression levels were not significantly different betweenNR-AS andARvalves (Fig.1A). On theotherhand, ST2 expression was markedly up-regulated in NR-AS compared with AR valves. The molecular weight of ST2 was approximately 50 kDa, but not 100 kDa (Fig. 1B). Next, we assessed IL-33 and ST2 expression by histological analyses. Hematoxylin–eosin staining showed many inflammatory cells closed to calcified and neovascular lesions in NR-AS valves (Fig. 2A). In contrast, neither inflammatory cells, nor calcified lesions, nor neovascular International Journal of Cardiology 168 (2013) 529–630

Strut Coverage After Paclitaxel-Eluting Stent Implantation in the Superficial Femoral Artery

In the superficial femoral artery (SFA), quantitative analysis for vascular healing response after self-expanding nitinol bare metal stent (BMS) or drug-eluting stent (DES) implantation is limited. The purpose of this study was to evaluate the endothelial strut coverage after nitinol paclitaxel-

Impact of analysis interval size on the quality of optical frequency domain imaging assessments of stent implantation for lesions of the superficial femoral artery.

This study aimed to investigate the influence of analysis interval size on optical frequency domain imaging (OFDI) assessment of stent therapy for lesions of the superficial femoral artery (SFA). Background. No consensus or validating data are available with respect to the methodology of intravascular imaging analysis for the peripheral arteries. Methods. OFDI was performed for 30 SFA lesions, during endovascular therapy and at the 6‐month follow‐up. Initially, lumen and stent borders were traced at 1‐mm axial intervals. Volumes were calculated using a PC‐based software, and the volume index (VI) was defined as the volume divided by the stent length. Two additional OFDI analyses were performed using 2‐mm and 5‐mm intervals, thereby reducing the number of cross‐sectional image frames analyzed. Results. The mean stent length was 89.7 ± 35.2 mm. The mean difference in baseline minimum lumen area (MLA) was 0.4 mm2 between MLA values from the 1‐mm and 2‐mm interval analyses, and 2.2 mm2 between MLA values from the 1‐mm and 5‐mm interval analyses. In volumetric analysis, there were excellent correlations and good agreements for stent, lumen, and neointimal VI measurements obtained on the basis of different analysis intervals. Conclusions. Using large intervals in OFDI analyses of SFA lesions resulted in few differences in measurement variability of volumetric parameters. However, planar analysis for MLA assessment can be susceptible to high variability when large intervals are applied.

The utility of intravascular ultrasound for the diagnosis and management of spontaneous coronary artery dissection in a middle-aged woman with acute inferior myocardial infarction

Spontaneous coronary artery dissection (SCAD) is an infrequent cause of acute myocardial ischemia and is associated with various pathophysiologies, such as pregnancy, postpartum, and collagen diseases. It is frequently fatal and most cases are diagnosed at autopsy. Therefore, the early diagnosis of SCAD and initiation of treatment may be life saving. In this report, we describe a case of SCAD of right coronary artery, possibly triggered by transient high blood pressure, with no apparent atherosclerotic involvement detected by intravascular ultrasound (IVUS) and successfully treated with stent implantation. The IVUS helped us to confirm the diagnosis, navigate the guidewire into the true lumen, and understand the mechanism for the appearance of a lotus root formation.