Ten Saita

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.

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.

Impact of stent diameter on vascular response after self-expanding paclitaxel-eluting stent implantation in the superficial femoral artery ☆

BACKGROUND The optimal sizing of self-expanding paclitaxel-eluting stents (PES) in the treatment for superficial femoral artery (SFA) lesions is unclear. This study sought to investigate the influence of PES diameter on stent patency in SFA lesions using optical frequency domain imaging (OFDI). METHODS A total of 20 de novo SFA lesions were randomized 1:1 to receive either self-expanding PES with a nominal diameter of 6mm or 8mm. Follow-up angiography and OFDI was scheduled six months after stent implantation, and volumetric OFDI analysis was performed to evaluate vascular response to the stents. Volume index (VI) was defined as the volume divided by the stent length. The primary end point was lumen VI at the 6-month follow-up. Secondary end point was minimum lumen diameter (MLD) by quantitative vascular angiography (QVA) at the follow-up. RESULTS Stent length was 78.0±23.9mm in the 6-mm group and 70.0±23.6mm in the 8-mm group (p=0.46). Baseline QVA data were also similar between the two groups. MLD immediately after stent implantation was similar between the two groups (4.2±0.5mm in the 6-mm group and 3.9±0.5mm in the 8-mm group, p=NS). At the 6-month follow-up, MLD was greater in the 8-mm group compared to the 6-mm group (4.0±1.0mm vs. 3.2±0.4mm, p<0.05). Stent VI was larger in the 8-mm group (28.4±6.7mm3/mm vs. 22.2±1.2mm3/mm, p=0.01). Neointimal VI was similar between the two groups (5.8±2.9mm3/mm vs. 5.2±2.6mm3/mm, p=0.68). Lumen VI was greater in the 8-mm group (23.2±7.6mm3/mm vs. 17.3±2.6mm3/mm, p=0.04). CONCLUSIONS Chronic stent enlargement resulted in greater lumen area after implantation of self-expanding PES with a large diameter at the mid-term follow-up. Stent diameter might be important for stent patency in procedure with PES for SFA lesions.

Right Sinus of Valsalva Aneurysm Causing Acute Myocardial Infarction

Received July 1, 2015; revised manuscript received August 26, 2015; accepted August 27, 2015; released online September 28, 2015 Time for primary review: 9 days Division of Cardiovascular Medicine and Coronary Heart Disease, Department of Internal Medicine (A.S., K.F., M.S., T.I., K.M., H.T., T.H., T.S., M.N., T.M., M.I.), Department of Surgical Pathology (H.H.), Department of Cardiovascular Surgery (M.R., Y.M.), Hyogo College of Medicine, Nishinomiya, Japan Mailing address: Masaharu Ishihara, MD, PhD, Professor, Division of Coronary Heart Disease, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Japan. E-mail: ishifami@fb3.so-net.ne.jp ISSN-1346-9843 doi: 10.1253/circj.CJ-15-0709 All rights are reserved to the Japanese Circulation Society. For permissions, please e-mail: cj@j-circ.or.jp Right Sinus of Valsalva Aneurysm Causing Acute Myocardial Infarction

Impact of low tissue backscattering by optical coherence tomography on endothelial function after drug-eluting stent implantation

This study evaluated the impact of optical coherence tomography (OCT)-derived low-backscattered tissue on mid-term coronary endothelial function after drug-eluting stent (DES) implantation. Although OCT enables detailed in vivo evaluation of neointimal tissue characterization after DES implantation, its association with physiological vascular healing response is unclear. Thirty-three stable angina pectoris patients underwent OCT examination and endothelial function testing with intracoronary infusion of incremental doses of acetylcholine 8-month after DES implantation in a single lesion of the left anterior descending artery. Neointimal tissue was classified into two patterns based on the predominant OCT light backscatter: high backscatter and low backscatter. Although the presence of uncovered or malapposed stent strut was not associated with the degree of vasoconstriction, the degree of vasoconstriction was significantly greater in the DES with low-backscattered neointima than in the DES without low-backscattered neointima (− 32.1 ± 25.7 vs. − 4.1 ± 20.1%, p = 0.003). Moreover, there was an inverse linear relationship between low backscatter tissue index and degree of vasoconstriction after acetylcholine infusion (r = 0.50 and p = 0.003). The endothelium-dependent vasomotor response after 8-month of DES was impaired in patients with low neointimal tissue backscatter on OCT imaging. OCT assessment of low-backscattered tissue may be used as surrogate markers for impairment of endothelial function after DES.

Neoatherosclerosis after paclitaxel-eluting stent implantation: Ex vivo intravascular image and histopathology: Pathology of neoatherosclerosis

To the Editor: In-stent neoatherosclerosis is a new problem for the late drug-eluting stent (DES) failure. Although a previous paper described that neoatherosclerosis accounts for approximately one third of late and very late stent thrombosis after first-generation DES implantation, we harbor doubts for the high prevalence of the neoatherosclerosis by our expert experiences as pathologist. We need to clarify the clinical prevalence of neoatherosclerosis after DES implantation in the real world, particularly vulnerable neoathorosclerosis which initiate the prospective clinical events. In addition, the etiology of the neoatherosclerosis remains unclear and accumulation of cases with pathological examination is of importance. Recent clinical observation demonstrated that secondgeneration DES is not more protective against neoatherosclerosis compared with the first-generation DES. Although a few histological studies of neoatherosclerosis had been described using the specimens of cadavers, the comparison between intravascular imaging and histopathology of neoatherosclerosis at the consistent section has not been sufficiently demonstrated. We could speculate that the number of patients with long-term DES implantation in their coronary artery tree will increase annually. In this viewpoint, it is of great importance to understand the intravascular image of neoatherosclerosis with histological validation. We examined postmortem ex vivo optical frequency domain imaging (OFDI) for vulnerable neoatherosclerosis after DES implantation, which may contribute to the future clinical event. Comparison between intravascular imaging and corresponding histology of neoatherosclerosis was clearly documented and illustrated in this report. A seventy-year-old female was admitted to our hospital due to cardiogenic shock and died of heart failure one day after administration. She suffered diabetic nephropathy and had hemodialysis for 12 years. Paclitaxel-eluting stent (PES; TAXUS, 3.0 32, Boston Scientific, Natick, MA) was implanted in the proximal portion of right coronary artery 5 years before. An autopsy revealed no evidence of acute myocardial necrosis and acute coronary thrombosis including stent implanted segment. Epicardial coronary arteries were removed from the heart and side branches were tied off to preserve the perfusion pressure of 80mm Hg during the following procedures. Ex vivo OFDI (Terumo Corporation, Tokyo, Japan) was examined before fixation by 20% buffered formalin. After recording the ex vivo imaging, the whole stent implanted segment was fixed and embedded in plastic in order to prepare the histological tissue section with stent struts. Five micrometer thick plastic sections with stent struts were cut by a sharp tungsten knife and stained with hematoxylin-eosin. The ex vivo OFDI clearly demonstrated low intensity signal with high-backscattering in the neointima at the mid portion of stent implanted segment (Fig. 1a). In lowintensity-signal lesions, stent struts cannot be clearly visualized by OFDI because of the high-backscattering. Histology of corresponding lesion demonstrated by OFDI showed that the PES was implanted over the eccentric fibrocalcific plaque and the lumen was narrowed down by intimal hyperplasia (Fig. 1b). Cholesterin crystals and cluster of foam cells (Fig. 1c) within the neointima were clearly identified and these histological features were consistent with neoatherosclerosis. Massive inflammation remained in the media close to the stent struts. Inflammatory cells were composed by lymphocytes and plasma cells, predominantly (Fig. 1d). Necrotic core in the neointima was covered with a thin fibrous cap. These histological features indicated vulnerable neointima formation over fibrocalcific plaque 5 years after PES implantation. On OFDI, it is widely accepted that lipid-rich necrotic core of native coronary plaque appears as low signal intensity mass. In contrast, it had been described that a high intensity signal with high backscattering reflects the presence of foamy macrophages in the intima. However, by our comparison study between ex vivo intravascular image and histopathology, lesion of dense macrophage infiltration in the intima demonstrated a low intensity signal with high backscattering by OFDI. Dense macrophage infiltration in the neointima as shown in the current case, which is more alarming lesion than scattering macrophage infiltration, presented as a low intensity signal with high backscattering. In this manner, it is reasonable that the stent struts underneath the neoatherosclerosis cannot be visualized by high-backscattering on OFDI. Stent struts behind organized fibrin thrombus can be visible because OFDI signals are not attenuated by these materials. Therefore, it is crucial to detect the neoatherosclerosis whether stent struts behind the low signal intensity area are visible or invisible by OFDI. The question arises whether the “neoatherosclerosis” is derived from penetrated native plaque or newly developed