Rika Kawakami

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.

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.

Distribution of myofibroblast and tenascin-C in cystic adventitial disease: Comparison with ganglion

Cystic adventitial disease (CAD) is a rare peripheral artery disorder which shows the development of gelatinous cysts in the adventitia. Although several theories for the pathogenesis of CAD have been postulated, the etiology of CAD remains unclear. Histological examination of three CAD cases revealed that these cyst walls were composed of fibrous tissue and lacked both epithelial and endothelial lining. The surfaces of these cysts were partially covered with spindle‐shaped cells, similar to the interstitial cells within the cyst wall. A pool of mucinous material in the adventitia was evident. Distribution of vimentin‐positive spindle‐shaped cells and scattered CD68‐positive oval‐shaped cells in the cyst wall was revealed by immunohistochemistry. A part of vimentin‐positive spindle‐shaped cells demonstrated to be positive for α‐smooth muscle actin, indicating the presence of myofibroblasts in the cyst wall. A focal tenascin‐C‐positive area was observed in the cyst wall of our CAD cases. Presence of two different cell types, proliferation of myofibroblasts and expression of tenascin‐C were consistent with those of cyst walls of 20 surgically resected ganglions. These results suggest that CAD may arise as capsular synovial structures, similar to ganglion cysts.

Histopathological validation of optical coherence tomography findings of the coronary arteries

Optical coherence tomography (OCT), a catheter-based imaging modality for the visualization of coronary arteries, is widely used during percutaneous coronary intervention to improve the understanding of the anatomy of coronary artery stenosis and to elucidate the mechanisms of atherosclerosis. In this review, we provide a short description of the histopathological validations of OCT for visualizing atherosclerotic plaques and vascular healing response after drug-eluting stent (DES) implantation. Because OCT measures the intensity of light returning from within a tissue, tissue having a higher heterogeneity of optical index of refraction, such as microcalcification deposition and foam cell accumulation on the luminal surface, may exhibit stronger optical scattering that appears as a thin-cap fibroatheroma image. Furthermore, even if OCT shows exposed uncovered stent struts, some of the struts could be re-endothelialized. In our ex vivo histopathological experience, re-endothelialization at the surface of stent struts was confirmed by histopathological analysis, although OCT images showed exposed uncovered struts after DES implantation. Therefore, careful interpretation is required to assess tissue morphology and stent strut coverage by OCT.

Initial pathological responses of second-generation everolimus-eluting stents implantation in Japanese coronary arteries: Comparison with first-generation sirolimus-eluting stents

BACKGROUND The clinical benefit of second-generation drug-eluting stents (2nd DES) has been established, compared to first-generation drug-eluting stents (1st DES). However, pathological response after 2nd DES implantation remains unclear, particularly in the Japanese population. METHODS Using specimens obtained by autopsy, we compared the histology between 2nd DES (41 sections) and 1st DES (38 sections) lesions within 1 year after stent implantation to evaluate early tissue reaction in Japanese patients. Stent segments were fixed with 10% buffered formalin and embedded in plastic, followed by hematoxylin-eosin and Massons trichrome staining. Ratio of covered stent struts was calculated, and the area of fibrin deposition was morphometrically evaluated. The degree of inflammation around struts was examined semi-quantitatively (score 0-3). RESULTS The ratio of covered struts and mean fibrin area of 2nd DES were 0.69±0.05 and 658.0±173.4μm2. Those of 1st DES were 0.44±0.12 and 3107.5±1405.9μm2. In the 2nd DES, there was significantly less fibrin deposition and a higher covered struts ratio. The inflammation score was significantly lower in 2nd DESs compared to 1st DESs (1.02±0.16 vs. 1.19±0.54, p<0.05). CONCLUSIONS Histopathological analysis showed advanced healing process in 2nd DES compared with 1st DES lesions. These results are consistent with clinical beneficial outcome of 2nd DES implantation.

Protruding In-Stent Mass After Bioresorbable Polymer Sirolimus-Eluting Stent ― Ex Vivo Intravascular Imaging and Histopathology ―

(Figure 1C). After perfusion fixation of the heart under the normal diastolic pressure by 10% buffered formalin for 24 h, epicardial coronary arteries were removed from the heart. The whole stent segment was embedded in plastic (Technovit 8100; Heraeus Kulzer, Wehrheim, Germany) with the stent struts. Histological sections stained by hematoxylin-eosin and Masson’s trichrome showed a convex mass lesion (Figure 2A) composed of cholesterin crystals, macrophage foam cells and necrotic debris over the stent struts (Figure 2B). Although we could not confirm the endothelial cell coverage due to the technical difficulties of immunohistochemistry using the plastic embedded sections, the luminal surface of the mass was partially covered with thin and flat cells, consistent with endothelial cells. Part of the luminal surface, however, lacked the cell coverage with fibrin A 70-year-old man was hospitalized due to polymyositis and died of pneumonia 1 week after admission. Sirolimus-eluting bioresorbable polymer coated stent (Ultimaster; Terumo, Tokyo, Japan) had been implanted in the circumflex artery 2 months previously. He had been prescribed aspirin 100 mg/day and clopidogrel 75 mg/day. An autopsy was performed followed by ex vivo intravascular ultrasound (IVUS; Terumo), optical frequency domain imaging (OFDI; Terumo) and coronary angioscopy (CAS; FiberTech, Tokyo, Japan). IVUS and OFDI showed a convex-shaped mass with echo attenuation, and protruding mass with a smooth surface accompanied by high backscattering within the stent-implanted segment, respectively (Figure 1A,B; Movie S1). CAS showed a yellowish polypoid lesion over the stent struts. Red thrombus adhesion was observed at the base of the protruding mass lesion

Ulcerated plaque of coronary artery: Insights from ex vivo images of optical frequency domain imaging and histopathology

To the Editor: It is known that episodes of plaque rupture are frequent and occasionally result in acute coronary syndrome (ACS). In vivo imaging studies in patients with ACS demonstrated evidence of multiple plaque ruptures other than the culprit lesion. Furthermore, recent intravascular ultrasound study demonstrated that the natural evolution and long-term impact of plaque ruptures in untreated segments were not accompanied by clinical events. However the ulcerated coronary artery plaque is still a thorny lesion in the clinical practice. A 78-year-old male died of sepsis and an autopsy was performed. The ex vivo optical frequency domain imaging (OFDI; TerumoCorporation, Tokyo, Japan) revealed a large ulceration, which was directly connected to the true lumen at the proximal portion of right coronary artery (Fig. 1a). The false lumen, which was separated by tissue showing a homogeneous, high intensity signal from the true vessel lumen, was clearly illustrated at the distal segment of ulceration by OFDI (Fig. 1b). Pathological examination revealed the ulcer formation without a necrotic core in the intima. Large disruption of fibrous cap and connection between true and false lumen were apparent (Fig. 1c). The adjacent distal section demonstrated the true and false lumen separated by fibrous septum (Fig. 1d). Fresh mural thrombus was not identified in the false lumen, and the false cavity was completely covered with endothelial cells, which were confirmed byCD31 immunohistochemistry (Fig. 1d, inset). The remodeling index of the ulcerated plaque was 1.05. Approximately 5 mm proximal section from the ulcerated plaque showed atherosclerotic plaque with necrotic core formation. The segment demonstrated a remodeling index of 1.45. The patient’s coronary artery demonstrated severe stenosis with atherosclerotic plaque formation in the left anterior descending artery and circumflex artery. We believe that the pathogenesis of coronary ulcerated lesion is a plaque rupture followed by the washing away of the necrotic core content. Although the histological finding of these sections indicated a previous plaque rupture (healed plaque rupture), no scar was observed in the posterior wall of the left ventricle. Plaque rupture is the most common lesion underlying ACS. However, pathological study has suggested evidence of silent

Ex vivo optical frequency domain imaging and histopathology of malapposed drug eluting stent in coronary artery

To the Editor: Drug eluting stents (DESs) significantly reduce the incidence of stent restenosis and target lesion revascularization in the coronary artery tree. However, late and very late stent thrombosis have been raised as the new problem after DES implantation. Stent malapposition is observed frequently by intravascular imaging in patients who underwent DES implantation. Although some previous studies have suggested that stent malapposition is associated with stent thrombosis, others have failed to demonstrate such association. We have identified malapposed DES 65 months after stent deployment in our autopsy case, and compared the ex vivo intracoronary imaging and histopathology of corresponding lesion. A 70-year-old female was admitted to our hospital due to cardiogenic shock and died of heart failure 1 day after administration. A paclitaxel-eluting stent (Taxus, Boston Scientific, Valencia, CA, USA) was implanted to the right coronary artery 65 months previously. Dual-antiplatelet therapy (DAPT) had been continued for five years until her death. An autopsy was performed followed by an ex vivo optical frequency domain imaging (ODFI; Terumo Corporation, Tokyo, Japan) and a pathological examination. Optical frequency domain imaging revealed malapposed struts at the proximal stent edge (Fig. 1a). The serial movie of OFDI revealed that the malapposition site was covered by homogenous membranous tissue without evidence of plaque and/or thrombus prolapse into the lumen. Histopathology of the corresponding site demonstrated that part of the stent struts were not attached to the vessel wall (Fig. 1b). These struts were completely covered by connective tissue with superficial

ASSESSMENT OF PERI-STRUT LOW INTENSITY AREAS IDENTIFIED BY OPTICAL COHERENCE TOMOGRAPHY AFTER STENT IMPLANTATION: AN EX VIVO HISTOLOGICAL VALIDATION STUDY

The histology of peri-strut low intensity areas (PLIA) identified by optical coherence tomography (OCT) is still not well assessed by human autopsy. A total of 15 stents (7 bare-metal stents; BMS, 8 drug-eluting stents; DES) implanted human coronary artery were collected from 5 cadavers. The

TWO DISTINCT HISTOLOGICAL FEATURES OF CHRONIC TOTAL OCCLUSION IN HUMAN CORONARY ARTERY: AN AUTOPSY STUDY

Chronic total occlusions (CTO) pathology has been described in a few, small studies. The purpose of this study was to clarify the histological characteristics of CTO in the human coronary artery. We evaluated cardiac specimens from 95 consecutive autopsy cases in our hospital between 2010 and 2015