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Neither the actual in vivo tissue temperatures reached with 90W/4sec-very high-power short-duration (vHPSD) ablation for atrial fibrillation nor the safety and efficacy profile have been fully elucidated.We conducted a porcine study in which, after right thoracotomy, we implanted 6-8 thermocouples epicardially in the superior vena cava, right pulmonary vein, and esophagus close to the inferior vena cava. We compared tissue temperatures close to a QDOT MICRO catheter, between during 90W/4sec-vHPSD ablation during ablation index (AI: target 400)-guided 50W-HPSD ablation, both targeting a contact force of 8-15 g.Maximum tissue temperature reached during 90W/4sec-vHPSD ablation did not differ significantly from that during 50W-HPSD ablation (49.2±8.4ºC versus 50.0±12.1ºC; P=0.69) and correlated inversely with distance between the catheter tip and the thermocouple, regardless of the power settings (r=-0.52 and r=-0.37). Lethal temperature (≥50°C) was best predicted at a catheter tip-to-thermocouple distance cut-point of 3.13 and 4.27 mm, respectively. All lesions produced by 90W/4sec-vHPSD or 50W-HPSD ablation were transmural. Although there was no difference in the esophageal injury rate (50% versus 66%, P=0.80), the thermal lesion was significantly shallower with 90W/4sec-vHPSD ablation than with 50W-HPSD ablation (381.3±127.3 versus 820.0±426.1μm from the esophageal adventitia; P=0.039).Actual tissue temperatures reached with 90W/4sec-vHPSD ablation appear similar to those with AI-guided 50W-HPSD ablation, with the distance between the catheter tip and target tissue being shorter for the former. Although both ablation settings may create transmural lesions in thin atrial tissues, any resulting esophageal thermal lesions appear shallower with 90W/4sec-vHPSD ablation. This article is protected by copyright. All rights reserved.

Moraxella lacunata(M. lacunata) is a Gram-negative bacterium, which rarely causes serious infection. This is a rare case report of acute glomerulonephritis diagnosed by pathological findings in a child accompanied byM. lacunatainfection. The patient showed hematuria, proteinuria and hyperkalemia requiring emergency hemodialysis. After hospitalization,M. lacunatabacteremia became apparent. Pathological findings showed an increase in glomerulus inflammatory cells and glomerular C3 deposition was observed in the renal tissue biopsy. Final diagnosis was endocapillary proliferative glomerulonephritis. Clinical reports ofM. lacunatainfection requiring emergency hemodialysis in children are rare. Previous reports have suggested that lowered immune competency with chronic kidney disease may be a risk factor associated with serious invasive cases ofM. lacunatainfection. However, detailed clinical laboratory data and pathological findings have not been identified in previous case reports. Our case directly indicated complement activity and acute glomerulonephritis withM. lacunatainfection. Although there are various causes for acute glomerulonephritis, infection-related glomerulonephritis (IRGN) is an important concept.M. lacunatainfection might have a potential risk for IRGN with dysregulation of complement activity leading to serious and invasive clinical conditions than previously considered.

A 52-year-old man, with a history of allergic rhinitis and without coronary risk factors, transferred to our hospital because of cardiac arrest. Coronary angiography revealed no significant stenosis in left coronary arteries ([Figure 1A][1]), and mild stenosis in right coronary artery ([Figure 1B

Purpose Optical frequency domain imaging (OFDI) is widely used to characterize lipidic-atherosclerotic plaques, shown as signal-poor regions with diffuse borders, in clinical setting. Given that lipid components are common to both fibroatheroma (FA) and pathological intimal thickening (PIT), it is unclear whether OFDI can be used to accurately distinguish between FA and PIT. This study evaluated the differences in OFDI findings between FA and PIT in comparison with histopathology. Methods A total of 631 histological cross-sections from 14 autopsy hearts were analyzed for the comparison between OFDI and histological images. Of those, 190 (30%) sections were diagnosed with PIT and 120 (19%) with FA. All OFDI images were matched with histology and the OFDI signal attenuation rate was calculated from an exponential. The lipid length was measured longitudinally, and the lipid arc was measured with a protractor centered in the center of the lumen. Results There was no significant difference in the OFDI signal attenuation rate between FA and PIT (3.09 ± 1.04 versus 2.79 ± 1.20, p = 0.13). However, the lipid length was significantly longer and the maximum lipid arc was significantly larger in FA than in PIT (7.5 [4.3–10.3] mm versus 4.3 [2.7–5.8] mm, p < 0.0001, and 125 [101–174]° versus 96 [74–131]°, p < 0.0001, respectively). Conclusions OFDI may be capable of discriminating advanced lipid plaques from early stage atherosclerosis based on the longitudinal and circumferential extent of signal-poor region.

BACKGROUND Coronary angioscopy (CAS) is used to comprehensively evaluate vascular responses after drug-eluting stent (DES) implantation. This study sought to evaluate the capability of CAS for evaluating DES strut coverage grade and color grade of the intima compared with histological images in coronary autopsy specimens. Methods and Results: A total of 23 DES extracted from 11 autopsy hearts were imaged by CAS. All stent segments were graded as white or yellow according to the luminal surface color, and thrombus was evaluated according to a previous report. Neointimal coverage over the DES was graded as 0 (stent struts fully visible) to grade 3 (stent struts fully embedded and invisible). Of 76 segments, neointimal coverage was graded as 0 in 35 (46%), 1 in 22 (29%), 2 in 8 (11%), and 3 in 11 (14%). The neointimal thickness increased significantly with increasing neointimal coverage grade on angioscopy. Neointimal color was graded as white in 40 (53%) and yellow in 36 segments (47%). Histological analysis revealed that yellow neointima contained fibroatheroma, foam cells accumulation or superficial calcium deposition. A thrombus was identified in 13 segments. Thrombi adherent around the stent strut were partly intimal erythrocyte accumulation around the strut. CONCLUSIONS In-stent yellow segment had atherosclerotic components. CAS could evaluate vascular status comprehensively after DES implantation.

A 76-year-old female presented with cognitive impairment and multiple brain infarcts and died of massive subcortical cerebral hemorrhage. A premortem clinical diagnosis was not possible. She did not show apparent microbleeds on brain images during her lifetime. An autopsy revealed vasculitis at various stages with amyloid β deposition and granulomatous reaction in cortical and leptomeningeal arteries, although almost vasculitic processes were in the healing stage, suggestive of the inactive stage of the disease process. Affected vessels were strictly limited to the brain. The final pathological diagnosis of the autopsy was amyloid β-related angiitis. Genotype analyses of ApoE revealed ApoE ε3/ε3 genotype, low risk for Alzheimer's disease. On retrospective examination, the titer of anti-amyloid β autoantibody in cerebrospinal fluid was rather high in our case, but the exact clinical significance remains unknown. Since microbleeds on brain images are diagnostic findings in patients with cerebral amyloid angiopathy-associated conditions, it is very difficult to make an accurate diagnosis of amyloid β-related angiitis without typical microbleeds or open brain biopsy like our case. Keywords: Amyloid β-related angiitis, Cerebral amyloid angiopathy, ApoE, Subcortical cerebral hemorrhage, Primary central nervous system vasculitis

Embolic myocardial infarction (MI) caused by infective endocarditis (IE) is rare, but it is increasingly recognized as an important complication. This complication typically occurs in patients with aortic valve endocarditis during the acute phase of the infection. It is also known to have a high mortality rate; however, the best practice for its management is unclear owing to scarce available data. In addition, most cases of embolic acute MI (AMI) caused by IE are indirectly diagnosed with a combination of angiographic examination such as coronary angiography or cardiac computed tomography. Herein, we report a case of fatal embolic ST-elevation MI (STEMI) caused by mitral valve IE during the healed phase, which was clearly proven by the pathology findings.

Introduction: The use of drug-coated balloons (DCB) is a promising technique to treat in-stent restenosis without adding another metal scaffold. Clinical non-inferiority of DCB for treatment of in-stent restenosis (ISR) has been demonstrated compared to drug eluting stents (DES) implantation. However, pathology of neointima treated by DCB remains unclear. Aim: Pathological study of neointima after DCB treatment for ISR has not been reported. This study aimed to examine the tissue response after DCB treatment and plain old balloon angioplasty (POBA) for ISR pathologically, by using atherosclerotic femoral artery of porcine model. Methods: Using micromini pigs fed high-cholesterol, high-fat diet for 3 months, we stented bare metal stents in femoral arteries. After one month of stenting, dilatation of in-stent region by using DCB, and non-compliance balloon (NCB) as POBA were performed. Optimal coherence tomography and angioscopy showed drug adhesion on luminal surface. One month after the balloon expansion, treated arteries were dissected and stent segments were fixed with 10% buffered formalin and embedded in plastic. Stents were segmented at 3mm intervals and histologic sections were prepared. The neointimal area and blood vessel area were morphometrically evaluated, and the ratio of neointimal area per blood vessel area was calculated. Additionally, number of cells per 1mm 2 neointimal area was counted with digital morphometry. Results: We compared the histology between DCB (n=3, 18 histological sections) and POBA (n=3, 18 histological sections) lesions. The ratio of neointimal area per blood vessel area treated by DCB was 0.17 ± 0.01, while that of POBA was 0.21 ± 0.01 (P value = 0.02) respectively. Additionally, the number of cells per 1mm 2 neointimal area was significantly less in the neointima dilated by DCB (1940.9 ± 150.9), compared to that dilated by NCB (2599.8 ± 190.3) (P value = 0.01). These results suggest that DCB treatment after ISR prevents neointimal thickening by inhibiting proliferation of smooth muscle cells. Conclusions: We examined the pathology of in-stent neointima dilated by DCB in peripheral artery of atherosclerotic porcine model. Pathological analysis showed suppressed neointimal proliferation after DCB compared to POBA.

Introduction: Third-generation drug-eluting stent (3rd DES) is widely used in percutaneous coronary intervention. Clinical superiority of 3rd DES has been demonstrated, however, pathological response after 3rd DES remains unclear. We aimed to examine the histology after 3rd DESs in low-density lipoprotein receptor knockout (LDLR -/-) minipigs’ coronary arteries. Methods: Using LDLR -/- minipigs, second-generation drug-eluting stents (2nd DESs) and 3rd DESs were deployed in coronary arteries. Two weeks (n = 2) or four weeks (n = 4) after stent implantation, coronary angiography for the follow up was performed. For evaluation of the features of neointima, optical coherence tomography (OCT) examination was performed in all stented vessels. The stent-implanted arteries were dissected immediately after OCT and investigated histologically. Results: OCT analysis for four-week models showed that the thickness of neointima over 3rd DESs was significantly thinner than that over 2nd DESs (3rd DESs; 43.29 ± 3.29 μm vs. 2nd DESs; 61.67 ± 5.51 μm, P = 0.009). In two-week models, numerous inflammatory cells were observed on the luminal side of 2nd DESs’ struts, while this response was absent in 3rd DESs. Fibrin deposition around 3rd DES’s strut was 2347.9 ± 875.6 μm 2 , while that around 2nd DES’s strut was 4738.9 ± 691.0 μm 2 (P = 0.041) in four-week models. Moreover, when defining the density of smooth muscle cells as ratio of hematoxylin-eosin stained area, it was significantly higher in the neointima above 3rd DESs than that above 2nd DESs in four-week models (3rd DESs; 0.373 ± 0.011 vs. 2nd DESs; 0.265 ± 0.030, P = 0.026). Although neointima over 3rd DES was thin, the density of smooth muscle cells that compose the neointima was higher and seemed to be well-matured. Conclusion: Our pathological analysis showed advanced healing process in 3rd DES compared to 2nd DES lesions. This result may attributed to the absence or the presence of polymer applied on the luminal side of struts, which triggers severe inflammation in the early term after stent implantation, leading to formation of fibrin deposition, unnecessary neointimal thickening, and inhibition of neointimal maturation.

Background Metabolic syndrome is a cluster of conditions including obesity, insulin resistance, hypertension, and abnormal cholesterol, which increases the cardiovascular risk. Metabolic syndrome or obesity has been reported to provide systemic inflammation and oxidative stress. Increased epicardial fat volume is a manifestation of obesity or metabolic syndrome. Those systemic and local conditions related to obesity or metabolic syndrome have been linking to the risk of atrial fibrillation (AF). The underlying mechanisms of obesity linking epicardial fat to AF progression have not been fully examined. Purpose To investigate the impact of obesity linked to epicardial fat on electrophysiologic and anatomical AF substrates. Methods Twenty dogs aged 3 years were divided into four groups (n=5 per each): normal diet for over 20 weeks (control group [median body weight: 12.0 kg]), rapid atrial pacing (RAP) for last 4–15 (median 8) weeks during a normal diet for the same period (RAP group [10.5 kg]), high-fat diet (HFD) maintained for over 20 weeks without RAP (MetS group [16.0 kg]), and RAP for last 4–12 (median 6) weeks during HFD maintained for 24 weeks (MetS-RAP group [17.0 kg]), respectively. Activation/voltage maps of the atria during sinus rhythm were created with Ensite NavX mapping system. The effective refractory period (ERP) at 5 left atrial (LA) and pulmonary vein (PV) sites (LA appendage [LAA], LA body, right and left superior PVs, and inferior PV), and AF inducibility by burst LAA pacing were determined. At study completion, hearts were excised for histopathological and gene expression analyses. Results The LA pressure was more significantly increased in MetS than the MetS-RAP, RAP, and control groups (22.5 [17–28.8] mmHg vs. 14.0 [10.5–16.3] mmHg, 10.5 [7.4–17.2] mmHg and 10.7 [9.6–13.5] mmHg, respectively, P Conclusions AF vulnerability was associated with increased LA pressures and fibrofatty infiltration from epicardial fat in the MetS group, and with fibrofatty infiltration from epicardial fat with subtle fibrosis in the MetS-RAP group. This suggested that fibrofatty infiltration and epicardial fat plays an important role in AF pathogenesis in obese patients. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Grant-in-Aid for Scientific Research (KAKENHI)

Background To date, there have been no data available regarding the diagnostic performance of optical frequency domain imaging (OFDI) for in vivo histological classification of atherosclerotic lesions. This study investigated whether OFDI can be used to diagnose and classify histological atherosclerotic lesions in the coronary artery by ex vivo histological examinations. Methods Three-hundred-fifteen histological cross-sections from 21 autopsy hearts were matched with the OFDI images. Histological cross-sections were classified into six categories: adaptive intimal thickening (AIT), pathological intimal thickening (PIT), fibrous cap atheroma (FA), fibrocalcific plaque (FC), calcified nodule, and healed erosion/rupture. The five observers with different years of experience in the interpretation of OFDI provided a single diagnosis for the OFDI scans of each cross-section according to the aforementioned six histological categories. The diagnostic accuracy and interobserver variability of lesion types for each OFDI observer were determined using histology as the gold standard. Results The overall agreement rates between OFDI and histopathologic diagnosis for OFDI observers 1–5 were 81%, 70%, 68%, 61%, and 50% (κ values of 0.75, 0.61, 0.58, 0.49, and 0.36), respectively. Although the diagnostic accuracy of OFDI for detecting AIT and FC was excellent for all five observers, the sensitivity, and positive predictive values of OFDI for detecting PIT and FA were low in proportion to years of experience. Conclusion The diagnostic accuracy of atherosclerotic tissue properties from OFDI scans correlated with the observers' years of experience, especially when lesions contained lipid components.

Triglyceride deposit cardiomyovasculopathy (TGCV) is a newly identified disease that was discovered in individuals who required cardiac transplantation in Japan in 2008. Defective intracellular lipolysis causes triglyceride (TG) accumulation in the myocardium and coronary artery vascular smooth muscle cells, which results in severe heart failure and coronary artery disease with poor prognosis. A known cause of TGCV is a genetic deficiency of adipose triglyceride lipase (ATGL), a rate-limiting enzyme in the intracellular hydrolysis of TG. TGCV is classified into primary TGCV with ATGL mutations and idiopathic TGCV without ATGL mutations. Since its discovery, the Japan TGCV Study Group has attempted to elucidate its pathophysiology, develop diagnostic procedures, and specific treatment. Myocardial scintigraphy with iodine-123-β-methyl iodophenyl-pentadecanoic acid ((123)I-BMIPP) is a unique imaging modality for evaluating myocardial lipolysis in vivo. The washout rate of (123)I-BMIPP is an essential indicator for the diagnosis of TGCV. Along with our efforts to provide awareness of and insights into this disease concept, we found that the cumulative number of clinically diagnosed patients has reached >200 and the cases are distributed throughout Japan. In addition, we successfully completed three investigator-initiated clinical trials of a potential therapeutic agent (CNT-01) for TGCV, which was assigned by the Ministry of Health, Labour, and Welfare, Japan, under the SAKIGAKE Designation System in June 2020. Here, we provide the Diagnostic Criteria 2020 for TGCV in order to further promote this “rare and intractable disease” project.

•Uterine neuroectodermal tumors (NETs) are uncommon malignant neoplasm with poor prognosis.•Ganglion-like cells with fibrillary background as major component of uterine NETs are extremely rare.•We present a patient affected by uterine NET with frequent ganglion-like cells, resembling ganglioneuroblastoma.•This case report is important to define the pathogenesis and establish better treatments for neuroectodermal tumors.

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 Masson's 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 ± 173.4 μm 2 . Those of 1st DES were 0.44 ± 0.12 and 3107.5 ± 1405.9 μm 2 . 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 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.

We experienced a diagnostically challenging case of Carney complex (CNC). A 24-year-old woman had a past history of surgical removal of multiple cutaneous tumors in the childhood. She was followed as a patient of neurofibromatosis type 1 (NF1) and referred to our hospital for further treatment after she grew up to adulthood. At our hospital, several cutaneous tumors were excised, and the pathological diagnosis was myxoma arising from not deep soft tissue but cutis (so-called cutaneous myxoma). Despite previous clinical diagnosis of NF1, because of the probability of CNC, detailed systemic examination was undertaken including radiological and endocrinological tests. Imaging techniques showed multiple lumps in both breasts, a mass in left atrium and nodular lesions in adrenal glands. Serum ACTH level was markedly suppressed. Surgically resected specimens revealed breast myxomas, cardiac myxoma and primary pigmented nodular adrenocortical disease (PPNAD). These findings met the diagnostic criteria for CNC. Genetic analysis revealed known non-sense mutation of PRKAR1A c.124C>T (p.R42X) (ClinVar ID 41382). Her 50-year-old mother was also shown to have cardiac myxomas, radiological finding of breast myxomatosis and the same PRKAR1A mutation as her daughter. In the present case, the accurate diagnosis of CNC was difficult not only because CNC is a rare disease but also because skin pigmentation was not obvious. Since cardiac myxoma might result in poor or fatal outcome, early and accurate diagnosis of CNC and subsequent systemic investigation including heart are important. Although pediatric cutaneous myxomas are rare, multiple cutaneous myxomas might suggest the possibility of CNC. In such cases, systemic investigation should be done for the accurate diagnosis. Keywords: Carney complex, Cutaneous myxoma, PPNAD, PRKAR1A mutation

A 50-year-old woman diagnosed with vasospastic angina presented to our hospital with repeated typical chest pain. The patient experienced cardiac arrest 14 years previously because of the vasospasm ([Figure 1A][1]). Although the patient was prescribed multiple medications for more than 10 years

We report the case of a 38-year-old woman who was admitted for acute cerebral infarction linked to a cardiac calcified amorphous tumor (CAT) and related mitral annular calcification (MAC). The cardiac mass was removed, and mitral valve replacement surgery was performed. Pathological examination revealed an amorphous accumulation of degenerating material within both lesions, indicating that build-up of calcium along the mitral annulus and subsequent rupture of the fibrotic tissue may be involved in the initiation and progression of CAT.

Background Third-generation drug-eluting stent (3rd DES) is commonly used now in percutaneous coronary intervention, and it has not only thinner struts, easier delivery than second-generation drug-eluting stent (2nd DES), but also abluminal biodegradable polymer. Clinical superiority of 3rd DES has been demonstrated compared to 1st and 2nd DESs. However, pathological response after 3rd DES implantation remains unclear. Purpose Pathological study of coronary artery after 3rd DES implantation have not been reported as far as we have referred to the previous studies. This study aimed to examine the initial tissue response after 3rd DES and 2nd DES implantation within one year. Methods Using specimens obtained by autopsy, we compared the histology between 3rd DES (n=3, 8 histological sections) and 2nd DES (n=6, 41 histological sections) lesions within 1 year after stent implantation to evaluate early tissue reaction. Stent segments were fixed with 10% buffered formalin and embedded in plastic, followed by hematoxylin–eosin, Masson's trichrome and elastica van Gieson. Ratio of covered stent struts by neointima was calculated. The thickness of neointima and the area of fibrin deposition were morphometrically evaluated. The degree of inflammation around struts was examined semi-quantitatively (score 0–3). Results The ratio of covered struts and thickness of neointima of 3rd DES were 0.84±0.04 and 68.2±10.3μm, while those of 2nd DES were 0.69±0.05 and 30.4±4.8μm respectively. The inflammation score was similar between two groups (1.00±0.14 vs. 1.02±0.16). The area of fibrin deposition around the struts was larger in 3rd DES compared with 2nd DES (1276.6±490.3μm2 vs. 658.0±173.4μm2). These results suggest that the 3rd DES may obtain prompt as well as rich covering of struts in the initial term after DES implantation. Although the biological feature of the polymers in 3rd and 2nd DESs is different, the inflammatory responses after both 3rd and 2nd DESs implantation were similar, at least within one year after deployment. The degree of inflammation was mild, less than approximately 50 inflammatory cells (score 1) around the struts. Conclusions Our pathological analysis showed advanced healing process in 3rd DES compared with 2nd DES lesions in the viewpoint of strut coverage by neointima. Observation of long-term pathological response may be required to evaluate the superiority of bioabsorbable polymer in 3rd DES.

For atherosclerotic cardiovascular diseases (ACD), gene therapy may be a potential therapeutic strategy; however, lack of effective and safe methods for gene delivery to atherosclerotic plaques have limited its potential therapeutic applications. To overcome this limitation, we developed a novel antibody-based gene delivery system (anti-HB-EGF/NA vector) by chemically crosslinking antibodies against human heparin-binding epidermal growth factor-like growth factor (HB-EGF). It has been shown to be excessively expressed in human atherosclerotic plaques and NeutrAvidin (NA) for conjugating biotinylated siRNA. Immunofluorescence staining and quantitative flow cytometry analysis using human HB-EGF-expressing cells showed both antibody-mediated selective cellular targeting and efficient intracellular delivery of conjugated biotin-fluorescence. Moreover, we demonstrated antibody-mediated significant and selective gene knockdown via conjugation with anti-HB-EGF/NA vector and biotinylated siRNA (anti-HB-EGF/NA/b-siRNA) in vitro. Furthermore, using high fat-fed human HB-EGF knock-in and apolipoprotein E-knockout (Hbegf hz/hz; Apoe-/-) mice, we demonstrated that the anti-HB-EGF/NA vector, conjugating biotin-fluorescence, increasingly accumulated within the atherosclerotic plaques of the ascending aorta in which human HB-EGF expression levels were highly elevated. Moreover, in response to a single intravenous injection of anti-HB-EGF/NA/b-siRNA in a dose-dependent manner, qPCR analysis of laser-dissected atherosclerotic plaques of the ascending aorta showed significant knockdown of the reporter gene expression. These results suggest that the anti-HB-EGF antibody-mediated siRNA delivery could be a promising delivery system for gene therapy of ACD.

Third-generation drug-eluting stent (3rd DES) is widely used in percutaneous coronary intervention. Clinical superiority of 3rd DES has been demonstrated compared to second-generation drug-eluting stent (2nd DES). However, pathological response after 3rd DES implantation remains unclear. This study

Thoracic venous aneurysms are rare, and bleeding is possible. A 9-year-old female patient presented with a thoracic wall mass. No blood flow was observed in the mass, and a chronic expanding haematoma was suspected based on the differential diagnosis. However, the venous structure was identified in the wall of the mass on pathological examination, and the diagnosis of the venous aneurysm was thereby established. Because the venous aneurysm contains fresh blood and bleeding can be profuse when such lesions are not properly handled during a surgical procedure, making the visibility of the surgeon poor, the venous aneurysm must be included in the differential diagnosis.

Background Embolism during percutaneous coronary intervention (PCI) causes microcirculation impairment. The aim of this study was to clarify the relationship between the pathological characteristics of tissue captured by distal protection device (DPD) and amount of tissue accumulated in DPD. Methods and Results: A total of 671 consecutive lesions in PCI using DPD were examined. The amount of necrotic debris, fibrous tissue, calcified particle, platelet thrombus and organized thrombus in the DPD baskets was histologically evaluated. The DPD tissue amount was assessed semi-quantitatively, and the relationship between the captured DPD tissue characteristics and tissue amount was investigated. On pathology, 40.7% of the lesions had necrotic debris, 41.4% had fibrous tissue, and 18.0% had calcified particle. The prevalence of lesions in patients with acute coronary syndrome (ACS) was 62.1%. Tissue amount score distribution was as follows: score 1 (tissue invisible), 3.9%; score 2 (tissue clinging to the basket), 52.0%; score 3 (tissue accumulated at the bottom of the basket), 38.5%; and score 4 (tissue accumulated in more than half of the basket), 5.7%. On multivariate analysis, necrotic debris and fibrous tissue were associated with greater tissue amount as well as clinical presentation of ACS. Conclusions The presence of atherosclerotic plaque component, such as necrotic debris and fibrous tissue, might be a risk for distal embolism during PCI.

We report the case of a 38-year-old woman who was admitted for acute cerebral infarction linked to a cardiac calcified amorphous tumor (CAT) and related mitral annular calcification (MAC). The cardiac mass was removed, and mitral valve replacement surgery was performed. Pathological examination revealed an amorphous accumulation of degenerating material within both lesions, indicating that build-up of calcium along the mitral annulus and subsequent rupture of the fibrotic tissue may be involved in the initiation and progression of CAT.

Objective— Although iron is an essential element for maintaining physiological function, excess iron leads to tissue damage caused by oxidative stress and inflammation. Oxidative stress and inflammation play critical roles for the development of abdominal aortic aneurysm (AAA). However, it has not been investigated whether iron plays a role in AAA formation through oxidative stress and inflammation. We, therefore, examined whether iron is involved in the pathophysiology of AAA formation using human AAA walls and murine AAA models. Approach and Results— Human aortic walls were collected from 53 patients who underwent cardiovascular surgery (non-AAA=34; AAA=19). Murine AAA was induced by infusion of angiotensin II to apolipoprotein E knockout mice. Iron was accumulated in human and murine AAA walls compared with non-AAA walls. Immunohistochemistry showed that both 8-hydroxy-2′-deoxyguanosine and CD68-positive areas were increased in AAA walls compared with non-AAA walls. The extent of iron accumulated area positively correlated with that of 8-hydroxy-2′-deoxyguanosine expression area and macrophage infiltration area in human and murine AAA walls. We next investigated the effects of dietary iron restriction on AAA formation in mice. Iron restriction reduced the incidence of AAA formation with attenuation of oxidative stress and inflammation. Aortic expression of transferrin receptor 1, intracellular iron transport protein, was increased in human and murine AAA walls, and transferrin receptor 1–positive area was similar to areas where iron accumulated and F4/80 were positive. Conclusions— Iron is involved in the pathophysiology of AAA formation with oxidative stress and inflammation. Dietary iron restriction could be a new therapeutic strategy for AAA progression.

Objectives This study sought to assess the accuracy of optical coherence tomography (OCT), gray-scale intravascular ultrasound (IVUS), and their combination for detecting thin-cap fibroatheromas (TCFA). Background The extent to which the imaging characteristics of OCT and IVUS correlate with histologically defined TCFA is unknown. Methods IVUS and OCT examinations identified focal plaques in 165 coronary arteries from 60 autopsy hearts. A total of 685 pairs of images of OCT and IVUS were compared with histology. By OCT, a TCFA was defined as a signal-poor region with diffuse borders and cap thickness Results With histology as the gold standard, the sensitivity, specificity, positive predictive value, negative predictive value, and overall diagnostic accuracy for OCT-derived TCFA were 100%, 97%, 41%, 100%, and 98%, respectively. The corresponding numbers for IVUS-derived TCFA were 92%, 93%, 19%, 99%, and 93%, respectively. The histological findings underlying the false positive diagnoses of OCT for TCFA included large amounts of foam cell accumulation on the luminal surface, large amounts of microcalcifications at the surface, large amounts of hemosiderin accumulation, or organized thrombus. In contrast, histological causes of mischaracterization of TCFA by IVUS were mostly TCFA. When both OCT and IVUS criteria for TCFA were required to be met, the sensitivity, specificity, positive predictive value, negative predictive value, and overall diagnostic accuracy were 92%, 99%, 69%, 99%, and 99%, respectively. Conclusions In the present study, neither OCT nor IVUS were optimal to detect TCFA. The combined use of OCT and IVUS may improve TCFA detection accuracy.

Objective: To evaluate the incidence of cervical angiopathy caused by radiation therapy for head and neck cancer. Methods: Segments of 57 cervical arteries were obtained during surgery for head and neck malignant tumors and divided into two groups (irradiated group and non-irradiated group) based on the treatment prior to vascular resection. In order to evaluate vascular injury after radiation therapy, we examined the degree of medial atrophy, medial fibrosis, smooth muscle cell (SMC) differentiation in the media and intima, intimal hyperplasia and endothelial cell (EC) injury. Sections of arterial segments were stained with hematoxylin-eosin, Elastica van Gieson and Masson’s trichrome, and immunohistochemistry for α-smooth muscle actin (α-SMA), smoothelin, S100A4 and CD31 in the resected vessels was conducted. Results: The median interval between the completion of radiation therapy and vascular resection was nine months. No significant differences were observed between the two groups in terms of medial atrophy, medial fibrosis and intimal hyperplasia. The ratio of the smoothelin-positive area per α-SMA-positive area in the media and the S100A4-positive proportion in the intima, indicating the degree of differentiation of the medial SMC and dedifferentiation of the intimal SMC, respectively, showed no significant differences, despite the tendency toward a lower smoothelin-positive area per α-SMA-positive area in the media of the irradiated arteries. The EC coverage revealed on CD31 immunohistochemistry was significantly decreased, with mural thrombus adhesion, in the irradiated group. Conclusions: The ECs of small arteries are damaged by irradiation. Although we did not confirm the statistical significance of medial SMC dedifferentiation, a decreased expression of smoothelin tended to be observed in the media of the irradiated arteries. Our findings provide histopathological evidence of irradiation angiopathy in head and neck cancer and may help to improve the surgical safety of microvascular anastomosis and determine the treatment strategy for head and neck tumors.

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. Methods and results 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.