Frequency and Distribution of Sheet and Nodular Calcification in Coronary Arteries in Japanese Patients.

Whether a nodular calcification (NC), which is the precursor to intracoronary thrombosis, is focally or diffusely distributed in the coronary tree has major implications for ongoing efforts to identify. This study aimed to investigate the frequency and spatial distribution patterns of sheet calcification (SC) and NC in a 3-vessel examination of autopsied human hearts.A total of 323 coronary artery specimens from 110 cadavers were obtained from autopsy cases. After fixation and decalcification, the coronary artery trees were cut every 5 mm into 4-µm transverse cross-sections for histological assessment. An SC was defined as a plate-like calcification of > 1 quadrant of the vessel or > 3 mm in diameter, and NC as nodular calcium deposits separated by fibrin, and a deposit size > 1 mm in diameter.Of the 6,306 histological cross-sections, SCs and NCs were identified in 1,627 (26%) and 233 (4%) cross-sections, respectively. SCs and NCs had a similar distribution pattern in all 3 coronary arteries. In the left anterior descending artery (LAD), NCs were predominantly located in the proximal segment: the first 45 mm from the LAD ostium (72%) and the first 60 mm from the LAD ostium (84%), respectively. However, NCs were evenly distributed throughout the length of the coronary artery in the right coronary artery (RCA) and left circumflex artery (LCX).NCs coexisted with SCs, and tended to cluster in predictable parts within the proximal segments of the LAD, but were evenly distributed throughout the RCA and LCX in coronary arteries from cadavers.

Pathology of Critical Limb Ischemia; Comparison of Plaque Characteristics Between Anterior and Posterior Tibial Arteries.

AIMS: Though the number of patients with peripheral arterial disease (PAD) and critical limb ischemia (CLI) is increasing, few histopathological studies of PAD, particularly that involving below-the-knee arteries, has been reported. We analyzed the pathology of anterior tibial artery (ATA) and posterior tibial artery (PTA) specimens obtained from patients who underwent lower extremity amputation due to CLIMethods: Dissected ATAs and PTAs were subjected to ex-vivo soft X-ray radiography, followed by pathological examination using 860 histological sections. This protocol was approved by the Ethics Review Board of Nihon University Itabashi Hospital (RK-190910-01) and Kyorin University Hospital (R02-179). RESULTS: The calcified area distribution was significantly larger in PTAs than in ATAs on soft X-ray radiographic images (ATAs, 48.3% ±19.2 versus PTAs, 61.6% ±23.9; p＜0.001). Eccentric plaque with necrotic core and macrophage infiltration were more prominent in ATAs than in PTAs (eccentric plaque: ATAs, 63.7% versus PTAs, 49.1%; p＜0.0001, macrophage: ATAs, 0.29% [0.095 - 1.1%] versus PTAs, 0.12% [0.029 - 0.36%]; p＜0.001), histopathologically. Thromboembolic lesions were more frequently identified in PTAs than in ATAs (ATAs, 11.1% versus PTAs 15.8%; p＜0.05). Moreover, post-balloon injury pathology differed between ATAs and PTAs. CONCLUSIONS: Histological features differed strikingly between ATAs and PTAs obtained from CLI patients. Clarifying the pathological features of CLI would contribute to establishing therapeutic strategies for PAD, particularly disease involving below-the knee-arteries.

Intravenous Semaphorin 3A Administration Maintains Cardiac Contractility and Improves Electrical Remodeling in a Mouse Model of Isoproterenol-Induced Heart Failure.

The effects of recombinant semaphorin 3A (Sema3A) on myocardial contractility and electrical remodeling in mice with isoproterenol (ISP) -induced heart failure were investigated.C57BL/6J mice intraperitoneally received ISP (480 mg/kg/day, ISP group; n = 24) or saline (control group; n = 31) for 14 days. Twenty-one ISP-treated mice received 0.5 mg/kg Sema3A intravenously on days 7 and 11 (ISP+Sema3A group). The sympathetic nervous system was activated upon ISP treatment, but was reduced upon Sema3A administration. Greater myocardial tissue fibrosis was observed in the ISP group than in the control group. However, fibrosis was not significantly different between the ISP+Sema3A and control groups. Fractional shortening of the left ventricle was lower in the ISP group than in the control group and was restored in the ISP+Sema3A group (control, 53 ± 8%; ISP, 37 ± 7%; ISP+Sema3A, 48 ± 3%; P < 0.05). Monophasic action potential duration at 20% repolarization (MAPD20) was prolonged in the ISP group (compared to control group), but this was reversed upon Sema3A administration (control, 29 ± 3 ms; ISP, 35 ± 6 ms; ISP+Sema3A, 29 ± 3 ms; P < 0.05). qPCR revealed Kv4.3, KChIP2, and SERCA2 downregulation in the ISP group and upregulation in the ISP+Sema3A group; however, Western blotting revealed similar changes only for Kv4.3 (P < 0.05).Intravenous Sema3A may maintain myocardial contractility by suppressing the sympathetic innervation of the myocardium and reducing myocardial tissue damage, in addition to restoring MAPD via Kv4.3 upregulation.

Histopathological Evaluation of Pulmonary Thromboendarterectomy Specimens of Chronic Thromboembolic Pulmonary Hypertension.

AIMS: Chronic thromboembolic pulmonary hypertension (CTEPH) is a condition with a poor prognosis in which the pulmonary arteries are occluded by organized thrombi. Pulmonary thromboendarterectomy (PEA) is an effective treatment for CTEPH; however, the literature on its histopathological examination is lacking. This study aimed to investigate the histopathological findings and protein and gene expression in PEA specimens, establish an optimal histopathological evaluation method, and clarify the mechanisms of thrombus organization and disease progression in CTEPH. METHODS: In total, 50 patients with CTEPH who underwent PEA were analyzed. The patients were categorized according to their clinical data into two groups: good and poor postoperative courses. The relationship between their histopathological findings and the clinical course was examined. Immunohistochemical studies confirmed the expression of oxidants, antioxidants, and smooth muscle cell (SMC) differentiation markers and their changes during the progression of thrombus organization. The mRNA expression analysis of 102 samples from 27 cases included oxidants, antioxidants, and vasoconstrictor endothelin-1. RESULTS: In the PEA specimens, colander-like lesions (aggregations of recanalized blood vessels with well-differentiated SMCs) were significantly more common in the good postoperative course group than in the poor postoperative course group; analysis of proteins and genes proposed that oxidative and antioxidant mechanisms were involved. In the colander-like lesions, there was an increase in endothelin-1 mRNA and protein expression of endothelin receptor A. CONCLUSIONS: Colander-like lesions in PEA specimens must be identified. Additionally, SMC differentiation in recanalized vessels and the expression of vasoconstrictors and their receptors may contribute to the progression of CTEPH.

In vivo tissue temperatures during 90 W/4 sec-very high power-short-duration (vHPSD) ablation versus ablation index-guided 50 W-HPSD ablation: A porcine study.

INTRODUCTION: Neither the actual in vivo tissue temperatures reached with 90 W/4 s-very high-power short-duration (vHPSD) ablation for atrial fibrillation nor the safety and efficacy profile have been fully elucidated. METHODS: We conducted a porcine study (n = 15) 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 90 W/4 s-vHPSD ablation during ablation index (AI: target 400)-guided 50 W-HPSD ablation, both targeting a contact force of 8-15 g. RESULTS: Maximum tissue temperature reached during 90 W/4 s-vHPSD ablation did not differ significantly from that during 50 W-HPSD ablation (49.2 ± 8.4°C vs. 50.0 ± 12.1°C; p = .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 90 W/4 s-vHPSD or 50 W-HPSD ablation were transmural. Although there was no difference in the esophageal injury rate (50% vs. 66%, p = .80), the thermal lesion was significantly shallower with 90 W/4 s-vHPSD ablation than with 50W-HPSD ablation (381.3 ± 127.3 vs. 820.0 ± 426.1 µm from the esophageal adventitia; p = .039). CONCLUSION: Actual tissue temperatures reached with 90 W/4 s-vHPSD ablation appear similar to those with AI-guided 50 W-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 90 W/4 s-vHPSD ablation.

In vivo tissue temperature during lesion size index-guided 50W ablation versus 30W ablation: A porcine study.

BACKGROUND: Neither the actual in vivo tissue temperatures reached with lesion size index (LSI)-guided high-power short-duration (HPSD) ablation for atrial fibrillation nor the safety profile has been elucidated. METHODS: We conducted a porcine study (n = 7) 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 reached during 50 W-HPSD ablation with those reached during standard (30 W) ablation, both targeting an LSI of 5.0 (5-15 g contact force). RESULTS: Tmax  (maximum tissue temperature when the thermocouple was located ≤5 mm from the catheter tip) reached during HPSD ablation was modestly higher than that reached during standard ablation (58.0 ± 10.1°C vs. 53.6 ± 9.2°C; p = .14) and peak tissue temperature correlated inversely with the distance between the catheter tip and the thermocouple, regardless of the power settings (HPSD: r = -0.63; standard: r = -0.66). Lethal temperature (≥50°C) reached 6.3 ± 1.8 s and 16.9 ± 16.1 s after the start of HPSD and standard ablation, respectively (p = .002), and it was best predicted at a catheter tip-to-thermocouple distance cut point of 2.8 and 5.3 mm, respectively. All lesions produced by HPSD ablation and by standard ablation were transmural. There was no difference between HPSD ablation and standard ablation in the esophageal injury rate (70% vs. 75%, p = .81), but the maximum distance from the esophageal adventitia to the injury site tended to be shorter (0.94 ± 0.29 mm vs. 1.40 ± 0.57 mm, respectively; p = .09). CONCLUSIONS: Actual tissue temperatures reached with LSI-guided HPSD ablation appear to be modestly higher, with a shorter distance between the catheter tip and thermocouple achieving lethal temperature, than those reached with standard ablation. HPSD ablation lasting <6 s may help minimize lethal thermal injury to the esophagus lying at a close distance.

Potential of optical frequency domain imaging for differentiation between early and advanced coronary atherosclerosis.

PURPOSE: This study evaluated whether optical frequency domain imaging (OFDI) accurately distinguish between fibroatheroma (FA) and pathological intimal thickening (PIT) compared 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. The OFDI signal attenuation rate was calculated from an exponential. The lipid length was measured longitudinally by detection of sequential OFDI frames within a plaque segment containing lipids. The lipid arc was measured with a protractor centered in the center of the lumen. The fibrous cap thickness was defined as the minimum thickness of the signal rich band overlying PIT and FA. 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, the maximum lipid arc was significantly larger, and the fibrous cap thickness was significantly thinner in FA than in PIT (7.5 [4.3-10.3] mm versus 4.3 [2.7-5.8] mm, p < 0.0001, 125 [101-174]° versus 96 [74-131]°, p < 0.0001, and 220 [167-280] µm versus 260 [190-332] µm, p = 0.019). CONCLUSIONS: This study revealed OFDI may have the potential capability for discriminating FA from PIT based on the longitudinal and circumferential extent of lipid plaque, although the OFDI signal attenuation rate was similar between FA and PIT.

[Giant Anastomotic Aneurysm Associated with Albumin/Glutaraldehyde Sealant as a Late Complication after Acute Aortic Dissection Surgery:Report of a Case].

A 74-year-old woman was taken to our hospital with a chief complaint of chest and back pain. She was diagnosed with Stanford type A acute aortic dissection and underwent ascending aortic replacement. Fifteen months after surgery, a giant anastomotic aneurysm was found at the proximal and distal anastomoses on chest computed tomography (CT), and reoperation was indicated. Following sternal re-entry, anastomotic dehiscence was found where BioGlue, albumin/glutaraldehyde sealant, had been applied during the previous surgery, and caused aneurysm. Severe postoperative adhesion precluded extensive surgery, and redo replacement of the ascending aorta was carried out. Histopathological examination revealed extensive necrosis of smooth muscle cells in the aortic wall at the anastomotic site and a marked inflammatory cell infiltration around the aortic wall and the artificial graft, and association of BioGlue use was suggested. The use of appropriate tissue adhesives to reinforce the dissected aortic wall is important, as well as careful long-term follow-up.

Restriction of SARS-CoV-2 replication in the human placenta.

Although SARS-CoV-2 can infect human placental tissue, vertical transmission is rare. Therefore, the placenta may function as a barrier to inhibit viral transmission to the foetus, though the mechanisms remain unclear. In this study, we confirmed the presence of the SARS-CoV-2 genome in human placental tissue by in situ hybridization with antisense probes targeting the spike protein; tissue staining was much lower when using sense probes for the spike protein. To the best of our knowledge, this is the first evidence directly indicating inefficient viral replication in the SARS-CoV-2-infected placenta. Additional studies are required to reveal the detailed mechanisms.

Autopsy and Cardiac Magnetic Resonance Image Case of Bevacizumab-Related Cardiomyopathy.

We report an autopsy case of a 69-year-old female with cervical cancer. She was given bevacizumab-containing chemotherapy for 4 months. After two years of chemotherapy, she developed congestive heart failure (CHF) with left ventricular dysfunction. Cardiac magnetic resonance (CMR) imaging revealed late gadolinium enhancement (LGE) of linear mid-wall delayed enhancement located in the basal to the mid-septal wall, suggesting bevacizumab-related cardiotoxicity. Although she was treated with cardioprotective medications and discharged, she eventually died from worsening CHF a year later, and we conducted an autopsy. Histopathological examination revealed diffuse fibrosis in the myocardium, and the area where LGE was present on CMR showed thinning and wavy changes in cardiomyocytes with diffuse interstitial fibrosis and edema.

Cardiac calcified amorphous tumor with sustained ventricular tachycardia.

Cardiac calcified amorphous tumors are rare non-neoplastic intracavitary masses with unknown cause. A 60-year-old man presented with sustained ventricular tachycardia. Transthoracic echocardiography and contrast-enhanced angio-computed tomography demonstrated an expanding 73 × 40 mm sized calcified mass in the left ventricle. He underwent successful total removal of the mass and cryo-ablation at the normal myocardial border. Histopathological examination confirmed a diagnosis of cardiac calcified amorphous tumors. The postoperative course was uneventful, without ventricular tachycardia recurrence. To our knowledge, this is the first reported case of confirmed cardiac calcified amorphous tumors causing ventricular tachycardia and treated by surgical resection combined with cryo-ablation.

Actual tissue temperature during ablation index-guided high-power short-duration ablation versus standard ablation: Implications in terms of the efficacy and safety of atrial fibrillation ablation.

BACKGROUND: Actual in vivo tissue temperatures and the safety profile during high-power short-duration (HPSD) ablation of atrial fibrillation have not been clarified. METHODS: We conducted an animal study in which, after a 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 recorded tissue temperatures during a 50 W-HPSD ablation and 30 W-standard ablation targeting an ablation index (AI) of 400 (5-15 g contact force). RESULTS: Maximum tissue temperatures reached with HSPD ablation were significantly higher than that reached with standard ablation (62.7 ± 12.5 vs. 52.7 ± 11.4°C, p = 0.033) and correlated inversely with the distance between the catheter tip and thermocouple, regardless of the power settings (HPSD: r = -0.71; standard: r = -0.64). Achievement of lethal temperatures (≥50°C) was within 7.6 ± 3.6 and 12.1 ± 4.1 s after HPSD and standard ablation, respectively (p = 0.003), and was best predicted at cutoff points of 5.2 and 4.4 mm, respectively. All HPSD ablation lesions were transmural, but 19.2% of the standard ablation lesions were not (p = 0.011). There was no difference between HPSD and standard ablation regarding the esophageal injury rate (30% vs. 33.3%, p > 0.99), with the injury appearing to be related to the short distance from the catheter tip. CONCLUSIONS: Actual tissue temperatures reached with AI-guided HPSD ablation appeared to be higher with a greater distance between the catheter tip and target tissue than those with standard ablation. HPSD ablation for <7 s may help prevent collateral tissue injury when ablating within a close distance.

Case report: Anti-N-methyl-D-aspartate receptor antibody-associated autoimmunity triggered by primary central nervous system B-cell lymphoma.

Background: We herein detail our experience with a unique patient with a primary central nervous system (PCNS) B-cell lymphoma concomitant with anti-N-methyl-d-aspartate receptor (NMDAR) antibodies that satisfied the criteria of "probable anti-NMDAR encephalitis (ProNMDARE)" based on the Graus criteria 2016. Case presentation: A 73-year-old Japanese woman presented with acute pyrexia, agitation, and disturbance of consciousness. She gradually developed a reduction in speech frequency and truncal dystonia causing abnormal posture. Brain magnetic resonance imaging (MRI) demonstrated high-intensity lesions in the bilateral frontal lobes, and her cerebrospinal fluid revealed mild pleocytosis. She was diagnosed with acute encephalitis and treated with acyclovir and intravenous dexamethasone; however, no improvement was observed. She was transferred to our hospital 6 weeks after the onset of her symptoms, and anti-NMDAR antibodies were identified in her cerebrospinal fluid through indirect immunolabeling with rat brain frozen sections and cell-based assays with NR1/NR2 transfected HEK cells. Follow-up MRI showed enlargement of the lesions in the right frontal lobe with gadolinium enhancement, suggesting a brain tumor. Stereotactic surgery was implemented, with subsequent pathological examination revealing that the tumor was consistent with diffuse large B-cell lymphoma (DLBCL) without evidence of systemic satellite lesions. Stereotactic irradiative therapies were then added to her treatment regimen, which partly improved her neurological symptoms with only mild cognitive dysfunction still remaining. A decrease in anti-NMDAR antibody titer was also confirmed after immunotherapy and tumor removal. Conclusions: We herein report our experience with a novel case of PCNS-DLBCL masquerading as anti-NMDAR encephalitis that satisfied the diagnostic criteria of "proNMDARE." Treatment, including tumor removal, ameliorated disease severity and antibody titers of the patient. Our findings suggest that anti-NMDAR antibody-associated autoimmunity can be triggered by PCNS B-cell tumors, although primary brain tumors need to be excluded before establishing a diagnosis of autoimmune encephalitis.

Rosai-Dorfman disease of thymus with elevated serum anti-acetylcholine receptor antibody: a case report.

Rosai-Dorfman disease is a rare disorder of histiocytic proliferation in lymph nodes and at extranodal sites. We herein describe a patient with isolated Rosai-Dorfman disease in the thymus with elevated anti-acetylcholine receptor antibody. We examined the relationship between Rosai-Dorfman disease and elevated anti-acetylcholine receptor antibody. To our knowledge, elevated anti-acetylcholine receptor antibody has not been reported in isolated thymic Rosai-Dorfman disease.

Diagnostic Accuracy of Optical Frequency Domain Imaging for Identifying Necrotic Cores with Intraplaque Hemorrhage in Advanced Human Carotid Plaques.

This study investigated whether optical frequency domain imaging (OFDI) can identify carotid artery vulnerable plaque characteristics, focusing on lipid-rich necrotic core (NC) and intraplaque hemorrhage (IPH). Fourteen patients scheduled for carotid endarterectomy underwent OFDI scan during preoperative angiography. Atherosclerotic plaque specimens obtained from carotid endarterectomy were cut every 3-4 mm into 4-µm transverse cross-sections and stained with standard methods. Each cross-section was matched with OFDI, and histologically classified into either fibrous, calcific, pathological intimal thickening (PIT), and NC. Of 75 histologic cross-sections, 6 were categorized as fibrous (8%), 18 as calcific (24%), 9 as PIT (12%), and 42 as NC (56%). Tissues categorized as NC had significantly higher OFDI signal attenuation rates than the other tissues (p <0.001), followed by PIT, calcific, and fibrous tissues. The receiver operating characteristic analysis indicated that attenuation rates of >0.023 and >0.031 predicted the presence of NC and IPH with high areas under the curve of 0.91 and 0.88, respectively. OFDI provides potential capability for the detection of NCs with IPH of carotid artery plaques by quantitatively analyzing the attenuation rate.

Automated classification of coronary atherosclerotic plaque in optical frequency domain imaging based on deep learning.

BACKGROUND AND AIMS: We developed a deep learning (DL) model for automated atherosclerotic plaque categorization using optical frequency domain imaging (OFDI) and performed quantitative and visual evaluations. METHODS: A total of 1103 histological cross-sections from 45 autopsy hearts were examined to compare the ex vivo OFDI scans. The images were segmented and annotated considering four histological categories: pathological intimal thickening (PIT), fibrous cap atheroma (FA), fibrocalcific plaque (FC), and healed erosion/rupture (HER). The DL model was developed based on pyramid scene parsing network (PSPNet). Given an input image, a convolutional neural network (ResNet50) was used as an encoder to generate feature maps of the last convolutional layer. RESULTS: For the quantitative evaluation, the mean F-score and IoU values, which are used to evaluate how close the predicted results are to the ground truth, were used. The validation and test dataset had F-score and IoU values of 0.63, 0.49, and 0.66, 0.52, respectively. For the section-level diagnostic accuracy, the areas under the receiver-operating characteristic curve produced by the DL model for FC, PIT, FA, and HER were 0.91, 0.85, 0.86, and 0.86, respectively, and were comparable to those of an expert observer. CONCLUSIONS: DL semantic segmentation of coronary plaques in OFDI images was used as a tool to automatically categorize atherosclerotic plaques using histological findings as the gold standard. The proposed method can support interventional cardiologists in understanding histological properties of plaques.