Computational Investigation and Histopathological Validation of Interaction Between Stent Graft and Aorta in Retrograde Type A Dissection After TEVAR in Canine Models

Purpose: Retrograde type A dissection (RTAD) after thoracic endovascular aortic repair (TEVAR) has been a major drawback of endovascular treatment. To our knowledge, no studies have simulated and validated aortic injuries caused by stent grafts (SGs) in animal models. Therefore, the aim of this study was to evaluate and quantify the SG–aorta interaction through computational simulations and to investigate the underlying mechanism through histopathological examinations. Methods: Two custom-made Fabulous® (DiNovA Meditech, Hang Zhou, China) SGs were implanted in 2 canine aortas with a 5-mm difference in the distance in landing locations. The aortic geometries were extracted from RTAD and non-RTAD cases. A computational SG model was assembled based on the implanted SG using the software Pro-ENGINEER Wildfire 5.0 (PTC Corporation, Needham, Mass). TEVAR simulations were performed 7 times for each canine model using Abaqus software (Providence, RI, USA), and the maximum aortic stress (MAS) was calculated and compared among the groups. Three months after SG implantation, the canine aortas were harvested, and were examined using hematoxylin and eosin staining and Elastica Van Gieson (EVG) staining to evaluate histopathological changes. Results: In the computational models for both canines, MAS was observed at the proximal bare stent (PBS) at aortic greater curve. The PBS generated higher stress toward the aortic wall than other SG parts did. Moreover, the MAS was significantly higher in canine No.1 than in canine No.2 (0.415±0.210 versus 0.200±0.160 MPa) (p<0.01). Notably, in canine No.1, an RTAD developed at the MAS segment, and histopathological examinations of the segment showed an intimal flap, a false lumen, elastin changes, and medial necrosis. RTAD was not observed in canine No.2. In both SG-covered aortas, medial necrosis, elastic fiber stretching, and inflammatory infiltration were seen. Conclusion: The characteristic MAS distribution remained at the location where the apex of the PBS interacted with the aortic wall at greater curve. RTAD histopathological examinations showed intimal damage and medial necrosis at the proximal landing zone, at the same MAS location in computational simulations. The in vivo results were consistent with the computational simulations, suggesting the MAS at greater curve may cause RTAD, and the potential application of computational simulation in the mechanism study of RTAD.

Isolated Dissection of the Ductus Arteriosus Associated with Sudden Unexpected Intrauterine Death

We report five cases of sudden intrauterine death due to premature closure of the ductus arteriosus. In four cases, this was caused by dissecting the hematoma of the ductus arteriosus with intimal flap and obliteration of the lumen. In one case, the ductus arteriosus was aneurysmatic, with lumen occlusion caused by thrombus stratification. No drug therapy or free medication consumption were reported during pregnancy. The time of stillbirth ranged between 26 and 33 gestational weeks. We performed TUNEL analysis for apoptosis quantification. The dissecting features were intimal tears with flap formation in four of the cases, just above the origin of the ductus arteriosus from the pulmonary artery. The dissecting hematoma of the ductus arteriosus extended downward to the descending aorta and backward to the aortic arch with involvement of the left carotid and left subclavian arteries. TUNEL analysis showed a high number of apoptotic smooth muscle cells in the media in two cases. Abnormal ductal remodeling with absence of subintimal cushions, lacunar spaces rich in glycosaminoglycans (cystic medial necrosis), and smooth muscle cell apoptosis were the pathological substrates accounting for failure of remodeling process and dissection.

Atherosis of trophoblast type: A specific form of decidual vasculopathy distinct from atherosis of macrophage type

Background: There are three types of decidual vasculopathy, namely, acute atherosis, fibrinoid medial necrosis and mural arterial hyerptrophy. Persistence of vascular trophoblasts is also known to be related to maternal vascular malperfusion, but detailed study is lacking. Material and methods: A total 1017 placentas from 2021 were collected with clinical, neonatal and placental information, and routine placental pathology examination was performed. Decidual vasculopathy was classified based on the new classification scheme including atherosis of macrophage type atherosis of trophoblast type, fibrinoid medial necrosis, mural arterial hypertrophy and mixed type vasculopathy. The significance of these morphologic changes were examined based on the clinical, neonatal and placental pathology features. Results: Decidual vasculopathy is classified as classic type, mural hypertrophy and mixed type. Classic type vasculopathy is further separated as atherosis and fibrinoid medial necrosis. Atherosis is defined as atherosis of macrophage type and atherosis of trophoblast type. Each category of decidual vasculopathy was evaluated in association with maternal, neonatal and placental pathologic findings. Atherosis of macrophage type and mixed type vasculopathy showed statistically significant association with preeclampsia/pregnancy induced hypertension, low birth weight and low placental weight. Atherosis of trophoblast type was associated with lower placental weight but not with specific clinical features. There is no neonatal sex dimorphism in decidual vasculopathy. Conclusion: Atherosis of trophoblast type is a distinct pathologic feature in late pregnancy, and it is associated with lower placental weight. New classification of decidual vasculopathy helps with better stratification and categorization of placental maternal vascular abnormalities.

Pathology of the Aorta and Aorta as Homograft

The aorta is not a rigid tube, it is an “organ” with lamellar units, consisting of elastic fibers, extracellular matrix and smooth muscle cells in between as parenchyma. Several diseases may occur in the natural history of the aorta, requiring replacement of both semilunar cusps and ascending aorta. They may be congenital defects, such as bicuspid aortic valve and isthmal coarctation with aortopathy; genetically determined, such as Marfan and William syndromes; degenerative diseases, such as atherosclerosis and medial necrosis with aortic dilatation, valve incompetence and dissecting aneurysm; inflammatory diseases such as Takayasu arteritis, syphilis, giant cell and IgM4 aortitis; neoplasms; and trauma. Aortic homografts from cadavers, including both the sinus portion with semilunar cusps and the tubular portion, are surgically employed to replace a native sick ascending aorta. However, the antigenicity of allograft cells, in the lamellar units and interstitial cells in the cusps, is maintained. Thus, an immune reaction may occur, limiting durability. After proper decellularization and 6 months’ implantation in sheep, endogenous cell repopulation was shown to occur in both the valve and aortic wall, including the endothelium, without evidence of inflammation and structural deterioration/calcification in the mid-term. The allograft was transformed into an autograft.

Age-Related Changes in the Canine Aorta

Degenerative changes in the aorta are commonly observed in both dogs and humans, and those changes that occur with age morphologically overlap with those observed in genetic or degenerative diseases. Therefore, recognition of age-related aortic changes is important for diagnosticians, as such histologic findings should be distinguished from lesions of specific diseases. The aortas from 37 dogs without clinical cardiovascular disease ranging in age from 2 months to 15 years were divided into 3 cohorts to assess age-relatedness, and evaluated histologically using standardized nomenclature and diagnostic criteria adapted and modified from the human literature. We found that the histopathologic severity scores for intimal thickening, translamellar medial fibrosis, loss of smooth muscle cell nuclei, and medial microcalcification were higher in older dogs, whereas the scores for both intralamellar and translamellar mucoid extracellular matrix accumulation (“cystic medial necrosis”) were not different among age groups. Dogs with translamellar medial fibrosis and aortic medial microcalcification were significantly older compared with dogs without these findings, while the presence of aortic medial chondro-osseous metaplasia was not related to age. Taken together, we demonstrate a range of age-related aortic histologic changes in dogs without clinical cardiovascular disease and suggest that integration of signalment and clinical data can aid in the differentiation of such findings from non-age-related disease processes.

Balloon Angioplasty of Infrapopliteal Arteries: A Systematic Review and Proposed Algorithm for Optimal Endovascular Therapy

Endovascular revascularization has been increasingly utilized to treat patients with chronic limb-threatening ischemia (CLTI), particularly atherosclerotic disease in the infrapopliteal arteries. Lesions of the infrapopliteal arteries are the result of 2 different etiologies: medial calcification and intimal atheromatous plaque. Although several devices are available for endovascular treatment of infrapopliteal lesions, balloon angioplasty still comprises the mainstay of therapy due to a lack of purpose-built devices. The mechanism of balloon angioplasty consists of adventitial stretching, medial necrosis, and dissection or plaque fracture. In many cases, the diffuse nature of infrapopliteal disease and plaque complexity may lead to dissection, recoil, and early restenosis. Optimal balloon angioplasty requires careful attention to assessment of vessel calcification, appropriate vessel sizing, and the use of long balloons with prolonged inflation times, as outlined in a treatment algorithm based on this systematic review. Further development of specific devices for this arterial segment are warranted, including devices for preventing recoil (eg, dedicated atherectomy devices), treating dissections (eg, tacks, stents), and preventing neointimal hyperplasia (eg, novel drug delivery techniques and drug-eluting stents). Further understanding of infrapopliteal disease, along with the development of new technologies, will help optimize the durability of endovascular interventions and ultimately improve the limb-related outcomes of patients with CLTI.

Endovascular Embolization of a Dissected External Carotid Artery Pseudoaneurysm in a Young Female with Neurofibromatosis Complicated by Preeclampsia

Carotid artery pseudoaneurysms are infrequently encountered in clinical practice. Major contributory etiologies include blunt trauma, infections, cystic medial necrosis, fibromuscular dysplasia, arteriosclerosis, and congenital abnormalities. The authors report an exceedingly rare case of a dissected external carotid artery pseudoaneurysm in a 26-year-old female patient with neurofibromatosis complicated by preeclampsia at 28-week period of gestation, safely and successfully treated by coil embolization.

Genetic testing for bicuspid aortic valve

Bicuspid aortic valve (BAV) is a congenital defect in which the aortic valve has two rather than three leaflets. In many patients valve function may be normal but valve decompensation may occur due to other associated congenital abnormalities and secondary valve and aortic complications. Decompensation manifests as stenosis or regurgitation and thoracic aortic aneurysm and dissection. Cystic medial necrosis plays an important role in the pathogenesis of BAV. Prevalence of BAV is estimated at 0.5-2.0%. In children, 70-85% of stenotic aortic valves are bicuspid, compared to at least 50% in adults. BAV has autosomal dominant inheritance. This Utility Gene Test was developed on the basis of an analysis of the literature and existing diagnostic protocols. It is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials.

Genetic diseases of the aorta: aortic diseases associated with bicuspid aortic valves

There is a genetic cause of bicuspid aortic valve. Dilatation of the aortic root and ascending aorta has long been considered genetically determined too and treated accordingly. In recent years, basic research combined with advanced cardiac imaging has made a strong case for another cause of this dilatation: an altered flow profile in the ascending aorta due to the abnormal geometry of the bicuspid valve, leading to an area of altered wall shear stress, which in turn leads to remodelling of the aortic wall, with apoptosis of vascular smooth muscle cells and disruption of media layer as a result. These histological changes, previously referred to as cystic medial necrosis, form the basis of a loss of structural integrity of the aortic wall, which makes it prone to dilatation, dissection, and rupture.