Patients with a bicuspid aortic valve have an extreme high risk to develop a thoracic aortic aneurysm and dissection (TAAD). TAADs form a leading cause of death worldwide, with the majority of... Show morePatients with a bicuspid aortic valve have an extreme high risk to develop a thoracic aortic aneurysm and dissection (TAAD). TAADs form a leading cause of death worldwide, with the majority of deaths be-ing preventable if individuals at risk are identified and properly managed. Risk stratification for TAADs in bicuspidy is so far solely based on the aortic diameter. Exclusive use of aortic wall dimension, as in the current guidelines, is however not sufficient in selecting patients vulnerable for future aortic wall complications. Moreover, there are no effective medical treatments for TAADs to retain progressive aortic dilatation and thus prevent or delay aortic complications. Only surgical replacement of the aorta increases life expectancy in patients with a risk for a TAAD. Therefore, the next major challenge in the manage-ment of TAADs is the development of a personalized patient-tailored risk stratification for early detection of patients with an increased risk for TAADs, who will benefit from surgical resection of the aorta. Sev-eral signaling pathways have been studied in recent times to develop a patient specific risk stratification model. In this paper we discuss TGF-,B signaling and downstream signalers as potential markers for fu-ture aortic complications in bicuspid aortic valve patients.(c) 2022 Elsevier Inc. All rights reserved. Show less
Background: A bicuspid aortic valve (BAV) is the most common congenital cardiac malformation. The development of the aortic valve is closely related to the development of the ascending aorta,... Show moreBackground: A bicuspid aortic valve (BAV) is the most common congenital cardiac malformation. The development of the aortic valve is closely related to the development of the ascending aorta, associated with structural differences in the bicuspid aorta. Here we describe the non-dilated ascending aortic wall in bicuspid aortic valve patients. Methods: BAV (n = 41) and tricuspid aortic valve (TAV) (n = 18) non-dilated ascending aortic wall samples were studied. We investigated the following features of the aortic wall: vessel wall thickness, endothelial cell morphology, atherosclerosis, and elastic lamellae organization. Medial pathologic features encompass-ing elastic fiber thinning, fragmentation and degeneration, overall medial degeneration, mucoid extracel-lular matrix accumulation, and smooth muscle cell nuclei loss were studied. Furthermore, we included apoptosis, periaortic inflammation, and the level of expression of differentiated vascular smooth muscle cells. Results: The non-dilated BAV ascending aortic wall is characterized by a significantly thinner intimal layer, without features of atherosclerosis ( P < .001). The medial layer is significantly thicker ( P < .001) with more mucoid extracellular matrix accumulation ( P < .001). All other medial pathologic features were more prominent in the TAV ( P < .001). The media has significantly less differentiated vascular smooth muscle cells ( P < .001) between the neatly regulated elastic lamellae which are thinner in the BAV as compared to the TAV ( P < .0 0 01). Conclusions: The BAV ascending aorta without dilatation is characterized by a differentiation def ect of vascular smooth muscle cells in the media and a significantly thinner intimal layer without overt patho-logic features.(c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ) Show less
Grewal, N.; Girdauskas, E.; DeRuiter, M.; Goumans, M.J.; Poelmann, R.E.; Klautz, R.J.M.; Gittenberger-de Groot, A.C. 2019
Background: A bicuspid aortic valve (BAV) is the most common congenital cardiac malformation and is associated with ascending aortic dilation in 60%-80% of patients. In this study, we aimed to... Show moreBackground: A bicuspid aortic valve (BAV) is the most common congenital cardiac malformation and is associated with ascending aortic dilation in 60%-80% of patients. In this study, we aimed to address the role of hemodynamic influences on the development of aortopathy in BAV patients.Patient and methods: BAV (n=36) and tricuspid aortic valve (TAV) patients (n=17) undergoing aortic valve replacement underwent preoperative flow magnetic resonance imaging (MRI) assessment to detect the area of maximal flow-induced stress in the proximal aorta. Based on these MRI data, paired ascending aortic wall samples [i.e., area of maximal jet impact (jet sample) and the opposite aortic wall (nonjet sample)] were collected during surgery. To study and describe the effects of jet stream on the complete vascular wall, a pathology score was developed based on the recently published aortic consensus paper statement on surgical pathology of the aorta using routine histologic stainings (resorcin fuchsin, hematoxylin-eosin, and Movat) and immunohistochemistry (alpha smooth muscle actin, smooth muscle 22 alpha, platelet endothelial cell adhesion molecule).Results: Comparing the jet and nonjet samples in both BAV and TAV, regions of maximal jet impact did not show any difference in the pathology score in the adventitia and the middle and outer media. In the jet samples, the inner media however showed loss of actin expression in both BAV (P<.0001) and the TAV (P=.0074), and the intimal thickness was significantly enlarged in both patient groups (BAV P=.0005, TAV P=.0041), which was not accompanied by loss of elastic lamellae or vascular smooth muscle cell nuclei.Conclusions: In our study population, we could not demonstrate a potential distinct role for hemodynamics in the development of aortopathy in BAV patients even if corrected for aortic diameter, raphe position, or whether the valve is stenotic or regurgitant. The intimal layer and inner media however showed alterations in all jet specimens. (C) 2019 The Authors. Published by Elsevier Inc. Show less
Purpose: Improve mapping and registration of longitudinal view on histopathology vessels in a three-dimensional alignment procedure for postmortem quantitative coronary plaque analyses. This new... Show morePurpose: Improve mapping and registration of longitudinal view on histopathology vessels in a three-dimensional alignment procedure for postmortem quantitative coronary plaque analyses. This new procedure is applied and results shown using calcified coronary plaque analyses within post-mortem computed tomography angiography (PMCTA), optical coherence tomography (OCT) and the gold standard of histopathology.Results: In total, 338 annotated histopathology images were included, 166 PMCTA transversal images and 285 OCT images were aligned in the comparison. The results from the comparison using the alignment procedure showed overall that the calcified plaques seem to be overestimated by PMCTA and underestimated by OCT.Conclusions: The 3D fusion approach, aligning the images of PMCTA, OCT and histopathology as gold standard allowed for a slice-based comparison of the different modalities. The results showed that PMCTA overestimates the calcified plaques while OCT underestimates these, compared to histopathology. (C) 2018 Elsevier Inc. All rights reserved. Show less
