A case of unilateral vascular hypoplasia is presented. A female patient was born with a complex aortic archanatomy - a double aortic arch with an interrupted left arch. Surgical correction was... Show moreA case of unilateral vascular hypoplasia is presented. A female patient was born with a complex aortic archanatomy - a double aortic arch with an interrupted left arch. Surgical correction was performed at the age of 3 months. The patient was also noted to have had an ipsilateral large infantile haemangioma. These findings raised the suspicion of the diagnosis of PHACE syndrome. PHACE syndrome is an acronym for Posterior fossa abnormalities, Haemangioma, Arterial anomalies, Cardiac anomalies and Eye anomalies. Future research is needed to elucidate the underlying pathophysiology in PHACE syndrome. Show less
A case of unilateral vascular hypoplasia is presented. A female patient was born with a complex aortic archanatomy - a double aortic arch with an interrupted left arch. Surgical correction was... Show moreA case of unilateral vascular hypoplasia is presented. A female patient was born with a complex aortic archanatomy - a double aortic arch with an interrupted left arch. Surgical correction was performed at the age of 3 months. The patient was also noted to have had an ipsilateral large infantile haemangioma. These findings raised the suspicion of the diagnosis of PHACE syndrome. PHACE syndrome is an acronym for Posterior fossa abnormalities, Haemangioma, Arterial anomalies, Cardiac anomalies and Eye anomalies. Future research is needed to elucidate the underlying pathophysiology in PHACE syndrome. Show less
BackgroundPatients with a bicuspid aortic valve (BAV) have an increased risk to develop aortic complications. Many studies are pointing towards a possible embryonic explanation for the development... Show moreBackgroundPatients with a bicuspid aortic valve (BAV) have an increased risk to develop aortic complications. Many studies are pointing towards a possible embryonic explanation for the development of both a bicuspid aortic valve as well as a defective ascending aortic wall in these patients. The fetal and newborn ascending aortic wall has however scarcely been studied in bicuspid aortic valve patients. We hypothesize that early histopathological defects might already be visible in the fetal and pediatric ascending aortic wall of bicuspid aortic valve patients, indicating at an early embryonic defect.MethodsNon-dilated BAV ascending aortic wall samples were collected (n = 40), categorized in five age groups: premature (age range 17.5 weeks + days GA till 37.6 weeks + days GA) 2. neonate (age range 1 – 21 days) 3. infant (age range 1 month – 4 years) 4. adolescent (age range 12 years – 15 years) and 5. adult (age range 41 – 72 years). Specimen were studied for intimal and medial histopathological features.ResultsThe premature ascending aortic wall has a significantly thicker intimal and significantly thinner medial layer as compared to all other age categories (p < 0.05). After birth the intimal thickness decreases significantly. The medial layer increases in thickness before adulthood (p < 0.05) with an increasing number of elastic lamellae (p < 0.01) and interlamellar mucoid extracellular matrix accumulation (p < 0.0001). Intimal atherosclerosis was scarce and medial histopathological features such as overall medial degeneration, smooth muscle cell nuclei loss and elastic fiber fragmentation were not appreciated in the BAV ascending aortic wall of any age.ConclusionsThe main characteristics of a bicuspid ascending aortic wall are already present before adulthood, albeit not before birth. Considering the early manifestations of ascending aortic wall pathology in bicuspid aortic valve patients, the pediatric population should be considered while searching for markers predictive for future aortopathy. Show less
A bicuspid aortic valve (BAV) is the most prevalent congenital cardiac deformity, which is associated with an increased risk to develop a thoracic aortic aneurysm and/or an aortic dissection as... Show moreA bicuspid aortic valve (BAV) is the most prevalent congenital cardiac deformity, which is associated with an increased risk to develop a thoracic aortic aneurysm and/or an aortic dissection as compared to persons with a tricuspid aortic valve. Due to the high prevalence of a BAV in the general population and the associated life-long increased risk for adverse vascular events, BAV disease places a considerable burden on the public health. The aim of the present review is to discuss the role of transforming growth factor beta (TGF-ss) signaling in the development of the vascular wall and on how this complex signaling pathway may be involved in thoracic aortic aneurysm formation in tricuspid and BAV patients. 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
This thesis is separated in two parts (Part I and Part II) in which normal and abnormal heart development are studied and related to congenital heart disease, in particular to the etiology of... Show moreThis thesis is separated in two parts (Part I and Part II) in which normal and abnormal heart development are studied and related to congenital heart disease, in particular to the etiology of supraventricular arrhythmias in fetuses and neonates. Part I describes the development of the posterior heart field derived venous pole of the heart specifically in correlation to the role of Shox2 and podoplanin in that particular area. Furthermore, the developmental processes in this region seem to have an important role in the anlage of the cardiac conduction system and epicardial lineage development of the heart. In the second part of this thesis (Part II) the aetiology of a specific subtype of supraventricular tachycardias i.e. atrioventricular reentry tachycardias (AVRTs) are related to normal heart development in human and mouse. AVRTs are one of the most common types of tachyarrhythmias at the perinatal period of development. We demonstrate that perinatal AVRTs might be related to incomplete formation of the isolating annulus fibrosus resulting in the temporary persistence of accessory myocardial connections between the atria and ventricles. We furthermore, demonstrate the late outcome of fetal brady- and tachyarrhythmia cases. Show less
