Objective Bicuspid aortic valve (BAV) has been associated with less atherosclerosis as compared with tricuspid aortic valve (TAV) patients. It, however, remains unclear whether this reflects the... Show moreObjective Bicuspid aortic valve (BAV) has been associated with less atherosclerosis as compared with tricuspid aortic valve (TAV) patients. It, however, remains unclear whether this reflects the older age of TAV patients and/or accumulation of atherosclerotic risk factors or that the BAV phenotype is atheroprotective. Therefore, we compared the atherosclerotic disease burden of BAV and TAV patients, with that of the general (age-matched) population.Methods The prevalence of coronary artery disease (CAD) and CAD risk factors in BAV and TAV patients who underwent aortic valve surgery were compared with the Dutch general practitioners registry data. BAV (n=454) and TAV (n=1101) patients were divided into four groups: BAV with aortic valve stenosis (BAV-AoS), BAV with aortic valve regurgitation (BAV-AR), TAV with AoS (TAV-AoS) and TAV with AR (TAV-AR). The atherosclerotic disease burden of each group was compared with that of the corresponding age cohort for the general population.Results CAD risk factors hypertension and hypercholesterolaemia were more prevalent in the surgery groups than the age-matched general population (all p<0.001). All BAVs (BAV-AoS and BAV-AR) and TAV-AR had a similar incidence of CAD history as compared to the age-matched general populations (p=0.689, p=0.325 and p=0.617 respectively), whereas TAV-AoS had a higher incidence (21.6% versus 14.9% in the age-matched general population, p<0.001).Conclusions Stenotic TAV disease is part of the atherosclerotic disease spectrum, while regurgitant TAV and all BAVs are not. Although the prevalence of cardiovascular risk factors is higher in all BAV patients, the prevalence of CAD is similar to the general population. Show less
Dolmaci, O.B.; Legue, J.; Lindeman, J.H.N.; Driessen, A.H.G.; Klautz, R.J.M.; Brakel, T.J. van; ... ; Grewal, N. 2021
Background Bicuspid aortic valve (BAV) is the most common congenital cardiac malformation, which is often complicated by aortic valve stenosis (AoS). In tricuspid aortic valve (TAV), AoS strongly... Show moreBackground Bicuspid aortic valve (BAV) is the most common congenital cardiac malformation, which is often complicated by aortic valve stenosis (AoS). In tricuspid aortic valve (TAV), AoS strongly associates with coronary artery disease (CAD) with common pathophysiological factors. Yet, it remains unclear whether AoS in patients with BAV is also associated with CAD. This study investigated the association between the aortic valve morphological features and the extent of CAD.Methods and Results A single-center study was performed, including all patients who underwent an aortic valve replacement attributable to AoS between 2006 and 2019. Coronary sclerosis was graded on preoperative coronary angiographies using the coronary artery greater even than scoring method, which divides the coronaries in 28 segments and scores nonobstructive (20%-49% sclerosis) and obstructive coronary sclerosis (>49% sclerosis) in each segment. Multivariate analyses were performed, controlling for age, sex, and CAD risk factors. A total of 1296 patients (931 TAV and 365 BAV) were included, resulting in 548 matched patients. Patients with TAV exhibited more CAD risk factors (odds ratio [OR], 2.66; 95% CI, 1.79-3.96; P<0.001). Patients with BAV had lower coronary artery greater even than 20 (1.61 +/- 2.35 versus 3.60 +/- 2.79) and coronary artery greater even than 50 (1.24 +/- 2.43 versus 3.37 +/- 3.49) scores (P<0.001), even after correcting for CAD risk factors (P<0.001). Patients with TAV more often needed concomitant coronary revascularization (OR, 3.50; 95% CI, 2.42-5.06; P<0.001).ConclusionsPatients with BAV who are undergoing surgery for AoS carry a lower cardiovascular risk profile, correlating with less coronary sclerosis and a lower incidence of concomitant coronary revascularization compared with patients with TAV. Show less
(1) Background: The pathophysiologic basis of an acute type A aortic dissection (TAAD) is largely unknown. In an effort to evaluate vessel wall defects, we systematically studied aortic specimens... Show more(1) Background: The pathophysiologic basis of an acute type A aortic dissection (TAAD) is largely unknown. In an effort to evaluate vessel wall defects, we systematically studied aortic specimens in TAAD patients. (2) Methods: Ascending aortic wall specimens (n = 58, mean age 63 years) with TAAD were collected. Autopsy tissues (n = 17, mean age 63 years) served as controls. All sections were studied histopathologically. (3) Results: Pathomorphology in TAAD showed predominantly moderate elastic fiber fragmentation/loss, elastic fiber thinning, elastic fiber degeneration, mucoid extracellular matrix accumulation, smooth muscle cell nuclei loss, and overall medial degeneration. The control group showed significantly fewer signs of those histopathological features (none-mild, p = 0.00). It was concluded that the dissection plane consistently coincides with the vasa vasorum network, and that TAAD associates with a significantly thinner intimal layer p = 0.005). (4) Conclusions: On the basis of the systematic evaluation and the consistent presence of diffuse, pre-existing medial defects, we hypothesize that TAAD relates to a developmental defect of the ascending aorta and is caused by a triple-hit mechanism that involves (I) an intimal tear; and (II) a diseased media, which allows (III) propagation of the tear towards the plane of the vasa vasorum where the dissection further progresses. Show less
Grewal, N.; Gittenberger-de Groot, A.C.; Thusen, J. von der; Wisse, L.J.; Bartelings, M.M.; DeRuiter, M.C.; ... ; Poelmann, R.E. 2020
Background: Patients with a bicuspid aortic valve (BAV) have an increased risk for aortic dilation and dissection. In this study, we provide a histological stratification of the developing aorta in... Show moreBackground: Patients with a bicuspid aortic valve (BAV) have an increased risk for aortic dilation and dissection. In this study, we provide a histological stratification of the developing aorta in the tricuspid aortic valve (TAV) and the BAV populations as a reference for future studies on aortopathy and related syndromes. Methods: Non-dilated TAV and BAV ascending aortic wall samples were collected, including 60 TAV (embryonic-70 years) and 32 BAV specimens (fetal-72 years, categorized in eight age groups. Results: In TAV, intimal development starts in the neonatal phase. After birth, the thickness of the medial layer increases significantly by increase of elastic lamellae up to and including the "young child" phase stabilizing afterwards. The BAV shows already prenatal intimal thickening becoming significantly thinner after birth subsequently stabilizing. In BAV, increase in elastic lamellae is seen between the young child and the adolescent phases, stabilizing afterwards. Conclusions: Vascular development in TAV is described in three phases: maturation, stabilization, and degeneration. For BAV, the development can be described in two phases: maturation (already prenatally) and degeneration. After birth, the development of the aorta is characterized by degeneration, leading to weakening of the ascending aortic wall and increasing the risk of aortopathy. Show less
Grewal, N.; Gittenberger-de Groot, A.C.; Thusen, J. von der; Wisse, L.J.; Bartelings, M.M.; DeRuiter, M.C.; ... ; Poelmann, R.E. 2020
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
The prevalence of aortic dilation and related complications as rupture and dissection is higher in patients with a bicuspid aortic valve (BAV) as compared to patients with a tricuspid aortic valve ... Show moreThe prevalence of aortic dilation and related complications as rupture and dissection is higher in patients with a bicuspid aortic valve (BAV) as compared to patients with a tricuspid aortic valve (TAV), although not every individual carries this increased risk. It is therefore essential to identify those patients who are less susceptible for aortic wall pathology, as preventive ascending aortic surgery would not be necessary in this group. Since aortic diameter as a criterion for surgery is only decisive at population level, it would be very valuable to have tailored risk stratification at patient level. The purpose of this thesis was therefore to investigate the possibility to identify patients with BAV, without apparent dilation, with an increased susceptibility for future complications as aortic dilation and dissection. Furthermore the biological mechanism underlying aortic wall pathology in BAV was compared to a known genetically determined syndrome with an increased risk of aortopathy being Marfan syndrome. Show less
