scholarly journals Disturbed nitric oxide signalling gives rise to congenital bicuspid aortic valve and aortopathy

2020 ◽  
Vol 13 (9) ◽  
pp. dmm044990
Author(s):  
Joshua C. Peterson ◽  
Lambertus J. Wisse ◽  
Valerie Wirokromo ◽  
Tessa van Herwaarden ◽  
Anke M. Smits ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Aortic Valve ◽  
Bicuspid Aortic Valve ◽  
Neural Crest Cell ◽  
Ascending Aorta ◽  
Aortic Aneurysms ◽  
Aortic Dilation ◽  
Elastic Fibres ◽  
Increased Risk

ABSTRACTPatients with a congenital bicuspid aortic valve (BAV), a valve with two instead of three aortic leaflets, have an increased risk of developing thoracic aneurysms and aortic dissection. The mechanisms underlying BAV-associated aortopathy are poorly understood. This study examined BAV-associated aortopathy in Nos3−/− mice, a model with congenital BAV formation. A combination of histological examination and in vivo ultrasound imaging was used to investigate aortic dilation and dissections in Nos3−/− mice. Moreover, cell lineage analysis and single-cell RNA sequencing were used to observe the molecular anomalies within vascular smooth muscle cells (VSMCs) of Nos3−/− mice. Spontaneous aortic dissections were found in ascending aortas located at the sinotubular junction in ∼13% of Nos3−/− mice. Moreover, Nos3−/− mice were prone to developing aortic dilations in the proximal and distal ascending aorta during early adulthood. Lower volumes of elastic fibres were found within vessel walls of the ascending aortas of Nos3−/− mice, as well as incomplete coverage of the aortic inner media by neural crest cell (NCC)-derived VSMCs. VSMCs of Nos3−/− mice showed downregulation of 15 genes, of which seven were associated with aortic aneurysms and dissections in the human population. Elastin mRNA was most markedly downregulated, followed by fibulin-5 expression, both primary components of elastic fibres. This study demonstrates that, in addition to congenital BAV formation, disrupted endothelial-mediated nitric oxide (NO) signalling in Nos3−/− mice also causes aortic dilation and dissection, as a consequence of inhibited elastic fibre formation in VSMCs within the ascending aorta.

scholarly journals Fate of mild-to-moderate bicuspid aortic valve disease untreated during ascending aorta replacement

2020 ◽  
Author(s):  
Alessandro Verzini ◽  
Marta Bargagna ◽  
Guido Ascione ◽  
Alessandra Sala ◽  
Davide Carino ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Bicuspid Aortic Valve ◽  
Ascending Aorta ◽  
Term Survival ◽  
Kaplan Meier ◽  
Aortic Root Surgery ◽  
Increased Risk ◽  
Aorta Replacement ◽  
Ascending Aorta Replacement

Background: Bicuspid aortic valve (BAV) is the most common congenital heart defect and it is responsible for an increased risk of developing aortic valve and ascending aorta complications. In case of mild to moderate BAV disease in patients undergoing supracoronary ascending aorta replacement, it is unclear whether a concomitant aortic valve replacement should be performed. Methods: From June 2002 to January 2020, 75 patients with mild-to-moderate BAV regurgitation (± mild-to-moderate stenosis) who underwent isolated supracoronary ascending aorta replacement were retrospectively analyze. Clinical and echocardiographic follow-up was 100% complete (mean: 7.4±3.9 years, max 16.4). Kaplan Meier estimates were employed to analyze long-term survival. Cumulative incidence function for time to re-operation, recurrence of aortic regurgitation (AR)≥3+ and aortic stenosis (AS) greater than moderate, with death as competing risk, were computed. Results: There was no hospital mortality and no cardiac death occurred. Overall survival at 12 years was 97.4±2.5%, 95% CI [83.16-99.63]. At follow-up there were no cases of aortic root surgery whereas 3 patients underwent AV replacement. At 12 years the CIF of reoperation was 2.6±2.5%, 95% CI [0.20-11.53]. At follow up, AR 3+/4+ was present in 1 pt and AS greater than moderate in 3. At 12 years the CIF of AR>2+/4+ was 5.1±4.98% and of AS>moderate 6.9±3.8%. Conclusions: In our study mild to moderate regurgitation of a BAV did not significantly worse at least up to 10 years after isolated supracoronary ascending aorta replacement.

scholarly journals The Development of the Ascending Aortic Wall in Tricuspid and Bicuspid Aortic Valve: A Process from Maturation to Degeneration

2020 ◽  
Vol 9 (4) ◽  
pp. 908
Author(s):  
Nimrat Grewal ◽  
Adriana C. Gittenberger-de Groot ◽  
Jan von der Thusen ◽  
Lambertus J. Wisse ◽  
Margot M. Bartelings ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Young Child ◽  
Bicuspid Aortic Valve ◽  
Aortic Wall ◽  
Age Groups ◽  
Intimal Thickening ◽  
Aortic Dilation ◽  
Future Studies ◽  
Increased Risk ◽  
Two Phases

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 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.

scholarly journals Low and Oscillatory Wall Shear Stress Is Not Related to Aortic Dilation in Patients With Bicuspid Aortic Valve

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Lydia Dux-Santoy ◽  
Andrea Guala ◽  
Julio Sotelo ◽  
Sergio Uribe ◽  
Gisela Teixidó-Turà ◽  
...  
Keyword(s):  
Shear Stress ◽  
Aortic Valve ◽  
Wall Shear Stress ◽  
Healthy Volunteers ◽  
Aortic Arch ◽  
Bicuspid Aortic Valve ◽  
Ascending Aorta ◽  
Oscillatory Shear ◽  
Aortic Dilation ◽  
Wall Shear

Objective: To assess the relationship between regional wall shear stress (WSS) and oscillatory shear index (OSI) and aortic dilation in patients with bicuspid aortic valve (BAV). Approach and Results: Forty-six consecutive patients with BAV (63% with right-left-coronary-cusp fusion, aortic diameter ≤ 45 mm and no severe valvular disease) and 44 healthy volunteers were studied by time-resolved 3-dimensional phase-contrast magnetic resonance imaging. WSS and OSI were quantified at different levels of the ascending aorta and the aortic arch, and regional WSS and OSI maps were obtained. Seventy percent of BAV had ascending aorta dilation. Compared with healthy volunteers, patients with BAV had increased WSS and decreased OSI in most of the ascending aorta and the aortic arch. In both BAV and healthy volunteers, regions of high WSS matched regions of low OSI and vice versa. No regions of both low WSS and high OSI were identified in BAV compared with healthy volunteers. Patients with BAV with dilated compared with nondilated aorta presented low and oscillatory WSS in the aortic arch, but not in the ascending aorta where dilation is more prevalent. Furthermore, no regions of concomitant low WSS and high OSI were identified when BAV were compared according to leaflet fusion pattern, despite the well-known differences in regional dilation prevalence. Conclusions: Regions with low WSS and high OSI do not match those with the highest prevalence of dilation in patients with BAV, thus providing no evidence to support the low and oscillatory shear stress theory in the pathogenesis of proximal aorta dilation in the presence of BAV.

Ascending aorta mechanics in bicuspid aortopathy: controversy or fact?

2020 ◽  
pp. 021849232092873
Author(s):  
Dimitrios C Iliopoulos ◽  
Dimitrios P Sokolis
Keyword(s):  
Mechanical Properties ◽  
Aortic Valve ◽  
Bicuspid Aortic Valve ◽  
Ascending Aorta ◽  
Aortic Aneurysms ◽  
Aortic Dilatation ◽  
Aged Patients ◽  
Thoracic Aortic Aneurysms ◽  
Maximal Diameter ◽  
Sole Criterion

Bicuspid aortic valve is the most common congenital cardiovascular defect, often associated with proximal aortic dilatation, and the ideal management strategy is debated. The inconsistency in previous and present guideline recommendations emphasizes the insufficiency of the maximal diameter as the sole criterion for prophylactic repair. Our ability to guide clinical decisions may improve through an understanding of the mechanical properties of ascending thoracic aortic aneurysms in bicuspid compared to tricuspid aortic valve patients and non-aneurysmal aortas, because dissection and rupture are aortic wall mechanical failures. Such an understanding of the mechanical properties has been attempted by several authors, and this article addresses whether there is a controversy in the accumulated knowledge. The available mechanical studies are briefly reviewed, discussing factors such as age, sex, and the region of mechanical examination that may be responsible for the lack of unanimity in the reported findings. The rationale for acquiring layer-specific properties is presented along with the main results from our recent study. No mechanical vulnerability of ascending thoracic aortic aneurysms was evidenced in bicuspid aortic valve patients, corroborating present conservative guidelines concerning the management of bicuspid aortopathy. Weakening and additional vulnerability was evidenced in aged patients and those with coexisting valve pathology, aortic root dilatation, hypertension, and hyperlipidemia. Discussion of these results from age- and sex-matched subjects, accounting for the region- and layer-specific aortic heterogeneity, in relation to intact wall results and histologic confirmation, helps to reconcile previous findings and affords a universal interpretation of ascending aorta mechanics in bicuspid aortopathy.

scholarly journals Pregnancy in women with bicuspid aortic valve

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
S Belkadi ◽  
O Milleron ◽  
L Eliahou ◽  
F Arnoult ◽  
G Delorme ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Dissection ◽  
Bicuspid Aortic Valve ◽  
Ascending Aorta ◽  
Aortic Diameter ◽  
Z Score ◽  
Aortic Dilation ◽  
Genetic Syndrome ◽  
Pregnancy And Postpartum ◽  
Ascending Aortic Diameter

Abstract Background Aortic dissection during pregnancy is uncommon, however, the risk of aortic dissection is increased if there is underlying aortopathy. Bicuspid aortic valve (BAV) is common in the general population and is associated with the presence of an aortic aneurysm, but this condition is mostly asymptomatic and ignored in women of childbearing age. Data on pregnancy in patients with BAV are scarce, and guidelines on this topic are based on the consensus opinion of experts. The risk of occurrence of aortic dissection as a function of aortic diameter during pregnancy remains poorly known in women with BAV. Purpose To investigate demographic and echocardiographic characteristics and aortic events associated with pregnancy in women with BAV and to estimate ascending aortic diameter at the time of pregnancy. Methods We performed a retrospective study using data from our tertiary centre. All women seen at our centre between 1996 and 2020 with BAV, at least 1 pregnancy, and no genetic syndrome were included. We have collected data from echocardiograms performed in and out of our centre and aortic events. Assuming from the literature an annual aortic dilation rate of 0.2 mm at the sinus of Valsalva and 0.4 mm at the tubular ascending aorta, we estimated ascending aortic size and Z-score at the time of pregnancy. Results We identified 47 women with BAV with occurrence of 103 pregnancies. The median age of BAV diagnosis was 43 years. The aorta was measured at a median of 13.3 years since the last delivery. At BAV diagnosis, the median largest ascending aortic diameter was 44mm, and the median Z-score was +4.3. Ascending aortic diameter was ≥40mm in 37/47 (79%) and Z-score ≥2 in 44/47 (94%). No aortic dissection was observed during pregnancy and postpartum in all 103 pregnancies. At the time of pregnancy, the estimated median diameter of the ascending aorta was 37mm and the estimated median Z-score was +3.3. The largest aortic diameter during pregnancy was estimated to be ≥40mm in 36/103 pregnancies, ≥45mm in 13/103, and ≥50mm in 1/103; Z-score was estimated to be ≥2 in 81/103 and ≥4 in 40/103. Type A aortic dissection occurred in 1 woman, 13 years after pregnancy, and type B aortic dissection in 1 woman, 14 years after pregnancy. Planned surgery was performed in 8 women at a median of 17.5 years after the last pregnancy: 1 isolated aortic valve replacement and 7 prophylactic aortic surgeries associated with aortic valve surgery. Conclusions In our population of women with BAV, pregnancy is not associated with the occurrence of aortic dissection even though, when estimating aortic diameter at the time of pregnancy, the rate of aortic dilation was high (Z-score ≥2 in 81/103 pregnancies). Prospective studies of a large population of women with BAV are needed to assess the risk of aortic complication during pregnancy according to aortic diameter. FUNDunding Acknowledgement Type of funding sources: None.

scholarly journals Hemodynamic Environment Characteristics in the Ascending Aorta After Dilation Formed for the Bicuspid Aortic Valve Patients

2020 ◽  
Author(s):  
Tie Zheng ◽  
Shuai Zhu ◽  
Shijie Lu ◽  
Jiafu Ou ◽  
Jun-Ming Zhu
Keyword(s):  
Aortic Valve ◽  
Bicuspid Aortic Valve ◽  
Numerical Models ◽  
Flow Patterns ◽  
Ascending Aorta ◽  
Aortic Dilatation ◽  
Aortic Dilation ◽  
Distribution Features ◽  
Ascending Aortic Diameter ◽  
Asymmetrically Distributed

Abstract Background: The bicuspid aortic valve is one of the common congenital heart anomalies in adults. Although many studies have proved the coincidence between bicuspid aortic valve and the occurrence of ascending aortic dilation, seldom study has focused on the hemodynamic environments after the dilation already formed. Four numerical models of bicuspid aortic valve were constructed in this study, based on medical images, with different ascending aortic dilation levels. The diameters of ascending aortic are 3.5cm, 4.0cm, 4.5cm and 5.0cm, respectively; while, the size and the geometry of other parts are fixed. Then hemodynamics in these models was simulated numerically and the flow patterns and loading distributions were investigated. Aim of this study is to investigate the hemodynamic environment characteristics in the ascending aorta after dilation formed for the bicuspid aortic valve (BAV) patients. Results: Hemodynamics environments in the dilated ascending aorta were simulated, with different level of dilation. As the diameter increases, the blood flow becomes more disturbing. The wall shear stress at the ascending aortic decreases while oscillatory shear index increases with the increase of diameter. The pressure at ascending aortic increases as the diameter increases. Moreover, all these hemodynamic parameters described above are asymmetrically distributed with the increase of ascending aortic diameter and more parts of aorta would be affected with the increasing ascending aorta diametersConclusions: The study revealed that the ascending aortic dilation levels can significantly influence the magnificent and distribution of the dynamics. There are altered flow patterns, pressure difference, WSS and OSI distribution features in bicuspid aortic valve patients with valvular dilation. As the extent of aortic dilatation increases, more parts of aorta like aortic arch should be paid more attention to when an individual is referred for surgery

scholarly journals Plasma Metabolomic Profiling Associates Bicuspid Aortic Valve Disease and Ascending Aortic Dilation with a Decrease in Antioxidant Capacity

2020 ◽  
Vol 9 (7) ◽  
pp. 2215
Author(s):  
Neus Martínez-Micaelo ◽  
Carme Ligero ◽  
Borja Antequera-González ◽  
Alexandra Junza ◽  
Oscar Yanes ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Antioxidant Capacity ◽  
Bicuspid Aortic Valve ◽  
Plasma Levels ◽  
Density Lipoprotein ◽  
Endothelial Damage ◽  
Alpha Tocopherol ◽  
Paraoxonase 1 ◽  
Aortic Dilation ◽  
Increased Risk

Background: The bicuspid aortic valve (BAV) is the most common cardiac congenital disease and is associated with an increased risk of developing ascending aorta dilation; which can have fatal consequences. Currently; no established risk biomarkers exist to facilitate the diagnosis and prognosis of BAV. Methods: Using an untargeted metabolomic approach; we identified the levels of metabolites in plasma samples and compared them depending on the bicuspid or tricuspid morphology of the aortic valve. Including those patients with ascending aortic dilation and/or aortic stenosis (n = 212), we analyzed the role possibly played by alpha-Tocopherol in BAV disease; considering its association with the pathophysiological characteristics of BAV and biomarkers related to inflammation, oxidative stress and endothelial damage, as well as characteristics related to alpha-Tocopherol functionality and metabolism. Results: We found that BAV patients; especially those with ascending aortic dilation; presented lower antioxidant capacity; as determined by decreased plasma levels of alpha-Tocopherol; paraoxonase 1 and high-density lipoprotein (HDL), as well as increased levels of C-reactive protein (CRP; a biomarker of inflammation) and endothelial microparticles (EMPs; an endothelial damage biomarker). By applying random forest analyses; we evaluated the significant screening capacity of alpha-Tocopherol; CRP and EMPs to classify patients depending on the morphology of the aortic valve. Discussion: Our findings support the role of decreased antioxidant capacity; increased inflammation and endothelial damage in the pathogenesis of BAV and the progression of aortic dilation. Moreover; determining the plasma levels of alpha-Tocopherol; CRP and EMPs could improve BAV diagnosis in large populations.

P3373Predictors of dilatation of ascending aorta in patients with bicuspid aortic valve, a longitudinal multicenter study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
I Dentamaro ◽  
A Sao-Aviles ◽  
G Teixido ◽  
L Galian ◽  
L Gutierrez ◽  
...  
Keyword(s):  
Risk Factors ◽  
Aortic Valve ◽  
Aortic Stenosis ◽  
Bicuspid Aortic Valve ◽  
Multicenter Study ◽  
Aortic Root ◽  
Ascending Aorta ◽  
Annual Growth ◽  
Aortic Dilation ◽  
Male Sex

Abstract Introduction The bicuspid aortic valve (BAV) is frequently associated to dilation of the ascending aorta. Some cross-sectional studies have related the aortic dilation with morphotype and valvular dysfunction. The aim of this longitudinal multicenter study was to analyze the progression of the aortic dilation and to identify its predictors. Methods We included 459 patients (mean age 52±17; 325 men 70.8%) with BAV, without aortic coarctation. The BAV morphotype, significant valvular dysfunction and dilation of the aortic root and ascending aorta were established by echocardiography. The patients were followed annually, with an average of 7.5±3.2 years. Results 77% of the patients had BAV with a fusion between left and right cusps, 21% between right and non coronary cusps and 2% between left and non coronary cusps, with a raphe in 77% of these patients. Risk factors included: 35% hypertension, 20% smoking, 5% diabetes and 18% dyslipidemia. The baseline study showed a maximum root diameter of 36±6.2 mm and ascending aorta of 39±8.1 mm. In 7% the aortic root was>45 mm, while in 32% the ascending aorta>45 mm. There was no valvular dysfunction in 17% of patients, while the 8% had significant aortic stenosis and 35% significant aortic regurgitation. The annual growth of the aortic root was 0.33±0.2 mm and for the ascending aorta was 0.38±0.3 mm. At the end of follow-up, 16% of the patients had a root>45 mm and 41% an ascending aorta>45 mm. The annual progression of aortic diameters was not related to valvular morphotype, valvular dysfunction or cardiovascular risk factors. The univariate analysis showed a significant relationship between the annual growth of the aortic root and arterial hypertension (p=0.028) and the annual growth of the ascending aorta with the male sex (p=0.019), smoking (p=0.046) and significant (moderate or severe) aortic stenosis (p=0.013). Diabetes mellitus and the presence of raphe were found to be slightly protective (p=0.049 and p=0.031, respectively). In the multivariate analysis, only the male sex and significant aortic stenosis were independent predictors of dilation of the ascending aorta. Conclusions In patients with bicuspid aortic valve, the progression of the dilation of the aortic root is related to hypertension and the growth of the ascending aorta with the male sex and the presence of significant aortic stenosis. Both bicuspid valve morphotype, basal aortic diameter or age were not related to the progression of aortic dilation.

scholarly journals The Role of Bicuspid Aortic Valve in Aortic Aneurysm Occurrence and Development

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Vitaliy Kravchenko ◽  
Ivan Kravchenko ◽  
Olha Pantas ◽  
Valentyna Zakharova
Keyword(s):  
Surgical Treatment ◽  
Aortic Valve ◽  
Aortic Aneurysm ◽  
Aortic Arch ◽  
Histological Examination ◽  
Bicuspid Aortic Valve ◽  
Ascending Aorta ◽  
Aortic Aneurysms ◽  
Ascending Aortic Aneurysm

The paper presents the data on the diagnosis of bicuspid aortic valve (BAV) disease in the patients operated for ascending aortic (AA) aneurysm. A brief historical review of the study of the BAV problem is presented; the data on the BAV incidence in the development of ascending aortic aneurysm and its dissection, the results of surgical treatment of BAV disease in patients with AA aneurysm are displayed. The objective of the research was to study the role of the bicuspid aortic valve in the occurrence (dissection) of ascending aortic aneurysms. Materials and methods The retrospective analysis of the patients operated at the institute during the period of 1.01.2013 to 1.01.2019 for ascending aortic aneurysm or aneurysms of both ascending aorta and aortic arch confirmed that aneurysm occurrence (dissection) was caused by the presence of bicuspid valve. During this time, 1120 patients were operated on for ascending aortic aneurysm or aneurysms of both ascending aorta and aortic arch. 340 (30.4%) patients with diagnosed and confirmed BAV disease were included in the analysis. BAV diagnosis was based on echocardiography with obligatory intraoperative confirmation and on the basis of histological examination. Histological examination of the fragments of the aortic wall and aortic valve taken during operations was performed in 68 (20.0%) patients. Results and discussion BAV is the most common of all cardiac failures with a prevalence of up to 2% in the population constituting up to 30-50% of cases among the patients with aortal disorders. Two-dimensional echocardiography gives better results and provides an opportunity to detect BAV in 95% of cases, which was confirmed by our studies. According to our research, cases with BAV included 30.4% of all possible aneurysm causes, and BAV as a cause of dissection was noted in 46 (13.5%) of all dissecting aneurysms. Regarding the results of the surgical treatment, 2 patients out of 340 operated at the hospital stage died constituting 0.6%. Conclusions Among all ascending aortic aneurysms or aneurysms of both ascending aorta and aortic arch, BAV was determined as their cause in 30.4% of cases. Dissection (rupture) of the aortic aneurysm occurred in 13.5% of patients with aneurysm and bicuspid valve and thus required an urgent surgery.  Patients with BAV require lifelong care.

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