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.

Abstract 15169: De Novo Variants of USP10 in Early Onset Bicuspid Aortic Valve Disease

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Siddharth K Prakash ◽  
Angela T Yetman ◽  
Hector I Michelena ◽  
Malenka M Bissell ◽  
Yuli Y Kim ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Bicuspid Aortic Valve ◽  
Early Onset ◽  
Rare Variants ◽  
De Novo ◽  
Late Onset ◽  
Copy Number Variants ◽  
Aortic Aneurysms ◽  
Thoracic Aortic Aneurysms ◽  
Aortic Dissections

Introduction: Bicuspid Aortic Valve (BAV), the most common congenital heart defect, is a major cause of aortic regurgitation or stenosis requiring valve replacement and thoracic aortic aneurysms predisposing to acute aortic dissections (TAD). The spectrum of BAV ranges from severe early onset valve and aortic complications to sporadic late onset disease. Hypothesis: Early onset BAV (EBAV) cases with valve or aortic complications that require intervention prior to age 30 are enriched for rare genetic variants that cause BAV and TAD. Methods: We performed whole exome sequencing of 147 EBAV cases in 141 families who were enrolled in the UTHealth Bicuspid Aortic Valve Research Registry. Candidate variants in the EBAV cohort (26% female, mean age 18, 44% with TAD) were compared to unselected controls from the Genome Aggregation Database (gnoMAD) and the Database of Genotypes and Phenotypes (dbGAP). We considered variants with minor allele frequencies (MAF) < 1%, Combined Annotation Dependent Depletion (CADD) scores > 25, and damaging (Polyphen-2) or deleterious (SIFT) functional prediction scores. Genomic copy number variants (CNVs) were detected using CoNIFER and prioritized when deletions involved genes with probability of loss intolerance (pLI) > 0.9. Variants were validated using quantitative PCR or Sanger sequencing. Results: We identified 6 rare variants of USP10 in 6 EBAV families (4% of cohort): 4 CNVs (2 duplications and 2 deletions) that are rare in dbGAP controls (4 in 15,414) and 2 deleterious rare missense variants (MAF<5x10 -5 in gnoMAD). Two of the 4 CNVs were de novo events in trios. In contrast, rare deleterious variants of the known causal BAV genes NOTCH1 (1), ROBO4 (1), GATA4 (1), GATA5 (1), and SMAD6 (4) were found in 7 total families. USP10 encodes a ubiquitin peptidase that is required for endothelial Notch signaling during vascular development. Conclusions: We identified rare and de novo variants of USP10 that implicate USP10 as a new candidate gene for BAV.

scholarly journals Bicuspid Aortic Valve Disease and Ascending Aortic Aneurysms: Gaps in Knowledge

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Katie L. Losenno ◽  
Robert L. Goodman ◽  
Michael W. A. Chu
Keyword(s):  
Aortic Valve ◽  
Bicuspid Aortic Valve ◽  
Aortic Valve Disease ◽  
Aortic Aneurysms ◽  
Valve Disease ◽  
Cardiac Anomaly ◽  
Aortic Dilatation ◽  
Congenital Cardiac Anomaly ◽  
Valvular Stenosis ◽  
Ongoing Surveillance

The bicuspid aortic valve is the most common congenital cardiac anomaly in developed nations. The abnormal bicuspid morphology of the aortic valve results in valvular dysfunction and subsequent hemodynamic derangements. However, the clinical presentation of bicuspid aortic valve disease remains quite heterogeneous with patients presenting from infancy to late adulthood with variable degrees of valvular stenosis and insufficiency and associated abnormalities including aortic coarctation, hypoplastic left heart structures, and ascending aortic dilatation. Emerging evidence suggests that the heterogeneous presentation of bicuspid aortic valve phenotypes may be a more complex matter related to congenital, genetic, and/or connective tissue abnormalities. Optimal management of patients with BAV disease and associated ascending aortic aneurysms often requires a thoughtful approach, carefully assessing various risk factors of the aortic valve and the aorta and discerning individual indications for ongoing surveillance, medical management, and operative intervention. We review current concepts of anatomic classification, pathophysiology, natural history, and clinical management of bicuspid aortic valve disease with associated ascending aortic aneurysms.

The Value of Circulating Biomarkers in Bicuspid Aortic Valve-Associated Aortopathy

2016 ◽  
Vol 66 (04) ◽  
pp. 278-286 ◽  
Author(s):  
Shiho Naito ◽  
Mathias Hillebrand ◽  
Alexander Bernhardt ◽  
Annika Jagodzinski ◽  
Lenard Conradi ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Risk Stratification ◽  
Bicuspid Aortic Valve ◽  
Aortic Aneurysms ◽  
Conventional Imaging ◽  
Circulating Biomarkers ◽  
Screening Process ◽  
Cross Sectional ◽  
Thoracic Aortic Aneurysms ◽  
Definition Of

AbstractTraditional risk stratification model of bicuspid aortic valve (BAV) aortopathy is based on measurement of maximal cross-sectional aortic diameter, definition of proximal aortic shape, and aortic stiffness/elasticity parameters. However, conventional imaging-based criteria are unable to provide reliable information regarding the risk stratification in BAV aortopathy, especially considering the heterogeneous nature of BAV disease. Given those limitations of conventional imaging, there is a growing clinical interest to use circulating biomarkers in the screening process for thoracic aortic aneurysms as well as in the risk-assessment algorithms. We aimed to systematically review currently available biomarkers, which may be of value to predict the natural evolution of aortopathy in individuals with BAV.

Fluid Structural Interaction of a Patient Specific Congenital Bicuspid Aortic Valve

2012 ◽  
Author(s):  
V. Govindarajan ◽  
H. S. Udaykumar ◽  
S. Vigmostad ◽  
M. M. Levack ◽  
J. H. Gorman ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Bicuspid Aortic Valve ◽  
Aortic Root ◽  
Aortic Aneurysms ◽  
Patient Specific ◽  
Aortic Dilatation ◽  
Structural Interaction ◽  
Aortic Pathology ◽  
Specific Geometry ◽  
Opening Phase

Congenital Bicuspid Aortic Valve (BAV) is a valvular anomaly where a patient is born with a valve with two leaflets instead of a normal tri-leaflet valve. It has also been reported that BAVs are prone to progressive calcification and also other complications such as ascending aortic dilatation, dissection and rupture [1]. The geometrical variations with the BAV may be a factor in altering the deformation and stresses on the leaflets resulting in calcification of the leaflets earlier than with normal tri-leaflet aortic valves. Altered flow patterns past BAV into the ascending aorta can also be anticipated. Analysis of flow dynamics during the opening phase, and the resultant fluid forces on the aortic root could improve our understanding of aortic aneurysms and dissections observed in patients with BAV [2]. In this study, the valvular deformation and the flow across a patient-specific BAV and root are simulated using the method of fluid structural interaction analysis. The patient-specific geometry is obtained employing 3D ultrasound images segmented as point cloud data and surfaces are constructed with commercial software GAMBIT using NURBS based connectivity. The opening phase of the valve is simulated under flow with physiological Reynolds number and with realistic material properties for the leaflets and the aortic root. Such an analysis on the dynamics of BAV with patient-specific geometry may be a useful tool in stratifying BAV patients that may be at risk in developing valvular and ascending aortic pathology.

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.

Abstract 3189: Prevalence of Bicuspid Aortic Valve in Turner Syndrome

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Vandana Sachdev ◽  
Lea Ann Matura ◽  
Stanislav Sidenko ◽  
Vincent Ho ◽  
Andrew Arai ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Turner Syndrome ◽  
Bicuspid Aortic Valve ◽  
Aortic Root ◽  
Ascending Aorta ◽  
Aortic Dilatation ◽  
Aortic Valves ◽  
Number Of Patients ◽  
Valve Structure ◽  
Asymptomatic Individuals

Women with Turner syndrome (TS) have an increased risk of congenital cardiovascular defects. Previous studies have reported a 10 –20% prevalence rate of bicuspid aortic valves and there are increasing reports of a vasculopathy that predisposes patients to aortic dilatation and dissection. This prospective study aimed to characterize aortic valve and aortic root structure in unselected asymptomatic individuals with TS. A total of 253 females aged 7– 67 years with karyotype proven TS were examined. Transthoracic echocardiography revealed a normal tricuspid aortic valve (TAV) in 162, a ‘probable TAV’ in 8 subjects, a bicuspid aortic valve (BAV) in 65 and ‘probable BAV’ in 3 subjects. The aortic valve could not be visualized by echocardiography in 15/253 or 6%. Magnetic resonance imaging (MRI) revealed valve structure in 11/12 of the probable cases (all confirmatory of the ‘probable’ diagnosis) and 12/15 of the non-visualized cases (8 BAV and 4 TAV), so only 3/253 subjects could not be visualized by either modality. The aortic valve was bicuspid in 76 of the 250 adequately imaged subjects (30%). Peak aortic valve flow was higher in BAV subjects (1.72±0.07 vs. 1.90v0.03 m/sec, P=0.0002), with one case of significant aortic stenosis. Among subjects with a BAV, aortic regurgitation was moderate or greater in ∼15%. Aortic diameters at the annulus, sinuses of Valsalva, sinotubular junction and ascending aorta were all significantly greater in the BAV group. Thirty patients in the BAV group (12%) had aortic root diameters that were outside of the 95% normal confidence limits based on Roman nomograms. Ascending aortic diameters by echo and MRI were highly correlated (r=0.77). In summary, echocardiography supplemented with MRI reveals an extraordinarily high prevalence of abnormal aortic valves in asymptomatic subjects with TS. The abnormal valve structure is associated with higher peak flows, evidence of clinically significant valvular dysfunction, and widening of the ascending aorta in a significant number of patients. All girls and women with TS should have careful echocardiographic evaluation upon diagnosis to identify the one in three asymptomatic individuals with an abnormal valve requiring monitoring for aortic root dilatation and valvular dysfunction.

scholarly journals Novel NOTCH1 mutations in patients with bicuspid aortic valve disease and thoracic aortic aneurysms

2007 ◽  
Vol 134 (2) ◽  
pp. 290-296 ◽  
Author(s):  
Stephen H. McKellar ◽  
David J. Tester ◽  
Marineh Yagubyan ◽  
Ramanath Majumdar ◽  
Michael J. Ackerman ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Bicuspid Aortic Valve ◽  
Aortic Valve Disease ◽  
Aortic Aneurysms ◽  
Valve Disease ◽  
Thoracic Aortic Aneurysms ◽  
Notch1 Mutations

scholarly journals Hemodynamic Characteristics of Dilated Ascending Aorta in Patients with Bicuspid Aortic Valve

2021 ◽  
Author(s):  
Tie Zheng ◽  
Shijie Lu ◽  
Shuai Zhu ◽  
Jiafu Ou ◽  
Jun-Ming Zhu
Keyword(s):  
Aortic Valve ◽  
Bicuspid Aortic Valve ◽  
Numerical Models ◽  
Outer Part ◽  
Flow Patterns ◽  
Ascending Aorta ◽  
Aortic Diameter ◽  
Aortic Dilatation ◽  
Distribution Features ◽  
Aortic Size

Abstract Objective: Aim of this study is to investigate the influence of aortic diameter on hemodynamic environment characteristics in patient with the bicuspid aortic valve (BAV) and dilated ascending aorta (AAo) .Methods: In this study, an MRI of one BAV patient with 4.5 cm AAo was collected and numerical model was constructed. Based on the images，the other three numerical models were constructed with different ascending aortic size with 4.0cm, 5.0cm and 5.5cm respectively while the size and the geometry of other parts were fixed. Then hemodynamics in these four models was simulated numerically and the flow patterns and loading distributions were investigated.Results: Hemodynamics environments in the AAo were simulated with different aortic size. As the aortic diameter increases, we find: 1. the blood flow becomes more disturbing;2.the wall pressure at ascending aortic is higher; 3. the wall shear stress at the ascending aortic decreases; 4.oscillatory shear index of the outer part on the proximal AAo increases;5. all these hemodynamic parameters described above are asymmetrically distributed in dilated AAo and more parts of aorta would be affected as the AAo dilatation progresses.Conclusions: The study revealed that the diameter of ascending aortic can significantly influence the magnitude and distribution of the dynamics. There are altered flow patterns, pressure difference, WSS and OSI distribution features in bicuspid aortic valve patients with vascular dilatation. As the extent of aortic dilatation increases especially exceed 5.5cm,this study support the recent guideline that aortic replacement should be considered .

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