scholarly journals Aortic Dilatation Associated With Bicuspid Aortic Valve: Relation to Sex, Hemodynamics, and Valve Morphology (the National Heart Lung and Blood Institute-Sponsored National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions)

2017 ◽  
Vol 120 (7) ◽  
pp. 1171-1175 ◽  
Author(s):  
Mary J. Roman ◽  
Norma L. Pugh ◽  
Richard B. Devereux ◽  
Kim A. Eagle ◽  
Kathryn Holmes ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Bicuspid Aortic Valve ◽  
National Registry ◽  
Aortic Aneurysms ◽  
Aortic Dilatation ◽  
Thoracic Aortic Aneurysms ◽  
Valve Morphology ◽  
Blood Institute ◽  
National Heart ◽  
National Heart Lung

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 Exercise Training in Athletes with Bicuspid Aortic Valve Does Not Result in Increased Dimensions and Impaired Performance of the Left Ventricle

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Laura Stefani ◽  
Giorgio Galanti ◽  
Gabriele Innocenti ◽  
Roberto Mercuri ◽  
Nicola Maffulli
Keyword(s):  
Aortic Valve ◽  
Left Ventricle ◽  
Bicuspid Aortic Valve ◽  
Negative Impact ◽  
Large Population ◽  
Aortic Dilatation ◽  
Cross Sectional ◽  
Valve Morphology ◽  
Progressive Enlargement

Background.Bicuspid aortic valve (BAV) is one of the most common congenital heart disease (0.9%–2%) and is frequently found in the athletes and in the general population. BAV can lead to aortic valve dysfunction and to a progressive aortic dilatation. Trained BAV athletes exhibit a progressive enlargement of the left ventricle (LV) compared to athletes with normal aortic valve morphology. The present study investigates the possible relationship between different aortic valve morphology and LV dimensions.Methods.In the period from 2000 to 2011, we investigated a total of 292 BAV subjects, divided into three different groups (210 athletes, 59 sedentaries, and 23 ex-athletes). A 2D echocardiogram exam to classify BAV morphology and measure the standard LV systo-diastolic parameters was performed. The study was conducted as a 5-year follow-up echocardiographic longitudinal and as cross-sectional study.Results.Typical BAV was more frequent in all three groups (68% athletes, 67% sedentaries, and 63% ex-athletes) than atypical. In BAV athletes, the typical form was found in 51% (107/210) of soccer players, 10% (21/210) of basketball players, 10% track and field athletics (20/210), 8% (17/210) of cyclists, 6% (13/210) swimmers, and 15% (32/210) of rugby players and others sport. Despite a progressive enlargement of the LV (P<0.001) observed during the follow-up study, no statistical differences of the LV morphology and function were evident among the diverse BAV patterns either in sedentary subjects or in athletes.Conclusion.In a large population of trained BAV athletes, with different prevalence of typical and atypical BAV type, there is a progressive nonstatistically significant enlargement of the LV. In any case, the dimensions of the LV remained within normal range. The metabolic requirements of the diverse sport examined in the present investigations do not seem to produce any negative impact in BAV athletes

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

Abstract 15097: Altered TGFβ Signalling Effector Molecules Contribute to Bicuspid Aortic Valve-associated Thoracic Aortopathy

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Candice L Dilworth ◽  
Francesca Sadnick ◽  
Sari Padang ◽  
Yaxin Lu ◽  
Elizabeth N Robertson ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Bicuspid Aortic Valve ◽  
Aortic Aneurysms ◽  
Extra Cellular Matrix ◽  
Matrix Metalloproteinase 2 ◽  
Compensatory Mechanism ◽  
Aortic Dilatation ◽  
Matrix Degradation ◽  
Tgfβ Signalling ◽  
Cellular Matrix

Upregulated TGFβ signalling plays a key role in mediating congenital thoracic aortic aneurysms (TAA), and has been implicated in bicuspid aortic valve-associated TAA (BAV-TAA). TGFβ is normally stored within the extra-cellular matrix via sequestration proteins bound to the microfibrillar protein, fibrillin. TGFβ is released in response to changes in these sequestration proteins, allowing TGFβ to exert its signalling effects. We hypothesised that in BAV-TAA the upregulation of TGFβ signalling will pathologically alter effector molecule expression, causing matrix degradation and altered TGFβ sequestration. Immunohistochemistry was used to quantify protein expression in aortic tissue from 8 human BAV-TAA and 6 normal controls. In BAV-TAA, TGFβ expression was elevated in all layers (2.5:1; p<0.05), particularly in the adventitia (3.4:1; p<0.001). Microfibril-associated glycoprotein-1 (MAGP-1), which promotes TGFβ release, was elevated (2:1; p<0.03), while latent TGFβ binding protein-1 (LTBP-1), which promotes TGFβ sequestration, was decreased (0.3:1; p=0.03). Matrix metalloproteinase-2 (MMP-2) and MMP-9 expression was elevated (2.6:1; p<0.005, 1.5:1; p<0.05, respectively), and MMP-3 expression was decreased (0.5:1; p<0.05). Fibrillin-1 expression was not altered. The observed changes in TGFβ sequestration proteins will increase unbound TGFβ, leading to upregulation of downstream signalling. The elevated levels of MMP-2 and MMP-9 mediate pathological matrix remodelling, leading to aortic dilatation. The paradoxical decrease in MMP-3 may represent a compensatory mechanism that attempts to reduce overall pathological MMP activity, in order to limit damage to the aortic wall. In conclusion, in BAV-TAA excessive TGFβ signalling is potentiated by reduced TGFβ sequestration, causing extra-cellular matrix degradation by MMPs. This supports the rationale for the use of angiotensin II receptor blockers in BAV-TAA.

Bicuspid aortic valve and aortopathy: novel prognostic predictors for the identification of high-risk patients

2020 ◽  
Author(s):  
Luca Longobardo ◽  
Scipione Carerj ◽  
Alessandra Bitto ◽  
Maurizio Cusmà-Piccione ◽  
Maria Ludovica Carerj ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Surgical Treatment ◽  
Aortic Valve ◽  
Bicuspid Aortic Valve ◽  
Primary Endpoint ◽  
Cox Regression ◽  
Aortic Surgery ◽  
Aortic Aneurysms ◽  
Aortic Dilatation ◽  
Cox Regression Analysis

Abstract Aims Bicuspid aortic valve (BAV) may be complicated by aortic aneurysms and dissection. This study aimed to evaluate the prognostic efficacy of markers from cardiac imaging, as well as genetic and new biomarkers, to early predict aortic complications. Methods and results We re-evaluated after a mean time of 48 ± 11 months 47 BAV patients who had undergone previous echocardiography for evaluation of aortic stiffness and 2D aortic longitudinal strain (LS) (by speckle-tracking analysis), and who had given a blood sample for the assessment of a single-nucleotide polymorphism of elastin gene (ELN rs2 071307) and quantification of elastin soluble fragments (ESF). Surgical treatment of aortic aneurysm/dissection was the primary endpoint, and an aortic dimension increase (of one or more aortic segments) ≥1 mm/year was the secondary endpoint. Nine patients underwent surgical treatment of ascending aorta (AA) aneurysms. Out of the 38 patients who did not need surgical intervention, 16 showed an increase of aortic root and/or AA dimension ≥1 mm/year. At multivariate Cox regression analysis, an impaired AA LS was an independent predictor of aortic surgery [P = 0.04; hazard ratio (HR) 0.961; 95% confidence interval (CI) 0.924–0.984] and aortic dilatation (P = 0.007; HR 0.960; 95% CI 0.932–0.989). An increased quantity of ESF was correlated (P = 0.015) with the primary endpoint at univariate Cox regression analysis but it did not keep statistical significance at multivariate analysis. Conclusion In BAV patients, impairment of elastic properties of the AA, as assessed by 2D LS, is an effective predictor of aortic complications.

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