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.

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 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

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 Wall Stress Distribution in Bicuspid Aortic Valve–Associated Ascending Thoracic Aortic Aneurysms

2020 ◽  
Vol 110 (3) ◽  
pp. 807-814 ◽  
Author(s):  
Axel Gomez ◽  
Zhongjie Wang ◽  
Yue Xuan ◽  
Andrew D. Wisneski ◽  
Michael D. Hope ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Stress Distribution ◽  
Bicuspid Aortic Valve ◽  
Wall Stress ◽  
Aortic Aneurysms ◽  
Thoracic Aortic Aneurysms

Abstract 113: Thoracic Aortic Aneurysms Associated With Bicuspid Aortic Valve Have Altered MicroRNA Expression

2018 ◽  
Vol 38 (Suppl_1) ◽  
Author(s):  
Stefanie S Portelli ◽  
Elizabeth N Robertson ◽  
Ratnasari Padang ◽  
Murat Kekic ◽  
Donna Lai ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Bicuspid Aortic Valve ◽  
Microrna Expression ◽  
Aortic Aneurysms ◽  
Thoracic Aortic Aneurysms

Aortic aneurysm: thoracic aortic aneurysm—diagnostic approach

ESC CardioMed ◽  
2018 ◽  
pp. 2570-2572
Author(s):  
Oliver Gaemperli ◽  
Udo Sechtem
Keyword(s):  
Aortic Valve ◽  
Aortic Aneurysm ◽  
Aortic Aneurysms ◽  
Diagnostic Approach ◽  
Cross Sectional ◽  
Safety Issues ◽  
Thoracic Aortic Aneurysms ◽  
Potential Safety ◽  
Valve Function ◽  
Choice Of Technique

The goals of the diagnostic approach to thoracic aortic aneurysms (TAAs) are to confirm the diagnosis, to measure diameter and define longitudinal extent, to determine involvement of the aortic valve and aortic branches, and to detect mural thrombus, dissection, and/or haematoma. A wide array of non-invasive and invasive imaging modalities is available to address all diagnostic challenges encountered in TAAs. Cross-sectional tomographic imaging methods are the preferred techniques for accurate measurement of TAA dimensions and extension, while echocardiography is crucial for assessing the aortic root and aortic valve function. The choice of technique should be based on patient factors and clinical scenario, but other factors such as operator skills, expertise and availability, costs, and potential safety issues of the techniques should be considered.

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