From the Guidelines
Genetic testing should be considered selectively for BAV patients who have a family history of thoracic aortic disease, syndromic features, or early-onset aortic dilation, as recommended by the 2022 ACC/AHA guideline for the diagnosis and management of aortic disease 1. The primary value of genetic testing is in risk stratification, as certain genetic variants may predict more aggressive aortic dilation requiring earlier surgical intervention or closer monitoring. For example, patients with FBN1 mutations may need aortic surgery at smaller aortic diameters compared to those without identified mutations. Additionally, genetic testing can guide family screening recommendations, as first-degree relatives of BAV patients with identified pathogenic variants should undergo echocardiographic screening. Some key points to consider in the management of BAV patients include:
- The use of TTE to evaluate valve morphology and function, as well as the diameter of the aortic root and ascending aorta 1
- The consideration of CT or MRI of the thoracic aorta when the diameter and morphology of the aortic root, ascending aorta, or both cannot be assessed accurately or completely by TTE 1
- The recommendation for a medical genetics evaluation in patients with a BAV and either HTAD or phenotypic features concerning for Loeys-Dietz syndrome 1
- The importance of screening all first-degree relatives by TTE to evaluate for the presence of a BAV, dilation of the aortic root and ascending aorta, or both 1 However, genetic testing should not replace regular imaging surveillance with echocardiography or CT/MRI for all BAV patients, as these remain the cornerstone of management regardless of genetic status. It is also important to note that the 2014 AHA/ACC guideline for the management of patients with valvular heart disease recommends serial evaluation of the size and morphology of the aortic sinuses and ascending aorta by echocardiography, CMR, or CT angiography in patients with a bicuspid aortic valve and an aortic diameter greater than 4.0 cm 1. Overall, the management of BAV patients requires a comprehensive approach that includes genetic testing, imaging surveillance, and regular follow-up to monitor for potential complications.
From the Research
Role of Genetic Testing in Bicuspid Aortic Valve Management
- Genetic testing plays a crucial role in managing patients with bicuspid aortic valve (BAV) by identifying genetic variants that contribute to the development of BAV and associated aortopathy 2, 3, 4, 5, 6.
- BAV has an autosomal dominant pattern of inheritance with reduced penetrance and variable expressivity, making genetic testing essential for diagnosing and managing the condition 2, 5.
- Next-generation sequencing (NGS) can improve the management of patients with complex BAV clinical pictures by identifying rare genetic variants that contribute to the development of BAV and associated aortopathy 2, 6.
Genetic Variants Associated with Bicuspid Aortic Valve
- Several genetic variants have been associated with BAV, including NOTCH1, FBN1, LTBP1, and TGFBR3 2, 4, 6.
- These variants can contribute to the development of BAV and associated aortopathy, and their identification can help guide management decisions 2, 4, 6.
- The presence of rare genetic variants can increase the risk of aortic root dilatation and dissection in patients with BAV 6.
Clinical Implications of Genetic Testing
- Genetic testing can help identify patients with BAV who are at increased risk of developing aortic root dilatation and dissection 6.
- This information can be used to guide management decisions, such as the timing and type of surgical intervention 2, 3.
- Genetic testing can also help identify family members who may be at risk of developing BAV and associated aortopathy, allowing for early screening and intervention 3, 5.