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Role of Genetic Testing in the Management of Aortic Disease

More than five percent of Americans over the age of 60 have aortic aneurysms. While aneurysms do not directly cause death, complications such as dissection or rupture account for more than 15,000 deaths each year. Consequently, aortic aneurysms constitute the 14th leading cause of death in the United States. Smoking cessation interventions and cholesterol medications have decreased the incidence of aortic aneurysms. Yet, the aging population, coupled with the global burden and heritable nature of cardiovascular diseases (CVDs), has created a demand for additional treatment and prevention strategies.

Cardiovascular genetics is an emerging subspecialty within cardiovascular medicine that has elucidated the genetic basis of multiple cardiac conditions, including arrhythmias, cardiomyopathies, lipid disorders, and vascular diseases. 2 Clinical genome sequencing and genetic testing can facilitate the diagnosis of heritable CVDs, identification of at-risk asymptomatic family members, and prenatal decision-making.

Medical and surgical experts at the USC Comprehensive Aortic Center collaborate in planning treatment and follow care for patients with complex aortic diseases. The following case study highlights the importance of interdisciplinary techniques, like genetic testing, in the clinical setting.

Case Study: Genetic Testing Indicated for Patient with Family History of Aortopathies

Dr. Sukgu Han and Dr. Fernando Fleischman

For over six years, cardiac surgeon Dr. Fernando Fleischman, and vascular surgeon Dr. Sukgu Han, have collaborated on the case of a 59-year-old man who initially presented with complicated type B aortic dissection and lower leg perfusion syndrome. This patient has an extensive surgical history at Keck Medicine of USC, beginning in April 2016. His first operation, a right to left femoral-femoral bypass, was emergent to return flow to his legs. In May 2016, he underwent a thoracic endovascular aortic repair (TEVAR) to fix his Type B dissection. Yet, despite the initial TEVAR, the patient's aorta continued to expand, requiring a second TEVAR In October 2016 and a third in April 2021.

Given the patient's significant maternal family history of aortic aneurysm and dissections, genetic testing was indicated. Inherited connective tissue disorders, such as Marfan syndrome (MFS), Loeys-Dietz syndrome (LDS), and Vascular Ehlers-Danlos syndrome (VEDS), are known to weaken aortic walls, increasing the risk of aortic aneurysm and, to a lesser extent, cerebral aneurysm. Therefore, the care team ordered a comprehensive aortopathy panel analyzing 35 genes associated with Familial Thoracic Aortic Aneurysms and Dissections (FTAAD), MFS, LOS, and VEDS. Although the clinical sensitivity of the ordered test for FTAAD is only 30-40%, the sensitivity is relatively high for MFS (93%), LOS (80-90%), and (>95%), demonstrating its reliability as a diagnostic tool.

In conjunction with clinical evaluation, genetic testing ruled out connective tissue disorders and any known FTAAD genes. Genetic testing also identified c.188C>A, a variant of unknown significance (VUS), in the TGFB3 gene, which is implicated in LDS and non-syndromic aortic aneurysms and dissections. A VUS may be benign, or it may cause disease; thus, despite the lack of information regarding the role of tl1e c.188C>A variant in CVDs, widespread genetic testing may provide alternative findings.

In addition to regular aortic surveillance, genetic testing may soon become the standard of care for aortic a11eurysrns. Because this patient has a significant family history of aortic aneurysm, the care team cannot rule out a genetic cause. For that reason, genetic testing should be repeated in the future as more TGFB3 variants become identified. Furthermore, because no one in the patient's family has had genetic testing, first-degree relatives should consider baseline screening for aortic pathologies by their primary care physicians.


About USC Comprehensive Aortic Center

At Keck Medical Center, we know that time is of the essence for patients with aortic pathologies. That is why USC's Comprehensive Aortic Center offers immediate access to lifesaving care for patients in need of emergent treatment through its Rapid Transfer Program, which guarantees transport by ambulance or helicopter within two hours. The Comprehensive Aortic Center is the largest referral center in Southern California for the evaluation and treatment of aortic emergencies, like ruptured aortic aneurysms, acute aortic dissection, and occlusive disease, as well as non-emergent aortic disorders.

Primarily known as a center of surgical excellence, the USC Comprehensive Aortic Center tailors its treatment options to meet each patient's unique needs. Cardiac and Vascular surgeons and cardiovascular medicine specialists at Keck Medical Center collaborate to provide a spectrum of endovascular and open aortic procedures. The multidisciplinary program offers state-of-the-art screenings, diagnostic tests, innovative noninvasive treatments, and specialized therapies. Our exclusive focus gives us an advantage in treating conditions and rare cases that present unique challenges. The Center's physicians deliver advanced, patient-centered care to individuals whose health is threatened by cardiovascular disease, while our scientists investigate treatment and prevention therapies to improve patient outcomes. Our groundbreaking research continues to push the frontiers of medical technology, resulting in innovative approaches for endovascular aneurysm repair and thoracic endovascular aortic repair therapies.

At the USC Comprehensive Aortic Center, we value our relationships with our referring physicians, and our goal is to work with you. We are committed to serving your patients, being responsive and compassionate, and providing the highest level of care.

Refer a patient by emailing or calling (323) 442-5849