Clinical Interpretation of Genetic Variants in the Evaluation and Management of Thoracic Aortic Aneurysm and Dissection

BACKGROUND: We aimed to elucidate clinical implications of genetic variant interpretation in assessing disease severity and progression in thoracic aortic aneurysm and dissection (TAAD) patients. METHODS: Consecutive TAAD patients with aortic root and/or ascending aortic aneurysms seen between2011 and 2020 were included. Serial echocardiography, family history of TAAD, and management information were retrospectively collected and analyzed. Patients were classified into gene-positive (Gen-P),variants of uncertain significance, and gene-negative (Gen-N) groups. RESULTS: A total of 407 patients were included: mean age 53.7 15.4 years, 64.4% men, and 38% with reported family history of TAAD. Thirty-seven (9.1%)were Gen-P; 147 (36.1%) had a variant of uncertain significance. The maximal aneurysm diameter was4.78 mm larger in Gen-P than the other groups (P<.001). In162 unoperated TAAD patients with serial echocardiographic measurements, aneurysms enlarged at a significantly higher rate in the Gen-P (1.36 mm/year, 95% CI: 0.77-1.95) than variants of uncertain significance and Gen-N groups (0.83 mm/year vs0.89 mm/year, respectively;P<.001). Aneurysms were 20% more likely torequire surgical intervention for every millimeter increase in diameter. When considered on an individual basis, the highest growth rates were found in the variants of uncertain significance group. CONCLUSIONS: While aneurysms linked to variants of uncertain significance demonstrate average growth rates comparable to those in Gen-N, close follow-up and genetic counseling in the variants of uncertain significance group are recommended for assessment of pathogenicity on a case-by-case basis. Early familial gene testing in TAAD is important to develop individualized preventive and therapeutic criteria. & Oacute;2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, andsimilar technologies.