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. 2025 Jun 24;85(24):2343-2352.
doi: 10.1016/j.jacc.2025.04.020.

Characterization of Arterial Aneurysms in Loeys-Dietz Syndrome

Andrew W Koefoed  1 , Anna L Huguenard  2 , Gabrielle W Johnson  1 , Elena Deych  3 , Dongchuan Guo  4 , Dianna M Milewicz  4 , Alan C Braverman  5
Affiliations

Characterization of Arterial Aneurysms in Loeys-Dietz Syndrome

Andrew W Koefoed et al. J Am Coll Cardiol. .

Abstract

Background: The presence of extra-aortic arterial aneurysms (AAs) is notable in Loeys-Dietz syndrome (LDS) compared with other heritable thoracic aortic diseases (HTADs). However, the characteristics of AAs in LDS are poorly characterized to date.

Objectives: We sought to determine the prevalence, characteristics, and clinical outcomes of AAs in LDS.

Methods: A retrospective cohort study of LDS patients evaluated at Washington University in St Louis School of Medicine/Barnes-Jewish Hospital between 1998 and 2023 was performed. Clinical information, imaging data, and outcomes related to AAs were compiled.

Results: A total of 103 patients (53% female) from 60 families with LDS 1 through 5 caused by pathogenic/likely pathogenic variants in TGFBR1, TGFBR2, SMAD3, TGFB2, and TGFB3 were included. The median age was 44 years, and median follow-up was 6 years. In total, 77 AAs were identified in 43 patients: 17 AAs in 9 patients with TGFBR1 variants, 33 AAs in 15 patients with TGFBR2, 15 AAs in 8 patients with SMAD3, 9 AAs in 8 patients with TGFB2, and 3 AAs in 3 patients with TGFB3. The median age at AA diagnosis was 40 years; 75% of AAs were in the arch vessels or cerebral circulation. On univariate analysis, aortic event (type A/B dissection or prophylactic aortic surgery) at baseline and prophylactic aortic surgery at baseline were associated with the presence of an AA. Hypertelorism, bifid uvula, and arterial tortuosity approached statistical significance. A multivariate model to predict AA included baseline prophylactic aortic surgery and arterial tortuosity. Of those with vs without AA on initial imaging, 61% and 35%, respectively, presented with previous aortic events. Seventeen percent of AAs enlarged over time, and 38% of AAs that enlarged led to clinical events (prophylactic surgery, dissection, or rupture). Overall, AA-related events occurred in 22% of AAs and throughout the arterial tree. AAs were repaired by open surgical and endovascular techniques.

Conclusions: AAs commonly occur in patients with LDS and may occur throughout the arterial tree. Importantly, AAs may lead to clinical events including arterial dissection and rupture. Head to pelvis imaging at diagnosis and during follow-up is recommended in LDS to evaluate for AAs and their complications.

Keywords: Loeys-Dietz syndrome; aorta; arterial aneurysms; heritable thoracic aortic disease.

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Conflict of interest statement

Funding Support and Author Disclosures Dr Braverman's research is supported by the Neidorff Aortopathy and Master Clinician Fellowship Program at Washington University in St Louis School of Medicine and the Pam and Ron Rubin Fund in the Cardiovascular Division, Department of Medicine, Washington University School of Medicine in St Louis. Dr Milewicz's research is supported by the Genetic Aortic Disorder Association of Canada, Ontario, Canada, The John Ritter Foundation, Los Angeles, California, USA, and NIH R01HL109942. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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