MD Candidate Dalhousie University Halifax, Nova Scotia, Canada
Background: Recent advances have identified genetic triggers for thoracic aortopathies (TAA), which cause progressive proximal aortic dilation and type A aortic dissections. Screening of at-risk relatives is recommended for early detection, monitoring, and surgical intervention to prevent dissection. This is typically applied to probands presenting at age < 60. However, age cut-offs and the effectiveness and outcomes of real-world family screening have not been evaluated. Studies to date have been limited by small numbers, variable use of genetic and imaging data and reliance on resource-intensive cascade screening rather than patient-initiated (family letter) screening. To address all this, we evaluated outcomes of patient-initiated family screening for TAA at the Maritime Connective Tissue Clinic (CTC), a large real world cohort, including predictors of a positive family screen
METHODS AND RESULTS: A retrospective review of 1022 probands and 1473 of their family members screened at the CTC (2009–2024) was conducted. Probands were included if they had TAA or a bicuspid aortic valve (BAV), and at least one of: extravascular features, presentation < 60, a mid-sized artery aneurysm (MSA) or a known family history of TAA . Data collected on screened probands and family members included demographics, aortic history, extravascular features, imaging and genetic testing results. Family members screened positive if they had TAA, BAV or MSA. Proband mean age at presentation was 51.1 with 27% being over age 60. Among probands, 43.5% has at least one family member screened, with an average of 3 relatives per proband. 27.6% of family members screened positive. Upon multivariate analysis of proband specific factors, apre-existing family history of TAA was the only variable predictive of a positive family screen(p = 0.0003). Age of presentation over 60 was not predictive. Multivariate analysis of family member specific factors revealed that extravascular features (p < 0.0001), closer relation to the proband (p = 0.0149), male sex (p < 0.0001) and older age at screening (p < 0.0001) all predicted a positive screen. Genetic testing was much less effective than imaging as a family screening strategy, because of 36% of probands being offered genetic testing, only 72% following through and of these 26% having an identifiable mutation.
Conclusion: Imaging first, patient-initiated family screening has a high yield of affected individuals. Further research is needed into supports for probands in promoting family screening. Arbitrary proband age cutoff for family screening is not supported by our data. These findings show the effectiveness of structured family screening programs for TAA.
