Systematic Review of Studies That Have Evaluated Screening Tests in Relatives of Patients Affected by Nonsyndromic Thoracic Aortic Disease

Abstract

BackgroundNonsyndromic thoracic aortic diseases (NS‐TADs) are often silent entities until they present as life‐threatening emergencies. Despite familial inheritance being common, screening is not the current standard of care in NS‐TADs. We sought to determine the incidence of aortic diseases, the predictive accuracy of available screening tests, and the effectiveness of screening programs in relatives of patients affected by NS‐TADs.Methods and ResultsA systematic literature search on PubMed/MEDLINE, Embase, and the Cochrane Library was conducted from inception to the end of December 2017. The search was supplemented with the Online Mendelian Inheritance in Man database. A total of 53 studies were included, and a total of 2696 NS‐TAD relatives were screened. Screening was genetic in 49% of studies, followed by imaging techniques in 11% and a combination of the 2 in 40%. Newly affected individuals were identified in 33%, 24%, and 15% of first‐, second‐, and third‐degree relatives, respectively. Familial NS‐TADs were primarily attributed to single‐gene mutations, expressed in an autosomal dominant pattern with incomplete penetrance. Specific gene mutations were observed in 25% of the screened families. Disease subtype and genetic mutations stratified patients with respect to age of presentation, aneurysmal location, and aortic diameter before dissection. Relatives of patients with sporadic NS‐TADs were also found to be affected. No studies evaluated the predictive accuracy of imaging or genetic screening tests, or the clinical or cost‐effectiveness of an NS‐TAD screening program.ConclusionsFirst‐ and second‐degree relatives of patients affected by both familial and sporadic NS‐TADs may benefit from personalized screening programs.

Two-Dimensional Aortic Size Normalcy: A Novelty Detection Approach

“…Though recommended, screening strategies of relatives of patients with non-syndromic TA aneurysm are affected by heterogeneous criteria used for defining aortic dilatation and by uncertainty regarding effectiveness, costs and psychological impact [ 25 ]. Q-score could find application as a unique tool for these screening programs, over a wide age-range, for each aortic level, and providing a global assessment.…”

Postpartum aortic dissection. A case report and review of literature

“…Marfan, Ehlers-Danlos, Loeys-Dietz and Turner syndrome, or bicuspid aortic valve, are conditions associated with an increased risk for aortic dissection, but non-syndromic cases have also been described in literature. Even though in some of these cases a familiarity for dissection may be reported, sporadic cases of non syndromic aortic dissections may occur [ 6 ]. Specifically for pregnancy, aortic dissection has been described previously in patients without risk factors [ 2 ]…”

Report of a Delphi exercise to inform the design of a research programme on screening for thoracic aortic disease

“…There was strong consensus among clinicians and patients that relatives of those with aortic disease should undergo routine imaging in addition to genetic testing, so as to identify the relatives at risk even in case of a negative genetic test, a circumstance that may happen, as shown in a recent systematic review, in up to 70% of familial forms of non-syndromic thoracic aortic diseases [4]. It is expected that this percentage will drop as the number of causative genes identified in thoracic aortic diseases increases.…”

“…The long latency period, the ready availability of cross sectional imaging, and the emergence of high through-put genetic testing all support the introduction of targeted screening in people at risk of non-syndromic aortic disease. Imaging techniques can identify clinically silent aortic disease in up to 56% of asymptomatic relatives of patients with non-syndromic thoracic aortic disease [ 4 ]. Pathogenic variants are common even where there is no syndrome features or clear family history [ 4 , 5 ].…”

“…Imaging techniques can identify clinically silent aortic disease in up to 56% of asymptomatic relatives of patients with non-syndromic thoracic aortic disease [ 4 ]. Pathogenic variants are common even where there is no syndrome features or clear family history [ 4 , 5 ]. It is therefore reasonable to assume that high-risk non-syndromic phenotypes will also benefit from intensive surveillance, strict blood pressure control, and early surgery.…”