Primary Non-Aortic Lesions Are Not Rare in Marfan Syndrome and Are Associated with Aortic Dissection Independently of Age.

PURPOSE: The study sought to estimate the prevalence of primary non-aortic lesions (PNAL) unrelated to extension of aortic dissection (AD) in a cohort of patients with Marfan syndrome (MFS). METHODS: Adult patients presenting with pathogenic FBN1 mutations and an available pan-aortic contrast-enhanced CTA in eight French MFS clinics from April to October 2018 were included. Clinical and radiological data, particularly the presence of aortic lesions and PNAL (including aneurysm and ectasia), were retrospectively analyzed. RESULTS: Out of 138 patients, 28 (20.3%) had PNAL. In total, 27 aneurysms in 13 patients and 41 ectasias in 19 patients were reported mainly in the subclavian, iliac, and vertebral segments. Four patients (31%) with aneurysms and none with ectasia required prophylactic intervention during follow-up (median: 46 months). In multivariate analysis, factors associated with PNAL were history of AD (OR = 3.9, 95%CI: 1.3-12.1, p = 0.018), history of previous descending aortic surgery (OR = 10.3, 95%CI: 2.2-48.3, p = 0.003) and age (per 10 years OR = 1.6, 95%CI: 1.1-2.4, p = 0.008). CONCLUSION: PNAL is not rare in MFS patients with evolutive aortic disease. Natural history may differ between aneurysms and ectasia, emphasizing the need for standardized definitions and systematic screening for PNAL.

Aortic Function's Adaptation in Response to Exercise-Induced Stress Assessing by 1.5T MRI: A Pilot Study in Healthy Volunteers.

AIM: Evaluation of the aortic "elastic reserve" might be a relevant marker to assess the risk of aortic event. Our aim was to compare regional aortic elasticity at rest and during supine bicycle exercise at 1.5 T MRI in healthy individuals. METHODS: Fifteen volunteers (8 men), with a mean age of 29 (23-41) years, completed the entire protocol. Images were acquired immediately following maximal exercise. Retrospective cine sequences were acquired to assess compliance, distensibility, maximum rates of systolic distension and diastolic recoil at four different locations: ascending aorta, proximal descending aorta, distal descending aorta and aorta above the coeliac trunk level. Segmental aortic pulse wave velocity (PWV) was assessed by through plane velocity-encoded MRI. RESULTS: Exercise induced a significant decrease of aortic compliance and distensibility, and a significant increase of the absolute values of maximum rates of systolic distension and diastolic recoil at all sites (p<10-3). At rest and during stress, ascending aortic compliance was statistically higher compared to the whole descending aorta (p≤0.0007). We found a strong correlation between the rate pressure product and aortic distensibility at all sites (r = - 0.6 to -0.75 according to the site, p<10-4). PWV measured at the proximal and distal descending aorta increased significantly during stress (p = 0.02 and p = 0.008, respectively). CONCLUSION: Assessment of regional aortic function during exercise is feasible using MRI. During stress, aortic elasticity decreases significantly in correlation with an increase of the PWV. Further studies are required to create thresholds for ascending aorta dysfunction among patients with aneurysms, and to monitor the impact of medication on aortic remodeling.

The type of variants at the COL3A1 gene associates with the phenotype and severity of vascular Ehlers-Danlos syndrome.

Vascular Ehlers-Danlos syndrome (vEDS) is a rare and severe autosomal dominant disorder caused by variants at the COL3A1 gene. Clinical characteristics and course of disease of 215 molecularly proven patients (146 index cases and 69 relatives) were analysed. We found 126 distincts variants that were divided into five groups: (1) Glycine substitutions (n=71), (2) splice-site and in-frame insertions-deletions (n=36), (3) variants leading to haplo-insufficiency (n=7), (4) non-glycine missense variants within the triple helix (n=4 variants), and (5) non-glycine missense variants or in-frame insertions-deletions, in the N- or C-terminal part of the protein (n=8). Overall, our cohort confirmed the severity of the disease with a median age at first complication of 29 years (IQR 22-39), the most frequent being arterial (48%) and digestive (24%) ruptures. Groups 2 and 1 were significantly more severe than groups 3-5, with extreme median ages at first major complication of 23-47 years. Patients of groups 3-5 had a less typical phenotype and remarkably absence of digestive events. The distribution of glycine-replacing amino acids was strongly biased towards more destabilizing residues of the collagen assembly. Thus the natural course of vEDS and the clinical phenotype of patients are influenced by the type of COL3A1 variant. This study also confirms that patients with variants located in the C- and N-termini or leading to haplo-insufficiency have milder course of the disease and less prevalent diagnostic criteria. These findings may help refine diagnostic strategy, genetic counselling and clinical care.