Study of Arterial Properties by Ultra-high Frequency Ultrasound in Fibromuscular Dysplasia and Vascular Ehlers-Danlos Syndrome

Background: Fibromuscular dysplasia (FMD) is an idiopathic, systemic, non-atherosclerotic, non-inflammatory vascular disease leading to stenosis, aneurysms, dissections and occlusion of small and medium-sized arteries, with possible life-threatening complications. Recent data suggest that FMD is not so rare as previously thought, showing a prevalence up to 4%, but it is mostly undiagnosed. FMD mainly involves renal and internal carotid arteries, thus its clinical manifestations include hypertension and stroke. However, increasing evidence from large registries point out that FMD is a systemic disease, with a very high prevalence of multiple districts involvement.

Vascular Ehlers Danlos Syndrome (V-EDS) is a rare vascular disease (prevalence 1/150000), due to heterozygous mutations of COL3A1 gene, coding for collagen tipe III, with dominant autosomic transmission. V-EDS patients are predisposed to spontaneous ruptures in the vascular, intestinal districts and in many others.

In FMD, vascular subclinical alterations may be observed in usually usually not affected arterial districts, such as the common carotid artery and the radial artery. In a previous experience, Boutouyrie and colleagues discovered a peculiar phenotype in the common carotid artery of individuals with renal FMD. This pattern, known as "triple signal", is characterized by a supernumerary acoustic interface, located between the blood-intima and the media- adventitia interfaces and detected by either the B-mode or the radiofrequency equipment, which may correspond to medial hyperplasia. The "triple signal" pattern, though present in a small proportion of hypertensive patients, was able to accurately discriminate FMD individuals and in particular to identify familiar cases. Furthermore, c-IMT was higher in FMD, while diameter and elasticity were superimposable to hypertensive control group.

Nevertheless, the study of non-affected and easily accessible medium and small-sized arteries, such as the radial artery, with similar diameter and histology of affected arteries such as the renal, cerebral and coronary arteries, might be even more informative in FMD. This has been recently made possible by the commercial availability of ultra-high frequency ultrasound for human use. The machine is equipped with transducers up to 70 MHz and allows imaging superficial tissues with a spatial resolution up to 30 μm (axial) and 65 μm (lateral). Preliminary results by using ultrahigh frequency ultrasound, confirmed an increased radial wall thickness in FMD patients in comparison to age-, sex- and BP-matched controls. Most strikingly, wall ultrastructure was extensively subverted in FMD patients: the two echogenic layers corresponding to the elastic laminae presented a lower echogenicity and a greater inhomogeneity as compared to healthy individuals.

Methods: This is a cross-sectional study, recruiting 60 individuals with FMD and 30 individuals with V-EDS. Patients will be recruited by the Clinical Pharmacology Unit of the Hopital Europeen George Pompidou, during their routine visit for the ultrasound evaluation of the carotid arteries by echotracking. In that occasion, supplementary images of carotid, radial and digital arteries will be acquired by ultrahigh frequency ultrasound (VevoMD; Fujifilm-Visualsonics: Toronto, Canada).