Patient case: 63-year-old female with aortic aneurysm; genetic feature: ACTA2

Clinical trial: Evaluation of Aortic Stiffness as a Prognostic Indicator of Aortic Dilatation in Patients With Bicuspid Aortic Valve (BAV) by Multimodal Imaging (MRI, Echocardiography and Ultrafast Ultrasound Imaging)

Summary: The objective is the development and validation of morphological markers informative of aortic dilatation in order to improve the precision of the risk of aneurysm of the thoracic aorta and of acute aortic syndrome for patients with bicuspid aortic valve (BAV).
  The primary objective of this study is to demonstrate a correlation between the aortic local pulse wave velocity (PWV) measured with MRI and the progression of the thoracic aorta diameters measured by MRI after a follow-up of 2 years.

Detailed description: Background Bicuspid Aortic Valve (BAV) is the most common congenital heart defect with prevalence around 1 to 2% of the general population . It is defined by the presence of two functional cusps with less than three parallel zones of apposition between the cusps. This different valve's morphology is associated with a spectrum of valvular (aortic stenosis and insufficiency) and aortic complications (aneurysm and dissection). Indeed, the valvular abnormality is associated with changes in the aortic arch with an increase in the incidence of ascending aortic aneurysm unrelated to valvular functional impairment. The mechanisms responsible for aortic involvement are still incompletely understood but combine, in varying proportions, a constitutional fragility (linked to a common embryological origin of the aortic valve and the aortic arch) and to the haemodynamic modifications, generated by the specific morphology of BAV .
  Current risk prediction of aneurysm development is currently performed only with the ascending aortic diameter, associated with history of aortic coarctation and familial history of dissection. Moreover, aortic dilatation may occur after aortic valve replacement alone, necessitating a second intervention, with a higher surgical risk. Improvement of the aortopathy evaluation is therefore a major stake in the evaluation of the BAV patient.
  Studies of the biomechanical properties of the BAV aortic wall converge towards an increase in arterial stiffness as well as in other elastopathies such as Marfan's disease. Thus, measurements of aortic distensibility in trans-thoracic echocardiography (TTE) or MRI, or the measurement of the Pulse Wave Velocity (PWV) are significantly different case of BAV compared to the general population. However, no prospective study has demonstrated the prognostic role of these morphological biomarkers in the prediction of aortic dilation.
  From a biomechanical point of view, the vessel's rupture appears when the mechanical stress applied to the wall exceeds the material resistance properties. The aortic resistance evaluation requires the use of different imaging modalities which propose the measurement of stiffness parameters. Circumferential stiffness (with TTE or MRI) can be evaluated by measuring the distensibility. In addition, longitudinal stiffness can be evaluated by measuring the local PWV.
  We aim at better defining the vascular involvement of BAV patients by determining the prognostic role of functional parameters as non-invasive predictive factors for aortic dilation.
  Hypothesis:
  1.Main hypothesis The main hypothesis is that the progression of aortic dilation is dependent on the longitudinal and circumferential aortic stiffness in case of BAV.
  The investigators will therefore try to demonstrate a correlation between the local PWV measurements in MRI, combined with a simultaneous measurement of the non-invasive central pressure (SphygmoCor XCEL®, Atcor Medical ©), with the segmental aortic size progression. The investigators hope to define new biomarkers aortic dilation prediction.
  1.Secondary hypothesis
  -  The measurement of the local PWV of the common carotid artery, measured with UF, is correlated with the progression of the aortic dilation.
  -  The measurement of aortic distensibility at the Valsalva sinus and ascending tubular aortic levels, measured in TTE or MRI, correlates with the progression of aortic dilation.
  Originality and innovative aspects - Prospective evaluation of the different aortic segments dilatation in case of BAV: Few studies have prospectively evaluated the aortic dilation progression in BAV. There are currently no prognostic markers of dilatation validated in this group.
  - Use of aortic MRI combined with central pressure measurement as a prognostic evaluation tool for aortopathy associated with BAV: Following the development of 4D MRI in cardiovascular imaging, evaluation of the aorta is possible by studying both the wall's movements during the cardiac cycle and the wall shear stress evaluation. This makes possible to obtain, at each part of the thoracic aorta, measures of circumferential distensibility, local PWV, and shear stress.
  Coupling these two imaging modalities is particularly interesting in the aortic evaluation of BAV due to the involvement of the flow changes in aortic stiffness.
  - Use of the common carotid artery stiffness as a prognostic evaluation tool for aortopathy associated with BAV independently of the aortic diameter Due to the common embryological origin of aorta and the common carotid arteries, aortopathy associated with BAV is associated with an increase in of the common carotid arteries stiffness.
  The evaluation of the carotid artery will therefore help to evaluate the correlation between carotid rigidity and progression of aortic dilation.
  - Evaluation of the local PWV as carotid stiffness biomarker Ultrasound analysis will also be innovative, with the use of a fine ultrasonic method with very high frame rate (more than 10,000 images per second) developed by the Langevin Institute (Mathias Fink, Michael Tanter and Mathieu Pernot). The collaboration between the Langevin Institute and the H.E.G. lead to numerous publications both in the vascular and cardiac levels. The vascular medicine department has an Aixplorer® prototype with vascular and cardiac applications on site. The advantage of this technology is its ultrafastecho mode with very high temporal resolution which allows the vascular level to visualize and to calculate the speed of the arterial pulse wave which is correlated to the local rigidity.
  The use of this innovative technique in aortic bicuspidy will hopefully validate the evaluation of the carotid velocity of the pulse wave as an easily accessible prognostic marker of aortic dilation.
  Purpose of the research
  The objective is the development and validation of morphological markers informative of aortic dilatation in order to improve the precision of the risk of aneurysm of the thoracic aorta and of acute aortic syndrome for patients with BAV.
  The primary objective of this study is to demonstrate a correlation between the aortic local PWV measured with MRI and the progression of the thoracic aorta diameters measured by MRI after a follow-up of 2 years
  The secondary objectives are:
  1. To demonstrate a correlation between the progression of the dilatation of the different segments of the thoracic aorta with the following measures:
  -  Aortic distensibility measured in MRI at the Valsalva sinus and at the ascending tubular aortic level.
  -  Aortic distensibility measured in TTE of the same segments in TM and in B mode .
  -  Carotid pulse rate measured on carotid arteries by UF.
  2. To demonstrate a correlation between the progression of the dilatation of the different segments of the thoracic aorta with the following environmental risk factors:
  -  Active Smoking
  -  Diabetes
  -  Hypertension
  -  Familial form of aortic BAV (defined by the presence of a relative, 1st or 2nd degree, with BAV or thoracic aortic aneurysm)
  -  Morphological type of BAV
  -  Aortic coarctation

Eligibility: Inclusion Criteria:
  -  Adults over 18 years of age,
  -  confirmed BAV by TTE computed tomography or MRI.
  -  Adults benefiting from a social security scheme,
  -  having received information on the research
  -  having signed the consent form
  Exclusion Criteria:
  -  Patient with a syndromic form of BAV:
  -  Loeys-Dietz syndrome,
  -  Turner syndrome
  -  Williams-Beuren syndrome
  -  Shone syndrome

Relevance to patient case: not relevant