Hemodynamic Characteristics of Dilated Ascending Aorta in Patients with Bicuspid Aortic Valve


 Objective: Aim of this study is to investigate the influence of aortic diameter on hemodynamic environment characteristics in patient with the bicuspid aortic valve (BAV) and dilated ascending aorta (AAo) .Methods: In this study, an MRI of one BAV patient with 4.5 cm AAo was collected and numerical model was constructed. Based on the images，the other three numerical models were constructed with different ascending aortic size with 4.0cm, 5.0cm and 5.5cm respectively while the size and the geometry of other parts were fixed. Then hemodynamics in these four models was simulated numerically and the flow patterns and loading distributions were investigated.Results: Hemodynamics environments in the AAo were simulated with different aortic size. As the aortic diameter increases, we find: 1. the blood flow becomes more disturbing;2.the wall pressure at ascending aortic is higher; 3. the wall shear stress at the ascending aortic decreases; 4.oscillatory shear index of the outer part on the proximal AAo increases;5. all these hemodynamic parameters described above are asymmetrically distributed in dilated AAo and more parts of aorta would be affected as the AAo dilatation progresses.Conclusions: The study revealed that the diameter of ascending aortic can significantly influence the magnitude and distribution of the dynamics. There are altered flow patterns, pressure difference, WSS and OSI distribution features in bicuspid aortic valve patients with vascular dilatation. As the extent of aortic dilatation increases especially exceed 5.5cm,this study support the recent guideline that aortic replacement should be considered .


Introduction
The bicuspid aortic valve (BAV) is one of the common congenital heart anomalies in adults. BAV is an inherited form of heart disease in which two of the leaflets of the aortic valve fuse during embryonic development resulting in a two-leaflet valve (bicuspid valve) instead of the normal three-leaflet valve (trileaflet valve) 1,2 .
Previous studies have revealed two-leaflet valve will alter the physiological flow patterns in the ascending aorta (AAo)，and the abnormal pulsatile flow patterns have effects on the endothelial cells of the arterial wall, then activate the remodeling process of artery wall,which cause the dilatation of AAo 3,4,5 . Therefore，the threshold for aortic repair is lower in aortopathy with BAV than normal. In 2020 ACC/AHA guideline， whether surgery is required in BAV mainly depends on the diameter of the AAo， especially in those diameters exceed 5.0 cm. And lifelong serial evaluation (MRI,CT, echocardiography) is reasonable in BAV with diameter of AAo exceed 4.0cm 6 .
Although many studies have proved the coincidence between BAV and the occurrence of ascending aortic dilatation 7,8 , few studies have focused on the hemodynamic environments in different diameter of AAo. We think that it is very vital to investigate and present the hemodynamic environments in different diameter of AAo for BAV patients.This study will help to discover the hemodynamic changes with the different diameters of AAo and provide further understanding of the aortic dilatation in patients with BAV.

Patient
This study was approved by local ethics committee (2016047X, Beijing Anzhen Hospital, Capital Medical University). This patient is 51 years old male, whose information was collected on August 3, 2016 in Anzhen hospital. He has BAV with left/right cusp fusion and mild-stenosis as well as dilated ascending aortic with diameter of 4.5 cm by echocardiography. We confirmed the patient doesn't have history of hypertension, hyperlipidemia, coarctation of aorta, aortic dissection or Marfan syndrome.

Numerical model of the aorta
The numerical model of the aorta was established based on the MRI data (in-plane resolution of 512 by 512 pixels with a pixel size of 0.7 mm and slice thickness of 1.25 mm, total 600 images). This MRI was obtained by the Trio Tim 3.0 T MRI scanner of

Boundary conditions and flow models
Transient analysis was adopted to investigate the pulsatility of blood flow. No-slip boundary conditions were assigned at the wall in all cases. The numerical simulation was based on the three-dimensional incompressible Navier-Stokes equations and continuity equations: Where u ⃗ and p represent the fluid velocity vector and the pressure respectively.
ρ denotes the blood density( ρ = 1050 kg/m 3 ), and τ is stress tensor. It was assumed that blood is incompressible, and blood has same kinematic viscosity and density of Newtonian fluid 9,10 .
Time-varying velocity profile was imposed at the inlet of the aorta, based on the flow velocity waveforms that had been obtained from the in vivo measurements. The flow rates entering the brachiocephalic, left common carotid, and left subclavian arteries were specified to be 12%, 5% and 8% of the blood flow rate entering the aortic root, respectively 11,12 .
The average Reynolds numbers (Reave) based on the average flow velocity (Vave) at peak systole is 1149. The Womersley numbers(α) is 22.5 and the blood flow is assumed to be laminar. The calculation time step and cardiac cycle were set to 0.01s and 0.8s, respectively. To minimize the influence of initial flow conditions, all simulations were carried out by a commercial finite-volume-based CFD solver (Fluent14.5, ANSYS, Inc., USA) for six cardiac cycles to achieve a periodic solution, and the results presented here were obtained in the sixth cycle.

Derived Hemodynamic Parameters
Derived hemodynamic wall parameters include the velocity, pressure, WSS, and oscillatory shear index (OSI). WSS is an analytical factor used to describe the dynamic friction between the viscous fluid and the solid wall, which is caused by the lateral movement of the viscous fluid. The time-averaged wall shear stress (TAWSS) is obtained by averaging the WSS in a cardiac cycle and is a better representative of WSS.
OSI reflects the cyclic departure of the WSS (or velocity) vector from predominant direction of blood flow and is calculated as equation (4): where   is wall shear stress and T is one cardiac cycle. The OSI values vary from 0 to 0.5: 0 represents unidirectional flow, and 0.5 signifies complete oscillatory flow.
In order to describe the results intuitively, five featured moments selected from one cardiac cycle based on the velocity waveform of the aortic inlet, including the early systolic phase (t=0.10s), the peak systolic phase (t=0.17s), the late systolic phase (t=0.29s), the maximum regurgitation phase (t=0.43s) and stable diastolic phase(t=0.51s), respectively. They were showed in Fig.2.

Results
Flow velocity, patterns and ratio    AAo is dilated to the diameter of 5.5cm, the maximum velocity is obviously highest among models; 3. the area with high velocity is shifted to the left displaying a greater asymmetry with larger aorta.

Pressure
The largest pressure difference (based on the ascending aortic inlet pressure) occurs at peak systolic, when blood flow velocity is the highest. The pressure difference from aortic annulus to AAo is depicted in Fig.5 . As the AAo diameter increases, the area of high pressure in AAo increases accordingly, especially in diameter is 5.5cm.

Discussion
This study constructed four numerical model with different diameters of AAo using one BAV patient's MRI images, to investigated how the hemodynamic environments of AAo will vary under the same boundary conditions. It revealed that BAV patients with vascular dilatation have altered hemodynamic environments, especially with diameter of 5.5cm.Compared to the other models, M4 has shifted higher velocity region to outer region, increased areas of high pressure and low WSS in AAo, resulting in the higher OSI in outer which overtakes inner first.
The shifted velocity region represents the eccentric flow jet directed toward the wall of the proximal AAo, and the local pressure induced by turbulence of blood flow， which is an important determinant of vascular enlargement, aneurysm growth. In a study on aortic aneurysm, it found rupture occurred in regions of predicted flow recirculation where low WSS and thrombus deposition predominated, rather regions where have high pressure and WSS 14 . In this study, more low WSS areas can be showed in M4 in Fig.6(t=0.17s),we could guess that M4 are much more dangerous than the others. Meanwhile, elevated OSI levels are accompanied by low WSS serve as indicators for vascular injury together.
These results indicate the AAo with diameter of 5.5cm becomes more unstable, and the step-wise influence is more remarkable when compared 5.0cm to 5.5cm with 4.0cm to 4.5cm or 4.5cm to 5.0cm. The findings support the recent guideline by AHA/ACC 6 , which recommended the intervention to replace the aorta when its diameter >5.5cm, even if the BAV patients are asymptomatic. And in the real patients, the hemodynamic environments of AAo could be worse, because these hemodynamic parameters alternations are likely to lead to consecutive aortic wall remodeling, which gradually results in the expansion of the arterial vessels, and make the aorta wall thinner, the wall tension increased and vascular stiffness and elasticity decreased, which means the opportunity of aortic adverse events (dissection, rupture, or death) increases 15,16,17 .
Although novel indexes like ascending aortic length was developed to aid risk stratification 18  In patients with BAV and AAo dilatation, we could use CFD numerical simulation to make an assessment and find the hemodynamics in patients with abnormal point to predict disease progression timely. This could provide hemodynamic basis for surgery in the future. It will help to study the disease mechanism, timing of surgery, and determination of surgical options.

Declarations
Ethics approval and consent to participate Written informed consent was obtained from the subject for the publication of this study and any accompanying, in accordance with the regulations of the local ethics committee (2016047X, Beijing Anzhen Hospital, Capital Medical University).

Consent for publication
Consent for publication was obtained for the patient's data included in the study.

Availability of data and materials
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request, and most data generated or analyzed during this study are included in this published article and its supplementary information files.

Competing interests
The authors declare that they have no competing interests.