Mechanobiology of Bicuspid Aortic Valve Aortopathy

The bicuspid aortic valve (BAV)

The bicuspid aortic valve (BAV) is the most common congenital valvular defect and is present in 2-3% of the general population. While the BAV is essentially characterized by the presence of two leaflets, it exists in different morphologic phenotypes. The most prevalent type-I morphology features two cusps of unequal size (resulting from the fusion of two of the three leaflets), and a fibrous raphe at the location of congenital fusion. While 71% of type-I BAVs result from the fusion between the left- and right-coronary leaflets (LR subtype), 15% feature right- and non-coronary cusp fusion (RN subtype) and 3% present with non- and left-coronary cusp fusion (NL subtype). Downstream of the valve is the ascending aorta that stems from the sinotubular junction and extends to the aortic arch.

 

BAV aortopathy

Patients with a BAV often experience a normal life. However, the BAV is a major risk factor for aortic disorders such as aortic dilation, a disease which consists of the abnormal enlargement of the ascending portion of the aorta. In BAV patients, this condition typically develop faster than in individuals with a normal valve. If left untreated, BAV dilation can lead to dissection and ultimately rupture. While both genetics and hemodynamics have been identified as potential drivers of aortic dilation, the exact etiology remains largely unkown, which has hampered the development of robust clinical guidelines and treatment options.

 

Aorta hemodynamics

 
Experimental studies

To measure the pulsatile flow characteristics in TAV and BAV aortas, we designed a left-heart simulator capable of replicating the flow conditions of the left heart in terms of aortic and ventricular pressures and cardiac output. The flow loop is driven by a programmable pulse generator and a series of diaphragm accumulators mimicking ventricular function. The compliance and resistance of the vasculature are replicated using adjustable compliance and resistance modules. The test section consists of an optically accessible valve-aorta chamber capable of accomodating native tissue aortic valves and an anatomically realistic and compliant aorta phantom. This setup was used along with a PIV system (LaVision Inc) to measure the flow characteristics in the aorta downstream of a TAV and three BAV morphotypes (LR: left-right coronary leaflet fusion, NL: non-left-coronary leaflet fusion, RN: right-non-coronary leaflet fusion). The measurements reveal the alignment of the TAV jet parallel to the axis of the aorta and the skewness of the BAV jets toward the aortic wall convexity (LR- and NL-BAV cases). The BAV jet skewness also increases the degree of flow rotationality between the aortic root and the middle section of the ascending aorta.

 
Computational studies

Our group has also designed unified valve-aorta FSI models to model the interactions between valve leaflets and aortic flow. These sophisticated models have been used to quantify for the first time global and local hemodynamic differences between TAV and BAV aorta flow patterns. The simulations reveal the increased flow skewness generated by type-I BAVs relative to the TAV, as well as the dependence of the degree of jet skewness on the BAV morphotype. As already observed clinically using PC-MRI, the BAVs also generate peripheral streamlines that wrap around the central orifice jet to generate right-handed helical flow patterns.

FSI simulations in TAV and BAV aortas

Aorta mechanobiology

The ascending aorta (AA) downstream of a BAV is prone to asymmetric dilation and dissection. Interestingly, the site of dilation seems to correlate with the type of BAV leaflet fusion. For example, BAVs with left-right coronary cusp fusion promote dilation in the convexity of the AA wall. This apparent correlation suggests a role for hemodynamic stress abnormalities in the development of BAV aortopathy. As a first step toward the investigation of the potential causality between BAV aorta hemodynamics and asymmetric aortic dilation, our lab has quantified and compared the remodeling response of aortic wall tissue subjected ex vivo to the native wall shear stress (WSS) present in the convexity and concavity of TAV and BAV AAs. The results indicated the particular susceptibility of the WSS environment present on the convexity of the BAV AA to promote tissue remodeling via MMP-9 expression and activation.

Did you know?

  • The cardiovascular system

    The cardiovascular system consists of the heart, the blood vessels, and the blood. Its function is to transport oxygen, nutrients, hormones, and cellular waste products throughout the body.

  • The heart

    The heart is the pump that drives blood flow throughout the cardiovascular system. It weighs about 300 grams and beats 70 times per minute. It pumps about 5 liters of blood every minute. The two ventricles of the heart pump blood to the lungs, and to the different organs and tissues in the body, respectively.

  • The aortic valve

    The aortic valve achieves unidirectional blood flow between the left ventricle and the aorta. It normally consists of three leaflets that open during systole and close during diastole, under the pressure difference established between the ventricle and the aorta.

  • What is a bicuspid aortic valve?

    The bicuspid aortic valve is the most common congenital valvular defect and affects 2% of the population. While a normal aortic valve consists of three leaflets, the bicuspid aortic valve forms with only two, as a result of fusion between two adjacent leaflets.

  • What is calcific aortic valve disease?

    Calcific aortic valve disease is the most common aortic valve disorder. It affects 4% of adults over 65 years of age and consists of the formation of calcific lesions on the valve leaflets.

  • What is discrete subaortic stenosis?

    Discrete subaortic stenosis is a type of constriction that is caused by the presence of a fibrous ring below the aortic valve, anywhere between the aortic valve and the mitral valve. It results in a restricted outflow from the left ventricle into the aorta.

  • Computational fluid dynamics (CFD)

    Computational fluid dynamics (CFD) is the science of predicting fluid flow, heat transfer, mass transfer, chemical reactions and related phenomena by solving the mathematical equations which govern these processes using a numerical approach.

  • Particle image velocimetry (PIV)

    Particle image velocimetry (PIV) is an optical method of flow visualization used to obtain instantaneous velocity measurements in a flow field. Tracer particles are used to seed the flow and are illuminated using a laser sheet. The motion of the seeding particles is used to calculate the local flow velocity field.

© 2018 MSCBL | All rights reserved