In normal hearts, blood passes from the left ventricle to the aorta through a tunnel called the left ventricular outflow tract (LVOT). Discrete subaortic stenosis (DSS) is a congenital heart disease that results in the formation of a fibro-membranous tissue at the base of the LVOT. This tissue membrane prevents blood flow from leaving the heart. Heart surgery is the only current option to manage the disease, but up to 30% of patients have an aggressive form of DSS in which the membrane recurs, and these patients may have to undergo further cardiothoracic surgery. The inability to elucidate the root cause of membrane formation has hampered the development of effective treatments and diagnosis methods.
While the reasons for the formation of the membrane remain to be elucidated, ventricles with anatomical anomalies seem to be more prone to DSS. Left ventricles (LVs) with a steep aortoseptal angle (AoSA) for example are associated with a higher prevalence of DSS than normal ventricles. This observation motivates new studies aimed at characterizing the flow abnormalities present in abnormal ventricle anatomies and their effects on the biology of the endocardial cells lining the ventricle.
In collaboration with scientists at Rice University, Texas Children's Hospital and Baylor College of Medicine, our laboratory has developed new computational and expeirmental tools to quantify these flow abnormalities. This work has the potential to help prevent fibrotic lesions by identifying targets in advance. That ability could also help treat other fibrotic cardiovascular diseases associated with altered flow.
In order to investigate experimentally the ventricular hemodynamic abnormalities potentially driving DSS, a test chamber was developed by our lab to replicate the flow conditions of a morphologically normal and abnormal (steep AoSA) LV in terms of aortic pressure and cardiac output. The ventricular chamber is modular, allowing flow measurements to be made for two different AoSA values: 130° (normal) and 110° (abnormal/steepened). The flow loop within which the chamber is placed is driven by a programmable pulse generator, which pumps air into the bottom of the chamber, deforming a compliant membrane and thus ejecting working fluid. The test section consists of a series of optically-accessible acrylic components which accommodate both a mechanical bileaflet valve and a native tissue valve mounted in the mitral and aortic position, respectively. The setup will soon be used along with a particle image velocimetry (PIV) system to measure the flow characteristics and wall shear stress (WSS) in the LVOT region of interest throughout the cardiac cycle.
Our group has recently evidenced the applicability of a computational strategy to the characterization of the hemodynamic impact of a steep AoSA in a contracting human LV reconstructed from multiple-slice cine magnetic resonance images. Three cases were considered: 1) normal AoSA, 2) steepened AoSA, and 3) steepened AoSA with a DSS membrane. The obstruction was represented as a thin semi-lunar membrane attached at the base of the LVOT. Two-way coupling between the deforming LV and the flow was achieved in ANSYS 18 (ANSYS Inc). LV wall mechanics were modeled using an isotropic linear elastic formulation with mechanical properties representative of the average passive/active properties obtained from the literature. LV ejection was simulated by imposing a time-dependent pressure condition on the LV wall and a wall condition on the mitral valve orifice. While the steepened AoSA generated the same LVOT flow structure as the normal AoSA, it resulted in a 6% increase in LVOT velocity at peak ejection. The presence of the DSS lesion generated substantial flow alterations characterized by a recirculation bubble immediately downstream of the lesion, increased LVOT jet skewness toward the lower wall and stenotic conditions marked by a 12% increase in maximum LVOT velocity at peak ejection. In addition, the steepened AoSA resulted in WSS abnormalities both upstream and downstream of the site prone to DSS lesion formation (24% increase in region 1, 22% decrease in region 2, vs. normal LV). These preliminary models demonstrate the feasibility and benefits of computational flow techniques to CFD for the hemodynamic characterization of DSS, and suggest the existence of supra-physiologic WSS levels on the endocardial region prone to DSS lesion formation.
A two-dimensional patient-specific left ventricle model was constructed from cine MRI data. Using this data, the complex motion of the ventricular wall can be precisely simulated. Abnormal blood flow patterns in the presence of a changing AoSA and DSS, as well as key quantities thought to lead to membrane formation, can be characterized. Furthermore, the specific implementation of the myocardial wall deformation data allows for the input of other patient-specific geometries at the valve area. This hybrid generalized-patient-specific method effectively means that multiple patient-specific geometries can be imaged, constructed, and simulated within a very short amount of time and without the need for extensive preprocessing. With the implementation of fluid-structure interaction modeling strategies, our group is experimenting with the addition of aortic valve leaflet geometries and mechanics. This innovating approach will not only allow for the elucidation of intraventricular hemodynamics, but also examine forces which cause secondary diseases associated with DSS.
|2D flow simulations showing vorticity and velocity fields in: a normal LV (left), a LV with a steep AoSA (middle), and a LV with DSS (right)|
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 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 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.
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.
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.
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) 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) 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.