Biomechanical analysis of hypoplastic left heart syndrome and calcific aortic stenosis: a statistical and computational study

2021 Fall.Includes bibliographical references.Cardiovascular diseases are a leading cause of death in the United States. In this dissertation, a congenital heart disease (CHD) and a valvular disease are discussed. CHDs occur in ~5% of live births. Structural CHDs can be complex and difficult to treat, such as hypoplastic left heart syndrome (HLHS) in which the left ventricle is generally underdeveloped, representing ~9% of all congenital heart diseases. Calcific aortic stenosis is one of the most common valvular diseases in which valves thicken and stiffen, and in some cases nodular deposits form, limiting valve function that may result in flow regurgitation and outflow obstruction. The overarching hypothesis of this research is that patient-specific heart geometry and valve characteristics are linked to cardiovascular diseases and may play an important role in regulating hemodynamics within the heart. This hypothesis is studied through three specific aims. In specific aim 1, a computational fluid dynamics study was developed to quantify the hemodynamic characteristics within the right ventricles of healthy fetuses and fetuses with HLHS, using 4D patient-specific ultrasound scans. In these simulations, we find that the HLHS right ventricle exhibits a greater cardiac output than normal; yet, hemodynamics are relatively similar between normal and HLHS right ventricles. Overall, this study provides detailed quantitative flow patterns for HLHS, which has the potential to guide future prevention and therapeutic interventions, while more immediately providing additional functional detail to cardiologists to aid in decision making. The specific aim 2 is a comprehensive review in which we highlight underlying molecular mechanisms of acquired aortic stenosis calcification in relation to hemodynamics, complications related to the disease, diagnostic methods, and evolving treatment practices for calcific aortic stenosis and, bioprosthetic or native aortic scallop intentional laceration (BASILICA) procedure to free coronary arteries from obstruction. In specific aim 3, we use statistical trends and relationships to identify the role of patient-specific aortic valve characteristics in post-BASILICA coronary obstruction. The findings of this study shows that in addition to direct anatomical measurements of the aortic valve, the aspect ratios of the anatomical features are important in determining the cause of post-BASILICA coronary obstruction. The overall significance of this dissertation is that computational and statistical analysis of patient's specific flow hemodynamics and geometric characteristics can provide more insight into the cardiovascular disease and treatment approaches which can ultimately assist surgeons with procedural planning

Biomechanical analysis of aortic valve calcification and post-procedural paravalvular leak

2016 Spring.Includes bibliographical references.Cardiovascular disease is a leading cause of death accounted for 17.3 million people annually. Aortic valve calcification (AVC) and stenosis are the most common diseases among valvular heart diseases. Severe AVC and stenosis will need the standard surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR) for patients who are at high risk for open heart surgery. Post-procedural paravalvular leak (PVL) is a common complication which occurs around the implanted stent in a significant population of patients who undergo valve replacement, requiring significant interventions. The overarching hypothesis of this research is that anatomic characteristics of patients’ native aortic valve play an important role in both calcification processes and post-procedural PVL occurrence. This hypothesis is studied through two specific Aims. Aim 1 was designed to determine what anatomic and biological parameters as well as hemodynamic factors are associated with severity of aortic valve calcification. In this aim, patient-specific geometric characteristics were extracted using 3D image reconstruction of patient CT data, and their relation with cusp specific calcification was evaluated using multiple regression analysis. The results of this analysis indicated that severity of calcification is significantly correlated with coronary calcification as well as the size of sinus of valsava and sinotubular junction (all p-values<0.05). In Aim 2, we investigated the relationship among patients’ calcification level and anatomic parameters of their native aortic valve as well as the risk of post-procedural PVL occurrence. Using a logistic regression analysis model we show that large calcification deposition (p-value<0.001) and large ratio of sinus of valsava to annulus (p-value<0.02) of native aortic valve can predict probability of post-procedural PVL occurrence. The overall significance of this study is that bioengineering analysis of pre-procedural CT data can be utilized towards better TAVR planning as well as basic understanding of the pathogenesis of AVC

Effect of Left and Right Coronary Flow Waveforms on Aortic Sinus Hemodynamics and Leaflet Shear Stress: Correlation with Calcification Locations

Coronary flow induces hemodynamic alterations in the aortic sinus region. The objectives of this study are to: (1) investigate the differences among sinus hemodynamics and leaflet wall shear stresses engendered by the left versus right versus non-coronary flow and (2) correlate respective wall shear stresses with leaflet calcification in patients. A left heart simulator flow loop with a tunable coronary circuit provided physiological coronary flow waveforms corresponding to the left coronary cusp case (LCC), right coronary cusp case (RCC), and non-coronary cusp case (NCC). High spatio-temporal resolution particle image velocimetry was conducted to quantify leaflet wall shear stress and sinus vorticity fields and to measure aortic leaflet tip kinematics. Thirty-one patients with severe calcific aortic valve disease were segmented from CT data for the calcific volumes in their respective left, right, and non-coronary cusps. Leaflet tip position during systole shows the RCC has a wider leaflet opening compared to LCC and NCC. Velocity and vorticity fields combined with leaflet position data show that sinus vorticity is diminished (peak ~ 43 s−1) in the LCC while RCC and NCC maintain high vorticity (~ 1200 and ~ 950 s−1 respectively). WSS magnitudes greater than 0.3 Pa show 20 and 81% greater occurrences in the LCC and RCC respectively compared to NCC. Significant differences [X2 (2, n = 31) = 7.31, p = 0.0258] between the calcification levels in each cusp of the patient population. Coronary flow differences between LCC, RCC, and NCC show significant impact on leaflet kinematics and sinus flow hemodynamics. Clinical data correlations of the coronary flow cases indicate the left coronary cusp has a higher likelihood of calcification compared to the right

Effect of Left and Right Coronary Flow Waveforms on Aortic Sinus Hemodynamics and Leaflet Shear Stress: Correlation with Calcification Locations

Coronary flow induces hemodynamic alterations in the aortic sinus region. The objectives of this study are to: (1) investigate the differences among sinus hemodynamics and leaflet wall shear stresses engendered by the left versus right versus non-coronary flow and (2) correlate respective wall shear stresses with leaflet calcification in patients. A left heart simulator flow loop with a tunable coronary circuit provided physiological coronary flow waveforms corresponding to the left coronary cusp case (LCC), right coronary cusp case (RCC), and non-coronary cusp case (NCC). High spatio-temporal resolution particle image velocimetry was conducted to quantify leaflet wall shear stress and sinus vorticity fields and to measure aortic leaflet tip kinematics. Thirty-one patients with severe calcific aortic valve disease were segmented from CT data for the calcific volumes in their respective left, right, and non-coronary cusps. Leaflet tip position during systole shows the RCC has a wider leaflet opening compared to LCC and NCC. Velocity and vorticity fields combined with leaflet position data show that sinus vorticity is diminished (peak ~ 43 s21) in the LCC while RCC and NCC maintain high vorticity (~ 1200 and ~ 950 s21 respectively). WSS magnitudes greater than 0.3 Pa show 20 and 81% greater occurrences in the LCC and RCC respectively compared to NCC. Significant differences [X2 (2, n = 31) = 7.31, p = 0.0258] between the calcification levels in each cusp of the patient population. Coronary flow differences between LCC, RCC, and NCC show significant impact on leaflet kinematics and sinus flow hemodynamics. Clinical data correlations of the coronary flow cases indicate the left coronary cusp has a higher likelihood of calcification compared to the right.</p