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

Computed Tomography-Derived 3D Modeling to Guide Sizing and Planning of Transcatheter Mitral Valve Interventions

A plethora of catheter-based strategies have been developed to treat mitral valve disease. Evolving 3-dimensional (3D) multidetector computed tomography (MDCT) technology can accurately reconstruct the mitral valve by means of 3-dimensional computational modeling (3DCM) to allow virtual implantation of catheter-based devices. 3D printing complements computational modeling and offers implanting physician teams the opportunity to evaluate devices in life-size replicas of patient-specific cardiac anatomy. MDCT-derived 3D computational and 3D-printed modeling provides unprecedented insights to facilitate hands-on procedural planning, device training, and retrospective procedural evaluation. This overview summarizes current concepts and provides insight into the application of MDCT-derived 3DCM and 3D printing for the planning of transcatheter mitral valve replacement and closure of paravalvular leaks. Additionally, future directions in the development of 3DCM will be discussed

Transcatheter Mitral Valve Replacement: Structural and Hemodynamic Analysis

Transcatheter mitral valve replacement (TMVR) is being developed to become a substitute therapy for surgery in prohibitive or high surgical risk patients to treat severe mitral regurgitation. A limited number of TMVR systems are under clinical evaluation. However, transcatheter mitral valve (TMV) long-term durability and hemodynamic performance is not known. TMV durability and hemodynamics must match with that of surgical bioprostheses for potential commercialization of TMVR. Experimental and computational approaches were used to find the leaflets’ three-dimensional anisotropic mechanical properties in a transcatheter Edwards SAPIEN 3 valve and a surgical Carpentier-Edwards PERIMOUNT Magna mitral valve and finite element (FE) simulations were conducted to obtain the stress distribution on both valves. Moreover, to visualize the flow field within the left heart, steady-state computational fluid dynamics (CFD) simulations were run. The FE simulations demonstrated that in a cardiac cycle, at peak systole, the highest stress value in the two bioprostheses was 4.75 and 16 MPa for the surgical and transcatheter heart valve, respectively. After studying the leaflet stress distributions and flow field, long-term durability may potentially be different between the two models. The results of CFD simulations could potentially show that TMVs with supra-annular positioning have a higher risk of leaflet thrombosis as opposed to the intra-annular position

Assessment and management of structural heart disease in an ageing population.

Structural heart disease interventions represent a rapidly evolving branch of percutaneous treatments to correct valvular lesions that were previously treated surgically, or simply not addressed. In the past decade, the therapeutic landscape for patients with degenerative aortic valve stenosis (AS) and secondary mitral regurgitation (MR) has changed dramatically. As transcatheter innovations continue to develop, cardiac physiologists and clinicians alike are challenged by the need to more accurately discriminate between those who will benefit from intervention, and those who will not. Interpreting valvular function in the setting of impaired contractile performance and/or poor arterial compliance is especially difficult. Hemodynamic loading conditions in these settings are often unique, and not adequately accounted for using traditional cardiac imaging techniques. Load independent assessment of contractile function requires the simultaneous measurement of left ventricular (LV) pressure, volume and flow in order to determine the relationship between these parameters at various points in the cardiac cycle. Our work incorporates advances in cardiac magnetic resonance and echocardiography imaging techniques to allow better non-invasive assessment of ventricular mechanics and ventricular-vascular interactions in response to structural aortic and mitral valve interventions. We have devised precise and accurate non-invasive tools to quantify LV and aortic pressure, LV volume and aortic flow, and have coalesced this data to determine the LV pressure-volume and aortic pressure-flow relationships in patients with degenerative AS and secondary MR. It is our intention that the development of high-quality non-invasive data on ventricular contractility and ventricular-vascular coupling, will provide a better platform to evaluate cardiovascular performance in those with valvular heart disease

Energetic and Hemodynamic Characteristics of Paravalvular Leak Following Transcatheter Aortic Valve Replacement

Transcatheter aortic valve replacement (TAVR) has emerged as an alternative treatment for inoperable and high risk patients with severe symptomatic aortic stenosis. TAVR short and medium term results are very promising, however paravalvular leak (PVL) post-TAVR still represents a significant complication. PVL post-TAVR is shown to be an independent predictor of short-term and long-term mortality. Despite, its importance and prevalence, with a wide range of reported incidences, only few studies addressed the PVL after TAVR. In the present study, first, the mathematical lumped parameter model is used to model the simplified circulatory system in presence of PVL and to evaluate the performance of TAVR by computing the variation of the left ventricle stroke work (LVSW) under several pre-TAVR and post-TAVR conditions. Results show that in a large majority of cases, TAVR significantly reduced LVSW. However, in cases with pre-existing aortic stenosis conditions with trace/mild aortic regurgitation, it did not significantly reduce LVSW or even led to an increase. Second, a three-dimensional (3D) computational fluid dynamics (CFD) simulation is performed in order to investigate the effect of PVL on the diastolic flow-field characteristics post-TAVR. Results show that PVL leads to significant disturbances in blood flow, which characterized by high speed jets, coherent structures and markedly elevated shear stress on both sides of the implanted aortic leaflets, which could promote a more rapid degeneration of the valve leaflets. Results could be useful in understating the hemodynamics of PVL post-TAVR and estimating some important parameters, which could not be obtained during the medical assessment (e.g. wall shear stress). Also, they could be a help in the process of choosing the appropriate valve for TAVR procedure, based on comparing the pre and post TAVR different scenarios

Pressure, volume and flow: studies of ventricular, valvular and vascular haemodynamics in the human cardiovascular system

BACKGROUND: Pressure, volume and flow form the three pillars of quantification in cardiovascular physiology. Newer approaches to their assessment provide opportunities to further assess their interactions. METHODS: 4 projects were conducted. Project 1 evaluated mechanisms of myocardial oxygen supply:demand imbalance in 3682 healthy volunteers using aortic pressure-time integrals measured with radial arterial tonometry (AT) and generalised transfer function. Project 2 evaluated the acute left ventricular (LV) contractile response to transcatheter mitral valve replacement (TMVR) in 9 high-risk patients. Intraoperative left and right heart catheterisation, 3D transoesophageal echocardiography and pressure-volume analyses were performed at baseline, immediately following TMVR and late post-TMVR. Project 3 mathematically evaluated the current definition of paradoxical low-flow, low-gradient aortic stenosis (PLFLGAS) by deriving an equation for LV end-diastolic volume in terms of mean pressure gradient, aortic valve area and LV ejection fraction. Project 4 evaluated feasibility and reproducibility of non-invasive LV pressure-volume and aortic pressure-flow quantification in 21 patients who underwent simultaneous AT and cardiovascular magnetic resonance imaging (CMRI). RESULTS: In project 1, more unfavourable age-related myocardial oxygen supply:demand profiles were seen in women than men, driven by sex differences in arterial aging, pressure wave reflection and cardiac ejection duration. In project 2, TMVR caused acute LV dilatation and reduction in contractility, but changes returned to baseline by a median time of 17 minutes. LV end-diastolic pressure and forward stroke volume were preserved at the three study timepoints. In project 3, the derived LV end-diastolic volume equation incorporating defining criteria for PLFLGAS could not mathematically resolve the combined input parameters based on current definitions, raising concerns regarding the internal consistency of the consensus definition. In project 4, non-invasive LV pressure-volume and aortic pressure-flow analyses, using simultaneous AT and CMRI, were feasible, reproducible and showed good and appropriately directed correlation to more conventional markers of cardiovascular function. CONCLUSIONS: Newer approaches to pressure, volume and flow assessment can lead to better understanding of the interactions between the ventricles, valves and vasculature in states of health and disease

Hot Topics in Echocardiography

Echocardiography is still the most used imaging technique for the evaluation of cardiac anatomy and function and today it plays an essential role in daily decision making. The echocardiographic technology and its applications have widely developed in the last years leading to a better diagnostic accuracy. On the other hand echocardiography specialists have new clinical questions to answer. Echocardiography meets the growing need for non-invasive imaging in the expanding heart failure population and during structural heart interventions. The new percutaneous therapies need, a precise evaluation of cardiac dimensions and a complete understanding of the spatial relationships between cardiac structures. Echocardiography is of paramount importance both during the patient evaluation and guiding the procedure. This book tries to give an in depth evaluation about the specific issues that a modern cardiovascular imaging specialist is asked to answer nowadays

Biomechanics of transapical mitral valve implantation

2014 Summer.Includes bibliographical references.Heart disease is the number one killer in the United States. Within this sector, valve disease plays a very important role: Approximately 6% of the entire population has either prolapse or stenosis of the mitral valve and this percentage only increases when looking only at the elderly population. Transapical mitral valve implantation has promised to be a potential therapy for high-risk patients presenting with MR; however it is unclear what the best method of securing a valve within the mitral annulus may be to provide a safe and efficient valve replacement. The objective of this research is to study and understand the underlying biomechanics of fixation of transapical mitral valves within the native mitral annulus. Two different transapical mitral valve prosthesis designs were tested: One valve design has a portion of the leaflets atrialized such that it has a shorter stent height and the valve itself sits within the native annulus, the other design is not atrialized and protrudes further into the left ventricle. The valves were implanted in a left heart simulator to assess leaflet kinematics and hemodynamics using high speed imagery and particle image velocimetry techniques. An in vitro passive beating heart model was then used to assess the two different fixation methods (namely, anchored at the apex vs. anchored at the annulus) with respect to paravalvular regurgitation. Leaflet kinematics and hemodynamics revealed proper leaflet coaptation and acceptable pressure gradients and inflow fillings; however, both designs yielded elevated turbulence stresses within the ventricle. At 60 beats per minute, leaflet opening and closing times were both under 0.1 seconds, max Reynolds shear stresses were between 40 and 60 N/m2 and maximum velocities were approximately 1.4 m/s. Assessment of the different fixation methods during implantation revealed the superiority of the atrialized valve when anchored at the annulus (p<0.05), but showed no such comparison during tethered implantation. In addition to the results of statistical testing, observations show that the importance of the relationship between ventricular stent height and fixation method compared with native anatomy plays an important role in overall prosthesis function regardless of implantation method

The development of a transcatheter mitral valve

Transcatheter heart valve replacements avoid the main risks associated with conventional open heart surgery and so is the preferred replacement technique for high-risk patients with aortic stenosis. Due to technical challenges, adaptation for the mitral position is still in early stages of research. The aim of this project was to develop the novel UCL transcatheter mitral valve (TMV) based on a prior conceptual design. The UCL TMV is designed to treat mitral regurgitation (MR) and is based on the UCL transcatheter aortic valve (TAV) which is retrievable, repositionable and has enhanced anchoring and sealing. The UCL TMV leaflets, which ensure unidirectional blood flow, are novel because they mimic native mitral valve morphology by having two leaflets, being D-shaped and conical. Their optimal design criterion and two key design parameters were identified using a failure mode and effects analysis and numerical simulations were used to select a design with acceptable stress levels and maximum coaptation area. The optimal leaflets were prototyped as a surgical valve to evaluate their performance against available commercial device designs and were then incorporated in TMV prototypes, and assessed for hydrodynamic performance, both of which exceeded international standard requirements. Durability assessment of the TMV is ongoing and very encouraging; currently withstanding > 80 million cardiac cycles. In conclusion, the results presented and ongoing durability assessments for the UCL TMV indicate it could be a new and effective treatment option for severe MR in high-risk patients whom are declined surgical interventions