Lucia Mirabella

Fontan hemodynamics from 100 patient-specific cardiac magnetic resonance studies: a computational fluid dynamics analysis.

OBJECTIVES This study sought to quantify average hemodynamic metrics of the Fontan connection as reference for future investigations, compare connection types (intra-atrial vs extracardiac), and identify functional correlates using computational fluid dynamics in a large patient-specific cohort. Fontan hemodynamics, particularly power losses, are hypothesized to vary considerably among patients with a single ventricle and adversely affect systemic hemodynamics and ventricular function if suboptimal. METHODS Fontan connection models were created from cardiac magnetic resonance scans for 100 patients. Phase velocity cardiac magnetic resonance in the aorta, vena cavae, and pulmonary arteries was used to prescribe patient-specific time-averaged flow boundary conditions for computational fluid dynamics with a customized, validated solver. Comparison with 4-dimensional cardiac magnetic resonance velocity data from selected patients was used to provide additional verification of simulations. Indexed Fontan power loss, connection resistance, and hepatic flow distribution were quantified and correlated with systemic patient characteristics. RESULTS Indexed power loss varied by 2 orders of magnitude, whereas, on average, Fontan resistance was 15% to 20% of published values of pulmonary vascular resistance in single ventricles. A significant inverse relationship was observed between indexed power loss and both systemic venous flow and cardiac index. Comparison by connection type showed no differences between intra-atrial and extracardiac connections. Instead, the least efficient connections revealed adverse consequences from localized Fontan pathway stenosis. CONCLUSIONS Fontan power loss varies from patient to patient, and elevated levels are correlated with lower systemic flow and cardiac index. Fontan connection type does not influence hemodynamic efficiency, but an undersized or stenosed Fontan pathway or pulmonary arteries can be highly dissipative.

Geometric characterization of patient-specific total cavopulmonary connections and its relationship to hemodynamics.

Total cavopulmonary connection (TCPC) geometries have great variability. Geometric features, such as diameter, connection angle, and distance between vessels, are hypothesized to affect the energetics and flow dynamics within the connection. This study aimed to identify important geometric characteristics that can influence TCPC hemodynamics. Anatomies from 108 consecutive patients were reconstructed from cardiac magnetic resonance (CMR) images and analyzed for their geometric features. Vessel flow rates were computed from phase contrast CMR. Computational fluid dynamics simulations were carried out to quantify the indexed power loss and hepatic flow distribution. TCPC indexed power loss correlated inversely with minimum Fontan pathway (FP), left pulmonary artery, and right pulmonary artery diameters. Cardiac index correlated with minimum FP diameter and superior vena cava (SVC) minimum/maximum diameter ratio. Hepatic flow distribution correlated with caval offset, pulmonary flow distribution, and the angle between FP and SVC. These correlations can have important implications for future connection design and patient follow-up.

Applications of variational data assimilation in computational hemodynamics

The development of new technologies for acquiring measures and images in order to investigate cardiovascular diseases raises new challenges in scientific computing. These data can be in fact merged with the numerical simulations for improving the accuracy and reliability of the computational tools. Assimilation of measured data and numerical models is well established in meteorology, whilst it is relatively new in computational hemodynamics. Different approaches are possible for the mathematical setting of this problem. Among them, we follow here a variational formulation, based on the minimization of the mismatch between data and numerical results by acting on a suitable set of control variables. Several modeling and methodological problems related to this strategy are open, such as the analysis of the impact of the noise affecting the data, and the design of effective numerical solvers. In this chapter we present three examples where a mathematically sound (variational) assimilation of data can significantly improve the reliability of the numerical models. Accuracy and reliability of computational models are increasingly important features in view of the progressive adoption of numerical tools in the design of new therapies and, more in general, in the decision making process of medical doctors.

Computational simulations of flow dynamics and blood damage through a bileaflet mechanical heart valve scaled to pediatric size and flow.

Despite pressing needs, there are currently no FDA approved prosthetic valves available for use in the pediatric population. This study is performed for predictive assessment of blood damage in bileaflet mechanical heart valves (BMHVs) with pediatric sizing and flow conditions. A model of an adult-sized 23 mm St. Jude Medical (SJM) Regent(™) valve is selected for use in simulations, which is scaled in size for a 5-year old child and 6-month old infant. A previously validated lattice-Boltzmann method (LBM) is used to simulate pulsatile flow with thousands of suspended platelets for cases of adult, child, and infant BMHV flows. Adult BMHV flows demonstrate more disorganized small-scale flow features, but pediatric flows are associated with higher fluid shear stresses. Platelet damage in the pediatric cases is higher than in adult flow, highlighting thrombus complication dangers of pediatric BMHV flows. This does not necessarily suggest clinically important differences in thromboembolic potential. Highly damaged platelets in pediatric flows are primarily found far downstream of the valve, as there is less flow recirculation in pediatric flows. In addition, damage levels are well below expected thresholds for platelet activation. The extent of differences here documented between the pediatric and adult cases is of concern, demanding particular attention when pediatric valves are designed and manufactured. However, the differences between the pediatric and adult cases are not such that development of pediatric sized valves is untenable. This study may push for eventual approval of prosthetic valves resized for the pediatric population. Further studies will be necessary to determine the validity and potential thrombotic and clinical implications of these findings.

Energetic Implications of Vessel Growth and Flow Changes Over Time in Fontan Patients

BACKGROUND As patients with a single-ventricle physiology age, long-term complications inherent to this population become more evident. Previous studies have focused on correlating anatomic and hemodynamic performance, but there is little information of how these variables change with time. Vessel growth and flow rate changes were quantified using cardiac magnetic resonance and their effects on hemodynamics were assessed, which could affect the long-term outcome. METHODS Forty-eight patients with a lateral tunnel or extracardiac conduit Fontan who underwent two cardiac magnetic resonance scans (average interval, 5.1 ± 2.3 years) were studied. Total cavopulmonary connection anatomic and flow variables were reconstructed and normalized to body surface area(1/2). Total cavopulmonary connection hemodynamic efficiency (indexed power loss) was obtained through computational fluid dynamic modeling. RESULTS Absolute vessel diameters increased with time, normalized diameters decreased, and vessel mean flow rates remained unchanged. Indexed power loss changed significantly in the cohort, as well as in patients in whom the minimum normalized left pulmonary artery decreased. Age at first scan and connection type (lateral tunnel or extracardiac conduit) were not associated with changes in indexed power loss. CONCLUSIONS We present the largest serial cardiac magnetic resonance Fontan cohort to date. Although flow rates increased proportionally to body surface area, vessel diameters did not match somatic growth. As a result, energy losses increased significantly with time in the cohort analyzed.

Fontan Pathway Growth: A Quantitative Evaluation of Lateral Tunnel and Extracardiac Cavopulmonary Connections Using Serial Cardiac Magnetic Resonance

BACKGROUND Typically, a Fontan connection is constructed as either a lateral tunnel (LT) pathway or an extracardiac (EC) conduit. The LT is formed partially by atrial wall and is assumed to have growth potential, but the extent and nature of LT pathway growth have not been well characterized. A quantitative analysis was performed to evaluate this issue. METHODS Retrospective serial cardiac magnetic resonance data were obtained for 16 LT and 9 EC patients at 2 time points (mean time between studies, 4.2 ± 1.6 years). Patient-specific anatomies and flows were reconstructed. Geometric parameters of Fontan pathway vessels and the descending aorta were quantified, normalized to body surface area (BSA), and compared between time points and Fontan pathway types. RESULTS Absolute LT pathway mean diameters increased over time for all but 2 patients; EC pathway size did not change (2.4 ± 2.2 mm vs 0.02 ± 2.1 mm, p < 0.05). Normalized LT and EC diameters decreased, while the size of the descending aorta increased proportionally to BSA. Growth of other cavopulmonary vessels varied. The patterns and extent of LT pathway growth were heterogeneous. Absolute flows for all vessels analyzed, except for the superior vena cava, proportionally to BSA. CONCLUSIONS Fontan pathway vessel diameter changes over time were not proportional to somatic growth but increases in pathway flows were; LT pathway diameter changes were highly variable. These factors may impact Fontan pathway resistance and hemodynamic efficiency. These findings provide further understanding of the different characteristics of LT and EC Fontan connections and set the stage for further investigation.

Effect of Fontan geometry on exercise haemodynamics and its potential implications

Objective Exercise intolerance afflicts Fontan patients with total cavopulmonary connections (TCPCs) causing a reduction in quality of life. Optimising TCPC design is hypothesised to have a beneficial effect on exercise capacity. This study investigates relationships between TCPC geometries and exercise haemodynamics and performance. Methods This study included 47 patients who completed metabolic exercise stress test with cardiac magnetic resonance (CMR). Phase-contrast CMR images were acquired immediately following supine lower limb exercise. Both anatomies and exercise vessel flow rates at ventilatory anaerobic threshold (VAT) were extracted. The vascular modelling toolkits were used to analyse TCPC geometries. Computational simulations were performed to quantify TCPC indexed power loss (iPL) at VAT. Results A highly significant inverse correlation was found between the TCPC diameter index, which factors in the narrowing of TCPC vessels, with iPL at VAT (r=−0.723, p<0.001) but positive correlations with exercise performance variables, including minute oxygen consumption (VO2) at VAT (r=0.373, p=0.01), VO2 at peak exercise (r=0.485, p=0.001) and work at VAT/weight (r=0.368, p=0.01). iPL at VAT was negatively correlated with VO2 at VAT (r=−0.337, p=0.02), VO2 at peak exercise (r=−0.394, p=0.007) and work at VAT/weight (r=−0.208, p=0.17). Conclusions Eliminating vessel narrowing in TCPCs and reducing elevated iPL at VAT could enhance exercise tolerance for patients with TCPCs. These findings could help plan surgical or catheter-based strategies to improve patients’ exercise capacity.

MRI-based Protocol to Characterize the Relationship Between Bicuspid Aortic Valve Morphology and Hemodynamics

Bicuspid aortic valve (BAV) is the most common congenital heart defect and can lead to severe complications. Many studies have been conducted to evaluate the potential of geometric and hemodynamic biomarkers to predict BAV-related aortopathy. This work proposes a novel semi-automatic protocol to characterize geometry and hemodynamics of aorta and aortic valve based on 2D cine and 4D flow MRI data. The protocol was applied to 12 BAV and 12 control subjects. Statistical differences between the groups were identified and linear regression models were investigated to elucidate the potential of this protocol to investigate the risk of disease progression. Statistical differences between the groups were found for orifice eccentricity, aorta diameter, velocity, jet angle and flow displacement. Key findings of the regression analysis include the association in the proximal ascending aorta between aorta diameter and mean velocity (negative), jet angle (positive) and flow displacement (positive), in the combined cohort. Positive association between flow displacement in the proximal aorta and orifice jet angle in TAV subjects was found. This study represents a pilot application of a protocol for standardized assessment of aortic geometry and hemodynamics associated with BAV disease. Its limited need for user input is advantageous for large cohort studies.

Valve mediated hemodynamics and their association with distal ascending aortic diameter in bicuspid aortic valve subjects: Valve Mediated Hemodynamics in BAV Patients

Valve mediated hemodynamics have been postulated to contribute to pathology of the ascending aorta (AAo). The objective of this study is to assess the association of aortic valve morphology and hemodynamics with downstream AAo size in subjects with bicuspid aortic valve (BAV) disease.

Patient-Specific Surgery Planning for the Fontan Procedure

For children born with single ventricle heart defects, the Fontan procedure (right heart bypass via connection of caval veins to pulmonary arteries) is the palliative procedure of choice. Previous research has demonstrated strong coupling between the geometric characteristics of the surgical construct and the resulting patient-specific hemodynamics, which may relate to the numerous chronic morbidities seen in these patients. The combination of medical imaging, computer graphics and computational fluid simulations has introduced a powerful new paradigm for these procedures: providing the means to model the various options and evaluate the resulting characteristics. This paper details these methodologies, their application to planning interventions, and their contributions to generalizable knowledge of Fontan hemodynamics.