Severity of Fontan-Associated Liver Disease Correlates with Fontan Hemodynamics.

Fontan-palliated patients are at risk for the development of Fontan-associated liver disease (FALD). In this study, we performed a detailed hemodynamic and hepatic assessment to analyze the incidence and spectrum of FALD and its association with patients' hemodynamics. From 2017 to 2019, 145 patients underwent a detailed, age-adjusted hepatic examination including laboratory analysis (FibroTest®, n = 101), liver ultrasound (n = 117) and transient elastography (FibroScan®, n = 61). The median patient age was 16.0 years [IQR 14.2], and the median duration of the Fontan circulation was 10.3 years [IQR 14.7]. Hemodynamic assessment was performed using echocardiography, cardiopulmonary exercise capacity testing and cardiac catheterization. Liver ultrasound revealed hepatic parenchymal changes in 83 patients (70.9%). Severe liver cirrhosis was detectable in 20 patients (17.1%). Median liver stiffness measured by FibroScan® was 27.7 kPa [IQR 14.5], and the median Fibrotest® score was 0.5 [IQR 0.3], corresponding to fibrosis stage ≥ 2. Liver stiffness values and Fibrotest® scores correlated significantly with Fontan duration (P1 = 0.013, P2 = 0.012). Exercise performance was significantly impaired in patients with severe liver cirrhosis (P = 0.003). Pulmonary artery pressure and end-diastolic pressure were highly elevated in cirrhotic patients (P1 = 0.008, P2 = 0.003). Multivariable risk factor analysis revealed Fontan duration to be a major risk factor for the development of FALD (P < 0.001, OR 0.77, CI 0.68-0.87). In the majority of patients, hepatic abnormalities suggestive of FALD were detectable by liver ultrasound, transient elastography and laboratory analysis. The severity of FALD correlated significantly with Fontan duration and impaired Fontan hemodynamics. A detailed hepatic assessment is indispensable for long-term surveillance of Fontan patients.

Multiblock High Order Large Eddy Simulation of Powered Fontan Hemodynamics: Towards Computational Surgery.

Children born with only one functional ventricle must typically undergo a series of three surgeries to obtain the so-called Fontan circulation in which the blood coming from the body passively flows from the Vena Cavae (VCs) to the Pulmonary Arteries (PAs) through the Total Cavopulmonary Connection (TCPC). The circulation is inherently inefficient due to the lack of a subpulmonary ventricle. Survivors face the risk of circulatory sequelae and eventual failure for the duration of their lives. Current efforts are focused on improving the outcomes of Fontan palliation, either passively by optimizing the TCPC, or actively by using mechanical support. We are working on a chronic implant that would be placed at the junction of the TCPC, and would provide the necessary pressure augmentation to re-establish a circulation that recapitulates a normal two-ventricle circulation. This implant is based on the Von Karman viscous pump and consists of a vaned impeller that rotates inside the TCPC. To evaluate the performance of such a device, and to study the flow features induced by the presence of the pump, Computational Fluid Dynamics (CFD) is used. CFD has become an important tool to understand hemodynamics owing to the possibility of simulating quickly a large number of designs and flow conditions without any harm for patients. The transitional and unsteady nature of the flow can make accurate simulations challenging. We developed and in-house high order Large Eddy Simulation (LES) solver coupled to a recent Immersed Boundary Method (IBM) to handle complex geometries. Multiblock capability is added to the solver to allow for efficient simulations of complex patient specific geometries. Blood simulations are performed in a complex patient specific TCPC geometry. In this study, simulations without mechanical assist are performed, as well as after virtual implantation of the temporary and chronic implants being developed. Instantaneous flow structures, hepatic factor distribution, and statistical data are presented for all three cases.

Biomechanical Analysis of Age-Dependent Changes in Fontan Power Loss.

The hemodynamics in Fontan patients with single ventricles rely on favorable flow and energetics, especially in the absence of a subpulmonary ventricle. Age-related changes in energetics for extracardiac and lateral tunnel Fontan procedures are not well understood. Vorticity (VOR) and viscous dissipation rate (VDR) are two descriptors that can provide insights into flow dynamics and dissipative areas in Fontan pathways, potentially contributing to power loss. This study examined power loss and its correlation with spatio-temporal flow descriptors (vorticity and VDR). Data from 414 Fontan patients were used to establish a relationship between the superior vena cava (SVC) to inferior vena cava (IVC) flow ratio and age. Computational flow modeling was conducted for both extracardiac conduits (ECC, n = 16) and lateral tunnels (LT, n = 25) at different caval inflow ratios of 2, 1, and 0.5 that corresponded with ages 3, 8, and 15+. In both cohorts, vorticity and VDR correlated well with PL, but ECC cohort exhibited a slightly stronger correlation for PL-VOR (>0.83) and PL-VDR (>0.89) than that for LT cohort (>0.76 and > 0.77, respectively) at all ages. Our data also suggested that absolute and indexed PL increase (p < 0.02) non-linearly as caval inflow changes with age and are highly patient-specific. Comparison of indexed power loss between our ECC and LT cohort showed that while ECC had a slightly higher median PL for all 3 caval inflow ratio examined (3.3, 8.3, 15.3) as opposed to (2.7, 7.6, 14.8), these differences were statistically non-significant. Lastly, there was a consistent rise in pressure gradient across the TCPC with age-related increase in IVC flows for both ECC and LT Fontan patient cohort. Our study provided hemodynamic insights into Fontan energetics and how they are impacted by age-dependent change in caval inflow. This workflow may help assess the long-term sustainability of the Fontan circulation and inform the design of more efficient Fontan conduits.

In Silico Evaluation of a Self-powered Venous Ejector Pump for Fontan Patients.

PURPOSE: The Fontan circulation carries a dismal prognosis in the long term due to its peculiar physiology and lack of a subpulmonic ventricle. Although it is multifactorial, elevated IVC pressure is accepted to be the primary cause of Fontan's high mortality and morbidity. This study presents a self-powered venous ejector pump (VEP) that can be used to lower the high IVC venous pressure in single-ventricle patients. METHODS: A self-powered venous assist device that exploits the high-energy aortic flow to lower IVC pressure is designed. The proposed design is clinically feasible, simple in structure, and is powered intracorporeally. The device's performance in reducing IVC pressure is assessed by conducting comprehensive computational fluid dynamics simulations in idealized total cavopulmonary connections with different offsets. The device was finally applied to complex 3D reconstructed patient-specific TCPC models to validate its performance. RESULTS: The assist device provided a significant IVC pressure drop of more than 3.2 mm Hg in both idealized and patient-specific geometries, while maintaining a high systemic oxygen saturation of more than 90%. The simulations revealed no significant caval pressure rise (< 0.1 mm Hg) and sufficient systemic oxygen saturation (> 84%) in the event of device failure, demonstrating its fail-safe feature. CONCLUSIONS: A self-powered venous assist with promising in silico performance in improving Fontan hemodynamics is proposed. Due to its passive nature, the device has the potential to provide palliation for the growing population of patients with failing Fontan.

Functional hepatic deterioration determined by 13C-methacetin breath test is associated with impaired hemodynamics and late Fontan failure in adults.

Background: Despite improved survival a substantial number of Fontan patients eventually develop late failure. Fontan-associated liver disease (FALD) is the most frequent end-organ dysfunction. Although impaired hemodynamics and Fontan failure correlate with FALD severity, no association between hepatic functional metabolic impairment and Fontan hemodynamics has been established. Hypothesis: Metabolic liver function measured by liver maximum function capacity test (LiMAx®) correlates with Fontan hemodynamics and Fontan failure. Methods: From 2020 to 2022, 58 adult Fontan patients [median age: 29.3 years, IQR (12.7), median follow-up time after Fontan operation: 23.2 years, IQR (8.7)] were analyzed in a cross-sectional study. Hemodynamic assessment included echocardiography, cardiopulmonary exercise testing and invasive hemodynamic evaluation. Fontan failure was defined based on commonly applied clinical criteria and our recently composed multimodal Fontan failure score. Results: LiMAx® test revealed normal maximum liver function capacity in 40 patients (>315 µg/h*kg). In 18 patients a mild to moderate impairment was detected (140-314 µg/h*kg), no patient suffered from severe hepatic deterioration (≤ 139 µg/kg*h). Fontan failure was present in 15 patients. Metabolic liver function was significantly reduced in patients with increased pulmonary artery pressure (p = 0.041. r = -0.269) and ventricular end-diastolic pressure (p = 0.033, r = -0.325), respectively. In addition, maximum liver function capacity was significantly impaired in patients with late Fontan failure (289.0 ± 99.6 µg/kg*h vs. 384.5 ± 128.6 µg/kg*h, p = 0.007). Conclusion: Maximum liver function capacity as determined by LiMAx® was significantly reduced in patients with late Fontan failure. In addition, elevated pulmonary artery pressure and end-diastolic ventricular pressure were associated with hepatic functional metabolic impairment.

Analysis of Inlet Velocity Profiles in Numerical Assessment of Fontan Hemodynamics.

Computational fluid dynamic (CFD) simulations are widely utilized to assess Fontan hemodynamics that are related to long-term complications. No previous studies have systemically investigated the effects of using different inlet velocity profiles in Fontan simulations. This study implements real, patient-specific velocity profiles for numerical assessment of Fontan hemodynamics using CFD simulations. Four additional, artificial velocity profiles were used for comparison: (1) flat, (2) parabolic, (3) Womersley, and (4) parabolic with inlet extensions [to develop flow before entering the total cavopulmonary connection (TCPC)]. The differences arising from the five velocity profiles, as well as discrepancies between the real and each of the artificial velocity profiles, were quantified by examining clinically important metrics in TCPC hemodynamics: power loss (PL), viscous dissipation rate (VDR), hepatic flow distribution, and regions of low wall shear stress. Statistically significant differences were observed in PL and VDR between simulations using real and flat velocity profiles, but differences between those using real velocity profiles and the other three artificial profiles did not reach statistical significance. These conclusions suggest that the artificial velocity profiles (2)-(4) are acceptable surrogates for real velocity profiles in Fontan simulations, but parabolic profiles are recommended because of their low computational demands and prevalent applicability.

The Advantages of Viscous Dissipation Rate over Simplified Power Loss as a Fontan Hemodynamic Metric.

Flow efficiency through the Fontan connection is an important factor related to patient outcomes. It can be quantified using either a simplified power loss or a viscous dissipation rate metric. Though practically equivalent in simplified Fontan circulation models, these metrics are not identical. Investigation is needed to evaluate the advantages and disadvantages of these metrics for their use in in vivo or more physiologically-accurate Fontan modeling. Thus, simplified power loss and viscous dissipation rate are compared theoretically, computationally, and statistically in this study. Theoretical analysis was employed to assess the assumptions made for each metric and its clinical calculability. Computational simulations were then performed to obtain these two metrics. The results showed that apparent simplified power loss was always greater than the viscous dissipation rate for each patient. This discrepancy can be attributed to the assumptions derived in theoretical analysis. Their effects were also deliberately quantified in this study. Furthermore, statistical analysis was conducted to assess the correlation between the two metrics. Viscous dissipation rate and its indexed quantity show significant, strong, linear correlation to simplified power loss and its indexed quantity (p < 0.001, r > 0.99) under certain assumptions. In conclusion, viscous dissipation rate was found to be more advantageous than simplified power loss as a hemodynamic metric because of its lack of limiting assumptions and calculability in the clinic. Moreover, in addition to providing a time-averaged bulk measurement like simplified power loss, viscous dissipation rate has spatial distribution contours and time-resolved values that may provide additional clinical insight. Finally, viscous dissipation rate could maintain the relationship between Fontan connection flow efficiency and patient outcomes found in previous studies. Consequently, future Fontan hemodynamic studies should calculate both simplified power loss and viscous dissipation rate to maintain ties to previous studies, but also provide the most accurate measure of flow efficiency. Additional attention should be paid to the assumptions required for each metric.

Using a Novel In Vitro Fontan Model and Condition-Specific Real-Time MRI Data to Examine Hemodynamic Effects of Respiration and Exercise.

Several studies exist modeling the Fontan connection to understand its hemodynamic ties to patient outcomes (Chopski in: Experimental and Computational Assessment of Mechanical Circulatory Assistance of a Patient-Specific Fontan Vessel Configuration. Dissertation, 2013; Khiabani et al. in J Biomech 45:2376-2381, 2012; Taylor and Figueroa in Annu Rev Biomed 11:109-134, 2009; Vukicevic et al. in ASAIO J 59:253-260, 2013). The most patient-accurate of these studies include flexible, patient-specific total cavopulmonary connections. This study improves Fontan hemodynamic modeling by validating Fontan model flexibility against a patient-specific bulk compliance value, and employing real-time phase contrast magnetic resonance flow data. The improved model was employed to acquire velocity field information under breath-held, free-breathing, and exercise conditions to investigate the effect of these conditions on clinically important Fontan hemodynamic metrics including power loss and viscous dissipation rate. The velocity data, obtained by stereoscopic particle image velocimetry, was visualized for qualitative three-dimensional flow field comparisons between the conditions. Key hemodynamic metrics were calculated from the velocity data and used to quantitatively compare the flow conditions. The data shows a multi-factorial and extremely patient-specific nature to Fontan hemodynamics.