A One Dimensional (1D) Computational Fluid Dynamics Study of Fontan-Associated Liver Disease (FALD)

TL;DR

This work tackles Fontan-associated liver disease (FALD) by developing a patient-specific 1D-CFD model of the liver vasculature to predict pressure, flow, wall shear stress ($ au_w$), and tissue perfusion in HLHS and DORV patients. The 1D framework solves for $p(x,t)$, $q(x,t)$, and $A(x,t)$ along portal and hepatic arteries, maps terminal flows to liver tissue, and simulates progression by increasing downstream resistance to represent FALD; it also assesses sensitivity to inflow waveform and geometry. Results show that HLHS with a reconstructed aorta exhibits higher portal venous and hepatic arterial pressures than the DORV control, and these pressures rise further under FALD, accompanied by elevated WSS in hepatic vessels and more uneven liver perfusion; KL divergence quantifies the growing mismatch relative to the DORV baseline as FALD advances. The study provides mechanistic insight into how Fontan hemodynamics drive portal hypertension and vascular remodeling in the liver, highlighting regions at risk for fibrosis and offering a quantitative basis for risk stratification and monitoring in Fontan patients.

Abstract

Fontan-Associated Liver Disease (FALD) is a disorder arising from hemodynamic changes and venous congestion in the liver. This disease is prominent in patients with hypoplastic left heart syndrome (HLHS). Although HLHS patients typically survive into adulthood, they have reduced cardiac output due to their univentricular physiology (i.e., a Fontan circuit). As a result, they have insufficient blood delivery to the liver. In comparison, patients with double outlet right ventricle (DORV), also having a univentricular circuit, have lower incidence of FALD. In this study, we use a patient-specific, one-dimensional computational fluid dynamics (1D-CFD) model to predict hemodynamics in the liver of an HLHS patient and compare predictions with an age- and size-matched DORV control patient. Additionally, we simulate FALD conditions in the HLHS patient to predict hemodynamic changes across various stages of disease progression. Our results show that the HLHS patient has a higher portal venous pressure compared to the DORV patient. This difference is exacerbated as FALD conditions progress. The wall shear stress (WSS) is also higher than normal for the HLHS patient, suggesting vascular remodeling. WSS decreases slightly under FALD conditions, consistent with the development of portal hypertension. Perfusion analysis gives insight into regions of liver tissue at risk for fibrosis development, showing increasing pressures and reduced flow throughout the liver tissue fed by the portal vein under FALD conditions. Our results provide insight into the specific hemodynamic changes in Fontan circulation that can cause FALD.

Figures (9)

• Figure 1: (a) healthy heart with two ventricles. (b) hypoplastic left heart syndrome (HLHS) heart. (c) double outlet right ventricle (DORV) heart with a ventricular septal defect. (d) HLHS heart with a Fontan repair. This patient has undergone aortic reconstruction. (e) DORV heart with a Fontan repair. Patients in (d) and (e) both have a total cavopulmonary connection with the main pulmonary artery connected to the inferior vena cava.
• Figure 2: (a) The Fontan circulation, including flow to the liver. The right heart pumps blood into the aorta, which feed the liver via the portal vein, supplying 70% of the blood, and the hepatic artery, supplying 30% of the blood rocha2012liver. From the liver, blood is drained into the systemic veins, which passively is passing through the pulmonary circuit returning to the right heart. (b) 3D rendering of the hepatic artery (blue-green) and portal vein (red) vasculatures extracted from a CT scan from a healthy adult. Centerlines extracted from VMTK are shown in black. The network generated is scaled to the height and weight of the two subjects analyzed here. (c) Inflow waveforms (mL/s) the hepatic artery and portal vein for the two patients. The DORV patient has a greater occurrence of sub-oscillations, that is reflective waves after the initial peak, at the inlet of both networks.
• Figure 3: Network adapted from alyssa2022 used to calculate the inflow to the liver. Flow in vessel 34 feeds the hepatic artery, and flow from vessels 36, 40, and 42 enters the portal vein.
• Figure 4: Workflow chart. The number (1-8) corresponds to simulations described in \ref{['sec:sim']}. DORVn refers to the DORV patient network geometry, HLHSn refers to the HLHS patient network geomtery, and DORVp refers to the DORV parameters listed in Table \ref{['table:parameters']}. Figures of results for simulations 5-8 can be found in the supplement.
• Figure 5: Pressure and flow predictions for the DORV, HLHS, and simulated FALD HLHS patient in the portal network. We see that as the degree of FALD increase, the peak of the flow waveform is slightly shifted to the left, with systolic pressures slightly increasing.