Abstract
Fontan associated liver disease is a common complication in patients with Fontan circulation, who were born with a single functioning heart ventricle. The hepatic venous pressure gradient (HVPG) is used to assess liver health and is a surrogate measure of the pressure gradient across the entire liver (portal pressure gradient (PPG)). However, it is thought to be inaccurate in Fontan patients. The main objectives of this study were (1) to apply an existing detailed lumped parameter model (LPM) of the liver to Fontan patients using patient-specific clinical data and (2) to determine whether HVPG is a suitable measurement of PPGs in these patients. An existing LPM of the liver blood circulation was applied and tuned to simulate patient-specific liver hemodynamics. Geometries were collected from seven adult Fontan patients and used to evaluate model parameters. The model was solved and tuned using waveform measurements of flows, inlet and outlet pressures. The predicted ratio of portal to hepatic venous pressures is comparable to in vivo measurements. The results confirmed that HVPG is not suitable for Fontan patients, as it would underestimate the portal pressures gradient by a factor of 3 to 4. Our patient-specific liver model provides an estimate of the pressure drop across the liver, which differs from the clinically used metric HVPG. This work represents a first step toward models suitable to assess liver health in Fontan patients and improve its long-term management.
Issue Section:
Research Papers
References
1.
Munsterman
,
I. D.
,
Duijnhouwer
,
A. L.
,
Kendall
,
T. J.
,
Bronkhorst
,
C. M.
,
Ronot
,
M.
,
van Wettere
,
M.
,
van Dijk
,
A. P. J.
,
Drenth
,
J. P. H.
, and
Tjwa
,
E. T. T. L.
, 2018
, “
The Clinical Spectrum of Fontan-Associated Liver Disease: Results From a Prospective Multimodality Screening Cohort
,” Eur. Heart J.
,
40
(13
), pp. 1057
–1068
.10.1093/eurheartj/ehy6202.
Schwartz
,
M. C.
,
Sullivan
,
L.
,
Cohen
,
M. S.
,
Russo
,
P.
,
John
,
A. S.
,
Guo
,
R.
,
Guttenberg
,
M.
, and
Rand
,
E. B.
, 2012
, “
Hepatic Pathology May Develop Before the Fontan Operation in Children With Functional Single Ventricle: An Autopsy Study
,” J. Thorac. Cardiovasc. Surg.
,
143
(4
), pp. 904
–909
.10.1016/j.jtcvs.2011.08.0383.
Wells
,
M. L.
,
Fenstad
,
E. R.
,
Poterucha
,
J. T.
,
Hough
,
D. M.
,
Young
,
P. M.
,
Araoz
,
P. A.
,
Ehman
,
R. L.
, and
Venkatesh
,
S. K.
, 2016
, “
Imaging Findings of Congestive Hepatopathy
,” RadioGraphics
,
36
(4
), pp. 1024
–1037
.10.1148/rg.20161502074.
Abbasi Bavil
,
E.
,
Yang
,
H. K.
,
Doyle
,
M. G.
,
Kim
,
T. K.
,
Karur
,
G. R.
,
Bhagra
,
C.
,
Bhagra
,
S.
,
Oechslin
,
E. N.
,
Ross
,
H. J.
,
Roche
,
S. L.
,
Gonzalez
,
R. A.
,
Amon
,
C. H.
,
Mertens
,
L.
, and
Wald
,
R. M.
, 2020
, “
Cardiovascular and Abdominal Flow Alterations in Adults With Morphologic Evdence of Liver Disease Post Fontan Palliation
,” Int. J. Cardiol.
,
317
, pp. 63
–69
.10.1016/j.ijcard.2020.05.0645.
Shetty
,
S.
,
Lalor
,
P. F.
, and
Adams
,
D. H.
, 2018
, “
Liver Sinusoidal Endothelial Cells—Gatekeepers of Hepatic Immunity
,” Nat. Rev. Gastroenterol. Hepatol.
,
15
(9
), pp. 555
–567
.10.1038/s41575-018-0020-y6.
Suk
,
K. T.
, 2014
, “
Hepatic Venous Pressure Gradient: Clinical Use in Chronic Liver Disease
,” Clin. Mol. Hepatol.
,
20
(1
), pp. 6
–14
.10.3350/cmh.2014.20.1.67.
Kendall
,
T. J.
,
Stedman
,
B.
,
Hacking
,
N.
,
Haw
,
M.
,
Vettukattill
,
J. J.
,
Salmon
,
A. P.
,
Cope
,
R.
,
Sheron
,
N.
,
Millward-Sadler
,
H.
,
Veldtman
,
G. R.
, and
Iredale
,
J. P.
, 2008
, “
Hepatic Fibrosis and Cirrhosis in the Fontan Circulation: A Detailed Morphological Study
,” J. Clin. Pathol.
,
61
(4
), pp. 504
–508
.10.1136/jcp.2007.0523658.
Téllez
,
L.
,
de Santiago
,
E. R.
, and
Albillos
,
A.
, 2018
, “
Fontan-Associated Liver Disease
,” Rev. Esp. Cardiol.
,
71
(3
), pp. 192
–202
.10.1016/j.recesp.2017.10.0149.
Velpula
,
M.
,
Sheron
,
N.
,
Guha
,
N.
,
Salmon
,
T.
,
Hacking
,
N.
, and
Veldtman
,
G. R.
, 2011
, “
Direct Measurement of Porto-Systemic Gradient in a Failing Fontan Circulation
,” Congenital Heart Dis.
,
6
(2
), pp. 175
–178
.10.1111/j.1747-0803.2010.00451.x10.
Kung
,
E.
,
Pennati
,
G.
,
Migliavacca
,
F.
,
Hsia
,
T. V.
,
Figliola
,
R.
,
Marsden
,
A.
, and
Giardini
,
A.
, 2014
, “
A Simulation Protocol for Exercise Physiology in Fontan Patients Using a Closed Loop Lumped-Parameter Model
,” ASME J. Biomech. Eng.
,
136
(8
), p. 081007
.10.1115/1.402727111.
Watrous
,
R. L.
, and
Chin
,
A. J.
, 2014
, “
Model-Based Comparison of the Normal and Fontan Circulatory Systems—Part I: Development of a General Purpose, Interactive Cardiovascular Model
,” World J. Pediatr. Congenital Heart Surg.
,
5
(3
), pp. 372
–384
.10.1177/215013511452945012.
Koeken
,
Y.
,
Arts
,
T.
, and
Delhaas
,
T.
, 2012
, “
Simulation of the Fontan Circulation During Rest and Exercise
,” Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBS)
, Aug. 28–Sept. 1, San Diego, CA
, pp. 6673
–6676
.10.1109/EMBC.2012.634752513.
Chugunova
,
M.
,
Doyle
,
M. G.
,
Keener
,
J. P.
, and
Taranets
,
R. M.
, 2019
, “
Use of Mathematical Modeling to Study Pressure Regimes in Normal and Fontan Blood Flow Circulations
,” Math. Ind. Case Stud.
,
10
(1
), pp. 1
–28
.10.1186/s40929-019-0019-914.
Debbaut
,
C.
,
Vierendeels
,
J.
,
Casteleyn
,
C.
,
Cornillie
,
P.
,
Loo
,
D. V.
,
Simoens
,
P.
,
Van Hoorebeke
,
L.
,
Monbaliu
,
D.
, and
Segers
,
P.
, 2012
, “
Perfusion Characteristics of the Human Hepatic Microcirculation Based on Three-Dimensional Reconstructions and Computational Fluid Dynamic Analysis
,” ASME J. Biomech. Eng.
,
134
(1
), p. 011003
.10.1115/1.400554515.
Ho
,
C. M.
,
Lin
,
R. K.
,
Tsai
,
S. F.
,
Hu
,
R. H.
,
Liang
,
P. C.
,
Sheu
,
T. W. H.
, and
Lee
,
P. H.
, 2010
, “
Simulation of Portal Hemodynamic Changes in a Donor After Right Hepatectomy
,” ASME J. Biomech. Eng.
,
132
(4
), p. 041002
.10.1115/1.400095716.
Peeters
,
G.
,
Debbaut
,
C.
,
Cornillie
,
P.
,
De Schryver
,
T.
,
Monbaliu
,
D.
,
Laleman
,
W.
, and
Segers
,
P.
, 2015
, “
A Multilevel Modeling Framework to Study Hepatic Perfusion Characteristics in Case of Liver Cirrhosis
,” ASME J. Biomech. Eng.
,
137
(5
), p. 051007
.10.1115/1.402928017.
Debbaut
,
C.
,
Monbaliu
,
D.
,
Casteleyn
,
C.
,
Cornillie
,
P.
,
Loo
,
D. V.
,
Masschaele
,
B.
,
Pirenne
,
J.
,
Simoens
,
P.
,
Hoorebeke
,
L. V.
, and
Segers
,
P.
, 2011
, “
From Vascular Corrosion Cast to Electrical Analog Model for the Study of Human Liver Hemodynamics and Perfusion
,” IEEE Trans. Biomed. Eng.
,
58
(1
), pp. 25
–35
.10.1109/TBME.2010.206522918.
Plaats
,
A. V.
,
Hart
,
N. A.
,
Verkerke
,
G. J.
,
Leuvenink
,
H. G. D.
,
Verdonck
,
P.
,
Ploeg
,
R. J.
, and
Rakhorst
,
G.
, 2004
, “
Numerical Simulation of the Hepatic Circulation
,” Int. J. Artif. Organs
,
27
(3
), pp. 222
–230
.10.1177/03913988040270030919.
Audebert
,
C.
,
Peeters
,
G.
,
Segers
,
P.
,
Laleman
,
W.
,
Monbaliu
,
D.
,
Korf
,
H.
,
Trebicka
,
J.
,
Vignon-Clementel
,
I. E.
, and
Debbaut
,
C.
, 2018
, “
Closed-Loop Lumped Parameter Modeling of Hemodynamics During Cirrhogenesis in Rats
,” IEEE Trans. Biomed. Eng.
,
65
(10
), pp. 2311
–2322
.10.1109/TBME.2018.279394820.
Wang
,
T.
,
Liang
,
F.
,
Zhou
,
Z.
, and
Shi
,
L.
, 2017
, “
A Computational Model of the Hepatic Circulation Applied to Analyze the Sensitivity of Hepatic Venous Pressure Gradient (HVPG) in Liver Cirrhosis
,” J. Biomech.
,
65
, pp. 23
–31
.10.1016/j.jbiomech.2017.09.02321.
Fredenburg
,
T. B.
,
Johnson
,
T. R.
, and
Cohen
,
M. D.
, 2011
, “
The Fontan Procedure: Anatomy, Complications, and Manifestations of Failure
,” RadioGraphics
,
31
(2
), pp. 453
–463
.10.1148/rg.31210502722.
Abdel-Misih
,
S. R. Z.
, and
Bloomston
,
M.
, 2010
, “
Liver Anatomy
,” Surg. Clin. North Am.
,
90
(4
), pp. 643
–653
.10.1016/j.suc.2010.04.01723.
Pater
,
L.
, and
Berg
,
J.
, 1964
, “
An Electrical Analogue of the Entire Human Circulatory System
,” Med. Electron. Biol. Eng.
,
2
(2
), pp. 161
–166
.10.1007/BF0248421524.
George
,
S. M.
,
Eckert
,
L. M.
,
Martin
,
D. R.
, and
Giddens
,
D. P.
, 2015
, “
Hemodynamics in Normal and Diseased Livers: Application of Image-Based Computational Models
,” Cardiovasc. Eng. Technol.
,
6
(1
), pp. 80
–91
.10.1007/s13239-014-0195-525.
Rani
,
H. P.
,
Sheu
,
T. W. H.
,
Chang
,
T. M.
, and
Liang
,
P. C.
, 2006
, “
Numerical Investigation of Non-Newtonian Microcirculatory Blood Flow in Hepatic Lobule
,” J. Biomech.
,
39
(3
), pp. 551
–563
.10.1016/j.jbiomech.2004.11.02926.
Wang
,
P. J.
,
Li
,
W. C.
,
Xi
,
G. M.
,
Wang
,
H. Q.
,
Zhang
,
Z. H.
,
Yao
,
B. C.
,
Tang
,
W.
,
Deng
,
Z. H.
, and
Zhang
,
X. H.
, 2009
, “
Biomechanical Study of Hepatic Portal Vein in Humans and Pigs and Its Value in Liver Transplantation
,” Transplant. Proc.
,
41
(5
), pp. 1906
–1910
.10.1016/j.transproceed.2008.10.09727.
Wachsberg
,
R. H.
,
Angyal
,
E. A.
,
Klein
,
K. M.
,
Kuo
,
H. R.
, and
Lambert
,
W. C.
, 1997
, “
Echogenicity of Hepatic Versus Portal Vein Walls Revisited With Histologic Correlation
,” J. Ultrasound Med.
,
16
(12
), pp. 807
–810
.10.7863/jum.1997.16.12.80728.
Willemet
,
M.
,
Chowienczyk
,
P.
, and
Alastruey
,
J.
, 2015
, “
A Database of Virtual Healthy Subjects to Assess the Accuracy of Foot-to-Foot Pulse Wave Velocities for Estimation of Aortic Stiffness
,” Am. J. Physiol.: Heart Circ. Physiol.
,
309
(4
), pp. H663
–H675
.10.1152/ajpheart.00175.201529.
Truskey
,
G. A.
,
Yuan
,
F.
, and
Katz
,
D. F.
, 2009
, Transport Phenomena in Biological Systems
, 2nd ed.,
Pearson
, Franklin Lakes, NJ
.30.
Debbaut
,
C.
,
Monbaliu
,
D. R. L.
, and
Segers
,
P.
, 2014
, “
Validation and Calibration of an Electrical Analog Model of Human Liver Perfusion Based on Hypothermic Machine Perfusion Experiments
,” Int. J. Artif. Organs
,
37
(6
), pp. 486
–498
.10.5301/ijao.500033731.
Mcavoy
,
N. C.
,
Semple
,
S.
,
Richards
,
J. M.
,
Robson
,
A. J.
,
Patel
,
D.
,
Jardine
,
A. G.
,
Leyland
,
K.
,
Cooper
,
A. S.
,
Newby
,
D. E.
, and
Hayes
,
P. C.
, 2016
, “
Differential Visceral Blood Flow in the Hyperdynamic Circulation of Patients With Liver Cirrhosis
,” Aliment. Pharmacol. Ther.
,
43
(9
), pp. 947
–954
.10.1111/apt.1357132.
Hadaegh
,
F.
,
Shafiee
,
G.
,
Hatami
,
M.
, and
Azizi
,
F.
, 2012
, “
Systolic and Diastolic Blood Pressure, Mean Arterial Pressure and Pulse Pressure for Prediction of Cardiovascular Events and Mortality in a Middle Eastern Population
,” Blood Press.
,
21
(1
), pp. 12
–18
.10.3109/08037051.2011.58580833.
Lebrec
,
D.
,
Sogni
,
P.
, and
Vilgrain
,
V.
, 1997
, “
Evaluation of Patients With Portal Hypertension
,” Baillières Clin. Gastroenterol.
,
11
(2
), pp. 221
–241
.10.1016/S0950-3528(97)90037-334.
Bari
,
K.
, and
Garcia-Tsao
,
G.
, 2012
, “
Treatment of Portal Hypertension
,” World J. Gastroenterol.
,
18
(11
), pp. 1166
–1175
.10.3748/wjg.v18.i11.116635.
Reynolds
,
T. B.
,
Ito
,
S.
, and
Iwatsuki
,
S.
, 1970
, “
Measurement of Portal Pressure and Its Clinical Application
,” Am. J. Med.
,
49
(5
), pp. 649
–657
.10.1016/S0002-9343(70)80131-036.
Kutty
,
S. S.
,
Peng
,
Q.
,
Danford
,
D. A.
,
Fletcher
,
S. E.
,
Perry
,
D.
,
Talmon
,
G. A.
,
Scott
,
C.
,
Kugler
,
J. D.
,
Duncan
,
K. F.
,
Quiros-Tejeira
,
R. E.
, and
Kutty
,
S.
, 2014
, “
Increased Hepatic Stiffness as Consequence of High Hepatic Afterload in the Fontan Circulation: A Vascular Doppler and Elastography Study
,” Hepatology
,
59
(1
), pp. 251
–260
.10.1002/hep.26631Copyright © 2021 by ASME
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