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Effect of Fontan operation on liver stiffness in children with single ventricle physiology

  • Ultrasound
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Abstract

Objectives

Assess liver stiffness using ultrasound point shear wave elastography (US P-SWE) in children before and after the Fontan operation.

Methods

Eighteen children undergoing the Fontan operation were prospectively enrolled. Eight US P-SWE measurements were obtained from the right hepatic lobe before surgery, and at multiple postoperative time points. Temporally related inferior vena cava pressure (IVC) data was collected from medical records, when available. Changes in mean liver shear wave speed (SWS) were assessed using a mixed-effect model with post hoc Tukey correction. Changes in IVC pressure were evaluated using the Wilcoxon signed-rank test. A p value less than 0.05 was considered significant.

Results

Mean age at enrolment was 33.5 ± 10.5 months. Baseline mean liver SWS was normal at 1.18 ± 0.29 m/s, increased to 2.28 ± 0.31 m/s at 2.5 ± 1.2 days (p < 0.0001) and to 2.22 ± 0.38 m/s at 7.5 ± 1.4 days (p < 0.0001). Five subjects returned at a mean of 185 ± 28 days, and mean liver SWS remained elevated at 2.08 ± 0.24 m/s (p < 0.0001). Mean IVC pressure increased from 7.2 ± 2.6 mmHg at baseline to 16.44 ± 3.3 mmHg at 2.2 ± 0.8 days post-surgery (p = 0.004).

Conclusion

The Fontan operation immediately and chronically increases liver stiffness and IVC pressure. Our study provides further evidence that congestion is a key driver of Fontan-associated liver disease.

Key points

• The Fontan operation triggers immediate hepatic congestion and marked liver stiffening.

• Congestion, not fibrosis, drives early increased liver stiffness in Fontan patients.

• Hepatic congestion persists chronically for months after the Fontan operation.

• Congestion confounds shear wave elastography as a post-Fontan liver fibrosis biomarker.

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Abbreviations

FALD:

Fontan-associated liver disease

IVC:

Inferior vena cava

MR:

Magnetic resonance

P-SWE:

Point shear wave elastography

SWE:

Shear wave elastography

SWS:

Shear wave speed

US:

Ultrasound

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Acknowledgments

The scientific guarantor of this publication is Frank W. DiPaola, MD. The authors of this manuscript declare relationships with the following companies: Dr. Dillman discloses that he receives unrelated, unrestricted, investigator-initiated research funding from Siemens Medical Solutions USA, Inc. The authors have no other conflicts of interest to disclose. This research was funded by a pilot grant provided by the Michigan Institute for Clinical and Health Research (MICHR), University of Michigan, Ann Arbor, MI (CTSA 2UL1TR000433).

Aishwarya Parameswaran, MS, of the Michigan Institute for Clinical and Health Research (MICHR) and one of the authors, has significant statistical expertise and kindly provided statistical advice for this manuscript. Institutional review board approval was obtained. Written informed consent was obtained from all subjects (patients) in this study. Methodology: prospective, cohort study, performed at one institution.

Author information

Authors and Affiliations

  1. Division of Pediatric Gastroenterology, Department of Pediatrics, C.S. Mott Children’s Hospital, University of Michigan Health System, 1500 East Medical Center Drive, Ann Arbor, MI, 48109, USA

    Frank W. DiPaola

  2. Division of Pediatric Cardiology, Department of Pediatrics, C.S. Mott Children’s Hospital, University of Michigan Health System, 1500 East Medical Center Drive, Ann Arbor, MI, 48109, USA

    Kurt R. Schumacher & Caren S. Goldberg

  3. Division of Pediatric Cardiology, Department of Pediatrics, Seattle Children’s Hospital, 4800 Sand Point Way NE, Seattle, WA, 98105, USA

    Joshua Friedland-Little

  4. Michigan Institute for Clinical and Health Research (MICHR), University of Michigan, 2800 Plymouth Road, Building 400, Ann Arbor, MI, 48109, USA

    Aishwarya Parameswaran

  5. Department of Radiology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH, 45229, USA

    Jonathan R. Dillman

Authors
  1. Frank W. DiPaola
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  2. Kurt R. Schumacher
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  3. Caren S. Goldberg
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  4. Joshua Friedland-Little
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  5. Aishwarya Parameswaran
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  6. Jonathan R. Dillman
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Corresponding author

Correspondence to Frank W. DiPaola.

Electronic supplementary material

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Supplementary Fig. 1

Diagrams of cardiac anatomy (using the example of hypoplastic left heart syndrome in which the right ventricle is the single functional ventricle) and direction of hepatic venous return before and after the Fontan operation. a Cardiac anatomy prior to the Fontan operation demonstrating that hepatic venous return (via the inferior vena cava) is routed through the right atrium and to the right ventricle and is not exposed to the pressure within the pulmonary circulation (PA), since this pathway is blocked with a surgically placed patch. There is lower pressure within the inferior vena cava and normal liver stiffness. b Cardiac anatomy following the Fontan operation, in which a surgically placed baffle now routes hepatic venous return directly to the pulmonary circulation. The inferior vena cava and liver are now exposed to the pressure within the pulmonary circulation resulting in higher pressure within the inferior vena cava and increased liver stiffness. IVC inferior vena cava, Ao aorta, LA left atrium, PA pulmonary artery, RA right atrium, RV right ventricle (GIF 61 kb)

(GIF 62 kb)

High resolution image (TIF 4833 kb)

High resolution image (TIF 4833 kb)

Supplementary Fig. 2

Pressure curve demonstrating changes in blood pressure across the circulation in a patient before and after the Fontan operation. Blood pressure increases dramatically within the right ventricle (RV) as blood is ejected into the aorta (Ao), and then blood pressure falls as blood traverses the systemic circulation. In the pre-Fontan circulation, blood pressure falls to comparatively lower values within the inferior vena cava (IVC) and right atrium (RA) because these structures are not in direct communication with the pressure within the pulmonary circulation (P). In contrast, in the post-Fontan circulation, there is an elevated pressure within the inferior vena cava and right atrium (which results in increased liver stiffness) because these structures communicate directly with the pulmonary circulation. Blue deoxygenated blood, purple partially oxygenated blood, red fully oxygenated blood. (Figure elements adapted from Gewillig M and Goldberg DJ. Failure of the Fontan circulation. Heart Fail Clin. 2014;10(1):105-116) (GIF 29 kb)

High resolution image (TIFF 4937 kb)

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DiPaola, F.W., Schumacher, K.R., Goldberg, C.S. et al. Effect of Fontan operation on liver stiffness in children with single ventricle physiology. Eur Radiol 27, 2434–2442 (2017). https://doi.org/10.1007/s00330-016-4614-x

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  • DOI: https://doi.org/10.1007/s00330-016-4614-x

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