Abstract
Fontan patients are at risk for hepatic fibrosis; however, risk factors are unclear. We performed a multivariate analysis in a small cohort of 14 patients (7–24 years old, mean 15) with Fontan circulation, undergoing cardiac catheterization and transvenous liver biopsies, all demonstrating fibrosis. We found by stepwise regression analysis that the history of pulmonary atresia was a predictor of higher total hepatic fibrosis scores than a history of unobstructed pulmonary blood flow (p = 0.002). Other variables including age, time from Fontan, hemodynamic measurements, and laboratory values were not predictive of total fibrosis scores at p values <0.05. Hepatic fibrosis scores between those born with pulmonary atresia versus unrestricted pulmonary blood flow may reflect differences in pulmonary circulatory physiology, resulting from differences in pulmonary vascular development.
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References
Abman SH, Steinhorn RH (2011) The normal fetal and neonatal pulmonary circulation. In: Yuan JX-Y et al (eds) Textbook of pulmonary vascular disease. Springer, New York, pp 135–146
Berger RMF (1998) Biomechanical and molecular aspects of pulmonary vascular disease in children with congenital heart disease. Erasmus University, Rotterdam, p 36
Bulut OP, Romero R, Mahle WT, McConnell M, Braithwaite K, Shehata BM, Gupta NA, Vos M, Alazraki A (2013) Magnetic resonance imaging identifies unsuspected liver abnormalities in patients after the Fontan procedure. J Pediatr 163:201–206
Chen Q, Tulloh R, Caputo M, Stoica S, Kia M, Parry AJ (2014) Does the persistence of pulsatile antegrade pulmonary blood flow following bidirectional Glenn procedure affect long term outcome?. Eur J Cardiothorac Surg Apr 30 [Epub ahead of print]
Demirtürk OS, Güvener M, Coşkun I, Yildirim SV (2013) Results of additional pulsatile pulmonary blood flow with bidirectional Glenn cavopulmonary anastomosis: positive effect on main pulmonary artery growth and less need for Fontan conversion. Heart Surg Forum 16:E30–E34
Evans WN, Winn BJ, Yumiaco NS, Galindo A, Rothman A, Acherman RJ, Restrepo H (2014) Transvenous hepatic biopsy in stable Fontan patients undergoing cardiac catheterization. Pediatr Cardiol 35:1273–1278
Ferns SJ, El Zein C, Multani K, Sajan I, Subramanian S, Polimenakos AC, Ilbawi MN (2013) Is additional pulsatile pulmonary blood flow beneficial to patients with bidirectional Glenn? J Thorac Cardiovasc Surg 145:451–454
Galie PA, Nguyen DH, Choi CK, Cohen DM, Janmey PA, Chen CS (2014) Fluid shear stress threshold regulates angiogenic sprouting. Proc Natl Acad Sci USA 111:7968–7973
Ginde HohenwalterMD, Foley WD, Sowinski J, Bartz PJ, Venkatapuram S, Weinberg C, Tweddell JS, Earing MG (2013) Noninvasive assessment of liver fibrosis in adult patients following the Fontan procedure. Congenit Heart Dis 7:235–242
Hall SM, Hislop AA, Haworth SG (2002) Origin, differentiation, and maturation of human pulmonary veins. Am J Respir Cell Mol Biol 26:333–340
Haworth SG, Reid L (1977) Quantitative structural study of pulmonary circulation in the newborn with aortic atresia, stenosis, or coarctation. Thorax 32:121–128
Haworth SG, Reid L (1977) Quantitative structural study of pulmonary circulation in the newborn with pulmonary atresia. Thorax 32:129–133
Johnson RJ, Sauer U, Bühlmeyer K, Haworth SG (1985) Hypoplasia of the intrapulmonary arteries in children with right ventricular outflow tract obstruction, ventricular septal defect, and major aortopulmonary collateral arteries. Pediatr Cardiol 6:137–143
Johnson JA, Cetta F, Graham RP, Smyrk TC, Driscoll DJ, Phillips SD, John AS (2013) Identifying predictors of hepatic disease in patients after the Fontan operation: a postmortem analysis. J Thorac Cardiovasc Surg 146:140–145
Jones RC, Capen DE (2011) Pulmonary vascular development. In: Yuan JX-J et al (eds) Textbook of pulmonary vascular disease. Springer, New York, p 46
Kendall TJ, Stedman B, Hacking N, Haw M, Vettukattill JJ, Salmon AP, Cope R, Sheron N, Millward-Sadler H, Veldtman GR, Iredale JP (2008) Hepatic fibrosis and cirrhosis in the Fontan circulation: a detailed morphological study. J Clin Pathol 61:504–508
Kutty SS, Peng Q, Danford DA, Fletcher SE, Perry D, Talmon GA, Scott C, Kugler JD, Duncan KF, Quiros-Tejeira RE, Kutty S (2014) Increased hepatic stiffness as consequence of high hepatic afterload in the Fontan circulation: a vascular Doppler and elastography study. Hepatology 59:251–260
Lee KJ (2009) Transcatheter intervention on the central pulmonary arteries-current techniques and outcomes. In: Redington A, Anderson RH, Van AGS (eds) Congenital diseases in the right heart. Springer, London, p 78
Lindsey SE, Butcher JT, Yalcin HC (2014) Mechanical regulation of cardiac development. Front Physiol 5:318. doi:10.3389/fphys.2014.00318eCollection
Peng T, Morrisey EE (2013) Development of the pulmonary vasculature: current understanding and concepts for the future. Pulm Circ 3:176–178
Ranade SS, Qiu Z, Woo SH, Hur SS, Murthy SE, Cahalan SM, Xu J, Mathur J, Bandell M, Coste B, Li YS, Chien S, Patapoutian A (2014) Piezo1, a mechanically activated ion channel, is required for vascular development in mice. Proc Natl Acad Sci USA 111:10347–10352
Rychik J, Veldtman G, Rand E, Russo P, Rome JJ, Krok K, Goldberg DJ, Cahill AM, Wells RG (2012) The precarious state of the liver after a Fontan operation: summary of a multidisciplinary symposium. Pediatr Cardiol 33:1001–1012
Schachtner SK, Wang Y, Scott Baldwin H (2000) Qualitative and quantitative analysis of embryonic pulmonary vessel formation. Am J Respir Cell Mol Biol 22:157–165
Schwartz MC, Sullivan L, Cohen MS, Russo P, John AS, Guo R, Guttenberg M, Rand EB (2012) Hepatic pathology may develop before the Fontan operation in children with functional single ventricle: an autopsy study. J Thorac Cardiovasc Surg 143:904–909
Schwartz MC, Sullivan LM, Glatz AC et al (2013) Portal and sinusoidal fibrosis are common on liver biopsy after Fontan surgery. Pediatr Cardiol 34:135–142
Swift AJ, Telfer A, Rajaram S, Condliffe R, Marshall H, Capener D, Hurdman J, Elliot C, Kiely DG, Wild JM (2014) Dynamic contrast-enhanced magnetic resonance imaging in patients with pulmonary arterial hypertension. Pulm Circ 4:61–70
Tuder RM, Abman SH, Braun T, Capron F, Stevens T, Thistlethwaite PA, Haworth SG (2009) Development and pathology of pulmonary hypertension. J Am Coll Cardiol 54:S3–S9
Wallihan DB, Podberesky DJ, Marino BS, Sticka JS, Serai S (2013) Relationship of MR elastography determined liver stiffness with cardiac function after Fontan palliation. J Magn Reson Imaging. doi:10.1002/jmri.24496 [Epub ahead of print]
Wu FM, Opotowsky AR, Raza R, Harney S, Ukomadu C, Landzberg MJ, Valente AM, Breitbart RE, Singh MN, Gauvreau K, Jonas MM (2014) Transient elastography may identify fontan patients with unfavorable hemodynamics and advanced hepatic fibrosis. Congenit Heart Dis. doi:10.1111/chd.12159 [Epub ahead of print]
Zhang XT, Liu YL, Ruan YM, Yu CT (2006) [Relationship between the quantitative structural study of lung and the right ventricle outflow tract reconstruction in infants with tetralogy of Fallot]. [Article in Chinese] Zhongguo Yi Xue Ke Xue Yuan Xue Bao 28:402–405
Acknowledgments
We wish to thank the interventional radiologists of Radiology Specialists at Sunrise Children’s Hospital and Medical Center who performed the transvenous hepatic biopsies including Drs. Demetrice Davis, Steven Davis, Kelly Gardner, Sunil Gujrathi, Aaron Peterson, and Matthew Rainey.
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Evans, W.N., Acherman, R.J., Winn, B.J. et al. Fontan Hepatic Fibrosis and Pulmonary Vascular Development. Pediatr Cardiol 36, 657–661 (2015). https://doi.org/10.1007/s00246-014-1061-9
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DOI: https://doi.org/10.1007/s00246-014-1061-9