BACKGROUND: The aim of this study was to analyze the relation between the hepatic fibrosis markers, liver morphology and hemodynamics assessed by magnetic resonance imaging (MRI) after total cavopulmonary connection (TCPC). MATERIALS AND METHODS: Adult patients after TCPC performed in childhood between 1993 and 2003 are the subjects of this observational study. The follow-up protocol consisted of clinical and echocardiographic examination, liver elastography, cardiopulmonary exercise test, MRI hemodynamics and liver morphology assessment and direct enhanced liver fibrosis (ELF) test. RESULTS: The cohort consisted of 39 patients (46% female) with a median age at study 26 (IQR 23-28) years and interval from TCPC 21 (IQR 20-23) years. There was no correlation between ELF test and any MRI variables, but procollagen III amino-terminal peptide (PIIINP), a single component of ELF test, correlated significantly with ventricular end-diastolic volume (r = 0.33; p = 0.042) and inferior vena cava flow (r = 0.47; p = 0.003). Fifteen (38%) patients with liver nodules had compared to other 24 patients higher end-diastolic volume (ml/m2) 102.8 ± 20.0 vs. 88.2 ± 17.7; p = 0.023, respectively. PIIINP correlated significantly with inferior vena cava flow (r = 0.56; p = 0.030) and with end-diastolic volume (r = 0.53; p = 0.043), but only in patients with liver nodules. CONCLUSION: Gradual progression of liver fibrosis, particularly hepatic arterialization caused by liver nodules formation, increases inferior vena cava flow and subsequent ventricular volume overload may further compromise single ventricle functional reserve in adult patients after TCPC.

Children's Heart Centre 2nd Faculty of Medicine Charles University Prague and Motol University Hospital Prague Czechia

Department of Cardiovascular Surgery 2nd Faculty of Medicine Charles University Prague and Motol University Hospital Prague Czechia

Department of Medical Chemistry and Clinical Biochemistry 2nd Faculty of Medicine Charles University Prague and Motol University Hospital Prague Czechia

Department of Radiology 2nd Faculty of Medicine Charles University Prague and Motol University Hospital Prague Czechia

Department of Rehabilitation and Sports Medicine 2nd Faculty of Medicine Charles University Prague and Motol University Hospital Prague Czechia

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de Leval MR, Kilner P, Gewillig M, Bull C. Total cavopulmonary connection: a logical alternative to atriopulmonary connection for complex fontan operations. J Thorac Cardiovasc Surg. (1988) 96:682–95. PubMed

Marcelletti C, Corno A, Giannico S, Marino B. Inferior vena cava-pulmonary artery extracardiac conduit. A new form of right heart bypass. J Thorac Cardiovasc Surg. (1990) 100:228–32. PubMed

Plappert L, Edwards S, Senatore A, De Martini A. The epidemiology of persons living with fontan in 2020 and projections for 2030: development of an epidemiology model providing multinational estimates. Adv Ther. (2022) 39:1004–15. 10.1007/s12325-021-02002-3 PubMed DOI PMC

Van De Bruaene A, Claessen G, Salaets T, Gewillig M. Late fontan circulatory failure. What drives systemic venous congestion and low cardiac output in adult fontan patients? Front Cardiovasc Med. (2022) 9:825472. 10.3389/fcvm.2022.825472 PubMed DOI PMC

Hilscher MB, Wells ML, Venkatesh SK, Cetta F, Kamath PS. Fontan-associated liver disease. Hepatology. (2022) 75:1300–21. 10.1002/hep.32406 PubMed DOI

Téllez L, Rodríguez-Santiago E, Albillos A. Fontan-associated liver disease: a review. Ann Hepatol. (2018) 17:192–204. 10.5604/01.3001.0010.8634 PubMed DOI

Fisher DJ, Geva T, Feltes TF, Cecchin F, Nihill MR, Grifka R, et al. Lifelong management of patients with a single functional ventricle. Tex Heart Inst J. (1995) 22:284–95. PubMed PMC

Illinger V, Materna O, Slabý K, Jičínská D, Kovanda J, Koubský K, et al. Exercise capacity after total cavopulmonary anastomosis: a longitudinal paediatric and adult study. ESC Heart Fail. (2021) 9:337–44. 10.1002/ehf2.13747 PubMed DOI PMC

Whitehead KK, Harris MA, Glatz AC, Gillespie MJ, DiMaria MV, Harrison NE, et al. Status of systemic to pulmonary arterial collateral flow after the fontan procedure. Am J Cardiol. (2015) 115:1739–45. 10.1016/j.amjcard.2015.03.022 PubMed DOI PMC

Vali Y, Lee J, Boursier J, Spijker R, Löffler J, Verheij J, et al. Enhanced liver fibrosis test for the non-invasive diagnosis of fibrosis in patients with NAFLD: a systematic review and meta-analysis. J Hepatol. (2020) 73:252–62. 10.1016/j.jhep.2020.03.036 PubMed DOI

Chaloupecký V, Svobodová I, Hadacová I, Tomek V, Hucín B, Tláskal T, et al. Coagulation profile and liver function in 102 patients after total cavopulmonary connection at mid term follow up. Heart. (2005) 91:73–9. 10.1136/hrt.2003.026419 PubMed DOI PMC

Kaulitz R, Haber P, Sturm E, Schäfer J, Hofbeck M. Serial evaluation of hepatic function profile after fontan operation. Herz. (2014) 39:98–104. 10.1007/s00059-013-3811-5 PubMed DOI

Wu FM, Kogon B, Earing MG, Aboulhosn JA, Broberg CS, John AS, et al. Liver health in adults with fontan circulation: a multicenter cross-sectional study. J Thorac Cardiovasc Surg. (2017) 153:656–64. 10.1016/j.jtcvs.2016.10.060 PubMed DOI

Goldberg DJ, Surrey LF, Glatz AC, Dodds K, O’Byrne ML, Lin HC, et al. Hepatic fibrosis is universal following fontan operation, and severity is associated with time from surgery: a liver biopsy and hemodynamic study. J Am Heart Assoc. (2017) 6:e004809. 10.1161/JAHA.116.004809 PubMed DOI PMC

Possner M, Gordon-Walker T, Egbe AC, Poterucha JT, Warnes CA, Connolly HM, et al. Hepatocellular carcinoma and the fontan circulation: clinical presentation and outcomes. Int J Cardiol. (2021) 322:142–8. 10.1016/j.ijcard.2020.08.057 PubMed DOI

Bryant T, Ahmad Z, Millward-Sadler H, Burney K, Stedman B, Kendall T, et al. Arterialised hepatic nodules in the fontan circulation: hepatico-cardiac interactions. Int J Cardiol. (2011) 151:268–72. 10.1016/j.ijcard.2010.05.047 PubMed DOI

Panvini N, Dioguardi Burgio M, Sartoris R, Maino C, Van Wettere M, Plessier A, et al. Mr imaging features and long-term evolution of benign focal liver lesions in budd-chiari syndrome and fontan-associated liver disease. Diagn Interv Imaging. (2022) 103:111–20. 10.1016/j.diii.2021.09.001 PubMed DOI

Téllez L, Rodríguez de Santiago E, Minguez B, Payance A, Clemente A, Baiges A, et al. Prevalence, features and predictive factors of liver nodules in fontan surgery patients: the valdig fonliver prospective cohort. J Hepatol. (2020) 72:702–10. 10.1016/j.jhep.2019.10.027 PubMed DOI

Munsterman ID, Duijnhouwer AL, Kendall TJ, Bronkhorst CM, Ronot M, van Wettere M, et al. The clinical spectrum of fontan-associated liver disease: results from a prospective multimodality screening cohort. Eur Heart J. (2019) 40:1057–68. 10.1093/eurheartj/ehy620 PubMed DOI

Shin YR, Kim SU, Lee S, Choi JY, Park HK, Yoo JE, et al. Noninvasive surrogates are poor predictors of liver fibrosis in patients with fontan circulation. J Thorac Cardiovasc Surg. (2021) [Epub ahead of print]. 10.1016/j.jtcvs.2021.12.028 PubMed DOI

Gudowska M, Gruszewska E, Panasiuk A, Cylwik B, Swiderska M, Flisiak R, et al. High serum N-terminal propeptide of procollagen Type III concentration is associated with liver diseases. Prz Gastroenterol. (2017) 12:203–7. 10.5114/pg.2017.70474 PubMed DOI PMC

López B, González A, Díez J. Circulating biomarkers of collagen metabolism in cardiac diseases. Circulation. (2010) 121:1645–54. 10.1161/circulationaha.109.912774 PubMed DOI

Huttin O, Kobayashi M, Ferreira JP, Coiro S, Bozec E, Selton-Suty C, et al. Circulating multimarker approach to identify patients with preclinical left ventricular remodelling and/or diastolic dysfunction. ESC Heart Fail. (2021) 8:1700–5. 10.1002/ehf2.13203 PubMed DOI PMC

Trusty PM, Wei Z, Rychik J, Russo PA, Surrey LF, Goldberg DJ, et al. Impact of hemodynamics and fluid energetics on liver fibrosis after fontan operation. J Thorac Cardiovasc Surg. (2018) 156:267–75. 10.1016/j.jtcvs.2018.02.078 PubMed DOI

Trusty PM, Wei ZA, Rychik J, Graham A, Russo PA, Surrey LF, et al. Cardiac magnetic resonance-derived metrics are predictive of liver fibrosis in fontan patients. Ann Thorac Surg. (2020) 109:1904–11. 10.1016/j.athoracsur.2019.09.070 PubMed DOI

Eipel C, Abshagen K, Vollmar B. Regulation of hepatic blood flow: the hepatic arterial buffer response revisited. World J Gastroenterol. (2010) 16:6046–57. 10.3748/wjg.v16.i48.6046 PubMed DOI PMC

Bocca C, Novo E, Miglietta A, Parola M. Angiogenesis and fibrogenesis in chronic liver diseases. Cell Mol Gastroenterol Hepatol. (2015) 1:477–88. 10.1016/j.jcmgh.2015.06.011 PubMed DOI PMC

Caro-Dominguez P, Chaturvedi R, Chavhan G, Ling SC, Yim D, Porayette P, et al. Magnetic resonance imaging assessment of blood flow distribution in fenestrated and completed fontan circulation with special emphasis on abdominal blood flow. Korean J Radiol. (2019) 20:1186–94. 10.3348/kjr.2018.0921 PubMed DOI PMC

Ohuchi H, Miyazaki A, Negishi J, Hayama Y, Nakai M, Nishimura K, et al. Hemodynamic determinants of mortality after fontan operation. Am Heart J. (2017) 189:9–18. 10.1016/j.ahj.2017.03.020 PubMed DOI

Moller S, Bernardi M. Interactions of the heart and the liver. Eur Heart J. (2013) 34:2804–11. 10.1093/eurheartj/eht246 PubMed DOI