In spite of excellent long term survival the Fontan Kreutzer procedure commonly presents late failure due to end-organ damage. Several advances have been described to refine single ventricle management and surgical techniques. However, very little research has been dedicated to the lymphatic circulation in the precarious Fontan hemodynamic state. The lymphatic circulation is clearly affected since there is increased lymph production, which requires to be drained at a similar or higher pressure than it is produced, commonly resulting in chronic lymphedema. Chronic lymphedema induces fibrosis and end-organ failure even in normal circulation. Diverting lymph drainage to the low-pressured systemic atrium in Fontan may represent a valid alternative for the treatment of devastating complications as protein-losing enteropathy and plastic bronchitis and may prevent or decrease the development of end-organ fibrosis or failure.
FontanFBaudetE. Surgical repair of tricuspid atresia. Thorax. 1971;26(3):240–248.
2.
KreutzerGGalíndezEBonoHDe PalmaCLauraJP. An operation for the correction of tricuspid atresia. J Thorac Cardiovasc Surg. 1973;66(4):613–621.
3.
d’UdekemYIyengarAJGalatiJC. Redefining expectations of long-term survival after the Fontan procedure: twenty-five years of follow-up from the entire population of Australia and New Zealand. Circulation. 2014;130(11 suppl 1):S32–S38.
4.
PohCLZanninoDWeintraubRG. Three decades later: the fate of the population of patients who underwent the atriopulmonary Fontan procedure. Int J Cardiol. 2017;231:99–104.
5.
LasaJJGlatzACDagaAShahM. Prevalence of arrhythmias late after the Fontan operation. Am J Cardiol. 2014;113(7):1184–1188.
ChoiILeeSHongY-K. The new era of the lymphatic system: no longer secondary to the blood vascular system. Cold Spring Harb Perspect Med. 2012;2(4):a006445. doi:10.1101/cshperspect.a006445.
8.
BalukPFuxeJHashizumeH. Functionally specialized junctions between endothelial cells of lymphatic vessels. J Exp Med. 2007;204(10):2349–2362.
ChenJM. The thoracic duct: predictably unpredictable?J Thorac Cardiovasc Surg. 2015;150(3):497.
11.
TijerinaGOElizondoORRuizFROrtegónGEGuzmánLS. Morfología del conducto torácico y su importancia clínica. Med Univ. 2007;9(35):72–76.
12.
HessPRRawnsleyDRJakusZ. Platelets mediate lymphovenous hemostasis to maintain blood-lymphatic separation throughout life. J Clin Invest. 2014;124(1):273–284.
13.
SemoJNicenboimJYanivK. Development of the lymphatic system: new questions and paradigms. Development. 2016;143(6):924–935.
14.
AlitaloKCarmelietP. Molecular mechanisms of lymphangiogenesis in health and disease. Cancer Cell. 2002;1(3):219–227.
15.
KlotzLNormanSVieiraJM. Cardiac lymphatics are heterogeneous in origin and respond to injury. Nature. 2015;522(7554):62–67.
16.
IizukaSOnizukaMInagakiMIshikawaSMitsuiKMitsuiT. Analysis of thoracic duct flow waves using fast Fourier transform in sheep. Lymphology. 1999;32(1):22–28.
17.
HsiaTYKhambadkoneSBradleySMde LevalMR. Subdiaphragmatic venous hemodynamics in patients with biventricular and Fontan circulation after diaphragm placation. J Thorac Cardiovasc Surg. 2007;134(6):1397–1405.
18.
DatarSAGongWHeY. Disrupted NOS signaling in lymphatic endothelial cells exposed to chronically increased pulmonary lymph flow. Am J Physiol Heart Circ Physiol. 2016;311(1):H137–H145.
19.
DatarSAOishiPEGongW. Altered reactivity and nitric oxide signaling in the isolated thoracic duct from an ovine model of congenital heart disease with increased pulmonary blood flow. Am J Physiol Heart Circ Physiol. 2014;306(7):H954–H962.
20.
DoriYKellerMSRomeJJ. Percutaneous lymphatic embolization of abnormal pulmonary lymphatic flow as treatment of plastic bronchitis in patients with congenital heart disease. Circulation. 2016;133(12):1160–1170.
21.
PellicoroARamachandranJPIredaleJPFallowfieldJA. Liver fibrosis and repair: immune regulation of wound healing in a solid organ. Nat Rev Immunol. 2014;14(3):181–194.
22.
AlitaloK. The lymphatic vasculature in disease. Nat Med. 2011;17(11):1371–1380.
23.
TammelaTAlitaloK. Lymphangiogenesis: molecular mechanisms and future promise. Cell. 2010;140(4):460–476.
24.
GlasgowCGEl-ChemalySMossJ. Lymphatics in lymphangioleiomyomatosis and idiopathic pulmonary fibrosis. Eur Respir Rev. 2012;21(125):196–206.
25.
ZhangTGuanGLiuG. Disturbance of lymph circulation develops renal fibrosis in rats with or without contralateral nephrectomy. Nephrology (Carlton). 2008;13(2):128–138.
26.
QuinJWShannonAD. The influence of the lymph node on the protein concentration of efferent lymph leaving the node. Physiol. 1977;264(2):307–321.
27.
OhtaniOOhtaniY. Lymph circulation in the liver. Anat Rec (Hoboken). 2008;291(6):643–652.
28.
VollmarBWolfBSiegmundSKatsenADMengerMD. Lymph vessel expansion and function in the development of hepatic fibrosis and cirrhosis. Am J Pathol. 1997;151(1):169-175.
29.
WitteMHDumontAEColeWRWitteCLKinterK. Lymph circulation in hepatic cirrhosis. Ann Intern Med. 1969;70(2):303-310.
30.
ChungCIwakiriY. The lymphatic vascular system in liver diseases: its role in ascites formation. Clin Mol Hepatol. 2013;19(2):99–104.
31.
MoriMHebsonCShiodaK. Catheter-measured hemodynamics of adult Fontan circulation: associations with adverse event and end-organ dysfunctions. Congenit Heart Dis. 2016;11(6):589–597.
32.
RychikJ. The relentless effects of the Fontan paradox. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 2016;19(1):37–43.
33.
SarinSKSethiKKNandaR. Measurement and correlation of wedged hepatic, intrahepatic, intrasplenic and intravariceal pressures in patients with cirrhosis of liver and non-cirrhotic portal fibrosis. Gut. 1987;28(3):260–266.
34.
HsiaTYKhambadkoneSDeanfieldJETaylorJFMigliavaccaFDe LevalMR. Subdiaphragmatic venous hemodynamics in the Fontan circulation. J Thorac Cardiovasc Surg. 2001;121(3):436–447.
35.
AgnolettiGFerraroGBordeseR. Fontan circulation causes early, severe liver damage. Should we offer patients a tailored strategy?Int J Cardiol. 2016;209:60–65.
36.
KiesewetterCHSheronNVettukattillJJ. Hepatic changes in the failing Fontan circulation. Heart. 2007;93(5):579–584.
37.
VelpulaMSheronNGuhaNSalmonTHackingNVeldtmanGR. Direct measurement of porto-systemic gradient in a failing Fontan circulation. Congenit Heart Dis. 2011;6(2):175–178.
38.
RychikJGui YangS. Relation of mesenteric vascular resistance after Fontan operation and protein-losing enteropathy. Am J Cardiol, 2002;90(6):672–674.
39.
YuJJYunTJYunSC. Low pulmonary vascular compliance predisposes post-Fontan patients to protein-losing enteropathy. Int J Cardiol. 2013;165(3):454–457.
40.
OhuchiHYasudaKMiyazakiA. Haemodynamic characteristics before and after the onset of protein losing enteropathy in patients after the Fontan operation. Eur J Cardiothorac Surg. 2013;43(3):e49–e57.
41.
MeadowsJGauvreauKJenkinsK. Lymphatic obstruction and protein-losing enteropathy in patients with congenital heart disease. Congenit Heart Dis. 2008;3(4):269–276.
42.
DoriYKellerMSFogelMA. MRI of lymphatic abnormalities after functional single-ventricle palliation surgery. AJR Am J Roentgenol. 2014;203(2):426–431.
43.
KochilasLKShepardCWBerryJMChinAJ. Ultrasonographic imaging of the cervical thoracic duct in children with congenital or acquired heart disease. Echocardiography. 2014;31(9):E282–E286.
44.
GeorgopoulosPMowatCMcMillanDCKingstoneKGhoshSStanleyAJ. Is portal hypertension associated with protein-losing enteropathy?J Gastroenterol Hepatol. 2005;20(1):103–107.
45.
MenonKVShahVKamathPS. The Budd-Chiari syndrome. N Engl J Med. 2004;350(6):578–585.
46.
McIntoshGHMorrisB. The lymphatics of the kidney and the formation of renal lymph. J Physiol. 1971;214(3):365–376.
47.
SeegerHBonaniMSegererS. The role of lymphatics in renal inflammation. Nephrol Dial Transplant. 2012;27(7):2634–2641.
48.
PeãoMNAguasAPde SáCMPereiraASGrandeNR. Scanning electron microscopy of the deep lymphatic network of the murine lung as viewed in corrosion casts. Lymphology. 1993;26(1):42–48.
49.
LeakLV. Lymphatic removal of fluids and particles in the mammalian lung. Environ Health Perspect. 1980;35:55–76.
RaczJManeGFordM. Immunophenotyping and protein profiling of Fontan-associated plastic bronchitis airway cast. Ann Am Thorac Soc. 2013;10(2):98–107.
52.
WolffDTimmerAvan MelleJP. Adverse pulmonary vascular remodeling in the Fontan circulation. J Heart Lung Transplant. 2015;34(3):404–413.
53.
PrasseAMüller-QuernheimJ. Non-invasive biomarkers in pulmonary fibrosis. Respirology. 2009;14(6):788–795.
54.
KazerooniEAMartinezFJFlintA. Thin-section CT obtained at 10-mm increments versus limited three-level thin-section CT for idiopathic pulmonary fibrosis: correlation with pathologic scoring. AJR Am J Roentgenol. 1997;169(4):977–983.
55.
WithanaNPMaXMcGuireHM. Non-invasive imaging of idiopathic pulmonary fibrosis using cathepsin protease probes. Sci Rep. 2016;6:19755.
56.
GursuHAErdoganIVaranB. Oral budesonide as a therapy for protein-losing enteropathy in children after the Fontan operation. J Card Surg. 2014;29(5):712–716.
57.
ShangXKLiYPLiuM. Efficacy of endothelin receptor antagonist bosentan on the long-term prognosis in patients after Fontan operation. Zhonghua Xin Xue Guan Bing Za Zhi. 2013;41(12):1025–1028.
58.
JohnASJohnsonJAKhanMDriscollDJWarnesCACettaF. Clinical outcomes and improved survival in patients with protein-losing enteropathy after the Fontan operation. J Am Coll Cardiol. 2014;64(1):54–62.
59.
RyersonLGoldbergCRosenthalAArmstrongA. Usefulness of heparin therapy in protein-losing enteropathy associated with single ventricle palliation. Am J Cardiol. 2008;101(2):248–251.
60.
KogonBMcConnellMBookW. Fontan conversion with hepatic vein exclusion: a means for hepatic preservation in single ventricle heart disease. Cardiol Young. 2016;26(3):582–585.
61.
BrizardCPLaneGKAlexGCheungMM. Original surgical procedure for the treatment of protein-losing enteropathy in Fontan patients: report of two midterm successes. Circulation. 2016;134(8):625–627.
62.
HraškaV. Decompression of thoracic duct: new approach for the treatment of failing Fontan. Ann Thorac Surg. 2013;96(2):709–711.
63.
AntónioMGordoAPereiraCPintoFFragataIFragataJ. Thoracic duct decompression for protein-losing enteropathy in failing Fontan circulation. Ann Thorac Surg. 2016;101(6):2370–2373.
64.
JacobsMLNorwoodWIJr. Fontan operation: influence of modifications on morbidity and mortality. Ann Thorac Surg. 1994;58(4):945–951.
65.
BrizardCPGoussefNChachquesJCCarpentierAF. Model of complete separation of the hepatic veins from the systemic venous system. Ann Thorac Surg. 2000;70(6):2096–2101.
66.
SchneiderDJBanerjeeAMendelsohnAMNorwoodWIJr. Hepatic venous malformation after modified Fontan procedure with partial hepatic vein exclusion. Ann Thorac Surg. 1997;63(4):1177–1179.
67.
StarlingEH. On the absorption of fluid from the connective tissue spaces. J Physiol. 1896;19(4):312–326.
68.
FoldiMPappN. The role of lymph circulation in congestive heart failure. Jap Circ J. 1961;25(7):703.
69.
WegriaRZekertHWalterKE. Effect of systemic venous pressure on drainage of lymph from the thoracic duct. Am J Physiol. 1963;204:284–288.
70.
DumontAEClaussRHReedGETiceDA. Observations on lymph drainage in patients with congestive heart failure: comparison with findings in hepatic cirrhosis. N Engl J Med. 1963;269:949–952.
71.
ZottiELesageABradhamRNignoneRSealyWYoungW. Prevention and treatment of experimentally induced ascites in dogs by thoracic duct to vein shunt. Surgery. 1966;60(1):28–34.
72.
ColeWRWitteMHKashSLRodgerMBleischWRMuelheimsGH. Thoracic duct-to-pulmonary vein shunt in the treatment of experimental right heart failure. Circulation. 1967;36(4):539–543.
73.
BargerACRichardsonGSRoeBB. Method for producing chronic cardiac failure in dogs. Proc Soc Exp Biol Med. 1950;73(1):113–116.
74.
DeliusRERademeckerMAde LevalMRElliottMJStarkJ. Is a high-risk biventricular repair always preferable to conversion to a single ventricle repair?J Thorac Cardiovasc Surg. 1996;112(6):1561–1568.
75.
KaramlouTPoynterJAWaltersHLIII. Long-term functional health status and exercise test variables for patients with pulmonary atresia with intact ventricular septum: a Congenital Heart Surgeons Society study. J Thorac Cardiovasc Surg. 2013;145(4):1018–1025.
