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Three Part Question

In [patients with an intrapulmonary shunt accompanying anomalous hepatic venous drainage] does [redirection of the hepatic venous drainage to the lungs] improve [patient hypoxemia]

Clinical Scenario

You are scheduled to perform corrective surgery on a 3-year-old boy with a diagnosis of secundum atrial septal defect (ASD). The child presented with progressive cyanosis of one year's duration accompanied by easy fatigability on exercise. There were no indications of hepatic disease. On physical examination, clubbing was noted. Oxygen saturation was 74% in room air, and hemoglobin was 21 g/dl. Echocardiography demonstrated an interrupted inferior vena cava with azygos continuation to a right superior vena cava and a small secundum ASD. Heart catheterization was performed revealing anomalous drainage of all hepatic veins into the left atrium and a small secundum ASD with no measurable cross shunting. Contrast echocardiography confirmed the presence of a pulmonary arteriovenous malformation. You explain to the boy's father that during surgery you will be diverting the hepatic flow and coronary sinus from the left to the right atrium using an autologous pericardial patch. The father asks if this procedure will improve his child's oxygen saturation and if the child will regain a normal level of activity. You are unable to answer him to your satisfaction and therefore you resolve to check the literature for evidence of regression of intrapulmonary shunts after surgical correction of anomalous hepatic venous drainage.

Search Strategy

Medline 1966 to January 2005 using OVID interface.
[exp arteriovenous malformations/OR arteriovenous fistula/OR shunt.mp] and (exp cyanosis/OR hypoxemia.mp]

Search Outcome

Our survey of the literature revealed 704 papers among which only 3 case reports of 4 cases of anomalous hepatic venous drainage into the left atrium were similar to our case. Cross-checking the reference lists provided an additional 10 papers with 11 cases. These papers were reviewed in full and are presented in the table. In 7 of the reported cases, the hepatic venous drainage was due to a cardiac surgical shunt procedure; in 2, it was due to unintentional surgical exclusion of the hepatic venous flow from the pulmonary circulation; and in 6, it was congenital.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Guenthard et al, 1990, UK	1	Case report (level 5)	11-year-old girl with cyanosis after Blalock shunt for subpulmonary stenosis	Hepatic vein drained to right sided physiological left atrium; subpulmonary stenosis; common atrium; common atrioventricular valve
Hirayama et al, 1991, Japan	1	Case report (level 5)	5-year-old boy	Double-outlet right ventricle; mitral atresia; pulmonic stenosis
Knight, 1995, Australia	1	Case report (level 5)	Infant with progressive hypoxemia after Kawashima operation	Left atrium isomerism; double-outlet right ventricle; hypoplastic left ventricle; subpulmonic stenosis; azygos extension of inferior vena cava	Intrapulmonary shunt regressed after anomalous hepatic venous blood was redirected
Fernandez-Mortorell et al, 1996, USA	2	Case report (level 5)	5 year old girl with cyanosis following fenestrated Fontan procedure for tricuspid atresia; anomalous hepatic vein to right atrium was included in the pulmonary venous atrium following the procedure	Double-outlet right ventricle; hypoplastic left ventricle; anomalous pulmonary venous drainage to right atrium	Awaiting surgical intervention, the 5 year old patient had cardiac arrest in the intensive care unit and could not be resuscitated After surgical ligation of the accessory hepatic vein to the pulmonary venous atrium, oxygen saturation was 90%
			2-year-old boy with cyanosis following Fontan procedure; anomalous hepatic venous drainage as above	Double-outlet right ventricle; mitral atresia; pulmonary atresia; D-malposition of the great vessels
Tofeig, 1998, UK	1	Case report (level 5)	67-month-old boy underwent Fontan procedure after which cyanosis developed because of hepatic venous entry into the pulmonary venous atrium	Right atrium isomerism; common atrium; small left ventricle with atrioventricular septal defect; double-outlet right ventricle; pulmonic stenosis	Hepatic venous return to left atrium was occluded with a septal occluder, with restoration of normal oxygenation
Duncan et al, 1999, USA	1	Case report (level 5)	12 year old with cyanosis	Visceral heterotaxia; dextrocardia; large ventricular septal defect, right ventricular outflow tract obstruction; secundum atrial septal defect; left inferior vena cava; azygos extension of inferior vena cava; drainage of hepatic veins to the left atrium	At 5 years oxygenation saturation was at 95% after creation of an intracardial tunnel to direct the hepatic veins to the right atrium
Nagai et al, 1966, Japan	1	Case report (level 5)	12 year old girl	Left atrium communicated with coronary sinus through a 1.5 cm ostium; hepatic vein opened to the coronary sinus
Yee, 1968, Australia	1	Case report (level 5)	20 month old boy with cyanosis	Tetralogy of Fallot; anomalous pulmonary venous drainage into right atrium; right-sided aortic arch; patent foramen ovale; bicuspid pulmonary valve
Mantri et al, 1994, India	1	Case report (level 5)	12 year old girl	Infundibular pulmonic stenosis; bifurcated inferior vena cava with drainage into coronary sinus and entry of hepatic vein
Lee et al, 1998, USA	1	Case report (level 5)	6-year-old boy with cyanosis and clubbing	Interrupted inferior vena cava with azygous continuation to a right superior vena cava; anomalous drainage of hepatic veins into the left atrium	Intrapulmonary shunt resolved at 12 months after hepatic veins diverted to the right atrium
Johnson et al, 2002, USA	1	Case report (level 5)	11 year old boy with total anomalous systemic venous return	Hemizygous continuation of a left-sided inferior vena cava to a left-sided superior vena cava which drained to the left atrium; hepatic veins also drained to the left atrium. Right sided superior vena cava was absent and a secondary atrial septal defect was present	At 18 months, pulse oximetry was 98% in room air. No intracardiac shunting and no return of microbubble to left heart on echocardiography
Stoller et al, 20013, USA	1	Case report (level 5)	50-year old woman with life-long hypoxemia and digital clubbing	Inferior vena cava interruption with azygos continuation and anomalous hepatic venous drainage into left atrium	At 3 months, resolution of associated intrapulmonary shunt

Comment(s)

We suspect that the intrapulmonary shunt in the reported patients was caused by the exclusion of hepatic venous blood from the lungs. Indeed, this process has been amply described in children undergoing Glenn shunt (superior vena cava to right pulmonary artery anastomosis), Fontan procedure (atriopulmonary anastomosis to allow bilateral pulmonary arterial flow), and Kawashima operation for tricuspid atresia, which are associated with a 21% rate of intrapulmonary shunts [Srivastava]. The shunts have been shown to regress when the hepatic venous drainage is diverted back through the pulmonary circulation [Tofeig, Johnson]. Furthermore, intrapulmonary shunt was described in 2 patients with anomalous hepatic venous drainage to the left atrium accompanying the interruption and azygos extension of the inferior vena cava [Lee]; again, the shunt regressed with surgical correction of the anomalous venous drainage. In an earlier report of anomalous hepatic venous drainage into the left atrium, Yee suggested that the malformation involves an abnormal enlargement of the sinus venosus (the precursor of the heart) and preservation of the right subcardinal vein, thus inviting an embryologic explanation. The putative mechanism underlying the development of intrapulmonary shunts apparently involves the exclusion of a hepatic factor from the pulmonary circulation [Knight, Duncan]. Duncan et al, proposed that this factor may be an inhibitor of endothelial proliferation. This notion was supported by their observation of lakes of dilated, thin-walled vessels and chains of clustered small vessels in the lungs of 2 children with post-cardiac-surgery intrapulmonary shunts. The similar development of intrapulmonary vascular dilatations in patients with hepatopulmonary syndrome, and their reversal after liver transplantation [Lange], invites speculation that nitric oxide is implicated in the vascular changes [Soderman, Fallon]. Further evidence of a humoral mediator in cases of anomalous hepatic venous drainage is provided by the reversal of the intrapulmonary shunt after surgical diversion of the anomalous hepatic venous blood into the pulmonary circulation, in addition to the ipsilateral, single-lung angiographic appearance of the intrapulmonary shunt when hepatic venous blood is excluded from only one lung [Srivastava]. In summary, the prior reports documenting the disappearance of intrapulmonary shunts once the hepatic venous drainage is diverted to the right atrium suggest that exclusion of hepatic venous blood from the lungs can predispose the patient to a reversible intrapulmonary shunt

Clinical Bottom Line

The presence of an anomalous hepatic venous return accompanied by cyanosis may lead to the development of pulmonary arteriovenous malformations. If surgical redirection of hepatic venous flow to the pulmonary arterial system is possible, it should be undertaken to prevent or treat the pulmonary arteriovenous malformations and their sequelae. With proper repair, intrapulmonary shunts due to pulmonary arterial exclusion of hepatic venous return can be rapidly reversed.

References

1. Guenthard J, Carvalho JS, Anderson RH, Rigby ML. Hepatic venous connection to a persistent inferior caval vein in left isomerism. Eur Heart J 1990;11:845–847.
2. Hirayama T, Imai Y, Kurosawa H, Nakae S, Fukuchi S, Hoshino S. [Fontan procedure for DORV with mitral atresia and anomalous hepatic vein connection to the left atrium: advantage of leaving right to left shunt in situ]. Nippon Kyobu Geka Gakkai Zasshi 1991;39:76–80. Article in Japanese.
3. Knight WB, Mee RBB. A cure for pulmonary arteriovenous fistulas? Ann Thorac Surg 1995;59:999–1001.
4. Fernandez-Mortorell P, Sklansky MS, Lucas VW, Kashani LA, Cocalis MW, Jamieson SW, Rothman A. Accessory hepatic vein to pulmonary venous atrium as a cause of cyanosis after the Fontan operation? Am J Cardiol 1996;77:1386–1387.
5. Tofeig M, Walsh KP, Arnold R. Transcatheter occlusion of a post-Fontan residual hepatic vein to pulmonary venous atrium communication using the Amplatzer septal occluder. Heart 1998;79:624–626.
6. Duncan BW, Kneebone JM, Chi EY, Hraska V, Isik FF, Rosenthal GL, Jones TK, Starnes SL, Lupinetti FM. A detailed histologic analysis of pulmonary arteriovenous malformations in children with cyanotic congenital heart disease. J Thorac Cardiovasc Surg 1999;117:931–938.
7. Agnoletti G, Borghi A, Annecchino FP, Crupi G. Regression of pulmonary fistulas in congenital heart disease after redirection of hepatic venous flow to the lungs. Ann Thorac Surg 2001;72:909–911.
8. Nagai I, Oda Y, Kawada K, Yamamota K, Iri H. [Case of communication of the left atrium and the coronary sinus complicated by anomalous hepatic vein return.]. Kyobu Geka 1966;19:363–366. Article in Japanese.
9. Yee KF. Anomalous termination of a hepatic view in the left atrium. Arch Pathol 1968;85:219–223.
10. Mantri RR, Bajaj R, Shrivastava S. Multiple anomalies of caval veins in a patient with pulmonic stenosis. Int J Cardiol 1994;46:172–174.
11. Lee J, Menkis AH, Rosenberg HC. Reversal of pulmonary arteriovenous malformation after diversion of anomalous hepatic drainage. Ann Thorac Surg 1998;65:848–849.
12. Johnson TR, Schamberger MS, Brown JW, Girod DA. Resolution of acquired pulmonary arteriovenous malformations in a patient with total anomalous systemic venous return. Pediatr Cardiol 2002;23:210–212.
13. Stoller SK, Hoffman RM, White RD, Mee RBB. Anomalous hepatic venous drainage into the left atrium: an unusual cause of hypoxemia. Respir Care 2003;48:58–62.
14. Srivastava D, Preminger T, Lock JE, Mandell V, Keane JF, Mayer JE, Kozakewich H, Spevak PJ. Hepatic venous blood and the development of pulmonary arteriovenous malformations in congenital heart disease. Circulation 1995;92:1217–1222.
15. Lange PA, Stoller JK. The hepatopulmonary syndrome. Ann Intern Med 1995;122:521–529.
16. Soderman C, Leone A, Furst V, Persson MG. Endogenous nitric oxide in exhaled air from patients with liver cirrhosis. Scand J Gastroenterol 1997;32:591–597.
17. Fallon MB, Abrans GA, Luo B, Hou Z, Dai J, Jud DD. The role of endothelial nitric oxide synthase in the pathogenesis of a rat model of hepatopulmonary syndrome. Gastroenterology 1997;113:606–614.