Discussion

Extracardiac or intracardiac right-to-left shunts are potential causes of refractory cyanosis, apart from haemoglobin disorders.^{Reference Porepa, Benson, Manson and Friedman1} The presence of an anomalous hepatic venous return is exceedingly unusual in the setting of biventricular repair of CHD.^{Reference Stoller, Hoffman, White and Mee2} It represents nevertheless a well-known issue in patients with heterotaxy syndrome who undergo the Fontan pathway, when the hepatic veins are separated from the inferior caval vein and are not redirected towards the pulmonary circulation inducing the development of pulmonary arteriovenous malformations.^{Reference Srivastava, Preminger and Lock3} These can also be favoured by a portosystemic shunt: chest CT scan and abdominal Doppler ultrasound are very useful in this context and lung perfusion scintigraphy can help to exclude an intrapulmonary shunt, besides the ultrasound microbubble test.^{Reference Rodríguez-Roisin and Krowka4}

Although anomalous hepatic venous connections are expected with left atrial isomerism given the usual azygos continuation of the inferior caval vein, multiple hepatic drainage as in the first case is very rare: the 3 hepatic veins usually merge at the diaphragmatic level before draining into a right-sided, left-sided or common atrium. To reverse pulmonary arteriovenous malformations and cyanosis, diversion of hepatic flow from the left to the right atrium with a baffle was depicted in literature, but the coronary sinus still drained into the left atrium causing some level of desaturation.^{Reference Lee, Menkis and Rosenberg5} Section and reimplantation of the common hepatic vein orifice, or intra-atrial implantation of a prosthetic vascular graft conduit were also reported, but these were not deemed possible in the first patient, respectively because of the distance between the culprit hepatic vein and the right-sided atrium, in addition to the risks of thrombosis and infection.^{Reference Stoller, Hoffman, White and Mee2,Reference Johnson, Schamberger, Brown and Girod6} Intracardiac rerouting of a single hepatic vein without conduit, as described here, seems therefore an interesting alternative and has not yet been reported.

Pulmonary arteriovenous malformations can also be associated with cyanosis only while standing, in the setting of platypnea-orthodeoxia syndrome. The latter is characterised by dyspnoea and arterial desaturation, defined by a drop in oxygen saturation of more than 5% while in the upright position, which improves upon recumbency, often associated with an extracardiac or intracardiac shunt including atrial septal defect. This syndrome is a well-known cause of cyanosis in the elderly, when the ascending aorta is dilated, or after thoracic surgery, causing a preferential blood flow across the atrial defect with or without increased right atrial pressure.^{Reference Agrawal, Palkar and Talwar7} This syndrome has not been depicted in younger children, when the upright position echocardiography is rarely performed.^{Reference Cetiner, Uyan and Celiker8} Although normally caused by acquired disorders, a rare example of foetal disorder leading to neonatal platypnea-orthodeoxia has been described here.

In the second case, 2 mechanisms may explain the right-to-left shunt mainly during upright position and crying: intermittently high right atrial pressure functionally and abnormal cardiac anatomy. Functionally, the increased venous return and right atrial pressure during the first-phase deep inspiration of crying followed by increased intrathoracic pressure during the second-phase strain may explain the inversion of the shunt observed in the present report.^{Reference Dinwiddie, Pitcher-Wilmott, Schwartz, Shaffer and Fox9} Additionally, right atrial pressure has been shown to rise during the first seconds after standing up independently from intrathoracic pressures.^{Reference Sprangers, Wesseling, Imholz, Imholz and Wieling10} Moreover, the ductus venosus plays the role of an antenatal flow regulator allowing full development of the hepatic venous vascularisation and limiting the blood arriving to the heart: its absence may have caused the left portal agenesis and the antenatal overflow from the umbilical vein to the right cardiac chambers directly and to the left heart through the patent foramen ovale.^{Reference Pacheco, Brandão, Montenegro and Matias11} The resulting antenatal global heart dilatation led to significant ventricular hypertrophy with persisting neonatal right ventricular hypertrophy, despite the resolution of overflow with umbilical vein closure, and decreased compliance which could have contributed to the baseline increased right atrial pressure. However, invasive pressure and compliance assessment were not realised as the newborn was clinically well apart from cyanosis and improved progressively.

Anatomically, the ductus venosus agenesis associated with the abnormal umbilical vein to the right atrium induced aortic dilatation and tricuspid valve deformation, altogether causing the atrial septum tilting with flow redirection towards the defect favoured by the prominent Eustachian valve as reported in literature.^{Reference Agrawal, Palkar and Talwar7} Indeed, a counter-clockwise heart rotation with atrial septal plane horizontalisation has been suggested in literature as the classical anatomical deformation explaining platypnea-orthodeoxia in adults bringing the interatrial septum closer to the opening of the inferior caval vein, a similar orientation of the inferior caval vein perpendicular to the septum was found in the current study (Fig. 2a).^{Reference Zanchetta, Rigatelli and Ho12} Further, traumatic tricuspid valve and papillary muscle distortion causing tricuspid regurgitation has been associated with platypnea-orthodeoxia, although no significant tricuspid regurgitation was noticed in the present second case.^{Reference Hsu, Leu, Lu, Yu and Hsu13} Besides, in literature, a newborn with direct umbilical vein to the right atrium and ductus venosus agenesis had no reported cyanosis for at least 2 months after birth but there was no tricuspid deformation.^{Reference Fa and Brewer14} The progressive resolution of the relative aortic dilatation and tricuspid distortion and of the right ventricular hypertrophy allowed improvement of saturation. Percutaneous atrial shunt closure could be suggested in the absence of spontaneous closure in case of persistent cyanosis or significant left-to-right shunt after potential normalisation of the tricuspid and aortic abnormalities.

Eventually, heterotaxy including interruption of the inferior caval vein, as in the first case, and abnormal direct umbilical vein to the right atrium, as in the second case, can be associated leading to poor outcome.^{Reference Jouk and Champetier15} Indeed, outcomes after prenatal diagnosis of ductus venosus agenesis depend on the presence of other malformations: partial portal vein agenesis is usually benign when isolated.^{Reference Nagy, Cernea and Dijmarescu16} To our knowledge, this is the first description of a platypnea-orthodeoxia syndrome in the neonate.