The subset of patients with visceral heterotaxy characterized by right isomerism is an uncommon cardiac anomaly.1, 2 The totally anomalous pulmonary venous drainage which is an essential part of this syndrome has a markedly less favourable prognosis when compared to totally anomalous pulmonary venous connection seen in isolation.2 The association of this combination with major aortopulmonary collateral arteries is extremely rare.3 We describe our experience with such a case, reviewing the literature specifically with its implication on the management in the postoperative period.
Case report
A female Caucasian neonate, weighing 2880 grams, was born at term with an antenatal diagnosis of complex congenital cardiac disease. She developed cyanosis shortly after birth, with a saturation of oxygen of 30%, and was started on Prostaglandin E2. She was ventilated and transferred urgently to the regional paediatric cardiac unit.
On arrival, trans-thoracic echocardiography confirmed the existence of a constellation of major cardiac anomalies, including a right-sided heart, isomerism of the right atrial appendages, common atrioventricular junction guarded by a common valve, biventricular atrioventricular connections to a left ventricular dominant ventricular mass, double outlet right ventricle with infundibular and valvar pulmonic stenosis, and infra-diaphragmatic totally anomalous pulmonary venous drainage. In essence, she had complex cyanotic congenital heart disease producing a functionally univentricular situation. An urgent repair of the infracardiac totally anomalous pulmonary venous drainage was performed on the third day of life.
A median sternotomy was performed. Cardio-pulmonary bypass was initiated with aorto-right atrial cannulation, and the repair was performed under deep hypothermic circulatory arrest at 18 degrees Celsius. The common atrium was opened, and a wide anastomosis was performed between the atrium and the common pulmonary venous confluence. The vertical vein was ligated. The periods required for cardio-pulmonary bypass and deep hypothermic circulatory arrest, respectively, were 90 and 38 minutes. Postoperatively, her haemodynamic situation stabilized with minimal inotropic support. Further recovery was delayed by chylothorax and coagulase negative staphylococcal sepsis.
A major concern then became her ventilator dependency, which persisted two weeks after the repair despite maintaining saturations of oxygen above 94%. The chest X-ray at this time showed pulmonary plethora (Fig. 1), and echocardiograms confirmed a good repair. In view of the unexplained pulmonary plethora, and the inability to wean from mechanical ventilation, we proceeded to cardiac catheterization and angiography. This confirmed the echocardiographic findings. The pulmonary arteries were hypoplastic, and both lungs were additionally supplied by major aorto-pulmonary collateral arteries (Fig. 2a). She underwent percutaneous transcatheter occlusion of four major collateral arteries using a total of 26 coils (Fig. 2b). The upper lobe of the right lung was supplied exclusively by collateral arteries from the right subclavian artery, which were not embolised. Subsequent to the embolisation, the chest X-ray showed reduced flow of blood to the lungs (Fig. 1b). It then proved possible to wean from the ventilator, and she was subsequently discharged back to her local hospital. On follow-up at 12 months of age, she is doing remarkably well.

Figure 1. The Chest X-ray taken subsequent to the repair (a) shows plethoric lung fields. After discovering and blocking the collateral arteries, there was a reduction noted in the pulmonary plethora (b).

Figure 2. The angiogram (a) reveals the presence of four major aorto-pulmonary collateral arteries, which were successfully occluded (b) using coils.
Discussion
The variant of visceral heterotaxy syndromes characterized by isomerism of the right atrial appendage is known to be a complex form of congenital cardiac disease associated with high morbidity and mortality. In such patients, the blood from the lungs always returns to the heart in anomalous fashion, even if the pulmonary veins connect to one or other atrial chamber, simply because the appendages on both sides are of right morphology. Hence, all patients with right isomerism must have totally anomalous pulmonary venous connection. Some authors were mistaken, therefore, when they argued that totally anomalous pulmonary venous drainage was seen in only 87% of these patients.1 The infracardiac variant of totally anomalous connection makes up about one-third of the overall pattern of pulmonary venous drainage.2 Despite improvement in survival for simple cases, management of totally anomalous pulmonary venous drainage in the setting of other associated cardiac lesions remains challenging.2 Over the decade, operative mortality for simple cases decreased from 26% to 8%, but mortality for complex cases remained constant at 52%.2 Multivariable analysis identified only functionally univentricular hearts, and associated cardiac lesions, as predictors of operative mortality.2 A more aggressive approach is suggested by early recognition and assessment of these critically ill infants, followed by early surgery.4
Pulsed Doppler ultrasound has been used to characterize the patterns of venous flow from the lungs in the fetus with totally anomalous pulmonary venous drainage and associated complex congenital cardiac lesions.5 Echocardiography is a reliable tool for the assessment of these cyanotic neonates. In neonates with totally anomalous pulmonary venous drainage, the sites of drainage and profiles of flow through the pulmonary veins can be exactly determined by Doppler echocardiography preoperatively, which makes cardiac catheterization unnecessary.6 Cardiac catheterization is reserved for cases where the diagnosis is the mixed variant of totally anomalous pulmonary venous drainage.7 Helical computed tomographic angiography with differential colour imaging technique and three-dimensional reconstruction is an alternative to cardiac catheterisation.8 It provides precise spatial information of complicated vascular anomalies, and clearly demonstrates any pulmonary venous obstruction when there is totally anomalous pulmonary venous drainage.8
Uemura et al.3 found supply to the lungs through systemic-to-pulmonary collaterals in only 3% of the patients they examined with pulmonary atresia and right isomerism.3 As far as we know, however, thus far there has been no successful correction reported of the combination of right isomerism and infra-cardiac totally anomalous pulmonary venous connection with pulmonary arteries supply via major aorto-pulmonary collateral arteries. This unique association, which has a dramatic impact on the pathophysiology subsequent to surgical repair, seems to be due to a developmental insult early in the embryonic formation of the supporting vasculature of the lung. A structural study using quantitative morphometric techniques of the pulmonary circulation and of the heart in totally anomalous pulmonary venous drainage as seen in early infancy led to some interesting observations. When the connection is infra-diaphragmatic, obstruction to pulmonary venous return develops soon after birth, preventing any large increase in flow of blood to the lungs. Thus, neither the pulmonary arteries nor the right ventricle become dilated.9 Examination of the pulmonary parenchyma from such patients has demonstrated hypoplasia of the small pulmonary arteries, elucidating the mechanism underlying the poor outcome in these patients.10 In addition, the association of pulmonary stenosis in our patient must also have contributed to decreased flow of blood to the lungs in fetal life, promoting the development and persistence of the major aorto-pulmonary collateral arteries.
Acknowledgement
We thanks Bharati Sinha, Department of Neonatal Medicine, Royal London Hospital, and Mike Blackburn, Department Pediatric Cardiology, Leeds General Infirmary, Leeds Teaching Hospitals, Leeds, for their help in revising our manuscript. We thank Mr. S. Powell and Ms Ezenee Kolbaba, Department of Medical Illustration, Leeds General Infirmary, Leeds Teaching Hospitals, Leeds, United Kingdom for their help with illustration.