Persistent pulmonary hypertension of the newborn is a complex disease in the neonatal population, with a heterogeneous aetiology. Persistent pulmonary hypertension may be isolated but also occurs in association with meconium aspiration syndrome, pneumonia, left-to-right intracardiac shunts, and congenital heart disease. Early treatment, regardless of the aetiology, is crucial because advanced disease may be less responsive to therapy.Reference Barst, McGoon and Torbicki 1 Anomalous origin of one pulmonary artery, an uncommon congenital cardiac malformation, is a rare cause of persistent pulmonary hypertension.
Case report
A female infant born prematurely at 33 weeks of gestation by vaginal delivery was admitted to the neonatal intensive care unit for respiratory distress. The Apgar scores were 4 at 1 minute and 6 at 5 minutes. The patient weighed 1890 g at birth and was the third child of non-consanguineous parents. The mother was healthy and had no perinatal complications. On initial examination, the patient was found to be cyanotic with an oxygen saturation of 70%. The patient was intubated and administered surfactants; however, the clinical course of the patient progressively deteriorated. Echocardiographic examination revealed enlargement of the right atrium and ventricle, a large patent ductus arteriosus 4 mm in size with a bidirectional shunt, tricuspid regurgitation (peak velocity, 3.8 milliseconds), a mean pulmonary artery pressure of 60 mmHg, and dilation of the main pulmonary artery. The right pulmonary artery was not visualised on the echocardiogram. The pulmonary venous return from the right lung was normal. After the diagnosis of pulmonary hypertension was made, medical treatments with oral sildenafil, inhaled nitric oxide and magnesium sulphate, and intravenous iloprost were started. However, the clinical course of the patient continued to deteriorate.
Upon follow-up, computed tomography angiography was performed to detail the cardiac anatomy. Contrast-enhanced computed tomography angiography showed that the right pulmonary artery originated from the innominate artery and that the origin of the right pulmonary artery was stenotic. The main pulmonary artery of the right ventricle had just one left branch. The arcus aorta, descending aorta, and the branch of the arcus aorta were normal, whereas the ascending aorta was considerably wider than normal. The location of the ductus was at the left, arising from the left subclavian artery and connecting with the pulmonary artery on the same side (Fig 1).
Figure 1 Contrast-enhanced computed tomography angiography showing that the right pulmonary artery originated from the innominate artery and that the left pulmonary artery originated from the right ventricle.
After 15 days of birth, the oxygenation saturation index decreased, and inhaled nitric oxide therapy was discontinued. The intravenous iloprost dose was decreased gradually, and sildenafil treatment was discontinued subsequently.
The clinical course of the patient improved, and she was transferred to a surgical referral centre for corrective surgery at 40 days of age. During surgery, the right pulmonary artery was freed from the innominate artery, and an end-to-side anastomosis between the right and main pulmonary artery was created. The patient recovered with supportive care, and no specific additional treatment was needed.
Discussion
Pulmonary hypertension is a normal and necessary situation for the foetus. A dramatic cardiopulmonary transition occurs at birth to facilitate the transition to gas exchange by the lung, characterised by a rapid decrease in pulmonary vascular resistance and pulmonary artery pressure and a 10-fold increase in pulmonary blood flow. The consequence of failure of a normal cardiopulmonary transition is persistent pulmonary hypertension.Reference Steinhorn 2 Persistent pulmonary hypertension may be isolated but is associated with perinatal risk factors, including maternal use of non-steroidal anti-inflammatory agents and selective serotonin reuptake inhibitors as well as pulmonary parenchymal diseases such as meconium aspiration and pneumonia. Non-pulmonary causes include left-to-right intracardiac shunts, congenital heart disease, idiopathic pulmonary hypertension, and portal hypertension.Reference Delaney and Cornfield 3
Persistent pulmonary hypertension is a source of considerable mortality and morbidity in newborns, and early treatment of persistent pulmonary hypertension, regardless of the aetiology, is crucial because advanced disease may be less responsive to treatment.Reference Barst, McGoon and Torbicki 1 Anomalous origin of one pulmonary artery from the aorta is a rare congenital heart anomaly, accounting for only 0.12% of all congenital heart diseases. It usually presents in early infancy with heart failure and rapid development of pulmonary hypertension.Reference Kutsche and Van Mierop 4
Pressure in the pulmonary artery arising from the aorta is systemic in almost all patients, and the pressure in the pulmonary artery arising from the pulmonary trunk elevates until reaching a systemic or suprasystemic level. This phenomenon has not been fully explained, but several mechanisms have been postulated as the cause of bilateral pulmonary hypertension; these include circulating vasoconstrictor substances, neurogenic cross-over from an unprotected lung, and development secondarily after left ventricular failure.Reference Keane, Maltz, Bernhard, Corwin and Nadas 5 Anomalous origin of one pulmonary artery may occur in isolation or may be associated with patent ductus arteriosus, tetralogy of Fallot, an aortopulmonary window, an atrial septal defect, isthmic hypoplasia, and an interrupted aortic arch.Reference Garg, Talwar and Kothari 6 – Reference Kajihara, Imoto and Sakamoto 10 The patient described here had patent ductus arteriosus.
Diagnosis of anomalous origin of one pulmonary artery can be achieved by echocardiography, conventional angiography, computed tomography angiography, and magnetic resonance angiography. Echocardiography is the primary imaging technique in congenital cardiac diseases; however, some cases cannot be easily diagnosed by echocardiography.Reference Garg, Talwar and Kothari 6 – Reference Prifti, Bonacchi and Murzi 8 , Reference Kajihara, Imoto and Sakamoto 10 In this case, although anomalous origin of one pulmonary artery could not be demonstrated by echocardiographic examination, computed tomography angiography showed that the right pulmonary artery originated from the innominate artery and that the left pulmonary artery originated from the right ventricle. Different malformations associated with anomalous origin of one pulmonary artery and diagnostic methods described in the literature are summarised in Table 1. Pulmonary hypertension was associated with an anomalous origin of one pulmonary artery in most of the cases.Reference Garg, Talwar and Kothari 6 – Reference Kajihara, Imoto and Sakamoto 10
Table 1 Associations between pulmonary hypertension and anomalous origin of one pulmonary artery in infants in the literature.
AoC = coarctation of the aorta; ASD = atrial septal defect; CT = computed tomography; PDA = patent ductus arteriosus; PFO = patent foramen ovale; PH = pulmonary hypertension; TOF = tetralogy of Fallot; VSD = ventricular septal defect
Management of persistent pulmonary hypertension typically requires integration of therapeutic strategies simultaneously directed towards pulmonary hypertension and, if present, the underlying lung causes. The primary goal of therapy is to selectively lower the pulmonary vascular resistance. Pharmacological management (e.g. dopamine), aims to normalise systemic pressures while relieving pulmonary hypertension and thus minimise the risk of right-to-left shunting. Owing to its rapid and selective effect, inhaled nitric oxide is the first-choice therapy even though many other non-selective pulmonary vasodilators can be used, such as magnesium sulphate, sildenafil, nitroprusside, prostaglandin, or isoproterenol. If all other treatments fail, extracorporeal membrane oxygenation can also be used.
In conclusion, persistent pulmonary hypertension is a source of considerable mortality and morbidity in newborns. Anomalous origin of one pulmonary artery should be considered in patients with refractory persistent pulmonary hypertension. The development of pulmonary hypertension is ascribed to several mechanisms, and some cases are not easily revealed by echocardiography alone. Therefore, advanced imaging techniques should be used for patients with pulmonary hypertension resistant to medical treatment.
Acknowledgements
The authors thank S. Suna Oğuz and Ugur Dilmen for their help and advice.
Financial Support
This research received no specific grant from any funding agency, commercial or not-for-profit organisation.
Conflicts of Interest
None.
