Summary
Unilateral absence of pulmonary artery (UAPA) is a rare malformation that can present as an isolated lesion or may be associated with other congenital heart defects. UAPA is often associated with other congenital cardiovascular anomalies, such as tetralogy of Fallot, atrial septal defect, coarctation of aorta, right aortic arch, truncus arteriosus and pulmonary atresia. Diagnosis of UAPA is very difficult and is based on taking a complete medical history, physical examination and imaging examinations. Clinical symptoms include exercise intolerance, haemoptysis and recurrent respiratory infections. Adult patients with UAPA are often asymptomatic. There is no consensus regarding the treatment for UAPA. The therapeutic approach should be based on symptoms of the patient, pulmonary artery anatomy and associated aortopulmonary collaterals. Treatment options for these patients include partial or total pneumonectomy, closure of selected collateral arteries not solely responsible for pulmonary blood flow or a primary versus staged pulmonary artery anastomosis. This review summarizes pathophysiology, symptomatology and current diagnosis and treatment of this disease.
Résumé
L’absence unilatérale de l’artère pulmonaire est une malformation rare dont le mode de présentation peut être unique, isolée ou associée à d’autres cardiopathies congénitales. Elle est souvent associée en effet à la tétralogie de Fallot, la communication interauriculaire, la coarctation aortique, l’arche aortique droit, la persistance du canal artériel ou l’atrésie pulmonaire. Le diagnostic de l’absence unilatérale de l’artère pulmonaire est difficile, fondé un interrogatoire complet, un examen physique et clinique exhaustif. La symptomatologie inclut la dyspnée à l’effort, l’hémoptysie et les infections respiratoires récurrentes. Les patients adultes porteurs de cette pathologie sont souvent asymptomatiques. Il n’y a pas de consensus concernant le traitement de l’absence unilatérale de l’artère pulmonaire. L’approche thérapeutique doit être orientée par la symptomatologie décrite par le patient, l’anatomie artérielle pulmonaire et associée aux collatérales aorto-pulmonaires mises en évidence. Les options thérapeutiques incluent une pneumonectomie partielle ou totale sur l’occlusion sélective des artères collatérales et pas seulement responsables du flux artériel pulmonaire ou encore une anastomose réglée de l’artère pulmonaire. Cette revue résume la physiopathologie, la symptomatologie et les modalités diagnostiques et thérapeutiques de cette affection rare.
Background
Unilateral absence of pulmonary artery (UAPA) is a very rare congenital cardiovascular malformation. It was first described by Frentzel in 1868; in his initial paper, Frentzel reported that 30% of patients with this finding could remain asymptomatic until adult life .
Pool et al. reviewed 32 cases before 1962, whereas Shakibi et al. studied 47 cases from 1962 to 1976. Ten Harkel et al. added a review of 107 cases from 1978 to 2000. The prevalence of isolated UAPA without associated cardiac anomalies ranged from 1 in 200,000 to 1 in 300,000 adults . In 2011, Bockeria et al. found 352 cases of UAPA in the world literature. In 237 of these cases, UAPA was associated with congenital heart defects .
Most patients who have no associated cardiac anomalies have only minor or absent symptoms and survive into adulthood. Isolated UAPA without other cardiac anomalies is rare. Adult patients with UAPA are often asymptomatic and therefore undiagnosed. They present with exercise intolerance, haemoptysis or are incidentally detected during chest radiography.
There is no consensus on treatment of UAPA. The choice of treatment is based on symptoms of the patient, pulmonary artery (PA) anatomy and associated aortopulmonary collaterals, associated cardiovascular anomalies and pulmonary hypertension (PHT).
In this review, we summarize the pathophysiology, symptomatology, diagnosis and current treatment of UAPA.
Pathophysiology and embryogenesis of unilateral absence of pulmonary artery
The embryologic explanation for the origin of the absent PA is believed to be as follows. The intrapulmonary pulmonary arteries arise from the lung buds and the extrapulmonary pulmonary arteries arise from the proximal portion of the sixth aortic arch. The main PA is derived from the truncoaortic sac. The ductus arteriosus, which forms from the distal portion of the sixth arches, connects to the primitive dorsal aorta, which becomes the underside of the aortic arch ipsilateral to the arch or the base of the innominate artery contralateral to the arch. An absent PA is caused by the involution of the proximal sixth aortic arch and persistence of the connection of the intrapulmonary PA to the distal sixth aortic arch. It has been pointed out that all reported cases of absent PA with satisfactory angiographical, surgical or autopsy documentation had a ductus arteriosus or ligamentum ipsilateral to the absent PA . The preferred terms for this condition have thus been suggested to be “PA proximal interruption”, “non-confluent PA” or “ductal origin of the distal PA” .
If the ductus arteriosus closes after birth, the ipsilateral intrapulmonary PA will lose its source of blood supply and diminish in size and thus will not be visible with imaging .
In early embryonic development, transient systemic-to-pulmonary collateral arteries may arise during two extended periods. During maldevelopment of the pulmonary outflow tract, these transient connections may persist as systemic-to-pulmonary collateral arteries.
The timing and extent of pulmonary outflow tract maldevelopment may determine the origin and distribution of the collateral arteries. When pulmonary obstruction occurs at a very late stage of foetal development or after birth, bronchial arteries can develop into systemic-to-pulmonary collateral arteries . Fadel et al. showed that PA occlusion stimulates angiogenesis in the systemic circulation of the ipsilateral lung and increases systemic-to-pulmonary blood flow.
After a period of pulmonary occlusion, revascularization normalizes the systemic blood flow to the lung and induces a partial loss of collateral vessels. It has been shown that, in congenital heart disease, certain aortopulmonary collateral arteries have a marked histological similarity to the ductus arteriosus .
Collaterals to the affected lung usually arise from bronchial arteries , but have also been documented to arise from intercostal, subdiaphragmatic, subclavian and even coronary arteries . It is argued that these connections can persist in human beings as aortopulmonary collateral vessels, in certain cases with abnormalities in the pulmonary part of the cardiac outflow tract .
Clinical symptoms and complications of unilateral absence of pulmonary artery
UAPA is twice as common on the right side. According to a study by Bockeria et al. among 182 patients with isolated UAPA, the right PA was absent in 60% of cases (109/182) . It is, however, noteworthy that about 80% of the reported cases involving the left PA have been associated with other congenital cardiovascular anomalies, such as tetralogy of Fallot, atrial septal defect, coarctation of aorta, right aortic arch, truncus arteriosus, patent ductus arteriosus and pulmonary atresia . Two types of presentations are described. The first presentation is the one seen in infants, where they usually present with congestive cardiac failure and PHT . The other presentation is in older patients, who are often asymptomatic; they present with exercise intolerance (18–40%), haemoptysis (20%) or are incidentally detected during chest radiography . A literature review by Ten Harkel et al. found that PHT was present in 44%, haemoptysis in 20%, recurrent pulmonary infections in 37% and limited exercise tolerance in 40% of patients with isolated UAPA. The prognosis depends on associated cardiovascular anomalies and the degree of PHT. Overall mortality in this series was 7% . Recurrent pulmonary infections, decreased exercise tolerance and mild dyspnoea during exertion are the most common symptoms . The aetiology of recurrent infections observed in patients with UAPA is likely to be multifactorial. Lack of arterial blood flow to the affected lung may result in poor delivery of inflammatory cells to sites of inflammation and impaired ciliary function. In addition, poor blood flow to the affected lung may result in alveolar hypocapnia, leading to secondary bronchoconstriction and mucous trapping. Chronic infection can lead to bronchiectasis in some patients . Haemoptysis in patients with UAPA is caused by excessive collateral circulation . Haemoptysis may be self-limiting for many years , but can also lead to massive pulmonary haemorrhage and death .
The incidence of PHT among the patients with unilateral absence of PA has been reported to be between 19% and 44% in different case series .
PHT may result from blood flow directed away from the absent PA to the remaining PA. Increased blood flow in the contralateral PA leads to shear stress within the endothelium, with subsequent release of vasoconstrictive compounds, such as endothelin. Chronic vasoconstriction of the pulmonary arterioles may lead to remodelling, resulting in increased resistance of the pulmonary vasculature and PHT.
Infants with isolated absence of the one of the PAs frequently present with PHT . Pool et al. documented medial hypertrophy of the PA of the normal lung (opposite to the affected side) in 53% of 17 patients. The affected lung (lacking a PA) was free of these changes in 83% of cases. Haworth et al. described the changes in the right and left PA after ligation of the left PA and ductus arteriosus in an animal model (14 newborn pigs). In the right lung, pulmonary arterial pressure and resistance fell to normal after birth; however, structurally, muscularity remained high in arteries less than 75 μm in diameter. The left PA and branches were small, with a disorganized elastin wall structure, although the muscularity of the arteries in the left side was reduced. The mean PA pressure was elevated (20–35 mmHg), along with features of hypertrophied right ventricle . Other reasons postulated for PHT were insufficient elasticity of the pulmonary vascular bed of the normal side receiving full cardiac output and abnormal response to vasoconstrictor . Pool et al. opined that those patients with isolated unilateral absence of PA who develop PHT generally do so at an early age and die from right heart failure. However, if PHT does not develop at an early age, it is unlikely that it will develop later.