Introduction

APVS is a rare but important cardiac cause of respiratory distress in the newborn. In the 1950s and ’60s during the development of pediatric cardiology and cardiac surgery, absent pulmonary valve syndrome (APVS) was often referred to as “a variant of tetralogy of Fallot characterized by absent or rudimentary pulmonary valve tissue, severe pulmonary regurgitation, and aneurysmal dilatation of the main and mediastinal branch arteries” (Fig. 1) [1, 2].

Fig. 1
figure 1

Diagram illustrates absence of the pulmonary valve, with huge central pulmonary arteries compressing the main bronchi. Br.=bronchus, L.L.L.=left lower lobe, L.P.A.=left pulmonary artery, L.U.L.=left upper lobe, P.T.=pulmonary trunk, R.L.L.=right lower lobe, R.M.L.=right middle lobe, R.P.A.=right pulmonary artery, R.U.L.=right upper lobe (Reprinted with permission from Ref. [2])

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The causes of airway problems in APVS are different from those encountered in cases of vascular rings. APVS has compliant bronchi and bronchial compression caused by adjacent pulmonary artery dilatation (Fig. 2). Commonly, patients with APVS will continue to have respiratory difficulty if there has been insufficient reduction of the dilated central and pulmonary arteries causing severe bronchial compression.

Fig. 2
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Case 1. Chest radiograph of a 2-month-old with APVS shows right lower and partial right upper lobe atelectasis from the obstructive bronchial compression

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The usual case of APVS has absence of normally functioning pulmonary valve tissue, annular thickening, a VSD, absence of the ductus arteriosus, and aneurysmal dilatation of the main, right, and left pulmonary arteries. The patient’s cardiac disease, primary pulmonary insufficiency, is often not very severe. The inherent disease of the airways, a result of long-standing in utero compression by the tortuous dilated pulmonary arteries, can lead to severe bronchial compression and can eventually be lethal. Several recent articles have appeared in the surgical and intensive care literature addressing the short-term and long-term airway problems [2–4].

In the past, conventional imaging was not a vital part of management for these patients. This was partly related to inability to image the airway appropriately. Plain films in the preoperative neonatal period showed hyperaeration or, rarely, obstructive emphysema (which could be fluid-filled), and occasionally a large hilar mass on either side of the mediastinum. Diagnosis was made by angiography and later echocardiography without direct concern or attention to the airway disease.

We will report from our experience with APVS patients, all of whom were followed with plain films and who despite surgical valvular repair (with reduction of the main, right, and left pulmonary arteries) had persistent short-term and long-term airway problems of varying severity. Two of these patients eventually needed tracheotomy. After tracheotomy failed to alleviate the patients’ symptoms, MRI was performed to assess cardiac function and revealed severe persistent right and left bronchial collapse caused by the enlarged hilar pulmonary arteries (Fig. 3). Eventually, repeat surgery with careful reduction of the hilar and central pulmonary arteries relieved the bronchial compression and alleviated the airway disease. Two of the patients who had serious airway problems also had DiGeorge syndrome (22Q.11 deletions), which is present in many APVS patients.

Fig. 3
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Case 1. Coronal (a, b) and axial (c, d) MRI images show bilateral areas of atelectasis, the narrowed mainstem bronchi (solid white arrows) from the pulmonary artery dilatation (dashed white arrow) and resultant areas of atelectasis

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Case 1

A 2-month-old infant with APVS who had surgical repair, including patching of the outflow tract and reduction plasty of the main right and left pulmonary arteries, could not be weaned off the ventilator. The chest radiograph shows multiple areas of atelectasis (Fig. 2). MRI was performed to assess cardiac function and showed severe narrowing of the airways from the dilated pulmonary arteries (Fig. 3).

Case 2

A 2-year-old child born with APVS initially had surgical repair at an outside hospital with valve replacement and central pulmonary artery plasty. However, the patient could never be weaned off the ventilator after the initial surgery. Eventually, the patient required a tracheotomy. Magnification views of the airways performed with a Thoreus filter demonstrate the tracheotomy tube and marked bilateral bronchial narrowing (Fig. 4). MRI demonstrates severe narrowing by the dilated pulmonary arteries (Fig. 5). No thymus is identified. Incidentally noted are other DiGeorge syndrome anomalies, including a right-side aortic arch and a butterfly vertebral body. The second surgery performed at our institution focused on plication and reduction of the peripheral pulmonary arteries. After the second surgery, the patient was weaned from the ventilator and eventually discharged.

Fig. 4
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Case 2. Magnified airway images of a 2-year-old with APVS with marked narrowing of the mainstem bronchi (white arrow)

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Fig. 5
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Case 2. Selected coronal (a, b) and sequential axial (c, d, e, f) MR images show the normal-caliber trachea (dashed arrows) and carina with marked narrowing of the right and left mainstem bronchi (solid white arrows). Additionally, the absence of a normal thymus is noted. Incidentally noted are a right-side aortic arch and a butterfly vertebral body

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Discussion

Although the first reference of absent pulmonary valve syndrome is attributed to an article in 1847 by Chevers [5], the case reported in the American Heart Journal (1927) by Kurtz, Sprague and White [6] is really the first reference of the modern era of medical literature. It describes an 11-year-old boy who was cyanotic at birth, had recurrent lifelong infections, and tired easily on exertion. After the patient died from ruptured appendicitis, autopsy revealed absence of the pulmonic valve and a 5-cm main pulmonary artery. In the 1950s, APVS was thought to be part of the spectrum including tetralogy of Fallot starting with the article published by Rowe, Vlad, and Keith [7] (1955) with a single case describing a patient who was thought to have tetralogy of Fallot but had massively enlarged central pulmonary arteries that reverted to normal size at the hilum. By 1969, Durnin et al. [8] had collected 14 patients with absence of the pulmonary valve and ventricular septal defects, still referred to as tetralogy of Fallot variants. At this point, mortality for repaired tetralogy of Fallot was low, but nine of these 14 APVS patients died. That paper’s discussion makes no mention of airway disease. In 1976, Emmanoulides et al. [9] first noted agenesis of the ductus arteriosus as a common finding in cases of absent pulmonary valve and hypothesized that the resultant in utero elevated right heart pressure from the absent ductus prevents development of a normal pulmonic valve. In the early ’70s, an association between APVS and DiGeorge syndrome was noted in a paper by Rose et al. [10]. Eventually, chromosome 22, which is responsible for DiGeorge syndrome and resultant hypocalcemia, was found in many of the patients with APVS. It is now confirmed that the syndrome is highly associated with DiGeorge syndrome and chromosome 22.Q11 deletions and can also have associated hypocalcemia [13]. Interestingly, in the paper by Kurtz et al. [6], the 11-year-old patient was noted to have an increased incidence of infections, raising the possibility of DiGeorge syndrome in that patient. In the ’80s and early ’90s, autopsy studies detailing the inherent abnormalities of the bronchi begin to appear [11]. In 1982, Rabinovitch et al. [11] described abnormal peripheral bronchial generations and decreased alveolar multiplication in patients with APVS. In 1990, Momma et al. [12] hypothesized and proved that a teratogenic agent, N,N’-bis-(dichloroacetyl)-1,8-octamethylenediamine (bis-diamine), which inhibits the normal action of neural crest cells in cardiovascular organogenesis, would cause absent pulmonary valve syndrome and absence of the ductus arteriosus, creating a rat model for this disease (Fig. 6).

Fig. 6
figure 6

Color photographs of a rat heart with teratogenic APVS. Note the massively dilated pulmonary artery (PA), in comparison to the adjacent aorta. (Reprinted with permission from Ref. [10])

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Currently, patients with APVS are often diagnosed in utero, with prenatal US revealing aneurysmal dilatation of the pulmonary artery [13, 14]. Post-delivery, conventional preoperative radiographs show huge, massively dilated pulmonary arteries. Some patients develop obstructive emphysema and adjacent areas of atelectasis. There might be fluid retention noted on the initial neonatal chest radiograph [15].

Some infants with less severe airway disease survive with intubation, but many of these patients are difficult to extubate. A subgroup of these patients might eventually require tracheotomies, which do not alleviate the distal airway disease. Another group of patients might survive the neonatal period unaffected only to present later in life with airway difficulties and bronchospasm. Recently, Zucker and others [16] have divided these patients, based on the presence of an intact ventricular septum, into an early presenting cohort and one that presents later in life [16].

APVS is best thought of as a syndrome that has its own intricacies. Specifically, the inherent bronchial compression of APVS is distinct and can involve the mainstem bronchi well out into the hilar regions. Many post-operative patients are noted to have difficulty ventilating or remain ventilator dependent. This inherent airway disease is not seen in tetralogy of Fallot. Thus, though rare, APVS deserves mention as a vascular anomaly with associated bronchial compression causing respiratory difficulties. It carries a significant immediate mortality and morbidity.

This is in contrast to vascular rings, where surgical repair of the constriction relieves the airway symptoms, as the tracheal bronchial tree is inherently normal. In this group, mortality and morbidity is negligible. But it is also different from pulmonary slings patients (anomalous left pulmonary artery), who can have complete cartilaginous tracheal and bronchial rings and also have significant morbidity and mortality.

In APVS, surgical correction of the pulmonary insufficiency and valvular disease with limited reduction of the central arteries might ignore the distal pulmonary artery enlargement and resultant bronchial compression. Therefore, many pediatric cardiac surgeons recognize the importance of more extensive reduction plasty of the pulmonary arteries as far away from the hilum as possible as part of the same repair [2]. Others suggest a different approach – to correct the airway compression by translocation of the pulmonary artery anterior to the aorta and away from the airways. This technique has the potential to reduce or eliminate bronchial compression by the pulmonary artery [4]. A few papers and reports have advocated the use of airway stents to treat the bronchial compression [3].

Conclusions

Pediatric cardiologists and radiologists performing MRI for evaluation of the post-operative cardiac anatomy and function must remember to assess inherent airway disease. The diagnosis of bronchial compression is often difficult on plain films and cannot be assessed on echocardiograms; however, it is often easily accomplished by cross-sectional imaging. In patients with APVS and ongoing respiratory difficulties, dedicated airway assessment should be performed. This can be obtained either by CT scanning or MRI [17]. Although both can provide excellent cross-sectional imaging and reconstruction techniques, MRI does not involve radiation and is better at assessing the patient’s cardiac disease.