Definition and Morphology
Absent pulmonary valve syndrome is a rare congenital cardiac malformation that was first described anatomically by Chevers in 1847. The first clinical case report was published in 1927, the typical anatomy described in a 58-year-old with chronic cyanosis and clubbing. Fundamentally, the intracardiac anatomy is that of tetralogy of Fallot, but the characteristic morphologic feature of this lesion is the complete absence of the pulmonary valve leaflets or the presence of vestigial remnants that are usually dysplastic nodules guarding a small ventriculopulmonary junction. This results in a variable degree of right ventricular outflow tract obstruction, significant pulmonary regurgitation, right ventricular enlargement, and often gross dilation of the pulmonary arteries ( Fig. 49.1 ). This last anomaly has been attributed to absence of the arterial duct in utero, which is the norm, although there are occasional reports in which a patent duct is present. Case series and reports have also described the characteristic outflow tract and pulmonary artery features in the presence of an intact ventricular septum, and association with other cardiac malformations, including tricuspid atresia, type B interrupted aortic arch, and atrioventricular septal defects.
Epidemiology and Genetics
The overall frequency of this defect remains unknown because it was often miscategorized in earlier epidemiologic studies. More recent reports quote a prevalence that ranges from 1% to 6% of patients with tetralogy of Fallot, corresponding to approximately 1 in 500 (0.2% to 0.4%) liveborn infants with congenital heart disease. Prenatal echocardiographic studies report a higher prevalence (1%); however, this difference can be attributed to significant intrauterine and perinatal mortality.
Although the association with microdeletion of chromosome 22q11 and phenotypic features of DiGeorge syndrome has been widely reported in patients with tetralogy of Fallot and absent pulmonary valve syndrome, it has not been identified in patients with isolated agenesis or dysplasia of the pulmonary valve. Smaller reports have also identified similar phenotypes with deletions in the 18q chromosome in humans and as an effect of exposure to the teratogenic agent bis -diamine in rat models.
Tetralogy of Fallot with Absent Pulmonary Valve
Clinical Presentation and Diagnosis
Most patients with tetralogy of Fallot and absent pulmonary valve present in infancy or early childhood because of the significant hemodynamic compromise from the severe pulmonary regurgitation, left-to-right (heart failure) or right-to-left (cyanosis) shunting through the ventricular septal defect, or airway obstruction secondary to bronchial compression from the aneurysmally dilated branch pulmonary arteries (see Chapter 42 for further discussion of airway compression secondary to vascular causes). At the worst end of the spectrum, such compression may lead to profound air trapping and lung hyperinflation, lobar emphysema, and tension pneumothorax. Rabinovitch and associates suggested that not only were the larger bronchi compressed by the massively dilated pulmonary arteries, but there was also a unique branching pattern of the pulmonary arteries that impaired alveolar multiplication, with consequent compression of smaller intrapulmonary bronchi. The outcome for neonates who present with severe airway disease is particularly poor. Other risk factors for in utero demise or early postnatal death include severe pulmonary regurgitation with gross ventricular dilation and failure which, in turn, is more likely if there is neither a persistent duct or a ventricular communication. In view of the increased intrauterine and perinatal mortality, the importance of prenatal screening and diagnosis with fetal echocardiography has been stressed in several studies. Razavi et al. reported a series of 24 fetuses with absent pulmonary valve syndrome, of which only three (15%) eventually survived after appropriate and immediate intervention in highly specialized centers.
These severe phenotypes are, thankfully, rare. The most common clinical presentation is with neonatal cyanosis, often with some degree of respiratory distress. Clinical findings on examination vary, depending on the degree of respiratory involvement, but most will have some evidence of lung hyperinflation; and on auscultation there will be a single second heart sound and the typical “to-and-fro” murmur of significant right ventricular outflow obstruction and pulmonary regurgitation.
Cardiac imaging is essential for the early diagnosis and management of these patients. The chest radiograph performed around the time of birth often shows significant cardiac enlargement (because of the pulmonary regurgitant volume load in utero), aneurysmally dilated pulmonary arteries, and hyperinflation of the lung lobes with a shift of the mediastinum clearly demonstrated. Echocardiography is considered the primary diagnostic method, with most patients having the pathognomonic features of tetralogy of Fallot, albeit often with less severe infundibular stenosis, rudimentary pulmonary valve tissue, and color flow Doppler findings consistent with significant right ventricular outflow obstruction and pulmonary regurgitation. The enlarged pulmonary arteries will be obvious, but if there is concern for bronchial compression, then additional cross-sectional imaging may be required. Indeed, evaluation with high-resolution computed tomography (CT) or cardiac magnetic resonance imaging is particularly useful to assess the more distal pulmonary arterial tree and the airways.
Management and Outcome
Optimal management of the neonate with absent pulmonary valve syndrome depends on early diagnosis, preferably prenatally, repeated antenatal evaluation, and early postnatal assessment. Nonetheless, most patients, in whom there is no significant airway disease, may remain symptom-free for some time and may undergo repair electively between 3 and 6 months of age. However, immediate postnatal support will be required for those with associated airway compression and, if suspected, delivery in the presence of a multidisciplinary team that can provide immediate support may be optimal. Airway patency and respiratory support are the primary goals, and this may necessitate intubation, mechanical ventilation, and sometimes even extracorporeal membrane oxygenation to avoid barotrauma in those with extreme air trapping. For these patients, complete surgical repair, including ventricular septal defect closure, infundibular resection, and reconstruction of the right ventricular outflow tract with a valved conduit (homograft or bioprosthetic valve), is often required in the early neonatal period. Several strategies have been proposed for the relief of the bronchial compression, including combined anterior and posterior plication of the pulmonary arteries and, more recently, translocation of the pulmonary artery anterior to the aorta and away from the airways (LeCompte maneuver), the latter of which has been reported with very good intermediate results. The use of endobronchial stents has also been advocated in some reports.
The long-term outcomes of large cohorts of patients with tetralogy and absent pulmonary valve syndrome have been reported in several series, with survival rates ranging from 82% to 93% in the first year and 79% to 87% at 5 years. Perhaps unsurprisingly, given the almost routine use of valved conduits at the time of initial repair, the recent study from Hickey and associates found that the absent pulmonary valve variant was associated with higher risk of late reoperation or pulmonary valve replacement compared with other forms of tetralogy of Fallot, when serially studied over a 40-year period.
Long-Term Follow-Up
In the postoperative follow-up of these patients, it is important to focus on the form and function of the pulmonary valve implant, the fate of the aneurysmal pulmonary arteries after plication, the respiratory function, and right ventricular function ( Box 49.1 ). Issues relating to residual pulmonary stenosis, regurgitation, and right ventricular function are similar to those found in patients with postoperative tetralogy of Fallot and are discussed in Chapter 47 . The characteristic chest radiography and high-resolution CT appearances of patients after repair of absent pulmonary valve and tetralogy of Fallot are shown in Figs. 49.2 and 49.3 . Some of these patients may be prone to ongoing respiratory difficulties after surgical repair. This has been attributed to the persistence of intrapulmonary bronchial compression even after successful surgical repair.
