Pulmonary atresia without ventricular septal defect is a critical cyanotic congenital heart disease, characterized by the complete absence of connection between the right ventricle and the pulmonary artery, in a morphologically biventricular heart with an intact interventricular septum. Unlike the form with a VSD, in which blood may have an alternative outflow path to the lungs, in the absence of an interventricular communication, pulmonary blood flow is entirely dependent on a patent ductus arteriosus, making the condition incompatible with life without prompt treatment.
There is no direct outflow tract from the right ventricle to the pulmonary circulation.
The right ventricle, depending on the severity of the atresia and associated tricuspid valve dysplasia, may show varying degrees of hypoplasia, up to being virtually rudimentary. In some cases, ventriculo-coronary fistulae are present, connecting the right ventricular cavity to the epicardial coronary arteries, sometimes resulting in coronary perfusion dependence on right ventricular pressure. In these patients, any attempt to decompress the right ventricle can trigger acute myocardial ischemia.
Pulmonary atresia without VSD accounts for approximately 1–3% of all congenital heart diseases, with an estimated incidence of 0.7–1 per 10,000 live births. It is more common in males and may be associated with other cardiac or extracardiac anomalies, including complex genetic syndromes such as 22q11.2 deletion.
Given the exclusive ductal dependency of pulmonary flow, early diagnosis and treatment are essential for neonatal survival and to establish the appropriate therapeutic pathway.
Pulmonary atresia without ventricular septal defect is a congenital malformation that arises during early embryogenesis, between the fifth and eighth weeks of gestation, during the formation of the conotruncal septum and the right ventricular outflow tract. The defect consists of the failure of the pulmonary valve to open, resulting in a completely atretic valve that blocks blood flow from the right ventricle to the lungs.
The interventricular septum remains intact, and the right ventricle, having no outlet, may exhibit various degrees of hypoplasia, potentially becoming rudimentary. In many cases, there is associated dysplasia of the tricuspid valve, which further impairs its development and function.
Genetic mutations affecting early cardiac development have been described, particularly in the NKX2.5, JAG1, and TBX1 genes. Atresia may be part of more complex syndromes such as the 22q11.2 microdeletion, although in most cases it occurs as an isolated malformation.
The pathophysiology is dominated by the dependence on the ductus arteriosus to ensure blood flow to the lungs. After birth, spontaneous closure of the ductus results in a complete interruption of pulmonary perfusion, leading to severe hypoxemia, metabolic acidosis, and an imminent risk of hemodynamic collapse.
In some neonates, elevated right ventricular pressure may give rise to ventriculo-coronary fistulae, causing coronary perfusion to depend on the right ventricle. In such cases, any intervention that lowers right ventricular pressure may provoke acute myocardial ischemia and life-threatening complications.
The clinical picture of pulmonary atresia without VSD appears within the first hours of life, with symptoms dominated by severe central cyanosis, a direct sign of the inability to oxygenate blood in the absence of spontaneous pulmonary flow. The severity of the presentation depends on the patency of the ductus arteriosus, which is the only route for pulmonary perfusion: as it begins to close, the newborn rapidly develops refractory hypoxemia, metabolic acidosis, and signs of systemic compromise.
In the perinatal history, the neonate may initially appear well oxygenated, but after a few hours may develop progressive desaturation, feeding difficulties, lethargy, or irritability. Without treatment, the condition evolves into cardiovascular collapse. Sometimes, cyanosis is initially misattributed to respiratory disease, delaying diagnosis: failure to improve with oxygen therapy should always raise suspicion of a cyanotic congenital heart defect.
In patients with ventriculo-coronary fistulae and coronary circulation dependent on the right ventricle, signs of early myocardial ischemia may occur: tachycardia, peripheral hypoperfusion, wall motion abnormalities on echocardiography, or—in severe cases—sudden cardiac arrest.
On physical examination, cyanosis is typically uniform and persistent, with weak peripheral pulses in advanced cases. Heart sounds may be normal or diminished, and no murmurs are usually heard due to the absence of flow through the pulmonary valve. In some neonates, a continuous murmur from a patent ductus arteriosus may be present, or a holosystolic murmur in the case of significant tricuspid regurgitation.
The diagnosis of pulmonary atresia without ventricular septal defect is a neonatal emergency and requires a high index of clinical suspicion. The first clue is the presence of marked central cyanosis that persists and does not respond to oxygen therapy, in an otherwise well-formed newborn. This, combined with signs of systemic hypoperfusion, should promptly suggest a cyanotic congenital heart disease, particularly one in which pulmonary flow is ductus-dependent.
Pre- and post-ductal pulse oximetry may show values below 80%, often unresponsive to 100% oxygen administration. The absence of murmurs or typical auscultatory findings may delay diagnosis in non-specialized centers. Although chest X-ray is not diagnostic, it may suggest a congenital heart defect if it shows a normal or small cardiac silhouette with decreased pulmonary vascular markings.
Diagnostic confirmation is obtained through transthoracic echocardiography, which reveals the absence of flow across the pulmonary valve, a patent ductus arteriosus, an intact ventricular septum, and the morphology of the right ventricle and tricuspid valve. The study should also assess coronary flow, paying particular attention to the possible presence of ventriculo-coronary fistulae, often visible with color or pulsed Doppler. If coronary circulation appears dependent on the right ventricle, cardiac catheterization may be necessary for detailed anatomic definition and potential selective coronary angiography.
Other investigations, such as cardiac MRI or CT angiography, play a limited role in the neonatal period but may be useful later for planning reconstructive strategies or assessing right ventricular growth. Arterial blood gas analysis confirms the presence of hypoxemia and acidosis, while the ECG typically shows sinus rhythm with right axis deviation, right atrial enlargement, and sometimes inverted T waves in the right precordial leads.
Initial treatment aims to ensure neonatal survival by maintaining ductus-dependent pulmonary blood flow. Continuous intravenous infusion of prostaglandin E1 is essential to keep the ductus arteriosus open and sustain oxygenation. The newborn should be stabilized in an intensive care unit, with hemodynamic monitoring and ventilatory support if needed.
The long-term surgical strategy depends on the morphology and function of the right ventricle, tricuspid valve competence, and the presence or absence of coronary fistulae with dependent circulation. If the right ventricle is rudimentary or the tricuspid valve severely dysplastic, a univentricular palliation pathway is pursued, similar to that used in hypoplastic left heart syndrome or severe forms of PA-IVS.
The typical sequence includes:
In patients with a hypoplastic but still functional right ventricle, a 1.5-ventricle palliation may be considered, in which the superior vena cava is connected to the pulmonary artery while the right ventricle continues to pump the inferior systemic venous return. In a highly selected minority of cases, where a well-developed right ventricle, competent tricuspid valve, and absence of coronary dependence are present, a biventricular repair can be planned, involving pulmonary valvulotomy, outflow tract reconstruction, and progressive closure of the ductus arteriosus.
Prognosis is closely tied to the chosen therapeutic strategy and the initial anatomical conditions. In patients undergoing univentricular palliation, long-term survival has significantly improved, though Fontan physiology carries risks: diastolic dysfunction, systemic venous hypertension, congestive hepatopathy, and thromboembolic events. Quality of life depends on preserved cardiac function, absence of arrhythmias, and adequate somatic growth. In rare cases with successful biventricular repair, hemodynamic outcomes are superior, though the pathway requires careful selection and often multiple corrective procedures over time.
Complications of pulmonary atresia without ventricular septal defect vary depending on the treatment approach. In untreated neonates, closure of the ductus arteriosus rapidly leads to cardiorespiratory collapse and death. Even in the preoperative phase, prolonged hypoxemia may result in end-organ damage, especially cerebral ischemia, lactic acidosis, and multiorgan dysfunction.
In patients with coronary circulation dependent on the right ventricle, sudden decompression of the cavity during valvulotomy or attempts to restore outflow can lead to acute myocardial infarction or ventricular fibrillation. This risk must be carefully assessed preoperatively using imaging and selective catheterization.
In the long term, patients following the Fontan pathway may experience chronic complications: single ventricle dysfunction, atrial arrhythmias, venous stenosis, protein-losing enteropathy, and congestive liver cirrhosis. For this reason, regular multidisciplinary follow-up is essential, including cardiology, hepatology, and nutritional evaluations.
Finally, neurocognitive impairments are more common in patients who experienced perinatal hypoxemia or underwent multiple early surgeries. Learning difficulties, reduced attention span, and fine motor disorders may emerge during school age, requiring targeted support interventions.