eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Cardiology

Tetralogy of Fallot With Absent Pulmonary Valve

Author: Prema Ramaswamy, MD, Co-director of Pediatric Cardiology, Maimonides Medical Center; Assistant Professor, Department of Pediatrics, Mount Sinai School of Medicine
Coauthor(s): Kurt Pflieger, MD, FAAP, Active Staff, Department of Pediatrics, Lake Pointe Medical Center
Contributor Information and Disclosures

Updated: Jul 17, 2008

Introduction

Background

Tetralogy of Fallot (TOF) with absent pulmonary valve is a rare congenital anomaly characterized by features of TOF with either rudimentary ridges or the complete absence of pulmonic valve tissue. Congenital absence of the pulmonary valve with an intact ventricular septum occurs but is much less common. The absence of mature pulmonary valve tissue leads to severe pulmonary regurgitation. This is often associated with massive dilatation of the pulmonary arteries, which is characteristic of this syndrome.

An interesting feature of this anomaly is that the ductus arteriosus is frequently absent. However, when the pulmonary valve is absent and the ventricular septum is intact, a normal ductus arteriosus is also generally present.¹

Pathophysiology

TOF consists of a malalignment ventricular septal defect, infundibular pulmonary stenosis, overriding aorta, and right ventricular hypertrophy (see Media file 1). The absence of a functioning pulmonary valve gives rise to pulmonary regurgitation (insufficiency) that may result in aneurysmal dilation of the main and branch pulmonary arteries, which can compress the tracheobronchial tree. In addition to compression of the larger bronchi, Rabinovitch et al (1982) described abnormal tufts of the smaller pulmonary arteries that compress the intrapulmonary bronchi.² They further reported a reduction of the number of alveoli. This may explain why surgical relief of the larger airway compression alone is not always effective in reversing the severe obstructive respiratory disease.

The pulmonary valve annulus is usually hypoplastic, and this results in some degree of pulmonary stenosis. The stenosis is typically mild, and the pathophysiology in this condition is such that, after the immediate neonatal period, a net left-to-right shunt is observed. This and the airway obstruction due to the dilated pulmonary arteries are the hallmarks of the condition. In the immediate neonatal period, cyanosis may be present, which is a result of increased pulmonary vascular resistance causing a right-to-left shunt at the level of the ventricular septal defect. After the fall in pulmonary vascular resistance, respiratory difficulties are the most prominent symptom in severe cases.

Frequency

United States

TOF is the most common cause of cyanotic heart disease and may occur at a rate of 1-3 cases per 1000 live births. However, TOF with absent pulmonary valve is rare, and approximately 3% of patients with TOF have the absent pulmonary valve syndrome.

Mortality/Morbidity

Mortality and morbidity rates in patients with TOF with absent pulmonary valve syndrome far exceed those of patients with normal physiology who have typical TOF. Patients are at risk for hypoxemia, heart failure, respiratory failure, and combinations of these events. The size of the pulmonary valve annulus and, therefore, severity of pulmonary regurgitation substantially influence patient morbidity and mortality. Patients with a smaller, more stenotic annulus are subject to risks akin to those of typical TOF. Patients with a large annulus and, therefore, more severe pulmonary regurgitation are at greater risk of morbidity and mortality. Patients with severe bronchial obstruction develop symptoms in the early neonatal period. As the airways increase in size and strength, these symptoms may decrease. However, this usually cannot be expected to occur until approximately age 9months.

• Hypoxemia: The newborn may demonstrate significant cyanosis until pulmonary vascular resistance falls, after which the degree of hypoxemia reflects the severity of pulmonary annular stenosis. A larger pulmonary annulus produces less stenosis, and, therefore, intracardiac shunting may primarily be left-to-right, resulting in minimal cyanosis. The patient with more severe annular hypoplasia presents more similarly to the patient with typical TOF.
• Heart failure: Congestive heart failure (CHF) can occur as a result of a large left-to-right ventricular shunt. This contributes to an enlarged left atrium, which, along with dilated pulmonary arteries, results in airway compression. The presence of significant tricuspid regurgitation also increases the risk of heart failure.
• Respiratory failure: In patients with more severe pulmonary regurgitation, aneurysmal dilation of pulmonary arteries can cause air trapping due to bronchial compression. This process can be localized or diffuse and may be severe.

Age

TOF with absent pulmonary valve can be accurately diagnosed based on fetal echocardiography findings. Galindo et al report that many fetuses with absent pulmonary valve syndrome have an increased nuchal thickness in the first trimester; this may help with earlier recognition of the defect.³ They found the 22q11 microdeletion to be the most common associated karyotype anomaly; it was present in 21% of their patients. Their results confirmed that the outlook for these patients remains extremely poor, as only 2 of 14 patients ultimately survived. Other authors have reported similar prognosis findings.^4,5 Symptoms are noted soon after birth in patients in whom fetal detection failed to reveal the condition. In early infancy, patients fall into 2 groups: those with severe respiratory problems in whom medical management fails in the first year of life and those with less severe respiratory symptoms.

Clinical

History

In a fetus, severe pulmonary regurgitation may cause heart failure, and this may result in fetal hydrops and intrauterine death. According to some suggestions, only fetuses in which the ductus is restrictive or absent are able to survive to term.¹ In fetuses that survive to term, respiratory symptoms develop soon after birth. Cyanosis may be present early because of the high pulmonary vascular resistance.

• Cyanosis usually does not progress as it does in typical tetralogy of Fallot (TOF) in patients with an intact pulmonary valve. As the pulmonary vascular resistance falls, the cyanosis decreases as the left-to-right shunt increases.
• Patients may present in severe or critical respiratory distress due to tracheal or bronchial obstruction early in infancy.

Physical

• Cyanosis, if present, is mild in most cases. The newborn may demonstrate more significant cyanosis because of both higher hemoglobin concentration and higher pulmonary vascular resistance. Stenosis can predominate in patients with a significantly hypoplastic pulmonic annulus. Such patients, therefore, demonstrate more cyanosis.
  • Respiratory distress may be evident with variable auscultatory findings consistent with atelectasis, hyperinflation, or consolidation.
  • CHF evidenced by increased heart rate, respiratory rate, hepatomegaly, and cardiomegaly, with an increase in the pulmonary blood flow, is noted after the normal fall in the pulmonary vascular resistance.
  • The precordium is hyperactive with a right ventricular lift.
• Cardiac auscultation reveals the following:
  • The first heart sound is normal. The second sound is single because of the absence of the pulmonic component. The aortic component may be accentuated.
  • The murmur in this condition is characteristic and is a systolic and diastolic (to-and-fro) murmur best heard in the pulmonic area. The murmur is rough in quality and radiates widely over the lung fields. A short pause between the systolic and diastolic components is noted; this helps differentiate this murmur from that of a patent ductus arteriosus.

Causes

Etiologic factors are not known in most cases. Absent pulmonary valve syndrome has been reported in association with chromosomal abnormalities that involve chromosomes 6 and 7.^6,7 More recently, the association with a deletion of chromosome 22 and DiGeorge syndrome has also been reported in about 25% of cases.^8,9,4,3

Emmanoulides et al (1976) were the first to highlight the association of this condition with the absence of the ductus arteriosus.¹⁰ They proposed a pathogenetic link between the lack of the ductus arteriosus and pulmonary artery dilation and the absent pulmonary valve. They argued that, because most of the blood that enters the pulmonary artery does not have the usual egress through the ductus arteriosus, the blood returns to the right ventricle through the somewhat stenotic pulmonic annulus; thus, it contributes to the dilation of the pulmonary arteries and the possible nondevelopment of the pulmonic valve. This blood then crosses the ventricular septal defect to feed the lower resistance placental circulation through the left ventricle.

This theory has been challenged on the basis that TOF with absent pulmonary valve syndrome occasionally presents with a ductus arteriosus.¹¹ Ettedgui et al suggested poststenotic dilation as the mechanism for the dilated pulmonary arteries. One study reported that reversal of end diastolic umbilical flow in fetuses at 10-14 weeks' gestation who have absent pulmonary valve with patent ductus arteriosus is a poor prognostic sign; this suggests that the frequent absence of a ductus in later pregnancy in patients with TOF with absent pulmonary valve is a result of preselection and that only those fetuses with small or absent ductuses are able to survive to term.¹²

Others have postulated that agenesis of the ductus arteriosus results from obliteration of a still immature artery slightly later in development rather than from complete failure of a sixth arch artery to develop.¹³ Rabinovitch et al have suggested that some congenital weakness of the pulmonary arteries may be present, although the histological findings are not specific.² Some authors believe that the described changes are the result of increased wall stress similar to the changes seen in pulmonary hypertensive arteriopathy. No such wall abnormalities have been demonstrated in peripheral pulmonary arteries.

In fetuses with a ductus arteriosus, the direction of flow through the ductus is controversial. Lakier et al concluded that the flow was from the pulmonary artery to the descending aorta because of lower placental resistance.¹⁴ However, others dispute this and contend that the flow of blood occurs from the aorta into the pulmonary artery, and, because no pulmonic valve is present, the diastolic pressures between the aorta and the ventricles equalize, leading to ventricular dysfunction and impairment of the diastolic filling of the ventricles.^15,1

If the ventricular septum is intact, this affects only the right ventricle and may be the pathogenetic mechanism of membranous tricuspid atresia described in association with absent pulmonary valve and intact ventricular septum.^16,1 Yeager et al suggest that TOF with dysplastic pulmonary valve may be more common than apparent from clinical experience but that it is generally lethal in a fetus with a large ductus arteriosus because the function of both ventricles is adversely effected. Only fetuses in which the ductus is restrictive or absent are able to survive to term.¹

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