Tetralogy of Fallot With Absent Pulmonary Valve 

Updated: Nov 22, 2015
Author: Prema Ramaswamy, MD; Chief Editor: Howard S Weber, MD, FSCAI 

Overview

Background

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

The image below compares the pulmonary artery branching between healthy patients and those with absent pulmonary valve syndrome.

Pulmonary artery branching in a healthy person and Pulmonary artery branching in a healthy person and in a patient with absent pulmonary valve syndrome.

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

See Tetralogy of Fallot, Tetralogy of Fallot With Pulmonary Stenosis, and Tetralogy of Fallot With Pulmonary Atresia for more information on these topics.

For patient education information, see Tetralogy of Fallot.

Pathophysiology

Tetralogy of Fallot (TOF) consists of a malalignment ventricular septal defect (VSD), infundibular pulmonary stenosis, overriding aorta, and right ventricular hypertrophy (RVH).

The absence of a functioning pulmonary valve gives rise to pulmonary regurgitation (insufficiency) that results in aneurysmal dilatation of the main and branch pulmonary arteries, which can compress the tracheobronchial tree (see the following image). In addition to compression of the larger bronchi, Rabinovitch et al described abnormal tufts of the smaller pulmonary arteries that compress the intrapulmonary bronchi.[2] The investigators 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.

Drawing showing absence of the pulmonary valve wit Drawing showing absence of the pulmonary valve with features of tetralogy of Fallot. Note the small nubbins of tissue at the pulmonary valve annulus in the center of the drawing. Characteristic muscular right ventricular hypertrophy and infundibular pulmonary stenosis are present. A right aortic arch, a ventricular septal defect with overriding aortic valve, and massively dilated main and branch pulmonary arteries are present.

The pulmonary valve annulus is usually hypoplastic, resulting in pulmonary stenosis. The stenosis is not typically severe 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 (PVR) causing a right-to-left shunt at the level of the VSD or the inability to effectively ventilate the patient. After the fall in pulmonary vascular resistance, respiratory difficulties are the most prominent symptom in severe cases.

Etiology

Etiologic factors for tetralogy of Fallot (TOF) with absent pulmonary valve are not known in most cases. Chromosomal abnormalities, absence of the ductus arteriosus, and other theories have been proposed.

Chromosomal abnormalities

Absent pulmonary valve syndrome has been reported in association with chromosomal abnormalities that involve chromosomes 6 and 7,[3, 4] as well as in association with a deletion of chromosome 22 and DiGeorge syndrome in about 25% of cases.[5, 6, 7, 8]

Absence of ductus arteriosus

Emmanoulides et al were the first to highlight the association of absent pulmonary valve syndrome with the absence of the ductus arteriosus.[9] The investigators proposed a pathogenetic link between the lack of the ductus arteriosus and pulmonary artery dilatation 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 (RV) through the somewhat stenotic pulmonic annulus; thus, it contributes to the dilatation of the pulmonary arteries and the possible nondevelopment of the pulmonic valve.[9] This blood then crosses the ventricular septal defect (VSD) to feed the lower resistance placental circulation through the left ventricle (LV).

However, this theory has been challenged on the basis that tetralogy of Fallot with absent pulmonary valve syndrome occasionally presents with a ductus arteriosus.[10] Ettedgui et al suggested poststenotic dilation as the mechanism for the dilated pulmonary arteries.[10]

One study reported that reversal of end-diastolic umbilical flow in fetuses at 10-14 weeks' gestation is a poor prognostic sign seen in patients with absent pulmonary valve and a patent ductus arteriosus; this suggests that the frequent absence of a ductus in later pregnancy in patients with tetralogy of Fallot with absent pulmonary valve is a result of preselection and that only those fetuses with a small or absent ductus arteriosus are able to survive to term.[11]

Other theories

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.[12] Rabinovitch et al have suggested that some congenital weakness of the pulmonary arteries may be present, although the histologic 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; however, 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.[13] However, other authors 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.[1, 14]

If the ventricular septum is intact, this affects only the RV and may be the pathogenetic mechanism of the membranous tricuspid atresia described in association with absent pulmonary valve and intact ventricular septum.[1, 15] Yeager et al suggest that tetralogy of Fallot 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 affected.[1] Only fetuses in which the ductus is restrictive or absent are able to survive to term.[1]

Prognosis

Prognosis in patients with tetralogy of Fallot (TOF) with absent pulmonary valve is directly related to the degree of tracheobronchial obstruction secondary to pulmonary artery dilatation. Airway compromise is the predominant concern, including atelectasis, pneumothorax, and pneumonia.

Neonates with severe respiratory distress soon after birth are most at risk for early death. Infants who require surgery early in life have a worse prognosis than those repaired at a later date.

Galindo et al reported that many fetuses with absent pulmonary valve syndrome have an increased nuchal thickness in the first trimester and that the 22q11 microdeletion is the most common associated karyotype anomaly (21% of their patients); these findings suggest an extremely poor outlook in these patients (only 2 of 14 patients in the study ultimately survived).[5] Other authors have reported similar prognosis findings.[6, 16]

In a Japanese study, patent ductus arteriosus appeared to be a good prognostic factor for fetal and postnatal outcomes, whereas polyhydramnios, hydrops fetalis, and balloon type (vs clover type) pulmonary configuration were associated with poor prognosis.[17]

Mortality/morbidity

Mortality and morbidity rates in patients with tetralogy of Fallot with absent pulmonary valve syndrome far exceed those of patients with normal physiology who have typical tetralogy of Fallot. 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 tetralogy of Fallot. 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 9 months.

Hypoxemia

The newborn may demonstrate significant cyanosis until pulmonary vascular resistance (PVR) 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 tetralogy of Fallot.

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.

 

Presentation

History

Symptoms are noted soon after birth in patients in whom fetal detection failed to reveal the condition. In early infancy, patients with tetralogy of Fallot (TOF) with absent pulmonary valve 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.

In a fetus, severe pulmonary regurgitation may cause heart failure, and this may result in fetal hydrops and intrauterine death. It has been suggested that only fetuses in whom the ductus is restrictive or absent are able to survive to term.[1] In fetuses that survive to term, respiratory symptoms develop immediately after birth due to tracheal or bronchial obstruction.

Cyanosis may also present early because of the high pulmonary vascular resistance. Cyanosis usually does not progress as it does in typical tetralogy of Fallot in patients with an intact pulmonary valve. As the pulmonary vascular resistance (PVR) falls, the cyanosis decreases as the left-to-right shunt increases.

Physical Examination

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 (PVR). 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.

Congestive heart failure (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 PVR.

The precordium is hyperactive with a right ventricular lift.

Cardiac auscultation

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.

 

DDx

Diagnostic Considerations

Absent pulmonary valve syndrome may occur in isolation without the presence of a ventricular septal defect (VSD). This rare anomaly usually causes severe distress at birth, especially when associated with a patent ductus arteriosus (PDA), because it can result in severe right ventricular (RV) dysfunction.[1]

A pulmonary artery may arise directly from the aorta. Absence of the left pulmonary artery has been reported. A nonrestrictive ductus arteriosus is more likely to be present in this scenario.[18]

Differential Diagnoses

 

Workup

Approach Considerations

Tetralogy of Fallot (TOF) with absent pulmonary valve can be accurately diagnosed based on fetal echocardiography findings. Galindo et al reported 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.[5] They also found the 22q11 microdeletion to be the most common associated karyotype anomaly, which was present in 21% of their patients.[5]

A report on the utility of fetal MRI in a fetus with TOF with absent pulmonary valve documents its ability not only to assess the size of the pulmonary arteries, but also the symmetry of the aeration of the lungs secondary to obstruction and over inflation. In addition, the volume of the lungs can be determined. All these factors can then allow better anticipation of the patient's postnatal management, including the use of extracorporeal mechanical ventilation and early surgery.[19]

Obtain a hemogram (complete blood cell [CBC] count) to determine hemoglobin and hematocrit levels. In addition, an arterial blood gas (ABG) study can provide useful information in a sick infant.  The use of pulse oximetry on any extremity will indicate the severity of the pulmonary outflow tract obstruction and the need for supplemental oxygen or additional intervention. 

Electrocardiography (ECG) demonstrates the presence of right ventricular hypertrophy (RVH) and greater left ventricular (LV) forces than typical for TOF (some show actual LV enlargement). Right atrial enlargement may also be present.

A study suggests that preoperative pulmonary function testing (PFT) in patients with TOF with absent pulmonary valve may help clinicians manage mechanical ventilation in these patients.[20] Markedly elevated airway resistance as well as flow limitation in medium to small airways with a mild reduction of forced vital capacity were noted. In postoperative patients evaluated with varying levels of positive end expiratory pressure (PEEP), there was improvement in tidal volume and reduced obstruction with PEEP greater than 10 cm H2O.[20]

Radiologic Studies

Radiography, echocardiography, and magnetic resonance imaging (MRI) are imaging modalities that have been used in the evaluation of tetralogy of Fallot (TOF) with absent pulmonary valve.

Chest radiography

Chest radiography usually reveals aneurysmally dilated central pulmonary arteries with otherwise normal peripheral pulmonary vascularity. Cardiomegaly results from dilation of the right ventricle (RV), particularly its outflow tract (infundibulum).

Other pulmonary parenchymal abnormalities may be evident (eg, atelectasis, pneumonic infiltrate, lobar emphysema, hyperinflation). The air trapping may cause a herniation of a lobe.

A right aortic arch may be found in some patients.

Echocardiography

Echocardiography is usually diagnostic in this condition. Findings similar to those of tetralogy of Fallot include the characteristic large ventricular septal defect (VSD), enlarged anteriorly displaced aorta, and RV hypertrophy.

The conal septum is displaced anteriorly, but the RV infundibulum is patent and may be dilated if the degree of pulmonic regurgitation is substantial.

The pulmonary annulus demonstrates some degree of hypoplasia, and pulmonary valve leaflets are not observed.

The pulmonic trunk (main pulmonary artery) and proximal right and left pulmonary arteries are dilated in proportion to the degree of pulmonic regurgitation. This is also true for the RV, which is enlarged and demonstrates paradoxical septal motion.

Four key echocardiographic features of absent pulmonary valve syndrome that appear to differentiate it from tetralogy of Fallot are as follows[21] :

  • Absence of pulmonary valve or presence of pulmonary valve dysplasia
  • Concurrent stenosis and regurgitation at the pulmonary annulus
  • Significant aneurysmal dilatation in the areas of the pulmonary arteries
  • Increased rather than decreased pulmonary artery pressure

Doppler echocardiography

Doppler echocardiography demonstrates turbulence through the RV outflow tract. Pulmonary regurgitation is readily identified, but the ductus arteriosus is rare. Flow across the VSD is not turbulent, because the defect is large and unrestrictive and is generally bidirectional.

Magnetic resonance imaging

An MRI may be used to obtain the above information and has the added advantage of lack of radiation exposure.

Cardiac Catheterization and Angiography

Echocardiography in the typical patient provides all of the information necessary to plan surgical repair. Unusual anatomy or the presence of some complicating additional defects rarely requires the need to perform catheterization in order to plan surgical intervention.

Abnormal pulmonary artery distribution and branching with possible peripheral pulmonary stenosis may be identified.

Catheterization may be appropriate in patients with absence of the left pulmonary artery or origin of a pulmonary artery directly from the aorta.

Right ventricular angiography demonstrates the stenotic pulmonic annulus with the dilated right and left pulmonary arteries. This has been called the "Mickey Mouse" appearance.

 

Treatment

Approach Considerations

Pulmonary complications are the common cause of infant mortality in patient with tetralogy of Fallot (TOF) with absent pulmonary valve. In a neonate with respiratory distress, transfer to a tertiary care facility with pediatric critical care specialists, pediatric cardiologists, and pediatric cardiothoracic surgeons is expected.

Exacerbation of emphysematous changes and atelectasis from minor respiratory embarrassment, such as an upper respiratory infection, may cause severe problems in the affected neonate. Respiratory syncytial virus (RSV) infection is particularly hazardous for these patients.

Placing the infant in a prone position may be beneficial for respiratory effort; it has been reported to be helpful both preoperatively and postoperatively.[22] However, this sleeping position is not recommended unsupervised, because it increases risk of sudden infant death syndrome (SIDS). Takabayashi et al have recommended use of the prone position along with bilateral pillows to avoid compression of the sternum.[23]

Maturation of the tracheobronchial tree in infants older than 1 year reduces pulmonary obstructive symptoms, presumably by strengthening the underlying cartilaginous structures.

Patients with severe bronchial obstruction present a distinct management problem. If an infant develops respiratory acidosis with retention of carbon dioxide, assisted ventilation may be indicated; however, mechanical ventilation in these patients is of great concern, because once a patient is dependent on positive pressure ventilation, weaning from the respirator can be very difficult. If used, pressure settings should be as low as possible.

Surgical Intervention

Critically ill patients require urgent surgical repair. Early surgical correction is preferred in symptomatic patients.[24] In asymptomatic infants and those with only mild symptoms, surgery is usually deferred until later in childhood.[25]

Consultation with a pediatric cardiologist and a pediatric cardiothoracic surgeon is essential.

Repair techniques and controversies

Surgical repair techniques vary in accordance with the particular anatomy in a given patient, especially the severity of pulmonary artery dilation. The repair depends on achieving integrity of pulmonary circulation, which one report suggests is best achieved by using right ventricle–to–pulmonary artery conduit or inserting a pulmonary valve.[24]

Definitive repair includes intracardiac repair of as well as the elimination of bronchial compression. Therefore, any intracardiac surgery needs to be accompanied with excision of the main, right, and left pulmonary arteries.[26] However, this is not always uniformly helpful because, as mentioned earlier, abnormalities may be present at the pulmonary arteriolar level.

Another area of controversy is whether to insert a valve in the pulmonic position via a homograft or a bioprosthetic valve conduit which typically degenerates (stenosis or insufficiency) fairly quickly in neonates.[18, 27, 28] However, one report argues that the use of a valveless right ventricle–to–pulmonary artery connection, combined with catheter-based intervention, reduces the likelihood of reoperation necessitated by homograft placement.[29]

Other approaches have been suggested to reduce the bronchial compression. One such approach includes translocation of the pulmonary artery anterior to the aorta and away from the airways.[30]

External airway stenting and intracardiac repair

Sakamoto et al described external stenting of the airway along with intracardiac repair, another ingenious approach.[31] This group placed a separate graft and patch around the respiratory tract. The authors pointed out that suturing the first graft on the border region between the cartilaginous portion and membranous portion is important and not to completely encircle the trachea, because this may then hamper growth of the airway.[31] They argued that external stenting of the airway was likely to be more effective than endobronchial stenting.

Postoperative Monitoring

Airway morbidity dictates the postoperative recovery and prognosis of neonates from older patients with tetralogy of Fallot (TOF) with absent pulmonary valve. The overall survival is linked to the airway pathology, which is the cause of morbidity and mortality. Preoperative intubation and ventilation are risk factors predictive of poor outcome. (See Prognosis.)

Repair in the critically ill neonate is urgent, high risk, fraught with postoperative complications, and carries a high mortality rate. However, 2 surgical reviews provided a more optimistic picture when surgical strategies are individualized and combined with aggressive postoperative ventilatory management and additional interventions aiming to relieve airway obstruction.[25, 29]

Surgical repair of aneurysmal pulmonary arteries in infants does not necessarily eliminate respiratory symptoms due to persistent bronchial narrowing. These patients require close and regular outpatient follow-up.

Patients in whom repair is successful require regular outpatient visits to monitor right ventricular function, hemodynamics of the homograft, if used, and cardiac rhythm stability.

 

Medication

Medication Summary

No specific medications for tetralogy of Fallot (TOF) with absent pulmonary valve are indicated. Anticongestive therapy is of limited benefit in the treatment of heart failure.

Inotropic agents

Class Summary

Positive inotropic agents increase the force of contraction of the myocardium and are used to treat acute and chronic congestive heart failure (CHF). Some of these drugs may also increase or decrease the heart rate (ie, positive or negative chronotropic agents), provide vasodilatation, or improve myocardial relaxation. These additional properties influence the choice of drug for specific circumstances.

Digoxin (Lanoxin)

Digoxin is a cardiac glycoside with direct inotropic effects in addition to indirect effects on the cardiovascular system. This agent acts directly on cardiac muscle, increasing myocardial systolic contractions. Its indirect actions result in increased carotid sinus nerve activity and enhanced sympathetic withdrawal for any given increase in mean arterial pressure.

Diuretic agents

Class Summary

Diuretic agents promote excretion of water and electrolytes by the kidneys. These drugs are used to decrease pulmonary or systemic edema.

Furosemide (Lasix)

Furosemide increases excretion of water by interfering with the chloride-binding cotransport system which, in turn, inhibits sodium and chloride reabsorption in the ascending loop of Henle and distal renal tubule.