Fetal TOF - Absent Pulmonary Valve Syndrome

Case of Tetralogy of Fallot with absent pulmonary valve. There is overriding aorta with a large ventricular septal defect (VSD). There is signs of pulmonary stenosis and severe pulmonary insufficiency, leading to severe main and branch pulmonary and  arteries dilatation (the LPA and RPA are aneurysmal - whale tale sign). The arterial duct is not patent, as commonly seen in this disease and possibly contributive to the dilatation (absence of a pop-off leading to progressive enlargement). Absent pulmonary valve syndrome may be found in TOF-Absent pulmonary valve (or Absent pulmonary valve syndrome with VSD), or in the context of absent pulmonary valve syndrome with intact ventricular septum and tricuspid atresia (Non-Fallot type APVS). Non-Fallot type of APVS may also be seen without tricuspid atresia. Absent pulmonary valve syndrome may be suspected in the presence of "Bow Tie" or ballooning of pulmonary arteries, also known as the "whale tale sign".

More on post-natal Tetralogy of Fallot here.

Again, one may appreciate in 2D B-mode the significant enlargement of the pulmonary arteries (Bow Tie pulmonary arteries or whale tale sign). The VSD may be observed briefly in the sweep.

Other sweeps outlining the pulmonary arteries. 

2D mode and Colour mode outlining the MPA enlargement. Colour mode outlines the to-and-fro flow secondary to the significant pulmonary regurgitation. 

View showing the dilatation of the LPA and RPA. 

Colour indicates retrograde flow in the LPA and RPA from the pulmonary insufficiency, as well as some degree of acceleration in systole - outlining the moderate underlying hypoplasia of the pulmonary annulus (leading to post-natal pulmonary stenosis). 

Colour free with the Red colour (insufficiency), Blue colour (anterograde acceleration) and the last screenshot outlines the rudimentary pulmonary valve. 

2D clips with a sweep outlining the VSD and LVOT. 

View for the measurement of the VSD.

The above views of the aortic arch are outlining the absence of a ductus arteriosus - common in this disease. 

Understanding Tetralogy of Fallot with Absent Pulmonary Valve Syndrome

Tetralogy of Fallot with Absent Pulmonary Valve Syndrome (TOF/APVS) is a relatively rare congenital heart disease, accounting for approximately 2% to 6% of all Tetralogy of Fallot (TOF) cases. While it shares some features with classic TOF, its distinctive characteristics and clinical presentation set it apart.

Key Features and Pathology:

TOF/APVS is defined by the absence or severe underdevelopment of the pulmonary valve leaflets. Instead of functional leaflets, there may be a rudimentary or uneven rim of valve tissue. This leads to a stenotic and regurgitant right ventricular outflow tract (RVOT). The condition is nearly always associated with the morphological features of Tetralogy of Fallot itself.

The primary anatomical features include:

• Absent or Dysplastic Pulmonary Valve: The pulmonary valve leaflets are either completely absent or are rudimentary and dysplastic, meaning they are malformed and do not coapt (close properly). The annulus (the ring where the valve is located) is typically small and stenotic.

• Ventricular Septal Defect (VSD): There is a large, non-restrictive ventricular septal defect, which is subaortic and generally extends into the membranous septum, consistent with a malalignment-type VSD typical of TOF.

• Overriding Aorta: The aorta overrides the ventricular septum.

• Right Ventricular Hypertrophy: The right ventricle becomes hypertrophied due to the RVOT obstruction and overriding aorta (RV exposed to systemic pressures). However, in neonates, this is not a unique distinguishing feature as some degree of right ventricular hypertrophy is normal at birth.

• Massively Dilated Pulmonary Arteries: This is arguably the most typical and significant feature. The main pulmonary artery and often its branches (right and/or left pulmonary arteries) are aneurysmally dilated and pulsatile. This massive dilation can cause bronchial compression and severe respiratory distress by pressing on the tracheal-bronchial tree and esophagus.

Pathophysiology and Clinical Presentation:

The combination of pulmonary stenosis (narrowing) and pulmonary regurgitation (backflow of blood) creates a characteristic systolic-diastolic "to-and-fro" murmur audible at the pulmonic area. The severity of the clinical presentation depends largely on the extent of pulmonary artery enlargement and the resulting airway compression and respiratory compromise.

• Symptoms: Infants may present with cyanosis (bluish discoloration due to low oxygen levels in the blood) and respiratory distress. Unlike classic TOF, hypoxic spells are typically not observed in TOF/APVS, and cyanosis may be absent or mild unless severe airway issues are present. Severely compromised neonates require immediate medical management to ensure adequate ventilation and oxygenation. 

Diagnosis with Echocardiography:

Echocardiography is typically sufficient to diagnose TOF/APVS. It allows for comprehensive assessment of the heart's anatomy and function. Key echocardiographic findings include:

• Overriding aorta and visualization of pulmonary valve echoes.

• Ventricular septal defect (VSD) visualization in various views, appearing as an area of echocardiographic dropout. A parasternal or subcostal long-axis view is best for demonstrating the anterior override. A parasternal short-axis view is crucial for documenting pulmonary valve echoes and is mandatory for distinguishing VSD types.

• Dilated right ventricle and abnormal septal motion.

• Documentation of a restrictive pulmonary valve annulus with thick ridges and absence of real, moving leaflets on dynamic viewing from a parasternal short axis view.

• Visualization of an aneurysmally dilated main pulmonary artery and its branches, which may be massively dilated and pulsating, especially from a suprasternal notch approach. Doppler examination will show varying degrees of increased forward flow velocity and significant pulmonary regurgitation.

• Assessment of pulmonary insufficiency and stenosis, RVOT anatomy, ventricular function, atrioventricular valve function, and coronary arteries.

Associated Conditions:

TOF/APVS is most commonly associated with other cardiac lesions, including a VSD and absent arterial duct. While 80% of patients with APV will also have TOF, it can rarely occur in isolation or with tricuspid atresia. A microdeletion on chromosome 22q11 (associated with DiGeorge syndrome) is noted in about 65% of children with TOF and absent pulmonary valve. The presence of anomalous coronary arteries should be excluded before surgery.

Embryological Considerations:

The exact mechanisms behind the development of TOF/APVS are not fully understood. It is thought that hemodynamic disturbances, particularly pulmonary regurgitation, contribute to the abnormal structural changes and progressive dilation of the central pulmonary arteries, rather than a primary genetic abnormality of the arterial wall. The absence of the ductus arteriosus, which is often seen in these patients, might play a role in this severe pulmonary regurgitation during fetal development.

Management and Treatment:

Immediate postnatal medical management is crucial for severely compromised neonates to ensure adequate ventilation and oxygenation. If possible, symptomatic patients are stabilized to promote somatic growth. Some may require positive pressure ventilation (invasive or non-invasive) to "stent the airways". Severe cases may benefit from prone positioning and eventually airway surgery with ENT.

Surgical repair is the primary treatment. The surgical strategy aims for complete repair of the defect, which involves:

• Closure of the VSD.

• Relief of the right ventricular outflow tract obstruction.

• Reduction (plication) of the enlarged branch pulmonary arteries, often with implantation of a valved conduit to replace the absent pulmonary valve.

Prognosis and Long-Term Outlook:

While early surgical mortality is low, long-term survival can be significantly limited, and the reintervention rate is high. Reoperations are primarily needed for recurrent airway disease and complications related to the pulmonary valve or pulmonary arteries.

Differentiation from Other Conditions:

TOF/APVS is rarely confused with other lesions due to its characteristic loud "to-and-fro" murmur. While similar murmurs may be heard with conditions like sinus of Valsalva fistula or aortic-left ventricular tunnel, these typically also present with a wide systemic arterial pulse pressure. Ultrasound examination can usually differentiate these conditions. The clinical manifestation of TOF/APVS is also distinct from classic Tetralogy of Fallot.

Presentation on TOF - Absent Valve by Louise Gervais and Jean-Francois Trudel