Tetralogy of Fallot

What is Tetralogy of Fallot (TOF)?

Tetralogy of Fallot (TOF) is one of the common congenital heart diseases, which is characterized by the presence of a severe pulmonary artery stenosis, a large VSD, displacement of the aorta to the right ventricle and hypertrophy of the right ventricle. 

Embryology

The morphogenesis of TOF is inextricably linked with the formation of pulmonary arteries. The pulmonary trunk is formed by dividing the conotruncus.

Conotruncus (the embryonic truncus) – is the term, which includes two closely related structures of the embryonic heart: the conus arteriosus and the arterial truncus, which are responsible for the formation of the aorta and the pulmonary artery. Conotruncus is the outflow tract of the heart of a 2-3 week embryo. Normally, at the 4-5 week of fetal development, conotruncus is divided by a spiral septum into relatively equal in size large vessels: the aorta and the pulmonary trunk.

Depending on the degree of violation of the absorption and rotation of conotruncus, a wide spectrum of defects is formed, one of which is Tetralogy of Fallot. The basis of the formation of Fallot's tetrad is the underdevelopment of the infundibular part of the right ventricle or the conus.

Anatomy

Four typical signs of this defect are: large VSD, obstruction of the outflow tract of the right ventricle (pulmonary stenosis), hypertrophy of the right ventricle, dextroposition or overriding aorta.

The morphological basis of this congenital heart disease is a presence of a large VSD and the stenosis of the pulmonary artery. Ventricular hypertrophy is a consequence of the stenosis, as well as its volume overload. The position of the aorta may be variable.

It is difficult to characterize the “usual” location of the VSD. Most often, it is located at the intersection with the plane of the aortic valve. In this case, the valve is the edge of the defect, so the defect can be described as a cone, the base of which is the aortic valve.

In most cases, obstruction of the outflow tract of the right ventricle is in the form of infundibular muscle stenosis. The valve ring and pulmonary trunk are hypoplastic, less often there is a pulmonary valve atresia. Branches of the pulmonary artery are usually narrowed, with the presence of variable peripheral stenosis. The initial section of the left pulmonary artery is particularly prone to stenosis.

Tetralogy of Fallot is often combined with other congenital heart defects.

Classification

In connection with the features of hemodynamics, there are three clinical and anatomical forms of tetralogy of Fallot:

1. TOF with pulmonary stenosis;
2. TOF with agenesis of the pulmonary artery;
3. TOF with pulmonary atresia.

Hemodynamics

Due to the presence of large VSD, the peak systolic pressure in both ventricles is the same. The direction and magnitude of blood ejection at the defect level depends on the severity of pulmonary artery stenosis. Due to the fact that the pressure in the right ventricle increases slowly than in the left ventricle, there is a slight shunt from left to right in the early systole, even among patients with severe pulmonary stenosis. Blood shunt from left to right is observed in the presence of moderate pulmonary stenosis, and the volume of pulmonary blood flow is higher than the systemic.

In the presence of more pronounced stenosis of the pulmonary artery, pulmonary and systemic resistance are almost equal, therefore, the blood shunt is bidirectional. In the presence of severe stenosis, the direction of blood shunt is from right to left, with depleted pulmonary blood flow. Pulmonary venous return is also reduced, and most of the blood enters the aorta from the right ventricle, which causes a low level of oxygenation.

Cardiac output is usually normal or slightly increased.

The localization of VSD and the degree of displacement of the aorta to a small extent affect the hemodynamics. 

Infundibular stenosis has a dynamic character among some patients, which explains the inconsistent severity of cyanosis and shortness of dyspnea-cyanotic attacks. Because the pressure in the right ventricle is equal to systemic, severe hypertrophy of the right ventricle is absent. 

At rest, the pH and pCO2 levels among patients with Tetralogy of Fallot do not differ from the norm. The level of pO2 depends on the degree of the pulmonary stenosis. Oxygenation of arterial blood can sometimes decrease to a critical level, for example, when the patient has slight or moderate physical activity. This is easy to determine by pulse oximetry. The main reason for the drop in blood oxygen saturation is a decrease in the resistance of systemic vessels, due to mental and physical stress, which leads to an increase in the right-left blood shunt.



Blood oxygen saturation also decreases with the onset of dyspnea-cyanotic attack, which is accompanied by metabolic acidosis. Attacks occur among patients who have dynamic muscle stenosis, not fixed by fibrosis. 

The etiology of dyspnea-cyanotic attacks is not exactly known, but it is assumed that they arise due to reasons, that lead to an increase in oxygen demand in combination with a decrease in PaO2 and pH and an increase in PaCO2. This leads to hyperventilation, an increase in venous return, an increase in right - left shunting, and a further decrease in PaO2 and pH. As a result of ongoing hypoxia, the resistance of arterial vessels decreases and the right – left shunt increases.

Diagnostics

• Echocardiography, CT. Visualization of the main morphological features of the Tetralogy of Fallot.
• ECG. Changes may be non-specific. Deviation of the heart axis to the right due to hypertrophy of the right ventricle.
• Chest X-ray. A depleted pulmonary pattern can be detected, the apex of the heart is usually elevated, and there is a notch on the left side of the heart (a retraction of the arc of the pulmonary artery). The combination of tetralogy of Fallot with the absence of a pulmonary valve causes a pronounced violation of the X-ray picture. 
• The shadow of the heart is enlarged, the arc can be located on the right. A characteristic sign of the anomaly is aneurysmal expansion of the proximal right and left pulmonary arteries.
• Cardiac catheterization with aortography. It is used in case of unsatisfactory visualization of the structures of the heart and blood vessels using other methods, or in cases of the presence of any additional anomalies.

Clinical presentation

Clinical presentation depends on the severity of the pulmonary stenosis, which is the most variable component of the tetrad. 

Cyanosis, hypoxia can be expressed in a newborn, while a teenager may not have severe symptoms. Cyanosis can be observed from the moment of the birth of the child, or may appear later.

Some children have a clinical picture of large VSD with increased pulmonary blood flow and even congestive heart failure. 

As pulmonary stenosis progresses, these children show a more typical clinical picture of TOF, congestive heart failure disappears and mild cyanosis appears.

Episodes of severe cyanosis with impaired breathing and even with loss of consciousness are called “cyanotic”, “hypercyanotic” or “dyspnea-cyanotic” attacks. Such attacks are observed more often from 2-4 months of age. Attacks often occur in the morning, after crying, feeding or defecating and can intensify with physical activity. The child becomes restless, cries for a long time, cyanosis intensifies, breathing becomes frequent and difficult.

A pose on the side with knees pressed to the stomach is characteristic for patients with tetralogy of Fallot. This symptom often manifests itself at an early age. Children feel more comfortable in this position, as oxygenation of arterial blood increases.Most patients with tetralogy of Fallot have systolic murmur on the left sternal border in the middle or upper third of it, due to stenosis of the pulmonary artery.

A characteristic feature of tetralogy of Fallot with pulmonary atresia is systolic-diastolic murmur on the left sternal border in the middle and upper third.

Treatment

Therapy is aimed at reducing hypoxemia and its consequences, the correction of metabolic disorders. To prevent dyspnea-cyanotic attacks, patients are prescribed beta-blockers. The appearance of attacks is considered as an indication for surgical correction of the defect. The purpose of the radical operation is to close the VSD and eliminate obstruction of the outflow tract of the right ventricle, avoiding the occurrence of significant regurgitation.

Radical correction can be performed as a primary operation with favorable anatomy of the pulmonary artery, usually in the first year of the patient’s life, or as the second stage of correction after palliative operation (inter-arterial anastomoses, balloon dilatation of pulmonary stenosis, and reconstruction of the outflow part of the right ventricle without closure of VSD). 



Early surgery is indicated for patients with agenesis of the pulmonary artery, before compression of the tracheobronchial tree and respiratory failure develop. Primary radical correction, in which obstruction of the right ventricular outflow tract is eliminated and the interventricular septal defect is closed with a patch is preferred to this concept.