Rush Center for Congenital
and Structural Heart Disease







This occurs in about 0.19-0.26/1,000 live births. It constitutes 8% of all congenital heart diseases. It is the most common cyanotic congenital heart disease beyond 1 week of age.  





Malaignment of the outflow septum anteriorly is thought to leave a defect in the ventricular septum, cause the right ventricular outflow to become narrow and the aorta to override the ventricular septal defect.  The following is a description of the normal outflow tract septation:

The cardiac outflow tract include the ventricular outflow tract and the aortopulmonary septum. There has been much debate regarding this process, the following is a summary of various theories.

Kramer (1942) suggested that there are three embryological areas, the conus, the truncus and the pulmonary arterial segments. Each segment develop two opposing ridges of endocardial tissue, the opposing pair of ridges and those from various segments meet to form the septum separating the two outflow tracts and the aortopulmonary trunks. The aortopulmonary septum is formed by ridges separating the fourth (future aortic arch) and the sixth (future pulmonary arteries) aortic arches. The truncus ridges are formed at the area where the semilunar valves are destined to be formed, therefore forming the septum between the ascending aorta and the main pulmonary artery. The conus ridges form just below the semilunar valves and from the septation between the right and left ventricular outflow tracts.

Van Mierop (1979), agrees that there are three pairs of ridges forming in the aortopulmonary, truncus and conus regions, however, he states that the pairs of ridges fuse independently and later on fuse with each other to complete the septation. His theory indicate that the truncus ridges form first, and as they fuse they form a truncal septum which then fuses with the aortopulmonary septum which is formed by invagination of the dorsal wall of the aortic sac between the fourth and the sixth aortic arch arteries.

Asami(1980), follow Van Mieropís theory, however, he believes that these ridge fuse in the opposite direction of what Van Mierop has indicated, i.e. from the outflow tract to the aortopulmonary region.

Pexieder(1978, 1984) and Orts Llorca et al (1982), believe that there are only tow septa, a conotruncal (or bulbar) and an aortopulmonary septum.

Bartlings et al (1989), believe that the septation process of the ventricular outflow tracts, pulmonary and aortic valves and the great vessels is mostly caused by a single septation complex, which they termed aortopulmonary septum, a term they used reluctantly because the septation complex is actually at the future valve level and not in-between the great vessels, however, they refrained from introducing a new term, so as not to introduce yet another term in a field where there abundance of confusing terminology. This septation complex develops at the junction of the muscular ventricular outflow tract with the aortopulmonary vessel. This junction has a saddle shape, this will determine the fact that the RVOT is long with short main pulmonary artery and the LVOT is short with longer ascending aorta.

The border between the myocardial wall of the outlet and the mesenchymal vessel wall is very well demarcated. The endocardial cushion tissue forms six valve swellings, underneath which two ridges are formed which are opposed to the myocardial layer. A mesenchymal arch forms within the endocardial tissue, the two limbs of the arch are in contact with the myocardium of the ventricular outflow. These bulges within the outflow tract are positioned dextroposteriorly on the parietal wall and sinsitroanteriorly on the right side of the primary septum.

Myocardium in contact with the mesenchymal arch grow rapidly and form the bulk of the outflow septum and is continuous with the primary fold on the parietal wall of the right ventricle and the myocardium on the right side of the primary septum





The ventricular septal defect is located in the membranous septum, it is subaortic and sometimes extends to the subpulmonic valve area. The VSD is large causing equalization of LV and RV pressures. These defects do not usually get smaller and are not known to close spontaneously. The right ventricular outflow tract is hypoplastic and almost always obstructive. Occasionally at birth the RVOT shows no significant obstruction and results in the so-called "pink" tetralogy of Fallot. Mild hypertrophy of the moderator band and ventricular septal defect should be distinguished from tetralogy of Fallot as the prognosis is different in each case. The pulmonary valve annulus is typically small in tetralogy of Fallot and the leaflets are deformed. The main pulmonary arteries in contrast to pulmonary stenosis is small as well as the branch pulmonary arteries. There might be branch pulmonary artery stenosis as well as peripheral pulmonary artery stenosis in addition to the RVOT and pulmonary valvar stenosis. Bronchial arterial collaterals are sometimes present which connect to the peripheral pulmonary arteries. The main pulmonary artery is occasionally atretic and the pulmonary arteries are fed either by patent ductus arteriosus or collateral vessels. The aortic valve is typically large.

Ten per cent (10%) of tetralogy of Fallot patients have pulmonary atresia. Of those patients, 70% have the pulmonary arteries fed by patent ductus arteriosus and 30% by collateral. In patients who have collateral blood vessels supplying the pulmonary arteries the pulmonary arteries may be significantly small which would necessitate utilizing the collaterals in a unifocalization process. Forty per cent (40%) of patients with tetralogy of Fallot have patent foramen ovale and 25% have a right aortic arch. As the incidence of anomalous coronaries are also higher in patients with tetralogy of Fallot than the normal population where it is seen in 5%. The left anterior descending artery might originate from the right coronary artery and pass in front of the right ventricular tract which is an important thing to know since the surgeon may attempt opening the RVOT and causing damage to the left anterior descending artery.






RVOT and pulmonary stenosis causing significant resistance to right ventricular outflow causes blood to shunt right to left.  The extent of right to left shunting is determined by the severity of the stenosis.  VSD tends to be large and non obstructive.,  Patients with TOF do not develop CHF, unless there is an alternant pulmonary blood flow such as with PDA or collaterals.

Cyanosis is determined by the extent of right to left shunting at the VSD.




Clinical Manifestations


The right ventricular outflow tract obstruction may be minimal in the beginning leading to significant left-to-right shunting at the VSD with symptoms and signs of congestive heart failure. As the right ventricular outflow tract becomes more and more obstructive the pulmonary vascular resistance will exceed the systemic vascular resistance and right-to-left shunting will occur causing cyanosis. Cyanosis is influenced by hemoglobin level and therefore if it is low it may not be evident. Cyanosis induces an increase in the hemoglobin concentration and increase in erythropoietin production. When there are large or multiple collaterals from the systemic arterial circulation to the pulmonary arterial circulation there will be minimal cyanosis as pulmonary blood flow will be increased. The long systolic murmur of tetralogy of Fallot is secondary to the turbulent flow across the RVOT obstruction and pulmonary stenosis and not due to the VSD. Twenty-five per cent (25%) of tetralogy of Fallot patients are cyanotic at birth and 75% of patients become cyanotic at 1 year of age. Spells of hypercyanosis are uncommon in the first six months of life. They are most common in infants and toddlers. They again become rare in children more than 4 years of age.

Squatting helps to relieve cyanotic spells possibly due to increase in systemic vascular resistance because of kinking of femoral arteries as well as in a decrease in the venous return. Due to deformity of the pulmonary valve there may be a single second heart sound. When continuous murmurs are auscultated this might indicate the presence of a PDA or collateral vessels.






There is typically right ventricular hypertrophy with right axis deviation. Superior axis deviation is seen in patients with tetralogy of Fallot and AV canal defect. Right ventricular hypertrophy and left ventricular hypertrophy is seen in acyanotic infants with left-to-right shunting causing congestive heart failure.





The mediastinum is narrow due to small or atretic pulmonary arteries.  The left ventricular apex is uplifted due to RVH.  These two features give the boot shaped heart.
The pulmonary vascular markings are reduced due to RVOT and pulmonary valve stenosis.  Increased pulmonary vascular markings indicate presence of PDA or collaterals.





Echocardiography will show the cardiac defect including the VSD, right ventricular outflow tract obstruction and pulmonary stenosis. The peripheral branch pulmonary arteries will not be appreciated by echocardiography. Flow across patent ductus arteriosus and collaterals could be appreciated although the extent of the collaterals and where they originate from and how they feed the pulmonary arteries may not be fully appreciated by echocardiography.  



Cardiac Catheterization


In straight-forward, clear tetralogy of Fallot there may not be a need for cardiac catheterization. However, if the peripheral pulmonary arterial anatomy is unclear than cardiac catheterization may be indicated to evaluate the peripheral pulmonary arteries and collateral circulation. In addition, the coronary arteries need to be studied.  






Cyanotic spells:

These typically occur when babies or toddlers are upset leading to increase in the catecholamines and consequently increase in the right ventricular outflow tract obstruction and more right-to-left shunting at the ventricular septal defect level. The first line of treatment should be to ask a parent to hold and comfort the child, usually this will break the spell. When holding the child it is best to place him in the knee-chest position to increase the systemic vascular resistance. When this fails then one might utilize one of the following measures:

1. Morphine subcutaneously or intravenously will cause a negative inotropic pressure and left-

to-right ventricular outflow tract obstruction. In addition, it has a sedative analgesic effect that

might cause the child to relax with less catecholamines and less RVOT obstruction.

Beta blockers such as an Esmolol drip or intravenous Inderal will cause a negative inotropic

effect and less RVOT obstruction thus breaking the cyanotic spell.

Vasoconstrictors such as a drip of Epinephrine or Phenylephrine Hydrochloride will cause vasoconstriction and elevation of the systemic vascular resistance with less right-to-left shunting.

Complete repair is typically done at 6 months to 1 year of age. Some surgeons have tried to preserve the integrity of the pulmonic valve to lessen the extent of pulmonary insufficiency by not placing a transannular patch. However, some of these patients would have significant residual pulmonary stenosis.




Course and Prognosis


Unrepaired the right ventricular outflow tract obstruction will continue to increase with more right-to-left shunting at the VSD and more cyanosis. The hematocrit will continue to increase and polycythemia would result. The right ventricular pressure might exceed that of the systemic when occasionally the tricuspid valve tissue is incorporated in the VSD causing VSD restriction. Such patients will have a poor surgical outcome because of RV strain. Aortic valve regurgitation seen in tetralogy of Fallot will increase with time because of increased pulmonary stenosis and more right-to-left shunting with increase of blood volume flow across the aortic valve resulting in aortic valve deformity and insufficiency. This will also explain the higher incidence of aortic insufficiency in patients with tetralogy of Fallot and pulmonary atresia. One should always think of subacute bacterial endocarditis in patients with aortic insufficiency since this valve is the most likely area of subacute bacterial endocarditis in patients with tetralogy of Fallot. Left pulmonary artery stenosis or even atresia could develop later on and not necessarily noted right after birth. When this occurs there will be increase in pulmonary blood flow to the right lung developing as pulmonary hypertension. In patients with pulmonary hypertension with tetralogy of Fallot it will be important to either preserve the integrity of the pulmonic valve or place a prosthetic pulmonary valve since insufficiency might be significant. The only time that pulmonary vascular obstructive disease is noted in patients with tetralogy of Fallot are those that were palliated many years ago with Potts or Waterston shunts.

Arrhythmias are frequent with tetralogy of Fallot. Premature ventricular contractions either focal or multifocal or even runs of V-tach are sometimes noted. The older the age of the child at the time of repair the more likely that they would develop arrhythmias.

Myocardial dysfunction is a more prominent problem in patients who are repaired at an older age, those with dysrhythmia and those with residual postoperative defects, for example, ventricular septal defect (18% of patients required re-operation for one reason or another). Late death in patients with tetralogy of Fallot occur in approximately 5% of repaired patients.

Brain abscess should be ruled out in any patients with CNS symptoms. This was a more frequent occurrence in the past as these lesions were not repaired until 4-5 years of age. Cerebral vascular accidents secondary to hypoxia particularly in those with anemia and due to polycythemia. Brain abscess should be ruled out in any patients with CNS symptoms. Scoliosis may result which is also common in other cyanotic congenital heart diseases. This is more common in females than males.









This is an uncommon variation of tetralogy of Fallot. The pulmonary valve leaflets are represented by nubbins of tissue. The clinical picture is dominated by pulmonary insufficiency rather than pulmonary stenosis.

The anatomy is the same as tetralogy of Fallot except that the right ventricular outflow tract is not excessively restrictive. The pulmonary arteries are dilated and sometimes aneurysmal. The pulmonary artery dilatation may extend beyond what is expected from pulmonary insufficiency to several generations of pulmonary arteries causing bronchial constrictions.


Clinical Manifestations:

A systolic and diastolic murmur is present. This represents pulmonary stenosis and pulmonary insufficiency.

The chest x-ray shows aneurysmal dilatation of the main pulmonary artery.

The cardiac catheterization is important to delineate the peripheral pulmonary arteries.

Management is delayed as much as possible because of the need to place a valve, usually a homograft. Surgery is done earlier in patients with dilated distal pulmonary arteries and respiratory distress to halt further progress of bronchoconstriction. Pulmonary arteries could be plicated during surgery. Hypercyanotic spells are not a feature of this type of tetralogy of Fallot.




In tetralogy of Fallot with AV canal presentation is similar to that of typical tetralogy of Fallot. The electrocardiogram shows superior axis deviation with right ventricular hypertrophy. In almost all instances the anterior atrioventricular valve leaflet is free floating. Due to the complexity of this congenital heart disease, cardiac catheterization is almost always performed. Surgery is usually done at 1 year of age where the AV canal and tetralogy of Fallot are repaired simultaneously. There is a higher instance of Down syndrome in comparison to other types of tetralogy of Fallot.




This typically occurs due to hypertrophy of the moderator muscle bundle. In these instances the right ventricular apex pressure is higher than the rest of the right ventricle. During surgical repair the moderator muscle bundle should be severed so as to eliminate the pressure gradient


Tetralogy of Fallot with pulmonary atresia

Eighteen per cent (18%) of patients with tetralogy of Fallot have pulmonary atresia. Pulmonary atresia can be congenital or acquired. The VSD is of the malalignment type and there might be other types of VSD seen. Like tetralogy of Fallot with pulmonary stenosis 25% of these patients have a right aortic arch. Although in some estimates that is thought to be as frequent as 50%.

These patients have collaterals, 70% of the them have patent ductus arteriosus feeding into the pulmonary arteries and 30% of such patients have collateral vessels. Collateral vessels could come from the descending aorta or the brachiocephalic arteries. Collateral vessels may feed one side of the lungs, both sides or cross to the opposite side. Collaterals are typically from the thoracic aorta and less common from the subclavian artery and rarely from the descending aorta directly or left carotid artery. Embryologically, the lungs are supplied by primitive blood vessels from the descending aorta and in patients with pulmonary atresia these vessels may persist as collaterals. Bronchial arteries may supply the blood to the lungs. Pulmonary arterial pressure tends to be normal or below normal because of narrowing of collateral and pulmonary hypertension is not frequently encountered in these kind of cases. Symptom cyanosis is not very clear since there is an increase in pulmonary blood flow to multiple collaterals and the patient presents with congestive heart failure more than cyanosis.

Cardiac catheterization is necessary in all such patients except those that are severely cyanotic and require an urgent systemic to pulmonary arterial shunt placement. In the cardiac catheterization the pulmonary arteries should be studied as well as the collateral circulation and coronary artery anatomy as well as other VSDís that might be associated with a malalignment VSD. Patients with increased pulmonary blood flow and congestive heart failure could benefit from coil occlusion of collateral vessels. Pulmonary arteries grow best if they have increased pulmonary blood flow and particularly if it is from the right ventricle. Therefore, increasing pulmonary blood flow through the pulmonary arteries is important to do as soon as possible to allow the pulmonary arteries to grow and enable complete repair. If collateral blood vessels provide the lung segments with blood not provided through the pulmonary artery then incorporation of that collateral through a process of vena focalization should be considered. Three-quarters (3/4) of the total lung capacity should be incorporated in the repair, i.e., 15 of the 20 segments or 1-1/2 lung should be incorporated in the unifocalization repair. Systemic to pulmonary arterial collaterals should be either included in the unifocalization process or occluded by cause in the cath lab.