Tetralogy of Fallot With Pulmonary Stenosis 

Tetralogy of Fallot (TOF) with pulmonary stenosis is the common form of tetralogy of Fallot, and it is the focus of this article.

Tetralogy of Fallot is a conotruncal defect resulting from anterior malalignment of the infundibular septum. This single morphologic defect gives rise to the 4 main components of Tetralogy of Fallot: (1) ventricular septal defect (VSD), (2) aortic valve overriding the ventricular septum, (3) narrowing of the right ventricular (RV) outflow tract (RVOT), and (4) RV hypertrophy (RVH).

A uniform etiology may explain this anatomic tetrad. That is, the monology of anterior deviation of the infundibular septum causes hypoplasia of the subpulmonary infundibulum and thus accounts for all components of the tetrad.

Tetralogy of Fallot is the most common cyanotic heart defect seen in children beyond infancy and occurs in 10% of all congenital defects. Furthermore, tetralogy of Fallot is the most common cyanotic congenital lesion that is likely to result in survival to adulthood. It is also the most common complex lesion to be encountered in the adult population after repair. Environmental associations with tetralogy of Fallot include maternal diabetes mellitus, retinoic acid exposure, and maternal phenylketonuria (PKU). This defect has a frequent association with the 22q11 chromosomal deletion and can also be seen associated with trisomy 21, 18, or 13. Other possible genetic associations are currently an ongoing area of active research.

Complex forms include tetralogy of Fallot with absent pulmonary valve and tetralogy of Fallot with pulmonary atresia with or without major aortopulmonary collateral arteries (MAPCAs).

See also Tetralogy of Fallot, Tetralogy of Fallot With Pulmonary Atresia, and Tetralogy of Fallot With Absent Pulmonary Valve.

Historical information

Tetralogy of Fallot holds a central place in the history of surgery for congenital heart disease. Tetralogy of Fallot is the first cyanotic cardiac lesion to be successfully managed with surgical palliation and is one of the first cardiac lesions to undergo successful intracardiac repair.

On November 29, 1945, Alfred Blalock performed the first systemic-to-pulmonary artery shunt procedure to palliate tetralogy of Fallot in a child by increasing pulmonary blood flow.^[1] Blalock used a subclavian artery–to–pulmonary artery anastomosis, which was named the Blalock-Taussig shunt (BT shunt) after the cardiac surgeon who initially performed the operation on human children and a cardiologist, Helen B. Taussig. The anastomosis was developed in the animal research laboratory at Johns Hopkins University by the surgical technician Vivien T. Thomas working with Blalock. This was the first truly successful palliation of congenital heart disease and created an international sensation. "Blue babies" from all over the world came to the Johns Hopkins Hospital in Baltimore to be treated.

In 1946, Potts et al described a descending aorta–to–pulmonary artery systemic-to-pulmonary artery shunt (Potts-Smith shunt).^[2] In 1962, Waterston described an ascending aorta–to–pulmonary artery systemic-to-pulmonary artery shunt.^[3] The Potts-Smith and Waterston type shunt procedures were technically easier to perform than classic BT shunting in small infants. However, both the Potts-Smith and Waterston shunts often resulted in excessive pulmonary blood flow, distortion of the pulmonary artery, and problems during subsequent complete tetralogy of Fallot repair. As a consequence, these 2 shunts are essentially no longer used.

The classic BT shunt procedure developed in 1945 involved direct end-to-end anastomosis between the subclavian artery and the pulmonary artery. This technique required transection of the subclavian artery. At The Great Ormond Street Hospital for Children in London, England, Professor Marc deLeval modified this procedure using an interposition conduit between subclavian artery and pulmonary artery. Known as the modified BT shunt, this is currently the most commonly used systemic-to–pulmonary artery shunt. Synonyms for the modified BT shunt include the deLeval shunt and the GOS shunt.

Since the introduction of cardiopulmonary bypass, the trend has been for early and complete repair. C. Walt Lillehei performed the first successful intracardiac repairs by using cross-circulation, an innovative technique involving parental bypass in which the patient's circulation is attached to and supported by the parent's circulation.^[4] In 1954, Lillehei and Varco performed the first intracardiac repair of tetralogy of Fallot by using parental cross-circulation at the University of Minnesota. They closed a ventricular septal defect (VSD) and relieved an RVOT obstruction (RVOTO) under direct vision.

Although this innovative technique was the first surgical procedure with the potential for a 200% mortality rate (patient and parent), it also acted as a stimulus for the subsequent development of a functional mechanical cardiopulmonary bypass machine. In 1955, Kirklin performed the first successful repair of tetralogy of Fallot with a pump oxygenator 90 miles away from the University of Minnesota at the Mayo Clinic.^[5] Currently, the cardiopulmonary bypass machine is used to perform complete intracardiac repair of tetralogy of Fallot (see Corrective Surgery).

The following 4 diagnostic subgroups of tetralogy of Fallot (TOF) are described^{[6, 7]} : (1) tetralogy of Fallot with absent pulmonary valve syndrome; (2) tetralogy of Fallot with common atrioventricular (AV) canal; (3) tetralogy of Fallot with pulmonary atresia; and (4) tetralogy of Fallot with pulmonary stenosis.

Tetralogy of Fallot with absent pulmonary valve syndrome

Tetralogy of Fallot with absent pulmonary valve syndrome is a form of tetralogy of Fallot with a severely dysplastic pulmonary valve and markedly dilated pulmonary arteries. This relatively rare lesion represents only 3-5% of all cases of tetralogy of Fallot. Tetralogy of Fallot with an absent pulmonary valve is commonly associated with respiratory difficulties. Severe problems with oxygenation—and especially ventilation—are thought to be related to bronchial compression secondary to the marked pulmonary artery dilatation.

Tetralogy of Fallot with common AV canal

Tetralogy of Fallot with common AV canal (AV septal defect [AVSD]) is the presence of both tetralogy of Fallot and complete AVSD. This rare lesion represents only 2% of all cases of Tetralogy of Fallot. Complete surgical repair of this lesion is riskier than repair of tetralogy of Fallot or AVSD alone. Nevertheless, combined complete repair is possible and usually successful.

Tetralogy of Fallot with pulmonary atresia

Tetralogy of Fallot with pulmonary atresia is a form of pulmonary atresia with ventricular septal defect (VSD) in which the intracardiac anatomy is tetralogy of Fallot. Tetralogy of Fallot with pulmonary atresia is commonly associated with hypoplastic branch pulmonary arteries and may be associated with major aortopulmonary collateral arteries (MAPCAs).

Tetralogy of Fallot with pulmonary stenosis

As noted in the introductory section, tetralogy of Fallot with pulmonary stenosis is the common form of tetralogy of Fallot. In this condition, pulmonary stenosis may be at the subvalvar, valvar, or supravalvar level, or it may involve any combination of these 3 levels.

The ventricular septal defect (VSD) in tetralogy of Fallot (TOF) is a perimembranous defect with extension into the subpulmonary region. Additional muscular VSDs may be present.

Right ventricular (RV) outflow tract obstruction (RVOTO) is present in the majority of cases of TOF, but it may be variable in severity. In addition to the subpulmonic obstruction, stenosis often coexists at the valvar and supravalvar levels. The pulmonary valve is atretic in the most severe form of the anomaly (15%). In some children, pulmonary atresia develops over time (tetralogy of Fallot with acquired pulmonary atresia).

The pulmonary annulus and main pulmonary artery are hypoplastic in most patients. The pulmonary artery branches are usually small, with variable peripheral stenosis. Narrowing at the origin of the left pulmonary artery is particularly common.

Systemic collateral arteries feeding into the lungs are occasionally present, especially in severe cases of tetralogy of Fallot such as tetralogy of Fallot with pulmonary atresia.

Other associated anomalies include a right aortic arch (present in 25% of patients); atrial septal defect (ASD), typically secundum ASD or patent foramen ovale; and patent ductus arteriosus (PDA).

Abnormal coronary arteries are present in about 5% of patients with tetralogy of Fallot. The most common abnormality is the left anterior descending (LAD) coronary artery arising from the right coronary artery (RCA) and passing over the RVOT. This coronary anomaly can necessitate modification of the surgical approach, because a transannular ventriculotomy may jeopardize the LAD that arises from the RCA.

Complications of the surgery for repair of tetralogy of Fallot with pulmonary stenosis include the following:

• Hemorrhage
• Infection
• Heart block
• Residual or recurrent ventricular septal defect (VSD)
• Residual or recurrent right ventricular (RV) outflow tract obstruction (RVOTO)
• Pulmonary insufficiency
• RV dysfunction
• Heart failure

The overall outcome after surgical repair of tetralogy of Fallot (TOF) has steadily improved since the technique was initially developed. The continued improvement in outcome can be attributed to improved intraoperative technique, including the avoidance of excessive RVOT muscle resection, improved cardiopulmonary bypass techniques (especially for infants), and improved postoperative care.

In the current era, survival to discharge after repair in most reported series is 95-99%, whereas in the early 1980s, the survival rate after tetralogy of Fallot repair was approximately 90%. Thus, the current mortality risk for uncomplicated tetralogy of Fallot repair should approach 0%.

In a historical series, late survival was documented in 814 patients undergoing complete repair at the University of Alabama at Birmingham as 93% at 1 month and at 1 year, 92% at 5 years, and 87% at 20 years.^[8] These survival rates were only slightly less than those of an age-matched, race-matched, and sex-matched control population. In the current era, late survival should even be better than it was in this series.

In the earliest days of surgical repair, postoperative complete heart block was a major problem. The rate of postoperative complete heart block decreased to 5% in earlier series and less than 1% in most recent series.

When the Society of Thoracic Surgeons Congenital Heart Surgery Database was used to analyze data from 941 patients undergoing tetralogy of Fallot repair in 1998-2003, tetralogy of Fallot with pulmonary stenosis was present in 888 patients; tetralogy of Fallot with absent pulmonary valve syndrome was present in 34 patients; and tetralogy of Fallot with common atrioventricular canal (AVSD) was present in 19 patients.^[9] The overall survival after discharge was 98.7%, with the highest risk among patients with tetralogy of Fallot with absent pulmonary valve syndrome, who had a survival rate to discharge of only 91.2%. The incidence of insertion of a permanent pacemaker due to heart block was only 0.5%.^[9]