Tetralogy of Fallot – Overview, Risk Factors and Treatment

Definition

Tetralogy of Fallot is a combination of four heart defects that can result in a baby turning blue or cyanotic because of a lack of oxygen in the blood. It usually is diagnosed in infancy.

The heart consists of four chambers: the two upper chambers, called atria, where blood enters the heart; and the two lower chambers, called ventricles, where blood is pumped out of the heart. Valves that act as one-way doors control the flow between the chambers and between the arteries. The heart also has been pictured as two side-by-side pumps with one side pumping blood into the lungs and the other side pumping blood from the lungs back to the body.

Blood is pumped from the right side of the heart up through the pulmonary valve and the pulmonary artery to the lungs, where the blood is filled with oxygen. From the lungs, the blood travels back down to the left atrium and left ventricle and is then pumped through another big blood vessel called the aorta to the rest of the body.

Tetralogy of Fallot is a combination of four different heart problems that include:

Pulmonary stenosis: A condition where the pulmonary artery (that carries blue blood from the right ventricle to the lungs to be oxygenated) is blocked. Either the muscle below or above the valve, or the valve itself, may be too narrow or underdeveloped, impeding blood flow.

Ventricular septal defect (VSD): A hole between the ventricles, the heart’s two lower pumping chambers.

Overriding aorta: The aorta (the largest blood vessel in the heart, which carries pink blood to the body) is not positioned correctly and straddles both the right and left ventricles just above the VSD.

Right ventricular (RV) hypertrophy: The right ventricle is the lower heart chamber of the heart that pumps blue blood to the pulmonary arteries. Hypertrophy is when the chamber’s muscle wall becomes thickened, where it is normally thin. This occurs in TOF because of the extra effort the muscle exert with TOF anatomy.

Epidemiology

TOF is the most common form of cyanotic congenital heart disease. It comprises approximately 3.5% of infants born with congenital heart disease and 8-10% of cyanotic cases. Worldwide reported prevalence of TOF is 0.28 per 1,000 live births. There is no gender predilection.

Pathophysiology of Tetralogy of Fallot

The development of the human heart starts around the 20th day of gestation, with the fusion of the outer endocardial tubes into a single tubular structure, the cardiac tube. Subsequently, the cardiac tube folds and loops, with the development of an atrium that is cranial and dorsal, and a primitive ventricle is moving downward, ventrally, and to the right. The right ventricle is the dominant chamber in the embryo and fetus, receiving 65% of the venous return, and is the main contributor to the lower part of the body, the placenta, and the lungs. The right ventricle can be described by three components: the inlet, which consists of the tricuspid valve chordae tendineae and papillary muscles; the trabeculated apical myocardium; and the infundibulum or conus. The exact embryologic process that contributes to the development of tetralogy of Fallot still is unknown, but an association that had been observed is an anterior and cephalad deviation of the infundibular septum that results in a misaligned ventricular septal defect, with an overriding aortic root causing a subsequent right ventricular outflow obstruction.

The ventricular septal defects seen in patients with tetralogy of Fallot are usually perimembranous that can extend into the muscular septum. Different factors can contribute to the right ventricular outflow obstruction, including the pulmonary valve that is usually bicuspid and stenotic, the hypoplastic pulmonary valve annulus, the deviation of the infundibular septum that causes a subvalvular obstruction, and the hypertrophy of the muscular bands in this region. The degree of the overriding aorta usually varies and receives blood flow from both ventricles. The physiological process surrounding the hypercyanotic episodes or “Tet spells” in tetralogy of Fallot consist of either a decrease in systemic vascular resistance or an increase in pulmonary resistance contributing to a right-to-left shunt across the ventricular septal defect, causing marked desaturation

Tetralogy of Fallot Risk factors

While the exact cause of tetralogy of Fallot is unknown, some things might increase the risk of a baby being born with this condition. Risk factors for tetralogy of Fallot include:

• A viral illness during pregnancy, such as rubella (German measles)
• Drinking alcohol during pregnancy
• Poor nutrition during pregnancy
• A mother older than age 40
• A parent who has tetralogy of Fallot
• The presence of Down syndrome or DiGeorge syndrome in the baby

Causes of Tetralogy of Fallot

Doctors don’t know what causes most cases of tetralogy of Fallot and other congenital heart defects.

Certain conditions or factors that occur during pregnancy may raise your risk for having a child with tetralogy of Fallot. These conditions and factors include:

• German measles (rubella) and some other viral illnesses
• Poor nutrition
• Overuse of alcohol
• Age (being older than 40)
• Diabetes

Heredity may play a role in causing tetralogy of Fallot. An adult who has tetralogy of Fallot may have an increased chance of having a baby with the condition.

Children who have certain genetic disorders, such as Down syndrome and DiGeorge syndrome, often have congenital heart defects, including tetralogy of Fallot.

Scientists continue to search for the causes of tetralogy of Fallot and other congenital heart defects.

Tetralogy of Fallot Symptoms

Cyanosis is a very common sign. Healthy babies can sometimes also have bluish skin around the mouth or eyes from prominent veins under the skin, but their lips and tongue look pink. Babies who have low oxygen levels in the blood usually have blue lips and tongues in addition to bluish skin.

A child with TOF might have sudden episodes of deep cyanosis, called “hypercyanotic spells” or “Tet spells,” during crying or feeding. Older children who have Tet spells will often instinctively squat down, which helps to stop the spell.

Other signs include:

• Heart murmur
• Fussiness
• Tiring easily
• Difficulty breathing
• Rapid heartbeat (palpitations)
• Fainting
• “Clubbing,” where the skin or bones around the tips of fingers are widened or rounded

Complications

If left untreated, it can cause these problems:

• Blood clots (which may be in the brain causing stroke)
• Infection in the lining of the heart and heart valves (bacterial endocarditis)
• Abnormal heart rhythms (arrhythmias)
• Heart failure
• Death

Diagnosis and test

Your child’s doctor may have heard a heart murmur during a physical examination and referred your child to a pediatric cardiologist for a diagnosis. In this case, the heart murmur is caused by the turbulence of blood flowing through the obstruction from the right ventricle to the pulmonary artery. Symptoms your child exhibits will also help with the diagnosis.

A pediatric cardiologist specializes in the diagnosis and medical management of congenital heart defects, as well as heart problems that may develop later in childhood. The cardiologist will perform a physical examination, listening to the heart and lungs and make other observations that help in the diagnosis. The location within the chest that the murmur is heard best, as well as the loudness and quality of the murmur (such as harsh or blowing) will give the cardiologist an initial idea of which heart problem your child may have. Diagnostic testing for congenital heart disease varies by the child’s age, clinical condition and institutional preferences. Some tests that may be recommended include the following:

Chest X-ray: A diagnostic test that uses X-ray beams to produce images of internal tissues, bones and organs onto film.

Electrocardiogram (ECG or EKG): A test that records the electrical activity of the heart, shows abnormal rhythms (arrhythmias or dysrhythmias), and detects heart muscle stress.

Echocardiogram (echo): A procedure that evaluates the structure and function of the heart by using sound waves recorded on an electronic sensor that produce a moving picture of the heart and heart valves.

Cardiac catheterization: A cardiac catheterization is an invasive procedure that gives very detailed information about the structures inside the heart. Under sedation, a small, thin, flexible tube (catheter) is inserted into a blood vessel in the groin and guided to the inside of the heart. Blood pressure and oxygen measurements are taken in the four chambers of the heart, as well as the pulmonary artery and aorta. Contrast dye is also injected to more clearly visualize the structures inside the heart.

Tetralogy of Fallot treatment and medications

Medical treatment

Squatting: Parents may observe the infants squatting or keeping their knees to their chest – this manoeuvre helps increase venous return, therefore increasing systemic resistance. Parents should be advised to put the child in this position whilst awaiting medical review.

Prostaglandin (PG) infusion: This helps maintain PDA in the more severe-extreme forms of TOF and must be started urgently following delivery to avoid the neonate collapsing. Depending on local practice, either PGE1 (alprostadil) or PGE2 (dinoprostone) may be used. Side effects to note include apnoeas, bradycardia and hypotension.

Beta-blockers: propranolol is commonly used in both “tet” spells and prophylaxis in moderate-severe disease. It works by reducing the heart rate thus venous return.

Morphine: Reduces respiratory drive therefore also reduces hyperpnoea

Saline 0.9% bolus can be used in “tet” spells as a volume expander to increase pulmonary blood flow through the RVOTO.

Surgical treatment

Palliative

Transcatheter RVOT stent insertion: this is sometimes done in the neonatal period for infants with severe-extreme TOF to relieve RVOTO. This is done to buy time until the child is bigger whilst providing a patent passage for pulmonary blood flow.

Modified Blalock-Taussig (BT) shunt: This procedure aims to mimic a PDA and increase pulmonary blood flow before definitive repair. It can be done either by anastomosis of the subclavian artery to the pulmonary artery or by creating an artificial shunt using synthetic material (usually GoreTex). The latter is called a modified BT shunt.

Other alternatives include insertion of an RV to PA conduit (to bypass the RVOTO) and PA banding (to reduce pulmonary overloading, especially in pink TOF with mild PS).

Definitive repair:

• Performed under cardiopulmonary bypass via median sternotomy, this involves RVOT stenosis resection, RVOT/pulmonary artery augmentation and VSD patch closure. Depending on the degree of PS, PV is either repaired or spared.
• Timing depends on severity of symptoms but usually not performed younger than 3 months old or older than 4 years.
• Post-operative care: immediately following surgery, the child will require stabilisation in Cardiac Intensive Care Unit (CICU). Once they are well enough they will be stepped down to the cardiology ward prior to discharge.

Prevention

No known prevention exists for Tetralogy of Fallot.