Baby with stethoscope on back
12 August 2015

What Is Tetralogy of Fallot?

In their recently-filed lawsuit, a family from Illinois claims their son was born with a rare combination of congenital heart defects, collectively known as tetralogy of Fallot, after being exposed to the anti-nausea drug Zofran during early fetal development.

While this is the first Zofran claim to be filed in relation to tetralogy of Fallot, the majority of lawsuits name heart defects allegedly caused by Zofran.

Tetralogy Of Fallot: Symptoms, Complications & Treatment

Tetralogy of Fallot (ToF) is characterized by a combination of four congenital heart defects that occur together:

1. Ventricular Septal Defect – a hole between the heart’s right and left ventricles.

Ventricles, the heart’s lower chambers, receive blood from the organ’s upper chambers, the atria, and pump it out, either toward the lungs for oxygen or toward the rest of the body to nourish cells and body tissues.

But with an incomplete barrier separating the ventricles imperfectly, oxygen-rich blood is allowed to mix with deoxygenated, or oxygen-poor, blood. When this mixture of blood is pumped out toward the body, it only contains a portion of the oxygen necessary to sustain physical function.

2. Overriding Aorta – a large artery is connected to two heart chambers, rather than one

In healthy human hearts, the aorta is the body’s primary artery, transporting oxygenated blood from the left ventricle up and out toward the lower and upper body.

In children with tetralogy of Fallot, the aorta is positioned directly over their ventricular septal defect, “straddling” both left and right ventricles. In this position, the artery can easily transport both oxygenated and deoxygenated blood together, decreasing the total amount of oxygen delivered to body tissues.

3. Pulmonary Stenosis – a valve controlling blood flow to the lungs is thick and abnormally narrow

On the heart’s right side, the pulmonary valve opens and closes to allow blood flow from the right ventricle to the lungs, where blood cells will pick up oxygen before returning to the heart.

Babies born with ToF have abnormally thick pulmonary valves that can’t open easily. Some of the oxygen-poor blood that would normally pass through the pulmonary artery is directed away instead, and flows through the ventricular septal defect and directly out to the body.

Most children with tetralogy of Fallot also have some obstructions above and below the narrow pulmonary valve, impeding blood flow further.

4. Right Ventricular Hypertrophy

Since the body is receiving significantly less oxygen than it demands, the heart’s right ventricle is forced to pump at high pressure all the time, straining to force adequate amounts of blood to the lungs for oxygen.

This is a little like exercise; the right ventricle’s muscle walls grow stronger, thicker and, eventually, inflexible. But inflexible muscles make it even harder for the chamber to pump a sufficient volume of blood.

“Tetralogy” simply means something made up of four components.

Tetralogy of Fallot CDC Diagram

Symptoms Of Tetralogy Of Fallot

While symptoms vary depending on the severity of obstructions limiting oxygen supply, many babies present with cyanosis.

This bluish tint to the skin, fingernails and lips is caused by insufficient oxygen levels reaching body tissues close to the skin. Cyanosis gave tetralogy of Fallot its colloquial name: blue baby syndrome.

While tetralogy of Fallot is usually repaired during infancy, babies who have not yet undergone surgery can have “tet spells.” In response to strenuous activities like crying, babies will become extremely blue, have difficulty breathing or become fatigued and limp. Some babies faint during tet spells.

Since some babies with ToF tire easily, they may have trouble feeding and experience “failure to thrive,” in which they fail to meet their developmental goals.

Doctors may be able to identify a “heart murmur” in children born with ToF, a sound created by abnormal blood flow. But some babies with ToF won’t have heart murmurs, and some children with healthy hearts present the characteristic sound, too.

Clubbing,” in which the nails and tips of fingers appear round and enlarged, is associated with tetralogy of Fallot, although adequate studies have not yet confirmed the link.

Can Tetralogy Of Fallot Be Treated?

Yes.

Left untreated, tetralogy of Fallot places children and young adults at an increased risk for numerous life-threatening complications, including infective endocarditis, a bacterial infection that inflames the heart’s inner lining. In most cases, progressively worsening ventricular hypertrophy will lead to right-sided heart failure, impaired heart function, and eventually death.

Unrepaired, ToF carries a 75% survival rate after one year, 60% after four years, 30% after ten years and 5% after forty years. Thankfully, modern surgical methods can successfully repair tetralogy of Fallot in the vast majority of cases.

Until 1944, ToF was considered untreatable. But that year, a team at Johns Hopkins University successfully completed the first palliative (relieving a problem but not treating its underlying cause) procedure for Tetralogy of Fallot.

The surgery was pioneered by Vivien Thomas, a black lab assistant who, despite his undeniable brilliance, was forced to enter through the back door of Johns Hopkins’ School of Medicine. Thomas’ achievements would later be honored with an honorary doctorate. The 2004 HBO film Something The Lord Made dramatizes Thomas’ struggle against overt racism and rise to prominence as an educator of America’s most notable surgeons.

Open Heart Surgery

Today, curative procedures have taken precedence over Thomas’ palliative treatment. According to the University of California San Francisco, tetralogy of Fallot is universally treated with open heart, or “intracardiac,” surgery.

The timing of this procedure varies widely, although many infants are now operated on before the age of one. In most cases, the surgery has two related goals: widening or replacing the narrowed pulmonary valve and closing the ventricular septal defect with a patch. By fixing these primary defects, tetralogy of Fallot’s associated effects can be expected to subside.

Sometimes surgeons will decide that an infant isn’t ready for a full corrective procedure yet. In this case, a temporary procedure can be performed: by placing a “shunt” between the aorta and pulmonary artery, surgeons hope to increase total blood flow toward the lungs. When a child is ready for “intracardiac” surgery, the shunt can be removed.

After repair, children will require regular checkups with a pediatric cardiologist.

How Common Is Tetralogy Of Fallot?

According to Cleveland Clinic, around 1 out of every 2,000 babies are born with tetralogy of Fallot every year. The US Centers for Disease Control reports a slightly higher incidence: 1 out of every 2,518 US babies.

ToF is, however, the most common cyanotic congenital heart defect, the category of abnormalities which cause low blood oxygen levels.

More commonly, children will be born with one of tetralogy of Fallot’s component defects: ventricular septal defect.

Researchers from Portland’s Oregon Health & Science University concluded that 1 out of every 238 babies born in Atlanta between 1998 and 2005 had a ventricular septal defect. The CDC currently employs this number as our best estimate of VSD’s true incidence.

Statistics do not currently exist for the incidence of pulmonary stenosis or overriding aorta; only 14 states currently track congenital abnormalities in an adequate way, and lack of resources means they generally track only the most common types.

Tetralogy Of Fallot & Genetic Syndromes

More than 15% of children born with tetralogy of Fallot are found to have genetic syndromes, abnormalities of DNA that can cause additional birth defects and seem to increase the risk of developing ToF.

The National Association for Child Development reports that between 40% and 60% of all children born with Down syndrome have congenital heart defects; a small, but statistically significant, number are born with tetralogy of Fallot.

Children born with DiGeorge Syndrome, in which a portion of chromosome 22 is missing, are most often born with developmental delays, low blood calcium levels, impaired immune system function, a cleft palate and congenital heart defects, often tetralogy of Fallot.

What Causes Tetralogy Of Fallot?

For the 85% of children born with tetralogy of Fallot, but not diagnosed with a genetic syndrome, the specific causes of the condition will likely never be known.

Researchers do, however, believe that most congenital abnormalities are caused by genetic mutations, environmental factors (including teratogenic pharmaceutical drugs, ones that alter fetal development adversely) or a combination of both.

During embryonic development, tetralogy of Fallot has been traced to the formation of the aorticopulmonary septum, which develops from earlier structures around 37 days of gestation.

Note that this occurs between 5 and 6 weeks after the beginning of pregnancy, when most women begin to experience the symptoms of morning sickness. As a result, women are likely to be prescribed Zofran just when their unborn babies are at the highest risk for developing an abnormality of the aorticopulmonary septum.