TETROLOGY OF FALLOT

Tetralogy of Fallot (TOF) is a type of heart defect present at birth. Symptoms at birth may vary
from none to severe. Later there is typically episodes of bluish color to the skin When affected
babies cry or have a bowel movement, they may develop a "tet spell" where they turn very blue,
have difficulty breathing, become limp, and occasionally lose consciousness. Other symptoms
may include a heart murmur, finger clubbing and easy tiring upon breastfeeding.

HISTORY

Tetralogy of Fallot was initially described in 1671 by Niels Stensen. A further description was
published in 1888 by the French physician Étienne-Louis Arthur Fallot, after whom it is
named. In 1924, Maude Abbott coined the term "tetralogy of Fallot".
The first surgical repair was carried out in 1944 at Johns Hopkins.The procedure was conducted
by surgeon Alfred Blalock and cardiologist Helen B. Taussig, with Vivien Thomas also
providing substantial contributions and listed as an assistant.[3] This first surgery was depicted in
the film Something the Lord Made. It was actually Helen Taussig who convinced Alfred Blalock
that the shunt was going to work. 15-month-old Eileen Saxon was the first person to receive
a Blalock-Thomas-Taussig shunt. Furthermore, the Blalock-Thomas-Taussig procedure, initially
the only surgical treatment available for tetralogy of Fallot, was palliative but not curative. The
first total repair of tetralogy of Fallot was done by a team led by C. Walton Lillehei at
the University of Minnesota in 1954 on an 11-year-old boy. Total repair on infants has had
success from 1981, with research indicating that it has a comparatively low mortality rate. Today
the adult TOF population continues to grow and is one of the most common congenital heart
defect seen in adult outpatient clinics
ANATOMY OF HEART
The normal heart has four chambers. The two upper chambers known as atria are separated from
each other by a fibrous partition known as the atrial septum. The two lower chambers are known
as ventricles and are separated from each other by the ventricular septum. Valves connect the
atria (left and right) to their respective ventricles. The valves allow for blood to be pumped
through the chambers. Blood travels from the right ventricle through the pulmonary artery to the
lungs where it receives oxygen. The blood returns to the heart through pulmonary veins and
enters the left ventricle. The left ventricle sends the now oxygen-filled blood into the main artery
of the body (aorta). The aorta sends the blood throughout the body.

Epidemiology
Tetralogy of Fallot is the most common cyanotic heart condition in children who have survived
untreated beyond the neonatal age, with the need for an intervention in the first year of life. It
accounts for 7% to 10% of congenital defects, affecting males and females equally and occurring
in 3 to 5 of every 10,000 live births.
ETIOLOGY
Its cause is thought to be due to environmental or genetic factors or a combination. It is
associated with chromosome 22 deletions and DiGeorge syndrome.[22]
Specific genetic associations include: JAG1,[23] NKX2-
5,[24] ZFPM2,[25] VEGF,[26] NOTCH1, TBX1, and FLT4.[27]
Embryology studies show that it is a result of anterior malalignment of the aorticopulmonary
septum, resulting in the clinical combination of a VSD, pulmonary stenosis, and an overriding
aorta.[18] Right ventricular hypertrophy develops progressively from resistance to blood flow
through the right ventricular outflow tract.

RISK FACTORS
Risk factors include a mother who uses alcohol, has diabetes, is over the age of 40, or
gets rubella during pregnancy.[5][10] It may also be associated with Down syndrome.
Four malformations
"Tetralogy" denotes four parts, here implying the syndrome's four anatomic defects.[2] This is not
to be confused with the similarly named teratology, a field of medicine concerned with abnormal
development and congenital malformations (including tetralogy of Fallot). Below are the
four heart malformations that present together in tetralogy of Fallot:

Heart with tetralogy of fallot A: Pulmonary stenosis; B: Overriding aorta; C: Ventricular septal
defect (VSD); D: Right ventricular hypertrophy
Ventricular Septal Defect
The heart has an inner wall that separates the two chambers, called a septum. The septum stops
mixing of the blood between the two sides. A ventricular septal defect is a hole in the septum
that causes oxygen-rich blood (left ventricle) and the oxygen-poor blood (right ventricle) to mix.
Pulmonary Stenosis
This defect is the narrowing of the pulmonary valve, which flows oxygen poor blood into the
pulmonary artery and from there the blood travels to the lungs to pick up oxygen. Pulmonary
stenosis is when the pulmonary valve cannot open fully, making the heart work harder and
results in a lack of blood reaching the lung.
Right Ventricular Hypertrophy
The muscle of the right ventricle is thicker due to the right side of the heart receiving excessive
blood flow from the left side of the heart through the ventricular septal defect and working
harder.
Overriding Aorta
In a normal heart, the aorta is attached to the left ventricle and allows oxygen-rich blood to flow
throughout the body. In a tetralogy of Fallot heart, the aorta is located between both the left and
the right ventricle. This causes oxygen-poor blood from the right ventricle to flow into the aorta
instead of the pulmonary artery. If infants with tetralogy of Fallot are not treated, the symptoms
usually become progressively more severe. Blood flow to the lungs may be further decreased and
severe cyanosis may cause life-threatening complications. The exact cause of tetralogy of Fallot
is not known.

Additional anomalies[edit]
In addition, tetralogy of Fallot may present with other anatomical anomalies, including:[34][35]
 1. stenosis of the left pulmonary artery, in 40%
2. a bicuspid pulmonary valve, in 60%
3. right-sided aortic arch, in 25%
4. coronary artery anomalies, in 10%
5. a patent foramen ovale or atrial septal defect, in which case the syndrome is sometimes
called a pentalogy of Fallot[36]
6. an atrioventricular septal defect
7. partially or totally anomalous pulmonary venous return
Tetralogy of Fallot with pulmonary atresia (pseudotruncus arteriosus) is a severe variant[37] in
which there is complete obstruction (atresia) of the right ventricular outflow tract, causing an
absence of the pulmonary trunk during embryonic development.[38] In these individuals, blood
shunts completely from the right ventricle to the left where it is pumped only through the aorta.
The lungs are perfused via extensive collaterals from the systemic arteries, and sometimes also
via the ductus arteriosus.

Pathophysiology
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 with
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
DIAGNOSIS
Congenital heart defects are now diagnosed with echocardiography, which is quick, involves no
radiation, is very specific, and can be done prenatally.
Echocardiography establishes the presence of TOF by demonstrating a VSD, RVH, and aortic
override. Many patients are diagnosed prenatally. Color Doppler (type of echocardiography)
measures the degree of pulmonary stenosis. Additionally, close monitoring of the ductus
arteriosus is done in the neonatal period to ensure that there is adequate blood flow through the
pulmonary valve.[40] [41]
In certain cases, coronary artery anatomy cannot be clearly viewed using echocardiogram. In this
case, cardiac catheterization can be done.[42]
Form a genetics perspective, it is important to screen for DiGeorge in all babies with TOF.[42]
Before more sophisticated techniques became available, chest x-ray was the definitive method of
diagnosis. The abnormal "coeur-en-sabot" (boot-like) appearance of a heart with tetralogy of
Fallot is classically visible via chest x-ray, although most infants with tetralogy may not show
this finding.[43] The boot like shape is due to the right ventricular hypertrophy present in TOF.
Lung fields are often dark (absence of interstitial lung markings) due to decreased pulmonary
blood flow.[41]
Electrocardiography shows right ventricular hypertrophy (RVH), along with right axis
deviation.[40] RVH is noted on EKG as tall R-waves in lead V1 and deep S-waves in lead V5-V6
The diagnosis of tetralogy of Fallot is confirmed by clinical evaluation and physical
examination. A variety of specialized tests including electrocardiogram, echocardiogram,
and cardiac catheterization may be performed to aid in diagnosis and therapy. When
tetralogy of Fallot is present, x-ray studies usually reveal a normal-sized heart that is
characteristically boot-shaped (coeur en sabot). Periodic measurements of systemic blood
oxygen saturation and hemoglobin are also advisable. Infants with this disorder usually
have a relatively loud murmur over the upper left breastbone.
CLINICAL MANIFESTATIONS

Signs & Symptoms

The symptoms of tetralogy of Fallot vary widely from person to person. The severity of the
symptoms, which may range from mild to severe, is related to the degree of blood flow
obstruction from the right ventricle.
Tetralogy of Fallot may be present at birth or emerge within the first year of life. The most
common symptom of this disorder is abnormal bluish discoloration of the skin (cyanosis). This
may occur while the child is at rest or crying. The mucous membranes of the lips and mouth,
fingertips, and toenails may be particularly blue due to the lack of oxygen. Affected infants may
have difficulty breathing (dyspnea); as a result, they tend to play for short periods and then rest.
Other symptoms may include a heart murmur, easy fatigability, poor appetite, slow weight gain,
heart murmurs, an abnormal increase in the numbers of red blood cells (polycythemia), fingers
and toes with wide, enlarged tips and overhanging nails (clubbing), and/or delayed physical
growth.
Some infants with tetralogy of Fallot may experience episodes of severe cyanosis and breathing
difficulty (paroxysmal hypercyanotic attack or “blue” or “tet” spells). During these episodes, the
infant may become restless, extremely cyanotic while gasping for air and nonresponsive to
parent’s voices. In extreme situations, infants may pass out. A characteristic squatting position
may be assumed to help assist breathing. Severe attacks may lead to the loss consciousness, and
occasionally to convulsions or temporary paralysis on one side of the body (hemiparesis). These
spells may last for a few minutes to a few hours and may be followed by periods of muscle
weakness and a prolonged period of sleep.

Tetralogy of Fallot results in low oxygenation of blood. This is due to:[15]

 Mixing of oxygenated and deoxygenated blood in the left ventricle via the ventricular septal
defect (VSD)
 Preferential flow of the mixed blood from both ventricles through the aorta because of the
obstruction to flow through the pulmonary valve. This is known as a right-to-left shunt.
Infants with TOF -a cyanotic heart disease- have low blood oxygen saturation.[16] Blood
oxygenation varies greatly from one patient to another depending on the severity of the anatomic
defects.[9] Typical ranges vary from 60% to around 90%.[16] Depending on the degree of
obstruction, symptoms vary from no cyanosis or mild cyanosis to profound cyanosis at birth.[9] If
the baby is not cyanotic then it is sometimes referred to as a "pink tet".[17] Other symptoms
include a heart murmur which may range from almost imperceptible to very loud, difficulty in
feeding, failure to gain weight, retarded growth and physical development, labored breathing
(dyspnea) on exertion, clubbing of the fingers and toes, and polycythemia.[2] The baby may turn
blue with breast feeding or crying.[2]
Tet spells
Infants and children with unrepaired tetralogy of Fallot may develop "tet spells".[15] These are
acute hypoxia spells, characterized by shortness of breath, cyanosis, agitation, and loss of
consciousness.[18] This may be initiated by any event -such as anxiety, pain, dehydration, or
fever-[19] leading to decreased oxygen saturation or that causes decreased systemic vascular
resistance, which in turn leads to increased shunting through the ventricular septal defect.[15]
Clinically, tet spells are characterized by a sudden, marked increase in cyanosis followed
by syncope.[18]
Older children will often squat instinctively during a tet spell.[15] This increases systemic
vascular resistance and allows for a temporary reversal of the shunt. It increases pressure on the
left side of the heart, decreasing the right to left shunt thus decreasing the amount of
deoxygenated blood entering the systemic circulation

MANAGEMENT

Standard Therapies

Treatment
The definitive treatment for tetralogy of Fallot is surgery (i.e., Blalock-Taussig shunting
procedure, aortic/pulmonary shunt, intracardiac repair, balloon pulmonary valvuloplasty and/or
valve replacement). Surgical correction of this heart malformation is best accomplished during
infancy. Selection of the exact surgical procedure is based on the severity of symptoms and
extent of the malformation.
The surgeon will widen the pulmonary valve and the passage from the right ventricle to the
pulmonary artery is enlarged. A patch covers the hole in the septum to repair the ventricular
septal defect. By resolving the VSD and the pulmonary valve problems, it fixes the other two
defects.
Temporary surgery may be recommended babies are too weak or small to have the full repair
surgery; the full repair surgery will be performed when the baby is stronger. A tube or a “shunt”
is placed between a large artery branching off the aorta and the pulmonary artery. It creates a
pathway for blood to travel to the lungs to get oxygen. The tube is removed during the full repair
surgery.
When early repair is not possible, other surgical measures may be taken during infancy or early
childhood.
Prior to surgery, treatment to control symptoms (palliative) may include the maintenance of
adequate fluid intake (hydration), monitoring of hemoglobin levels in the blood, and the
avoidance of strenuous exercise. Heart medications (i.e., digitalis) may be prescribed to help
control irregular heartbeats (arrhythmias), rapid heartbeats, and/or heart failure.
Episodes of severe symptoms or “blue spells” (hypoxia) may require the administration of
supplemental oxygen, morphine, and/or other drugs that improve oxygen concentration. The
knee-chest position may also bring some symptomatic relief. Sodium bicarbonate may be
administered to lower abnormally high levels of acid in the blood (acidosis). The drug
propranolol may be given to help prevent future spells and to reduce their severity. Drugs that
help to remove excess fluid from the body (diuretics), dietary salt restriction, and bed rest may be
effective in treating congestive heart failure.
Antibiotics may be prescribed to infants with tetralogy of Fallot to help prevent infections
(prophylaxis) because children with this disorder are susceptible to bacterial infection of the
heart (endocarditis). Respiratory infections must be treated vigorously and early. Children should
be given antibiotics at times of predictable risk (e.g., tooth extractions and surgery). Other
treatment is symptomatic and supportive.
Although the risk for tetralogy of Fallot in the siblings of infants with this disorder is thought to
be very low, genetic counseling may be of benefit for parents and other family members.
MEDICL MANAGEMENT

Tet spells
Tet spells may be treated with beta-blockers such as propranolol, but acute episodes require rapid
intervention with morphine or intranasal fentanyl[45] to reduce ventilatory drive, a vasopressor
such as phenylephrine, or norepinephrine to increase systemic vascular resistance, and IV fluids
for volume expansion.[46]
Oxygen (100%) may be effective in treating spells because it is a potent pulmonary vasodilator
and systemic vasoconstrictor. This allows more blood flow to the lungs by decreasing shunting
of deoxygenated blood from the right to left ventricle through the VSD. There are also simple
procedures such as squatting and the knee chest position which increase systemic vascular
resistance and decrease right-to-left shunting of deoxygenated blood into the systemic
circulation.[46][47]
If the spells are refractory to the above treatments, people are usually intubated and sedated. The
treatment of last resort for tet spells is extracorporeal membrane oxygenation (ECMO) along
with consideration of Blalock Taussig shunt (BT shunt).[46]
SURGICAL MANAGEMENT
Total surgical repair[edit]
Total surgical repair of TOF is a curative surgery. Different techniques can be used in
performing TOF repair. However, a transatrial, transpulmonary artery approach is used for most
cases.[48] The repair consists of two main steps: closure of the VSD with a patch and
reconstruction of the right ventricular outflow tract.[49]
This open-heart surgery is designed to relieve the right ventricular outflow tract stenosis by
careful resection of muscle and to repair the VSD.[50] Additional reparative or reconstructive
surgery may be done on patients as required by their particular cardiac anatomy.[51][52]
Timing of surgery in asymptomatic patients is usually between the ages of 2 months to one
year.[53] However, in symptomatic patients showing worsening blood oxygen levels, severe tet-
spells (cyanotic spells), or dependence on prostaglandins from early neonatal period (to keep the
ductus arteriosus open) need to be planned fairly urgently.[53]
Potential surgical repair complications include residual ventricular septal defect, residual residual
outflow tract obstruction, complete atrioventricular block, arrhythmias, aneurysm of right
ventricular outflow patch, and pulmonary valve insufficiency.[54] Long term complications most
commonly include pulmonary valve regurgitation, and arrhythmias.[55]
Total repair of tetralogy of Fallot initially carried a high mortality risk, but this risk has gone
down steadily over the years. Surgery is now often carried out in infants one year of age or
younger with less than 5% perioperative mortality[56]. Post surgery, most patients enjoy an active
life free of symptoms.[56] Currently, long term survival is close to 90%.[57] Today the adult TOF
population continues to grow and is one of the most common congenital heart defect seen in
adult outpatient clinics.[58]
Palliative surgery[edit]
Initially surgery involved forming a side to end anastomosis between the subclavian artery and
the pulmonary artery -i.e a systemic to pulmonary arterial shunt.[49] This redirected a large
portion of the partially oxygenated blood leaving the heart for the body into the lungs, increasing
flow through the pulmonary circuit, and relieving symptoms. The first Blalock-Thomas-Taussig
shunt surgery was performed on 15-month-old Eileen Saxon on November 29, 1944 with
dramatic results.[59]
The Potts shunt[60] and the Waterston-Cooley shunt[61][62] are other shunt procedures which were
developed for the same purpose. These are no longer used.
Currently, palliative surgery is not normally performed on infants with TOF except for extreme
cases.[63] For example, in symptomatic infants, a two-stage repair (initial systemic to arterial
shunt placement followed by total surgical repair) may be done.[64] Potential complications
include inadequate pulmonary blood flow, pulmonary artery distortion, inadequate growth of the
pulmonary arteries, and acquired pulmonary atresia.
NURSING MANAGEMENT
Specific considerations and routine care  Preoperative considerations o Neonates with tetralogy of
Fallot  Management based on the degree of outflow tract obstruction  Mild to moderate outflow
tract obstruction 10 o Anticipate discharge until surgery scheduled between 4-6 months o Discharge
teaching for parents/caregivers - specific information for hypercyanotic (“Tet”) spells

Complications
Short Term Complications
Common complications in the immediate postoperative period are residual ventricular septal
defects, as well as persistence of right ventricular outflow obstruction. Arrhythmias can follow
tetralogy repair, with risk of ventricular tachycardia, atrial fibrillation/flutter, and intra-atrial
reentrant tachycardia. ECG will usually appear with a right bundle branch block or left bundle
branch block pattern associated with wide complex tachycardia. Sudden cardiac death can
present with post-repaired patients. Risk factors for tachyarrhythmias and sudden cardiac death
include older age at repair, male gender, transient complete heart block beyond postoperative day
three, and QRS duration greater than 180 miliseconds.
Long-Term Complications
Adult patients with congenital heart disease are increasing in an approximate estimate of 5% per
year, surpassing the pediatric population. Longterm consequences seen with these patients
include right ventricular volume overload from pulmonary insufficiency, right ventricular
aneurysm from outflow patch or from ventriculotomy, distal pulmonary artery obstruction,
ventricular hypertrophy, chamber enlargement, biventricular dysfunction, and aortic root dilation
and insufficiency. The three leading causes of mortality in patients with repaired tetralogy of
Fallot are arrhythmia, heart failure, and complications from reoperations. Risk of sudden death
increases after 30 years of procedure to 6% to 9%; some of the factors associated with this risk
are QRS duration greater than 180 miliseconds, older age at repair (greater than 3 years),
significant pulmonary valve or tricuspid valve regurgitation, history of syncope, multifocal
premature ventricular contractions, and ventricular tachycardia. The most common indication for
reoperation is pulmonary insufficiency, and criteria for pulmonary valve replacement have been
based on the severity measured by the regurgitant fraction on magnetic resonance or CT scan.
Parameters seen with these studies are right and left ventricular end-systolic and end-diastolic
volume indices, ejection fractions, and presence of aneurysm causing obstructive outflow.
Patient can have exercise intolerance, signs and symptoms of heart failure, syncope, and
sustained ventricular tachycardia. Pulmonary valve replacement also can be obtained by
transcatheter pulmonary valve approach.
Pregnancy Complications
Women who had complete repair of tetralogy of Fallot have similar outcomes in comparison
with the general obstetric population. Increased pregnancy complication are related to the level
of pulmonary hypertension and the severity of the pulmonary regurgitation with right or left
ventricular dysfunction. Females with moderate right ventricle hypertension or those who have
had a palliative shunt have an increased risk for fetal demise. Offspring of women with tetralogy
carry a risk of congenital heart disease in 3% to 5% in comparison with 0.8% of the general
population. If 22q11 deletion is present, the chance of transmitting the affected chromosome is
50%, with high risk of having an associated congenital heart defect.

Prognosis[edit]
Untreated, tetralogy of Fallot rapidly results in progressive right ventricular hypertrophy due to
the increased resistance caused by narrowing of the pulmonary trunk.[33] This progresses to heart
failure which begins in the right ventricle and often leads to left heart failure and dilated
cardiomyopathy. Mortality rate depends on the severity of the tetralogy of Fallot. If left
untreated, TOF carries a 35% mortality rate in the first year of life, and a 50% mortality rate in
the first three years of life.[66] Patients with untreated TOF rarely progress to adulthood.[55]
Patients who have undergone total surgical repair of tetralogy of Fallot have improved
hemodynamics and often have good to excellent cardiac function after the operation with some
to no exercise intolerance (New York Heart Association Class I-II).[67] Long-term outcome is
usually excellent for most patients, however residual post surgical defects -such as pulmonary
regurgitation, pulmonary artery stenosis, residual VSD, right ventricular dysfunction, right
ventricular outflow tract obstruction, and sudden death- may affect life expectancy and increase
the need for reoperation.[56]
Within 30 years after correction, 50% of patients will require reoperation.[55] The most common
cause of reoperation is a leaky pulmonary valve (pulmonary valve insufficiency).[55] This is
usually corrected with a procedure called pulmonary valve replacement.

Summary
Tetralogy of Fallot is the most common form of cyanotic congenital heart disease. Cyanosis is
the abnormal bluish discoloration of the skin that occurs because of low levels of circulating
oxygen in the blood. Tetralogy of Fallot consists of the combination of four different heart
defects: a ventricular septal defect (VSD); obstructed outflow of blood from the right ventricle to
the lungs (pulmonary stenosis); a displaced aorta, which causes blood to flow into the aorta from
both the right and left ventricles (dextroposition or overriding aorta); and abnormal enlargement
of the right ventricle (right ventricular hypertrophy). The severity of the symptoms is related to
the degree of blood flow obstruction from the right ventricle.