Tetralogy of Fallot: Diagnosis and Management

Abstract

Tetralogy of Fallot is a complex heart defect characterized by the presence of a multilevel right ventricular outflow pathway, resulting in right ventricular hypertrophy and misalignment of the ventricular septal defect with aortic overlap. The pulmonary valve is usually small and dysplastic, as is the pulmonary artery. In Tetralogy of Fallot with pulmonary atresia, it represents the most advanced form of Tetralogy of Fallot, the pulmonary stress valve. Tetralogy of Fallot with the absence of a pulmonary valve is a rare form of the disease, in which only inactive remains of the pulmonary valve are present. A hallmark of this condition is the rapid expansion of the pulmonary artery and its branches, causing compression of the airways. The aim of this review is to explain the nature of the disease and to show the available methods of treatment. Patients with Fallot tetralogy live for more than 15-20 years after their initial surgery. The biggest problem they face is the recurrence of valvular disease.

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*Corresponding author: Email: omarelsaka0808@gmail.com;
Asian Journal of Research in Medicine and Medical Science
4(1): 18-31, 2022; Article no.AJRMMS.829
Tetralogy of Fallot: Diagnosis and Management
Omar Elsaka a*, Moneer Ayman Noureldean a, Mohamed Adel Gamil a,
Mostafa Tarek Ghazali a, Ashraf Hamada Abd Al-Razik a and Dalia Hisham a
a Department of Cardiology, Mansoura University, Faculty of Medicine, Mansoura Manchester Medical
Program (MMMP), Mansoura, Egypt.
Authors’ contributions
This work was carried out in collaboration among all authors. All authors read and approved the final
manuscript.
Received 08 November 2021
Accepted 16 January 2022
Published 21 January 2022
ABSTRACT
Tetralogy of Fallot is a complex heart defect characterized by the presence of a multilevel right
ventricular outflow pathway, resulting in right ventricular hypertrophy and misalignment of the
ventricular septal defect with aortic overlap. The pulmonary valve is usually small and dysplastic, as
is the pulmonary artery. In Tetralogy of Fallot with pulmonary atresia, it represents the most
advanced form of Tetralogy of Fallot, the pulmonary stress valve. Tetralogy of Fallot with the
absence of a pulmonary valve is a rare form of the disease, in which only inactive remains of the
pulmonary valve are present. A hallmark of this condition is the rapid expansion of the pulmonary
artery and its branches, causing compression of the airways. The aim of this review is to explain the
nature of the disease and to show the available methods of treatment. Patients with Fallot tetralogy
live for more than 15-20 years after their initial surgery. The biggest problem they face is the
recurrence of valvular disease.
Keywords: Aortic override; cardiac surgery; coronary arteries; tetralogy of fallot.
1. INTRODUCTION
One of the most prevalent congenital cardiac
abnormalities in the tetralogy of Fallot (TOF),
which includes right ventricular (RV) outflow tract
restriction (infundibular stenosis), ventricular
septal defect (VSD), overriding aorta, and RV
hypertrophy. Untreated patients have a 50%
mortality rate by the age of six, but in the modern
era of cardiac surgery, children with basic forms
of tetralogy of Fallot have a decent long-term
survival rate and a high quality of life. It's crucial
to note, however, that corrective surgery for
tetralogy of Fallot performed as a youngster is
not the same as curative surgery. As a result,
many children who have had their tetralogy of
Fallot corrected live to maturity and are seen in
cardiology clinics. Some people who never had
surgery for mild tetralogy as children may
present as adults with a variety of symptoms,
while others who just had a palliative operation
(such as shunt insertion) may also present as
adults with a variety of symptoms [1].
Review Article

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2. ETIOLOGY AND RISK FACTORS
Tetralogy of Fallot happens during the
development of the baby's heart during
pregnancy. In most cases, the cause is unknown.
Fallot tetralogy is made up of four defects:
Pulmonary valve stenosis (narrowing of the lung
valve): Blood flow to the lungs is reduced when
the valve that divides the lower right chamber of
the heart (right ventricle) from the primary blood
vessel leading to the lungs (pulmonary artery)
narrows. The muscle underlying the pulmonary
valve may also be affected by the constriction.
The pulmonary valve does not always form
properly (pulmonary atresia). A hole in the wall
(septum) that separates the two lower chambers
of the heart (ventricular septal defect): A hole in
the wall (septum) that separates the two lower
chambers of the heart (ventricular septal defect)
(left and right ventricles). The hole causes
oxygen-poor right ventricle blood to mix with
oxygen-rich left ventricle blood. This results in
inefficient blood flow and a reduction in oxygen-
rich blood supply to the organism. The defect
eventually can weaken the heart [2].
The body's major artery (aorta) shifts: The aorta
normally branches off the left ventricle. The aorta
is in the improper place in the tetralogy of Fallot.
It's relocated to the right and sits just above the
heart's hole (ventricular septal defect). As a
result, both the right and left ventricles send
blood to the aorta, which is a mixture of oxygen-
rich and oxygen-poor. Right ventricular
hypertrophy (thickening of the right lower heart
chamber): When the heart's pumping function is
overworked, the muscular wall of the right
ventricle thickens. This could cause the heart to
harden, weaken, and eventually fail as a result of
this. Some children and adults with tetralogy of
Fallot may also have other heart defects, such as
an atrial septal defect (hole between the upper
chambers of the heart), a right aortic arch, or
coronary artery abnormalities [2].
While the specific etiology of tetralogy of Fallot is
unknown, there are some factors that may raise
the likelihood of a baby being born with the
disorder. A viral illness during pregnancy, such
as rubella (German measles), drinking alcohol
during pregnancy, poor nutrition during
pregnancy, a mother older than 40, a parent with
tetralogy of Fallot, and the presence of Down
syndrome or DiGeorge syndrome in the baby are
all risk factors for tetralogy of Fallot [2].
3. PATHOPHYSIOLOGY
Pathophysiology in children with tetralogy of
Fallot: Although genetic studies reveal a complex
etiology, the cause(s) of most congenital heart
disorders (CHDs) are unknown.
Methylenetetrahydrofolate reductase (MTHFR)
gene polymorphism may be a tetralogy of the
Fallot susceptibility gene (TOF). More recently, it
has been discovered that the VEGF genetic
polymorphisms -2578C>A and -634C>G may be
linked to an increased risk of tetralogy of Fallot,
although the 936C>T polymorphism may lessen
the risk. Maternal rubella (or other viral
infections) during pregnancy, poor prenatal
nutrition, maternal alcohol use, maternal age
greater than 40 years, maternal phenylketonuria
(PKU) birth abnormalities, and diabetes are all
prenatal variables linked to a higher prevalence
of tetralogy of Fallot. Tetralogy of Fallot is more
common in children with Down syndrome, as well
as infants with fetal hydantoin syndrome or fetal
carbamazepine syndrome [3].
Tetralogy of Fallot can also be linked to a
spectrum of lesions known as CATCH 22 since it
is one of the conotruncal abnormalities (cardiac
defects, abnormal facies, thymic hypoplasia, cleft
palate, hypocalcemia). Deletions of a stretch of
chromosomal band 22q11 may be discovered
through cytogenetic examination (DiGeorge
critical region). Conotruncal deformities have
been found to be reproduced by ablating neural
crest cells. The DiGeorge syndrome and
branchial arch anomalies are linked to these
defects. The degree of right ventricular (RV)
outflow tract obstruction affects the
hemodynamics of tetralogy of Fallot (RVOTO). In
most cases, the ventricular septal defect (VSD) is
nonrestrictive, and the pressures in the right and
left ventricles (RV and LV) are equalized. The
intracardiac shunt is from right to left if the
obstruction is substantial, and pulmonary blood
flow may be significantly reduced. The patent
ductus arteriosus (PDA) or bronchial collaterals
may be responsible for blood flow in this case
(Fig. 1) [3].

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Fig. 1. Pathophysiology of Tetralogy of Fallot [4]
Pathophysiology in adults with tetralogy of Fallot:
In the past, doctors frequently requested routine
echocardiograms in adult patients with tetralogy
of Fallot who were followed in the clinic after
surgery as a child. At the time, pulmonary valve
insufficiency was thought to be a relatively
benign and insignificant observable
phenomenon, similar to tricuspid regurgitation.
Because the majority of those infected were
asymptomatic, they were never treated.
However, as these individuals were observed
over time, it became clear that they were
developing serious RV dysfunction and
arrhythmias. The RV dilation caused by
pulmonary valve insufficiency is linked to fibrosis
and significant myocardial damage, which leads
to a reduction in exercise endurance and, in the
majority of cases, ventricular arrhythmias. Most
individuals with chronic RV function are
asymptomatic at first, but when compensatory
mechanisms fail and the ejection fraction falls,
symptoms emerge. If the condition is not treated
at this stage, the RV dysfunction is irreversible.
The arrhythmias occur as a result of progressive
dilatation and stretching of the right atrium and
RV [5].
Arrhythmias: Clinically significant atrial
arrhythmias are mostly reentry arrhythmias, but
they can also include atrial tachycardia and atrial
fibrillation. Patients with corrected tetralogy of
Fallot experience these atrial arrhythmias in 10-
35 percent of cases. Ventricular arrhythmias and
sudden death have been reported in people who
have had their tetralogy of Fallot corrected.
Patients who die suddenly generally have
moderate to severe pulmonary valve
insufficiency at the time of death, according to
case studies. In patients with modest pulmonary
valve insufficiency, ventricular arrhythmias are
less prevalent. Overall, patients who survive
tetralogy of Fallot surgery have a far higher risk
of late sudden death than their age-matched
peers [6].
4. PRESENTATION
Feeding difficulties are prevalent in newborns
with tetralogy of Fallot, and failure to thrive (FTT)
is common. Unless bronchopulmonary collaterals
are present, infants with pulmonary atresia may
become markedly cyanotic as the ductus
arteriosus shuts. Some youngsters have just
adequate pulmonary blood flow and do not
appear cyanotic; these children are
asymptomatic until their pulmonary blood supply
is exhausted. Some infants with tetralogy of
Fallot do not display indications of cyanosis at

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birth, although they may acquire bluish pale skin
during crying or feeding later (ie, "Tet" spells).
Hypoxic tet spells are potentially fatal,
unpredictable events that can occur in patients
with tetralogy of Fallot who are not cyanotic.
Spasm of the infundibular septum, which
exacerbates the RV outflow tract obstruction, is
thought to be part of the process. Simple
measures can be used to break these spells [7].
Squatting is a common way for older children
with tetralogy of Fallot to enhance pulmonary
blood flow. Squatting is a compensatory
technique that is diagnostically important in
newborns with tetralogy of Fallot. Squatting
reduces the amount of the right-to-left shunt
across the ventricular septal defect by increasing
peripheral vascular resistance (PVR) (VSD).
Exertional dyspnea frequently gets worse as you
get older. The older youngster may experience
hemoptysis as a result of the bronchial collaterals
rupturing. The unusual patient may be cyanotic
but not noticeably so, or cyanotic but
asymptomatic until adulthood. Cyanosis usually
worsens with age and pulmonary vascular
expansion, necessitating surgical intervention.
Acidosis, stress, infection, posture, exercise,
beta-adrenergic agonists, dehydration, and
ductus arteriosus closure can all worsen
cyanosis in newborns with tetralogy of Fallot [8].
The most common shunt is from right to left, with
blood flowing through the VSD into the left
ventricle (LV), resulting in cyanosis and high
hematocrit. Bidirectional shunting may occur
when the pulmonary stenosis is modest. The
infundibular stenosis in some cases is minor, and
the primary shunt is from left to right, resulting in
a pink tetralogy. Although such patients may not
appear cyanotic, their systemic circulation is
frequently deficient in oxygen. The infundibular
septum hypertrophy usually causes symptoms to
worsen. RV hypertrophy increased right-to-left
shunting, and systemic hypoxemia occurs when
the RVOTO deteriorates [9].
Adults with Fallot tetralogy are presented as
follows: The severity of the anatomic
abnormalities is directly related to the clinical
symptoms of tetralogy of Fallot (TOF) in adults.
Even after surgery, it's critical to remember that,
despite the curative nature of the process, it's
really a long-term palliative procedure. The
operation simply corrects the anatomic
abnormalities; it does not treat the cause or
prevent the RV and pulmonary arteries from
continuing to alter anatomically. As a result, most
patients who undergo corrective surgery will
experience some form of symptom associated
with RV and RVOTO dysfunction at some point.
For at least the first two decades after surgery,
the majority of people with repaired tetralogy of
Fallot had no symptoms. Mild pulmonary valve
insufficiency commonly manifests in the second
decade of life and is asymptomatic. However,
pulmonary valve insufficiency worsens over time,
and patients develop symptoms. Lack of exercise
endurance, palpitations, and a steady
deterioration in basic functions may be common
concerns at the time [9].
5. COMPLICATIONS
Infection of the inner lining of the heart or a heart
valve caused by a bacterial infection is a
potential consequence of the tetralogy of Fallot
(infective endocarditis). Antibiotics may be
prescribed by your or your child's doctor prior to
certain dental operations to avoid infections that
could lead to this infection. Untreated tetralogy of
Fallot frequently leads to serious difficulties over
time, which can lead to death or incapacity by the
time a person reaches maturity. Tetralogy of
Fallot surgical complications include: Long-term
problems are common after open-heart surgery
to fix tetralogy of Fallot defects (intracardiac
repair), even though most babies and adults
recover well. A leaking pulmonary valve (chronic
pulmonary regurgitation), in which blood spills
back into the pumping chamber, is one possible
complication (right ventricle), the tricuspid valve
that is leaking, Ventricular septal defects are
holes in the wall between the ventricles that may
continue to leak after repair or require re-healing.
Right ventricle enlargement or a malfunctioning
left ventricle Arrhythmias (irregular heartbeats),
Coronary artery disease, Aortic root dilation
(enlargement of the ascending aorta), and
sudden cardiac death. Regular checkups with a
cardiac doctor who specializes in treating
persons with congenital heart disease (pediatric
cardiologist or adult congenital cardiologist) are
critical [10].
6. EPIDEMIOLOGY
Tetralogy of Fallot (TOF) represents about 7% -
10% of congenital heart disease (CHDs), and is
the most common cyanotic CHD, with 0.23-0.63
cases per 1,000 births. The disease affects one-
third of all CHD in patients under 15; in adults,
Fallot tetralogy has an average of 1 in 3,500 to 1
in 4,300 people. In most cases, Fallot tetralogy
occurs occasionally and is rare. Incidence in
children of affected parents is 1-5% and occurs

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22
more often in men than in women. The disease is
associated with extracardiac disorders such as
cleft lip and palate, hypospadias, and skeletal
and craniofacial abnormalities. Genetic studies
indicate that in some patients with Fallot
tetralogy, there may be 22q11.2 removal and
other changes in the microscopic copy number.
Adult patients with Fallot tetralogy currently
represent the largest group of patients who
underwent congenital heart surgery. Although the
exact number of these adults is unknown
because many are lost or never followed, it is
estimated that more than two-thirds of affected
children undergoing Fallot tetralogy at an early
age will reach adulthood, one study showing a
survival rate of 94% of 168 patients 16 years and
older that have been easily repaired. For people
born with this condition, the survival rate for 30
years is more than 75%, as long as these people
are medically monitored. Limited data to date
suggest that Fallot adult tetralogy is equally
common for both sexes. The majority of elderly
patients with adjusted Fallot tetralogy exist after
the second or third decade of life. Men and
women seem to be equally affected by
symptoms as they grow older [11].
7. PROGNOSIS
In the current era of heart surgery, children with
simple forms of tetralogy of fall (TF) live longer,
healthier lives with the best quality of life. Recent
results show that the majority of survivors are in
the New York Heart Association (NYHA)
Category I, although many exercise systems
have been cut in some way. About 75% of
children who recover at an early age will live 10
to 3 years without any major consequences.
However, after the first twenty years of life,
symptoms begin to appear due to the
regeneration of the pulmonary valve. This is the
mark of most of the survivors in the fourteenth
century of life. Adult patients with Fallot surgery
operation have no symptoms for 10 to 15 years,
but when they reach the age of 15, symptoms
begin to appear in these patients as well.
Although secondary surgery reduces mortality,
most of them are younger than age-related
control studies without a history of congenital
heart disease. Severe diagnosis is made in
adults with recalcitrant arrhythmias and right
heart failure [12].
Sudden death from ventricular arrhythmia has
been reported in 1-5% of patients in later life and
the cause is unknown. Cavity dysfunction is
suspected to be the cause. One study found that
left ventricular dysfunction increases the risk of
life-threatening arrhythmia. Continuous cardiac
monitoring is essential in adults. It has long been
suspected that some children may inherit a
tendency to develop a QT syndrome. A study by
Chiu in 2012 confirmed this suspicion. Most
survivors up to the age of 30 suffer from severe
heart failure (CHF), although their injections have
been identified as producing low hemodynamic
rates, although rarely, and these people live
longer. The survival of 80-year-old patients has
been reported. Thanks to advanced surgical
techniques, a 40% reduction in deaths
associated with tetralogy of Fallot from 1979 to
2005 was observed [13].
8. DIAGNOSIS
8.1 Laboratory Studies
The following laboratory tests may be useful in
the evaluation of adult patients with tetralogy of
Fallot (TOF): CBC (complete blood cell) count:
Some people may have a little anemia, but
polycythemia is uncommon without cyanosis. In
patients with cyanosis and bleeding, the
coagulation profile may be aberrant. Arterial
blood gas (containing serum lactate, base
excess, and oxygen partial pressure [PO2]): In
patients undergoing surgical repair of tetralogy of
Fallot, the patient's oxygenation status, serum
lactate levels, and base excess value appear to
be predictive markers for mortality. Blood
cultures: In feverish individuals, get blood
cultures to rule out endocarditis or sepsis [14].
8.2 Electrocardiography
With a right bundle branch block, the
electrocardiogram (ECG) will usually
demonstrate right ventricular (RV) hypertrophy.
The RV mass and volume will be larger the
longer the QRS interval is. Furthermore, a QRS
interval of greater than 180 milliseconds (ms) is a
strong indicator of the onset of ventricular
arrhythmias and sudden death. The rate of
change in the QRS interval is another ECG
parameter that has been shown to predict the
likelihood of ventricular arrhythmias and sudden
death. A rapid increase (>3.5 ms/year) is linked
to an increased risk of death. In the absence of
an extension of the QRS interval, a rapid change
in the rate of change is also a notable event.
Finally, in these patients, variations in heart rate
are a predictor of abrupt death. The ECG will
detect atrial tachycardia or atrial fibrillation in
other cases (Fig. 2) [15].

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Fig. 2. Electrocardiography of Tetralogy of Fallot [15]
8.3 Cardiac Catherization
When adults with tetralogy of Fallot (TOF)
present, echocardiography is frequently the first
test of choice. However, cardiac catheterization
may be required in some circumstances to
determine the pressures in the right ventricle and
pulmonary artery, as well as the position and size
of the ventricular septal defect and the status of
the pulmonary arteries. When the heart
architecture cannot be properly described by
echocardiography, when pulmonary artery
disease is a worry, or if an aberrant coronary
artery or pulmonary hypertension is suspected,
cardiac catheterization is also required (Fig. 3)
[16].
8.4 Imaging Studies
The imaging studies used in the fallopian
tuberculosis test (TOF) include chest
radiographs, magnetic resonance imaging (MRI),
and echocardiography [18].
Fig. 3. Cardiac Catherization for Tetralogy of Fallot [17]

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8.5 Radiography
The chest x-ray may show cardiomegaly and
substantial right ventricular (RV) shadowing, or it
may be normal. Although the classic boot-
shaped heart (Coeur en sabot) is a hallmark of
tetralogy of Fallot in infants, with diminished
vascularity in the lungs and diminished
prominence of the pulmonary arteries, this
classic shape of the heart is not always seen in
adults with tetralogy of Fallot (Fig. 4) [19].
8.6 Echocardiography
In adult patients with tetralogy of Fallot, color-
flow echocardiography is always performed to
examine overall cardiac function, valve condition,
and the presence of any residual ventricular
septal defect (VSD), ductus arterosus, or atrial
septal defect. It's worth noting that, while
echocardiography can examine valve structure, it
can't see the coronary anatomy in an adult
patient. This imaging modality can also indicate
the severity and grade of any obstruction in the
RV outflow tract (RVOT) (Fig. 5) [21].
8.7 Magnetic Resonance Imaging
For assessing RV function and size, as well as
estimating pulmonary regurgitant volume, MRI
has become the gold standard. When a
pulmonary valve disease is suspected, an MRI is
the first test to run. This imaging modality can
map the velocity of pulmonary regurgitation and
can be used to assess the pulmonary arteries,
the state of the RVOT, and the existence of
VSDs and/or RV hypertrophy, as well as the
aorta size. Intracardiac pressures, gradients, and
blood flows can all be measured using MRI.
Branch pulmonary artery stenosis can be
detected with MRI, which could be contributing to
pulmonary valve insufficiency and the creation of
aortopulmonary collaterals. These findings are
more common in people who have pulmonary
atresia and have tetralogy of Fallot. Screening:
Some pediatric cardiology facilities specialize in
treating tetralogy of Fallot children. Even if there
are no symptoms, they recommend a baseline
MRI of the heart. The data can then be used to
track the patient's progress over the next three to
seven years [22].
Fig. 4. X-Ray for Tetralogy of Fallot (Boot Shaped Heart) [20]
Fig. 5. Echocardiography for Tetralogy of Fallot [21]

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9. TREATMENT
Pulmonary insufficiency has no effective medical
treatment. Despite the use of afterload-reducing
medications and diuretics, most patients with
tetralogy of Fallot (TOF) who have pulmonary
insufficiency do not benefit and the illness
worsens. Some cardiologists prescribe sildenafil
to patients with high pulmonary artery pressures.
Long-term investigations on the effects of this
drug in adult patients with tetralogy of Fallot are,
however, limited. Place adults who have
developed acute cyanosis in a knee-chest
posture. Additionally, offer oxygen and
intravenous (IV) morphine. In severe situations,
IV propranolol might be utilized to ease the right
ventricular outflow tract obstruction by relaxing
the infundibular muscular spasm. Pulmonary
vasodilator drugs: Drugs that dilate the
pulmonary vasculature and reduce pulmonary
insufficiency are being studied. Early research
with nitric oxide suggests that such a method
could be effective. Sildenafil has been used to
treat these people, but there have been no long-
term studies to see if it can stop the pulmonary
insufficiency from progressing [23].
9.1 Surgical Treatment
Almost all patients undergo surgical resection
within the first year of life after a TOF is
diagnosed. In the short term, treatment with
prostaglandins may be needed to maintain
patent ductus arteriosus. In addition, some
patients may require digoxin or diuretics if there
are signs of heart failure. Treatment of hyper
cyanotic spells is aimed at improving pulmonary
blood flow. These include drugs that increase
systemic vascular resistance to drug
administration such as oxygen, knee/chest
posture, morphine, venous fluid, sodium
bicarbonate, beta-blockers, or phenylephrine.
Surgical correction is required if the baby has
progressive cyanosis or is showing signs of an
episode of hyper cyanosis. There are two
common surgical procedures: The Blalock-
Taussig shunt creates a shunt between the aorta
and pulmonary artery using the subclavian
artery. This is used as a treatment for infants
who are not approved for headaches due to
premature ejaculation, hypoplastic pulmonary
arteries, or coronary artery anatomy. Patients will
need additional surgery as this is not a surgical
procedure (Fig. 6) [24].
Intracardiac correction is the simplest correction
for patients with TOF and is the preferred
method. This includes the closure of the
ventricular septal defect and the extension of the
RVOT with relief from all obstruction sources. In
some cases, the valve may need to be removed
to clear the obstruction (Fig. 7) [26].
Fig. 6. The Blalock-Taussig Shunt for Tetralogy of Fallot [25]

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Fig. 7. Intracardiac Surgery for Tetralogy of Fallot [27]
9.2 Automatic Implantable Cardioverter
Defibrillator
Despite the surgical correction, some individuals
continue to experience ventricular arrhythmias,
putting them at a higher risk of sudden death. An
automated implantable cardioverter-defibrillator
may be beneficial for these patients. The
technique is relatively safe and can be done
under local anesthetic (Fig. 8) [28].
Fig. 8. Implantable cardioverter defibrillator [29]

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9.3 Radiofrequency Ablation
Radiofrequency ablation (RFA) has only recently
become a viable alternative for treating
arrhythmias in adult patients with tetralogy of
Fallot. This procedure may aid in the treatment of
atrial or ventricular arrhythmias [29].
9.4 Guidelines (2018 AHA/ACC
guidelines)
In August 2018, the American Heart
Association/American College of Cardiology
(AHA/ACC) updated their 2008 guideline for
adult congenital heart disease (CHD) care. The
following are their suggestions for the tetralogy of
Fallot (TOF). Patients with tetralogy of Fallot
(repaired or unrepaired) should be managed and
cared for by a cardiologist who specializes in
CHDs. Interventions involving congenital heart
lesions in adults with CHD (cardiac surgery,
catheter-based interventional cardiac
procedures, electrophysiologic procedures)
should be conducted by those who have
experience with adult CHD procedures as well as
a cardiologist who specializes in adult CHD.
Repaired tetralogy of Fallot is classified as
intermediate complexity by the AHA/ACC
anatomic/physiologic (AP) classification. For
cardiac imaging in patients with tetralogy of
Fallot, experts in ultrasonography,
echocardiography, and cardiac magnetic
resonance imaging (CMRI) are preferable. In
adults with CHD, use a routine 12-lead
electrocardiogram (ECG) with the serial
assessment based on the specific CHD AP
categorization or whenever symptoms emerge or
worsen [30].
When symptoms of a potential arrhythmic
etiology arise in patients with CHD who are at
risk for tachyarrhythmia, bradyarrhythmia, or
heart block, the doctor should use ambulatory
ECG monitoring. Measure QRS duration with an
ECG in individuals who have had their tetralogy
of Fallot repaired and who are being evaluated
for cardiac resynchronization therapy (CRT). In
the assessment of right ventricular (RV) size and
function in repaired tetralogy of Fallot, systemic
RVs, and other conditions associated with RV
volume and pressure overload, CMRI, cardiac
computed tomography (CCT) scanning,
transesophageal echocardiography (TEE),
and/or cardiac catheterization may be superior to
transthoracic echocardiography (TTE). Tetralogy
of Fallot is usually associated with DiGeorge
(velocardiofacial syndrome) and Down
syndromes, among other cardiac abnormalities
[30].
9.5 Diagnostic Recommendations
In patients with repaired tetralogy of Fallot, CMRI
can be used to measure ventricular size and
function, pulmonary valve function, pulmonary
artery (PA) anatomy, and left heart anomalies.
Before doing right ventricle-to-PA conduit
stenting or transcatheter valve installation in a
repaired tetralogy of Fallot, obtain coronary
artery compression testing. Adults with tetralogy
of Fallot and extra risk factors for sudden cardiac
death may benefit from programmed ventricular
stimulation (SCD). When adequate data cannot
be obtained noninvasively in the setting of
arrhythmia, heart failure, unexplained ventricular
dysfunction, suspected pulmonary hypertension,
or cyanosis in patients with repaired tetralogy of
Fallot, cardiac catheterization with angiography,
if indicated, is reasonable to assess
hemodynamics [31].
9.6 Therapeutic Recommendations
For patients with corrected tetralogy of Fallot and
moderate or higher pulmonary regurgitation (PR)
and otherwise unexplained cardiovascular
symptoms, pulmonary valve replacement
(surgical or percutaneous) is advised for
symptomatic alleviation. In asymptomatic
patients with corrected tetralogy of Fallot with
ventricular enlargement or dysfunction and a
moderate or larger PR, pulmonary valve
replacement (surgical or percutaneous) is
suitable for preserving ventricular size and
function. In people with tetralogy of Fallot and
several risk factors for SCD, primary prevention
with an implanted cardioverter-defibrillator (ICD)
is acceptable. Adults with corrected tetralogy of
Fallot and moderate or greater PR with additional
abnormalities requiring surgical intervention may
be candidates for surgical pulmonary valve
replacement. Adults with corrected tetralogy of
Fallot and moderate or severe PR and ventricular
tachyarrhythmia may consider pulmonary valve
replacement in addition to arrhythmia therapy
[31].
9.7 RV-to-PA Conduit
Before RV-to-PA conduit stenting or
transcatheter valve installation, coronary artery
compression testing with simultaneous coronary
angiography and high-pressure balloon dilation in
the conduit is recommended. Evaluate for

Elsaka et al.; AJRMMS, 4(1): 18-31, 2022; Article no.AJRMMS.829
28
conduit problems in patients with stented RV-to-
PA conduits with worsening pulmonary stenosis
(PS) or PR, including fluoroscopy to check for
stent fracture and blood cultures to check for
infective endocarditis. Cardiac catheterization is
recommended for people with an RV-to-PA
conduit with arrhythmia, congestive heart failure,
unexplained ventricular dysfunction, or cyanosis.
Adults with RV-to-PA conduit and moderate or
greater PR or moderate or greater stenosis with
impaired functional capacity or arrhythmia may
benefit from RV-to-PA conduit treatments.
Asymptomatic adults with RV-to-PA conduit and
severe stenosis or regurgitation with reduced RV
ejection fraction or RV dilatation may benefit from
RV-to-PA conduit treatments (Fig. 9) [32].
10. DISCUSSION
Several operations in elderly patients have
reported different postoperative results with
mortality rates ranging from 6% to 10%. Some
studies have shown a 5-year survival rate of
more than 90% and 86% within 10 years.
However, while the short-term effects after a
pulmonary valve change are very good, the long-
term effects are just as bad. In almost all case
series, many patients have undergone relapses
and/or pacemaker implantation procedures, and
some people persist in increasing RVOT
pressure. Some even need to replace the
cleaning valves. Postoperative follow-up of adults
with tetralogy of Fallot showed that pulmonary
valve replacement also delayed or reversed the
progression of other problems associated with
pulmonary valve dysfunction, including right
ventricular dysfunction and tricuspid valve
recurrence. However, the question of whether
surgery improves ventricular arrhythmias
remains controversial. Some short-term studies
have shown a lower incidence of arrhythmias in
the postoperative period, but other long-term
studies have shown no differences. In general,
arrhythmias persist even after surgery in most
patients with tetralogy of Fallot who have
undergone pulmonary valve replacement [33].
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 [33].
Fig. 9. The Rastelli procedure (RV-to-PA conduit) [32]

Elsaka et al.; AJRMMS, 4(1): 18-31, 2022; Article no.AJRMMS.829
29
It was previously believed that surgery for
tetralogy of Fallot was curative. It is now
recognized that even after radical correction, a
significant number of patients undergoing
pediatric surgery appear as adults with
symptoms of pulmonary valve insufficiency and
arrhythmias. In the past, many of these children
who had corrected tetralogy of Fallot were either
unable to be tracked or persecuted because they
falsely believed that their heart disease had
healed. Careful monitoring of all children with
tetralogy of Fallot is currently recommended, as
many children show symptoms by the age of 13.
Some children's heart centers specialize in the
care of patients with tetralogy of Fallot. They
recommend a simple magnetic resonance image
scan of the heart, even in the absence of
symptoms. The results can be used to monitor
patients for changes every 3-7 years [33].
11. CONCLUSION
Today, some Fallot tetralogy patients live more
than 15-20 years after their first surgery. The
biggest problem they face is the development of
valvular disease. It seems that many of them
need a heart replacement. Most people try
pericardial homographs, and only time will tell
how long these valves will last. However, there
have been major advances in percutaneous
technology and tissue engineering in the last
decade, and the role of surgery may be
diminished. Percutaneous Valve Replacement:
With new technologies and endovascular
technology, the ability to replace percutaneous
pulmonary valves will become a reality shortly.
For example, the melody transcatheter
pulmonary valve can be percutaneously inserted
through a female vein with the guidance of
fluoroscopy. Preliminary reports indicate that the
procedure is workable and safe. These few case
reports show that after valve implantation, there
has been a slight decrease in valve function and
ventricular size, as well as a significant
improvement in exercise endurance.
Overall, the best 20-year survival rate for TOF
patients is over 90%. Complications of TOF
surgical repair include arrhythmias, especially
ventricular tachycardia (VT), and arterial
arrhythmias. In addition, patients may have
increased right ventricular hypertrophy or
residual pulmonary stenosis and increased blood
flow to the right ventricle. Chronic complications
include additional surgery, neurodevelopmental
delay, and myocardial fibrosis. Pediatric
cardiologists should closely monitor patients to
control these short-term and long-term
complications.
CONSENT
It is not applicable.
ETHICAL APPROVAL
It is not applicable.
COMPETING INTERESTS
Authors have declared that no competing
interests exist.
REFERENCES
1. Refaat MM, Ballout J, Mansour M. Ablation
of atrial fibrillation in patients with
congenital heart disease. Arrhythm
Electrophysiol Rev. 2017 ;6(4):191-4.
2. Maury P, Sacher F, Rollin A, et al.
Ventricular arrhythmias and sudden death
in tetralogy of Fallot. Arch Cardiovasc Dis.
2017;110(5):354-62.
3. Fraser CD, Bacha EA, Comas J, Sano S,
Sarris GE, Tsang VT. Tetralogy of Fallot.
Semin Thorac Cardiovasc Surg.
2015;27(2):189-204.
4. Bhardwaj V, Kapoor PM, Irpachi K, Ladha
S, Chowdhury UK. Basic arterial blood gas
biomarkers as a predictor of mortality in
tetralogy of Fallot patients. Ann Card
Anaesth. 2017;20 (1):67-71.
5. Boechat MI, Ratib O, Williams PL, Gomes
AS, Child JS, Allada V. Cardiac MR
imaging and MR angiography for
assessment of complex tetralogy of Fallot
and pulmonary atresia. Radiographics.
2005;25(6):1535-46.
6. Gabriele B, Maurizio B, Marco B. Does
pharmacological therapy still play a role in
preventing sudden death in surgically
treated tetralogy of Fallot?. Mini Rev Med
Chem. 2018;18(6):490-4.
7. Faccini A, Micheletti A, Negura DG, et al.
Heart failure in grown-up congenital heart
disease. Minerva Cardioangiol.
2018;66(3):329-36.
8. Marinho C, Alho I, Guerra A, Rego C,
Areias J, Bicho M. The methylene-
tetrahydrofolate reductase gene variant
(C677T) as a susceptibility gene for
tetralogy of Fallot. Rev Port Cardiol.
2009;28(7-8):809-12.

Elsaka et al.; AJRMMS, 4(1): 18-31, 2022; Article no.AJRMMS.829
30
9. Lee CN, Su YN, Cheng WF, et al.
Association of the C677T
methylenetetrahydrofolate reductase
mutation with congenital heart diseases.
Acta Obstet Gynecol Scand. 2005;
84(12):1134-40.
10. Li X, Liu CL, Li XX, Li QC, Ma LM, Liu GL.
VEGF gene polymorphisms are associated
with risk of tetralogy of Fallot. Med Sci
Monit. 2015;21:3474-82.
11. Anabtawi A, Mondragon J, Dodendorf D,
Laskey WK. Late-stage left ventricular
dysfunction in adult survivors of tetralogy
of Fallot repair in childhood. Open Heart.
2017;4(2):e000690.
12. Rauch R, Hofbeck M, Zweier C, et al.
Comprehensive genotype-phenotype
analysis in 230 patients with tetralogy of
Fallot. J Med Genet. 2010;47(5):321-31.
13. Pillutla P, Shetty KD, Foster E. Mortality
associated with adult congenital heart
disease: trends in the US population from
1979 to 2005. Am Heart J. 2009 Nov.
158(5):874-9.
14. Diller GP, Kempny A, Liodakis E, et al. Left
ventricular longitudinal function predicts
life-threatening ventricular arrhythmia and
death in adults with repaired tetralogy of
fallot. Circulation. 2012;125(20):2440-6.
15. Chiu SN, Wu MH, Su MJ, et al. Coexisting
mutations/polymorphisms of the long QT
syndrome genes in patients with repaired
tetralogy of Fallot are associated with the
risks of life-threatening events. Hum
Genet. 2012;131(8):1295-304.
16. Dluzniewska N, Podolec P, Miszalski-
Jamka T, et al. Effect of ventricular
function and volumes on exercise capacity
in adults with repaired tetralogy of Fallot.
Indian Heart J. 2018;70(1):87-92.
17. Gaydos SS, Varga-Szemes A, Judd RN,
Suranyi P, Gregg D. Imaging in adult
congenital heart disease. J Thorac
Imaging. 2017;32(4):205-16.
18. Bokma JP, de Wilde KC, Vliegen HW, et
al. Value of cardiovascular magnetic
resonance imaging in noninvasive risk
stratification in tetralogy of Fallot. JAMA
Cardiol. 2017;2(6):678-83.
19. Scalone G, Gomez-Monterrosas O, Fiszer
R, Szkutnik M, Galeczka M, Bialkowski J.
Combined strategy of Waterston shunt
percutaneous occlusion and medical
treatment with sildenafil for management of
pulmonary hypertension in an adult patient
with corrected tetralogy of Fallot. Postepy
Kardiol Interwencyjnej. 2017;13(3):277-8.
20. McRae ME, Coleman B, Atz TW, Kelechi
TJ. Patient outcomes after transcatheter
and surgical pulmonary valve replacement
for pulmonary regurgitation in patients with
repaired tetralogy of Fallot: A quasi-meta-
analysis. Eur J Cardiovasc Nurs. 2017;
16(6):539-53.
21. Bhagra CJ, Hickey EJ, Van De Bruaene A,
Roche SL, Horlick EM, Wald RM.
Pulmonary valve procedures late after
repair of tetralogy of Fallot: current
perspectives and contemporary
approaches to management. Can J
Cardiol. 2017 ;33(9):1138-49.
22. Pragt H, van Melle JP, Javadikasgari H, et
al. Mechanical valves in the pulmonary
position: an international retrospective
analysis. J Thorac Cardiovasc Surg. 2017;
154(4):1371-8.e1.
23. Therrien J, Marx GR, Gatzoulis MA. Late
problems in tetralogy of Fallot--recognition,
management, and prevention. Cardiol Clin.
2002;20(3):395-404.
24. Ezzat VA, Ryan MJ, O'Leary J, et al.
Radiofrequency ablation of atrial
tachyarrhythmias in adults with tetralogy of
Fallot - predictors of success and outcome.
Cardiol Young. 2017; 27(2):284-93.
25. Davidson J, Tong S, Hancock H, Hauck A,
da Cruz E, Kaufman J. Prospective
validation of the vasoactive-inotropic score
and correlation to short-term outcomes in
neonates and infants after cardiothoracic
surgery. Intensive Care Med. 2012;38(7):
1184-90.
26. Menting ME, van den Bosch AE, McGhie
JS, et al. Assessment of ventricular
function in adults with repaired Tetralogy of
Fallot using myocardial deformation
imaging. Eur Heart J Cardiovasc Imaging.
2015;16(12):1347-57.
27. Lindsey CW, Parks WJ, Kogon BE, Sallee
D 3rd, Mahle WT. Pulmonary valve
replacement after tetralogy of Fallot repair
in preadolescent patients. Ann Thorac
Surg. 2010;89(1):147-51.
28. Bokma JP, Geva T, Sleeper LA, et al. A
propensity score-adjusted analysis of
clinical outcomes after pulmonary valve
replacement in tetralogy of Fallot. Heart.
2018;(9):738-44.
29. Heng EL, Gatzoulis MA, Uebing A, et al.
Immediate and midterm cardiac
remodeling after surgical pulmonary
Vvalve replacement in adults with repaired
tetralogy of Fallot: a prospective
cardiovascular magnetic resonance and

Elsaka et al.; AJRMMS, 4(1): 18-31, 2022; Article no.AJRMMS.829
31
clinical study. Circulation. 2017;
136(18):1703-13.
30. Mitropoulos FM, Kanakis MA, Ntellos C, et
al. Pulmonary valve replacement in
patients with corrected tetralogy of Fallot. J
Cardiovasc Thorac Res. 2017;9(2):71-7.
31. Caruana M, Grech V. A first population-
based long-term outcome study in adults
with repaired tetralogy of Fallot in Malta.
Congenit Heart Dis. 2017;12(3):301-8.
32. Kanter KR, Kogon BE, Kirshbom PM,
Carlock PR. Symptomatic neonatal
tetralogy of Fallot: repair or shunt?. Ann
Thorac Surg. 2010;89(3):858-63.
33. Tsang FH, Li X, Cheung YF, Chau KT,
Cheng LC. Pulmonary valve replacement
after surgical repair of tetralogy of
Fallot. Hong Kong Med J. 2010;16(1):26-
30.
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