Tetralogy of Fallot
(TOF) is a congenital heart defect
classically understood to involve four anatomical abnormalities
(although only three of them are always present). It is the most
heart defect, representing
55-70%, and the most common cause of blue baby syndrome
It was described in 1672 by Niels
, in 1773 by Edward Sandifort, and in 1888 by the French
physician Étienne-Louis Arthur
, for whom it is named.
Primary four malformations
" denotes a four-part phenomenon
in various fields, including literature
and the four parts the syndrome's name implies are its four
. This is not to be confused with
the similarly named teratology
, a field
of medicine concerned with abnormal development and congenital
malformations, which thereby includes
tetralogy of Fallot
as part of its subject matter.
As such, by definition, tetralogy of Fallot involves exactly four
malformations which present
Tetralogy of Fallot
|A: Pulmonary stenosis
||A narrowing of the right ventricular outflow tract and can
occur at the pulmonary valve (valvular
stenosis) or just below the pulmonary valve
(infundibular stenosis). Infundibular pulmonic stenosis is mostly
caused by overgrowth of the heart muscle wall (hypertrophy of the
septoparietal trabeculae), however the events leading to the
formation of the overriding aorta are also believed to be a cause.
The pulmonic stenosis is the major cause of the malformations, with
the other associated malformations acting as compensatory
mechanisms to the pulmonic stenosis. The degree of stenosis varies
between individuals with TOF, and is the primary determinant of
symptoms and severity. This malformation is infrequently described
as sub-pulmonary stenosis or subpulmonary
|B: Overriding aorta
||An aortic valve with biventricular
connection, that is, it is situated above the ventricular septal
defect and connected to both the right and the left ventricle. The
degree to which the aorta is attached to the right ventricle is
referred to as its degree of "override." The aortic root can be
displaced toward the front (anteriorly) or directly above the
septal defect, but it is always abnormally located to the right of
the root of the pulmonary artery. The degree of override is quite
variable, with 5-95% of the valve being connected to the right
|C: ventricular septal
||A hole between the two bottom chambers (ventricles) of the
heart. The defect is centered around the most superior aspect of
the ventricular septum (the outlet septum), and in the majority of
cases is single and large. In some cases thickening of the septum
(septal hypertrophy) can narrow the margins of the defect.
|D: Right ventricular
||The right ventricle is more
muscular than normal, causing a characteristic boot-shaped
(coeur-en-sabot) appearance as seen by chest X-ray. Due to the
misarrangement of the external ventricular septum, the right
ventricular wall increases in size to deal with the increased
obstruction to the right outflow tract. This feature is now
generally agreed to be a secondary anomaly, as the level of
hypertrophy generally increases with age.
There is anatomic variation between the hearts of individuals with
tetralogy of Fallot. Primarily, the degree of right ventricular
outflow tract obstruction varies between patients and generally
determines clinical symptoms and disease progression.
In addition, tetralogy of Fallot may present with other anatomical
Tetralogy of Fallot with pulmonary atresia
- stenosis of the left pulmonary
artery, in 40% of patients
- a bicuspid pulmonary
valve, in 40% of patients
- right-sided aortic arch,
in 25% of patients
- coronary artery anomalies, in
10% of patients
- a foramen ovale or atrial septal defect, in which case the
syndrome is sometimes called a pentalogy of
- an atrioventricular
- partially or totally anomalous pulmonary venous
- forked ribs and scoliosis
) is a severe variant in which
there is complete obstruction (atresia) of the right ventricular
outflow tract, causing an absence of the pulmonary trunk during
embryonic development. 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
Epidemiology and etiology
Tetralogy of Fallot occurs in approximately 400 per million live
Its cause is thought to be due to environmental or genetic factors
or a combination. It is associated with chromosome 22 deletions and
Specific genetic associations include:
It occurs slightly more often in males than in females.
studies show that it is a
result of anterior malalignment of the conal septum
, resulting in the clinical
combination of a VSD, pulmonary stenosis, and an overriding aorta.
Right ventricular hypertrophy results from this combination, which
causes resistance to blood flow from the right ventricle.
Pathophysiology and symptoms
Tetralogy of Fallot results in low oxygenation
of blood due to the mixing of
oxygenated and deoxygenated blood in the left ventricle via the VSD
and 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
. The primary symptom
is low blood oxygen saturation with or without cyanosis
from birth or developing in the first year
of life. If the baby is not cyanotic then it is sometimes referred
to as a "pink tet". 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, dyspnea on
exertion, clubbing of the fingers and toes, and polycythemia
Children with tetralogy of Fallot may develop "tet spells". The
precise mechanism of these episodes is in doubt, but presumably
results from a transient increase in resistance to blood flow to
the lungs with increased preferential flow of desaturated blood to
the body. Tet spells are characterized by a sudden, marked increase
in cyanosis followed by syncope, and may result in hypoxic brain
injury and death. Older children will often squat during a tet
spell, which cuts off circulation to the legs and therefore
improves blood flow to the brain and vital organs.
The abnormal "coeur-en-sabot
(boot-like) appearance of a heart with tetralogy of Fallot is
easily visible via chest x-ray, and before more sophisticated
techniques became available, this was the definitive method of
diagnosis. Congenital heart defects are now diagnosed with
echocardiography, which is quick, involves no radiation, is very
specific, and can be done prenatally.
Emergency management of tet spells
Prior to corrective surgery, children with tetralogy of Fallot may
be prone to consequential acute hypoxia (tet spells), characterized
by sudden cyanosis and syncope. These may be treated with beta-blockers
such as propranolol
, but acute episodes may require
rapid intervention with morphine
ventilatory drive and a vasopressor such as epinephrine
, or norepinephrine
to increase blood pressure.
Oxygen is ineffective in treating hypoxic spells because the
underlying problem is lack of blood flow through the lungs and not
oxygenation within the lungs. There are also simple procedures such
as squatting in the knee-chest position which increases aortic wave
reflection, increasing 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.
The condition was initially thought untreatable until surgeon
, cardiologist Helen B. Taussig
, and lab assistant Vivien Thomas
at Johns Hopkins University
developed a palliative surgical procedure, which involved forming
an anastomosis between the subclavian artery and the pulmonary
artery (See movie "Something the
"). It was actually Helen Taussig who convinced Alfred
Blalock that the shunt was going to work. 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 greatly relieving symptoms in patients. The first Blalock-Thomas-Taussig shunt
surgery was performed on 15-month old Eileen Saxon
with dramatic results.
The Potts shunt and the Waterston-Cooley shunt are other shunt
procedures which were developed for the same purpose. These are no
Currently, Blalock-Thomas-Taussig shunts are not normally performed
on infants with TOF except for severe variants such as TOF with
pulmonary atresia (pseudotruncus arteriosus).
Total surgical repair
The Blalock(-Thomas)-Taussig procedure was the only surgical
treatment until the first total surgical repair was performed in
1954. Between 1944 and when total repair became available at major
surgical centers in the early 1960s, many infants and children were
treated palliatively with Blalock(-Thomas)-Taussig
This first total repair was performed by C. Walton
at the University of Minnesota in 1954 on a 11 year
old boy. The first successful total repair on an infant at one
years of age, was performed in 1991, on Brittany Leska, now
Brittaney Seaber. Total repair initially carried a high mortality
risk which has consistently improved over the years. Surgery is now
often carried out in infants 1 year of age or younger with a <5%
perioperative="" mortality.="" The="" surgery="" generally=""
involves="" making="" incisions="" into="" the="" heart=""
muscle,="" relieving="" right="" ventricular="" outflow="" tract=""
stenosis="" by="" careful="" resection="" of="" and="" repairing=""
VSD="" using="" a="" Gore-Tex="" patch="" or="" homograft.=""
Additional="" reparative="" reconstructive="" work="" may="" be=""
done="" on="" patients="" as="" required="" their="" particular=""
Untreated, tetralogy of Fallot rapidly results in progressive right
ventricular hypertrophy due to the increased resistance on the
right ventricle. This progresses to heart failure (dilated
cardiomyopathy) which begins in the right heart and often leads to
left heart failure. Actuarial survival for untreated tetralogy of
Fallot is approximately 75% after the first year of life, 60% by
four years, 30% by ten years, and 5% by forty years.
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). Surgical
success and long-term outcome greatly depends on the particular
anatomy of the patient and the surgeon's skill and experience with
this type of repair.
Ninety percent of patients with total repair as infants develop a
progressively leaky pulmonary valve as the heart grows to its adult
size but the valve does not. Patients also often have damage to the
electrical system of the heart from surgical incisions, causing
abnormalities as detected by EKG and/or arrhythmias.
Long-term follow up studies show that patients with total repair of
TOF are at risk for sudden cardiac death and for heart failure.
Therefore, lifetime follow-up care by an adult congenital
cardiologist is recommended to monitor these risks and to recommend
treatment, such as interventional procedures or re-operation, if it
Antibiotic prophylaxis is indicated during dental treatment in
order to prevent infective
. The use of antibiotics is no longer required by
cardiologists and varies from case to case.
Notable people born with the defect