The tetralogy

1) Stenosis of pulmonary artery

2) VSD
3) Overiding aorta =Deviation of the origin of aorta to the right of the
VSD instead of into the left ventricle
4) Concentric right ventricular hypertrophy

EPIDEMIOLOGY The prevalence of TOF in the United States is

approximately 4 to 5 per 10,000 live births. Equal in males females

Associated findings

Approximately 25 percent of patients have a right aortic arch. This is particularly important
to identify if one is contemplating a palliative shunt.

Abnormalities of the coronary arteries, such as the left anterior

descending arising from the right coronary artery, are seen in about 9
percent of patients [6]. These are important to identify prior to complete repair,
since the course of the artery may run directly across the right ventricular outflow
tract; inadvertent transection could have catastrophic consequences.

Occasionally, patients have significant aorticopulmonary collateral vessels that may

require attention prior to or at the time of surgery.

Approximately 15 percent of patients with TOF present with associated syndromes [9,13-19]:

Down syndrome (trisomy 21).

Alagille syndrome (mutations in JAG1). TOF as the sole manifestation of JAG1

mutations without other evidence of Alagille syndrome has also been reported [20].
(See "Inherited disorders associated with conjugated hyperbilirubinemia", section on
'Alagille syndrome'.)

DiGeorge and velocardiofacial syndromes (deletion on chromosome 22q11). There may

be susceptibility genes for TOF within the latter region of chromosome 22q11 in children
without extracardiac anomalies [18,21,22], and 22q11.2 deletion syndrome is unrecognized
in many adult patients with TOF
The physiologic consequences of TOF are largely dependent upon the
degree of right ventricular outflow obstruction. Since the VSD is typically
large and unrestrictive, the pressure in the right ventricle reflects that of the left
ventricle. As a result, the direction of blood flow across the VSD will be determined
by the path of least resistance for blood flow, not by the size of the VSD. If the
resistance to blood flow across the obstructed right ventricular outflow tract is less
than the resistance to flow out of the aorta into the systemic circulation, blood will
naturally shunt from the left ventricle to the right ventricle and into the pulmonary
bed. In this situation, there is predominately a left-to-right shunt and the patient will
be acyanotic.

As the degree of right ventricular outflow obstruction increases, the resistance to

blood flow into the pulmonary bed also increases. If the right ventricular obstruction
is significant enough to increase resistance, it will be easier for blood to cross the
VSD from the right ventricle into the left ventricle and go out the aorta, which now
becomes the path of least resistance. This right-to-left shunt across the VSD will
result in a large volume of desaturated blood entering the systemic circulation and
cyanosis and polycythemia will ensue

One of the physiologic characteristics of TOF is that the right ventricular

outflow obstruction can fluctuate. An individual with minimal cyanosis can
develop a dynamic increase in right ventricular outflow tract obstruction with a
subsequent increase in right-to-left shunt and the development of cyanosis. In the
most dramatic situation, there can be near occlusion of the right ventricular outflow
tract with profound cyanosis. These episodes are often referred to as "tet spells" or
"hypercyanotic spells". The exact etiology of these episodes is unclear,
although there have been a number of proposed mechanisms, including
increased infundibular contractility, peripheral vasodilatation,
hyperventilation, and stimulation of right ventricular mechanoreceptors

SEVERITY

Children with severe obstruction and inadequate pulmonary flow typically present in the
immediate newborn period with profound cyanosis.

Children with moderate obstruction and balanced pulmonary and systemic flow may be
noticed during elective evaluation for a murmur. These children may also present with
hypercyanotic (tet) spells when RVOT is obstructed during periods of agitation. In
addition, some affected newborns will be detected by an evaluation prompted by a failed
oximetry screening test.
 Children with minimal obstruction may present with pulmonary overcirculation and heart
failure.

Murmur The murmur in TOF is due primarily to the right ventricular outflow
obstruction, not the VSD. The murmur is typically crescendo-decrescendo with a
harsh systolic ejection quality; it is appreciated best along the left mid to upper
sternal border with radiation posteriorly. It can, however, have a more regurgitant
quality that can be easily mistaken for a VSD. (See "Auscultation of cardiac
murmurs in adults".)

The murmur is due both to the degree of obstruction and to the amount of flow
across the obstruction. In TOF, unlike isolated valvar pulmonary stenosis, the
amount of flow across the right ventricular outflow tract will decrease as the
obstruction increases, due to the shunting of blood right-to-left across the VSD.
Thus, as the obstruction increases, the murmur will become softer. During severe
hypercyanotic (tet) spells, the murmur may actually disappear due to the markedly
diminished flow across the obstruction.

DIAGNOSIS The diagnosis of TOF is generally made by echocardiography. Cardiac

cath if more info needed

ECHO

Cardiac catheterization Although echocardiography can reveal the anatomy in many

patients with TOF, cardiac catheterization may still be necessary to further delineate the
structure. It is particularly helpful for assessing levels of right ventricular outflow obstruction,
branch pulmonary artery stenosis or hypoplasia, coronary artery anatomy, presence of
aorticopulmonary collaterals, and presence of accessory ventricular septal defects.

Xray-can show boot sign, but not right away

A complete study must address:

The location and number of VSDs

The anatomy and severity of right ventricular outflow tract obstruction

The coronary artery and aortic arch anatomy

Cardiac catheterization can also play a therapeutic role in some patients with TOF.
Balloon valvuloplasty of the pulmonary valve can improve pulmonary flow in many
children; there may also be an increase in pulmonary valve annulus size that may
decrease the need for transannular patch repair

MEDICAL MANAGEMENT The need for medical intervention is dependent on the

degree of right ventricular outflow tract (RVOT) obstruction.

Patients with severe obstruction have inadequate pulmonary flow, and typically
present in the immediate newborn period with profound cyanosis. These patients
may need urgent therapy.

Patients with moderate obstruction and balanced pulmonary and systemic flow
usually come to clinical attention during elective evaluation for a murmur. These
children may also present with hypercyanotic ("tet") spells when RVOT is obstructed
during periods of agitation. In addition, some affected newborns will be detected by
an evaluation prompted by a failed oximetry screening test.

Patients with minimal obstruction may present with increased pulmonary blood
flow and heart failure.

Neonates with severe RVOT obstruction Neonates with severe RVOT

obstruction present with profound hypoxemia and cyanosis. These patients may
require intravenous prostaglandin therapy (also known as alprostadil) to maintain
ductal patency and pulmonary flow PRIOR TO surgical repair

Tet spells Hypercyanotic (or "tet") spells present as periods of profound cyanosis
that occur because of episodes of almost total RVOT obstruction. They typically
arise when an infant becomes agitated or in older, uncorrected children after
vigorous exercise.

The management of hypercyanotic "tet" spells requires a rapid and aggressive step-
wise treatment. Escalation to the next step is dependent on the patient's response.

Treatment starts with placement of the patient in a knee-chest position to increase

systemic vascular resistance, which promotes movement of blood from the right
ventricle into the pulmonary circulation rather than the aorta.

Oxygen should be administered as it acts as a pulmonary vasodilator and a

systemic vasoconstrictor.
If these fail, they are followed by intravenous therapy of morphine (0.1 mg/kg per
dose) and an intravenous fluid bolus (10 to 20 cc/kg normal saline). The mechanism
of action of morphine is unclear, while fluids improve right ventricle (RV) filling and
pulmonary flow. The role of bicarbonate therapy to treat an associated lactic
acidosis is uncertain. (See "Approach to the child with metabolic acidosis", section
on 'Cardiac patients'.)

If the above measures fail, intravenous beta blockers (eg, propranolol, 0.1 mg/kg
per dose, or esmolol, 0.1 mg/kg per dose) can be administered. The presumed
mechanism of benefit is relaxation of the RVOT with improved pulmonary blood flow.
If this is insufficient, systemic afterload can be increased with intravenous
phenylephrine (5 to 20 mcg/kg per dose), which, as with assumption of the knee-
chest position, promotes right ventricular flow into the pulmonary circulation rather
than the aorta.

If all of these measures fail, emergency complete surgical repair or an emergency

aorticopulmonary shunt (ie, Blalock-Taussig shunt) is necessary.

Heart failure Some patients with minimal obstruction and increased pulmonary
blood flow may develop heart failure symptoms, and require pharmacologic
treatment that includes digoxin and a loop diuretic (eg, furosemide). In these
patients, an angiotensin converting enzyme inhibitor or receptor blocker, often used
in patients with heart failure due to other conditions, is not used because of
concerns that the drop in systemic vascular resistance may promote a
hypercyanotic ("tet") spell.

Antibiotic prophylaxis Based on the American Heart Association (AHA)

guidelines for all patients with unrepaired cyanotic congenital heart disease,
antibiotic prophylaxis is administered to prevent bacterial endocarditis until surgical
correction is performed.

SURGICAL PROCEDURES Currently, most patients with TOF undergo

intracardiac repair as their initial intervention by one year of age, and over half
before six months of age [2]. However, palliative shunts may be needed for infants
during a medically refractory hypercyanotic ("tet") spell or for those with severe
right ventricular outflow tract (RVOT) obstruction who may not be initially
acceptable candidates for intracardiac repair due to prematurity, hypoplastic
pulmonary arteries, or coronary artery anatomy.

Palliative shunts Palliative shunts are not commonly performed in children with
TOF in the current era. However, for the following patients, palliative procedures
through a systemic to pulmonary shunt provide stable pulmonary blood flow
required for survival, and allow a deferral of elective complete repair:
Infants who cannot undergo intracardiac repair (eg, premature)

Infants who have severe RVOT obstruction

Patients with a medically refractory severe hypercyanotic ("tet") spell

Patients with coronary anatomy complicating initial complete repair in the

perinatal period

Approach

the RVOT is enlarged by opening the RVOT and pulmonary valve, resecting the subinfundibular
muscle bundles, and patching the area open with transannular patch

Short-term outcomes Short-term outcome is excellent for neonates or young

infants who have undergone surgical repair, with perioperative mortality ranging
from 0 to 3 percent