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Chapter 424Cyanotic Congenital Heart Lesions : Lesions Associated with Decreased

Pulmonary Blood Flow
424.1Tetralogy of Fallot

DanielBernstein

Tetralogy of Fallot is one of the conotruncal family of heart lesions in which the primary defect is an anterior
deviation of the infundibular septum (the muscular septum that separates the aortic and pulmonary outflows).
The consequences of this deviation are the 4 components: (1) obstruction to right ventricular outflow
(pulmonary stenosis), (2) a malalignment type of ventricular septal defect (VSD), (3) dextroposition of the aorta
so that it overrides the ventricular septum, and (4) right ventricular hypertrophy (Fig. 424-1). Obstruction to
pulmonary arterial blood flow is usually at both the right ventricular infundibulum (subpulmonic area) and the
pulmonary valve. The main pulmonary artery may be small, and various degrees of branch pulmonary artery
stenosis may be present. Complete obstruction of right ventricular outflow (pulmonary atresia with VSD) is
classified as an extreme form of tetralogy of Fallot (Chapter 424.2). The degree of pulmonary outflow
obstruction determines the degree of the patient's cyanosis and the age of first presentation.

Figure 424-1 Physiology of the tetralogy of Fallot. Circled numbers represent oxygen saturation values. The numbers next to the
arrows represent volumes of blood flow (in L/min/m 2 ). Atrial (mixed venous) oxygen saturation is decreased because of the
systemic hypoxemia. A volume of 3L/min/m 2 of desaturated blood enters the right atrium and traverses the tricuspid valve. Two
liters flows through the right ventricular outflow tract into the lungs, whereas 1L shunts right to left through the ventricular septal
defect (VSD) into the ascending aorta. Thus, pulmonary blood flow is two thirds normal (Qp:Qs [pulmonary-to-systemic blood flow
ratio] of 0.7 : 1). Blood returning to the left atrium is fully saturated. Only 2L of blood flows across the mitral valve. Oxygen saturation
in the left ventricle may be slightly decreased because of right-to-left shunting across the VSD. Two liters of saturated left ventricular
blood mixing with 1L of desaturated right ventricular blood is ejected into the ascending aorta. Aortic saturation is decreased, and
cardiac output is normal.

Pathophysiology
The pulmonary valve annulus may range from being nearly normal in size to being severely hypoplastic. The
valve itself is often bicuspid or unicuspid and, occasionally, is the only site of stenosis. More commonly, the
subpulmonic or infundibular muscle, known as the crista supraventricularis, is hypertrophic, which contributes to

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the subvalvar stenosis and results in an infundibular chamber of variable size and contour. When the right
ventricular outflow tract is completely obstructed (pulmonary atresia), the anatomy of the branch pulmonary
arteries is extremely variable. A main pulmonary artery segment may be in continuity with right ventricular
outflow, separated by a fibrous but imperforate pulmonary valve; the main pulmonary artery may be moderately
or severely hypoplastic but still supply part or all of the pulmonary bed; or the entire main pulmonary artery
segment may be absent. Occasionally, the branch pulmonary arteries may be discontinuous. Pulmonary blood
flow may be supplied by a patent ductus arteriosus (PDA) or by multiple major aortopulmonary collateral
arteries (MAPCAs) arising from the ascending and descending aorta and supplying various lung segments.

The VSD is usually nonrestrictive and large, is located just below the aortic valve, and is related to the posterior
and right aortic cusps. Rarely, the VSD may be in the inlet portion of the ventricular septum (atrioventricular
septal defect). The normal fibrous continuity of the mitral and aortic valves is usually maintained, and if not (due
to the presence of a subaortic muscular conus) the classification is usually that of double outlet right ventricle
(Chapter 424.5). The aortic arch is right sided in 20% of cases, and the aortic root is usually large and overrides
the VSD to varying degrees. When the aorta overrides the VSD by more than 50% and if there is a subaortic
conus, this defect is classified as a form of double-outlet right ventricle; however, the circulatory dynamics are
the same as that of tetralogy of Fallot.

Systemic venous return to the right atrium and right ventricle is normal. When the right ventricle contracts in the
presence of marked pulmonary stenosis, blood is shunted across the VSD into the aorta. Persistent arterial
desaturation and cyanosis result, the degree dependent on the severity of the pulmonary obstruction.
Pulmonary blood flow, when severely restricted by the obstruction to right ventricular outflow, may be
supplemented by a PDA. Peak systolic and diastolic pressures in each ventricle are similar and at systemic
level. A large pressure gradient occurs across the obstructed right ventricular outflow tract, and pulmonary
arterial pressure is either normal or lower than normal. The degree of right ventricular outflow obstruction
determines the timing of the onset of symptoms, the severity of cyanosis, and the degree of right ventricular
hypertrophy. When obstruction to right ventricular outflow is mild to moderate and a balanced shunt is present
across the VSD, the patient may not be visibly cyanotic (acyanotic or pink tetralogy of Fallot). When
obstruction is severe, cyanosis will be present from birth and worsen when the ductus begins to close.

Clinical Manifestations
Infants with mild degrees of right ventricular outflow obstruction may initially be seen with heart failure caused
by a ventricular-level left-to-right shunt. Often, cyanosis is not present at birth; but with increasing hypertrophy
of the right ventricular infundibulum as the patient grows, cyanosis occurs later in the 1st yr of life. In infants
with severe degrees of right ventricular outflow obstruction, neonatal cyanosis is noted immediately. In these
infants, pulmonary blood flow may be partially or nearly totally dependent on flow through the ductus arteriosus.
When the ductus begins to close in the 1st few hours or days of life, severe cyanosis and circulatory collapse
may occur. Older children with long-standing cyanosis who have not undergone surgery may have dusky blue
skin, gray sclerae with engorged blood vessels, and marked clubbing of the fingers and toes. Extracardiac
manifestations of long-standing cyanotic congenital heart disease are described in Chapter 428.

In older children with unrepaired tetralogy, dyspnea occurs on exertion. They may play actively for a short time
and then sit or lie down. Older children may be able to walk a block or so before stopping to rest.
Characteristically, children assume a squatting position for the relief of dyspnea caused by physical effort; the
child is usually able to resume physical activity after a few minutes of squatting. These findings occur most
often in patients with significant cyanosis at rest.

Paroxysmal hypercyanotic attacks (hypoxic, blue, or tet spells) are a particular problem during the 1st
2yr of life. The infant becomes hyperpneic and restless, cyanosis increases, gasping respirations ensue, and
syncope may follow. The spells occur most frequently in the morning on initially awakening or after episodes of
vigorous crying. Temporary disappearance or a decrease in intensity of the systolic murmur is usual as flow
across the right ventricular outflow tract diminishes. The spells may last from a few minutes to a few hours.
Short episodes are followed by generalized weakness and sleep. Severe spells may progress to
unconsciousness and, occasionally, to convulsions or hemiparesis. The onset is usually spontaneous and
unpredictable. Spells are associated with reduction of an already compromised pulmonary blood flow, which,
when prolonged, results in severe systemic hypoxia and metabolic acidosis. Infants who are only mildly
cyanotic at rest are often more prone to the development of hypoxic spells because they have not acquired the
homeostatic mechanisms to tolerate rapid lowering of arterial oxygen saturation, such as polycythemia.

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Depending on the frequency and severity of hypercyanotic attacks, one or more of the following procedures
should be instituted in sequence: (1) placement of the infant on the abdomen in the knee-chest position while
making certain that the infant's clothing is not constrictive, (2) administration of oxygen (although increasing
inspired oxygen will not reverse cyanosis caused by intracardiac shunting), and (3) injection of morphine
subcutaneously in a dose not in excess of 0.2mg/kg. Calming and holding the infant in a knee-chest position
may abort progression of an early spell. Premature attempts to obtain blood samples may cause further
agitation and be counterproductive.

Because metabolic acidosis develops when arterial PO2 is <40mmHg, rapid correction (within several minutes)
with intravenous administration of sodium bicarbonate is necessary if the spell is unusually severe and the child
shows a lack of response to the foregoing therapy. Recovery from the spell is usually rapid once the pH has
returned to normal. Repeated blood pH measurements may be necessary because rapid recurrence of acidosis
may ensue. For spells that are resistant to this therapy, intubation and sedation are often sufficient to break the
spell. Drugs that increase systemic vascular resistance, such as intravenous phenylephrine, can improve right
ventricular outflow, decrease the right-to-left shunt, and improve the symptoms. -Adrenergic blockade by the
intravenous administration of propranolol (0.1mg/kg given slowly to a maximum of 0.2mg/kg) has also been
used. Growth and development may be delayed in patients with severe untreated tetralogy of Fallot, particularly
when their oxygen saturation is chronically <70%. Puberty may also be delayed in patients who have not
undergone surgery.

The pulse is usually normal, as are venous and arterial pressures. In older infants and children, the left anterior
hemithorax may bulge anteriorly because of long-standing right ventricular hypertrophy. A substernal right
ventricular impulse can usually be detected. A systolic thrill may be felt along the left sternal border in the 3rd
and 4th parasternal spaces. The systolic murmur is usually loud and harsh; it may be transmitted widely,
especially to the lungs, but is most intense at the left sternal border. The murmur is generally ejection in quality
at the upper sternal border, but it may sound more holosystolic toward the lower sternal border. It may be
preceded by a click. The murmur is caused by turbulence through the right ventricular outflow tract. It tends to
become louder, longer, and harsher as the severity of pulmonary stenosis increases from mild to moderate;
however, it can actually become less prominent with severe obstruction, especially during a hypercyanotic spell
due to shunting of blood away from the right ventricular outflow through the aortic valve. Either the 2nd heart
sound is single, or the pulmonic component is soft. Infrequently, a continuous murmur may be audible,
especially if prominent collaterals are present.

Diagnosis
Roentgenographically, the typical configuration as seen in the anteroposterior view consists of a narrow base,
concavity of the left heart border in the area usually occupied by the pulmonary artery, and normal overall heart
size. The hypertrophied right ventricle causes the rounded apical shadow to be uptilted so that it is situated
higher above the diaphragm than normal and pointing horizontally to the left chest wall. The cardiac silhouette
has been likened to that of a boot or wooden shoe (coeur en sabot) (Fig. 424-2). The hilar areas and lung
fields are relatively clear because of diminished pulmonary blood flow or the small size of the pulmonary
arteries, or both. The aorta is usually large, and in about 20% of patients it arches to the right, which results in
an indentation of the leftward-positioned air-filled tracheobronchial shadow in the anteroposterior view.

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Figure 424-2 Chest x-ray of an 8yr old boy with the tetralogy of Fallot. Note the normal heart size, some elevation of the cardiac
apex, concavity in the region of the main pulmonary artery, right-sided aortic arch, and diminished pulmonary vascularity.

The electrocardiogram demonstrates right axis deviation and evidence of right ventricular hypertrophy. A
dominant R wave appears in the right precordial chest leads (Rs, R, qR, qRs) or an RSR pattern. In some
cases, the only sign of right ventricular hypertrophy may initially be a positive T wave in leads V3R and V1. The
P wave is tall and peaked suggesting right atrial enlargement (see Fig. 417-6).

Two-dimensional echocardiography establishes the diagnosis (Fig. 424-3) and provides information about the
extent of aortic override of the septum, the location and degree of the right ventricular outflow tract obstruction,
the size of the pulmonary valve annulus and main and proximal branch pulmonary arteries, and the side of the
aortic arch. The echocardiogram is also useful in determining whether a PDA is supplying a portion of the
pulmonary blood flow. In a patient without pulmonary atresia, echocardiography usually obviates the need for
catheterization before surgical repair.

Figure 424-3 Echocardiogram in a patient with the tetralogy of Fallot. This parasternal long-axis two-dimensional view
demonstrates anterior displacement of the outflow ventricular septum that resulted in stenosis of the subpulmonic right ventricular
outflow tract, overriding of the aorta, and an associated ventricular septal defect. Ao, overriding aorta; LA, left atrium; LV, left
ventricle; RV, right ventricle.

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Cardiac catheterization demonstrates a systolic pressure in the right ventricle equal to the systemic pressure,
since the right ventricle is connected directly to the overriding aorta. If the pulmonary artery is entered, the
pressure is markedly decreased, although crossing the right ventricular outflow tract, especially in severe
cases, may precipitate a tet spell. Pulmonary arterial pressure is usually lower than normal, in the range of 5-
10mmHg. The level of arterial oxygen saturation depends on the magnitude of the right-to-left shunt; in pink
tets, the systemic oxygen saturation may be normal, whereas in a moderately cyanotic patient at rest, it is
usually 75-85%.

Selective right ventriculography will demonstrate all of the anatomical features. Contrast medium outlines the
heavily trabeculated right ventricle. The infundibular stenosis varies in length, width, contour, and distensibility
(Fig. 424-4). The pulmonary valve is usually thickened, and the annulus may be small. In patients with
pulmonary atresia and VSD, echocardiography alone is not adequate to assess the anatomy of the pulmonary
arteries and MAPCAs. Cardiac CT is extremely helpful, and cardiac catheterization with injection into each
arterial collateral is indicated. Complete and accurate information regarding the size and peripheral distribution
of the main pulmonary arteries and any collateral vessels (MAPCAs) is important when evaluating these
children as surgical candidates.

Figure 424-4 Lateral view of a selective right ventriculogram in a patient with the tetralogy of Fallot. The arrow points to an
infundibular stenosis that is below the infundibular chamber (C). The narrowed pulmonary valve orifice is seen at the distal end of
the infundibular chamber.

Aortography or coronary arteriography outlines the course of the coronary arteries. In 5-10% of patients with the
tetralogy of Fallot, coronary artery abnormalities may be present, most commonly an aberrant coronary artery
crossing over the right ventricular outflow tract; this artery must not be cut during surgical repair. Verification of
normal coronary arteries is important when considering surgery in young infants who may need a patch across
the pulmonary valve annulus. Echocardiography can usually delineate the coronary artery anatomy;
angiography is reserved for cases in which questions remain.

Complications

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Before the age of corrective surgery, patients with tetralogy of Fallot were susceptible to several serious
complications. For this reason, most children undergo complete repair (or in some cases palliation) in infancy,
and therefore these days these complications are rare. Cerebral thromboses, usually occurring in the cerebral
veins or dural sinuses and occasionally in the cerebral arteries, are a sequelae of extreme polycythemia and
dehydration. Thromboses occur most often in patients younger than 2yr. These patients may have iron-
deficiency anemia, frequently with hemoglobin and hematocrit levels in the normal range (but too low for
cyanotic heart disease). Therapy consists of adequate hydration and supportive measures. Phlebotomy and
volume replacement with albumin or saline are indicated in extremely polycythemic patients who are
symptomatic.

Brain abscess is less common than cerebral vascular events and extremely rare today. Patients with a brain
abscess are usually older than 2yr. The onset of the illness is often insidious and consists of low-grade fever or
a gradual change in behavior, or both. Some patients have an acute onset of symptoms that may develop after
a recent history of headache, nausea, and vomiting. Seizures may occur; localized neurologic signs depend on
the site and size of the abscess and the presence of increased intracranial pressure. CT or MRI confirms the
diagnosis. Antibiotic therapy may help keep the infection localized, but surgical drainage of the abscess is
usually necessary (Chapter 596).

Bacterial endocarditis may occur in the right ventricular infundibulum or on the pulmonic, aortic, or, rarely,
tricuspid valves. Endocarditis may complicate palliative shunts or, in patients with corrective surgery, any
residual pulmonic stenosis or VSD. Heart failure is not a usual feature in patients with tetralogy of Fallot, with
the exception of some young infants with pink or acyanotic tetralogy of Fallot. As the degree of pulmonary
obstruction worsens with age, the symptoms of heart failure resolve and eventually the patient experiences
cyanosis, often by 6-12mo of age. These patients are at increased risk for hypercyanotic spells at this time.

Associated Anomalies
A PDA may be present, and defects in the atrial septum are occasionally seen. A right aortic arch occurs in
20% of patients, and other anomalies of the pulmonary arteries and aortic arch may also be seen. Persistence
of a left superior vena cava draining into the coronary sinus is common but not a concern. Multiple VSDs are
occasionally present and must be diagnosed before corrective surgery. Coronary artery anomalies are present
in 5-10% and can complicate surgical repair. Tetralogy of Fallot may also occur with an atrioventricular septal
defect, often associated with Down syndrome.

Congenital absence of the pulmonary valve produces a distinct syndrome that is usually marked by signs of
upper airway obstruction (Chapter 422.1). Cyanosis may be absent, mild, or moderate; the heart is large and
hyperdynamic; and a loud to-and-fro murmur is present. Marked aneurysmal dilatation of the main and branch
pulmonary arteries results in compression of the bronchi and produces stridulous or wheezing respirations and
recurrent pneumonia. If the airway obstruction is severe, reconstruction of the trachea at the time of corrective
cardiac surgery may be required to alleviate the symptoms.

Absence of a branch pulmonary artery, most often the left, should be suspected if the roentgenographic
appearance of the pulmonary vasculature differs on the two sides; absence of a pulmonary artery is often
associated with hypoplasia of the affected lung. It is important to recognize the absence of a pulmonary artery
because occlusion of the remaining pulmonary artery during surgery seriously compromises the already
reduced pulmonary blood flow.

As one of the conotruncal malformations, tetralogy of Fallot can be associated with DiGeorge syndrome or
Shprintzen velocardiofacial syndrome, also known by the acronym CATCH 22 (cardiac defects, abnormal
facies, thymic hypoplasia, cleft palate, hypocalcemia). Cytogenetic analysis using fluorescence in situ
hybridization demonstrates deletions of a large segment of chromosome 22q11 known as the DiGeorge critical
region. Deletion or mutation of the gene encoding the transcription factor Tbx1 has been implicated as a
possible cause of DiGeorge syndrome, although several other genes have been identified as possible
candidates or modifier genes.

Treatment
Treatment of tetralogy of Fallot depends on the severity of the right ventricular outflow tract obstruction. Infants

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with severe tetralogy require urgent medical treatment and surgical intervention in the neonatal period. Therapy
is aimed at providing an immediate increase in pulmonary blood flow to prevent the sequelae of severe hypoxia.
The infant should be transported to a medical center adequately equipped to evaluate and treat neonates with
congenital heart disease under optimal conditions. Prolonged, severe hypoxia may lead to shock, respiratory
failure, and intractable acidosis and will significantly reduce the chance of survival, even when surgically
amenable lesions are present. It is critical that normal body temperature be maintained during the transfer since
cold increases oxygen consumption, which places additional stress on a cyanotic infant, whose oxygen delivery
is already limited. Blood glucose levels should be monitored because hypoglycemia is more likely to develop in
infants with cyanotic heart disease.

Neonates with marked right ventricular outflow tract obstruction may deteriorate rapidly because, as the ductus
arteriosus begins to close, pulmonary blood flow is further compromised. The intravenous administration of
prostaglandin E1 (0.01-0.20?g/kg/min), a potent and specific relaxant of ductal smooth muscle, causes
dilatation of the ductus arteriosus and usually provides adequate pulmonary blood flow until a surgical
procedure can be performed. This agent should be administered intravenously as soon as cyanotic congenital
heart disease is clinically suspected and continued through the preoperative period and during cardiac
catheterization. Because prostaglandin can cause apnea, an individual skilled in neonatal intubation should be
readily available.

Infants with less severe right ventricular outflow tract obstruction who are stable and awaiting surgical
intervention require careful observation. Acyanotic patients can fairly quickly progress to having cyanotic
episodes. Prevention or prompt treatment of dehydration is important to avoid hemoconcentration and possible
thrombotic episodes. Oral propranolol (0.5-1mg/kg every 6hr) had been used in the past to decrease the
frequency and severity of hypercyanotic spells, but with the excellent surgical results available today, surgical
treatment is now indicated as soon as spells begin.

Infants with symptoms and severe cyanosis in the 1st mo of life usually have marked obstruction of the right
ventricular outflow tract. Two options are available in these infants. The first is corrective open heart surgery
performed in early infancy and even in the newborn period in critically ill infants. This approach has widespread
acceptance today with excellent short- and long-term results and has supplanted palliative shunts (see later) for
most cases. Early total repair carries the theoretical advantage that early physiologic correction allows for
improved growth of the branch pulmonary arteries. In infants with less severe cyanosis who can be maintained
with good growth and absence of hypercyanotic spells, primary repair is performed electively at between 4 and
6mo of age.

Corrective surgical therapy consists of relief of the right ventricular outflow tract obstruction by resecting
obstructive muscle bundles and by patch closure of the VSD. If the pulmonary valve is stenotic, as it usually is,
a valvotomy is performed. If the pulmonary valve annulus is too small or the valve is extremely thickened, a
valvectomy may be performed, the pulmonary valve annulus split open, and a transannular patch placed across
the pulmonary valve ring. The surgical risk of total correction in major centers is <5%. A right ventriculotomy
was once the standard approach; a transatrial-transpulmonary approach is routinely performed to reduce the
long-term risks of a large right ventriculotomy. In patients in whom repair has been delayed to childhood,
increased bleeding in the immediate postoperative period may be a complicating factor due to their extreme
polycythemia.

The second option, more common in previous years, is a palliative systemic-to-pulmonary artery shunt
(Blalock-Taussig shunt) performed to augment pulmonary artery blood flow. The rationale for this surgery,
previously the only option for these patients, is to augment pulmonary blood flow to decrease the amount of
hypoxia and improve linear growth, as well as augment growth of the branch pulmonary arteries. The modified
Blalock-Taussig shunt is currently the most common aortopulmonary shunt procedure and consists of a Gore-
Tex conduit anastomosed side to side from the subclavian artery to the homolateral branch of the pulmonary
artery (Fig. 424-5). Sometimes the shunt is brought directly from the ascending aorta to the main pulmonary
artery and in this case is called a central shunt. The Blalock-Taussig operation can be successfully performed in
the newborn period with shunts 3-4mm in diameter and has also been used successfully in premature infants.

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Figure 424-5 Physiology of a Blalock-Taussig shunt in a patient with the tetralogy of Fallot. Circled numbers represent oxygen
saturation values. The intracardiac shunting pattern is as described for Figure 424-1. Blood shunting left to right across the shunt
from the right subclavian artery to the right pulmonary artery increases total pulmonary blood flow and results in a higher oxygen
saturation than would exist without the shunt (see Fig. 424-1).

Postoperative complications after a Blalock-Taussig shunt include chylothorax, diaphragmatic paralysis, and
Horner syndrome. Postoperative pulmonary overcirculation leading to symptoms of cardiac failure may be
caused by too large a shunt; its treatment is described in Chapter 436. Vascular problems other than a
diminished radial pulse and occasional long-term arm length discrepancy are rarely seen in the upper extremity
supplied by the subclavian artery used for the anastomosis.

After a successful shunt procedure, cyanosis diminishes. The development of a continuous murmur over the
lung fields after the operation indicates a functioning anastomosis. A good continuous shunt murmur may not
be heard until several days after surgery. The duration of symptomatic relief is variable. As the child grows,
more pulmonary blood flow is needed and the shunt eventually becomes inadequate. When increasing
cyanosis develops rapidly, thrombosis of the shunt should be suspected, often requiring emergent surgery.

Prognosis
After successful total correction, patients are generally asymptomatic and are able to lead unrestricted lives.
Uncommon immediate postoperative problems include right ventricular failure, transient heart block, residual
VSD with left-to-right shunting, and myocardial infarction from interruption of an aberrant coronary artery.
Postoperative heart failure (particularly in patients with a large transannular outflow patch) may require
anticongestive therapy. The long-term effects of isolated, surgically induced pulmonary valvular insufficiency
are still being defined as more patients with repaired tetralogy of Fallot reach middle age, but insufficiency is
generally well tolerated through adolescence. Many patients after tetralogy repair and all of those with
transannular patch repairs have a to-and-fro murmur at the left sternal border, usually indicative of mild outflow
obstruction and mild to moderate pulmonary insufficiency. Patients with more marked pulmonary valve
insufficiency also have moderate to marked heart enlargement and may develop tricuspid regurgitation as the
tricuspid valve annulus dilates. These patients will develop a holosystolic murmur at the lower left sternal
border. Patients with a severe residual gradient across the right ventricular outflow tract may require
reoperation, but mild to moderate obstruction is usually present and does not require reintervention.

Follow-up of patients 5-20yr after surgery indicates that the marked improvement in symptoms is generally

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maintained. Asymptomatic patients nonetheless have lower than normal exercise capacity, maximal heart rate,
and cardiac output. These abnormal findings are more common in patients who underwent placement of a
transannular outflow tract patch and may be less frequent when surgery is performed at an early age. As these
children move into adolescence and adulthood, some (more commonly those with transannular patches) will
develop right ventricular dilation due to severe pulmonary regurgitation. After reaching adulthood, careful
lifelong follow-up by a specialist in adult congenital heart disease is important. Serial echocardiography and
magnetic resonance angiography (MRA) are valuable tools for assessing the degree of right ventricular dilation,
the presence of right ventricular dysfunction, and for quantifying the regurgitant fraction. Valve replacement is
indicated for those patients with increasing right ventricular dilation and tricuspid regurgitation.

Conduction disturbances can occur after surgery. The atrioventricular node and the bundle of His and its
divisions are in close proximity to the VSD and may be injured during surgery; however, permanent complete
heart block after tetralogy repair is rare. When present, it should be treated by placement of a permanently
implanted pacemaker. Even transient complete heart block in the immediate postoperative period is rare; it may
be associated with an increased incidence of late-onset complete heart block and sudden death. In contrast,
right bundle branch block is quite common on the postoperative electrocardiogram. The duration of the QRS
interval has been shown to predict both the presence of residual hemodynamic derangement and the long-term
risk of arrhythmia and sudden death. Research is ongoing to determine the effectiveness of biventricular pacing
(in which a pacemaker is used to resynchronize the activation of the right and left ventricles) in improving
hemodynamics in those patients with long ventricular conduction delays.

A number of children have premature ventricular beats after repair of the tetralogy of Fallot. These beats are of
concern in patients with residual hemodynamic abnormalities; 24-hr electrocardiographic (Holter) monitoring
studies should be performed to be certain that occult short episodes of ventricular tachycardia are not
occurring. Exercise studies may be useful in provoking cardiac arrhythmias that are not apparent at rest. In the
presence of complex ventricular arrhythmias or severe residual hemodynamic abnormalities, prophylactic
antiarrhythmic therapy, catheter ablation, or implantation of an implantable defibrillator is warranted. Re-repair
is indicated if significant residual right ventricular outflow obstruction or severe pulmonary insufficiency is
present, because arrhythmias may improve after hemodynamics are restored to a more normal level.

Bibliography

ApitzC,WebbGD,RedingtonAN:Tetralogy of Fallot.Lancet2009;374:1462-1470.

BoudjemlineY,FermontL,Le BidoisJ,et al:Prevalence of 22q11 deletion in fetuses with conotruncal cardiac

defects: a 6-year prospective study.J Pediatr2001;138:520-524.

DubinAM,FeinsteinJA,ReddyVM,et al:Electrical resynchronization: a novel therapy for the failing right

ventricle.Circulation2003;107:2287-2289.

GreenwaySC,PereiraAC,LinJC,et al:De novo copy number variants identify new genes and loci in isolated
sporadic tetralogy of Fallot.Nat Genet2009;41:931-935.

GriffinHR,HallDH,TopfA,et al:Genetic variation in VEGF does not contribute significantly to the risk of congenital
cardiovascular malformation.PLoS ONE2009;4:e4978.

JonasRA:Early primary repair of tetralogy of Fallot.Semin Thorac Cardiovasc Surg Pediatr Card Surg
Annu2009;12:39-47.

MalhotraSP,HanleyFL:Surgical management of pulmonary atresia with ventricular septal defect and major
aortopulmonary collaterals: a protocol-based approach.Semin Thorac Cardiovasc Surg Pediatr Card Surg
Annu2009.145-151.

MomenahTS,El OakleyR,Al NajashiK,et al:Extended application of percutaneous pulmonary valve

implantation.J Am Coll Cardiol2009;53:1859-1863.

ReddyVM,McElhinneyDB,AminZ,et al:Early and intermediate outcomes after repair of pulmonary atresia with
ventricular septal defect and major aortopulmonary collateral arteries: experience with 85
patients.Circulation2000;101:1826-1832.

mk:@MSITStore:C:\Users\fadel\Desktop\Nelson-'s-Textbook-of-Pediatrics.-19th-ed.-2011... 7/24/2014
MD Consult: Page 10 of 10

SchultzAH,WernovskyG:Late outcomes in patients with surgically treated congenital heart disease.Semin

Thorac Cardiovasc Surg Pediatr Card Surg Annu2005;8:145-156.

WaldRM,HaberI,WaldR,et al:Effects of regional dysfunction and late gadolinium enhancement on global right
ventricular function and exercise capacity in patients with repaired tetralogy of Fallot.Circulation2009;119:1370-
1377.

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