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									Pathology Lab IV - Congenital Heart Disease
                                          Arben Santo

CASE OUTLINE.                                      3. Compare and contrast left-to-right and
Case Presentation: Paul S.                         right-to-left shunts.
Introduction                                       4. Describe atrial septal defect, and discuss
Pathophysiology of circulation in congenital       types, pathology, pathophysiology and
heart disease                                      clinical manifestations of this malformation.
Atrial septal defect (ASD)                         5. Describe ventricular septal defect, and
Patent foramen ovale (PFO)                         discuss types, pathology, pathophysiology
Ventricular septal defect (VSD)                    and clinical manifestations.
Tetralogy of Fallot                                6. Describe tetralogy of Fallot, and discuss
Coarctation of the aorta                           pathology, pathophysiology and clinical
                                                   manifestations of this condition.
OBJECTIVES.                                        7. Describe coarctation of the aorta, and
At the completion of this case study, the          discuss its pathology, pathophysiology and
student will be able to:                           clinical manifestations
1. Define congenital heart disease and
describe the most frequent types.                  REFERENCES.
2. Describe types of pathophysiologic              1. Robbins and Cotran Pathologic Basis of
alterations of circulation in congenital heart     Disease, 8th edition, 2010, pages 537-545.
disease.                                           2. Hurst’s The Heart, 11th edition, 2004,
                                                   pages 1785-1883.

Two-year-old Paul was brought for evaluation of failure to thrive. He has not been gaining
weight normally and tends to tire easily while playing. Pregnancy and delivery were
uncomplicated, and a physical examination showed a well-developed child with no cyanosis.
There is no jugular venous distension and no liver enlargement. The point of maximal intensity
was displaced to the left, and a harsh holosystolic murmur was auscultated at the left sternal
border. Biventricular hypertrophy was evident from the ECG.
Chest radiograph showed enlarged heart and dilated pulmonary vessels. Echocardiography
showed a moderate infracristal defect in the ventricular septum. Cardiac catheterization showed
moderate pulmonary hypertension with normal pulmonary vascular resistance. A diagnosis of
ventricular septal defect was madeand the child was scheduled for cardiac surgical intervention.

Congenital heart disease is a general term used to describe abnormalities of the heart and blood
vessels that are present from birth. Much such disorders arise from faulty embryogenesis during
gestational weeks 3 through 8, when major cardiovascular structures from.

The incidence of congenital heart disease is approximately 1% of the pediatric population.
Almost one third of infants who are born with heart malformations have critical disease. Without
early treatment they would die in infancy or childhood. The remainder has cardiac defects that do
not represent a threat to life or require surgery and survive to adult life. The mildest form of heart
malformation may even not become evident until adulthood (e.g. atrial septal defect, coarctation
of aorta).

Twelve cardiac malformations count for about 85% of cases; their relative frequencies are
presented in Table 1. Bicuspid aortic valve is the single most common congenital heart
malformation. It may be present in as many as 1-2% of the general population. Because the
bicuspid aortic valves are not stenotic during childhood, they are entirely silent during the first
three decades of life, and they are not included in the overall incidence of congenital heart

The varied structural heart malformations give rise to three different patterns of circulatory
alterations (Table 2).
1. Left-to-right shunting.
The term “shunt” refers to an abnormal connection allowing blood to flow directly from one side
of the cardiac circulation to the other. A left-to-right shunt allows a portion of the pulmonary
venous return (i.e. oxygenated blood) to escape back to the right heart rather than being pumped
to the aorta, thereby reducing cardiac output by the amount of the shunted volume. Tissue
oxygen delivery is reduced. The ratio of total pulmonary blood flow to total systemic blood flow,
the Qp/Qs ratio, is a useful tool for quantifying the net shunt. A Qp/Qs ratio of 1:1 is normal and
indicates that there is no shunting. A Qp/Qs ratio of > 1:1 indicates that pulmonary flow exceeds
systemic flow and defines a net left-to-right shunt. The most important types of congenital heart
disease causing left-to-right shunt are atrial septal defect, ventricular septal defect and patent
ductus arteriosus.

A left-to-right shunt imposes a significant volume overload on the right heart, main pulmonary
artery and pulmonary vasculature. The consequences are enlargement of the right heart and main
pulmonary artery. On the other hand the left ventricular output decreases because of the reduced
preload. If the left ventricular output is not enough to meet the demands of the body, the patient
will display growth retardation.
2. Right-to-left shunting.
Right-to-left shunt causes a mixture of unoxygenated blood from the right heart (systemic
venous return) with oxygenated blood returning from the pulmonary circulation. The oxygen
content of the systemic arterial blood falls in proportion of the volume of systemic venous blood
mixing with the normal pulmonary venous return. With the reduced oxygen content, even with
an increased left ventricular output, tissue oxygen delivery falls and the work capacity of the
muscles is limited. A Qp/Qs ratio of < 1:1 indicates a net right-to-left shunt. Right-to-left shunts
are associated with left heart volume overload. Detection and localization of the shunt are
accomplished by noting a decrease in O2 content as blood is sampled in the left heart chambers
and aorta. The most important types of congenital heart disease causing right-to-left shunt are
tetralogy of Fallot, transposition of great arteries, persistent truncus arteriosus, tricuspid atresia,
total anomalous pulmonary venous connection, Eisenmenger syndrome, and Ebstein anomaly.
These malformations are referred to as “cyanotic congenital heart disease”. A right-to left shunt
leads to severe hypoxemia, central cyanosis and clubbing. Right-to-left shunting does not
respond to oxygen administration. The partial pressure of CO2 is normal as the patient increases
minute ventilation to blow off CO2 derived from the shunt.
3. Obstruction.
Some congenital cardiac malformations (e.g. coarctation of the aorta, aortic valvular stenosis and
pulmonary valvular stenosis) produce narrowing of the ventricular outflow tract, semilunar
valves or great arteries. An obstruction in any of these pathways increases ventricular afterload.
Ventricular hypertrophy occurs in response, which results in thicker chamber walls, normal
systolic performance but reduced chamber compliance and higher filling pressures in the atrium.
With severe noncompliance (ventricular diastolic dysfunction) pulmonary venous congestion
may occur (with pulmonary edema) or systemic venous congestion may occur with jugular
venous distension, liver enlargement, ascites and peripheral edema.
All patients with hemodynamically significant obstructions of large ventriculoarterial pathways
present with a heart murmur, the result of the turbulent flow created as blood passes under
pressure through the stenosis.

Atrial septal defect (ASD) is an abnormal opening in the atrial septum caused by incomplete
tissue formation that allows communication of blood between the left and the right atria. ASD
allows pulmonary venous return to pass from the left to the right atrium, resulting in right atrial
and right ventricular chamber dilation, the extent of which depends on the size of the shunt.
ASD is one of the most commonly recognized congenital cardiac anomalies in adults, but it is
rarely diagnosed and even less commonly results in disability in infants.
Patients, especially those with small or isolated defects, are usually asymptomatic through the
first 3 decades of life, though more than 70% become impaired by the 5th decade.

Five basic types of atrial septal defects are known.
1. Ostium secundum. Ostium secundum defect represent nonclosure of the foramen ovale. It is
the most common yet least serious type of ASDs (70% of all ASDs).
(A) Location. This defect occurs in the area of the fossa ovalis and presumably results from
excessive fenestration or resorption of septum primum. The patent foramen ovale usually results
from abnormal resorption of the septum primum during the formation of the foramen secundum.
(B) Embryological development of atrial septum. During fetal development, the rudimentary
atrium is divided by the septum primum which grows toward the developing atrioventricular
valves, except for an inferior space that is the ostium primum. Ostium primum remains a narrow
passageway between atria but later completely closes. However, before this occurs, a central
perforation appears in septum primum, allowing continuous unrestricted flow from the right
atrium to the left atrium. This perforation, the second opening in the septum primum, is
called ostium secundum. As the atria expand to either side of the truncus arteriosus, a fold is
produced within the atria just to the right of septum primum. This passively formed fold
is septum secundum.

The leading edge of septum secundum is concave in shape and is called the foramen ovale. It
comes to overlay the ostium secundum but does not interfere with blood flow from right to left
through ostium secundum. After birth, with onset of pulmonary blood flow and elevation of left
atrial pressure, the septum primum is pushed against the septum secundum, effectively closing
the ostium secundum.
Anatomically, the foramen ovale comprises overlapping portions of septum primum and septum
secundum, acting as a one-way flap valve allowing continuous right-to-left flow during fetal life.
After birth, septum primum fuses to septum secundum, completing septation of the atria.
2. Ostium primum. Ostium primum defect is located at the lower portion of the atrial septum, at
the level of tricuspid and mitral valves. It is caused by incomplete fusion of septum primum with
endocardial cushion.
3. Sinus venosus. Sinus venosus defect is located in the upper portion of the atrial septum near
the entry of superior vena cava. It is due to abnormal fusion between embryologic sinus venosus
and the atrium.
4. Coronary sinus. Coronary sinus defect is characterized by unroofed coronary sinus and
persistent left superior vena cava that drains into the left atrium.
5. Common atrium. There are rare cases in which there is only a common atrium, the atrial
septa do not develop at all. Another name for this uncommon anomaly is cor triloculare

A left-to-right shunt occurs because the right atrium and ventricle are more distensible than the
left counterparts and not because of significant pressure differences between the two atria.
1. Volume overload. The magnitude of the shunt is usually described by the Qp/Qs ratio, where
Qp is the pulmonary flow, and Qs is the systemic flow. Atrial septal defect is considered
significant when it is > 5 mm in diameter. In this case the Qp/Qs >= 1.5:1 i.e. the volume of
blood going to lungs is at least 1.5 times larger than the volume of blood going to aorta. Qp/Qs
ratios can be estimated by Doppler echocardiography or by cardiac catheterization. Significant
atrial septal defects impose a volume overload on the right atrium and the right ventricle. The
right atrium, the right ventricle and the main pulmonary artery become enlarged. Most patients
tolerate the large volume load on the right heart and pulmonary circuit quite well for many years.
In some cases the pulmonary flow may be 2-4 times the systemic flow.
2. Pulmonary vascular disease and pulmonary arterial hypertension. If pulmonary vascular
disease occurs, it usually does not so before the 3rd decade. The earliest morphologic lesion is
intimal thickening in arterioles. The pulmonary arterial pressure then rises, followed by the
development of medial hypertrophy of muscular pulmonary arteries and appearance of plexiform
lesions. The right ventricular wall hypertrophies and atherosclerosis may occur in the major
pulmonary arteries. With the development of pulmonary artery hypertension, the left-to-right
shunt decreases because of the increased pressures in the right heart. In some patients this
process continues until there is eventually shunt reversal with a right-to-left atrial septal defect
flow. The phenomenon in which a left-to-right shunt (caused by atrial or ventricular septal
defect) progresses to shunt reversal is known as Eisenmenger syndrome.

1. Symptoms and signs.
Most children with ASD are typically asymptomatic. Diagnosis is made following the discovery
of a murmur, during a routine health maintenance examination.
On physical examination children show normal growth and development, but the majority of
them have a slender habitus.
The two components of the second heart sound are characteristically widely split with the
interval of splitting fixed, i.e. it does not wary with respiration. This is due to increased right
heart volume load and delay in closure of the pulmonary valve.
A midsystolic murmur of grade 2 to 3 intensity is found over the pulmonary artery in the 2nd left
intercostal space. This is due to markedly increased pulmonary blood flow and relative
pulmonary stenosis. A diastolic murmur over the lower left sterna border is due to increased flow
across the tricuspid valve.
The right-to-left shunting is reflected by cyanosis and clubbing.
Only 5% of ASD cases are symptomatic in the first year of life. These patients display
congestive heart failure, and recurrent chest infections.
2. Chest radiography.
Chest X-ray shows mild-to-moderate cardiac enlargement caused by dilatation of the right atrium
and the right ventricle. The main and branch pulmonary arteries are large and prominent. The left
atrium is not dilated.
3. Electrocardiogram.
An rSR’ pattern in lead V1 is characteristic and indicates right ventricular enlargement. The QRS
axis is slightly directed to the right (+100, the normal range of QRS axis is -30 degrees to +90
4. Cardiac catheterization.
There is significant increase in oxygen saturation in the blood samples drawn from the right
atrium, right ventricle and mail pulmonary artery (85%, reference level 75%) compared with
those obtained from the superior or inferior vena cava (75%, reference level 75%).Pulmonary
arterial and right ventricular systolic pressures are normal or only slight elevated. The right and
left atrial pressures are identical.
5. Echocardiogram.
Two-dimensional and Doppler echocardiography with color flow mapping permits visualization
of atrial septal defects of various types, as well as increased right atrial and right ventricular
6. Natural history.
Children with atrial septal defect are rarely symptomatic but symptoms become more common in
the 2nd and 3rd decade. By age 40 the majority of patients develop the symptoms associated with
ASD. There are four common clinical presentations of ASD in the adult population:
(A) Congestive heart failure. Adult patients complain of progressive shortness of breath with
exertion. The mechanism of congestive heart failure is a volume overload in the right ventricle
and pulmonary arteries in combination with an inefficient left ventricle because of a
continuously reduced preload.
(B) Atrial arrhythmias. Atrial fibrillation results from stretching of the conduction system in the
enlarged atrium.
(C) Stroke. Stroke caused by paradoxical embolization of thrombus through the defect. Although
patients have a net left-to-right shunt through the defect, virtually all have transient flow reversal
with Valsalva maneuver.
(D) Pulmonary vascular disease. Pulmonary vascular disease with serious pulmonary artery
hypertension affects 15% of the adult ASD population. Pulmonary arterial hypertension results
in right ventricular failure, high right ventricular end diastolic volumes impede filling from the
right atrium.

Patent foramen ovale (PFO) is another communication in the atrial septum.

Fusion of the septum primum and the septum secundum closes the foramen ovale. Complete
closure occurs in most individuals. However in 30% of people, incomplete fusion leads to the
persistence of the flap valve, and a probe can be passed from the right atrium to the left atrium
via the foramen ovale.

Because it is present in all newborns, a patent foramen ovale technically is not a “congenital”
defect. Since the left atrial pressure exceedes the right atrial pressure the septum primum is
pushed rightward, against the septum secundum, shutting the flap of the patent foramen ovale.
When the right atrial pressure rises intermittently with Valsalva maneuver or other isometric
strains, the leaflets of the patent foramen ovale may separate with leftward excursion of septum
primum, allowing flow from the right atrium to the left atrium.

In general patients with patent foramen ovale are never identified because they have no
symptoms. Paradoxical thromboembolism is the most frequent clinical presentation. Although
thromboembolic events to noncritical organs such as spleen, liver and kidney may go unnoticed,
cerebral embolization may produce transient ischemic attack.
A number of clinical syndromes are related to patent foramen ovale, including migraine
headache, hypoxemia, and decompression illness in drivers. The mechanism of the migraine
relationship to persistent foramen ovale remains unknown. Hypoxemia may occur in a patient
with patent foramen ovale, deep venous thrombosis and pulmonary thromboembolism. When the
right ventricular performance id diminished secondary to pulmonary thromboembolic event, the
raised right heart pressures favor a right-to-left flow across the patent foramen ovale.
Decompression illness is presumed secondary to right-to-left air embolization through the
persistent foramen ovale in divers.

A ventricular septal defect (VSD) is a congenital abnormal opening in the ventricular septum that
allows communication of blood between the left and right ventricles. VSD can occur as an
isolated lesion or in combination with other congenital cardiac anomalies.

VSD is the most common congenital heart defect encountered after bicuspid aortic valve. VSD
accounts for 25-40% of all cardiac malformations at birth.

There are several types of ventricular septal defect.
1. Membranous defect.
Membranous defect lies in the LV outflow tract just below the aortic valve. This occurs in the
membranous septum with defects in the adjacent muscular portion of the septum. Membranous
defect is the most common type of VSDs and account for 80% of such defects.
2. Supracristal defect.
Supracristal defect accounts for 5% of isolated VSDs in the United States but 30% of isolated
VSDs in Japan. This type involves the right ventricular and aortic outflow regions.
3. Muscular defect.
Muscular defects (trabecular) are entirely bounded by the muscular septum and are often
multiple. The term Swiss-cheese septum has been used to describe multiple muscular VSDs.
These VSDs account for 10% of all defects.
4. Posterior defect.
Posterior defects lie posterior to the septal leaflet of the tricuspid valve and involve the inflow
portion of the septum. About 5% of VSDs are of this type.
The consequences of VSD depend on the size of the defect and the pulmonary vascular
1. Pathophysiology of small septal ventricular defects.
A small defect offers a large resistance to flow. There is no elevation of right ventricular or
pulmonary arterial pressure and the left-to-right shunt is small. This type of defect imposes little
physiologic burden on the heart, although patients are always at risk for infective endocarditis.
2. Pathophysiology of moderate septal ventricular defects.
A defect of moderate size allows a large left-to-right shunt with resulting left atrial hypertension
and dilatation and left ventricular volume overload. The development of pulmonary vascular
disease is unusual.
2. Pathophysiology of large septal ventricular defects.
A defect of large size (equal or greater than the aortic valve orifice) offers virtually no resistance
to flow and systemic pressures are present in both the ventricles, the aorta and the pulmonary
artery. The relative resistance of the two vascular beds directly governs the proportion of blood
entering the two circulations. At birth, pulmonary vascular resistance is high and there is little if
any left-to-right shunting despite the presence of a large defect. This resistance to flow gradually
falls over the first few weeks of life, permitting a progressively greater amount of blood to flow
through the defect. In some infants with large defects, the left ventricular volume overload
eventually leads to left ventricular “failure” with elevated left ventricular end-diastolic and left
atrial pressures and pulmonary congestion.

1. Symptoms and signs.
(A) Clinical presentation of small defects. Infants of children with a small isolated defect are
asymptomatic. A holosystolic murmur along the lower left sternal border is characteristic. The
second heart sund is not accentuated since the pulmonary arterial pressure is normal.
(B) Clinical presentation of large defects. Infants with a large defect are restless, irritable and
underweight. They have a left-to-right shunt and pulmonary hypertension. Auscultatory findings
include a holosystolic murmur at the lower left sternal border, commonly associated with a thrill
at the same area. The second heart sound is narrowly split, with a loud pulmonary component.
The third heart sound gallops at the apex. Moderate respiratory distress and hepatic enlargement
may be present. With the passage of time, one may observe signs of a diminishing left-to-right
shunt with less dyspnea, and improved weight gain. This clinical improvement may be a result of
the defect becoming smaller.
(C) Eisenmenger syndrome. The clinical picture of advanced pulmonary vascular disease
secondary to a congenital left-to-right shunt, or Eisenmenger syndrome, is that of a relatively
comfortable older child, or young adult with mild cyanosis and clubbing in whom one find a
prominent a wave in the jugular venous pulse, a second heart sound that is narrowly split or
virtually single with a very loud pulmonary component. A diastolic murmur of pulmonary
regurgitation or systolic murmur of tricuspid regurgitation may appear.
2. Chest radiograph.
In the presence of a small defect, the heart’s size and shape and the pulmonary blood flow are
barely altered.
With large defects, there is moderate to marked enlargement of the heart, with prominence of the
main pulmonary arterial segment and impressive overcirculation in the peripheral lung fields.
The left atrium is dilated.
With increasing pulmonary obstructive vascular disease there is diminution in heart size toward
normal, while the central pulmonary arteries remain dilated.
The peripheral pulmonary arterial markings become attenuated and a “pruned” effect is produced
in the outer third of the lung fields.
3. ECG.
With a small defect the ECG features are normal.
With large defect the mean QRS axis tends to remain oriented to the right and there is no
regression in right ventricular voltage (as it normally occurs in newborns). The left ventricular
voltages gradually increase resulting in a pattern of biventricular hypertrophy within the first
weeks of life.
The left atrial and right atrial enlargements are usually present.
With the development of pulmonary vascular disease, the mean QRS axis tends to remain
oriented to the right but the evidence of left ventricular and left atrial hypertrophy lessens or
4. Echocardiogram.
Two-dimensional imaging, pulsed-wave Doppler with color-flow mapping and continuous-wave
Doppler echocardiography permit the identification of the defect, the position of the opening and
its relations to other hart structures.
5. Cardiac catheterization.
Catheterization studies show an increase in oxygen saturation at the right ventricular level
reflecting the left-to-right ventricular shunt. With small defects the right ventricular and
pulmonary artery pressures are normal.
With large defects these pressures are near the systemic levels and the mean left atrial pressure
may be elevated to the range of 10-15 mm Hg (normal left atrial pressure is about 8 mm Hg).

1. Pulmonary hypertension.
Pulmonary hypertension is a common complication of large VSDs (and many other congenital
heart diseases), and the status of the pulmonary vascular bed often is the principal determinant of
the clinical manifestations, the course, and whether surgical treatment is feasible.
2. Pulmonary vascular obstructive disease.
Left-to-right shunting first leads to increased pulmonary blood flow, which is followed by the
development of pulmonary vascular obstructive disease (PVOD) in the small pulmonary arteries.
Obstructive structural changes within the pulmonary vascular bed are associated with elevations
of pulmonary vascular resistance. For this reason POVD is complicated ultimately with
pulmonary arterial hypertension. Patients with large left-to-right shunts can be complicated with
increased pulmonary arterial pressures near the systemic levels.
Pulmonary vascular resistance is normally high at birth (8-10 Wood units), but falls rapidly
immediately after birth, owing to onset of ventilation and subsequent release of hypoxic
pulmonary vasoconstriction. By 8 weeks it has reached the normal adult level of 1-3 Wood units.

These changes are associated by a gradual dilatation of pulmonary arteries, thinning of the
muscular walls and the development of new arteries and arterioles. This latter process contributes
to over 90% of the intraacinar pulmonary vessels present in adults.
In patients with large left-to-right shunts the diminution of the pulmonary muscle mass and
pulmonary resistance is less rapid and of a lesser magnitude than in a normal infant. Chronic
increased blood flow produces a characteristic series of histopathologic changes in the smaller
pulmonary arteries and arterioles which are classified into 6 grades. Grade 1 is medial
hypertrophy; grade 2 consists of intimal proliferation leading to severe narrowing of the vascular
lumen; grade 3 ensues with intimal proliferation leading to occlusion of smaller pulmonary
arteries; grade 4 is characterized by development of generalized dilatation of distal arteries and
the appearance of plexiform lesions; grade 5 is the thinning and fibrosis of media associating
plexiform lesions; the last grade 6 consists of necrotizing arteritis of pulmonary small blood
As obliterative changes in the pulmonary vascular bed develop, pulmonary resistance increases
and pulmonary blood flow generally decreases. Eventually a point is reached where surgical
closure of the defect will produce only a small diminution of blood flow and pulmonary arterial
pressure. At this point surgery is not recommended since the benefits are minimal. Without
surgery these patients survive as examples of Eisenmenger syndrome, in which pulmonary
vascular resistance is equal or greater than systemic vascular resistance and at least some right-
to-left shunting occurs. Some of these patients can survive for several decades and lead
productive lives, with relatively mild symptoms and few limitations. The presence of ventricular
defects is a useful “blow off’ for increasing pulmonary arterial hypertension. This situation is
defined as a pulmonary vascular resistance of 11 Wood units and a Qp/Qs (pulmonary/systemic
blood flow) ratio of 1.5:1.

Fortunately the majority of VSDs are small and do not present a serious clinical problem.
Approximately 25% of these small defects close spontaneously by 18 months, 50% by 4 years
and 75% by 10 years. Even large defects tend to become smaller but the likelihood of eventual
spontaneous closure is much lower (in the range of 50%).
Congestive heart failure is an inevitable complication of a large VSD. The risk of death with
congestive heart failure is in the range of 11%.
Children with a pulmonary artery systolic pressure higher than 50% of the systemic arterial
systolic pressure are at risk for pulmonary obstructive vascular disease. Pulmonary obstructive
vascular disease becomes progressively less likely to regress after the first year of life.
The risk of infective endocarditis in patients with VSD is 4-10%.

Tetralogy of Fallot is characterized by four features: (1) biventricular origin of the aorta above a
large (2) ventricular septal defect, (3) obstruction to pulmonary blood flow and (4) right
ventricular hypertrophy.

Tetralogy of Fallot is the most common cyanotic heart defect. Tetralogy of Fallot occurs in 10%
of all congenital heart defects.

Tetralogy of Fallot is a conotruncal defect resulting from anterior malalignment of the
infundibular (aorticopulmonary) septum. This single morphologic defect gives rise to the 4 main
components of the malformation: ventricular septal defect, aortic valve overriding the ventricular
septum, narrowing of the right ventricular outflow tract, and right ventricular hypertrophy.

Pulmonary stenosis is due to the right ventricular infundibular subpulmonary hypertrophy, with
an enlarged infundibular muscle obstructing blood flow into the pulmonary artery. The
infundibulum’s exhibits a significant degree of stenosis and is the dominant site of obstruction to
pulmonary blood flow that is characteristic of tetralogy. The pulmonary valve is often malformed,
usually being either bicuspid or unicuspid.
Because of the abnormal division of infundibular septum, the aorta is displaced into a more
dextral position overlying the ventricular septal defect. The ventricular septal defect is
immediately below the overriding aorta.
Characteristically the pulmonary trunk and pulmonary arteries are thin-walled and with narrow
lumen (hypoplasia). The heart is hypertrophied as to give it a boot shape.

When associated atrial septal defect exists, this anomaly is referred to as “pentalogy of Fallot”.

1. Right-to-left shunting.
Since the ventricular septal defect is large with an area about as great as that of the aortic valve,
both ventricles and the aorta have essentially the same systolic pressures.
However the pulmonary stenosis is severe causing a right-to-left shunting, arterial desaturation
and subsequent polycythemia. When the pulmonary stenosis is very severe, collateral vessels to
the lungs arise from aorta to sustain pulmonary blood flow.
The right ventricle is “protected” from excessive pressure and work, since the right ventricular
systolic pressure cannot exceed the left ventricular one because of the large VSD. Therefore
heart failure is uncommon.
2. Hypercyanotic episodes.
Hypercyanotic episodes (hypoxic spells) in patients with tetralogy are of uncertain origin. It is
likely that some episodes are caused by unusual hyperactivity of muscular fibers in the right
ventricular outflow tract that exaggerate the infundibular stenosis, increasing pulmonary
resistance and thus increasing right-to-left shunting. Some spells may be caused by a decrease in
peripheral resistance and systemic arterial pressure, which also may cause the right-to-left
shunting to increase and pulmonary blood flow to decrease.

1. Symptoms and signs.
(A) Cyanosis. Tetralogy of Fallot is the most common congenital heart defect that causes
cyanosis. Pentalogy of Fallot is not distinguished clinically from the tetralogy of Fallot.

Most of patients are diagnosed by prenatal ultrasound or present in the first days or weeks of life
with a heart murmur. If the right ventricular obstruction is severe, cyanosis is present at birth and
is exacerbated when the ductus closes. If the right ventricular obstruction is milder, the infant
may be acyanotic with left-to-right flow through the VSD and occasionally may develop heart
failure. In this group right ventricular obstruction gradually increases, reducing the left-to-right
shunt; eventually, when infundibular resistance and pulmonary resistance exceed systemic
resistance, right-to-left shunting develops and cyanosis results.
Dyspnea with exertion occurs commonly in toddlers, but signs of congestive heart failure do not
appear during childhood unless there is a superimposed illness, such as anemia or infective
(B) Hypercyanotic episodes. Attacks of suddenly increasing cyanosis associated with hyperpnea
or hypoxic spells are common between ages 2 months and 2 years. They occur mostly in the
morning and are associated with irritability. The frequency and duration wary widely, but
prolonged episodes can lead to syncope, seizure and death.
(C) Squatting and clubbing of the fingers. Growth is usually normal, unless cyanosis is
extreme. Squatting with exercise is common from 1.5 to 10 years of age. Clubbing of the fingers
and toes occurs after 3 months of age and is proportional to the level of cyanosis.
A systolic thrill may be palpable at the left midsternal border with a harsh midsystolic murmur in
that location. The murmur ends before the second heart sound which is characteristically single.
2. Chest radiograph.
The total heart size is usually normal on chest X-rays but right ventricular enlargement is present
in the lateral view. Pulmonary flow is diminished. The pulmonary segment on posteroanterior X-
rays is concave and the apex is elevated, giving the “coeur en sabot” (boot-shaped) contour.
3. ECG.
In tetralogy of Fallot, the mean QRS axis of the ECG is usually to the right, between +90 and +
210 degrees. There is right ventricular hypertrophy, with a tall R wave in the right precordial
leads and a deep S wave in the left leads. Some of these patients have right atrial hypertrophy.
4. Echocardiogram.
Two-dimensional echocardiography can delineate the anatomic components of tetralogy.
5. Cardiac catheterization.
The right ventricular systolic pressure is equal to the pressure in the left ventricle and aorta. The
pressure in the pulmonary artery is normal or low. Systemic arterial oxygen saturation is reduced
because of the right-to-left shunting from the right ventricle to the left one.

Progressive hypoxemia in the first years of life is expected. Survival to adult life is rare without
palliation or correction. The presence of additional sources of blood supply (aorto-pulmonary
collaterals) modifies the rate of progress to cyanosis and its complications. Bacterial endocarditis
is a serious complication. In the second half of 1900s a palliative intervention, such as Blalock-
Taussig shunt (a graft between the subclavian artery and the ipsilateral pulmonary artery) was
common. The corrective surgery is now the procedure of choice and now is performed at any age.

The right-to-left shunt in the tetralogy of Fallot leads to hypoxemia and its sequelae: cyanosis,
clubbing, polycythemia, brain abscess, exercise intolerance and cerebrovascular accidents.
1. Cyanosis.
Cyanosis is a bluish tinge to the color of the skin caused by the presence of at least 3-5 g/dL of
reduced hemoglobin.
2. Clubbing.
Clubbing is a deformity of fingers and fingernails consisting in the thickening of the whole distal
finger (resembling a drumstick). There is also an associated loss of the normal <165˚ angle
between the nailbed and the fold.
3. Polycythemia.
Polycythemia is the exaggeration of red cell production to maintain the oxygen carrying capacity
of the blood. The increased hemoglobin concentration at any given oxygen saturation will result
in more reduced hemoglobin, thus exaggerating cyanosis.
4. Brain abscess.
The CNS can be target of cerebrovascular accidents or brain abscess. These accidents occur to
anemic patients and are due directly to extreme hypoxia. Cerebrovascular accidents when occur
to polycythemic patients are due to sludging i.e., increases blood viscosity secondary to
hematocrits in the range of 65% or higher.
Brain abscess is due to bacteremia primarily with mouth organisms that cross from the venous
system to the arterial system right to left from shunting.
Coarctation of the aorta is a discrete narrowing of the distal segment of the aortic arch. In infants
the lesion lies either opposite to the ductus or in a preductal location. In adolescents and adults it
is usually at the ligamentum arteriosum.

The characteristic lesion is a deformity at the media of the aorta that involves the anterior,
superior and posterior walls and is represented by a curtain-like infolding of the wall that causes
the lumen to be narrowed and eccentric. The principal cardiac anomaly is left ventricular
hypertrophy. The proximal aorta may show a moderate degree of cystic medial necrosis. Beyond
the coarctation, the lining may show a localized jet lesion.
Prominent collaterals are characteristic in older infants, children and adolescents. They may be
divided into anterior and posterior systems. The anterior system originates with the internal
mammary arteries and makes use of the epigastric arteries in the ebdominal wall to supply the
lower extremities. The posterior system involves parascapular arteries connected with the
posterior intercostal arteries and carries blood to the distal aortic compartment for the supply of
the abdominal viscera.

The most commonly associated defects are tubular hypoplasia of the aortic arch, patent ductus
arteriosus, and ventricular septal defect. A bicuspid aortic valve is present in 46% of cases.
In some infants left ventricular endocardial fibroelastosis may be associated.
Approximately 45% of children with Turner syndrome have coarctation.

Coarctation of the aorta occurs in approximately 4% of all infants and children with congenital
heart disease. Age at detection of coarctation of the aorta is dependent on severity of obstruction
and coexistence of other lesions. Studies continue to document that coarctation of the aorta is
often missed in the first year of life.

In most instances, both the systolic and diastolic arterial pressures above the coarctation are
elevated. Below the coarctation, the systolic pressure is lower than in the upper extremities, and
the diastolic pressure is usually near or slightly below the normal range.
The mechanism of upper extremity hypertension appears to involve the increased resistance to
aortic flow produced by the coarctation itself, the decreased capacity and distensibility of the
vessels into which the left ventricle ejects and humoral factors.

1. Symptoms and signs.
The clinical manifestations of aortic coarctation mainly depend on the degree of obstruction after
ductal closure, on the degree of developed collateral circulation, and on the presence of
associated cardiac lesions.
(A) Classic ‘adult’ type of coarctation. In favorable cases, an isolated aortic coarctation results in
mild-to-moderate obstruction after complete ductal closure at 7–10 days of life. This leads to
the classic ‘adult’ type of aortic coarctation, with a constricted segment opposite the ductus and a
collateral flow that starts developing during fetal life and continues thereafter.
Patients are asymptomatic and coarctation is discovered during a routine physical examination
for athletic participation or employment. On physical examination, patients have (a) blood
pressure discrepancies between the upper and lower extremities, (b) systolic murmur best heard
posteriorly over the thoracic spine (interscapular and left infrascapular area), and (c) reduced
lower extremity pulses to palpation.
Frequently the blood pressure discrepancies are small, thus masking the lesion that may be
discovered only after many years or decades, mainly for its sequelae. These are represented by
(a) arterial hypertension, (b) left ventricular hypertrophy and subsequent congestive heart failure,
(c) aortic dissection or (d) intracranial aneurysmal lesions.
(B) ‘Neonatal’ type of coarctation.
In the severe forms of aortic coarctation, the neonate or infant quickly becomes severely
symptomatic, with tachypnea, tachycardia, and increased work of breathing. In the ‘neonatal’
type, collateral circulation is absent or inadequate as long as the ductus remains open, and
pulmonary hypertension is always present. When the ductus is open, systemic hypertension is
mild, but femoral femoral pulses are quite normal. During the first 2 weeks of life, closure of the
ductus arteriosus may severely alter the circulatory system. The lower body becomes severely
hypoperfused, and acidosis and renal failure suddenly occur; the left ventricle acutely fails and
dilates as systemic resistance abruptly increases. Mitral regurgitation and left-to-right shunt
across the stretched foramen ovale, together with right ventricular dilatation, contribute to
massive cardiomegaly uniformly seen at chest roentgenogram. Clinically, the patient is moribund
and resuscitation must be started immediately together with prostaglandin E1 infusion, which
results in ductus reopening and lower body perfusion with reversal of congestive heart failure.
Therefore, heart failure in isolated aortic coarctation has a bimodal distribution. It occurs in
about 65% of infants, it is uncommon between 1 and 30 years of age, and it develops again in
patients surviving more than 40 years.
2. Chest radiograph.
The pattern is one of cardiac enlargement in a symptomatic infant and pulmonary edema. In
older and asymptomatic children the heart’s size is generally at the upper limits of normal with a
left ventricular prominence.
A figure “3” configuration of the left margin of the aorta at the level of coarctation may be seen
in frontal views. The upper curve is formed by the dilated aorta just above the coarctation, the
central indentation by the coarctation itself, and the lower curve by the post-stenotic dilatation
below the constricted segment.

Notching of the inferior margin of the ribs from pressure erosion by tortuous and enlarged
intercostals arteries acting as collaterals is seldom present before 7-8 years of age.
3. ECG.
The electrocardiogram of a symptomatic infant reflects right ventricular or biventricular
hypertrophy. T wave inversion in the left precordial leads is common.
In older asymptomatic children the ECG is usually normal or may indicate left ventricular and
left atrial hypertrophy.
4. Echocardiogram.
Two-dimensional echocardiographic imaging permits visualization of the coarctation. In infants
with heart failure left ventricular dilatation and decreased contractility are common.
5. Cardiac catheterization.
Study of symptomatic infants characteristically reveals left atrial and left ventricular
hypertension and a significant systolic pressure difference between the left ventricle and the
femoral artery.

In the era before surgical intervention, 50% of all patients with coarctation died within the first 3
decades. The median age of death was 31 years. Death was most frequently caused by a
complication of hypertension such as heart failure, stroke, or aortic dissection.
Surgical therapy is the preferred treatment for aortic coarctation. Coarctation of the aorta can be
successfully corrected by resection with end-to-end anastomosis. Approximately 80% of patients
are asymptomatic for about 20 years following surgery. However, patients are at increased risk
of developing recurrent hypertension, congestive heart failure, premature atherosclerosis,
ischemic heart disease, thromboembolic stroke, infective endarteritis and aortic rupture.

                      1.                              complications of congenital heart
Berta is a 4-year-old girl. A heart
murmur is noted during her preschool                        Brain abscess
physical examination. An
echocardiogram reveals a large defect                       Pneumonia
between the right and the left atrium                       Mycardial infarction
occupying the floor of fossa ovalis. The
limbus and the margins of fossa ovalis                      Paradoxical embolism
were well formed on the edge of the
                                                            Pulmonary hypertension
defect. What is the most likely
diagnosis?                                                                   3.

     Atrial septal defect, common atrium              Berta is a 4-year-old girl. A heart
                                                      murmur is noted during her preschool
     Atrial septal defect, ostium secundum            physical examination. An
                                                      echocardiogram reveals a large defect
     Atrial septal defect, ostium primum
                                                      between the right and the left atrium
     Atrial septal defect, sinus venosus              occupying the floor of fossa ovalis. The
                                                      limbus and the margins of fossa ovalis
     Atrial septal defect, coronary sinus             were well formed on the edge of the
                      2.                              defect. What pathophysiologic pattern of
                                                      circulatory alterations is Berta most
Gail, a 15-year-old girl, is brought to ER            likely to have?
with heart palpitations and dyspnea. Her
past medical history is significant for an                  Obstruction of the left ventricular
unrepaired atrial septal defect. Physical                   outflow tract or aorta
examination reveals cyanosis, distended
jugular veins, liver enlargement and a                      Left-to-right shunt
systolic ejection murmur over the                           Obstruction of the right ventricular
pulmonary artery in the 2nd left                            outflow tract or pulmonary arteries
intercostal space. The patient has most
likely developed which of the following                     No shunt, no obstruction
     Right-to-left shunt                      (interscapular area and left infrascapular
                                              area). There is hypertension in the
                     4.                       upper extremities and low blood
                                              pressure in both legs. What is the
The number and size of ventricular            appropriate diagnosis?
septal defects does not influence the
morbidity and mortality in infants with
ventricular septal defects.                        Pentalogy of Fallot
                                                   Eisenmenger syndrome
                                                   Atrial septal defect
                                                   Coarctation of the aorta
                                                   Ventricular septal defect
Daniel, a 2-year-old child, is suspected                           7.
of having a small ventricular septal
defect. Which of the following is the         Olga, an 8-month-old girl with Turner
most common initial presentation (signs       syndrome, is brought to ER by her
or symptoms) of this defect?                  parents who complain that their
                                              daughter is breathing rapidly and not
     Brain abscess                            eating. Physical examination reveals
                                              rapid breathing (tachypnea), pallor,
     Cyanosis on exertion and crying          absent femoral pulses, and a murmur
     Systolic murmur over the left            heard posteriorly over the thoracic spine
     parasternal region, noted on a routine   (interscapular area and left infrascapular
     clinical examination in an               area). There is hypertension in the
     asymptomatic child                       upper extremities and low blood
                                              pressure in both legs. What
     Failure to thrive and feeding            pathophysiologic pattern of circulatory
     difficulties                             alterations is Olga most likely to have?
     Clubbing and/or history of squatting
                     6.                            Obstruction of the right ventricular
                                                   outflow tract or pulmonary arteries
Olga, an 8-month-old girl with Turner              Obstruction of the left ventricular
syndrome, is brought to ER by her                  outflow tract or aorta
parents who complain that their
daughter is breathing rapidly and not              No shunt, no obstruction
eating. Physical examination reveals               Right-to-left shunt
rapid breathing (tachypnea), pallor,
absent femoral pulses, and a murmur                Left-to-right shunt
heard posteriorly over the thoracic spine

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