Congenital Heart Diseases

Special Pathology

Congenital heart diseases

abnormalities of the heart or great vessels that are
present at birth
faulty embryogenesis during gestational weeks 3 through 8
major cardiovascular structures develop.

Congenital malformations of the heart encompass a

broad spectrum of defects,
severe anomalies that cause death in the perinatal period,
mild lesions that produce only minimal symptoms, even in adult
life.

Generally accepted incidence is approximately 1% of live

births
higher in premature infants and in stillborns.

Most common type of heart disease among children.

 Patients surviving with congenital heart disease

is increasing rapidly
Because of clinical advances
by 2020 there will be an estimated 750,000 adults
with congenital heart disease.

Surgery can correct the hemodynamic

abnormalities
repaired heart may still not be completely normal
Although adaptive initially, such changes can elicit
late-onset arrhythmias, ischemia, or myocardial
dysfunction, sometimes many years after surgery

Myocardial hypertrophy and a cardiac

remodeling brought about by the congenital
defect may be irreversible.

 General concepts regarding the etiology of

congenital malformations
unknown in almost 90% of cases.
Environmental factors,
congenital rubella infection, are causal in many
instances.

Genetic factors are also clearly involved,

as evidenced by familial forms of congenital heart
disease
well-defined associations with certain
chromosomal abnormalities (e.g., trisomies 13, 15,
18, and 21 and Turner syndrome).

 Cardiac morphogenesis
involves multiple genes
tightly regulated to ensure an effective embryonic
circulation.
Key steps involve specifying cardiac cell fate, morphogenesis
and looping of the heart tube, segmentation and growth of the
cardiac chambers, cardiac valve formation, and connection of
the great vessels to the heart.

The molecular pathways controlling such cardiac

development
provide a foundation for understanding the basis of some
congenital heart defects.

Several congenital heart diseases are associated with

mutations in transcription factors.
Mutations of the TBX5 transcription factor cause the atrial and
ventricular septal defects seen in Holt-Oram syndrome.
Mutations in the transcription factor NKX2.5 are associated
with isolated atrial septal defects (ASDs).

 Since different cardiac structures can share the same

developmental pathways,
dissimilar lesions may be related to a common genetic defect

The unifying feature of many outflow tract defects is the

abnormal development of neural crest-derived cells,
whose migration into the embryonic heart is required for outflow tract
formation.

In particular, genes located on chromosome 22 have a

major role in forming the conotruncus, the branchial arches,
and the human face;
Now known that deletions of chromosome 22q11.2 underlie 15% to
50% of outflow tract abnormalities.
can also cause developmental anomalies of the fourth branchial arch
and derivatives of the third and fourth pharyngeal pouches
leading to thymic and parathyroid hypoplasia
resultant immune deficiency (Di George syndrome) and hypocalcemia.

 Twelve disorders account for 85% of

congenital heart disease; their frequencies
are shown in Table.
Congenital heart diseases can be
subdivided into three major groups:
Malformations causing a left-to-right shunt
Malformations causing a right-to-left shunt
(cyanotic congenital heart diseases)
Malformations causing obstruction

Malformation

Incidence per Million Live Births

Ventricular septal defect

4482

42

Atrial septal defect

1043

10

Pulmonary stenosis

836

Patent ductus arteriosus

781

Tetralogy of Fallot

577

Coarctation of the aorta

492

Atrioventricular septal defect

396

Aortic stenosis

388

Transposition of the great arteries

388

Truncus arteriosus

136

Total anomalous pulmonary venous connection

120

Tricuspid atresia

118

TOTAL

9757

 Shunt
abnormal communication between chambers or blood vessels.
Depending on pressure relationships, shunts permit the flow of blood
from the left heart to the right heart (or vice versa).
Right-to-left shunt
dusky blueness of the skin (cyanosis) results
pulmonary circulation is bypassed
poorly oxygenated blood enters the systemic circulation.

Left-to-right shunts
increase pulmonary blood flow
not associated (at least initially) with cyanosis
expose the low-pressure, low-resistance pulmonary circulation to
increased pressure and volume, resulting in right ventricular hypertrophy
and-eventually-right-sided failure.

obstructive congenital heart disease

Some developmental anomalies obstruct vascular flow by narrowing the
chambers, valves, or major blood vessels;
A complete obstruction is called an atresia.
In some disorders (e.g., tetralogy of Fallot), an obstruction (pulmonary
stenosis) is associated with a shunt (right-to-left through a ventricular
septal defect [VSD]).

 Left-to-right shunts;
most common type of congenital cardiac malformation (Fig.)
atrial and ventricular septal defects, and patent ductus arteriosus.
Atrial septal defects are typically associated with increased pulmonary
blood volumes
ventricular septal defects and patent ductus arteriosus result in both
increased pulmonary blood flow and pressure.

These malformations can be asymptomatic or can cause fulminant

CHF at birth.
Cyanosis is not an early feature of these defects, but it can occur
late,
Eisenmenger syndrome.
after prolonged left-to-right shunting has produced pulmonary hypertension
sufficient to yield right-sided pressures that exceed those on the left and thus
result in a reversal of blood flow through the shunt

Rationale for early intervention, either surgical or nonsurgical

Once significant pulmonary hypertension develops,
structural defects of congenital heart disease are considered irreversible

 ASDs
normal atrial septation (Fig.)
begins as an ingrowth of the septum primum from the dorsal wall of the
common atrial chamber toward the developing endocardial cushion;
a gap, termed the ostium primum, initially separates the two.

Continued growth and fusion of the septum with the endocardial cushion
ultimately obliterates the ostium primum; however,
a second opening, ostium secundum, now appears in the central area of the
primary septum
allowing continued flow of oxygenated blood from the right to left atria, essential
for fetal life

As the ostium secundum enlarges, the septum secundum makes its

appearance adjacent to the septum primum.
This septum secundum proliferates to form a crescent-shaped structure
overlapping a space termed the foramen ovale.

The foramen ovale is closed on its left side by a flap of tissue derived from
the primary septum;
this flap acts as a one-way valve that allows right-to-left blood flow during
intrauterine life.

At the time of birth, falling pulmonary vascular resistance and rising

systemic arterial pressure causes left atrial pressures to exceed those in
the right atrium;
result is a functional closure of the foramen ovale.

In most individuals the foramen ovale is permanently sealed by fusion of the

primary and secondary septa, although a
minor degree of patency persists in about 25% of the general population.

 Abnormalities in this sequence result in the development

of the various ASDs;
three types are recognized
ostium secundum ASD
The most common (90%) is the, which
occurs when the septum secundum does not enlarge sufficiently to
cover the ostium secundum

Ostium primum ASDs are

less common (5% of cases); these
occur if the septum primum and endocardial cushion fail to fuse and
are often associated with abnormalities in other structures derived
from the endocardial cushion (e.g., mitral and tricuspid valves).

The sinus venosus ASDs

(5% of cases) are located near the entrance of the superior vena
cava and have been
associated with frameshift mutations in the NKX2.5 transcription
factor.

Morphology
Ostium secundum
ASDs are typically smooth-walled defects near the foramen ovale,
usually without other associated cardiac abnormalities. Because of the
left-to-right shunt, hemodynamically significant lesions are accompanied by
increased volume load on the right side of the heart
right atrial and ventricular dilation, right ventricular hypertrophy, and dilation of the
pulmonary artery

Ostium primum
ASDs occur at the lowest part of the atrial septum
can extend to the mitral and tricuspid valves, reflecting the close relationship
between development of the septum primum and endocardial cushion.
Abnormalities of the atrioventricular valves are usually present, typically in
the form of a cleft in the anterior leaflet of the mitral valve or septal leaflet of
the tricuspid valve.
In more severe cases, the ostium primum defect is accompanied by a VSD
and severe mitral and tricuspid valve deformities, with a resultant common
atrioventricular canal.

Sinus venosus
ASDs are located high in the atrial septum
often accompanied by anomalous drainage of the pulmonary veins into the
right atrium or superior vena cava.

 Clinical Features
ASDs
most common defects to be first diagnosed in adults.
less likely to spontaneously close
left-to-right shunts, as a result of the
lower pressures in the pulmonary circulation and right side of the heart.
well tolerated, especially if they are less than 1 cm in diameter; even
larger lesions do not usually produce any symptoms in childhood.

With time, however, pulmonary vascular resistance can increase,

resulting in pulmonary hypertension.
less than 10% of patients with uncorrected ASD.

The objectives of surgical closure of ASDs are;

reversal of the hemodynamic abnormalities and the
prevention of complications, including heart failure, paradoxical
embolization, and irreversible pulmonary vascular disease.

Mortality is low
postoperative survival is comparable to that of a normal population.

Ostium primum defects are more likely to be associated with

evidence of CHF, in part because of the high frequency of
associated mitral insufficiency.

 VSDs
Incomplete closure of the ventricular septum allows left-to-right
shunting
Most common congenital cardiac anomaly at birth
Normally formed by the fusion of;
an intraventricular muscular ridge that grows upward from the apex
of the heart with
a thinner membranous partition that grows downward from the
endocardial cushion.

The basal (membranous) region is the site of approximately 90%

of VSDs
last part of the septum to develop

Overall incidence in adults is lower than that of ASDs

more common at birth than ASDs,
most VSDs close spontaneously in childhood,

Commonly associated with other cardiac malformations

Roughly 30% of VSDs occur in isolation

 Morphology
Size and location of VSDs are variable;
minute defects in the muscular or membranous
portions of the septum
large defects involving virtually the entire septum.

Defects with a significant left-to-right shunt;

right ventricle is hypertrophied and often dilated

The diameter of the pulmonary artery is

increased;
increased volume ejected by the right ventricle.

Vascular changes typical of pulmonary

hypertension are common

 Clinical Features
Small VSDs;
may be asymptomatic
those in the muscular portion of the septum may close
spontaneously during infancy or childhood.

Larger defects;
severe left-to-right shunt,
often complicated by pulmonary hypertension and CHF.
Progressive pulmonary hypertension;
resultant reversal of the shunt and cyanosis,
earlier and more common in patients with VSDs than ASDs;
Needs early surgical correction

Small- or medium-sized defects;

produce jet lesions in the right ventricle
prone to superimposed infective endocarditis.

 Patent ductus arteriosus

During intrauterine life;
blood flow from the pulmonary artery to the aorta
bypassing the unoxygenated lungs

Shortly after birth; the ductus constricts in response to;

increased arterial oxygenation,
decreased pulmonary vascular resistance, and
declining local levels of prostaglandin E2.

In healthy term infants

functionally nonpatent within 1 to 2 days after birth;
complete, structural obliteration occurs within the first few months of
extrauterine life to form the ligamentum arteriosum.

Ductal closure is often delayed (or even absent) in infants with

hypoxia
resulting from respiratory distress or heart disease

PDAs account for about 7% of cases of congenital heart lesions;

90% are isolated defects
remaining occur with other congenital defects, most commonly VSDs.

 Morphology
The ductus arteriosus arises from the left
pulmonary artery and joins the aorta just distal to
the origin of the left subclavian artery.
Proximal pulmonary arteries, left atrium, and
ventricle can become dilated
In PDAs some of the oxygenated blood flowing out
from the left ventricle is shunted back to the lungs
resultant volume overload

Right heart hypertrophy and dilation.

With the development of pulmonary hypertension,
atherosclerosis of the main pulmonary arteries and
proliferative changes in more distal pulmonary vessels

 Clinical Features
PDAs;
high-pressure left-to-right shunts,
audible as harsh "machinery-like" murmurs.

A small PDA - no symptoms

larger bore defects - lead to the Eisenmenger syndrome
with cyanosis and CHF.
The high-pressure shunt also predisposes affected
individuals to infective endocarditis
There is general agreement that isolated PDAs should be
closed as early in life as is feasible,
Preservation of ductal patency
by administering prostaglandin E
critically important for infants with various forms of congenital
heart disease wherein the
PDA is the only means to provide systemic or pulmonary blood
flow (e.g., aortic or pulmonic atresia).

Ironically, then, the ductus can be either life threatening

or lifesaving.

 Right-to-Left Shunts
Cardiac malformations associated with right-to-left shunts
are distinguished by
cyanosis at or near the time of birth.
poorly oxygenated blood from the right side of the heart is
introduced directly into the arterial circulation.

Two of the most important conditions associated with

cyanotic congenital heart disease are;
tetralogy of Fallot
transposition of the great vessels (Fig.)

Clinical findings associated with severe, long-standing

cyanosis;
clubbing of the fingertips (hypertrophic osteoarthropathy) and
polycythemia

In addition, right-to-left shunts permit venous emboli to

bypass the lungs and directly enter the systemic
circulation
paradoxical embolism

 Tetralogy of Fallot
5% of all congenital cardiac malformations, tetralogy of Fallot
most common cause of cyanotic congenital heart disease
The four features of the tetralogy are;
(1) VSD,
(2) obstruction to the right ventricular outflow tract (subpulmonic
stenosis),
(3) an aorta that overrides the VSD, and
(4) right ventricular hypertrophy

All of the features result from anterosuperior displacement of the

infundibular septum, so that there is
abnormal division into the pulmonary trunk and aortic root.

Even untreated, some tetralogy patients can survive into adult

life
Clinical severity largely depends on the degree of the pulmonary
outflow obstruction.

 Morphology
The heart is large and "boot shaped" in tetralogy of
Fallot as a result of;
right ventricular hypertrophy;
the proximal aorta is typically larger than normal, with a
diminished pulmonary trunk.
The left-sided cardiac chambers are normal sized, while the
right ventricular wall is markedly thickened and may even
exceed that of the left.
The VSD lies in the vicinity of the membranous portion of the
interventricular septum, and the aortic valve lies immediately
over the VSD
The pulmonary outflow tract is narrowed, and, in a few
cases, the pulmonic valve may be stenotic

Additional abnormalities are present in many cases,

including PDA or ASD;
actually beneficial in many respects, because they permit
pulmonary blood flow.

Clinical Features
The hemodynamic consequences of tetralogy of Fallot are;
right-to-left shunting,
decreased pulmonary blood flow,
increased aortic volumes.

The extent of shunting (and the clinical severity) is determined by the

amount of right ventricular outflow obstruction.
If the pulmonic obstruction is mild, the condition resembles an isolated VSD,
because the high left-sided pressures on the left side cause a left-to-right shunt
with no cyanosis.

More commonly, marked stenosis causes significant right-to-left shunting

consequent cyanosis early in life.

As patients with tetralogy grow, the pulmonic orifice does not enlarge,
despite an overall increase in the size of the heart.
Hence, the degree of stenosis typically worsens with time resulting in increasing
cyanosis.

The lungs are protected from hemodynamic overload by the pulmonic

stenosis, so that pulmonary hypertension does not develop.

As with any cyanotic heart disease, patients develop erythrocytosis with

attendant hyperviscosity, and hypertrophic osteoarthropathy; the rightto-left shunting also increases the risk for infective endocarditis,
systemic emboli, and brain abscesses.
Surgical correction of this defect is now possible in most instances.

 Transposition of the Great Arteries

Discordant connection of the ventricles to
their vascular outflow
The embryologic defect
abnormal formation of the truncal and
aortopulmonary septa;
aorta arises from the right ventricle and the
pulmonary artery emanates from the left ventricle
(Fig.)

The atrium-to-ventricle connections are

normal (concordant)
right atrium joining right ventricle and
left atrium emptying into left ventricle.

 The functional outcome;

separation of the systemic and pulmonary
circulations
a condition incompatible with postnatal life
shunt exists for adequate mixing of blood and
delivery of oxygenated blood to the aorta.

stable shunt (35%)

Patients with TGA and a VSD

unstable shunts (65%)

Patients with only a patent foramen ovale or PDA
can close and often require surgical intervention
within the first few days of life.

 Morphology
TGA has many variants;
abnormal origin of the pulmonary trunk and aortic
root
patients surviving beyond the neonatal period;
Varying combinations of ASD, VSD, and PDA

Right ventricular hypertrophy;

functions as the systemic ventricle

Left ventricle becomes somewhat atrophic;

support the low-resistance pulmonary circulation

 Clinical Features
Early cyanosis
predominant manifestation of TGA

The outlook for neonates with TGA depends on;

the degree of the shunting
the magnitude of the tissue hypoxia
the ability of the right ventricle to maintain systemic pressures.

Procedures that enhance arterial oxygen saturation;

Infusions of prostaglandin E2
maintain patency of the ductus arteriosus

Atrial septostomy
create ASDs

Even with stable shunting, most uncorrected TGA

patients still die within the first months of life.
Consequently, affected individuals usually undergo
corrective surgery (switching the great arteries) within
weeks of birth.

 Congenital Obstructive Lesions

Obstruction to blood flow can occur at the
level of the heart valves or within a great
vessel.
Obstruction can also occur within a chamber
subpulmonic stenosis in tetralogy of Fallot.

Relatively common examples of congenital

obstruction include;
pulmonic valve stenosis,
aortic valve stenosis or atresia
coarctation of the aorta.

 Aortic Coarctation
relatively common structural anomaly
most important form of obstructive congenital heart
disease.
Males are affected twice as often as females;
females with Turner syndrome frequently have aortic coarctation

Two classic forms have been described (Fig):

"infantile" form with hypoplasia of the aortic arch proximal to a
PDA, and an
"adult" form in which there is a discrete ridgelike infolding of the
aorta, just opposite the ligamentum arteriosum distal to the arch
vessels.

Coarctation of the aorta may occur as a solitary defect

more than 50% of cases, it is accompanied by a bicuspid
aortic valve.
Congenital aortic stenosis, ASD, VSD, or mitral regurgitation may
also occur.
In some cases berry aneurysms in the circle of Willis coexist.

 Morphology
Preductal ("infantile") coarctation;
tubular narrowing of the aortic segment between the left
subclavian artery and the ductus arteriosus
usually patent
main source of blood delivered to the distal aorta.
Because the right side of the heart must perfuse the body distal
to the narrowing, the
right ventricle is typically hypertrophied and dilated
pulmonary trunk is also dilated to accommodate the increased blood
flow.

Postductal ("adult") coarctation;

more common
sharply constricted by a ridge of tissue at or just distal to the
ligamentum arteriosum
made up of smooth muscle and elastic fibers that are continuous
with the aortic media and are lined by a thickened layer of intima.

The ductus arteriosus is closed.

Proximal to the coarct, the aortic arch and its branch vessels are
dilated and, in older patients, often atherosclerotic
left ventricle is hypertrophic.

Clinical Features
depend almost entirely on the severity of the narrowing and the patency
of the ductus arteriosus.
Preductal coarctation of the aorta with a PDA;

usually leads to manifestations early in life, hence the older designation of

infantile coarctation
cause signs and symptoms immediately after birth.
delivery of poorly oxygenated blood through the ductus arteriosus produces
cyanosis localized to the lower half of the body.
Femoral pulses are almost always weaker than those of the upper
extremeties.
Many such infants do not survive the neonatal period without intervention

Postductal coarctation of the aorta without a PDA;

usually asymptomatic, and the disease may go unrecognized until well into
adult life
upper extremity hypertension, due to poor perfusion of the kidneys, but weak
pulses and a lower blood pressure in the lower extremities.
Claudication and coldness of the lower extremeties result from arterial
insufficiency.
Adults tend to show exuberant collateral circulation "around" the coarctation
involving markedly enlarged intercostal and internal mammary arteries;
expansion of the flow through these vessels leads to radiographically visible
"notching" of the ribs.

SUMMARY

Congenital Heart Disease

Defects of cardiac chambers or the great vessels;
Shunting of blood between the right and left circulation or cause outflow
obstructions.
Left-to-right shunts
most common and typically involve
ASDs, VSDs, or a PDA. These lesions
result in chronic right-sided pressure and volume overload that eventually
causes pulmonary hypertension with reversal of flow and right-to-left shunts
with cyanosis (Eisenmenger syndrome).

Right-to-left shunts
tetralogy of Fallot or transposition of great vessels
cyanotic lesions from the outset and are associated with polycythemia,
hypertrophic osteoarthropathy, and paradoxical emboli.

Obstructive lesions include aortic coarctation; the

clinical severity of the lesion depends the degree of stenosis and the
patency of the ductus arteriosus.

Congenital Heart Disease

A general term to describe abnormalities of
the heart or great vessels that are present
from birth.

Congenital Heart Disease

Three major categories:
1.left-to-right shunt
(Acyanotic heart disease)

2.right-to-left shunt
(Cyanotic heart disease)

3.obstruction
(Stenosis / Atresia)

Acyanotic Heart Disease

Atrial Septal Defect (ASD),
Ventricular Septal Defect (VSD),
Patent Ductus Arteriosus (PDA), and
Atrioventricular Septal Defect
(AVSD).

Ventricular Septal Defect (VSD)

Atrial Septal Defect

(ASD)

Cyanotic Heart Disease

Tetralogy of Fallot (TOF)
Transposition of great arteries
(TGA)
Truncus Arteriosus
Tricuspid Atresia
Total Anomalous Pulmonary
Venous Connection (TAPVC)

Tetralogy of Fallot

Transposition of the Great Arteries

Tricuspid Atresia

Truncus Arteriosus

Obstructive
Congenital
Anomalies
1. Coarctation of Aorta
2. Pulmonary Stenosis and
Atresia
3. Aortic Stenosis and Atresia

Pulmonary Valve
Stenosis and Atresia

Hypoplastic Left Heart

Syndrome

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