2018/2019

Tutor Guide

CASE 5
Cardiovascular System

Faculty of Medicine
Universitas Padjadjaran
System : Cardiovascular
Week theme : Embriology of the Heart
Trigger case : Tetralogy of Fallot (SKDI competency level 2)
Week schedule : Two meetings
Sequence and pacing : 1st Meeting: page 1 – epilogue
2nd Meeting: discussion

Theme:
The purpose of this week’s topic is to review the anatomy, physiology, embryology of the normal heart, fetal and
prenatal circulation, epidemiology, pathogenesis, pathophysiology, diagnosis and management of Congenital
Heart Disease (Ventricular Septal Defect, Atrial Septal Defect, Patent Ductus Arteriosus and Tetralogy Fallot)

Learning Objectives:

At the end of the week the student should be able to:

1. Review physiology of the normal heart.
2. Explain the embryology of the normal heart
3. Explain briefly of heart development
4. Explain the differentiation between adult & fetal circulation
5. Describe about biochemistry of reduction and oxidation of Hemoglobin
6. Explain the embryology of Ventricular Septal Defect, Atrial Septal Defect, Patent Ductus Arteriosus,
Tetralogy of Fallot
7. Explain the pathophysiologic of Ventricular Septal Defect, Atrial Septal Defect, Patent Ductus Arteriosus,
Tetralogy of Fallot
8. Demonstrate the signs and symptoms of Congenital Heart Disease (Ventricular Septal Defect, Atrial Septal
Defect, Patent Ductus Arteriosus, Tetralogy of Fallot).
9. Explain the radiological, ECG and echocardiographic findings of Ventricular Septal Defect, Atrial Septal
Defect, Patent Ductus Arteriosus, Tetralogy of Fallot
10. Elaborate on the definition, epidemiology, pathogenesis, pathophysiology of Ventricular Septal Defect,
Atrial Septal Defect, Patent Ductus Arteriosus, Tetralogy of Fallot
11. Describe epidemiology, pathogenesis, pathophysiology of Congenital Heart Disease in adult (Ventricular
Septal Defect, Atrial Septal Defect, Patent Ductus Arteriosus, Tetralogy of Fallot )
12. Describe the management of Ventricular Septal Defect, Atrial Septal Defect, Patent Ductus Arteriosus,
Tetralogy of Fallot
13. Students will be introduced to concept of distributive justice in the context of health care, through learning
various type of health insurance, the direction of policy on health care insurance in countries such as United
States, Canada, Scandinavian countries, and Asian countries, particularly Indonesia, including issues related
to health care budget and doctor’s fee.

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 PAGE 1

You are a doctor at an out patient clinic when X, an 18-months-old girl from low socio-economic family came to your
office with bluish discoloration of the lips, tongue and fingertips.

History of illness

She had bluish discoloration of the lips, tongue and fingertip, which was noticed since 6 months old and seemed to
increase gradually as she was grown up. The bluish discoloration was more prominent during crying. She also often
squatted after she ran or during playing. Her growth and development were normal and she had no sign of heart
failure.
She was born as a fifth child, term infant, and spontaneous delivery and uneventful. Birth weight was 3000 grams.
No remarkable family history of congenital heart disease or hereditary disease.

INSTRUCTIONS:
1. Identify the patient’s problem
2. Generate a list of hypotheses
3. What further information do you need from the patient that might help to diagnose?

Guiding questions for tutor:

1. What contributes to the coloration of blood?
2. What is the difference between blood circulation in fetus and in adult?

PAGE 2

Physical examination:
Fully alert, mild to moderate cyanosis
Temperature : 370 C
Pulse : 100 beat per minute, regular, equal, full.
Respiration : 36/min, without any retraction
Blood pressure : 90/65 mmHg on the right arm
HEENT : Lips and tongue were cyanotic
Neck : normal
Heart : a long loud 4/6 systolic ejection murmur best heard at the upper left sternal borders
Lungs : clear to auscultation and resonant to percussion over all fields
Abdomen : liver& spleen was not palpable
Extremities : cyanosed and clubbed of the fingers, brisk capillary refill, palpable pulse
Neurologic examination: unremarkable

INSTRUCTIONS:
1. According to this information, does your hypothesis change?
2. What any further information do you need?

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 PAGE 3

Laboratory: Hct: 60%; Hb: 18 g%.

Pulse oxymetry: 70% at the right arm and the right leg.

Chest x ray:
• Right ventricular hypertrophy
• Boot shape
• Decreased pulmonary vascular markings
• A concave main pulmonary artery segment

Electrocardiography:
• Right axis deviation
• Right atrial hypertrophy
• Right ventricular hypertrophy

Echocardiography showed:
• A large perimembranous ventricular septal defect (VSD)
• Overriding of the aorta
• Infundibular and valvular pulmonary stenosis
• Right ventricular hypertrophied
• Confluent pulmonary arteries
• Intact atrial septum and duct was closed.

INSTRUCTIONS:
1. May this information confirm your hypothesis?
2. Is there any condition for further investigation?

Guiding questions for tutor:

1. How does the ventricle septum of the heart form?

PAGE 4

She might be able to undergo cardiac catheterization and total correction operation Hasan Sadikin Hospital Bandung
by using BPJS Insurance that might cover her operation costs. However the insurance does not cover the
transportation and parent’s living cost during stay in hospital.

INSTRUCTIONS:
1. Explain the ethical issue based on her parents problems?
2. What do you suggest to resolve the problems?

EPILOGUE

When she was 3 years old, she underwent heart catheterization and followed by a total correction surgery. Her
postoperative course was uneventful and now she is studying at a kindergarten with normal growth and
development.

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TUTOR GUIDE
Case synopsis

X-, an 18 month old girl

Bluish discoloration (Cyanosis) of the lips, tongue and fingertip

History of illness
Cyanosis
Cyanosis is a bluish discoloration of the skin mucous membranes resulting from an increased concentration of
reduced hemoglobin. Clinical cyanosis occurs when the amount of reduced hemoglobin in the cutaneous vein
reaches a critical level, about 5 g/100 mL. The critical level of reduced hemoglobin in the cutaneous vein may result
from either desaturation of arterial blood or increased extraction of oxygen by peripheral tissue. The latter occurs
in the presence of normal arterial saturation that results from a sluggish flow of blood (e.g., circulatory shock,
hypovolemic, vasoconstriction from cold). Cyanosis secondary to desaturation of arterial blood is called central
cyanosis, cyanosis with normal arterial oxygen saturation is called peripheral cyanosis. Cyanosis may result from a
number of causes

Squatted
Squatted is a special posture commonly seen in children with right-to-left shunts. This posture increases arterial
oxygen saturation, probably by temporarily trapping desaturated blood in the lower extremities

Hypoxic spell
Hypoxic spell (also called cyanotic spell, hypercyanotic spell, “tet” spell) of TOF requires immediate recognition and
appropriate treatment, because it can lead to serious complication of the central nervous system. Hypoxic spell are
characteristic by a paroxysm of hyperpnea (i.e., rapid and deep respiration), irritability and prolonged crying,
increasing cyanosis, and decreasing intensity of the heart murmur. Hypoxic spell occur in infants, with a peak
incidence between 2 and 4 months of age. These spell usually occur in the morning after crying, feeding, or
defecation. A severe spell may lead to limpness, convulsion, cerebrovascular accident, or even death. There appears
to be no relationship between the degree of cyanosis at rest and the likelihood of having hypoxic spell. Treatment
of the hypoxic spell strives to break the vicious circle of the spell.
Physicians may use one or more of the following to treat the spell.
1. The infant should be picked up and held in a knee-chest position.
2. Morphine sulfate, 0.2 mg/kg administered subcutaneously or intramuscularly, suppresses the
respiratory center and abolishes hyperpnoea.
3. Oxygen is usually administered, but it has little demonstrable effect on arterial oxygen saturation.
4. Acidosis should be treated with sodium bicarbonate (NaHCO3), 1 mEq/kg administered intravenously.
The same dose can be repeated in 10 to 15 minutes, NaHCO3 reduces the respiratory center-simulating
effect of acidosis.

With the preceding treatment, the infant usually becomes less cyanotic, and the heart murmur becomes louder,
which indicates an increased amount of blood flowing through the stenotic right ventricular outflow tract. If the
hypoxic spell does not fully respond to these measures, the following medications can be tried:
1. Vasoconstrictors such as phenylephrine (Neo-Snephrine), 0.002 mg/kg administered intravenously, may
be effective.
2. Ketamine, 1 to 3 mg/kg (average of 2 mg/kg) administered intravenously over 60 seconds, work well. It
increases the systemic vascular resistance and sedates the infant.
3. Propanolol, 0.01 to 0.25 mg/kg (average 0.05 mg/kg) administered by slow intravenous push, reduces
the heart rate and may reverse the spell.

No sign of heart failure.

This is discussed in greater detail in heart failure case

Echocardiography
Echocardiography is a procedure used to assess the heart's structures and function. Echocardiography is also called
echo, cardiac ultrasound or ultrasonography, cardiac Doppler, transthoracic echocardiography, or TTE. A small

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probe called a transducer is placed on your child's chest and sends out ultrasonic sound waves at a frequency too
high to be heard. When the transducer is placed on your child's chest in certain locations and at certain angles, the
ultrasonic sound waves move through the skin and other body tissues to the heart tissues, where the waves bounce
(or "echo") off of the heart structures. The transducer picks up the reflected waves and sends them to a computer.
The computer interprets the echoes into an image of the heart walls and valves.

Cardiac catheterization.
Heart /cardiac catheterization involves the passage of a catheter (a thin flexible tube) into the right or left side of
the heart. In general, this procedure is performed to obtain diagnostic information about the heart or its blood
vessels or to provide treatment in certain types of heart conditions.
Cardiac catheterization can be used to determine pressure and blood flow in the heart's chambers, collect blood
samples from the heart, and examine the arteries of the heart with an x-ray technique called fluoroscopy.
Fluoroscopy provides immediate ("real-time") visualization of the x-ray images on a screen and provides a
permanent record of the procedure.

Propanolol
Reduces the heart rate
To prevent hypoxic spell while waiting for an optimal time for corrective surgery in countries where open-heart
surgical procedures are not well established for small infants,

Family History: not significant

History of CHDs in close relatives increases the chance of CHD in a child. When one child is affected, the risk of
recurrence in siblings is about 3%, which is a threefold increase

Tutorial 2
Heart: a long loud systolic ejection murmur heard at the middle and upper left sternal borders
This murmur originates from the pulmonary stenosis

Clubbing fingers
Clubbing is caused by soft issue growth under the nail bed as consequence of central cyanosis. The mechanism for
soft issue growth is unclear. One hypothesis is that megakaryocytes present in the systemic venous blood may be
responsible for the change. In normal persons, platelets are formed from cytoplasm of the megakaryocytes by
fragmentation during their passage through the pulmonary circulation. The cytoplasm of megakaryocytes contains
growth factors (e.g., platelet-derived growth factor and transforming growth factor B). In patients with right-to-left
shunts, megakaryocytes with their cytoplasm may enter the systemic circulation, become trapped in the capillaries
of the digits, and release growth factors, which in turn cause clubbing. Clubbing usually does not occur until a child
is 6 months or older, and it is seen first and is most pronounced in the thumb. In the early stage, it appears as
shininess and redness of the fingertips. When fully developed, the fingers and toes became thick and wide and have
convex nail beds. Clubbing is also seen in patients with liver disease or sub-acute bacterial endocarditis and on a
hereditary basis without cyanosis.

Neurologic: Normal
Either very high hematocrit levels or iron-deficient red blood cells place individuals with cyanotic congenital heart
defects at risk for disorders of the central nervous system, such as brain abscess and vascular stroke. Cyanotic
congenital heart defects account for 5% to 10% of all cases of brain abscesses. The predisposition for brain abscesses
may partially result from the fact that right-to-left intracardiac shunts may bypass the normally effective phagocytic
filtering actions of the pulmonary capillary bed. This predisposition may also result from the fact that polycythemia
and the consequent high viscosity of blood lead to tissue hypoxia and micro infarction of the brain, which are later
complicated by bacterial colonization. However, subacute bacterial endocarditis is rarely associated with a brain
abscess. The triads of symptoms of brain abscesses are fever, headache, and focal neurological deficit.
Vascular stroke caused by embolization arising from thrombus in the cardiac chamber or in the systemic
veins may be associated with surgery or cardiac catheterization. Cerebral venous thrombosis may occur, often in
infants younger than 2 years of age who have cyanosis and relative iron-deficiency anemia. A possible explanation
for these findings is that microcytosis further aggravates hyper viscosity resulting from polycythemia.

Laboratory:
Hct: 60%; Hb: 18 g%.

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Polycythemia
Low arterial oxygen content stimulates bone marrow through erythropoietin release from the kidneys and produces
an increased number of red blood cells (more accurately, erythrocytosis). Polycythemia, with a resulting increase in
oxygen carrying capacity, benefits cyanotic children. However, when the hematocrit reaches 65% or higher, a sharp
increase in the viscosity of blood occurs, and the polycythemic respons becomes disadvantageous, particularly if
there is congestive heart failure (CHF). Some cyanotic infants have a relative iron deficiency state, with normal or
lower than normal hemoglobin and hypochromic on blood smear. Although less cyanotic, these infants are usually
more symptomatic and improve when iron therapy raises the hemoglobin. Normal hemoglobin in a cyanotic patient
represents a relative anemic state.

Laboratory:
Hct: 70%; Hb: 15 g%.
Oxygen saturation:70%

Hb reduce: 30% x 15 g%= 5

Clinical cyanosis occurs when the amount of reduced hemoglobin in the cutaneous vein reaches a critical level,
about 5 g/100 mL. The level of hemoglobin greatly influences the occurrence of cyanosis. Normally about 2 g/100
mL of reduced hemoglobin is present in the venules, so an additional 3 g/100 mL of reduced hemoglobin in arterial
blood produces clinical cyanosis. Cyanosis is recognized at a higher level of oxygen saturation in patients with
polycythemia and at a lower level of oxygen saturation in patients with anemia. For a normal person with
hemoglobin of 15 g/100 mL, 3 g of reduced hemoglobin results from 20% desaturation. Thus, cyanosis occurs when
the oxygen saturation is reduced to about 80%. In a person with polycythemia and hemoglobin of 20 g/100mL, 3 g
of reduced hemoglobin result from only 15% desaturation (or 85% arterial saturation). Conversely, in a patient with
a marked anemia (hemoglobin of 6 g/100mL), 3 g of reduced hemoglobin results from 50% desaturation, with the
appearance of cyanosis at about 50% arterial saturation.

Tutorial 3
Chest x ray
• Mild right ventricular hypertrophic
• Boot shape
• Pulmonary vascular markings were decreased
• A concave main pulmonary artery segment

Electrocardiography showed:
• Right axis deviation
Is present when the QRS axis is greater than the upper limit of normal for the patient’s age.
• Right atrial hypertrophy
Tall P wave (> 3mm)
• Right ventricular hypertrophy

Echocardiography showed
• A large perimembranous outlet ventricular septal defect (VSD) and overriding of the aorta
• Severe infundibular and valvular pulmonary stenosis was found
• Right ventricular hypertrophied
• No atrial septal defect (ASD) & patent ductus arteriosus (PDA)

• Conclusion: Tetralogy of fallot

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Tetralogy of Fallot (TOF)

Prevalence
TOF occurs in 10% of all congenital heart defects. This is the most common cyanotic heart defect seen in children
beyond infancy.

Pathology
The classic description of TOF
• Ventricular septal defect (VSD) - an opening in the ventricular septum, or dividing wall between the two
lower chambers of the heart known as the right and left ventricles.
• Pulmonary (or right ventricular outflow tract) obstruction - a muscular obstruction in the right ventricle,
just below the pulmonary valve, that decreases the normal flow of blood. The pulmonary valve may also
be small.
• Overriding aorta - the aorta is shifted towards the right side of the heart so that it sits over the ventricular
septal defect.

"Tetralogy" refers to four heart problems. The fourth problem is that the right ventricle becomes enlarged as it tries
to pump blood past the obstruction into the pulmonary artery

Pathophysiology
Normally, oxygen-poor (blue) blood returns to the right atrium from the body, travels to the right ventricle, and
then is pumped through the pulmonary artery into the lungs where it receives oxygen. Oxygen-rich (red) blood
returns to the left atrium from the lungs, passes into the left ventricle, and then is pumped through the aorta out
to the body.
In tetralogy of Fallot, blood flow within the heart varies, and is largely dependent on the size of the ventricular septal
defect, and how severe the obstruction is in the right ventricle.
• With mild right ventricle obstruction, the pressure in the right ventricle can be slightly higher than the left.
Some of the oxygen-poor (blue) blood in the right ventricle will pass through the VSD to the left ventricle,
mix with the oxygen-rich (red) blood there, and then flow into the aorta. The rest of the oxygen-poor
(blue) blood will go its normal route to the lungs. These children may have slightly lower oxygen levels
than usual, but may not appear blue.
• With more serious obstruction in the right ventricle, it is harder for oxygen-poor (blue) blood to flow into
the pulmonary artery, so more of it passes through the VSD into the left ventricle, mixing with oxygen-rich
(red) blood, and then moving on out to the body. These children will have lower than normal oxygen levels
in the bloodstream, and may appear blue, especially whenever the pressure in the right ventricle is very
high and large amounts of oxygen-poor (blue) blood passes through the VSD to the left side of the heart.

Clinical manifestations
History
1. A heart murmur is audible at birth.
2. Most patients are symptomatic with cyanosis at birth or shortly thereafter. Dyspnea on exertion, squatting,
or hypoxic spells develop later, even in mildly cyanotic in infants.
3. Infants with acyanotic TOF may be asymptomatic or may show signs of CHF from a large left-to-right
ventricular shunt.
4. Immediately after birth, severe cyanosis is seen in patients with TOF and pulmonary atresia.

Physical Examination
1. Varying degrees of cyanosis, tachypnea,and clubbing are present.
2. An RV tap along the left sternal border and a systolic thrill at the upper and mid-left sternal borders are
commonly present (50%).
3. An ejection click that originates in the aorta may be audible. The S2 is usually single, because only the aortic
component can be heard. A long, loud (grade 3-5/6) ejection-type systolic murmur is heard at the mid and
upper left sternal borders. This murmur originates from the pulmonary stenosis but may be easily confused
with the holosystolic regurgitant murmur of a VSD. The more severe the obstruction of the right ventricular
outflow tract, the shorter and softer the systolic murmur. In a deeply cyanotic neonate with TOF with
pulmonary atresia, heart murmur is either absent or very soft, although a continuous murmur representing
PDA may occasionally be audible.
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 4. In the acyanotic form, a long systolic murmur, resulting from VSD and infundibular stenosis, is audible along
the entire left sternal border, and cyanosis is absent. Thus ausculatory findings resemble those of a small-
shunt VSD, but the ECG shows right ventricle hypertrophy (RVH) or combined ventricle hypertrophy (CVH).

Electrocardiography
1. Right axis deviation (RAD) (+ 120 to + 150 degrees) is present in cyanotic TOF. In the acyanotic form, the
QRS axis is normal.
2. Right ventricle hypertrophy is usually present, but the strain pattern is unusual. CVH may be seen in the
acyanotic form. RAH is occasionally present.

X-ray Studies
Cyanotic Tetralogi of Fallot
1. The heart size is normal or smaller than normal, and pulmonary vascular markings are decreased. “Black”
lung are field as seen in TOF with pulmonary atresia.
2. A concave main PA segment with an upturned apex (i.e., “boot shaped” heart or coer en sabot) is
characteristic.
3. Right atrial enlargement (25% ) and right arch (25%) may be present.

Natural history
1. Infants with acyanotic TOF gradually become cyanotic. Patients who are already cyanotic become more
cyanotic as a result of the worsening condition of the infundibular stenosis and polycythemia.
2. Polycythemia develops secondary to cyanosis.
3. Physicians need to watch for the development of relative iron- deficiency (i.e.,hypochromic) state
4. Hypoxic spells may develop in infants
5. Growth retardation may be present if cyanosis is severe.
6. Brain abscess and cerebrovascular accident rarely occur
7. Endocarditis is occasionally a complication.
8. Some patients, particularly those with severe TOF, develop aortic regurgitation
9. Coagulopathy is a late complication of a long-standing cyanosis.

Management
Medical
1. Physicians should recognize and treat hypoxic spell. It is important to educate parents to recognize spell
and know what to do.
2. Oral propranolol therapy, 0.5 to 1.5 mg/kg every 6 hours, is occasionally used to prevent hypoxic spell
while waiting for an optimal time for corrective surgery in countries where open-heart surgical
procedures are not well established for small infants,
3. Balloon dilatation of the right ventricular outflow tract and pulmonary valve, thought not widely
practiced has been attempted to delay repair for several month.
4. Maintenance of good dental hygiene and practice of antibiotic prophylaxis against SBE are important
5. Relative iron-deficiency anemia should be detected and treated. Anemic children are more susceptible
to cerebrovascular complications. Normal hemoglobin or hematocrit values or decreased red blood
indicate an iron- deficiency state in cyanotic patients.

Surgical: Widening RVOT (infundibular resection) + VSD closure

VENTRICULAR SEPTAL DEFECT (VSD)

Prevalence
VSD is the most common form of congenital heart defect and accounts for 15% to 20% of all such defects, not
including those occurring as part of cyanotic congenital heart defects.

Pathology
1. The ventricular septum may be divided into a small membranous portion and a large muscular portion .The
muscular septum has three components – the inlet septum, the trabecular septum, and the outlet (infundibular)
septum. The trabecular septum is further divided into central, marginal, and apical portions. A VSD may be
classified as a perimembranous, inlet, outlet (infundibular), central muscular, marginal muscular, or apical
muscular defect
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 a. The membranous septum is a relatively small area immediately beneath the aortic valve. The membranous
defect involves varying amounts of muscular tissue adjacent to the membranous septum (perimembranous
VSD). According to the accompanying defect in the adjacent muscular septum, perimembranous VSDs have
been called perimembranous inlet (atrioventricular [AV] canal type), perimembranous trabecular, or
perimembranous outlet (tetralogy type) defects. Perimembranous defects are most common (70%).
b. Outlet defects account for 5% to 7% of all VSDs in the Western world and about 30% in Far Eastern countries.
The defect is located in the outlet septum, and part of this rim is formed by the aortic and pulmonary
annulus. It has been called supracristal, conal, subpulmonary, or subarterial defect.
c. Inlet defects account for 5% to 8% of all VSDs. The defect is located posterior and inferior to the
perimembranous defect, beneath the septal leaflet of the tricuspid valve, and inferior to the papillary
muscle of the conus when seen from the RV
d. Trabecular (muscular) defects account for 5% to 20% of all VSDs. They frequently appear to be multiple
when viewed from the right side. Central muscular defect is posterior to the septal band. Apical muscular
defect is near the cardiac apex and is difficult to visualize and repair. The marginal defects are usually
multiple, small, and tortuous. The “Swiss cheese” type of multiple muscular defects is extremely difficult to
close surgically.
2. The defects vary in size, ranging from tiny defects without hemodynamic significance to large defects with
accompanying CHF and pulmonary hypertension.
3. The bundle of His is related to the posteroinferior quadrant of perimembranous defects and the superoanterior
quadrant of inlet muscular defects. Defects in other parts of the septum are usually unrelated to the conduction
tissue.
4. In an infundibular defect, the right coronary cusp or the aortic valve may herniate through the defect. This may
result in an actual reduction of the VSD shunt but may produce aortic regurgitation (AR) and cause an
obstruction in the right ventricular outflow tract. A similar herniation of the right and/or non-coronary cusp
occasionally occurs through perimembranous defects.

Pathophysiology
when there's a large opening between the ventricles, a large amount of oxygen-rich (red) blood from the heart's
left side is forced through the defect to the right side. Then it's pumped back to the lungs, even though it's already
been refreshed with oxygen. This is inefficient, since blood that's already been to the lungs is returning there, and
blood that needs to go to the lungs is being displaced. The heart, which has to pump an extra amount of blood, is
overworked and may enlarge.

Clinical manifestations
History
1. With a small VSD, the patient is asymptomatic with normal growth and development.
2. With a moderate to large VSD, delayed growth and development, decreased exercise tolerance, repeated
pulmonary infections, and CHF are relatively common during infancy.
3. With long-standing pulmonary hypertension, a history of cyanosis and a decreased level of activity may be
present.

Physical Examination
Infants with small VSDs are well developed and acyanotic. Before 2 or 3 months of age, infants with large VSDs may
have poor weight gain or show signs of CHF. Cyanosis and clubbing may be present in patients with pulmonary
vascular obstructive disease (Eisenmenger’s syndrome).
1. A systolic thrill may be present at the lower left sternal border. Precordial bulge and hyperactivity are
present with a large-shunt VSD.
2. The intensity of the P2 is normal with a small shunt and moderately increased with a large shunt. The S2 is
loud and single in patients with pulmonary vascular obstructive disease. A grade 2-5/6 regurgitant systolic
murmur is audible at the lower left sternal border. It may be holosystolic or early systolic. An apical diastolic
rumble is present with a moderate to large shunt.
3. With infundibular VSD, a grade 1-3/6 early diastolic decrescendo murmur of AR may be audible. This
murmur occurs because of herniation of an aortic cusp.

Electrocardiography
1. With a small VSD, the ECG is normal.

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 2. With a moderate VSD, left ventricular hypertrophy (LVH) and occasional left atrial hypertrophy (LAH) may
be seen.
3. With a large defect, the ECG shows combined ventricular hypertrophy (CVH) with or without LAH
4. If pulmonary vascular obstructive disease develops, the ECG shows RVH only.

X-ray Studies
1. Cardiomegaly of varying degrees is present and involves the LA, left ventricle (LV), and RV (sometimes).
Pulmonary vascular markings increase. The degree of cardiomegaly and the increase in pulmonary vascular
markings directly relate to the magnitude of the left-to-right shunt.
2. In pulmonary vascular obstructive disease, the main PA and the hilar PAs enlarge noticeably, but the peripheral
lung fields are ischemic. The heart size is usually normal.

Natural history
1. Spontaneous closure occurs in 30% to 40% of patients with membranous VSDs and muscular VSDs during the
first 6 months of life. It occurs more frequently in small defects. These VSDs do not become bigger with age;
rather, the decrease in size. Inlet defects and infundibular defects do not become smaller or close spontaneously.
2. CHF develops in infants with large VSDs, but usually not until 6 to 8 weeks of age.
3. Pulmonary vascular obstructive disease may begin to develop as early as 6 to 12 months of age in patients with
large VSDs, but the resulting right-to-left shunt usually does not develop until the teenage years.
4. Infundibular stenosis may develop in some infants with large defects and result in a decrease in the magnitude
of the left-to-right shunt (i.e., acyanotic TOF), with an occasional production of a right-to-left shunt.
5. Infective endocarditis rarely occurs.

Management
Understanding the natural history of a VSD is important when planning its management.

Medical
1. Treatment of CHF, if it develops, is indicated with digoxin and diuretics for 2 to 4 months to see if growth failure
can be improved. Frequent feedings of high-calorie formulas, either by nasogastric tube or oral feeding, may
help. Anemia, if present, should be corrected by oral iron therapy.

2. No exercise restriction is required in the absence of pulmonary hypertension.

3. Maintenance of good dental hygiene and antibiotic prophylaxis against infective endocarditis are important

Intervention:
1. Surgical
2. Non-surgical (transcatheter occlusion)

ATRIAL SEPTAL DEFECT

Prevalence
ASD (ostium secundum defect) occurs as an isolated anomaly in 5% to 10% of all congenital heart defects. It is more
common in females then males (male-female ratio 1:2). About 30-50% of children with congenital heart defect have
an ASD as part of the cardiac defect.

Pathology
1. Three types of ASD exist-secundum defect, primum defect, and sinus venosus defect. Patent foramen ovale
(PFO) does not ordinarily produce intracardiac shunt.
2. Ostium secundum defect is the most common type of ASD accounting for 50% to 70% of all ASDs. This defect
is present at the site of fossa ovalis, allowing left-to-right shunting of blood from the left atrium (LA) to the
right atrium (RA) .Anomalous pulmonary venous return is present in about 10% cases.
3. Ostium primum defects occurs in about 30% of all ASDs, if those that occur as part of a complete ECD are
included. Isolated ostium primum ASD occurs in about 15% of ASD.
4. Sinus venosus defect, which occurs in about 10% of all ASDs, is most commonly located at the entry of the
superior vena cava (SVC) into the RA (superior vena caval type) and rarely at the entry of the inferior vena
cava (IVC) into the RA (inferior vena cava type). The right pulmonary veins may drain anomalously into the
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 RA. More commonly, the right pulmonary veins enter normally into the RA. True anomalous venous return
of the right pulmonary veins into the IVC occurs in the scimitar syndrome
5. A roofed coronary sinus is a rare communication between the coronary sinus and the LA, which produces
clinical pictures similar to other types of ASD.
6. Mitral valve prolapse (MVP) occurs in 20% of patients with either ostium secundum or sinus venosus defect.

Pathophysiology
Normally, oxygen-poor (blue) blood returns to the right atrium from the body, travels to the right ventricle, and
then is pumped into the lungs where it receives oxygen. Oxygen-rich (red) blood returns to the left atrium from
the lungs, passes into the left ventricle, and then is pumped out to the body through the aorta.
An atrial septal defect allows oxygen-rich (red) blood to pass from the left atrium, through the opening in the
septum, and then mix with oxygen-poor (blue) blood in the right atrium.

Clinical manifestation
History. Infants and children with ASDs are usually asymptomatic.
Physical examination A relatively slender body build is typical (The body weight of many is less than the 10 th
percentile.)
1. A widely split and fixed second heart sound and grade 2-3/6 systolic ejection murmur are characteristic
findings of ASD in older infants and children. With a large left-to-right shunt, a mid-diastolic rumble resulting
from relative tricuspid stenosis may be audible at the lower left sternal border.
2. The typical auscultatory findings may be absent in infants, even infants who have a large defect.

Electrocardiography
Right axis deviation of +90 to +180 degrees and mild right ventricular hypertrophy (RVH) or right bundle branch
block (RBBB) with an rsR’ pattern in V1 are typical findings.

X-ray Studies
1. Cardiomegaly with an enlargement of the RA and right ventricle (RV) is present.
2. A prominent pulmonary artery (PA) segment and increased pulmonary vascular markings can be seen

Natural history
1. Earlier reports indicated that spontaneous closure of the secundum defect occurred in about 40% of
patients in the first 4 years of life (actually between 14% and 55% of patients). The defect may decrease in
size in some patients. However, a more recent report indicates the overall rate of spontaneous closure to
be 87%. In patients with an ASD <3 mm in size diagnosed before 3 months of age, spontaneous closure
occurs in 100% of patients at 1 ½ years of age. Spontaneous closure occurs more than 80% of the time in
patients with defect between 3 and 8 mm before 1 ½ years of age. An ASD with a diameter >8 mm rarely
closes spontaneously.
2. Most children with an ASD remain active and asymptomatic. Rarely, congestive heart failure (CHF) can
develop in infancy.
3. If a large defect is untreated, CHF and pulmonary hypertension develop in adults who are in their 20s and
30s.
4. With or without surgery, atrial arrhythmias (flutter or fibrillation) may occur in adults.
5. Infective endocarditis does not occur in patients with isolated ASDs. Therefore subacute bacterial
endocarditis (SBE prophylaxis) is unnecessary for these patients unless their condition is associated with
other defects.
6. Cerebrovascular accident, resulting from paradoxical embolization through an ASD, is a rare complication.

Management
Medical
1. Exercise restriction is unnecessary.
2. Prophylaxis for infective endocarditis is not indicated unless the patient has associated MVP.
3. In infants with CHF, medical management is recommended because of its high success rate and the
possibility of spontaneous closure of the defect.
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Intervention:
1. Surgical
2. Non surgical (Transcatheter closure)

Patent Ductus Arteriosus

Prevalence
PDA occurs in 5% to 10% of all congenital heart defects, excluding premature infants. It is more common in female
than in males (male-female ratio 1: 3). PDA is a common in premature infants

Pathology
1. There is a persistent patency of a normal fetal structure between the left PA and the descending aorta, that
is, about 5 to 10 mm distal to the origin of the left subclavian artery.
2. The ductus is usually cone shaped with a small office to the PA, which is restrictive to blood flow. The ductus
may be short or long, straight to tortuous.

Clinical manifestations
History
1. Patients are usually asymptomatic when the ductus is small.
2. A large-shunt PDA may cause a lower respiratory tract infection, atelectasis, and CHF (accompanied by
tachypnea and poor weight gain).

Physical Examination
1. Tachycardia and exertional dyspnea may be present in children with a large-shunt PDA. With pulmonary
vascular obstructive disease, a right-to-left ductal shunt result in cyanosis only in the lower half of the body
(i.e., differential cyanosis).
2. The precordium is hyperactive. A systolic thrill may be present at the upper left sternal border. Bounding
peripheral pulses with wide pulse pressure (with elevated systolic pressure and lower diastolic pressure)
are characteristics findings.

3. The P2 is usually normal, but its intensity may be accentuated if pulmonary hypertension is present. A grade
1-4/6 continuous (“machinery”) murmur is best audible at the left infraclavicular area or upper left sternal
border. The heart murmur may be crescendo systolic at the upper left sternal border in small infants or
infants with pulmonary hypertension. An apical diastolic rumble may be heard when the PDA shunt is large.

Electrocardiography.
The ECG findings for PDA are similar to those for VSD. A normal ECG or LVH is seen with small to moderate PDA.
CVH is seen with large PDA. If pulmonary vascular obstructive disease develops, RVH may be seen.

X-ray studies.
X-ray findings are also similar to those of VSD.
1. Chest ray film may be normal with small shunt PDA
2. Cardiomegaly of varying degrees occurs with enlargement of the LA, LV and ascending aorta. Pulmonary
vascular marking are increased.
3. With pulmonary vascular obstructive disease, the heart size is normal, with a normal marked prominence
of the PA segment and hillar vessels.

Natural history
1. Unlike PDA in premature infants, spontaneous closure of PDA does not usually occur in full-term infants.
This is because the PDA in term infants results from a structural abnormality of the ductal smooth muscle
rather than a decreased responsiveness of the premature ductus to oxygen
2. CHF and/or recurrent pneumonia develop if a large PDA with pulmonary hypertension remains untreated.

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 3. Pulmonary vascular obstructive disease may develop if a large PDA with pulmonary hypertensions remains
untreated.
4. SBE, which may be more frequent with small PDAs than with large ones, may occur.
5. Although rare, an aneurysm of PDA may develop possibly rupture.

Management
Medical
Interventional pediatric cardiology
Surgery

Departments involved:
Pediatric (Sri Endah Rahayuningsih, Rahmat Budi Kuswiyanto)
▪ Cardiology (Pintoko)
▪ Medical Biology
▪ Anatomy
▪ Physiology (Jimmy Setiadinata)
▪ Radiology (Soehartinah K. Antono)
▪ Clinical Pathology (Anna Tjandrawati)
▪ Anatomy Pathology
▪ Pharmacology (Armaya Ariyoga)
▪ Biochemistry (Nugraha Sutadipura)

Figure 11.8 Frontal section through the heart of a 30-day embryo showing the primary interventricular foramen and entrance
of the atrium into the primitive left ventricle. Note the bulboventricular flange. Arrows, direction of blood flow.

Development of the Sinus Venosus

In the middle of the fourth week, the sinus venosus receives venous blood from the right and left sinus horns (Fig.
11.10A). Each horn receives blood from three important veins: (a) the vitelline or omphalomesenteric vein, (b) the
umbilical vein, and (c) the common cardinal vein. At first communication between the sinus and the atrium is wide.
Soon, however, the entrance of the sinus shifts to the right (Fig. 11.10B). This shift is caused primarily by left-to-
right shunts of blood, which occur in the venous system during the fourth and fifth weeks of development.
With obliteration of the right umbilical vein and the left vitelline vein during the fifth week, the left sinus horn rapidly
loses its importance (Fig. 11.10B). When the left common cardinal vein is obliterated at 10 weeks, all that remains
of the left sinus horn is the oblique vein of the left atrium and the coronary sinus (Fig. 11.11). As a result of left-to-
right shunts of blood, the right sinus horn and veins enlarge greatly. The right horn, which now forms the only

13
communication between the original sinus venosus and the atrium, is incorporated into the right atrium to form the
smooth-walled part of the right atrium (Fig. 11.12).
Its entrance, the sinuatrial orifice, is flanked on each side by a valvular fold, the right and left venous valves (Fig.
11.12A). Dorsocranially the valves fuse, forming a ridge known as the septum spurium (Fig. 11.12A). Initially the
valves are large, but when the right sinus horn is incorporated into the wall of the atrium, the left venous valve and
the septum spurium fuse with the developing atrial septum (Fig. 11.12C). The superior portion of the right venous
valve disappears entirely. The inferior portion develops into two parts: (a) the valve of the inferior vena cava, and
(b) the valve of the coronary sinus (Fig. 11.12C ).
The crista terminalis forms the dividing line between the original trabeculated part of the right atrium and the
smooth-walled part (sinus venarum), which originates from the right sinus horn (Fig. 11.12C).

Figure 11.12 Ventral view of coronal sections through the heart at the level of the atrioventricular canal to show development
of the venous valves. A. 5 weeks C. Fetal stage. The sinus venarum (blue) is smooth walled; it derives from the right sinus horn.
Arrows, blood flow.

Formation of the Cardiac Septa

The major septa of the heart are formed between the 27th and 37th days of development, when the embryo grows
in length from 5 mm to approximately 16 to 17 mm. One method by which a septum may be formed involves two
actively growing masses of tissue that approach each other until they fuse, dividing the lumen into two separate
canals (Fig. 11.13, A and B). Such a septum may also be formed by active growth of a single tissue mass that
continues to expand until it reaches the opposite side of the lumen (Fig. 11.13C ). Formation of such tissue masses
depends on synthesis and deposition of extracellular matrices and cell proliferation. The masses, known as
endocardial cushions, develop in the atrioventricular and conotruncal regions. In these locations they assist in
formation of the atrial and ventricular (membranous portion) septa, the atrioventricular canals and valves, and
the aortic and pulmonary channels.

11.13 A and B. Septum formation by two actively growing ridges that approach each other until they fuse. C. Septum formed
by a single actively growing cell mass. D, E, and F. Septum formation by merging of two expanding portions of the wall of the
heart. Such a septum never completely separates two cavities.

The other manner in which a septum is formed does not involve endocardial cushions. If, for example, a narrow
strip of tissue in the wall of the atrium or ventricle should fail to grow while areas on each side of it expand rapidly,
a narrow ridge forms between the two expanding portions (Fig. 11.13,D and E).
When growth of the expanding portions continues on either side of the narrow portion, the two walls approach
each other and eventually merge, forming a septum (Fig. 11.13 F ). Such a septum never completely divides the
original lumen but leaves a narrow communicating canal between the two expanded sections. It is usually closed

14
secondarily by tissue contributed by neighboring proliferating tissues. Such a septum partially divides the atria and
ventricles.

CLINICALCORRELATES
Endocardial Cushions and Heart Defects
Because of their key location, abnormalities in endocardial cushion formation contribute to many cardiac
malformations, including atrial and ventricular septal defects and defects involving the great vessels (i.e.,
transposition of the great vessels and tetralogy of Fallot). Since cells populating the conotruncal cushions include
neural crest cells and since crest cells also contribute extensively to development of the head and neck,
abnormalities in these cells, produced by teratogenic agents or genetic causes, often produce both heart and
craniofacial defects in the same individual.

SEPTUM FORMATION IN THE COMMON ATRIUM

At the end of the fourth week, a sickle-shaped crest grows from the roof of the common atrium into the lumen. This
crest is the first portion of the septum primum (Figs. 11.12 A and 11.14, A and B). The two limbs of this septum
extend toward the endocardial cushions in the atrioventricular canal. The opening
between the lower rim of the septum primum and the endocardial cushions is the ostium primum (Fig. 11.14, A and
B). With further development, extensions of the superior and inferior endocardial cushions grow along the edge of
the septum primum, closing the ostium primum (Fig. 11.14, C and D). Before
closure is complete, however, cell death produces perforations in the upper portion of the septum primum.
Coalescence of these perforations forms the ostium secundum, ensuring free blood flow from the right to the left
primitive atrium (Fig. 11.14, B and D).
When the lumen of the right atrium expands as a result of incorporation of the sinus horn, a new crescent-shaped
fold appears. This new fold, the septum secundum (Fig. 11.14, C and D), never forms a complete partition in the
atrial cavity (Fig. 11.14G ). Its anterior limb extends downward to the septum in the atrioventricular canal. When
the left venous valve and the septum spurium fuse with the right side of the septum secundum, the free concave
edge of the septum secundum begins to overlap the ostium secundum (Fig. 11.12, A and B).
The opening left by the septum secundum is called the oval foramen (foramen ovale). When the upper part of the
septum primum gradually disappears, the remaining part becomes the valve of the oval foramen. The passage
between the two atrial cavities consists of an obliquely elongated cleft (Fig. 11.14, E –G ) through which blood from
the right atrium flows to the left side (arrows in Figs. 11.12B and 11.14E ).
After birth, when lung circulation begins and pressure in the left atrium increases, the valve of the oval foramen is
pressed against the septum secundum, obliterating the oval foramen and separating the right and left atria. In about
20% of cases, fusion of the septum primum and septum secundum is incomplete, and a narrow oblique cleft remains
between the two atria. This condition is called probe patency of the oval foramen; it does not allow intracardiac
shunting of blood.

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Figure 11.14 Atrial septa at various stages of development. A. 30 days (6 mm). B. Same stage as A, viewed from the right. C. 33
days (9 mm). D. Same stage as C, viewed from the right E. 37 days (14 mm). F. Newborn. G. The atrial septum from the right;
same stage as F.

Further Differentiation of the Atria

While the primitive right atrium enlarges by incorporation of the right sinus horn, the primitive left atrium is likewise
expanding. Initially, a single embryonic pulmonary vein develops as an outgrowth of the posterior left atrial wall,
just to the left of the septum primum (Fig. 11.15A). This vein gains connection with veins of the developing lung
buds. During further development, the pulmonary vein and its branches are incorporated into the left atrium,
forming the large smooth-walled part of the adult atrium. Although initially one vein enters the left atrium,
ultimately four pulmonary veins enter (Fig. 11.15B) as the branches are incorporated into the expanding atrial wall.

Figure 11.15 Coronal sections through the heart to show development of the smoothwalled portions of the right
and left atrium. Both the wall of the right sinus horn (blue) and the pulmonary veins (red) are incorporated into the
heart to form the smooth-walled parts of the atria.

In the fully developed heart, the original embryonic left atrium is represented by little more than the trabeculated
atrial appendage, while the smooth-walled part originates from the pulmonary veins (Fig. 11.15). On the right side
the original embryonic right atrium becomes the trabeculated right atrial appendage containing the pectinate
muscles, and the smooth-walled sinus venarum originates from the right horn of the sinus venosus.

SEPTUM FORMATION IN THE ATRIOVENTRICULAR CANAL

At the end of the fourth week, two mesenchymal cushions, the atrioventricular endocardial cushions, appear at
the superior and inferior borders of the atrioventricular canal (Figs. 11.16 and 11.17). Initially the atrioventricular
canal gives access only to the primitive left ventricle and is separated from the bulbus cordis by the
bulbo(cono)ventricular flange (Fig. 11.8). Near the end of the fifth week, however, the posterior extremity of the
flange terminates almost midway along the base of the superior endocardial cushion and is much less prominent
than before (Fig. 11.17). Since the atrioventricular canal enlarges to the right, blood passing through the
atrioventricular orifice now has direct access to the primitive left as well as the primitive right ventricle.
In addition to the superior and inferior endocardial cushions, the two lateral atrioventricular cushions appear on
the right and left borders of the canal (Figs. 11.16 and 11.17). The superior and inferior cushions, in the meantime,
project further into the lumen and fuse, resulting in a complete division of the canal into right and left
atrioventricular orifices by the end of the fifth week (Fig. 11.16).

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Figure 11.17 A. Frontal section through the heart of a day 35 embryo. At this stage of development blood from the atrial cavity
enters the primitive left ventricle as well as the primitive right ventricle. Note development of the cushions in the
atrioventricular canal. Cushions in the truncus and conus are also visible. Ring, primitive interventricular foramen. Arrows, blood
flow.

Atrioventricular Valves
After the atrioventricular endocardial cushions fuse, each atrioventricular orifice is surrounded by local
proliferations of mesenchymal tissue (Fig. 11.18A). When the bloodstream hollows out and thins tissue on the
ventricular surface of these proliferations, valves form and remain attached to the ventricular wall by muscular
cords (Fig. 11.18B). Finally, muscular tissue in the cords degenerates and is replaced by dense connective tissue. The
valves then consist of connective tissue covered by endocardium. They are connected to thick trabeculae in the wall
of the ventricle, the papillary muscles, by means of chordae tendineae (Fig.11.18C ). In this manner two valve leaflets,
constituting the bicuspid, or mitral, valve, form in the left atrioventricular canal, and three, constituting the tricuspid
valve, form on the right side.

17