Congenital Heart Diseases

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Congenital Heart Diseases

• Special Pathology

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• 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.

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• 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.

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• 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).

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• 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).

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• 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.

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• 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

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Malformation Incidence per Million Live Births
Ventricular septal defect 4482 42
Atrial septal defect 1043 10
Pulmonary stenosis 836 8
Patent ductus arteriosus 781 7
Tetralogy of Fallot 577 5
Coarctation of the aorta 492 5
Atrioventricular septal defect 396 4
Aortic stenosis 388 4
Transposition of the great arteries 388 4
Truncus arteriosus 136 1
Total anomalous pulmonary venous connection 120 1
Tricuspid atresia 118 1
TOTAL 9757  
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• 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).

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• 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

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• 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.

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• 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.

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• 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.

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• 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.

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• 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

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• 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

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• 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.

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• 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.

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• 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

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• 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.

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• 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

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• 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.

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• 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.

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• 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 right-to-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.

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• 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.

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• 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.

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• 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

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• 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.

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• 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.

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• 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.

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• 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.

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• 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.

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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.

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

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Congenital Heart Disease

• Three major categories
• left-to-right shunt (Acyanotic
  heart disease)
• right-to-left shunt
  (Cyanotic heart disease)
• obstruction (Stenosis
  / Atresia)

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Acyanotic Heart Disease

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

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Ventricular Septal Defect (VSD)
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Atrial Septal Defect (ASD)
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Cyanotic Heart Disease

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

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Tetralogy of Fallot
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Transposition of the Great Arteries
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Tricuspid Atresia
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Truncus Arteriosus
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Obstructive Congenital Anomalies

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

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Pulmonary Valve Stenosis and Atresia
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Hypoplastic Left Heart Syndrome
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• Teachers open the door but you must walk through
  it yourself.

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Thanks