Congenital heart diseases are abnormalities present at birth during weeks 3 through 8 of gestation. They affect around 0.5% of births and are caused by errors in heart development involving transcription factors and signaling pathways. Major types include septal defects which allow shunting between the left and right sides of the heart, obstructive lesions which block blood flow, and abnormalities in the arrangement of the great arteries. Clinical features vary depending on which areas of the heart are involved and range from no symptoms to cyanosis. Many types can be treated surgically or with catheter procedures.

1. Congenital heart
diseases

2. • Abnormalities of the heart or great vessels that are
present at birth
• Gestational weeks 3 through 8

3. Incidence
• up to 0.5%
• among the most prevalent birth defects and are the
most common type of pediatric heart disease.

4. Cardiac Development.
• caused by errors during cardiac morphogenesis.
• precursors originate --- lateral mesoderm and move to
midline in two migratory waves to create ----- first and
second heart fields by about day 15.
• Both fields contain multipotent progenitor cells that
can produce all of the major cell types of the heart:
endocardium, myocardium, and smooth muscle cells.
• each heart field is differentially marked by the
expression of distinct gene sets.
• first heart field expresses -- transcription factor H and 1
• second heart field expresses --- transcription factor
Hand2 and the secreted protein fibroblast growth
factor-10.

5. • each heart field --give rise to particular portions of the
heart.
• left ventricle largely first heart field
• second heart field become the outflow tract, right ventricle,
and most of the atria
• By day 20--- beating tube, which loops to the right
andbegins to form the basic heart chambers
• two other critical events occur:
• (1) neural crest–derived cells migrate into the outflow tract --
formation of the aortic arches
• (2) interstitial connective tissue --- enlarges to produce swellings
known as endocardial cushions.
• By day 50, further septation of the ventricles, atria, and
atrioventricular valves produces a four-chambered heart.

6. • depends on a network of transcription factors ----
regulated by --signaling pathways,
• the Wnt, hedgehog, (VEGF), bone morphogenetic
factor, TGFβ, FGF, and Notch pathways
• In addition – hemodynamic forces play an
important role in cardiac development

9. • inherited defects that involve genes that encode
transcription factors;
• transient environmental stresses during the first
trimester

10. Etiology and Pathogenesis
• Sporadic genetic abnormalities are the major
known causes of congenital heart disease.
• single gene mutations, small chromosomal losses,
and additions or deletions of whole chromosomes
(trisomies and monosomies). In the
• GATA4, TBX5, and NKX2-5---- atrial and ventricular
septal defects

12. • deletion 22q11.2----- DiGeorge syndrome
• syndrome, the fourth branchial arch , third and
fourth pharyngeal pouches (thymus, parathyroids,
and heart) develop abnormally.
• The syndrome --- multiple deficits
• CATCH-22:
• cardiac abnormality, abnormal facies, thymic
aplasia, cleft palate, and hypocalcemia

13. • Turner syndrome (monosomy X) and trisomies 13,
18, and 21.
• 40% of patients with Down syndrome have CHD
• environmental factors,
• congenital rubella infection,
• gestational diabetes
• teratogen exposure
• Nutritional factors --- folate supplementation during
early pregnancy may reduce congenital heart disease
risk.
• alcohol

14. Clinical Features.
Three major categories:
• Malformations causing a left-to-right shunt
• Malformations causing a right-to-left shunt
• Malformations causing an obstruction
• Malpositions of heart

15. • A shunt is an abnormal communication between
chambers or blood vessels
• pressure gradients from the left (systemic) side to the
right (pulmonary) side of the circulation or vice versa.
• right-to-left shunt--- hypoxemia and cyanosis ---- result
because the pulmonary circulation is bypassed
• Right to- left shunts can allow emboli -- paradoxical
embolism
• “clubbing” of the tips of the fingers and toes as well as
polycythemia.

16. • left-to-right shunts increase pulmonary blood flow, but
are not initially associated with cyanosis.
• elevate both volume and pressure in the normally low-
pressure, low-resistance pulmonary circulation.
• Muscular pulmonary arteries ---- medial hypertrophy
and vasoconstriction.
• prolonged pulmonary arterial vasoconstriction
stimulates the development of irreversible obstructive
intimal lesions --- frank atherosclerotic lesions.
• The right ventricle --- hypertrophy.
• Eventually, pulmonary vascular resistance = systemic
levels--- right-to-left shunt --- poorly oxygenated blood
into the systemic circulation (Eisenmenger syndrome).

18. • Obstructive congenital heart disease occurs when
there is abnormal narrowing of chambers, valves,
or blood vessels.
• A complete obstruction --- atresia.

20. Left-to-Right Shunts
• Pink babies
• most common CHD
• ASD, VSD, and PDA.
• ASD increases volumes, VSD and PDA--- both flow
and pressure.

22. Atrial Septal Defect
• abnormal, fixed openings in the atrial septum
• caused by incomplete tissue formation
• Communication of blood between the left and right
atria
• ASDs -- usually asymptomatic until adulthood
• ASD should not be confused with patent foramen
ovale , which represents the failure to close a
foramen (hole) that is part of normal development.

23. • The septum primum -- sits posteriorly between the
right and left atria and partially separates them-----
anterior opening, called the ostium primum---- fetal
development.
• Before the growing septum primum completely
obliterates the ostium primum, it develops a second
posterior opening called the ostium secundum.
• The septum secundum is a subsequent membranous
ingrowth located to the right and anterior of the
septum primum.
• As the septum secundum grows-- opening called the
foramen ovale
--- continuous with the ostium secundum
• The septum secundum enlarge -- FLAP--- covers the
foramen ovale on its left side

24. • the valve opens only when the pressure is greater
in the right atrium.
• In fetal life--- pulmonary circulation pressure is
greater than that of the systemic circulation---
foramen ovale is normally open.
• At birth----pulmonary vascular pressures drop----
the valve of the foramen ovale closes

25. MORPHOLOGY
classified according to -- location.
• Secundum ASD (90% of all ASD)
• These are usually not associated with other
anomalies
• may be of any size, multiple or fenestrated.
• Primum anomalies (5% of ASD)
• Associated with AV valve abnormalities and/or a
VSD.
• Sinus venosus defects (5%) are located near the
entrance of the superior vena cava

27. Clinical Features
• Infant tires easily when feeding
• left-to-right shunt---- pulmonary vascular resistance
is less and compliance of right ventricle is much
greater
• Pulmonary blood -- two to four times normal
• A murmur --- excessive flow through the
pulmonary valve.
• ASDs -- well tolerated till age 30
• Surgical or catheter-based closure

28. Patent Foramen Ovale
• small hole created by an open flap of tissue in the
atrial septum at the oval fossa.
• at birth -- flap closes -- 80% of people.
• 20% of people-- flap can open when there is more
pressure on the right side of the heart
• sustained pulmonary hypertension or even
transient increases in right-sided pressures-- during
a bowel movement, coughing, or sneezing- brief
periods of right-to-left shunting

29. Ventricular Septal Defect
• incomplete closures -- ventricular septum,
• free communication -- left to right ventricles

30. • classified --- size and location
• Most are size of the aortic valve orifice
• 90%occur in the region of the membranous septum
(membranous VSD)
• The remainder occur below the pulmonary valve
(infundibular VSD) or within the muscular septum.
• Single
• Muscular septum may be multiple so-called “Swiss-
cheese” septum

33. • Clinical Features.
• depend on the size and associated with right-sided
malformations.
• Large --- difficulties from birth
• smaller -- well tolerated for years
• 50% of small muscular VSDs close spontaneously
• Large defects are usually membranous or infundibular,
• left-to-right shunting--- right ventricular hypertrophy
and pulmonary hypertension ---- ultimately resulting in
shunt reversal, cyanosis, and death.
• Surgical or catheter-based closure

34. Patent Ductus Arteriosus
• The ductus arteriosus arises from the pulmonary artery
and joins the aorta
• Intrauterine blood flow from the pulmonary artery to
the aorta--- bypassing the lungs.
• functionally closed after 1 to 2 days
• increased arterial oxygenation---- decreased pulmonary
vascular resistance--- declining prostaglandin E2.
• ligamentum arteriosum.
• Ductal closure is often delayed (or even absent) in
infants with hypoxia (due to respiratory distress or heart
disease),
• PDAs account for about 7% of cases of congenital heart
disease

36. • continuous harsh “machinery-like” murmur.
• PDA is usually asymptomatic at birth
• Upto -- 2cm long, 1 cm dia
• large shunts, the additional volume and pressure
overloads eventually produce obstructive changes
in small pulmonary arteries, leading to reversal of
flow and its associated consequences.

37. Right-to-Left Shunts
• Blue babies
• cyanosis (cyanotic congenital heart disease)
• Tetralogy of Fallot the most common in this group
• transposition of the great arteries
• The others include persistent truncus arteriosus,
tricuspid atresia, and total anomalous pulmonary
venous connection.

38. Tetralogy of Fallot
• (1) VSD
• (2) obstruction of the right ventricular outflow tract
(subpulmonary stenosis)
• (3) an aorta that overrides the VSD
• (4) right ventricular hypertrophy
• anterosuperior displacement of the infundibular
septum.

41. Morphology.
• heart -- enlarged -- “boot-shaped”
• The aortic valve forms the superior border of the VSD,
thereby overriding the defect and both ventricular
chambers.
• The obstruction to right ventricular outflow --- due to
narrowing of the infundibulum (subpulmonic stenosis)
can be accompanied by pulmonary valvular stenosis.
• Aortic valve insufficiency or an ASD may also be
present; a right aortic arch is present in about 25% of
cases.

42. Clinical Features.
• survive into adult life;
• depend primarily on the severity of the subpulmonary
stenosis, since this determines the direction of blood
flow.
• If mild--- resembles an isolated VSD, and the shunt may
be left-to-right, without cyanosis (so-called “pink
tetralogy”).
• severe obstruction, right-sided pressures approach or
exceed left-sided pressures-- right-to-left shunting ---
cyanosis (classic TOF).
• The more severe the subpulmonic stenosis, the more
hypoplastic are the pulmonary arteries (i.e., smaller
and thinner-walled), and the larger is the overriding
aorta.

43. Transposition of the Great Arteries
• TGA produces ventriculoarterial discordance.
• aorta -- arises from right ventricle
• pulmonary artery --- from the left ventricle.
• atrium-to-ventricle connections are normal
(concordant),
• Embryologic defect ----abnormal formation of the
truncal and aortopulmonary septa.
• Separation of the systemic and pulmonary circulations
• incompatible with life unless a shunt

46. • . Patients with TGA and a VSD (approximately 35%)
often have a stable shunt.
• patent foramen ovale or ductus arteriosus for blood
mixing (approximately 65%) is problematic.

47. Tricuspid Atresia
• complete occlusion of the tricuspid valve orifice.
• the mitral valve is larger than normal
• right ventricular hypoplasia
• circulation can be maintained by right-to-left
shunting through an interatrial communication
(ASD or patent foramen ovale), in addition to a VSD

48. Obstructive Lesions
• Congenital obstruction can occur at the level of the
heart valves or within a great vessel.
• Common examples include aortic or pulmonary
valve stenosis or atresia, and coarctation of the
aorta.

49. Coarctation of the Aorta
• common structural anomalies.
• twice as common in M
• There are two classic forms:
• (1) an “infantile” form—often symptomatic in early
childhood—tubular hypoplasia
• (2) an “adult” form --- ridgelike infolding of the aorta
just opposite the closed ductus arteriosus (ligamentum
arteriosum)
• solitary defect or is accompanied by a bicuspid aortic
valve

51. • Clinical manifestations ---severity of the narrowing and the
patency of the ductus arteriosus.
Coarctation of the aorta with a PDA usually manifests early in life;
• the delivery of unsaturated blood through the PDA produces
cyanosis localized to the lower half of the body.
coarctation of the aorta without a PDA--- . Most children are
asymptomatic
• Hypertension in the upper extremities with weak pulses and
hypotension in the lower extremities--- claudication and coldness
• Development of collateral circulation -- through enlarged
intercostal and internal mammary arteries------- visible erosions
(“notching”) of the undersurfaces of the ribs.
• murmurs -- throughout systole; sometimes “thrill”
• long-standing pressure -- left ventricular hypertrophy.

52. Pulmonary Stenosis and Atresia
• obstruction at the level of the pulmonary valve.
• This can be mild to severe
• isolated or part of a more complex anomaly—
either TOF or TGA
• Right ventricular hypertrophy typically develops,

53. Aortic Stenosis and Atresia
• obstruction of the aortic valve
• can occur at three locations: valvular, subvalvular,
and supravalvular.
• hypoplasia of the left ventricle and ascending aorta
• The ductus must be open to allow blood flow to the
aorta and coronary arteries