- The document reviews the development of the heart from early progenitor cells to the fully formed organ. - Cardiac progenitor cells migrate to the cardiogenic field and are induced by endoderm to form the primitive heart tube, which initially lies above the neural plate but is overgrown as the brain develops. - The heart tube loops to the right to place the ventricles in line with the atria. Septa then develop to divide the atria and ventricles and form the interventricular foramen which will later close. - The sinus venosus is incorporated into the right atrium as venous blood flow biases to the right side. Molecular signals including NKX2.5 and TB

1. DEVELOPMENT OF HEART
A REVIEW
-DrKrishnaKanth

2. Establishment of the
Cardiogenic Field
► The vascular system appears in the middle of the third
week.
► Cardiac progenitor cells lie in the epiblast.
► They migrate through the streak.
► Cells destined to form cranial segments of the heart, the
outflow tract, migrate first, and cells forming more caudal
portions, right ventricle, left ventricle, and sinus venosus,
respectively, migrate in sequential order.
► The cells proceed toward the cranium and position
themselves rostral to the buccopharyngeal membrane and
neural folds.
► Here they reside in the splanchnic layer of the lateral plate
mesoderm

3. ► late in the presomite stage of development, they
are induced by the underlying pharyngeal
endoderm to form cardiac myoblasts.
► Blood islands also appear in this mesoderm
► horseshoe-shaped “cardiogenic field”.
► pericardial cavity.
► In addition to the cardiogenic region, other blood
islands appear bilaterally, parallel and close to the
midline of the embryonic shield. These islands
form a pair of longitudinal vessels, the dorsal
aortae.

4. ►Initially,
the central portion of
the cardiogenic area is anterior to
the buccopharyngeal membrane
and the neural plate.
Rapid development and flexion of
the head, With closure of the neural
tube and formation of the brain
vesicles, however, the central
nervous system grows cephalad so
rapidly that it extends over the central
cardiogenic area and the future
pericardial cavity.
Two lateral extensions of cardiac
tissue become hollowed out to
form a pair of endothelial tubes,
which soon fuse to form the
primitive cardiac tube.

5. ► The developing heart tube bulges more and more into the pericardial
cavity.
► Initially, however, the tube remains attached to the dorsal side of the
pericardialcavity by a fold of mesodermal tissue, the dorsal
mesocardium
 No ventral mesocardium is ever formed
► With further development, the dorsal mesocardium disappears,
creating the transverse pericardial sinus, which connects both
sides of the pericardial cavity. The heart is now suspended in the
cavity by blood vessels at its cranial and caudal poles
► Mesothelial cells from the region of the sinus venosus migrate over the
heart to form the epicardium.

6. ► Thus the heart tube consists of three layers:
(a) the Endocardium, forming the
internal endothelial lining of the heart;
(b) the Myocardium, forming the
muscularwall & ( c)
the Epicardium or visceral
pericardium, covering the outside of the
tube. This outer layer is responsible for
formation of the coronary arteries,including
their endothelial lining and smooth muscle.

7. The primitive cardiac tube has five zones:
the arterial trunk
the bulbus cordis )
} some would call these two together
the ventricle ) the primitive ventricle, with inlet
and outlet portions
the atrium
and the sinus venosus
The arterial trunk will divide to separate the pulmonary and systemic supply.
The bulbus and the ventricle will differentiate into the right and left ventricles.

8. ► The atrial portion, initially a paired structure outside the pericardial cavity,
forms a common atrium and is incorporated into the pericardial cavity
► The atrioventricular junction remains narrow and forms the
atrioventricular canal, which connects the common atrium and the early
embryonic ventricle.
► The bulbus cordis is narrow except for its proximal third. This portion will
form the trabeculated part of the right ventricle
► The midportion, the conus cordis, will form the outflow tracts of both
ventricles.
► The distal part of the bulbus, the truncus arteriosus, will form the roots and
proximal portion of the aorta and pulmonary artery
► The junction between the ventricle and the bulbus cordis, externally
indicated by the bulboventricular sulcus , remains narrow.
► It is called the primary interventricular foramen

9. •The fold of the loop is principally at the junction of bulbus cordis and ventricle. Note in
panel C that the two end up side by side.
•Left ventricle will develop from the ventricle, and the right ventricle will develop from
the bulbus cordis. (And an l-loop will
result in ventricular inversion with the left ventricle on the right .)(for more, see “The Anatomy of
Ventricular Looping….Jorg Manner Clinical Anatomy Jan 2009 21-35)
•Note also that the arterial trunk is above the developing right ventricle.

10. The cardiac tube grows at a greater
longitudinal rate then the rest of the
embryo, causing it to fold. As it does this
it falls to the right. This is known as
d-looping. It may fall to the left in an
l-loop: this will lead to a malformed heart.
normal d-loop l-loop

11. ► The cephalic portionof the tube bends
ventrally, caudally, and to the right.
► The atrial (caudal) portion shifts
dorsocranially and to the left.
► This bending, which may be due to cell
shape changes, creates the cardiac loop.
It is complete by day 28.

12. Molecular Regulation of
Cardiac Development
► Signals from anterior (cranial) endoderm induce a heart-forming region
in overlying splanchnic mesoderm by turning on the transcription factor
NKX2.5 .
 The signals require secretion of bone morphogenetic proteins (BMPs)
2 and 4 and inhibitors (crescent) of WNT genes in the endoderm and
lateral plate mesoderm
► This combination later, plays a role in septation and in development of
the conduction system
► NKX2.5 contains a homeodomain and is a homologue of the gene
tinman, which regulates heart development in Drosophila.
► TBX5 is another transcription factor that contains a DNA-binding motif
known as the T-box. Expressed later than NKX2.5, it plays a role in
septation.

14. 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.
► 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. 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.
► 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

15. Opposite the dividing atrioventricular
valve, the posterior walls of the atria
are beginning to lateralise. The
symmetrical systemic venous system
biases its growth to the right and
many of its left sided structures
disappear or involute. Thus the
systemic veins drain to the right side.

16. ► 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 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
► Its entrance, the sinuatrial orifice, is flanked on each side by a valvular fold,
the right and left venous valves.
► Dorsocranially the valves fuse, forming a ridge known as the septum
spurium
► 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.
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)

18. A septum is developing down the
middle of the atrium, probably in a
similar way to the ventricular septum
in that it is a ridge left behind as the
atrial walls grow away from it.
The to the left of the septum, the primary
pulmonary vein grows and seeks out
the primitive pulmonary venous complex.
As growth proceeds, the primary
vein is absorbed into the atrial wall
as showed here, to achieve the adult
form of separate left and right lung
drainage.

19. This is an actual looped heart
Note that the ventricular mass is
now in line with the atria
By the end of the fourthweek,
the two primitive ventricles
begin to expand.
This is a cutaway showing
the beginnings of the ventricular
septum. The ventricles will develop
as outpouchings from this position,
in the direction of the arrows.

20. ► This is accomplished by continuous
growth of the myocardium on the
outside and continuous diverticulation
and trabecula formation on the inside
► The medial walls of the expanding
ventricles become apposed and
gradually merge, forming the
muscular interventricular septum

21. the “septal crest”

22. lumen of the original tube,
here.
It forms a communication
between the ventricles: persistence of
it will result in the commonest
of ventricular septal defects, the
perimembraneous VSD

23. ► The interventricular foramen, above the
muscular portion of the interventricular septum,
shrinks on completion of the conus septum.
► During further development, outgrowth of tissue
from the inferior endocardial cushion along the top
of the muscular interventricular septum closes the
foramen.
This tissue fuses with the abutting parts of the
conus septum.
► Complete closure of the interventricular foramen
forms the membranous part of the
interventricular septum.

24. ► The masses, known as endocardial cushions,
develop in the atrioventricular and
conotruncal regions.
► Inthese locations they assist in formation of the
atrial and ventricular (membranous portion )
septa, the atrioventricular canals and
valves, and the aortic and pulmonary
channels.
► 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).

27. The septum primum, which is the first septum to develop,
is an incomplete thin-walled partition,in which
the anteroinferior free edge is above the atrioventricular canal
and becomes lined by tissue derived from the superior,
and inferior endocardial cushions.
 Before the resultant interatrial opening (ostium primum)
becomes sealed by endocardial cushion tissue, programmed
cell death in an area near the anterosuperior aspect of
the septum primum creates small cribriform perforations.
These perforations coalesce to form a large, second interatrial
communication (ostium secundum) maintaining
interatrial blood flow.
At this time, to the right of the first septum, an anterosuperior
infolding of the atrial roof occurs and forms
a second septal structure (septum secundum).

28. It expands posteroinferiorly as a thick-walled muscular ridge
to form an incomplete partition that overlies the ostium
secundum. As atrial septation is accomplished, septum
secundum forms the limbus of the fossa ovalis and septum
primum forms the valve of the fossa ovalis

29. This diagram is a little more true. The septum secundum is not really a true intracavitary
septum, but is a fold of atrial wall invaginating from the superior surface.
As atrial septation is accomplished, septum secundum forms
the limbus of the fossa ovalis and septum primum forms
the valve of the fossa ovalis.
The channel for interatrial blood flow through the ostium secundum is known
as the foramen ovale.

30. Here is someone else’s interpretation

31. Some authors subscribe to the feeling that the septum
septum secundum primum does not actually fenestrate, but that it
and the septum secundum form eccentrically
overlapping flanges.
In any event, where the two cross in the middle
is the oval fossa if they overlap completely, or is a
secundum atrial septal defect if they leave a gap.
LA
RA
Ao
septum primum

33. ► 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.
► 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.
► 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.

34. ► 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.

37. The ventricles position themselves and the great vessels spiral down
to cross the circulation before the truncal septum fuses with the
superior margin of the septal crest.
Inferior to this, the posterior part of the septal crest is heading towards the AV valve,
which itself is dividing into the mitral and tricuspid valves
Four cushions (AVC) have
developed at the A/V junction; the
superior and inferior cushions will
meet to divide the AV orifice (AVO)
into the tricuspid and mitral valves.
The inferior septal crest (VS)
will aim to meet the divided valve
where the cushions fuse.

38. Atrioventricular Valves
► After the atrioventricular endocardial cushions fuse, each
atrioventricular orifice is surrounded by local proliferations of
mesenchymal tissue.
► 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.
► 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 thewall of the ventricle, the
papillary muscles, by means of chordae tendineae
In this manner two valve leaflets, constituting the bicuspid, or
mitral, valve, form in the left atrioventricular canal, and three,
constituting thetricuspid valve, form on the right side.

39. CLINICAL CORRELATES
► Heart and vascular abnormalities make up the largest category of
human birth defects, accounting for 1% of malformations among live-
born infants.The incidence among stillborns is 10 times as high.
► It is estimated that 8%of cardiac malformations are due to genetic
factors, 2% are due to environmental agents, and most are due to a
complex interplay between genetic andenvironmental influences
(multifactorial causes).
► Classic examples of cardiovacular teratogens include rubella virus
and thalidomide. Others include isotretinoin (vitamin A),
alcohol, and many other compounds.
► Maternal diseases,such as insulin-dependent diabetes and
hypertension, have also been linked to cardiac defects.
► 33% of children with chromosomal abnormalities have a congenital
heart defect, with an incidence of nearly 100% in children with trisomy
18.

40. ► mutations in the heart-specifying gene NKX2.5, on chromosome 5q35,produce
atrial septal defects (secundum type) and atrioventricular conduction delays in
an autosomal dominant fashion.
► Mutations in the TBX5 gene result in Holt-Oram syndrome, characterized
by preaxial (radial) limb abnormalitiesand atrial septal defects.
► One of the most significant defects is the ostium secundum
defect,characterized by a large opening between the left and right atria. It is
caused either by excessive cell death and resorption of the septum primum or by
inadequate development of the septum secundum.
► The most serious abnormality in this group is complete absence of the atrial
septum. This condition, known as common atrium or cor triloculare
biventriculare, is always associated with serious defects elsewhere in the
heart.
► premature closure of the oval foramen, leads to massive hypertrophy of
the right atrium and ventricle and underdevelopment of the left side of the heart.
Death usually occurs shortly after birth.
► Endocardial cushions of the atrioventricular canal not only divide this canal
into a right and left orifice, but also participate in formation of the membranous
portion of the interventricular septum and in closure of the ostium primum.

41. ► Whenever the cushions fail to fuse, the result is a
persistent atrioventricular canal, combined
with a defect in the cardiac septum. This septal
defect has an atrial and a ventricular component,
separated by abnormal valve leaflets in the single
atrioventricular orifice.
► Occasionally, endocardial cushions in the
atrioventricular canal partially fuse. The result is a
defect in the atrial septum, but the interventricular
septum is closed. This defect, the ostium
primum defect, is usually combined with a cleft
in the anterior leaflet of the tricuspid valve.

42. Persistence of AV Canal & Ostium Primum

43. And to finish, a word on the AV valves. Looking back
on this image from a few slides ago, you may have
noticed that the way the septum seals off the “VSD”
space is not a simple line.
The area in question becomes the membranous septum, and is offset towards the mitral valve
resulting in a portion that is interventricular (MSV) and one that is between the LV and the
right atrium (MSA). You will meet this anatomy again in echocardiography and in your
understanding of the atrioventricular septal defects (“canal” defects). It allows the
wedging of the aortic valve between the mitral and tricuspid valves described before.
Well, that’s it. I do hope it has helped. On the next slide I have classified some congenital
malformations on the underlying embryological fault: feel free to give it a try.

45. ► Faulty development of the endocardial cushions and of the atrioventricular
septum is thought to be responsible for the broad range of AVSDs. In partial
AVSDs, incomplete fusion of the superior and inferior endocardial cushions
results in a cleft in the midportion of the anterior mitral leaflet, often associated
with mitral regurgitation. In contrast, complete AVSD is associated with lack of
fusion between the superior and inferior cushions and, consequently, with the
formation of separate anterior and posterior bridging leaflets along the
subjacent ventricular septum
► Failure of the endocardial cushions to fuse creates a defect in the
atrioventricular septum. The primum atrial septal component of this defect is
usually large. This results in downward displacement of the anterior mitral
leaflet to the level of the septal tricuspid leaflet . In AVSDs, the atrioventricular
valves have the same septal insertion level in contrast to the leaflet
arrangement in the normal heart . The distance from the cardiac crux to the left
ventricular apex is foreshortened, and the distance from the apex to the aortic
valve is increased

46. Septum Formation in Truncus &
Conus
► During the fifth week, pairs of opposing ridges appear in the truncus.
► These ridges, the truncus swellings, or cushions, lie on the right
superior wall (right superior truncus swelling ) and on the left
inferior wall (left inferior truncus swelling )
► The right superior truncus swelling grows distally and to the left, and
the left inferior truncus swelling grows distally and to the right.
► Hence, while growing toward the aortic sac, the swellings twist around
each other, foreshadowing the spiral course of the future septum
► After complete fusion, the ridges form the aorticopulmonary
septum, dividing the truncus into an aortic and a pulmonary
channel.

47. ► When the truncus swellings appear, similar swellings (cushions)
develop along the right dorsal and left ventral walls of the conus
cordis.
► The conus swellings grow toward each other and distally to unite with
the truncus septum.
► When the two conus swellings have fused, the septum divides the
conus into an anterolateral portion (the ouflow tract of the right
ventricle) and a posteromedial portion (the outflow tract of the left
ventricle).
► Neural crest cells, migrating from the edges of the neural folds in the
hindbrain region, contribute to endocardial cushion formation in both
the conus cordis and truncus arteriosus.
► Abnormal migration, proliferation, or differentiation of these cells
results in congenital malformations in this region, such as tetralogy of
Fallot , pulmonary stenoses, transposition of the great vessels and
persistent truncus arteriosus.
► Since neural crest cells also contribute to craniofacial development, it
is not uncommon to see facial and cardiac abnormalities in the same
individual.

49. Now for the arterial trunk.
This structure does truly septate,
but embryologically it is a simple
coronal division in its embryonic
straight position.
It will end up as a spiral
The septation extends upwards from
the valves to end just beyond
the origin of the paired sixth aortic arches,
where it seals off against the posterior truncal wall.
As the sixth arch vessels are destined to be the
branch pulmonary arteries, the posterior channel is now
the main pulmonary artery. The anterior channel is the aorta.
This is why the aorta always arches over the pulmonary
arteries from anterior to posterior, no matter what
other cardiac abnormality is present.

50. Because of the looping, the septating
arterial trunk will be dragged to the
right , and twisted as well.
As a result the ascending aorta
comes to lie to the right of the
pulmonary artery.
Note that the looping brings the
trunk close to the AV canal.
The aorta is now poorly placed to attach itself to the
left ventricle and some mechanism is needed to
drag it to the left but still leave the PA over the right
ventricle.

51. At this stage, as we saw before, the ventricular mass is centralising in front of the AV
canal so that separate atria can serve each ventricle. If we take a view downwards
onto the crest of the septum, looking from the atria, we see something like this:
anterior
See how close the outlet
is to the inlet. If the gap
between them fails to grow
with the rest of the heart, in
the fully formed heart the two
right will be in continuity.

52. A surge of growth beneath the pulmonary artery
pushes it up, forward and right (black arrows). The gap
between the aorta and the inlet valve remains small
and fibroses (dotted line). These processes pin the
aortic valve to the rim of the developing mitral valve
as everything around them expands.
aorta
pulmonary artery
As a result, the aorta arises from the
left ventricle while the pulmonary
artery has risen over the right ventricle.
Once the gap between the truncal
septum and the septal crest obliterates,
the systemic and pulmonary supplies
will have been separated, and
connected to the correct ventricle.

53. And so now you can compare the flow scheme on the left with the more lifelike image
on the right
RPA = right pulmonary artery
LPA = left pulmonary artery
APS = aortopulmonary
(truncal) septum
RVO = RV outflow
LVO = LV outflow

54. Semilunar Valves
► When partitioning of the truncus is almost complete,
primordia of the semilunar valves become visible as small
tubercles found on the main truncus swellings.
► One of each pair is assigned to the pulmonary and aortic
channels, respectively.
► A third tubercle appears in both channels opposite the
fused truncus swellings. Gradually the tubercles hollow out
at their upper surface, forming the semilunar valves.
► Recent evidence shows that neural crest cells contribute to
formation of these valves.

55. Viewing the mature anatomy form the atrial side, the two atrioventricular valves
have assumed their circular orifice shapes. The aortic valve, as we have discussed,
is in continuity with the mitral annulus: the AV valves have separated slightly at the
top, allowing the aortic valve to wedge between the mitral and tricuspid annuli, coming
to rest very close to the tricuspid annulus. The pulmonary valve remains pushed
up and forward, though still in continuity with the aortic valve.

56. This pattern of connections between the annuli of the four cardiac valves constitutes the
fibrous “skeleton” of the
heart, here viewed from
pulmonary the front.
Note that the commissures of the
aortic and pulmonary valves
reflect their common origin with
aortic
one commissure of each still in
line with its old partner.
The
coronary artery origins will always
be from the sinuses adjacent to
the common commissure, even in
congenital abnormalities of aortic
position and/or connection.
tricuspid mitral

57. CLINICAL CORRELATES
► Ventricular septal defect (VSD):
VSD is often associated with abnormalities
in partitioning of the conotruncal region.

59. Tetralogy Of Fallot
► Fallot's name refers to the tetrad of right ventricular outflow obstruction, aortic override,
ventricular septal defect, and right ventricular hypertrophy.
► It is safe to say, however, that the most characteristic and hallmark finding is the
subpulmonic stenosis created by the deviation of the outlet, or conal, septum
► The obstruction is further exacerbated by hypertrophy of the muscular outlet septum, the
parietal right ventricular free wall, and components of the septomarginal trabeculations
► All patients with TOF demonstrate anterior and cephalad
deviation of this outlet septum, and the degree and nature
of this deviation determine the severity of subpulmonic
obstruction
► The ventricular septal defect in TOF most frequently has fibrous continuity between the
tricuspid and aortic valve, and hence may be considered a true perimembranous defect

60. Persistent truncus
arteriosus
► Results when the conotruncal ridges fail to fuse
and to descend toward the ventricles
► The pulmonary artery arises some distance
above the origin of the undivided truncus.
► Since the ridges also participate in formation of the
interventricular septum, the persistent truncus is
always
accompanied by a defective interventricular
septum.
► The undivided truncus thus overrides both
ventricles and receives blood from both sides.

61. Transposition of the great
vessels
► occurs when the conotruncal septum fails to follow
its normal spiral course and runs straight down.
► As a consequence, the aorta originates from the
right ventricle, and the pulmonary artery originates
from the left ventricle.
► sometimes is associated with a defect in the
membranous part of the interventricular septum.
► Since neural crest cells contribute to the formation
of the truncal cushions, insults to these cells
contribute to cardiac-defects
involving the outflow tract.

62. Double Outlet Ventricle
► Double Outlet Ventricle refers to abnormal
ventriculo arterial alignment in which both
arteries appear to arise exclusively or
predominantly from morphological right or
left ventricle

63. Formation of the Conducting
System of the Heart
► Initially the pacemaker for the heart lies in the caudal part
of the left cardiac tube.
► Later the sinus venosus assumes this function, and as the
sinus is incorporated into the right atrium, pacemaker
tissue lies near the opening of the superior vena cava.
Thus, the sinuatrial node is formed.
► The atrioventricular node and bundle (bundle of
His) are derived from two sources: (a) cells in the left wall
of the sinus venosus, and (b) cells from the atrioventricular
canal.
► Once the sinus venosus is incorporated into the right
atrium, these cells lie in their final position at the base of
the interatrial septum.

64. Vascular Development
► When pharyngeal arches form during the fourth and fifth weeks of
development,each arch receives its own cranial nerve and its own
artery.
► These arteries, the aortic arches, arise from the aortic sac, the
most distal part of the truncus arteriosus.
► The aortic arches are embedded in mesenchyme of the pharyngeal
arches and terminate in the right and left dorsal aortae. (In the region
of the arches the dorsal aortae remain paired, but caudal to this region
they fuse to form a single vessel.)
► Division of the truncus arteriosus by the aorticopulmonary septum
divides the outflow channel of the heart into the ventral aorta and
the pulmonary artery.
► The aortic sac then forms right and left horns, which subsequently give
rise to the brachiocephalic artery and the proximal segment of the
aortic arch, respectively.

65.  first aortic arch has disappeared, although a small portion persists
to form the maxillary artery.
► second aortic arch: Disappears. The remaining portions of this arch
are the hyoid and stapedial arteries.
► The third aortic arch forms the common carotid artery and the
first part of the internal carotid artery. The remainder of the
internal carotid is formed by the cranial portion of the dorsal aorta. The
external carotid artery is a sprout of the third aortic arch.
► The fourth aortic arch persists on both sides, but its ultimate fate is
different on the right and left sides. On the left it forms part of the arch
of the aorta, between the left common carotid and the left subclavian
arteries.
► On the right it forms the most proximal segment of the right subclavian
artery, the distal part of which is formed by a portion of the right dorsal
aorta and the seventh intersegmental artery .
► The fifth aortic arch either never forms or forms incompletely and
then regresses.

66. ► The sixth aortic arch, also known as the
pulmonary arch, gives off an important
branch that grows toward the developing
lung bud.
► On the right side the proximal part becomes
the proximal segment of the right pulmonary
artery.
► The distal portion of this arch loses its
connection with the dorsal aorta and
disappears. On the left the distal part
persists during intrauterine life as the
ductus arteriosus.

67. CLINICAL CORRELATES
► Ductus Arteriosus :
► Under normal conditions the ductus arteriosus is functionally closed
through contraction of its muscular wall shortly after birth to form the
ligamentum arteriosum.
► Anatomical closure by means of intima proliferation takes 1 to 3 months.
► coarctation of the aorta :
► aortic lumen below the origin of the left subclavian artery is
significantly narrowed.
► Since the constrictionmay be above or below the entrance of the
ductus arteriosus, two types, preductal and postductal, may be
distinguished.
► The cause of aortic narrowing is primarily an abnormality in the media
of the aorta, followed by intima proliferations.

68. ► In the preductal type the ductus arteriosus persists, whereas in the
postductal type, which is more common, this channel is usually
obliterated.

69. What if?..............
- then you get
the truncal septum fails to fuse with the septal crest?
- perimembraneous VSD
the truncal septum is deviated to the PA side?
- tetralogy of Fallot
the truncal septum fails to develop?
- truncus arteriosus
the ventricular septum fails to reach the AV valve?
- AV septal defects
the arterial trunk stays over the RV but does divide?
- double outlet RV
the aortic valve pushes up and right instead of the pulmonary?
- transposition of the great vessels
the ventricles fail to centralise over the AV valve
- double inlet left ventricle (commonest form of single ventricle)
the loop is to the left?
- ventricular inversion (RV on the left, LV on the right)
and of course, combinations exist!
This is just a rough summary, but I hope you get the idea. Can you see now why
double outlet RV is common and double outlet LV is very rare? Similarly double inlet LV
is common, double inlet RV rare? And why a VSD so commonly accompanies problems of
connection of the ventricles to the great vessels.

70. Septal Defects
Atrial Septal Defects
► Any opening in the atrial septum, other than a competent
foramen ovale, is an atrial septal defect (ASD).
► Atrial septal defects are classified according to their
location relative to the fossa ovalis
 1) Interatrial communications in the region of the fossa
ovalis may represent either a true secundum ASD or a
valvular incompetent patent foramen ovale
 2) Defects anterior to the fossa ovalis (primum defects)
(often are associated with a cleft in the anterior leaflet of
the mitral valve )

71. ► 3) Those posterior and superior to the fossa ovalis, the sinus venosus
defects, usually occur in conjunction with anomalous connection of the
right pulmonary veins.
► 4) Finally, interatrial communications at the expected site of the
coronary sinus ostium are often associated with an unroofed coronary
sinus and left atrial connection of a persistent left superior vena cava.
►

73. Ventricular Septal Defects

74. ► Defects involving the membranous septum with extension into the adjacent
inlet, outlet, or muscular septum are termed perimembranous defects. A
perimembranous defect lies in the outflow tract of the left ventricle immediately
beneath the aortic valve. Synonyms include membranous defect and
infracristal defect. When viewed from the right side of the heart, the defect is
beneath the crista supraventricularis and posterior to the papillary muscle of
the conus (Fig. 32.1B). This is the location for approximately 80% of defects
seen at surgery or at autopsy
► These defects may involve varying amounts of muscular tissue adjacent to the
membranous septum and have been variously subclassified as
perimembranous inlet, perimembranous muscular, or perimembranous outlet
VSD, depending on the extension of the defect. Minor anomalies of the
tricuspid valve, which may be acquired secondary to left-to-right shunting,
frequently are associated with perimembranous defects
► These anomalies take the form of extra septal leaflet tissue or pouches that
can partially or completely occlude the defect. These pouches have been
called aneurysms of the ventricular septum and can be associated with
spontaneous closure of the VSD.

75. ► With the perimembranous defect, there can be a variable degree of anterior
malalignment between the infundibular septum and the anterior ventricular
septum such that the aortic valve appears to override the defect (9). Posterior
or leftward malalignment also occurs, producing subaortic stenosis
► When the septal commissure of the tricuspid valve is deficient at its
attachment to the atrioventricular membranous septum, a left
ventricular–to–right atrial shunt can occur (10). Such defects normally are
associated with both left ventricular–to–right ventricular and left
ventricular–to–right atrial shunting
► Rarely, a defect can occur in the atrioventricular septum (Gerbode's defect)
that produces an isolated left ventricular–to–right atrial shunt
► Defects in the outflow tract of the right ventricle beneath the pulmonary valve
have been called supracristal, infundibular, conal, subpulmonary, or doubly
committed subarterial defects
► Outlet VSDs constitute approximately 5% to 7% of defects seen at
surgery or autopsy, except in Japan and other Far Eastern countries,
where the incidence is approximately 30%

76. ► Inlet defects that are posterior and inferior to the membranous defect, beneath
the septal leaflet of the tricuspid valve, and inferior to the papillary muscle of
the conus have been called atrioventricular septal defects
► Defects in the muscular septum are frequently multiple and make up 5% to
20% of defects found at surgery or autopsy
► Apical defects are the most common and frequently are difficult to visualize
from the right ventricle because they are usually multiple with bordering and
overlying trabeculae and tortuous channels
► Apical defects are the most common and frequently are difficult to visualize
from the right ventricle because they are usually multiple with bordering and
overlying trabeculae and tortuous channels
► Another type of muscular defect is the central defect (Fig. 32.1B), which is
posterior to the trabecula septomarginalis (septal band of the crista) and in the
midportion of the septum. Commonly, it is partially hidden by overlying
trabeculae when viewed from the right ventricle and can give the impression of
multiple defects
►

77. ► Small muscular defects near the septal–free wall margins have been termed
marginal or anterior defects. These defects are usually multiple, small,
tortuous, and distributed along the ventricular septal–free wall margins
► Prolapse of one of the aortic valve cusps may occur with outlet or
perimembranous VSDs

79. Anyway, the relocation of the aorta to the left requires an appreciation of the modelling power
of differential growth.
All this is happening as the embryo is rapidly growing, even though it is only millimetres long.
day 9
day 13

80. ► Concurrently with atrial septation, the left horn of
the sinus venosus forms the coronary sinus, and
the right sinus horn becomes a part of the right
atrium.
► Infolding at the sinoatrial junction forms the right
and left venous valves. Whereas the right venous
valve is maintained and forms the rudimentary
valves of the inferior vena cava (eustachian valve)
and the coronary sinus (thebesian valve), the left
venous valve becomes fused to the superior,
posterior, and inferior margins of the fossa ovalis.