MeSH
| ductus arteriosus, patent |
ligamentum arteriosus (arterial
ligament) |
vascular ring |
|
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|
Abstract
Patent ductus arteriosus (PDA),
one of the most common congenital heart defects, is an abnormal persistence
of a patent lumen in the arterial duct due to an arrest of the natural
process of closure after it has served its function as a vital channel
in fetal circulation. The histological feature of the arterial duct is
entirely different from its adjoining arteries and many intrinsic substances
mediate in the process of its normal closure. When existing in isolation,
catheter or surgical intervention is usually used for its treatment. Ductal
aneurysm is a rare type of PDA. The PDA associated with other congenital
heart disease has variable morphology and closing it naturally or by intervention
may produce critical symptoms. The PDA and its ligament which represents
a closed arterial duct can be part of a vascular ring with abnormal aortic
arch formation. It is important to understand the morphological features
of PDA so as to choose the optimal strategy for treatment.
Introduction
Patent ductus arteriosus (PDA) is
one of the most common congenital cardiovascular malformation which accounts
for 5 to 10 % in all congenital heart disease. 1 It can occur
as an isolated anomaly or in association with other cardiac anomalies,
like pulmonary atresia, coarctation of the aorta or hypoplastic left heart
syndrome.
In the normal heart with a left aortic
arch, the arterial duct arises from the left pulmonary artery very close
to the bifurcation of the pulmonary trunk and connects to the transition
area between aortic arch and descending aorta just distal to the origin
of the left subclavian artery. In normal fetal development, the arterial
duct is a crucial channel in the circulation conveying deoxygenated blood
to the descending aorta.
Normally, the arterial duct closes
after the baby is born. Physiologic closure usually occurs soon after birth
and the duct is occluded anatomically within 3 months. Very occasionally
it narrows and occludes prematurely during fetal life. In some patients,
however, the duct fails to close after birth and its lumen remains widely
patent.2 This condition is commonly diagnosed as PDA. It is
very important for the treatment of PDA to understand the morphology and
the closing process of the duct.
Embryology of the arterial duct
In the normal early embryonic stage,
the arterial duct exists bilaterally on both right and left sides but the
right duct becomes atrophied at around Carnegie stage sixteen (37 to 40
days post embryonic gestation)(Fig1). The arterial duct is formed from
the left sixth embryonic aortic arch from which the pulmonary artery also
originates. Their histological compositions of the arterial walls are entirely
different.3
Figure 1: Embryonic development
of the normal aortic arch. The arterial duct exists bilaterally on both
right and left sides at Carnegie stage 16 (37-40 days of post embryonic
gestation). After stage 16, the right-sided arterial duct is atrophied
and the right dorsal aorta is obliterated at stage 18 (44-48 days). At
the end of arch development (stage 23; 56-60 days) the arterial duct connects
to the aortic arch just distal to the left subclavian artery. CA= carotid
artery; D= ductus arteriosus; SCA= subclavian artery.
In normal embryogenesis, the duct
connects the ipsilateral arch, usually the left-sided aortic arch that
is derived from the embryonic fourth arch. The ductal insertion is at the
inner curvature of the arch just distal to the ipsilateral left subclavian
artery. The latter is derived from cephalad migration of the seventh intersegmental
artery on the left side. When the arterial duct is contralateral to the
aortic arch, it arises from the brachiocephalic artery or ipsilateral subclavian
artery. Rarely, this abnormal origin of the duct can cause isolation of
the subclavian artery or right pulmonary stenosis during normal closure
of the duct if ductal tissue has extended into the adjoining vessels.4
The isolated right subclavian artery is then supplied retrogradely via
the vertebral artery.
Histology and anatomical closure
of the arterial duct
Histologically, the wall of the
arterial duct is easily distinguishable from the fibro-elastic walls of
the aorta and pulmonary trunk/artery (Fig. 2).5, 6 While the
great arteries have walls composed of elastic layers, the ductal wall is
mainly muscular. The wall of the normal arterial duct is lined on its luminal
aspect by an intimal layer of endothelial cells that overlies an internal
elastic lamina. The elastic lamina is fragmented and sometimes split up
into several layers. It is interrupted by intimal cushions that lie underneath
it. The media of the ductal wall mainly consists of circularly arranged
smooth muscle cells with minimal elastic fibres in between. The inner layer
of the media has been described as having a longitudinal arrangement of
the muscle bundles whereas the muscle bundles in the outer layer are circularly
arranged (Fig2). However, the methodical studies of von Hayek found the
media to be composed of two spiral arrangements of smooth muscles that
are in opposite directions.7 The outer spiral is more acute,
giving the impression of circularly arranged smooth muscle fibres whereas
the inner spiral is more gradual so the fibres appear longitudinal.
Figure 2: Histologic sections
through two normal ducts from neonates. (A)This longitudinal section shows
the distinctive appearance of the ductal wall composed mainly of smooth
muscle compared to the walls of the aorta and pulmonary trunk which are
composed primarily of elastic tissue. (B) This transverse section shows
the intimal cushions (c) that protrude toward the ductal lumen. m=media.
[trichrome stain]
The process of the closure of the
arterial duct occurs in two steps.8 The first stage is due to
constriction of the smooth muscle in the media of the ductal wall, which
produces shortening and an increase in wall thickness. This change of the
wall of the arterial duct develops significant ischemic hypoxia which leads
to produce several protein factors, such as vascular endothelial growth
factor, transforming growth factor and other inflammatory mediators. At
the same time, the intimal cushions (or mounds) enhance the thickening
of the ductal wall by proliferation of connective tissue and, later, increase
in elastic tissue while smooth muscle fibres become less conspicuous. The
cushions disrupt the internal elastic membrane and form swollen protrusions
into the ductal lumen. Cushions along opposite walls gradually unite and
finally obliterate the lumen. Macroscopically, the intimal cushions give
the luminal surface of the ductal wall an irregular appearance whereas
the walls of the adjoining great arteries are usually smooth. The first
step is more evident at the pulmonary end than the aortic end which may
remain open as an aortic ampulla after the remaining part of the duct has
become occluded and ligamentous.
The second stage of the closure is
due to proliferation of connective tissue in the intima and media. Atrophy
of smooth muscle cells ultimately transforms the muscular vessel into a
non-contractile ligament represented by a mass of dense elastic and fibrous
tissue that occasionally contains a slit-like lumen. This process continues
several weeks. The arterial duct is completely closed by 8 weeks of age
in 88% of infants with a normal cardiovascular system.9
Mechanism of functional closure
of the arterial duct
It is well known that oxygen tension
and prostaglandins have significant effects on ductal closure. They act
directly on the smooth muscle of the duct but in opposite directions with
increasing oxygen tension constricting the duct and prostaglandins relaxing
it. Reduction of prostaglandin synthesis by cyclooxgenase (COX) inhibitor
causes ductal constriction in the fetus.10
Furthermore, there are various vasoactive
substances (including; nitric oxide, bradykinin, endogenous catecholamines)
which mediate ductal closure. Nitric oxide is a vasodilater which contributes
to patency of the duct. In both animal and human studies, nitric oxide
inhibitor has been shown to cause strong constriction of the duct with
non-steroid anti-inflammatory drug (indomethacin).11
Morphology of PDA
Isolated PDA
The most common malformation is
PDA occurring in isolation. Histologically, the internal elastic lamina
in the PDA is generally intact and the intimal cushions are absent or are
less well formed than normal (Fig. 3).6
Figure 3: Histology image
showing part of a persistently patent duct cut in cross-section. The internal
elastic lamina is intact and appears as a black line lining the ductal
lumen. Intimal cushions are barely formed, leaving a widely patent lumen.
[elastic van Geison stain]
The PDA connects the upper descending
aorta to the bifurcation of the main pulmonary artery (pulmonary trunk)
close to the origin of the left pulmonary artery. Ductal anatomy varies
in terms of its size (length and diameter), its shape, and its topography
in relation to adjacent structures. In the fetus and the newborn the duct
is wide and appears as a direct continuation of the pulmonary trunk. From
the pulmonary bifurcation, it runs nearly parallel to the aortic arch and
unites with the beginning of the descending aorta approximately 1cm distal
to the origin of the left subclavian artery. It enters the descending aorta
at an acute angle of 30° to 35° and overlaps its aortic entrance
when viewed in antero-posterior projection. When it is large it bulges
beyond the lateral wall of the aorta. In the fetus the pulmonary end of
the duct is related to the left border of the sternum and the second left
costal cartilage but it shifts lower into the second interspace in the
first few months after birth. This corresponds posteriorly to the level
of the sixth rib and the sixth intercostal space. From anterior to posterior
the inferior surface of the duct is related to the left pulmonary artery,
the recurrent laryngeal nerve, the left bronchus, and the left vagus nerve.
The usual size of the duct in the
newborn varies from 7 to 11mm long and 4 to 5mm in diameter. However, extreme
lengths or diameters can occur. The shape of the duct varies considerably.
Morphologically, the duct may be tubular, funnel shaped, long and meandering,
short or have no length at all (window duct), or is aneurysmal (Fig. 4,5,6).
The classification of Krichenko and colleagues12 based on the
appearance of the ductal lumen on angiography and the location of the ductal
insertions relative to the air shadow of the trachea is a useful aid when
considering interventional device closure.
Figure 4: The tubular shaped
duct. (A)This neonatal duct is widely patent. The pulmonary trunk, duct
and descending aorta forms a continuous channel. (B) This angiogram of
a tubular duct that is without a restrictive lesion to flow. This shape
could be unsuitable for catheter occlusion by coils owing to the risk of
coil embolization. (Arch= aortic arch; PT= pulmonary trunk; DAo= descending
aorta)
Figure 5: The short duct.
(A)This PDA (arrow) is extremely short and resembles a window between the
pulmonary bifurcation and the underside of the aortic arch. (B)This angiocardiogram
shows a duct with a similar morphology. Arch= aortic arch; DAo= descending
aorta; LPA= left pulmonary artery; PDA= patent arterial duct; PT= pulmonary
trunk; RPA= right pulmonary artery
Figure 6: The aneurysmal
duct. This specimen viewed from the front shows a long duct with an aneurysmal
bulge (arrow).
Usually the PDA has a tubular shape
or it may be funnel-shaped with a wide aortic orifice and a considerably
narrower pulmonary end which is restrictive to flow (Fig. 7). The aortic
ampulla is prominent. The narrower orifice is thought to represent the
site of initial impetus for closure.
Figure 7: Angiographic image
of a funnel-shaped duct. The PDA arises from the inner curvature of the
upper descending aorta. The pulmonary end is very narrow and restrictive
to flow. Arch= aortic arch; PDA= patent arterial duct; PT= pulmonary trunk,
DAo= descending aorta
The short duct may be narrowed at
its aortic end and also appear funnel-shaped.13 Occasionally,
the duct may have no length and the opening resembles a window between
the aorta and pulmonary artery (Fig 5). Coil embolization and reopening
of the ductal channel is the most common complication when treating this
shape of PDA using the transcatheter route.14 Video-Assisted
Transscopic Surgery or conventional surgery, can be considered in this
type.15 The window duct will likely require patch closure rather
than ligation.
The tubular shaped duct has a uniform
calibre or it may have a constriction in the middle giving its lumen an
hour-glass appearance. In some cases, there are multiple constrictions
within.
Ducts that are long and meandering
or form right angles are rarely seen in isolation. They are more often
associated with other congenital heart defects.
The aneurysmal arterial duct is rare
type. Most cases result from partial closure of the aortic end after the
pulmonary end has occluded, trapping blood to from a clot in the ductal
lumen. (Fig. 6) Others are aneurysmal ducts with narrow openings at both
ends suggesting the closure process was initiated at both ends but not
within the duct itself. The probable complications of both types are dissection,
rupture or thromboemboli. In case of aneurysmal dilatation, left vocal
cord paralysis can occur by compression of the left laryngeal nerve.
PDA in association with other
congenital heart disease
There are various morphological
features of the arterial duct with other congenital heart anomalies. In
hearts with severe right heart obstructive lesion like pulmonary atresia
or stenosis patency of the duct is important for blood supply to the lungs.
Generally, the duct is wider than normal but is narrower than the aorta.
In cases with pulmonary atresia the duct may be long, considerably more
tortuous, narrow, and may insert at right angles to the aorta (Fig. 8).16
Figure 8: Two specimens of
long and meandering (curly) duct indicated with white arrows. (A)This specimen
viewed from the front has muscular atresia of the right ventricular outflow
tract. (B)This specimen with critical valvar pulmonary stenosis and double
outlet right ventricle is viewed from the left side. Ao= aorta; LPA= left
pulmonary artery; PT= pulmonary trunk.
In the duct-dependent systemic circulation
like hypoplastic left heart syndrome or interrupted aortic arch ductal
constriction can cause critical symptoms in early infancy. Usually the
duct is straight with a tubular shape and is significantly wider than the
aorta (Fig. 9).17 Extensions of ductal tissue into the aortic
lumen of hypoplastic left heart can be a substrate for coarctation lesion.
Figure 9: This specimen viewed
from the front shows a widely patent arterial duct associated with aortic
atresia in the setting of hypoplastic left heart syndrome. The aortic arch
and coronary arteries are supplied retrogradely via the arterial duct.
AAo= ascending aorta; Arch= aortic arch; DAo= descending aorta; PT= pulmonary
trunk.
PDA with aortic arch malformation
PDA is most frequently found on
the left side but it is occasionally found on the right side in association
with a right aortic arch and mirror-imaged arrangement of the neck and
arm arteries. In abnormal development of the embryonic aortic arch, the
PDA, or its ligament, can contribute to the formation of a vascular ring
that encircles the trachea and esophagus.
There are several patterns of vascular
rings involving the arterial duct.18 The right aortic arch with
retroesophageal component occasionally forms vascular ring when it is tethered
to the left pulmonary artery by a left duct that arises from the upper
part of the descending aorta. As part of the right aortic arch and retroesophageal
right subclavian artery lie behind the oesophagus, the trachea and esophagus
become surrounded by the ascending aorta, the pulmonary trunk and the left
PDA (or ligament) (Fig10).
Figure 10: This ‘aerial’
view of a right aortic arch with left ductal ligament(arrows) shows the
vascular ring around the trachea(T) and esophagus(Eso) pedicle. AAo= ascending
aorta; LSc= left subclavian artery; PT= pulmonary trunk.
The left aortic arch with right descending
aorta is a possible combination for vascular ring, but it is uncommon.19
In combination with right PDA or ligament the left aortic arch forms a
vascular ring. A rare situation was reported in a patient with dextrocardia
in whom the left-sided PDA caused tracheal compression.
Conclusions
PDA can show various shapes with
or without associated congenital heart and vascular anomalies. Nowadays,
there are several choices for treating PDA – pharmacologic, surgery or
transcatheter intervention. Selection of treatment depends on the shape
and size of the PDA, age of patient, and hemodynamic condition. Appreciation
of the location and morphological features of PDA is necessary for selecting
the optimal treatment option for the individual patient.
Acknowledgement
The Cardiac Morphology Unit receives
funding support from the Royal Brompton and Harefield Hospital Charitable
Fund
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Contact information
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Siew
Yen Ho
National Heart & Lung Institute,
Imperial College London
Guy Scadding Building, Dovehouse
Street, London, SW3 6LY
Tel: 0207 351 8751
Fax: 0207 351 8230
yen.ho@imperial.ac.uk
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