35
Patent Ductus Arteriosus
JOHN F. KEANE AND DONALD C. FYLER
DEFINITION
The ductus is functionally closed in about 90% of full-
term infants by 48 hours of age. Persistent, some intermit-
tent, patency for up to 10 days after birth is encountered in
patients with circulatory or ventilatory abnormalities and for
even longer periods in premature infants. For this chapter,
patency of the ductus beyond a few days, and without
other significant cardiac lesions, is considered abnormal.
PREVALENCE
The reported incidence of patent ductus in infants ranges
from 0.1381 to 0.8 per 1000 live births,2 the former value
from earlier years among mostly ill infants and the latter in
more recent times in the echocardiographic era. At Children’s
Hospital Boston, the number of patients seen, among all
age groups, with a patent ductus during the past 14 years
has been smaller than during the preceding 15 years
(Exhibit 35-1), related in part to our coding system, contin-
ued expansion of neonatology, and the more widespread
use of catheter-based closure techniques.
Not only does patency of the ductus arteriosus persist
longer among premature infants, but prematurity also
accounts for some of the patent ductus arteriosus seen long
after infancy. Children born of mothers who have rubella
around the time of conception have a high incidence of
patent ductus. Maternal rubella is thought to be the cause
of its seasonal incidence, which was noted before immuniza-
tion was widely introduced. Children born at high altitudes
more often have a persistently patent ductus than those
born at sea level. The number increases as the altitude
increases, suggesting that patency is a direct function of
ambient oxygen.
ANATOMY
The ductus arteriosus is derived from the left sixth
embryologic arch and connects the origin of the left main
pulmonary artery to the aorta, just below the left subcla-
vian artery. During fetal life, the ductus is as large or larger
than the ascending aorta and carries outflow from the right
ventricle to the descending aorta (Fig. 35-1). Within hours
of birth, the ductus closes, usually at the pulmonary end,
often leaving behind a remnant on the aorta, a ductus diver-
ticulum. Occasionally, a diverticulum persists at the point
of origin from the pulmonary artery as well. With a right
aortic arch, the ductus is usually left sided, although rarely
it arises in a mirror image, entering the right pulmonary
artery. Bilateral ductus is rare. In pulmonary atresia, the
ductus is small because the left-to-right flow it carries is a
small fraction of that normally passing right-to-left to the
aorta in the fetus. In patients with tetralogy of Fallot, the
ductus is often absent.
The ductus closes through muscular constriction a few
hours after birth. Later, there is obliteration of the lumen,
initially by a pile up of endothelium and, finally, by complete
occlusion through thrombosis, the ductus withering to a
fibrous strand. The histopathology of a persistently patent
ductus is different from that found in a normal ductus not yet
closed, suggesting that persistent patency is usually a primary
anomaly and not a secondary effect.3,4 On histologic
617
618 Congenital Heart Disease

Exhibit 35–1 examination, the ductus is notably edematous, friable, and

Children’s Hospital Boston Experience lacerated after the use of prostaglandins.5,6
1988–2002 It is proposed that strands of ductal muscle sometimes
Patent Ductus Arteriosus snare the descending aorta, causing coarctation,7,8 or ensnare
the proximal pulmonary artery, producing stenosis at the
There were 544 patients (59% female) with a primary
origin of the left pulmonary artery. That constriction of the
diagnosis of patent ductus arteriosus. Among these were
aorta is associated with a right-to-left shunting duct, whereas
61 (11%) with a specific syndrome, 12 (2%) with respiratory
constriction of the pulmonary artery is associated with a
problems, 1 with endocarditis, and 1 with pulmonary vascular
left-to-right shunt (i.e., in patients with tetralogy of Fallot)
obstructive disease.
remains an intriguing curiosity.
Closure of the ductus by surgery (thoracotomy, video-
In premature infants, the process of ductal closure is the
assisted thoracic surgery [VATS]) or by catheter-delivered
same but is delayed, sometimes for weeks. The baby is born
devices was undertaken in 252 (46%) patients.
too soon; ductal closure occurs on schedule. However, not
Age at all close. The incidence of persistent patency of the ductus
Procedure Thoracotomy VATS Device well past infancy in patients who were premature is greater
than it is in the normal population.
<1 mo 31 6 0
1–12 mo 21 10 6
1–5 yr 15 27 72
PHYSIOLOGY
6–10 yr 2 11 26
11+ yr 0 16 49
With the first respiratory gasps after birth, pulmonary
Total 69 70 153
arteriolar resistance falls abruptly; the ductus arteriosus
There were only two deaths, both in the thoracotomy group reverses its flow and begins to shunt from left to right.
and both less than 1 month of age, one occurring the Normally, the ductus begins to close with the first gasping
following day in a 1.3-kg premature neonate with a large respiration, and in a matter of hours, the ductus may be
infected intracardiac mass and necrotizing anterocolitis. functionally closed. If the ductus remains widely patent,
The other infant died 4 days after surgery, before which a there is equilibration of the aortic and pulmonary arterial
diaphragmatic hernia repair had been carried out and pressures. In this situation, the pulmonary resistance falls,
extracorporeal membrane oxygenation had been necessary. causing increasing left-to-right shunting and congestive
failure. If the ductus is large and there is continued eleva-
tion of pulmonary resistance, it may become irreversible,
although pulmonary vascular disease is rare before the first
birthday.
When there is a persistently large runoff from the aorta
to the pulmonary artery, there is excessive blood flow to
the lungs, left atrium, left ventricle, and ascending aorta
(Fig. 35-2), with enlargement of these structures in propor-
tion to the size of the left-to-right shunt. The volume over-
load within the thorax is great enough that blood transfusion
after ductal ligation is rarely needed. The larger the runoff,
the greater is the arterial pulse pressure, and the more
striking the peripheral pulsations. When there is a large
volume overload, the flap covering the foramen ovale may
become incompetent, allowing additional left-to-right shunt-
ing and further volume overload.
The mechanism of ductal closure is a complex interaction
of the level of arterial oxygen, circulating prostaglandins,
genetic predetermination, and unknown factors.9 Low
FIGURE 35–1 Anatomic drawing of a large persistent patent oxygen tension is a factor in maintaining ductal patency in
ductus arteriosus. the fetus, and the sharp increase in arterial oxygen saturation
From Fyler DC [ed]. Nadas’ Pediatric Cardiology. Philadelphia: with the first breath is thought to be the initiating step in
Hanley & Belfus, 1992. ductal closure. On the other hand, high ambient oxygen
 Patent Ductus Arteriosus
FIGURE 35–2 Diagram of the hemodynamics in a patient with a
patent ductus arteriosus and moderate pulmonary hypertension.
Note the low pulmonary venous oxygen that results from a combi-
nation of excess pulmonary flow, congestive heart failure, and
pulmonary infection. Note also the wide pulmonary arterial and
aortic pulses.
From Fyler DC [ed]. Nadas’ Pediatric Cardiology. Philadelphia:
Hanley & Belfus, 1992
does not help to close a persistently patent ductus, although
the increased incidence of patent ductus in infants born at
high altitudes is thought to be the result of low ambient
oxygen.10,11
Prostaglandin E1 is a powerful ductal dilator.12 Prosta-
glandins may be required to maintain ductal patency in
utero; in the fetus, their blood levels are high, are found in
the wall of the ductus arteriosus, and are also supplied by
the placenta. At birth, the levels fall owing to cessation of the
placental source and increased pulmonary blood as they
are catabolized in the lung; in adults, serum levels are very
low.13–15 The reciprocal relation between the effects of oxygen
and prostaglandins varies with maturity. Oxygen is more
effective in promoting ductal closure in the mature infant
and less in the immature. Prostaglandin E1 is more effec-
tive in promoting ductal patency in the premature infant
and less effective in the mature.
Indomethacin given to the baby, or corticosteroids given
to the mother,15 will promote ductal closure. In the natural
course of events, the ductus regularly and inappropriately
closes in the first days of life even though the baby depends
619
on left-to-right (pulmonary atresia) or right-to-left (inter-
rupted aortic arch) shunting to survive.
CLINICAL MANIFESTATIONS
Patency of the ductus arteriosus in a full-term or older
infant or child (female-to-male ration of 2:1) produces symp-
toms and signs proportionate to the amount of blood passing
into the pulmonary circulation. When the ductal shunt is
small, the only abnormality may be the presence of a murmur.
When the ductus is large, symptoms of congestive heart
failure or pulmonary hypertension may be present, and the
murmur may not be typical.
Most children are discovered to have a murmur within
days or weeks of birth. The murmur is not characteristically
continuous in the early weeks of life, but it is recognized as
a systolic murmur. If the ductus is large, symptoms of
congestive heart failure (tachypnea, dyspnea, intercostal or
subcostal retractions, hepatomegaly, or growth failure) may
signal the cardiac problem. These children are not cyanotic
unless there is pulmonary edema.
Classically, in the older child, there is a crescendo systolic
murmur, peaking in intensity at aortic closure and contin-
uing into diastole as a high-frequency, decrescendo dias-
tolic murmur (Fig. 35-3). Usually, though not invariably,
the diastolic component of the murmur extends the entire
length of diastole. Often, there are coarse sounds (clicks or
“shaking dice” noises) during systole, which contribute to
the typical machinery sound. The murmur is loudest at
the second left intercostal space; maximal intensity anywhere
else should raise concern about the diagnosis of a patent
ductus arteriosus. In the small infant, it is uncommon to
hear the diastolic component of the murmur even if the
ductus is large. In older infants with a large ductus and
equilibration of aortic and pulmonary pressures, there may
be only a systolic murmur, usually recognizable because
FIGURE 35–3 Diagram of the machinery murmur of patent
ductus arteriosus. Typically, the murmur is maximally loud at the
time of the second heart sound (S2); clicking noises (C) in systole
contribute to the machinery sound.
From Fyler DC [ed]. Nadas’ Pediatric Cardiology. Philadelphia:
Hanley & Belfus, 1992.
620 Congenital Heart Disease
of its location, its crescendo quality, and the clicks. When
the ductus is large, there is often an apical diastolic rumble
(because of excessive mitral valve flow) that is hard to differ-
entiate from the transmitted sounds of the loud continuous
murmur.
The presence of a continuous murmur of crescendo–
decrescendo quality, loudest at the time of the second sound,
with systolic clicks, and located in the second left intercostal
space should be interpreted as resulting from a patent
ductus arteriosus. Among other causes of these findings,
the most common is an aortopulmonary window; however,
even here, the size of the window is usually so big that a
continuous murmur is unusual. Other problems that could
more or less mimic these findings include the following:
1. A venous hum is usually louder when the patient is
sitting rather than lying down, and it may be louder to
the right of the sternum. Hums have an evanescent
quality, changing with respiration as well as position.
2. A fistula between a coronary artery and a cardiac cham-
ber may produce a continuous murmur of crescendo–
decrescendo quality, which is usually not loudest at the
second left intercostal space. The murmur may be louder
in systole or diastole, depending on the hemodynamics
(see Chapter 52).
3. A ruptured sinus of Valsalva also produces a continuous
murmur, not previously heard, which most often is also
loudest at the second left interspace.
4. Tetralogy of Fallot with pulmonary atresia and collat-
eral circulation produces continuous murmurs, which
are heard all over the front and back of the chest, and if
there are sufficient collaterals, the patient may not be
visibly cyanotic.
Usually, all these possibilities are readily eliminated by
cardiac auscultation.
In patients with a patent ductus arteriosus, heart failure is
a feature of early infancy and is rare after the age of 6 months.
The peripheral arterial pulsations depend on the size of
the ductus and the size of the shunt. The larger the ductus
and the larger the left-to-right shunt, the more prominent
are the peripheral arterial pulsations.
Electrocardiography
The electrocardiogram is normal when there is a small
ductus; it shows left ventricular hypertrophy with a some-
what larger ductus and shows combined ventricular hyper-
trophy with a large ductus and pulmonary hypertension.
When pulmonary vascular disease dominates the clinical
picture, there may be only right ventricular hypertrophy.
Because the presence of a continuous murmur and significant
right ventricular hypertrophy are contradictory observations,
careful investigation of patients with this combination of
findings is required.
Chest X-Ray
The aorta, left ventricle, left atrium, pulmonary vessels,
and main pulmonary arteries are enlarged in proportion
to the amount of left-to-right shunt and may appropriately
affect the cardiac silhouette on the plain chest film.
Echocardiography
On two-dimensional echocardiography, the ductus is
easily visualized, and shunting is outlined with color-flow
mapping (Fig. 35-4). If the ductal flow is significant, enlarge-
ment of the left atrial and ventricular chambers is evident.
Estimations of pulmonary artery pressure may be made using
the tricuspid regurgitation jet if present and by continuous-
wave color Doppler. Although there is usually a gradient of
pressure observed between the aorta and pulmonary artery,
absence of a gradient may be taken as evidence of pulmonary
hypertension at the systemic level. In 60% of patients,
incompetence of the foramen ovale allowing left-to-right
shunting is evident on color-flow Doppler.16
Cardiac Catheterization
Cardiac catheterization for diagnostic purposes has not
been used for many decades except in very rare instances
of diagnostic uncertainty and to study pulmonary resist-
ance response to vasodilators such as oxygen and nitric
oxide when pulmonary hypertension is present (Fig. 35-5).
It is, however, very commonly used for interventional closure
using a variety of occluding devices.
MANAGEMENT
Interrupting the left-to-right shunt is the goal of manage-
ment of an uncomplicated patent ductus arteriosus. The
reasons for intervention include elimination of congestive
heart failure and promotion of growth in the small infant,
prevention of infective endocarditis, and pulmonary vascu-
lar disease. For practical purposes, every isolated patent
ductus arteriosus without associated problems should be
closed. Although age and size are not a consideration in
surgical management, even in the smallest babies, closure
in the catheterization laboratory is generally delayed if feasi-
ble until later in the first year of life because of peripheral
vessel injury risks. If the patient has failed to thrive or
has overt congestive heart failure, the ductus should be
interrupted. Legitimate reservations arise when the ductus
 Patent Ductus Arteriosus 621

A B

FIGURE 35–4 A, High left parasternal view of a large patent

ductus arteriosus (PDA) between the proximal descending aorta
(DA) and the main pulmonary artery (MPA). The anatomic rela-
tionship of the PDA arising above left pulmonary artery (LPA),
which is superior to the right pulmonary artery (RPA) origin,
is shown. B, Color-flow Doppler mapping confirms the presence
of flow as the red color jet of the PDA flow is seen to enter the
MPA. C, Spectral Doppler is used to show the timing and velocity
of flow across the PDA. In this case, there is mostly low-velocity
left-to-right flow (signal above the baseline indicates a positive
Doppler shift reflecting flow toward the transducer) with transient
right-to-left flow in early systole (negative Doppler shift).

is small and of little physiologic consequence, particularly
in those with the so-called silent ductus in whom, in the
absence of a murmur, a small ductus is identified echocar-
diographically; because of the risk for endocarditis17 and
ease and effectiveness of closure techniques, most investi-
gators would recommend closure.
Closure can be accomplished with minimal risk using a
variety of techniques (see Exhibit 35-1). Surgical manage-
ment for many decades involved a thoracotomy with ductal
occlusion (preferably by division to prevent recurrence),
with excellent results at all ages and sizes. The past decade
has seen increasing use of video-assisted thorascopic surgery
(VATS; see Chapter 59) with remarkable success even in
the tiniest of premature babies.18–22 In the small number of
whom this has not been feasible, the traditional thoracotomy
approach has been used. Recently, robotic assistance with
closure has been introduced23 (see Chapter 59). Closure
using interventional catheterization techniques has been
increasingly used over the past two decades. In the current
era, it is particularly appealing because it can be done on
an outpatient basis24 and avoids the thoracotomy scar of
the traditional surgical approach. It is technically easiest to
do when the ductus is quite restrictive, has length, and has
an ampulla at the aortic end. As the technique has evolved,
a wide variety of devices have been used25,26 (Fig. 35-6);
currently, coils are the most frequently used and are most
effective in small lesions,27 with results comparable to those
seen in VATS-treated patients.28
622 Congenital Heart Disease
A B C measure pulmonary resistance in room air, in oxygen alone,
FIGURE 35–5 Pulmonary and aortic pressure tracings in a
3-year-old child with a large patent ductus arteriosus and elevated
pulmonary vascular resistance. A, Breathing 100% oxygen. The
pulmonary artery pressure is lower at the time the left-to-right
shunt was very large. B, Breathing room air. The pressures are
virtually identical at the time the left-to-right shunt was minimal
and estimated pulmonary vascular resistance was prohibitively
high. C, With the ductus occluded by a balloon. Note the wide
separation of pressures. The ductus was later divided, and the
child is well without evidence of heart disease.
From Fyler DC [ed]. Nadas’ Pediatric Cardiology. Philadelphia:
Hanley & Belfus, 1992.
COURSE
After the first successful closure of a ductus by Gross in
1938,29 surgery for this lesion became so widespread that a
real natural history picture was no longer available. In a
retrospective review by Campbell in 1968,30 high infant
mortality, spontaneous closure, endocarditis, heart failure,
and pulmonary vascular obstructive disease were described,
with a mortality rate of 60% by age 60 years. At present, it
is reasonable to suggest, particularly with widespread use
of echocardiography, that diagnosis is being made at a
A B
FIGURE 35–6 Descending aortic cinegrams, lateral view, in a
1-year-old infant with a patent ductus arteriosus (PDA) before
(A) and (B) after closure with a Grifka device (arrow).
younger age, and virtually all cases are being closed either
surgically or with devices.
It is now extremely rare to encounter a patient with vascu-
lar obstructive disease; this can occur by age 2 years in an
untreated large lesion. In such a patient, the characteristic
murmur may be absent, the peripheral pulses may not be
bounding, and the heart may not be very large. The elec-
trocardiogram may show pure right ventricular hypertrophy.
On chest x-ray, a large main pulmonary artery may be visible
(Fig. 35-7). If the degree of pulmonary vascular obstruction
is uncertain clinically, cardiac catheterization is necessary to
and with a vasodilator such as nitric oxide, with the ductus
open and with it temporarily occluded with a balloon. If
the resistance value is less than 8.0 Wood units in room air
and if there is a significant decrease with the previously
mentioned maneuvers, then, especially in the very young,
closure by device may be undertaken at that time or by
surgery shortly thereafter. Without surgery, survival for
several decades with vascular obstructive disease may occur.
Differential cyanosis is common in older patients with mini-
mal, if any, cyanosis of the lips and fingers being evident
because fully saturated blood comes to these sites from the
FIGURE 35–7 Chest x-ray in a young woman with a large patent
ductus arteriosus and advanced pulmonary vascular disease.
This patient died within a year after this picture was taken. Note
the very large main pulmonary artery and the near normal size
of the heart.
From Fyler DC [ed]. Nadas’ Pediatric Cardiology. Philadelphia:
Hanley & Belfus, 1992.
 Patent Ductus Arteriosus
left ventricle, whereas clubbing and obvious cyanosis of the
toes result from the right-to-left shunting through the ductus
into the descending aorta. This shunt of desaturated blood
also results in increased renal erythropoietin and hemoglo-
bin production, with surprisingly high levels of the latter in
the face of minimal upper body desaturation.
An untreated patent ductus arteriosus is a favored site
for infective endocarditis. The chance of developing endo-
carditis has been estimated at 0.45% per year.30 Closure of
the ductus eliminates this possibility.31
Ductal ligation has been followed by later appearance of
a left-to-right shunt because of either incomplete ligation
or recanalization. Dividing the ductus and oversewing the
stumps prevents recanalization. The difficulties and dangers
of division, although small, are nonetheless sufficient that
some surgeons favor ligation.
In the past, late spontaneous closure of a small patent
ductus, largely based on auscultation, was noted on a few
occasions; since the advent of echocardiography and color
flow, this is now rarely encountered.
VARIATIONS
Ductus Arteriosus in Premature Infants
Functional closure of the ductus arteriosus occurs in some
90% of full-term newborns within a couple of days.32 In
premature infants, the ductus persists in many, with those
of clinical significance being more common in the smallest
babies, many with respiratory distress syndrome, and may
add significant morbidity and mortality.33 Measurement of
blood levels of brain natriuretic peptide early may help in
predicting such patients.34
Prevalence
Of 1700 infants weighing less than 1750 g at birth, 20.5%
had a patent ductus arteriosus15; 42% of these weighed less
than 1000 g, and 7% weighed more than 1500 g.35 Among
146 older infants with patent ductus arteriosus, 19% weighed
less than 2 kg at birth, and 17% were born after less than
34 weeks of gestation.
Anatomy
The gross and histopathologic anatomy of a premature
ductus arteriosus is indistinguishable from that of the normal
patent ductus arteriosus.36
Physiology
The level of pulmonary resistance in premature infants
is less than it is in full-term babies. This, coupled with
persistent patency of the ductus, favors the early appearance
of left-to-right shunt, which may be excessive. The presence
623
of respiratory distress promotes continued patency of the
ductus because of hypoxemia, and this aggravates respiratory
difficulty either because of congestive heart failure or
because of the excessive pulmonary blood volume associated
with the shunt, which compromises the intrathoracic volume
available for respiration. Pulmonary venous oxygen desat-
uration and pulmonary hypertension were constant features
of premature infants who underwent cardiac catheterization
in the early days of studying this problem.
Clinical Manifestations
Although prominence of the peripheral pulses is a good
indication that the ductus is large enough to cause problems,
the murmur in premature infants is usually atypical, rarely
being more than a systolic murmur, and not necessarily
crescendo. Indeed, any systolic murmur in a very small
premature baby should be considered indicative of a patent
ductus arteriosus until proved otherwise.35 Rarely, a prema-
ture infant may have a known patent ductus with no audible
murmur.
Electrocardiography
The electrocardiogram shows tachycardia, right-axis devi-
ation, and right ventricular hypertrophy that is rarely in
excess of that normally expected for the age.
Chest X-Ray
The chest x-ray is dominated by signs of the respira-
tory distress syndrome. There is commonly enough gross
pulmonary opacity to obscure the cardiac shadow completely.
Echocardiography
Two-dimensional echocardiography with color flow
diagnoses the ductus, and serial observations provide infor-
mation on size and shunt magnitude changes in response
to indomethacin therapy.
Cardiac Catheterization
Cardiac catheterization is not used for this condition.
Management
In general, the initial management includes hematocrit
level maintenance, ventilatory support, fluid restriction, and
diuretic therapy. In those ventilated and weighing less than
1000 g, indomethacin is recommended even in the absence
of a significant left-to-right shunt, and in those weighing
greater than 1000 g, only when signs relating to a significant
shunt appear.37 If significant patency persists or recurs,
another course of indomethacin is given. Using this approach,
a 79% closure rate has been achieved.15 Surgery is recom-
mended for those not responding37,38; although ligation has
been the traditional approach, in recent years the VATS
technique has been very successful13,18 (see Chapter 59).
624 Congenital Heart Disease
The use of prophylactic indomethacin in the absence of a
ductus in these babies, although it decreases the ductal
and severe periventricular and intraventricular hemor-
rhage rates, is controversial.39 It does not decrease the dura-
tion of oxygen therapy or ventilatory support, nor the
incidence of bronchopulmonary dysplasia,40–43 nor does
it improve survival without neurosensory impairment at
18 months44; it is thus not generally recommended.
Course
The overall mortality rate in one large series by the age of
1 year was about 20%,15 mainly due to pulmonary insuffi-
ciency, intracranial hemorrhage, necrotizing enterocolitis,
and sepsis. It is unlikely that the ductus played the dominant
role in the ultimate outcome for these babies; severe unto-
ward events and death were caused mostly by prematurity
and the respiratory distress syndrome. It must be remem-
bered that at 1 year of age, 65% to 70% of the original group
were alive without major handicaps.
The mortality associated with surgical closure (VATS or
ligation) has improved significantly (see Chapter 59; see
Exhibit 35-1).
The surviving small premature babies require continued
observation for some months because ductus may remain
patent or reopen later, whether they are treated medically
or surgically.32
Aneurysm of the Ductus Arteriosus
Aneurysm of the closed ductus arteriosus is a variation
of the normal ductus diverticulum (the remnant of the
ductus at the point of attachment of the aorta). When the
diverticulum is large, it is described as an aneurysm. Rarely,
the aneurysmal diverticulum may cause obstruction of the
aorta,45 develop clots, obstruct the pulmonary artery,46,47
be a source of emboli, become infected, or rupture.
Maternal Rubella
The dreadful consequences of maternal rubella about the
time of conception are no longer seen because of immuniza-
tions. In the past, those affected were often blind, deaf,
and retarded, and many had a patent ductus arteriosus.
The ductus varied in size. Closure did not improve growth
even when the vessel was large. Peripheral pulmonary steno-
sis was also commonly present.
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