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     Director of Pediatric Cardiology Fellowship Program, Associate
Professor, Department of Pediatrics, Baylor College of Medicine

Updated: Jun 1, 2010



 




Patent ductus arteriosus (PDA) is one of the more common congenital heart defects. The
presentation widely varies. Depending on the size of the patent ductus arteriosus, the gestational
age of the neonate, and the pulmonary vascular resistance, a premature neonate may develop life-
threatening pulmonary overcirculation in the first few days of life. Conversely, an adult with a
small patent ductus arteriosus may present with a newly discovered murmur well after
adolescence.

During fetal life, the ductus arteriosus is a normal structure that allows most of the blood leaving
the right ventricle to bypass the pulmonary circulation and pass into the descending aorta.
Typically, only about 10% of the right ventricular output passes through the pulmonary vascular
bed.

The ductus arteriosus is a remnant of the distal sixth aortic arch and connects the pulmonary
artery at the junction of the main pulmonary artery and the origin of the left pulmonary artery to
the proximal descending aorta just after the origin of the left subclavian artery. Most typically, it
is a left aortic remnant. A right-sided patent ductus arteriosus can occur, or the ductus arteriosus
can be present on both the right and the left. Although a left ductus arteriosus is a normal
structure during normal fetal development, the presence of a right ductus arteriosus is usually
associated with other congenital abnormalities of the cardiovascular system, most typically
involving the aortic arch or conotruncal development.

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A patent ductus arteriosus produces a left-to-right shunt. In other words, it allows blood to go
from the systemic circulation to the pulmonary circulation. Therefore, pulmonary blood flow is
excessive (see the image below).
 
   
 
  
 
  



  
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The magnitude of the excess pulmonary blood flow depends on relatively few factors. The larger
the internal diameter of the narrowest portion of the ductus arteriosus, the larger the left-to-right
shunt. If the ductus arteriosus is restrictive, then the length of the narrowed area also affects the
magnitude of the shunt. A longer ductus is associated with a smaller shunt. Finally, the
magnitude of the left-to-right shunt is partially controlled by the relationship of the pulmonary
vascular resistance to the systemic vascular resistance.

If the systemic vascular resistance is high and/or the pulmonary vascular resistance is low, the
flow through the ductus arteriosus is potentially large. Beginning at the ductus arteriosus, the
course of blood flow in a typical patent ductus arteriosus with pulmonary overcirculation is as
follows: patent ductus arteriosus, pulmonary arteries, pulmonary capillaries, pulmonary veins,
left atrium, left ventricle, aorta, patent ductus arteriosus. Therefore, a large left-to-right shunt
through a patent ductus arteriosus results in left atrial and left ventricular enlargement.
Additionally, the pulmonary veins and the ascending aorta can be dilated with a sufficiently large
patent ductus arteriosus. Also, if little or no restriction is present at the level of the patent ductus
arteriosus, pulmonary hypertension results.

The ductus arteriosus is normally patent during fetal life. This patency is promoted by continual
production of prostaglandin E2 (PGE2) by the ductus. Prostaglandin antagonism, such as
maternal use of nonsteroidal anti-inflammatory medications, can cause fetal closure of the ductus
arteriosus. This can be associated with severe fetal cardiovascular compromise.

Normally, functional closure of the ductus arteriosus occurs by about 15 hours of life in healthy
infants born at term. This occurs by abrupt contraction of the muscular wall of the ductus
arteriosus, which is associated with increases in the partial pressure of oxygen (PO2) coincident
with the first breath. This was first demonstrated by multiple experiments in the 1940s and has
been subsequently confirmed. Although the neonatal ductus appears to be highly sensitive to
changes in arterial oxygen tension, the actual reasons for closure or persistent patency are
complex and involve manipulation by the autonomic nervous system, chemical mediators, and
the ductal musculature.
Although functional closure usually occurs in the first few hours of life, true anatomic closure, in
which the ductus loses the ability to reopen, may take several weeks. Cassels et al defined true
persistence of the ductus arteriosus as a patent ductus arteriosus present in infants older than 3
months.[1 ]

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The estimated incidence in children born at term is between 0.02% and 0.006% of live births.
This incidence is increased in children who are born prematurely, children with a history of
perinatal asphyxia, and, possibly, children born at high altitude. Perinatal asphyxia usually only
delays the closure of the ductus, and, over time, the ductus typically closes without specific
therapy.

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As many as 20% of neonates with respiratory distress syndrome have a patent ductus arteriosus.
In babies who are less than 1500 g at birth, many studies show the incidence of a patent ductus
arteriosus to exceed 30%. The increased patency in these groups is thought to be due to both
hypoxia in babies with respiratory distress and immature ductal closure mechanisms in
premature babies. Premature babies, particularly low birthweight neonates, are more likely to
have problems related to patent ductus arteriosus. Spontaneous closure of the patent ductus
arteriosus in premature neonates is common, but respiratory distress and impaired systemic
oxygen delivery (congestive heart failure) often drive the need for therapy to effect ductal
closure in this group. Low birthweight neonates with a patent ductus arteriosus are more likely to
develop chronic lung disease.

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In the preantibiotic era, Campbell et al estimated the natural history mortality rates for untreated
patent ductus arteriosus to be 0.42% per year from age 2-19 years, 1-1.5% per year in the third
decade, 2-2.5% per year in the fourth decade, and 4% per year in persons older than 40 years.[2
]
Currently, with the availability of antibiotics to treat endocarditis and low-risk surgery and
catheter techniques to obliterate the patent ductus arteriosus, the mortality rate appears to be
quite low except in the extremely premature infant.

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The female-to-male ratio is 2:1 if not associated with other risk factors. In patients in whom the
patent ductus arteriosus is associated with a specific teratogenic exposure, such as congenital
rubella, the incidence is equal between the sexes.

 
The ductus arteriosus is always patent in the fetus if the cardiovascular system is otherwise
normal. Normally, the ductus arteriosus closes functionally in the first 10-18 hours of life.
Prematurity, perinatal distress, and hypoxia delay closure of the ductus arteriosus; however, most
children who are found to have a ductus arteriosus have no history of precedent risk factors.

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The typical child with a patent ductus arteriosus (PDA) is asymptomatic. A history of premature
birth, perinatal distress, or perinatal hypoxia may be present.

Some series have suggested that children born at extreme altitude have an increased incidence of
a persistent patent ductus arteriosus. Occasionally, a history of feeding difficulties and poor
growth during infancy, described as failure to thrive, is found. However, frank symptoms of
congestive heart failure are rare.

In the low birthweight premature infant, diagnosing a patent ductus arteriosus on auscultation
may be difficult. Babies that have a more severe clinical course of hyaline membrane disease
may have a higher prevalence of patent ductus arteriosus. The exact reason for this is unclear.

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As many as one third of children with patent ductus arteriosus are small for their age. In the
presence of significant pulmonary overcirculation, tachypnea, tachycardia, and a widened pulse
pressure may be found.

Findings upon cardiac examination include the following:

—? If the left-to-right shunt is large, precordial activity is increased, with the magnitude of
increased activity related to the magnitude of left-to-right shunt.
—? The apical impulse is laterally displaced. A thrill may be present in the suprasternal notch
or in the left infraclavicular region.
—? The first heart sound (S1) is typically normal. The second heart sound (S2) is often
obscured by the murmur. Phonocardiographic data from the past suggested the
occurrence of paradoxical splitting of S2 related to premature closure of the pulmonary
valve and a prolonged ejection period across the aortic valve.
—? In 1898, Gibson described the classic murmur. Subsequently, the classic patent ductus
arteriosus murmur has been referred to as a machinery murmur, which is continuous. The
murmur may be accentuated in systole. Typically, the murmur is loudest at the left upper
chest. If the pulmonary-to-systemic blood ratio approaches or exceeds 2:1, an apical flow
rumble, caused by high flow into the left ventricle, is frequently present. Also, because
flow through the left ventricle into the aorta is increased, an aortic ejection murmur may
be present. If the patent ductus arteriosus is small, the amplitude of the murmur may
increase with inspiration as pulmonary impedance drops.
The peripheral pulses are often referred to as bounding. This is related to the high left ventricular
stroke volume, which may cause systolic hypertension. The phenomenon of bounding pulses also
is caused by the low diastolic pressure in the systemic circulation as blood runs off from the
aorta into the pulmonary circulation.

In the low birthweight premature infant, the classic signs of a patent ductus arteriosus are usually
absent. The classic continuous murmur is rarely heard. A rough systolic murmur may be present
along the left sternal border, but a small baby with a large patent ductus arteriosus and significant
pulmonary overcirculation may have no murmur. In that case, typically, precordial activity is
increased and peripheral pulses are bounding. The increased precordial activity is caused by the
large left ventricular stroke volume. Bounding pulses are caused by the relatively low systemic
arterial blood pressure due to the continuous runoff of blood from the aorta into the pulmonary
artery.

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Familial cases of patent ductus arteriosus have been recorded, but a genetic cause has not been
determined. In infants born at term who have a persistent patent ductus arteriosus, the recurrence
rate among siblings is 5%. Some early evidence suggests that as many as one third of cases are
caused by a recessive trait labeled PDA1, located on chromosome 12, at least in some
populations.

Several chromosomal abnormalities are associated with persistent patency of the ductus
arteriosus. Implicated teratogens include congenital rubella (associated with patent ductus
arteriosus and pulmonary artery branch stenosis), fetal alcohol syndrome, maternal amphetamine
use, and maternal phenytoin use.

     

Aortopulmonary Septal Defect
Coronary Artery Fistula
Sinus of Valsalva Aneurysm
Tetralogy of Fallot With Absent Pulmonary Valve

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Venous hum
Atrioventricular malformation

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The following studies are indicated in patent ductus arteriosus (PDA).

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If significant left-to-right shunt through the patent ductus arteriosus is present, the pulmonary
arteries, pulmonary veins, left atrium, and left ventricle are enlarged. Also, the ascending aorta
may be prominent.

Usually, chest radiographic findings are normal until the magnitude of the ratio of pulmonary to
systemic circulation (QP/QS) exceeds 2:1. With marked pulmonary overcirculation, pulmonary
edema may occur. In elderly individuals, the patent ductus arteriosus may calcify and may be
visible on a standard radiograph.

   
 

The echocardiographic findings are typically diagnostic. Relying on alternative imaging

techniques to make the diagnosis of patent ductus arteriosus is unusual. By 2-dimensional
echocardiography, the patent ductus arteriosus can be seen most easily in the parasternal short
axis view and from the suprasternal notch. The classic patent ductus arteriosus connects the
junction of the main pulmonary artery and the left pulmonary artery with the aorta just below and
opposite the left subclavian artery.

If no other abnormalities are present, Doppler echocardiography reveals continuous flow from
the aorta into the main pulmonary artery. If the magnitude of the left-to-right shunt is large,
continued flow around the aortic arch into the ductus arteriosus in diastole and flow reversal in
the descending aorta are evident. Also, variable levels of continuous flow in the branch
pulmonary arteries related to the magnitude of shunt are observed. As the shunt magnitude
increases, increased flow in the pulmonary veins is evident and the left atrium enlarges. With a
small or moderate-sized patent ductus arteriosus, the left ventricular size is often normal, but as
shunt magnitude increases, the left ventricular diastolic size also increases.

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With a small patent ductus arteriosus, the ECG findings are typically normal. Left ventricular
hypertrophy may be present with a larger patent ductus arteriosus. This is typically seen as tall R
waves in the lateral precordial leads (V6).

In the neonate, especially the premature neonate with a large patent ductus arteriosus, T-wave
inversion and ST segment depression may be present, suggesting ischemia or a supply-demand
mismatch. This is thought to be related to increased myocardial work due to the left-to-right
shunt and pulmonary overcirculation in the face of low aortic and coronary diastolic blood
pressure due to the runoff of blood from the aorta into the pulmonary arteries.

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The premature neonate with a significant patent ductus arteriosus (PDA) is usually treated with
intravenous indomethacin or ibuprofen.[3 ]This has been quite successful in most patients.
Whether results with intravenous indomethacin are superior to those with surgical closure of the
patent ductus arteriosus, even in the premature neonate in whom the safety of the surgery is a
concern, is unclear.[4 ]

Intravenous indomethacin was the standard drug treatment until the last few years. A few years
ago, intravenous ibuprofen was approved by the US Food and Drug Association (FDA).
Ibuprofen and indomethacin are equally effective; however, other differences are noted.
Indomethacin appears to decrease the incidence of intraventricular hemorrhage. Ibuprofen has
less renal toxicity.

A meta-analysis by Ohlssen et al found ibuprofen is as effective as indomethacin in closing a

patent ductus arteriosus and reduces the risk of necrotizing enterocolitis and transient renal
insufficiency associated with indomethacin.[5 ]

Although diuretics and fluid restriction have been recommended for the treatment of
symptomatic neonates, no rigorously collected data support this approach. In fact, a systematic
review of furosemide use in preterm neonates with respiratory distress syndrome showed no
long-term benefits and an increased risk of symptomatic patent ductus arteriosus.[6 ]

Spontaneous closure is common. If significant respiratory distress or impaired systemic oxygen

delivery is present, therapy is usually prudent. Intravenous indomethacin (or the new preparation
of intravenous ibuprofen) is frequently effective in closing a patent ductus arteriosus if it is
administered in the first 10-14 days of life. Another option is surgical ligation, discussed in
Surgical Care.

After the first birthday, the most common treatment for a patent ductus arteriosus is occlusion at
cardiac catheterization. In fact, as catheterization techniques advance, the ability to close defects
in smaller infants has also been reported with high levels of success. Over the last 4 decades,
many techniques and devices have been used for patent ductus arteriosus occlusion. For many
years, the most common device used for patent ductus arteriosus occlusion has been a Gianturco
spring occluding coil. In experienced hands with proper patient selection, this has become a
procedure associated with high success and low morbidity. Coil occlusion is best suited to close
a patent ductus arteriosus with a minimal internal diameter of less than 2.5 mm. Success is usual
with a patent ductus arteriosus diameter of 2.5-3 mm, but a larger patent ductus arteriosus is
probably best served by alternate techniques.

More recently, the Amplatzer patent ductus arteriosus device has expanded the ability to close
patent ductus arteriosus at cardiac catheterization. This device is more reliable and easier to
implant in a large patent ductus arteriosus than spring occluding coils. Other occlusion devices
remain under investigation. Most patients with an isolated patent ductus arteriosus can have
successful treatment by catheterization after the first few months of life.

Typically, complete occlusion is achieved at catheterization. Occasionally, a tiny residual left-to-

right shunt remains at the end of the procedure, which closes by thrombus formation over the
following days or weeks. Left-to-right shunt rarely persists through a partially occluded patent
ductus arteriosus. Usually, the magnitude of the shunt is significantly smaller than prior to
occlusion. Due to concerns about the long-term risk of endocarditis, this residual defect should
be closed. Often, this can be accomplished with a second catheter procedure. Rare reports
describe association of a persistently patent ductus after occlusion attempts with hemolysis or
endocarditis.

Procedural risks of patent ductus arteriosus occlusion by catheter are few and largely influenced
by the experience of the physician performing the procedure. These risks include embolization of
the device being used to occlude the patent ductus arteriosus, blood vessel injury, and stroke. In
the case of device embolization, the device can usually be retrieved by transcatheter techniques,
and a second device can be successfully placed in the patent ductus arteriosus.


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Surgical ligation or surgical ligation and division remain the standard treatment of large patent
ductus arteriosus that require treatment in infancy. This is a particularly successful procedure in
the hands of an experienced pediatric cardiovascular surgeon. The techniques are reviewed in
Patent Ductus Arterious: Surgical Perspective.

When performed by an experienced pediatric cardiac surgeon, patent ductus arteriosus ligation is
a low-risk procedure with excellent results. This is true even in the smallest premature babies.
The risks include hemorrhage, vessel damage, ligation of the wrong vessel (left pulmonary artery
or aorta), recurrent laryngeal nerve or phrenic nerve damage, or infection.

While indomethacin therapy is preferred in most intensive care nurseries as the first-line
approach to effect patent ductus arteriosus closure, the benefits of this approach over surgical
ligation are not obvious. In most studies that attempt to evaluate differences in the outcomes for
indomethacin therapy and surgical closure, results are similar. A Cochrane Database Systematic
Review failed to demonstrate that the net harm-to-benefit ratio favored either surgical ligation or
medical therapy.[3 ] Observational studies suggest that surgical ligation is associated with higher
likelihood of chronic lung disease, retinopathy of prematurity, and neurosensory
impairment. These data may be questionable because surgical ligation is not available in every
nursery, whereas medical therapy is widely available.

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Consultation with a pediatric cardiologist and pediatric cardiovascular surgeon may be indicated.


 
In the presence of symptoms of pulmonary overcirculation or pulmonary hypertension related to
a patent ductus arteriosus (PDA), closing the patent ductus arteriosus is usually most prudent;
therefore, anticongestive therapy is not discussed. Intravenous indomethacin or intravenous
ibuprofen is used to treat patent ductus arteriosus in the neonate.
In a prospective, randomized, controlled trial, Attridge et al studied whether measuring b-type
natriuretic peptide (BNP) concentrations can be used to reduce the number of indomethacin
doses for patent ductus arteriosus and, thus, reduce nephrotoxicity.[7 ]Results showed that patients
in the BNP-guided group received fewer primary indomethacin doses compared with the group
that was not guided by BNP concentrations. Renal toxicity is associated with indomethacin, and
dose reduction guided by BNP may reduce this risk.

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In the neonate, ductal patency appears to be related to continued production of prostaglandin.

This is particularly true in the premature infant; therefore, prostaglandin inhibition can affect
ductal closure.


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This is the only medication indicated for PDA closure available in the United States.
Prostaglandins, especially E-type prostaglandins, maintain the patency of the ductus. Thus,
inhibition of prostaglandin synthesis by indomethacin results in constriction of the ductus
arteriosus.







Not indicated

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Many dosage regimens are noted, and the dose depends on postnatal age (PNA) at time of first
dose; one example is as follows:
PNA <48 hours: 0.1 mg/kg IV q12h for 3 doses
PNA 2-7 days: 0.2 mg/kg IV q12h for 3 doses
PNA >7 days: 0.25 mg/kg IV q12h for 3 doses

  

Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects;
probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effects
of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and
thiazides; may increase PT when taking anticoagulants (watch for signs of bleeding); may
increase risk of methotrexate toxicity; phenytoin levels may be increased when administered
concurrently

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Documented hypersensitivity; GI bleeding; anuria

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Caution with intraventricular hemorrhage (particularly if active hemorrhage), renal failure,

thrombocytopenia, and severe hyperbilirubinemia; increases risk of acute renal failure in patients
with preexisting renal disease or compromised renal perfusion; reversible leukopenia may occur
(discontinue if persistent leukopenia, granulocytopenia, or thrombocytopenia); adjust dosage
interval with renal insufficiency


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The mechanism of action that results in PDA closure in neonates is not known; however,
ibuprofen is an inhibitor of prostaglandin synthesis. Indicated to close a clinically significant
PDA in premature infants who weigh between 500-1500 g at ” 32 wk GA when usual medical
management (eg, fluid restriction, diuretics, respiratory support) is ineffective.







Not indicated

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Premature infants with birth weight 500-1500 g and ” 32 wk GA: 10 mg/kg IV for first dose,
then 5 mg/kg IV for second and third doses after 24 and 48 h, respectively
Infuse each dose over 15 min

  

None reported

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Proven or suspected infection that is untreated; congenital heart disease in whom patency of the
PDA is necessary for satisfactory pulmonary or systemic blood flow (eg, pulmonary atresia,
severe tetralogy of Fallot, severe coarctation of the aorta); active bleeding, especially intracranial
hemorrhage or GI bleeding; thrombocytopenia, coagulation defects, necrotizing enterocolitis,
significant renal impairment

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May decrease urinary output, if anuria or marked oliguria (urinary output <0.6 mL/kg/h) occurs
at scheduled time of second or third doses, do not administer these doses until lab confirms
normal renal function; if ductus arteriosus closes or size is significantly reduced after first dose,
no further doses are necessary; dilute prior to administration; do not infuse via same IV port as
TPN; use extravasation precautions (drug irritating to tissues); may alter usual signs of infection;
may inhibit platelet aggregation

 


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Typically, hospitalization following treatment for patent ductus arteriosus (PDA) is minimal.
Patients who have catheter closure of patent ductus arteriosus are usually sent home on the day
of the procedure. Even patients who have standard surgery with a thoracotomy rarely are
hospitalized for longer than 2 or 3 days.

The appropriate care and length of hospitalization of premature neonates with a patent ductus
arteriosus are primarily determined based on abnormalities of other organ systems. However,
babies who have effective closure of patent ductus arteriosus appear to have shorter hospital
stays than babies whose patent ductus arteriosus remains a problem.

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Once the patent ductus arteriosus is closed, no special limitations or care is necessary. Most
physicians recommend antibiotic prophylaxis at times of risk of bacteremia for 6-12 months
following closure, whether by catheter or surgery.

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Complications include the following:

—? Endocarditis
—? Congestive heart failure
—? Pulmonary vascular obstructive disease
—? Aortic rupture

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Typically, following patent ductus arteriosus closure, patients experience no further symptoms
and have no further cardiac sequelae.

Premature infants who had a significant patent ductus arteriosus are more likely to develop
bronchopulmonary dysplasia.
 

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Some canine breeds, such as certain strains of poodle, have a large prevalence of patent ductus
arteriosus.