Patent ductus arteriosus (PDA) is one of the more common congenital heart defects. Depending on the size of the PDA, 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 PDA 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 PDA can occur, or the ductus arteriosus can be present on both the right and the left. While a left ductus arteriosus is a normal structure during normal fetal development, the presence of a right ductus arteriosus usually is associated with other congenital abnormalities of the cardiovascular system, most typically involving the aortic arch or conotruncal development.
PATHOPHYSIOLOGY
A PDA 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. The magnitude of the excess pulmonary blood flow is dependent 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 controlled partially 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 large. Beginning at the ductus arteriosus, the course of blood flow in a typical PDA with pulmonary overcirculation is as follows: PDA, pulmonary artery, pulmonary capillaries, pulmonary veins, left atrium, left ventricle, aorta, PDA. Therefore, a large left-to-right shunt through a PDA results in left atrial and left ventricular enlargement. Additionally, the pulmonary veins and the ascending aorta can be dilated with a sufficiently large PDA. Also, if little or no restriction exists at the level of the PDA, 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 confirmed subsequently. Even though 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.
Even though functional closure usually occurs in the first few hours of life, true anatomic closure, where the ductus loses the ability to reopen, may take several weeks. Cassels defined true persistence of the ductus arteriosus as a PDA present in infants older than 3 months.
FREQUENCY
In the US: 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.
MORTALITY/MORBIDITY
The low birthweight premature infant: As many as 20% of neonates with respiratory distress syndrome have a PDA. In babies who are less than 1500 g at birth, many studies show the incidence of a PDA 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 PDA. Spontaneous closure of the PDA 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 PDA are more likely to develop chronic lung disease.
Otherwise healthy infants, children, adolescents, and adults: In the preantibiotic era, Campbell estimated the natural history mortality rates for untreated PDA to be 0.42% per year from age 2-19 years, 1.0-1.5% per year in the third decade, 2.0-2.5% per year in the fourth decade, and 4% per year in persons older than 40 years. Currently, with the availability of antibiotics to treat endocarditis and low-risk surgery and catheter techniques to obliterate the PDA, the mortality rate appears to be quite low except in the extremely premature infant.
SEX
The female-to-male ratio is 2:1 if not associated with other risk factors. In patients in whom the PDA is associated with a specific teratogenic exposure, such as congenital rubella, the incidence is equal between the sexes.
AGE
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.
