In the normal fetus, the ductus arteriosus is a vascular structure connecting the PAs and the descending aorta. The PA end of the ductus usually arises from the proximal left pulmonary artery (LPA) just after the bifurcation of the main pulmonary artery (MPA). High fetal pulmonary arteriolar resistance combined with relatively low placental and fetal systemic vascular resistance results in right to left (PA to aorta) flow across the ductus. Patency of the ductus in this scenario is influenced to a varying degree by a number of factors, including blood oxygen content and circulating prostaglandins.

With a baby’s first breath, alveolar oxygen concentration increases, resulting in pulmonary vasodilation. In addition, removal of the low resistance placenta from systemic circulation decreases the ratio of pulmonary vascular resistance (R_p) to systemic vascular resistance (R_s). This drop in R_p/R_s produces a change in direction of blood flow across the ductus arteriosus, which then flows from aorta to PA. At this point in the transition to postnatal life, the ductus arteriosus is exposed to systemic arterial pO₂, which in room air at sea level is near 100 mm Hg. This high systemic arterial pO₂ causes vasoconstriction of the ductus arteriosus through mechanisms that have not been completely elucidated. Smooth muscle contraction may be promoted by oxygen-sensitive potassium channels that in turn activate voltage-sensitive calcium channels that allow calcium influx into smooth muscle cells, resulting in smooth muscle contraction (6,21). Other mechanisms may also be involved (7).

Initial, “functional” closure of the ductus arteriosus is caused by smooth muscle contraction resulting from increased blood pO₂ and decreased concentration of circulating prostaglandins. Functional closure occurs within the first 24 hours of life in about half of all healthy, term neonates and is nearly universal by 72 hours of life (22). Even after functional closure the ductus can still be “re-opened” within the first few days of life by the administration of PGE₁.

In most cases, the constriction of the ductus begins at the PA end and progresses along its course toward the aortic end. Because most PDAs result from incomplete ductal closure rather than a complete lack of constriction, the narrowest diameter of the PDA is usually closer to the PA. The aortic end of the ductus is usually wider in diameter and is often referred to as the ductal ampulla.

Following functional closure of the ductus arteriosus, lower pO₂ and thickening of the ductal walls due to smooth muscle contraction produce hypoxia of the inner layers of the ductus. This hypoxia leads to cell destruction and fibrosis, and ultimately, anatomic (permanent) obliteration of the ductal lumen (23,24,25). The fibrous strand that remains in place of the ductus arteriosus is known as the ligamentum arteriosum.

Persistent patency of the ductus arteriosus after birth is much more common among preterm neonates than among otherwise healthy, term neonates. One proposed factor that may contribute to this increased risk of PDA is persistence of relatively low arterial pO₂ in the preterm neonate (5). This low pO₂ may result from poor alveolar-capillary oxygen diffusion due to immature lungs. It may also be compounded by persistently elevated pulmonary vascular resistance leading to right-to-left shunting across the ductus. Low pO₂ by itself, however, is insufficient to explain the increased incidence of PDA in premature infants. Animal studies have suggested that the premature ductus may be less responsive to the vasoconstrictive effects of O₂ (8). Furthermore, because PGE₂ is primarily metabolized in the lungs, infants with premature lungs may manifest impaired metabolism and elevated circulating levels of PGE₂. Others have suggested that ductal tissue in the premature neonate may contain increased levels of NO synthetase, and that higher levels of circulating NO may be primarily responsible for patency of the ductus in that population (26).

Children born at high altitude have a higher incidence of PDA. At extremely high altitude, the incidence may be 30 times greater than at sea level. This increased risk has been attributed to lower blood pO₂ due to decreased ambient oxygen concentration (27,28).

PDA is a common associated finding in the presence of other more severe congenital cardiovascular defects. A PDA may be necessary to support oxygenation and oxygen delivery in “ductal-dependent” cyanotic and obstructive defects. While it is not exactly known why PDA is more common in these situations, this increased incidence is likely due to decreased ductal blood pO₂. In ductal-dependent lesions, ductal constriction often occurs even in the setting of severe cyanosis and should be managed with exogenous PGE₁ administration.

Congenital rubella syndrome (CRS) is a constellation of congenital abnormalities that includes growth retardation due to placental insufficiency, deafness, cataracts, congenital heart defects, and neonatal purpura with thrombocytopenia. CRS results from rubella infection usually within the first 16 weeks of gestation (29,30). The most common congenital heart defects associated with CRS are PDA and branch PA stenosis. PDA occurs in 60% to 70% of patients with CRS. The histology of PDA in CRS has been described as “immature” and may result from an arrest in ductal development due to the rubella virus (31).

The relative frequency of PDA in the general population argues against a single genetic or environmental cause. However, epidemiologic data support an increased risk of PDA (approximately 3%) among siblings of affected individuals, suggesting that there is a genetic predisposition in some families (32). One group identified a recessive gene locus (12q24) that may be accountable for up to one-third of PDAs in their study population (33). However, this population had a higher rate of PDA (approximately 15% of congenital heart defects) and a high rate of parental consanguinity, suggesting that this recessive gene may contribute less to the incidence of PDA in other cultures.

Char syndrome is an autosomal dominant “heart-hand” syndrome associated with PDA. Typical facial features include short philtrum, prominent lips (sometimes referred to as “duck-billed”), flattened nasal bridge with upturned nose, and abnormalities of the fifth finger (often absence or hypoplasia of the phalanges). A missense mutation in the TFAP2B gene on chromosome 6p has been shown to cause Char syndrome (34,35,36). Subsequent to this
discovery, mutations in TFAP2B have been identified in cases of familial PDA without the clinical phenotype of Char syndrome (37,38).

The normal ductus arteriosus travels from the anterior surface of the aortic isthmus to the origin of the LPA. Passing to the left of the trachea, it is designated a “left-sided” ductus. The origin of the ductus from the aorta is inferior to its connection with the LPA such that the ductus runs anterior and superior in its course from aorta to PA. The left recurrent laryngeal nerve courses along the left side of the ductus before hooking under the ductus and heading cephalad. The anatomic arrangement of the recurrent laryngeal nerve relative to the ductus arteriosus is an important consideration during surgical ligation.

Morphologic classification of PDAs was largely established in the late 1980s by the group from Hospital for Sick Children in Toronto (39). They identified five reasonably consistent ductal morphologies based upon the location of the narrowest diameter of the vessel (Fig. 31.1):

Type A refers to a “funnel”- or “conical”-shaped PDA consisting of a prominent ductal ampulla on the aortic end. The ampulla tapers quickly and the narrowest diameter of the ductus is at the PA end. Type A morphology is by far the most common, comprising about 65% of all PDAs in the study from Toronto.

Type B, sometimes referred to as a “window-type” ductus, has a much shorter course and the narrowing is at the aortic end without a significant ductal ampulla and was found in 18% of patients. Both Type A and Type B were further subclassified in the original article based upon the anterior–posterior relationship of the ductal narrowing to the trachea.

Type C PDA is long and tubular without significant narrowing along its course.

Type D PDA has multiple areas of constriction.

Type E PDA is long with a narrowing that is well anterior to the trachea.

In the Toronto series, Types C, D, and E each comprised less than 10% of PDAs.

While the typical ductus is left sided and usually falls into one of the morphologic types described above, there can be tremendous variation, particularly in the presence of other congenital cardiovascular abnormalities. A right-sided ductus that travels to the right of the trachea and enters the base of the right pulmonary artery (RPA) is an unusual finding. A right-sided ductus can be seen with a left or right aortic arch and may be a component of a vascular ring. In some cases, the ductus arteriosus can originate from the brachiocephalic branches of the aorta rather than from the aorta itself.

The chest x-ray of a patient with a restrictive PDA is often normal or nonspecific. With a larger ductus, there may be pulmonary vascular congestion. Left atrial enlargement may result in inferior
compression of the left mainstem bronchus. For very large PDAs, the cardiac silhouette may be enlarged due to left atrial and left ventricular enlargement.

Electrocardiographic (ECG) findings are neither sensitive nor specific for PDA. A hemodynamically insignificant PDA will not cause any notable ECG changes. With larger PDAs, the ECG may show widened P waves, reflecting left atrial enlargement. Changes suggestive of left ventricular hypertrophy may be seen in the presence of a significant, chronic PDA shunt, including tall R waves in I, II, II, aVL, V₅, or V₆ and tall S waves in V₁ or V₂. Rarely, ischemic ST segment changes have been reported in the presence of significant left-to-right diastolic runoff, resulting in coronary steal. Oxygen supplementation during anesthesia for PDA closure may increase the Q_p/Q_s and exacerbate coronary hypoperfusion in such cases (40).

Echocardiography is the principal imaging modality needed to assess the PDA and its hemodynamic effects. On 2-D echocardiography, the usual left-sided PDA is most consistently seen between the origin of LPA and proximal descending aorta, distal to origin of left subclavian artery (41,42,43,44,45,46). Typical views to assess PDA are parasternal short-axis, high-left parasternal short-axis, and suprasternal sagittal views. From parasternal short-axis view (Fig. 31.2, Video 31.1), the PDA is seen originating from the junction of LPA and MPA, and connecting to the proximal descending aorta. A high-left parasternal view (Fig. 31.3, Video 31.2) is directed in the plane of LPA and angulated to visualize the “trifurcation,” where the MPA appears to divide into three vessels—the RPA, LPA, and PDA. This view is optimal for displaying the complete length of PDA and also provides a good angle for spectral Doppler interrogation.

Color Doppler imaging in these planes can show the direction and relative amount of shunt across a PDA (22,47,48,49). Left-to-right shunt is easily seen as the direction of blood flow from aorta to PA is in opposite direction of the forward flow in the branch PAs and descending aorta. However, a PDA with right-to-left shunt or low-velocity left-to-right shunt can be difficult to visualize by color Doppler. Lowering the Nyquist limit to detect low-velocity shunt is helpful for diagnosis. A PDA that is difficult to visualize, such as small PDA with low-velocity shunt, can be more reliably seen in a sagittal plane in the high-left parasternal position, on a sweep from LPA to descending aorta. Vertical or tortuous PDAs commonly are associated with other congenital heart disease (50).
A “reverse” or vertical PDA is usually seen in cases of pulmonary atresia. This type is best visualized from a suprasternal sagittal view in the plane of aortic arch. The ductus is seen arising from the undersurface of the distal aortic arch. Sometimes the direction of shunt in a tortuous PDA is difficult to assess with color Doppler alone. Pulse wave interrogation can help in clarifying the direction of shunt, especially in case of low-velocity or bidirectional shunting (51,52). The pulse wave Doppler cursor usually is positioned at the PA end of the PDA.

Continuous wave Doppler interrogation usually is used to assess the pressure gradient between the aorta and PA, but may be contaminated by blood flow in LPA. Pressure gradient estimation by Doppler echocardiography is not reliable in a tortuous PDA. Pulse wave Doppler assessment is used to assess the hemodynamic significance of a PDA, which is more important than its actual size. The clinical decision of whether to close a PDA is usually made on the basis of its hemodynamic effect. A PDA in a patient with low PA pressure will have continuous left-to-right shunt on color and spectral Doppler assessment (Fig. 31.4). Whereas, in case of elevated PA pressure, the shunt is bidirectional (Fig. 31.5). A hemodynamically significant PDA has continuous diastolic antegrade flow into the LPA. Diastolic run-off from descending aorta can be seen as pan-diastolic flow reversal on pulse wave Doppler interrogation of descending aorta from a suprasternal notch or subcostal view (Fig. 31.6). A large left-to-right shunt also manifests volume overload of left heart structures. Left atrial and left ventricular volumes are increased with increased flow velocities on pulmonary venous Doppler profile.

Echocardiography alone is almost always adequate for assessing the anatomy and hemodynamic effects of PDA. Computed tomography angiography (CTA) or cardiac magnetic resonance (CMR) imaging can be used in rare situations when echocardiography is limited due to poor acoustic windows or when other anomalies are suspected, such as coarctation of aorta or vascular rings (53). More often, a small PDA is incidentally discovered on a CTA or CMR study performed for a different indication. Visualization of a PDA on CTA or CMR is dependent on the accurate timing of contrast injection to opacify the duct. For optimal opacification of the PDA, the contrast is timed to
the aorta in a patient with low PA pressure (Fig. 31.7). If the contrast is timed to the PA, left-to-right shunting from aorta through PDA creates a filling defect in the proximal LPA. With elevated PA pressure, such as Eisenmenger syndrome, the PDA is best seen when contrast is timed to the PA (Fig. 31.8). Flow quantification by phase contrast imaging in CMR examination is useful in assessing the ratios of pulmonary to systemic blood flow (Q_p/Q_s).