The ductus arteriosus is a normal vascular connection between the pulmonary arterial trunk and the proximal descending thoracic aorta, and is an essential component of the fetal circulation. During fetal life, it allows right-to-left shunting of maternally-derived oxygenated placental blood to the systemic circulation, bypassing the high-resistance pulmonary bed. Following birth, increases in oxygen tension and a drop in pulmonary vascular resistance trigger spontaneous closure (contraction and subsequent fibrosis) of the ductus. Patent ductus arteriosus (PDA) is the persistence of the ductus as a vascular structure (rather than a ligamentous connection) beyond the early neonatal period, leading to unabated left-to-right shunting between the aorta and pulmonary artery with subsequent pulmonary overcirculation.

With an incidence of 1 in 2500 to 5000 births, PDA is the second most common congenital cardiac malformation.¹ Although recognition of the presence of the ductus arteriosus during fetal circulation dates to Galen, it was not until 1907 that John Monro first suggested surgical ligation of PDA in an address to the Philadelphia Academy of Surgery.² Thirty-one years later, in 1938, the first operation was attempted by Graybiel and Stieder in a 22-year-old woman with bacterial endocarditis involving the arterial duct.³ Although the PDA was successfully ligated, the patient succumbed to infection and gastrointestinal complications a week later. Although primacy is still disputed, Robert Gross is credited, later in that same year, with the first ligation of a PDA in a 7-year-old child with severe heart failure.⁴ Although a PDA can today be interrupted through interventional or minimally invasive techniques, operative ligation remains a model of finest surgical practice: predictable anatomy, minimal morbidity, and excellent outcomes.

Early in fetal development, the aortic sac is connected to paired dorsal aortae through six arterial arches (see Chapter 84).^5,6 The normal ductus arteriosus develops from the dorsal portion of the left sixth arch. However, because of the bilateral symmetry of the arterial system, arterial ducts can be bilateral or absent, right- or left-sided (the latter being by far the most common variant). The sixth arches develop from the plexus of capillaries that supply the developing buds. These capillaries initially arise from the aortic sac but later join the dorsal aorta. When the arterial segments separate to form the aorta and pulmonary trunk, the sixth arches remain connected to the pulmonary trunk. On the right, the dorsal sixth arch regresses, and the ventral portion becomes the proximal right pulmonary artery. On the left, the ventral sixth arch is incorporated into the main pulmonary trunk, while the dorsal portion remains to become the ductus arteriosus.

The fetal ductus arteriosus normally originates from the pulmonary trunk as a continuation of the lesser curve of the aortic arch, a few millimeters distal and opposite to the origin of the left subclavian artery. It is typically a short and wide vessel of variable length, lying posteriorly to the left main bronchus with the vagus nerve coursing anterior to it. When there is a right-sided aortic arch, the ductus usually arises from the proximal descending aorta in conjunction with the left subclavian artery. The pulmonary end of the ductus is narrower than the aortic end and is invested by the pericardial reflection, while the aortic end is invested by the parietal pleura. The length of the ductus in infancy varies between 2 and 8 mm, with the diameter ranging from 4 to 12 mm. The left recurrent laryngeal nerve branches off the vagus and encircles the inferomedial wall of the duct before ascending behind the aortic arch into the tracheoesophageal groove (Fig. 63-1).

The wall of the ductus arteriosus differs histologically from that of the adjoining aorta and pulmonary artery. Instead of the circumferential layers of elastic fibers, the media of the ductus is made up of smooth muscle cells arranged into a poorly organized spiral outer layer and a longitudinal inner layer that protrudes centrally to join the intima at “cushion” points. Large gaps between intimal cushions are filled with mucinous substance and called “mucoid lakes.” The internal elastic intima is thicker than that of other vascular structures, forming wavy layers adjacent to the intimal cushions. The medial smooth muscle is particularly sensitive to PGE₁ and PGI₂, which cause, respectively, relaxation/dilatation and increased oxygen tension. The latter promotes ductal constriction.^7,8

The first stage of ductal closure occurs within 15 to 20 hours after birth. This is triggered by a rapid decrease in plasma concentration of prostaglandins (due to loss of maternal supply) and accelerated metabolism (by increased pulmonary blood flow). In addition, increased PaO₂ inhibits prostaglandin synthetase, further blunting the level of circulating prostaglandins. The physiologic consequence of these changes is contraction of the smooth muscle in the ductal wall media, with subsequent thrombosis. The second stage of ductal closure is completed within 2 to 3 weeks of birth. This occurs by fibrous proliferation in the intima with necrosis of the inner layer of the media and hemorrhage into the wall. Development of neointimal mounds is stimulated by vascular endothelial growth factor. The result is the permanent sealing of the lumen and the development of a fibrous ligamentum arteriosum. The ductus is closed by 8 weeks of age in 88 percent of infants with a normal cardiovascular system. Failure of this process results in persistent patency of the ductus arteriosus. Because of the immaturity of the ductal tissue, preterm infants respond poorly to increases in oxygen tension and therefore become the patient population at highest risk of developing PDA persistence. Inability of the immature lungs to clear circulating vasodilators may also contribute to ductal persistence. The incidence of PDA increases from 7 percent in very low-birth-weight infants to as high as 42 percent in extremely low-birth-weight neonates.

As pulmonary vascular resistance falls shortly after birth, increased left-to-right shunting across the PDA results in decreased systemic perfusion and a high left ventricular volume load, with decreased pulmonary compliance. The magnitude of the shunt (Q_p:Q_s) depends on the size of the ductus, as well as on the balance between systemic and pulmonary vascular resistance. In the absence of fixed pulmonary hypertension, when Q_p:Q_s is low, the hemodynamic effect of the PDA is insignificant and physiologic derangements are minimal. With a hemodynamically significant PDA, Q_p:Q_s is high, and increased pulmonary runoff in systole and diastole becomes detrimental to systemic pressure, leading to end-organ hypoperfusion. Furthermore, high pulmonary blood flow increases pulmonary artery pressure and, if left uncorrected, can lead to permanent pulmonary vascular disease. The clinical features of a hemodynamically significant PDA are similar to those of left-sided heart failure, with tachypnea, frequent respiratory infections, pulmonary edema, and failure to thrive. Premature infants with a PDA may present with substantial metabolic acidosis, oliguria, respiratory decompensation, and necrotizing enterocolitis.

A hemodynamically insignificant PDA may present subtly later in life. In this setting, left ventricular failure does not develop and symptoms are absent in infancy and childhood. A murmur is usually detected on routine physical examination, leading to the echocardiographic diagnosis of PDA.

A rare late mode of presentation of a PDA is infective endocarditis. The presence of a PDA may alter the local vascular immune response mechanisms or cause endothelial damage, providing a nidus for bacterial colonization. In the preantibiotics era, the average age of death in patients with a PDA surviving beyond infancy was 36 years, and infective endocarditis accounted for 45 percent of such deaths.⁹

Physical examination and echocardiography represent the cornerstones for the diagnosis of PDA. The patient will present with a widened pulse pressure, a hyperactive precordium, and an occasional systolic thrill. A continuous “machinery-like” murmur radiating from the pulmonic area to the midclavicle is characteristic. Electrocardiography may demonstrate left ventricular hypertrophy and left atrial enlargement. Chest radiography may show cardiomegaly with increased pulmonary markings and enlarged pulmonary trunk. Transthoracic Doppler echocardiography is diagnostic, showing the accelerated, narrow jet flow originating from the proximal descending aorta into the left pulmonary artery (Fig. 63-2). Cardiac catheterization is currently reserved for interventional device closure after echocardiographic diagnosis. Catheterization is also indicated in the older child with a large ductus and cyanosis due to right-to-left shunting at the ductal level in order to define the reversibility of pulmonary hypertension. If pulmonary resistance is over 75 percent of systemic and is unresponsive to nitric oxide and oxygen administration, PDA closure is contraindicated.

Traditionally, the presence of a PDA is an indication for closure. With the improved sensitivity of diagnostic modalities, the very small and hemodynamically insignificant ductus can be detected. Although likely not warranting early intervention, small PDAs can still be a potential site for bacterial endarteritis and will require monitoring.

Treatment strategies include pharmacologic closure, percutaneous closure in the catheterization laboratory, video- assisted thoracoscopic (VATS) hemoclip occlusion and conventional posterolateral thoracotomy with ligation. Percutaneous closure is effective in the treatment of children and adults with PDA. Primary surgical closure is reserved for premature newborns, small infants, and patients who have failed device closure. A randomized trial has demonstrated that early surgical ligation of PDA in neonates reduces the need for mechanical ventilation and oxygen supplementation, shortens hospital stay, and decreases the incidence of retrolental fibroplasia and necrotizing enterocolitis when compared to pharmacologic closure.¹⁰ However, initial attempt at pharmacologic PDA closure remains the initial therapeutic modality at most institutions.

Pharmacologic treatment is successful in achieving PDA closure in up to 60 percent of premature infants.⁵ A combined strategy of fluid restriction, diuretics, and indomethacin is used. Indomethacin has been utilized clinically since 1976 to facilitate ductal closure in premature infants¹¹ but is rarely successful in full-term neonates. Contraindications to indomethacin use in preterm infants include hyperbilirubinemia, sepsis, coagulopathy, gastrointestinal bleeding, and renal insufficiency. If indomethacin use is contraindicated or fails, surgical closure is undertaken. Preterm infants typically undergo two to three courses of indomethacin (12–24 h apart) before being considered for surgical closure.