Patent ductus arteriosus and aortopulmonary window

Anatomical considerations

The incidence of isolated persistent patency of the ductus has been estimated at 1:2000 to 1:5000 births, or about 10% to 12% of all varieties of congenital heart disease. The pulmonary orifice of the ductus is located immediately to the left of the bifurcation of the pulmonary trunk near the origin of its left branch ( Figs. 17.1 and 17.2 ; Video 17.1 ). The aortic orifice is located immediately distal to the origin of the left subclavian artery ( Figs. 17.1–17.3 ). A patent ductus can be long and narrow or short and wide, with all gradations in between ( Figs. 17.3–17.5 ; Videos 17.2 – 17.4 ). Closure consistently begins at the pulmonary arterial end, so the ductus assumes the shape of a truncated cone that is larger at its aortic end (see Figs. 17.3 , 17.4 , and 17.6 ). ^, A widely patent aortic end with a sealed pulmonary end is the substrate for a ductal aneurysm (see Figs. 17.6 and 17.7 ). Patency confined to the pulmonary end is exceptional. Anatomical variations include bilateral patent ductus, ^, left-sided patent ductus with right aortic arch, right-sided patent ductus with right aortic arch, patent ductus or ligamentum arteriosum as a component of a vascular ring ( Fig. 17.8 ), and dissection of the aorta with extension into a patent ductus.

Despite its seeming anatomical simplicity, the ductus arteriosus is a complex structure. The fetal ductus is a major anatomical component of a contiguous intrauterine great arterial system consisting of pulmonary trunk/ductus/aortic continuity that delivers 85% of right ventricular output into the descending aorta. Persistent fetal circulation is a designation applied to an intrauterine right-to-left ductal shunt that persists after birth. Persistent patency of the ductus arteriosus is abnormal and therefore undesirable, although certain forms of congenital heart disease depend on neonatal ductal patency for survival. Ductal-dependent circulations include malformations in which a patent ductus is the only source of pulmonary arterial blood flow (pulmonary atresia with intact ventricular septum), the only source of systemic arterial blood flow (aortic atresia or complete interruption of the aortic arch), or the only source of bidirectional blood flow (simple complete transposition of the great arteries) (see relevant chapters).

The ductus arteriosus is derived from the sixth aortic arch. By the fourth month of gestation, ductal tissue has become distinctive, differing histologically from pulmonary arterial and aortic tissue. At 16 weeks’ gestation, the ductus consists of a muscular arterial channel with an endothelium separated by an internal elastic lamina and a thin subendothelial layer. The media differs at the aortic and pulmonary ends, so ductal media can be aortic, pulmonary, or mixed. As gestation continues, the intima thickens, and the subendothelial layer is invaded by cells from the media that disrupt the internal elastic lamina. At term, the mature ductus harbors conspicuous intimal cushions that protrude into the lumen. The ductus is then capable of contraction— functional closure —which is followed by anatomical closure that uniformly begins at the pulmonary arterial end (see Fig. 17.5 and see earlier). Anatomical closure follows a sequence of immunohistochemical and ultrastructural changes, ^, namely:

• 1.

  separation of endothelium from internal elastic lamina;

• 2.

  enfolding and ingrowth of endothelial cells;

• 3.

  migration of undifferentiated medial smooth muscle cells into the subendothelium;

• 4.

  fragmentation of the internal elastic lamina;

• 5.

  sealing of the lumen by endothelial cell apposition;

• 6.

  accumulation of lipid droplets; and

• 7.

  intimal and subendothelial degenerative changes that spread centrally and peripherally and result in disappearance of endothelial cells at luminal apposition lines.

The normal process of functional closure begins within 10 to 15 hours after birth and is virtually complete (probe patent) by the second week of extrauterine life. The ductus is an anatomically closed ligamentum arteriosum 2 to 3 weeks after birth. ^{, ,} When a ductus is destined to remain patent , the intrauterine subendothelial internal elastic lamina lies adjacent to the intimal cushions, endothelial cells adhere to the elastic lamina, and subendothelial edema with enfolding of endothelial cells does not occur. ^, A ductus that remains patent in full-term infants after 3 months of extrauterine life harbors the histological features of persistent patency just described. Spontaneous closure is then unlikely. ^{, ,}

In utero ductal tone is determined by an interplay between the constricting effect of oxygen (relatively weak because of low fetal pO2) and the dilating effect of endogenous prostaglandin E2. ^, Prostaglandin synthetase inhibitors administered to mammalian fetuses or to pregnant ewes constrict the fetal ductus and deprive the fetal right ventricle of its only outlet. As term approaches, the ductus becomes less responsive to prostaglandin E2 and more responsive to oxygen, setting the stage for constriction that begins a few hours after birth in full-term infants. Functional closure is closely coupled to the increase in extrauterine ambient oxygen tension which exerts a direct constricting effect on the ductal wall (see earlier). Oxygen-induced constriction has been related to inhibition of voltage-gated potassium channels. Flow through the closing ductus is transiently bidirectional. Left-to-right flow then decreases rapidly during the next 12 hours and cannot be detected at 48 hours. Anatomical closure is the culmination of morphological changes accrued during intrauterine ductal maturation (see earlier). ^{, ,} In addition, apoptosis and smooth muscle cell proliferation have been assigned a role in anatomical closure.

In normal preterm infants, delayed closure of the ductus arteriosus is common. Premature neonates with a gestational age of 30 weeks or more usually experience spontaneous ductal closure within a time frame that corresponds to the closure time in full-term infants. ^, In full-term infants, spontaneous closure is unlikely after 3 months of age ^, and, in premature infants, is unlikely after 1 year of age ( Fig. 17.9 ). Exceptional examples of spontaneous closure have been documented between 5 and 6 years of age, between 7 and 14 years, after 17 years, and at age 19 years.

Persistent patency of the ductus in premature infants sometimes coincides with respiratory distress, but the distress may not improve with subsequent ductal closure. ^{, ,} Patent ductus in preterm infants is associated with reduced cerebral blood flow due a steal effect caused by the aortic-to-pulmonary shunt, rather than by a limited capacity of the preterm left ventricle to achieve adequate cardiac output. ^, Prolonged suboptimal cerebral oxygenation due to a patent ductus may impair brain growth, leading to adverse neurodevelopmental outcomes. Decreased blood flow through the abdominal aorta can also reduce perfusion of the liver, gut, and kidneys, leading to hepatic failure, renal insufficiency, and necrotizing enterocolitis.

First trimester maternal rubella with rash carries an 80% incidence of intrauterine viral infection, deafness, and cataracts ( Fig. 17.10 ), and congenital heart disease in two thirds of offspring. Patent ductus arteriosus accounts for a third of the congenital malformations and is characterized by maturational arrest and an immature ductal wall of the type found at 16 weeks’ gestation (see earlier).

Physiological consequences

The physiological consequences of persistent patency of the ductus arteriosus depend on five variables: (1) the size of the ductus, (2) pulmonary vascular resistance, (3) the adaptive response of the left ventricle to volume overload, (4) prematurity, and (5) respiratory distress. When the ductus is restrictive , pulmonary vascular resistance is normal, right ventricular afterload is normal, and the hemodynamic consequences are negligible. When the ductus is moderately restrictive and pulmonary vascular resistance is normal or nearly so, right ventricular afterload is not significantly affected, and continuous aortic-to-pulmonary flow imposes only a moderate volume load on the left ventricle ( Figs. 17.11 and 17.12 ; Videos 17.5 and 17.6 ; see also Video 17.1 ). About 95% of isolated patent ductuses are restrictive or moderately restrictive. When the ductus is non-restrictive , systolic pressure in the aorta and pulmonary trunk equalize at systemic level, so the direction of blood flow depends on the relative resistances in the systemic and pulmonary vascular beds ( Figs. 17.13–17.15 ; Video 17.7 ; see also Videos 17.3 and 17.4 ). If pulmonary resistance is lower than systemic, a left-to-right shunt is established, imposing volume overload on the left ventricle, while right ventricular afterload remains at systemic level (see Fig. 17.2 A). When pulmonary vascular resistance exceeds systemic, the shunt is reversed (see Fig. 17.2 B). Volume overload of the left ventricle is then curtailed, pressure overload of the right ventricle remains at systemic level, and the pulmonary vascular bed exhibits histological changes similar to primary pulmonary hypertension or Eisenmenger syndrome (see Chapter 14 ). ^,

Prolonged exposure to ductal patency in the preterm infant can result in early and significant remodeling of the left heart to be larger and more spherical, with a corresponding increase in volume. This compensatory cardiac physiology represents an adaptive change to the volume overload induced by a patent ductus arteriosus.