Chapter 20 Patent Ductus Arteriosus Aortopulmonary Window
In 1593, Giambattista Carcano, Professor of Anatomy in Pavia, an ancient town in northern Italy, described the ductus arteriosus in his book on the great cardiac vessels of the fetus.1 However, Leo Bottali came to be associated with the arterial duct, the duktus arteriosus persisten, even though he misapplied the term to the foramen ovale.1 It was not until Karl von Rokitansky’s handbook of 1844 and his beautifully illustrated monograph of 1852 that patent ductus arteriosus was recognized as a specific congenital malformation.2 The first section of this chapter is concerned with persistent patency of the ductus arteriosus. The second section is devoted to aortopulmonary window, often called aortopulmonary or aorticopulmonary septal defect, an anomaly that is embryologically unrelated to patent ductus but that is physiologically and clinically similar.
The incidence rate 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.3 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 (Figures 20-1 and 20-2). The aortic orifice is located immediately distal to the origin of the left subclavian artery (see Figures 20-1 and 20-2). A patent ductus can be long and narrow or short and wide, with all gradations in between (Figures 20-3, 20-4, and 20-5). 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 Figures 20-3 and 20-4).4,5 A widely patent aortic end with a sealed pulmonary end is the substrate for a ductal aneurysm (Figure 20-6).6–9 Patency confined to the pulmonary end is exceptional.10 Anatomic variations include bilateral patent ductus,11,12 left-sided patent ductus with right aortic arch,13 right-sided patent ductus with right aortic arch,14 patent ductus or ligamentum arteriosum as a component of a vascular ring (Figure 20-7),15 and dissection of the aorta with extension into a patent ductus.16
Despite its seeming anatomic simplicity, the ductus arteriosus is a complex structure. The fetal ductus is a major anatomic component of a contiguous intrauterine great arterial system that consists of pulmonary trunk/ductus/aortic continuity that delivers 85% of right ventricular output into the descending aorta.17 Persistent fetal circulation is a designation applied to an intrauterine right-to-left ductal shunt that persists after birth (see Chapter 14).18 Persistent patency of the ductus arteriosus is abnormal and therefore undesirable, although certain forms of congenital heart disease depend for survival on neonatal ductal patency. 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.19 At 16 weeks of gestation, the ductus consists of a muscular arterial channel with an endothelium separated by an internal elastic lamina and a thin subendothelial layer.19 The media differs at the aortic and pulmonary ends, so ductal media can be aortic, pulmonary, or mixed.4 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 is capable of contraction, functional closure, which is followed by anatomic closure that uniformally begins at the pulmonary arterial end (see previous).4 Anatomic closure follows a sequence of immunohistochemical and ultrastructural changes, namely4,19: (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.4 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.5,17,20 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.4,19 A ductus that remains patent in full-term infants after 3 months of extrauterine life harbors the histologic features of persistent patency just described. Spontaneous closure is then unlikely.19,21,22
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 E2.23,24 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.24 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.25 Functional closure is closely coupled to the increase in extrauterine ambient oxygen tension that exerts a direct constricting effect on the ductal wall (see previous). Oxygen-induced constriction has been related to inhibition of voltage-gated potassium channels.26 Flow through the closing ductus is transiently bidirectional. Left-to-right flow25 then decreases rapidly during the next 12 hours and cannot be detected at 48 hours.27 Anatomic closure is the culmination of morphologic changes accrued during intrauterine ductal maturation (see previous).4,19,28 In addition, apoptosis and smooth muscle cell proliferation have been assigned a role in anatomic closure.29
In healthy preterm infants, delayed closure of the ductus arteriosus is common.30–33 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.31,32 In full-term infants, spontaneous closure is unlikely after 3 months of age,21,22 and in premature infants, it is unlikely after 1 year of age (Figure 20-8).22 Exceptional examples of spontaneous closure have been documented between 5 and 6 years of age, between 7 and 14 years,34 after 17 years,35 and at age 19 years.
Figure 20-8 X-ray from the 21-day-old premature male with a widely patent ductus arteriosus. The phonocardiogram is shown in Figure 20-10. Pulmonary blood flow is increased, the heart is considerably enlarged, and a thymus (arrows) obscures the base. By age 4 months, the ductus had spontaneously closed, the thymus had disappeared, and the x-ray was virtually normal.
Persistent patency of the ductus in premature infants sometimes coincides with respiratory distress, but the distress may not improve with subsequent ductal closure.31,32,36 Patent ductus in preterm infants is associated with reduced cerebral blood flow from 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.37,38
First-trimester maternal rubella with rash carries an 80% incidence rate of intrauterine viral infection39; deafness and cataracts (Figure 20-9). Congenital heart disease affects two thirds of offspring. Patent ductus arteriosus accounts for a third of the congenital malformations22 and is characterized by maturational arrest and an immature ductal wall of the type found at 16 weeks of gestation (see previous).22
The physiologic 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. About 95% of isolated patent ductuses are restrictive or moderately restrictive. When the ductus is nonrestrictive, 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.40 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 Figure 20-2, upper). When pulmonary vascular resistance exceeds systemic, the shunt is reversed (see Figure 20-2, lower). 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 histologic changes similar to primary pulmonary hypertension or Eisenmenger’s syndrome (see Chapters 14 and 17).35,41
history
A newborn is typically pronounced healthy and discharged as a well baby. As neonatal pulmonary vascular resistance falls, a left-to-right shunt is established, the ductus murmur emerges, and the diagnosis becomes apparent. Less commonly, a neonate comes to attention because of low birth weight, systemic hypoperfusion, or congestive heart failure without an incriminating ductus murmur (Figure 20-10).33,42 Absence of a murmur does not necessarily mean that the ductus has closed.17 A ductus can be patent but silent because of the direction of the jet as it enters the pulmonary artery.43 No correlation has been found between the presence of a murmur and the size of the arterial duct.43 Doppler echocardiography occasionally detects a tiny patent ductus in infants without auscultatory signs of its presence,44 or auscultation detects a tiny ductus in adults in whom the diagnosis had been missed (see Figure 20-40). Closure of a patent ductus is occasionally the result of healed infective endocarditis45,46 or thrombotic occlusion.47,48
Figure 20-10 Phonocardiograms at the second left intercostal space in a 21-day-old premature male with a nonrestrictive patent ductus arteriosus (see x-ray in Figure 20-8). The low-frequency filter (upper tracing) shows a fourth heart sound (S4). The high-frequency filter (lower tracing) shows a normal first heart sound (S1) and an unimpressive early to midsystolic ductal murmur (SM) that fades before a loud single second heart sound (S2).
In 1561, Vesalius described a valve or membrane in a patent ductus arteriosus.49 A valve-like structure was subsequently found in stillborn human fetuses and in newborn rabbits,49 and in 1903, a necropsy report called attention to a perforated ductal valve.50 Taussig51 confirmed the presence of a membranous valve at the pulmonary end of a ductus and theorized that rupture might account for the sudden appearance of a ductus murmur, an event occasionally witnessed in children or young adults. A continuous murmur intermittently appeared and disappeared in a patient with a veil-like valve at the pulmonary end of a ductus,52 and the abrupt appearance of a loud continuous murmur was described in a 55-year-old man with a ductal membrane.53 Rarely, a closed lumen is reopened by spontaneous intramural dissection of a ductal aneurysm or by propagation of aortic dissection into the ductus.16
Patent ductus arteriosus predominates in females, with a gender ratio of 2 or 3 to 1.35 Female prevalence is even greater in older patients.54 There is a tendency for recurrence of patent ductus in siblings55–57 and in the offspring of parents with patent ductus.55 Familial recurrence has been reported in three generations of a single family.58 Identical twins may both have a patent ductus, or the ductus may be patent in only one twin. Canine patent ductus is more common in females and can be hereditary.59
In offspring of gravida with maternal rubella, patent ductus arteriosus and pulmonary artery stenosis coexist as congenital malformations (see Chapter 11).60–62 Maternal rubella resulted in patent ductus arteriosus in one of a twin pair; the other twin had pulmonary artery stenosis. Low birth weight and failure to thrive are features of the rubella syndrome, even if the ductus is restrictive. A seasonal incidence of patent ductus in late winter and early spring coincided with the peak incidence of rubella.62
Persistent patency of the ductus arteriosus is about six times more prevalent in high-altitude locations than in sea-level locations.63 A predilection for increased pulmonary vascular resistance is a feature of high-altitude births with patent ductus.63 The predilection exists even when the ductus is restrictive.63
Congestive heart failure is the most common cause of death directly related to patent ductus.35 Rarely, death is from dissection or rupture of a ductal aneurysm64 or from rupture of a hypertensive aneurysmal pulmonary trunk.65,66 Aneurysm of a nonpatent ductus (see Figure 20-6) can be complicated by rupture, by spontaneous intramural dissection, by systemic embolism, by infection, by recurrent laryngeal nerve paralysis, by compression of the pulmonary trunk, or by hemorrhagic erosion into the esophagus or tracheobronchial tree.8,9
Infective endarteritis occurs with a restrictive patent ductus because of the high-velocity left-to-right shunt but does not occur with a nonrestrictive ductus and reversed shunt.35 The infection is located at the narrow pulmonary arterial end of the ductus or at the site of an intimal jet lesion in the pulmonary artery opposite the ductus. Susceptibility has not been determined for a tiny clinically silent ductus detected only with Doppler echocardiography (see Figure 20-40; see previous).67
Abnormal patterns of cerebral arterial blood flow in infants, especially preterm neonates with a nonrestrictive patent ductus, predispose to central nervous system ischemia and hemorrhage into the germinal matrix.38,68,69 Increased pulse pressure and major fluctuations of blood flow velocity caused by opening and closing of a ductus may rupture capillaries of the germinal matrix and cause intraventricular hemorrhage. A sharp decrease in diastolic arterial flow velocity can act as a steal from the cerebral circulation.68
After the first year of life, most patients with patent ductus arteriosus are asymptomatic. Beginning with the second decade, the risk of infective endarteritis exceeds the risk of congestive heart failure.35,54,70 In the third decade, more and more patients with a moderately restrictive ductus experience heart failure,35,54 and those with a restrictive ductus remain asymptomatic. A 20-year-old man with a patent ductus had been a cross-country runner, and an active schoolmistress died at the age of 85 years because of gastrointestinal bleeding. A number of reports have called attention to survival beyond age 60 years (see Figure 20-16)35,71–75: an elderly woman presented with biventricular failure in her 81st year,76 and a patient died at 90 years of age.77
Figure 20-16 Tracings from an 84-year-old woman with a moderately restrictive patent ductus arteriosus (see x-ray in Figure 20-38). The murmur in the second left intercostal space (2 LICS) continues through the second heart sound that was timed by the dicrotic notch of the carotid pulse (CAR). The continuous murmur then faded, rendering late diastole murmur-free.
A nonrestrictive patent ductus with Eisenmenger’s syndrome is accompanied by the multisystem systemic disorders of cyanotic congenital heart disease (see Chapter 17).78,79 Isotonic exercise with an Eisenmenger’s ductus causes leg fatigue without dyspnea because an exercise-induced increase in right-to-left shunt is channeled into the descending aorta (Figures 20-2 and 20-11) distal to the respiratory center and the carotid body, precluding hypoxia-induced stimulation.78–81 Hypertrophic osteoarthropathy is confined to the lower extremities.82–84 In an Eisenmenger’s ductus, left ventricular failure is absent because volume overload of the left heart is curtailed. A dilated hypertensive pulmonary trunk may cause hoarseness by compressing the recurrent laryngeal nerve. Angina and syncope are not features of nonrestrictive patent ductus with reserved shunt because right ventricular pressure cannot exceed systemic.79 Cyanosis is missed if the feet are not examined (see section Physical Appearance). A young girl came to attention because she noticed that when she sat in a warm bath, her toes were blue but her fingers were pink.
Constriction or closure of the fetal ductus deprives the right ventricle of its only outlet, so neonates present with massive tricuspid regurgitation and right-to-left interatrial shunts.24 Salicylates cause constriction of the fetal ductus, so the history should include enquiries about maternal use of aspirin. Salicylate levels can be determined on umbilical cord blood.85
Physical appearance
Maternal rubella is characterized by low birth weight and failure to thrive, irrespective of ductal patency, ductal size, or shunt volume.86,87 An underdeveloped child with a patent ductus should therefore be examined for cataracts, deafness, and mental retardation (see Figure 20-9).86,87 Another distinctive phenotype is the clinodactly (overlapping fingers), rocker bottom feet, and lax skin of Trisomy 18 (Figure 20-12).88,89 Char syndrome is an inherited disorder that maps to chromosome 6p12-p21 and is characterized by ptosis, a flat profile, a very short philtrum, patulous duck-bill lips, facial dysmorphism, and abnormalities of the hands.90–93 The recurrence rate in offspring of an affected parent is 50%.92
Differential cyanosis and clubbing are important physical signs of patent ductus with reversed shunt (see Figures 20-2 and 20-11; see previous).79,94 The toes are cyanosed and clubbed because unsaturated blood is selectively delivered to the lower extremities. A small amount of unsaturated blood often enters the left subclavian artery, so the digits of the left hand, especially the thumb, are mildly cyanosed and clubbed (see Figure 20-11 A). The fingers of the right hand are normal because unsaturated blood does not reach the right subclavian artery. In the rare presence of bilateral patent ductuses with reversed shunt, the right arm is cyanosed because the right subclavian artery receives desaturated blood from the pulmonary artery via the right ductus arteriosus.12
Patients who are old enough to follow instructions should be examined sitting or squatting with their hands placed alongside their feet or on the dorsum of their feet to facilitate comparison of fingers and toes (see Figure 20-11A). The right and left thumbs should be compared (see Figure 20-11A). Differential cyanosis is exaggerated by isotonic exercise or by warming the hands and feet, which are maneuvers that increase skin blood flow and exaggerate the color differences. In neonates with persistent fetal circulation, the right-to-left ductal shunt may cause distinctive differential cyanosis confined to the head, right shoulder, and right arm with a demarcation line that runs obliquely from above the left shoulder to below the right axilla.18
Arterial pulse
Wide systemic pulse pressure is an important physical sign of patent ductus arteriosus with a large left-to-right shunt.40,94 This sign is especially useful in symptomatic neonates without a ductus murmur. However, the arterial pulse may be weak in preterm infants in whom systemic flow is reduced by the steal effect associated with aortopulmonary shunting (see previous).37,38 The typical pulse is characterized by a brisk rise, a single or bisferiens peak, and a rapid collapse (Figure 20-13). Diastolic flow from aortic root into pulmonary trunk lowers the aortic diastolic pressure, and a large left ventricular stroke volume with forceful left ventricular contraction maintains or elevates aortic systolic pressure. The carotid, brachial, femoral, and even dorsalis pedis pulses can be bounding.94 The superficial palmar arch as it crosses the heads of the metacarpals is sometimes evident as a visible pulsation. In a child with a large patent ductus, an erythematous wheal caused by a mosquito bite blushed and blanched synchronously with the pulse.95
Precordial movement and palpation
George A. Gibson96 wrote, “When the ductus arteriosus is permanently patent, a very distinct thrill is to be felt—a thrill which distinctly follows the systole of the heart and persists until the diastolic phase has existed for some time.”2
