Abstract
Patent ductus arteriosus (PDA) is a congenital heart defect that can exist as an isolated lesion or as a component part of many other congenital heart defects. A PDA is essential for fetal development, but it should close shortly after birth. Ductal patency persisting beyond 24 hours after birth is considered to be a PDA. In some cases of complex congenital heart disease a PDA is necessary for survival of the patient, and in other cases the PDA is a persistent anomaly that serves no particular value to the patient and, when large, can contribute to left heart failure or even elevation of pulmonary artery resistance from prolonged left-to right-shunt. The diagnosis is typically made by echocardiography, which can also be useful in evaluating the patient for other commonly associated cardiac and extracardiac defects. Treatment can be medical or interventional depending on the size and age of the patient as well as other factors. Interventions can be surgical or performed with devices in the cardiac catheterization laboratory. A PDA is usually an easily treated defect that can be “cured,” and a patient with a successful treatment for an isolated PDA should have no important lifelong limitations or disability related to the PDA. The evolution of surgical treatment for PDA has helped to stimulate the application of bedside surgery in the intensive care unit for selected cardiac problems.
Key Words
Congenital heart defect, Patent ductus arteriosus, Left-to-right shunt
The ductus arteriosus is a vascular connection between the systemic and pulmonary circulations, which although vital during fetal development, can lead to severe morbidity and mortality when persistent postnatally. Paradoxically, the ductus arteriosus can also be essential for survival in some congenital heart defects. Typically the ductus arteriosus is a communication between the main pulmonary trunk and the descending aortic arch, distal to the left subclavian takeoff. A patent ductus arteriosus is essential for survival during fetal development to divert pulmonary flow into the systemic circulation (because there is no need during fetal development for pulmonary perfusion). After birth, pulmonary artery flow is typically directed toward the lungs, and the ductus normally closes during the first day after birth. Failure of the ductus to close in this timely fashion (within 15 to 24 hours) is given the nomenclature of a patent ductus arteriosus (PDA). Although a PDA is an associated finding in numerous congenital lesions (and occasionally necessary for life after birth), this chapter will concentrate on the isolated form of PDA in infants, children, and young adults.
Fetal Circulation
During gestation the ductus arteriosus and foramen ovale provide necessary right-to-left shunts of blood returning from the placenta into the fetal systemic circulation. This systemic perfusion from the ductus exists in the fetus because the lungs (during fetal development) are not ventilated and thus pulmonary vascular resistance (PVR) is high. Additionally, anatomic positioning of the foramen ovale preferentially causes a shunt of blood with the highest oxygen saturation returning from the inferior vena cava to the head vessels on ascending aortic arch. The ductus arteriosus, however, shunts a significantly higher volume of relatively desaturated blood returning from the superior vena cava to the descending aortic arch. As a result, those tissues with the highest metabolic demand, the brain and myocardium, preferentially receive more oxygenated blood than the rest of the developing organ systems. After birth, spontaneous ventilation begins, PVR drops, and with the right-to-left shunt across the ductus into the aorta no longer vital, spontaneous closure of the ductus arteriosus begins.
Mechanism of Spontaneous Closure
The spontaneous closure of the ductus arteriosus starts proximally and moves distally toward the aorta, occurring in two stages: functional and anatomic. Although the ductus arteriosus may appear similar to the aortic and pulmonary arteries, it differs in that it has a media composed primarily of circumferentially layered smooth muscle cells and minimal elastin fibers. Additionally, mucoid lakes, which consist of subintimal pools of a poorly characterized mucoid substance, help to distinguish the ductal tissue as unique from surrounding pulmonary artery and aortic tissue. Functional ductal closure typically occurs within the first 10 to 15 hours after birth. This first stage occurs due to medial smooth muscle contraction, which is stimulated by exposure to four principal postnatal changes: (1) increased arterial oxygen tension, (2) decreased mean ductal pressure, (3) decreased circulating prostaglandin E 2 (PGE 2 ), and (4) decreased density of PGE 2 receptors in the ductal intima and media. As the smooth muscle cells of the ductus arteriosus contract, ductal wall thickness increases, and the intimal cushions shorten and protrude, resulting in the functional closure of the ductus arteriosus.
The second, anatomic phase of closure occurs as a result of ischemia to the medial tissue, induced by the functional closure, and is generally completed in a few days to weeks after birth. The resultant hypoxia in the ductal wall from contraction of the media induces medial cell necrosis and transcription of various growth factors. These growth factors promote proliferative subendothelial deposition of extracellular matrix and concomitant neointimal thickening. Additionally, extensive wall hypoxia inhibits endogenous production of prostaglandins and nitric oxide, permanently preventing any dilatation of ductal wall. The end result is a constricted, fibrous structure known as the ligamentum arteriosum. Failure of spontaneous closure results in the persistent patency of the ductus arteriosus.
It is also important to note that ductal closure is also highly affected by gestational age. As previously mentioned, increased oxygen tension promotes ductal constriction, whereas prostaglandins promote ductal dilatation. In the full-term infant the ductus arteriosus is much more sensitive to the partial pressure of oxygen; however, in the preterm infant the ductus arterious is more sensitive to prostaglandin E 1 (PEG 1 ). This helps to explain why decreased gestational age at birth (i.e., prematurity ) is an inherent risk factor for PDA.
Anatomy and Embryology
The ductus arteriosus develops from the distal portion of the sixth aortic arch ( Fig. 43.1 ), and in the majority of persons connects the main pulmonary trunk or proximal left pulmonary trunk to the isthmus of the descending aortic arch, approximately 5 to 10 mm distal to the takeoff of the left subclavian artery. The shape, length, diameter, and course of the ductus arteriosus can be highly variable, which is important to consider when selecting the best interventional therapy. Typically, though, the ductus is somewhat conical in shape, being broader at the base of the aorta than at the pulmonary trunk. The ductus may also exist as left, right, or bilateral in projection, where the connection may occur from the proximal left or right pulmonary trunk to any position on the aortic arch or, rarely, brachiocephalic vessels. In a right aortic arch the ductus travels in a retroesophageal fashion and can create a vascular ring (see Chapter 44 ).
Perhaps the most important anatomic relationship for the surgeon to be aware of is the nearness of the ductus to the left recurrent laryngeal nerve, which controls the left vocal cord. During its course into the thoracic cavity, the left recurrent laryngeal nerve separates from the vagus nerve anterior to the aorta and then wraps around the ductus, anterior to posterior, before ultimately slinging superiorly into the tracheoesophageal groove. In the event that the ductus connects to the aorta more proximally along the arch, the recurrent nerve may separate and double back under the aorta in a retrograde fashion. Damage to the nerve can result in temporary or permanent ipsilateral vocal cord paralysis, which can be associated with feeding difficulties postoperatively such as aspiration.
Risk Factors
The incidence of isolated PDA in the United States is approximately 1 in 2000 to 2500 live births and is believed to constitute approximately 7% to 10% of all congenital heart defects. There is a 2 : 1 incidence among females compared with males. By far the greatest risk factor for PDA, however, is prematurity. The incidence of PDA increases with lower gestational age (77% at 28 weeks) and also with low birth weight (30% of infants weighing less than 2500 g). A proposed explanation for this is that in the preterm infant circulating PEG 2 is more prevalent due a lack of first-pass metabolism as a result of lung immaturity. Additionally, it has been demonstrated that first-trimester exposure to rubella of nonimmunized mothers produced cardiovascular anomalies in 60% of infants, the most common of which was PDA. Other associations include fetal hydantoin syndrome, warfarin exposure in utero, Down syndrome, and trisomy 13. A PDA may also be more common in babies born at high altitude.
Pathophysiology
As previously mentioned, the ductus arteriosus typically closes within the first day after birth. In the event patency persists, the pathophysiology relates directly to the degree of flow reversal (from the aorta through the ductus into the pulmonary arteries) as a consequence of the decline in PVR that occurs naturally with a newborn’s first breath. Because systemic vascular resistance (SVR) is much higher than PVR, a left-to-right shunt will commonly occur across the patent ductus. Thus the degree of left-to-right shunting across a PDA is primarily affected by PVR, as well as by the size of the PDA, because SVR is usually high. Blood travels along the path of least resistance, and, as a result, oxygenated blood from the aorta can flow retrograde across the patent ductus into the pulmonary circulation, where it is recirculated back to the left side of the heart. This results in an increased volume and subsequent workload for both the left atrium and ventricle. Over time this recirculation of cardiac output causes left atrial enlargement and left ventricular dilatation and hypertrophy. Ultimately, depending on the degree of shunting, irreversible pulmonary hypertension can ensue, leading to right-sided heart failure.
Although the degree of left-to-right shunting via the patent ductus is largely dependent on the relationship between SVR and PVR, not all PDAs are created equal, and the impact of a PDA on the physiology and clinical condition of the patient during the first weeks to months of life can be quite variable.
Large PDAs with a substantial left-to-right shunt (usually characterized by a Q p :Q s >2 : 1) can result in left heart failure, manifested by pulmonary overcirculation and edema (with tachypnea), left atrial and left ventricular dilatation, and increased cardiac work. Large PDAs are inherently less restrictive to flow from the systemic to pulmonary circulations, and, as a result, the degree of left-to-right shunting can be severe. In addition to left atrial dilatation and left ventricular strain, this additional blood volume can permanently alter the pulmonary vascular bed. Histologic studies have demonstrated that with the persistent increased blood flow there is increased medial smooth muscle in the pulmonary arterial vessels. Irreversible pulmonary vascular disease ensues when subendothelial cellular proliferation and deposition leads to intimal damage, resulting in both thrombosis and fibrosis of the smaller pulmonary arterioles. This may result in severe pulmonary hypertension and, ultimately, right-sided heart failure. Although this sequelae of consequences is unusual in the modern era, it can occur if a large PDA is left untreated. In patients with severe and irreversible pulmonary hypertension, closure of the PDA is contraindicated.
In medium-sized PDAs, a moderate left-to-right shunt (Q p :Q s of 1.5-2.0) may be well compensated for by the left ventricle and produce minimal symptoms. In these patients, pulmonary artery pressures may be only mildly to moderately elevated, and it is primarily the size (length and diameter) of the ductus that regulates the degree of shunting rather than the ratio of SVR to PVR. These patients may be completely asymptomatic, or they may experience poor feeding, dyspnea, and growth retardation as sequelae of failing to meet the body’s metabolic demand.
The natural course of small PDAs (Q p :Q s <1.5) is typically uneventful. The additional workload of the net left-to-right shunt is slight and is well compensated by the left ventricle. Left ventricular failure and pulmonary hypertension do not occur. Patients may be asymptomatic their entire lives, and the discovery of a PDA may simply be an incidental finding if a murmur is investigated later in life and results in obtaining an echocardiogram.
Infants and children with large PDAs, if symptomatic, tend to present with signs and symptoms of congestive heart failure. This can range from a murmur heard on physical examination to tachypnea and signs of pulmonary overcirculation on chest x-ray examination. Premature neonates with a significant PDA may present on days 3 to 4 of life with unexplained respiratory distress and metabolic acidosis that is recalcitrant to ventilator support. There are large PDAs that are vital for survival in certain complex congenital heart defects (either as a source of pulmonary blood flow in patients with restricted pulmonary flow or for systemic blood flow in cases of restricted aortic flow). These large PDAs, because they are critical for survival, are not the focus of this chapter. The most common presentation for a PDA (outside the neonatal period) is a murmur being heard in an otherwise asymptomatic child.
Other known complications of a persistent ductus, although rare, are worth mentioning. Endocarditis, although now rare in patients with PDA, was a leading cause of mortality before the widespread adoption of prophylactic antibiotics and surgical repair. When endocarditis does occur, vegetations can typically be visualized on the pulmonic end of the ductus, and, consequently, septic emboli ejected to the lungs may form pulmonary abscesses. Such cases are initially managed conservatively with antibiotics and then referred for surgery. Another exceedingly rare but emergent complication of a persistent ductus is aneurysm. Ductus arteriosus aneurysm can occur either spontaneously or secondarily as a complication of prior intervention. Aneurysm of the ductus is an immediate indication for surgical repair due to the high risk of rupture and infection; unrepaired, the mortality has been reported as high as 91%. There have been only limited case studies of ductal aneurysm in patients with inherited collagen vascular disease. Additional complications, such as laryngeal nerve palsy, have been also reported.
Diagnosis
Diagnosis of PDA in the newborn and infant starts with a good history and physical examination. In preterm newborns there must be a high index of suspicion for any patient with respiratory deterioration despite adequate ventilator support. Failure to gain weight adequately is common. Although systolic pressure is typically maintained, patients with a hemodynamically significant shunt may present with a widened pulse pressure due to diastolic runoff. A murmur may be present also: classically, a III/VI+ crescendo-decrescendo, “machine-like” murmur, which is best auscultated at the left upper sternal border. Electrocardiogram may be normal or demonstrate left ventricular hypertrophy. Chest x-ray examination can show increased pulmonary vascular markings and interstitial fullness but is also frequently unremarkable.
The hallmark for diagnosis is ultrasonography. Two-dimensional echocardiography with color flow and Doppler can be used to diagnose a majority of PDAs in the newborn ( Fig. 43.2 ). Cardiac catheterization is rarely indicated for diagnosis (unless pulmonary hypertension is suspected), although it is becoming the preferred method for treatment of PDAs in appropriately selected patients. Likewise, other imaging modalities such as computed tomography scan or magnetic resonance imaging, although they can demonstrate a PDA, are usually not necessary. Once the diagnosis is made, and this is usually easily done by echocardiography, the team can decide from numerous options on the best plan of management.
