Patent Ductus Arteriosus

The ductus arteriosus (DA) is a fetal blood vessel that connects the pulmonary artery and the aorta. In fetal life, gas exchange of oxygen and carbon dioxide is undertaken by the maternal placenta and not the fetal lungs. The small amount of blood that passes through the pulmonary circulation is important for vascular growth but not for gas exchange. When oxygenated blood returns from the placenta via the umbilical vein to the fetal heart, it may take 1 of 2 pathways to bypass the pulmonary circulation. First, most of the fetal blood volume is shunted right to left (right atrium to left atrium) across the foramen ovale, bypassing the right heart and pulmonary circulation completely. The remaining blood in the right atrium crosses the tricuspid valve into the right ventricle, then courses across the right ventricular outflow tract to the main pulmonary artery. Most of this blood is then shunted right to left (pulmonary artery to aorta) across the DA into the descending aorta, supplying oxygenated blood to the lower half of the body. After delivery to the tissues, deoxygenated blood returns to the placenta via the umbilical arteries, and the cycle repeats.Typically, after a term birth, the lungs inflate with the first breath and pulmonary blood flow increases. With the increased oxygen content of circulating blood and chemical changes, the DA spontaneously constricts, causing functional ductal closure within the first several days after birth, soon followed by complete anatomical closure. When this process fails to occur normally, especially in the absence of persistently elevated pulmonary artery pressures or significant cyanotic congenital heart disease, the result is a patent DA (PDA). Infants who are born preterm are at particularly high risk for the ductus remaining patent because the normal closure process can be significantly delayed. When the ductus remains open, left to right (aorta to pulmonary artery) shunting can result in pulmonary overcirculation. Over time, especially in premature infants, this may lead to pulmonary edema, chronic lung disease, pulmonary hypertension, and respiratory failure requiring prolonged mechanical ventilation. If a PDA is suspected based on clinical signs and symptoms such as a murmur, tachypnea, or pulmonary edema, an echocardiogram should be obtained to assess ductal presence, size, morphology, amount of left to right shunting, and presence of left heart dilation. An echocardiogram can also be obtained to assess for ST-segment changes. Many PDAs require no treatment, but when they are deemed hemodynamically significant, closure may be performed using medical management with a nonsteroidal anti-inflammatory drug (NSAID), surgery, or a transcatheter approach. Surgical closure provides immediate resolution of ductal shunting.For PDAs refractory to medical therapy in premature infants, surgery has been the most widely performed method of closure because of its long-standing track record. However, surgery may result in hemodynamic instability and the need for increased respiratory support in the postoperative period. In addition, surgical ligation carries the risk of inadvertent vascular injury or ligation of the wrong vessel, as well as vocal cord or diaphragmatic paralysis and chylothorax.Although catheter-based PDA closure has been the standard of care for larger infants, children, and adolescents, it has not until recently been routinely performed in premature and low-birthweight infants given concerns for high rates of procedural complications (device embolization, vascular injury) and lack of appropriately sized devices. Today, with advances in device technology, nearly all types of PDAs can be closed in the catheterization laboratory, including the type F or “fetal type” PDA, which occurs more often in premature infants.The Medtronic micro vascular plug system (MVP™; Medtronic, Minneapolis, MN) and the Amplatzer Piccolo™ device (Abbott, Abbott Park, IL) have been designed specifically for use in premature and low-birthweight neonates. The unique shape of the MVP without retention discs makes it useful for closure of the often tubular-shaped premature or type F PDA. The Amplatzer Piccolo device is available in small diameters and has a soft delivery cable, making it suitable for ductal occlusion in premature and low-birthweight infants, and it is approved for this indication by the Food and Drug Administration (FDA). Both of these devices require delivery systems of very small diameter, minimizing risk of injury to the diminutive, fragile vessels of the premature newborn. Also, these devices can be deployed through the pulmonary artery, allowing the procedure to be performed using the femoral vein without arterial access, with fluoroscopic and transthoracic echocardiographic guidance.Although a PDA may cause significant morbidity in premature infants, a subset of infants with congenital cyanotic heart diseases such as tetralogy of Fallot, transposition of the great arteries, and pulmonary atresia require patency of their DA to provide adequate pulmonary blood flow. Ductal patency is maintained with an intravenous infusion of prostaglandin E (PGE) 1 until a permanent source of pulmonary blood flow is secured by either deploying a stent to keep the duct open or placing a shunt surgically.The Blalock-Taussig-Thomas (BTT) shunt has been used since 1944 as a reliable surgical means for providing pulmonary blood flow. In recent years, a catheter-based procedure, PDA stenting, has emerged as an alternative to the BTT shunt. This technique was first described in 1992 with the use of stents that were hand-crimped onto balloons. Newer low-profile, flexible delivery systems with the stent premounted on the delivery balloon are being used successfully. Today’s stents require smaller sheaths, and the lower profile results in enhanced maneuverability. In addition, interventionalists are now using alternative access sites (eg, the axillary artery or common carotid artery) to improve the precision of stent placement. Finally, the use of modern drug-eluting stents, including the Synergy™ (Boston Scientific, Marlborough, MA) and the Resolute Onyx™ (Medtronic), has resulted in larger ductal lumen diameters with decreased need for reintervention compared with traditional bare metal stents such as the Rebel™ (Boston Scientific) and the Multi-Link Vision™ (Abbott). These stents, which are designed for use in adult coronary arteries, are currently used off-label for pediatric ductal stenting. Overall, recent comparison studies have shown PDA stenting to be comparable with or superior to the BTT shunt regarding mortality and rates of procedural complications, and with shorter lengths of stay in the ICU and larger branch pulmonary arteries on follow-up measurement. These benefits, however, may come at the cost of higher rates of reintervention.In conclusion, important technological and procedural advancements for both PDA occlusion and stenting during the past decade have allowed PDA device closure for premature infants and PDA stenting for ductal-dependent pulmonary blood flow to become reasonable alternatives to surgical PDA ligation and BTT shunt placement. Prospective randomized trials addressing both of these contemporary topics are currently being implemented and will hopefully shed light on some important remaining unanswered questions. Concurrently, devices and techniques will continue to evolve, resulting in improved care for these vulnerable patients.The medical treatment of the DA, whether to hasten closure or maintain patency, centers around the action of prostaglandins. PGE2 is a potent smooth muscle relaxant, and under normal physiologic circumstances its levels decline shortly after birth along with rising oxygen tension, both factors leading to constriction of the DA muscle and, thus, its functional closure. When PGE2 levels do not wane, muscular contraction is inhibited and the DA remains patent. NSAIDs inhibit the enzyme cyclooxygenase, which promotes the conversion of arachidonic acid to prostaglandins. Both indomethacin and ibuprofen are NSAIDs widely used as cyclooxygenase inhibitors to cut off production of PGE2, thereby promoting contraction of the DA and its closure. The opposite strategy is used when the situation, as with certain cyanotic heart diseases, calls for maintaining DA patency to allow for adequate pulmonary blood flow: a synthetic PGE1 is infused to relax smooth muscle, inhibiting contraction and, thus, closure of the DA.