Introduction
The patent ductus arteriosus [PDA] is the most common cardiac condition affecting neonates [1]. While there has been several studies and thousands of publications on the topic, the decision to treat the PDA is still strongly debated among cardiologists, surgeons, and neonatologists [2–4].
Numerous studies have found an association with untreated PDAs and significant neonatal morbidities [5–7]. When left untreated, the PDA and resulting left-to-right shunt can compromise systemic perfusion. Determining the volume of the shunt is a crucial step in deciding the course of action for premature infants with a PDA. Physicians use their clinical assessment, echocardiography, and indicators of systemic hypoperfusion or pulmonary over-circulation in order to quantify the shunt but this process has not been standardized [8, 9] and thus varies across institutions. While increased morbidity is associated with PDA, the management options have been linked to adverse outcomes [10–12]; which leads to debate over whether or not to treat the PDA [2]. Furthermore, if and when a PDA needs to be treated, how do we treat it? [13] This chapter intends to outline the current literature about the embryology, pathophysiology, and treatment approaches for the PDA in the premature infant in 2020.
History
The PDA was the first congenital heart lesion that was surgically repaired. This was performed by Dr. Robert Gross in 1938 [14]. In the Second century, Galen was one of the first to describe a notion of blood traveling between the heart and the lungs. This concept was later developed into a complete anatomical and physiologic description of PDA many centuries later. In 1989, Krichenko et al. [15] angiographically classified the PDA based on the ductal lumen at the aortic and pulmonary ends. Closure of the PDA in a premature neonate with respiratory distress syndrome [RDS] was first detailed by Dr. ML Powell in 1963 [16]. With the increasing survival of preterm neonates, the consequent increase in PDA closures in preterm infants and the special morphologic characteristics of the preterm ductus, the PDA was reclassified in 2016 to aid with the choice of device used for transcatheter device closure in this population [17].
Embryology
At the early embryonic stage, the ductus arteriosus [DA] is present on the right and left sides but the right atrophies between 37 and 40 days of embryonic gestation [18]. The DA is created from the same embryonic structure that makes the pulmonary artery: the left 6th aortic arch. The DA attaches to the inner curve of the arch, distal to the left subclavian artery. There is a high resistance within the pulmonary vasculature [19] during development of the fetal lungs. Due to this degree of resistance, blood travels from the left pulmonary artery, through the DA, and into the descending aorta which preserves right ventricular function [20]. If the DA were to close prematurely in utero, the right ventricular afterload increases and the fetus is at risk to develop right heart failure and fetal hydrops [21].
Histology
Histologically, the walls of the DA are mainly muscular in contrast to the walls of the adjacent aorta and pulmonary artery, which are fibro-elastic [22]. The DA is comprised of smooth muscle fibers which are arranged in longitudinal and spiral layers and surrounded by concentric layers of elastic tissue. The great arteries are composed primarily of elastic fibers arranged circumferentially. After birth, the medial smooth muscle fibers contract in response to the exposure to oxygen-rich ambient air [23]. This leads to constriction of the lumen and shortening of the DA length which begins at the pulmonary end until there is functional closure between 24 and 48 h. The second stage of closure involves proliferation of the medial and intimal connective tissue and smooth muscle atrophy which leads to the conversion of a muscular vessel into a ligamentous non-contractile structure, the ligamentum arteriosum over the next 3 weeks [24]. Vascular endothelial growth factor [VEGF] has been thought to be involved in DA closure. However, VEGF polymorphism rs2010963 status has not been shown to affect PDA incidence or successful treatment with cyclooxygenase inhibitors in preterm infants [25].
Physiology
The predominant cardiac output in fetal life bypasses the lungs via right to left shunting at the DA. This is possible due to the low systemic vascular resistance from the placenta and the high pulmonary vascular resistance in the lungs. Systemic vascular resistance is increased after birth when the cord is clamped [26]. In addition, due to ventilation, the pulmonary vascular resistance is decreased and pulmonary blood flow is increased. This causes blood to shunt left to right through the DA. In term infants, predominant left to right shunting occurs within 10 min and is entirely left to right within 24 h of life [27].
PDA in the Premature Neonate
The incidence of PDA is inversely related to the gestational age. It remains open at 4 days of age in 10% of neonates born at 30–37 weeks, 80% of those between 25 and 28 weeks gestation and 90% born 1.4, there is likely left-sided volume overload secondary to increased blood return from the lungs. Another important echocardiographic measurement includes reversal of flow in diastole in the abdominal aorta suggestive of a substantial shunt [i.e., evidence of systemic steal [Figure 3]]. Individually, these indices are not specific to a PDA but when presenting together in a premature infant with RDS, it is reasonable to believe there is a hemodynamically significant PDA present. Although there are numerous suggested protocols for assessment of a hsPDA [49, 50, 58–61], there is no validated protocol that confirms the echocardiographic information with real-time hemodynamic information from cardiac catheterization.
Figure 1. [A] Transthoracic Echocardiogram [parasternal short axis image with color Doppler] demonstrating the relative size of the patent ductus arteriosus [PDA] in comparison to the left pulmonary artery [LPA] and right pulmonary artery [RPA]. [B] Post-transcatheter PDA closure.
Figure 2. Transthoracic Apical 4-chamber view showing left atrial and ventricular dilation suggestive of a hemodynamically significant PDA.
Figure 3. Abdominal Aorta Doppler pattern showing diastolic flow reversal indicative of a hemodynamically significant PDA.
Echocardiography can also be useful as a predictive measure of whether a PDA will become hemodynamically significant. One study found that the ductal anatomy during the first 12 h of life, specifically a ductal length