Obstacles to the Early Diagnosis and Management of Patent Ductus Arteriosus

Abstract

Sharada H Gowda, 1 Ranjit Philip, 2 Mark F Weems 3 1 Department of Pediatrics and Division of Neonatology, Baylor College of Medicine, Houston, TX, USA; 2 Department of Pediatrics, Division of Cardiology, Le Bonheur Children's Hospital, University of Tennessee Health Science Center, Memphis, TN, USA; 3 Department of Pediatrics, Division of Neonatology, Le Bonheur Children's Hospital, University of Tennessee Health Science Center, Memphis, TN, USA Correspondence: Mark F Weems, University of Tennessee Health Science Center, Department of Pediatrics, Division of Neonatology, 853 Jefferson Ave, Rout Bldg E201, Memphis, TN, 38163, USA, Tel +1 901-448-5950, Fax +1 901-448-1691, Email "What we know is little, and what we are ignorant of is immense"; the last words of Laplace still apply to the diagnosis and management of the patent ductus arteriosus (PDA). Despite decades of research, we are searching for the right approach to care for patients with PDA. Nuances of myocardial structural changes and cardiopulmonary interactions with prolonged exposure to excess pulmonary blood flow have played an important role in decision-making. The availability of medical treatments with poor efficacy and, historically, surgical ligation as the only available definitive therapy further widened the gap between observation and definitive closure. As more extremely low birth weight neonates born at earlier gestational ages survive, we are faced with a population whose physiological immaturity and structural alignment of the myocardium predisposes them to myocardial dysfunction and dysregulated vascular tone. Therefore, it may be time to replace historical approaches with a more precise patient-centric therapeutic model. A comprehensive serial echocardiography assessment of the heart function, hemodynamic significance, and clinical context with respect to pulmonary insufficiency and gut perfusion aids the neonatologist in making PDA management decisions. A targeted approach balances risks and benefits of therapy, avoids treatment for infants likely to have early spontaneous closure, and limits prolonged exposure to the pathologic PDA shunt in high-risk infants. There is significant variability in the diagnosis and treatment of the PDA, both within and across centers. This review highlights the clinical obstacles contributing to the variability and illustrates the need for a standardized approach to PDA diagnosis and management. Keywords: preterm, neonate, echocardiogram, neonatology, cardiology, shunt "What we know is little, and what we are ignorant of is immense"; it is said that these were Laplace's last words before his death. 1 Laplace's law and his alleged last words still hold true in PDA physiology and management a few centuries later. The ductus arteriosus (DA) was discovered as early as the second century, AD. Galen first described a fetal shunt from the pulmonary artery to the aorta, circumventing the lungs. 2 A remnant of the sixth embryonic aortic arch, this connection between the left pulmonary artery and aorta allows the majority of right-sided cardiac output to bypass the lungs, sending blood flow to the descending aorta, feeding the systemic circulation and returning blood to the placenta via umbilical arteries (Figure 1A). The ductal tissue maintains patency in utero by multiple mechanisms, most prominently prostaglandin E2 (PGE2). Over time, the ductal tissue changes in morphology and response to chemical mediators such that the ductus at term gestation is significantly different from the preterm ductus. 3 Figure 1 Illustration of the ductal shunt over time. Arrows indicate the direction of blood flow across the ductus. ( A ) The fetal duct is a physiologic right to left shunt allowing right ventricular output to supply systemic circulation. ( B ) In the transitional period after birth, the shunt becomes bidirectional or left to right before spontaneous closure. ( C ) In the case of a prolonged patent ductus, a pathologic left to right shunt contributes to pulmonary over circulation and dilation of the left atrium and the left ventricle. By the 16th century, spontaneous closure of the DA had been described, but understanding the mechanism of closure remains incomplete. 4 At delivery, simultaneous decreases in placenta-derived PGE2 and pulmonary vascular resistance with an increase in blood oxygen content contribute to ductal constriction. 5 In the term infant, this typically leads to functional closure within hours of birth. Compression of vaso vasorum supplying the ductal smooth muscle leads to tissue necrosis and permanent closure. The preterm infant, however, is at risk for prolonged patent ductus arteriosus (PDA) due to underdevelop -Abstract Truncated-