Successful Use of Prostaglandin Infusion in a Two-Month-Old With Coarctation of the Aorta and Ventricular Dysfunction.

Abstract

We present the unique case of coarctation of the aorta with ventricular dysfunction in a 2-month-old with respiratory syncytial virus bronchiolitis. In this infant, prostaglandin infusion relieved obstruction at the aortic isthmus and led to improved ventricular function, without significant reopening of the ductus arteriosus. The ductus arteriosus (DA) is a fetal blood vessel that connects the pulmonary artery and the aorta. Ductal patency is maintained during fetal life by prostaglandins produced by the placenta and low oxygen content in the fetal blood.1Akkinapally S. Hundalani S.G. Kulkarni M. et al.Prostaglandin E1 for maintaining ductal patency in neonates with ductal-dependent cardiac lesions.Cochrane Database Syst Rev. 2018; 2: CD011417PubMed Google Scholar After birth, the reduction in circulating prostaglandins and increased oxygen concentration in the newborn blood promotes ductal constriction and subsequent closure. The duct is functionally closed by 12-24 hours after birth, with complete closure occurring within 2-3 weeks.1Akkinapally S. Hundalani S.G. Kulkarni M. et al.Prostaglandin E1 for maintaining ductal patency in neonates with ductal-dependent cardiac lesions.Cochrane Database Syst Rev. 2018; 2: CD011417PubMed Google Scholar Coarctation of the aorta is caused by ectopic ductal tissue around the aortic lumen in the aortic isthmus. As normal constriction of the DA occurs, the ectopic ductal tissue also constricts the aortic lumen and leads to further obstruction. Severe obstruction leads to left ventricular dysfunction and poor organ perfusion, and can be lethal without surgical intervention.2McFarland C.A. Truong D.T. Pinto N.M. et al.Implications of left ventricular dysfunction at presentation for infants with coarctation of the aorta.Pediatr Cardiol. 2021; 42: 72-77Crossref PubMed Scopus (4) Google Scholar Exogenous prostaglandin infusion is used in coarctation of the aorta to reopen the DA to allow for blood to shunt from the pulmonary artery to the distal aorta, thus improving distal organ perfusion. Furthermore, prostaglandins can relieve the aortic coarctation by relaxing the ectopic ductal tissue in the aorta.1Akkinapally S. Hundalani S.G. Kulkarni M. et al.Prostaglandin E1 for maintaining ductal patency in neonates with ductal-dependent cardiac lesions.Cochrane Database Syst Rev. 2018; 2: CD011417PubMed Google Scholar We present the oldest known case of prostaglandin infusion leading to improved ventricular function in a 2-month-old infant with coarctation of the aorta. A 2-month-old male infant, birth weight 2736 g, born at 37+4 weeks of gestation via an uncomplicated spontaneous vaginal delivery, presented with a history of nasal congestion, cough, and respiratory distress. He was diagnosed with respiratory syncytial virus bronchiolitis and was admitted to the paediatrics ward for high-flow oxygen requirements. Subsequently, he had increasing respiratory requirements and was escalated to noninvasive positive pressure ventilation. He was tachycardic, but importantly, 4-limb blood pressures and pre- and postductal saturations were normal. There were no signs of haemodynamic compromise. However, a grade 3/6 systolic ejection murmur at the right upper sternal border with radiation to the clavicles was noted. Thus, echocardiogram was performed, which showed coarctation of the aorta and left ventricular dysfunction. With this finding, he was transferred to the nearest tertiary care paediatric intensive care unit. On transfer, 4-limb blood pressures were as follows: right arm 109/74 mm Hg, right leg 111/76 mm Hg, left arm 83/68 mm Hg, and left leg 107/85 mm Hg. Femoral pulses were present but difficult to palpate. Initial blood gas was normal (pH 7.40, CO2 43, bicarbonate 27.9, and lactate 1.1). Repeat echocardiogram showed severe coarctation of the aorta with a very small isthmus (0.29 cm, Z score −5.99; Fig. 1A). There was mild transverse arch hypoplasia (proximal transverse 0.46 cm, Z score −2.57; distal transverse 0.43 cm, Z score −2.54), moderate ventricular dysfunction with the ejection fraction of 37%, mild concentric ventricular hypertrophy, and bicuspid aortic valve with mild stenosis (peak gradient 21 mm Hg, aortic valve annulus 0.63 cm, Z score −2.3) and mild ascending aortic dilation. The DA was closed, and there were no signs of pulmonary hypertension. Given the patient’s ventricular dysfunction and respiratory syncytial virus bronchiolitis, he was determined to be at increased risk for surgical complications. Thus, although success had never been reported in a 2-month-old, and taking into consideration the clinical stability of the patient, prostaglandin infusion at 0.025 μg/kg/min was initiated. On repeat echocardiogram 24 hours later, the isthmus diameter increased to 0.36 cm (Fig. 1B) and there was a tiny patent DA. Left ventricular function also improved to an ejection fraction of 44%. In the days following, repeat echocardiogram showed ongoing increases in isthmus diameter (up to 0.4 cm) and normalization in ventricular function (ejection fraction 62%). Clinically, the patient had stronger femoral pulses and was normotensive. Prostaglandin infusion was tolerated well with no apnoeas, fevers, bradycardic episodes, or other side effects. The patient remained haemodynamically stable with no signs of end organ dysfunction. The patient remained admitted to the paediatric intensive care unit for 6 days. During this time, he was weaned from all respiratory support and never required intubation. He was started on nasogastric tube feeds and tolerated this well. On day 6 of admission, he was transferred to a paediatric cardiac surgery centre for surgical repair. The patient underwent an end-to-end anastomosis repair of the coarctation and DA ligation via left thoracotomy. Intraoperative course was uncomplicated, but postoperatively, he did have hypertension and required a brief nitroprusside infusion and course of captopril. Most recent echocardiogram at 4 months postoperatively shows mild residual coarctation with normal function. Our case is the first to highlight the successful use of prostaglandin E1 (PGE1) in a 2-month-old patient with coarctation of the aorta and moderate ventricular dysfunction. In our case, the main effect of PGE1 was in relieving the obstruction through improvement in coarctation size, whereas the duct remained trivial. This supports the mechanism whereby PGE1 relaxes ductal extant tissue in the aortic wall, ultimately relieving narrowing and improving pressure gradient and flow even in the presence of a closed duct. By this mechanism, afterload to the left ventricle is reduced and ventricular function recovers. The Skodaic theory of coarctation pathophysiology supports this and posits that abnormal extension of ductal tissue into and encircling the aortic wall contributes to obstruction in coarctation.3Liberman L. Gersony W.M. Flynn P.A. et al.Effectiveness of prostaglandin El in relieving obstruction in coarctation of the aorta without opening the ductus arteriosus.Pediatr Cardiol. 2004; 25: 49-52Crossref PubMed Scopus (26) Google Scholar Histologic studies also support this mechanism by illustrating the presence of ductal tissue surrounding the isthmus in a substantial proportion of coarctation patients.3Liberman L. Gersony W.M. Flynn P.A. et al.Effectiveness of prostaglandin El in relieving obstruction in coarctation of the aorta without opening the ductus arteriosus.Pediatr Cardiol. 2004; 25: 49-52Crossref PubMed Scopus (26) Google Scholar There have been 8 previously reported cases of PGE1 successfully relieving obstruction and improving forward flow in the presence of a closed DA that have been summarized in Table 1.3Liberman L. Gersony W.M. Flynn P.A. et al.Effectiveness of prostaglandin El in relieving obstruction in coarctation of the aorta without opening the ductus arteriosus.Pediatr Cardiol. 2004; 25: 49-52Crossref PubMed Scopus (26) Google Scholar, 4Bansal N. Balakrishnan P.L. Aggarwal S. Prostaglandin infusion in neonate with severe coarctation of the aorta with closed ductus arteriosus—a case report and review of the literature.World J Pediatr Congenit Heart Surg. 2020; 11: NP239-NP243Crossref PubMed Scopus (1) Google Scholar, 5Desai A.R. Maiya S. Inwald D. Slavik Z. Prostaglandin in aortic coarctation and closed arterial duct—treatment beyond ductal re-opening.Cor Vasa. 2013; 55: e460-e462Crossref Google Scholar All patients were diagnosed postnatally with age at diagnosis ranging from 2 to 49 days. Our case represents the oldest case of PGE1 success at 2 months of age (65 days). Heyman et al.6Heymann M.A. Berman W. Rudolph A.M. Whitman V. Dilatation of the ductus arteriosus by prostaglandin E1 in aortic arch abnormalities.Circulation. 1979; 59: 169-173Crossref PubMed Google Scholar previously reported a case of a 5-month-old, but prostaglandins did not lead to DA dilation or improvement in forward flow.Table 1Previous reported cases of infants with coarctation of the aorta successfully treated with PGE1First authorYear of publicationAge at diagnosis (d)Gestational age (wk)Birth weight (g)PGE1 dose (μg/kg/min)Other medications and treatment usedHascoet199231309000.05Indomethacin (before diagnosis)FurosemideDigoxinMechanical ventilationCallahan1998936 (twin)17490.1DopamineLiberman20042Term0.05-0.2Liberman200421Term0.1BicarbonateDopamine dobutamineFurosemideLiberman200449Term0.2BicarbonateMechanical ventilationDopamineCarroll200693518000.1DigoxinDesai201315Term0.1-0.5Mechanical ventilationBansal2018932 (triplet)11650.025-0.05PGE1, prostaglandin E1. Open table in a new tab PGE1, prostaglandin E1. In all previously reported cases, as well as our own, PGE1 was tolerated well without significant side effects. However, our case represents the lowest dose of prostaglandin that led to haemodynamic success at 0.025 μg/kg/min. Bansal et al.4Bansal N. Balakrishnan P.L. Aggarwal S. Prostaglandin infusion in neonate with severe coarctation of the aorta with closed ductus arteriosus—a case report and review of the literature.World J Pediatr Congenit Heart Surg. 2020; 11: NP239-NP243Crossref PubMed Scopus (1) Google Scholar began with a 0.025 μg/kg/min dose but required an increase of up to 0.05 μg/kg/min for haemodynamic improvement in a 9-day-old. Thus, the authors hypothesized that the prostaglandin effect may be dose dependent. Our case supports that even relatively low doses of prostaglandin may be successful. This is supported by a recent chart review of 154 infants with ductal-dependent congenital heart disease, which illustrated that a starting dose of 0.01 μg/kg/min was effective for 83% of patients.7Vari D. Xiao W. Behere S. et al.Low-dose prostaglandin E1 is safe and effective for critical congenital heart disease: is it time to revisit the dosing guidelines?.Cardiol Young. 2021; 31: 63-70Crossref Scopus (2) Google Scholar A recent single-centre retrospective cohort study estimated that 11% of patients with coarctation of the aorta had moderate-to-severe dysfunction at diagnosis (defined as an ejection fraction of less than 40%).2McFarland C.A. Truong D.T. Pinto N.M. et al.Implications of left ventricular dysfunction at presentation for infants with coarctation of the aorta.Pediatr Cardiol. 2021; 42: 72-77Crossref PubMed Scopus (4) Google Scholar Patients with poor function were found to be older at diagnosis and had increased morbidity with increased length in ventilatory support and intensive care stay when compared with patients without ventricular dysfunction.2McFarland C.A. Truong D.T. Pinto N.M. et al.Implications of left ventricular dysfunction at presentation for infants with coarctation of the aorta.Pediatr Cardiol. 2021; 42: 72-77Crossref PubMed Scopus (4) Google Scholar Although our case illustrates an infant with a significant improvement in function preoperatively, most infants with ventricular dysfunction recover well postoperatively, with full recovery of function reported within as little as 6 days.2McFarland C.A. Truong D.T. Pinto N.M. et al.Implications of left ventricular dysfunction at presentation for infants with coarctation of the aorta.Pediatr Cardiol. 2021; 42: 72-77Crossref PubMed Scopus (4) Google Scholar Cases that continue to have ventricular dysfunction are most often those with significant systemic hypertension before diagnosis or when repair occurs after 4 years of age. Low birth weight and prematurity are also associated with poorer outcomes.2McFarland C.A. Truong D.T. Pinto N.M. et al.Implications of left ventricular dysfunction at presentation for infants with coarctation of the aorta.Pediatr Cardiol. 2021; 42: 72-77Crossref PubMed Scopus (4) Google Scholar In summary, our case highlights the successful use of prostaglandin infusion in a 2-month-old patient with coarctation of the aorta and moderate ventricular dysfunction. This represents the oldest reported case of haemodynamic success with prostaglandin infusion with a significant improvement of ventricular function preoperatively. This supports the use of prostaglandin infusion in relieving obstruction in neonates with coarctation by relaxing ectopic ductal tissue surrounding the isthmus and not just by maintaining DA patency. We show that in our patient this was achieved with low-dose prostaglandin infusion.Novel Teaching Points•Prostaglandin infusion relieved obstruction at the aortic isthmus and led to improved ventricular function in a 2-month-old.•Haemodynamic effects can be achieved with low-dose prostaglandin infusion.