Inadvertent irreversible closure of arterial duct following therapeutic use of transplacental indomethacin in a fetus with severe Ebstein's anomaly and circular shunt.

We report on a fetal case of Ebstein's anomaly with severe tricuspid regurgitation, functional pulmonary atresia and progressive circular shunting (CS) across a widely patent ductus arteriosus (DA) and regurgitant pulmonary valve, contributing to significant systemic hypoperfusion. To mitigate the extent of CS and allow the pregnancy to continue, maternal non-steroidal anti-inflammatory drug (NSAID) therapy with indomethacin was started at 33 + 5 weeks to induce DA constriction. Rather than achieving the desired narrowing of the DA, the treatment led to its complete closure and only minimal antegrade flow across the pulmonary valve. While closure of the DA resulted in the anticipated improvement in fetal hemodynamics, at birth, the child was at risk of severe hypoxemia and its consequences due to the lack of adequate pulmonary perfusion. Reduction and eventual discontinuation of the NSAID treatment did not result in DA reopening. Our experience illustrates the risk of unintended irreversible DA closure when NSAIDs are used to treat CS. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Cardiomyopathy presenting prenatally with functional tricuspid and pulmonary atresia.

Cardiomyopathy is a rare diagnosis in the fetus that usually presents as a dilated, poorly functioning ventricle. We present the case of a fetus that developed functional tricuspid and pulmonary atresia due to progressive right ventricular cardiomyopathy. The baby was supported with prostaglandin and inotropic infusions after delivery, eventually weaning off without need for surgical intervention. This case illustrates the prenatal findings that evolved and the successful postnatal management.

Aortopulmonary window with pumonary atresia with ventricular septal defect with D-transposition of great arteries: extremely rare anomaly.

Aortopulmonary window (APW) is rare a congenital heart disease accounting for 0.1%-0.2% of all congenital heart defects. The 35% of the APW has been associated with wide variety of other structural heart diseases such as ventricular septal defect, persistent ductus arteriosus, arch anomalies and coronary artery anomalies. To the best of our knowledge, only six cases of APW with pulmonary atresia with ventricular septal defect has been described in the literature. It resembles the type 1 truncus arteriosus, and differentiation from this condition is important prior to surgical correction. We present a case of 14-year-old girl child; she was diagnosed with APW with pulmonary atresia with ventricular septal defect and D transposition of great arteries with the help of echocardiography, cardiac catheterisation and cardiac CT.

Pulmonary vasodilator therapy in tetralogy of Fallot with pulmonary atresia and major aortopulmonary collaterals: case series and review of literature.

We present the use of pulmonary vasodilators in three adult patients with unrepaired tetralogy of Fallot, pulmonary atresia, aortopulmonary collaterals, and segmental pulmonary arterial hypertension. Patients improved by 1-2 NYHA classes with modest exercise-tolerance increase, and remained stable without side effects during 2.5, 10, and 14 years. Literature review revealed five studies with pulmonary vasodilators in heterogeneous, mostly repaired patient populations.

Transient hypertrophic pyloric stenosis due to prostoglandin infusion.

Prostaglandin E1 (PGE1) is widely used in ductus-dependant congenital heart disease to maintain the patency of ductus. Hypertrophic pyloric stenosis (HPS) due to gastric mucosal proliferation is a rare complication of prolonged PGE infusion. A male newborn who developed HPS during PGE1 infusion is presented to discuss the clinical features and treatment modalities of PGE-related transient HPS. The boy was 2500 g and born at 35 weeks of gestation from a 23-year-old mother. He was admitted to neonatal intensive care with breathing difficulty and cyanosis. His echocardiography revealed pulmonary atresia, ventricular septal defect and major aorta-pulmonary collateral (MAPCA). PGE infusion with a dose of 0.05 mcg kg⁻¹ was initiated. At the 8th day of infusion, he developed non-billous vomiting. Ultrasonographic evaluation revealed 1.9 cm length of pyloric channel and 0.5 cm of wall thickness on 11th day and diagnosed as HPS. On 42th postnatal day, he underwent MAPCA closure, right modified Blalock-Taussi shunt and repair of pulmonary artery bifurcation with bovine patch. PGE infusion was stopped and enteral nutrition was started on 8th postoperative day. Control ultrasonography on 12th postoperative day revealed normal pyloric channel length (0.9 cm) and wall thickness (0.3 cm). Prolonged use of PGE infusion in neonates with congenital heart disease may cause transient HPS. The clinical and radiological features of HPS relieves after stopping PGE infusion. It should be kept in mind that HPS due to PGE infusion can be transient and pyloromyotomy should be kept for patients with persistent findings.

Dexmedetomidine attenuates hypoxemia during palliative reconstruction of the right ventricular outflow tract in pediatric patients.

The objective of this study was to investigate whether the α agonist dexmedetomidine has the ability to attenuate hypoxemia in pediatric patients undergoing palliative pulmonary artery reconstruction.From January 2009 to January 2013, a total of 25 pediatric patients with Tetralogy of Fallot, pulmonary atresia (ventricular septal defect), or persistent truncus arteriosus (I) were enrolled in our study. Due to hypoplastic pulmonary arteries, all patients received palliative pulmonary artery reconstruction. During the perioperative period, they were allocated to receive either dexmedetomidine (bolus dose of 0.3 µg/kg followed by an infusion of 0.2-0.3 µg/kg/h, n = 15) or control drug (n = 10) intravenously. Any desaturation was recorded. Heart rate, mean arterial pressure, pulse oximetry, and arterial blood gas parameters were measured during the perioperative period.There were no significant differences between the groups in hemodynamic variables. The arterial oxygen saturation and arterial blood gas parameters increased in the dexmedetomidine groups (P < 0.05).These findings suggest that the injection of dexmedetomidine can attenuate hypoxemia during palliative pulmonary artery reconstruction in pediatric patients.

Pulmonary artery blood flow patterns in fetuses with pulmonary outflow tract obstruction.

OBJECTIVES: Fetuses with pulmonary outflow tract obstruction (POTO) have altered blood flow to the pulmonary vasculature. We sought to determine whether pulmonary vascular impedance, as assessed by the pulsatility index (PI), is different in fetuses with POTO compared with normal controls. METHODS: Branch pulmonary artery PI was evaluated in age-matched normal control fetuses (n=22) and 20 POTO fetuses (pulmonary stenosis n=15, pulmonary atresia n=5). Pulsed-wave Doppler was performed in the proximal (PA1), mid (PA2) and distal (PA3) branch pulmonary artery. The direction of flow in the ductus arteriosus was noted. The study and control groups were compared with Student's t-test and ANOVA. A linear mixed model evaluated the relationship between PI and ductus arteriosus flow patterns. RESULTS: There was no difference in PI between control, pulmonary stenosis and pulmonary atresia subjects at PA1 and PA2; however, there was a significant difference at PA3. Subjects with pulmonary atresia had a lower PI at PA3 than did controls (P=0.003) and pulmonary stenosis subjects (P=0.003). Subjects with retrograde flow in the ductus arteriosus had lower PIs in PA2 and PA3 than did those with antegrade flow (P=0.01 and 0.005, respectively). The PI in PA3 was lower in fetuses that required prostaglandin postnatally than in those that did not (P=0.008). CONCLUSIONS: Fetuses with pulmonary atresia or severe pulmonary stenosis with retrograde flow in the ductus arteriosus have decreased PI in the distal pulmonary vasculature. Our findings indicate the capacity of the fetal pulmonary vasculature to vasodilate in response to anatomical obstruction of flow.

Prolonged prostaglandin E1 therapy in a neonate with pulmonary atresia and ventricular septal defect and the development of antral foveolar hyperplasia and hypertrophic pyloric stenosis.

Prostaglandin E1 (alprostadil) is widely used for maintaining the patency of ductus arteriosus in ductus-dependent congenital heart defects in neonates to improve oxygenation. Among more common side effects are fever, rash, apnoea, diarrhoea, jitteriness, and flushing. More severe side effects are brown fat necrosis, cortical hyperostosis, and gastric outlet obstruction, most commonly the result of antral foveolar hyperplasia or hypertrophic pyloric stenosis. We report on an infant with a ductus-dependent congenital heart defect who developed symptoms and sonographic evidence of focal foveolar hyperplasia and hypertrophic pyloric stenosis after prolonged treatment with prostaglandin E1. Gastrointestinal symptoms persisted after corrective cardiac surgery, and pyloromyotomy was required. Study of the case and of available literature showed an association between the total dose of prostaglandin E1 administered and duration of treatment and the development of gastric outlet obstruction. We conclude that if patients are treated with a prostaglandin E1 infusion, careful monitoring for symptoms and signs of gastric outlet obstruction is required.

Prostaglandin therapy for ductal patency: how long is too long?

UNLABELLED: The management of neonates born with duct-dependent congenital heart defects in association with prematurity or low birth weight is challenging. We describe two preterm and low birth weight infants with duct-dependent congenital heart disease where cardiac surgery was successfully delayed by maintaining ductal patency using a prolonged prostaglandin infusion. This allowed time for growth and maturation and therefore reduced the risks associated with surgery and cardiopulmonary bypass. CONCLUSION: Maintenance of ductal patency by a prolonged prostaglandin infusion in low birth weight or preterm infants with duct-dependent congenital heart disease is a viable option that allows cardiac surgery to be delayed whilst awaiting further growth and development.

Sildenafil therapy in complex pulmonary atresia with pulmonary arterial hypertension.

BACKGROUND: Complex pulmonary atresia (CPA) i.e. pulmonary atresia with ventricular septal defect and major aorto-pulmonary collaterals (MAPCAs) or Tetralogy of Fallot with MAPCAs frequently have a clinical course complicated by development of pulmonary arterial (PA) hypertension. METHODS: A cross-sectional retrospective review of patients >16 years with CPA or Tetralogy of Fallot with MAPCAs and PA hypertension treated with sildenafil was conducted. Case notes were reviewed for baseline and follow-up (after sildenafil) characteristics. RESULTS: Five patients, 4 female, median age 28 (range 18 to 47) years, were identified. All patients experienced symptomatic improvement: 2 of 4 wheelchair bound patients responded dramatically and walked 345 and 157 m respectively in 6 min following sildenafil therapy. One of the 4 with marked PA arborization abnormalities and severe ventricular dysfunction had initial symptomatic improvement. Another patient improved from walking less 100 m to climbing 2 flights of stairs. Arterial saturations improved in 2 cases from 70 and 60% to 87 and 84% respectively, whilst arterial saturations remained static in 1 case despite embolization of a classical Blalock-Taussig shunt. One patient with PA arborization/diminished PA bed was unable to tolerate sildenafil. CONCLUSIONS: Sildenafil is well tolerated and leads to symptomatic improvement and better saturations in the majority of patients with CPA with PA hypertension when used in isolation or as an adjunct to percutaneous PA angioplasty.

Prolonged treatment with prostaglandin in an infant born with extremely low weight.

We describe an infant with duct-dependent cardiac disease diagnosed prenatally who was born prematurely, and at extremely low weight. Treatment by infusion of prostaglandin maintained ductal patency for 66 days, permitting weight to be gained whilst under the care of a regional unit for neonatal intensive care prior to transfer for palliative cardiac surgery.

The harlequin color change and association with prostaglandin E1.

The harlequin color change is an unusual cutaneous phenomenon observed in newborn infants as transient, benign episodes of a sharply demarcated erythema on half of the infant, with simultaneous contralateral blanching. In this report, two newborns with congenital heart anomalies demonstrated the harlequin color change, one whose skin findings showed a course related to the dose of systemic prostaglandin E1, suggesting a possible association. The benign, self-limited nature of the color change mandates that prostaglandin E1 not be discontinued for this reason. The entity is likely more common than the paucity of reports in the world literature suggests, and all physicians should recognize its graphic appearance to avoid unnecessary exposure to agents in an effort to treat it.

Functional pulmonary atresia in neonatal Marfan's syndrome: successful treatment with inhaled nitric oxide.

Functional pulmonary atresia is characterized by a structurally normal pulmonary valve not opening during right ventricular ejection. We report this rare condition in a premature newborn of a twin pregnancy, in which fetal echocardiography findings were consistent with critical pulmonary stenosis. After birth, features of neonatal Marfan's syndrome were noted. Echocardiography showed a morphologically normal but immobile pulmonary valve with continuous regurgitation. Right ventricular pressure was subsystemic. In this case, initial treatment with nitric oxide, followed by pharmacological duct closure, was successful. Differentiating between anatomic and functional pulmonary valve atresia may be difficult. The echocardiographic criteria are discussed.

The development of hypertrophic pyloric stenosis in a patient with prostaglandin-induced foveolar hyperplasia.

BACKGROUND: Hypertrophic pyloric stenosis (HPS) has been described in association with several obstructive antropyloric lesions including idiopathic foveolar hyperplasia (gastric mucosal hypertrophy), feeding tubes, eosinophilic gastroenteritis, and hypertrophic antral polyps. Non obstructive antral webs have also been described with HPS. PATIENT AND METHODS: We present a case of gastric-outlet obstruction in association with HPS, namely, prostaglandin-induced foveolar hyperplasia. This entity has been previously described, but rarely in association with HPS. We report a female infant requiring prostaglandin therapy for pulmonary atresia who developed dose-related prostaglandin-induced foveolar hyperplasia and symptoms of progressive non-bilious vomiting. RESULTS: Initially, ultrasonography demonstrated evidence of antral mucosal hypertrophy as the cause for gastric-outlet obstruction. The patient subsequently developed progressive thickening of the antropyloric muscle, resulting in sonographic appearances of hypertrophic pyloric stenosis. Pyloromyotomy was eventually required for treatment of HPS. CONCLUSION: A common denominator of most of the above-described entities is thickening and/or hypertrophy of the antral mucosa. We suggest that the antropyloric musculature may hypertrophy in an effort to overcome the gastric-outlet obstruction caused by the adjacent thickened antral mucosa. In other words, these entities may represent examples of "secondary" hypertrophic pyloric stenosis.

Increase in pulmonary arterial diameter under prostaglandin E1 therapy in infants with cyanotic congenital heart disease.

We studied the change in pulmonary arterial diameter under prostaglandin E1 (PGE1) therapy in infants with ductus-dependent cyanotic heart disease (pulmonary atresia). Ten infants undergoing administration of PGE1 for more than 2 weeks were selected for this study. A classic Blalock-Taussig (BT) shunt was performed in seven patients and a modified BT shunt in three. The shunt was successful in all patients. The internal diameters of the right and left pulmonary arteries were measured before and after the start of PGE1 therapy using two-dimensional echocardiography. The pulmonary arterial index (PA index) was calculated to correct the diameters for body surface area. Both pulmonary arteries enlarged during the first week of PGE1 therapy in all 10 patients. Further increases in the two diameters were observed even after the first week of treatment in nine patients. Both the mean diameters at 2 weeks after the start of PGE1 were about 50% larger than the initial diameters (right; increased from 3.1 to 4.7 mm; left; increased from 3.0 to 4. 4 mm). Of the eight patients given PGE1 for more than 3 weeks, four showed no changes in pulmonary arterial diameters after the first 2 weeks and the remaining four showed a slight increase. PA indexes also showed a rapid increase during the first 2 weeks and no significant change thereafter. We suggest that, in infants with pulmonary atresia and small pulmonary arteries, the optimal pulmonary artery size for BT shunt insertion is achieved after 2 weeks of PGE1 infusion, with no further significant increase in size being observed after this time.

Management of functional pulmonary atresia with isoproterenol in a neonate with Ebstein's anomaly.

Ebstein's anomaly is a rare congenital cardiac anomaly showing significant clinical manifestations with a high mortality rate in the neonatal period. The prognosis of the patient is essentially determined by the severity in morphological changes, however, high pulmonary vascular resistance in the neonatal period may aggravate tricuspid regurgitation and lead to functional pulmonary atresia. We describe a critically ill neonate with morphologically mild Ebstein's anomaly who was successfully managed with intensive care including isoproterenol administration for functional pulmonary atresia. Isoproterenol is a potent pulmonary vasodilator with inotropic and chronotropic effects, and seemed to decrease the pulmonary vascular resistance allowing increased antegrade blood flow to the pulmonary artery and improved cardiac output. If tachycardia is not present, isoproterenol administration is recommended in critically ill neonates with anatomically mild Ebstein's anomaly and no associated cardiac defects.

Histologic study of the small pulmonary arteries in 38 patients with pulmonary atresia and intact ventricular septum.

The structure of the small pulmonary arteries was studied during autopsies performed on 38 patients with pulmonary atresia with intact ventricular septum. The thicknesses of the media of these small pulmonary arteries measured using a quantitative morphometric method varied widely. However, there was a notable tendency toward thinning of the media, especially in neonates. In cases in which the patient had undergone prostaglandin E1 treatment, the media was thinner, which suggests that the longer the treatment, the thinner the media. Intimal lesions were observed in 18 of the 38 patients (47%), including 12 of the 22 neonates (55%). Intimal lesions were also found in the patients with thinner media. Based on these results, we propose that organized thrombus formation and intimal proliferation are more likely to develop in patients with reduced pulmonary blood flow, such as in those with pulmonary atresia and intact ventricular septum. In prostaglandin-treated patients, an imbalance between the markedly thinner median muscle and the relatively higher pulmonary blood flow and pressure may contribute to fibrous intimal proliferation. Small pulmonary arteries with a strikingly thinner media may be vulnerable to higher pressure, predisposing the patient to the development of intimal lesions.