A 6-day-old female presents to the emergency department (ED) floppy with agonal respirations, poor capillary refill, and absent femoral pulses. The patient was born full-term at another hospital via elective repeat cesarean section. The pregnancy and delivery were uncomplicated, and the patient was discharged home with her mother from the hospital. The patient was tolerating 2 ounces of formula every 2 hours without any difficulty and visited her pediatrician for an initial visit the day of presentation. Her mother had concerns about rapid breathing, but the pediatrician reported that her evaluation was within normal limits. That afternoon, the patient became increasingly fussy and was refusing feeds. She began to “gasp” and appeared pale to her parents. Emergency medical services was called and the patient was transported to the ED for evaluation.
In the ED, the patient was gray, floppy with agonal respirations, and had an oxygen saturation of 70% on pulse oximetry with hepatomegaly on physical examination. The patient was intubated; sepsis protocol was initiated, including blood culture and urine cultures, as well as administration of ceftazidime and vancomycin. Isotonic intravenous (IV) fluid boluses were given for resuscitation with no significant response in blood pressure or heart rate. The chest radiograph revealed cardiomegaly and hepatomegaly (Figure 1). Exam was notable for palpable brachial pulses but absent femoral pulses bilaterally. Given these findings and the patient’s age, ductal dependent congenital heart disease was suspected and prostaglandin E1 (PGE1) was ordered. The patient was transferred to the pediatric intensive care unit (PICU) for further management.
Patient’s initial chest and abdominal radiograph. Presence of cardiomegaly and hepatomegaly are notable.
Images courtesy of Jarrett Linder, MS, MD.
Interrupted Aortic Arch
In the PICU, bedside echocardiogram revealed interrupted aortic arch (IAA), ventricular septal defect (VSD), minimal flow through a thread-like ductus arteriosus, and severely depressed cardiac function (Figure 2). Closure of her ductus arteriosus significantly reduced her systemic blood flow other than to her carotid arteries, resulting in fulminant cardiogenic shock. While awaiting PGE1, which would re-open the ductus arteriosus, the patient experienced a bradycardic arrest and received resuscitation with chest compressions, IV epinephrine, sodium bicarbonate, and calcium administration. PGE1 was started and titrated to therapeutic doses. She had return of spontaneous circulation 20 minutes after initial resuscitation efforts. The patient was continued on epinephrine and dopamine infusions. Her blood pressure improved, and milrinone was added due to continued depressed cardiac function. Her initial laboratory results post-arrest showed lactate levels greater than 20 mg/dL; her liver function tests (LFTs) were elevated to AST 115 IU; ALT 124 IU, with indications of coagulopathy (INR 3.5, PT 33.5 seconds, PTT 195.6 seconds); and acute renal failure (BUN 39 mg/dL, Cr 2.2 mg/dL), all due to cardiogenic shock.
Echocardiogram still image from a study performed soon after presentation. Subcostal view of the right ventricular outflow tract. Blood travels across the pulmonary valve (red arrow) to the main pulmonary artery, then across the very small patent ductus arteriosus (diameter demonstrated with green arrows) to the descending aorta. There is no superior segment of the descending aorta, which confirms the diagnosis of interrupted aortic arch.
Her post-arrest stabilization continued for several days. She had positive blood cultures with methicillin-resistant Staphylococcus aureus (MRSA), thought to be related to emergent line placement and intraosseous access to provide medications during the resuscitation. She received a prolonged antibiotic course prior to repair. Her elevated LFTs, coagulopathy, and acute renal failure resolved over the next 3 weeks with supportive care and maintenance of ductal patency with PGE1.
Follow-up echocardiogram confirmed the diagnosis of IAA type B with anterior malalignment VSD and hypoplastic aortic valve with hypoplastic left ventricular outflow tract. Serial echocardiograms followed the ductal shunt. The initial bidirectional shunt eventually became purely right-to-left, preserving systemic blood flow, as her cardiac function improved and pulmonary and systemic vascular resistance became physiologic. She remained intubated with a continuous PGE1 infusion during this stabilization course and for surgical preparation.
On day 25 after birth, the patient underwent surgical palliation with primary anastomosis of the aortic arch segments, PDA ligation, and VSD closure. This resulted in normal circulation with separate blood flow to the lungs and the body. She was observed postoperatively for arrhythmia, typical for most congenital heart surgeries. Additionally, her liver and renal function were closely monitored due to her history of multisystem injury on presentation.
Revisiting Ductal-Dependent Lesions
The ductus arteriosus is a normal structure in all fetal hearts. In utero, the ductus arteriosus remains patent due to low fetal oxygen tension as well as the presence of arachidonic acid metabolites including prostaglandin (PGE2) and prostacyclin (PGI2) produced by the placenta. These metabolites are produced locally and act upon prostanoid receptors, causing ductus arteriosus vasodilation. Ductal patency allows oxygen-rich placental blood to bypass the pulmonary circulation and shunt right-to-left to fetal systemic circulation. Initial breaths after delivery cause an increase in pulmonary oxygen tension and depolarization of the smooth muscle intima within the ductus arteriosus, resulting in contraction. Additionally, a decrease in circulating PGE2 and PGI2 due to placental detachment results in a decrease of the vasodilatory effects on the ductus arteriosus smooth muscle. Functional closure occurs within 24 to 48 hours of birth. Anatomical closure occurs within 2 to 3 weeks, where fibrosis occurs and results in an irreversible closure.1
Critical congenital heart disease (CCHD) is defined as a ductal-dependent congenital heart defect requiring surgical or percutaneous intervention via cardiac catheterization before 1 year of age. CCHD occurs in 25% of all congenital heart disease cases. Most cases of CCHD can be diagnosed with prenatal ultrasound or fetal echocardiogram. If not prenatally diagnosed, CCHD can be stable in the newborn nursery due to persistent ductal patency, and the patient may only be diagnosed after discharge, ductal closure, and development of cardiac symptoms at home.2
Ductal-dependent lesions can be classified into two categories: ductal-dependent systemic circulation (limits to venous return to or outflow from the left side of the heart, resulting in right-to-left flow across the ductus to provide systemic perfusion, but with cyanotic blood) or ductal-dependent pulmonary circulation (limits to pulmonary blood flow, requiring left-to-right ductal shunting, which preserves lung perfusion and oxygenation, but at the expense of systemic blood flow). Table 1 provides a differential diagnosis for ductal-dependent lesions.2
Differential Diagnosis for Ductal-Dependent Congenital Heart Disease
Signs and symptoms of CCHD can be subtle prior to complete ductal closure. Diagnosis requires an astute physician who can recognize the at-risk infant.2
Diagnostic evaluation of dyspnea, poor feeding, and poor perfusion should include consideration of cardiac causes. Exam findings consistent with CCHD include differential pulses between right and left arms, or between the upper and lower extremities. Further investigations include pulse oximetry and hyperoxia testing. The latter is performed by obtaining an arterial blood gas at baseline and after administration of 100% supplemental oxygen. An arterial oxygen partial pressure less than 220 mm Hg warrants further evaluation, and a value of less than 100 mm Hg is strongly suggestive of cyanotic congenital heart disease (CHD).2 Chest radiographs can be utilized to evaluate for pulmonary over-circulation, as well as cardiomegaly and will frequently show evidence of hepatomegaly. Certain patterns of cardiac silhouetting may be supportive of specific CHD diagnoses, including the “boot-shaped heart” pattern of tetralogy of fallot, the “egg-on-a-string pattern” seen in transposition of the great arteries, or the “snowman” appearance of total anomalous pulmonary venous return.
Due to the potential for significant morbidity and mortality with late diagnosis of CCHD, referral for urgent echocardiogram and cardiology consultation is necessary with the slightest suggestion of CHD. Echocardiography is noninvasive and rapidly provides diagnostic information.2
Pulse Oximetry in the Nursery
Prior to the introduction of pulse oximetry screening as part of routine newborn care before nursery discharge, 25% of all CCHD cases were discharged from the hospital undetected.3 Delayed diagnosis is related to multiple morbidities, including adverse neurodevelopmental outcomes such as issues with motor function, speech and language development, and executive function. Delayed diagnosis is also related to increased mortality in this patient population.4 To reduce the volume of undiagnosed CCHD in the immediate newborn period, the U.S. Department of Health and Human Services Secretary’s Advisory Committee on Heritable Diseases in Newborns and Children (SACHDNC) recommended that CCHD screening via pulse oximetry be added to the recommended uniform screening panel. The screening recommendations have been endorsed by the March of Dimes, the American Association of Pediatrics, and the American Heart Association.4 Several states have mandated pulse oximetry screening prior to discharge from the newborn nursery.
The current recommendations for a standardized approach toward pulse oximetry screening of CCHD include the following:
- Pre-ductal measurement of oxygen saturation in the right hand.
- Post-ductal measurement of oxygen saturation in either foot.
- Measurements should be obtained after 24 hours of life.
- A positive screen is detected if any measurement is less than 90%; if both pre- and post-ductal saturations are less than 95%; or if there is a greater than 3% difference between the pre- and post-ductal saturations for three separate measurements occurring at least 1 hour apart from one another.
A positive screen results in an immediate referral for an echocardiogram, preferably performed by a pediatric echocardiographic technician and read by a pediatric cardiologist.4
There are seven primary lesions targeted by CCHD screening: hypoplastic left heart syndrome, pulmonary atresia, tetralogy of fallot, total anomalous pulmonary venous return, transposition of the great arteries, tricuspid atresia, and truncus arteriosus. These lesions are the most common types of congenital heart diseases associated with cyanosis and have viable surgical palliation that can be lifesaving in the neonatal period.5 Though not directly targeted by the published recommendations, rarer cyanotic lesions such as critical aortic stenosis, coarctation of the aorta, interrupted aortic arch, and Ebstein’s anomaly can also be detected with neonatal pulse oximetry screening.4 IAA is only picked up by CCHD screening in about 50% of cases, and these children are at risk for delayed diagnosis.4
Interrupted Aortic Arch
IAA results from posterior malalignment of the basilar portion of the ventricular septum in the embryonic heart. This results in a ventricular septal defect, displacement, and hypoplasia of the aortic valve, and diminished flow into the ascending aorta. There is progressive abnormal development of a continuous intimal lining in the aortic arch, which results in interruption. The ascending aorta is often hypoplastic, whereas there is independent development of a separate descending component of the arch arising from the ductus arteriosus.5 This interruption can arise in different locations relative to the branching of the left subclavian, left carotid, and innominate arteries, classified as types A, B, and C. In type A, the interruption occurs distal to the left subclavian artery. In type B, the interruption occurs between the left common carotid and the left subclavian arteries. In type C, the interruption occurs between the innominate artery and the left carotid artery.6 Type B is the most common and is associated with 22q11 deletion in up to 75% of cases. Figure 3 provides a pictorial depiction of the classification schema of IAA.
Classification system of interrupted aortic arch. Type A occurs distal to the left subclavian artery. Type B occurs between the left common carotid and the left subclavian arteries. Type C occurs between the innominate artery and the left carotid artery. Ao = ascending aorta; LPA = left pulmonary artery; MPA = main pulmonary artery; PDA = patent ductus arteriosus; RCC = right common carotid artery; RPA = right pulmonary artery; RS = right subclavian artery. The innominate artery or the right brachiocephalic artery is the first branch of the aortic arch and divides into the RS and the RCC.
IAA is very rare, with an incidence of three cases per 1 million live births. Patients require neonatal supportive care, continuous PGE1 infusion, and urgent referral for neonatal surgical repair in the first days to weeks of life, depending on presentation. Mortality is 90% if untreated, with rare cases of persistent ductal patency or unusual arch anatomy reported.5 Repair involves reanastomosis of the discontinuous aortic arch segments, closure of the ventricular septal defect, and ligation of the patent ductus arteriosus. Repair becomes much more complicated in cases of significant hypoplasia of the aortic valve and/or ascending aorta, in which case the main pulmonary artery is used to augment the aorta, and an exogenous conduit is used to direct blood from the right ventricle to the pulmonary arteries.
The delayed diagnosis in this case resulted in our patient’s presentation in fulminant cardiogenic shock with multisystem organ failure. She required extensive stabilization and supportive care prior to surgical repair. Fetal diagnosis, newborn screening, and/or careful clinical examination may have resulted in detection of IAA in our patient prior to ductal closure. PGE1 is a lifesaving medication in ductal-dependent cardiac lesions and should be started immediately when a ductal-dependent lesion is a suspected diagnosis. Although rare, CHD is the most common congenital defect and can be detected and effectively treated.
- Schneider DJ, Moore JW. Patent ductus arteriosus. Circulation. 2006;114(17):1873–1882. doi:10.1161/CIRCULATIONAHA.105.592063 [CrossRef]
- Yun SW. Congenital heart disease in the newborn requiring early intervention. Korean J Pediatr. 2011;54(5):183–191. doi:10.3345/kjp.2011.54.5.183 [CrossRef]
- Bradshaw EA, Martin GR. Screening for critical congenital heart disease: advancing detection in the newborn. Curr Opin Pediatr. 2012;24(5):603–608. doi:10.1097/MOP.0b013e328357a843 [CrossRef]
- Mahle WT, Newburger JW, Matherne GP, et al. Role of pulse oximetry in examining newborns for congenital heart disease: a scientific statement from the American Heart Association and American Academy of Pediatrics. Circulation. 2009;120(5):447–458. doi:10.1161/CIRCULATIONAHA.109.192576 [CrossRef]
- Akdemir R, Ozhan H, Erbilen E, et al. Isolated interrupted aortic arch: a case report and review of the literature. Int J Cardiovasc Imaging. 2004;20(5):389–392. doi:10.1023/B:CAIM.0000041940.14780.1c [CrossRef]
- Axt-Fliedner R, Kawecki A, Enzensberger C, et al. Fetal and neonatal diagnosis of interrupted aortic arch: associations and outcomes. Fetal Diagn Ther. 2011;30(4):299–305. doi:10.1159/000332982 [CrossRef]
Differential Diagnosis for Ductal-Dependent Congenital Heart Disease*
|Left-Sided Obstruction (Systemic Circulation Impaired)
||Right-Sided Obstruction (Pulmonary Circulation Impaired)
|Hypoplastic left heart syndrome
||Tetralogy of fallot with pulmonary atresia
|Critical aortic stenosis
|Coarctation of the aorta
||Critical pulmonary stenosis
|Interrupted aortic arch
||Severe Ebstein’s anomaly
||Complete transposition of the great arteries with intact interventricular septum