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AUTHOR AND EDITOR INFORMATION
Section 1 of 11  
Author: Alvin J Chin, MD, Professor of Pediatrics, Division of Cardiology, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine
Alvin J Chin is a member of the following medical societies: American Association for the Advancement of Science and American Heart Association
Editors: Charles Berul, MD, Assistant Professor, Department of Pediatrics, Harvard Medical School; Senior Associate, Department of Cardiology, Children's Hospital of Boston; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Ameeta Martin, MD, Associate Professor, Department of Pediatrics, Section of Pediatric Cardiology, University of Nebraska College of Medicine; Gilbert Herzberg, MD, Assistant Professor, Department of Pediatrics, Section of Pediatric Cardiology, New York Medical College; Steven Neish, MD, Director of Pediatric Cardiology Fellowship Program, Department of Pediatrics, Baylor College of Medicine; Clinical Director of Pediatric Cardiology, Texas Children's Heart Center; Director, Brown Foundation Heart Clinic, Texas Children's Hospital
Author and Editor Disclosure
Synonyms and related keywords:
interrupted aortic arch, IAA, IAA type A, IAA type B, IAA type C, interrupted left aortic arch, nonrestrictive ventricular septal defect, ductus arteriosus, large aortopulmonary window, truncus arteriosus, CHARGE syndrome, coloboma, heart disease, atresia choanae, retarded growth and development, CNS anomalies, genital hypoplasia, deafness, ear anomalies, DiGeorge syndrome, aortic valve and subaortic stenosis
Background
Interrupted aortic arch (IAA) is a relatively rare genetic disorder that usually occurs in association with a nonrestrictive ventricular septal defect and ductus arteriosus or, less commonly, with a large aortopulmonary window or truncus arteriosus. Although most cases occur in normally connected great arteries, IAA can coexist with any ventriculoarterial alignment and also with single ventricle. IAA and complete common atrioventricular canal can be observed in the context of coloboma, heart disease, atresia choanae, retarded growth and development and/or CNS anomalies, genital hypoplasia, and ear anomalies and/or deafness (CHARGE) syndrome, which is usually caused by mutations in CHD7 on chromosome 8q12.1. Approximately 50% of patients with IAA have DiGeorge syndrome. Surgical reconstruction of the arch is now relatively straightforward; hence, attention is increasingly focused on the preoperative identification and surgical management of the aortic valve and subaortic stenosis found in approximately one half of cases. IAA is the first cardiovascular pattern formation anomaly to be demonstrated to have a genetic basis in both mouse and human. Embryology Approximately one half of patients with IAA have a deletion of a 1.5-3 Mb region of chromosome band 22q11.2, the most common deletion syndrome in humans. Among the 30 genes deleted, the T-box gene TBX1 appears to be responsible for most aspects of the DiGeorge phenotype. In addition, 2 independent lines of evidence suggest that IAA type A is etiologically different from IAA type B (see Anatomy below for definition of types). The variety of associated ventricular septal defects is different in the 2 types. The prevalence of 22q11.2 hemizygosity is also different; approximately three fourths of patients with IAA type B have the deletion, whereas exceedingly few patients with IAA type A have the deletion. Anatomy IAA has been classified into 3 types (A, B, and C) based on the site of aortic interruption. In type A interrupted left aortic arch, the arch interruption occurs distal to the origin of the left subclavian artery. In type B interrupted left aortic arch, the interruption occurs distal to the origin of the left common carotid artery. In type C interrupted left aortic arch, the interruption occurs proximal to the origin of the left common carotid artery. In any of the 3 types, the right subclavian artery may arise normally or abnormally; the 2 most common abnormal sites are distal to the left subclavian artery (aberrant right subclavian artery) and from a right ductus arteriosus (isolated right subclavian artery). Type B interruptions account for about two thirds of cases, type A occur in about one third of cases, and type C are present in less than 1% of cases.
Pathophysiology
During fetal development, left ventricular output supplies the arterial circulation proximal to the interruption whereas right ventricular output supplies arterial circulation distal to the interruption via the left ductus arteriosus. Postnatally, this arrangement continues, with the addition of the pulmonary blood flow to the load of the left ventricle.
Frequency
United States
The incidence is approximately 2 cases per 100,000 live births.
Mortality/Morbidity
Circulatory compromise manifested by metabolic acidosis begins when the ductus arteriosus constricts, thus decreasing flow to the circulation distal to the arch interruption. Prior to this, even severe aortic and subaortic hypoplasia is physiologically masked because of the presence of the ventricular septal defect. Patients are at risk for severe low output syndrome (ie, cardiogenic shock) because of both the effect of profound metabolic acidosis on cardiac performance and the reduced distal systemic arterial circulation imposed by falling pulmonary vascular resistance.
Age
Nearly all patients with IAA present in the first 2 weeks of life when the ductus arteriosus closes. Most patients present in the first day of life.
History
Symptoms in the neonate include tachypnea, poor feeding, and lethargy.
Physical
- Recognizing interrupted aortic arch (IAA) is difficult prior to reduction in the caliber of the ductus arteriosus. The hallmark thereafter is a mottled or grey appearance to the lower body, representing poor perfusion to that portion of the circulation located distal to the arch interruption.
- A difference in systolic blood pressure between the right arm and the lower extremities may or may not be present. Frequently, a lack of discrepancy in blood pressure is due to the profound reduction in cardiac performance. If the right subclavian artery is aberrant, no disparity occurs between the systolic blood pressure in the right arm and that in the lower extremities because the right subclavian origin is distal to the arch interruption.
- Although a difference in oxygen saturation between the right arm and the lower body may occur in cases without an aberrant right subclavian artery, this can be quite subtle in cases of high pulmonary blood flow. In normally connected great arteries, the oxygen saturation is higher in the right arm than in the lower body. In IAA with transposition of the great arteries, the reverse occurs.
- The first heart sound is normal. The second heart sound is usually single.
- A grade 2 or grade 3 systolic ejection murmur is usually present at the base, representing pulmonary blood flow. The mid diastolic rumble of flow-related mitral stenosis is uncommonly heard in neonates.
- The liver is usually normal in size, but in neonates, this is principally a reflection of intravascular volume status.
- Facial dysmorphism is frequently present because approximately 50% of patients with IAA have DiGeorge syndrome.
Causes
Abnormalities in any of the cell types involved in formation or patterning the pharyngeal arch arteries (ie, pharyngeal endoderm, pharyngeal mesoderm, endothelium, neural crest) can produce IAA. For example, TBX1 has a cell-autonomous function in the pharyngeal mesoderm. Several single-gene mouse knockouts display IAA as a principal phenotype. Among these are global nulls in TBX1, in the winged-helix transcription factors FOXC1 (formerly known as MF-1) and FOXC2 (formerly known as MFH1), in the secreted protein semaphorin 3C, in the myocardin-related transcriptional coactivator MRTF-B, and in the genes that encode components of the endothelin-1/endothelin A receptor-mediated signaling pathway.1 Patients with the neural crest–specific GATA6 mutation also display IAA type B. Approximately 90% of patients with DiGeorge syndrome have deletions within 22q11, which includes TBX1. Rarely, individuals with DiGeorge syndrome have point mutations in TBX1.
Coarctation of the Aorta
DiGeorge Syndrome
Neonatal Sepsis
Velocardiofacial Syndrome
Lab Studies
- The most helpful blood test is the ABG to confirm the presence of metabolic acidosis.
- A serum calcium measurement is occasionally informative because many patients with interrupted aortic arch (IAA) have DiGeorge syndrome, including the hypoparathyroidism phenotype.
- Fluorescent in situ hybridization (FISH) can reveal the typical 22q11.2 deletion seen in 85-90% of patients with DiGeorge syndrome.
Imaging Studies
- Two-dimensional echocardiography and Doppler analysis
- Two-dimensional echocardiography is diagnostic for IAA. In addition, it can usually provide at least indirect evidence for the presence or absence of aberrant right subclavian artery. Occasionally, the presence of an isolated right subclavian artery can be detected. A suprasternal frontal sweep followed by left oblique and sagittal cuts is recommended.
- Color-flow Doppler analysis may assist in the ultrasonographic tracing of such vessels by rapidly distinguishing them from venous structures. Furthermore, in the patient whose ductus arteriosus has markedly reduced in size, 2-dimensional and Doppler analysis can be used to monitor the effect of exogenous prostaglandin E1 on this structure.
- The size and anatomic type of the ventricular septal defect can also be identified. In the setting of a large ventricular septal defect, additional small ventricular septal defects can be missed, just as with cardiac catheterization. The most important contribution of 2-dimensional echocardiography to the preoperative characterization of patients with IAA is the display of the aortic outflow region. The presence of thymus can be ascertained as well.
- Echocardiography also demonstrates the site of arch interruption, the size and anatomic type of the ventricular septal defect, the morphology of the aortic valve, and the anatomic severity of subaortic hypoplasia. Aortic valve and subaortic abnormalities are present in 50-80% of patients with IAA.
- Chest radiography
- Findings on chest radiography vary.
- Cardiothymic silhouette may be normal or increased. Patients with DiGeorge syndrome may have an absent thymus.
- Pulmonary vascularity may be normal or increased.
Other Tests
Common electrocardiography findings include right ventricular hypertrophy and ST-T wave abnormalities. Occasionally, QT prolongation is evident because of DiGeorge syndrome–related hypocalcemia.
Procedures
Cardiac catheterization reveals the site of arch interruption, the size and anatomic type of ventricular septal defect, and the anatomic severity of subaortic hypoplasia. Cardiac catheterization also reveals whether the right subclavian artery is aberrant.
Medical Care
Evaluation as an inpatient in an intensive care setting is advised. Intravenous prostaglandin E1 is indicated promptly to maintain patency of the ductus arteriosus. The need for an arterial line and assisted ventilation can be judged best from the initial ABG measurement.
Surgical Care
- The arch interruption itself is usually treated with side-to-side anastomosis, rather than with conduit interposition. If the subaortic region is of good size, the ventricular septal defect is usually closed with a patch at the same occasion.
- When a malalignment-type ventricular septal defect is present, the infundibular septum is not only misplaced but is also frequently hypoplastic. Hence, significant subaortic narrowing is frequently difficult to ameliorate with mere resection of infundibular septal muscle.
- Two alternative approaches have been adopted: the Ross-Konno procedure and the Norwood-Rastelli procedure.
- In the Ross-Konno procedure, the aortic outflow region is directly enlarged (Konno) and the aortic valve is replaced with a pulmonary valve autograft (Ross).2 The coronary arterial ostia must be relocated to the autograft, and some sort of right ventricle–to–main pulmonary artery conduit is interposed (Ross). One relative contraindication to the Ross-Konno procedure is an unfavorable coronary artery pattern because this may well limit the efficacy of the Konno procedure.
- In the Norwood-Rastelli procedure, an interventricular baffle allows left ventricular blood to reach not only the aortic outflow but also the pulmonary annulus (Rastelli), and the main pulmonary artery is transected.3 The proximal portion is anastomosed to the ascending aorta (Norwood) while the distal portion is connected to the right ventricle via a conduit (Rastelli).
Consultations
- Cardiothoracic surgeon
- Cardiologist
- Geneticist
Diet
No special diet is required.
Activity
No exercise restrictions are necessary in later childhood if coexistent subaortic (and/or aortic) hypoplasia has been sufficiently relieved in earlier childhood.
Preoperatively, administer alprostadil (IV prostaglandin E1). No special medications are required postoperatively.
Drug Category: Prostaglandins
Alprostadil (PGE1) is used for treatment of ductal dependent cyanotic congenital heart disease, which is due to decreased pulmonary blood flow.
| Drug Name | Alprostadil (Prostin VR) |
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| Description | Used to maintain patency of the ductus arteriosus in neonates with ductal-dependent congenital heart disease until surgery can be performed. Has direct vasodilatation action on the ductus arteriosus and vascular smooth muscle. |
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| Pediatric Dose | Initial infusion: 0.05-0.1 mcg/kg/min IV
Maintenance infusion: 0.01-0.4 mcg/kg/min IV, titrate to the lowest effective dose
Usual maintenance dose: 0.1 mcg/kg/min IV, but reducing the dosage by 50-90% is often possible |
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| Contraindications | Respiratory distress syndrome; persistent fetal circulation |
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| Interactions | Coadministration with heparin may increase aPTT |
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| Pregnancy | X - Contraindicated; benefit does not outweigh risk
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| Precautions | May cause apnea, seizures, fever, hypotension, pulmonary overcirculation, or inhibition of platelet aggregation; use cautiously in neonates with bleeding tendencies |
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Further Inpatient Care
- Admit for diagnostic testing and surgical intervention.
Further Outpatient Care
- Following surgical reconstruction, echocardiographic and Doppler evaluation of the adequacy of the repair should be performed.
In/Out Patient Meds
- Inpatient medication may require a preoperative administration of intravenous prostaglandin E1 (0.1 mcg/kg/min).
- No special medications are required postoperatively.
Transfer
- Transfer may be required for further diagnostic evaluation and surgical intervention.
Complications
- Persistent subaortic and aortic stenosis
- Residual ventricular septal defect
- Narrowing at the site of arch surgery
Prognosis
- In most cases, with good surgical repair, the prognosis is excellent.
Medical/Legal Pitfalls
- Failure to recognize symptoms and signs of interrupted aortic arch (IAA)
- Failure to recognize inadequately relieved subaortic stenosis, aortic stenosis, or both
| Media file 1:
Sections A, B, and C show successive views during a suprasternal frontal ultrasonographic sweep of the superior mediastinum in a healthy patient. In a left aortic arch, the first brachiocephalic vessel (A) courses to the right (B) and bifurcates (C). Section D shows the left anterior oblique view of an aortogram in a patient with coarctation (thick arrow). Section E is the echocardiographic left oblique equivalent view of a normal aortic arch. Abbreviations are as follows: a = aorta, ao = aorta, ASC = ascending aorta, i = innominate vein, inn a = innominate artery, LC = left common carotid artery, LS = left subclavian artery, RCCA = right common carotid artery, RSCA = right subclavian artery, s = superior vena cava, v = vertebral artery. |
 |  View Full Size Image | |
Media type: Ultrasound
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| Media file 2:
Section A depicts a subcostal frontal echocardiogram of interrupted aortic arch (IAA) type B with transposition of the great arteries. Section B shows a high parasternal echocardiogram showing that the innominate artery (Inn A) and left common carotid artery (LCCA) arise from the ascending aorta (a ao). In section C, the left subclavian artery (LSCA) arises from the descending aorta (desc ao), which is perfused by the ductus arteriosus. |
 | View Full Size Image | |
Media type: Echo
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| Media file 3:
This is the suprasternal sagittal ultrasonographic view of the patient shown in Media file 2. Arch continuity has now been restored by a side-to-side anastomosis. Abbreviations are as follows: a ao = ascending aorta and desc ao = descending aorta. |
 | View Full Size Image | |
Media type: Ultrasound
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Interrupted Aortic Arch excerpt Article Last Updated: Oct 2, 2007
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