eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Cardiology
Interrupted Aortic Arch
Updated: Oct 6, 2009
Introduction
Background
Interrupted aortic arch (IAA) is a relatively rare genetic disorder that usually occurs in association with a nonrestrictive ventricular septal defect (VSD) and ductus arteriosus or, less commonly, with a large aortopulmonary window or truncus arteriosus.1 Although most cases occur in normally connected great arteries, interrupted aortic arch can coexist with any ventriculoarterial alignment and also with severe underdevelopment of one ventricle. The rare cases that involved interrupted aortic arch, aortic valve atresia, and VSD have been complex; two have presented with circle of Willis–dependent coronary blood flow,2,3 and two have presented with bilateral ductus in which coronary blood flow depended on the patency of the right ductus arteriosus.4,5
Interrupted aortic arch 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 8q12.1.6 Approximately 50% of patients with interrupted aortic arch have DiGeorge syndrome; in these cases, the interrupted aortic arch is usually type B, although cases of type A or type C have also been reported.
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. Interrupted aortic arch 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 interrupted aortic arch have a hemizygous deletion of a 1.5-3 Mb region of chromosome band 22q11.2,7,8 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 the etiology of many cases of interrupted aortic arch type A is different from the etiology of interrupted aortic arch type B (see below for definition of types). The variety of associated VSDs is different in the 2 types of interrupted aortic arch.9 The prevalence of 22q11.2 hemizygosity is also different; approximately three fourths of patients with interrupted aortic arch type B have the deletion, whereas exceedingly few patients with interrupted aortic arch type A have the deletion.
Anatomy
Interrupted aortic arch 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).10 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.
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.
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.
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.
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 VSD. 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 interrupted aortic arch present in the first 2 weeks of life when the ductus arteriosus closes. Most patients present in the first day of life.
Clinical
History
- Symptoms of interrupted aortic arch (IAA) in the neonate include tachypnea, poor feeding, and lethargy.
Physical
- Recognizing interrupted aortic arch 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 interrupted aortic arch 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 interrupted aortic arch have DiGeorge syndrome.
Causes
Abnormalities in any of the cell types involved in formation or patterning the pharyngeal arch arteries (ie, pharyngeal endoderm,11 pharyngeal mesoderm, endothelium, neural crest) can produce interrupted aortic arch. For example, Tbx1 has a cell-autonomous function in the pharyngeal mesoderm.12
More than 25 single-gene mouse knockouts display interrupted aortic arch as a principal phenotype. Mouse mutants displaying interrupted aortic arch are as follows:
- Foxc113,14
- Foxc2
- Tbx115,16,17
- Fgf8 hypomorph
- Sema3C18,19
- Nrp1
- VEGF-A ( knockout of 164 isoform)
- Cited 2
- Crkl
- ET-120
- ETA
- ECE-1
- FLNA
- Zic3
- Dnahc5
- MRTF-B
- Sox4
- AP2α
- Neural crest–specific knockout of GATA621
- Gbx2
- Ltbp1L
- TGFβ2
- TGFβRII
- Bmp4
- RXR
- RAR
Although most of these mouse mutants display interrupted aortic arch type B, at least 2 (Ltbp1L22 and the myocardin-related transcriptional coactivator Mrtf-B23 ) can also display interrupted aortic arch type C. Approximately 90% of patients with DiGeorge syndrome have deletions within 22q11, which includes Tbx1. Rarely, individuals with DiGeorge syndrome have point mutations in Tbx1.24 Patients with DiGeorge syndrome usually have interrupted aortic arch type B, but examples of type A and type C have been reported. Polymorphisms in 5,10 methylenetetrahydrofolate reductase (MTHFR)25 and hemizygous deletion of chromosome 1q21.126 can be associated with interrupted aortic arch type A.
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| References |
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Further Reading
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, subaortic stenosis, treatment, diagnosis
