Interrupted Aortic Arch

Interrupted Aortic Arch

INTRODUCTION

Background: Interrupted aortic arch (IAA) is a relatively rare genetic disorder that occurs in association with a usually 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 CHARGE association (coloboma, heart disease, atresia choanae, retarded growth and development and/or CNS anomalies, genital hypoplasia, and ear anomalies and/or deafness). Approximately 50% of IAA patients have DiGeorge syndrome.

Surgical reconstruction of the arch is now considered straightforward; hence, attention is increasingly focused on the preoperative identification and surgical management of the aortic valve and subaortic hypoplasia found in approximately 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

The embryology of this lesion is still unknown. However, approximately half of IAA patients have a deletion of a 1.5-3 Mb region of chromosome band 22q11.2, the most common deletion syndrome in humans. Although 30 genes lie within the 3 Mb deleted region, which ones contribute to the IAA phenotype is not known. In addition, 2 independent lines of evidence suggest that IAA type A is etiologically different from IAA type B (see “Anatomy” 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, while exceedingly few patients with IAA type A have the deletion.

In 1999, Lindsay et al deleted the region of mouse chromosome 16 (Df1), which is homologous to the human chromosome band 22q11.2. Heterozygously Df1-deleted mice display IAA type B, and this phenotype can be rescued by genetic complementation using a chromosome duplicated for Df1. This argues strongly that the Df1/+ phenotype results from haploinsufficiency of gene(s) located within the Df1 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 while 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:

In the US: The incidence is approximately 2 cases per 100,000 live births.

Mortality/Morbidity: Circulatory compromise manifested by metabolic acidosis begins when the ductus arteriosus reduces in caliber, 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 because of both the effect of the 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 as the ductus arteriosus closes. Most patients present in the first day of life.

CLINICAL

History: Symptoms in the neonate include tachypnea, poor feeding, and lethargy.

Physical:

Recognizing 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.

Finally, because approximately 50% of IAA patients have DiGeorge syndrome, facial dysmorphism is frequently present.

Causes: Abnormal cranial neural crest proliferation, migration, survival, or terminal function is hypothesized to be causal. This hypothesis is grounded largely on the basis of ablation studies in the chick and targeted gene disruptions in the mouse. The actual cause of human IAA is unknown, but progress has been made in the understanding of DiGeorge syndrome, which frequently coexists.

Genetic causes

Several single-gene mouse knockouts display IAA as a principal phenotype. Among the genes investigated are the ones encoding the winged helix transcription factors MF-1 and MFH-1 and those encoding components of the endothelin-1/endothelin A receptor-mediated signaling pathway.

Approximately 90% of patients with DiGeorge syndrome have deletions within 22q11. This fact leads to the current model that the syndrome results from haploinsufficiency for a gene or genes mapping to this deleted region.

DIFFERENTIALS

Coarctation of the Aorta
DiGeorge Syndrome
Neonatal Sepsis
Velocardiofacial Syndrome

WORKUP

Lab Studies:

The most helpful blood test is the arterial blood gas (ABG) to confirm the presence of metabolic acidosis.

A serum calcium measurement is occasionally informative because many IAA patients have DiGeorge syndrome, including the hypoparathyroidism phenotype.

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 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 IAA patients is the display 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 are variable.

Cardiothymic silhouette may be normal or increased.

Pulmonary vascularity may be normal or increased.

Other Tests:

Electrocardiography: Common findings include right ventricular hypertrophy and ST-T wave abnormalities. Occasionally, QT prolongation is evident because of DiGeorge syndrome–related hypocalcemia.

Procedures:

Cardiac catheterization

Cardiac catheterization demonstrates the site of arch interruption, the size and anatomic type of ventricular septal defect, and the anatomic severity of subaortic hypoplasia.

Cardiac catheterization also displays whether the right subclavian artery is aberrant.

TREATMENT

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 introduction of 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 exists, the infundibular septum is not only misplaced, but also frequently hypoplastic. Hence, significant subaortic narrowing is difficult to ameliorate with mere resection of infundibular septal muscle. Two alternative approaches have been adopted: the Ross-Konno operation and the Norwood-Rastelli operation. In the former, the aortic outflow region is directly enlarged and the aortic valve is replaced with a pulmonary valve autograft. In the latter, an interventricular baffle allows left ventricular blood to reach not only the aortic outflow but also the pulmonary annulus, and the main pulmonary artery is transected. The proximal portion is anastomosed to the ascending aorta while the distal portion is connected to the right ventricle via a conduit.

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.

MEDICATION

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) -- 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.
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
Contraindications Respiratory distress syndrome; persistent fetal circulation
Interactions Coadministration with heparin may increase aPTT
Pregnancy X - Contraindicated in pregnancy
Precautions May cause apnea, seizures, fever, hypotension, pulmonary overcirculation, or inhibition of platelet aggregation; use cautiously in neonates with bleeding tendencies

FOLLOW-UP

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 IV 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, the prognosis is excellent.

MISCELLANEOUS

Medical/Legal Pitfalls:

Failure to recognize symptoms and signs of IAA

Failure to recognize inadequately relieved subaortic stenosis, aortic stenosis, or both

PICTURES

Caption: Picture 1. Interrupted aortic arch. 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.

Picture Type: Image

Caption: Picture 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.

Picture Type: Image

Caption: Picture 3. Interrupted aortic arch. This is the suprasternal sagittal ultrasonographic view of the patient shown in Image 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.

Picture Type: Image