Interrupted Aortic Arch

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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, 7] 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. There is considerable phenotypic overlap between CHARGE and DiGeorge syndromes. [8]

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. [9] Interrupted aortic arch is the first cardiovascular pattern formation anomaly to be demonstrated to have a genetic basis in both mouse and human.

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, [10, 11] the most common deletion syndrome in humans. Among the 35-50 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. [12] 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.

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). [13] 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.

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. With naturally occurring ductal closure and/or fall in pulmonary vascular resistance after birth, the circulation to the lower part of the body is compromised, resulting in a shocklike state. 

Abnormalities in any of the cell types involved in formation or patterning the pharyngeal arch arteries (ie, pharyngeal endoderm, [14]  pharyngeal mesoderm, endothelium, neural crest) can produce interrupted aortic arch. For example, Tbx1 has a cell-autonomous function in the pharyngeal mesoderm. [15]

More than 25 single-gene mouse knockouts display interrupted aortic arch as a principal phenotype. Mouse mutants displaying interrupted aortic arch are as follows:

Foxc1  [16, 17]

Foxc2

Tbx1  [18, 19, 20]

Fgf8 hypomorph

Sema3C  [21, 22]

Nrp1

VEGF-A ( knockout of 164 isoform)

Cited 2

Crkl

ET-1  [23]

ETA

ECE-1

FLNA

Zic3

Dnahc5

MRTF-B

Sox4

AP2α

Hoxa1  [24]

Gbx2

Ltbp1L

TGFβ2

TGFβRII

Bmp4

RXR

RAR

Although most of these mouse mutants display interrupted aortic arch type B, at least 2 (Ltbp1L  [25]  and the myocardin-related transcriptional coactivator Mrtf-B  [26]  ) can also display interrupted aortic arch type C.

Additional double knockouts or tissue-specific single-gene knockouts with interrupted aortic arch include Chd7Tbx1 compound heterozygotes, [27] Six1Eya1 double nulls, [28]  second heart field-specific dominant-negative mastermind-like, [29]  neural crest-specific Dicer knockout, [30, 31]  neural crest – specific knockout of GATA6,  [32]  neural crest – specific knockout of Hdac3,  [33] Tbx1 domain-specific knockout of Bmp4, [34]  vascular smooth muscle – specific removal of integrin β 1, [35] α5αv double null, [36]  and Fgf8 hypomorphFgf10 heterozygotes. [37]

Approximately 90% of patients with DiGeorge syndrome have deletions within 22q11, which includes TBX1. Rarely, individuals with DiGeorge syndrome have point mutations in TBX1.  [38]  Patients with DiGeorge syndrome usually have interrupted aortic arch type B, but examples of type A and type C have been reported. Hemizygous deletion of chromosome 1q21.1 [39]  can be associated with interrupted aortic arch type A.

The incidence is approximately 2 cases per 100,000 live births.

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. Although the vast majority of the IAA cases present in neonates, presentation in childhood, early adulthood, and even in the elderly has been reported. [40, 41, 42, 43, 44, 45, 46] This may be related to persistence of the ductus arteriosus, alternative collateral circulation, and/or a balanced circulation. 

In most cases of interrupted aortic arch (IAA), with good surgical repair, the prognosis is excellent.

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.

Complications in patients with IAA:

Persistent subaortic and aortic stenosis [47]

Residual ventricular septal defect

Narrowing at the site of arch surgery

Gruber PJ, Epstein JA. Development gone awry: congenital heart disease. Circ Res. 2004 Feb 20. 94(3):273-83. [Medline].

Dibardino DJ, Heinle JS, Andropoulos DA, Kerr CD, Morales DL, Fraser CD Jr. Aortic atresia and type B interrupted aortic arch: diagnosis by physiologic cerebral monitoring. Ann Thorac Surg. 2005 May. 79(5):1758-60. [Medline].

Tannous HJ, Moulick AN, Jonas RA. Interrupted aortic arch and aortic atresia with circle of Willis-dependent coronary perfusion. Ann Thorac Surg. 2006 Aug. 82(2):e11-3. [Medline].

Decaluwe W, Delhaas T, Gewillig M. Aortic atresia, interrupted aortic arch type C perfused by bilateral arterial duct. Eur Heart J. 2005 Nov. 26(21):2333. [Medline].

Norwood WI, Stellin GJ. Aortic atresia with interrupted aortic arch: reparative operation. J Thorac Cardiovasc Surg. 1981 Feb. 81(2):239-44. [Medline].

Jongmans MC, Admiraal RJ, van der Donk KP, Vissers LE, Baas AF, Kapusta L. CHARGE syndrome: the phenotypic spectrum of mutations in the CHD7 gene. J Med Genet. 2006 Apr. 43(4):306-14. [Medline].

Corsten-Janssen N, Kerstjens-Frederikse WS, du Marchie Sarvaas GJ, Baardman ME, Bakker MK, Bergman JE, et al. The Cardiac Phenotype in Patients with a CHD7 Mutation. Circ Cardiovasc Genet. 2013 May 15. [Medline].

Corsten-Janssen N, Saitta SC, Hoefsloot LH, McDonald-McGinn DM, Driscoll DA, Derks R, et al. More Clinical Overlap between 22q11.2 Deletion Syndrome and CHARGE Syndrome than Often Anticipated. Mol Syndromol. 2013 Jun. 4(5):235-45. [Medline]. [Full Text].

Alsoufi B, Schlosser B, McCracken C, et al. Selective management strategy of interrupted aortic arch mitigates left ventricular outflow tract obstruction risk. J Thorac Cardiovasc Surg. 2015 Sep 28. [Medline].

Goldmuntz E, Clark BJ, Mitchell LE. Frequency of 22q11 deletions in patients with conotruncal defects. J Am Coll Cardiol. 1998 Aug. 32(2):492-8. [Medline].

Marino B, Digilio MC, Persiani M. Deletion 22q11 in patients with interrupted aortic arch. Am J Cardiol. 1999 Aug 1. 84(3):360-1, A9. [Medline].

Chin AJ, Jacobs ML. Morphology of the ventricular septal defect in two types of interrupted aortic arch. J Am Soc Echocardiogr. 1996 Mar-Apr. 9(2):199-201. [Medline].

Mulay AV, Watterson KG. Isolated right subclavian artery, interrupted aortic arch, and ventricular septal defect. Ann Thorac Surg. 1997 Apr. 63(4):1163-5. [Medline].

Arnold JS, Werling U, Braunstein EM, Liao J, Nowotschin S, Edelmann W. Inactivation of Tbx1 in the pharyngeal endoderm results in 22q11DS malformations. Development. 2006 Mar. 133(5):977-87. [Medline].

Zhang Z, Huynh T, Baldini A. Mesodermal expression of Tbx1 is necessary and sufficient for pharyngeal arch and cardiac outflow tract development. Development. 2006 Sep. 133(18):3587-95. [Medline].

Iida K, Koseki H, Kakinuma H. Essential roles of the winged helix transcription factor MFH-1 in aortic arch patterning and skeletogenesis. Development. 1997 Nov. 124(22):4627-38. [Medline].

Winnier GE, Kume T, Deng K. Roles for the winged helix transcription factors MF1 and MFH1 in cardiovascular development revealed by nonallelic noncomplementation of null alleles. Dev Biol. 1999 Sep 15. 213(2):418-31. [Medline].

Jerome LA, Papaioannou VE. DiGeorge syndrome phenotype in mice mutant for the T-box gene, Tbx1. Nat Genet. 2001 Mar. 27(3):286-91. [Medline].

Lindsay EA, Vitelli F, Su H. Tbx1 haploinsufficieny in the DiGeorge syndrome region causes aortic arch defects in mice. Nature. 2001 Mar 1. 410(6824):97-101. [Medline].

Merscher S, Funke B, Epstein JA. TBX1 is responsible for cardiovascular defects in velo-cardio-facial/DiGeorge syndrome. Cell. 2001 Feb 23. 104(4):619-29. [Medline].

Feiner L, Webber AL, Brown CB, Lu MM, Jia L, Feinstein P. Targeted disruption of semaphorin 3C leads to persistent truncus arteriosus and aortic arch interruption. Development. 2001 Aug. 128(16):3061-70. [Medline].

Gitler AD, Lu MM, Epstein JA. PlexinD1 and semaphorin signaling are required in endothelial cells for cardiovasculardevelopment. Dev Cell. 2004 Jul. 7(1):107-16. [Medline].

Yanagisawa H, Hammer RE, Richardson JA. Role of Endothelin-1/Endothelin-A receptor-mediated signaling pathway in the aortic arch patterning in mice. J Clin Invest. 1998 Jul 1. 102(1):22-33. [Medline].

Makki N, Capecchi MR. Cardiovascular defects in a mouse model of HOXA1 syndrome. Hum Mol Genet. 2011 Oct 4. [Medline].

Todorovic V, Frendewey D, Gutstein DE, Chen Y, Freyer L, Finnegan E. Long form of latent TGF-beta binding protein 1 (Ltbp1L) is essential for cardiac outflow tract septation and remodeling. Development. 2007 Oct. 134(20):3723-32. [Medline].

Li J, Zhu X, Chen M, Cheng L, Zhou D, Lu MM. Myocardin-related transcription factor B is required in cardiac neural crest for smooth muscle differentiation and cardiovascular development. Proc Natl Acad Sci U S A. 2005 Jun 21. 102(25):8916-21. [Medline].

Cleary JO, McCue K, Price AN, et al. Micro-MRI phenotyping of a novel double-knockout mouse model of congenital heart disease. J Cardio Mag Res. 2010. 12(Suppl 1):P1.

Guo C, Sun Y, Zhou B, et al. A Tbx1-Six1/Eya1-Fgf8 genetic pathway controls mammalian cardiovascular and craniofacial morphogenesis. J Clin Invest. 2011 Apr 1. 121(4):1585-95. [Medline]. [Full Text].

High FA, Jain R, Stoller JZ, et al. Murine Jagged1/Notch signaling in the second heart field orchestrates Fgf8 expression and tissue-tissue interactions during outflow tract development. J Clin Invest. 2009 Jul. 119(7):1986-96. [Medline]. [Full Text].

Huang ZP, Chen JF, Regan JN, et al. Loss of microRNAs in neural crest leads to cardiovascular syndromes resembling human congenital heart defects. Arterioscler Thromb Vasc Biol. 2010 Dec. 30(12):2575-86. [Medline]. [Full Text].

Nie X, Wang Q, Jiao K. Dicer activity in neural crest cells is essential for craniofacial organogenesis and pharyngeal arch artery morphogenesis. Mech Dev. 2011 Mar-Apr. 128(3-4):200-7. [Medline].

Lepore JJ, Mericko PA, Cheng L, Lu MM, Morrisey EE, Parmacek MS. GATA-6 regulates semaphorin 3C and is required in cardiac neural crest for cardiovascular morphogenesis. J Clin Invest. 2006 Apr. 116(4):929-39. [Medline].

Singh N, Trivedi CM, Lu M, et al. Histone Deacetylase 3 Regulates Smooth Muscle Differentiation in Neural Crest Cells and Development of the Cardiac Outflow Tract. Circ Res. 2011 Sep 29. [Medline].

Nie X, Brown CB, Wang Q, Jiao K. Inactivation of Bmp4 from the Tbx1 expression domain causes abnormal pharyngeal arch artery and cardiac outflow tract remodeling. Cells Tissues Organs. 2011. 193(6):393-403. [Medline]. [Full Text].

Turlo KA, Noel OD, Vora R, LaRussa M, Fassler R, Hall-Glenn F, et al. An essential requirement for ß1 integrin in the assembly of extracellular matrix proteins within the vascular wall. Dev Biol. 2012 May 1. 365(1):23-35. [Medline]. [Full Text].

van der Flier A, Badu-Nkansah K, Whittaker CA, et al. Endothelial alpha5 and alphav integrins cooperate in remodeling of the vasculature during development. Development. 2010 Jul. 137(14):2439-49. [Medline]. [Full Text].

Watanabe Y, Miyagawa-Tomita S, Vincent SD, et al. Role of mesodermal FGF8 and FGF10 overlaps in the development of the arterial pole of the heart and pharyngeal arch arteries. Circ Res. 2010 Feb 19. 106(3):495-503. [Medline]. [Full Text].

Yagi H, Furutani Y, Hamada H. Role of TBX1 in human del22q11.2 syndrome. Lancet. 2003 Oct 25. 362(9393):1366-73. [Medline].

Christiansen J, Dyck JD, Elyas BG, Lilley M, Bamforth JS, Hicks M, et al. Chromosome 1q21.1 contiguous gene deletion is associated with congenital heart disease. Circ Res. 2004 Jun 11. 94(11):1429-35. [Medline].

Suntratonpipat S, Bamforth SD, Johnson AL, ET AL. Childhood presentation of interrupted aortic arch with persistent carotid ducts. World J Pediatr Congenit Heart Surg. 2015 Apr. 6 (2):335-8. [Medline].

Tasar M, Yaman ND, Eyileten Z, Uysalel A. Surgical Treatment of isolated interrupted aortic arch in a young female diagnosed during pregnancy. Ann Vasc Surg. 2015. 29 (4):842.e15-7. [Medline].

Patel DM, Maldjian PD, Lovoulos C. Interrupted aortic arch with post-interruption aneurysm and bicuspid aortic valve in an adult: a case report and literature review. Radiol Case Rep. 2015 Oct. 10 (3):5-8. [Medline].

Belitsis G, Finch JR, Shore DF, Rosendahl UP. Pseudoaneurysm at the origin of the left subclavian artery following type A interrupted aortic arch repair in adulthood, London, United Kingdom. J Thorac Cardiovasc Surg. 2016 Jan. 151 (1):e17-9. [Medline].

Sharma SK, Ameta D, Shukla A, et al. Aortopulmonary window and interrupted aortic arch with Eisenmenger syndrome in an adult. Circulation. 2015 Sep 29. 132 (13):e157-9. [Medline].

Mendoza Diaz PM, Herrera Gomar M, Rojano Castillo J. Interrupted aortic arch in an adult and myocardial infarction. Rev Esp Cardiol (Engl Ed). 2016 Feb. 69 (2):212. [Medline].

Benincasa S, Fineschi M, Ceccherini C, Pierli C. [Interrupted aortic arch in a 68-year-old female with hypertension] [Italian]. G Ital Cardiol (Rome). 2015 Apr. 16 (4):258-9. [Medline].

Jacobs ML, Chin AJ, Rychik J. Interrupted aortic arch. Impact of subaortic stenosis on management and outcome. Circulation. 1995 Nov 1. 92(9 Suppl):II128-31. [Medline].

Gursu HA, Varan B, Oktay A, Ozkan M. A case of neonatal arterial thrombosis mimicking interrupted aortic arch. Turk Pediatri Ars. 2015 Jun. 50 (2):118-22. [Medline].

Belangero SI, Bellucco FT, Cernach MC, et al. Interrupted aortic arch type B in A patient with cat eye syndrome. Arq Bras Cardiol. 2009 May. 92(5):e29-31, e56-8. [Medline]. [Full Text].

Apfel HD, Levenbraun J, Quaegebeur JM. Usefulness of preoperative echocardiography in predicting left ventricular outflow obstruction after primary repair of interrupted aortic arch with ventricular septal defect. Am J Cardiol. 1998 Aug 15. 82(4):470-3. [Medline].

Burri M, Kasnar-Samprec J, Cleuziou J, et al. Creating an arc-shaped aorta: use of the subclavian artery for interrupted aortic arch repair. Ann Thorac Surg. 2015 Feb. 99 (2):648-52. [Medline].

Hirooka K, Fraser CD Jr. Ross-Konno procedure with interrupted aortic arch repair in a premature neonate. Ann Thorac Surg. 1997 Jul. 64(1):249-51. [Medline].

Steger V, Heinemann MK, Irtel von Brenndorff C. Combined Norwood and Rastelli procedure for repair of interrupted aortic arch with subaortic stenosis. Thorac Cardiovasc Surg. 1998 Jun. 46(3):156-8. [Medline].

Zhang H, Cheng P, Hou J, Li L, Liu H, Liu R, et al. Regional cerebral perfusion for surgical correction of neonatal aortic arch obstruction. Perfusion. 2009 Sep 16. [Medline].

Alvin J Chin, MD Emeritus Professor of Pediatrics, University of Pennsylvania School of Medicine

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Ameeta Martin, MD Clinical Associate Professor, Department of Pediatric Cardiology, University of Nebraska College of Medicine

Ameeta Martin, MD is a member of the following medical societies: American College of Cardiology

Disclosure: Nothing to disclose.

Syamasundar Rao Patnana, MD Professor of Pediatrics and Medicine, Division of Cardiology, Emeritus Chief of Pediatric Cardiology, University of Texas Medical School at Houston and Children’s Memorial Hermann Hospital

Syamasundar Rao Patnana, MD is a member of the following medical societies: American Academy of Pediatrics, American Pediatric Society, American College of Cardiology, American Heart Association, Society for Cardiovascular Angiography and Interventions, Society for Pediatric Research

Disclosure: Nothing to disclose.

Charles I Berul, MD Professor of Pediatrics and Integrative Systems Biology, George Washington University School of Medicine; Chief, Division of Cardiology, Children’s National Medical Center

Charles I Berul, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, American Heart Association, Cardiac Electrophysiology Society, Heart Rhythm Society, Pediatric and Congenital Electrophysiology Society, Society for Pediatric Research

Disclosure: Received research grant from: Medtronic.

Interrupted Aortic Arch

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