Corrected Transposition of the Great Arteries (c-TGA)

Corrected transposition of the great arteries (c-TGA), also known as levo-transposition of the great arteries (L-TGA), is a rare complex cardiac malformation characterized by discordant atrioventricular and ventriculoarterial connections, usually associated with other cardiovascular abnormalities.  
Clinical severity ranges from symptom-free cases to conditions requiring one or more surgical interventions [1,2].

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C-TGA makes up about 8-20% of all TGA cases and accounts for 0.4-0.5% of all congenital cardiac anomalies, with a prevalence of 3 per 100,000 live births [1-3]. The recurrence risk of c-TGA is approximately 2% in first-degree relatives [4-5]. Inconsistent data regarding gender predominance of the c-TGA is stated in the literature, ranging from no significant gender predominance to predominant male incidence 1,6:1 [6-7].
 

The etiology of the c-TGA is unknown and probably multi-factorial. Familial incidence is rare and has a recurrence risk of about 2% in first-degree relatives [4-5]. Associated chromosomal abnormalities are also uncommon [8-9].
 

If the fetal situs is normal (situs solitus), that is the atrial chambers are in their usual position, the right-sided morphological right atrium is connected to the right-sided morphological left ventricle through a mitral valve, and the left-sided morphological left atrium is connected to the left-sided morphological right ventricle via the tricuspid valve. Such an atrioventricular arrangement is called atrioventricular discordance. c-TGA is also characterized by ventriculoarterial discordance, which means that the pulmonary artery arises from the morphological left ventricle without a sub-pulmonary infundibulum (pulmonary-mitral fibrous continuity). The pulmonary valve is wedged between the atrial septum and the mitral valve. The interatrial septum is moved away from the interventricular septum with an abnormal arrangement of the conduction system. The aorta arises from the morphologicallright ventricle. The great vessels are parallel without the normal crossing of the outflow tract with the aorta to the left and anterior. If the ven0-atrial connection is normal this arrangement results in hemodynamic compensation. It is called ‘’physiological correction’’ because after birth systemic venous blood ejects to the pulmonary artery and the pulmonary venous blood ejects to the aorta [10, 11, 12].
 

About 85% of cases of c-TGA are associated with other cardiac malformations, typically ventricular septal defects, obstruction of the sub-pulmonary outflow tract, and tricuspid valve malformations. Cardiac malpositions, dextrocardia or mesocardia, can occur in 20% of these cases. Arrhythmia is also common in c-TGA due to abnormal pathways of the conduction system.  Approximately 20% of prenatally diagnosed cases demonstrate AV block usually in the third trimester. Some cases may be associated with aortic arch abnormalities and re-entrant tachycardia [13, 14].
 

Detailed segmental-sequential examination of the heart is essential for the diagnosis of the c-TGA. Cardiac axis deviations, mesocardia, dextrocardia, fetal bradycardia, and dysplastic tricuspid valve may raise suspicion of c-TGA even in the first trimester or during an early second-trimester scan and should lead to more detailed cardiac examination [13, 14, 15, 16]. 

The diagnostic approach can be divided into three basic steps.

Step 1

Recognition of fetal visceral situs. c-TGA is typically associated with normal situs solitus, but situs inversus and situs ambiguous have also been reported in cases of c-TGA [15, 16].

Step 2

The fundamental precondition of the diagnosis is the proper identification of some typical morphological features of ventricular chambers and the demonstration of inverted atrioventricular connections. The presence of a moderator band helps to recognize the right ventricle which in cases with situs solitus is located on the left side of the heart. Careful demonstration of attachment of the chordae tendineae to the papillary muscles is helpful for recognizing ventricular morphology. The left ventricle papillary muscles originate from the free wall, while the right ventricle papillary muscles originate from the interventricular septum [15,16]. There are also other morphological elements used to distinguish the right and left ventricles, but theose mentioned above are usually sufficient  for characterization of anatomy during prenatal scanning. Colour Doppler may be useful to delineate the anatomy of the chambers and to demonstrate tricuspid valve regurgitation during an early fetal cardiac examination.
During this step, using the above-mentioned morphologic features of cardiac chambers, we should demonstrate that the left atrium is connected to the right ventricle and the right atrium is connected to the left ventricle. This atrioventricular discordance raises suspicion of c-TGA.

Step 3

Identification of atrioventricular discordance should prompt inspection of therelation of the great vessels (outflow tracts) to the cardiac ventricles. The outflow tracts can be visualized at the level of the three-vessel view or three-vessel-trachea view [14, 15, 16]. In cases of c-TGA, the right-side, and most anterior ventricle is the left ventricle and connects to the main pulmonary artery. Bifurcation of the pulmonary artery into right and left pulmonary branches can be used as an indicator and characteristic feature of the pulmonary artery. On contrary, the aorta arises posteriorly from the left-sided morphological right ventricle. Branches of the aortic arch can also be used as a characteristic feature of the aorta [15, 16].
The three-vessel view of the heart is always abnormal in c-TGA. In a normal heart, at the level of the three-vessel view, the pulmonary artery is the anteriorly located vessel, but in the case of the c-TGA, at this level, the aorta is located anteriorly and leftward to the pulmonary artery [14, 16].
As was mentioned before, about 85% of the c-TGA cases are associated with another cardiac malformation, so, examiners should also pay attention to detection of these possible associated findings [13, 16]. 
 

Isolated ventricular inversion (AVD-VAC), and complete transposition of the great arteries (d -TGA) are the two cardiac anomalies in the differential diagnosis of c-TGA. They all share a parallel arrangement of the great arteries a. The AVD-VAC is characterized by a discordant atrioventricular connection, but a concordant ventriculoarterial connection. The d-TGA has a concordant atrioventricular connection with a discordant ventriculoarterial connection [16].
 

The outcome of c-TGA depends on associated cardiac pathology and ranges from symptom-free cases to cases requiring surgical interventions. 
 

Suspected cases of the c-TGA during routine prenatal screening should be referred to specialized centers where detailed fetal morphology and echocardiography can be evaluated. Isolated c-TGA without extracardiac anomalies carries a very low risk for chromosomal anomalies. Some authors recommend invasive testing when the c-TGA is associated with extracardiac anomalies. Association of the c-TGA with chromosomal anomalies, 22q11.2 syndromes, and primary ciliary dyskinesia have been reported in some studies [17, 18].
 

1.    Samánek M, Vorísková M. Congenital heart disease among 815,569 children born between 1980 and 1990 and their 15-year survival: a prospective Bohemia survival study. Pediatr Cardiol. 1999 Nov-Dec;20(6):411-7. doi: 10.1007/s002469900502. PMID: 10556387.
2.    Atallah J, Rutledge JM, Dyck JD. Congenitally corrected transposition of the great arteries (atrioventricular and ventriculoarterial discordance). In: Allen HD, Driscoll DJ, Shaddy RE, Feltes TF, eds. Moss & Adams’ Heart Disease in Infants, Children, and Adolescents. Lippincott Williams & Wilkins; 2013:1147-1160.
3.    Ferencz C, Rubin JD, Loffredo CA, Magee CA. Epidemiology of Congenital Heart Disease. The Baltimore-Washington Infant Study 1981-1989. Futura Publishing Company; 1993.
4.    Becker TA, Van Amber R, Moller JH, Pierpont MEM. Occurrence of cardiac malformations in relatives of children with transposition of the great arteries. Am J Med Genet. 1996;66:28-32.
5.    Piacentini G, Digilio M.C, Capolino R, et al. Familial recurrence of heart defects in subjects with congenitally corrected transposition of the great arteries.  Am J Med Genet . 2005;137(2):176–180.
6.    Silvia G.V. Alvarez and Lisa K. Hornberger Transposition of the great arteries. In: Yagel S, Silverman NH, Gembruch U, Cohen SM. Fetal Cardiology: Embryology, Genetics, Physiology, Echocardiographic Evaluation, Diagnosis and Perinatal Management of Cardiac Diseases. New York, Informa.; 3rd Edition; Taylor & Francis, 2019.
7.    David J. Barron, Oliver Stumper, William J. Brawn, Diane E. Spicer, Robert H. Anderson. Congenitally Corrected Transposition. In: Wernovsky G. Anderson's Pediatric Cardiology. Elsevier; 2020:697-714
8.    Dietz, H. (1994). Epidemiology of congenital heart disease: The Baltimore-Washington infant study 1981-1989, C. Ferencz, J.D. Rubin, C.A. Loffredo, and C.A. Magee, eds., Mount Kisco, NY: Futura Publishing Company, 353 pages. Genetic Epidemiology, 11(5), 455–456.
9.    Pradat P, Francannet C, Harris JA, Robert E. The epidemiology of cardiovascular defects, part I: a study based on data from three large registries of congenital malformations. Pediatr Cardiol. 2003 May-Jun;24(3):195-221. doi: 10.1007/s00246-002-9401-6. Epub 2003 Mar 14. PMID: 12632215.
10.    Freedom RM (1999) Congenitally corrected transposition of the great arteries: definitions and pathologic anatomy. Prog Pediatr Cardiol 10(1):3–16
11.    Allwork SP, Bentall HH, Becker AE, Cameron H, Gerlis LM, Wilkinson JL, Anderson RH. Congenitally corrected transposition of the great arteries: morphologic study of 32 cases. Am J Cardiol. 1976 Dec;38(7):910-23. doi: 10.1016/0002-9149(76)90804-3. PMID: 998526.
12.    Anderson RH, Becker ae, Arnold r, Wilkinson Jl: The conducting tissues in congenitally corrected transposition. Circulation 1974;50:911–923.
13.    Paladini, D., Volpe, P., Marasini, M., Russo, M. G., Vassallo, M., Gentile, M., & Calabrò, R. (2006). Diagnosis, characterization, and outcome of congenitally corrected transposition of the great arteries in the fetus: a multicenter series of 30 cases. Ultrasound in Obstetrics & Gynecology, 27(3), 281–285. doi:10.1002/uog.2715 
14.    Vorisek CN, Enzensberger C, Willomeit S, et al. Prenatal diagnosis and outcome of congenitally corrected transposition of the great arteries—a multicenter report of 69 cases. Ultraschall Med. 2020.
15.    Zhang, Y., Cai, A., Sun, W., Guo, Y., & Zhao, Y. (2011). Prenatal diagnosis of fetal congenitally corrected transposition of the great arteries. Prenatal Diagnosis, 31(6), 529–535.doi:10.1002/pd.2734.
16.    Bravo-valenzuela, N. J., Carrilho, M. C., Peixoto, A. B., Bezerra, M. S., & Araujo Júnior, E. (2018). Anatomically corrected malposition of the great arteries: a challenging fetal diagnosis. The Journal of Maternal-Fetal & Neonatal Medicine, 1–5.doi:10.1080/14767058.2018.1457640
17.    Srivastava D, Olson EN. A genetic blueprint for cardiac development. Nature. 2000;407:221-226.
18.    Vorisek CN, Enzensberger C, Willomeit S, et al. Prenatal diagnosis and outcome of congenitally corrected transposition of the great arteries—a multicenter report of 69 cases. Ultraschall Med. 2020.
 

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