Definition and Classifications

CTGA is defined by ventriculoarterial discordance. It also can be described by the inlet-outlet features of the ventricles: the presence of subaortic infundibulum (Fig. 44-1), the absence of subpulmonary infundibulum, and mitral-pulmonary fibrous continuity (Fig. 44-2). Subaortic infundibulum implies a connection of the aorta to the infundibulum, which is a morphologic feature of the RV. The absence of subpulmonary infundibulum means that the pulmonary trunk is not connected to the RV. Because fibrous continuity of the inlet-outlet valves is a feature of the LV, a mitral-pulmonary fibrous continuity implies that the pulmonary trunk is connected to the LV.

FIGURE 44-1 Cardiac-gated CTA of a newborn with CTGA. This RV inlet-outlet view shows a superior vena cava (SVC) draining into a right atrium (RA). The RA is connected to the right ventricle (RV), which in turn is connected to an anteriorly located aorta (Ao). The subaortic infundibulum and the surrounding conal muscle (black arrowheads) separate the aortic valve from the tricuspid valve.

FIGURE 44-2 Cardiac-gated CTA of a newborn with CTGA. This LV inlet-outlet view shows the left atrium (LA) connected to the left ventricle (LV), which in turn is connected to the pulmonary trunk (PA). The absence of a subpulmonic infundibulum allows the pulmonary valve to be in contact with the mitral valve (arrow). They are said to be in fibrous continuity.

CTGA is known by a number of other names. Because CTGA comprises 90% of all transposition cases, it is sometimes referred simply as transposition of the great arteries. Other designations are simple transposition and dextrotransposition of the great arteries (D-TGA). The letter D refers to D-loop of the ventricles and not the positional relationship of the great arteries. D-loop refers to the rightward folding of the heart tube during early embryologic development. This crucial event leads to the normal positions of the LV and RV at birth (Fig. 44-3). Usually, D-TGA corresponds with the physiology of CTGA, but this is not always the case. In situs inversus, the CTGA physiology corresponds to L-loop ventricles and CCTGA physiology corresponds to D-loop ventricles. To avoid confusion, it is best to use the terms CTGA and CCTGA, which correctly describe the underlying physiology.

FIGURE 44-3 Cardiac-gated CTA of a patient with pulmonary hypertension. This four-chamber view shows coarse trabeculation in the RV, exaggerated by hypertrophy. The positions of the RV and LV are normal, consistent with D-loop.

There is no officially adopted classification for CTGA. Because the clinical presentation, prognosis, and treatment options are greatly influenced by the associated anomalies, it is useful to divide CTGA according to these anomalies into those with intact ventricular septum (CTGA-IVS), those with ventricular septal defect but without left ventricular outflow obstruction (CTGA-VSD), and those with ventricular septal defect and left ventricular outflow obstruction (CTGA-VSD-LVOTO).

CCTGA is defined by the presence of atrioventricular and ventriculoarterial discordance. Alternative names for CCTGA are corrected transposition, double discordance, and levotransposition of the great arteries (L-TGA). In a patient with normal situs, L-TGA implies L-loop ventricles (Fig. 44-4) and atrioventricular discordance, in addition to ventriculoarterial discordance. Like D-TGA, the term L-TGA is best avoided in favor of CCTGA.

FIGURE 44-4 MRI steady-state free precession image of a patient with CCTGA. This four-chamber view shows that the positions of the right ventricle (RV) and the left ventricle (LV) are reversed, consistent with L-loop.

Van Praagh proposed a three-letter scheme that labels the sidedness of the atrial, ventricular, and arterial segments,⁶ and it has been used to categorize various anatomic manifestations of TGA. In this scheme, the first letter denotes the atrial situs, with S meaning solitus and I meaning inversus. The second letter denotes the ventricular loop, with D meaning D-loop, and L meaning L-loop. The third letter denotes the positions of the great arteries, with D meaning that the aortic root is on the right side of the pulmonary root (Fig. 44-5) and L meaning that the aortic root is on the left side of the pulmonary root (Fig. 44-6). In situs solitus and CTGA, the most common segmental anatomy is S, D, D, although S, D, L exists in a minority of cases. In situs inversus and CTGA, the most common pattern is I, L, L, which is the mirror image of S, D, D. In CCTGA, the segmental anatomy is usually S, L, L for situs solitus and I, D, D for situs inversus. Van Praagh and coworkers,⁷ in a pathology series of CCTGA, reported one case of S, L, D.

FIGURE 44-5 Cardiac-gated CTA a newborn with CTGA. This axial view shows that the aorta (Ao) is located anterior and to the right of the pulmonary artery (PA). The great arteries are in D-position.

FIGURE 44-6 MRI steady-state free precession image of a patient with CCTGA. The position of the pulmonary trunk (PA) is implied at the junction between the left and right main pulmonary arteries. This axial view shows that the aorta (Ao) is anterior and to the left of the pulmonary trunk (PA). The great arteries are in L-position.

Epidemiology and Genetics

CTGA occurs in 5% to 7% of cases of congenital heart disease, with an incidence of 20 to 30/100,000 live births. It is the second most common cyanotic heart disease, behind tetralogy of Fallot, and it is the most common cyanotic heart disease that manifests in the neonatal period. There is no known racial predilection, but there is a 2 : 1 male predominance. CTGA has been reported in trisomies 18 and 21,⁸ although the vast majority of cases have no identified genetic defect. Chromosomal 22q11 deletion, commonly found in conotruncal anomalies, is not associated with CTGA. Furthermore, the risk of recurrence in the offspring of individuals with CTGA is very low.⁹ It has a greater incidence in mothers with diabetes. These observations suggest that genetics may play a less important role in the development of CTGA than environmental factors, possibly intrauterine hormonal disturbance or exposure to teratogens. CTGA is rarely associated with other extracardiac anomalies, with the possible exception of coarctation.

CCTGA occurs in 0.5% to 1.4% of cases of congenital heart disease. It is rare among congenital cardiac anomalies and is much less common than CTGA. Its incidence is on a par with Ebstein anomaly and interrupted aortic arch. Like CTGA, its inheritance pattern is multifactorial, without clear genetic association. There is a slight male predominance.

Etiology and Pathophysiology

Associated Cardiac Anomalies

In most cases of CTGA, the ventricular septum is intact. The most common associated anomaly is VSD, occurring in 40% to 45% of cases. Perimembranous VSD and muscular VSD are about equally common, followed by atrioventricular canal defect. The presence of a VSD is important for survival because it allows the mixing of oxygenated and deoxygenated blood in the otherwise disconnected pulmonary and systemic circulations. The second most common associated anomaly is left ventricular outflow tract (LVOT) obstruction, occurring in 25% of cases. The obstruction can be valvular at the pulmonary valve or subvalvular. In the latter, the cause of obstruction may be fibrous membrane, ring, shelf, septal muscular hypertrophy, septal aneurysm, or septal attachment of chordae tendineae of the mitral valve. In a mechanism similar to that of hypertrophic cardiomyopathy, LVOT obstruction may cause systolic anterior motion (SAM) of the mitral anterior leaflet, worsening the LVOT obstruction and causing mitral regurgitation. The physiologic effects of LVOT obstruction are decreased pulmonary flow and increased cyanosis. Uncommonly, coarctation coexists with CTGA in 5% of cases.

The relative positions of the great arteries in CTGA are variable. In normal anatomy, the aortic root is located posterior and to the right of the pulmonary root. In 90% of CTGA cases, the aortic root is located anterior and to the right of the pulmonary root. Uncommonly, in 10% of cases, the aortic root is located anterior and to the left of the pulmonary artery. This leads to the S, D, L designation in the Van Praagh segmental labeling scheme described earlier. Rarely, the aortic root can be posterior to the pulmonary root.

Knowledge of the coronary artery anatomy is crucial for the surgical management of CTGA. In CTGA, as in normal cardiac anatomy, the two main coronary arteries most often arise from the two aortic sinuses of Valsalva closest to, or facing, the pulmonary valve. In the most common coronary pattern for CTGA, which occurs in 67% of cases, the right coronary artery (RCA) originates from the right facing sinus and the left main coronary artery (LMCA) originates from the left facing sinus (Fig. 44-7). The LMCA then bifurcates into the left anterior descending (LAD) artery and left circumflex (LCx) artery, as expected. Less commonly, the LCx arises from the RCA in 22% of cases. Other variations include a single RCA (9.5%), a single LMCA (3%), reversed RCA and LMCA (3%), and others (Fig. 44-8).¹¹

FIGURE 44-7 Cardiac-gated CTA of a patient with CTGA. In this short-axis view, the aorta (Ao) and pulmonary trunk (PA) are in D-position. The left main coronary artery (LMCA) and the right coronary artery (RCA) arise from the aortic sinuses facing the pulmonary trunk. This is the most common coronary pattern for CTGA.

FIGURE 44-8 Cardiac-gated CTA of a patient with CTGA. This is an uncommon coronary pattern in which the right coronary artery (RCA) and left anterior descending artery (LAD) arise together from the left-facing sinus, whereas the left circumflex artery (LCx) arises alone from the posterior right-facing sinus. Transplantation of these coronary arteries in an arterial switch operation was thought to be impossible, and the patient underwent atrial switching.

Only a small fraction (1% to 9%) of CCTGA cases are isolated without any associated anomalies.¹² The most common associations are VSD and pulmonary stenosis. VSD occurs in 60% to 80% of cases (Fig. 44-9). It can be of any type and the VSD can be multiple. Pulmonary stenosis occurs in 30% to 50% of cases, and it can be valvular or subvalvular. There is a frequent association with tricuspid abnormalities, which include dysplastic leaflets, Ebstein-like displacement of the leaflets, and a tricuspid valve straddling the ventricular septum. Other less common associated anomalies are atrial septal defect (ASD), patent ductus arteriosus (PDA), pulmonary atresia, mitral valve abnormalities, coarctation, and interrupted aortic arch. CCTGA manifests with dextrocardia in 25% of cases and situs inversus in 5% of cases.

FIGURE 44-9 MRI steady-state free precession image of a patient with CCTGA. This LV inlet-outlet view shows a large ventricular septal defect (arrow) shunting flow into the left ventricle (LV) and then out the pulmonary artery. A pulmonary artery band is in place (arrowheads) to restrict this flow and prevent pulmonary vascular obstructive disease. Note that the right atrium (RA) is connected to the morphologic LV, consistent with atrioventricular discordance.

An important feature of CCTGA is the abnormal development and position of the atrioventricular (AV) node. In normal anatomy, the AV node is located at a relatively posterior position near the tricuspid septal leaflet in an area known as the triangle of Koch. In CCTGA, this posterior AV node may be absent and replaced by an anterior AV node. This anterior node is fragile and can be damaged by fibrosis or surgical trauma, leading to heart block. In some cases, both the posterior and anterior AV nodes are present. Their expected locations must be recognized during surgery to avoid damage.

The aortic root position is typically anterior and to the left of the pulmonary root. Together with normal situs and L-loop ventricle, S, L, L is the most common segmental description for CCTGA. Variations in coronary anatomy are common, but the branching pattern of the coronary arteries generally follows the ventricles. Because the left ventricle is positioned on the right, the LMCA commonly arises from the right-facing sinus and travels to the right before branching into a LAD and a LCx. The latter lies in the right atrioventricular groove. Similarly, the RCA commonly arises from the left-facing sinus and lies in the left atrioventricular groove. Single coronary origin is also common.¹³

Clinical Presentation

The early onset of cyanosis in CTGA can be understood from its unique physiology. In utero, the fetal circulation is composed of parallel pulmonary and systemic circulations. Two right-to-left shunts are established at the fossa ovalis of the atrial septum and at the PDA. Both shunts reduce pulmonary flow through the nonfunctioning lungs. The organ in which oxygen exchange occurs is the placenta, connected to the systemic circulation through the umbilical vein and arteries. Transposing the fetal great arteries produces no physiologic effect because they are connected by the PDA. This arrangement allows the fetus to grow normally.

At birth, the placenta no longer serves as the organ of oxygen exchange. During the transition from fetal to adult circulation, the fossa ovalis and PDA close, bringing the ventilated lungs into serial connection with the systemic circulation. CTGA, by conducting deoxygenated blood from the RV to the aorta and oxygenated blood from the LV to the pulmonary artery, disconnects the pulmonary circulation from the systemic circulation. This configuration is not viable.

In practice, some mixing of the oxygenated and deoxygenated blood occurs through shunts between the pulmonary and systemic circulations, providing some oxygen to the systemic organs. The degree of cyanosis depends on (1) the size and direction of these shunts and (2) the degree of obstruction to the pulmonary flow. In CTGA-IVS, the most common anatomic arrangement, shunting is limited and the neonate presents with cyanosis within hours of birth. Cyanosis worsens as the PDA closes in the first few days of life. Prognosis in this scenario is poor, with a 30% survival rate at 1 month. In CTGA-VSD, the VSD is usually large and mixing occurs freely at the ventricular level. Patients may present with mild cyanosis, even after the PDA closes. As the pulmonary resistance drops in the first week of life, a large shunting from the systemic RV to pulmonary LV may occur. This can lead to congestive heart failure and later pulmonary vascular obstructive disease. The latter is the cause of pulmonary hypertension and Eisenmenger syndrome. The survival rate at 1 year is 50%, which is better than that for CTGA-IVS. In CTGA-VSD-LVOTO, the LVOT obstruction limits flow to the pulmonary circulation. The physiology in this situation is similar to that of tetralogy of Fallot. Severe obstruction would lead to diminished pulmonary flow and worsening cyanosis. Little obstruction would lead to large shunting and the same outcome as CTGA-VSD. If the obstruction is balanced just right, the pulmonary circulation may be protected from harmful shunt flow at a level of tolerable cyanosis. The survival rate for CTGA-VSD-LVOTO is 50% at 3 years, with some surviving into adulthood. Left untreated, the overall survival rates for CTGA are 70% at 1 week, 50% at 1 month, and 10% at 1 year.¹⁴