D-transposition of the great arteries (D-TGA): Anatomy, clinical features, and diagnosis

INTRODUCTION — Transposition of the great arteries (TGA) is a ventriculoarterial discordant lesion in which the aorta arises from the right ventricle and the pulmonary artery from the left ventricle. In the dextro- or D-looped type (D-TGA), the ventricles are oriented so that the right ventricle is positioned to the right of the left ventricle and the origin of the aorta is anterior and rightward to the origin of the pulmonary artery (figure 1). D-TGA is a form of cyanotic heart disease because there are two parallel circulations.

The anatomy, pathophysiology, clinical features, and diagnosis of D-TGA will be presented here. The management and outcome of D-TGA are discussed separately. (See "D-transposition of the great arteries (D-TGA): Management and outcome".)

Levo- or L-looped TGA (L-TGA; also commonly referred to as congenitally corrected TGA) is discussed separately. (See "L-transposition of the great arteries (L-TGA): Anatomy, clinical features, and diagnosis" and "L-transposition of the great arteries (L-TGA): Management and outcome".)

EPIDEMIOLOGY — The prevalence of TGA in the United States is estimated to be 2 to 5 per 10,000 live births [1,2]. TGA accounts for approximately 3 percent of all congenital heart disease (CHD) disorders and almost 20 percent of all cyanotic CHD defects [2].

EMBRYOLOGY AND PATHOGENESIS

Embryology — The specific developmental aspects that result in ventriculoarterial discordance in D-TGA are not fully delineated. It is hypothesized that the morphogenesis of D-TGA is due to the abnormal growth and development of the bilateral subarterial conus.

In normal cardiac development, the subaortic conus and subpulmonary conus are present in the first month of gestation as the great arteries are positioned superior to the right ventricle. Typically, the subaortic conus is resorbed at approximately 30 to 34 days into gestation, which allows for migration of the aortic valve inferiorly and posteriorly into its normal position above the left ventricle. Subaortic conal resorption also leads to the characteristic fibrous continuity between the mitral and aortic valve within the left ventricle. The pulmonary valve retains its association with the right ventricle due to the persistence of the subpulmonary conus [3].

In D-TGA, however, the subpulmonary conus is resorbed, which allows for posterior migration of the pulmonary valve and the development of fibrous continuity between the pulmonary and mitral valve. The unabsorbed subaortic conus forces the aortic valve anteriorly, where it abnormally engages with the morphologic right ventricle. The range in the size and orientation of the subaortic conus is thought to create much of the variability of the coronary arteries' origins and course [4].

Genetics — Unlike many other forms of congenital heart disease (CHD), D-TGA is not associated with any particular genetic abnormality or familial inheritance pattern. The prevalence of CHD in siblings of affected children is no higher than that of the general population [5].

In addition, patients with D-TGA rarely have noncardiac anomalies, which commonly accompany other forms of CHD [6].

In particular, DiGeorge (22q11 deletion), which is associated with other conotruncal lesions, is not commonly associated with D-TGA [7,8]. Testing for the 22q11 deletion in patients with D-TGA will likely have a higher yield if there is also laterality or branching abnormalities of the aortic arch, which are more common in patients with DiGeorge syndrome [9]. (See "DiGeorge (22q11.2 deletion) syndrome: Clinical features and diagnosis", section on 'Cardiac anomalies'.)

ANATOMY

D-TGA — In normal cardiac anatomy, the aorta is positioned posterior and to the right of the main pulmonary artery (figure 2). Also, the morphologic right ventricle has a large outflow tract component known as the infundibulum or the conus arteriosus [3].

In D-TGA, the subpulmonary conus is absent and the subaortic conus fails to resorb, resulting in the aorta being positioned anterior and slightly rightward of the pulmonary artery (figure 1). These changes cause the aorta to arise from the right ventricle and the pulmonary artery from the left ventricle (ventriculoarterial discordance).

The dextro connotation of D-TGA refers to the looping of the ventricles during cardiac morphogenesis that positions the right ventricle to the right of the morphologic left ventricle. This provides a shorthand moniker to help differentiate this form of transposition from levo-transposition of the great arteries (L-TGA). (See "L-transposition of the great arteries (L-TGA): Anatomy, clinical features, and diagnosis".)

Other cardiac anomalies — In addition to ventriculoarterial discordance, there are other cardiac anomalies or functional defects that are often seen in patients with D-TGA. Simple D-TGA describes patients without another cardiac defect, whereas complex D-TGA describes those with an additional cardiac lesion.

●Ventricular septal defect (VSD) – VSD occurs in approximately 50 percent of patients with D-TGA. The associated VSD can be found in any region of the ventricular septum [10]. (See "Isolated ventricular septal defects (VSDs) in infants and children: Anatomy, clinical features, and diagnosis", section on 'Anatomy'.)

Patients with a VSD are more likely to have additional cardiac anomalies, which may include pulmonary stenosis or atresia, overriding or straddling of an atrioventricular valve, and/or coarctation or interruption of the aorta.

The presence and size of a VSD may have significant impact on clinical presentation. (See 'Presentation' below.)

●Left ventricular outflow tract obstruction – Left ventricular outflow tract obstruction is common in D-TGA, occurring in up to 25 percent of patients [11]. The obstruction may be dynamic or anatomical:

•In patients with an intact ventricular septum, the systemic right ventricular pressure causes the interventricular septum to bow into the left ventricular cavity, causing dynamic obstruction between the mitral valve and the septum. Surgical correction of the parallel circulations typically eliminates this functional obstruction. This form of obstruction is rare in neonates as elevated pulmonary vascular resistance and the presence of a large patent ductus arteriosus result in near systemic pressure of the left ventricle, reducing this "septal bulge" [4].

•Patients with D-TGA and VSD are at greater risk for more severe anatomical left ventricular outflow tract obstruction such as pulmonary stenosis or atresia. This subset of D-TGA patients has a higher incidence of aortic arch obstruction including coarctation and interruption of the aorta.

●Mitral and tricuspid valve abnormalities – Abnormalities of the mitral and tricuspid valves are more common when a VSD is present and have implications for surgical correction [12-14]. (See "D-transposition of the great arteries (D-TGA): Management and outcome", section on 'Surgery'.)

These abnormalities may include:

•Straddling tricuspid valves (septal chordal attachments of the tricuspid valve extend into the left ventricle)

•Overriding valves (valve allows direct flow into the left ventricle without straddling chordae)

●Coronary artery variations – Anatomy of the coronary arteries in patients with D-TGA is variable, and it is important to delineate the anatomy of the coronary arteries prior to surgical intervention as it may impact the surgical approach and procedure. (See "D-transposition of the great arteries (D-TGA): Management and outcome", section on 'Surgery'.)

Normally, the left main coronary artery arises from the left coronary ostium above the aortic valve. It divides into the left anterior descending artery, which courses along the epicardial surface of the interventricular septum, and the circumflex artery, which travels in the left atrioventricular groove, and posteriorly toward the crux of the heart. The right coronary artery, originating from the right coronary ostium, courses posteriorly in the right atrioventricular groove and typically gives rise to the posterior descending artery (90 percent of cases).

In D-TGA, the coronaries typically arise from the sinuses of Valsalva that face the pulmonary artery and follow the shortest course to their intended distribution. In the "usual" pattern (present in approximately two-thirds of patients with D-TGA), the left main coronary artery originates from the anterior and leftward-facing sinus, while the right coronary artery arises from the posterior and rightward-facing sinus [15].

Other coronary artery variations may include an unusual epicardial course, multiple coronary ostia arising from the same sinus of Valsalva, or the proximal course of a coronary artery passing between the two great vessels, which is described as intramural (figure 3 and table 1) [4].

PHYSIOLOGY — D-TGA prior to surgical repair is physiologically uncorrected, which means that the systemic and pulmonary circulations are parallel circuits. Deoxygenated systemic venous blood drains appropriately into the right atrium and then is pumped from the right ventricle back to the systemic circulation via the aorta. Oxygenated pulmonary venous blood returns to the left atrium and ventricle and is then recirculated to the lungs via the pulmonary artery (figure 1). This circulation is incompatible with life unless there is communication between the two parallel circuits. Mixing can occur either intracardiac across a patent foramen ovale or a ventricular or atrial septal defect (VSD or ASD), or via extracardiac connections including a patent ductus arteriosus or the bronchopulmonary collateral circulation.

The fetus tolerates the in utero circulation of D-TGA without much difficulty. Oxygen-rich blood from the umbilical vein is largely directed from the right atrium across the fossa ovalis and into the left ventricle, where it is pumped into the pulmonary artery and across the ductus arteriosus into the systemic circulation. The vascular resistance provided by the placenta is lower than the pulmonary capillary bed, which allows for right-to-left blood flow through the ductus arteriosus and into the descending aorta (figure 4). (See "Physiologic transition from intrauterine to extrauterine life", section on 'Fetal circulation'.)

However, one potential fetal problem is that the normal flow of oxygen-rich blood toward the head and neck vessels is disrupted by the inability to pump the oxygenated blood directly into the ascending aorta from the left ventricle.

After delivery, the stability of the newborn is largely dependent upon the degree of mixing between the two parallel circulations. For viability, some degree of oxygenated pulmonary venous return must make its way to the systemic capillary bed (effective systemic blood flow), while a similar degree of systemic venous return must enter the pulmonary capillary system (effective pulmonary blood flow). Oxygen saturations and the degree of hypoxemia largely depend upon the amount of intercirculatory mixing that occurs through the intracardiac and extracardiac connections.

Thus, postnatal management focuses on optimizing intercirculatory mixing, which is achieved by balancing the effective pulmonary and systemic blood flows. This mixing occurs most efficiently at the level of the atria as lower pressure differences allow for bidirectional flow across the atrial septum; flow can occur in both systole and diastole. Intracardiac (eg, VSDs) and extracardiac (eg, patent ductus arteriosus) mixing at other sites is more limited due to the presence of larger pressure gradients, which typically direct blood in only one direction. Shunting of blood preferentially towards either the systemic or pulmonary circulation tend to results in clinical deterioration [3,4].

CLINICAL FEATURES

Presentation — The clinical features of D-TGA depend upon the degree of mixing between the two parallel circulations and the presence of other cardiac anomalies. Patients generally present during the neonatal period.

The following clinical features are typically observed during physical examination:

●Cyanosis – The degree of cyanosis is determined by the amount of intercirculatory mixing, which is particularly affected by the presence and size of an atrial septal defect (ASD). A ventricular septal defect (VSD) may also result in improved intracardiac mixing and less cyanosis. Cyanosis is not affected by exertion (eg, crying or feeding) or the use of supplemental oxygen.

Infants with mild cyanosis may lack other apparent signs, and the lesion may be detected solely on the basis of a failed pulse oximetry screen. (See "Newborn screening for critical congenital heart disease using pulse oximetry".)

•Neonates with an intact ventricular septum – Neonates with an intact ventricular septum typically present with severe cyanosis during the newborn period. The severity is modified by the presence of other cardiac abnormalities that facilitate mixing, such as a patent ductus arteriosus and/or interatrial shunting. These infants are at the greatest risk for neonatal death, especially when the patent ductus arteriosus closes, resulting in decreased circulatory mixing. (See 'Natural course' below.)

•Neonates with a VSD – The size of the VSD dictates the amount of mixing that occurs between the two circulatory systems. Infants with a small VSD may get little additional mixing over those without a VSD. As a result, their presentation is usually similar to those with an intact ventricular septum. Infants with large VSDs may have mild or clinically inapparent cyanosis.

●Reverse differential cyanosis – Infants with D-TGA associated with pulmonary hypertension, coarctation of the aorta, or interrupted aortic arch may present with reverse differential cyanosis (ie, higher postductal saturations than preductal saturations). This is due to the right-to-left ductal shunting of blood into the descending aorta that is more fully saturated than that entering the ascending aorta.

●Tachypnea – Most patients have respiratory rates greater than 60 breaths per minute; however, they usually appear relatively comfortable without other signs of respiratory distress such as retractions, grunting, or flaring. Infants with large VSDs may present with more severe respiratory distress due to heart failure by three to four weeks of age.

●Murmurs – Murmurs are not a prominent feature, unless there is a small- to moderate-sized VSD or left ventricular outflow tract obstruction.

•When there is a VSD, a pansystolic murmur (movie 1) is usually present within a few days after birth at the lower left sternal border. The intensity of the murmur is dependent on the turbulence of blood flow through the septal defect. (See "Isolated ventricular septal defects (VSDs) in infants and children: Anatomy, clinical features, and diagnosis", section on 'Cardiac findings'.)

•In patients with left ventricular outflow obstruction (eg, pulmonic stenosis (movie 2)), there may be a systolic ejection murmur along the upper left sternal border. The intensity of the murmur is dependent both on the degree of obstruction and the amount of blood flow across the obstruction.

●Diminished pulses – Diminished femoral pulses may be seen in patients who also have coarctation of the aorta or interruption of the aortic arch (5 percent of patients). (See "Clinical manifestations and diagnosis of coarctation of the aorta".)

Chest radiograph and electrocardiogram — A chest radiograph and electrocardiogram (ECG) are often obtained in the evaluation of patients with suspected cyanotic congenital heart disease. Findings on these tests are nonspecific.

●Chest radiography – The classic chest radiograph features a heart with an "egg on a string" appearance, which is thought to be a result of the great arteries forming a narrowed vascular pedicle when transposed [3]. However, in the first few days after birth, the chest radiograph in newborns with D-TGA often shows a normal cardiothymic silhouette. Despite having marked hypoxemia, the pulmonary vascular markings are often normal, though they may be increased. Infants with a large VSD or a straddling tricuspid valve may develop signs of excessive pulmonary blood flow, cardiomegaly, and congestive heart failure on chest radiograph after a few days.

●ECG – The ECG is often normal in newborns with D-TGA. Right-axis deviation and right ventricular hypertrophy are normal findings in the first few days after birth and may be the only findings present on ECG in a newborn with D-TGA.

Natural course — Without intervention, most infants with D-TGA will die within the first year of life. Approximately 30 percent of untreated patients die in the first week, 50 percent in the first month, and 90 percent within the first year of life [4].

DIAGNOSIS — Because of the high risk of neonatal mortality, it is important to establish the diagnosis of D-TGA early. Although the diagnosis may be made antenatally, many cases are diagnosed after delivery.

Fetal diagnosis — D-TGA is one of the more difficult congenital heart defects to diagnose by fetal ultrasound. Screening ultrasounds that primarily focus on a four-chamber view of the heart will miss D-TGA due to the absence of ventricular size discrepancy. The prenatal accuracy is increased when the outflow tracts are evaluated to determine whether the great arteries cross normally. This was demonstrated in a study conducted in the Canadian province of Alberta from 2003 through 2015 (before and after obstetrical ultrasound guidelines were updated in 2010 with recommendations to routinely perform cardiac outflow tract assessment) [16]. Prenatal detection rates for D-TGA improved from 14 percent in the era before the guidelines were updated (2003 to 2010) to 50 to 77 percent in the years following the updated guidelines (2011 to 2015). (See "Congenital heart disease: Prenatal screening, diagnosis, and management", section on 'Standard cardiac evaluation'.)

Certain fetal echocardiographic parameters, particularly the size of the foramen ovale, correlate with the degree of postnatal hypoxia and need for balloon atrial septostomy (BAS) [17-20]. However, these parameters do not reliably predict which neonates will require urgent BAS. Thus, for all cases of prenatally diagnosed D-TGA, delivery should occur at a facility that has a level III neonatal intensive care unit, pediatric cardiology expertise, and resources to perform urgent BAS, if necessary. (See "Congenital heart disease: Prenatal screening, diagnosis, and management", section on 'Delivery planning' and "D-transposition of the great arteries (D-TGA): Management and outcome", section on 'Prenatal diagnosis and management'.)

Postnatal diagnosis — The diagnosis of D-TGA is based on clinical suspicion of an underlying cyanotic congenital heart defect and is primarily confirmed by echocardiography. Suspicion of cyanotic congenital heart disease (CHD) is made based on the presence of cyanosis, respiratory symptoms, and a failed pulse oximetry screen. (See "Identifying newborns with critical congenital heart disease", section on 'Clinical features' and "Newborn screening for critical congenital heart disease using pulse oximetry".)

Echocardiography — The diagnosis of D-TGA is generally made by two-dimensional echocardiography and Doppler examination. Subcostal imaging of the heart demonstrates a great artery that branches into the left and right pulmonary arteries arising from the posterior left ventricle, and short-axis or parasagittal plane imaging shows the aorta rising anteriorly from the right ventricle (image 1).

The echocardiographic testing should systematically delineate atrioventricular or ventriculoarterial connections, the presence or absence of other commonly associated cardiac anomalies such as a ventricular septal defect (VSD), and the coronary artery anatomy. (See 'Other cardiac anomalies' above.)

●The presence and size of the atrial level communication is critical to determine the amount of intercirculatory mixing. Measurement of restriction to flow by using color Doppler should be performed.

●The ventricular septum should be evaluated for any VSD. The presence of a VSD, particularly an anterior malalignment type, increases the probability that the patient will have aortic arch anomalies [4]. Patients with complex transposition, including a VSD and coarctation, are at higher risk for surgical morbidity and mortality [21].

●Detection of any abnormalities of the atrioventricular valves and the relationships of the chordal attachments to the ventricular septum and outflow tracts must be well understood prior to surgery.

●Evaluation for a patent ductus arteriosus and, if present, determination of the degree of shunting should be performed.

●Coronary artery anatomy is typically delineated with echocardiography, and it is rarely necessary to perform other forms of diagnostics such as angiography or cardiac magnetic resonance imaging to help clarify the coronary artery anatomy. Coronary artery variations must be well delineated prior to surgical intervention (table 1).

Cardiac catheterization — Angiography is seldom required to make the diagnosis of D-TGA. However, coronary angiography remains the gold standard for elucidating coronary arteries' courses and origins and is used, at times, for patients with coronary anatomy that cannot be determined confidently with echocardiography prior to surgical intervention.

The most important role for cardiac catheterization in patients with D-TGA is performance of BAS to increase mixing between the two circulatory systems. This procedure is performed in patients with severe hypoxemia as a consequence of inadequate mixing and has extended survival for these infants until surgical palliation can be performed. (See "D-transposition of the great arteries (D-TGA): Management and outcome", section on 'Balloon atrial septostomy'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Congenital heart disease in infants and children".)

SUMMARY AND RECOMMENDATIONS

●Anatomy and physiology – D-transposition of the great arteries (D-TGA) is characterized by the aorta arising from the right ventricle and the pulmonary artery originating from the left ventricle (ventriculoarterial discordance). This defect results in the creation of two parallel circulations in which deoxygenated systemic venous blood returns to the right atrium and is sent back to the systemic circulation via the right ventricle and aorta, while simultaneously, oxygenated pulmonary venous blood returning to the left atrium is pumped back to the lungs via the left ventricle and pulmonary artery (figure 1). (See 'Anatomy' above and 'Physiology' above.)

Other cardiac abnormalities that may occur in association with D-TGA include (see 'Other cardiac anomalies' above):

•Ventricular septal defect (VSD)

•Left ventricular outflow tract obstruction

•Aortic arch obstruction

•Mitral and tricuspid valve abnormalities

•Coronary artery anatomical variations (table 1 and figure 3)

These defects may impact cardiac function and mixing between the two circulatory systems and have an impact on surgical approach. (See "D-transposition of the great arteries (D-TGA): Management and outcome", section on 'Surgery'.)

●Prevalence and natural history – D-TGA is one of the more common cyanotic congenital heart disease (CHD) lesions, with an estimated prevalence of 2 to 5 per 10,000 live births. Without prompt treatment, the risk of mortality is high. (See 'Epidemiology' above and 'Natural course' above.)

●Lack of genetic association – Unlike other forms of CHD, D-TGA is not associated with any genetic abnormality or familial inheritance pattern. D-TGA is also less frequently associated with noncardiac anomalies compared with other CHD defects. (See 'Genetics' above.)

●Presentation – Clinical findings depend upon the degree of mixing between the two circulatory systems and the presence of other cardiac anomalies. Typical findings include cyanosis and tachypnea. Murmurs are not a prominent feature, unless there is a VSD or left ventricular outflow tract obstruction. (See 'Presentation' above.)

●Diagnosis – D-TGA may be diagnosed prenatally or postnatally. (See 'Diagnosis' above.)

•Fetal diagnosis – D-TGA is one of the more difficult CHD defects to detect by fetal ultrasound. Prenatal diagnosis is enhanced if sonographic screening includes views of the outflow tracts. (See 'Fetal diagnosis' above and "Congenital heart disease: Prenatal screening, diagnosis, and management".)

•Postnatal diagnosis – The postnatal diagnosis of D-TGA is based on clinical suspicion for cyanotic CHD and is confirmed by echocardiography (image 1). (See 'Postnatal diagnosis' above.)