Transposition of the Great Arteries

Etiology

The etiology for transposition of the great arteries is unknown; however, it is presumed to be multifactorial. Currently, there are two main theories regarding the embryological mechanisms of TGA development:

• De la Cruz proposed the theory that the aortopulmonary septum fails to spiral at the level of the infundibulum thus causing a linear development of the septum and TGA. [2]
• The second theory, proposed by Goor and Edwards, suggests that TGA is caused by abnormal resorption or underdevelopment of the subpulmonary conus, with persistence of the subaortic conus. [3]

Epidemiology

The prevalence of TGA is 4.7 per 10,000 live births. TGA accounts for three percent of all congenital heart disease and 20 percent of cyanotic heart disease.[4]

Pathophysiology

Knowledge of normal conotruncal septum formation facilitates understanding of D-TGA development. In the fifth week of gestation, opposing pairs of ridges form in the truncus arteriosus. These ridges are termed the right superior truncus swelling and the left inferior truncus swelling. The right superior truncus swelling grows distally and to the left while the left inferior truncus swelling grows distally and to the right. The result is twisting of the swellings around each other and the foreshadowing of the anatomically normal spiral septum.  

Simultaneously, swellings in the dorsal and ventral walls of the conus cordis appear and grow toward each other and distally. Eventually, these swellings fuse with each other, as well as the truncus septum, thus dividing the conus cordis into anterolateral (right ventricular outflow tract) and posteromedial (left ventricular outflow tract) portions. 

Equally important to septal formation, is the migration of neural crest cells through pharyngeal arches three, four, and six, and to the heart. There, they contribute to endocardial cushion formation in the truncus arteriosus and conus cordis, as well as lengthening of the outflow tracts. Any insult to the migration of neural crest cells can cause tetralogy of Fallot, truncus arteriosus, and TGA. It is not uncommon to see cardiac and craniofacial defects in the same individual since neural crest cells also contribute to craniofacial development.

Transposition of the great arteries occurs when the aorticopulmonary septum fails to spiral. This can be due to defects in the maturation of the right superior truncus swelling and the left inferior truncus swelling, fusion of the conus swellings with the aorticopulmonary septum, or adversities in neural crest development or migration.

The pathological defects in D-TGA cause a detrimental change in cardiac physiology. Due to the existence of two parallel circuits, deoxygenated blood continues to circulate systemically, and oxygenated blood continually flows through the pulmonary circuit. Parallel channels are incompatible with life unless mixing between deoxygenated and oxygenated blood occurs. Mixing can occur via an atrial or ventricular septal defect, patent ductus arteriosus, or through collateral bronchopulmonary circulation. Interventional cardiologists may also perform a balloon atrial septostomy (BAS) to facilitate mixing between the atria. [1] 

Several common cardiac anomalies that can occur in patients with D-TGA can include:

• Ventriculoseptal defects
• Left ventricular outflow tract obstruction
• Mitral and tricuspid valve abnormalities
• Coronary artery variations

A lesser known form of TGA is levo-TGA (L-TGA). In this case, the left ventricle is positioned to the right of the right ventricle. Mainly, the ventricles are on opposite sides of the heart. The pulmonary trunk and aorta arise in their anatomically correct orientations, however, since the ventricles are reversed, the aorta is fused with the right ventricle, and the pulmonary trunk is combined with the left ventricle. The resultant flow of blood in a patient with L-TGA is as follows: Deoxygenated blood enters the anatomically correct right atrium, passes through the mitral valve into the left ventricle, and is pumped into the pulmonary trunk to the lungs. From the lungs, the oxygenated blood enters the left atrium, passes through the tricuspid valve, and into the right ventricle where blood is then pumped into the aorta. Since the flow of blood in patients with L-TGA passes through the normal systemic and pulmonary circuits, L-TGA is sometimes termed anatomically correct TGA. [5]

History and Physical

Antenatally, TGA is challenging to diagnose. Screening ultrasounds do not routinely reveal TGA in-utero.

Postnatal:

The clinical features of D-TGA are solely dependent on the degree of mixing between the parallel circuits. Most patients present with signs and symptoms during the neonatal period (first 30 days of life). The following are the typical clinical manifestations of TGA:

• Cyanosis: The degree of cyanosis is dependent on the amount of mixing between the two parallel circuits. Factors affecting intracardiac mixing include the size and presence of an ASD or VSD. Cyanosis is not affected by exertion or supplemental oxygen. [6]
• Tachypnea: Patients usually have a respiratory rate higher than 60 breaths per minute but without retractions, grunting, or flaring and appear comfortable.
• Murmurs: murmurs are not typically present unless a small VSD or pulmonic stenosis exists. A murmur resulting from a VSD will be pansystolic and prominent at the lower left sternal border. Pulmonic stenosis causes a systolic ejection murmur at the upper left sternal border. [7]

Patients with L-TGA are typically unaffected until later in life when the right ventricle can no longer compensate for the increased afterload of the systemic circulation. These patients present with signs and symptoms of heart failure. [7]

Evaluation

As previously stated, D-TGA is difficult to detect on fetal ultrasound due to the absence of differences in ventricle size. [8] Postnatally, when a cardiac disease is suspected based on clinical exam, echocardiography is performed. Echocardiography will reveal the aberrant origins of the aorta and pulmonary trunk as well as any associated intracardiac defects. Other studies often performed include:

• Electrocardiography: Often normal but may show right axis deviation and right ventricular hypertrophy
• Chest radiography: The classic radiographic features of TGA is an “egg on a string” appearance.
• Cardiac catheterization: Angiography is rarely used to diagnose TGA; however, it is the gold standard for elucidating the origins of the coronary arteries. Cardiac catheterization is routinely used in D-TGA to perform a balloon septostomy in patients with severe cyanosis.[9]

Treatment / Management

Initial management of patients with D-TGA centers on ensuring adequate oxygenation. Prostaglandin E1 administration stabilizes patients by attempting to keep the ductus arteriosus patent and performing a balloon atrial septostomy (BAS). Once the patient is hemodynamically stable, corrective surgery can be performed. [10] [11](B3)

Surgical repair of D-TGA is usually undertaken within the first week of life. There are currently two commonly used surgical procedures for D-TGA:

• Arterial switch operation (ASO):  The arterial switch operation is the standard procedure for patients with D-TGA without major pulmonic stenosis. During the ASO, the surgeon will transect both the pulmonary trunk and aorta then translocate them to their anatomically correct positions. The coronary arteries are mobilized and reimplanted into the aortic trunk. If a VSD is present., it is also repaired during this time. [12]
• Rastelli procedure: The Rastelli procedure is indicated in patients presenting with D-TGA, a large VSD, and pulmonary stenosis. During this procedure, the VSD is closed using a baffle. By doing so, oxygenated blood from the left ventricle is directed into the aorta. A conduit is then placed from the right ventricle to the pulmonary artery thus shunting deoxygenated blood into the pulmonary artery. [13]
(B3)

Other corrective procedures exist including the Mustard and Senning procedure, Nakaidoh procedure, Réparation à l'Etage ventriculaire (REV) procedure, and Yasui procedure however these are less commonly performed. [14](B2)

Differential Diagnosis

• Double-Outlet Right Ventricle
• Tricuspid Atresia
• Pulmonary Atresia
• Tetralogy of Fallot     
• Total anomalous pulmonary venous return
• Truncus arteriosus

Prognosis

The prognosis for patients with D-TGA is generally excellent following surgical correction. Current survival rates are greater than 90%. The ASO has the best long-term survival and functional outcome. Some studies report a >95% rate survival at fifteen to twenty-five years following discharge. [15][16]

Complications

Several complications can result following corrective operations. These include:

• Arrhythmias [17]
• Obstruction or leakage of the baffle (Rastelli Procedure) 
• Pulmonary artery stenosis 
• Coronary artery stenosis
• Aortic root dilation 
• Aortic regurgitation [18]