Transposition and malposition of great arteries

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Introduction and Morphology

Transposition of the great arteries (TGA) accounts for approximately 5% of all congenital heart disease with an incidence of 3.5 per 10,000 live births.
There is a significant male preponderance, with a ratio ranging from 1.5:1 up to 3.2:1.
The condition is more frequently observed in the infants of diabetic mothers and in Caucasian infants compared to those of African-American heritage.
TGA is rarely associated with common genetic syndromes (such as Turner, Noonan, Williams, Marfan, or Trisomy 21) or aneuploidy, though a 22q11.2 microdeletion should be ruled out if other anomalies are present.
The mean recurrence risk for a congenital cardiac lesion in a sibling is remarkably low, estimated at 0.2%.
The primary morphological hallmark is atrioventricular concordance paired with ventriculoarterial discordance.
The right atrium connects to the morphologic right ventricle, which discordantly connects to the aorta.
The left atrium connects to the morphologic left ventricle, which discordantly connects to the pulmonary artery.
The aorta typically arises anteriorly and to the right of the pulmonary artery, representing a dextro-positioned (d-TGA) configuration.
Morphologically, there is a subaortic conus present instead of the normally expected subpulmonic conus, and the great vessels maintain a parallel, non-crossing relationship.
Approximately 50% of patients with TGA will have an associated ventricular septal defect (VSD), and anomalous coronary arteries are seen in 10-15% of patients.
Coronary artery origins are described using the Leiden convention: looking from the non-adjacent aortic sinus toward the pulmonary trunk, sinus #1 is to the right hand and sinus #2 is to the left hand. The most common pattern involves the left anterior descending and circumflex arteries arising from sinus #1, and the right coronary artery arising from sinus #2.

Pathophysiology and Fetal Circulation

Due to ventriculoarterial discordance, the systemic and pulmonary circulations run as two parallel circuits rather than in series.
Deoxygenated systemic venous blood returns to the right atrium and right ventricle, and is inappropriately ejected via the aorta back to the body.
Oxygenated pulmonary venous blood returns to the left atrium and left ventricle, and is ejected directly back to the lungs via the pulmonary artery.
Survival in the newborn period absolutely depends on the mixing of oxygenated and deoxygenated blood through communications at the atrial (patent foramen ovale/ASD), ventricular (VSD), or arterial (patent ductus arteriosus) levels.
The hemodynamics depend heavily on the effective pulmonary blood flow (QpEF), which is the proportion of deoxygenated blood that travels to the lungs, and effective systemic blood flow (QsEF), which is the oxygenated blood distributed to the body.
In fetuses with TGA, oxygen-rich blood from the inferior vena cava and ductus venosus is directed across the foramen ovale into the left heart and is subsequently pumped out the pulmonary artery.
This highly oxygenated blood in the fetal pulmonary circulation can cause pulmonary vasodilation and increased pulmonary blood flow in utero, which subsequently increases pulmonary venous return and elevates left atrial pressures.
The elevated left atrial pressure in utero can result in restriction of the foramen ovale flap and a significantly smaller foramen ovale after 28 weeks of gestation.
Following birth, a drop in pulmonary vascular resistance redirects ductal flow from the aorta to the pulmonary circulation, increasing left atrial return and forcing the foramen ovale open against the elevated right atrial pressures typical of TGA.

Clinical Manifestations

Infants with TGA and an intact ventricular septum (IVS) usually present with severe, life-threatening cyanosis and tachypnea within the first hours or days of life as the ductus arteriosus begins to close.
Very early in the postnatal period, right-to-left shunting across the ductus arteriosus may result in reverse differential cyanosis (oxygen saturations are higher in the lower extremities than in the upper extremities).
In patients with TGA and a large VSD, presentation may be delayed to 4-10 weeks of age when pulmonary vascular resistance falls; these infants typically develop congestive heart failure due to pulmonary overcirculation.
TGA with a VSD and pulmonary stenosis mirrors the clinical presentation of Tetralogy of Fallot, presenting with cyanosis and a systolic murmur.

Diagnostic Investigations

Auscultation

The precordial impulse may appear normal, or a parasternal heave may be appreciated.
The first heart sound is normal.
The second heart sound (S2) is typically single and loud (representing anterior aortic valve closure), though it may be normally split.
Murmurs may be completely absent, or a soft grade 1 to 2 ejection systolic murmur may be audible at the mid-left sternal border.
The presence of a harsh holosystolic murmur at the lower left sternal border indicates the presence of a VSD.
An apical third heart sound (S3) gallop or a mid-diastolic rumble may be heard if pulmonary blood flow is significantly increased.

Chest Radiograph (CXR)

The classic pathognomonic finding is the "egg on a string" or "egg on side" appearance of the cardiac silhouette.
This appearance is driven by a narrowed upper mediastinum (because the great vessels run parallel rather than crossing) and a globular heart shape (due to right and left atrial enlargement).
The thymic shadow is frequently absent, accentuating the narrow pedicle.
In the early newborn period, pulmonary blood flow generally appears normal but will become plethoric as pulmonary vascular resistance drops or if a VSD is present.

Electrocardiogram (ECG)

The ECG in a neonate with TGA is usually normal for age, demonstrating the expected right-axis deviation and right ventricular hypertrophy characteristic of the newborn period.
In TGA with a VSD, biventricular hypertrophy may develop.

Echocardiography

Echocardiography provides the definitive diagnosis by confirming the transposed ventricular-arterial connections.
The subcostal sweep clearly demonstrates the posterior pulmonary artery arising from the left ventricle and bifurcating into its branches, while the anterior aorta arises from the right ventricle without bifurcating.
Parasternal short-axis views reveal two circular semilunar valves side-by-side, with the aorta typically positioned anteriorly and to the right.
Color and pulsed-wave Doppler are indispensable for evaluating the size and direction of flow across the patent foramen ovale (PFO), VSD, and ductus arteriosus.
A bowing atrial septum (>50%), hypermobile septum, or an angle of the septum primum <30 degrees suggests a restrictive atrial communication requiring immediate intervention.

Cardiac Catheterization

Diagnostic cardiac catheterization is rarely needed unless there are complex associated anomalies, questionable coronary artery anatomy, or concerns regarding coarctation of the aorta.
The primary role of catheterization is therapeutic: performing a Balloon Atrial Septostomy (Rashkind procedure) under fluoroscopic or echocardiographic guidance to tear the septum primum and establish reliable atrial mixing.

Antenatal Diagnosis and Management

Fetal diagnosis is made via obstetric ultrasound evaluating the outflow tracts; the standard four-chamber view may appear completely normal.
The diagnosis relies heavily on the abnormal three-vessel and trachea view, producing an "I-sign" where a single anteriorly displaced aorta is visualized instead of the normal "V" shaped convergence of the ductal and aortic arches.
Prenatal detection significantly improves outcomes by allowing for planned delivery at 39-40 weeks of gestation at a tertiary care center equipped with pediatric cardiothoracic surgery and extracorporeal membrane oxygenation (ECMO) capabilities.
Maternal hyperoxia testing can be used during fetal echocardiography to assess pulmonary vasoreactivity; changes in the septum primum position or foramen ovale flow during maternal oxygen administration may predict the postnatal need for a balloon atrial septostomy.

Medical Management

The immediate postnatal priority is stabilization and ensuring adequate mixing between the parallel circulations.
An intravenous infusion of Prostaglandin E1 (PGE1) at 0.05-0.1 µg/kg/min must be initiated promptly to maintain or reopen the ductus arteriosus.
Metabolic acidosis and hypoglycemia must be corrected, and the infant should be kept warm to prevent hypothermia from exacerbating acidosis.
If hypoxemia is severe despite PGE1, emergent Balloon Atrial Septostomy (BAS) is indicated to relieve left atrial pressure and guarantee bidirectional mixing.
Elective intubation and positive pressure ventilation may be needed to manage heart failure or to stabilize the patient for septostomy or surgical intervention.

Surgical Management

Arterial Switch Operation (ASO) / Jatene Procedure

The Arterial Switch Operation is the definitive treatment of choice for TGA with intact ventricular septum and is ideally performed within the first 1 to 2 weeks of life.
Operating within this narrow window is critical; as pulmonary vascular resistance falls, the left ventricular pressure decreases, causing the left ventricular muscle mass to rapidly regress. If delayed, the left ventricle will be unable to pump against the high-pressure systemic circulation.
The procedure is performed under cardiopulmonary bypass with hypothermia and cardioplegic arrest.
The aorta and pulmonary artery are transected above the sinotubular junction.
The coronary arteries are excised from the native aortic root along with a "button" of surrounding tissue and are translocated to the neoaortic root (the proximal native pulmonary artery).
The LeCompte maneuver is routinely employed, bringing the distal pulmonary artery bifurcation anterior to the ascending aorta before completing the anastomoses.
Any associated VSDs are closed during the same operation.
If a patient presents late (after 6-8 weeks) with a deconditioned left ventricle, a two-stage approach is utilized: initial placement of a pulmonary artery band (to "retrain" the left ventricle by increasing its afterload) and an aortopulmonary shunt, followed by the ASO months later.

Atrial Switch Operations (Mustard or Senning Procedures)

Historically the procedure of choice, the atrial switch is now reserved for patients whose complex anatomy (e.g., untransferable coronary arteries or irreparable left ventricular outflow tract obstruction) precludes the ASO.
These procedures involve extensive atrial reconstruction utilizing pericardial or synthetic baffles to redirect systemic venous return to the left ventricle (and out the pulmonary artery) and pulmonary venous return to the right ventricle (and out the aorta).
This leaves the morphologic right ventricle to function permanently as the systemic pumping chamber.

Complex TGA Repairs (Rastelli or Nikaidoh Procedures)

In the subset of patients (approximately 5%) with TGA, a VSD, and significant pulmonary outflow tract obstruction, standard ASO is contraindicated.
The Rastelli procedure involves baffling the left ventricle through the VSD to the aorta and placing an extracardiac valved conduit from the right ventricle to the pulmonary artery.
The Nikaidoh procedure involves aortic translocation, where the entire aortic root is harvested and moved posteriorly over the left ventricle, and the right ventricular outflow tract is reconstructed anteriorly.

Postoperative Complications and Long-Term Follow-up

Following the Arterial Switch Operation (ASO)

Short- and mid-term survival is exceptional, with survival rates exceeding 95-99% at expert centers.
The most frequent long-term complication and primary reason for reoperation is right ventricular outflow tract obstruction, particularly stenosis at the branch pulmonary arteries secondary to the LeCompte maneuver.
Neoaortic root dilation and varying degrees of neoaortic valve regurgitation occur progressively, though the need for surgical aortic valve intervention remains relatively low.
Coronary artery insufficiency (stenosis or occlusion) due to manipulation at the time of transfer affects up to 8% of patients, requiring surveillance imaging (CMR, CCT, or stress testing) in asymptomatic adults.
Neurodevelopmental monitoring is essential; patients are at risk for fine and gross motor delays, speech delays, and deficits in executive function, working memory, and visual-spatial skills related to bypass times and preoperative hypoxia.

Following the Atrial Switch Operation (Mustard or Senning)

Long-term survival is markedly lower, with 30-year survival rates estimated at 60-70%.
Progressive failure of the systemic right ventricle is ubiquitous, occurring in 50% of patients by age 35.
Dilation of the right ventricle leads to secondary severe systemic tricuspid valve regurgitation.
Extensive atrial suture lines result in a high incidence of arrhythmias; loss of sinus rhythm, sick sinus syndrome, and atrial flutter affect over 50% of patients by age 25.
Sudden cardiac death is a significant risk, and prophylactic cardioverter-defibrillator (ICD) implantation is indicated in high-risk patients with a history of syncope or documented ventricular arrhythmias.
Baffle obstruction is common, particularly stenosis of the superior vena cava limb, which may remain clinically silent due to decompression via the azygous venous system but can severely complicate transvenous pacemaker placement.
Baffle leaks can lead to significant right-to-left or left-to-right shunting, further compromising hemodynamics.