Transposition of the Great Arteries: Classification, Epidemiology, Pathophysiology, Clinical Features, Diagnosis, Management

Transposition of the Great Arteries (TGA)

~Introduction

Transposition of the Great Arteries (TGA) is a severe congenital heart defect in which the two main arteries leaving the heart—the aorta and the pulmonary artery—are switched (transposed) from their normal positions. In this condition, the aorta arises from the right ventricle, and the pulmonary artery arises from the left ventricle. This anatomical reversal results in two parallel circulations instead of the normal series circulation, leading to a life-threatening situation where oxygen-rich blood and oxygen-poor blood circulate separately without adequate mixing.

TGA accounts for approximately 5–7% of all congenital heart defects and is the most common cyanotic congenital heart disease presenting in the newborn period. Without intervention, it is fatal in the first few weeks or months of life. Early diagnosis and surgical correction have dramatically improved survival rates, making TGA one of the most successfully treatable complex congenital cardiac defects today.

~Normal Anatomy and Circulation

In normal cardiac anatomy:

• The right atrium receives deoxygenated blood from the body and pumps it into the right ventricle, which sends the blood to the lungs via the pulmonary artery.

• The left atrium receives oxygenated blood from the lungs and pumps it into the left ventricle, which then sends it to the body via the aorta.

This configuration ensures that deoxygenated blood is sent to the lungs for oxygenation and oxygenated blood is delivered to the systemic circulation.

~Anatomy in Transposition of the Great Arteries

In TGA:

• The aorta arises from the right ventricle, and

• The pulmonary artery arises from the left ventricle.

This creates two parallel circulations:

1. Systemic circulation: Deoxygenated blood returns from the body to the right atrium → right ventricle → aorta → body (without going to the lungs).

2. Pulmonary circulation: Oxygenated blood from the lungs returns to the left atrium → left ventricle → pulmonary artery → lungs (without reaching the body).

Without a communication (mixing) between these two circulations—such as an atrial septal defect (ASD), ventricular septal defect (VSD), or patent ductus arteriosus (PDA)—oxygenated and deoxygenated blood cannot mix, leading to severe hypoxemia and cyanosis.

~Embryology and Pathogenesis

The heart develops from a simple tubular structure that undergoes looping and septation to form the four chambers and great vessels. Normally, the conotruncal (outflow tract) septum spirals during development, aligning the aorta with the left ventricle and the pulmonary artery with the right ventricle.

In TGA, failure of the conotruncal septum to spiral results in a straight septation, causing the aorta to connect with the right ventricle and the pulmonary artery with the left ventricle. The exact cause of this developmental error is not fully understood but may involve genetic and environmental factors.

~Classification of TGA

TGA can be divided into two main categories based on the relationship of the atria and ventricles:

1. D-Transposition of the Great Arteries (D-TGA):

   • The most common and clinically significant form.

   • Aorta is positioned anterior and to the right of the pulmonary artery.

   • There is atrioventricular concordance but ventriculoarterial discordance.

   • Cyanosis is severe and presents at birth.

2. L-Transposition of the Great Arteries (L-TGA):

   • Also called “congenitally corrected TGA” (ccTGA).

   • There is both atrioventricular and ventriculoarterial discordance.

   • Blood flow is physiologically corrected, so cyanosis is minimal or absent initially.

   • However, over time, the morphological right ventricle (serving as systemic ventricle) may fail.

This article primarily focuses on D-Transposition of the Great Arteries, as it represents the classical and critical neonatal presentation.

~Epidemiology

• Incidence: approximately 20–30 cases per 100,000 live births.

• Accounts for 5–7% of all congenital heart defects.

• Male predominance (male-to-female ratio ≈ 3:1).

• Often diagnosed prenatally by fetal echocardiography or within the first few hours after birth due to cyanosis.

~Associated Cardiac Anomalies

Many infants with TGA have additional cardiac defects that permit mixing between systemic and pulmonary circulations, which are essential for survival before surgery. Common associated defects include:

• Atrial septal defect (ASD) – 30–40%

• Ventricular septal defect (VSD) – 40–50%

• Patent ductus arteriosus (PDA) – 40%

• Left ventricular outflow tract obstruction

• Pulmonary stenosis

• Coarctation of the aorta

~Pathophysiology

In D-TGA, because the systemic and pulmonary circuits are in parallel, oxygenated blood repeatedly circulates between the lungs and left heart, while deoxygenated blood circulates between the body and right heart.
The only way oxygenated blood reaches systemic circulation is through mixing at the atrial, ventricular, or ductal level.

Therefore, the degree of cyanosis and systemic oxygenation depends on the extent of this mixing:

• Minimal mixing → profound cyanosis and acidosis → early death.

• Adequate mixing (large ASD or VSD) → better oxygenation but risk of heart failure due to pulmonary overcirculation.

Over time, the right ventricle (RV), which supplies systemic circulation, undergoes hypertrophy due to increased afterload, while the left ventricle (LV) may regress in function because it pumps into the low-pressure pulmonary system.

~Clinical Features

Neonatal Period

• Cyanosis within minutes to hours after birth (most prominent feature).

• Tachypnea and respiratory distress without significant murmur.

• Poor feeding, lethargy, and failure to thrive.

• Metabolic acidosis due to tissue hypoxia.

• In cases with VSD, symptoms of congestive heart failure may dominate after a few days as pulmonary blood flow increases.

Physical Examination

• Cyanosis unresponsive to oxygen therapy.

• Tachycardia and tachypnea.

• Single loud second heart sound (S2) due to anterior position of the aorta.

• Murmurs (if VSD or PDA present).

• Hepatomegaly if heart failure develops.

~Diagnosis

Early diagnosis is crucial for survival. The following tools are used:

1. Pulse Oximetry Screening

Newborn screening with pulse oximetry detects hypoxemia. Saturation <90% despite oxygen therapy raises suspicion for TGA or other cyanotic heart diseases.

2. Chest X-Ray

• “Egg-on-a-string” appearance: narrow superior mediastinum due to abnormal aortic position and cardiomegaly.

• Increased pulmonary vascular markings if VSD or PDA is present.

3. Electrocardiogram (ECG)

• Shows right ventricular hypertrophy (RVH) due to systemic workload.

• Right axis deviation.

4. Echocardiography

• Gold standard diagnostic tool.

• Shows parallel course of great arteries, with aorta arising from the right ventricle and pulmonary artery from the left ventricle.

• Evaluates associated defects (ASD, VSD, PDA).

5. Cardiac Catheterization

• Used when non-invasive imaging is inconclusive or before intervention.

• Measures oxygen saturation and pressure gradients.

• Can be therapeutic (balloon atrial septostomy).

6. Fetal Echocardiography

• Detects TGA prenatally, allowing early postnatal management planning.

~Immediate Management

Neonates with TGA are medical emergencies. The goal is to maintain adequate oxygenation and promote mixing between systemic and pulmonary circulations.

1. Prostaglandin E1 (PGE1) infusion:

   • Keeps the ductus arteriosus patent, allowing blood to mix and oxygenate.

   • Administered intravenously at 0.01–0.1 µg/kg/min.

2. Balloon Atrial Septostomy (Rashkind Procedure):

   • Performed in the catheterization lab if interatrial communication is inadequate.

   • A balloon-tipped catheter is passed into the left atrium via the foramen ovale and abruptly withdrawn to enlarge the opening, enhancing blood mixing.

3. Oxygen and Ventilatory Support:

   • Supplemental oxygen improves saturation marginally but is still supportive.

4. Correction of Acidosis and Heart Failure:

   • Administer sodium bicarbonate, inotropes, and diuretics as needed.

Definitive surgical correction is required for survival beyond the neonatal period.

~Surgical Management

1. Arterial Switch Operation (Jatene Procedure):

• Standard and preferred surgical treatment for D-TGA.

• Performed within the first 2–3 weeks of life.

• The aorta and pulmonary artery are transected and reattached to the correct ventricles (aorta to left ventricle, pulmonary artery to right ventricle).

• The coronary arteries are reimplanted into the new aorta.

• Restores normal physiology and left ventricle assumes systemic workload.

2. Atrial Switch Procedures (Senning and Mustard Operations):

• Historical surgeries performed before the advent of the arterial switch.

• Create intra-atrial baffles to redirect blood flow at the atrial level.

• Physiologically correct but anatomically uncorrected—right ventricle remains systemic.

• Associated with long-term complications: arrhythmias, systemic RV failure.

3. Rastelli Procedure:

• Performed when TGA coexists with large VSD and pulmonary stenosis.

• Involves channeling left ventricular outflow to the aorta through the VSD and connecting the right ventricle to the pulmonary artery via a conduit.

~Postoperative Care and Complications

After the arterial switch operation, infants are monitored for:

• Coronary insufficiency (due to reimplantation issues)

• Pulmonary artery stenosis

• Neoaortic root dilation or regurgitation

• Arrhythmias

• Residual shunts or obstruction

Long-term survival after arterial switch exceeds 90–95%, but regular follow-up is essential to monitor cardiac function.

~Complications of Unrepaired TGA

If left untreated:

• Severe hypoxemia → metabolic acidosis → multi-organ failure.

• Heart failure due to right ventricular overload.

• Pulmonary hypertension (especially in cases with large VSD).

• Death usually occurs within the first year of life.

~Long-Term Prognosis

The arterial switch operation has revolutionized TGA outcomes:

• Survival rate: >90% at 10 years.

• Quality of life: Excellent, with near-normal physical activity.

• Lifelong follow-up: Required for coronary artery patency, neoaortic dilation, and arrhythmias.

Adults with repaired TGA should be monitored by adult congenital heart disease specialists to detect late complications such as ventricular dysfunction or valvular disease.

~Transposition of the Great Arteries (L-TGA or ccTGA)

In L-TGA, the heart’s connections are “double discordant”:

• The right atrium connects to the morphological left ventricle, which pumps into the pulmonary artery.

• The left atrium connects to the morphological right ventricle, which pumps into the aorta.

Thus, despite the anatomic inversion, circulation is physiologically corrected, and cyanosis is minimal. However, long-term problems occur because the right ventricle is not designed to sustain systemic pressures, leading to systemic RV failure, tricuspid regurgitation, and heart block in adulthood.

~Recent Advances

• Fetal intervention research: Improved prenatal diagnosis through high-resolution fetal echocardiography allows planning for immediate postnatal care.

• Hybrid procedures: Combining catheter-based and surgical techniques for complex cases.

• Coronary artery imaging: Advanced CT/MRI techniques enhance postoperative follow-up.

• Stem cell therapy and tissue-engineered grafts: Being explored to manage postoperative cardiac dysfunction and conduit failure.

~Conclusion

Transposition of the Great Arteries is a life-threatening congenital malformation that disrupts normal blood circulation between the heart and lungs. Early recognition, prompt stabilization with prostaglandins and balloon atrial septostomy, and timely surgical correction—especially the arterial switch operation—have transformed the prognosis of this once-fatal disease into one with excellent long-term survival and quality of life. Continuous advances in prenatal detection, surgical innovation, and lifelong cardiac follow-up promise even better outcomes for patients with TGA in the future.