Transposition of the great vessels

Transposition of the great arteries (TGA), also known as transposition of the great vessels, is a rare congenital heart defect present at birth in which the two main arteries carrying blood away from the heart—the aorta and the pulmonary artery—are reversed in their positions, leading to parallel circulations of oxygenated and deoxygenated blood that severely limits oxygen delivery to the body.^[1] This cyanotic condition disrupts normal blood flow, where oxygen-rich blood from the lungs recirculates back to the lungs instead of reaching the body, and oxygen-poor blood from the body returns to the heart without proper oxygenation.^[2] Without intervention, it is life-threatening, but surgical correction typically allows for long-term survival.^[3] TGA primarily occurs in two forms: dextro-transposition of the great arteries (d-TGA), the more common type, in which the aorta arises from the right ventricle and the pulmonary artery from the left ventricle, often accompanied by other defects like a ventricular septal defect (VSD) or atrial septal defect (ASD) that may allow some blood mixing; and congenitally corrected TGA (ccTGA or l-TGA), a rarer variant where the ventricles are also reversed, potentially maintaining adequate blood flow initially but leading to progressive heart complications over time.^[1] The exact cause is usually unknown, though it arises during early fetal heart development between weeks 4 and 7 of pregnancy, with risk factors including maternal rubella infection, diabetes, smoking, alcohol use, or certain medications during pregnancy.^[1] d-TGA affects approximately 1 in 3,957 live births in the United States (based on data from 2016–2020), accounting for about 928 cases annually, and TGA is more common in males.^[3][4] Symptoms of d-TGA typically appear shortly after birth and include cyanosis (bluish or grayish skin, especially around the lips and nails due to low oxygen levels), rapid or pounding heartbeat, weak pulse, shortness of breath, poor feeding, and failure to gain weight, with severity depending on the presence of mixing defects like VSD or patent ductus arteriosus (PDA).^[1] In ccTGA, symptoms may be absent or mild in infancy but can emerge later as heart failure, arrhythmias, or valve problems.^[1] Diagnosis often occurs prenatally via fetal echocardiogram or postnatally through newborn pulse oximetry screening, chest X-ray, electrocardiogram (ECG), or confirmatory echocardiogram, enabling prompt intervention.^[3] Treatment for TGA is surgical and urgent, with the arterial switch operation—performed within the first few weeks of life—being the preferred method for d-TGA, which repositions the arteries to their correct ventricles and reconstructs the aorta and pulmonary artery; for ccTGA, management may involve monitoring or later surgeries like the double switch procedure if complications arise.^[5] Initial stabilization often includes prostaglandin infusions to keep the PDA open for blood mixing and balloon atrial septostomy (Rashkind procedure) via cardiac catheterization to improve oxygenation until surgery.^[2] With timely treatment, survival rates exceed 90%, though lifelong follow-up with a cardiologist is essential to monitor for potential complications such as coronary artery issues, arrhythmias, heart failure, or the need for reoperations.^[6]

Classification

Dextro-transposition of the great arteries

Dextro-transposition of the great arteries (d-TGA) is a cyanotic congenital heart defect characterized by ventriculo-arterial discordance, in which the aorta arises entirely from the morphological right ventricle and the pulmonary artery from the morphological left ventricle, while atrioventricular concordance is preserved.^[7] This results in the great arteries running in parallel rather than in series, with the aorta typically positioned anterior and to the right of the pulmonary artery in the majority of cases.^[8] The morphological right ventricle supports the systemic circulation, pumping deoxygenated blood back to the body, while the morphological left ventricle sustains the pulmonary circulation, recirculating oxygenated blood to the lungs.^[7] In the immediate postnatal period, survival depends on adequate mixing of oxygenated and deoxygenated blood to prevent profound cyanosis and hypoxemia. This mixing occurs primarily through a patent foramen ovale (PFO), which is present in nearly all newborns, or through an atrial septal defect (ASD) or ventricular septal defect (VSD) if associated defects exist; a patent ductus arteriosus (PDA) may also provide temporary mixing until it closes.^[8] Without sufficient shunting, neonates develop severe cyanosis within hours to days of birth, as the parallel circulations fail to oxygenate systemic blood effectively.^[7] d-TGA accounts for approximately 20-25% of all cyanotic congenital heart diseases and occurs in about 1 in 4,000 live births worldwide.^[9] It represents 5-7% of all congenital heart defects overall, with a male predominance of 2-3:1.^[10] Associated cardiac lesions are common and influence management; a VSD is present in 40-50% of cases, allowing better mixing but complicating surgical correction, while pulmonary stenosis affects 5-10% and obstructs pulmonary blood flow from the left ventricle.^[11] Other less frequent associations include coronary artery anomalies, which occur in up to 30% but are not always hemodynamically significant at birth.^[7]

Congenitally corrected transposition of the great arteries

Congenitally corrected transposition of the great arteries (ccTGA), also known as L-transposition of the great arteries, is a rare congenital heart defect characterized by both atrioventricular and ventriculoarterial discordance, resulting in a physiologically "corrected" circulation where systemic venous blood reaches the pulmonary circulation and pulmonary venous blood reaches the systemic circulation despite the transposed great vessels.^[7] In this arrangement, the morphological left ventricle is connected to the pulmonary artery, while the morphological right ventricle is connected to the aorta, leading to the right ventricle functioning as the systemic pump.^[12] Anatomically, the great arteries are typically L-malposed, with the aorta positioned anterior and to the left of the pulmonary artery, and the heart often exhibits mesocardia or levoposition of the aorta.^[13] This condition accounts for less than 1% of all congenital heart defects, with an estimated incidence of approximately 1 in 33,000 live births.^[7] It is more common in males and has a recurrence risk of about 2% in first-degree relatives.^[14] Common associated lesions include ventricular septal defects in 70-80% of cases, pulmonary stenosis or other left ventricular outflow tract obstructions in 25-50%, and tricuspid valve abnormalities—such as Ebstein-like malformation—leading to systemic atrioventricular valve regurgitation in up to one-third of patients.^[12] Complete heart block occurs in about 30% due to an abnormal anterior atrioventricular conduction pathway.^[7] Physiologically, ccTGA allows for initially normal blood flow without significant cyanosis in the neonatal period, as the double discordance maintains separate pulmonary and systemic circulations.^[14] However, over time, the morphological right ventricle, unadapted to high systemic pressures, often develops progressive dysfunction and failure, exacerbated by tricuspid regurgitation or associated obstructions, leading to symptoms that typically manifest in adolescence or adulthood.^[13] Echocardiography is the primary diagnostic tool, revealing the discordant connections and associated anomalies.^[7]

Associated cardiac lesions

Transposition of the great vessels (TGV) is classified as simple when it occurs without significant associated cardiac defects, particularly an intact ventricular septum, requiring adequate mixing of oxygenated and deoxygenated blood through an atrial septal defect (ASD), patent foramen ovale (PFO), or patent ductus arteriosus (PDA) for postnatal survival.^[10] In contrast, complex TGV involves transposition alongside additional congenital anomalies, such as a ventricular septal defect (VSD), pulmonary stenosis or atresia, coronary artery anomalies, or subaortic stenosis, which alter hemodynamics and necessitate tailored interventions.^[15] Among patients with dextro-transposition of the great arteries (D-TGA), a VSD is the most common associated lesion, occurring in 30-50% of cases and often located in the perimembranous or subpulmonary region.^[16] Pulmonary stenosis or atresia affects approximately 5-10% of D-TGA cases, typically in combination with a VSD, while subaortic stenosis or left ventricular outflow tract obstruction is seen in about 5-15%, potentially due to abnormal conal tissue.^[10] Coronary artery patterns are abnormal in 30-40% of D-TGA patients, with variations such as intramural courses or single coronary ostia that can complicate surgical reimplantation and increase perioperative risk.30551-9/fulltext) These associated lesions significantly influence the classification and management of TGV, distinguishing isolated cases amenable to arterial switch operation from complex forms requiring procedures like VSD closure or pulmonary artery banding in infancy, and ultimately the Rastelli procedure for those with VSD and pulmonary outflow obstruction to establish an intraventricular baffle and right ventricle-to-pulmonary artery conduit.^[15] Rare associations include the Taussig-Bing anomaly, a variant characterized by double outlet right ventricle (DORV) with subpulmonary VSD and transposed great arteries, occurring in fewer than 5% of transposition cases and often necessitating specialized arterial switch techniques.^[17] Similarly, DORV with transposition-like features represents another infrequent overlap, comprising about 2-3% of complex cyanotic defects and impacting surgical planning due to variable great artery relationships.^[10]

Pathophysiology

Anatomical features

In transposition of the great vessels (TGV), also known as transposition of the great arteries (TGA), the aorta arises from the morphological right ventricle, and the pulmonary artery arises from the morphological left ventricle, resulting in ventriculoarterial discordance that contrasts with the normal anatomy where the aorta originates from the left ventricle and the pulmonary artery from the right ventricle.^[7] This abnormal connection creates parallel circulations, with the aorta positioned to receive oxygenated blood from the pulmonary circuit and the pulmonary artery receiving deoxygenated blood from the systemic circuit.^[18] Positional variations differ between subtypes. In dextro-transposition of the great arteries (D-TGA), the ventricles typically exhibit a D-loop configuration, with the right ventricle positioned to the right of the left ventricle, and the aorta located anterior and to the right of the pulmonary artery.^[7] In congenitally corrected TGA (ccTGA), an L-loop ventricular arrangement is common, placing the left ventricle to the right of the right ventricle, with the aorta anterior and to the left of the pulmonary artery in a parallel rather than crossed orientation.^[19] The morphological right ventricle, which is thinner-walled and less adapted for high-pressure systemic output compared to the left ventricle, serves as the systemic ventricle in both D-TGA and ccTGA, increasing its susceptibility to long-term failure, particularly in ccTGA where atrioventricular discordance also occurs.^[7] Associated features often include an obligatory atrial septal defect (ASD) or patent foramen ovale (PFO) to permit intercirculatory mixing at the atrial level, present in nearly all cases of D-TGA.^[18] A patent ductus arteriosus (PDA) is frequently observed and plays a key role in initial postnatal perfusion by allowing additional mixing between the systemic and pulmonary circulations.^[18] Coronary artery anomalies are common, occurring in approximately 33% of D-TGA cases, with variations such as a single coronary ostium in about 2% and the circumflex artery arising from the right coronary artery in around 16%; these patterns are critical for surgical planning during procedures like the arterial switch operation.^[20]

Hemodynamic effects

In dextro-transposition of the great arteries (D-TGA), the ventriculoarterial discordance results in two parallel circulatory circuits: deoxygenated systemic venous blood returns to the right atrium and ventricle, then enters the aorta to recirculate to the body, while oxygenated pulmonary venous blood returns to the left atrium and ventricle, then enters the pulmonary artery to recirculate to the lungs.^[7] This configuration prevents effective gas exchange between the systemic and pulmonary circulations, rendering it incompatible with sustained life without intercirculatory mixing.^[7] Survival depends on mechanisms that allow bidirectional shunting and mixing of oxygenated and deoxygenated blood, primarily at the atrial level through a patent foramen ovale (PFO) or atrial septal defect (ASD), or at the ventricular level via a ventricular septal defect (VSD); additional mixing can occur through a patent ductus arteriosus (PDA), which provides flow from the pulmonary artery to the descending aorta.^[7] Without adequate shunts for mixing, the low pulmonary vascular resistance leads to increased pulmonary blood flow, often resulting in a pulmonary-to-systemic flow ratio (Qp/Qs) greater than 1, exacerbating systemic hypoxemia by recirculating more oxygenated blood to the lungs.^[21] The degree of mixing determines the severity of physiological consequences, including profound cyanosis with arterial oxygen saturations typically ranging from 50% to 80%, unresponsiveness to supplemental oxygen, and metabolic acidosis due to anaerobic metabolism from poor systemic oxygenation.^[7] Inadequate mixing can also lead to heart failure as the ventricles face increased workload without benefiting from proper oxygenation.^[7] In congenitally corrected transposition of the great arteries (ccTGA), the double discordance (atrioventricular and ventriculoarterial) physiologically "corrects" the circulation at birth, allowing initially balanced pulmonary and systemic flows with deoxygenated blood reaching the lungs and oxygenated blood the body.^[22] However, the morphologic right ventricle serves as the systemic pump, which over time is prone to progressive dysfunction, often compounded by tricuspid valve regurgitation in the systemic position, leading to right ventricular dilation and eventual heart failure.^[23] Associated lesions like VSDs can maintain hemodynamic balance initially but may contribute to long-term volume overload if not addressed.^[22]

Epidemiology and Risk Factors

Incidence and prevalence

Transposition of the great vessels (TGV), also known as transposition of the great arteries (TGA), has an overall incidence of approximately 1 in 3,000 to 5,000 live births worldwide.^[24] In the United States, as of 2024, the incidence is about 1 in 3,348 live births for TGA (approximately 1,097 cases annually) and 1 in 3,957 for dextro-transposition of the great arteries (d-TGA, approximately 928 cases annually).^[25] Dextro-transposition of the great arteries (D-TGA) accounts for 75% to 90% of all TGV cases, while congenitally corrected TGA (ccTGA) represents a smaller proportion, occurring at a rate of about 1 in 33,000 live births.^[7] This condition constitutes 3% to 5% of all congenital heart defects and up to 20% of cyanotic congenital heart diseases.^[9] The incidence equates to roughly 20 to 30 cases per 100,000 live births annually.^[26] Transposition of the great arteries occurs more frequently among white populations than in other ethnic groups.^[27] A notable male predominance exists, with a male-to-female ratio of 2:1 to 3:1.^[24] The incidence of TGV has remained stable over time, but prenatal screening advancements have enhanced detection rates, rising from about 6% in the 1990s to 38% or higher in recent years, thereby reducing the number of undiagnosed cases at birth.^[28] Without intervention, mortality for D-TGA approaches 90% within the first year of life due to severe cyanosis and heart failure.^[24] In contrast, ccTGA allows for 50% to 70% survival into adulthood without symptoms in cases lacking significant associated lesions, though progressive complications often emerge later.^[29] Familial recurrence risk for TGV is low, estimated at 1% to 5% among siblings of affected individuals, consistent with a polygenic inheritance pattern.^[10][30]

Etiological factors

The etiology of transposition of the great vessels (TGV), also known as transposition of the great arteries (TGA), is largely unknown in the majority of cases, with approximately 80-90% lacking a clearly identifiable cause and suggesting a multifactorial inheritance pattern involving complex interactions between genetic and environmental factors.^[31] Genetic factors play a significant role in a subset of TGV cases, particularly those associated with mutations in genes involved in cardiac development and laterality determination. Mutations in GDF1 (growth differentiation factor 1), a gene encoding a protein in the TGF-β superfamily crucial for left-right axis formation, have been linked to TGA, often in the context of heterotaxy syndromes.^[32] Similarly, mutations in ZIC3 (zinc finger protein of the cerebellum 3), an X-linked gene regulating nodal signaling and embryonic patterning, are associated with TGA, including isolated dextro-transposition and cases with incomplete penetrance in familial pedigrees.^[33] The 22q11.2 deletion syndrome, involving hemizygous deletion of multiple genes on chromosome 22q11, increases susceptibility to conotruncal defects like TGA, with affected individuals showing disrupted neural crest migration essential for outflow tract septation.^[34] Familial recurrence occurs in 1-5% of cases and is frequently tied to heterotaxy, where abnormal visceral situs predisposes to discordant ventriculoarterial connections.^[30] Maternal conditions during pregnancy elevate the risk of TGV through disrupted fetal cardiac morphogenesis. Pre-existing or gestational diabetes mellitus confers a 3- to 5-fold increased risk, likely due to hyperglycemia-induced oxidative stress and altered retinoid signaling that impair outflow tract alignment.^[35] Maternal rubella infection, especially in the first trimester, is a recognized teratogen associated with TGA, as the virus interferes with endothelial cell function and vascular development in the conotruncus.^[36] Exposure to retinoic acid, whether therapeutic (e.g., for acne) or excessive, heightens TGA incidence by ectopic signaling that disrupts neural crest cell contribution to the aorticopulmonary septum, as demonstrated in animal models.^[37] Additional teratogenic influences contribute to TGV, often via interference with retinoic acid pathways or laterality establishment. Prenatal alcohol exposure acts as a teratogen by inducing retinoic acid deficiency, increasing the odds of dextro-TGA by approximately 1.6-fold through inhibition of sonic hedgehog signaling and abnormal conotruncal rotation.^[38] Anticonvulsant use, such as phenytoin, is linked to TGA risk as part of broader fetal hydantoin syndrome, where the drug's metabolites cause vascular disruption and hypoxia in the developing outflow tract.^[39] TGV is also associated with laterality defects, including situs inversus, where reversed organ positioning accompanies discordant great vessel origins, reflecting shared disruptions in nodal cilia function during gastrulation.^[40] Non-genetic risk factors further modulate TGV susceptibility, independent of direct teratogens. Advanced parental age, particularly maternal age over 40 or paternal age exceeding 45, correlates with higher TGA incidence due to accumulated de novo mutations or epigenetic changes affecting cardiogenesis.^[41] Low socioeconomic status is associated with elevated rates, potentially through indirect exposures like poor nutrition, limited prenatal care, or environmental pollutants that exacerbate multifactorial risks.^[42]

Clinical Presentation

Neonatal symptoms

Newborns with dextro-transposition of the great arteries (D-TGA) typically present with symptoms within the first few hours to days of life, primarily due to inadequate mixing of oxygenated and deoxygenated blood in the parallel circulatory pathways.^[3][16] The hallmark sign is profound central cyanosis, manifesting as a blue or gray discoloration of the skin, lips, and mucous membranes, resulting from severe hypoxemia as oxygen-poor blood recirculates systemically without sufficient pulmonary oxygenation.^[1][7] Accompanying features include tachypnea and respiratory distress from compensatory efforts to improve oxygenation, as well as poor feeding and lethargy due to the overall hypoxic state.^[3][36] On physical examination, a loud, single second heart sound (S2) is often audible, attributed to the anterior position of the aorta, with murmurs typically absent unless a ventricular septal defect (VSD) or pulmonary stenosis is present.^[16][7] Hepatomegaly may develop secondary to right ventricular strain and early congestive heart failure, particularly in cases with associated lesions.^[43] In cases with intact ventricular septum and restrictive atrial communication, severe symptoms often emerge within the first 24 hours, exacerbated by the physiological closure of the patent foramen ovale (PFO) or ductus arteriosus (PDA), which further limits intercirculatory mixing.^[16] Without adequate mixing, the condition progresses rapidly to metabolic acidosis, worsening lethargy, and cardiogenic shock as tissue perfusion deteriorates from profound hypoxemia.^[7][16] A key diagnostic clue is the persistence or worsening of cyanosis despite supplemental oxygen administration, distinguishing D-TGA from primary pulmonary diseases where oxygenation typically improves.^[16][7]

Presentation in congenitally corrected cases

In congenitally corrected transposition of the great arteries (ccTGA), the double discordance of atrioventricular and ventriculoarterial connections results in physiologically normal circulation, often leading to a delayed clinical presentation compared to discordant transposition. Approximately 80-90% of cases have associated cardiac lesions that may influence symptoms. While many patients with isolated ccTGA remain asymptomatic into adulthood, with studies indicating that over 70% may be free of heart failure by age 45, though subtle symptoms can occur.^[44][7] During childhood, affected individuals may exhibit subtle signs such as exercise intolerance or arrhythmias, including complete heart block, which carries an annual progression risk of about 2%. An incidental heart murmur from an associated ventricular septal defect (VSD) can also prompt evaluation, though many cases evade detection without associated lesions.^[45][46] In adulthood, presentation commonly involves heart failure, developing in approximately 25-30% of patients with isolated ccTGA and up to 60-70% with associated lesions by age 45, driven by systemic right ventricular dysfunction or significant tricuspid regurgitation acting as the systemic atrioventricular valve. Other manifestations include infective endocarditis, particularly in those with VSDs, or worsening arrhythmias leading to atrioventricular block. Complex cases with additional anomalies carry elevated risks of subaortic stenosis or pulmonary hypertension, exacerbating symptoms. Diagnosis frequently occurs incidentally during routine cardiac screening or evaluation prompted by family history of congenital heart disease.^{[44][47][48][49]}

Diagnosis

Prenatal and imaging techniques

Prenatal diagnosis of transposition of the great arteries (TGA) primarily relies on fetal echocardiography, which is typically performed between 18 and 22 weeks of gestation as part of routine anomaly scanning or targeted evaluation in high-risk pregnancies. The four-chamber view of the fetal heart often appears normal in isolated TGA cases, as the ventricular arrangement is typically concordant, which can make early detection challenging without additional views.^[50] However, the three-vessel and trachea (3VT) view reveals characteristic abnormalities: instead of the normal three vessels (pulmonary artery, aorta, and superior vena cava) arranged in a typical alignment, only two vessels are visible, with the aorta positioned anterior and parallel to the pulmonary artery, often appearing as a single large vessel with the superior vena cava displaced rightward.^[51] Color Doppler imaging further supports the diagnosis by demonstrating parallel blood flows in the great arteries, contrasting with the normal crossing pattern, and can assess associated features like ventricular septal defects if present.^[50] Detection rates for TGA prenatally vary by setting and expertise but generally range from 20% to 50% in high-resource environments with access to specialized fetal cardiology services, though rates have improved to 38%-68% in recent studies with optimized screening protocols.^[52][28] These rates reflect the condition's subtlety, as the four-chamber view misses up to half of cases without expert outflow tract evaluation. If heterotaxy syndrome is suspected alongside TGA—due to additional findings like abnormal systemic or pulmonary venous drainage—genetic screening via amniocentesis may be recommended to identify chromosomal abnormalities, such as those associated with laterality defects, although TGA itself has a low direct genetic linkage in most cases.^[53][50] The primary advantages of prenatal detection include enabling planned delivery at a tertiary care center equipped for immediate neonatal stabilization, such as initiation of prostaglandin E1 infusion to maintain patency of the ductus arteriosus and ensure mixing of oxygenated and deoxygenated blood postnatally.^[54] This proactive approach has been shown to reduce neonatal mortality from approximately 11%-25% in undiagnosed cases to near 0% in prenatally identified ones, alongside minimizing hypoxic complications.^[55] Limitations persist, however, including a high false-negative rate—exceeding 50% in non-expert settings due to the normal appearance in standard views and technical challenges in visualizing posterior structures like the pulmonary artery bifurcation—and the fact that routine screening is not universally applied in low-risk pregnancies, potentially delaying diagnosis until after birth.^[50][28]

Postnatal confirmation

Routine newborn pulse oximetry screening, measuring oxygen saturation in the right hand (pre-ductal) and a lower limb (post-ductal), detects discrepancies such as SpO₂ below 95% or a difference greater than 3% that may indicate cyanotic congenital heart defects like transposition of the great vessels (TGV), prompting immediate further evaluation.^[3] Postnatal confirmation of TGV typically begins with clinical suspicion due to central cyanosis in the neonate, prompting a series of diagnostic tests to differentiate cardiac from pulmonary causes and delineate anatomy. The hyperoxia test serves as an initial bedside evaluation, involving administration of 100% oxygen for 10-15 minutes followed by measurement of arterial partial pressure of oxygen (PaO₂). In TGV, particularly D-transposition of the great arteries (D-TGA), PaO₂ fails to rise above 150 mmHg, indicating inadequate mixing of oxygenated and deoxygenated blood consistent with cyanotic congenital heart disease rather than primary pulmonary pathology.^[56] Echocardiography is the gold standard for definitive postnatal diagnosis, providing non-invasive visualization of cardiac anatomy in real time. It confirms ventriculoarterial discordance by demonstrating the aorta arising from the morphological right ventricle and the pulmonary artery from the left ventricle, often with parallel vessel orientations rather than the normal crossing pattern; subxiphoid and parasternal views assess ventricular looping, outflow tracts, and any associated defects like ventricular septal defect (VSD). Additionally, it evaluates shunt directions across atrial or ductal communications and maps coronary artery origins and patterns, which are crucial for surgical planning. In congenitally corrected TGV (ccTGV), echocardiography identifies atrioventricular and ventriculoarterial discordance, revealing the morphological left ventricle as the systemic pump connected to the pulmonary artery.^[7][24] Chest radiography supports the diagnosis by revealing characteristic features, such as the "egg-on-a-string" or "egg-on-side" silhouette in D-TGA due to the narrow mediastinum from anterior-posterior vessel alignment, often with mild cardiomegaly and increased pulmonary vascular markings indicating good pulmonary blood flow. In ccTGV, findings are less specific but may show cardiomegaly if associated lesions like VSD are present. Electrocardiography (ECG) typically demonstrates right ventricular hypertrophy and right-axis deviation in D-TGA, reflecting the right ventricle's role as the systemic pump; the ECG is often normal in uncomplicated cases but may show biventricular hypertrophy with significant left ventricular outflow obstruction. In ccTGV, ECG frequently reveals abnormal Q waves in the right precordial leads (V1-V3) due to inverted ventricular activation, with absent Q waves in left precordial leads, alongside possible first-degree atrioventricular block or complete heart block in up to 2% of cases.^[7][24][57] Cardiac catheterization is reserved for complex or ambiguous cases where echocardiography is inconclusive, allowing direct measurement of intracardiac pressures, oxygen saturations, and visualization of shunts to quantify mixing efficiency. It also facilitates urgent interventions, such as the Rashkind balloon atrial septostomy procedure, which enlarges the atrial septum via balloon inflation to improve atrial-level mixing and alleviate severe cyanosis in D-TGA neonates with restrictive foramen ovale. In ccTGV, catheterization may assess associated anomalies like pulmonary stenosis or tricuspid regurgitation hemodynamics.^[7][24]

Management

Surgical corrections

The primary surgical correction for dextro-transposition of the great arteries (D-TGA) is the arterial switch operation (ASO), which anatomically repositions the aorta and pulmonary artery to their correct ventricular origins, typically performed within the first 2-3 weeks of life once the infant is hemodynamically stable.^[7] The procedure involves transecting the great vessels above the sinuses of Valsalva, switching their positions, mobilizing and reimplanting the coronary arteries into the neo-aortic root, and often incorporating the Lecompte maneuver to position the pulmonary bifurcation anterior to the neo-aorta for unobstructed left ventricular outflow.^[7] Survival rates exceed 95% at 15-25 years post-discharge for hospital survivors.^[7] Prior to ASO, many neonates with D-TGA require balloon atrial septostomy (BAS) as an emergent palliative intervention to improve mixing of oxygenated and deoxygenated blood in cases of severe cyanosis due to a restrictive atrial septum.^[7] Performed via cardiac catheterization, BAS enlarges the atrial septal defect by inflating a balloon catheter (such as the Z-5 model) across the foramen ovale and rapidly withdrawing it, typically under general anesthesia and within the first few days of life.^[58] This procedure, first described by Rashkind and Miller in 1966, is essential for stabilizing critically ill infants until definitive surgery.^[58] In complex D-TGA cases associated with a ventricular septal defect (VSD) and pulmonary outflow obstruction, alternative procedures like the Rastelli or Nikaidoh operations are employed instead of isolated ASO. The Rastelli procedure redirects left ventricular outflow to the aorta via an intracardiac baffle across the VSD while establishing right ventricular-to-pulmonary artery continuity with a valved conduit, addressing the anatomical mismatch.^[7] The Nikaidoh procedure, used less frequently for similar anatomies, involves translocating the aortic root posteriorly to align with the left ventricle and reconstructing the pulmonary outflow, often combined with VSD closure.^[7] For congenitally corrected transposition of the great arteries (ccTGA), surgical intervention depends on symptoms and associated lesions; asymptomatic patients with preserved systemic right ventricular function may undergo watchful waiting due to the risks of surgery outweighing benefits in stable cases.^[59] Symptomatic ccTGA often requires a double-switch operation to restore the left ventricle as the systemic pump, combining an atrial switch (such as Mustard or Senning procedure using baffles or flaps to redirect venous return) with an arterial switch or Rastelli for ventricular-arterial concordance.^[59] These anatomical repairs yield better long-term survival compared to physiologic repairs, though they carry risks like heart block and conduit stenosis.^[59] Over time, surgical approaches for both D-TGA and ccTGA have shifted from physiologic atrial baffling techniques (Mustard/Senning), which redirect blood flow but leave the morphologic right ventricle as the systemic pump and are now rarely used due to high rates of arrhythmias and ventricular failure, to preferred anatomical corrections like ASO for superior long-term hemodynamics.^[7]

Supportive and long-term care

Supportive care for transposition of the great arteries (TGA) begins preoperatively with measures to stabilize neonates and maintain adequate oxygenation until surgical intervention. Prostaglandin E1 infusion is administered to keep the patent ductus arteriosus (PDA) open, allowing mixing of oxygenated and deoxygenated blood to improve systemic saturation.^[7] Mechanical ventilation is often employed to correct metabolic acidosis and support respiratory function in critically ill infants presenting with severe cyanosis.^[7] Postoperatively, following procedures such as the arterial switch operation, patients require close monitoring in an intensive care setting to manage potential complications. Anticoagulation therapy, typically with heparin or warfarin, may be initiated for patients with atrial baffles from older repairs to prevent thrombus formation, while antiarrhythmic medications like beta-blockers or amiodarone are used to address conduction abnormalities or arrhythmias.^[60] Serial echocardiography is essential for detecting neoaortic regurgitation, with interventions considered if significant ventricular dilation or symptoms develop.^[60] Long-term care emphasizes regular surveillance to preserve cardiac function and prevent complications. Annual or biennial echocardiography is recommended to assess ventricular performance, neoaortic root dilation, and pulmonary artery patency.^[60] Endocarditis prophylaxis with antibiotics is advised prior to dental or invasive procedures in patients with prosthetic materials or residual defects.^[7] In congenitally corrected TGA (ccTGA), exercise restrictions are tailored based on systemic right ventricular function, often limiting competitive sports if moderate stenosis or reduced capacity is present to avoid arrhythmias or heart failure.^[61] A multidisciplinary approach involving cardiologists, psychologists, and other specialists is crucial for holistic management. Neurodevelopmental delays or adverse outcomes affect approximately 25-55% of survivors due to factors including perioperative hypoxia, with increased needs for special education and higher ADHD prevalence, necessitating early screening and interventions like educational support.^[62][63] Pregnancy in corrected patients is high-risk, particularly in ccTGA, with increased maternal arrhythmias and fetal loss rates around 15-20% requiring preconception counseling and close obstetric monitoring.^[64]

Prognosis

Short-term outcomes

The arterial switch operation (ASO) for D-transposition of the great arteries (D-TGA) demonstrates favorable short-term outcomes in modern pediatric cardiac centers, with 30-day mortality rates around 1.7% and in-hospital mortality approximately 2.4%.^[65] Overall short-term survival to discharge reaches 92-95% in systematic reviews of large cohorts, though early deaths are often linked to coronary artery transfer issues or postoperative low cardiac output syndrome.^[66] Interventions for congenitally corrected transposition of the great arteries (ccTGA), such as double switch procedures or tricuspid valve repairs, carry lower perioperative mortality risks of 2-5% compared to D-TGA repairs, reflecting less urgent neonatal presentation but necessitating vigilant monitoring for early reoperations due to systemic right ventricle strain.^[67] Several factors influence these short-term outcomes. Low birth weight under 2.5 kg is associated with a 2- to 4-fold increased risk of early mortality, stemming from heightened vulnerability to hemodynamic instability and surgical stress. Conversely, prenatal diagnosis significantly mitigates early death risk, reducing first-year mortality from 11.4% in undiagnosed cases to 0% in detected ones by enabling prompt postnatal stabilization and timely surgery.^[68] Postoperative morbidity remains a key concern, with transient neurologic injuries occurring in 2-11% of ASO patients, often related to perioperative hypoxia or embolic events.^[69] Low-output syndrome necessitating extracorporeal membrane oxygenation (ECMO) support affects about 3.5% of cases and substantially elevates mortality risk, though survival to decannulation exceeds 50% in experienced units.^[65] As of 2025, short-term survival remains >95% in high-resource settings with experienced centers.^[70] Global disparities markedly affect short-term results, with in-hospital mortality reaching 15% in developing nations—substantially higher than in high-resource settings—primarily due to delayed surgical intervention from limited prenatal screening and access to specialized care.^[71]

Long-term complications

In patients with D-transposition of the great arteries (D-TGA) who undergo the arterial switch operation (ASO), neoaortic root dilation develops in 60-70% by adulthood, often progressing due to inherent vascular abnormalities and surgical factors.^[72] Supravalvular pulmonary stenosis affects approximately 10% of cases, typically arising from anastomotic tension or pulmonary artery distortion during surgery.^[73] Arrhythmias occur in 5-15% of patients long-term, including atrial flutter and ventricular ectopy, linked to myocardial scarring or chronotropic incompetence.^[17] For congenitally corrected transposition of the great arteries (ccTGA), systemic right ventricle dysfunction progresses, with heart failure developing in approximately 30% of patients with simple ccTGA by age 45, driven by chronic pressure overload and progressive myocardial dysfunction.^[74] Tricuspid regurgitation often progresses due to annular dilation and right ventricular remodeling, exacerbating heart failure.^[75] Complete heart block develops in up to 30% over a lifetime, with an annual incidence of around 2%, attributable to abnormal conduction tissue positioning.^[76] Neurodevelopmental issues, including learning disabilities, affect 20-30% of survivors, primarily associated with preoperative cyanosis causing hypoxic brain injury and impaired white matter maturation.^[77] These deficits encompass delays in executive function, attention, and language, independent of surgical technique but worsened by delayed intervention.^[78] Reintervention rates post-correction range from 10-20%, commonly for conduit replacement in complex cases or baffle obstruction in atrial switch repairs, with pulmonary artery interventions being most frequent.^[79][65] Most patients achieve good quality of life, with 80-90% in New York Heart Association (NYHA) class I, though D-TGA survivors face reduced life expectancy compared to the general population due to cumulative cardiovascular strain, with long-term survival exceeding 90% at 30 years.^[80] Supportive care, including regular imaging and arrhythmia monitoring, helps mitigate these risks.^[81]

History

Early descriptions

The earliest documented recognition of transposition of the great vessels occurred through postmortem examinations in the late 18th century. In 1797, Scottish pathologist Matthew Baillie provided the first detailed anatomical description of the condition in the second edition of his work Morbid Anatomy of Some of the Most Important Parts of the Human Body, based on an autopsy of a child about two months old, noting the aorta arising from the right ventricle and the pulmonary artery from the left ventricle, accompanied by a patent foramen ovale and a small ventricular septal defect.^[82] This observation highlighted the ventriculoarterial discordance central to the defect, though Baillie's account focused on gross pathology without clinical context. In 1814, John Richard Farre coined the term "transposition of the great arteries" in his pathological inquiries, describing the vessels' abnormal crossing over the ventricular septum in autopsy specimens.^[24] French physician Étienne-Louis Arthur Fallot, in his 1888 publication Contribution à l'anatomie pathologique de la maladie bleue in Marseille Médical, classified transposition as one of the primary cyanotic congenital defects, grouping it with conditions causing persistent hypoxemia due to parallel circulations, based on series of postmortem cases.^[83] Throughout the 19th century, further contributions emphasized descriptive pathology rather than surgical intervention, as the era lacked effective treatments. These reports underscored the lesion's role in severe, early-onset cyanosis, observed clinically as deep blue discoloration in neonates shortly after birth, often leading to rapid deterioration without a mixing lesion like a patent ductus arteriosus or septal defect. In the early 20th century, pediatric cardiologist Helen Taussig advanced understanding of "blue baby" syndromes, including TGA, through clinical observations that paved the way for surgical interventions. Prior to the 1950s, the etiology remained obscure, with clinical correlations limited to noting profound cyanosis and heart failure in affected infants, as diagnostic tools like angiography were not available until the 1930s.^[84] Prevalence estimates from early 20th-century postmortem series indicated transposition accounted for approximately 5% of congenital heart disease cases, reflecting its relative rarity but high lethality. Societally, the condition contributed to undifferentiated "blue baby" syndromes, resulting in near-universal infant mortality within months, often misattributed to general respiratory or infectious causes in an era without precise diagnostics.^[84]

Major surgical milestones

The surgical treatment of transposition of the great arteries (TGA) evolved from palliative interventions to anatomical corrections, markedly improving survival rates over the decades. The first major milestone was the 1948 introduction of the Blalock-Hanlon septectomy by Alfred Blalock and C. Rollins Hanlon, a closed-heart palliative procedure that created an atrial septal defect to allow mixing of systemic and pulmonary venous blood, addressing the parallel circulations in TGA.^[85] This operation, performed without cardiopulmonary bypass, represented the initial viable approach for infants, though it did not correct the anatomical defect and carried risks of arrhythmia and baffle obstruction.^[85] In the mid-20th century, physiological corrections via atrial-level redirection emerged as the next advancement. Åke Senning performed the first successful atrial switch operation in 1957 at Karolinska Hospital in Stockholm, using autologous atrial tissue flaps to redirect venous return without extracardiac material, achieving long-term palliation in select cases.^[85] Building on this, William Thornton Mustard refined the technique in 1963 at Toronto's Hospital for Sick Children, introducing the Mustard procedure with a synthetic or pericardial baffle to baffle systemic venous blood to the left ventricle and pulmonary venous blood to the right ventricle, which became the standard for TGA repair until the 1980s.^[85] These atrial switches improved survival to over 80% in experienced centers but were limited by complications such as systemic right ventricular failure and baffle leaks.^[86] The shift to anatomical correction marked a pivotal era, beginning with early unsuccessful attempts at arterial switching in the 1950s. William Mustard tried arterial switches in 1954 on three infants, all of whom succumbed due to coronary complications and myocardial ischemia.^[87] Similarly, Charles A. Bailey's 1952 hypothermia-assisted switchover operations on TGA patients failed postoperatively.^[87] The breakthrough came in 1975 when Adib D. Jatene at the University of São Paulo conducted the first successful arterial switch operation (ASO) on a 40-day-old infant, transposing the aorta and pulmonary artery to their anatomical positions while reimplanting the coronary arteries, restoring normal blood flow.^[85] This procedure, detailed in Jatene's seminal 1976 publication in Arquivos Brasileiros de Cardiologia, laid the foundation for modern TGA repair.^[88] Subsequent refinements solidified the ASO as the gold standard. In 1981, Michel Lecompte introduced the Lecompte maneuver during ASO, positioning the pulmonary bifurcation anterior to the aorta to reconstruct the neopulmonary outflow tract without prosthetic material, reducing long-term reintervention needs.^[85] By 1984, Aldo R. Castaneda and colleagues at Boston Children's Hospital demonstrated the feasibility and superiority of neonatal ASO, confirming that the neonatal left ventricle could support systemic circulation post-switch, leading to its widespread adoption and survival rates exceeding 90% in contemporary series.^[85] These developments transformed TGA from a condition with near-certain early mortality to one with excellent prognosis when repaired early.^[86]