Dextro-transposition of the great arteries (d-TGA) is a severe cyanotic congenital heart defect characterized by an abnormal connection between the ventricles and the great arteries.
The aorta arises anteriorly from the right ventricle and the pulmonary artery posteriorly from the left ventricle.
This results in an anatomical configuration where the systemic and pulmonary circulations run in parallel and do not communicate, thereby preventing the passage of oxygenated blood to the systemic circulation. In the absence of intercirculatory shunts, the condition is incompatible with life unless other patency defects are present that allow blood flow between the two circuits.
The main shunts that make d-TGA compatible with life include:
d-TGA accounts for approximately 5–7% of all congenital heart defects, with an incidence of about 2–4 per 10,000 live births. It is the most common anomaly with concordant ventricles and discordant great arteries, and is one of the leading causes of early neonatal cyanosis unresponsive to oxygen therapy.
Timely recognition and early surgical correction are critical for survival and long-term quality of life.
Dextro-transposition of the great arteries is a congenital cardiac malformation that originates during the early stages of embryogenesis, generally between the fifth and eighth weeks of gestation, when the ventriculo-arterial connections are forming. Under normal conditions, the conotruncal septum (a structure that divides the outflow tract into two separate channels) undergoes a spiral rotation, allowing the ventricles to align crosswise with their respective great arteries.
If this spiraling process fails or is incomplete, a discordant ventriculo-arterial connection occurs, with the aorta arising anteriorly from the right ventricle and the pulmonary artery posteriorly from the left ventricle. This configuration, while maintaining atrioventricular concordance, leads to a complete separation of systemic and pulmonary blood flow.
The precise causes are not fully understood, but include genetic abnormalities in cardiac development, especially involving genes related to conotruncal morphogenesis (NKX2.5, GATA4, ZIC3), as well as disorders of neural crest cell migration, which contribute to the formation of the arterial septum. Some cases of transposition occur in syndromic contexts (such as 22q11.2 deletion, heterotaxy syndromes), although most d-TGA cases are isolated and sporadic.
Alongside these direct causes, there are several modifiable risk factors that, while not etiological per se, increase the likelihood of developing d-TGA. These include pregestational maternal diabetes, prenatal exposure to teratogenic substances (such as isotretinoin, alcohol, and certain anticonvulsants), and a family history of congenital heart disease. Some studies have also reported a slight increase in risk with advanced maternal age or pre-pregnancy obesity.
From a pathophysiological standpoint, d-TGA creates two independent and parallel circulatory circuits: systemic venous blood enters the right atrium, flows into the right ventricle, and is ejected into the aorta—returning to the body without oxygenation; simultaneously, oxygenated pulmonary blood returns to the left atrium, flows into the left ventricle, and is re-circulated to the lungs via the pulmonary artery. This leads to severe systemic hypoxemia, incompatible with life unless intracardiac communications are present.
Neonatal survival is possible only if there are blood flow shunts allowing mixing between the two circuits.
The structures most commonly involved include:
The degree of blood mixing depends on the size and direction of the shunt: if these communications are narrow or absent, the newborn quickly develops severe cyanosis, metabolic acidosis, and multiorgan failure.
The pathophysiology of transposition is further complicated by the lack of functional preparation of the left ventricle. In an untreated neonate, the left ventricle pumps against the low pulmonary pressure and undergoes early structural regression, making it unable to support systemic circulation later on. Conversely, the right ventricle, which is structurally unsuited for systemic load, hypertrophies rapidly but evolves into right ventricular dysfunction and early heart failure.
An additional vulnerability factor is represented by coronary artery anomalies, which in d-TGA may have atypical courses that complicate coronary reimplantation during the arterial switch operation. In particular, an interarterial course or a single coronary origin are high-risk variants for perioperative or late myocardial ischemia.
Without surgical correction, transposition rapidly leads to refractory hypoxemia and neonatal death. The complex hemodynamic nature of this defect requires high diagnostic expertise, early clinical stabilization, and timely surgical planning within the first weeks of life.
The clinical picture of dextro-transposition of the great arteries is dominated by severe central cyanosis that manifests early, often within the first hours after birth. Symptom severity mainly depends on the degree of blood mixing between the two circuits: the more extensive and bidirectional the shunt, the better the systemic oxygenation and the milder the initial symptoms. Conversely, in the absence of effective communications, the condition rapidly progresses to worsening respiratory and circulatory failure.
The perinatal history must carefully investigate any signs of early neonatal distress, feeding difficulties, lethargy or irritability, and maternal conditions predisposing to congenital heart disease, such as diabetes, teratogen exposure, or family history. In many cases, suspicion may arise prenatally through fetal echocardiography, which can identify the great arteries’ malalignment and allow for coordinated postnatal management in specialized pediatric cardiac centers.
In term newborns with uncorrected transposition, the main signs and symptoms include:
In the presence of a large ventricular septal defect or a patent ductus arteriosus, cyanosis may be less pronounced, but signs of pulmonary overcirculation and high-output heart failure are more common. In such cases, as early as the first week of life, one may observe:
On physical examination, cyanosis is almost always evident. Peripheral pulses are usually well palpable, except in cases with reversed systemic flow through the ductus arteriosus. In patients with a ventricular septal communication, a holosystolic murmur may be heard along the left sternal border, while in cases with a large patent ductus, a continuous murmur may be present. Accentuated second heart sound may also be noted, related to the anterior position of the aorta.
It is important to note that about one-third of newborns with d-TGA do not present audible murmurs in the absence of associated shunts. In these cases, the diagnosis may be delayed if cyanosis is mistakenly attributed to respiratory conditions. The failure of oxygen therapy to improve oxygen saturation is a crucial clinical clue that should prompt suspicion of a cyanotic congenital heart disease, of which transposition is among the most critical emergencies.
The diagnosis of dextro-transposition of the great arteries must be prompt and accurate, given the critically emergent nature of the condition and the high risk of early neonatal mortality. Clinical suspicion arises in the presence of deep, persistent central cyanosis unresponsive to oxygen therapy, in an otherwise healthy full-term newborn. When the clinical picture is not explainable by a respiratory condition, a cardiac origin must be considered, particularly a cyanotic congenital heart defect with separate blood flows.
Pre- and post-ductal pulse oximetry may reveal markedly low saturations (SpO₂ < 75–80%) that do not improve with high-flow oxygen. This finding, along with the clinical history, indicates the urgency of echocardiographic evaluation. In high-risk newborns—such as those born to diabetic mothers or with a family history of congenital heart disease—routine saturation screening in the first hours of life can lead to earlier diagnosis.
The gold standard test is transthoracic echocardiography (TTE), which enables direct visualization of the ventriculo-arterial connections. In cases of transposition, the following features are observed:
When anatomical definition is suboptimal, transesophageal echocardiography or cardiac computed tomography (CT) may be used, especially to assess coronary anatomy prior to surgery. Cardiac magnetic resonance imaging (MRI) is indicated in the follow-up of older patients to provide detailed morpho-functional assessment.
Cardiac catheterization today plays a secondary role in diagnosis but may be employed when echocardiographic findings are unclear or to perform a balloon atrial septostomy (Rashkind procedure) in neonates with inadequate intercirculatory mixing.
The neonatal electrocardiogram is often non-diagnostic, possibly appearing normal or showing only signs of right ventricular hypertrophy. Chest X-ray may show the classic “egg-on-a-string” heart silhouette and increased pulmonary vascular markings, but it does not provide a definitive diagnosis.
In critical cases, arterial blood gas analysis reveals severe hypoxemia and metabolic acidosis, with elevated lactate levels as an indicator of tissue hypoperfusion. These data support the urgency of intervention.
Diagnosis is thus based on a careful integration of clinical suspicion, echocardiographic imaging, and hemodynamic assessment, all of which must be carried out as quickly as possible to ensure neonatal survival and allow for early surgical correction.
Dextro-transposition of the great arteries is a neonatal cardiac emergency requiring a therapeutic strategy structured in three successive phases: hemodynamic stabilization, enhancement of intercirculatory shunting, and definitive surgical correction. The timing and appropriateness of each intervention directly affect outcomes.
The initial goal is to ensure adequate blood mixing between the two circuits. In neonates with a closed ductus arteriosus or a restrictive patent foramen ovale, survival may be limited to a few hours. Intravenous infusion of prostaglandin E1 is crucial to maintain ductal patency, temporarily improving systemic oxygenation. This treatment requires continuous monitoring due to the risk of apnea and the potential need for mechanical ventilation.
In cases of inadequate atrial mixing, balloon atrial septostomy (Rashkind procedure) is performed—a catheter-based intervention that creates an effective communication between the atria. In many centers, this is a routine procedure in neonates with restrictive foramen ovale, carried out before corrective surgery.
The definitive correction is achieved with the arterial switch operation (Jatene procedure), which restores the proper ventriculo-arterial connections by transecting and reattaching the aorta and pulmonary artery to their respective ventricles. The coronary arteries are reimplanted into the neo-aorta—an especially critical phase for myocardial viability. The operation is ideally performed within the first 2–3 weeks of life, before the left ventricle loses its ability to sustain systemic pressure.
In patients with a regressed left ventricle, the procedure may be contraindicated. In such cases, an atrial switch operation (Senning or Mustard) may be used instead, redirecting blood flow at the atrial level while maintaining the original arterial anatomy. Although effective short-term, this approach carries increased long-term risks, including right ventricular dysfunction, arrhythmias, and venous obstructions.
Prognosis has dramatically improved with early arterial switch surgery. In specialized centers, operative mortality is below 5%, with long-term survival exceeding 90% and good quality of life. However, structured cardiologic follow-up is essential, including assessment of coronary anatomy, ventricular function, and potential stenoses of the reimplanted vessels.
Functional recovery depends on early diagnosis, absence of complex associated lesions, and successful coronary revascularization. Residual defects, coronary anomalies, or ventricular hypoplasia represent negative prognostic factors and may require ongoing monitoring or reinterventions.
Although d-TGA is now a surgically correctable congenital heart defect with excellent prognosis, it can still lead to significant complications in both the perioperative and long-term periods. The nature of these complications depends on the type of surgical correction performed, associated lesions, and the success of coronary revascularization.
In the neonatal phase and immediate postoperative period, the main risk is inadequate myocardial perfusion. During the arterial switch operation, the coronary arteries must be mobilized and reimplanted: anomalous origins or courses increase the risk of perioperative myocardial ischemia or infarction. Variants such as interarterial courses or single coronary origins are considered high-risk.
Another early complication is left ventricular dysfunction, especially in neonates with a deconditioned left ventricle due to delayed surgery. These cases may present with refractory hypotension, low cardiac output, and need for prolonged inotropic support. Left ventricular regression thus represents a relative contraindication to delayed surgery.
In long-term follow-up, the most frequent complication is branch pulmonary artery stenosis, often due to technical issues or asymmetric growth of the reimplanted vessels. Clinically, this may manifest with exertional dyspnea, pulmonary hypertension, and reduced exercise capacity, sometimes requiring percutaneous or surgical reintervention. The neo-aorta may also develop dilation or valvular insufficiency, though less commonly.
In patients treated with an atrial switch, now rarely used, chronic complications are more numerous and include:
Neurological impairment is another possible consequence, secondary to perinatal hypoxemia or perioperative cerebral hypoperfusion. Follow-up studies have shown a higher incidence of neurocognitive disorders, including learning difficulties, attention deficits, and fine motor skill issues, requiring specialized assessment.
A targeted multidisciplinary follow-up—including cardiologic, neurologic, and psychological evaluations—is essential for early identification of complications and ensuring optimal long-term quality of life.