L-transposition of the great arteries (L-TGA): Anatomy, clinical features, and diagnosis

INTRODUCTION — Levo- or L-looped transposition of the great arteries (L-TGA) is a rare form of congenital heart disease characterized by atrioventricular (AV) and ventriculoarterial discordance (figure 1). It is also commonly referred to as congenitally corrected TGA, double discordance, or ventricular inversion.

L-TGA usually does not present with cyanosis unless there are associated cardiac defects. Isolated L-TGA is "physiologically corrected" because systemic deoxygenated venous blood returns to the pulmonary circulation and oxygenated pulmonary venous blood returns to the systemic circulation. Patients with L-TGA are at increased risk for heart failure as adults due to progressive decline in systemic right ventricular (RV) function.

The anatomy, pathophysiology, clinical features, and diagnosis of L-TGA will be presented here. Management and outcome of L-TGA are discussed separately. (See "L-transposition of the great arteries (L-TGA): Management and outcome".)

Dextro-TGA (D-TGA) is also discussed separately. (See "D-transposition of the great arteries (D-TGA): Anatomy, clinical features, and diagnosis" and "D-transposition of the great arteries (D-TGA): Management and outcome".)

EMBRYOLOGY AND ANATOMY

Cardiac loop formation — Looping of the straight heart tube during the third week of gestation is one of the key embryologic processes for correct anatomic alignment of the four chambers of the heart. Normally, the primitive heart tube "loops" to the right (dextro or D loop), resulting in the normal morphologic position of the right ventricle (RV) to the right of the left ventricle (LV). However, looping to the left (levo or L loop) leads to abnormal positioning of the ventricles and to abnormal connections among the atrial, ventricular, and arterial segments of the heart.

Anatomy of L-transposition of the great arteries — L-TGA is characterized by atrioventricular (AV) and ventriculoarterial discordance. Coronary artery anatomy is variable.

●Cardiac anatomy – L-TGA is due to the abnormal leftward looping of the primitive heart, which results in the morphologic LV being positioned to the right of the morphologic RV, and to both AV and ventriculoarterial discordance (figure 1). In this lesion, deoxygenated systemic venous blood return flows from the correctly located right atrium to the discordant LV via the mitral valve and into the lung through the pulmonary arteries. Oxygenated blood flows from the lungs through the pulmonary veins to the left atrium into the discordant RV via the tricuspid valve and returns to the systemic circulation through the aorta [1]. The aorta is typically abnormally positioned anterior and to the left of the pulmonary artery.

L-TGA is commonly referred to as congenitally corrected TGA since the blood flows in the correct physiologic direction, resulting in normal oxygenation of the systemic venous return via the abnormally placed ventricles and great arteries [2].

Dextrocardia and situs inversus (where the heart is positioned and oriented in the right chest and there is inversion of the abdominal viscera) is another much less common variant of a congenitally corrected TGA. It is an anatomic mirror image of L-TGA and accounted for 2 out of 22 cases in a New Zealand case series of congenitally corrected TGA [3]. Although the anatomy of this lesion is different, the pathophysiology is the same. As a result, case series often combine the two entities in describing both the natural history and surgical outcome. In this topic review, L-TGA will be used to describe both anatomic variants.

Other terms used to describe L-TGA include ventricular inversion (referring to the reversal of ventricular positioning) and double discordance (referring to both the AV and ventriculoarterial discordance).

●Coronary artery anatomy – In patients with L-TGA, coronary artery anatomy is variable. In general, the usual distribution represents a mirror image of normal anatomy, with the origins of the coronary arteries arising from the posterior facing sinuses due to the anterior positioning of the aortic valve. The vessel originating from the right-sided sinus is considered the morphologic left coronary artery with a circumflex and anterior descending branch, while the vessel originating from the left-facing sinus would have the epicardial distribution of a morphologic right coronary artery.

EPIDEMIOLOGY AND ETIOLOGY — L-TGA is a rare form of congenital heart disease with a published incidence ranging from 0.02 to 0.07 per 1000 live births, accounting for <1 percent of congenital heart disease lesions [4-6].

The cause of L-TGA is likely multifactorial. Limited data suggest that both environmental and genetic factors contribute to its pathogenesis [1,7,8].

PATHOPHYSIOLOGY — The term congenitally or physiologically corrected TGA is used to describe the normal physiologic return of deoxygenated systemic venous blood to the heart and transport of oxygenated pulmonary venous return to the systemic circulation through the discordant ventricles and great arteries. As a result, patients with isolated L-TGA are asymptomatic at birth and during childhood.

However, isolated L-TGA is rare because associated cardiac lesions are present in over 90 percent of patients with L-TGA. In these patients, signs or symptoms are due to the pathophysiology of the associated cardiac defects. (See 'Associated cardiac abnormalities' below.)

In patients with anatomically uncorrected L-TGA (ie, persistent atrioventricular [AV] and ventriculoarterial discordance), the morphologic right ventricle (RV) is not well suited to perform the workload of the systemic ventricle over a normal lifespan. As a result, systemic ventricular failure (ie, systemic heart failure) is a common late complication in patients with L-TGA, including those without associated cardiac lesions. RV dysfunction is thought to be due to an unfavorable tripartite geometric configuration that does not adapt to pressure or volume overload [9]. The long-term systemic workload results in progressive tricuspid regurgitation that increases volume overload and contributes to ventricular dysfunction and failure [10]. It is also proposed that the single coronary arterial supply to the morphologic RV may increase the vulnerability of this ventricle to ischemia, particularly when hypertrophy is present [11].

CLINICAL MANIFESTATIONS

Antenatal presentation — Because prenatal diagnosis of L-TGA is challenging, most patients with L-TGA present after delivery. In one case series, 16 of 54 patients were diagnosed prenatally [12]. Of the 16 fetuses, one pregnancy was terminated, one fetus had an unknown outcome, and the other 14 were live born. (See 'Fetal diagnosis' below and "Congenital heart disease: Prenatal screening, diagnosis, and management", section on 'Standard cardiac evaluation'.)

Postnatal presentation — The postnatal presentation of L-TGA is dependent on the presence and type of additional cardiac abnormalities. Patients without another structural cardiac lesion are asymptomatic at birth. L-TGA is most commonly detected in the evaluation of symptomatic associated cardiac lesions, such as ventricular septal defect (VSD) or pulmonary ventricular outflow tract obstruction. Isolated L-TGA often presents later in life with features of systemic ventricular dysfunction, systemic atrioventricular (AV) valve regurgitation, or heart block.

Associated cardiac abnormalities — Another cardiac lesion is present in most cases of L-TGA (>90 percent) [13,14]. The associated lesion generally determines the signs and symptoms at the time of presentation. The following are the most common cardiac lesions associated with L-TGA, their relative frequency, and usual presenting signs or symptoms [1-3,14-16]:

●VSD occurs in 70 to 80 percent of patients with L-TGA. These defects can be found in any region of the ventricular septum; perimembranous VSDs are most common. Once the pulmonary vascular resistance sufficiently falls after birth, left-to-right shunting occurs across the VSD and a systolic murmur will be present. In severe cases, signs of heart failure may develop. (See "Isolated ventricular septal defects (VSDs) in infants and children: Anatomy, clinical features, and diagnosis", section on 'Clinical features'.)

●Pulmonary (ie, left ventricular [LV]) outflow tract obstruction has been reported in 30 to 60 percent of cases and often accompanies a large VSD. The obstruction is commonly subvalvular and is generally due to an aneurysm of the interventricular septum, fibrous tissue tags, or a discrete ring of subvalvular tissue. Less frequently, valvar pulmonary stenosis is the cause of LV outflow tract obstruction. Cyanosis is often a presenting finding in neonates with limited pulmonary blood flow due to major outflow tract obstruction and large VSD because of a significant pulmonary-to-systemic ventricular cardiac shunt.

●Tricuspid (systemic AV) valve abnormalities are observed at autopsy in up to 90 percent of L-TGA cases. Regurgitation is frequent and generally progressive [17]. Since this valve is associated with the systemic ventricle, tricuspid valve abnormalities have an important impact in the development of ventricular dysfunction and heart failure in older uncorrected patients. An Ebstein-like malformation of the tricuspid valve, which is usually accompanied by right ventricular (RV) dysfunction and failure, has been reported in 20 to 53 percent of patients with L-TGA [3,15]. Symptoms related to tricuspid valve abnormalities are dependent on the severity of the defect and are reviewed separately. (See "Ebstein anomaly: Clinical manifestations and diagnosis".)

●Mitral valve abnormalities, although less frequent than tricuspid abnormalities, still occur in 55 percent of cases in autopsy series [3]. These lesions include abnormal number of cusps, straddling chordal attachments of the subvalvar apparatus creating pulmonary outflow tract obstruction, and mitral valve dysplasia. This abnormality may not present with significant clinical findings.

Isolated L-transposition of the great arteries — L-TGA occurs as an isolated defect in <10 percent of affected patients. Patients with isolated L-TGA generally present later in life with signs and symptoms related to either arrhythmias or heart failure.

Complete heart block is the most common arrhythmia in patients with L-TGA with signs and symptoms of bradycardia, fatigue, and poor exercise tolerance. In L-TGA, the cardiac conduction system is often abnormal and unstable. Although the sinoatrial node is located in its normal position near the superior vena cava, the AV node is typically located along the anterosuperior margin of the VSD and is usually accompanied by an elongated His-Purkinje conduction system (His bundle); a second subsidiary AV node may also be noted in some cases [1-3]. These abnormalities are associated with progressive fibrosis with advancing age, which increases the risk of complete heart block (progressive incidence of 2 percent per year [2]) and reentrant tachyarrhythmias including Wolff-Parkinson-White syndrome. (See "Bradycardia in children" and "Ebstein anomaly: Clinical manifestations and diagnosis".)

Symptoms of heart failure (eg, dyspnea, fatigue, fluid retention, and decreased exercise tolerance) typically occur in adult patients with progressive dysfunction of the morphologic RV and increasing systemic tricuspid regurgitation (see 'Natural history' below) [18]. (See "Heart failure: Clinical manifestations and diagnosis in adults".)

Physical findings — The physical findings are usually due to the associated cardiac abnormalities.

●Murmur – A systolic murmur will often be present in the setting of associated cardiac anomalies. (See "Common causes of cardiac murmurs in infants and children".)

•A restrictive VSD produces a pansystolic harsh murmur (movie 1) (see "Isolated ventricular septal defects (VSDs) in infants and children: Anatomy, clinical features, and diagnosis")

•Pulmonic or subpulmonic stenosis produces a systolic ejection murmur (movie 2) (see "Pulmonic stenosis in infants and children: Clinical manifestations and diagnosis")

•A holosystolic murmur can also result from systemic tricuspid regurgitation, related to progressive valve dysfunction or the Ebstein-like valve abnormality (see "Ebstein anomaly: Clinical manifestations and diagnosis")

●Cyanosis – Cyanosis during the newborn period most likely results from either pulmonary atresia or critical pulmonary stenosis (approximately 10 percent of patients) and a large VSD. (See "Cardiac causes of cyanosis in the newborn".)

●Tachypnea – Patients with associated malformations may develop respiratory distress as a result of excessive pulmonary blood flow in the setting of a large VSD or from systemic AV (ie, tricuspid) valve regurgitation.

●Loud second heart sound – In patients with L-TGA, including those without any associated cardiac lesion, a common finding is a loud second heart sound due to aortic valve closure caused by the more anterior position of the aorta [15]. (See 'Anatomy of L-transposition of the great arteries' above.)

Electrocardiogram findings — In L-TGA, the interventricular septum is depolarized in the opposite direction of normal. This results in the characteristic electrocardiogram (ECG) findings of Q waves in the right precordial leads and an absence of Q waves in the left-sided precordial leads (waveform 1) [15]. These ECG findings may be misinterpreted as an inferior myocardial infarction [2]. In addition, patients may also have varying degrees of AV heart block due to abnormalities of the conduction system. As noted above, the risk of complete heart block rises over time with a 2 percent per year increase in incidence [2]. (See 'Isolated L-transposition of the great arteries' above.)

Chest radiograph findings — Approximately 25 percent of patients with L-TGA have mesocardia (ie, location of the apex of the heart in the midline of the thorax) or dextrocardia (ie, the heart is on the right side of the chest and the apex points to the right) [1]. In patients with levocardia (normal location), the leftward positioned aorta usually results in a prominence in the upper left border of the mediastinum.

NATURAL HISTORY — The natural history of L-TGA is largely determined by the presence of associated cardiac abnormalities and the progressive dysfunction of the morphologic right ventricle (RV) as the systemic pump [13,18,19]. In particular, tricuspid regurgitation is a concomitant risk factor for heart failure and mortality in adult patients because of increased volume load of the morphologic RV [1,10,13,17]. (See 'Pathophysiology' above.)

This was best illustrated in a large multicenter case series of 182 adult patients with congenitally corrected TGA. Heart failure was more common in patients with associated cardiac lesions than in those with an isolated lesion (51 versus 34 percent) [13]. By the age of 45 years, two-thirds of patients with associated lesions and one-quarter of patients without additional cardiac defects had developed heart failure symptoms. In the overall cohort, the risk of systemic ventricular dysfunction, systemic atrioventricular (AV) valve regurgitation, and ongoing rhythm disturbances increased with advancing age. Risk factors for heart failure included tricuspid regurgitation, tricuspid valve surgery, significant arrhythmia, history of open heart surgery, and pacemaker therapy.

In a case series of 44 adults with unoperated congenitally corrected TGA from a single tertiary center, similar findings were noted of an association between systemic AV valve regurgitation and significant RV (systemic) dysfunction in 26 patients (59 percent) [18]. Four patients eventually required cardiac transplantation.

DIAGNOSIS

Fetal diagnosis — The antenatal diagnosis of L-TGA can be quite difficult, especially if there are no other associated abnormalities that are more easily detected, such as a ventricular septal defect (VSD) or complete heart block. In affected fetuses without other cardiac defects, the four-chamber view could be interpreted as normal due to a lack of ventricular size discrepancy, as is true in fetuses with dextro-TGA (D-TGA) [20]. In both types of TGA, the diagnosis is typically made by an experienced fetal ultrasonographer who correctly observes that the great arteries are parallel in the three-vessel view and do not cross as is expected in normal cardiac anatomy. However, this finding is usually not appreciated in the routine antenatal ultrasound examination, which generally focuses on a four-chamber view of the heart and not on the anatomy of the great arteries.

Postnatal diagnosis — The diagnosis of L-TGA is made by echocardiography. Most patients (>90 percent) have additional associated cardiac defects that generally are the cause of any clinically apparent signs and symptoms [12]. (See 'Associated cardiac abnormalities' above.)

In patients without an associated symptomatic cardiac lesion, the diagnosis is made by echocardiography performed in symptomatic adults who present because of systemic ventricular dysfunction and heart failure [18]. In rare patients, bradycardia may be the initial presenting symptom due to conduction system abnormality that prompts further evaluation including an electrocardiogram (ECG). The characteristic findings on the ECG are suggestive of L-TGA, and the diagnosis is confirmed by echocardiography. (See 'Electrocardiogram findings' above.)

Echocardiography — Diagnosis of L-TGA is typically made by echocardiography. L-TGA is recognized by identifying the systemic location of the tricuspid valve and morphologic right ventricle (RV). The RV is characterized by coarse trabeculations, which differentiates it from the morphologic left ventricle (LV) with its fine trabeculations and smooth septal surface. These ventricular lesions are best seen from short-axis and apical four-chamber views.

In patients with L-TGA, the great arteries do not normally cross and are parallel to one another, with the aorta abnormally positioned anterior, superior, and to the left of the pulmonary artery. Subcostal imaging often provides the best views to demonstrate that the posterior, inferior, and rightward pulmonary artery is associated with the morphologic LV.

In addition, particular attention should be paid when evaluating the ventricular septum for defects since patients may have large inlet VSDs or smaller muscular VSDs. Due to the high incidence of abnormalities in the left-sided tricuspid valve, this structure should be evaluated for the apical displacement of the septal leaflet that is seen in Ebstein malformation [1,15].

DIFFERENTIAL DIAGNOSIS — The diagnosis in most patients with L-TGA is made incidentally during echocardiographic evaluation for antenatal diagnosis of congenital heart disease or symptoms related to other congenital heart defects, primarily ventricular septal defect (VSD) and pulmonary flow obstruction.

However, in most patients without associated symptomatic cardiac defects, the differential diagnosis includes conditions that present with symptoms suggestive of heart failure or complete heart block:

●Heart failure – The signs and symptoms of heart failure are nonspecific (dyspnea, fatigue, fluid retention, and decreased exercise tolerance). As a result, the differential diagnosis is broad and includes other cardiac conditions that present with heart failure (eg, myocarditis, cardiomyopathy, and ischemic heart disease) and noncardiac conditions such as chronic obstructive pulmonary disease and connective tissue disorders. Echocardiography will distinguish L-TGA from other causes of heart failure. (See "Heart failure: Clinical manifestations and diagnosis in adults" and "Determining the etiology and severity of heart failure or cardiomyopathy", section on 'Etiology'.)

●Complete heart block – The signs and symptoms of complete heart block are nonspecific (bradycardia, syncope, or exercise intolerance). Other conditions that can present with complete heart block include myocardial ischemia, drugs (eg, calcium channel blockers and beta blockers), cardiomyopathy, myocarditis, and idiopathic progressive cardiac conduction disease. Echocardiography will distinguish L-TGA from these other causes. (See "Etiology of atrioventricular block".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Congenital heart disease in infants and children".)

SUMMARY AND RECOMMENDATIONS

●Anatomy and embryology – Levo- or left-transposition of the great arteries (L-TGA; also referred to as congenitally corrected TGA, double discordance, or ventricular inversion) is a rare and complex form of congenital heart disease characterized by atrioventricular (AV) and ventriculoarterial discordance (figure 1). (See 'Anatomy of L-transposition of the great arteries' above.)

L-TGA results from abnormal left looping of the primitive heart such that the morphologic left ventricle (LV) is positioned to the right of the morphologic right ventricle (RV). This results in deoxygenated systemic venous blood returning to the discordant LV via the mitral valve and into the lung through the discordant transposed pulmonary arteries. Oxygenated blood flows from the lungs through the pulmonary veins through the left atrium into the discordant RV via the tricuspid valve and returns to the systemic circulation through the discordant aorta. (See 'Embryology and anatomy' above.)

●Clinical manifestations – In most cases of L-TGA (>90 percent), another cardiac lesion is present. In these patients, and the clinical manifestations are dependent on the associated cardiac lesion:

•Ventricular septal defect (VSD; present in 70 to 80 percent of patients with L-TGA) (see "Isolated ventricular septal defects (VSDs) in infants and children: Anatomy, clinical features, and diagnosis", section on 'Clinical features')

•Pulmonary ventricular outflow tract obstruction (present in 30 to 60 percent of patients with L-TGA) (see "Pulmonic stenosis in infants and children: Clinical manifestations and diagnosis", section on 'Clinical manifestations')

A small minority of patients do not have other associated structural defects. These patients usually present during adulthood with signs and symptoms of complete heart block, arrhythmias, systemic tricuspid valve regurgitation, or systemic RV dysfunction with ultimate heart failure. (See 'Clinical manifestations' above.)

●Electrocardiogram (ECG) and chest radiograph findings – Characteristic ECG findings of Q waves in the right precordial leads and an absence of Q waves in the left-sided precordial leads are seen in approximately 25 percent of affected patients. (See 'Electrocardiogram findings' above.)

The chest radiograph may demonstrate features of mesocardia or dextrocardia. (See 'Chest radiograph findings' above.)

●Diagnosis – The diagnosis of L-TGA is made by echocardiography, which demonstrates the inversion of the ventricles and the abnormal placement and parallel course of the great arteries. In most patients, the diagnosis is made as an incidental finding in a postnatal echocardiography, which is performed to evaluate for symptoms of the associated cardiac lesion. (See 'Diagnosis' above.)

●Differential diagnosis – In patients without associated symptomatic cardiac defects, the differential diagnosis includes conditions that present with symptoms suggestive of heart failure or complete heart block. L-TGA is distinguished from these conditions by echocardiography. (See 'Differential diagnosis' above.)

●Natural history – Patients with L-TGA are at risk for heart failure due to progressive dysfunction of the morphologic systemic RV and systemic tricuspid valve regurgitation. The risk of heart failure is greater in patients with L-TGA and associated cardiac lesions (eg, VSDs, pulmonary outflow tract, and tricuspid regurgitation) versus those with isolated L-TGA. (See 'Natural history' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges David R Fulton, MD, who contributed to an earlier version of this topic review.