Congenitally corrected (L-looped) transposition of the great arteries (ccTGA): Anatomy, clinical features, and diagnosis

INTRODUCTION — 

Congenitally corrected transposition of the great arteries (ccTGA; also called L-looped TGA [L-TGA], double discordance, or ventricular inversion) is a rare form of congenital heart disease characterized by atrioventricular (AV) and ventriculoarterial discordance (figure 1).

ccTGA usually does not present with cyanosis unless there are other associated cardiac defects. In ccTGA, blood flows in the correct physiologic direction, resulting in normal oxygenation of the systemic venous return via the abnormally placed ventricles and great arteries. However, patients with ccTGA are at risk of developing heart failure in adulthood due to progressive decline in systemic right ventricular (RV) function.

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

D-looped 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 — ccTGA is characterized by atrioventricular (AV) and ventriculoarterial discordance. Coronary artery anatomy is variable.

●Cardiac anatomy – ccTGA 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.

In ccTGA, 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 ccTGA. It is an anatomic mirror image of L-looped TGA and accounted for 2 out of 22 cases of ccTGA in one series [3]. Although the anatomy of this lesion is different, the physiology 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, the term ccTGA will be used to describe both anatomic variants.

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

●Coronary artery anatomy – Coronary artery anatomy is variable in patients with ccTGA. 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 — 

ccTGA 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 [4-7].

The cause of ccTGA is likely multifactorial. Limited data suggest that both environmental and genetic factors contribute to its pathogenesis [1,8,9].

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 ccTGA are asymptomatic at birth and during childhood.

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

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, chronic heart failure) is a common late complication in patients with unrepaired ccTGA, including unoperated patients with isolated ccTGA and patients with associated cardiac lesions who undergo surgical repair of the associated defect without addressing the AV and ventriculoarterial discordance. (See "Congenitally corrected (L-looped) transposition of the great arteries (ccTGA): Management and outcome", section on 'Patients managed with a physiologic-based approach'.)

RV dysfunction is thought to be due to an unfavorable tripartite geometric configuration that does not adapt to pressure or volume overload [10]. The long-term systemic workload results in progressive tricuspid regurgitation that increases volume overload and contributes to ventricular dysfunction and failure [11]. 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 [12].

CLINICAL MANIFESTATIONS

Antenatal presentation — Although prenatal detection of ccTGA is challenging, rates of prenatal suspicion of ccTGA and referral for fetal cardiac imaging have increased over time [7]. (See 'Fetal diagnosis' below and "Congenital heart disease: Prenatal screening, diagnosis, and management".)

In a multicenter study that reported outcomes of 194 fetuses diagnosed with ccTGA at a median gestational age of 23 weeks, 85 percent were live born; the pregnancy was terminated in 13 percent and fetal death occurred in 2 percent [7].

Postnatal presentation — The postnatal presentation of ccTGA depends upon the presence and type of associated cardiac abnormalities, which are present in most patients with ccTGA. In these patients, ccTGA is detected when echocardiography is performed to evaluate the signs and symptoms of the associated cardiac lesion(s). Less commonly, ccTGA occurs as an isolated defect. Patients with isolated ccTGA are asymptomatic at birth and generally present later in life with signs of chronic heart failure, systemic atrioventricular (AV) valve regurgitation, or heart block.

Associated cardiac abnormalities — In most cases of ccTGA (>90 percent), there are other associated cardiac defects, most commonly a ventricular septal defect (VSD) [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]:

●VSDs occur in 70 to 80 percent of patients with ccTGA. 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 (morphologic left ventricular [LV]) outflow tract obstruction occurs in 30 to 60 percent of cases and often accompanies a large VSD. The obstruction is usually 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.

●Abnormalities of the systemic AV valve (morphologic tricuspid valve) are observed at autopsy in up to 90 percent of ccTGA cases. AV valve regurgitation is common and it generally progresses over time [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 ccTGA [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 ccTGA — ccTGA occurs as an isolated defect in <10 percent of affected patients. Patients with isolated ccTGA generally present later in life with signs and symptoms related to either arrhythmias or heart failure.

●Complete heart block – Complete heart block is the most common arrhythmia in patients with ccTGA; it presents with signs and symptoms including bradycardia, fatigue, and poor exercise tolerance. (See "Acquired third-degree (complete) atrioventricular block".)

In ccTGA, 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.

Complete heart block can develop prenatally, and ccTGA should be considered in the differential diagnosis of fetal heart block [18]. (See "Fetal arrhythmias", section on 'Heart block'.)

●Heart failure – 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) [19]. (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 is uncommon. When present, it usually results from either pulmonary atresia or critical pulmonary stenosis and a large VSD. (See "Cyanotic congenital heart disease (CHD) in the newborn: Causes, evaluation, and initial management".)

●Tachypnea – Patients with associated cardiac defects 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 ccTGA, 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 ccTGA, 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 ccTGA' above.)

Chest radiograph findings — Approximately 25 percent of patients with ccTGA 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 ccTGA is largely determined by the presence of associated cardiac defects and the progressive dysfunction of the morphologic right ventricle (RV) as the systemic ventricle [13,19,20]. In particular, systemic atrioventricular (AV) valve (morphologic tricuspid valve) regurgitation is a concomitant risk factor for heart failure and mortality in adult patients because of the volume load it imposes on the morphologic RV [1,11,13,17]. (See 'Pathophysiology' above.)

Long-term outcomes for patients with unoperated ccTGA are described in greater detail separately. (See "Congenitally corrected (L-looped) transposition of the great arteries (ccTGA): Management and outcome", section on 'Patients managed with a physiologic-based approach'.)  

DIAGNOSIS

Fetal diagnosis — Antenatal diagnosis of ccTGA can be challenging, especially if there are no other associated abnormalities that are more easily detected, such as a ventricular septal defect (VSD) or complete heart block [7]. 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 D-looped TGA [21]. 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.

Postnatal diagnosis — The diagnosis of ccTGA 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 [22]. (See 'Associated cardiac abnormalities' above.)

Patients with isolated ccTGA usually present in adulthood with signs of heart failure or arrhythmia, and the diagnosis is confirmed by echocardiography.

Echocardiography — On echocardiography, ccTGA 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 ccTGA, 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 — 

Most patients with ccTGA have associated cardiac defects (most commonly a ventricular septal defect (VSD) and/or pulmonic stenosis), and the presentation is largely dependent on the other lesion(s). If not detected antenatally, these defects may present with an audible murmur and/or signs of heart failure. There are numerous other causes of heart murmurs and heart failure in children (table 1 and table 2). Ultimately, echocardiography is required to distinguish ccTGA from other causes of murmurs or heart failure. The approach to evaluating murmurs and heart failure in children is discussed separately. (See "Approach to the infant or child with a cardiac murmur" and "Heart failure in children: Etiology, clinical manifestations, and diagnosis".)

Less commonly, ccTGA presents as an isolated defect. These patients typically present in adulthood with signs of heart failure and/or cardiac rhythm disturbance (most commonly complete heart block). Echocardiography distinguishes ccTGA from other causes of heart failure or arrythmias. The approach to evaluating heart failure and heart block in adult patients is discussed separately. (See "Determining the etiology and severity of heart failure or cardiomyopathy" and "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 – Congenitally corrected transposition of the great arteries (ccTGA; also called L-looped TGA) 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.)

ccTGA 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 ccTGA (>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 minority of patients (<10 percent) 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 and 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 (waveform 1). (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.)