Definition

Physiologically “corrected” transposition of the great arteries (TGA) is an uncommon congenital heart defect characterized by discordant atrioventricular (AV) and discordant ventriculoarterial (VA) connections (double discordance) (Figure 27.1). The systemic veins join the right atrium, which is connected by a mitral valve to the subpulmonary left ventricle (LV). The left atrium receives pulmonary venous blood from the pulmonary veins and is connected by a tricuspid valve to the subaortic right ventricle (RV). The VA connections are also discordant such that the aorta arises from the morphologic RV and the pulmonary artery from the morphologic LV. Discordant AV and VA connections can occur in isolation; however, associated congenital cardiac anomalies are common.

Incidence

Physiologically “corrected” TGA is an uncommon congenital heart defect – too infrequent to deserve separate mention in a large study reporting the incidence of congenital heart defects [1]. It comprises less than 0.5% of all forms of congenital heart defects. Several sources have reported incidences ranging from two to seven per 100,000 live births [2]. In a study of more than 800,000 children born between 1980 and 1990, the prospective Bohemia Survival Study yielded a prevalence of three per 100,000 live births; this accounted for 0.4% of all congenital heart defects in this study [3].

Developmental considerations and etiology

The etiology of physiologically “corrected” TGA is unknown. The primitive heart tube with the sinus venosus and the atrium at one end and the conotruncus at the other end does not loop to the right (D‐loop) as in the normal heart; instead, it loops to the left (L‐loop). This leftward looping brings the future RV to the left and the LV to the right. In the case of physiologically “corrected” TGA, this abnormal looping is associated with discordant connections between the ventricles and great arteries likely as a result of abnormal septation of the truncus arteriosus.

Both genetic and environmental factors have been implicated in the etiology of this congenital heart defect [4–6]. The recurrence of TGA (concordant AV connection/discordant VA connection, D‐loop TGA) and physiologically “corrected” TGA (discordant AV and VA connections, L‐loop TGA) in the same family suggests a pathogenetic link between these two anatomically different malformations [5]. Genetic syndromes in association with physiologically “corrected” TGA are uncommon.

Morphology and classification

Anatomy

There may be usual arrangement of the viscera and atria (situs solitus) or a mirror‐image arrangement (situs inversus); the cardiac orientation can be levocardia, dextrocardia, or mesocardia.

Usual arrangement of the atria (atrial situs solitus)

The majority (∼95%) of patients present with the usual arrangement of the atria (situs solitus); that is, the right atrium lies to the right of the left atrium (Figure 27.1a). The right‐sided superior vena cava and inferior vena cava connect to the right‐sided right atrium, which empties through the mitral valve into a right sided LV, which gives rise to a right‐sided, posterior pulmonary artery (Figure 27.2, Video 27.1). The mitral valve has two papillary muscles and is often in fibrous continuity with the cusps of the pulmonary valve (Figure 27.3, Video 27.2). The pulmonary veins are connected to the left‐sided left atrium, which empties through the tricuspid valve into the subaortic left‐sided RV, in an L‐type ventricular loop (Figure 27.2, Video 27.1). In contrast to the normal heart, the great arteries are in parallel, and the position of the ascending aorta is left and anterior in relation to the pulmonary trunk (Figures 27.3b and 27.4, Video 27.2 and 27.3).

Mirror‐image arrangement of the atria (atrial situs inversus)

Approximately 5% of patients with physiologically “corrected” TGA present with atrial situs inversus (Figure 27.1b): the left‐sided superior and inferior caval veins connect to the left‐sided right atrium, and the pulmonary veins connect to the right‐sided left atrium. As mentioned earlier, there are discordant AV and VA connections. There is a D‐type ventricular loop with the subaortic RV to the right of the subpulmonary LV (Figures 27.5 and 27.6, Video 27.4). The aorta is right‐sided and anteriorly located in relation to the pulmonary trunk. The subxiphoid long‐axis and apical four‐chamber windows are the best views to describe the right–left location relative to each ventricle and to differentiate between D‐ and L‐ventricular loops: the inflow of the RV usually lies to the right of the LV in the presence of D‐ventricular loop (Figures 27.5 and 27.6, Video 27.4), whereas it usually lies to the left in the presence of L‐ventricular loop (Figure 27.2, Video 27.1). However, spatial relationship of the ventricles can vary, and there are limitations to reliably take the right–left location relative to each other for the description of the ventricular loop (see Chapter 3 for details).

Cardiac orientation

The axis between the base of the heart and the apex can point to the left (levocardia), to the right (dextrocardia), or it can be in the midline (mesocardia). Approximately 75% of patients with physiologically “corrected” TGA present with levocardia.

Ventricular topology

Ventricular topology describes the internal organization of the ventricles and the spatial relationship of one ventricle to the other; it can be right‐ or left‐handed. The abnormal looping (L‐loop) results in a left‐hand pattern in the RV [13,14]: the left hand must be used to place the palm of the hand against the RV septal surface in such a way that the thumb points to the inlet and the fingers point to the outlet of the RV (in contrast to a D‐loop or a normal heart where the right hand must be used; see Chapter 3 for details).

Atrioventricular valves

The mitral valve has two papillary muscles without insertion to the interventricular septum. However, one‐fourth of the patients with physiologically “corrected” TGA may present with abnormalities of the mitral valve [15]. The tricuspid valve, which is left‐sided in situs solitus (usual arrangement) of the atria, is frequently dysplastic or Ebstein‐like (see “Common associated lesions” later).

Septal malalignment

Malalignment between the atrial septum and the inlet part of the ventricular septum in relation to the wedged position of the pulmonary outflow tract is a characteristic morphologic feature of discordant AV connection in patients with physiologically “corrected” TGA, and affects the position of the conduction system and the anatomy of the pulmonary outflow [16–18]. This abnormality of the conduction system poses a risk for spontaneous periprocedural complete heart block. The AV septal malalignment has been considered directly related to the presence and location of the ventricular septal defect (VSD) but is also present in cases with an intact ventricular septum. One of the consequences of this malalignment is the lack of the interventricular component of the membranous septum, located between the LV and the left atrium in these hearts (Figure 27.7, Video 27.5) [8]. In the presence of a VSD, the septal malalignment has implications for the size and extent of the VSD, the severity of LV (pulmonary) outflow tract obstruction, and the position of the conduction system [17,19]. The degree of septal malalignment is less pronounced in hearts with a small or atretic pulmonary artery or in patients with situs inversus (mirror‐image arrangement) of the atria than in those with severe left ventricular outflow tract obstruction or situs solitus [17].

Coronary arteries

Coronary artery anatomy and distribution have gained more attention in recent years because of the potential of a double switch procedure in the surgical management of physiologically “corrected” TGA. The coronary arteries reflect the ventricular topology. In patients with an L‐loop, there is a mirror‐image distribution of the coronary arteries, which follow the corresponding ventricles (Figure 27.8, Video 27.6 and 27.7) [20,21]. The epicardial distribution of the right‐sided coronary artery is that of a morphologically left coronary artery (circumflex and anterior descending coronary arteries); the left‐sided coronary artery follows the left‐sided AV groove and supplies the RV [20,22–25]. Although the origin and course of the coronary arteries show frequent variation [20,22,25,26], the origin and proximal branching pattern in physiologically “corrected” TGA appear to be more consistent than in simple TGA [25].

Coronary sinus

Knowledge of the anatomy of the coronary sinus and coronary venous system has become important as cardiac resynchronization therapy with implantation of pacemaker leads into the coronary sinus is increasingly considered as a therapeutic option. In normal anatomy, the coronary sinus courses posterior–inferior to the left atrium and connects to the right atrium [27,28]. In physiologically “corrected” TGA, the coronary sinus is expected to travel between the left atrium and the subaortic RV (which it predominantly drains) [29,30]. The coronary sinus can usually be imaged by echocardiography in the pediatric population. However, alternative imaging modalities are required for preprocedural planning to image the anatomy of the coronary venous system and its variations [28,29].

Common associated lesions

Physiologically “corrected” TGA may occur in isolation (rarely) or may be complicated by associated congenital heart defects. More than 90% of patients have associated defects [31–34] and the following triad of malformations is common: (i) VSD; (ii) LV (pulmonary) outflow tract obstruction; and (iii) anomalies of the tricuspid valve. Any combination of these anomalies can coexist.

Ventricular septal defect

Ventricular septal defects are common and can occupy any position, central perimembranous, inlet, trabecular muscular, outlet or malalignment, and to avoid confusion should be described according to the current nomenclature [35]. The incidence ranges between 60% and 80%, with a higher incidence described in clinical or specimen‐based studies [21,31] and somewhat lower incidence noted in fetal studies [36]. The VSD is frequently nonrestrictive and is often the result of malalignment between the atrial and ventricular septa. Outlet VSDs are the most common. If the defect is located in the inlet septum, the offsetting of the attachment of both AV valves is lost (Figure 27.9a), and can be sometimes associated with tricuspid valve straddling. Trabecular muscular VSDs can be single, multiple, or associated with other types of VSDs (Figure 27.9b, Video 27.8).

Left ventricular outflow tract obstruction

Left ventricular outflow tract (subpulmonary) obstruction is observed in up to 50% of patients with situs solitus and occurs at the subvalvar and/or valvar levels (Figure 27.10, Video 27.9–27.12). Isolated valvar pulmonary stenosis is rare, whereas combined subvalvar and valvar obstruction is common [31,32]. The subvalvar stenosis can be muscular or caused by a fibrous shelf, a ridge of fibrous tissue tags originating from any of the valves near the outflow tract. LV outflow tract obstruction can also result from accessory aneurysmal tricuspid valvar tissue prolapsing through a VSD, a large aneurysm of the membranous septum, or from systolic anterior motion of the mitral valve leaflets due to abnormal anatomy of the subvalvar apparatus and/or abnormal geometry of the LV (Figure 27.11, Video 27.13).

Abnormalities of the tricuspid valve

Abnormalities of the tricuspid valve are very common and occur in up to 90% of autopsy series; however, they are less frequently identified in the clinical setting [21,31,33,34,37]. The dysplastic tricuspid valve can occur with or without apical displacement of both the septal and posterior leaflets as in patients with concordant AV connection. Ebstein‐like malformation of the tricuspid valve in physiologically “corrected” TGA is different from the classic Ebstein anomaly in patients with concordant connection (Figures 27.12 and 27.13, Video 27.14–27.17). In discordant AV connections there is usually no rotational displacement of septal and posterior leaflets and the inlet portion of the RV myocardium is typically not dilated and thinned. The anterior tricuspid leaflet is usually not large and does not have a “sail‐like” appearance and the atrialized portion of the RV inflow is usually small. However, classic Ebstein anomaly of the left‐sided tricuspid valve and RV inflow can infrequently be seen in physiologically “corrected” TGA. Other abnormalities of the tricuspid valve include hypoplasia and double‐orifice tricuspid valve.

Other rare associated anomalies of the AV valves include straddling or overriding, anomalies that can significantly complicate surgical treatment if biventricular repair is considered [38].

Other associated anomalies

Aortic arch abnormalities (e.g., aortic atresia, coarctation, interrupted aortic arch) can be observed in hearts with discordant segmental alignments [39,40]. Subaortic obstruction should be suspected in these cases.

Pathophysiology

The discordant AV and VA connections result in a circulation that is in series, as in the normal heart; thus, the term physiologically “corrected.” In visceral‐atrial situs solitus, deoxygenated blood returning to the right atrium reaches the pulmonary circulation through the right‐sided LV, whereas the oxygenated pulmonary venous blood returns to the left atrium and reaches the systemic circulation through the left‐sided RV (see Figure 27.1a). In visceral‐atrial situs inversus, deoxygenated blood returning to the left‐sided right atrium reaches the pulmonary circulation through the left‐sided LV whereas the oxygenated pulmonary venous blood returns to the right‐sided left atrium and reaches the systemic circulation through the right‐sided RV (see Figure 27.1b). Thus, in the absence of associated anomalies, patients with physiologically “corrected” TGA are acyanotic and the congenital heart defect may remain undiagnosed. Complexity and severity of the associated intracardiac defects determine the pathophysiology, and the natural and “unnatural” history [31,41–48]. The subaortic RV supporting the systemic circulation remodels and develops concentric and eccentric hypertrophy, respectively. As the myocardium ages, the subaortic RV may fail, with subsequent dilation and development of hemodynamically relevant tricuspid regurgitation due to annular dilation and abnormal geometry of the RV (Figures 27.12 and 27.13, Video 27.14–27.17) [31,41,43,45–47].

Associated intracardiac defects have different pathophysiologic effects on the subaortic RV and pulmonary blood flow. Volume load of the subaortic RV can be caused by tricuspid regurgitation, a nonrestrictive VSD, or both. Severe tricuspid regurgitation can be caused by dysplasia of the tricuspid valve or by malcoaptation of the tricuspid valve leaflets as a consequence of a dilated, failing RV myocardium. Severe volume load of the RV can lead to heart failure symptoms during infancy, childhood, or adulthood. Severe tricuspid regurgitation represents a major risk factor, appears to drive RV systolic dysfunction and heart failure, and is linked to survival [45,47]. Hence, meticulous monitoring of RV systolic function and severity of tricuspid regurgitation is critical.

Left ventricular outflow tract (pulmonary) obstruction reduces pulmonary blood flow, alters the pressure load on the subpulmonary LV, alters the volume load of the subaortic RV, and modifies left and right ventriculoventricular interaction [46]. Tricuspid regurgitation is usually less severe in the presence of LV outflow tract obstruction because the interventricular septum shifts toward the RV secondary to the increased LV systolic pressure. The septal shift impacts RV geometry, can improve coaptation of the tricuspid valve leaflets, and potentially reduces the severity of tricuspid regurgitation. Shift of the interventricular septum and remodeling of the RV are the goal of pulmonary artery banding, performed for “training” the LV in preparation for a double switch procedure (Figures 27.12 and 27.13, Video 27.14–27.17) [46]. The presence of volume and/or pressure loads on both ventricles has an important impact on interventricular interaction and on morbidity and mortality [45–47].

Complete heart block due to abnormal location and course of the AV node and the bundle of His in this anatomy may be the first symptom in children, adolescents, or adults [16,31,49]. Thus, physiologically “corrected” TGA must be excluded in all patients who present with conduction abnormalities, such as second‐ or third‐degree AV block.