Definitions

Anatomic single ventricle refers to hearts with absence of either the right ventricular sinus (anatomic single left ventricle (LV)) or the left ventricular sinus (anatomic single right ventricle (RV)). Hearts in this category have only one ventricular sinus or body, anatomically as well as functionally [8,9]. The other chamber usually present in the ventricular mass is an infundibulum or outlet chamber, which does not contribute substantially to cardiac output. These include DILV, most double‐inlet RV (DIRV), most TA, and some hearts with mitral and aortic atresia and absent left ventricular cavity.

Functional single ventricle refers to a range of congenital cardiac anomalies characterized by absence or severe underdevelopment of a ventricular chamber or other complex anomalies in which reconstruction of biventricular circulation is deemed prohibitive. Hearts in this category may have two ventricular sinuses but one or both are incapable of sustaining an entire cardiac output [10]. Those in the latter category are discussed in other chapters and will only be listed here. Although not all cases of these defects have functionally one ventricle, many do and must be identified as soon as possible to maximize outcomes. Included are variants of hypoplastic left heart syndrome (Chapter 21), hypoplastic right heart syndrome (mostly pulmonary atresia with intact ventricular septum) (Chapter 18), straddling mitral valve (Chapter 15), straddling tricuspid valve (Chapter 14), unbalanced common atrioventricular (AV) canal (Chapter 16), congenitally physiologically corrected TGA (Chapter 27), Ebstein anomaly (Chapter 14), heterotaxy syndromes (Chapter 30), and superior‐inferior ventricles (SIV) and crisscross heart, which are included in this chapter.

Etiology

The genetic and/or environmental causes of these defects are poorly understood. Most cases appear to be sporadic although familial occurrences have been reported [11–14]. There are a few case reports of syndromic association of TA or other functionally single‐ventricle hearts [15–22]. Recent evidence suggests that pathogenic copy number variants may contribute to single‐ventricle abnormalities in approximately 10% of cases [23]. The recurrence risk among first‐degree relatives appears to be in the range associated with polygenic inheritance (2–5%) [24–27]. Maternal diabetes, especially if treated with insulin, appears to be a risk factor for double‐inlet ventricle [28].

Normal embryologic development

Concepts about development of most congenital heart defects are speculative because no one has ever observed active, in vivo development of a defective human heart. However, it is possible to infer likely mechanisms from what is known about normal human cardiac development and abnormal development in animal models. The following brief description of normal development is provided for comparison with the proposed abnormal development in subsequent sections.

During early looping, the heart tube is rather uniform with no clear demarcation of chambers. Cells from the second heart field are added to both ends of the heart tube as it elongates and loops [29]. The dorsal mesocardium, which initially joins the heart tube throughout its length to prepharyngeal mesoderm, degenerates in its mid‐portion [30] allowing the elongating heart tube to bend anteriorly and then rightward, called dextral or D‐looping [31]. As the heart chambers begin expansile growth from the outer curvature of the looping heart tube [32], the AV canal becomes apparent as a constriction between the common atrial chamber and the developing LV and the interventricular foramen as a constriction between the developing ventricles. The AV canal is exclusively aligned with the developing LV and the outflow continues from the inner curvature of the heart tube at the rostral end of the developing RV. Swellings or cushions develop in the AV canal as well as the outflow [33]. As the heart chambers continue to enlarge, the right side of the AV canal and the right atrium grow faster than the left, allowing the AV canal to expand below the right atrium and above the RV, creating a right ventricular inflow and establishing alignment of the right atrium with the RV through the right side of the AV canal [34]. At the same time, septation of the common atrium begins with growth of the septum primum or the primary atrial septum from the superior wall and invasion of the dorsal mesenchymal protrusion or vestibular spine from the posterior‐inferior wall [35]. These septal structures continue to grow into and septate the common atrium, finally fusing with the two main (superior and inferior) AV cushions. At that point the AV cushions fuse to each other as well, separating the AV canal into right and left halves, aligning the right atrium and ventricle and the left atrium and ventricle, respectively. Before completion of atrial septation, the septum primum, near its origin from the superior wall, breaks down forming the ostium secundum (the foramen ovale) and allowing continued communication between the right and left atria. The fused AV cushions then become draped over the muscular inflow ventricular septum that has developed on their ventricular side [36]. Meanwhile the outflow cushions fuse from distal to proximal under the influence of cardiac neural crest cells, dividing the outflow into aorta and pulmonary artery [37]. As this occurs, the proximal outflow undergoes counterclockwise rotation, as viewed from the ventricles, so that the aorta, which is anterior distally, comes to lie rightward and posterior proximally, and the pulmonary artery, which is posterior distally, moves anteriorly and leftward proximally [38]. The outflow septum, which developed by fusion and muscularization of the proximal parts of the outflow cushions, then inserts like a curtain onto the right side of the limbs of the primary interventricular foramen, aligning the aorta with the LV through the foramen and the pulmonary artery with the RV, and closing the communication between the left and right ventricular outflows [39]. The AV valves develop from the AV cushions by a process that involves thinning, elongation, and separation from underlying myocardium by apoptosis of cardiomyocytes [36]. The semilunar valves develop from the outflow cushions by excavation and thinning that also involves apoptosis, probably initiated by neural crest cells [40].

Embryologic development

Double‐inlet left ventricle is easily envisioned as an arrest of development at the stage where the AV canal has expanded under the right atrium but is still completely aligned with the developing LV. DILV is associated with leftward bending or looping (levo or L‐looping) of the heart tube in 65–70% of cases, whereas in 30–35% of cases dextro or D‐looping occurs. DILV is associated with failure of development and growth of the RV sinus. As the AV canal expands toward the inner curvature of the heart tube it becomes aligned with the right atrium. However, the expanding edge does not cross the primary foramen between the LV and outflow as it does in the normal heart. It is unclear if confinement of the AV canal to the LV is the primary mechanism and failure of RV development secondary, or the converse. In either case, atrial septation appears to proceed correctly with the septum primum and dorsal mesenchymal protrusion fusing with the superior and inferior AV cushions as they fuse to each other to form two AV valves. It is interesting that development of the AV valves proceeds rather normally despite lacking an underlying muscular ventricular septum over which to drape themselves. This is consistent with the concept that the AV valves develop from the AV cushions and not the underlying myocardium. The infundibulum or outlet chamber derives from the outflow portion or ascending limb of the heart tube and maintains its primitive connection with the LV, the primary outflow foramen, which would have become the interventricular foramen had the RV sinus developed. In fact, the size of the infundibular outlet chamber is somewhat variable and in some cases it appears that a small portion of right ventricular sinus might be present, especially in hearts where the outlet chamber extends inferiorly toward the diaphragmatic heart border. Alternatively, the larger size of the infundibular outlet chamber could be from expansion of the apical trabecular portion of the infundibulum.

Abnormal ventriculoarterial (VA) alignment, present in the great majority of these hearts, is most likely due to abnormal rotation of the outflow so that the proximal aorta remains anterior and the proximal pulmonary trunk posterior [41,42]. This abnormal rotation is also associated with persistence of the communication between the left ventricular outflow and the infundibular chamber due to failure of the conal (infundibular) septum to join the limbs of the primary outflow foramen [42]. Rarely, and essentially exclusively in D‐loop hearts, the rotation of the outflow occurs correctly, resulting in normally aligned great arteries (known as Holmes heart). Even in these cases, however, the outflow septum rarely completely closes the communication between the left ventricular outflow and the infundibular outflow chamber.

Anatomy

The systemic and pulmonary veins and atria are usually normal (for situs solitus). Although reported in situs inversus [43,44], such hearts are extraordinarily rare because situs inversus and DILV are both rare conditions.

The AV valves are often recognizable as having mitral or tricuspid valve morphology [45,46]. The morphology of the valve near the septal wall of the LV (see later) is often tricuspid in character and the one nearest the free wall more mitral (Figure 28.5). In other cases the valves are symmetrical, resembling each other more than either a mitral or tricuspid valve. Hypoplasia and stenosis of an AV valve is seen in up to 15–20% of hearts [46] (Figure 28.6). Rarely a common AV valve is aligned and connected to a single LV (common‐inlet single LV).

The LV chamber has a free wall with multiple papillary muscles and trabeculae on one side and a smooth septal wall on the other side (Figures 28.1–28.3). Note that the septal wall is the most characteristic feature of the LV and is present even when there is no RV sinus on the other side. Further, the presence of a smooth‐walled septum between the LV sinus on one side and the infundibular outlet chamber on the other side is the hallmark of single LV. A large muscle bundle, the posterior median ridge, is often present on the inferior or diaphragmatic wall of the LV, running from base to apex between the AV valves, and may be mistaken for a ventricular septum in some echocardiographic views (Figure 28.3a). As noted previously, an infundibular outlet chamber is uniformly associated with the LV (Figures 28.1b and 28.2b) and the AV valve closer to the septum can straddle into it (Figure 28.3) [9,46]. The connection between the LV and the infundibular outlet chamber is variously called a bulboventricular foramen, interventricular foramen, or ventricular septal defect.

In fact, the type and location of the communication is variable [46,47]. Most often it is the persisting part of the outflow foramen of the embryonic heart between the conal or infundibular septum (outlet septum) and the LV septal wall (Figures 28.1 and 28.3). The infundibular or outlet septum is readily identified between the semilunar valves because it is rarely correctly inserted into the muscular ventricular septum (Figures 28.1c and 28.2b). In other cases, the communication is a muscular defect between the mid or apical part of the infundibular outlet chamber and the LV (Figure 28.7). The size of the communication is also variable [46–48]. A small communication is a frequent cause of obstruction to whichever semilunar root arises from the infundibular outlet chamber. When the communication is through part of the primary outflow foramen, it is often large and unobstructed while more apical muscular communications are essentially always obstructed [46].

The situs or organization of the LV can be either solitus or D‐loop, or inversus or L‐loop (Figures 28.1a, 28.2b, and 28.3a). The hand rule is useful to distinguish between the types of LV organization [49]. One imagines placing the thumb in an AV valve, the palm against the septum, and the index finger in the outflow. If this can be done with the left hand, the LV is solitus or D‐loop. Alternatively, if a right hand is required, the LV is inverted or L‐loop. (Note that the handedness of the LV is opposite to that of the RV where the hand rule is more frequently applied.) The importance of determining ventricular situs or loop is threefold: first, the conduction system is usually superior to the outflow foramen in an inverted or L‐loop LV (with atrial situs solitus) but inferior in a solitus or D‐loop LV [50,51]; second, the VA alignment is essentially always transposition (discordance) when the LV is L‐looped whereas in 10% or so of DILV with a solitus or D‐loop LV, the great arteries are normally related [46]; and third, the epicardial course of the coronary arteries is determined by the arrangement of the ventricles [52].

When the great arteries are transposed, the pulmonary valve is typically wedged between the AV valves and is in fibrous continuity with both (Figures 28.1a and 28.3a), while the aortic valve is aligned with the infundibular outlet chamber and supported by infundibular muscle (Figures 28.1b and 28.3b). Conversely, in normally related great arteries it is the aorta that is wedged between the AV valves and the pulmonary artery arises from the infundibular outlet chamber. In any great artery relationship, accessory AV valve tissue may contribute to subvalvar obstruction of the posterior semilunar valve.

The coronary artery anatomy depends on the ventricular situs or loop because the epicardial coronary pattern seems to be determined by cues from the underlying ventricle. When the great arteries are malposed (transposition or double outlet), the arteries arise from the posterior, facing sinuses. In an L‐loop DILV, the morphologically left coronary artery is right‐sided and bifurcates into a small delimiting artery (analogous to the anterior descending artery) that runs in the groove between the LV and the infundibular outlet chamber and a circumflex artery that passes posteriorly in the right AV groove, giving off a variable number of atrial and ventricular branches along its course. The morphologically right coronary artery passes posteriorly in the left AV groove, giving off a posterior delimiting artery and a variable number of ventricular branches that run toward the apex. In D‐loop DILV with transposition of the great arteries (discordant VA alignment), the coronary pattern is just the mirror image of that described earlier. If the VA alignment is concordant (normally related great arteries), the coronary pattern is usually much like that seen in the normal heart where the ostia are in the anterior, facing sinuses.

The aortic arch is usually to the left of the trachea and branching is usually normal. The orientation of a left aortic arch is often from left‐anterior to right‐posterior in L‐transposed arteries as a result of the location of the ascending aorta. The branch pulmonary arteries are usually normal, even in hearts with subvalvar and/or valvar pulmonary stenosis.

The cardiotypes most frequently associated with DILV are: {S,L,L} (solitus atria, inverted L‐loop LV, leftward and anterior aorta) in ~60%; {S,D,D} (solitus atria, solitus D‐loop LV, rightward and anterior aorta) in ~20%; and {S,D,S} (solitus atria, solitus D‐loop LV, and solitus normally related great arteries) which carries the eponym Holmes heart (named after Andrew F. Holmes, the first Dean of the Medical Faculty of McGill University) in ~15% [46].

A number of associated defects can be seen with DILV. A secundum atrial septal defect is occasionally present but the atrial septum is often intact or has a small patent foramen ovale. Abnormalities of the AV valves, including hypoplasia or stenosis or regurgitation (Figure 28.6), are seen in a significant proportion [45,46]. Subvalvar obstruction of the posterior root – the one aligned with the LV – can be due to posterior malalignment of the infundibular septum, accessory AV valve tissue, or a fibromuscular ridge (Figures 28.1c and 28.2c). The portion of the primary outflow foramen between the LV and infundibular outlet chamber is frequently obstructed [46,47]. If the great arteries are transposed, this results in subaortic stenosis and often hypoplasia of the aorta with coarctation or even arch interruption [53]. Conversely, the obstruction is subpulmonary when the great arteries are normally related.

Physiology

DILV results in mixing of systemic and pulmonary venous blood in the LV. If mixing is complete, the oxygen saturation is similar in the aorta and pulmonary artery and determined by the ratio of pulmonary to systemic blood flow (Qp/Qs). Occasionally there can be remarkable streaming that produces a substantial difference between systemic and pulmonary arterial oxygen saturations. Obstruction of the outflow foramen with TGA favors pulmonary blood flow and diminishes systemic output but does the opposite with normally related great arteries.

LV volume overload is characteristic of essentially all forms of DILV because the LV must supply both systemic and pulmonary blood flow. The higher the Qp/Qs ratio is, the greater the LV volume overload and the higher the systemic oxygen saturation. Chronic volume overload results in LV dilation, eccentric hypertrophy, and eventually adverse remodeling. Obstruction to ventricular outflow or aortic arch obstruction causes concentric hypertrophy, myocardial fibrosis, and diastolic dysfunction. Concentric hypertrophy further narrows the outflow foramen, resulting in a positive feedback loop that can quickly lead to ventricular failure.

Excessive pulmonary blood flow, especially when associated with pulmonary hypertension, damages the pulmonary vascular endothelium and leads to progressive pulmonary vascular obstructive disease.

An atrial septal defect facilitates mixing and reduces streaming. AV valve regurgitation increases the ventricular volume overload. The effect of AV valve stenosis depends on which valve is involved and whether an atrial septal defect is present. In the absence of an atrial defect, stenosis of the left AV valve causes left atrial and pulmonary venous hypertension with pulmonary congestion and increased pulmonary arterial and venous smooth muscle. Conversely, right AV valve stenosis causes systemic venous hypertension with liver engorgement, peripheral edema, and serous effusion.

Treatment strategies

Neonatal palliation is usually undertaken for systemic outflow and/or aortic arch obstruction. Amalgamation of the aorta and pulmonary trunk is frequently used to bypass obstruction between the LV and the infundibular outlet chamber [54]. Some type of systemic–pulmonary shunt is then necessary to provide pulmonary blood flow. Usually this is a modified Blalock–Taussig shunt, although a left ventricle‐to‐pulmonary artery conduit is used in some instances. Another approach is enlargement of the outflow foramen [51]. Extensive aortic arch reconstruction may be necessary in cases of arch hypoplasia or interruption.

Severe pulmonary stenosis or atresia prompts creation of a surgically placed systemic–pulmonary shunt or, more recently, stenting of the ductus arteriosus. Patients with unrestricted pulmonary blood flow and no systemic outflow obstruction often undergo pulmonary artery banding within the first few weeks of life to treat heart failure symptoms, protect the pulmonary vasculature from adverse remodeling, and improve the outlook for subsequent Fontan palliation [55].

Patients with stenosis of an AV valve can benefit from creation of an atrial septal defect, either by interventional catheter procedure or surgery, to relieve systemic or pulmonary venous obstruction. Conversely, hemodynamically significant regurgitation of an AV valve may occur at any stage due to prolapse, dysplasia, annular dilation from volume loading, leaflet restriction, or a cleft. If severe, this may prompt plasty, replacement, or even patch closure of the valve with creation of an atrial defect, to relieve the volume overload. Such interventions carry substantial risk, with one series reporting approximately 17% hospital mortality after AV valve repair, replacement, or closure [56–58].

The long‐term strategy for these patients is staging toward a Fontan procedure, with creation of a bidirectional cavopulmonary anastomosis around age 4–6 months and completion of the Fontan procedure around age 2 years [59]. However, a recent report of favorable outcome in part of a group of patients who underwent septation in the mid‐1990s has resurrected interest in this as an alternative approach [60].

Embryologic development

The development of DIRV is more difficult to understand because there is never a time during normal cardiac development when the AV canal is completely aligned with the developing RV. Even the direction of looping of the heart tube is uncertain in most cases because there is no clear septal wall of the RV present and a rudimentary LV is demonstrable only in a minority of cases [61]. In the few cases where a small LV cavity is present, the loop appears to have been dextral in most. Expansion of the AV canal appears to be normal or nearly so because it becomes normally aligned with the right atrium. Further, the combined size of the two AV valves is substantially larger than either a single mitral or tricuspid valve. What allows the AV canal to become situated completely above the developing RV sinus is unclear. Either the LV cavity is absent or small primarily or it becomes so after losing alignment with the AV canal. Atrial septation proceeds normally as in DILV, resulting in division of the AV canal into two separate valves, both aligned with the RV. Again, it is interesting that the AV valves develop relatively normally despite absence of the muscular inflow septum. The outflow then develops in broad continuity with the underlying RV sinus without interposition of an outflow foramen as seen in DILV. The infundibular (outlet) septum divides the outflow into aortic and pulmonary components and comes to sit above the right ventricular cavity within the infundibular outflow muscular sleeve, which is the cranial continuation of the developing RV. Outflow rotation appears to be abnormal in most cases resulting in double‐outlet RV with side‐by‐side or otherwise malposed great arteries. On the other hand, rotation may approximate normal in hearts with a rightward and posterior aorta and anterior and leftward pulmonary artery. Uneven division of the outflow, with or without deviation of the infundibular septum, likely explains the hypoplasia and obstruction of either the pulmonary or aortic outflow seen frequently in DIRV.

Anatomy

Persistence of a left superior vena cava to coronary sinus and secundum atrial septal defect appear to be frequent findings [61]. The morphology of the AV valves resembles a normal mitral or tricuspid valve less frequently than in DILV (Figures 28.8 and 28.9). Hypoplasia or stenosis of one AV valve, most frequently the left, occurs in 25% or more of cases (Figure 28.8b and c) but more than mild regurgitation is uncommon [61]. A tiny “hip‐pocket” LV (Figure 28.8c) is present in up to 20–25% of patients [61], although some series have reported a higher prevalence [62]. It is located posteriorly near the AV groove and usually communicates with the RV through a ventricular septal defect. In such cases there are clearly two ventricular sinuses although the rudimentary LV can never function independently. The RV is often large, hypertrophied, and bizarrely shaped with a few large muscle bundles. There is a prominent posterior median ridge passing from base to apex between the AV valves (Figure 28.8b and 28.9), which often receives attachments of the AV valves. This can give the appearance of a ventricular septum on clinical imaging studies and has resulted in an erroneous diagnosis of two ventricular sinuses with multiple ventricular septal defects. A characteristic feature of DIRV is absence of a septal wall with a smooth basal endocardial surface (the left ventricular septal wall) as seen in DILV. In addition, the outflow of the heart continues broadly from the RV sinus with no constriction (outflow foramen) separating the infundibular outlet chamber from the large sinus portion of the ventricle as seen in DILV (Figures 28.8 and 28.9). The infundibular or outlet septum sits above the RV cavity, dividing the subarterial infundibular sleeve, and does not usually join a wall of the ventricular body. Uneven division of the outflow into subpulmonary and subaortic infundibula, with or without deviation of the outflow septum, is a frequent cause of obstruction, especially subpulmonary obstruction (Figures 28.8a and 28.9). Aortic arch obstruction regularly accompanies subaortic stenosis.

Right aortic arch seems to be somewhat more frequent than expected [61,62]. Branch pulmonary arteries are usually normal despite the prevalence of subpulmonary obstruction. Coronary arteries arise from the aortic sinuses facing the pulmonary root and form circumflex arteries in their respective AV grooves, giving off descending branches at irregular intervals around the heart [52].

The cardiotypes most frequently associated with DIRV are: {S,X,D} (solitus atria, indeterminate ventricular loop, rightward and anterior aorta) in ~50%; {S,D,D} (solitus atria, solitus D‐loop LV, rightward and anterior aorta) in ~15%; and {S,X,L} (solitus atria, indeterminate ventricular loop, and leftward and anterior aorta) in ~20% [61].

Physiology

The physiology of DIRV is rather similar to DILV in that both are common mixing lesions in the ventricle with the potential for outflow obstruction. Although the systemic and pulmonary arterial saturations are usually similar, and dependent on the Qp/Qs, considerable streaming can occur in some hearts. RV volume overload is characteristic of DIRV because the functional single ventricular chamber must pump both systemic and pulmonary blood flow. A higher Qp/Qs results in greater ventricular volume overload and higher systemic oxygen saturation. Chronic volume overload results in RV dilation, eccentric hypertrophy, and eventually adverse remodeling. Conversely, very cyanotic patients have a low Qp/Qs and only mild RV volume overload. Obstruction to ventricular outflow or aortic arch obstruction causes concentric hypertrophy, myocardial fibrosis, and diastolic dysfunction.

Although reduced pulmonary blood flow is more frequent, excessive pulmonary blood flow, especially with pulmonary hypertension, can lead to progressive pulmonary vascular obstructive disease.

As in DILV, in the absence of an atrial septal defect, stenosis of the right AV valve produces systemic venous obstruction and stenosis of the left AV valve results in pulmonary venous obstruction. Incompetence of either AV valve compounds the right ventricular volume overload.

Pulmonary outflow obstruction occurs frequently and, if severe, results in a ductus‐dependent pulmonary circulation. Systemic outflow obstruction is less common but can limit systemic flow and lead to hypoperfusion or shock. Marked limitation of aortic flow results in ductus‐dependent systemic circulation. Aortic arch hypoplasia, coarctation, or interrupted aortic arch often accompanies severe systemic outflow obstruction. Some patients have unobstructed pulmonary and aortic outflows resulting in pulmonary overcirculation once pulmonary vascular resistance decreases.

Treatment strategies

Initial palliation in DIRV is most often by creation of a systemic–pulmonary shunt for pulmonary stenosis or atresia [61,63]. More recently, transcatheter stenting of the ductus arteriosus has been used as a nonsurgical option to secure pulmonary blood flow. A small proportion of patients, those with subaortic obstruction, undergo amalgamation of the aorta and pulmonary artery to bypass the obstruction with creation of a systemic–pulmonary shunt as a source of pulmonary blood flow [61,63]. Arch reconstruction is often needed in these patients as well. Creation of an atrial septal defect can improve mixing and is indicated if one AV valve is stenotic. Long‐term palliation is staging toward a Fontan circulation with bidirectional cavopulmonary anastomosis around age 4–6 months and completion of Fontan around age 1–2 years [63].

Embryologic development

The mechanisms for abnormal superior‐inferior placement of the ventricles and for crossing of the ventricular inflows are likely related but separate, and at least partially independent. Horizontal formation of the ventricular septum, with a superior RV and inferior LV, could be due to incomplete looping [31]. Interruption of looping at an early stage, after formation of the “C” loop but before completion of the “S” loop, would result in variable failure of caudal and ventral descent of the outflow limb of the heart tube. The outflow remains cranial to the developing LV rather than descending to lie beside it. As the RV sinus balloons out of the proximal infundibulum (outflow), it is cranial or superior to the LV, rather than to the right or left of it, and the interventricular septum is horizontal. The ventricles can be either D‐loop (solitus or right‐handed) or L‐loop (inverted or left‐handed) so “S” looping can begin in either direction before arresting.

The mechanism for crossing of the axes of the AV valves seems to be real or apparent twisting or axial rotation of the ventricles while the atria and AV valves remain relatively fixed. A mechanism for twisting of the ventricles is unknown and the timing of this process is unclear but seems likely to be near the end of or even after completion of looping. Clockwise twisting of the ventricles in a D‐loop (and counterclockwise twisting in an L‐loop), as viewed from the apex, would explain both the crossing of the AV valves and the large angle observed between the atrial and ventricular septa [82]. Usually the septa are nearly parallel with an angle of <10° between them. In crisscross hearts, however, the angle can be as large as 150°. Twisting of the ventricles with fixed atria and distal outflow also explains the curved elongation of the inflow and outflow tracts often observed in these hearts.

Hypoplasia of the tricuspid valve and RV, seen in many cases of SIV and crisscross heart, could be due to entrapment of the right side of the AV canal between the ventricular and atrial septa, limiting its capacity for expansion. More rotation of the ventricular septum would lead to a smaller tricuspid valve and RV sinus. This concept is supported by the inverse relationship between the crossing angle of the AV valves, an indirect measure of twisting or rotation of the ventricles, and the size of the tricuspid valve and RV sinus seen in infants with this condition [83]. However, it is not known if hypoplasia of the tricuspid valve and RV sinus is primary, leading to abnormal placement of the ventricular septum, or secondary, resulting from the unusual location of the ventricular septum. The high prevalence of dextrocardia and mesocardia in patients with SIV and crisscross heart is likely related to failure to complete the looping process and/or reduced growth capacity of the RV [31].

The markedly abnormal outflow in these hearts is potentially explained by abnormal rotation of the outflow, as seen in many other types of abnormal VA alignment [38]. However, VA situs discordance frequently seen in these hearts (D‐loop ventricles with L‐malposition of the aorta or vice versa, see later) could also result from a rotation or twist of the ventricles that “pulls the outflow along.” Rotation of the outflow along with the ventricles would have the effect of inverting the relationship between the great arteries.