What are the Heterotaxy Syndromes?
Heterotaxy is derived from two Greek words: heteros, “other,” and taxis, “arrangement.” Hence, heterotaxy is an arrangement of the viscera that is other than normal (situs solitus) or its mirror image (situs inversus).
Although there is now much literature relevant to the understanding of the heterotaxy syndromes(s), from very early in their recognition and delineation, anomalies of the spleen were identified as important markers of these syndromes, namely, congenital asplenia and congenital polysplenia.
Later it was realized that visceral heterotaxy (scrambling of the situs) could also occur with a normally formed spleen. Consequently, the heterotaxy syndromes cannot be satisfactorily designated in terms of asplenia or polysplenia (because the spleen can be normally formed).
Thus, as the title of this chapter indicates, there are three different types of heterotaxy syndrome in terms of the status of the spleen: (1) the heterotaxy syndrome with asplenia; (2) the heterotaxy syndrome with polysplenia; and (3) the heterotaxy syndrome with a normally formed, but often right sided, spleen.
Other efforts have been made to characterize these syndromes in terms of bilateral right-sidedness (right isomerism) and bilateral left-sidedness (left isomerism). The asplenia syndrome was said, as a teaching mnemonic, to have bilateral right-sidedness: a bilaterally symmetrical liver, with a large lobe on both right and left sides; the inferior vena cava (IVC) was almost always intact (not interrupted), this being a right-sided feature; bilateral superior venae cavae (SVCs) (an SVC bilaterally also may be regarded as a bilaterally right-sided feature); the lungs are often bilaterally trilobed; both bronchi frequently eparterial; and both atrial appendages often being abnormally broad and triangular (resembling right atrial appendages bilaterally).
Conversely, the polysplenia syndrome may be regarded as having bilateral left-sidedness (left isomerism) , ; the lungs are often bilaterally bilobed; both bronchi are frequently hyparterial; the pulmonary veins may be ipsilateral, with the right veins draining into the right-sided atrium and the left veins draining into the left-sided atrium, suggesting that the left atrium (LA) is present bilaterally; the tips of the atrial appendages are often long and thin, like pointing fingers, resembling left atrial appendages bilaterally; and the gallbladder can be absent (absence of the gallbladder being remembered as a bilaterally left-sided feature because the gallbladder normally is a right-sided structure).
Initially, we thought these were wonderful and helpful mnemonics (memory aids), until we realized that some of our friends and colleagues thought them literal. Some people thought that the right atrium (RA) really could be bilateral, and that the LA also really could be bilateral. It was at this juncture that we started whispering into influential ears that right atrial “isomerism” and left atrial “isomerism” were just memory aids, not accurate anatomy. We were telling any who would listen that bilaterally RAs and bilaterally LAs in fact have never been documented.
Accurately speaking, we said, for the morphologically RA to be bilateral, there would have to be an IVC bilaterally, a coronary sinus bilaterally, a SVC bilaterally, a septum secundum with superior and inferior limbic band bilaterally, and a broad triangular atrial appendage bilaterally. This situation has never been documented in a single human being (conjoined twins excluded).
Accurately speaking, we added, for the morphologically left atrium to be bilateral, there would have to be four pulmonary veins bilaterally, septum primum bilaterally, and a long, thin, finger-like appendage bilaterally. Again, this situation has never been documented in a single human being (conjoined twins excluded).
To their credit, our colleagues listened, pondered, and agreed. However, some of them then retreated from atrial “isomerism” (an untenable position), to atrial appendage isomerism. Again, we whispered in influential ears that this position also is untenable, both factually and conceptually.
Factually, one does not always have a large triangular atrial appendage bilaterally in the asplenia syndrome; nor does one always have a long thin atrial appendage bilaterally in the polysplenia syndrome, as will be documented subsequently.
Conceptually, the idea of partial atrial isomerism—involving the atrial appendages only or the pectinate muscles only—is not isomerism. By analogy, consider the molecules of 0-glucose and L-glucose, which really are isomers. These molecules are isomers because each of the asymmetrical atoms in L-glucose is a mirror-image of the corresponding asymmetrical atoms in 0-glucose. If a molecule had only a few atoms that were mirror images of those in 0-glucose, such a molecule would not be considered a “partial” isomer of 0-glucose. Isomerism must involve the whole structure (the whole atrium, or the whole molecule). Partial isomerism is a contradiction in terms. Isomerism is binary: either it is present or it is not present. Conceptually and logically, isomerism cannot be partial. Or to put in another way, “partial” isomerism (appendages only or pectinate muscles only) is not isomerism.
At a less abstract level, consider a patient with right sided polysplenia. The left-sided IVC was interrupted. A large left-sided azygos vein connected with a left-sided SVC that drained into the left-sided atrium. The suprahepatic segment of the IVC also connected with the left-sided atrium, as did the coronary sinus.
The left-sided atrium had septum secundum’s superior and inferior limbic bands on its septal surface. The right-sided atrium received all of the pulmonary veins, and the septal surface of the right-sided atrium displayed a well-formed septum primum. The appendage of the left-sided atrium was broad, triangular, and anterior, whereas the appendage of the right-sided atrium was long, thin, and posterior.
This case was actually presented to one of us (RVP) at an international symposium in Tokyo. One final detail: The left-sided atrial appendage (that was broad, triangular, and anterior) also had at its tip a long, thin, projecting point.
What was the Atrial Situs?
We replied with no hesitation: situs inversus. But what about the finger-like tip of this right atrial appendage (RAA)? True, this part of the left-sided atrial appendage looks a little “leftish,” but it is not really the left atrial appendage (LAA). (The morphologically LAA was right-sided in this patient with visceroatrial situs inversus.) To insist that this pointed tip of the left-sided atrial appendage really is the LAA would be to state that this morphologically RA is a composite structure consisting mostly of the morphologically RA, but having an atrial appendage tip consisting of morphologically LAA.
Briefly, we think that the latter interpretation is both erroneous and absurd. To insist on LAA isomerism (literally) is to assert that this left-sided morphologically RA really does have the tip of its appendage composed of morphologically LAA myocardium. The assertion that this left-sided atrium really is composed of both right and left atrial myocardium is to say that it is a chimera. (In Greek mythology, Chimera was a fire-breathing female monster usually represented as a composite of a lion, a goat, and a serpent.) We think that such a composite atrium, literally composed of both morphologically right and left atrial myocardium, is highly improbable (and amusing). (We cannot imagine how one could literally have a morphologically RA, with the tip of its appendage composed of morphologically left atrial myocardium. Biologically, we think this is a joke. We hope that you too will see how funny this concept of atrial appendage isomerism really is.)
The foregoing, then, are the main reasons why we are presenting these cases as follows: (1) as the heterotaxy syndromes, because visceral heterotaxy is the only accurate anatomic common denominator (the spleen is not always abnormally formed); and (2) bearing in mind the status of the spleen—asplenia, or polysplenia, or occasionally with a normally formed spleen. Not only do the asplenia and the polysplenia syndromes have statistically significant anatomic differences (as will be shown), but also the clinical importance of the status of the spleen merits emphasis concerning susceptibility to fulminating and rapidly fatal infection by encapsulated gram-negative coliform bacilli during the first 6 months of life and by encapsulated gram-positive bacteria— mainly pneumococcus—thereafter. Another advantage of this approach is avoidance of the assertion that either right or left atrial isomerism or atrial appendage isomerism is present, thereby sidestepping these morphologic anatomic and conceptual errors.
The Essence of the Heterotaxy Syndromes
To the best of our present understanding, what is the essence of the heterotaxy syndromes? We think that the brief answer is anomalies of the visceral asymmetry and of midline associated defects. As will be seen, abnormalities of asymmetry do not necessarily mean the presence of visceral symmetry.
What structures are Involved?
Normally asymmetrical structures are typically involved: bronchi, lungs, liver, stomach, spleen, pancreas, gastrointestinal (GI) tract, IVC, SVC, azygos vein, coronary sinus, pulmonary veins, septum primum, septum secundum, atrioventricular (AV) valves, ventricles, conus arteriosus, great arteries, and the aortic arch. These normally asymmetrical structures do not necessarily become symmetrical in the heterotaxy syndromes, although they often do become less asymmetrical than normal.
How Many Kinds of Atrial Situs are There?
We think that there are really only two kinds of atrial situs: situs solitus (normal) and situs inversus (its mirror image). Atrial situs ambiguus is not a specific anatomic type of atrial situs. Atrial situs ambiguus only means that the basic type of atrial situs is undiagnosed.
The importance of realizing that the concept of atrial-level “isomerism” is erroneous in that this understanding then facilitates the diagnosis of the types of atrial situs (solitus or inversus) in the heterotaxy syndromes. It should be noted that lung isomerism does indeed exist.
Although “bilateral right-sidedness” or “right isomerism” and “bilateral left-sidedness” or “left isomerism” are helpful teaching mnemonics for the asplenia syndrome and the polysplenia syndrome, respectively, they should not be regarded as accurate morphologic anatomy.
What is the Morphologically Right Atrium?
As is presented in Chapter 3 , the key gross anatomic features are the IVC, the ostium of the coronary sinus, the septum secundum (superior and inferior limbic bands), and a large, triangular, anterior atrial appendage.
The key to diagnosing the atrial situs is to figure out which is the morphologically right atrium (RA). The connection of the IVC is a very highly reliable diagnostic marker of the RA. The IVC works even with interruption of the IVC, which is sometimes called absence of the IVC, because the suprahepatic segment of the IVC that connects with and identifies the RA is always present. The ostium of the coronary sinus is not always present; it can be atretic, or unidentifiable (absent), as is frequent with common AV canal because of associated unroofing of the coronary sinus. But when the ostium of the coronary sinus is present, it too is a highly reliable diagnostic marker of the RA, as is the large triangular anterior atrial appendage.
What is the Morphologically Left Atrium?
The morphologically LA is the other atrium, which has a small, finger-like, posterior atrial appendage. Typically (but not always), the LA has a septum primum—the flap valve of the foramen ovale—on its septal surface, and, normally, it receives the pulmonary veins.
When can we not Diagnose the Atrial Situs?
We cannot diagnose the atrial situs with confidence when the IVC and the atrial appendages appear to tell two different stories: for example, when the IVC is right-sided, and the large triangular atrial appendage is left sided, or vice versa. A right-sided IVC suggests visceroatrial situs solitus; but a left-sided morphologically right atrial appendage suggests atrial situs inversus. Which should one believe, the IVC or the appendages? From the scientific standpoint, we are not sure how to answer this question. From the practical hemodynamic standpoint, there is no doubt that the connections of the great veins (e.g., the IVC) are more important than the shape of the atrial appendages.
Consequently, we make the diagnosis of atrial situs ambiguus when we are not sure whether the atrial situs is solitus or inversus. Note that atrial situs ambiguus is not a specific third type of atrial situs. It may be a “scrambled” atrial situs solitus or a “scrambled” atrial situs inversus. Atrial situs ambiguus means nothing more.
Septum Primum Can Be Malpositioned
The septum primum—the flap valve of the foramen ovale—can be displaced into the morphologically LA. Then septum primum can lie to the left of the right pulmonary veins ( Fig. 29.1 ), resulting in partially anomalous pulmonary venous drainage into the RA, also known as ipsilateral pulmonary veins, which are quite frequent in the heterotaxy syndrome with polysplenia. Ipsilateral pulmonary veins means that the pulmonary veins are same-sided (Latin: ipse, “self,” latus, “side”).
The right pulmonary veins drain into the right-sided atrium, and the left pulmonary veins drain into the left-sided atrium. This is part of the mnemonic that characterizes the polysplenia syndrome—“bilateral left-sidedness”: the presence of pulmonary veins entering both atria is somewhat suggestive of a LA bilaterally (not really, but as an aide memoire).
Displacement of the septum primum to the left of the right pulmonary veins is, we think, what produces so-called ipsilateral pulmonary veins. The septum primum can be malaligned further to the left, lying to the left of the left pulmonary veins ( Fig. 29.2 ), resulting in totally anomalous pulmonary venous drainage (TAPVD) into the RA. Such marked leftward malalignment of the septum primum may erroneously suggest a common atrium with a supramitral stenosing membrane (see Fig. 29.2 ).
Understanding of the pathologic anatomy of leftwardly displaced septum primum ( Figs. 29.1 to 29.3 ) suggests its appropriate surgical management: excision of the malaligned septum primum and construction of a normally positioned atrial septum. Malalignment of the septum primum is associated with a newly recognized type of atrial septal defect (ASD): a septum primum malposition ASD. 15,46,153 Malposition of the septum primum into the morphologically LA is associated with leftward malalignment in visceroatrial situs solitus, and with rightward malalignment in visceroatrial situs inversus.
Whenever the pulmonary veins connect at the atrial level (except with the sinus), we think that the pulmonary veins are normally connected, because the relationships of the pulmonary veins with the sinus venosus are normal. The pulmonary veins connect within a horseshoe of sinus venosus tissue, typically composed of the right horn of the sinus venosus to the right (the medial venous part of the morphologically RA), and the left horn of the sinus venosus to the left and below (the persistent left SVC or the ligament of Marshall to the left, and the coronary sinus below). (The normal development of the sinus venosus and the pulmonary veins is presented diagrammatically in Fig. 29.4 .)
The realization that these partially or totally anomalously draining pulmonary veins are normally connected relative to both the right and left sinus horns, but not relative to the leftwardly malpositioned septum primum, leads us to realize the important distinction that exists between anomalous pulmonary venous drainage and anomalous pulmonary venous connection. In these cases (see Figs. 29.1 and 29.2 ), normally connected pulmonary veins drain anomalously because of malposition of the septum primum into the LA.
From the anatomic standpoint, the septum primum can be clearly seen from the right atrial view, because the superior limbic band of septum secundum is very deficient or absent (see Fig. 29.3 ). Indeed, our understanding of septum primum malposition and its importance began with a question from Dr. Luis Alday of Cordoba, Argentina: In a case of polysplenia with all pulmonary veins draining into the RA, why is the septum primum so well seen from within the right atrium? Normally, the septum primum is well seen only from within the left atrium. This question led to a surprising voyage of discovery.
In our experience, septum primum malposition has occurred predominantly in patients with the heterotaxy syndrome with polysplenia but can occur, rarely, in association with asplenia or with a right-sided but otherwise normally formed spleen.
The following study of the heterotaxy syndromes was first presented in part at the meeting of the American Heart Association in Dallas, Texas, November 8, 1998, and has not been published previously. In the interests of clarity and brevity, the findings are presented mainly in tables and figures ( Table 29.1 )
| Status of the Spleen | No. of Patients | % of Series |
|---|---|---|
| 95 | 57 |
| 68 | 40 |
| 5 | 3 |
Findings of Heterotaxy Syndrome With Asplenia
Sex: Males-to-females, 56/38 (1.5/1)
Age at Death: Mean, 22.3 ± 56 months; range, 0 (fetuses) to 35.7 years; and median, 34 days.
Lobation of the Lungs
The lobation of the lungs in 74 postmortem cases of the heterotaxy syndrome with asplenia is summarized in Table 29.2 .
| Findings | No. of Patients | % of Series a |
|---|---|---|
| 62 | 84 |
| 4 | 5 |
| 1 | 1 |
| 1 | 1 |
| 1 | 1 |
| 2 | 3 |
| 1 | 1 |
| 1 | 1 |
| 1 | 1 |
Although the pattern of bilaterally trilobed lungs was, as expected, by far the most common pattern of lung lobation found in these 74 postmortem cases of asplenia syndrome (84%), eight other patterns were also found ( Table 29.2 ). Hence, bilaterally trilobed lungs was by no means the only pattern of lung lobation associated with asplenia.
Types of Relationship Between the Great Arteries
The types of relationship between the great arteries—or, more accurately speaking—the types of ventriculoarterial alignment, are summarized in Table 29.3 .
| Types of Ventriculoarterial AlignmentTypes | No. of Patients (n = 95) | % of Series |
|---|---|---|
| 64 | 67 |
| 21 | 22 |
| 9 | 9 |
| 1 | 1 |
Double-outlet right ventricle (DORV) was by far the more common type of ventriculoarterial (VA) alignment (67%) in these 95 postmortem cases of asplenia syndrome. Transposition of the great arteries (TGA) was a distant second (22%). Third in prevalence were normally related great arteries (9%). Least frequent was anatomically corrected malposition (ACM) of the great arteries (1%). (See Chapter 32 for information concerning anatomically corrected malposition, a rare and hence unfamiliar anomaly.)
Double-Outlet Right Ventricle With Asplenia
The segmental anatomy of the 64 patients with DORV and asplenia is summarized in Table 29.4 . In Table 29.4 , it is noteworthy that DORV with D-loop ventricles was almost twice as common as DORV with L-loop ventricles: 66% versus 34%, respectively.
| Segmental Anatomy | No. of Patients (n = 64) | % of DORV a | ||
|---|---|---|---|---|
| 42 | 66 | ||
| 15 | 23 | ||
| 10 | 16 | ||
| 2 | 3 | ||
| 1 | 2 | ||
| 13 | 20 | ||
| 1 | 2 | ||
| 22 | 34 | ||
| 8 | 12 | ||
| 5 | 8 | ||
| 6 | 9 | ||
| 2 | 3 | ||
| 1 | 2 | ||
The atria were in situs solitus in 25 of 64 cases (39%), in situs inversus in 22 of 64 patients (34% which is a very high percentage), and in atria situs ambiguus (undiagnosed atrial situs) in 17 of 64 cases (27%). Hence, we thought it was possible to diagnose the basic type of atrial situs in 73% of these cases of the heterotaxy syndrome with asplenia.
DORV with D-loop ventricles displayed D-malposition of the great arteries (aortic valve to the right, dextro- or D- relative to the pulmonary valve) in 38 of 42 cases (90%) (see Table 29.4 ), L malposition of the great arteries in 3 of 42 patients (7%), and a solitus normally related great arteries type of conotruncus: DORV {I,D,“S”} in 1 of 42 cases (2%) (percentages rounded off to the nearest whole number).
One may well ask, What do we mean by solitus normally related great arteries in a case of DORV? Is that not a contradiction in terms? This, of course, is a good, logical question. Briefly, the answer is that a solitus normal type of infundibulum and great arteries can indeed be present with a VA alignment of DORV, as follows: The aortic valve is rightward, posterior, and inferior relative to the pulmonary valve. A subpulmonary conus is present, with aortic AV valvar direct fibrous continuity. The ventricular septum is displaced abnormally leftward, in association with an abnormal small morphologically LV. The resulting VA alignment is DORV. It is important to understand that DORV is not always the result of a conotruncal (really, an infundibular) malformation. An anomaly of the ventricles, ventricular septum, and AV valves also can result in DORV. With L-loop ventricles, DORV in the asplenia syndrome had L malposition of the great arteries (aortic valve levo- or L relative to the pulmonary valve) in 19 of 22 cases (86%), A-malposition of the great arteries (aortic valve antero- or A relative to the pulmonary valve) in 2 of 22 patients (9%), and D malposition of the great arteries in 1 of 22 cases (5%).
One of the advantages of segmental set analysis, as shown in Table 29.4 , is that it makes possible not only univariate analysis, as earlier (type of atrial situs, type of ventricular loop, and type of semilunar interrelationship), but it also facilitates multivariate analysis, that is, the various segmental combinations or sets that occurred. The most common segmental combination was DORV {S,D,D}, which was found in 15 of 64 patients (23%), that is, DORV with the segmental set of situs ambiguus (A) of the viscera with situs solitus (S) of the atria, concordant 0-loop ventricles (D), and D-malposition of the great arteries (D) (see Table 29.4 ). Second in frequency was DORV {I,D,D}, which occurred in 13 of 64 patients (20%), that is, DORV with the segmental set of visceral situs ambiguus (A), atrial situs inversus (I), discordant D-loop ventricles (D), and D-malposition of the great arteries (D). Third in prevalence was DORV {A,D,D}, which occurred in 10 of 64 patients (16%), that is, DORV with the segmental situs set of visceroatrial situs ambiguus (A) (the atrial situs being undiagnosed), D-loop ventricles (D), and D malposition of the great arteries (D). We hope that the meaning of the other eight segmental combinations will be self-evident in Table 29.4 . (For those who may not be familiar with segmental anatomy, please see Chapter 4 .)
What Does Double-Outlet Right Ventricle With Asplenia Look Like?
We shall present 3 cases photographically in an effort to answer this question. (It should be understood that by far the best way to learn the morphologic anatomy of DORV with asplenia—or indeed of any other form of complex congenital heart disease—is to study heart specimens personally, as is readily possible in the Cardiac Registry laboratory of Children’s Hospital in Boston and in similar laboratories elsewhere. Any photograph, no matter how good, reduces three-dimensional reality to two dimensions.)
Fig. 29.5 shows the exterior of the heart and left lung, viewed from the front. The patient was a 3 2⁄12-year-old girl (A69-61) with visceral heterotaxy, asplenia, DORV {S,D,D}, bilateral conus (subaortic and subpulmonary), with severe subpulmonary stenosis. Note that the morphologically RAA is large, broad, triangular, and anterior, whereas the LAA is much smaller, finger-like, and posterior. The hypertrophic morphologically RV is right-sided, whereas the hypertrophic morphologically left ventricle (LV) lies to the left of the anterior descending coronary artery and the great cardiac vein that demarcate the interventricular septum. Both great arteries arise above the RV (to the right of the plane of the ventricular septum; hence, the diagnosis of DORV can be strongly suspected based on external inspection), the large ascending aorta lying anterior and to the right of the much smaller main pulmonary artery (MPA). The right superior vena cava (RSVC) receives all of the pulmonary veins, with totally anomalous pulmonary venous connection (TAPVC) being present. The RSVC connected normally with the right-sided RA; thus, TAPVD was present. A large persistent left superior vena cava (LSVC) drained into the left-sided LA because of the characteristic coexistence of a large coronary sinus septal defect, also known as unroofing of the coronary sinus, which therefore has no discrete right atrial ostium and thus appears to be absent. The left innominate vein was absent, typical of bilateral SVCs. The left lung and the right lung were both trilobed, and both bronchi were eparterial.
The relations between the bronchi and the pulmonary artery branches require explanation ( Fig. 29.6 ). Normally, the right mainstem bronchus is short and broad, giving off the right upper lobe bronchus a relatively short distance below the carina. By contrast, the left mainstem bronchus is relatively long, thin, and sway backed because the upper lobe bronchus originates relatively further down the mainstem bronchus, farther away from the carina. Consequently, the right mainstem bronchus normally is the eparterial bronchus (in Greek, epi, “on or upon”) because this bronchus is above the level of the right pulmonary artery, whereas the long, thin, left mainstem bronchus passes all the way beneath the left pulmonary artery before giving off its upper lobe bronchus. Hence, the left mainstem bronchus normally is the hyparterial bronchus (Greek, hypo, “under”) (see Fig. 29.6 , top ). Fig. 29.7 shows the frontal P wave axis in asplenia.
In the heterotaxy syndrome with asplenia, both lungs typically are trilobed, as in Fig. 29.6 . Hence, the upper lobe had the larger, more anterior, triangular atrial appendage. All of the pulmonary veins connected with a common atrium to the left of a subdividing atrial strand that was interpreted as the inferior limbic band of septum secundum. All of the pulmonary veins connected with this left-sided atrium by a common orifice; that is, incomplete incorporation of the common pulmonary vein was present. The left-sided atrial appendage was smaller, more finger-like, and posterior relative to the right-sided atrial appendage. In view of the venous connections (the IVC and the common pulmonary vein) and the shapes of the atrial appendages, the diagnosis of situs solitus of the atria was made.
As is seen in Fig. 29.8A–B , a completely common AV canal (CCAVC), type C of Rastelli, was present. A large ventricular septal defect (VSD) of the AV canal type was confluent with the common atrium; that is, there was a large and complete AV septal defect (complete absence of the AV septum that normally subdivides the common AV canal, thereby normally producing a divided AV canal consisting of separate mitral and tricuspid canals). The complete AV septal defect was associated with a huge secundum type of ASD (absence of the septum primum, with a poorly formed superior and inferior limbic bands of septum secundum). This combination of a complete AV septal defect plus a huge secundum type of ASD together produced a common (essentially undivided) atrium.
The common AV valve is balanced; that is, it opens approximately equally into the right-sided and hypertrophied morphologically RV (see Fig. 29.8A ) and into the left-sided and hypertrophied morphologically LV (see Fig. 29.8B ). The RV is right-handed (see Fig 29.8A ) and the LV is left-handed (see Fig. 29.8B ); hence D-loop ventricles are present, both in terms of the relative spatial positions of the ventricles, and in terms of the ventricular situs (pattern of anatomic organization), which is well expressed and easily diagnosed in terms of ventricular chirality or handedness, as mentioned earlier.
Both great arteries originate above the morphologically RV; hence, DORV is present. A bilateral muscular conus arteriosus is present. The subaortic part of the conus is well developed, well expanded, and nonobstructive. There is aortic-AV fibrous discontinuity, produced by the interposition of the large subaortic conus.
There is severe pulmonary outflow tract stenosis (see Fig 29.8A ). Note the tight stenosis of the subpulmonary os infundibuli. The pulmonary infundibular stenosis has a punched-out appearance, typical of asplenia. The presence of a stenotic subpulmonary infundibulum prevents pulmonary-AV fibrous continuity.
This VSD of the AV canal type is remote from both semilunar valves, being separated from the aortic valve by a large and well-developed subaortic conus, and separated from the small pulmonary valve by a tightly stenotic subpulmonary infundibulum. Such VSDs are also described as noncommitted, meaning that the VSD is not confluent with (not committed to) either semilunar valve. From a hemodynamic standpoint, however, this VSD of the AV canal type is much more subaortic than subpulmonary because of the presence of severe subpulmonary infundibular stenosis and pulmonary valvar stenosis.
In DORV, it should be understood that subaortic, or subpulmonary, or doubly committed or noncommitted VSDs are not anatomic types of VSD. In other words, all noncommitted VSDs are not AV canal type defects. They can be muscular VSDs. They also can be conoventricular VSDs, but with a well-developed subaortic and subpulmonary conus. Hence, the relationship of the VSD to the semilunar valves is very important hemodynamically and surgically in DORV (and other so-called conotruncal anomalies), but these hemodynamic descriptions are not the same thing as anatomic types of VSD.
Looking at the LV (see Fig. 29.8B ), one sees that there are two well-developed and well-spaced left ventricular papillary muscle groups, thereby excluding potentially parachute mitral valve. In other words, after surgical repair of the common AV canal, one would not end up with a parachute mitral valve, with all chordae tendineae inserting into one focus (typically, into the anterolateral or superior papillary muscle group of the LV).
Diagnosis 0 (see Fig. 29.8A–B ): The heterotaxy syndrome with asplenia, DORV {S,D,D}, TAPVC to the RSVC, common atrium, CCAVC (type C), bilateral conus, and severe pulmonary outflow tract stenosis (infundibular and valvar). This is a typical case of the asplenia syndrome.
In Fig. 29.9 we present the heart specimen of a 3 3⁄12-year old boy with the heterotaxy syndrome with asplenia and DORV (MR 43). Fig. 29.9A is a right lateral view of the morphologically RA, the common AV canal, and a single RV. Note that the right-sided atrium has a broad triangular appendage and receives the IVC and SVC. The left-sided atrial appendage was smaller and more posterior (not shown). Hence, we made the diagnosis of situs solitus of the atria. There was TAPVC to the junction of the RSVC with the RA.
The coronary sinus septum was absent; that is, a large coronary sinus septal defect was present, resulting in unroofing of the coronary sinus. Consequently, a persistent LSVC drained directly into the LA, and there was no right atrial ostium of the coronary sinus, making it look as though the coronary sinus were absent. (We think that the posterior wall of the coronary sinus, that is, the posterior wall of the left sinus horn, is present, with only the anterior wall of the coronary sinus—the so-called coronary sinus septum—being absent.) The left innominate vein was absent, as is usual with bilateral SVCs.
A large secundum type of ASD is seen above and behind the inferior limbic band ( Fig. 29.9A ). A prominent ostium primum type of ASD is present in front of and below the inferior limbic band. Common AV canal is present, the common AV valve underlying both the RA and LA and opening into the single RV. Common-inlet RV is present, not double inlet right ventricle, because only one AV valve (a common AV valve) is present. No vestige of a morphologically LV could be identified (despite multiple incisions in the appropriate location). Hence, a single morphologically RV is present, meaning that no morphologically LV could be identified. However, we cannot exclude the possibility of the existence microscopically of some left ventricular myocardial cells. Instead, what we mean is that, despite an intensive and careful search, no remnant whatsoever of the LV was found. Because the LV is absent (unidentifiable), there can be no VSD, which is really an interventricular septal defect.
Hence, the question arises: Is this a complete form or a partial form of common AV canal? No VSD of the AV canal type can be present (because the LV is missing); thus, we do not know how to answer this question. We think that this anomaly—common inlet into a single RV—exposes one of the weaknesses in the classification of common AV canal: With a primum type of ASD, when there is a VSD of the AV canal type, we conventionally call this a complete form of common AV canal; but when there is no VSD of the AV canal type, we make the diagnosis of a partial form of common AV canal. However, in the present anomaly (common-inlet single RV), the point is that the usual classification of common AV canal breaks down, because the usual classification assumes the presence of an identifiable ventricular septum, which then makes it possible to determine the presence or absence of a VSD of the AV canal type.
It is because of this problem that we made the diagnosis of common AV canal (not otherwise qualified); we avoided making the diagnosis either of complete or partial common AV canal because we do not know which is anatomically accurate.
In Fig. 29.9B , we present an anterior view of this opened single RV. Note the coarse right ventricular type of trabeculae carneae everywhere. Again, the common AV valve can be seen opening from both atria into this single RV.
Note that the septal band is located anteriorly, superiorly, and to the left relative to the entering common AV valve. The myocardium beneath the septal band is the right ventricular sinus (or inflow tract) septal surface. The right ventricular free wall lies toward the reader’s left side. This is a right-handed, noninverted, D-loop type of RV. Note that the moderator band lies far toward the viewer’s right side, where it flows into the prominent anterior papillary muscle group of this single RV.
DORV is present, with both great arteries arising per force above this single RV. We say above the single RV intentionally, not from the single RV. Accurately speaking, the great arteries arise from the conus arteriosus, not directly from either ventricular sinus—in this case, not directly from the right ventricular sinus. The conus arteriosus is part of the conotruncal cardiac segment; that is, the conus “belongs to” the great arteries. The conus is how the great arteries connect with the ventricular sinuses. The conus is part of the ventricular outflow tracts (the conotruncus), not part of the ventricular inflow tracts (the sinuses or pumping portions). Consequently, we prefer, in the interests of accuracy, to say that both great arteries arise above the RV (not from the RV). We think that the best way to achieve clarity and to avoid confusion is to be as accurate as possible. A bilateral conus is present. The large unobstructed aortic outflow tract and aortic valve lie anteriorly and slightly to the left of the tightly stenotic pulmonary outflow tract, which has both infundibular and valvar stenosis. Note that, once again, the tightly stenotic pulmonary os infundibulum looks “punched out.” Indeed, it is reminiscent of a conal septal defect.
Diagnosis (see Fig 29.9A–B ): Heterotaxy syndrome with asplenia with DORV {S,D,L}, bilateral SVCs, absent left innominate vein, unroofing of the coronary sinus (the LSVC draining into the LA and the right atrial ostium of the coronary sinus being absent), TAPVC to the right superior vena septal defect, common AV valve, common-inlet RV, single RV (no remnant of the LV being found), bilateral conus, and severe pulmonary outflow tract stenosis (infundibular and valvar).
Heterotaxy Syndrome With Asplenia and Transposition of the Great Arteries
Of our 95 patients with the heterotaxy syndrome and asplenia, 21 (22%) had TGA (see Table 29.3 ). What kinds of TGA were associated with the asplenia syndrome? Their segmental anatomy and prevalences are summarized in Table 29.5 .
| Segmental Anatomy | No. of Patients (n = 21) | % of TGA a | ||
|---|---|---|---|---|
| 14 | 67 | ||
| 6 | 29 | ||
| 4 | 19 | ||
| 4 | 19 | ||
| 7 | 33 | ||
| 2 | 10 | ||
| 1 | 5 | ||
| 1 | 5 | ||
| 1 | 5 | ||
| 1 | 5 | ||
| 1 | 5 | ||
a Percentages rounded off to nearest whole number.
b Visceral situs inversus (I) with atrial situs solitus (S).
In these 21 patients with TGA in the asplenia syndrome, despite the presence of visceral heterotaxy (situs ambiguus), it was possible to diagnose the atrial situs with confidence in 15 cases (71%) (see Table 29.5 ). The atrial situs could not be diagnosed (it remained ambiguous) in 6 patients (29%). Asplenia and TGA represents a new and improved level of understanding of these complex cases. Unless one understands the atrial situs, one cannot really understand the heart diagnostically.
In the 15 patients with TGA in whom the atrial situs could be diagnosed, physiologically uncorrected (complete) TGA was present in 7 patients (47%) and physiologically corrected TGA was found in 8 cases (53%). In the series of TGA as a whole (n = 21), TGA could not be diagnosed as physiologically uncorrected or corrected in 6 (29%), because the atrial situs remained unknown. In these 15 patients with TGA and asplenia, congenitally physiologically uncorrected TGA occurred in two different anatomic types ( Table 29.6 ).
| Uncorrected TGA (n = 7) |
|
|
| Corrected TGA (n = 8) |
|
|
|
|
a Visceral situs inversus (I) with atrial situs solitus (S).
For brevity and convenience, we often omit “congenitally physiologically,” thinking that this will be understood. However, if there is any risk that physiologically uncorrected or corrected TGA could be misunderstood for surgically uncorrected or corrected TGA, we include the adverb “congenitally,” in the interests of clarity.
In physiologically uncorrected TGA, there is atrioventricular concordance, either {S,D,-} or {I,L,-}. In physiologically corrected TGA, there is AV discordance, either {S,L,-} or {I,D,-}. Both D-TGA and L-TGA can be physiologically uncorrected or corrected. To determine which, establish the presence of AV concordance or discordance, respectively.
What is really new about Tab1e 29.5 is that, to our knowledge, this is the first time that the majority of cases of TGA in the asplenia syndrome have been classified as physiologically uncorrected or corrected (time of writing February 1, 1999). This, in turn, is why the concepts of atrial situs ambiguus, atrial isomerism, and atrial appendage isomerism need to be understood, rather than believed. Understanding “opens the door” to the diagnosis of the atrial situs in many (but not all) cases of asplenia, leading to a more complete understanding of this form of complex congenital heart disease.
Ventriculoarterial Concordance With Asplenia
Although DORV is by far the most common type of VA alignment in the asplenia syndrome (67%), followed by TGA (22%), infrequently it is possible for VA concordance to occur (10%) either in the form of normally related great arteries, as in 9 of 95 cases (9%), or in the form of ACM of the great arteries, as in 1 of 95 cases (1%) (see Table 29.3 ). These cases of asplenia with VA concordance are presented in greater detail in Table 29.7 .
| Segmental Anatomy | No. of Patients (n = 10) | % of VAC | ||
|---|---|---|---|---|
| 6 | 60 | ||
| 5 | 50 | ||
| 1 | 10 | ||
| 4 | 40 | ||
| 1 | 10 | ||
| 2 | 20 | ||
| 1 | 10 | ||
Of these 10 patients with asplenia and VA concordance, the atrial situs was diagnosed in 8 (80%). Of the 9 patients with normally related great arteries, solitus normally related great arteries were present in 6 (67%), and inversus normally related great arteries were found in 3 (33%).
Isolated ventricular inversion was present in 1 patient (see Table 29.7 ): {S,L,S}. Solitus atria {S,-,-} were associated with L-loop ventricles {-,L,-} and solitus normally related great arteries {-,-,S}. Only the ventricles were inverted; hence, the name of this rare anomaly. Because there is only one intersegmental discordance (at the AV alignment), the circulations are physiologically uncorrected. Consequently, an atrial switch operation (Senning or Mustard procedure) is needed to produce physiologic and anatomic repair. Although the meaning of physiologic repair should be clear (systemic venous return to the pulmonary artery, and pulmonary venous return to the aorta), one may wonder, What does an anatomic repair mean? If one ends up with the morphologically LV supplying the aorta, and with the morphologically RV ejecting into the pulmonary artery—as one does, by definition, in {S,L,S}—one has an anatomic repair: the morphologically appropriate ventricle ejects into the appropriate great artery; that is, the morphologically LV ejects into the aorta, and the morphologically RV ejects into the pulmonary artery.
ACM of the great arteries, such as ACM {I,D,L} (see Table 29.7 ), means that the great arteries are malposed, but despite this fact, each malposed great artery nonetheless originates above the morphologically appropriate ventricle: aorta above the morphologically left ventricle, and pulmonary artery above the morphologically right ventricle (i.e., VA alignment concordance is present). Let’s think about this case of ACM {I,D,L}. There is only one intersegmental discordance, at the AV alignment. So you know that the systemic and pulmonary circulations are physiologically uncorrected. Consequently, such a patient should have an atrial switch operation, if feasible. You should end up with a physiologic repair (because of the atrial switch) and an anatomic repair (because of the nature ACM). Thus ACM of the great arteries may be congenitally physiologically corrected or congenitally physiologically uncorrected, as in this patient.
As is always the case, to the best of our present knowledge, the ventricles have looped in one direction (D-loop), whereas the infundibulum and great arteries have twisted in the opposite direction (L-malposition of the great arteries). This rare situation may explain why ACM is so uncommon: the ventricles and the great arteries have to twist in opposite directions to result in the VA alignment of ACM. ,
It is noteworthy that VA concordance is not synonymous with normally related great arteries because ACM also has VA concordance.
The Conus in Asplenia.
The anatomic types of conus arteriosus found in association with 94 postmortem cases of the heterotaxy syndrome with asplenia are summarized in Table 29.8 .
| Finding | No. of Cases (n = 94) | % of Series a |
|---|---|---|
| 56 | 60 |
| 25 | 27 |
| 13 | 14 |
Although a bilateral conus (subaortic and subpulmonary) is by far the most common type of infundibulum found in the asplenia syndrome, often in association with DORV ( Figs. 29.8 and 29.9 ), the conus can be subaortic (only) with pulmonary-AV fibrous continuity, typically with TGA; or the conus can be subpulmonary (only) with aortic-AV fibrous continuity and normally related great arteries.
The Superior Vena(e) Cava(e) With Asplenia
The anatomic status of the SVC(s) in the heterotaxy syndrome with asplenia is summarized, based on 72 postmortem cases, in Table 29.9 .
| Finding | No. of Patients (n = 72) | % of Series | ||
|---|---|---|---|---|
|
| SVC | 47 | 65 |
|
| 17 | 24 | |
|
| 8 | 11 | |
Bilateral SVCs was by far the most common pattern found in association with asplenia (65%). RSVC (only) was a distant second in prevalence (24%), and LSVC (only) was least frequent (11%).
Inferior Vena Cava With Asplenia
The anatomic status of the IVC in 76 postmortem cases of the heterotaxy syndrome with asplenia is presented in Table 29.10 . Several points are noteworthy (see Table 29.10 ):
- 1.
A left-sided IVC was even more common than a right-sided IVC (37% versus 32%, respectively).
- 2.
Almost one-quarter of our cases (23%) had lateral switching of the IVC, left-to-right being slightly more common than right-to-left (14% versus 9%, respectively). The morphogenesis of lateral shifting of the IVC by the intersubcardinal anastomosis is explained in Chapter 6 .
- 3.
The IVC can even be midline in the asplenia syndrome (3%).
- 4.
Although interruption of the IVC is common with polysplenia, such interruption is rare with asplenia but does occur (3%).
- 5.
Although there can rarely be two IVCs below the liver (1%), to our knowledge the IVC is never completely bilateral, below and above the liver, with the two IVCs connecting separately at the atrial level. We have seen a very rare and fascinating case (a patient of Drs. Stephen Sanders and John Murphy from Genolier, Switzerland), who was studied angiocardiographically. There were two separate IVCs, both of which connected with a subatrial venous sinus before entering a common atrium by an apparently single venous connection. Hence, this patient almost has two separate and complete IVCs.
- 6.
The IVC never connects directly with the morphologically LA, to the best of our present knowledge. However, the IVC can drain into the LA in several different ways (see Chapter 6 ), one of which is to connect with a coronary sinus that is unroofed, permitting the IVC to drain into the LA, as in 1 of these patients (1%).
| Findings | No. of Patients (n = 76) | % of Series a |
|---|---|---|
| 24 | 32 |
| 28 | 37 |
| 7 | 9 |
| 11 | 14 |
| 2 | 3 |
| 2 | 3 |
| 1 | 1 |
| 1 | 1 |
Pulmonary Veins in Asplenia Syndrome
The status of the pulmonary veins in 93 postmortem cases of the heterotaxy syndrome with asplenia may be summarized as follows. The pulmonary veins were anomalously connected in almost three-quarters of these patients with asplenia (74%), TAPVC being the rule (69%), and partially anomalous pulmonary venous connection being the exception (5%). Normally connected pulmonary veins were found in 26% ( Table 29.11 ). (We were surprised that the proportion of normally connected pulmonary veins in asplenia was this high, slightly more than one-quarter.)
| Findings | No. of Patients (n = 93) | % of Series a |
|---|---|---|
| 64 | 69 |
| 5 | 5 |
| 24 | 26 |
What anatomic types of TAPVC occurred in the asplenia syndrome? The findings are summarized in Table 29.12 . The most common form of TAPVC in the asplenia syndrome was the supracardiac type (40%), followed by the infracardiac type (15%), then the cardiac form (10%), and finally by the mixed variety (4%). (Again, these findings surprised us, we having previously thought that the infracardiac type was the most common with asplenia. Thus, we learned that our previous impression had been wrong.)
| Findings | No. of Patients (n = 64) | % of Series a (n = 93) | |||
|---|---|---|---|---|---|
| Totally anomalous | PVC | 64 | 69 | ||
| 37 | 40 | |||
| 9 | 10 | |||
| 14 | 15 | |||
| 4 | 4 | |||
What types of supracardiac TAPVC were associated with asplenia? The answer is summarized in Table 29.13 . It is noteworthy that in the heterotaxy syndrome with asplenia, the supracardiac type of TAPVC usually was not of the classic “snowman” variety, that is, from the horizontal vein connecting the right pulmonary hilum with the left pulmonary hilum, then by a vertical vein to the left innominate vein, and thence to the RSVC and the RA.21. The “snowman” variety of supracardiac TAPVC occurred in only 3% of this series of asplenic patients (see Table 29.13 ).
| Findings | No. of Patients (n = 37) | % of Series a (n = 93) | ||
|---|---|---|---|---|
| Supracardiac TAPVC | 37 | 40 | ||
| 21 | 23 | ||
| 12 | 13 | ||
| 3 | 3 | ||
| 1 | 1 | ||
The most common type was to the RSVC (23%), followed by to the LSVC (13%) (see Table 29.13 ). The least frequent form in this series was to the SVC-to-RA junction (1%) (see Table 29.13 ). What did the cardiac type of TAPVC involve? See Table 29.14 .
| Findings | No. of Patients (n = 9) | % of Series a (n = 93) |
|---|---|---|
| To RA | 9 | 10 |
All cases of TAPVC of the cardiac type in the asplenia syndrome connected with the morphologically RA, never with the coronary sinus. Delisle et al concluded that this type of TAPVC is characteristic of the asplenia syndrome, rarely if ever occurring in patients without visceral heterotaxy. What were the specific anatomic details of the infracardiac type of TAPVC in the asplenia syndrome? These findings are presented in Table 29.15 .
| Findings | No. of Patients (n = 14) | % of Series a (n = 93) |
|---|---|---|
| To ductus venosus | 14 | 15 |
All 14 cases of the infracardiac type of TAPVC with asplenia had a paraesophageal vein that went below the diaphragm and connected with the ductus venosus, constituting 15% of the series as a whole. None of our cases of the infracardiac type connected with any other intraabdominal vein. All cases were thought to have obstruction of the anomalous pulmonary venous pathway because of acute angulation of the paraesophageal vertical vein with the ductus venosus. The findings in mixed TAPVC with asplenia are summarized in Table 29.16 .
| Findings | No. of Patients (n = 8) | % of Series a (n = 93) | ||
|---|---|---|---|---|
| Mixed TAPVC | 4 | 4 | ||
| 1 | 1 | ||
| 1 | 1 | ||
| 1 | 1 | ||
| 1 | 1 | ||
The findings in partially anomalous pulmonary venous connection with asplenia are summarized in Table 29.17 .
- 1.
Our interpretation of ipsilateral pulmonary veins, that is, that it may well represent malposition of the septum primum to the left of the right pulmonary veins (see Fig. 29.1 ), has been mentioned previously and hence will not be reiterated here.
- 2.
Pattern 2 in Table 29.17 indicates that the right upper lobe pulmonary vein connected with the RSVC, whereas all of the other pulmonary veins connected normally with the LA.
- 3.
But what does pattern 3 (see Table 29.17 ) mean? All of the right pulmonary veins connected with the RSVC, whereas all of the left pulmonary veins connected with the LA. Hence, this patient with partially anomalous pulmonary venous connection also has mixed partially anomalous pulmonary venous connection because all of the pulmonary venous blood from each lung connects with different structures: the right lung’s pulmonary veins to the RSVC and the left lung’s pulmonary veins to LA.
| Findings | No. of Patients (n = 5) | % of Series a (n = 93) | ||
|---|---|---|---|---|
| Partially APVC | 5 | 5 | ||
| 3 | 3 | ||
| 1 | 1 | ||
| 1 | 1 | ||
The status of the atrial septum in the heterotaxy syndrome with asplenia is summarized in Table 29.18 .
| Findings | No. of Patients (n = 95) | % of Series a (n = 95) |
|---|---|---|
| 68 | 72 |
| 17 | 18 |
| 5 | 5 |
| 2 | 2 |
| 2 | 2 |
| 1 | 1 |
In these 95 postmortem patients with the asplenia syndrome, the atrial septum was normally formed (with a patent foramen ovale) in only 2%. A common atrium with a largely or totally absent atrial septum was the most frequent finding (72%). Second in frequency was the combination of a secundum ASD with a primum ASD (the latter being part of a common AV canal), this combination of secundum and primum ASDs being found in 18% of our asplenia patients. Third in frequency was a primum ASD only (without a secundum ASD), in 5%. Fourth was a secundum type of atrial septal defect (2%). Also at a 2% prevalence was a normally formed atrial septum, with a patent foramen ovale as the only finding.
Least in frequency (1%) was single RA, that is, absence of the morphologically LA and interatrial septum. This is an exceedingly rare malformation, a virtually unknown form of congenital heart disease.
The anatomic status of the AV valves in 95 postmortem patients with the heterotaxy syndrome and asplenia is summarized in Table 29.19 .
| Findings | No. of Patients | % of Series a (n = 95) | ||||
|---|---|---|---|---|---|---|
| 91 | 96 | ||||
| 77 | 81 | ||||
| 14 | 15 | ||||
| 4 | 4 | ||||
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