Basic Principles
- 1.
When the situs (or pattern of anatomic organization) of the subarterial infundibulum and the situs of the great arteries are the same (concordant), the great arteries are normally related.
- 2.
When the situs of the subarterial infundibulum and the situs of the great arteries are different (discordant), the great arteries are abnormally related.
- 3.
A well-developed subarterial muscular infundibulum prevents the embryonic great arterial switch from above the morphologically right ventricle (RV) to above the morphologically left ventricle (LV).
- 4.
Absence of a subarterial muscular infundibulum permits an embryonic great arterial switch from above the RV to above the LV. So the subarterial infundibulum is the embryonic great arterial “switch master.”
Segmental situs equations, including the situs of the subarterial infundibulum and the situs of the great arteries, help clarify infundibuloarterial situs comparison, which in turn determines whether the great arteries are normally or abnormally related.
Synergy also helps to explain the normal and abnormal relationships between the great arteries, as we shall see.
Types of Situs
In anatomy, there are two types of situs, or patterns of anatomic organization:
- 1.
situs solitus, the normal or usual pattern; and
- 2.
situs inversus, a mirror-image, characterized by right-left reversal, but without superoinferior or anteroposterior change.
Situs ambiguus is not a third type of situs. It means that the pattern of anatomic organization is ambiguous or uncertain and is therefore not diagnosed. Situs ambiguus is different from situs solitus and situs inversus. There is more than one anatomic type of situs ambiguus, as we shall see.
Grading Infundibular Development
The development of the subarterial infundibular free wall is highly variable and may be graded as follows:
| Grade 0 | Absent |
| Grade 1 | Severely underdeveloped |
| Grade 2 | Moderately underdeveloped |
| Grade 3 | Mildly underdeveloped |
| Grade 4 | Normally developed. |
Situs Equations
Equations based on the situs of the cardiac segments clarify and simplify the understanding of congenital heart disease. In this chapter, emphasis is placed on the situs of the subarterial infundibulum and on the situs of the great arteries because these are the keys to understanding normally and abnormally related great arteries.
Equation 26.1 , read from left to right, says: solitus normally related great arteries with the set of solitus atria, D-loop (solitus) ventricular, and solitus normally related great arteries equals zero development of the right-sided subaortic infundibular free wall plus a well-developed left-sided subpulmonary infundibular free wall.
In these subarterial infundibular situs equations, the formula or recipe for the infundibular situs lies to the right of the equal sign: 0R + 4L; and the situs of the great arteries is indicated by the third element of the segmental anatomy immediately to the left of the equal sign: {-,-, S } = the infundibuloarterial situs combination:
- 1.
The situs of the infundibulum is solitus normal, that is, 0R + 4L.
- 2.
The situs of the great arteries also is solitus normal, that is, {-,-,S}.
So, the infundibuloarterial situs combination is solitus normal–solitus normal, which is same–same, that is, concordant or normal. Why normal? Because the infundibular connector and the great arteries being connected are both of the same normal anatomic type. Both are in situs solitus. Plumbers know this. The connector and the pipes being connected must be of the same type. Otherwise, the pipes cannot be connected normally.
These same points can be made diagrammatically ( Fig. 26.1 ). In the solitus (noninverted) heart, as seen from the front, the aortic valve is to the right and the pulmonary valve is to the left . So in Equation 26.1 , you know that normally, the right-sided semilunar valve is the aortic valve, and the left-sided semilunar valve is the pulmonic valve (see Fig. 26.1 ).
The effect of D-loop formation is thought to produce about 90-degree dextrorotation at the semilunar valve level relative to the sagittal plane (see Fig. 26.1 , second column from the right ). Looking at the diagrams of solitus normally related great arteries (see Fig. 26.1 , third column from the right ), you can see the formula of the normal solitus subarterial infundibulum. There is no subaortic infundibular free-wall muscle, remote from the infundibular septum. This subaortic infundibular free-wall muscle has disappeared because of apoptosis (programmed cell death), which in turn makes possible aortic-mitral fibrous continuity via the intervalvar fibrosa in the LV, and often aortic-tricuspid fibrous continuity via the membranous ventricular septum. In contrast, the left-sided subpulmonary infundibular free wall develops well above the RV.
The normal infundibular situs solitus, that is, 0R + 4L, contains another “secret.” 0R means not only that there is no subaortic infundibular free-wall muscle because of apoptosis. 0R also means that the right-sided aorta has undergone an embryonic switch from above the RV to above the LV. Here is how this is thought to work:
- 1.
A well-developed subarterial infundibulum is thought to block or prevent an embryonic great arterial switch. A subarterial infundibulum acts as a platform on which a great artery stands and is held high.
- 2.
When there is no subarterial muscular platform, a great artery can move inferiorly, posteriorly, and leftward. Passing through the interventricular foramen, the great artery becomes left ventricular. So, the subarterial infundibulum may be regarded as the embryonic great arterial switch master.
Whenever the subaortic infundibulum is absent, as in the solitus normal heart— 0R + 4L—one should expect that the aorta has been switched from RV to LV in utero.
In Homo sapiens, the normal human embryonic aortic switch is produced by complete right-left asymmetry in the development of the subarterial infundibular free walls between 38 and 45 days of age in utero :
Equation 26.2 is inverted normally related great arteries.
This Equation 26.2 and Figure 26.2 (third column from the left) represent inverted normally related great arteries. In words, this equation says: Inverted normally related great arteries with the set of situs inversus of the atria, situs inversus of the ventricles (ventricular L-loop), and inverted normally related great arteries equals a well-developed, right-sided subpulmonary infundibular free wall plus absence of a left-sided subaortic infundibular free wall.
The infundibular situs is the inverted normal: 4R + 0L. The great arterial situs is the inverted normal: {-,-, I }. Thus, the infundibular situs—great arterial situs combination is inverted normal; that is, concordant or the same, which is normal in situs inversus totalis.
The inverted infundibular situs in Equation 26.2 to the right of the equal sign (4R + 0L) tells you the switch—no switch story. In situs inversus totalis, the right-sided great artery normally is the pulmonary artery ( Fig. 26.2 , third column from the left ), and there is a well-developed (grade 4) infundibulum beneath the main pulmonary artery (MPA). Knowing that a well-developed subarterial infundibulum blocks the embryonic great arterial switch, you realize that the pulmonary artery has not been switched and is still high above the left-sided morphologically right ventricle (RV). This is what 4R tells you.
What about 0 ? You know that in situs inversus totalis, the left-sided great artery is the aorta (see Fig. 26.2 , column 3 from the left ). And you also know that when there is no infundibular muscle beneath the aortic valvar free wall, this is a precondition for a great arterial switch. So you correctly conclude that the aorta has been switched from above the left-sided RV to above the right-sided LV.
Equations 26.3, 26.4, and 26.5 describe tetralogy of Fallot, with variable degrees of right ventricular outflow tract obstruction.
Tetralogy of Fallot (TOF) with the set of solitus atria, solitus (D-loop) ventricles, and solitus normally related great arteries typically has no infundibular muscle beneath the right-sided aortic valve. But the degree of hypoplasia and hence of obstruction of the left-sided subpulmonary infundibulum is highly variable:
1L indicates very severe obstruction.
2L means severe stenosis.
3L denotes mild to moderate stenosis.
As far as now known, the TOF was first described in 1671 by Niels Stensen, not by Arthur Fallot in 1888.
Morphometry has revealed that right ventricular hypertrophy is not present at birth in “TOF.” Right ventricular hypertrophy is a postnatally acquired sequelea.
In 1970, we proposed that the TOF is, in fact, just one malformation and its sequelae. The one malformation is hypoplasia of the subpulmonary infundibulum, which leads to pulmonary outflow tract obstruction (stenosis or atresia), a typically large subaortic ventricular septal defect (VSD), aortic overriding, and right ventricular hypertrophy (postnatally).
So, TOF might well be called the monology of Stensen. However, out of deference to common usage and in the interests of widespread comprehension, I shall continue to call this anomaly (or these anomalies) the tetralogy of Fallot.
What comes after TOF? What is closely related to TOF? We used to call it truncus arteriosus communis type A2. But now we have realized that the diagnosis of persistent common arterial trunk is wrong because the MPA can be absent. Abbott introduced the concept of a common (undivided) great arterial trunk in 1927. She thought this anomaly was “absence or rudimentary development of [the] aortic septum.” The concept of common aortopulmonary trunk also included the ideas that the semilunar valves and the infundibular septum are in common, because that is what the anatomy seemed to show. This was our interpretation in 1965.
But about 36 years later, in 2001, Dr. Alfredo Vizcaino, a pediatric cardiologist, friend, and colleague brought us a rare case in consultation from the Hospital Infantil de Mexico, Mexico City, Mexico that opened my eyes ( Fig. 26.3 ). The specimen of heart and lungs was that of a 2-day-old female infant who weighed 2200 g. A complete autopsy showed that the segmental cardiac anatomy was normal: {S,D,S}. The atrioventricular (AV) and ventriculoarterial (VA) alignments were normal. The septum primum was almost absent, resulting in a common atrium.
The MPA was of good size (9 mm in external diameter). But it gave origin to no pulmonary artery branches. The only outlet from the MPA was a patent ductus arteriosus (internal diameter 3 to 4 mm) that opened into the descending thoracic aorta (external diameter 9 mm). The ventricular septum was intact, and both ventricular outflow tracts were unremarkable. The right pulmonary artery (RPA) and left pulmonary artery (LPA) branches both originated from the aortic sac on the dorsal surface of the ascending aorta via a single ostium (internal diameter 3 mm). This ostium led into a short common pulmonary artery that then bifurcated into right and LPA branches. The opening into the short common pulmonary artery lay 8 mm above an unremarkable aortic valve and 7 mm below an unremarkable appearing innominate artery. The common pulmonary artery proceeded posteriorly for 5 mm and then bifurcated into the RPA and LPA branches, as noted earlier. The common pulmonary artery measured 4 mm in external diameter. The RPA and left LPA branches both measured 3 mm in external diameter.
This patient had a heterotaxy syndrome with polysplenia. There were two small splenuli, each weighing 1.5 g. Both lungs were bilobed. Both right and left mainstem bronchi were hypoarterial. The liver was bilaterally symmetrical, and the gallbladder was absent. The inferior vena cava was interrupted. An enlarged azygos vein drained into the right superior vena cava. There was also marked congenital stenosis of the lower trachea, with complete tracheal rings. Severe airway stenosis also involved the carina and the proximal mainstem bronchi, with luminal narrowing to a diameter of less than 1 mm. The aortic arch was left-sided, with marked tubular hypoplasia and severe preductal coarctation (internal diameter 1 mm) (see Fig. 26.3 ). Biventricular hypertrophy and enlargement were also present.
Additional associated congenital anomalies included tracheomalacia, stomach in the right upper quadrant, atresia of the first portion of the duodenum with annular pancreas, intestinal malrotation with cecum and appendix in the left upper quadrant, horseshoe kidneys, agenesis of the ovaries and fallopian tubes, atresia of the inferior one-third of the urinary bladder, atresia of the inferior one-third of the vagina, absence of the urethral meatus, and absence of the hymen and clitoris. Although this patient had the heterotaxy syndrome with polysplenia, she also had additional severe malformations, some of which were consistent with the XO Turner syndrome. Unfortunately, the karyotype was not done.
How were we to interpret Dr. Vizcaino’s amazing case? A normal MPA, but with no branches! And with the pulmonary artery branches arising from the posterior wall of the ascending aorta!
Fortunately I remembered a paper by Congdon that had been published in 1922 from the Contributions to Embryology of the Carnegie Institution of Washington, where I had studied their embryology collections and had done experimental embryology in 1966. I was well aware that this was an excellent source of highly reliable embryologic information. Congdon found that the RPA and LPA branches originate from the aortic sac on the dorsal surface of the ascending aorta at the 4-mm stage, when the human embryo is 24 to 26 days of age in utero, before the embryonic sixth arches have completely formed. Completion of both sixth aortic arches can occur as early as the 5-mm stage, 26 to 28 days of age in utero. Completion of both sixth aortic arches usually occurs by the 6-mm stage, at 28 to 30 days of age in utero. As soon as both sixth arches have been completely formed, they normally enlarge considerably, and both pulmonary artery branches migrate on the sixth arches and unite with the MPA. Thus, the normal pulmonary arterial system has a tripartite origin:
- 1.
The pulmonary artery branches arise from the aortic sac.
- 2.
The MPA originates from the truncus arteriosus.
- 3.
The RPA and LPA migrate on the ventral sixth aortic arches from the aortic sac to become confluent with the MPA at about 28 to 30 days of age in the normal human embryo.
Our interpretations of the foregoing data are as follows:
- 1.
In Vizcaino’s very rare case (see Fig. 26.3 ) with multiple congenital anomalies, the sixth aortic arches did not form normally. Consequently, the RPA and the LPA could not migrate and become confluent with the normally formed MPA. Consequently, the RPA and the LPA are unmigrated (see Fig. 26.3 ).
- 2.
In our case of so-called truncus arteriosus communis ( Fig. 26.4 ), the RPA and the LPA are still in their starting, premigration locations, arising from the aortic sac, because the RPA and the LPA have nowhere to migrate to—the MPA is absent. There is no vestige of the aortopulmonary septum because the MPA is absent. So, too, are the subpulmonary infundibulum and the pulmonary valve. Fig. 26.4 shows a solitary aorta with absence of the MPA, and unmigrated RPA and LPA.
Fig. 26.4
We and many others used to regard this kind of case as having truncus arteriosus communis, our type A2 in 1965. This was well before we came to understand the aortic sac as the site of origin of the pulmonary artery branches (about 2001). The heart presented in Fig. 26.3 was what opened my eyes. The above heart has a typical aortic sac giving rise to unmigrated pulmonary artery branches. The subpulmonary infundibulum, the pulmonary valve, and the main pulmonary artery are all absent. The right pulmonary artery (RPA) and the left pulmonary artery (LPA) are unmigrated, perhaps because they have nowhere to migrate to, because the main pulmonary artery is absent. The large subaortic ventricular septal defect is caused by absence of the subpulmonary infundibulum. The diagnosis is absence of the pulmonary outflow tract, that is, absence of the subpulmonary infundibulum, pulmonary valve, main pulmonary artery, and unmigrated pulmonary artery branches arising from the aortic sac. Is this pre-tetralogy of Fallot (TOF)? TOF is progressively more severe infundibular hypoplasia. But in TOF, the worst infundibular hypoplasia ever gets is infundibular atresia. But never infundibular absence. And not just infundibular absence. The whole pulmonary outflow tract is absent. AoA, Aortic arch; AL, anterior leaflet (of the tricuspid valve); LA Div, left anterior division (of top of septal band); LC, left coronary (leaflet of aortic valve); ML, muscle of Lancisi; MV, mitral valve; NC, noncoronary leaflet (of aortic valve); RC, right coronary (leaflet of aortic valve); RP Div, right posterior division of the top of the septal band; SB, septal band; SL, septal leaflet (of tricuspid valve); VSD, ventricular septal defect.
Reproduced with permission from Van Praagh R, Van Praagh S. The anatomy of common aorticopulmonary trunk (truncus arteriosus communis) and its embryologic implications, a study of 57 necropsy cases. Am J Cardiol. 1965;16:406.
By 2002, we understood that the normal pulmonary arterial system is a three-component system :
- 1.
the truncus arteriosus (arterial trunk) supplies the MPA:
- 2.
the aortic sac is where the RPA and LPA branches originate; and
- 3.
the sixth aortic arches are the third component that is necessary to connect component one (the MPA) and component two (the RPA and LPA branches). This is what Vizcaino’s case taught us, confirming what Congdon had published in 1922.
We also realized that it is impossible to have a common (undivided) aortopulmonary trunk if the subpulmonary infundibulum, the pulmonary valve, and the MPA are all absent . These data mean that we are dealing with a solitary aortic trunk (see Fig. 26.4 ), not with a common (undivided) aortopulmonary trunk. This also means that cases of truncus arteriosus communis persisens (persistent common arterial trunk) , need to be reinterpreted, which we have been doing previously and are endeavoring to do here.
How could we all have been so wrong? My best assessment is as follows. We did not know about, or had forgotten about, Congdon’s work in 1922, that is, that the RPA and the LPA originate from the aortic sac and then have to migrate on the sixth aortic arches to connect with the MPA. Congdon knew that the normal pulmonary arteries were a three-part system, which he described. Later investigators —the rest of us—seem to have assumed that the pulmonary arteries are one structure. We assumed that because the RPA and the LPA branches are present (see Fig. 26.4 ), the MPA “must” be present, even though there is no vestige of the aortopulmonary septum that would support the presence of an MPA in our type A2. We used to think that absence of aortopulmonary septation was the malformation. We did not know that the RPA and LPA could be present and that the MPA could be absent, because the pulmonary arteries are a composite three-part system. We did not know that the presence of the RPA and LPA arising from the aortic sac implies nothing, of necessity, concerning the MPA component of the arterial trunk (the truncus arteriosus).
We did not understand the silent testimony of the unmigrated RPA and LPA arising from the aortic sac. The most obvious “messages” being sent by the unmigrated RPA and LPA are:
- 1.
the MPA is absent, that is, there is nowhere for the RPA and the LPA to migrate to; or
- 2.
the sixth aortic arches—the transport system for the RPA and the LPA—are absent, or nonfunctional; or
- 3.
both 1 and 2.
Thus, the presence of unmigrated RPA and LPA supports the possibility that the MPA is absent. Because we now know that the pulmonary arteries normally are a three-component system, the presence of unmigrated RPA and LPA does not suggest that the MPA must be present, when there is no anatomic evidence that this is the case.
Why have I spent so much time on so-called truncus arteriosus communis type A2? Because it is perhaps the best example of “absence of [the] aortic septum,” including absence of septation at the level of the semilunar valves and infundibular septum. It is now clear that this classic concept of persistent common aortopulmonary trunk was, and is, a mistake; thus, I propose that this erroneous diagnosis be discontinued, in the interests of anatomic and developmental accuracy. It must be added that it is rarely possible for there to be almost total absence of the aortopulmonary septum, with normal separated semilunar valves and with an intact ventricular septum ( Fig. 26.5 ). I have never seen a case like this. This photograph was sent to me by Professor J. W. A. Duckworth, Professor of Anatomy, University of Toronto, Ontario, Canada. This is the heart of a 42-year-old white woman who dies of unrecognized pulmonary tuberculosis. The heart specimen is from the Department of Anatomy of the University of Edinburgh, Scotland.
