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Pathogenesis of transposition Complexes
Pathogenesis II.
of Transposition
Anomalies due to Faulty Transfer Posterior Great Artery* H. S. V.w
LODEWYK
T
HIS paper concerns itself largely with those cardiac anomalies which are often considered to be a form of transposition of the great vessels, but which, on embryologic grounds, should be sharply distinguished from true transposition complexes. These are dextroposition of the aorta (tetralogy of Fallot, Eisencomplex) and double outlet right menger ventricle (several types, including the TaussigBing complex). They do not form a homogeneous group pathogenetically and cannot always be sharply differentiated from each other, i.e., transitional forms are common. In all cases one of the great arteries originates anteriorly from the right ventricle; the other either springs from both ventricles, overriding a defect to a varying degree, or arises wholly from the right ventricle. Usually the pulmonary artery is the anterior vessel and the aorta the posterior. True transposition of the vessels
in which
case
may,
however,
the aorta
be an associated
is the anterior
vessel
anomaly, and
transposition
in the third
complexes
and last part
will
the
be discussed
of this series.
DEFINITIONS Dextroposition: The posterior vessel, whether it be the aorta or the pulmonary artery, originates from both ventricles above a ventricular septal defect. The vessel is said to “override” the defect. If the anterior vessel overrides an anteriorly located defect, a levoposition of that vessel is said to exist. When the position of the ventricles is inverted, as in total situs inversus or in isolated inversion of the ventricles, these terms should, of course,be reversed. De.rtro(Leuo)rotation: Here, as opposed to the nor* From the Department of Anatomy, McGill University, Hospital, Montreal, Canada. t Present address: Albany Medical Collcgr of Union
M.D.
Canada
mal, the apex of the heart is on the same side as the morphologic right atrium. In dextrorotation the right atrium is in its normal position; in levorotation the right atrium lies on the left side as part of a total 6itus inversus. Dextrocardia: The apex of the heart points to the right, and there is situs inversus of the atria and at least some of the other viscera, usually the lungs. Dextrocardia should not be confused with dextrorotation. Inversion: This term as used in more recent publications denotes mirror-image of the normal left-right relationships of all or some of the organs (complete or partial situs inversus) or of the cardiac ventricles only. The anteroposterior relationships remain normal. Transposition of the Great Vessels: Abbott’ defines transposition as “an alteration in the position of the two great vessels relative to the ventricles of the heart, or to each other at their origin, so that they spring either from reversed ventricles-the aorta from the right, and the pulmonary artery from the left chamber (complete transposition)-or from the ventricles to which they normally belong, but in reverse relationship (corrected transposition). This definition, as Harris and Farber2 have already pointed out, is too vague. They added the words: “and an alteration in the anteroposterior relationship of the great vessels, either at the ventricular insertion or in their spiraling.” According to Edwards3 and most present day authors, transposition is any congenital abnormality in the relationship of the great arterial vessels (or their This remnant) to each other and to the ventricles. definition includes: (1) cases in which the pulmonary artery springs from the right ventricle and the aorta from both, overriding a ventricular septal defect (dextroposition of the aorta as in tetralogy of Fallot) ; (2) cases in which both arteries originate from the right ventricle (double outlet right ventricle or partial transposition) ; and (3) cases in which the aorta originates anteriorly from a morphologic right ventricle and the pulmonary artery from a morphologic
pulmonary artery the posterior. It is for this reason that we shall use the more general terms anterior and posterior vessel in the body of this paper. True
of the
MIEROP, M.D.? and FREDERICK W. WIGLESWORTH, Montreal,
great
Complexes
and the Department
of Pathology,
University,
N. Y.
226
Albany.
PII< AMERICAN
The
Montrral
IOURNAL
OF
Children’s
CARDlOLOGY
Pathogenesis
of Transposition
left ventricle without ventricular inversion (complete transposition) or with ventricular inversion (“corrected” transposition). More recently there has been a tendency to exclude dextroposition of the aorta as a transposition complex. As will be shown in the body of this paper, the pathogeneses of dextroposition of the aorta, partial transposition, complete transposition and “corrected” transposition are dissimilar and unrelated. This will explain why dextroposition or partial transposition can and do occur in combination with true transposition with or without inversion of ventricles. On embryologic grounds we define true transposition of the great vessels as that condition in which the aorta lies anterior to the jndmonary artery and originates from a morphologic right ventricle anterior to the crista qbraventricularis 07 its remnanr. The pulmonary artery may originate from either ventricle or override a defect. HISTC~RICAL REVIEW
TABLE
Principal Anterior Xpt”lll
Embryological displacement
Hypnplasia Extreme rcptumor
persistence
vent&xlnr
llnnge
scpium
of the
ronus
of the bulho-
I
Origin of Postrrior
Ikror of the conus
of the rmnu hypoplasiz
Cases of Complete
II
According to Keith,e transposition complexes are caused by abnormal absorption of the bulbus cordis (our conus cordis, as described in Part I). Comparative anatomic studies led Robertson’ to agree mainly with Rokitansky’s views. Spitzer’sg theory is based on phylogenetic considerations and may be summarized as follows: With the development of lung breathing, cardiac septation becomes more refined and complete in an effort to gain a more complete separation of arterial and venous blood. Development of the bulboventricular loop and subsequent septation are greatly influenced by hydroclynamic forces occurring in the circulation. Since Ihe primitive heart tube is fixed at both ends, loop formation to the right will lead to torsion at the arterial end and detorsion at the venous pole. This torsion and detorsion increases with ascendence in the animal scale and becomes maximal in birds and mammals. Abnormalities in this process of torsion lead to cardiac anomalies and in certain cases to reopening of the reptiiian right aorta which, if a normal degree of torsion occurs, obliterates in mammals. Although Spitzer’s theory has had great influence on later investigators, it has been criticized by Pernkopf and WirtingerY and others, and somewhat later also by Lev and Saphir,“J on the very valid grounds that it cannot clarify many anomalies and it does not explain the pathogenesis, in man, of these anomailes. Pernkopf and Wirtingerg concluded that abnormalities in the absorption of the bulbus (our conus) cordis are more important in the production of cardiac anomalies than faulty torsion. Lev and Saphir’o postulated an abnormality in the formation of one of the bulbar ridges as responsible for transposition complexes. A recent ontogenetic theory on truncoconal malformations has been put forward by de la Cruz and da Rocha.” The theory is based on the embryology of the human heart as described by Davis,‘* Strreter13,14 and Kramer,‘5 as well as on the analysis of congenitally malformed hearts. It gives, in our opinion, the most realistic and satisfacrory explanation yet of anomalies involving the truncus and conus,
Only the more important publications dealing with transposition complexes will be briefly discussed. A detailed and comprehensive review has been given by Harris and Farber.* Peacock4 thought transposition of the great vessels was due to inflammatory pulmonary artery stenosis occurring in early embryonic life and resulting in a high right ventricular pressure and subsequent septal deviation to the left. In cases without pulmonary stenosis, the pathogenesis was thought to be an abnormal development of aorta and pulmonary artery from the truncus arteriosus. Abnormal development of the bulbar and ventricular septa was held responsible by Rokitansky5 for both the pulmonary artery stenosis and ventricular septal defect and resulted in transposition, the degree of which varied depending upon whether the aortic septum was merely deviated or abnormally rotated. In any event, the aortic septum is unable to meet the ventricular septum giving rise to a ventricular septal defect and a varying degree of transposition with one or both vessels arising from the wrong ventricle.
Eighty-two
Complexes.
Artery from Right Ventricle
Anomaly Tetralogy
so.
of Fallot
51,
with pulmonary valvular S~C~OSIS without pulmonary valvular stenosis with pulmonary atresia (pseudorrunrus) F.isenmenger complex Doubleoutlet
right
without
transposition
19 15 16 27
ventricle 14
without transposition, but with a subpulmonary septal defect and overriding pulmonary artery (Taussig-Bins complex)
2
with
transposition
8
with
transposition
and ventricular
inverkn
‘Total
AUGUST
1963
of (k%ccs
x2
228
Van Mierop
and Wiglesworth
FIG. 1. Projectional diagram of the base of the heart. septal defect. C, tetralogy of Fallot. D, Eisenmenger
although such postulates as delayed disappearance of the conoventricular flange may seem artificial in view of the multiple changes occurring in this area.
MATERIAL Among 600 hearts in the collections of the Department of Pathology, The Montreal Children’s Hospital and the Subdepartment of Thoracic Surgery, Albany Medical Center Hospital, Albany, N. Y., 177 exhibited some anomaly in the relation of the great arteries to each other or to their chambers. Eighty-two cases showed partial or complete origin of the posterior artery from the right ventricle (Table I). These cases represent the material to be discussed. In 71 there was a failure of transfer of the aorta to the left ventricle, i.e., dextroposition of the aorta or double outlet right ventricle. In 11 additional cases associated with true transposition, this failure concerned the pulmonary artery, it being the posterior vessel in these specimens. As was shown in Part I, for a normal transfer of the aortic root to the left ventricle it is necessary that (I) the cardiac loop be formed normally, (2) the conoventricular flange be shifted adequately to the left and eventually disappear, (3) the conus septum develop in the normal position and (4) it be of adequate size. Abnormal development of any or a combination of these, leads to incomplete transfer of the aorta (or the pulmonary artery in cases of complete transposition) to the left ventricle. It is, therefore, not surprising that the various malformations resulting from such developmental abnormalities cannot always be sharply defined from each other.
A, normal heart.
B, ventricular
complex.
DEXTROPOSITION OF THE AORTA The anteroposterior relationship of the great vessels is normal. The degree of dextroposition varies considerably from cases in which the position of the aortic root is almost normal to those in which the aorta originates almost entirely from the right ventricle. Dextroposition of the aorta in the great majority of cases is due either to (1) anterior displacement of the conus septum, resulting in right ventricular infundibular stenosis of varying degree with or without pulmonary valvular stenosis (tetralogy of Fallot), (2) hypoplasia or absence of the conus septum (Eisenmenger’s complex), or (3) a combination of these (transitional forms). In tetralogy of Fallot there is always infundiband the ventricular septal ular narrowing, defect is usuall>- large (Fig. 1C). There may or may not be stenosis of the pulmonary valve, which in either case may be bicuspid or triSince normal development of the cuspid. conus septum is necessary in closing the interventricular communication, any anomaly of the proximal portion of the conus septum results in a ventricular septal defect in the basilar ventricular septum. Since normally the conus septum contributes to the formation of the anterior leaflet of the of this tricuspid valv~,‘~ minor abnormalities ‘Xi,< AMERICAN
JOURNAL
OF
CARDlOL.OGY
Pathogenesis
of Transposition
Complexes.
II
229
FIG. 2. Projectional diagram of the base of the heart. A, double outlet right ventricle. B, Taussig-Bing complex. C, “extreme” Eisenmenger complex. D, “false” Taussig-Bing complex (transposition of the great vessels, ventricular septal defect and overriding pulmonary artery).
leaflet are almost always present in tetralogy of Fallot, as in all hearts where there are anomalies of the conus septum. The medial or conus papillary muscle is usually absent, or in some cases an analogous (but not homologous) structure is found in an abnormal place, usually along the posterior or superior margins of the ventricular septal defect. Extreme degrees of displacement of the conus septum may lead to atresia of the infundibulum and then usually also of the pulmonary valve. The pulmonary artery may be reduced to a fibrous band. This condition has been called pseudotruncus aorticus or truncus solitarius aorticus. In true Eisenmenger complex, a rare anomaly, there is no infundibular stenosis, and the ventricular septal defect is similar to that in tetralogy (Fig. 1D). In some cases the overriding of the aorta is so extreme that the vessel originates almost completely from the right ventricle, posterior and to the right of the dilated pulmonary artery (Fig. 2C). Again the tricuspid valve is abnormal in most cases. Since hypoplasia of the crista also often occurs in tetralogy and the pulmonary valve may be normal in the latter, no sharp anatomic distinction can be drawn between Eisenmenger’s complex and tetralogy of Fallot. Similarly anatomic differentiation between
isolated ventricular septal defect and Eisenmenger’s complex is often difficult. A ventricular septal defect of small or average size hidden behind the septal leaflet of the tricuspid valve, the presence of a medial papillary muscle, and a well developed crista rule out Eisenmenger’s complex in the anatomic sense. Eisenmenger’s original illustration17 shows the hypoplastic crista supraventricularis well. DOUBLE OUTLET RIGHT \7~~~~~~~~‘8 In the commonest type, there is a ventricular septal defect which forms the sole outlet for the left ventricle (lateral position of the arteries,” origin of both great arteries from the right ventricle’g). The pulmonary artery arises in its normal, anterior position, and the aorta originates wholly from the rightventricle and is located behind and to the right of the pulmonary artery. In some cases it may even approach the same frontal plane in which the pulmonary artery lies. Neufeld et al.lg distinguish two main types: (1) The aortic valve is continuous with the anterior leaflet of the mitral valve, as in normal hearts. (2) The aortic valve is separated from the mitral valve by a muscular band. The anatomic distinction between the first type and Eisenmenger’s complex is, in our opinion, only
Van Mierop
FIG. 3. Double outlet right valve and the aortic valve.
vcntriclc.
Note
the great
one of degree, and the pathogenesis is probably the same: hypoplasia and possibly some anterior displacement of the crista supraventricularis (Fig. lD, ZC). The second type, although functionally identical, is anatomically quite different (Fig. 2A, 3). The aorta originates from the right ventricle and is separated from the pulmonary artery by a muscular band (the crista supraventricularis) and from the tricuspid and mitral valves by a second band of muscle, which we believe to be a persistent bulbo(cono)ventricular flange. This second band may be large, as in Figure 3, or it may be rather insignificant. We have seen 2 additional cases in which both arteries originated from the right ventricle, but both hearts represented a much more primitive condition, due probably to an early developmental error in the formation of the cardiac loop (Fig. 4). In both cases there was juxtaposition of the atria; in 1 there was also inversion of the ventricles, transposition of the great vessels and atresia of the left A-V valve. The associated transposition of the great vessels in the latter case (with inversion of the ventricles) is to be expected (see Part III). ASSOCIATED
ANOM.4LIES
Double outlet sociated with any or combinations important ones are
and Wiglesworth
right ventricle may be asnumber of other anomalies of anomalies. The more as follows :
distanrc
brtwrcn
the antrrior
I4lct
of the mitral
Stenosis uf the Pulmonary Valor: Because of its functional similarity to tetralogy of Fallot, this anomaly has been called Fallot type of double outlet right ventricle.18 Atresia qf an A-V Value: If the mitral valve is atretic the left ventricle is often absent. The ventricular portion of the heart consists of a right ventricle from which both arteries arise. If a left ventricle is present, it is usually part of a common ventricle, i.e., the ventricular septum is absent. If the tricuspid valve is atretic, the heart consists of tile left ventricle and the conus part of the right ventricle, from which both arteries arise. A ventricular septal defect leads from the left ventricle into the conus (rudimentary outflow chamber). True transposition may be associated with double outlet right ventricle. In these cases the aorta is anterior and the pulmonary artery is posterior. lnuersion oj the Ventrides: If the primitive heart tube loops to the left instead of to the right, the primitive ventricle comes to lie on the right side and the bulbus cordis on the left. The morphologic left ventricle, therefore, also lies on the right and the morphologic right ventricle on the left. If subsequent development proceeds normally, the result will be a corrected transposition. Why the arteries in this condition are of necessity transposed will be explained in Part III. Cases have been reported in which both TI!E
AMERICAN
JOURNAI.
OF
CAR1)IOt.OC.Y
Pathogenesis
FIG. 4.
Unusual
of Transposition
type of double outlet right wntriclr.
This arteries originate from a left ventricle. is an embryologic impossibility, and it is possible that in reality one is dealing with a combination of double outlet right ventricle and inversion of the ventricles. Subpulmonary Ventricular Septal Defect (TaussigBing complex): In most cases of double outlet right ventricle the ventricular septal defect is located beneath the aorta. Occasionally, however, there is a defect much more anteriorly beneath the pulmonary artery. Such a defect may occur as an isolated lesion, and the pulmonary artery may then straddle it. The combination of this defect with double outlet right ventricle has been called complete transposition of the aorta and levoposition of the pulmonary artery by Taussig and Bing.“” Since then this anomaly has been known as the Taussig-Bing complex (Fig. 2B). Unfortunately-, as has been pointed out by de la Cruz and da Rocha” and Beuren,21 another totallv unrelated condition hzs been referred to by several authors as Taussig-Bing complex. The spurious Taussig-Bing heart is characterized by true transposition of the great vessels, i.e., the aorta arises anteriorly from the right ventricle and the posterior pulmonary artery overrides a posterior ventricular septal defect but originates mainly from the AUC,I-Sl’
196;
Complexes.
231
II
Vrr\- primitive hart.
left ventricle (Fig. 2D). This lesion is considerably more common than the true TaussigBing complex of which we have seen only two examples. Although Taussig and Bing do not specify the anteroposterior position of the aorta and pulmonary artery relative to each other, their figures leave little doubt that the pulmonary artery in their original case was anterior and the aorta right posterior. The term Ievoposition of the pulmonary artery also indicates this, since, strictly speaking, one would have to designate the pulmonary artery in the spurious Taussi,g-Bing as being dextroposed. %JhlMARY
AND
CONCLUSIONS
Ovekding of /he aorta may he due to (1) anterior displacement of the conus septum resulting in various degrees of infundibular stenosis (tetralogy of Fallot), (2) hypoplasia of the septum (Eisenmenger’s complex) or (3) both (transitional forms). In none of these cases can the ventricular septum be closed, and transfer of the aorta to the left ventricle is incomplete. Anomalies of the medial portion of the anterior tricuspid leaflet are common in both, since this portion of the valve is derived from the proximal conus septum. No sharp distinction can always be made between the two complexes since both
232
‘i’an
Mierop
displacement and hypoplasia ma)- occur together. I)ouDi~ outlet right ventricle results frvm incomplete recession of the bul boventricuiar flange, from abnormalities in the formation of the cardiac loop, or both. Cases of extreme dextroposition closely resemble double outlet right ventricle, both anatomically and functionally. However, in these cases the valve cusps of the posterior artery are continuous with the anterior leaflet of the mitral valve, whereas in double outlet right ventricle they are separated from each other by a band of muscle, the persistent conoLrentricular flange. The true Taussig-Bing complex is not a it is a form of double transposition complex; outlet right ventricle.
REFERENCES 1. 2. 3.
4. 5. 6. 7.
8.
9.
Modern Medicine. M. E. In OSLER, W. Edited by M&RAE, T. ed. 3, Vol. 4, p. 716. Philadelphia, 1928. Lea and Febiger. HARRIS, J. S. and FARBER, S. Transposition of the great cardiac vessels. Arch. Path., 28: 427, 1939. I~DWARDS, J. E. Congenital malformations of the heart and great vessels, In: GOULD, S. E. Pathology of the Heart, ed. 2, p. 354. Springfield, ill., 1960. Charles C Thomas. PEACOCK, T. B. On Maiformations of the Human Heart. London, 1866. J. Churchill. Die Defecte Der ScheideEON ROKITANSKY, C. wande des Herzens. Wien, 1875. Braumiiller. K;EITH, A. The Hunterian lectures on malformations of the heart. Lancel, 2: 433, 1909. RUBERTSON, J. I. Comparative anatomy of the bulbus cordis, with special reference to abnormal positions of the great vessels in the human heart. J. Path., 18:.!91,1913. SPITZER, A. Uber den Bauplan des normalen und missgebildeten Herzens. Versuch einer phylogenetischen Theorir. Virrhowr s4rch. path. Amt., 243: 81, 1923. P~RNKOPF, E. and WIKITNGER, 1%'. Ih Wesen der ‘Transposition im Gebiete des Hrrzcns. ein Versuch
and
Wiglesworth
10.
11.
12.
13.
14.
15.
&3BOTT,
16.
17.
18.
19.
20.
21.
dcr Erklarung auf entwicklungsgeschichter Grundlage. Vi?chnwsArch.path. Amt., 295: 143, 1935. LEV, M. and SAPI~R, 0. A theory of transposition of the arterial trunks based on the phylogenetic and ontogenetic development of heart. Arch. Path., 39: 172, 1945. DE I_A CRUI, M. C. and DA ROCHA, J. P. .4n ontogenetic theory for the explanation of congenital malformations involving the truncus and conus. Am. Heart J., 51: 782, 1956. DAVIS, C. L. Development of the human heart from its first appearance to the stage found in embryos of twenty paired somites. Contrib. EmbryoI., 19: 245, 1927. STREETER, G. L. Developmental horizons in human embryos. Description of age group XIII, embryo’s about 4-5 mm. long, and age group XIV, period of indentation of the lens vesicle. Cbnlrib. Embryol.. 31: 27, 1945. STREETER, G. L. Developmental horizons in human embryos. Description of age group xv, XVI, XVII, XVIII, being the third issue of a survey of the Carnegie Collection. Co&b. Embryol., 32: 133, 1948. KRAMER. T. C. The partitioning of the truncus and conus and the formation of the membranous portion of the interventricular septum in the human heart. Am. J. Amt., 71: 343, 1942. VAN MIEROP, L. H. S., ALLEY, R. D., KAUSEL, H. W. and STRANAHAN, A. Pathogenesis of transposition complexes. I. Embryology of the ventricles and great arteries. Am. J. Cardial., 12: 216, 1963. Die angeborenen Defecte der EISENMENCER, V. Kammerscheidcwand des Herzens. Ztschr. klin. Med., 32: 1, 1897. \~III-HA~~, A. C. Double outlet right \-entriclr; a partial transposition complex. Am. Hersrt J., 53: 928. 1957. NEuFELn, H. N., DUSHANE, I. W., WOOD, E. H., KIRKLIN! J. W. and EDWARDS, J. E. Origin of both great vessels from the right ventricle. I. Without pulmonary stenosis. Circulation, 23: 399, 1961. T.~usstc, H. B. and BING, R. J. Complete transposition of the aorta and a levoposition of the pulmonary artery. Am. Heart J., 37: 551, 1949. BEUREN, A. Differential diagnosis of the TaussigBing hrart from complete transposition of the great vessels with a posteriorly overriding pulmonary artery. Circulation, 27 : 1071,1960.
THE AMERICANJOURNALOF
CARDIOLOGY
of Transposition
Anomalies due to Faulty Transfer Posterior Great Artery* H. S. V.w
LODEWYK
T
HIS paper concerns itself largely with those cardiac anomalies which are often considered to be a form of transposition of the great vessels, but which, on embryologic grounds, should be sharply distinguished from true transposition complexes. These are dextroposition of the aorta (tetralogy of Fallot, Eisencomplex) and double outlet right menger ventricle (several types, including the TaussigBing complex). They do not form a homogeneous group pathogenetically and cannot always be sharply differentiated from each other, i.e., transitional forms are common. In all cases one of the great arteries originates anteriorly from the right ventricle; the other either springs from both ventricles, overriding a defect to a varying degree, or arises wholly from the right ventricle. Usually the pulmonary artery is the anterior vessel and the aorta the posterior. True transposition of the vessels
in which
case
may,
however,
the aorta
be an associated
is the anterior
vessel
anomaly, and
transposition
in the third
complexes
and last part
will
the
be discussed
of this series.
DEFINITIONS Dextroposition: The posterior vessel, whether it be the aorta or the pulmonary artery, originates from both ventricles above a ventricular septal defect. The vessel is said to “override” the defect. If the anterior vessel overrides an anteriorly located defect, a levoposition of that vessel is said to exist. When the position of the ventricles is inverted, as in total situs inversus or in isolated inversion of the ventricles, these terms should, of course,be reversed. De.rtro(Leuo)rotation: Here, as opposed to the nor* From the Department of Anatomy, McGill University, Hospital, Montreal, Canada. t Present address: Albany Medical Collcgr of Union
M.D.
Canada
mal, the apex of the heart is on the same side as the morphologic right atrium. In dextrorotation the right atrium is in its normal position; in levorotation the right atrium lies on the left side as part of a total 6itus inversus. Dextrocardia: The apex of the heart points to the right, and there is situs inversus of the atria and at least some of the other viscera, usually the lungs. Dextrocardia should not be confused with dextrorotation. Inversion: This term as used in more recent publications denotes mirror-image of the normal left-right relationships of all or some of the organs (complete or partial situs inversus) or of the cardiac ventricles only. The anteroposterior relationships remain normal. Transposition of the Great Vessels: Abbott’ defines transposition as “an alteration in the position of the two great vessels relative to the ventricles of the heart, or to each other at their origin, so that they spring either from reversed ventricles-the aorta from the right, and the pulmonary artery from the left chamber (complete transposition)-or from the ventricles to which they normally belong, but in reverse relationship (corrected transposition). This definition, as Harris and Farber2 have already pointed out, is too vague. They added the words: “and an alteration in the anteroposterior relationship of the great vessels, either at the ventricular insertion or in their spiraling.” According to Edwards3 and most present day authors, transposition is any congenital abnormality in the relationship of the great arterial vessels (or their This remnant) to each other and to the ventricles. definition includes: (1) cases in which the pulmonary artery springs from the right ventricle and the aorta from both, overriding a ventricular septal defect (dextroposition of the aorta as in tetralogy of Fallot) ; (2) cases in which both arteries originate from the right ventricle (double outlet right ventricle or partial transposition) ; and (3) cases in which the aorta originates anteriorly from a morphologic right ventricle and the pulmonary artery from a morphologic
pulmonary artery the posterior. It is for this reason that we shall use the more general terms anterior and posterior vessel in the body of this paper. True
of the
MIEROP, M.D.? and FREDERICK W. WIGLESWORTH, Montreal,
great
Complexes
and the Department
of Pathology,
University,
N. Y.
226
Albany.
PII< AMERICAN
The
Montrral
IOURNAL
OF
Children’s
CARDlOLOGY
Pathogenesis
of Transposition
left ventricle without ventricular inversion (complete transposition) or with ventricular inversion (“corrected” transposition). More recently there has been a tendency to exclude dextroposition of the aorta as a transposition complex. As will be shown in the body of this paper, the pathogeneses of dextroposition of the aorta, partial transposition, complete transposition and “corrected” transposition are dissimilar and unrelated. This will explain why dextroposition or partial transposition can and do occur in combination with true transposition with or without inversion of ventricles. On embryologic grounds we define true transposition of the great vessels as that condition in which the aorta lies anterior to the jndmonary artery and originates from a morphologic right ventricle anterior to the crista qbraventricularis 07 its remnanr. The pulmonary artery may originate from either ventricle or override a defect. HISTC~RICAL REVIEW
TABLE
Principal Anterior Xpt”lll
Embryological displacement
Hypnplasia Extreme rcptumor
persistence
vent&xlnr
llnnge
scpium
of the
ronus
of the bulho-
I
Origin of Postrrior
Ikror of the conus
of the rmnu hypoplasiz
Cases of Complete
II
According to Keith,e transposition complexes are caused by abnormal absorption of the bulbus cordis (our conus cordis, as described in Part I). Comparative anatomic studies led Robertson’ to agree mainly with Rokitansky’s views. Spitzer’sg theory is based on phylogenetic considerations and may be summarized as follows: With the development of lung breathing, cardiac septation becomes more refined and complete in an effort to gain a more complete separation of arterial and venous blood. Development of the bulboventricular loop and subsequent septation are greatly influenced by hydroclynamic forces occurring in the circulation. Since Ihe primitive heart tube is fixed at both ends, loop formation to the right will lead to torsion at the arterial end and detorsion at the venous pole. This torsion and detorsion increases with ascendence in the animal scale and becomes maximal in birds and mammals. Abnormalities in this process of torsion lead to cardiac anomalies and in certain cases to reopening of the reptiiian right aorta which, if a normal degree of torsion occurs, obliterates in mammals. Although Spitzer’s theory has had great influence on later investigators, it has been criticized by Pernkopf and WirtingerY and others, and somewhat later also by Lev and Saphir,“J on the very valid grounds that it cannot clarify many anomalies and it does not explain the pathogenesis, in man, of these anomailes. Pernkopf and Wirtingerg concluded that abnormalities in the absorption of the bulbus (our conus) cordis are more important in the production of cardiac anomalies than faulty torsion. Lev and Saphir’o postulated an abnormality in the formation of one of the bulbar ridges as responsible for transposition complexes. A recent ontogenetic theory on truncoconal malformations has been put forward by de la Cruz and da Rocha.” The theory is based on the embryology of the human heart as described by Davis,‘* Strreter13,14 and Kramer,‘5 as well as on the analysis of congenitally malformed hearts. It gives, in our opinion, the most realistic and satisfacrory explanation yet of anomalies involving the truncus and conus,
Only the more important publications dealing with transposition complexes will be briefly discussed. A detailed and comprehensive review has been given by Harris and Farber.* Peacock4 thought transposition of the great vessels was due to inflammatory pulmonary artery stenosis occurring in early embryonic life and resulting in a high right ventricular pressure and subsequent septal deviation to the left. In cases without pulmonary stenosis, the pathogenesis was thought to be an abnormal development of aorta and pulmonary artery from the truncus arteriosus. Abnormal development of the bulbar and ventricular septa was held responsible by Rokitansky5 for both the pulmonary artery stenosis and ventricular septal defect and resulted in transposition, the degree of which varied depending upon whether the aortic septum was merely deviated or abnormally rotated. In any event, the aortic septum is unable to meet the ventricular septum giving rise to a ventricular septal defect and a varying degree of transposition with one or both vessels arising from the wrong ventricle.
Eighty-two
Complexes.
Artery from Right Ventricle
Anomaly Tetralogy
so.
of Fallot
51,
with pulmonary valvular S~C~OSIS without pulmonary valvular stenosis with pulmonary atresia (pseudorrunrus) F.isenmenger complex Doubleoutlet
right
without
transposition
19 15 16 27
ventricle 14
without transposition, but with a subpulmonary septal defect and overriding pulmonary artery (Taussig-Bins complex)
2
with
transposition
8
with
transposition
and ventricular
inverkn
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AUGUST
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of (k%ccs
x2
228
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and Wiglesworth
FIG. 1. Projectional diagram of the base of the heart. septal defect. C, tetralogy of Fallot. D, Eisenmenger
although such postulates as delayed disappearance of the conoventricular flange may seem artificial in view of the multiple changes occurring in this area.
MATERIAL Among 600 hearts in the collections of the Department of Pathology, The Montreal Children’s Hospital and the Subdepartment of Thoracic Surgery, Albany Medical Center Hospital, Albany, N. Y., 177 exhibited some anomaly in the relation of the great arteries to each other or to their chambers. Eighty-two cases showed partial or complete origin of the posterior artery from the right ventricle (Table I). These cases represent the material to be discussed. In 71 there was a failure of transfer of the aorta to the left ventricle, i.e., dextroposition of the aorta or double outlet right ventricle. In 11 additional cases associated with true transposition, this failure concerned the pulmonary artery, it being the posterior vessel in these specimens. As was shown in Part I, for a normal transfer of the aortic root to the left ventricle it is necessary that (I) the cardiac loop be formed normally, (2) the conoventricular flange be shifted adequately to the left and eventually disappear, (3) the conus septum develop in the normal position and (4) it be of adequate size. Abnormal development of any or a combination of these, leads to incomplete transfer of the aorta (or the pulmonary artery in cases of complete transposition) to the left ventricle. It is, therefore, not surprising that the various malformations resulting from such developmental abnormalities cannot always be sharply defined from each other.
A, normal heart.
B, ventricular
complex.
DEXTROPOSITION OF THE AORTA The anteroposterior relationship of the great vessels is normal. The degree of dextroposition varies considerably from cases in which the position of the aortic root is almost normal to those in which the aorta originates almost entirely from the right ventricle. Dextroposition of the aorta in the great majority of cases is due either to (1) anterior displacement of the conus septum, resulting in right ventricular infundibular stenosis of varying degree with or without pulmonary valvular stenosis (tetralogy of Fallot), (2) hypoplasia or absence of the conus septum (Eisenmenger’s complex), or (3) a combination of these (transitional forms). In tetralogy of Fallot there is always infundiband the ventricular septal ular narrowing, defect is usuall>- large (Fig. 1C). There may or may not be stenosis of the pulmonary valve, which in either case may be bicuspid or triSince normal development of the cuspid. conus septum is necessary in closing the interventricular communication, any anomaly of the proximal portion of the conus septum results in a ventricular septal defect in the basilar ventricular septum. Since normally the conus septum contributes to the formation of the anterior leaflet of the of this tricuspid valv~,‘~ minor abnormalities ‘Xi,< AMERICAN
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229
FIG. 2. Projectional diagram of the base of the heart. A, double outlet right ventricle. B, Taussig-Bing complex. C, “extreme” Eisenmenger complex. D, “false” Taussig-Bing complex (transposition of the great vessels, ventricular septal defect and overriding pulmonary artery).
leaflet are almost always present in tetralogy of Fallot, as in all hearts where there are anomalies of the conus septum. The medial or conus papillary muscle is usually absent, or in some cases an analogous (but not homologous) structure is found in an abnormal place, usually along the posterior or superior margins of the ventricular septal defect. Extreme degrees of displacement of the conus septum may lead to atresia of the infundibulum and then usually also of the pulmonary valve. The pulmonary artery may be reduced to a fibrous band. This condition has been called pseudotruncus aorticus or truncus solitarius aorticus. In true Eisenmenger complex, a rare anomaly, there is no infundibular stenosis, and the ventricular septal defect is similar to that in tetralogy (Fig. 1D). In some cases the overriding of the aorta is so extreme that the vessel originates almost completely from the right ventricle, posterior and to the right of the dilated pulmonary artery (Fig. 2C). Again the tricuspid valve is abnormal in most cases. Since hypoplasia of the crista also often occurs in tetralogy and the pulmonary valve may be normal in the latter, no sharp anatomic distinction can be drawn between Eisenmenger’s complex and tetralogy of Fallot. Similarly anatomic differentiation between
isolated ventricular septal defect and Eisenmenger’s complex is often difficult. A ventricular septal defect of small or average size hidden behind the septal leaflet of the tricuspid valve, the presence of a medial papillary muscle, and a well developed crista rule out Eisenmenger’s complex in the anatomic sense. Eisenmenger’s original illustration17 shows the hypoplastic crista supraventricularis well. DOUBLE OUTLET RIGHT \7~~~~~~~~‘8 In the commonest type, there is a ventricular septal defect which forms the sole outlet for the left ventricle (lateral position of the arteries,” origin of both great arteries from the right ventricle’g). The pulmonary artery arises in its normal, anterior position, and the aorta originates wholly from the rightventricle and is located behind and to the right of the pulmonary artery. In some cases it may even approach the same frontal plane in which the pulmonary artery lies. Neufeld et al.lg distinguish two main types: (1) The aortic valve is continuous with the anterior leaflet of the mitral valve, as in normal hearts. (2) The aortic valve is separated from the mitral valve by a muscular band. The anatomic distinction between the first type and Eisenmenger’s complex is, in our opinion, only
Van Mierop
FIG. 3. Double outlet right valve and the aortic valve.
vcntriclc.
Note
the great
one of degree, and the pathogenesis is probably the same: hypoplasia and possibly some anterior displacement of the crista supraventricularis (Fig. lD, ZC). The second type, although functionally identical, is anatomically quite different (Fig. 2A, 3). The aorta originates from the right ventricle and is separated from the pulmonary artery by a muscular band (the crista supraventricularis) and from the tricuspid and mitral valves by a second band of muscle, which we believe to be a persistent bulbo(cono)ventricular flange. This second band may be large, as in Figure 3, or it may be rather insignificant. We have seen 2 additional cases in which both arteries originated from the right ventricle, but both hearts represented a much more primitive condition, due probably to an early developmental error in the formation of the cardiac loop (Fig. 4). In both cases there was juxtaposition of the atria; in 1 there was also inversion of the ventricles, transposition of the great vessels and atresia of the left A-V valve. The associated transposition of the great vessels in the latter case (with inversion of the ventricles) is to be expected (see Part III). ASSOCIATED
ANOM.4LIES
Double outlet sociated with any or combinations important ones are
and Wiglesworth
right ventricle may be asnumber of other anomalies of anomalies. The more as follows :
distanrc
brtwrcn
the antrrior
I4lct
of the mitral
Stenosis uf the Pulmonary Valor: Because of its functional similarity to tetralogy of Fallot, this anomaly has been called Fallot type of double outlet right ventricle.18 Atresia qf an A-V Value: If the mitral valve is atretic the left ventricle is often absent. The ventricular portion of the heart consists of a right ventricle from which both arteries arise. If a left ventricle is present, it is usually part of a common ventricle, i.e., the ventricular septum is absent. If the tricuspid valve is atretic, the heart consists of tile left ventricle and the conus part of the right ventricle, from which both arteries arise. A ventricular septal defect leads from the left ventricle into the conus (rudimentary outflow chamber). True transposition may be associated with double outlet right ventricle. In these cases the aorta is anterior and the pulmonary artery is posterior. lnuersion oj the Ventrides: If the primitive heart tube loops to the left instead of to the right, the primitive ventricle comes to lie on the right side and the bulbus cordis on the left. The morphologic left ventricle, therefore, also lies on the right and the morphologic right ventricle on the left. If subsequent development proceeds normally, the result will be a corrected transposition. Why the arteries in this condition are of necessity transposed will be explained in Part III. Cases have been reported in which both TI!E
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Pathogenesis
FIG. 4.
Unusual
of Transposition
type of double outlet right wntriclr.
This arteries originate from a left ventricle. is an embryologic impossibility, and it is possible that in reality one is dealing with a combination of double outlet right ventricle and inversion of the ventricles. Subpulmonary Ventricular Septal Defect (TaussigBing complex): In most cases of double outlet right ventricle the ventricular septal defect is located beneath the aorta. Occasionally, however, there is a defect much more anteriorly beneath the pulmonary artery. Such a defect may occur as an isolated lesion, and the pulmonary artery may then straddle it. The combination of this defect with double outlet right ventricle has been called complete transposition of the aorta and levoposition of the pulmonary artery by Taussig and Bing.“” Since then this anomaly has been known as the Taussig-Bing complex (Fig. 2B). Unfortunately-, as has been pointed out by de la Cruz and da Rocha” and Beuren,21 another totallv unrelated condition hzs been referred to by several authors as Taussig-Bing complex. The spurious Taussig-Bing heart is characterized by true transposition of the great vessels, i.e., the aorta arises anteriorly from the right ventricle and the posterior pulmonary artery overrides a posterior ventricular septal defect but originates mainly from the AUC,I-Sl’
196;
Complexes.
231
II
Vrr\- primitive hart.
left ventricle (Fig. 2D). This lesion is considerably more common than the true TaussigBing complex of which we have seen only two examples. Although Taussig and Bing do not specify the anteroposterior position of the aorta and pulmonary artery relative to each other, their figures leave little doubt that the pulmonary artery in their original case was anterior and the aorta right posterior. The term Ievoposition of the pulmonary artery also indicates this, since, strictly speaking, one would have to designate the pulmonary artery in the spurious Taussi,g-Bing as being dextroposed. %JhlMARY
AND
CONCLUSIONS
Ovekding of /he aorta may he due to (1) anterior displacement of the conus septum resulting in various degrees of infundibular stenosis (tetralogy of Fallot), (2) hypoplasia of the septum (Eisenmenger’s complex) or (3) both (transitional forms). In none of these cases can the ventricular septum be closed, and transfer of the aorta to the left ventricle is incomplete. Anomalies of the medial portion of the anterior tricuspid leaflet are common in both, since this portion of the valve is derived from the proximal conus septum. No sharp distinction can always be made between the two complexes since both
232
‘i’an
Mierop
displacement and hypoplasia ma)- occur together. I)ouDi~ outlet right ventricle results frvm incomplete recession of the bul boventricuiar flange, from abnormalities in the formation of the cardiac loop, or both. Cases of extreme dextroposition closely resemble double outlet right ventricle, both anatomically and functionally. However, in these cases the valve cusps of the posterior artery are continuous with the anterior leaflet of the mitral valve, whereas in double outlet right ventricle they are separated from each other by a band of muscle, the persistent conoLrentricular flange. The true Taussig-Bing complex is not a it is a form of double transposition complex; outlet right ventricle.
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4. 5. 6. 7.
8.
9.
Modern Medicine. M. E. In OSLER, W. Edited by M&RAE, T. ed. 3, Vol. 4, p. 716. Philadelphia, 1928. Lea and Febiger. HARRIS, J. S. and FARBER, S. Transposition of the great cardiac vessels. Arch. Path., 28: 427, 1939. I~DWARDS, J. E. Congenital malformations of the heart and great vessels, In: GOULD, S. E. Pathology of the Heart, ed. 2, p. 354. Springfield, ill., 1960. Charles C Thomas. PEACOCK, T. B. On Maiformations of the Human Heart. London, 1866. J. Churchill. Die Defecte Der ScheideEON ROKITANSKY, C. wande des Herzens. Wien, 1875. Braumiiller. K;EITH, A. The Hunterian lectures on malformations of the heart. Lancel, 2: 433, 1909. RUBERTSON, J. I. Comparative anatomy of the bulbus cordis, with special reference to abnormal positions of the great vessels in the human heart. J. Path., 18:.!91,1913. SPITZER, A. Uber den Bauplan des normalen und missgebildeten Herzens. Versuch einer phylogenetischen Theorir. Virrhowr s4rch. path. Amt., 243: 81, 1923. P~RNKOPF, E. and WIKITNGER, 1%'. Ih Wesen der ‘Transposition im Gebiete des Hrrzcns. ein Versuch
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dcr Erklarung auf entwicklungsgeschichter Grundlage. Vi?chnwsArch.path. Amt., 295: 143, 1935. LEV, M. and SAPI~R, 0. A theory of transposition of the arterial trunks based on the phylogenetic and ontogenetic development of heart. Arch. Path., 39: 172, 1945. DE I_A CRUI, M. C. and DA ROCHA, J. P. .4n ontogenetic theory for the explanation of congenital malformations involving the truncus and conus. Am. Heart J., 51: 782, 1956. DAVIS, C. L. Development of the human heart from its first appearance to the stage found in embryos of twenty paired somites. Contrib. EmbryoI., 19: 245, 1927. STREETER, G. L. Developmental horizons in human embryos. Description of age group XIII, embryo’s about 4-5 mm. long, and age group XIV, period of indentation of the lens vesicle. Cbnlrib. Embryol.. 31: 27, 1945. STREETER, G. L. Developmental horizons in human embryos. Description of age group xv, XVI, XVII, XVIII, being the third issue of a survey of the Carnegie Collection. Co&b. Embryol., 32: 133, 1948. KRAMER. T. C. The partitioning of the truncus and conus and the formation of the membranous portion of the interventricular septum in the human heart. Am. J. Amt., 71: 343, 1942. VAN MIEROP, L. H. S., ALLEY, R. D., KAUSEL, H. W. and STRANAHAN, A. Pathogenesis of transposition complexes. I. Embryology of the ventricles and great arteries. Am. J. Cardial., 12: 216, 1963. Die angeborenen Defecte der EISENMENCER, V. Kammerscheidcwand des Herzens. Ztschr. klin. Med., 32: 1, 1897. \~III-HA~~, A. C. Double outlet right \-entriclr; a partial transposition complex. Am. Hersrt J., 53: 928. 1957. NEuFELn, H. N., DUSHANE, I. W., WOOD, E. H., KIRKLIN! J. W. and EDWARDS, J. E. Origin of both great vessels from the right ventricle. I. Without pulmonary stenosis. Circulation, 23: 399, 1961. T.~usstc, H. B. and BING, R. J. Complete transposition of the aorta and a levoposition of the pulmonary artery. Am. Heart J., 37: 551, 1949. BEUREN, A. Differential diagnosis of the TaussigBing hrart from complete transposition of the great vessels with a posteriorly overriding pulmonary artery. Circulation, 27 : 1071,1960.
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