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Anatomic variations in the tetralogy of Fallot
Anatomic
variations
in the tetralogy
of Fallot
B. N. Satyanarayana Rao, M.B.B. S. Ray C. Anderson, M.D. Jesse E. Edwards, M.D. St. Paul, Minn.
I
n hearts bearing the complex of anomalies known as the tetralogy of Fallot, the anatomic features fall within certain parameters. Yet within these, there are variations of a number of features such as (1) the basis for and the degree of pulmonary stenoIsis, (2) the course and branching of the aortic arch, (3) the state of the major pulmonary arteries and of the ductus arteriosus, and (4) association of other anomalies. With these points in mind, an analysis was made Iof 85 specimens of heart exhibiting the characteristics of the tetralogy of Fallot. The report considers the various factors nalmed and attempts to show whether or not relationships exist between these several factors. Materials
and
methods
Eighty-five preserved specimens with the anatomic features of the tetralogy of Fallot from the Cardiovascular Registry of The Charles T. Miller Hospital and the Department of Pathology of The University of Minnesota were available for study. In the majority of cases, the aortic arch with its branches and the pulmonary arteries were
present in the specimen, although in isolated cases one or another of the structures studied was either absent or in an inadequate state for interpretation. In each case, the ventricular septal defect (VSD) was of the large variety, situated posterior to a vertical crista supraventricularis. The aorta straddled the VSD, thereby arising from both ventricles. Continuity of the aortic and mitral valves was present in each case. Three specimens with persistent common atrioventricular canal, in addition to the anatomic characteristics of the tetralogy of Fallot, were included in this series. Forty-one of the 85 specimens were from male patients and 41 from female patients. In 3 instances, the sex was unknown to us. The age at death ranged from two days to 45 years. The age was unknown in 6 cases, leaving 79 casesin Twhich both the age and sex were known (Fig. 1). In 49 cases,operation had been done, 40 of the patients dying in the early postoperative period and 9 being examples of “late deaths.” The specimens were examined for a number of features, including (1) the basis for pulmonary stenosis, (2) the nature of the
From
the Department of Pathology, The Charles T. Miller Hospital, St. Paul, Minn., and the Departments of Pediatrics and Pathology, The University of Minnesota, Minneapolis, Minn. This study was supported by Public Health Service Research Grant 5 R01 HE05694 and Research Training Grant 5 TO1 HE05570 from the National Heart Institute and by the Dwan Family Fund. Received for publication May 27, 1970. Reprint requests to: Jesse E. Edwards, M.D., Department of Pathology, The Charles T. Miller Hospital, 125 West College Avenue, St. Paul, Minn. 55102.
Vol. 81, No. 3.tpp. 361-371
March, 1971
American Heart Journal
361
Age,Years
O-l mo. lmo.-lyr.1 I - 5
q
= Male
q
6 -101 I I-201
21-3013!-40141-5(
=Femole
Fig. 1. Age at death and sex of 79 patients with tetralogy of FaIIot, the specimens from which formed the basis of this study.
pulmonary trunk and its branches, (3) the nature of the aortic arch and its branches, (4) the state of the ductus arteriosus, (5) the nature of the atria1 septum, (6) the presence of anomalies other than those which are part of the tetralogy complex, and (7) the association of bacterial endocarditis. Correlation was attempted between the presence of certain conditions and others. Results Pulmonary valve. Obstruction to pulmonary flow may reside in the pulmonary valve, the right ventricular infundibulum, or the pulmonary trunk. In each specimen, the pulmonary valve was inspected for the size of the annulus, the nature of the valve, the number of cusps, the number and status of the commissures, and the caliber of the aperture. Each pulmonary valve was classified as tricuspid (tricommissural), bicuspid (bicommissural) I unicuspid (rtnicommissural), domed, atretic, or absent. The structure of the unicuspid valve was like that seen in certain cases of congenital aortic stenosis previously described by Edwards1 The term ‘“domed” refers to a deformity of the pulmonary valve like that in pulmonary stenosis with intact ventricular septum.
Table I indicates the distribution of degrees of pulmonary stenosis and the structure of the pulmonary valve. In each of 21 specimens, the pulmonary valve was atretic and represented by tissue of varying thickness interposed between the infundibulum and the pulmonary trunk. From the ventricular aspect, the pulmonary valve could not be visualized except as the base of a cul-de-sac at the distal end of the infundibulum. In each case of pulmonary atresia, the infundibulum was severely narrowed. Among the 59 specimens in which some opening was present at the pulmonary valve and in which the nature of the pulmonary valve could be determined, the distribution of pulmonary valvular structure was as follows: bicuspid, 32 cases; tricuspid, 10; unicuspid, 8; domed, 7; and absent, 2. The caliber of the pulmonary valvular orifice was judged in comparison to that of the aortic orifice to develop designations of degrees of pulmonary valvular stenosis based upon comparison of diameters. 1. Normal: The diameter of the pulmonary orifice was greater than 80 per cent of the aortic valvular diameter. 2. Mild-to-moderate stenosis: The pulmonary valvular orifice was between 50 and 80 per cent of aortic orifice. 3. Severe stenosis: The pulmonary valvular orifice was less than Xl per cent of aortic. 4. Pulmonary atresia: There was no communication between the infundibulum of the right ventricle and the pulmonary trunk. The individual cusps of bicuspid valve were usually short with corresponding limitation in mobility so that some degree of stenosis was thought to be present in 27 of the 32 bicuspid valves (84 per cent). Five of the 10 tricuspid valves were stenokic on the basis of a narrow orifice associated with short, relatively rigid cusps, while in the remainder, the valve was not stenotic. Each unicuspid and cone-shaped pulmonary valve exhibited stenosis of mild-tomoderate or severe degree. Considering the limited amount of material, one could not observe a distinct trend for a type of pulmonary valve to be associated with a particular type of aortic arch. Among the 21 cases of pulmonary atresia, 2 right aortic arch was present in 9 cases
Anatomic
Table I. L?egree oj stenosis and structure Degree
of fxhonary
valvular None Mild-moderate Severe Pulmonary
of +lmonary
variations
in tetralogy oj Fallot
363
valve in 80 cases
Pulmonary valvestructur.3 _
stenosh
Tricus$id
a tresia
5 4 1 0
5 17 10 0
0 3 5 0
0 4 3 0
0 0 0 21
1 1 0 0
11 29 19 21
10
32
8
7
21
2
80
Total
Table II. Pulmonary
F@d
1 Uwicuspid
valvular and infundibular
/
Dome
Atretic
/
1
Absent
1
Total
stenosis as observed in 84 cases Pulmonary
vahlar
stenosis
Infundibulav ShOSiS
None
Mild-moderafe
/
Severe
/
A tresia
/
Total
None Mild-moderate Severe
0 1 10
2 15 13
2 1 19
0 0 21
4 17 63
Total
11
30
22
21
84
(43 per cent), the overall incidence of right aortic arch being 29 per cent. Right ventricuZar infundibulum. Table II shows the association of pulmonary valvular and infundibular stenosis in 84 specimens. Infundibular stenosis was judged on the basis of the expected size of the infundibulum for the specimen in question, taking into account the narrowest portion of the infundibulum and the length of the hypoplastic segment or the number of sites of constriction when there were more than one. The difficulty of evaluating the degree of functional obstruction in fixed specimens is well recognized. Among the 84 specimens in which the nature of the pulmonary valve and infundibulum was known, 52 had varying degrees of pulmonary valvular stenosis and 21 had pulmonary atresiia. There were 4 cases with no infundibular stenosis and, in each of these, the pulmonary valve was stenotic. Seventeen had mild-to-moderate infundibular stenosis and 63 showed severe infundibu-
-.
lar stenosis, including the 21 cases of pulmonary atresia. There was a strong tendency for the degree of infundibular obstruction to be concordant with the degree of valvular stenosis, although exceptions occurred as in 2 examples of severe valvular stenosis in which no infundibular stenosis occurred. In IO cases, the reverse was true, in that severe infundibular stenosis was associated with no valvular stenosis. Pulmonary arteries. In 78 specimens, the pulmonary trunk was available and, in 76, the 2 branches were present in the specimens. In one of the cases, the nature of the pulmonary valve could not be determined. The caliber of the pulmonary trunk was given certain designations by comparing its diameter to that of the aorta as follows: 1. Normal: The diameter of the pulmonary trunk was greater than 80 per cent of that of the aorta. 2. Moderate hypoplasia: The diameter of the pulmonary trunk was between 50 and 80 per cent of that of the aorta.
Normal Moderate hypoplasia Severe hypoplasia
5 4 0
0 25 0
0 5 12
Atretic Poststenotic
0I
04
10
29
dilatation
Total
Tubbe IV. Degree of infundibulur 75 cases
F
5 41 23
0
30
z
17
21
77
II
steno&s and caliber of the ;bulnzonnry trilnk
Pnbzonary In,fundibular stenosis
Severe hy$o@asia
as observed in
trunk
Atretic
None Mild-moderate Severe
0 0 6
1 14 26
2 1 20
0 0 3
1 1 3
4 16 58
Total
6
41
23
3
5
78
3. Severe hypoplasin: The diameter of the pulmonary trunk was less than 50 per cent of that of the aorta. 4. Atresia: There was no iumen in the pulmonary trunk which was represented by a fibrous-like strand of tissue. 5. Poststeno& dilatation: The relative size of the pulmonary trunk was disproportionately large compared to the orifice of the pulmonary valve. Among 41 specimens with moderate hypopfasia of the pulmonary trunk, only one showed a normal infundibulum and, in this case, there was a moderate degree of pulmonary valvular stenosis. Of the remaining, 14 had moderate and 26 had severe infundibular obstruction. Severe hypoplasia of the pulmonary trunk was strongly associated with major obstruction at the pulmonary valve and/or infundibulum. There were 23 specimens with severe hypoplasia of the pulmonary trunk, includ-
ing 2 with no infundibular stenosis but with moderate valvular stenosis and one with moderate infundibular and severe valvular stenosis. The remaining 20 showed severe infundibular stenosis, of which 12 manifested pulmonary atresia. There were 3 specimens with atresia of the pulmonary trunk, each of which also exhibited atresia at the level of the pulmonary valve. The basis for pulmonary stenosis varied among the 5 cases of poststenotic dilatation of the pulmonary trunk. In one, only the pulmonary valve was stenotic. In a second case, stenosis was present only in the infundibulum, and in 3 cases both the valve and infundibulum were stenotic. In comparing the pulmonary trunk with the pulmonary valve, there was a strong tendency for the caliber of the vessel to decrease as the number of pulmonary cusps decreased and as the degree of pulmonary valvular stenosis increased (Table I I I) m
Anatomic
variations
Table V. Obstruction to pulmonary flow whether infundibular of the pdmonary trunk as observedin 78 cases Pulmonary Obsiruction pulmonary
Mild-moderate Severe Pulmonary Total
in tetralogy
of Fallot
365
or valvular, or both, and the caliber
trunk
to $0~
atresia
: 0
14 20 7
0 12 11
0 0 3
2 3 0
17 40 21
6
41
23
3
5
78
Table IV shows the relationship of the severity of the infundibular stenosis to the nature of the pulmonary trunk in 78 cases. Among the 4 specimens with no infundibular stenosis, the pulmonary trunk showed moderate hypoplasia in one, severe hypoplasia in 2, and poststenotic dilatation in one. Mild-to-moderate infundibular stenosis was present in 16 specimens, 14 of which s#howedmoderate hypoplasia of the pulmonary trunk, one severe hypoplasia and one poststenotic dilatation of the pulmonary trunk. The 58 specimens with severe infundibular stenosis included 6 with a normal pulmonary trunk, 26 with moderate hypoplasia, 20 with severe hypoplasia, 3 with atresia ‘of the pulmonary trunk, and 3 with poststenotic dilatation. Severe infundibular stenosizi with only moderate pulmonary valvular stenosis had a strong tendency to be associated with only moderate hypoplasia of the pulmonary trunk. In contrast, when pulmonary valvular atresia was associated with severe infundibular stenosis, there was a wide range in the caliber of the pulmonary trunk. Among 21 specimens with pulmonary atresia and severe infundibular stenosis, 6 showed moderate hypoplasia, 12 severe hypoplasia, and, in 3, atresia of the pulmonary trunk was present. In each of the 6 casesof a normal pulmonary trunk, there was severe infundibular stenosis without valvular stenosis. If, in our material, one combines valvular and infundibular stenosis as a basis for obstruction to pulmonary flow, it becomes apparent that there is a direct relationship
between the degree of restriction in caliber of the pulmonary trunk, on one hand, and the severity of pulmonary obstruction, on the other (Table V). There is, however, a greater tendency for valvular stenosis rather than infundibular stenosis alone to exert an effect on restriction in the caliber of the pulmonary trunk (Tables III and IV). There was a strong tendency for the caliber of the right and left pulmonary arterial branches to be directly proportional to that of the pulmonary trunk, although in isolated instances the pulmonary trunk was severely hypoplastic while the branches showed lesser degrees of hypoplasia. In only 5 specimens was there a normal caliber of the pulmonary trunk and the 2 branches. Among 63 specimens with moderate or severe hypoplasia of the pulmonary trunk, the pulmonary artery branches were also hypoplastic. In 3 casesof moderate hypoplasia of the pulmonary trunk, there was localized stenosis of the branches, one bilateral and 2 unilateral. One of the latter was an example of socalled “absence of the left pulmonary artery” (“proximal interruption of the left pulmonary arch” or “origin of the left pulmonary artery from the left ductus arteriosus”). The left pulmonary artery was stenotic at its ductal origin and showed slight poststenotic dilatation beyond the ductus, although the caliber beyond that level was very narrow compared to the expected normal. In each of the 3 specimens with an atretic pulmonary trunk the branches were patent but hypoplastic. In
366
Satynnarayana
iTao, Anderson,
and Edwards
Tuble VI. Nature oj aortic arch and degree.: ojobstrm&wz to &kaona~y$ow or valvular as seen in 83 cases. Perce?ztages Teeresent those of subgroups
whether infmdibudar
Obstruction to pulmonary
$0~
Right
Mild-moderate
10 (23%) 9 (43%) 24
Atresia Total
Table
VII.
Left
m%‘c)
5
Severe
arch
Types
of aortic
arch
T&d
14 (74%) 33 (77YO)
19 (lQO%,) 43 (lQQ%)
12 (57YOI
21 (lOO%b)
59
arch and branches
83
in 82 casesof the tetralogy of Fallot
Types of aortic arch and brandzes Major class Double Left
Right
aortic aortic
aortic
arch
arch
arch
Number of specimens
/
.%&lass Both arches patent One arch patent Normal Aberrant Isolation
branches right subciavian artery of right subclavian artery
Mirror image branching Aberrant left subclavian artery Isolation of left subclavian artery
Total
the 5 casesof poststenotic dilatation of the pulmonary trunk, the branches were essentially of normal caliber. There was no apparent relationship between the type of aortic arch and the character of the pulmonary trunk and its branches. Aortic arch. There were 84 casesin which both the basis for obstruction to pulmonary flow and the status of the aortic arch were known. In 2 of these, the nature of the branching of the aortic arch could no% be determined. In one of the 84 cases, a double aortic arch was present. Among the remaining 83 specimens, a right aortic arch was present in 24 cases (29 per cent) and a left aortic arch in 59 cases (71 per cent) (Table VI). In the 24 wi%h a right aortic arch, there were 10 cases of severe obstruction to pulmonary flow at the infundibulum, the pulmonary
1 0 50 7 0
20 4 0 82
valve, or both, in addition to 9 cases of pulmonary atresia. Thus, 19 of 24 cases (77 per cent) wi th a right aortic arch manifested major obstruction to pulmonary flow. Among the 59 examples oi left aortic arch, major degrees of stenosis occurred in 45 cases (76 per centj. In 82 of the cases, the branches of the aortic arch were in an adequate state for interpretation (Table VII). The case of double aortic arch showed each arch to give rise to the common carotid and subclavian arteries of its side. In the 57 cases with a left arch, the usual branching occurred in 50, while 7 cases showed an aberrant right subclavian artery (12.5 per cent of caseswith left arch). Among the 24 cases of right aortic arch, 20 showed a pattern of mirror image branching. Four of the casesof right aortic arch showed an
Anatomic
variations
367
in tetralogy of Fallot
Table VIII. Nature of the aortic arch and the status of the ductgs arteriosus as observed in 80 cases, one of which was a case of double aortic arch with a ligamenturn arteriosum present on the left side Aorfic arch Total
Ductus arteriosus Right arch
I
Left arch
Absent Patent Ligamentous
I 4 13
12 1.5 28
19 19 41
Total
24
5.5
79
Table IX. Status of ductus arteriosus and the degreeof obstructio;vt to pulmonary flow whether infundibular, valvular, or both, as observedin 81 cases Degree of obstruction to pulmonary flow
status of ductus Mild-moderate
Severe
Pulmonary
atresia
Total
Absent Patent Ligament
2 2 14
12 5 25
5 12 4
19 19 43
Total
18
42
21
81
anoma’lous left subclavian artery (16.5 per cent of cases with right arch). In each case of anomalous subclavian artery, whether right or left, the artery crossed from its aortic origin to the opposite side of the body behind the esophagus. No cases of isolation of a subclavian artery2 (origin of artery from a ductus arteriosus) were encountered in this study. Ductus arteriosus. In each of 81 cases, the sta.tus of the ductus arteriosus could be determined and in each, except one, the nature of the aortic arch was known. Among 80 cases, the ductus arteriosus (or ligamentum arteriosum) was present on the left sid.ein 60 cases(including the case with double aortic arch), on the right side in one case, and absent in 19 cases (Table VIII). No casesof bilateral ductus arteriosus were encountered. In the one case of a right ductua arteriosus, a right aortic arch was present. In those casesof a left ductus and a right arch, the ductus extended from the base of the left subclavian artery which
arose from a left innominate artery and inserted into the left pulmonary artery. In each case of right arch with anomalous left subclavian artery the ductus arteriosus was absent. In one of the cases of a patent left-sided ductus arteriosus, the ductus was continuous with the peripheral end of the left pulmonary artery, while the proximal segment of the left pulmonary artery was absent. The 19 casesof absence of the ductus were distributed as follows: seven cases among 24 cases of right aortic arch (29 per cent) and 12 cases among 55 cases of leflt aortic arch (22 per cent). Patency of t.he ductus was encountered in 19 of the 61 caseswith a ductus (30 per cent). The distribution of patent ductus according to the degree of obstruction to pulmonary flow was as follows (Table IX). In 16 casesof mild-to-moderate obstruction to pulmonary flow and with a ductus present, the latter was patent in 2 cases. Comparable figures for severe pulmonary stenosis were 5 calsesof patent ductus among
Atrial
septzlm
-__-..
Degree of obstruction to pulmonary pow
,
__-.. Anatomically sealed
Valvular foramen
competent ovale 07
patent A
Total
SD
I
Mild-moderate Severe
Pulmonary atresia Total In 4 cases, a large defect in the lowermost part in the fourth case, the defect was associated
4 (21%) 9 (2070) 2 (9.5yo) 15
15 (79%)
of the atrial septum was present. In 3, the defect was part with normal tricuspid and mitral valves (with pulmonary
30 cases. In pulmonary atresia, the ductus was patent in 12 among 16 cases in which the ductus was present. Atrial septum. It was significant that a true or a potential interatrial communication was present in 70 of the 8.5 cases (82.5 per cent). In the majority (47 cases), this took the form of a valvular competent foramen ovale, while in 23 cases there was a persistent opening between the 2 atria. Usually, this appeared to result from a short valve of the foramen ovale yielding a true through-and-through opening of less than one centimeter in diameter at the fossa ovalis. A large defect in the lowermost aspect of the atria1 septum was present in 4 of the cases. In 3 of these, the defect was part of the complex of persistent common atrioventricular canal, while in one case the defect was associated with normal tricuspid and mitral valves. In spite of the fact that 35 per cent of the subjects in this study were infants below one year of age and 55 per cent were children under five years of age, these figures suggest a strong tendency for the atria1 septum to maintain some form of patency. Some tendency for persistence of an interatria1 communication seems to be related to the severity of obstruction to pulmonary flow (Table X). While there was essential difference between cases having varying degrees of pulmonary stenosis, cases with pulmonary atresia exhibited a higher incidence of an interatrial communication than those with the various degrees of pulmonary stenosis.
19 45 21
36 (80%) 19 (9Q.5%) 70
Associated
85 of persistent atresia).
A-V canal;
anomalies
Twenty-nine specimens had associated anomalies in addition to the components of the tetralogy. The following is a summary of observations in this regard. Left superior vena cava. A left superior vena cava was present in 9 specimens (10.6 per cent) and drained into the coronary sinus in each. Persistent common atrioventkular canal. In 3 specimens, the features of the tetralogy were associated with the characteristics of the complete form of persistent common atrioventricular canal, including its atria1 septal defect and cleft condition of the atrioventricular valves. In one of these cases, the -mitral aspect of the common atrioventricular valve exhibited a parachute mitral valve-like deformity in addition to an accessory orifice of the valve. Anomalies of the mitral valve. In addition to the cases with persistent common atrioventricular canal, there were 3 instances of associated anomalies of the mitral valve. One specimen showed localized hooding of the posterior leaflet associated with an accessory papillary muscle and accessory chordae. In the second specimen, a cleft was present in the anterior leaflet. The third case showed car triatriatum and anomalous chordae of the anterior leaflet of the mitral valve inserting into the ventricular septum, the latter causing subaortic stenosis. This specimen was from a subject with omphalocele, ectopia cordis, and a diaphragmatic hernia. Anomalies of the tricuspid valve. There
Volume Number
81 3
Anatomic
were 3 instances of anomalies of the tricuspid valve exclusive of the 3 cases with persistent common atrioventricular canal. A cleft in the septal leaflet of the tricuspid valve resulting in congenital tricuspid insufficiency was present in one specimen which also showed a systolic pocket of the left ven-tricle below the lower edge of the VSD. The second specimen was from a patient with Down’s syndrome in whom a cleft in the septal leaflet of the tricuspid valve and an atria1 septal defect at the fossa ovalis were ‘present. IBacterial endocarditis also involved the tricuspid valve in this case. In the third specimen with an anornalous tricuspid valve, the valve showed an accessory pouch. In addition, an anomalous muscle bundle of the right ventricle and hypoplasia of the right coronary artery were present. Miscellaneous conditions, each of which was enoountered once in the entire series, were: (1) Prolapse of the right aortic cusp with aortic insufficiency; (2) subaortic stenosis (mentioned under anomalies of mitral valve); (3) accessory orifice of the mitral valve (in association with persistent A-V canal) ; (4) aneurysm of the fossa ovalis; (5) dextroversion; (6) septal hypertrophy causing left ventricular outflow obstruction; (7) left umbilical vein draining directly into the coronary sinus and absence of ductus venosus; and (8) anomalous muscle bundle of the right ventricle causing subpulmona.ry stenosis (in a case with anomalous tricuspid valve). Bacterial
endocarditils
There were 5 specimens with evidence of bacterial endocarditis, the lesions being healed in the first 4. In 2, the infection appeared to have begun at the edges of a patch inserted to close the ventricular septal defect. The ages of the patients ranged from 15 to 39 years. Commlent
Though the tetralogy of Fallot has certain specific and well-recognized structural characteristics, a wide variation in the severity of the lesions and in association with other anomalies has been recognized.3-8 In this study, those cases showing the cardiac structure of the tetralogy of Fallot were so classified whether or not pulmonary
variations
in tetralogy of Fallot
369
atresia was associated. The relatively high incidence of cases with pulmonary atresia (21 of 85 cases) among our material may reflect a strong factor of selection. The basis for this is that patients with pulmonary stenosis tend to live longer and to be more likely to receive the benefits of corrective surgery than do those with pulmonary atresia. Among the cases of pulmonary stenosis, it was the usual finding that stenosis at the infundibulum a:nd pulmonary valve coexisted. It was relatively common, nevertheless, as has been recognized, that only the infundibulum would harbor the basis of obstruction to pulmonary flow (11 of 64 cases of pulmonary stenosis). In contrast, stenosis only at the pulmonary valve was uncommon, being present in only four of 64 cases of pulmonary stenosis. Some may disagree with the designation of the Iatter 4 casesas examples of the tetralogy. The basis for including these examples in our study was that, in each, the right ventricular infundibulum was a distinct tract, as in classical examples of tetralogy, but without stenosis. In each specimen with pulmonary atresia, there was hypoplasia of the entire right ventricular infunldibulum, the latter usually being represented by a small blind pouch anterior to the crista supraventricularis and terminating at the atretic pulmonary valve. In other instances, there was a very narrow, tortuous sinus-like tract leading to the atretic pulmonary valve. The structure of the pulmonary valve was studied in detail in our series.Adequate data regarding this subject are not available in reports of other seriesreviewed. This study showed a strong tendency for the number of commissures in the valve to decrease as the severity of the pulmonary stenosis increased. The degree of hypoplasia of the pulmonary trunk and pulmonary valvular abnormality in our series had a somewhat linear correlation. Increasing degrees of hypoplasia of the pulmonary trunk were associated with a diminishing number of cusps and commissures in the valve. Also, when the number of commissures in the pulmonary valve was decreased, the pulmonary valvular annulus was proportionately hypoplastic. There was no definite correlation between the degree of
370
Salyanauayaaa
Rae, Andersm,
Am-P. Heavf 3. March, 1971
and Edwards
infundibular stenosis and hypoplasia of the pulmonary trunk. Hypoplasia of the pulmonary trunk was invariably associated with varying degrees of hypoplasia of the pulmonary arterial branches. There were, however, instances in which severe hypoplasia of the pulmonary trunk was associated with only moderate hypoplasia of the pulmonary arterial branches. Even in the 3 specimens with atretic pulmonary trunk, the branches of the pulmonary artery were represented by patent but severely hypoplastic pulmonary arterial branches. There were 5 specimens with poststenotic dilatation of the pulmonary trunk, 3 of which were associated with severe infundibular stenosis. In 3 of these specimens, a bicuspid pulmonary valve was present and, in each of 2, the pulmonary valve was absent. The high incidence of an interatrial communication in tetralogy of Fallot has received relatively little attention in the past. It is of interest that only 15 of our cases (17.5 per cent) exhibited anatomic closure of the foramen ovale. The high incidence of patency of the foramen ovale is probably the result of the right ventricular hypertrophy coupled with a low volume of blood in the left atrium. The incidence of right aortic arch in this series (29 per cent) is comparable to the incidence in some of the other series. There has, however, been a wide discrepancy on the incidence of the right aortic arch among the several reported series.3-* It was hypothesized previously by one of the authors, Edwards, that there was a correlation between the severity of the pulmonary outflow obstruction and the incidence of right aortic arch. The analysis in this series, however, does not support this hypothesis. There were 7 casesof anomalous right subclavian artery with left aortic arch and 4 cases of anomalous left subclavian artery with right aortic arch. The incidence of anomalous subclavian artery is high compared to that in individuals without other malformations. In the general population, an anomalous right subclavian artery occurs in about one in 200 persons. Absence of the ductus arteriosus was fairly common in this series, being observed in 19 of 79 cases(25 per cent) with a slightly greater tendency for right aortic arch to be
associated with this condition than ‘left. It is interesting to speculate on absence of the ductus as a response to low volumes of pulmonary flow in association with ready communication of the aorta with the right ventricle. The incidence of absent ductus was about equal in cases with pulmonary atresia as with pulmonary stenosis. The tendency for association with right aortic arch may perhaps result from peculiarities of streaming in right aortic arch contrasted with left arch. Of interest was the occurrence of bacterial endocarditis in 5 of the patients, in 2 of whom the infection began at the site of surgical closure of the ventricular septal defect. The relatively older ages of the patients (age range 15 to 39 years) conforms with the tendency for bacterial endocarditis to involve older subjects more often than the young with congenital cardiac disease. Intracardiac malformations associated with the tetralogy of Fallot, although fairly numerous, tended, when present, to occur one per patient and probably reflects the phenomenon that the tetralogy has no particular affinity for association with a specific malformation, except, perhaps, persistent common atrioventricular canal. The latter condition was seen in 3 of the 85 cases of the tetralogy, the ages of the patients being 17 months, three years, and nine years. In a fourth case involving a 2-year-old boy, a defect in the lowermost part of the atria1 septum was associated with normal mitral and tricuspid valves. Two of the patients with persistent common atrioventricular canal had Down’s syndrome. An additional case with the Down’s syndrome had an intact atria1 septum with a cleft in the tricuspid valve. The relatively common occurrence of persistent common atrioventricular canal and of Down’s syndrome in our series may reflect a factor of selection, as one of the contributors of specimens is an institution for the mentally deficient. The relatively high incidence of patent ductus arteriosus may reflect the large proportion of infants in this series. Summary
Eighty-five specimens with a tetralogy of Fallot from patients varying in age from
Anatomic
infancy to adult life were studied for (1) the nature of the pulmonary valve, the right ventricular infundibulum, the pulmonary arteries, the aortic arch, and the atria1 septum and (2) the association of other anomalies and of bacterial endocarditis. The pulmonary valve was usually malformed, only 10 of the cases exhibiting a tricuspid pulmonary valve. In the majority of instances (32 cases), a bicuspid valve was present. Pulmonary valvular atresia occurred in 21 cases. A unicuspid, domeshaped, or absent pulmonary valve was seen in 8, 7, and 2 cases, respectively. Infundibular stenosis of some degree was present in all but 4 cases. Hypoplasia of the pulmonary trunk had a closer association with pulmonary valvular stenosis than with infundibular stenosis. A right aortic arch was observed in 24 cases (2!> per cent). The incidence of severe obstruction to pulmonary flow was about as common in cases of right aortic arch as in those with left arch. Absence of the ductus arteriosus was observed in 19 cases. An interatrial communication was present in 70 cases (82.5 per cent) and usually took the form of a valvular competent foramen ovale. Although associated intracardiac anomalies occurred in about 1.5 per cent of the cases, not all were functionally significant and there did not appear to be a tendency
variations
in tetralogy of Fallot
371
for the association of any one specific condition with the tetralogy. Persistent common atrioventriicular canal was seen in 3 cases. A persistent left superior vena cava occurred in 9 cases. Anomalous origin of the subclavian artery occurred more commonly than in tlhe general population. Bacterial endocarditis was observed in 5 cases. REFERENCES
1. 2.
3.
Edwards, J. E.: Pathologic aspects of cardiac valvular insufficiencies, Arch. Surg. (Chicago) 77:634, 1958. Stewart, J. R., Kincaid, 0. W., and Edwards, J. E.: An atlas of vascular rings and related malformations of the aortic arch system, Springfield, Ill.. 1964. Charles C Thomas. Publisher. D. 171. Feigin, I.; and Rosenthal, J.: Tetralogy of Fallot,
AIMER.HEARTJ.~~:~O~, 1943.
4.
5.
6.
7.
8.
Baffes, T. G., Johnson, F. R., Potts, W. J., and Gibson, S.: Anatomic variations in the tetralogy of Fallot, AMER. HEART J. 46:657, 1953. Brinton, W. D., and Campbell, M.: Necropsies in some congenital diseases of the heart, mainly Fallot’s tetralogy, Brit. Heart J. 15:335, 1953. Rowe, R. D., Vlad, P., and Keith, J. D.: Experiences with 180 cases of tetralogy of Fallot in infants and children, Canad. M. A. J. 73:23, 1955. Lev, M., and Eckner, F. A.: The pathologic anatomy of tetralogy of Fallot and its variations, Dis. Chest 45:251, 1964. Nagao, G. I., Daoud, G. I., McAdams, A. J., Schwartz, D. C., and Kaplan, S.: Cardiovascular anomalies associated with tetralogy of Fallot, Amer. J. Cardiol. 20:206, 1967
variations
in the tetralogy
of Fallot
B. N. Satyanarayana Rao, M.B.B. S. Ray C. Anderson, M.D. Jesse E. Edwards, M.D. St. Paul, Minn.
I
n hearts bearing the complex of anomalies known as the tetralogy of Fallot, the anatomic features fall within certain parameters. Yet within these, there are variations of a number of features such as (1) the basis for and the degree of pulmonary stenoIsis, (2) the course and branching of the aortic arch, (3) the state of the major pulmonary arteries and of the ductus arteriosus, and (4) association of other anomalies. With these points in mind, an analysis was made Iof 85 specimens of heart exhibiting the characteristics of the tetralogy of Fallot. The report considers the various factors nalmed and attempts to show whether or not relationships exist between these several factors. Materials
and
methods
Eighty-five preserved specimens with the anatomic features of the tetralogy of Fallot from the Cardiovascular Registry of The Charles T. Miller Hospital and the Department of Pathology of The University of Minnesota were available for study. In the majority of cases, the aortic arch with its branches and the pulmonary arteries were
present in the specimen, although in isolated cases one or another of the structures studied was either absent or in an inadequate state for interpretation. In each case, the ventricular septal defect (VSD) was of the large variety, situated posterior to a vertical crista supraventricularis. The aorta straddled the VSD, thereby arising from both ventricles. Continuity of the aortic and mitral valves was present in each case. Three specimens with persistent common atrioventricular canal, in addition to the anatomic characteristics of the tetralogy of Fallot, were included in this series. Forty-one of the 85 specimens were from male patients and 41 from female patients. In 3 instances, the sex was unknown to us. The age at death ranged from two days to 45 years. The age was unknown in 6 cases, leaving 79 casesin Twhich both the age and sex were known (Fig. 1). In 49 cases,operation had been done, 40 of the patients dying in the early postoperative period and 9 being examples of “late deaths.” The specimens were examined for a number of features, including (1) the basis for pulmonary stenosis, (2) the nature of the
From
the Department of Pathology, The Charles T. Miller Hospital, St. Paul, Minn., and the Departments of Pediatrics and Pathology, The University of Minnesota, Minneapolis, Minn. This study was supported by Public Health Service Research Grant 5 R01 HE05694 and Research Training Grant 5 TO1 HE05570 from the National Heart Institute and by the Dwan Family Fund. Received for publication May 27, 1970. Reprint requests to: Jesse E. Edwards, M.D., Department of Pathology, The Charles T. Miller Hospital, 125 West College Avenue, St. Paul, Minn. 55102.
Vol. 81, No. 3.tpp. 361-371
March, 1971
American Heart Journal
361
Age,Years
O-l mo. lmo.-lyr.1 I - 5
q
= Male
q
6 -101 I I-201
21-3013!-40141-5(
=Femole
Fig. 1. Age at death and sex of 79 patients with tetralogy of FaIIot, the specimens from which formed the basis of this study.
pulmonary trunk and its branches, (3) the nature of the aortic arch and its branches, (4) the state of the ductus arteriosus, (5) the nature of the atria1 septum, (6) the presence of anomalies other than those which are part of the tetralogy complex, and (7) the association of bacterial endocarditis. Correlation was attempted between the presence of certain conditions and others. Results Pulmonary valve. Obstruction to pulmonary flow may reside in the pulmonary valve, the right ventricular infundibulum, or the pulmonary trunk. In each specimen, the pulmonary valve was inspected for the size of the annulus, the nature of the valve, the number of cusps, the number and status of the commissures, and the caliber of the aperture. Each pulmonary valve was classified as tricuspid (tricommissural), bicuspid (bicommissural) I unicuspid (rtnicommissural), domed, atretic, or absent. The structure of the unicuspid valve was like that seen in certain cases of congenital aortic stenosis previously described by Edwards1 The term ‘“domed” refers to a deformity of the pulmonary valve like that in pulmonary stenosis with intact ventricular septum.
Table I indicates the distribution of degrees of pulmonary stenosis and the structure of the pulmonary valve. In each of 21 specimens, the pulmonary valve was atretic and represented by tissue of varying thickness interposed between the infundibulum and the pulmonary trunk. From the ventricular aspect, the pulmonary valve could not be visualized except as the base of a cul-de-sac at the distal end of the infundibulum. In each case of pulmonary atresia, the infundibulum was severely narrowed. Among the 59 specimens in which some opening was present at the pulmonary valve and in which the nature of the pulmonary valve could be determined, the distribution of pulmonary valvular structure was as follows: bicuspid, 32 cases; tricuspid, 10; unicuspid, 8; domed, 7; and absent, 2. The caliber of the pulmonary valvular orifice was judged in comparison to that of the aortic orifice to develop designations of degrees of pulmonary valvular stenosis based upon comparison of diameters. 1. Normal: The diameter of the pulmonary orifice was greater than 80 per cent of the aortic valvular diameter. 2. Mild-to-moderate stenosis: The pulmonary valvular orifice was between 50 and 80 per cent of aortic orifice. 3. Severe stenosis: The pulmonary valvular orifice was less than Xl per cent of aortic. 4. Pulmonary atresia: There was no communication between the infundibulum of the right ventricle and the pulmonary trunk. The individual cusps of bicuspid valve were usually short with corresponding limitation in mobility so that some degree of stenosis was thought to be present in 27 of the 32 bicuspid valves (84 per cent). Five of the 10 tricuspid valves were stenokic on the basis of a narrow orifice associated with short, relatively rigid cusps, while in the remainder, the valve was not stenotic. Each unicuspid and cone-shaped pulmonary valve exhibited stenosis of mild-tomoderate or severe degree. Considering the limited amount of material, one could not observe a distinct trend for a type of pulmonary valve to be associated with a particular type of aortic arch. Among the 21 cases of pulmonary atresia, 2 right aortic arch was present in 9 cases
Anatomic
Table I. L?egree oj stenosis and structure Degree
of fxhonary
valvular None Mild-moderate Severe Pulmonary
of +lmonary
variations
in tetralogy oj Fallot
363
valve in 80 cases
Pulmonary valvestructur.3 _
stenosh
Tricus$id
a tresia
5 4 1 0
5 17 10 0
0 3 5 0
0 4 3 0
0 0 0 21
1 1 0 0
11 29 19 21
10
32
8
7
21
2
80
Total
Table II. Pulmonary
F@d
1 Uwicuspid
valvular and infundibular
/
Dome
Atretic
/
1
Absent
1
Total
stenosis as observed in 84 cases Pulmonary
vahlar
stenosis
Infundibulav ShOSiS
None
Mild-moderafe
/
Severe
/
A tresia
/
Total
None Mild-moderate Severe
0 1 10
2 15 13
2 1 19
0 0 21
4 17 63
Total
11
30
22
21
84
(43 per cent), the overall incidence of right aortic arch being 29 per cent. Right ventricuZar infundibulum. Table II shows the association of pulmonary valvular and infundibular stenosis in 84 specimens. Infundibular stenosis was judged on the basis of the expected size of the infundibulum for the specimen in question, taking into account the narrowest portion of the infundibulum and the length of the hypoplastic segment or the number of sites of constriction when there were more than one. The difficulty of evaluating the degree of functional obstruction in fixed specimens is well recognized. Among the 84 specimens in which the nature of the pulmonary valve and infundibulum was known, 52 had varying degrees of pulmonary valvular stenosis and 21 had pulmonary atresiia. There were 4 cases with no infundibular stenosis and, in each of these, the pulmonary valve was stenotic. Seventeen had mild-to-moderate infundibular stenosis and 63 showed severe infundibu-
-.
lar stenosis, including the 21 cases of pulmonary atresia. There was a strong tendency for the degree of infundibular obstruction to be concordant with the degree of valvular stenosis, although exceptions occurred as in 2 examples of severe valvular stenosis in which no infundibular stenosis occurred. In IO cases, the reverse was true, in that severe infundibular stenosis was associated with no valvular stenosis. Pulmonary arteries. In 78 specimens, the pulmonary trunk was available and, in 76, the 2 branches were present in the specimens. In one of the cases, the nature of the pulmonary valve could not be determined. The caliber of the pulmonary trunk was given certain designations by comparing its diameter to that of the aorta as follows: 1. Normal: The diameter of the pulmonary trunk was greater than 80 per cent of that of the aorta. 2. Moderate hypoplasia: The diameter of the pulmonary trunk was between 50 and 80 per cent of that of the aorta.
Normal Moderate hypoplasia Severe hypoplasia
5 4 0
0 25 0
0 5 12
Atretic Poststenotic
0I
04
10
29
dilatation
Total
Tubbe IV. Degree of infundibulur 75 cases
F
5 41 23
0
30
z
17
21
77
II
steno&s and caliber of the ;bulnzonnry trilnk
Pnbzonary In,fundibular stenosis
Severe hy$o@asia
as observed in
trunk
Atretic
None Mild-moderate Severe
0 0 6
1 14 26
2 1 20
0 0 3
1 1 3
4 16 58
Total
6
41
23
3
5
78
3. Severe hypoplasin: The diameter of the pulmonary trunk was less than 50 per cent of that of the aorta. 4. Atresia: There was no iumen in the pulmonary trunk which was represented by a fibrous-like strand of tissue. 5. Poststeno& dilatation: The relative size of the pulmonary trunk was disproportionately large compared to the orifice of the pulmonary valve. Among 41 specimens with moderate hypopfasia of the pulmonary trunk, only one showed a normal infundibulum and, in this case, there was a moderate degree of pulmonary valvular stenosis. Of the remaining, 14 had moderate and 26 had severe infundibular obstruction. Severe hypoplasia of the pulmonary trunk was strongly associated with major obstruction at the pulmonary valve and/or infundibulum. There were 23 specimens with severe hypoplasia of the pulmonary trunk, includ-
ing 2 with no infundibular stenosis but with moderate valvular stenosis and one with moderate infundibular and severe valvular stenosis. The remaining 20 showed severe infundibular stenosis, of which 12 manifested pulmonary atresia. There were 3 specimens with atresia of the pulmonary trunk, each of which also exhibited atresia at the level of the pulmonary valve. The basis for pulmonary stenosis varied among the 5 cases of poststenotic dilatation of the pulmonary trunk. In one, only the pulmonary valve was stenotic. In a second case, stenosis was present only in the infundibulum, and in 3 cases both the valve and infundibulum were stenotic. In comparing the pulmonary trunk with the pulmonary valve, there was a strong tendency for the caliber of the vessel to decrease as the number of pulmonary cusps decreased and as the degree of pulmonary valvular stenosis increased (Table I I I) m
Anatomic
variations
Table V. Obstruction to pulmonary flow whether infundibular of the pdmonary trunk as observedin 78 cases Pulmonary Obsiruction pulmonary
Mild-moderate Severe Pulmonary Total
in tetralogy
of Fallot
365
or valvular, or both, and the caliber
trunk
to $0~
atresia
: 0
14 20 7
0 12 11
0 0 3
2 3 0
17 40 21
6
41
23
3
5
78
Table IV shows the relationship of the severity of the infundibular stenosis to the nature of the pulmonary trunk in 78 cases. Among the 4 specimens with no infundibular stenosis, the pulmonary trunk showed moderate hypoplasia in one, severe hypoplasia in 2, and poststenotic dilatation in one. Mild-to-moderate infundibular stenosis was present in 16 specimens, 14 of which s#howedmoderate hypoplasia of the pulmonary trunk, one severe hypoplasia and one poststenotic dilatation of the pulmonary trunk. The 58 specimens with severe infundibular stenosis included 6 with a normal pulmonary trunk, 26 with moderate hypoplasia, 20 with severe hypoplasia, 3 with atresia ‘of the pulmonary trunk, and 3 with poststenotic dilatation. Severe infundibular stenosizi with only moderate pulmonary valvular stenosis had a strong tendency to be associated with only moderate hypoplasia of the pulmonary trunk. In contrast, when pulmonary valvular atresia was associated with severe infundibular stenosis, there was a wide range in the caliber of the pulmonary trunk. Among 21 specimens with pulmonary atresia and severe infundibular stenosis, 6 showed moderate hypoplasia, 12 severe hypoplasia, and, in 3, atresia of the pulmonary trunk was present. In each of the 6 casesof a normal pulmonary trunk, there was severe infundibular stenosis without valvular stenosis. If, in our material, one combines valvular and infundibular stenosis as a basis for obstruction to pulmonary flow, it becomes apparent that there is a direct relationship
between the degree of restriction in caliber of the pulmonary trunk, on one hand, and the severity of pulmonary obstruction, on the other (Table V). There is, however, a greater tendency for valvular stenosis rather than infundibular stenosis alone to exert an effect on restriction in the caliber of the pulmonary trunk (Tables III and IV). There was a strong tendency for the caliber of the right and left pulmonary arterial branches to be directly proportional to that of the pulmonary trunk, although in isolated instances the pulmonary trunk was severely hypoplastic while the branches showed lesser degrees of hypoplasia. In only 5 specimens was there a normal caliber of the pulmonary trunk and the 2 branches. Among 63 specimens with moderate or severe hypoplasia of the pulmonary trunk, the pulmonary artery branches were also hypoplastic. In 3 casesof moderate hypoplasia of the pulmonary trunk, there was localized stenosis of the branches, one bilateral and 2 unilateral. One of the latter was an example of socalled “absence of the left pulmonary artery” (“proximal interruption of the left pulmonary arch” or “origin of the left pulmonary artery from the left ductus arteriosus”). The left pulmonary artery was stenotic at its ductal origin and showed slight poststenotic dilatation beyond the ductus, although the caliber beyond that level was very narrow compared to the expected normal. In each of the 3 specimens with an atretic pulmonary trunk the branches were patent but hypoplastic. In
366
Satynnarayana
iTao, Anderson,
and Edwards
Tuble VI. Nature oj aortic arch and degree.: ojobstrm&wz to &kaona~y$ow or valvular as seen in 83 cases. Perce?ztages Teeresent those of subgroups
whether infmdibudar
Obstruction to pulmonary
$0~
Right
Mild-moderate
10 (23%) 9 (43%) 24
Atresia Total
Table
VII.
Left
m%‘c)
5
Severe
arch
Types
of aortic
arch
T&d
14 (74%) 33 (77YO)
19 (lQO%,) 43 (lQQ%)
12 (57YOI
21 (lOO%b)
59
arch and branches
83
in 82 casesof the tetralogy of Fallot
Types of aortic arch and brandzes Major class Double Left
Right
aortic aortic
aortic
arch
arch
arch
Number of specimens
/
.%&lass Both arches patent One arch patent Normal Aberrant Isolation
branches right subciavian artery of right subclavian artery
Mirror image branching Aberrant left subclavian artery Isolation of left subclavian artery
Total
the 5 casesof poststenotic dilatation of the pulmonary trunk, the branches were essentially of normal caliber. There was no apparent relationship between the type of aortic arch and the character of the pulmonary trunk and its branches. Aortic arch. There were 84 casesin which both the basis for obstruction to pulmonary flow and the status of the aortic arch were known. In 2 of these, the nature of the branching of the aortic arch could no% be determined. In one of the 84 cases, a double aortic arch was present. Among the remaining 83 specimens, a right aortic arch was present in 24 cases (29 per cent) and a left aortic arch in 59 cases (71 per cent) (Table VI). In the 24 wi%h a right aortic arch, there were 10 cases of severe obstruction to pulmonary flow at the infundibulum, the pulmonary
1 0 50 7 0
20 4 0 82
valve, or both, in addition to 9 cases of pulmonary atresia. Thus, 19 of 24 cases (77 per cent) wi th a right aortic arch manifested major obstruction to pulmonary flow. Among the 59 examples oi left aortic arch, major degrees of stenosis occurred in 45 cases (76 per centj. In 82 of the cases, the branches of the aortic arch were in an adequate state for interpretation (Table VII). The case of double aortic arch showed each arch to give rise to the common carotid and subclavian arteries of its side. In the 57 cases with a left arch, the usual branching occurred in 50, while 7 cases showed an aberrant right subclavian artery (12.5 per cent of caseswith left arch). Among the 24 cases of right aortic arch, 20 showed a pattern of mirror image branching. Four of the casesof right aortic arch showed an
Anatomic
variations
367
in tetralogy of Fallot
Table VIII. Nature of the aortic arch and the status of the ductgs arteriosus as observed in 80 cases, one of which was a case of double aortic arch with a ligamenturn arteriosum present on the left side Aorfic arch Total
Ductus arteriosus Right arch
I
Left arch
Absent Patent Ligamentous
I 4 13
12 1.5 28
19 19 41
Total
24
5.5
79
Table IX. Status of ductus arteriosus and the degreeof obstructio;vt to pulmonary flow whether infundibular, valvular, or both, as observedin 81 cases Degree of obstruction to pulmonary flow
status of ductus Mild-moderate
Severe
Pulmonary
atresia
Total
Absent Patent Ligament
2 2 14
12 5 25
5 12 4
19 19 43
Total
18
42
21
81
anoma’lous left subclavian artery (16.5 per cent of cases with right arch). In each case of anomalous subclavian artery, whether right or left, the artery crossed from its aortic origin to the opposite side of the body behind the esophagus. No cases of isolation of a subclavian artery2 (origin of artery from a ductus arteriosus) were encountered in this study. Ductus arteriosus. In each of 81 cases, the sta.tus of the ductus arteriosus could be determined and in each, except one, the nature of the aortic arch was known. Among 80 cases, the ductus arteriosus (or ligamentum arteriosum) was present on the left sid.ein 60 cases(including the case with double aortic arch), on the right side in one case, and absent in 19 cases (Table VIII). No casesof bilateral ductus arteriosus were encountered. In the one case of a right ductua arteriosus, a right aortic arch was present. In those casesof a left ductus and a right arch, the ductus extended from the base of the left subclavian artery which
arose from a left innominate artery and inserted into the left pulmonary artery. In each case of right arch with anomalous left subclavian artery the ductus arteriosus was absent. In one of the cases of a patent left-sided ductus arteriosus, the ductus was continuous with the peripheral end of the left pulmonary artery, while the proximal segment of the left pulmonary artery was absent. The 19 casesof absence of the ductus were distributed as follows: seven cases among 24 cases of right aortic arch (29 per cent) and 12 cases among 55 cases of leflt aortic arch (22 per cent). Patency of t.he ductus was encountered in 19 of the 61 caseswith a ductus (30 per cent). The distribution of patent ductus according to the degree of obstruction to pulmonary flow was as follows (Table IX). In 16 casesof mild-to-moderate obstruction to pulmonary flow and with a ductus present, the latter was patent in 2 cases. Comparable figures for severe pulmonary stenosis were 5 calsesof patent ductus among
Atrial
septzlm
-__-..
Degree of obstruction to pulmonary pow
,
__-.. Anatomically sealed
Valvular foramen
competent ovale 07
patent A
Total
SD
I
Mild-moderate Severe
Pulmonary atresia Total In 4 cases, a large defect in the lowermost part in the fourth case, the defect was associated
4 (21%) 9 (2070) 2 (9.5yo) 15
15 (79%)
of the atrial septum was present. In 3, the defect was part with normal tricuspid and mitral valves (with pulmonary
30 cases. In pulmonary atresia, the ductus was patent in 12 among 16 cases in which the ductus was present. Atrial septum. It was significant that a true or a potential interatrial communication was present in 70 of the 8.5 cases (82.5 per cent). In the majority (47 cases), this took the form of a valvular competent foramen ovale, while in 23 cases there was a persistent opening between the 2 atria. Usually, this appeared to result from a short valve of the foramen ovale yielding a true through-and-through opening of less than one centimeter in diameter at the fossa ovalis. A large defect in the lowermost aspect of the atria1 septum was present in 4 of the cases. In 3 of these, the defect was part of the complex of persistent common atrioventricular canal, while in one case the defect was associated with normal tricuspid and mitral valves. In spite of the fact that 35 per cent of the subjects in this study were infants below one year of age and 55 per cent were children under five years of age, these figures suggest a strong tendency for the atria1 septum to maintain some form of patency. Some tendency for persistence of an interatria1 communication seems to be related to the severity of obstruction to pulmonary flow (Table X). While there was essential difference between cases having varying degrees of pulmonary stenosis, cases with pulmonary atresia exhibited a higher incidence of an interatrial communication than those with the various degrees of pulmonary stenosis.
19 45 21
36 (80%) 19 (9Q.5%) 70
Associated
85 of persistent atresia).
A-V canal;
anomalies
Twenty-nine specimens had associated anomalies in addition to the components of the tetralogy. The following is a summary of observations in this regard. Left superior vena cava. A left superior vena cava was present in 9 specimens (10.6 per cent) and drained into the coronary sinus in each. Persistent common atrioventkular canal. In 3 specimens, the features of the tetralogy were associated with the characteristics of the complete form of persistent common atrioventricular canal, including its atria1 septal defect and cleft condition of the atrioventricular valves. In one of these cases, the -mitral aspect of the common atrioventricular valve exhibited a parachute mitral valve-like deformity in addition to an accessory orifice of the valve. Anomalies of the mitral valve. In addition to the cases with persistent common atrioventricular canal, there were 3 instances of associated anomalies of the mitral valve. One specimen showed localized hooding of the posterior leaflet associated with an accessory papillary muscle and accessory chordae. In the second specimen, a cleft was present in the anterior leaflet. The third case showed car triatriatum and anomalous chordae of the anterior leaflet of the mitral valve inserting into the ventricular septum, the latter causing subaortic stenosis. This specimen was from a subject with omphalocele, ectopia cordis, and a diaphragmatic hernia. Anomalies of the tricuspid valve. There
Volume Number
81 3
Anatomic
were 3 instances of anomalies of the tricuspid valve exclusive of the 3 cases with persistent common atrioventricular canal. A cleft in the septal leaflet of the tricuspid valve resulting in congenital tricuspid insufficiency was present in one specimen which also showed a systolic pocket of the left ven-tricle below the lower edge of the VSD. The second specimen was from a patient with Down’s syndrome in whom a cleft in the septal leaflet of the tricuspid valve and an atria1 septal defect at the fossa ovalis were ‘present. IBacterial endocarditis also involved the tricuspid valve in this case. In the third specimen with an anornalous tricuspid valve, the valve showed an accessory pouch. In addition, an anomalous muscle bundle of the right ventricle and hypoplasia of the right coronary artery were present. Miscellaneous conditions, each of which was enoountered once in the entire series, were: (1) Prolapse of the right aortic cusp with aortic insufficiency; (2) subaortic stenosis (mentioned under anomalies of mitral valve); (3) accessory orifice of the mitral valve (in association with persistent A-V canal) ; (4) aneurysm of the fossa ovalis; (5) dextroversion; (6) septal hypertrophy causing left ventricular outflow obstruction; (7) left umbilical vein draining directly into the coronary sinus and absence of ductus venosus; and (8) anomalous muscle bundle of the right ventricle causing subpulmona.ry stenosis (in a case with anomalous tricuspid valve). Bacterial
endocarditils
There were 5 specimens with evidence of bacterial endocarditis, the lesions being healed in the first 4. In 2, the infection appeared to have begun at the edges of a patch inserted to close the ventricular septal defect. The ages of the patients ranged from 15 to 39 years. Commlent
Though the tetralogy of Fallot has certain specific and well-recognized structural characteristics, a wide variation in the severity of the lesions and in association with other anomalies has been recognized.3-8 In this study, those cases showing the cardiac structure of the tetralogy of Fallot were so classified whether or not pulmonary
variations
in tetralogy of Fallot
369
atresia was associated. The relatively high incidence of cases with pulmonary atresia (21 of 85 cases) among our material may reflect a strong factor of selection. The basis for this is that patients with pulmonary stenosis tend to live longer and to be more likely to receive the benefits of corrective surgery than do those with pulmonary atresia. Among the cases of pulmonary stenosis, it was the usual finding that stenosis at the infundibulum a:nd pulmonary valve coexisted. It was relatively common, nevertheless, as has been recognized, that only the infundibulum would harbor the basis of obstruction to pulmonary flow (11 of 64 cases of pulmonary stenosis). In contrast, stenosis only at the pulmonary valve was uncommon, being present in only four of 64 cases of pulmonary stenosis. Some may disagree with the designation of the Iatter 4 casesas examples of the tetralogy. The basis for including these examples in our study was that, in each, the right ventricular infundibulum was a distinct tract, as in classical examples of tetralogy, but without stenosis. In each specimen with pulmonary atresia, there was hypoplasia of the entire right ventricular infunldibulum, the latter usually being represented by a small blind pouch anterior to the crista supraventricularis and terminating at the atretic pulmonary valve. In other instances, there was a very narrow, tortuous sinus-like tract leading to the atretic pulmonary valve. The structure of the pulmonary valve was studied in detail in our series.Adequate data regarding this subject are not available in reports of other seriesreviewed. This study showed a strong tendency for the number of commissures in the valve to decrease as the severity of the pulmonary stenosis increased. The degree of hypoplasia of the pulmonary trunk and pulmonary valvular abnormality in our series had a somewhat linear correlation. Increasing degrees of hypoplasia of the pulmonary trunk were associated with a diminishing number of cusps and commissures in the valve. Also, when the number of commissures in the pulmonary valve was decreased, the pulmonary valvular annulus was proportionately hypoplastic. There was no definite correlation between the degree of
370
Salyanauayaaa
Rae, Andersm,
Am-P. Heavf 3. March, 1971
and Edwards
infundibular stenosis and hypoplasia of the pulmonary trunk. Hypoplasia of the pulmonary trunk was invariably associated with varying degrees of hypoplasia of the pulmonary arterial branches. There were, however, instances in which severe hypoplasia of the pulmonary trunk was associated with only moderate hypoplasia of the pulmonary arterial branches. Even in the 3 specimens with atretic pulmonary trunk, the branches of the pulmonary artery were represented by patent but severely hypoplastic pulmonary arterial branches. There were 5 specimens with poststenotic dilatation of the pulmonary trunk, 3 of which were associated with severe infundibular stenosis. In 3 of these specimens, a bicuspid pulmonary valve was present and, in each of 2, the pulmonary valve was absent. The high incidence of an interatrial communication in tetralogy of Fallot has received relatively little attention in the past. It is of interest that only 15 of our cases (17.5 per cent) exhibited anatomic closure of the foramen ovale. The high incidence of patency of the foramen ovale is probably the result of the right ventricular hypertrophy coupled with a low volume of blood in the left atrium. The incidence of right aortic arch in this series (29 per cent) is comparable to the incidence in some of the other series. There has, however, been a wide discrepancy on the incidence of the right aortic arch among the several reported series.3-* It was hypothesized previously by one of the authors, Edwards, that there was a correlation between the severity of the pulmonary outflow obstruction and the incidence of right aortic arch. The analysis in this series, however, does not support this hypothesis. There were 7 casesof anomalous right subclavian artery with left aortic arch and 4 cases of anomalous left subclavian artery with right aortic arch. The incidence of anomalous subclavian artery is high compared to that in individuals without other malformations. In the general population, an anomalous right subclavian artery occurs in about one in 200 persons. Absence of the ductus arteriosus was fairly common in this series, being observed in 19 of 79 cases(25 per cent) with a slightly greater tendency for right aortic arch to be
associated with this condition than ‘left. It is interesting to speculate on absence of the ductus as a response to low volumes of pulmonary flow in association with ready communication of the aorta with the right ventricle. The incidence of absent ductus was about equal in cases with pulmonary atresia as with pulmonary stenosis. The tendency for association with right aortic arch may perhaps result from peculiarities of streaming in right aortic arch contrasted with left arch. Of interest was the occurrence of bacterial endocarditis in 5 of the patients, in 2 of whom the infection began at the site of surgical closure of the ventricular septal defect. The relatively older ages of the patients (age range 15 to 39 years) conforms with the tendency for bacterial endocarditis to involve older subjects more often than the young with congenital cardiac disease. Intracardiac malformations associated with the tetralogy of Fallot, although fairly numerous, tended, when present, to occur one per patient and probably reflects the phenomenon that the tetralogy has no particular affinity for association with a specific malformation, except, perhaps, persistent common atrioventricular canal. The latter condition was seen in 3 of the 85 cases of the tetralogy, the ages of the patients being 17 months, three years, and nine years. In a fourth case involving a 2-year-old boy, a defect in the lowermost part of the atria1 septum was associated with normal mitral and tricuspid valves. Two of the patients with persistent common atrioventricular canal had Down’s syndrome. An additional case with the Down’s syndrome had an intact atria1 septum with a cleft in the tricuspid valve. The relatively common occurrence of persistent common atrioventricular canal and of Down’s syndrome in our series may reflect a factor of selection, as one of the contributors of specimens is an institution for the mentally deficient. The relatively high incidence of patent ductus arteriosus may reflect the large proportion of infants in this series. Summary
Eighty-five specimens with a tetralogy of Fallot from patients varying in age from
Anatomic
infancy to adult life were studied for (1) the nature of the pulmonary valve, the right ventricular infundibulum, the pulmonary arteries, the aortic arch, and the atria1 septum and (2) the association of other anomalies and of bacterial endocarditis. The pulmonary valve was usually malformed, only 10 of the cases exhibiting a tricuspid pulmonary valve. In the majority of instances (32 cases), a bicuspid valve was present. Pulmonary valvular atresia occurred in 21 cases. A unicuspid, domeshaped, or absent pulmonary valve was seen in 8, 7, and 2 cases, respectively. Infundibular stenosis of some degree was present in all but 4 cases. Hypoplasia of the pulmonary trunk had a closer association with pulmonary valvular stenosis than with infundibular stenosis. A right aortic arch was observed in 24 cases (2!> per cent). The incidence of severe obstruction to pulmonary flow was about as common in cases of right aortic arch as in those with left arch. Absence of the ductus arteriosus was observed in 19 cases. An interatrial communication was present in 70 cases (82.5 per cent) and usually took the form of a valvular competent foramen ovale. Although associated intracardiac anomalies occurred in about 1.5 per cent of the cases, not all were functionally significant and there did not appear to be a tendency
variations
in tetralogy of Fallot
371
for the association of any one specific condition with the tetralogy. Persistent common atrioventriicular canal was seen in 3 cases. A persistent left superior vena cava occurred in 9 cases. Anomalous origin of the subclavian artery occurred more commonly than in tlhe general population. Bacterial endocarditis was observed in 5 cases. REFERENCES
1. 2.
3.
Edwards, J. E.: Pathologic aspects of cardiac valvular insufficiencies, Arch. Surg. (Chicago) 77:634, 1958. Stewart, J. R., Kincaid, 0. W., and Edwards, J. E.: An atlas of vascular rings and related malformations of the aortic arch system, Springfield, Ill.. 1964. Charles C Thomas. Publisher. D. 171. Feigin, I.; and Rosenthal, J.: Tetralogy of Fallot,
AIMER.HEARTJ.~~:~O~, 1943.
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Baffes, T. G., Johnson, F. R., Potts, W. J., and Gibson, S.: Anatomic variations in the tetralogy of Fallot, AMER. HEART J. 46:657, 1953. Brinton, W. D., and Campbell, M.: Necropsies in some congenital diseases of the heart, mainly Fallot’s tetralogy, Brit. Heart J. 15:335, 1953. Rowe, R. D., Vlad, P., and Keith, J. D.: Experiences with 180 cases of tetralogy of Fallot in infants and children, Canad. M. A. J. 73:23, 1955. Lev, M., and Eckner, F. A.: The pathologic anatomy of tetralogy of Fallot and its variations, Dis. Chest 45:251, 1964. Nagao, G. I., Daoud, G. I., McAdams, A. J., Schwartz, D. C., and Kaplan, S.: Cardiovascular anomalies associated with tetralogy of Fallot, Amer. J. Cardiol. 20:206, 1967