The ventricular septal defect in complete transposition of the great arteries: Pathologic anatomy in 57 cases with emphasis on subaortic, subpulmonary, and aortic arch obstruction

The Ventricular Septal Defect in Complete Transposition of the Great Arteries: Pathologic Anatomy in 57 Cases with Emphasis on Subaortic, Subpulmonary, and Aortic Arch Obstruction ORNELLA MILANESI,MD, SlEWYEN He, PHD,GAETANO THIENE,MD, CARLA FRESCURA,MD, AND ROBERTH. ANDERSON, MD Fifty-seven heart specimens with complete transposition (concordant atrioventricular and discordant ventriculo-arterial connections) and ventricular septal defect were reviewed to establish the spectrum of morphology of the ventricular septal deficiency and to correlate the type of defect wiih presence of subarterial and aortic a r c h obstruction. The ventricular septal defect was single in 52 cases (27 perimembranous and 25 muscular) and multiple in five. A normal alignment between the outlet c o m p o n e n t and the rest of the muscular septum was present in 18 cases (10 perimembranous, five muscular, and three multiple). The defect was the consequence of septal malalignment in the other 39 specimens; 29 with rightward and 10 with leftward displacement of the outlet septum. Rightward displacement led to perimembranous defects in 16 cases and muscular defects in 12. In another instance, a perimembranous malalignment defect was a s s o c i a t e d with a muscular inlet defect. Subaortic s t e n o s i s due to either deviation of the outlet septum or prominence of the ventriculo-infundibular fold and septoparietal trabeculations was o b s e r v e d in 14 cases. Leftward displacement of the outlet septum w a s associated with one perimembranous and eight muscular defects and with multiple (muscular outlet plus muscular inlet) defects in another case. O f these, five cases showed subpulmonary stenosis. A o r t i c a r c h obstructions were present in 19 cases; 14 showed rightward malalignment of the outlet septum, which p r o d u c e d s u b a o r t i c stenosis. These findings suggest two things: I) Unlike the situation in hearts with "normally related" great arteries, most defects in complete transposition result from realalignment of the outlet septum, with many being of the muscular type. Rightward or leftward displacement of the outlet septum frequently results in subaortie or subpulmonary stenosis, respectively. 2) Aortic arch obstructions, although frequent, are not always associated with suhaortic stenosis. HUM PATHOL 18:392-396, 1987.

present study was designed to assess type and distribution of the defects in an autopsy series. MATERIALAND METHODS Fifty-seven heart specimens were reviewed with complete transposition and ventricular septal defect. Forty-one cases were taken from the anatomic collection of the Department of Pathology, University of Padua, and 16 were from the Cardiothoracic Institute, Brompton Hospital, London. They represent all of the cases with complete transposition and ventricular septal defect from these institutions. The hearts were from 36 male and 21 female patients. Age at death ranged from I day to 29 )'ears (median, 2 months). All hearts presented with situs solitus and left aortic arch. Three had been in the right chest (dextrocardia) and 54 in the left (levocardia). Left juxtaposition of the atrial appendages was observed in six hearts. Venous drainage anomalies consisted o f u n r o o f e d coronary sinus in one heart and partial anomalous pulmonary venotts connection in another. Mitral valve abnormalities were seen in seven cases: four had a cleft in the pulmonary leaflet, one a straddling valve, one a double orifice, and one a parachute valve. The tricuspid valve also was malformed in some cases. It was hypoplastic in three, dysplastic in one, exhibited a double orifice in one and an accessory leaflet in another. Particular attention was paid to the morphology of the ventricular septum, the presence of obstruction of the ventricular outflow tracts, and anomalies of the aortic arch. Defects within the septum were classified first according to their locations adjacent to the membranous or within the muscular components of the septum. 4,5 T h e perimembranous defects were identified by the presence of fibrous tissue of the central fibrous body in their postero-inferior rims. T h e muscular type had only muscular borders. A f u r t h e r distinction was made between hearts with normal alignment of the outlet septum with the rest of the septum and those with rightward or leftward displacement o f the outlet septum.

T h e occurrence rate o f associated ventricular septal defects in hearts with complete transposition (concordant atrioventricular and discordant ventricu l o - a r t e r i a l c o n n e c t i o n s ) has been r e p o r t e d as ranging from about 25 to 70 per cent. l-s T h e presence of single or multiple defects has considerable influence on the natural history of the condition and the planning of the oPtimal surgical repair. T h e Received from the Departments of Paediatrics and Pathology, Medical School, Padua, Italy; and the Department of Paediatrics, Cardiothoracic Institute, Brompton, London, U.K. Accepted for publication August 27, 1986. Supported by the National Research Council (C.N.R.) target project Preventive Medicine and Rehabilitation and subproject Perinatal Pathology and Its Sequelae, Rome, Italy and by the British Heart Fotmdation, London, England. Address correspondence and requests to Dr. Thiene: Institute of Pathological Anatomy, Via Gabelli, 61, 35121 Padova, Italy.

RESULTS

Type of Ventricular Septal Defect [Table 1) Single perimembranous defects were present in 27 hearts (47 per cent), single muscular defects in 25

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VENTRICULAR SEPTALDEFECT(Milanesi et al.]

FIGURE 1 (fop). Left ventricular view of a specimen with itsventricular septal defect [arrows] located between the outlet and trabecular component of the muscular septum. FIGURE 2 (bottom]. Left ventricular outlet views of two heads. The outlet septum is deviated into the right ventricle in the left figure and into the left ventricle in the right figure.

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FIGURE 3 (top). a, Rightward displacement of the outlet septum resulted in a muscular ventricular septal defect with a muscular postero-inferior border [arrows] b, The same sort of displacement resulted in a perimembranous vent~icular septal defect with fibrous continuiiy (arrows] between the pu/monary, mitral, and tricuspid valves. FIGURE 4 [bottom left]. Right ventricular view of a specimen with duplication of the septomarginal trabeculation [* - *). FIGURE 5 [bottom right]. Long-axis section of a specimen showing the leftward displacement of the outlet septum [*], which produced a muscular realalignment ventricular septal defect [arrows].

(44 per cent), and multiple defects in five (9 per cent). Eighteen cases (32 per cent) presented with normal septal alignment. O f these, 10 were perimembranous, five muscular, and three multiple. O f the five muscular defects, three were located at the junction between the outlet and trabecular components of the septum (fig. 1), while two were located in the inlet septum. O f the three cases with multiple defects, one was a "swiss cheese" type, and two were c o m b i n e d p e r i m e m b r a n o u s and muscular types.

Thirty-nine hearts (68 per cent) showed malalignmerit, with rightward displacement o f the outlet septum in 29 and leftward displacement in 10 (fig. 2). T h e displacement of the outlet septum to the right gave origin to a subpulmonary defect with overriding pulmonary valve, which was perimembranous (fig. 3a) in 16 cases and muscular (fig. 3b) in 12. Another muscular inlet defect was associated with a perimembranous defect in one of the hearts. In 12 cases, the tensor apparatus of the antero-septal commissure of 394

VENTRICULARSEPTALDEFECT[Milanesi et all

FIGIBtr. 6 [left}. Right ventdcular view of o specimen with rightward displacement of the outlet septum [*] contributing to a subaortic stenosis. Note the hypoplastic segment of the aortic arch. FIGURE 7 (right]. Septal bulge with superimposed fibrous plaque obstructing the ventricular outflow tract.

the tricuspid valve crossed the defect to insert into the medial papillary muscle located in the antero-superior rim. The medial muscle was part of a duplicated septomarginal trabeculation in two instances (fig. 4). The displacement of the outlet septum to the left gave origin to a subaortic defect with minimal overriding of the aortic vah'e. The defect was perimembranous in one case and muscular in eight (fig. 5). Among the latter group, one case had a muscular outlet defect associated with a muscular inlet defect. Hearts with Right Ventricular Outflow Tract Obstruction

Subaortic stenosis was present in 14 cases (25 per cent). It was caused by isolated rightward displacement of the outlet septum in six cases (fig. 6), displacement in conjunction with hypertrophied septoparietal trabeculations in six, and hypertrophied septoparietal trabeculations with huge ventriculo-infundibular folds in two. Of 14 cases with subaortic stenosis, aortic arch obstruction was observed in 12.

Aortic Arch Obstructions

Nineteen specimens (33 per cent) showed aortic arch anomalies. Coarctation was present in 15 cases, tubular hypoplasia in two, and atresia in two (one at the isthmus and one between tile left common carotid and left subclavian arteries). Rightward displacement o f tile outlet septum was found in 14 of these cases. As mentioned earlier, 12 hearts presented with some form of subaortic stenosis with or without displacement of the outlet septum. Hearts with Left Ventricular Outflow Tract Obstruction

Fourteen hearts (25 per cent) presented with left v e n t r i c u l a r o u t f l o w tract obstruction. A n o r m a l septal alignment was observed in six cases and malalignment in eight. In the former group, the stenosis w a s p r o d u c e d by disproportionate h y p e r t r o p h y of the ventricular septum together with a fibrous plaque in three cases (fig. 7), accessory tricuspid leaflet tissue crossing tile defect in one, and a stenotic and dysplastic puhnonary valve in two. In the setting of malalignment, the outlet septum was displaced to the right in three cases and to the left in five. When disTABLE '1. Type of Ventricular Septal Defect placed to the right, the left ventricular outflow tract Perimembranous Muscular Muhiple TOTAL obstruction was due to mitral valve straddling in one case, accessory tricuspid valve tissue in one, and anNormal e u r y s m o f the m e m b r a n o u s s e p t u m in a n o t h e r . alignment 10 5 3 18 When displaced to the left, the pulmonary stenosis Rightward displacement 16 12 I 29 was accomplished by deviation of the outlet septum Leftward together with fibrous subvalar stenosis in four cases displacement 1 8 1 10 and a dysplastic pulmonary valve in one. None of TOTAL 27 25 5 57 these hearts had aortic arch obstruction. 395

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DISCUSSION W h e n p r e s e n t in isolation (hearts with concord a n t ventriculo-arterial connections a n d " n o r m a l l y related" g r e a t arteries) the site o f ventricular septal defects in an a u t o p s y series is p r e d o m i n a n t l y perim e m b r a n o u s (83 p e r cent). 5 T h e d o m i n a n c e o f the p e r i m e m b r a n o u s location has been r e p o r t e d also in hearts with c o m p l e t e transposition. 2,6,7 In o u r series, however, the distribution between p e r i m e m b r a n o u s a n d m u s c u l a r locations is m o r e balanced (47 p e r cent p e r i m e n t b r a n o u s , 44 p e r cent muscular). T h e categorization o f defects into p e r i m e m b r a n o u s a n d mnscular types enables the prediction o f tire course o f the cardiac c o n d u c t i o n axis, which is o f particular relevance d u r i n g surgical repair. 8 W h e n a m u s c u l a r post e r o - i n f e r i o r b o r d e r is present, the c o n d u c t i o n axis is m o r e r e m o t e f r o m the r i m o f the defect a n d theref o r e less v u l n e r a b l e to surgical t r a u m a . T h e septal defects in c o m p l e t e transposition are located mostly in the s u b p u l m o n a r y position. Occasionally, they are the c o n s e q u e n c e o f a lack o f fusion b e t w e e n the outlet a n d t r a b e c u l a r c o m p o n e n t s o f the n o r m a l l y aligned septal structures. I n most hearts, h o w e v e r , t h e y a r e d u e to a m a l a l i g n m e n t o f t h e septal components. Malalignment of the ontlet s e p t u m to the right is the m o s t c o m m o n . Tire rightw a r d deviation is similar to that seen in double-outlet right ventricle with s u b p u l m o n a r y defect ("TaussigBing") hearts. I n a c c o r d a n c e with accepted practice, we h a v e c o n f i n e d o u r series to hearts with less t h a n 50 p e r cent o v e r r i d e o f the p n h n o n a r y valve a n d , t h e r e f o r e , e x c l u d e d hearts with double-outlet right v e n t r i c u l a r connections. Nonetheless, the ttearts with a p r e d o m i n a n t l y left v e n t r i c u l a r connection o f the o v e r r i d i n g p u l m o n a r y t r u n k a p p r o p r i a t e l y can be c o n s i d e r e d as T a u s s i n g - B i n g hearts. 9 A l t h o u g h the variant o f c o m p l e t e transposition with a v e n t r i c u l a r septal defect a n d s u b p u l m o n a r y stenosis is a well-reccognized entity, IA~ that with subaortic stenosis a n d aortic a r c h obstruction is relatively o b s c u r e . 2,~,14,15 T h e r e c e n t i n v e s t i g a t i o n o f M o e n e et al. 14 r e p o r t e d an incidence o f 5 p e r cent n a r r o w i n g o f the aortic a r c h in their series, wttereas the series o f Milanesi et al. 3 h a d an incidence rate o f 12 p e r cent. With r e g a r d to the right ventricular outflow tract, M o e n e et al. 2 o b s e r v e d a n a t o m i c obstruction d u e to a n t e r i o r d i s p l a c e m e n t (or deviation) o f the outlet s e p t u m with p r o m i n e n c e o f the ventriculoi n f u n d i b u l a r fold in 12 o f the studied 15 hearts with subaortic stenosis. T h e r e m a i n i n g three hearts had o b s t r u c t i o n s d u e to r e d u n d a n t m u s c u l a r tissue. T h e s e investigators c o n c l u d e d that tire deviation o f the outlet s e p t u m placed the p e r i m e m b r a n o u s defect in s u b p u l m o n a r y position. O u r observations c o n c n r with the s u b p u l m o n a r y position being d u e to rightw a r d m a l a l i g n m e n t , a h h o u g h a significant p r o p o r tion o f the defects in o u r series had a m u s c u l a r post e r o - i n f e r i o r rim. I n only 43 p e r cent o f o u r hearts with s u b a o r t i c stenosis was the latter d u e to p u r e r i g h t w a r d deviation o f the outlet s e p t u m . O t h e r obstructive lesions such as h y p e r t r o p h y o f the ventricu l o - i n f u n d i b u l a r fold, septoparietal trabeculations, a n d duplication o f the s e p t o m a r g i n a l trabeculation

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usually w e r e p r e s e n t as well. We observed, m o r e o v e r , that aortic a r c h obstruction was f r e q u e n t l y b u t not always associated with subaortic stenosis. Deviation o f the outlet s e p t u m to the left caused obstruction in only five o f the 14 hearts with p u h n o n a r y stenosis. O t h e r m e c h a n i s m s o f obstruction, such as d i s p r o p o r t i o n a t e septal h y p e r t r o p h y with fibrous plaques, were m o r e significant. M o r e o v e r , the leftw a r d d i s p l a c e m e n t o f the outlet s e p t u m was insufficient to p r o d u c e severe s u b p u l m o n a r y stenosis. I n contrast, the m o s t f r e q u e n t cause o f s u b p u l m o n a r y stenosis in series o f 19 hearts studied by Van Gils et al. 16 was deviation o f the outlet s e p t u m t o g e t h e r with p r o m i n e n c e o f the antero-lateral muscle b a n d o f the left ventricle.

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