Act0 Pzdintr Scclnd 64: 785-789, 1975
CAUSES OF DEATH IN TRANSPOSITION OF THE GREAT ARTERIES A Clinical and Autopsy Study of 140 Cases B. LANDTMAN, I. LOUHIMO. J. RAPOLA and LEENA TUUTERI From the Children’s Hospital, Unibsersity of Helsinki, Helsinki, Finlund
ABSTRACT. Landtman, B., Louhimo, I., Rapola, J. and Tuuteri, Leena. (The Children’s Hospital, University of Helsinki, Helsinki, Finland.) Causes of death in transposition of the great arteries. A clinical and autopsy study of 140 cases. Acta Paediatr Scand, 64: 785, 1975.-The causes of death were assessed in 140 infants and children with transposition of the great arteries studied clinically and post mortem. Half of the children were under one month old. Death occurred during the first year of life in 118 cases. Balloon atrial septostomy and/or cardiac surgery were performed in 37 cases, and 7 patients died following operations for extracardiac malformations. Congestive heart failure was the most common single cause of death, occurring in 109 cases. All but 7 patients were cyanotic. Extracardiac malformations were encountered in 39 patients and were considered a main cause of death in 22 of these. Various infections, mostly pneumonia, occurred in half of the cases. Forty-one patients had vascular accidents in various organs. These complications were more common in operated than in nonoperated cases. Miscellaneous causes of death, including hyaline membrane disease and/or pulmonary atelectases, occurred in 30 patients. The study illustrated the complex symptomatology and therapeutic problems presented by critically ill infants with transposition of the great arteries.
KEY WORDS: Transposition of the great arteries, causes of death in congenital heart disease
The poor outlook of children with transposition of the great arteries is well documented. In a review of 201 conservatively treated patients, Sharer (19) stated that only 45 survived the first year of life and that most deaths occurred in the neonatal period and early infancy. A mortality of 90% during the first year of life has been reported from some centers (6, 9). The introduction of balloon atrial septostomy ( 17) and subsequent hernodynamic correction ( 10) has dramatically changed the outlook for children with transposition. These procedures are now being performed in most cardiac centers and, as a result, many patients are now leading a normal life. The natural history of transposition and the 5 I -75287’6
results of septostomy and surgical procedures have been reviewed by several authors. In most of these studies, however, less attention has been paid to the assessment of the causes of death in conservatively and surgically treated cases. The present study aims at shedding further light on this question by reviewing clinical and autopsy findings in 140 infants and children with transposition treated and lost at our hospital during a 28-year period.
MATERIAL AND METHODS Transposition of the great arteries occurred in 140 of 1 OOO infants and children with congenital heart disease who came to autopsy at the Children’s Hospital in Helsinki from 1947 to September 1974. One-fourth of the patients with transposition were seen within the past 4 years. Since Acta Piediatr Srand 64
786
B . Landtman et al.
Table 1. Clinical and aictopsy data on 140 infants and children with transposition of the great arteries The figures indicate numbers of patients Sex Age Under 7 d 7d-I m 1-3 m 3-6 m 6 m-1 yr 1-3 yr 3-5 yr 5-12 yr Total
Total
M
F
36 29 25 23 5 15
22 16 20 13 3 10
2 5 140
I 4 89
14 13 5 10 2 5 I 1 51
Heart failure
Cyanosis
23 15 22 19 4
34 26 25 22 4
11
15
1
L
4 109
5 133
7
Noncardiac malformations 13 7 7 7 I 2 1 1
39
1967, balloon atrial septostomy has been performed in 61 cases. A total of 121 infants and children with transposition have undergone this procedure and/or cardiac surgery at the hospital. The definition of transposition was based on the main criteria suggested by Paul & van Praagh (16). Transposition with the aorta arising from the right ventricle and the pulmonary artery from the left occurred in 122 of the cases. Eleven patients had a double outlet right ventricle and 7 had transposition with a single ventricle. Needless to say, the anatomical differentiation of transposition from certain other complicated cardiac malformations was sometimes a question of interpretation. Information on the patients was collected from the autopsy reports and from the clinical records made on the children during treatment at the hospital. The assessment of the immediate cause of death was not always easy. Indeed, the causes were frequently multiple particularly in the neonates and young infants. In presenting the results, reference will therefore be made only to significant clinical findings and major pathological changes, without any attempt being made to separate primary from secondary causes of death in individual cases. Thirty-seven patients died following balloon atrial septostomy and/or cardiac surgery and 7 died after emergency operations for extracardiac malformations. The causes of death did not differ significantly in the children with “classical” transposition, a double outlet right ventricle, and transposition and a single ventricle. Hence, the three groups will be discussed together.
RESULTS Some main clinical and autopsy data on the 140 patients are summarized in Table 1. There were 89 boys and 5 1 girls. Moderate or severe asphyxia at birth occurred in 72 of the cases. Thirteen patients had a birth weight of less Acta Prediatr Scand 64
Infections
Various Vascular disaccidents orders
14 16
11
15
6 6
13 5 3 2
8
3
13 4 8 2 1 73
a
Septostomy and/or Other cardiac operasurgery tions 10
5
4 6 4 2 9
1 1
2
4
2
41
30
37
7
than 2500 g. The remaining children were comparatively heavy at birth (average 3 390 g) but most of them showed marked retardation in growth, their weight at the time of death being below the 23th percentile in 44% of the cases. Hence, a poor general condition was a common contributory cause of death. Death occurred during the first year of life in 118 cases (84%). Almost half of the patients were under one month and one-fourth less than 7 days old. Five patients, 2 of whom had a single ventricle, lived for more than 5 years. The oldest patien) was 12 years old. Associated cardiac anomalies were common. Ventricular and atrial septal defects occurred in 87 and 27 cases, respectively. A patent ductus arteriosus was present in 79 cases. Nineteen patients had pulmonic stenosis. Additional cardiovascular anomalies were encountered in 35 patients. These included coarctation of the aorta (8 cases), anomalies of the venous return (8 cases) and solitary cases of aortic and mitral stenosis, endocardia1 fibroelastosis, dextrocardia, common atrioventricular canal, single coronary artery, hypoplastic left heart syndrome, tricuspid atresia, etc. Most of the patients with these complicated lesions died during the neonatal period. Congestive heart failure was .a common clinical finding and a main cause of death in 109
Causes of death in transposition of the great arteries
cases (Table I). All but 7 patients were cyanotic. Pathological heart murmurs were often lacking in the neonates and occurred in 65 9% of all cases. Single or multiple extracardiac malformations were encountered in 39 patients (Table 1). These lesions were considered a main cause of death in 22 cases. The anomalies were confined to the central nervous system in 7 and to the lungs in 3 cases. Esophageal atresia (4 cases) and anal atresia (5 cases) were the most common malformations of the alimentary tract, encountered in 16 patients. Eleven patients had anomalies of the urinary system including hydronephrosis in 5 and agenesis of the kidney in 2 cases. Cleft palate (4 cases) and anomalies of the spine ( 5 cases) were the most common of 16 malformations of the skeleton. One patient had choanal atresia. Miscellaneous anomalies ( 18 cases) included situs inversus in 5 and asplenia in 4 cases. One patient had Down’s syndrome. Major extracardiac malformations were rare in the older children. Thus, of 22 patients over one year of age, only 4 had minor anomalies of other organs. Various infections contributed to the fatal outcome in 73 of the cases (Table 1). Pneumonia occurred in 58 patients. Other infections included gastroenteritis in 6 and septicemia in 5 cases. One patient had a brain abscess and one had carditis. Vascular accidents (hemorrhages and thromboembolism) occurred in 41 patients (Table 1). These lesions were encountered in the brain in 20, in the lungs in 16, and in abdominal organs in 10 cases. One patient had cardiac infarction. Various diseases were causes of death in 30 cases. These included hyaline membrane disease and/or atelectases of the lungs ( 15 cases) and solitary cases of nephropathies, hemolytic disease of the newborn, cerebral lesions, intussusception, etc. One child had a renal tumour. Five patients died following perforation of the heart during cardiac catheterization.
787
Balloon atrial septostomy and/or cardiac surgery were performed on 37 patients. Thirteen patients had balloon septostomy only. A Mustard operation was performed on 5 patients and 15 underwent shunt procedures or operative septostomy . Death occurred within a week after septostomy or surgery in 31 cases. Two of the patients had a double outlet right ventricle and 3 had transposition with a single ventricle. Cardiac anomalies, in addition to septa1 defects, patent ductus arteriosus and pulmonic stenosis, were encountered in 6 cases. Table 1 shows the age of the patient at the time of death. Twenty were under 3 months old. Extracardiac malformations were present in 8 patients but in only one was the anomaly considered a main cause of death. Vascular accidents were comparatively common, occurring in 18 of the cases. The incidence of heart failure and other main causes of death was by and large the same in surgically and conservatively treated cases. An additional 7 patients died following operations for extracardiac malformations. DISCUSSION Mortality statistics in transposition of the great arteries are not readily comparable because of differences in methods employed in published reports. Although the present study comprised a selected group of patients, it illustrates the complex symptomatology and therapeutic problems presented by critically ill infants with this cardiac malformation. Transposition occurred in 14% of 1000 cases of congenital heart disease in the present autopsy series. The incidence of transposition in autopsy series of congenital heart disease varies in reports from some other pediatric centres between 6.7 and 20.8% (4, 6, 7, 1 I , 18). There is nd evidence that the overall incidence of transposition in Finland has significantly changed during the time period covered by the study. One-fourth of the patients were seen during the past 4 years but, since the introduction of balloon atrial septostomy in Actu Pzdiutr Scnnd 64
788
B . Landtman et al.
1967, an increasing number of newborns suspected of having transposition are being referred to our hospital. The present study supports a common observation according to which transposition shows a male preponderance and the birth weight of the patients is comparatively high (19). The order of birth, on the other hand, did not significantly differ from that of Finnish children in general (8). Associated cardiovascular anomalies were somewhat more common in the present series than in autopsied cases of transposition reported from some other pediatric centres (6, 9, 12, 16, 19). Most authors agree that congestive heart failure augmented by a varying degree of hypoxia is the most common single cause of death in transposition. Heart failure occurred in 78 % of the patients in the present series and cyanosis was an almost constant finding. In a review of 308 fatal cases of transposition, Sharer (19) considered heart failure the primary cause of death in 90 and Liebman et al. (9) assessed that failure accounted for death in 71 of 282 autopsied cases. Surgical deaths were the most common in both these studies. Extracardiac causes of death were more common in the present than in many previous studies. Malformations of other vital organs occurred in 39 patients. Sharer (19) considered noncardiac anomalies a primary cause of death in only 2 of 308 cases of transposition and Liebman et a]. (9) did not mention that such malformations had contributed to the death of any of 282 patients studied post mortem. Several autopsy studies have shown an incidence of non-cardiac malformations in transposition of less than 5 % (3, 9, 18, 22) but an incidence of 23 95 was reported by Okada et al. (13) in an autopsy study of 196 cases. It should be mentioned that anomalies of other organs were less common in transposition than in other cardiac malformations in the present autopsy series (8). Various infections contributed to the fatal outcome in half of the cases. In some of the aforementioned studies, infections, mostly Actu Pzdiatr Scand 64
pneumonia, were considered a main cause of death in 10 to 25% of the cases ( 4 , 9 , 15, 19). A brain abscess occurred in one surgical case in the present series. Sharer (19) reported this complication in 4 of 409 autopsied cases of transposition. The occurrence of vascular accidents in transposition is well recognized. Oppenheimer (14) found such lesions in 37 of 180 cases studied post mortem. Of 43 infants with transposition palliated by balloon atrial septostomy 5 developed cerebrovascular accidents and 7 others showed seizure activity during the follow-up ( 1 ) . Parsons et al. (15) reported that 9 of 32 deaths following this procedure resulted from thrombosis mainly of the cerebral vessels. The present study supports an observation according to which vascular accidents are more common in surgically than in conservatively treated patients with congenital heart disease (2, 20, 21). Various other disorders such as hyaline membrane disease and nephropathies are to our knowledge not mentioned as causes of death in transposition in previous reports. The outlook of children with transposition of the great arteries depends on both the morphology of the heart malformation and the occurrence of primary extracardiac diseases and complications. These factors also govern the ultimate benefit derived from balloon atrial septostomy and cardiac surgery. Hoffman ( 5 ) has recently reviewed the difficulties involved in assessing the immediate cause of death in fatal cases of congenital heart disease. In order to show that death was due to the cardiac malformation only, there should be supportive clinical evidence which, however, is lacking in many autopsy reports. The high incidence of extracardiac causes of death in the present series suggests'that such disorders might explain differences in mortality statistics and operative results in transposition of the great arteries. ACKNOWLEDGEMENTS The study supported by a grant from Sigrid Juselius Foundation, Helsinki.
Causes of death in transposition of the great arteries
REFERENCES 1. Baker, F . , Baker, L . , Zoltun, R. & Zuberbuhler, J . R.:
2.
3.
4.
5.
6.
7.
8.
9.
10. 11.
Effectiveness of the Rashkind procedure in transposition of the great arteries. Circulation, 43: 1, 1971. Bertrong, M. & Sabiston, D. C., Jr: Cerebral lesions in congenital heart disease. A review of autopsies on one hundred and sixty-two cases. Johns Hopkins Med J , 89:384, 1951. Boesen, J., Melchior, J. C., Tersley, E. & Vendel, S.: Extracardiac congenital malformations in children with congenital heart disease. Acta Paedi'atr Scand, Suppl. 146: 28, 1963. Fontane, R. S. & Edwards, J . E.: Congenital cardiac disease; A review, of 357 cases studied pathologicully. W. B. Saunders, Philadelphia and London 1962. Hoffman, J. 1. E.: Natural history of congenital heart disease. Problems in its assessment with special reference to ventricular septal defects. circulation, 37: 97, 1968. Keith, J. D., Rowe, R. D. & Vlad, P.: Heart disease in infancy and childhood. MacMillan, New York 1967, 2nd ed. Lambert, E. C., Canent, R. V. & Hohn, A. R.: Congenital cardiac anomalies in the newborn. A review of conditions causing death or severe distress in the first month of life. Pediatrics, 37: 343, 1966. Landtman, B.: Clinical and morphological studies in congenital heart disease. A review of 777 cases. Acta Paediatr Scand, Suppl. 213, 1971. Liebman, J., Collum, L. & Belloc, N. D.: Natural history of transposition of the great arteries. Anatomy and birth and death characteristics. Circulation, 40: 237, 1969. Mustard, W. T.: Successful two-stage correction of transposition of the great vessels. Surgery, 55: 469, 1964. Nadas, A . S . & Fyler, D. C.: Pediatric cardiology. W. B. Saunders, Philadelphia-London-Toronto 1972, 3rd ed.
12. Noonan, A., Nadas, A. S., Rudolph, A. M. &Harris, G. B. C.: TransDosition of the ereat arteries. A correlation of clinical, physiologic and autopsy data. N Engl J Med. 263: 592, 1960.
-
789
13. Okada, R., Johnson, D. & Lev, M.: Extracardiac malformations associated with congenital heart disease. Arch Pathol, 85.649, 1968. 14. Oppenheimer, E. H.: Arterial thrombosis ( ? paradoxial embolism) in association with transposition of the great vessels. Johns Hopkins Med J , 124: 202, 1969. 15. Parsons, C. G., Astley, R., Burrows, F. G. 0. & Singh, S. P.: Transposition of the great arteries. A study of 65 infants followed for 1 to 4 years after balloon septostomy. Brit Heart J , 33: 725, 1971. 16. Paul, M. H., van Praagh, S. & van Praagh, R.: Transposition of the great arteries. In H. Watson (ed.): Paediutric cardiology. Lloyd-Luke, London 1968, p. 576. 17. Rashkind, W. J. & Miller, W. W.: Creation of an atrial septal defect without thoracotomy. JAMA, 196; 991, 1966. 18. Rowe, R. D. & Mehrizi, A,: The neonate with congenital heart disease. W. B. Saunders, PhiladelphiaLondon-Toronto 1966. 19. Sharer, R. M.: Complete transposition of the great arteries. Academic Press, New York and London 1973. 20. Terplan, K. L.: Patterns of brain damage in infants and children with congenital heart disease. Association with catherization and surgical procedures. Am J Dis Chiid, 125: 175, 1973. 21. Wigger, H. J., Bransilver, B. R. & Blanc, W. A,: Thrombosis due to catherization in infants and children. J Pediatr, 76: I , 1970. 22. Wiland, 0. K.: Extracardiac anomalies in association with congenital heart disease. Analysis of 200 necropsy cases. Lab Inrzest, 5 : 380, 1956. Submitted Febr, 17, 1975 Accepted April 2, 1975
(B. L.) The Children's Hospital University of Helsinki SF-00290 Helsinki 29 Finland
Acta Pzdiatr Scand 64
CAUSES OF DEATH IN TRANSPOSITION OF THE GREAT ARTERIES A Clinical and Autopsy Study of 140 Cases B. LANDTMAN, I. LOUHIMO. J. RAPOLA and LEENA TUUTERI From the Children’s Hospital, Unibsersity of Helsinki, Helsinki, Finlund
ABSTRACT. Landtman, B., Louhimo, I., Rapola, J. and Tuuteri, Leena. (The Children’s Hospital, University of Helsinki, Helsinki, Finland.) Causes of death in transposition of the great arteries. A clinical and autopsy study of 140 cases. Acta Paediatr Scand, 64: 785, 1975.-The causes of death were assessed in 140 infants and children with transposition of the great arteries studied clinically and post mortem. Half of the children were under one month old. Death occurred during the first year of life in 118 cases. Balloon atrial septostomy and/or cardiac surgery were performed in 37 cases, and 7 patients died following operations for extracardiac malformations. Congestive heart failure was the most common single cause of death, occurring in 109 cases. All but 7 patients were cyanotic. Extracardiac malformations were encountered in 39 patients and were considered a main cause of death in 22 of these. Various infections, mostly pneumonia, occurred in half of the cases. Forty-one patients had vascular accidents in various organs. These complications were more common in operated than in nonoperated cases. Miscellaneous causes of death, including hyaline membrane disease and/or pulmonary atelectases, occurred in 30 patients. The study illustrated the complex symptomatology and therapeutic problems presented by critically ill infants with transposition of the great arteries.
KEY WORDS: Transposition of the great arteries, causes of death in congenital heart disease
The poor outlook of children with transposition of the great arteries is well documented. In a review of 201 conservatively treated patients, Sharer (19) stated that only 45 survived the first year of life and that most deaths occurred in the neonatal period and early infancy. A mortality of 90% during the first year of life has been reported from some centers (6, 9). The introduction of balloon atrial septostomy ( 17) and subsequent hernodynamic correction ( 10) has dramatically changed the outlook for children with transposition. These procedures are now being performed in most cardiac centers and, as a result, many patients are now leading a normal life. The natural history of transposition and the 5 I -75287’6
results of septostomy and surgical procedures have been reviewed by several authors. In most of these studies, however, less attention has been paid to the assessment of the causes of death in conservatively and surgically treated cases. The present study aims at shedding further light on this question by reviewing clinical and autopsy findings in 140 infants and children with transposition treated and lost at our hospital during a 28-year period.
MATERIAL AND METHODS Transposition of the great arteries occurred in 140 of 1 OOO infants and children with congenital heart disease who came to autopsy at the Children’s Hospital in Helsinki from 1947 to September 1974. One-fourth of the patients with transposition were seen within the past 4 years. Since Acta Piediatr Srand 64
786
B . Landtman et al.
Table 1. Clinical and aictopsy data on 140 infants and children with transposition of the great arteries The figures indicate numbers of patients Sex Age Under 7 d 7d-I m 1-3 m 3-6 m 6 m-1 yr 1-3 yr 3-5 yr 5-12 yr Total
Total
M
F
36 29 25 23 5 15
22 16 20 13 3 10
2 5 140
I 4 89
14 13 5 10 2 5 I 1 51
Heart failure
Cyanosis
23 15 22 19 4
34 26 25 22 4
11
15
1
L
4 109
5 133
7
Noncardiac malformations 13 7 7 7 I 2 1 1
39
1967, balloon atrial septostomy has been performed in 61 cases. A total of 121 infants and children with transposition have undergone this procedure and/or cardiac surgery at the hospital. The definition of transposition was based on the main criteria suggested by Paul & van Praagh (16). Transposition with the aorta arising from the right ventricle and the pulmonary artery from the left occurred in 122 of the cases. Eleven patients had a double outlet right ventricle and 7 had transposition with a single ventricle. Needless to say, the anatomical differentiation of transposition from certain other complicated cardiac malformations was sometimes a question of interpretation. Information on the patients was collected from the autopsy reports and from the clinical records made on the children during treatment at the hospital. The assessment of the immediate cause of death was not always easy. Indeed, the causes were frequently multiple particularly in the neonates and young infants. In presenting the results, reference will therefore be made only to significant clinical findings and major pathological changes, without any attempt being made to separate primary from secondary causes of death in individual cases. Thirty-seven patients died following balloon atrial septostomy and/or cardiac surgery and 7 died after emergency operations for extracardiac malformations. The causes of death did not differ significantly in the children with “classical” transposition, a double outlet right ventricle, and transposition and a single ventricle. Hence, the three groups will be discussed together.
RESULTS Some main clinical and autopsy data on the 140 patients are summarized in Table 1. There were 89 boys and 5 1 girls. Moderate or severe asphyxia at birth occurred in 72 of the cases. Thirteen patients had a birth weight of less Acta Prediatr Scand 64
Infections
Various Vascular disaccidents orders
14 16
11
15
6 6
13 5 3 2
8
3
13 4 8 2 1 73
a
Septostomy and/or Other cardiac operasurgery tions 10
5
4 6 4 2 9
1 1
2
4
2
41
30
37
7
than 2500 g. The remaining children were comparatively heavy at birth (average 3 390 g) but most of them showed marked retardation in growth, their weight at the time of death being below the 23th percentile in 44% of the cases. Hence, a poor general condition was a common contributory cause of death. Death occurred during the first year of life in 118 cases (84%). Almost half of the patients were under one month and one-fourth less than 7 days old. Five patients, 2 of whom had a single ventricle, lived for more than 5 years. The oldest patien) was 12 years old. Associated cardiac anomalies were common. Ventricular and atrial septal defects occurred in 87 and 27 cases, respectively. A patent ductus arteriosus was present in 79 cases. Nineteen patients had pulmonic stenosis. Additional cardiovascular anomalies were encountered in 35 patients. These included coarctation of the aorta (8 cases), anomalies of the venous return (8 cases) and solitary cases of aortic and mitral stenosis, endocardia1 fibroelastosis, dextrocardia, common atrioventricular canal, single coronary artery, hypoplastic left heart syndrome, tricuspid atresia, etc. Most of the patients with these complicated lesions died during the neonatal period. Congestive heart failure was .a common clinical finding and a main cause of death in 109
Causes of death in transposition of the great arteries
cases (Table I). All but 7 patients were cyanotic. Pathological heart murmurs were often lacking in the neonates and occurred in 65 9% of all cases. Single or multiple extracardiac malformations were encountered in 39 patients (Table 1). These lesions were considered a main cause of death in 22 cases. The anomalies were confined to the central nervous system in 7 and to the lungs in 3 cases. Esophageal atresia (4 cases) and anal atresia (5 cases) were the most common malformations of the alimentary tract, encountered in 16 patients. Eleven patients had anomalies of the urinary system including hydronephrosis in 5 and agenesis of the kidney in 2 cases. Cleft palate (4 cases) and anomalies of the spine ( 5 cases) were the most common of 16 malformations of the skeleton. One patient had choanal atresia. Miscellaneous anomalies ( 18 cases) included situs inversus in 5 and asplenia in 4 cases. One patient had Down’s syndrome. Major extracardiac malformations were rare in the older children. Thus, of 22 patients over one year of age, only 4 had minor anomalies of other organs. Various infections contributed to the fatal outcome in 73 of the cases (Table 1). Pneumonia occurred in 58 patients. Other infections included gastroenteritis in 6 and septicemia in 5 cases. One patient had a brain abscess and one had carditis. Vascular accidents (hemorrhages and thromboembolism) occurred in 41 patients (Table 1). These lesions were encountered in the brain in 20, in the lungs in 16, and in abdominal organs in 10 cases. One patient had cardiac infarction. Various diseases were causes of death in 30 cases. These included hyaline membrane disease and/or atelectases of the lungs ( 15 cases) and solitary cases of nephropathies, hemolytic disease of the newborn, cerebral lesions, intussusception, etc. One child had a renal tumour. Five patients died following perforation of the heart during cardiac catheterization.
787
Balloon atrial septostomy and/or cardiac surgery were performed on 37 patients. Thirteen patients had balloon septostomy only. A Mustard operation was performed on 5 patients and 15 underwent shunt procedures or operative septostomy . Death occurred within a week after septostomy or surgery in 31 cases. Two of the patients had a double outlet right ventricle and 3 had transposition with a single ventricle. Cardiac anomalies, in addition to septa1 defects, patent ductus arteriosus and pulmonic stenosis, were encountered in 6 cases. Table 1 shows the age of the patient at the time of death. Twenty were under 3 months old. Extracardiac malformations were present in 8 patients but in only one was the anomaly considered a main cause of death. Vascular accidents were comparatively common, occurring in 18 of the cases. The incidence of heart failure and other main causes of death was by and large the same in surgically and conservatively treated cases. An additional 7 patients died following operations for extracardiac malformations. DISCUSSION Mortality statistics in transposition of the great arteries are not readily comparable because of differences in methods employed in published reports. Although the present study comprised a selected group of patients, it illustrates the complex symptomatology and therapeutic problems presented by critically ill infants with this cardiac malformation. Transposition occurred in 14% of 1000 cases of congenital heart disease in the present autopsy series. The incidence of transposition in autopsy series of congenital heart disease varies in reports from some other pediatric centres between 6.7 and 20.8% (4, 6, 7, 1 I , 18). There is nd evidence that the overall incidence of transposition in Finland has significantly changed during the time period covered by the study. One-fourth of the patients were seen during the past 4 years but, since the introduction of balloon atrial septostomy in Actu Pzdiutr Scnnd 64
788
B . Landtman et al.
1967, an increasing number of newborns suspected of having transposition are being referred to our hospital. The present study supports a common observation according to which transposition shows a male preponderance and the birth weight of the patients is comparatively high (19). The order of birth, on the other hand, did not significantly differ from that of Finnish children in general (8). Associated cardiovascular anomalies were somewhat more common in the present series than in autopsied cases of transposition reported from some other pediatric centres (6, 9, 12, 16, 19). Most authors agree that congestive heart failure augmented by a varying degree of hypoxia is the most common single cause of death in transposition. Heart failure occurred in 78 % of the patients in the present series and cyanosis was an almost constant finding. In a review of 308 fatal cases of transposition, Sharer (19) considered heart failure the primary cause of death in 90 and Liebman et al. (9) assessed that failure accounted for death in 71 of 282 autopsied cases. Surgical deaths were the most common in both these studies. Extracardiac causes of death were more common in the present than in many previous studies. Malformations of other vital organs occurred in 39 patients. Sharer (19) considered noncardiac anomalies a primary cause of death in only 2 of 308 cases of transposition and Liebman et a]. (9) did not mention that such malformations had contributed to the death of any of 282 patients studied post mortem. Several autopsy studies have shown an incidence of non-cardiac malformations in transposition of less than 5 % (3, 9, 18, 22) but an incidence of 23 95 was reported by Okada et al. (13) in an autopsy study of 196 cases. It should be mentioned that anomalies of other organs were less common in transposition than in other cardiac malformations in the present autopsy series (8). Various infections contributed to the fatal outcome in half of the cases. In some of the aforementioned studies, infections, mostly Actu Pzdiatr Scand 64
pneumonia, were considered a main cause of death in 10 to 25% of the cases ( 4 , 9 , 15, 19). A brain abscess occurred in one surgical case in the present series. Sharer (19) reported this complication in 4 of 409 autopsied cases of transposition. The occurrence of vascular accidents in transposition is well recognized. Oppenheimer (14) found such lesions in 37 of 180 cases studied post mortem. Of 43 infants with transposition palliated by balloon atrial septostomy 5 developed cerebrovascular accidents and 7 others showed seizure activity during the follow-up ( 1 ) . Parsons et al. (15) reported that 9 of 32 deaths following this procedure resulted from thrombosis mainly of the cerebral vessels. The present study supports an observation according to which vascular accidents are more common in surgically than in conservatively treated patients with congenital heart disease (2, 20, 21). Various other disorders such as hyaline membrane disease and nephropathies are to our knowledge not mentioned as causes of death in transposition in previous reports. The outlook of children with transposition of the great arteries depends on both the morphology of the heart malformation and the occurrence of primary extracardiac diseases and complications. These factors also govern the ultimate benefit derived from balloon atrial septostomy and cardiac surgery. Hoffman ( 5 ) has recently reviewed the difficulties involved in assessing the immediate cause of death in fatal cases of congenital heart disease. In order to show that death was due to the cardiac malformation only, there should be supportive clinical evidence which, however, is lacking in many autopsy reports. The high incidence of extracardiac causes of death in the present series suggests'that such disorders might explain differences in mortality statistics and operative results in transposition of the great arteries. ACKNOWLEDGEMENTS The study supported by a grant from Sigrid Juselius Foundation, Helsinki.
Causes of death in transposition of the great arteries
REFERENCES 1. Baker, F . , Baker, L . , Zoltun, R. & Zuberbuhler, J . R.:
2.
3.
4.
5.
6.
7.
8.
9.
10. 11.
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(B. L.) The Children's Hospital University of Helsinki SF-00290 Helsinki 29 Finland
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