Postoperative Pathology of Congenital Heart Disease
RICHARD VAN PRAAGH, MARC S. VISNER, BA
MD,
FACC
Busfon. Massachusefts
From the Departments of Cardiology and Pathology of the Children’s Hospital Medical Center and the Departments of Pediatrics, Pathology and the Fourth Year Class of Harvard Medical School, Boston, Mass. This study was supported in part by Program Project Grant K-10436 from the National Heart and Lung Institute. National Institutes of Health, Bethesda, Md. Manuscript received July 21, 1975; revised manuscript received January 9. 1976, accepted January 14, 1976. Address for reprints: Richard Van Praagh, MD, Children’s Hospital Medical Center, 300 Longwood Ave., Boston, Mass. 02115.
Complete and unselected data concerning the postoperative pathology of congenital heart disease are presented for the first time. This study was based on 2,365 autopsies performed at the Children’s Hospital Medical Center, Boston, in the 9 years from 1966 through 1974. Of these, 566 autopsies (25 percent) revealed congenital heart disease-236 performed in medically treated patients (41 percent) and 346 in surgically treated patients (59 percent). Tetralogy of Fallot, including cases with pulmonary outflow tract atresia and other associated malformations, was the congenital heart disease most often encountered in the postoperative autopsy series (66 cases, 25 percent of that series). D-transposition of the great arteries, including cases with other associated anomalies, was second (54 cases, 15.5 percent). Early death (hospital mortality) accounted for 320 (92 percent) of the 346 surgical cases; late death occurred in 26 patients (6 percent). Causes of late postoperative death included arrhythmias, excessively small ventricular septal defect with tricuspid atresia, massive hemoptysis, rupture of the pulmonary artery, cyanotic spell, congestive heart failure and infection. Prophylactic penicillin is recommended for patients with the asplenia syndrome because of thelr probably enhanced vulnerability to fulminating septicemia by encapsulated bacteria such as the pneumococcus. Completeness and lack of selection in reporting data are essential in the interests of perspective and comparability of findings.
In a recent meeting on emerging problems in adults and children after cardiac surgery, Engle’ posed the following difficult question: As assessed from the standpoint of cardiac pathology, what problems will patients with congenital heart disease encounter after cardiac surgery in the future? To consider this qu‘estion, we thought it necessary first to establish our past postoperative problems. Hence, this presentation is concerned with both past problems and future projections. In making this investigation, we found virtually no relevant reports. To our knowledge, comparable data have not been published previously. This finding in turn led us to appreciate how important it is that published data, whether pathologic findings or surgical results, be complete and unselected. Otherwise, it is not possible to make valid comparisons of data from different centers. Even within one center it is not possible to see an individual finding in accurate perspective unless the data are complete and unselected. Case Material A study was made of all autopsies performed in patients with congenital heart disease at the Children’s Hospital Medical Center in Boston in the 9 vears from 1966 through 1974. No case was omitted for any reason. During this time, 2,365 autopsies were performed. Of these, 586 revealed congenital heart disease.
August 1976
The American Journal of CARDIOLOGY
Volume 38
225
CONGENITAL HEART DISEASE-VAN
PRAAGH AND VISNER
Surgically treated patients ranged from a low of 50 percent of all autopsy cases of congenital heart disease in 1970 to a high of 71 percent in 1974 (average 59 percent from 1966 through 1974, Fig. 3, Table I). Early versus late deaths: Early death (hospital mortality) in 320 cases accounted for 92 percent of 348 postoperative autopsy cases of congenital heart disease from 1966 through 1974. Lizte death (after hospital discharge) in 28 cases accounted for 8 percent of postoperative autopsy cases of congenital heart disease during this 9 year period. The causes of late death in each of these 28 cases are summarized in Table II. Types of congenital heart disease: The cardiac anomalies associated with early and late postoperative death from 1966 through 1974 are summarized in Table III. For 7 of these 9 years (1970 and 1972 being the exceptions), tetralogy of Fallot, including cases with pulmonary outflow tract atresia and other associated malformations, and d-transposition of the great arteries, including cases with additional associated anomalies, were, respectively, the first and second or second and first most frequent types of congenital heart disease associated with postoperative autopsies. During this 9
Findings Frequency: The annual frequency of autopsy cases of congenital heart disease ranged from a low of 21 percent of all autopsies performed in 1967, to a high of 29 percent in 1969 (average 25 percent from 1966 through 1974, Fig. 1, Table I). Medical versus postsurgical autopsies: Medically treated patients, who underwent no cardiovascular surgery, ranged from a low of 29 percent of all autopsy cases of congenital heart disease in 1974 to a high of 50 percent in 1970 (average 41 percent from 1966 through 1974, Fig. 2, Table I).
-
1966.1967
1966
1969
1970
1971
FIGURE 1. Autopsy cases of congenital percent
of all autopsies
1972
1973
heat-f disease
1974
expressed
as
in each year.
60% 55 -
1966
1967
1966
1969
1970
1971
1972
1973
-
1974
1966’
1967 ’ 1966’1969
’ 1970 ’ 1971 ’ 1972 ’ 1973 ' 1974 '
FIGURE 2. Autopsy cases of medically treated congenital heart disease
FIGURE 3. Autopsy cases of surgically treated congenital heart disease
expressed as percent of all autopsy cases of congenital in each year.
(CHD) expressed as percent disease in each year.
heart disease
of all autopsy cases of congenital
heart
TABLE I Autopsy
Statistics, Children’s
Hospital
1966 Autopsy
Cases
All All with CHD* Medically treated+ Surgically treated+
Medical
1967
1968 ___
226
August 1976
Boston,
1969 ____
1966
Through
1970
1974
1971
1972
1973
1974
Total
no.
%
“0.
%
“0.
%
“0.
%
“0.
%
“0.
%
“0.
%
“0.
%
“0.
%
“0.
%
321 75 33 42
23 44 56
275 58 27 31
21 47 53
295 75 35 40
25 47 53
292 84 33 51
29 39 61
263 60 30 30
23 50 50
280 76 25 51
27 33 67
214 56 23 33
26 41 59
212 54 18 36
25 33 67
213 48 14 34
23 29 71
2,365 586 238. 348
25 41 59
Percentages for each year are percentages + Percentages for each year are percentages CHD = congenital heart disease. l
Center,
of all autopsies performed that year. of all autopsy cases of congenital heart disease that year.
The American Journal ot CARDIOLOGY
Volume 36
CONGENITAL HEART DISEASE-VAN
TABLE
II
Late Deaths
(by year) in Postoperative
Patients
(28 cases)
Year
no. (%)
1966
2 of 42 (5%)
ToF with block, 3 mo postop ToF, shunt occluded by SBE vegetations, 1 l/2 yr postop
1967
5 of 31 (16%)
D-TGA, meningitis 4 l/2 yr post ASD creation D-TGA, aspiration 14 mo post ASD creation Down’s syndrome, CCAVC and PS, CHF 2 yr post Potts procedure L-TGA, IS,L,Ll, VSD and complete A-V block, CHF 1 l/2 mo post pacemaker LCA from PA with EFE of LV, CHF 8 l/2 mo post LCA ligation
Diagnoses
PRAAGH AND VISNER
year period as a whole (Table IV), tetralogy of Fallot was the most common type of congenital heart disease in this series of postoperative autopsies (25.3 percent), and d-transposition of the great arteries was second (15.5 percent). Discussion
1968
0 of 40
1969
4 of 51 (8%)
ToF with block, 2 2/3 yr postop, pacemaker failure ToF, 2 l/3 yr post repair, recurrent VT Extreme PS with IVS, 3 7/12 yr post Waterston procedure, CHF, PAT ToF, 15 yr post pleural stripping, cyanotic spell
1970
2 of 30 (7%)
P Atr with IVS, 5 3/4 mo post Waterston procedure, arrhythmia Asplenia with PS, 3 mo post Waterston procedure, CHF
1971
5 of 51 (10%)
ToF, 19 yr post Potts, rupture of MPA ToF, 2 1;5 ir post 8-T VF during surcerv for soinal fusion ToF,B iI3 yr post B-T, sudden unexpected death, ? arrhythmia M Atr with TR. 4 516 yr post ASD, massive hemoptysis ToF, 7 314 yr post B-T, SBE with massive hemoptysis
1972
1 of 33 (3%)
Subaortic fibrous ring, 1 l/2 mo post repair, fatal hemorrhage from cerebral arteriovenous aneurysm
1973
3 of 36 (8%)
PDA division and MPA band, 3 7/12 yr, aneurysm of pars producing subaortic stenosis “Recoarctation” of aorta, 4 mo postop Asplenia, 5 l/6 yr post Waterston, fulminating pneumococcal septicemia
1974
6 of 34 (18%)
ToF, 6 112 yr post repair, recurrent VT-VF D-TGA blocked, 1 mo postop during pacemaker change D-TGA, 11 mo post Rastelli, infected patch from sternal abscess D-TGA, VSD, PS, 22 yr post Potts, rupture of RPA DORV with PS, 4 yr post pleurectomy, brain abscess L-TGA with left-sided T Atr and “subaortic stenosis,” 3 112 yr post ASD and MPA band, AF then VF
AF = atrial fibrillation; ASD = atrial septal defect; A-V = atrioventricular; B-T = Blalock-Taussig anastomosis; CCAVC = complete common atrioventricular canal; CHF = congestive heart failure; D = dextro; DORV = double outlet right ventricle; EFE = endocardial fibroelastosis; IVS = intact ventricular septum; L = levo; LCA = left coronary artery; LV = left ventricle; M Atr = mitral atresia; MPA = main pulmonary artery; PA = pulmonary artery; PAT = paroxysmal atrial tachycardia; P Atr * pulmonary atresia; PDA = patent ductus = postoperatively; PS = pulmonary stenosis; arteriosus; postop RPA = right pulmonary artery; SBE = subacute bacterial endocarditis; fS,L,LI = situs solitus of the viscera and atria; ventricular /-loop and /-transposition of great arteries; T Atr = tricuspid atresia; TGA = transposition of great arteries; ToF = tetralogy of Fallot; TR = tricuspid regurgitation; VF = ventricular fibrillation; VSD = ventricular septal defect; VT = ventricular tachycardia.
August
Since this is the first presentation of complete and unselected data concerning the postoperative pathologic findings in congenital heart disease, data from other centers are -needed to achieve a more complete and representative understanding of this topic. Congenital heart disease accounted for 25 percent of all autopsies performed at the Children’s Hospital Medical Center in Boston during the 9 year study period (Fig. 1, Table I) and was by far the leading cause of death at our hospital during the past decade. Leukemia plus lymphoma was second, constituting approximately 15 percent of all autopsies.2 Each of the other important causes of death accounted for 10 percent or less of all autopsies. These data are biased by the fact that our hospital is a referral center for major disease in infants and children. Congenital heart disease may also be the leading cause of death in other children’s hospitals, but such data are not now available. Our data show that among the autopsy cases of congenital heart disease, the percent of medical cases is decreasing (Fig. 2) and the percent of surgical cases is increasing (Fig. 3). These statistics are thought to reflect the fact that as our surgical management of congenital heart disease has continued to improve, fewer patients have been managed medically and more have been operated upon. Not only has the percent of-our surgical patients increased, but also the progressively more difficult forms of congenital heart disease have been managed surgically in recent years. In absolute numbers, as opposed to percentages, all autopsy cases are decreasing (Table I). This finding probably reflects the declining birth rate: Fewer autopsies of all kinds are being performed and there are fewer autopsy cases of congenital heart disease, whether medical or surgical, or both. Types of Congenital Heart Disease Tetralogy of Fallot, including cases with pulmonary outflow tract atresia and other associated anomalies, was the congenital heart disease most often associated with postoperative death, accounting for 25.3 percent of all postoperative autopsy cases of congenital heart disease (Table IV). D-transposition of the great arteries, including cases with additional associated anomalies, was second, constituting 15.5 percent of all postoperative necropsies. These are unfamiliar statistics. One must be careful not to misread these autopsy statistics as surgical mortality rates. They are not. Instead they are thought to reflect a difficult to dissect mixture of (1) frequency in surgical case load, and (2) surgical difficulty. Initially, we were surprised by these necropsy statistics. We had thought that tetralogy of Fallot was essentially a solved
1976
The Am&can
Journal of CARDIOLOGY
Volume 33
227
CONGENITAL HEART DISEASE-VAN
TABLE
PRAAGH AND VISNER
III
Malformations
Associated
with Surgical
Malformation
Death:
EarlY and Late Mortalitv
1966
1970
6 (14%)
Preductal TAPVC, Ao Atr
DORV
5 (12%)
Single ventricle Congenital mitral stenosis Truncus arteriosus P Atr with IVS Cardiac malpositions VSD
2 2 2 2
Ebstein’s anomaly T Atr CCAVC Abdominal coarctation MR AP window
1 (2%) 1 (2%)
(5%) (5%) (5%) (5%)
4 (13%)
T Atr
3 (10%)
Single LV TAPVC ASD I with MR Isolated ventricular
2 (6%)
1968
(40 Cases)
ToF
14 (35%)
D-TGA
10 (25%)
PS Premature closure of FO Ao Atr Right yentricular hypoplasia Rubella syndrome Polysplenia ASD II and VSD 1969 ToF
s 2 2 2
1ZI00 (5%) (5%) (5%)
1 1 1 1 1
(2.5%) (2.5%) (2.5%) (2.5%) (2.5%)
(51 Cases)
3 (6%)
IAA Asplenia Rubella syndrome DORV PS (valvular) Preductal coarctation
2 2 2 2 2 2
(4%) (4%) (4%) (4%) (4%) (4%)
228
August 1978
The Amgrican Journal of CARDIOLOGY
(51 Cases)
5 (10%) 5 (10%) 5 (10%)
PS Corrected Preductal AS M Atr
2 2 2 2 2
TGA coarctation
(4%) (4%) (4%) (4%) (4%)
1 (2%) 1 (2%) : 1 1 1 1 1 1 1 1
tzi00 (2%) (2%) (2%) (2%) (2%) (2%) (2%) (2%)
(33 Cases)
IVS
6 (18%)
ToF
5 (15%)
D-TGA TAPVC PDA
2 (6%) 2 (6%) 2 (6%)
Ao Atr DORV Corrected TGA AS Coarctation VSD DILV Subaortic fibrous ring VSD with aortic regurgitation IAA with AP window Isolated levocardia ASD I Truncus arteriosus with DiGeorge’s syndrome
1 1 1 1
ToF
Volume 38
(3%) (3%) (3%) (3%) (3%) (3%)
14 (27%)
1973
Ao Atr Single LV CCAVC ASD I with MR PDA TAPVC L-TGA
1 1 1 1 1 1
TAPVC D-TGA P Atr with IVS
P Atr with
10 (20%) IVS
with aortic rupture
1972
18 (35%)
D-TGA
2 (7%)
TGA
ACM IS, D, LI Overriding TV ASD I I, VSD, PDA Ebstein’s anomaly with PS Partial APVC to RA Aortic atresia Asplenia Aberrant LCA Ectopia cordis Absent PV leaflets VSD with MR Truncus arteriosus
and PS
L-TGA P Atr with IVS Asplenia ASD II Preductal coarctation
3 (10%) 3 (10%)
ToF
inversion
Annulo-aortic ectasia Down’s syndrome with CCAVC Truncus Al Ao Atr with IVS Aberrant LCA from MPA L-TGA VSD P Atr with IVS
supracardiac
1971
(31 Cases) 8 (26%)
4 (13%)
Cor triatriatum Truncus arteriosus VSD PS, VSD, AM6 DORV with PS Marfan’s syndrome
: 1z 00 1 (2%) 1 (2%)
D-TGA
6 (20%) coarctation
Corrected
z 1z100
ToF
(30 Cases)”
ToF
11 (26%)
D-TGA
1967
no. (%I
(42 Cases)
ToF
P Atr with
Malformation
no. f%)
(3%) (3%) (3%) (3%)
(36 Cases) 9 (25%)
D-TGA
5 (14%)
VSD PDA TAPVC Truncus arteriosus
3 3 2 2
(8%) (8%) (5.5%) (5.5%)
Rhabdomyoma Preductal coarctation P Atr with IVS Asplenia with septicemia Polysplenia
1 1 1 1 1
(3%) (3%) (3%) (3%) (3%)
CONGENITAL HEART DISEASE-VAN
TABLE
III
TABLE
(cont’d)
1973
IV
Malformations Found Most Often in 348 Postoperative Autopsy Cases of Congenital Heart Disease, 1966 Through 1974
no. f%)
Malformation (36 Cases) (cont’d)
1 (3%) :zEz T Atr AS Single LV DORV
PRAAGH AND VISNER
Tetralogy of Fallot* D-transposition of great arteries?
: K l(32, 1 (3%) 1 (3%)
no.
%
88 54
25.3 15.5
Including cases with pulmonary outflow tract atresia and other associated malformations. t Including cases with other associated anomalies. l
1974
(34 Cases) 8 (24%)
D-TGA ToF
7 (21%)
VSD
4 112%)
ASD
I
Preductal IAA
3 (9%) coarctation
Truncus arteriosus Down!s syndrome with CAVC and MPA band M Atr with DORV DORV, DI RV and PS PS, myxomatdus T Atr with D-TGA L-TGA with subaortic stenosis 1I,S,L,I 1 atrial noninversion
‘2 1:31 00 1 (3%) 1 (3%) 1 1 1 1 1 1
(3%) (3%) (3%) (3%) (3%) (3%)
Few Mustard procedures were performed for d-transposition of great arteries. ACM IS,D,LI = anatomically corrected maiposition of the great arteries with situs solitus of the viscera and atria, ventricular dfoop and I-malposition of the great arteries; AMB = anomalous muscle bundles; Ao Atr = aortic atresia; AP = aorticopulmonary; APVC = anomalous pulmonary venous connection; AS = aortic stenosis; ASD I and II = primum and secundum atrial septal defect; DILV = double inlet left ventricle; DIRV = double inlet right ventricle; FO = foramen ovale; IAA = interrupted aortic arch; Il.S.L,I 1 = situs inversus of the viscera, situs solitus of the atria, ventricular /-loop and inverted normal relation between the great arteries, MR = mitral regurgitation; PV = pulmonary valve; RA = right atrium; TAPVC = total anomalous pulmonary venous connection; TV = tricuspid valve. Other abbreviations as in Table II. l
surgical problem. However, the data do not support this assumption. Instead, the findings indicate that in terms of the absolute number of postoperative fatalities (as opposed to mortality rates), tetralogy of Fallot is our largest problem, followed by d-transposition of the great arteries. Whether this is also true of other diagnostic and therapeutic centers concerned with congenital heart disease is unknown because such information is not now available. Analysis of the postoperative autopsy statistics by year (Table III) also indicates that tetralogy of Fallot and d-transposition of the great arteries were the leading causes of postoperative death from congenital heart disease during this study period. In 7 of the 9 years (1970 and 1972 being the only exceptions), tetralogy and d-transposition of the great arteries were, respectively, the first and second or second and first most frequent types of congenital heart disease associated with postoperative autopsy. Late Mortality On the basis of available data, the frequency of late postoperative death does not appear to be increasing.
Table II merits careful scrutiny, each case being a story in itself. Several findings concerning these late postoperative deaths merit specific mention. Arrhythmias: Arrhythmias were important: tetralogy with A-V block (1966); tetralogy with A-V block and tetralogy with recurrent ventricular tachycardia (1969); pulmonary atresia with intact ventricular septum, presumed ventricular tachyarrhythmia (1970); tetralogy of Fallot after a Blalock-Taussig anastomosis, with ventricular fibrillation during operation for spinal fusion, presumably as a result of intraoperative hypotension (1971); and tetralogy of Fallot with recurrent ventricular tachycardia progressing to ventricular fibrillation (1974). In two cases, excessive right ventricular myocardial resection in tetralogy of Fallot was associated with recurrent ventricular tachyarrhythmias 2 and 6 l/2 years postoperatively (1969,1974). In patients with pulmonary atresia and intact ventricular septum supraventricular tachyarrhythmias and congestive heart failure developed apparently because of right atria1 enlargement (1969,197O). The possibility of a ventricular component in fatal arrhythmias in this disease must also be borne in mind, in view of the possibility of coronary arterial abnormalities (thick walls, small lumens, interruptions), sinusoids and the often striking myocardial bypass as right ventricular blood passes into the coronary arteries by way of sinusoids, followed by retrograde coronary blood flow. Obstructively small ventricular septal defect: In one case this developed in association with tricuspid atresia (left-sided). Since the patient also had Z-transposition of the great arteries {S,L,L), the obstructively small ventricular septal defect resulted in an unusual form of muscular “subaortic stenosis” (1974). It may be possible to enlarge such a ventricular septal defect surgically along its margin inferiorly, but probably not superiorly because of the conduction system in 1-loops, thereby relieving the muscular subaortic stenosis. Intraoperative mapping of the conduction system should make it possible to avoid block. Other causes of late death: Massive hemoptysis leading to late postoperative death in two cases was associated with subacute bacterial endocarditis (1971) and with pulmonary hypertension (1971). Rupture of a pulmonary artery occurred without known bacterial endocarditis in two cases approximately 20 years after
August 1976
The American Journal ol CARDIOLOGY
Volume 36
229
CONGENITAL HEART DISEASE-VAN
PRAAGH AND VISNER
the creation of a Potts anastomosis (1971,1974). A fatal cyanotic spell occurred in a patient with tetralogy of Fallot 15 years after pleural stripping (1969). Congestive heart failure led to late postoperative death in three cases in association with an excessively large Waterston or Potts anastomosis (1967,1969,1970). Infection: Infection was important: occlusion of a shunt in tetralogy of Fallot by vegetations of subacute bacterial endocarditis (1966); meningitis in surgically palliated d-transposition (1967); subacute bacterial endocarditis in tetralogy resulting in massive hemoptysis (1971); sternal abscess leading to infection of Rastelli conduit in d-transposition (1974); brain abscess in double outlet right ventricle with ventricular septal defect and pulmonary stenosis (1974); and fulminating pneumococcal septicemia in a 5 year old boy with asplenia (1973). Penicillin prophylaxis for the asplenia syndrome: The aforementioned 5 year old boy died less than 24 hours after the onset of a fulminating febrile illness that proved to be a pneumococcal septicemia. It is now known that the spleen performs an important role in the preliminary opsonization of encapsulated bacteria such as the pneumococcus with specific antibodies in order to facilitate their phagocytosis.3 This case, plus the new understanding of the immunologic role of the spleen in the body’s defenses against the pneumococcus, strongly suggested that one should give serious consideration to the possibility of providing prophylactic penicillin to patients with the asplenia syndrome, similar to that given to patients with a history of rheumatic fever. If one decides against such prophylaxis, then it would at least seem wise to give such patients large doses of penicillin at the first indication of a flu-like, febrile illness. However, the fulminating time course of the pneumococcal septicemia in our patient was so rapid and devastating, with profound leukopenia, that we now recommend penicillin prophylaxis for survivors of the asplenia syndrome with successful palliation. Future Projections Our findings strongly suggest that the major problem
of the postoperative patient with congenital heart disease, as seen from the standpoint of cardiac pathology, will continue to be hospital mortality (92 percent of our postoperative series) rather than late mortality (8 percent). However, the need for careful, long-term postoperative follow-up of patients with congenital heart disease is apparent, since many questions can be answered satisfactorily only in this way. In view of the relative consistency of the findings over the years, namely, that tetralogy of Fallot and dtransposition of the great arteries were the leading causes of death from congenital heart disease during 7 of the 9 years of this study period, it seems probable that in the near future, tetralogy of Fallot (including cases with pulmonary outflow tract atresia and other associated malformations) and d-transposition of the great arteries (including cases with other associated anomalies) will continue to be leading causes of postoperative death from congenital heart disease in terms of the absolute number of fatalities (as opposed to percent of fatalities). Efforts to improve the management of patients with tetralogy of Fallot and with d-transposition of the great arteries are clearly warranted.
Acknowledgment We thank Eleanor Monkouski for secretarial assistance, Donna Farina for art work, and Terence Wrightson, Marilee Caliendo and Pauline McRae for photography.
Addendum After completion of this paper, a study by Waldman et a1.4confirmed that the frequency of fulminating fatal septicemia with encapsulated bacteria is much greater in patients with congenital asplenia than in appropriate control subjects: Klebsiella and Escherichia coli before age 6 months, and pneumococcus and Haemophilus influenzae from age 6 months onward. Consequently, Waldman et a1.4 recommend continuous antibiotic prophylaxis in children and adults with congenital asplenia: amoxicillin (25 mg/kg per day in two divided doses, maximum 1 g/day) or ampicillin (50 mg/kg per day in four divided doses, maximum 2 g/day).
References 1. Meeting of New York Heart Association, January 15, 1975, New York, NY 2. Van Praagh R: Genetic implications of successful treatment of congenital heart disease. In. Heart Disease in Infancy, Diagnosis and Surgical Treatment, chap 13. (Barratt-Boyes BG, Neutze JM, Harris EA, ed). Edinburgh, London, Churchill Livingstone, 1973, p
230
August 1976
The American Journal 01 CARDIOLOGY
331 3. Lukens JN: Hemoglobin S, the pneumococcus and the spleen. Am J Dis Child 123:6-7, 1972 4. Waldman JD, Rosenthal A, Smith AL, et al: Sepsis in congenital asplenia. Submitted for publication
Volume 36
RICHARD VAN PRAAGH, MARC S. VISNER, BA
MD,
FACC
Busfon. Massachusefts
From the Departments of Cardiology and Pathology of the Children’s Hospital Medical Center and the Departments of Pediatrics, Pathology and the Fourth Year Class of Harvard Medical School, Boston, Mass. This study was supported in part by Program Project Grant K-10436 from the National Heart and Lung Institute. National Institutes of Health, Bethesda, Md. Manuscript received July 21, 1975; revised manuscript received January 9. 1976, accepted January 14, 1976. Address for reprints: Richard Van Praagh, MD, Children’s Hospital Medical Center, 300 Longwood Ave., Boston, Mass. 02115.
Complete and unselected data concerning the postoperative pathology of congenital heart disease are presented for the first time. This study was based on 2,365 autopsies performed at the Children’s Hospital Medical Center, Boston, in the 9 years from 1966 through 1974. Of these, 566 autopsies (25 percent) revealed congenital heart disease-236 performed in medically treated patients (41 percent) and 346 in surgically treated patients (59 percent). Tetralogy of Fallot, including cases with pulmonary outflow tract atresia and other associated malformations, was the congenital heart disease most often encountered in the postoperative autopsy series (66 cases, 25 percent of that series). D-transposition of the great arteries, including cases with other associated anomalies, was second (54 cases, 15.5 percent). Early death (hospital mortality) accounted for 320 (92 percent) of the 346 surgical cases; late death occurred in 26 patients (6 percent). Causes of late postoperative death included arrhythmias, excessively small ventricular septal defect with tricuspid atresia, massive hemoptysis, rupture of the pulmonary artery, cyanotic spell, congestive heart failure and infection. Prophylactic penicillin is recommended for patients with the asplenia syndrome because of thelr probably enhanced vulnerability to fulminating septicemia by encapsulated bacteria such as the pneumococcus. Completeness and lack of selection in reporting data are essential in the interests of perspective and comparability of findings.
In a recent meeting on emerging problems in adults and children after cardiac surgery, Engle’ posed the following difficult question: As assessed from the standpoint of cardiac pathology, what problems will patients with congenital heart disease encounter after cardiac surgery in the future? To consider this qu‘estion, we thought it necessary first to establish our past postoperative problems. Hence, this presentation is concerned with both past problems and future projections. In making this investigation, we found virtually no relevant reports. To our knowledge, comparable data have not been published previously. This finding in turn led us to appreciate how important it is that published data, whether pathologic findings or surgical results, be complete and unselected. Otherwise, it is not possible to make valid comparisons of data from different centers. Even within one center it is not possible to see an individual finding in accurate perspective unless the data are complete and unselected. Case Material A study was made of all autopsies performed in patients with congenital heart disease at the Children’s Hospital Medical Center in Boston in the 9 vears from 1966 through 1974. No case was omitted for any reason. During this time, 2,365 autopsies were performed. Of these, 586 revealed congenital heart disease.
August 1976
The American Journal of CARDIOLOGY
Volume 38
225
CONGENITAL HEART DISEASE-VAN
PRAAGH AND VISNER
Surgically treated patients ranged from a low of 50 percent of all autopsy cases of congenital heart disease in 1970 to a high of 71 percent in 1974 (average 59 percent from 1966 through 1974, Fig. 3, Table I). Early versus late deaths: Early death (hospital mortality) in 320 cases accounted for 92 percent of 348 postoperative autopsy cases of congenital heart disease from 1966 through 1974. Lizte death (after hospital discharge) in 28 cases accounted for 8 percent of postoperative autopsy cases of congenital heart disease during this 9 year period. The causes of late death in each of these 28 cases are summarized in Table II. Types of congenital heart disease: The cardiac anomalies associated with early and late postoperative death from 1966 through 1974 are summarized in Table III. For 7 of these 9 years (1970 and 1972 being the exceptions), tetralogy of Fallot, including cases with pulmonary outflow tract atresia and other associated malformations, and d-transposition of the great arteries, including cases with additional associated anomalies, were, respectively, the first and second or second and first most frequent types of congenital heart disease associated with postoperative autopsies. During this 9
Findings Frequency: The annual frequency of autopsy cases of congenital heart disease ranged from a low of 21 percent of all autopsies performed in 1967, to a high of 29 percent in 1969 (average 25 percent from 1966 through 1974, Fig. 1, Table I). Medical versus postsurgical autopsies: Medically treated patients, who underwent no cardiovascular surgery, ranged from a low of 29 percent of all autopsy cases of congenital heart disease in 1974 to a high of 50 percent in 1970 (average 41 percent from 1966 through 1974, Fig. 2, Table I).
-
1966.1967
1966
1969
1970
1971
FIGURE 1. Autopsy cases of congenital percent
of all autopsies
1972
1973
heat-f disease
1974
expressed
as
in each year.
60% 55 -
1966
1967
1966
1969
1970
1971
1972
1973
-
1974
1966’
1967 ’ 1966’1969
’ 1970 ’ 1971 ’ 1972 ’ 1973 ' 1974 '
FIGURE 2. Autopsy cases of medically treated congenital heart disease
FIGURE 3. Autopsy cases of surgically treated congenital heart disease
expressed as percent of all autopsy cases of congenital in each year.
(CHD) expressed as percent disease in each year.
heart disease
of all autopsy cases of congenital
heart
TABLE I Autopsy
Statistics, Children’s
Hospital
1966 Autopsy
Cases
All All with CHD* Medically treated+ Surgically treated+
Medical
1967
1968 ___
226
August 1976
Boston,
1969 ____
1966
Through
1970
1974
1971
1972
1973
1974
Total
no.
%
“0.
%
“0.
%
“0.
%
“0.
%
“0.
%
“0.
%
“0.
%
“0.
%
“0.
%
321 75 33 42
23 44 56
275 58 27 31
21 47 53
295 75 35 40
25 47 53
292 84 33 51
29 39 61
263 60 30 30
23 50 50
280 76 25 51
27 33 67
214 56 23 33
26 41 59
212 54 18 36
25 33 67
213 48 14 34
23 29 71
2,365 586 238. 348
25 41 59
Percentages for each year are percentages + Percentages for each year are percentages CHD = congenital heart disease. l
Center,
of all autopsies performed that year. of all autopsy cases of congenital heart disease that year.
The American Journal ot CARDIOLOGY
Volume 36
CONGENITAL HEART DISEASE-VAN
TABLE
II
Late Deaths
(by year) in Postoperative
Patients
(28 cases)
Year
no. (%)
1966
2 of 42 (5%)
ToF with block, 3 mo postop ToF, shunt occluded by SBE vegetations, 1 l/2 yr postop
1967
5 of 31 (16%)
D-TGA, meningitis 4 l/2 yr post ASD creation D-TGA, aspiration 14 mo post ASD creation Down’s syndrome, CCAVC and PS, CHF 2 yr post Potts procedure L-TGA, IS,L,Ll, VSD and complete A-V block, CHF 1 l/2 mo post pacemaker LCA from PA with EFE of LV, CHF 8 l/2 mo post LCA ligation
Diagnoses
PRAAGH AND VISNER
year period as a whole (Table IV), tetralogy of Fallot was the most common type of congenital heart disease in this series of postoperative autopsies (25.3 percent), and d-transposition of the great arteries was second (15.5 percent). Discussion
1968
0 of 40
1969
4 of 51 (8%)
ToF with block, 2 2/3 yr postop, pacemaker failure ToF, 2 l/3 yr post repair, recurrent VT Extreme PS with IVS, 3 7/12 yr post Waterston procedure, CHF, PAT ToF, 15 yr post pleural stripping, cyanotic spell
1970
2 of 30 (7%)
P Atr with IVS, 5 3/4 mo post Waterston procedure, arrhythmia Asplenia with PS, 3 mo post Waterston procedure, CHF
1971
5 of 51 (10%)
ToF, 19 yr post Potts, rupture of MPA ToF, 2 1;5 ir post 8-T VF during surcerv for soinal fusion ToF,B iI3 yr post B-T, sudden unexpected death, ? arrhythmia M Atr with TR. 4 516 yr post ASD, massive hemoptysis ToF, 7 314 yr post B-T, SBE with massive hemoptysis
1972
1 of 33 (3%)
Subaortic fibrous ring, 1 l/2 mo post repair, fatal hemorrhage from cerebral arteriovenous aneurysm
1973
3 of 36 (8%)
PDA division and MPA band, 3 7/12 yr, aneurysm of pars producing subaortic stenosis “Recoarctation” of aorta, 4 mo postop Asplenia, 5 l/6 yr post Waterston, fulminating pneumococcal septicemia
1974
6 of 34 (18%)
ToF, 6 112 yr post repair, recurrent VT-VF D-TGA blocked, 1 mo postop during pacemaker change D-TGA, 11 mo post Rastelli, infected patch from sternal abscess D-TGA, VSD, PS, 22 yr post Potts, rupture of RPA DORV with PS, 4 yr post pleurectomy, brain abscess L-TGA with left-sided T Atr and “subaortic stenosis,” 3 112 yr post ASD and MPA band, AF then VF
AF = atrial fibrillation; ASD = atrial septal defect; A-V = atrioventricular; B-T = Blalock-Taussig anastomosis; CCAVC = complete common atrioventricular canal; CHF = congestive heart failure; D = dextro; DORV = double outlet right ventricle; EFE = endocardial fibroelastosis; IVS = intact ventricular septum; L = levo; LCA = left coronary artery; LV = left ventricle; M Atr = mitral atresia; MPA = main pulmonary artery; PA = pulmonary artery; PAT = paroxysmal atrial tachycardia; P Atr * pulmonary atresia; PDA = patent ductus = postoperatively; PS = pulmonary stenosis; arteriosus; postop RPA = right pulmonary artery; SBE = subacute bacterial endocarditis; fS,L,LI = situs solitus of the viscera and atria; ventricular /-loop and /-transposition of great arteries; T Atr = tricuspid atresia; TGA = transposition of great arteries; ToF = tetralogy of Fallot; TR = tricuspid regurgitation; VF = ventricular fibrillation; VSD = ventricular septal defect; VT = ventricular tachycardia.
August
Since this is the first presentation of complete and unselected data concerning the postoperative pathologic findings in congenital heart disease, data from other centers are -needed to achieve a more complete and representative understanding of this topic. Congenital heart disease accounted for 25 percent of all autopsies performed at the Children’s Hospital Medical Center in Boston during the 9 year study period (Fig. 1, Table I) and was by far the leading cause of death at our hospital during the past decade. Leukemia plus lymphoma was second, constituting approximately 15 percent of all autopsies.2 Each of the other important causes of death accounted for 10 percent or less of all autopsies. These data are biased by the fact that our hospital is a referral center for major disease in infants and children. Congenital heart disease may also be the leading cause of death in other children’s hospitals, but such data are not now available. Our data show that among the autopsy cases of congenital heart disease, the percent of medical cases is decreasing (Fig. 2) and the percent of surgical cases is increasing (Fig. 3). These statistics are thought to reflect the fact that as our surgical management of congenital heart disease has continued to improve, fewer patients have been managed medically and more have been operated upon. Not only has the percent of-our surgical patients increased, but also the progressively more difficult forms of congenital heart disease have been managed surgically in recent years. In absolute numbers, as opposed to percentages, all autopsy cases are decreasing (Table I). This finding probably reflects the declining birth rate: Fewer autopsies of all kinds are being performed and there are fewer autopsy cases of congenital heart disease, whether medical or surgical, or both. Types of Congenital Heart Disease Tetralogy of Fallot, including cases with pulmonary outflow tract atresia and other associated anomalies, was the congenital heart disease most often associated with postoperative death, accounting for 25.3 percent of all postoperative autopsy cases of congenital heart disease (Table IV). D-transposition of the great arteries, including cases with additional associated anomalies, was second, constituting 15.5 percent of all postoperative necropsies. These are unfamiliar statistics. One must be careful not to misread these autopsy statistics as surgical mortality rates. They are not. Instead they are thought to reflect a difficult to dissect mixture of (1) frequency in surgical case load, and (2) surgical difficulty. Initially, we were surprised by these necropsy statistics. We had thought that tetralogy of Fallot was essentially a solved
1976
The Am&can
Journal of CARDIOLOGY
Volume 33
227
CONGENITAL HEART DISEASE-VAN
TABLE
PRAAGH AND VISNER
III
Malformations
Associated
with Surgical
Malformation
Death:
EarlY and Late Mortalitv
1966
1970
6 (14%)
Preductal TAPVC, Ao Atr
DORV
5 (12%)
Single ventricle Congenital mitral stenosis Truncus arteriosus P Atr with IVS Cardiac malpositions VSD
2 2 2 2
Ebstein’s anomaly T Atr CCAVC Abdominal coarctation MR AP window
1 (2%) 1 (2%)
(5%) (5%) (5%) (5%)
4 (13%)
T Atr
3 (10%)
Single LV TAPVC ASD I with MR Isolated ventricular
2 (6%)
1968
(40 Cases)
ToF
14 (35%)
D-TGA
10 (25%)
PS Premature closure of FO Ao Atr Right yentricular hypoplasia Rubella syndrome Polysplenia ASD II and VSD 1969 ToF
s 2 2 2
1ZI00 (5%) (5%) (5%)
1 1 1 1 1
(2.5%) (2.5%) (2.5%) (2.5%) (2.5%)
(51 Cases)
3 (6%)
IAA Asplenia Rubella syndrome DORV PS (valvular) Preductal coarctation
2 2 2 2 2 2
(4%) (4%) (4%) (4%) (4%) (4%)
228
August 1978
The Amgrican Journal of CARDIOLOGY
(51 Cases)
5 (10%) 5 (10%) 5 (10%)
PS Corrected Preductal AS M Atr
2 2 2 2 2
TGA coarctation
(4%) (4%) (4%) (4%) (4%)
1 (2%) 1 (2%) : 1 1 1 1 1 1 1 1
tzi00 (2%) (2%) (2%) (2%) (2%) (2%) (2%) (2%)
(33 Cases)
IVS
6 (18%)
ToF
5 (15%)
D-TGA TAPVC PDA
2 (6%) 2 (6%) 2 (6%)
Ao Atr DORV Corrected TGA AS Coarctation VSD DILV Subaortic fibrous ring VSD with aortic regurgitation IAA with AP window Isolated levocardia ASD I Truncus arteriosus with DiGeorge’s syndrome
1 1 1 1
ToF
Volume 38
(3%) (3%) (3%) (3%) (3%) (3%)
14 (27%)
1973
Ao Atr Single LV CCAVC ASD I with MR PDA TAPVC L-TGA
1 1 1 1 1 1
TAPVC D-TGA P Atr with IVS
P Atr with
10 (20%) IVS
with aortic rupture
1972
18 (35%)
D-TGA
2 (7%)
TGA
ACM IS, D, LI Overriding TV ASD I I, VSD, PDA Ebstein’s anomaly with PS Partial APVC to RA Aortic atresia Asplenia Aberrant LCA Ectopia cordis Absent PV leaflets VSD with MR Truncus arteriosus
and PS
L-TGA P Atr with IVS Asplenia ASD II Preductal coarctation
3 (10%) 3 (10%)
ToF
inversion
Annulo-aortic ectasia Down’s syndrome with CCAVC Truncus Al Ao Atr with IVS Aberrant LCA from MPA L-TGA VSD P Atr with IVS
supracardiac
1971
(31 Cases) 8 (26%)
4 (13%)
Cor triatriatum Truncus arteriosus VSD PS, VSD, AM6 DORV with PS Marfan’s syndrome
: 1z 00 1 (2%) 1 (2%)
D-TGA
6 (20%) coarctation
Corrected
z 1z100
ToF
(30 Cases)”
ToF
11 (26%)
D-TGA
1967
no. (%I
(42 Cases)
ToF
P Atr with
Malformation
no. f%)
(3%) (3%) (3%) (3%)
(36 Cases) 9 (25%)
D-TGA
5 (14%)
VSD PDA TAPVC Truncus arteriosus
3 3 2 2
(8%) (8%) (5.5%) (5.5%)
Rhabdomyoma Preductal coarctation P Atr with IVS Asplenia with septicemia Polysplenia
1 1 1 1 1
(3%) (3%) (3%) (3%) (3%)
CONGENITAL HEART DISEASE-VAN
TABLE
III
TABLE
(cont’d)
1973
IV
Malformations Found Most Often in 348 Postoperative Autopsy Cases of Congenital Heart Disease, 1966 Through 1974
no. f%)
Malformation (36 Cases) (cont’d)
1 (3%) :zEz T Atr AS Single LV DORV
PRAAGH AND VISNER
Tetralogy of Fallot* D-transposition of great arteries?
: K l(32, 1 (3%) 1 (3%)
no.
%
88 54
25.3 15.5
Including cases with pulmonary outflow tract atresia and other associated malformations. t Including cases with other associated anomalies. l
1974
(34 Cases) 8 (24%)
D-TGA ToF
7 (21%)
VSD
4 112%)
ASD
I
Preductal IAA
3 (9%) coarctation
Truncus arteriosus Down!s syndrome with CAVC and MPA band M Atr with DORV DORV, DI RV and PS PS, myxomatdus T Atr with D-TGA L-TGA with subaortic stenosis 1I,S,L,I 1 atrial noninversion
‘2 1:31 00 1 (3%) 1 (3%) 1 1 1 1 1 1
(3%) (3%) (3%) (3%) (3%) (3%)
Few Mustard procedures were performed for d-transposition of great arteries. ACM IS,D,LI = anatomically corrected maiposition of the great arteries with situs solitus of the viscera and atria, ventricular dfoop and I-malposition of the great arteries; AMB = anomalous muscle bundles; Ao Atr = aortic atresia; AP = aorticopulmonary; APVC = anomalous pulmonary venous connection; AS = aortic stenosis; ASD I and II = primum and secundum atrial septal defect; DILV = double inlet left ventricle; DIRV = double inlet right ventricle; FO = foramen ovale; IAA = interrupted aortic arch; Il.S.L,I 1 = situs inversus of the viscera, situs solitus of the atria, ventricular /-loop and inverted normal relation between the great arteries, MR = mitral regurgitation; PV = pulmonary valve; RA = right atrium; TAPVC = total anomalous pulmonary venous connection; TV = tricuspid valve. Other abbreviations as in Table II. l
surgical problem. However, the data do not support this assumption. Instead, the findings indicate that in terms of the absolute number of postoperative fatalities (as opposed to mortality rates), tetralogy of Fallot is our largest problem, followed by d-transposition of the great arteries. Whether this is also true of other diagnostic and therapeutic centers concerned with congenital heart disease is unknown because such information is not now available. Analysis of the postoperative autopsy statistics by year (Table III) also indicates that tetralogy of Fallot and d-transposition of the great arteries were the leading causes of postoperative death from congenital heart disease during this study period. In 7 of the 9 years (1970 and 1972 being the only exceptions), tetralogy and d-transposition of the great arteries were, respectively, the first and second or second and first most frequent types of congenital heart disease associated with postoperative autopsy. Late Mortality On the basis of available data, the frequency of late postoperative death does not appear to be increasing.
Table II merits careful scrutiny, each case being a story in itself. Several findings concerning these late postoperative deaths merit specific mention. Arrhythmias: Arrhythmias were important: tetralogy with A-V block (1966); tetralogy with A-V block and tetralogy with recurrent ventricular tachycardia (1969); pulmonary atresia with intact ventricular septum, presumed ventricular tachyarrhythmia (1970); tetralogy of Fallot after a Blalock-Taussig anastomosis, with ventricular fibrillation during operation for spinal fusion, presumably as a result of intraoperative hypotension (1971); and tetralogy of Fallot with recurrent ventricular tachycardia progressing to ventricular fibrillation (1974). In two cases, excessive right ventricular myocardial resection in tetralogy of Fallot was associated with recurrent ventricular tachyarrhythmias 2 and 6 l/2 years postoperatively (1969,1974). In patients with pulmonary atresia and intact ventricular septum supraventricular tachyarrhythmias and congestive heart failure developed apparently because of right atria1 enlargement (1969,197O). The possibility of a ventricular component in fatal arrhythmias in this disease must also be borne in mind, in view of the possibility of coronary arterial abnormalities (thick walls, small lumens, interruptions), sinusoids and the often striking myocardial bypass as right ventricular blood passes into the coronary arteries by way of sinusoids, followed by retrograde coronary blood flow. Obstructively small ventricular septal defect: In one case this developed in association with tricuspid atresia (left-sided). Since the patient also had Z-transposition of the great arteries {S,L,L), the obstructively small ventricular septal defect resulted in an unusual form of muscular “subaortic stenosis” (1974). It may be possible to enlarge such a ventricular septal defect surgically along its margin inferiorly, but probably not superiorly because of the conduction system in 1-loops, thereby relieving the muscular subaortic stenosis. Intraoperative mapping of the conduction system should make it possible to avoid block. Other causes of late death: Massive hemoptysis leading to late postoperative death in two cases was associated with subacute bacterial endocarditis (1971) and with pulmonary hypertension (1971). Rupture of a pulmonary artery occurred without known bacterial endocarditis in two cases approximately 20 years after
August 1976
The American Journal ol CARDIOLOGY
Volume 36
229
CONGENITAL HEART DISEASE-VAN
PRAAGH AND VISNER
the creation of a Potts anastomosis (1971,1974). A fatal cyanotic spell occurred in a patient with tetralogy of Fallot 15 years after pleural stripping (1969). Congestive heart failure led to late postoperative death in three cases in association with an excessively large Waterston or Potts anastomosis (1967,1969,1970). Infection: Infection was important: occlusion of a shunt in tetralogy of Fallot by vegetations of subacute bacterial endocarditis (1966); meningitis in surgically palliated d-transposition (1967); subacute bacterial endocarditis in tetralogy resulting in massive hemoptysis (1971); sternal abscess leading to infection of Rastelli conduit in d-transposition (1974); brain abscess in double outlet right ventricle with ventricular septal defect and pulmonary stenosis (1974); and fulminating pneumococcal septicemia in a 5 year old boy with asplenia (1973). Penicillin prophylaxis for the asplenia syndrome: The aforementioned 5 year old boy died less than 24 hours after the onset of a fulminating febrile illness that proved to be a pneumococcal septicemia. It is now known that the spleen performs an important role in the preliminary opsonization of encapsulated bacteria such as the pneumococcus with specific antibodies in order to facilitate their phagocytosis.3 This case, plus the new understanding of the immunologic role of the spleen in the body’s defenses against the pneumococcus, strongly suggested that one should give serious consideration to the possibility of providing prophylactic penicillin to patients with the asplenia syndrome, similar to that given to patients with a history of rheumatic fever. If one decides against such prophylaxis, then it would at least seem wise to give such patients large doses of penicillin at the first indication of a flu-like, febrile illness. However, the fulminating time course of the pneumococcal septicemia in our patient was so rapid and devastating, with profound leukopenia, that we now recommend penicillin prophylaxis for survivors of the asplenia syndrome with successful palliation. Future Projections Our findings strongly suggest that the major problem
of the postoperative patient with congenital heart disease, as seen from the standpoint of cardiac pathology, will continue to be hospital mortality (92 percent of our postoperative series) rather than late mortality (8 percent). However, the need for careful, long-term postoperative follow-up of patients with congenital heart disease is apparent, since many questions can be answered satisfactorily only in this way. In view of the relative consistency of the findings over the years, namely, that tetralogy of Fallot and dtransposition of the great arteries were the leading causes of death from congenital heart disease during 7 of the 9 years of this study period, it seems probable that in the near future, tetralogy of Fallot (including cases with pulmonary outflow tract atresia and other associated malformations) and d-transposition of the great arteries (including cases with other associated anomalies) will continue to be leading causes of postoperative death from congenital heart disease in terms of the absolute number of fatalities (as opposed to percent of fatalities). Efforts to improve the management of patients with tetralogy of Fallot and with d-transposition of the great arteries are clearly warranted.
Acknowledgment We thank Eleanor Monkouski for secretarial assistance, Donna Farina for art work, and Terence Wrightson, Marilee Caliendo and Pauline McRae for photography.
Addendum After completion of this paper, a study by Waldman et a1.4confirmed that the frequency of fulminating fatal septicemia with encapsulated bacteria is much greater in patients with congenital asplenia than in appropriate control subjects: Klebsiella and Escherichia coli before age 6 months, and pneumococcus and Haemophilus influenzae from age 6 months onward. Consequently, Waldman et a1.4 recommend continuous antibiotic prophylaxis in children and adults with congenital asplenia: amoxicillin (25 mg/kg per day in two divided doses, maximum 1 g/day) or ampicillin (50 mg/kg per day in four divided doses, maximum 2 g/day).
References 1. Meeting of New York Heart Association, January 15, 1975, New York, NY 2. Van Praagh R: Genetic implications of successful treatment of congenital heart disease. In. Heart Disease in Infancy, Diagnosis and Surgical Treatment, chap 13. (Barratt-Boyes BG, Neutze JM, Harris EA, ed). Edinburgh, London, Churchill Livingstone, 1973, p
230
August 1976
The American Journal 01 CARDIOLOGY
331 3. Lukens JN: Hemoglobin S, the pneumococcus and the spleen. Am J Dis Child 123:6-7, 1972 4. Waldman JD, Rosenthal A, Smith AL, et al: Sepsis in congenital asplenia. Submitted for publication
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