From 1952 to 1963, 1,000 consecutive children with congenital heart disease were evaluated by 1 of us (R.C.A.). Current information for 994 patients with 36,086 patient-years is available. Of these, 362 have died, 130 as adults, of whom 67 died from a cardiac cause. Of the remaining 638 patients, 632 were living, and 6 were lost to follow-up. The survival curves for ventricular septal defect, atrial septal defect, patent ductus arteriosus, and pulmonary stenosis paralleled the normal curve. Cyanotic patients had a markedly reduced curve, with 19% alive at 50 years. Most patients were New York Heart Association class I, with only 3 in class IV, each from noncardiac causes. In conclusion, this experience should be helpful to physicians caring for adults with congenital heart disease and provide an optimistic outlook for the patients with less complex conditions.
Since the development of cardiac operations in the 1940s and 1950s, our knowledge about congenital heart disease and our ability to treat affected children have expanded greatly. Because pediatric cardiology is a relatively new discipline, information about the long-term natural or surgically altered history of cardiac malformations is limited but increasing. Detailed information about patients with ventricular septal defect (VSD), aortic stenosis (AS), and pulmonary stenosis (PS) has been described in 2 excellent natural history studies. Along with other retrospective reviews of particular conditions, they provide important data on the natural history, but often for a shorter period. Previously, we reported a prospective study of our cohort of 1,000 patients initially seen in infancy or childhood and followed into adulthood. The survivors have now been followed for ≥43 years and ≤54 years. Their information provides valuable data about the course, survival, and clinical status of children with a cardiac malformation who were initially evaluated, on average, 50 years previously.
Methods
The medical records of 1,000 consecutive children with a cardiac anomaly initially referred to 1 of us (R.C.A.) for cardiac consultation were abstracted. Case acquisition occurred from March 1952 through December 1963. The patients were from our normal referral areas and constituted about 1/3 of pediatric cardiology patients evaluated at the University of Minnesota during the study period.
These patients have been surveyed periodically since their initial referral. A questionnaire was sent to all known survivors of the previous studies. If no response was received, the family members or friends previously identified by the patients were contacted to obtain information about the patient or the patient’s location. With the patient’s permission, additional information was sought from physicians, clinics, and hospitals. National death records and Internet web searches were also used to search for patients. The institutional review board of the University of Minnesota approved present study.
Results
Of the 1,000 patients, we had information available for 994, with a total of 36,086 patient-years of experience ( Table 1 ). Since their first evaluation at the University of Minnesota to December 31, 2006, 362 have died. Of the remaining patients, 632 were living and 6 were lost to follow-up. Of the 632 patients, the health status was known for 628 and unknown for 4 patients, who refused to provide information about their health.
| Diagnosis | Patients | Females | Years | Living | Age (yrs) | Years | LTF | Dead | Age (yrs) | Years | NYHA Class I | NYHA Class II | NYHA Class III | NYHA Class IV |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Ventricular septal defect | 262 | 143 | 11,307 | 216 | 48.1 | 10,387 | 1 | 45 | 20.5 | 920 | 202 | 12 | 0 | 1 |
| Ventricular septal defect + | 62 | 35 | 2,243 | 41 | 48.3 | 1,980 | 0 | 21 | 12.5 | 263 | 41 | 9 | 4 | 0 |
| Patent ductus arteriosus | 89 | 67 | 4,201 | 79 | 49.9 | 3,941 | 1 | 9 | 28.9 | 260 | 66 | 10 | 0 | 1 |
| Patent ductus arteriosus + | 13 | 8 | 447 | 9 | 46.7 | 420 | 0 | 4 | 6.7 | 27 | 5 | 3 | 0 | 0 |
| Aortic stenosis | 62 | 19 | 2,800 | 40 | 51.8 | 2,071 | 1 | 21 | 34.7 | 729 | 34 | 7 | 1 | 0 |
| Aortic stenosis + | 13 | 4 | 329 | 4 | 51.8 | 207 | 0 | 9 | 13.5 | 122 | 4 | 0 | 0 | 0 |
| Pulmonary stenosis | 73 | 37 | 3,293 | 61 | 49 | 3,040 | 1 | 11 | 23 | 253 | 53 | 3 | 2 | 0 |
| Pulmonary stenosis + | 23 | 10 | 913 | 17 | 50.5 | 858 | 0 | 6 | 9.2 | 55 | 11 | 4 | 0 | 0 |
| Atrial septal defect | 41 | 22 | 1,994 | 38 | 50.9 | 1,933 | 0 | 3 | 20.3 | 61 | 33 | 3 | 0 | 0 |
| Atrial septal defect + | 12 | 5 | 471 | 8 | 49.4 | 346 | 1 | 4 | 31.1 | 125 | 5 | 1 | 0 | 0 |
| Coarctation | 34 | 10 | 1,572 | 29 | 49.9 | 1,447 | 0 | 5 | 25.1 | 125 | 24 | 4 | 0 | 1 |
| Coarctation + | 18 | 9 | 636 | 11 | 48.5 | 533 | 0 | 7 | 14.7 | 103 | 9 | 2 | 0 | 0 |
| Atrioventricular septal defect | 42 | 28 | 1,008 | 16 | 48.7 | 779 | 0 | 26 | 8.8 | 229 | 10 | 3 | 2 | 0 |
| Tetralogy of Fallot | 65 | 34 | 1,550 | 24 | 45.6 | 1,139 | 1 | 40 | 10.3 | 411 | 18 | 5 | 1 | 0 |
| Tetralogy of Fallot + pulmonary atresia | 11 | 6 | 100 | 1 | 46.3 | 46 | 0 | 10 | 5.4 | 54 | 0 | 1 | 0 | 0 |
| Transposition of great arteries | 27 | 8 | 325 | 2 | 43.9 | 88 | 0 | 25 | 9.5 | 237 | 2 | 0 | 0 | 0 |
| Transposition of great arteries + ventricular septal defect | 19 | 15 | 54 | 0 | 0 | 0 | 0 | 19 | 2.8 | 54 | 0 | 0 | 0 | 0 |
| Supraventricular tachycardia | 22 | 14 | 345 | 2 | 46.6 | 93 | 0 | 20 | 12.6 | 252 | 0 | 2 | 0 | 0 |
| Tricuspid atresia | 12 | 8 | 197 | 2 | 46.7 | 93 | 0 | 10 | 11.5 | 104 | 0 | 0 | 2 | 0 |
| Total anomalous pulmonary venous connection | 10 | 7 | 41 | 0 | 0 | 0 | 0 | 10 | 4.1 | 41 | 0 | 0 | 0 | 0 |
| Congenitally corrected transposition of great arteries | 4 | 2 | 31 | 0 | 0 | 0 | 0 | 4 | 7.7 | 31 | 0 | 0 | 0 | 0 |
| Other | 85 | 33 | 2,225 | 32 | 48.2 | 1,544 | 0 | 53 | 12.9 | 681 | 17 | 9 | 3 | 0 |
| Total | 1,000 | 534 | 36,082 | 632 | 50.37 ± 6.14 | 33,945 | 6 | 362 | 15 ± 17.6 | 5,137 | 530 | 78 | 15 | 3 |
Of the 362 deaths, 209 occurred in the first decade of life, with 125 of these in the first year and another 34 in the second. A survival curve ( Figure 1 ) showed 37 deaths in the third decade, 35 in the fourth, 31 in the fifth, 26 in the sixth, and the remaining patient died at age 61 years. A total of 31 of the deaths occurred among the 60 adults with a cyanotic cardiac condition, some of whom had been operated on, and could be compared with the Kaplan-Meier curve for noncyanotic patients ( Figure 2 ). A total of 130 adults died, 67 from a cardiac cause, 52 from a noncardiac cause, and 11 from an unknown cause ( Table 2 ).
| Cause of Death | Patients (n) |
|---|---|
| Cardiac | |
| Sudden | 18 |
| Congestive heart failure | 8 |
| Cardiac malformation | 7 |
| Awaiting/after transplantation | 7 |
| Pulmonary vascular disease | 6 |
| Myocardial infarction | 5 |
| Cardiac reoperation | 4 |
| Ruptured aortic aneurysm | 3 |
| Infective endocarditis | 2 |
| Other individual cardiac problems | 7 |
| Subtotal | 67 |
| Noncardiac | |
| Malignancy | 13 |
| Accidental | 9 |
| Cerebral vascular event | 6 |
| Diabetes mellitus | 4 |
| Suicide | 4 |
| Alcohol or drugs | 3 |
| Subtotal | 52 |
| No identified cause | 11 |
| Total | 130 |
In the survivors, the New York Heart Association functional classification was class I in 530, class II in 78, class III in 15, and class IV in 3 (noncardiac disease in each of the 3).
The patients were grouped according to their cardiac anomaly, and information about the groups is listed in Table 1 . At the initial referral, 1952 to 1963, for many conditions, for example, complete transposition of the great arteries (TGA), a hypoplastic left or right ventricle, and total anomalous pulmonary venous connection, neither palliative nor corrective operations were available. The survival curve of these patients is shown in Figure 2 .
A total of 87 cardiac operations have been performed in 80 patients since our last report. Four deaths occurred. Of these 87 procedures, 66 were valve replacements: aortic in 47, mitral in 7, pulmonary in 3, tricuspid in 2, aortic valve plus ascending aortic replacement in 4, mitral plus tricuspid in 2, and mitral plus aortic in l.
Heart and heart–lung transplantation was performed in 4 and 1 patient, respectively, and all survived. Their ages ranged from 35 to 47 years. Of the 4 patients, 2 had congenitally corrected transposition and 1 TGA, all with a VSD and PS. The fourth was for cardiomyopathy in 1 patient with pulmonary valvotomy. The heart–lung transplantation was performed for 1 patient with TGA, an atrioventricular canal, and PS.
The other operations were closure of an atrial septal defect in 4 patients, correction of recoarctation in 2, a Fontan procedure in 2 (1 with tricuspid atresia and 1 with corrected transposition of the great vessels), and coronary arterial bypass in 1 patient aged 40 years with coexistent VSD and PS treated surgically at 5 years of age.
A total of 27 episodes of infective endocarditis occurred in 22 patients. Among 8 patients with tetralogy of Fallot (TOF), 12 episodes occurred, with another 4 episodes in 1 patient and 2 in 1 patient. Five episodes were associated with a coexistent Blalock-Taussig shunt, 3 episodes developed before the corrective operation, and 4 occurred after correction.
AS was the next most frequent condition associated with infective endocarditis, with 7 episodes occurring in 6 patients aged 7 to 32 years, followed for a total of 2,300 patient-years, for an incidence of 26.5/10,000 patient-years. Of these 6 patients, 1 died of the infection. Infective endocarditis occurred in 8 patients with other cardiac conditions: small VSD in 3, coarctation in 2 (each with a tricuspid aortic valve), valvar PS in 1, and congenitally corrected transposition of the great vessels, coexistent VSD, and PS in 2. One of these patients with a Blalock-Taussig shunt died.
In 30 adults, an abnormality of rhythm or conduction was reported. Of these 30 adults, 11 developed atrial fibrillation, 6 in patients with VSD, 4 of whom had been operated upon and 2 of whom had a persistent defect. The other 5 patients included 3 with postoperative AS, and 1 each after pulmonary valvotomy and atrial septal defect. A total of 11 patients had complete heart block, each after a cardiac operation, 5 for TOF, 4 in patients with AS, and 2 for atrioventricular canal. Finally, 8 patients had episodes of supraventricular tachycardia, and 1 had episodes of atrial flutter. These occurred in patients with atrial septal defect, VSD, patent ductus arteriosus, and AS.
A total of 31 patients (3%) developed a malignancy, 13 of which were fatal. Of the 31 patients, 5 developed breast cancer, 4 leukemia, 3 each skin and lung cancer, and 2 each cervical cancer, prostate cancer, and melanoma. One patient each developed renal, ovarian, endometrial, testicular, thyroid, oral, or rectal cancer. Finally, there were single instances of glioblastoma, neuroma, and an unknown tumor.
Diabetes mellitus was very common, developing in 23 patients. Other major medical illnesses were also found among the patients. Crohn’s disease developed in 5, multiple sclerosis in 4, fibromyalgia in 3, human immunodeficiency virus in 2, and chronic renal failure in 3. Additionally, 1 patient each developed sarcoidosis, muscular dystrophy, lupus erythematous, rheumatic arthritis, osteogenic imperfecta, Ehlers-Danlos syndrome, moya moya, and ulcerative colitis.
There were 23 patients with Down syndrome and 14 with material rubella syndrome. In addition, 5 patients had Noonan syndrome, 3 Williams syndrome, 2 Turner syndrome, 1 trisomy 18, 1 trisomy 13, 1 Goldenhar syndrome, 2 Holt-Oram syndrome, and 1 leprechaunism; 5 patients had an unknown syndrome.
The survival curves for the individual cardiac conditions are shown in Figure 3 . In patients with VSD, atrial septal defect, and patent ductus arteriosus, the Kaplan-Meier survival curves followed a normal curve. When these conditions were present with another malformation, the curves were significantly lower than normal, with AS showing a marked variation. AS resulted in an increased risk of sudden death and infective endocarditis (5 episodes, as discussed previously), and 35 of the 62 patients (56%) underwent valvotomy or valve replacement.
