(Circulation. 2000;102:883.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Cognitive Development After the Fontan Operation
Presented in part at the 68th Scientific Sessions of the American Heart Association, Anaheim, Calif, November 13–16, 1995, and published in abstract form (Circulation. 1995;92[suppl I]:I-121).
From the Departments of Cardiology (G.W., K.G., T.L.G., A.Z.W., J.B., J.W.N.), Neuroepidemiology (K.M.S., D.C.B.), Neurology (A.J.D.), and Cardiac Surgery (R.A.J., J.E.M.), Children’s Hospital and the Departments of Pediatrics (G.W., K.G., T.L.G., A.J.D., J.W.N.) and Surgery (R.A.J., J.E.M.), Harvard Medical School, Boston, Mass.
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background—Patients with a single ventricle have multiple risk factors for central nervous system injury, both before and after the Fontan procedure.
Methods and Results—A geographically selected cohort was invited to undergo standardized testing, including age-appropriate measures of intelligence quotient (IQ) and achievement tests. Historical information was obtained by chart review and patient questionnaires. Of the 222 eligible patients, 133 (59.9%) participated. Median age at testing was 11.1 years (range, 3.7 to 41.0 years), 6.0 years (range, 1.6 to 19.6 years) after surgery. Mean full-scale IQ was 95.7±17.4 (P<0.006 versus normal); 10 patients (7.8%) had full-scale IQ scores <70 (P=0.001). After adjustment for socioeconomic status, lower IQ was associated with the use of circulatory arrest before the Fontan operation (P=0.002), the anatomic diagnoses of hypoplastic left heart syndrome (P<0.001) and "other complex" (P=0.05), and prior placement of a pulmonary artery band (P=0.04). Mean composite achievement score was 91.6±15.4 (P<0.001 versus normal); 14 patients (10.8%) scored <70 (P<0.001). After adjustment for socioeconomic status, independent risk factors for low achievement scores included the diagnoses of hypoplastic left heart syndrome (P=0.004) and "other complex" (P=0.003) or prior use of circulatory arrest (P=0.03), as well as a reoperation with cardiopulmonary bypass within 30 days of the Fontan (P=0.01).
Conclusions—Most individual patients palliated with the Fontan procedure in the 1970s and 1980s have cognitive outcome and academic function within the normal range, but the performance of the cohort is lower than that of the general population.
Key Words: Fontan procedure • intelligence • risk factors • cardiopulmonary bypass
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Among patients with congenital heart disease, those with a functional single ventricle, ultimately palliated with the Fontan operation, are perhaps at greatest risk for neurological, cognitive, and psychological impairment. Many patients with a single ventricle have either duct-dependent systemic or pulmonary blood flow; closure of the ductus in the early neonatal period may result in profound cyanosis, acidosis, hypoxic-ischemic injury, or shock, with secondary effects on the brain.1 Many patients require multiple surgical procedures with cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA).2 In infancy and early childhood, failure to thrive is common3 4 and may adversely affect motor skills. Before the Fontan operation, all patients had chronic hypoxemia, which may impair later cognitive function.5 The potential for embolic events exists both before and after the Fontan.6 Finally, all are exposed to the psychological stress of having chronic cardiac disease.7
As the mortality risk for the Fontan operation has declined,8 9 the quality of life of survivors has come into focus. The purpose of the present study was to characterize cognitive function and academic achievement after the Fontan operation and to identify potential patient- and procedure-related risk factors influencing long-term cognitive outcome.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Patients
Between September 1992 and June 1994, we performed a cross-sectional review of the first 500 patients who underwent various modifications of the Fontan operation at Children’s Hospital in Boston between April 1973 and July 1991. Earlier reports describe the study population, methods of data acquisition, factors influencing early and late mortality, and late hemodynamic, electrophysiological, and functional results in the entire cohort.3 8 10 11 To each of the 363 known survivors, we mailed a questionnaire that included information on medications, medical history, functional state, education, and additional therapy.
In the present study, the known survivors were classified as "regional" (New England and New York) or "distant" patients; all regional patients were invited to return to Children’s Hospital for a comprehensive, age-specific cognitive and psychological assessment. Socioeconomic status (SES) was determined for the study participants with the Hollingshead Scale.12 Informed consent was obtained from subjects or their parents according to the guidelines of the institutional Committee on Human Investigation.
Cognitive Testing
We administered a series of tests that measured intellectual
function and academic skills. Testing was performed by a single
examiner, a clinical psychologist (K.M.S.) who was blinded to the
medical and cardiac histories of subjects at the time of testing. Two
subjects were tested in their homes at parental request; the remainder
were tested at the hospital.
The test battery varied according to age. Children from 3 to 5 years of
age were administered the Wechsler Preschool and Primary Scale of
Intelligence-Revised (WPPSI-R)13 ; subjects between 6 and
16 years of age were given the Wechsler Intelligence Scale for
Children–Third Edition (WISC-III)14 ; and those 
17 years
of age were given the Wechsler Adult Intelligence Scale-Revised
(WAIS-R).15 The scales on each test are made up of
individual subtests grouped into verbal and performance
subsections. The verbal subtests measure various skills involving use
of language and language-related abilities, whereas the
performance subtests involve primarily nonverbal reasoning
skills.
Achievement Testing
Academic performance for subjects 3 to 5 years of age
was evaluated with the Kaufman Assessment Battery for Children
Achievement Scale (K-ABC)16 ; for subjects >5 years of
age, the Wide Range Achievement Test-Revised (WRAT-R) was
administered.17 Individual subtest scores on both the
K-ABC and WRAT-R are derived and summed to yield overall composite
scores of preacademic (K-ABC) and academic (WRAT-R) functioning.
Learning Disability
Learning disabilities may be defined as underachievement
relative to a subject’s level of ability as measured by the
intelligence quotient (IQ) score. To identify individuals with
potential learning difficulties, subjects’ predicted achievement
scores were calculated from their IQ scores on the basis of the linear
relationship between achievement and ability in the general population.
The estimates were corrected for the inherent correlation between
ability and achievement, measurement error, and effect of regression to
the mean.18
Statistical Analysis
To evaluate the role of selection bias, we compared
perioperative data of the regional patients who
returned for developmental testing with that of the patients who were
alive with an intact Fontan circulation but who did not return; the
2-sample t and Wilcoxon rank-sum tests were used for
continuous measurements, and the 
2 test was
used for categorical measurements. The primary outcomes were the
continuous variables full-scale IQ, verbal and performance
IQ, and composite achievement score, as well as the binary indicator of
learning disability. Before the results from different testing
modalities were combined, mean scores for various age groups were
compared by use of the 2-sample t test for composite
achievement score and 1-way ANOVA for IQ scores. Linear regression was
used to analyze the continuous outcomes; logistic regression
methods were used for the binary outcome. In each case,
P
0.05 was required for retention in the final
multivariate model.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Study Patients
Patients who returned for developmental testing (Table 1
and Figure 1) and those who did not were
similar with respect to anatomic diagnoses, sex, age at Fontan, and
preoperative oxygen saturation. Furthermore, participants did not
differ from the 180 patients who completed a questionnaire but did not
undergo developmental testing with respect to current health status,
medication use, frequency of support service use, and reported physical
capability (P>0.05).3
|
|
Mean age at the time of testing was 14.1±8.8 years (median, 11.1
years; range, 3.7 to 41.0 years). The mean follow-up time was 6.8±3.8
years (median, 6.0 years; range, 1.6 to 19.6 years) after surgery.
Before the Fontan operation, 7 patients (5.3%) had a documented pH of
<7.25 at presentation, 10 (7.6%) had clinical seizures,
and 2 (1.5%) had had a stroke. The mean preoperative aortic oxygen
saturation (measured at cardiac catheterization, n=131)
was 82.8±6.5% (median, 83%; range, 48% to 94%). Surgical
procedures (n=209) before the Fontan operation were performed in 120
patients (90.2%) (Table 2). Circulatory
arrest before the Fontan procedure had been used in none of the
patients who were young adults (16 years of age) at the time of the
Fontan versus 9.5% of those between 4 and 16 years of age and 26.9%
of the youngest age group (<4 years, P=0.005). Operative
and hospital data from the Fontan procedure are shown in Table 3.
|
|
Questionnaire Data/School Performance
Age-appropriate questionnaire data were available in all 133
patients at a median follow-up time of 5.7 years (range, 1.5 to 19.1
years) after the Fontan operation. The questionnaire was completed by
31 (23.3%) of the patients, by the patients’ parents in 96 cases
(72.2%), and by "other" in 5 instances (3.7%), and identification
of the respondent was missing for 1 (0.7%). At the time of
questionnaire completion, 26 subjects were preschoolers (<6 years), 74
were school-age children (6 to 17 years), and 33 were adults (18
years). Current health was described as excellent in 45.1%, good in
47.4%, and fair in 7.5%. Medications were being taken by 67.7%. A
speech therapist had been used by 29.3%, an occupational therapist by
21.1%, a physical therapist by 24.8%, a neurologist by 20.3%, and a
psychiatrist by 15.8%. Among the school-age group, 16 subjects
(21.6%) were held back in school at some time; 3 (4.1%) were not in a
regular classroom.
Cognitive Testing
The parents of a 5-year-old child refused testing after arrival at
our center, 2 young children were untestable because of poor
cooperation, and 1 child had had a prior test in school and was not
retested. For 1 bilingual adult, a performance score was
available, but verbal and full-scale scores were not. No significant
differences were found among the mean IQ scores for the various age
groups (full-scale, P=0.7; verbal, P=0.2;
performance, P=0.2); the testing modalities were
therefore combined for further analysis (Table 4). The mean full-scale IQ of the
combined groups was 95.7±17.4, significantly lower than that expected
in the normal population (P=0.006; Figure 2A). Ten patients (7.8%) had full-scale
IQ scores <70 (ie, >2 SD below the normal mean of 100;
P=0.001). The mean verbal IQ was 96.6±18.1
(P=0.04); 8 subjects (6.3%) had scores <70
(P=0.02). The mean performance IQ was 95.6±16.4
(P=0.003); 11 patients (8.5%) had scores <70
(P<0.001). Higher SES was a strong predictor of higher IQ
and achievement scores (P<0.001) and was included as a
covariate in all regression models.
|
|
In a multivariate model containing SES and surgical
variables but not diagnosis (Table 5), lower full-scale IQ was significantly
associated with the use of circulatory arrest in procedures before the
Fontan (P=0.002). The percent variability in observed IQ
explained by SES was 16.1%, whereas the percent variability explained
by the prior use of circulatory arrest and other surgical variables
was 6.1%. When anatomic diagnosis was added to the model, hypoplastic
left heart syndrome (HLHS) and "other complex" were associated with
lower full-scale IQ (P<0.001 and P=0.05,
respectively; Figure 2B
), as was the presence of a prior
pulmonary artery band (P=0.04). When anatomic
diagnosis was added to the model, prior use of circulatory arrest was
no longer statistically significant. However, the strong correlation
between prior use of circulatory arrest and anatomic diagnosis—eg, all
patients with HLHS had a prior period of circulatory arrest—precluded
determination of which was the more important risk factor. Regression
results were similar when verbal IQ and performance IQ were
analyzed individually (Table 5).
|
Achievement Testing
Achievement testing was performed in 18 young children (K-ABC) and
112 older participants (WRAT-R) (Table 6). One patient did not take an
achievement test; 2 others were untestable because of poor cooperation
and do not have scores. Two significantly developmentally delayed
patients with very low scores were included in the analysis and
assigned an arbitrary value of 45. The mean composite achievement
scores were similar in the 2 different age groups (P=0.7);
therefore, the testing modalities were combined for further
analysis.
|
Compared with national normative data, patients who underwent the
Fontan procedure performed significantly worse than expected (Figure 3A); the mean composite achievement score
was 91.6±15.4 (P<0.001). A higher-than-expected number of
patients had scores >2 SD below the normal mean of 100; 13 patients
(10.0%) had scores <70 (P<0.001).
|
In a multivariate model containing SES (Table 7), a prior period of circulatory arrest
was associated with lower composite achievement scores
(P=0.02), as was an early major reoperation
(P=0.05). When anatomic diagnosis was added to the model,
HLHS and "other complex" were significantly associated with lower
composite achievement scores (P=0.004 and
P=0.003; Figure 3B), as was an early major
reoperation (P=0.01). SES alone explained 16.4% of the
variability in the composite achievement scores; together, prior
circulatory arrest and early major reoperation explained an additional
5.6% of the variability. Regression models excluding the 2 patients
with assigned composite achievement scores of 45 produced similar
results.
|
Learning Disability
A learning disability, ie, a lower composite achievement score
than would be expected from an individual’s level of ability as
measured by the full-scale IQ, was identified in 7 of 127 patients
(5.5%) for whom both scores were available. Greater probability of a
learning disability tended to be associated with lower SES
(P=0.07). However, no other patient- or procedure-related
variables were significantly associated with learning
disability.
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Despite multiple risk factors for adverse neurodevelopmental outcomes present among patients who have undergone the Fontan procedure, we found that the majority of individual patients have scores on standardized tests of cognitive ability and academic achievement within the normal range. As a group, however, Fontan patients had significantly lower scores on IQ and standardized achievement tests than the general population. SES was a very strong predictor of performance, similar to findings in the normal population19 and other at-risk patient groups.20 21 Additional independent risk factors for worse performance included the prior use of circulatory arrest and the need for a major reoperation early after the Fontan procedure.
Most prior reports suggest that the majority of children have normal intelligence and cognitive performance after cardiac surgery in infancy and early childhood, although group results may be slightly lower than those for the general population.22 23 The results in our sample of Fontan patients are similar to those reported for patients who have undergone surgery for other forms of complex congenital heart disease, such as transposition of the great arteries5 23 24 and tetralogy of Fallot.7 23 Patients with less complex forms of congenital heart disease have been shown to have cognitive function more similar to normal.23 Risk factors for adverse outcomes include coexisting central nervous system anomalies,25 26 27 the effects of untreated congenital heart disease on the developing brain,1 4 5 and the effects of cardiac surgery and CPB, particularly DHCA.23 24 28
Similar to the findings recently reported by Uzark et al,29 our study confirms that the prior use of circulatory arrest is a risk factor for worse cognitive performance and academic achievement after the Fontan operation. These data are consistent with results of a randomized trial of predominant DHCA versus predominant low-flow CPB in patients with d-transposition of the great arteries who underwent the arterial switch operation in early infancy. In sequential periods from the perioperative period to 4 years of age,24 28 30 those whose surgery had entailed longer periods of DHCA demonstrated worse neurological and developmental outcome. Although longer duration of circulatory arrest has been shown to be associated with adverse sequelae,23 28 30 31 its use may be unavoidable in many patients with the combination of single ventricle, aortic arch hypoplasia, and duct-dependent systemic blood flow.
As in other reports,29 32 the diagnosis of HLHS was a risk factor for poor outcome in this series; however, the number of patients was exceedingly small (n=5), and the effects of diagnosis were confounded by use of circulatory arrest in this group. Kern and colleagues33 reported a negative correlation between the duration of circulatory arrest during stage I reconstruction (mean, 56 minutes) and full-scale IQ. In our series, these patients represent an early portion of the learning curve with surgical management of this disease. The cognitive results in children with HLHS are likely to improve in patients operated on in the more current era,34 with advances in fetal diagnosis, neuroprotection during CPB, and better nutrition management. Interestingly, the results in our patients with HLHS and other complex lesions who underwent the Fontan operation are similar to those seen early after infant cardiac transplantation.35 36
The inferences permitted by this study are limited by several methodological considerations. We cannot exclude selection bias as a possible explanation for our findings. Although the patients included in this investigation did not differ significantly from other eligible patients who did not participate with respect to anatomic diagnosis, surgical procedures, or age at repair, we could not assess the comparability of study participants and nonparticipants with respect to SES or cognitive function. Also, we were unable to compare the SES of the study population to that of the general population. Finally, significant changes in patient selection and surgical technique have taken place over the 2-decade experience with the Fontan operation, thus limiting the generalizability of these results to the current approach in children with a single ventricle.
In conclusion, we found that most patients with a single ventricle palliated with the Fontan procedure in the 1970s and 1980s have long-term cognitive outcome and academic achievement within the normal range. Mean performance of the cohort, however, is lower than that in the general population. Risk factors for worse outcomes include certain diagnoses, particularly HLHS, and the use of DHCA. Future studies must include detailed, prospective assessments of the congenital and perinatal risk factors that may influence long-term cognitive outcome, in addition to the influence of surgical management strategies on hemodynamic and central nervous system outcomes.
|
Acknowledgments |
|---|
This work was supported in part by the Kobren Fund. We would like to thank the many cardiologists and surgeons whose patients participated in the study. We would also like to thank the Fontan Follow-up Coordinating Center Staff for their assistance with patient follow-up and data management and Emily Flynn McIntosh, who assisted with the figures.
|
Footnotes |
|---|
Reprint requests to Jane W. Newburger, MD, Department of Cardiology, 300 Longwood Ave, Boston, MA 02115.
Address correspondence to Gil Wernovsky, MD, Division of Pediatric Cardiology, Children’s Hospital of Philadelphia, 324 S 34th St, Philadelphia, PA 19104.
Received June 25, 1999; revision received March 13, 2000; accepted March 26, 2000.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Glauser TA, Rorke LB, Weinberg PM, et al. Acquired neuropathologic lesions associated with the hypoplastic left heart syndrome. Pediatrics. 1990;85:991–1000.
2. Mezrow C, Gandsas A, Sadeghi A, et al. Metabolic correlates of neurologic and behavioral injury after prolonged hypothermic circulatory arrest. J Thorac Cardiovasc Surg. 1995;109:959–975.[Abstract]
3.
Gentles TL, Gauvreau K, Mayer JE Jr, et al. Functional
outcome after the Fontan operation: factors influencing late morbidity.
J Thorac Cardiovasc Surg. 1997;114:392–403.
4. Aisenberg RB, Rosenthal A, Nadas AS, et al. Developmental delay in infants with congenital heart disease: correlation with hypoxemia and congestive heart failure. Pediatr Cardiol. 1982;3:133–137.[Medline] [Order article via Infotrieve]
5. Newburger JW, Silbert AR, Buckley LP, et al. Cognitive function and age at repair of transposition of the great arteries in children. N Engl J Med. 1984;310:1495–1499.[Abstract]
6. duPlessis AJ, Chang AC, Wessel DL, et al. Cerebrovascular accidents following the Fontan operation. Pediatr Neurol. 1995;12:230–236.[Medline] [Order article via Infotrieve]
7. DeMaso DR, Beardslee WR, Silbert AR, et al. Psychological functioning in children with cyanotic heart defects. J Dev Behav Pediatr. 1990;11:289–294.[Medline] [Order article via Infotrieve]
8.
Gentles TL, Mayer JE Jr, Gauvreau K, et al. Fontan
operation in five hundred consecutive patients: factors influencing
early and late outcome. J Thorac Cardiovasc Surg. 1997;114:376–391.
9.
Koutlas TC, Gaynor JW, Nicolson SC, et al. Modified
ultrafiltration reduces postoperative morbidity after
cavopulmonary connection. Ann Thorac Surg. 1997;64:37–43.
10. Fishberger SB, Wernovsky G, Gentles TL, et al. Long-term outcome in Fontan patients with pacemakers. Am J Cardiol. 1996;77:887–889.[Medline] [Order article via Infotrieve]
11.
Fishberger SB, Wernovsky G, Gentles TL, et al. Factors
influencing the development of atrial flutter following the Fontan
operation. J Thorac Cardiovasc Surg. 1997;113:80–86.
12. Hollingshead A. Four Factor Index of Social Status. New Haven, Conn: Yale University, Department of Sociology; 1975.
13. Wechsler D. Wechsler Preschool and Primary Scale of Intelligence–Revised Manual. San Antonio, Tex: Psychological Corp, Harcourt Brace Jovanovich, Inc; 1989.
14. Wechsler D. Wechsler Intelligence Scale for Children. 3rd ed. San Antonio, Tex: Psychological Corp, Harcourt Brace and Co; 1991.
15. Wechsler D. Wechsler Adult Intelligence Scale–Revised Manual. San Antonio, Tex: Psychological Corp, Harcourt Brace Jovanovich, Inc; 1981.
16. Kaufman AS, Kaufman NL. Kaufman Assessment Battery for Children. Circle Pines, Minn: Kaufman American Guidance Service Inc; 1983.
17. Jastak S, Wilkinson GS. Wide Range Achievement Test–Revised. Wilmington, Del: Jastak Associates Inc; 1984.
18.
Reynolds CR. Critical measurement issues in learning
disabilities. J Special Educ. 1984;18:451–476.
19. Broman SH, Nichols PL, Kennedy WA. IQ differences among race, sex, and socioeconomic subgroups. In: Broman SH, ed. Preschool IQ: Prenatal and Early Developmental Correlates. Hillsdale, NJ: Lawrence Erlbaum Associates; 1975.
20.
Hack M, Taylor G, Klein N, et al. School-age outcomes
in children with birth weights under 750 g. N Engl
J Med. 1994;331:753–759.
21. Bellinger DC, Leviton A, Sloman J. Antecedents and correlates of improved cognitive performance in children exposed in utero to low levels of lead. Environ Health Perspect. 1990;89:5–11.[Medline] [Order article via Infotrieve]
22.
Hesz N, Clark EB. Cognitive development in
transposition of the great vessels. Arch Dis Child. 1988;63:198–200.
23.
Oates R, Simpson J, Turnbull J, et al. The relationship
between intelligence and duration of circulatory arrest with deep
hypothermia. J Thorac Cardiovasc Surg. 1995;110:786–792.
24.
Bellinger DC, Wypij D, Kuban KCK, et al. Developmental
and neurologic status of children at 4 years of age after heart surgery
with hypothermic circulatory arrest or low-flow cardiopulmonary
bypass. Circulation. 1999;100:526–532.
25.
Glauser T, Rorke L, Weinberg P, et al. Congenital brain
anomalies associated with the hypoplastic left heart syndrome.
Pediatrics. 1990;85:984–990.
26.
McConnell JR, Fleming WH, Chu W, et al. Magnetic
resonance imaging of the brain in infants and children before and after
cardiac surgery: a prospective study. Am J Dis Child. 1990;144:374–378.
27.
Limperopoulos C, Majnemer A, Shevell MI, et al.
Neurologic status of newborns with congenital heart defects before open
heart surgery. Pediatrics. 1999;103:402–408.
28.
Newburger JW, Jonas RA, Wernovsky G, et al. A
comparison of the perioperative neurologic effects of
hypothermic circulatory arrest versus low-flow cardiopulmonary
bypass in infant heart surgery. N Engl J Med. 1993;329:1057–1064.
29.
Uzark K, Lincoln A, Lamberti JJ, et al.
Neurodevelopmental outcomes in children with Fontan repair of
functional single ventricle. Pediatrics. 1998;101:630–633.
30.
Bellinger DC, Jonas RA, Rappaport LA, et al.
Developmental and neurologic status of children after heart surgery
with hypothermic circulatory arrest or low-flow cardiopulmonary
bypass. N Engl J Med. 1995;332:549–555.
31. Wells FC, Coghill S, Caplan HL, et al. Duration of circulatory arrest does influence the psychological development of children after cardiac operation in early life. J Thorac Cardiovasc Surg. 1983;86:823–831.[Abstract]
32. Rogers BT, Msall ME, Buck GM, et al. Neurodevelopmental outcome of infants with hypoplastic left heart syndrome. J Pediatr. 1995;126:496–498.[Medline] [Order article via Infotrieve]
33.
Kern JH, Hinton VJ, Nereo NE, et al. Early
developmental outcome after the Norwood procedure for hypoplastic left
heart syndrome. Pediatrics. 1998;102:1148–1152.
34.
Mahle WT, Clancy RR, Moss E, et al. Neurodevelopmental
outcome and lifestyle assessment in school-aged and adolescent children
with hypoplastic left heart syndrome. Pediatrics. 2000;105:1082–1089.
35. Baum M, Chinnock R, Ashwal S, et al. Growth and neurodevelopmental outcome of infants undergoing heart transplantation. J Heart Lung Transplant. 1993;12:S211–S217.[Medline] [Order article via Infotrieve]
36.
Eke C, Gundry S, Baum M, et al. Neurologic sequelae of
deep hypothermic circulatory arrest in cardiac transplant infants.
Ann Thorac Surg. 1996;61:783–788.
This article has been cited by other articles:
 |
|
 |
|
  C. A. Joynt, C. M.T. Robertson, P.-Y. Cheung, A. Nettel-Aguirre, A. R. Joffe, R. S. Sauve, W. S.G. Biggs, N. J. Leonard, D. B. Ross, I. M. Rebeyka, et al. Two-year neurodevelopmental outcomes of infants undergoing neonatal cardiac surgery for interrupted aortic arch: A descriptive analysis J. Thorac. Cardiovasc. Surg., October 1, 2009; 138(4): 924 - 932. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. T. Mahle, J. W. Newburger, G. P. Matherne, F. C. Smith, T. R. Hoke, R. Koppel, S. S. Gidding, R. H. Beekman III, S. D. Grosse, and on behalf of the American Heart Association Congen Role of Pulse Oximetry in Examining Newborns for Congenital Heart Disease: A Scientific Statement From the American Heart Association and American Academy of Pediatrics Circulation, August 4, 2009; 120(5): 447 - 458. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. T. Mahle, J. W. Newburger, G. P. Matherne, F. C. Smith, T. R. Hoke, R. Koppel, S. S. Gidding, R. H. Beekman III, S. D. Grosse, and on behalf of the American Heart Association Congen Role of Pulse Oximetry in Examining Newborns for Congenital Heart Disease: A Scientific Statement from the AHA and AAP Pediatrics, August 1, 2009; 124(2): 823 - 836. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Sarajuuri, T. Lonnqvist, L. Mildh, I. Rajantie, M. Eronen, I. Mattila, and E. Jokinen Prospective follow-up study of children with univentricular heart: Neurodevelopmental outcome at age 12 months J. Thorac. Cardiovasc. Surg., January 1, 2009; 137(1): 139 - 145. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Warnes, R. G. Williams, T. M. Bashore, J. S. Child, H. M. Connolly, J. A. Dearani, P. del Nido, J. W. Fasules, T. P. Graham Jr, Z. M. Hijazi, et al. ACC/AHA 2008 Guidelines for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Develop Guidelines on the Management of Adults With Congenital Heart Disease) Developed in Collaboration With the American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons J. Am. Coll. Cardiol., December 2, 2008; 52(23): e143 - e263. [Full Text] [PDF]
|
|
|
|
|
|
C. A. Warnes, R. G. Williams, T. M. Bashore, J. S. Child, H. M. Connolly, J. A. Dearani, P. del Nido, J. W. Fasules, T. P. Graham Jr, Z. M. Hijazi, et al. ACC/AHA 2008 Guidelines for the Management of Adults With Congenital Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Adults With Congenital Heart Disease) Developed in Collaboration With the American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons J. Am. Coll. Cardiol., December 2, 2008; 52(23): 1890 - 1947. [Full Text] [PDF]
|
|
|
|
|
|
C. A. Warnes, R. G. Williams, T. M. Bashore, J. S. Child, H. M. Connolly, J. A. Dearani, P. del Nido, J. W. Fasules, T. P. Graham Jr, Z. M. Hijazi, et al. ACC/AHA 2008 Guidelines for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Develop Guidelines on the Management of Adults With Congenital Heart Disease): Developed in Collaboration With the American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons Circulation, December 2, 2008; 118(23): e714 - e833. [Full Text] [PDF]
|
|
|
|
|
|
C. A. Warnes, R. G. Williams, T. M. Bashore, J. S. Child, H. M. Connolly, J. A. Dearani, P. del Nido, J. W. Fasules, T. P. Graham Jr, Z. M. Hijazi, et al. ACC/AHA 2008 Guidelines for the Management of Adults With Congenital Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Adults With Congenital Heart Disease): Developed in Collaboration With the American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons Circulation, December 2, 2008; 118(23): 2395 - 2451. [Full Text] [PDF]
|
|
|
|
 |
|
 R. van der Rijken, G. Hulstijn-Dirkmaat, F. Kraaimaat, L. Nabuurs-Kohrman, A. Nijveld, B. Maassen, and O. Daniels Open-heart surgery at school age does not affect neurocognitive functioning Eur. Heart J., November 1, 2008; 29(21): 2681 - 2688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. G. Ohye, J. W. Gaynor, N. S. Ghanayem, C. S. Goldberg, P. C. Laussen, P. C. Frommelt, J. W. Newburger, G. D. Pearson, S. Tabbutt, G. Wernovsky, et al. Design and rationale of a randomized trial comparing the Blalock-Taussig and right ventricle-pulmonary artery shunts in the Norwood procedure. J. Thorac. Cardiovasc. Surg., October 1, 2008; 136(4): 968 - 975. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Atallah, I. A. Dinu, A. R. Joffe, C. M.T. Robertson, R. S. Sauve, J. D. Dyck, D. B. Ross, I. M. Rebeyka, and the Western Canadian Complex Pediatric Therapies F Two-Year Survival and Mental and Psychomotor Outcomes After the Norwood Procedure: An Analysis of the Modified Blalock-Taussig Shunt and Right Ventricle-to-Pulmonary Artery Shunt Surgical Eras Circulation, September 30, 2008; 118(14): 1410 - 1418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Wernovsky The Paradigm Shift Toward Surgical Intervention for Neonates With Hypoplastic Left Heart Syndrome Arch Pediatr Adolesc Med, September 1, 2008; 162(9): 849 - 854. [Full Text] [PDF]
|
|
|
|
|
|
A. J. Shillingford, M. M. Glanzman, R. F. Ittenbach, R. R. Clancy, J. W. Gaynor, and G. Wernovsky Inattention, Hyperactivity, and School Performance in a Population of School-Age Children With Complex Congenital Heart Disease Pediatrics, April 1, 2008; 121(4): e759 - e767. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Wernovsky Improving neurologic and quality-of-life outcomes in children with congenital heart disease: Past, present, and future J. Thorac. Cardiovasc. Surg., February 1, 2008; 135(2): 240 - 242. [Full Text] [PDF]
|
|
|
|
|
|
J. Li, G. Zhang, H. Holtby, A.-M. Guerguerian, S. Cai, T. Humpl, C. A. Caldarone, A. N. Redington, and G. S. Van Arsdell The influence of systemic hemodynamics and oxygen transport on cerebral oxygen saturation in neonates after the Norwood procedure J. Thorac. Cardiovasc. Surg., January 1, 2008; 135(1): 83 - 90. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Creighton, C. M.T. Robertson, R. S. Sauve, D. M. Moddemann, G. Y. Alton, A. Nettel-Aguirre, D. B. Ross, I. M. Rebeyka, and and the Western Canadian Complex Pediatric Therapi Neurocognitive, Functional, and Health Outcomes at 5 Years of Age for Children After Complex Cardiac Surgery at 6 Weeks of Age or Younger Pediatrics, September 1, 2007; 120(3): e478 - e486. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. G. McBride, P. M. Kirshbom, J. W. Gaynor, R. F. Ittenbach, G. Wernovsky, R. R. Clancy, T. B. Flynn, D. M. Hartman, T. L. Spray, R. E. Tanel, et al. Late cardiopulmonary and musculoskeletal exercise performance after repair for total anomalous pulmonary venous connection during infancy J. Thorac. Cardiovasc. Surg., June 1, 2007; 133(6): 1533 - 1539. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Karsdorp, W. Everaerd, M. Kindt, and B. J.M. Mulder Psychological and Cognitive Functioning in Children and Adolescents with Congenital Heart Disease: A Meta-Analysis J. Pediatr. Psychol., June 1, 2007; 32(5): 527 - 541. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Goldberg, E. L. Bove, E. J. Devaney, E. Mollen, E. Schwartz, S. Tindall, C. Nowak, J. Charpie, M. B. Brown, T. J. Kulik, et al. A randomized clinical trial of regional cerebral perfusion versus deep hypothermic circulatory arrest: Outcomes for infants with functional single ventricle J. Thorac. Cardiovasc. Surg., April 1, 2007; 133(4): 880 - 887. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Y. Alton, C. M.T. Robertson, R. Sauve, A. Divekar, A. Nettel-Aguirre, S. Selzer, A. R. Joffe, I. M. Rebeyka, D. B. Ross, and Western Canadian Complex Pediatric Therapies Proje Early childhood health, growth, and neurodevelopmental outcomes after complete repair of total anomalous pulmonary venous connection at 6 weeks or younger J. Thorac. Cardiovasc. Surg., April 1, 2007; 133(4): 905 - 911. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Visconti, D. Rimmer, K. Gauvreau, P. del Nido, J. E. Mayer Jr, I. Hagino, and F. A. Pigula Regional Low-Flow Perfusion Versus Circulatory Arrest in Neonates: One-Year Neurodevelopmental Outcome Ann. Thorac. Surg., December 1, 2006; 82(6): 2207 - 2213. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Gauvreau Hypothesis Testing: Proportions Circulation, October 3, 2006; 114(14): 1545 - 1548. [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Padula and A. M. Ades Neurodevelopmental Implications of Congenital Heart Disease NeoReviews, July 1, 2006; 7(7): e363 - e369. [Full Text] [PDF]
|
|
|
|
|
|
B. W. McCrindle, R. V. Williams, P. D. Mitchell, D. T. Hsu, S. M. Paridon, A. M. Atz, J. S. Li, J. W. Newburger, and for the Pediatric Heart Network Investigators Relationship of Patient and Medical Characteristics to Health Status in Children and Adolescents After the Fontan Procedure Circulation, February 28, 2006; 113(8): 1123 - 1129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Mitchell, R. F. Ittenbach, J. W. Gaynor, G. Wernovsky, S. Nicolson, and T. L. Spray Intermediate outcomes after the Fontan procedure in the current era J. Thorac. Cardiovasc. Surg., January 1, 2006; 131(1): 172 - 180. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Dent, J. P. Spaeth, B. V. Jones, S. M. Schwartz, T. A. Glauser, B. Hallinan, J. M. Pearl, P. R. Khoury, and C. D. Kurth Brain magnetic resonance imaging abnormalities after the Norwood procedure using regional cerebral perfusion J. Thorac. Cardiovasc. Surg., January 1, 2006; 131(1): 190 - 197. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. Schultz, G. P. Jarvik, G. Wernovsky, J. Bernbaum, R. R. Clancy, J. A. D'Agostino, M. Gerdes, D. McDonald-McGinn, S. C. Nicolson, T. L. Spray, et al. Effect of congenital heart disease on neurodevelopmental outcomes within multiple-gestation births J. Thorac. Cardiovasc. Surg., December 1, 2005; 130(6): 1511 - 1516. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Dent, J. P. Spaeth, B. V. Jones, S. M. Schwartz, T. A. Glauser, B. Hallinan, J. M. Pearl, P. R. Khoury, and C. D. Kurth Brain magnetic resonance imaging abnormalities after the Norwood procedure using regional cerebral perfusion J. Thorac. Cardiovasc. Surg., December 1, 2005; 130(6): 1523 - 1530. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R Kaulitz and M Hofbeck Current treatment and prognosis in children with functionally univentricular hearts Arch. Dis. Child., July 1, 2005; 90(7): 757 - 762. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Ghaferi and G. M. Hutchins Progression of liver pathology in patients undergoing the Fontan procedure: Chronic passive congestion, cardiac cirrhosis, hepatic adenoma, and hepatocellular carcinoma J. Thorac. Cardiovasc. Surg., June 1, 2005; 129(6): 1348 - 1352. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Licht, J. Wang, D. W. Silvestre, S. C. Nicolson, L. M. Montenegro, G. Wernovsky, S. Tabbutt, S. M. Durning, D. M. Shera, J. W. Gaynor, et al. Preoperative cerebral blood flow is diminished in neonates with severe congenital heart defects J. Thorac. Cardiovasc. Surg., December 1, 2004; 128(6): 841 - 849. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Connor, R. R. Arons, M. Figueroa, and K. M. Gebbie Clinical Outcomes and Secondary Diagnoses for Infants Born With Hypoplastic Left Heart Syndrome Pediatrics, August 1, 2004; 114(2): e160 - e165. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Gaynor, M. Gerdes, E. H. Zackai, J. Bernbaum, G. Wernovsky, R. R. Clancy, M. F. Newman, A. M. Saunders, P. J. Heagerty, J. A. D'Agostino, et al. Apolipoprotein E genotype and neurodevelopmental sequelae of infant cardiac surgery J. Thorac. Cardiovasc. Surg., December 1, 2003; 126(6): 1736 - 1745. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Culbert, D. A. Ashburn, G. Cullen-Dean, J. A. Joseph, W. G. Williams, E. H. Blackstone, and B. W. McCrindle Quality of Life of Children After Repair of Transposition of the Great Arteries Circulation, August 19, 2003; 108(7): 857 - 862. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Griffin, T. D. Elkin, and C. J. Smith Academic Outcomes in Children with Congenital Heart Disease Clinical Pediatrics, June 1, 2003; 42(5): 401 - 409. [Abstract] [PDF]
|
|
|
|
 |
|
 H Dittrich, C Buhrer, I Grimmer, S Dittrich, H Abdul-Khaliq, and P E Lange Neurodevelopment at 1 year of age in infants with congenital heart disease Heart, April 1, 2003; 89(4): 436 - 441. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Kirshbom, R. J. Myung, J. W. Gaynor, R. F. Ittenbach, S. M. Paridon, W. M. DeCampli, T. R. Karl, and T. L. Spray Preoperative pulmonary venous obstruction affects long-term outcome for survivors of total anomalous pulmonary venous connection repair Ann. Thorac. Surg., November 1, 2002; 74(5): 1616 - 1620. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Forbess, K. J. Visconti, C. Hancock-Friesen, R. C. Howe, D. C. Bellinger, and R. A. Jonas Neurodevelopmental Outcome After Congenital Heart Surgery: Results From an Institutional Registry Circulation, September 24, 2002; 106(12_suppl_1): I-95 - I-102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A P SALMON Hypoplastic left heart syndrome---outcome and management Arch. Dis. Child., December 1, 2001; 85(6): 450 - 451. [Full Text] [PDF]
|
|
|
|
|
|
J. M. Forbess, K. J. Visconti, D. C. Bellinger, and R. A. Jonas Neurodevelopmental Outcomes in Children After the Fontan Operation Circulation, September 18, 2001; 104 (2009): I-127 - I-132. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Perloff and C. A. Warnes Challenges Posed by Adults With Repaired Congenital Heart Disease Circulation, May 29, 2001; 103(21): 2637 - 2643. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||