Immunologic risk stratification of pediatric heart transplant patients by combining HLA-EMMA and PIRCHE-II.

Human leukocyte antigen (HLA) molecular mismatch is a powerful biomarker of rejection. Few studies have explored its use in assessing rejection risk in heart transplant recipients. We tested the hypothesis that a combination of HLA Epitope Mismatch Algorithm (HLA-EMMA) and Predicted Indirectly Recognizable HLA Epitopes (PIRCHE-II) algorithms can improve risk stratification of pediatric heart transplant recipients. Class I and II HLA genotyping were performed by next-generation sequencing on 274 recipient/donor pairs enrolled in the Clinical Trials in Organ Transplantation in Children (CTOTC). Using high-resolution genotypes, we performed HLA molecular mismatch analysis with HLA-EMMA and PIRCHE-II, and correlated these findings with clinical outcomes. Patients without pre-formed donor specific antibody (DSA) (n=100) were used for correlations with post-transplant DSA and antibody mediated rejection (ABMR). Risk cut-offs were determined for DSA and ABMR using both algorithms. HLA-EMMA cut-offs alone predict the risk of DSA and ABMR; however, if used in combination with PIRCHE-II, the population could be further stratified into low-, intermediate-, and high-risk groups. The combination of HLA-EMMA and PIRCHE-II enables more granular immunological risk stratification. Intermediate-risk cases, like low-risk cases, are at a lower risk of DSA and ABMR. This new way of risk evaluation may facilitate individualized immunosuppression and surveillance.

Incidence, characterization, and impact of newly detected donor-specific anti-HLA antibody in the first year after pediatric heart transplantation: A report from the CTOTC-04 study.

Data on the clinical importance of newly detected donor-specific anti-HLA antibodies (ndDSAs) after pediatric heart transplantation are lacking despite mounting evidence of the detrimental effect of de novo DSAs in solid organ transplantation. We prospectively tested 237 pediatric heart transplant recipients for ndDSAs in the first year posttransplantation to determine their incidence, pattern, and clinical impact. One-third of patients developed ndDSAs; when present, these were mostly detected within the first 6 weeks after transplantation, suggesting that memory responses may predominate over true de novo DSA production in this population. In the absence of preexisting DSAs, patients with ndDSAs had significantly more acute cellular rejection but not antibody-mediated rejection, and there was no impact on graft and patient survival in the first year posttransplantation. Risk factors for ndDSAs included common sensitizing events. Given the early detection of the antibody response, memory responses may be more important in the first year after pediatric heart transplantation and patients with a history of a sensitizing event may be at risk even with a negative pretransplantation antibody screen. The impact on late graft and patient outcomes of first-year ndDSAs is being assessed in an extended cohort of patients.

Cost-effectiveness of pediatric heart transplantation across a positive crossmatch for high waitlist urgency candidates.

Allosensitized children listed with a requirement for a negative prospective crossmatch have high mortality. Previously, we found that listing with the intent to accept the first suitable organ offer, regardless of the possibility of a positive crossmatch (TAKE strategy), results in a survival advantage from the time of listing compared to awaiting transplantation across a negative crossmatch (WAIT). The cost-effectiveness of these strategies is unknown. We used Markov modeling to compare cost-effectiveness between these waitlist strategies for allosensitized children listed urgently for heart transplantation. We used registry data to estimate costs and waitlist/posttransplant outcomes. We assumed patients remained in hospital after listing, no positive crossmatches for WAIT, and a base-case probability of a positive crossmatch of 47% for TAKE. Accepting the first suitable organ offer cost less ($405 904 vs. $534 035) and gained more quality-adjusted life years (3.71 vs. 2.79). In sensitivity analyses, including substitution of waitlist data from children with unacceptable antigens specified during listing, TAKE remained cost-saving or cost-effective. Our findings suggest acceptance of the first suitable organ offer for urgently listed allosensitized pediatric heart transplant candidates is cost-effective and transplantation should not be denied because of allosensitization status alone.

Comparison of listing strategies for allosensitized heart transplant candidates requiring transplant at high urgency: a decision model analysis.

Allosensitized children who require a negative prospective crossmatch have a high risk of death awaiting heart transplantation. Accepting the first suitable organ offer, regardless of the possibility of a positive crossmatch, would improve waitlist outcomes but it is unclear whether it would result in improved survival at all times after listing, including posttransplant. We created a Markov decision model to compare survival after listing with a requirement for a negative prospective donor cell crossmatch (WAIT) versus acceptance of the first suitable offer (TAKE). Model parameters were derived from registry data on status 1A (highest urgency) pediatric heart transplant listings. We assumed no possibility of a positive crossmatch in the WAIT strategy and a base-case probability of a positive crossmatch in the TAKE strategy of 47%, as estimated from cohort data. Under base-case assumptions, TAKE showed an incremental survival benefit of 1.4 years over WAIT. In multiple sensitivity analyses, including variation of the probability of a positive crossmatch from 10% to 100%, TAKE was consistently favored. While model input data were less well suited to comparing survival when awaiting transplantation across a negative virtual crossmatch, our analysis suggests that taking the first suitable organ offer under these circumstances is also favored.

Bartonella henselae-mediated disease in solid organ transplant recipients: two pediatric cases and a literature review.

Bartonella henselae, the etiologic agent of cat-scratch disease, causes a well-defined, self-limited syndrome of fever and regional lymphadenopathy in immunocompetent hosts. In immunocompromised hosts, however, B. henselae can cause severe disseminated disease and pathologic vasoproliferation known as bacillary angiomatosis (BA) or bacillary peliosis. BA was first recognized in patients infected with human immunodeficiency virus. It has become more frequently recognized in solid organ transplant (SOT) recipients, but reports of pediatric cases remain rare. Our review of the literature revealed only one previously reported case of BA in a pediatric SOT recipient. We herein present 2 pediatric cases, one of which is the first reported case of BA in a pediatric cardiac transplant recipient, to our knowledge. In addition, we review and summarize the literature pertaining to all cases of B. henselae-mediated disease in SOT recipients.

Incidental intracranial hemorrhage after uncomplicated birth: MRI before and after neonatal heart surgery.

We investigated the prevalence of intracranial hemorrhage (ICH) before and after neonatal heart surgery. We carried out pre- and postoperative MRI looking for brain lesions in 24 full-term newborns with known congenital heart disease. They underwent heart surgery with cardiopulmonary bypass (CPB), usually with deep hypothermic circulatory arrest (DHCA). The first MRI was 1-22 days after birth. There were 21 children born after uncomplicated vaginal delivery and three delivered by cesarean section (CS). ICH was seen in 13 (62%) of the vaginal delivery group but in none of the CS group. We saw subdural bleeding along the inferior surface of the tentorium in 11 (52%) and supratentorially in six (29%) of the 21 children with ICH. Small hemorrhages were present in the choroid plexus in seven (33%), in the parenchyma in one (5%) and in the occipital horn in one (5%). There were 26 foci of bleeding in these 21 patients (1.2 per patient). None was judged by formal neurologic examination to be symptomatic from the hemorrhage. Follow-up MRI after cardiac surgery was obtained in 23 children, showing 37 foci of ICH (1.6 per patient), but all appeared asymptomatic. Postoperatively, ICH had increased in 10 children (43%), was unchanged in seven (30%) and was less extensive in six (26%).

Exercise performance in tetralogy of Fallot: the impact of primary complete repair in infancy.

Primary complete repair (PCR) of tetralogy of Fallot (TOF) is now routinely performed in infancy. Although operative results are excellent, the impact on exercise performance is incompletely understood. We reviewed data of all children with TOF who underwent PCR at our institution and had subsequent maximal cycle ergometer exercise testing between January 1995 and December 2000. Of the 193 patients with TOF who underwent PCR, 57 (30%) underwent exercise testing; maximal tests were available for 50 of 57 (88%). Exercise performance of subjects who underwent PCR at <1 year of age was compared to that of those who underwent repair at >l year of age. The median age at PCR was 10.9 months; 28 subjects (56%) underwent PCR in infancy (<1 year). A transannular incision was employed in the repair in 41 subjects (82%). The mean age at exercise testing was 12.5 +/- 3.2 years. The mean maximal VO2 was 94.9 +/- 18.8% predicted and the mean maximal work rate was 98.0 +/- 20.8% predicted. In multivariate analysis PCR in infancy (age <1 year) was not associated with maximal VO2, peak work rate, peak heart rate, or arrhythmias. Only older age at testing and male gender were significantly associated with higher maximal VO2 (p = 0.005 and p = 0.002, respectively). Intermediate-term exercise performance in subjects who undergo PCR of TOF in early childhood is near normal. Performing PCR in the first year of life does not impact subsequent exercise performance.

Atrioventricular valve regurgitation in patients with single ventricle: impact of the bidirectional cavopulmonary anastomosis.

BACKGROUND: It is not known whether atrioventricular valve regurgitation (AVVR) can improve in some patients after the bidirectional cavopulmonary anastomosis (BCPA) without undertaking concomitant valvuloplasty. METHODS: We retrospectively reviewed our experience with patients who underwent the BCPA between June 1989 and June 2000 with specific attention to those patients with moderate or severe AVVR. The degree of AVVR was determined by color Doppler echocardiography. During the study period there were 576 patients who underwent BCPA at a median age of 6.8 months (range, 1.3 months to 4.8 years). The majority of subjects (66%) had a tricuspid valve as the systemic atrioventricular valve. Significant (moderate or severe) AVVR before BCPA was noted in 36 of 576 patients (6%) and was significantly more prevalent (8 of 52 patients, 15%; p = 0.01) in patients with a common atrioventricular canal. RESULTS: Of the 36 subjects with moderate or severe AVVR, 8 had interventions (6 valvuloplasty, 2 aortic arch dilation) at BCPA. There was 1 hospital death (2.8%). Of the remaining 27 survivors who did not undergo additional interventions at BCPA, improvement in AVVR (mild or none) was noted in 6 (22%) at intermediate follow-up (median, 2 years; range, 0.5 to 3.1 years). The presence of significant AVVR before BCPA was not significantly associated with hospital survival or intermediate-term freedom from death or transplantation. CONCLUSIONS: We conclude that AVVR improves in some patients after BCPA and that valvuloplasty is not justified in all patients with moderate preoperative AVVR.

Quantitative echocardiographic assessment of the performance of the functionally single right ventricle after the Fontan operation.

BACKGROUND: Performance of the functionally single right ventricle may deteriorate over time. Quantitative assessment of this chamber, however, is complicated by its asymmetric geometry. Automatic detection of borders, and the Doppler-derived index of myocardial performance, are echocardiographic techniques that allow for quantitative assessment regardless of ventricular shape. We sought to evaluate the mechanics of contraction and relaxation in the functionally single right ventricle using these parameters. METHODS: We evaluated systemic ventricular function in 35 asymptomatic patients with functionally single right ventricle, having a mean age of 7.8+/-3.1 years, who had undergone the Fontan procedure. We compared them with 32 age-matched normal controls using both automatic detection of borders and Doppler indexes. RESULTS: When compared with the controls, the group with a functionally single right ventricle demonstrated diminished systolic function as evidenced by a lower fractional change in area (42.7+/-10.1% vs. 54.6+/-10.5%, p = 0.001), and diminished diastolic function, as demonstrated by a greater reliance on atrial contraction to achieve ventricular filling (32.0+/-4.4% vs. 22.2+/-4.1%, p = 0.001). The mean index of myocardial performance in those with functionally single right ventricles was also greater than in controls (0.41+/-0.12 vs. 0.30+/-0.05, p = 0.001), and the indexed ejection time was shorter (0.35+/-0.05 vs. 0.39+/-0.05, p = 0.01), suggesting less efficient ventricular mechanics. CONCLUSIONS: These data demonstrate that the systolic and diastolic properties of the functionally single right ventricle differ significantly from those of the normal systemic left ventricle. Use of the echocardiographic techniques provide insight into ventricular mechanics in patients with functionally single ventricles, and may be valuable tools for serial quantitative follow-up.

Atrioventricular valve replacement in patients with a single ventricle.

BACKGROUND: Significant atrioventricular valve (AVV) insufficiency has been associated with increased mortality and morbidity in patients with single ventricle. Although many patients can be managed with valvuloplasty alone, some patients require AVV replacement. The optimal timing, outcome, and risk factors for AVV replacement in this population have not been described. METHODS: We retrospectively reviewed our experience with AVV replacement in patients with single ventricle from January 1984 to August 2000. Outcome variables included mortality and valve-related complications. RESULTS: Seventeen patients required AVV replacement. Prosthetic valve types included: St. Jude's valve in 14, Bjork-Shiley in 1, Hall-Kaster in 1, and Carpentier-Edwards in 1. Valve size ranged from 17 to 33 mm, Median age at valve replacement was 3.0 years (range 7 days to 17.3 years). Of the 16 subjects with normal atrioventricular conduction preoperatively, 7 (44%) developed postoperative complete heart block. Hospital mortality was 29%. Hospital mortality decreased significantly from 56% in 1984 to 1993 to no deaths from 1994 to 2000 (p = 0.03). Younger age (less than 2 years) at operation was also a risk factor for hospital mortality (p = 0.03). There were four late deaths in this series and 1 patient underwent heart transplantation. Of the surviving patients, none has required replacement of the prosthetic valve. No patients have had cerebrovascular accident subsequent to AVV replacement. Functional status is New York Heart Association functional class I in 5, class II in 1, and Class III in 1. CONCLUSIONS: Atrioventricular valve replacement can be performed in patients with single ventricle with acceptable morbidity and mortality. The development of postoperative complete heart block is common. Survival after AVV replacement has improved in recent years, and intervention before patients develop ventricular dysfunction and atrial arrhythmias may further improve outcome.

Allopurinol neurocardiac protection trial in infants undergoing heart surgery using deep hypothermic circulatory arrest.

OBJECTIVE: This pharmacologic protection trial was conducted to test the hypothesis that allopurinol, a scavenger and inhibitor of oxygen free radical production, could reduce death, seizures, coma, and cardiac events in infants who underwent heart surgery using deep hypothermic circulatory arrest (DHCA). DESIGN: This was a single center, randomized, placebo-controlled, blinded trial of allopurinol in infant heart surgery using DHCA. Enrolled infants were stratified as having hypoplastic left heart syndrome (HLHS) and all other forms of congenital heart disease (non-HLHS). Drug was administered before, during, and after surgery. Adverse events and the clinical efficacy endpoints death, seizures, coma, and cardiac events were monitored until infants were discharged from the intensive care unit or 6 weeks, whichever came first. RESULTS: Between July 1992 and September 1997, 350 infants were enrolled and 348 subsequently randomized. A total of 318 infants (131 HLHS and 187 non-HLHS) underwent heart surgery using DHCA. There was a nonsignificant treatment effect for the primary efficacy endpoint analysis (death, seizures, and coma), which was consistent over the 2 strata. The addition of cardiac events to the primary endpoint resulted in a lack of consistency of treatment effect over strata, with the allopurinol treatment group experiencing fewer events (38% vs 60%) in the entire HLHS stratum, compared with the non-HLHS stratum (30% vs 27%). In HLHS surgical survivors, 40 of 47 (85%) allopurinol-treated infants did not experience any endpoint event, compared with 27 of 49 (55%) controls. There were fewer seizures-only and cardiac-only events in the allopurinol versus placebo groups. Allopurinol did not reduce efficacy endpoint events in non-HLHS infants. Treated and control infants did not differ in adverse events. CONCLUSIONS: Allopurinol provided significant neurocardiac protection in higher-risk HLHS infants who underwent cardiac surgery using DHCA. No benefits were demonstrated in lower risk, non-HLHS infants, and no significant adverse events were associated with allopurinol treatment.congenital heart defects, hypoplastic left heart syndrome, induced hypothermia, ischemia-reperfusion injury, neuroprotective agents, allopurinol, xanthine oxidase, free radicals, seizures, coma.

Impact of prenatal diagnosis on survival and early neurologic morbidity in neonates with the hypoplastic left heart syndrome.

BACKGROUND: Prenatal echocardiography can identify the fetus that has complex congenital heart disease and may improve early management and surgical outcome. Prenatal diagnosis may be particularly beneficial to patients who have hypoplastic left heart syndrome (HLHS) and who are at risk for hypoxic-ischemic insult at presentation. OBJECTIVES: We sought to determine whether prenatal diagnosis reduces neurologic morbidity and operative mortality in patients who undergo palliative surgery for the HLHS. METHODS: Data from all patients who had HLHS, except for those with lethal genetic anomalies, and who were admitted to our institution between July 1992 and September 1997 were analyzed to assess the impact of prenatal diagnosis on preoperative management, neurologic morbidity, and surgical mortality. The primary outcome measures were hospital mortality and the incidence of adverse neurologic events (seizure or coma). RESULTS: There were 216 patients who had HLHS and were referred for surgical palliation, 79 (36.6%) of whom had been diagnosed prenatally. All patients who had been diagnosed prenatally were delivered in an advanced nursery and were started on prostaglandin E(1) on the first day of life. Patients whose HLHS was diagnosed postnatally were begun on prostaglandin E(1) later in life (median = day 2 [range = 1-28 days]). There were 4 preoperative deaths and 53 operative or postoperative deaths. Overall hospital mortality was 26.4% and did not differ between patients whose HLHS had been diagnosed prenatally and those whose HLHS had been diagnosed postnatally. With the use of multivariable analysis, prenatal diagnosis was associated with fewer adverse perioperative neurologic events in the patients whose HLHS had been diagnosed prenatally than in those whose HLHS had been diagnosed postnatally (odds ratio = 0.46). CONCLUSIONS: These data suggest that prenatal diagnosis has a favorable impact on treatment of patients who have HLHS and are undergoing staged palliation and reduces early neurologic morbidity. Prenatal diagnosis was not associated with reduced hospital mortality. It is possible that prenatal diagnosis may improve long-term neurologic outcome.

Exercise performance after the arterial switch operation for D-transposition of the great arteries.

Early- and intermediate-term results of the arterial switch operation for D-transposition of the great arteries (D-TGA) are encouraging. However, questions remain about the long-term outcome for these patients, especially with regard to exercise performance. Preliminary studies have demonstrated normal endurance time on treadmills. However, data regarding aerobic capacity and cardiopulmonary function are lacking. We report the cardiopulmonary performance of 22 school-age patients with D-TGA who underwent the arterial switch operation. Outcome variables included maximal oxygen consumption (VO2), maximal cardiac index, and peak heart rate. Patient and procedure-related variables were assessed for their association with outcome variables using linear and logistic regression. The mean values of maximal VO2 (113 +/- 19% predicted) and maximal cardiac index (96 +/- 18% predicted) were within normal limits for the pediatric population. Although the mean peak heart rate for the entire group (184 +/- 14 beats/min) was within normal limits, there were 7 subjects (32%) with chronotropic impairment. Significant ST-segment depression was seen in 2 subjects (9%). In regression analysis, surgery subsequent to the arterial switch was associated with lower maximal cardiac index (p = 0.01). Other variables were not significantly associated with maximal VO2, maximal cardiac index, and peak heart rate. In particular, chronotropic impairment was not significantly associated with maximal VO2 or maximal cardiac index. These findings demonstrate that cardiopulmonary performance during exercise is excellent after the arterial switch operation. The finding of ST-segment depression in some subjects supports the role of formal exercise testing in those patients participating in vigorous athletic activities.

Long-term developmental outcome of children with complex congenital heart disease.

As the mortality of neonatal and infant surgery for CHD continues to decrease, attention is now focused on long-term sequelae, especially later cognitive and neurologic function, in survivors. Although children with repaired or palliated CHD have an increased risk for neurocognitive deficits, most survivors are performing within the normal range for most standardized measures. Even those children at highest risk, such as patients with HLHS, are comparable with survivors of other congenital lesions, such as diaphragmatic hernia, or low-birth weight children. Continued efforts are underway to reduce cerebral injury before, during, and after congenital heart surgery.

Unexpected death after reconstructive surgery for hypoplastic left heart syndrome.

BACKGROUND: Although operative mortality for reconstructive surgery for hypoplastic left heart syndrome continues to improve, nonoperative mortality, especially in the first year of life, remains relatively high. A number of patients who are thought to be clinically well at hospital discharge die unexpectedly. The goal of the present study was to determine the incidence of and risk factors for unexpected death in patients with hypoplastic left heart syndrome. METHODS: Retrospectively, we determined the incidence of unexpected death among 536 patients with hypoplastic left heart syndrome who were discharged to home after stage I surgical procedure. To identify potential risk factors, a nested case-control analysis was undertaken. RESULTS: Unexpected death occurred in 22 of 536 patients (4.1%) discharged to home after stage I surgical procedure. The median age at unexpected death was 79 days (range, 25 to 227 days). Seizures preceded cardiac arrest in 2 patients, and ventricular arrhythmias were documented in 3 additional patients during attempted resuscitation. Autopsy studies were performed in 12 patients and identified residual lesions that may have contributed to death in 2 patients. In multivariate analysis documented perioperative arrhythmia and earlier year of stage I surgical procedure were associated with an increased risk for unexpected death (p = 0.03 and p = 0.04, respectively). There were 4 additional patients who had unexpected death after subsequent cavopulmonary operation at a median age of 1.6 years (range, 0.9 to 3.8 years). CONCLUSIONS: Unexpected death occurred in more than 4% of patients with hypoplastic left heart syndrome who were discharged to home after stage I surgical procedure and was most common in the first several months of life. Factors that may contribute to unexpected death include residual lesions, arrhythmias, and neurologic events, although in the majority of cases the cause remains largely unknown.

Neurologic and cognitive outcomes in children with congenital heart disease.

Advances in congenital heart surgery have resulted in the increased survival of infants born with complex congenital heart disease. Questions remain, however, about how these patients will develop and whether they will have normal, productive lives. To date, studies have shown that although the vast majority of children with congenital heart disease have normal outcomes, as a group they generally have higher rates of neurodevelopmental problems. The developmental sequelae include mild problems in cognition, attention, and neuromotor functioning. The etiology of neurologic deficits in this population appears to be multifactorial with preoperative, operative, and postoperative factors all contributing to outcome. Continued research and attempts to minimize neurologic injury and associated sequelae are of primary importance. Recent data suggest that advances in care already may be improving outcome after congenital heart surgery. Ongoing documentation of the long-term outcome in this population needs to be mandated, as does the implementation of environmental enrichment programs to help ameliorate the long-term consequences of congenital heart disease.

Survival after reconstructive surgery for hypoplastic left heart syndrome: A 15-year experience from a single institution.

BACKGROUND: There are limited data regarding the long-term survival of patients who have undergone reconstructive surgery for hypoplastic left heart syndrome (HLHS). We reviewed the 15-year experience at our institution to examine survival in the context of continued improvements in early operative results. METHODS AND RESULTS: Between 1984 and 1999, 840 patients underwent stage I surgery for HLHS. From review of medical records and direct patient contact, survival status was determined. The 1-, 2-, 5-, 10-, and 15-year survival for the entire cohort was 51%, 43%, 40%, 39%, and 39%, respectively. Late death occurred in 14 of the 291 patients discharged to home after the Fontan procedure, although only 1 patient has died beyond 5 years of age. Heart transplantation after stage I reconstruction was performed in 5 patients. Later era of stage I surgery was associated with significantly improved survival (P:<0.001). Three-year survival for patients undergoing stage I reconstruction from 1995 to 1998 was 66% versus 28% for those patients undergoing surgery from 1984 to 1988. Age >14 days at stage I and weight <2.5 kg at stage I were also associated with higher mortality (P:=0.004 and P:=0.01, respectively). Other variables, including anatomic subtype, heterotaxia, and age at subsequent staging procedures, were not associated with survival. CONCLUSIONS: Over the 15-year course of this study, early- and intermediate-term survival for patients with HLHS undergoing staged palliation increased significantly. Late death and the need for cardiac transplantation were uncommon.

Neurodevelopmental outcome and lifestyle assessment in school-aged and adolescent children with hypoplastic left heart syndrome.

OBJECTIVES: The purposes of this study are to describe the quality of life and cognitive function in school-aged children who have undergone staged palliation for hypoplastic left heart syndrome (HLHS), and to identify factors that are predictive of neurodevelopmental outcome in this population. METHODS: School-aged survivors with HLHS who had undergone palliative surgery at our institution were identified and mailed a questionnaire to assess subjectively quality of life, school performance, and incidence of medical complications. A subgroup of local patients underwent standardized testing of cognitive function and neurologic examination. These patients were compared with the larger (remote) group of questionnaire respondents to determine whether results may be generalizable to the entire HLHS population. Potential predictors of neurologic and cognitive outcome were tested for their association with test scores using multivariate regression analysis. RESULTS: Questionnaire results were obtained from 115 of 138 eligible children (83%; mean age: 9.0 +/- 2.0 years). Standardized testing was performed in 28 of 34 (82%) eligible local patients (mean age: 8.6 +/- 2.1 years). The majority of parents or guardians described their child's health as good (34%) or excellent (45%) and their academic performance as average (42%) or above average (42%). One third of the children, however, were receiving some form of special education. Chronic medication usage was common (64%); the incidence of medical complications was comparable to that previously reported in children with Fontan physiology. Cognitive testing of the local group demonstrated a median full scale IQ of 86 (range: 50-116). Mental retardation (IQ: <70) was noted in 18% of patients. In multivariate analysis, only the occurrence of preoperative seizures predicted lower full scale IQ. CONCLUSIONS: Although the majority of school-aged children with HLHS had IQ scores within the normal range, mean performance for this historical cohort of survivors was lower than that in the general population.