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This study was undertaken to assess the incidence, indications, and predisposing factors for pacemaker placement in a pediatric heart transplant population. From November 1985 to May 1994, 246 pediatric patients have undergone cardiac transplantation at Loma Linda University Medical Center. Seven (2.8%) have received pacemaker placement with an 8-50 month follow-up period. Median age at transplant was 462 days (0 days to 2.5 years). The median time to pacemaker placement was 190 days (18-1,672 days) after transplantation. Indications were sick sinus syndrome (SSS) in 5 and heart block in 2 patients (1 during acute rejection). Three patients with SSS underwent electrophysiology studies (EPS); 1 was normal and 2 showed sinus node dysfunction. The mode of pacing was VVIR in 6 patients and VVI in 1 patient. All 6 survivors are doing well and 5 patients' pacemakers still provide support. These 7 patients were compared with 185 pediatric patients (0 days to 12-years-old) transplanted during 1985 through 1993 who survived at least 6 months after transplantation. There was no correlation between the receipt of a pacemaker and graft cold ischemic time, rejection history, donor age, or recipient age at transplantation. The 5 patients with SSS had significantly lower average heart rates in the first month after transplantation (108 + or - 16 vs 130 + or - 12; P = 0.0002). The need for permanent pacemakers in this population is uncommon. Pacemakers, however, can be safely performed when necessary with excellent clinical results. [ABSTRACT FROM AUTHOR]

This study evaluated the procedural and long-term outcome of infants who underwent atrial septostomy while awaiting transplant. The results suggest that septostomy improved outcome in these patients although infants needing a transseptal perforation were at higher risk. [ABSTRACT FROM AUTHOR]

The International Pediatric Transplant Association convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post-transplant lymphoproliferative disorders (PTLD) after pediatric solid organ transplantation. This report addresses the outcomes of deliberations by the PTLD Management Working Group. A strong recommendation was made for reduction in immunosuppression as the first step in management. Similarly, strong recommendations were made for the use of the anti-CD20 monoclonal antibody (rituximab) as was the case for chemotherapy in selected scenarios. In some scenarios, there is uncoupling of the strength of the recommendations from the available evidence in situations where such evidence is lacking but collective clinical experiences drive decision-making. Of note, there are no large, randomized phase III trials of any treatment for PTLD in the pediatric age group. Current gaps and future research priorities are highlighted., (© 2024 Wiley Periodicals LLC.)

Background: The disproportionate effects of the human immunodeficiency virus (HIV) and the Coronavirus 2019 (COVID-19) on Black American communities highlight structural systems rooted in racism and must be addressed with national strategies that improve both biomedicine and social determinants of health., Purpose: The purpose of this study was to qualitatively examine the experiences and interpretations of experts in the HIV workforce (local, state, and national HIV-related organizations) regarding the state of HIV and COVID-19 among Black Americans., Methods: Within key informant interviews and a focus group recorded and transcribed verbatim, fifteen members of the HIV workforce and Black community described their experiences and provided insights to inform ending the negative outcomes resulting from HIV and COVID-19., Results: Data were analyzed using NVivo software, and eight themes emerged to address disease disproportionality through a Black lens. Themes reflected (1) accessing information and care; (2) key potential partners/stakeholders; (3) investing in Black communities; (4) governmental support; (5) increasing engagement and advocacy; (6) HIV-related community conversations; (7) developments since COVID-19; and (8) the Ending the HIV Epidemic (EHE) trajectory., Conclusions: Themes directly speak to recommendations to adjust education and policy strategies for HIV and COVID-19 prevention and intervention. Such recommendations, (1) amplifying Black voices, (2) investing sustainable dollars into Black communities, and (3) leaning into advocacy, can bolster the foundation for the HIV workforce and Black community to break ineffective response patterns and lead the fight against these systemic issues of inequity., (© 2024. The Author(s).)

The International Pediatric Transplant Association (IPTA) convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post-transplant lymphoproliferative disorder after solid organ transplantation in children. In this report from the Prevention Working Group, we reviewed the existing literature regarding immunoprophylaxis and chemoprophylaxis, and pre-emptive strategies. While the group made a strong recommendation for pre-emptive reduction of immunosuppression at the time of EBV DNAemia (low to moderate evidence), no recommendations for use could be made for any prophylactic strategy or alternate pre-emptive strategy, largely due to insufficient or conflicting evidence. Current gaps and future research priorities are highlighted., (© 2022 Wiley Periodicals LLC.)

The International Pediatric Transplant Association convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post-transplant lymphoproliferative disorders after solid organ transplantation in children. In this report from the Viral Load and Biomarker Monitoring Working Group, we reviewed the existing literature regarding the role of Epstein-Barr viral load and other biomarkers in peripheral blood for predicting the development of PTLD, for PTLD diagnosis, and for monitoring of response to treatment. Key recommendations from the group highlighted the strong recommendation for use of the term EBV DNAemia instead of "viremia" to describe EBV DNA levels in peripheral blood as well as concerns with comparison of EBV DNAemia measurement results performed at different institutions even when tests are calibrated using the WHO international standard. The working group concluded that either whole blood or plasma could be used as matrices for EBV DNA measurement; optimal specimen type may be clinical context dependent. Whole blood testing has some advantages for surveillance to inform pre-emptive interventions while plasma testing may be preferred in the setting of clinical symptoms and treatment monitoring. However, EBV DNAemia testing alone was not recommended for PTLD diagnosis. Quantitative EBV DNAemia surveillance to identify patients at risk for PTLD and to inform pre-emptive interventions in patients who are EBV seronegative pre-transplant was recommended. In contrast, with the exception of intestinal transplant recipients or those with recent primary EBV infection prior to SOT, surveillance was not recommended in pediatric SOT recipients EBV seropositive pre-transplant. Implications of viral load kinetic parameters including peak load and viral set point on pre-emptive PTLD prevention monitoring algorithms were discussed. Use of additional markers, including measurements of EBV specific cell mediated immunity was discussed but not recommended though the importance of obtaining additional data from prospective multicenter studies was highlighted as a key research priority., (© 2023 Wiley Periodicals LLC.)

Pediatric heart transplant recipients have been expected to be at higher risk of adverse events from developing COVID-19 infection. COVID-19 RNA PCR and antibody testing has been performed in our cohort of patients since March 15, 2020 and outcomes were reviewed. COVID-19 infection in our population of pediatric heart transplant recipients is common (21%), despite recommendations to avoid contact with others. Asymptomatic COVID-19 infection is common as well (55%). Despite the frequency of infection, COVID-19 is well tolerated in this population (5% admission from home; 0% mortality). A suppressed immune system does not significantly inhibit an antibody response in pediatric heart transplant recipients (>70% antibody seroconversion) and appears to persist, similar to those without transplantation (>90 days). Routine testing for COVID-19 via PCR and antibody testing enhances the ability to detect COVID-19 infection in asymptomatic patients and may help reduce unintended transmission to more susceptible individuals., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Primary transplantation was developed in the 1980s as an alternative therapy to palliative reconstruction of uncorrectable congenital heart disease. Although transplantation achieved more favorable results, its utilization has been limited by the availability of donor organs. This review examines the long-term outcomes of heart transplantation in neonates at our institution., Methods: The institutional pediatric heart transplant database was queried for all neonatal heart transplants performed between 1985 and 2017. Follow-up was obtained from medical records and an annually administered questionnaire. Overall survival and time to development of complications were estimated using the Kaplan Meier method. Univariate and multivariate analyses were performed to identify independent predictors of survival., Results: Heart transplantation was performed in 104 neonates. Median age was 17 days. Hypoplastic left heart syndrome (classic or variant) was the primary diagnosis in 77.8% of patients. Survival at 10 years and 25 years was 73.9% and 55.8%, respectively. At 20 years, freedom from allograft vasculopathy and lymphoproliferative disease was 72.0% and 81.9%, respectively. Freedom from re-transplantation was 81.4% at 20 years. Eight patients (7.6%) developed end-stage renal disease. By multivariate analysis, lower glomerular filtration rate and allograft vasculopathy were the only significant predictors of death., Conclusions: Neonatal heart transplantation remains a durable therapy with very acceptable long-term survival. Children transplanted in the newborn period have the potential to reach adulthood with minimal need for reintervention., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The newborn infant with severe cardiac failure owed to congenital structural heart disease or cardiomyopathy poses a daunting therapeutic challenge. The ideal solution for both might be cardiac transplantation if availability of hearts was not limiting and if tolerance could be induced, obviating toxicity of immunosuppressive therapy. If one could safely and effectively exploit neonatal tolerance for successful xenotransplantation of the heart, the challenge of severe cardiac failure in the newborn infant might be met. We discuss the need, the potential for applying neonatal tolerance in the setting of xenotransplantation and the possibility that other approaches to this problem might emerge., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Intravascular ultrasound (IVUS) has been routinely used in some centers to investigate cardiac allograft vasculopathy in pediatric heart transplant recipients. We present an alternative method using more sophisticated imaging software. This study presents a comparison of this method with an established standard method. All patients who had IVUS performed in 2014 were retrospectively evaluated. The standard technique consisted of analysis of 10 operator-selected segments along the vessel. Each study was re-evaluated using a longitudinal technique, taken at every third cardiac cycle, along the entire vessel. Semiautomatic edge detection software was used to detect vessel imaging planes. Measurements included outer and inner diameter, total and luminal area, maximal intimal thickness (MIT), and intimal index. Each IVUS was graded for severity using the Stanford classification. All results were given as mean ± standard deviation (SD). Groups were compared using Student t test. A P value <.05 was considered significant. There were 59 IVUS studies performed on 58 patients. There was no statistically significant difference between outer diameter, inner diameter, or total area. In the longitudinal group, there was a significantly smaller luminal area, higher MIT, and higher intimal index. Using the longitudinal technique, there was an increase in Stanford classification in 20 patients. The longitudinal technique appeared more sensitive in assessing the degree of cardiac allograft vasculopathy and may play a role in the increase in the degree of thickening seen. It may offer an alternative way of grading severity of cardiac allograft vasculopathy in pediatric heart transplant recipients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Significant racial disparity remains in the incidence of unfavorable outcomes following heart transplantation. We sought to determine which pediatric posttransplantation outcomes differ by race and whether these can be explained by recipient demographic, clinical, and genetic attributes. Data were collected for 80 black and 450 nonblack pediatric recipients transplanted at 1 of 6 centers between 1993 and 2008. Genotyping was performed for 20 candidate genes. Average follow-up was 6.25 years. Unadjusted 5-year rates for death (p = 0.001), graft loss (p = 0.015), acute rejection with severe hemodynamic compromise (p = 0.001), late rejection (p = 0.005), and late rejection with hemodynamic compromise (p = 0.004) were significantly higher among blacks compared with nonblacks. Black recipients were more likely to be older at the time of transplantation (p < 0.001), suffer from cardiomyopathy (p = 0.004), and have public insurance (p < 0.001), and were less likely to undergo induction therapy (p = 0.0039). In multivariate regression models adjusting for age, sex, cardiac diagnosis, insurance status, and genetic variations, black race remained a significant risk factor for all the above outcomes. These clinical and genetic variables explained only 8-19% of the excess risk observed for black recipients. We have confirmed racial differences in survival, graft loss, and several rejection outcomes following heart transplantation in children, which could not be fully explained by differences in recipient attributes., (© 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Pediatric heart transplant patients at our institution are immunosuppressed with a CNI and another immune-modulating agent without utilizing corticosteroids. Patients whose renal function worsened and who did not respond to CNI minimization had their CNI discontinued. The clinical history of 35 pediatric heart transplant patients with significant renal insufficiency whose CNI was discontinued was retrospectively analyzed. Data including serum creatinine and weight were collected before, at time of, and every 3-6 months after CNI discontinuation. This was used to calculate an eGFR. Cardiac allograft rejection and mortality data were also collected. CNI discontinuation occurred 39 times in 35 patients. The median eGFR significantly increased by 14 mL/min 3 months after CNI discontinuation and the increase continued to be significant (P≤.05) at 5 years. Freedom from rejection analysis showed no difference between graft rejection 2 years before versus after CNI discontinuation (P=.437). No mortality was associated with CNI discontinuation. Immunosuppression free of CNIs and corticosteroids appears to be a safe alternative in pediatric heart transplant patients with significant renal insufficiency. Furthermore, this strategy can significantly reverse renal insufficiency, even late after transplantation., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The introduction of cyclosporine revolutionized the practice of immunosuppression for solid organ transplant recipients, and has resulted in a significant increase in survival. While CNI use has been the mainstay of immunosuppressive therapy in pediatric heart transplantation, CNIs have been associated with an increased risk of nephropathy leading to significant morbidity and mortality. We evaluated the effect on renal function of a CNI minimization protocol using SRL in pediatric heart transplant patients with CNI induced renal insufficiency. An IRB approved retrospective chart review and case control study was performed. There were 20 patients identified with renal insufficiency who had been converted to SRL (target 5-8 ng/mL) and cyclosporine (target 50-75 vs. 125-150 ng/mL). Renal insufficiency was defined as isotopic (Indium 111 DTPA) GFR <60 mL/min per 1.73 m(2) or sCr >1 mg/dL. Outcome variables evaluated were GFR and sCr at time of conversion and at two yr post conversion. Comparison was made with case control subjects matched for age at Tx, time from Tx to conversion, and initial GFR. The median age at Tx = 81 days (S.D. ±26), median time of conversion after Tx = 10 yrs (s.d. ±0.65). Self-limited/treatable side effects included hypercholesterolemia (10), neutropenia (6), aphthous ulcer (3), edema (2), anemia (2), and tremor (1). One patient rejected in the two yr prior to conversion, and one patient had two rejection episodes following conversion. GFR at conversion for study group was 51 ± 14 vs. 60 ± 2 at two yr, p = 0.018. GFR at inclusion for control group was 56 ± 20 vs. 53 ± 21, p = 0.253. This report demonstrates that minimizing CNI exposure by addition of SRL to the immunosuppressant regimen in pediatric heart transplant recipients result in improved renal function in comparison to historically managed patients. Furthermore, immunotherapy with SRL and lower-dose CNI can effectively prevent rejection with an acceptable side-effect profile., (© 2011 John Wiley & Sons A/S.)

Successful infant heart transplantation has now been performed for over 25 years. Assessment of long term outcomes is now possible. We report clinical outcomes for322 patients who received their heart transplant during infancy. Actuarial graft survival for newborn recipients is 59% at 25 years. Survival has improved in the most recent era. Cardiac allograft vasculopathy is the most important late cause of death with an actuarial incidence at 25 years of 35%. Post-transplant lymphoma is estimated to occur in 20% of infant recipients by25 years. Chronic kidney disease grade 3 or worse is present in 31% of survivors. The epidemiology of infant heart transplantation has changed through the years as the results for staged repair improved and donor resources remained stagnant. Most centers now employ staged repair for hypoplastic left heart syndrome and similar extreme forms of congenital heart disease. Techniques for staged repair, including the hybrid procedure, are described. The lack of donors is described with particular note regarding decreased donors due to newer programs for appropriate infant sleep positioning and infant car seats. ABO incompatible donors are a newer resource for maximizing donor resources, as is donation after circulatory determination of death and techniques to properly utilize more donors by expanding the criteria for what is an acceptable donor. An immunological advantage for the youngest recipients has long been postulated, and evaluation of this phenomenon may provide clues to the development of accommodation and/or tolerance.

Background: There is always more demand than supply of organs in pediatric heart transplantation. Yet, potential donor organs are regularly declined for a variety of reasons, among them donor organ quality as determined by United Network for Organ Sharing (UNOS) refusal code 830 or its equivalent., Methods: For the study group institutional and UNOS databases (July 2000 to December 2008) were reviewed to examine outcomes of pediatric heart transplantation using donor hearts that had been previously refused one or more times because of organ quality. Variation between outcomes of this cohort and recipients who received primarily offered heart grafts in a single institution was analyzed., Results: In 29 recipients, transplantation or retransplantation was with heart grafts previously declined on the basis of quality. Recovery distances (p < 0.002) and graft cold ischemic times (p < 0.001) were significantly longer for declined hearts. Operative survival was 93% +/- 5.0% (27 of 29). Seven-year actuarial survival was 74% +/- 10.5%. At the present time, 24 of the 29 recipients (83%) are alive. These results do not vary statistically from those experienced by 84 recipients of 86 primarily offered donor organs during the same time., Conclusions: Despite longer distance recovery (ie, longer graft cold ischemic times), outcomes of pediatric heart transplantation using donor heart grafts refused on the basis of organ quality are highly competitive. Pediatric donor hearts should seldom be declined on the basis of organ quality (UNOS code 830).

Background: As infant and pediatric heart transplantation becomes more common, there is a growing need to better understand the causes of failure or death, if we are to continue to improve the outcome in these children., Methods: A multidisciplinary team reviewed all deaths occurring in the cohort of infants and children transplanted during the first 20 years of the Loma Linda Pediatric Heart Transplant program, with 2 additional years of follow-up beyond the 20-year accrual period, and classified them as to cause., Results: There were 169 deaths among 421 recipients, with a median follow-up of 9.7 years. Autopsy was performed in 128 cases. The causes of death, in decreasing order of frequency, included acute rejection (26.0%), infection (16.0%), cardiac allograft vasculopathy (CAV) (14.2%), technical issues (8.3%), acute graft dysfunction (6.5%), neoplasm (7.1%), chronic graft dysfunction (4.7%) and miscellaneous factors (10.1%), and in twelve deaths (7.1%) the cause was unclassified. Acute graft dysfunction and technical issues accounted for nearly two-thirds of the deaths in the first 30 days after transplant, while acute rejection resulted in the largest number of deaths after the first year (30.4%), with CAV a close second (23.5%)., Conclusions: Acute graft dysfunction and technical issues were the most frequent cause of early death. Late deaths were most often due to acute rejection and CAV, which differs somewhat from the experience reported in adults. Acute rejection was the single most important cause of late mortality, and resulted in a significant number of late sudden and unexpected deaths.

Background: Pediatric heart transplantation has now been successfully performed for more than 20 years. As survival rates have improved, more attention is now focused on long-term outcomes., Methods: This report reviews the literature on developmental outcomes after pediatric heart transplantation., Results: Pediatric patients undergoing heart transplantation generally can be expected to have developmental outcomes in the low-normal range, consistent with outcomes seen in other children with complex congenital heart disease requiring surgical intervention. When these children reach school age, or return to school, most can be expected to function reasonably well in mainstream school settings. A significant minority will require additional educational assistance. Approximately 10% will have significant neurologic impairment. In school, particular attention should be paid to evaluating the child for deficits in arithmetic and verbal skills. Performance may be better than predicted from IQ testing. Behavioral issues are common, with depression, concerns about social competence, and attention difficulties most frequently endorsed. This may pre-date transplantation in those who undergo transplantation during childhood and may improve with time. Parents more often report problem behaviors than teachers. Family resources and family coping skills are also strongly correlated with the child's emotions and coping skills., Conclusion: The pediatric heart transplant recipient's ability to transition from childhood into a happy and productive adult life can be significantly affected by his or her cognitive abilities, learning experiences, sense of self, and emotions. Attention to these factors is an important part of caring for these children.

Background: An increasing number of children are being referred for cardiac transplantation after (1) failing conventional corrective or palliative surgical reconstruction, (2) after stabilization with mechanical circulatory support devices, and (3) when primary graft failure or advanced cardiac allograft vasculopathy are established., Methods: The records of 417 infants and children (age range, 0-18 years) who underwent cardiac transplantation from November 1985 through December 2005 at Loma Linda University Children's Hospital were retrospectively reviewed. The pre-transplantation diagnosis was used to divide patients into 3 groups: primary cardiomyopathy (CM), 103; hypoplastic left heart syndrome (HLHS), 154; and other complex congenital heart disease (CCHD), 160. These groups were compared and analyzed for differences in early and late morbidity and mortality., Results: Operative mortality was significantly lower in the CM group compared with the HLHS (p < 0.02;) and CCHD groups (p < 0.01). Long-term actuarial recipient survival, however, was similar for all groups. The 15-year actuarial survival was 59% for the CM Group, 57% for the HLHS Group, and 50% for the CCHD Group. Actuarial survival after retransplantation is not statistically different from that with primary cardiac transplantation., Conclusion: Although peri-operative survival was lower in infants and children with HLHS and CCHD compared with those with CM, long-term survival has been the same for all groups. Late survival after retransplantation was not statistically different than among those with primary cardiac transplantation.

Objective: Children born with hypoplastic left heart syndrome (HLHS) may experience cardiac dysfunction after staged surgery or transplantation, which may worsen with age. We examined the hypothesis that exercise testing can address cardiovascular capacity and suggest interventions to improve quality of life., Study Design: Children with HLHS > or = 8 years old performed treadmill or bicycle ergometric testing at 4 centers. Results were compared with norms for age and sex., Results: Of the 42 participants, the mean age was 12.9 years (range, 8.5-17.0 years), 64% were boys, 20 had staged surgery, and 34 completed metabolic assessment. The percent of predicted maximal oxygen uptake (mVO2) was higher in younger children. Children aged 8 to 12 years achieved 70% of predicted mVO2; children aged 13 to 17 years achieved 60% of predicted mVO2 (P = .02). The percent of predicted peak heart rate trended higher in younger patients (83% versus 75%, P = .07). Electrocardiographic changes were more common in older children. In treadmill testing, patients who had a transplant had better exercise performance than patients who underwent staged surgery in percent of predicted exercise time (82% versus 54%, P < .0001) and peak rate-pressure product (241 x 10(3) versus 195 x 10(3), P = .02). The percent of predicted mVO2 did not differ between patients who had a transplant (66%) and patients who underwent staged surgery (61%, P = .25)., Conclusion: Children with HLHS showed considerable age-related decline in exercise performance, regardless of surgical strategy.

Background: Although tricuspid valve regurgitation (TR) after heart transplantation is a known complication, there has been little discussion of this subject in neonatal heart transplantation. We aim to elucidate the prevalence, etiology, and evolution of TR early after transplant in neonates., Methods: Eighty-five neonatal recipients were studied retrospectively by two-dimensional and Doppler echocardiography. The semiquantitative grading of TR was based on the ratio of regurgitation jet area to right atrial area., Results: Immediately after neonatal heart transplantation, TR was recognized in 47 patients (grade 1, n = 18; grade 2, n = 22; grade 3, n = 7; and grade 4, n = 0). Tricuspid regurgitation prevalence diminished from 55% to 19% with reduction in severity 1 year after transplantation. The prevalence of TR (grade 2 and grade 3) was affected by a donor/recipient body weight ratio of more than 2.0 (p = 0.004) and graft ischemia for more than 3 hours (p = 0.014). The ratio of donor and recipient right atria portion, which had a correlation with donor/recipient body weight ratio (r2 = 0.415, p < 0.0001), separated the four subgroups in terms of TR grade immediately after transplantation (p = 0.0064) and also at 1 year after transplantation in all surviving grafts from 1.48 +/- 0.54 to 0.8 +/- 0.32 (p < 0.0001). The Cox model found no significance for early posttransplant TR as a risk factor for graft survival., Conclusions: Early posttransplant TR was affected by atria geometrical disproportion and by graft ischemia. Tricuspid regurgitation was not a risk factor for graft survival because of its amelioration over time, perhaps induced by recipient growth and recovery of myocardial injury relating to graft procurement.

At Loma Linda University Children's Hospital, the medical information of 405 pediatric patients who received orthotopic cardiac transplantation were reviewed. Of those who died (n=136), 86% (n=117) underwent postmortem examinations, and the brain was examined in 61% (n=82, male=39). The number and type of intracranial lesions present were compiled, and these were matched to underlying functional cardiac disease categories. Intracranial abnormalities were present in 87%. Infarct was the most common primary central nervous system pathology in hypoplastic left heart syndrome (41%) but was also observed frequently in children with obstructive lesions (37%), cyanotic disease (31%), or cardiac shunting (29%). Secondary findings included extraparenchymal hemorrhage in obstructive lesions (31%); hypoxic changes occurred in 15% of patients with cyanotic disease and in 14% of those with cardiac shunting. Thirty-three percent of children with restrictive lesions had no neuropathology reported. Postmortem examination brain weights were matched against age and sex norms, with 29% of females and 36% of males below two standard deviations. These findings revealed that intracranial pathology was present in the majority of transplanted children who underwent postmortem examination, and that infarctive changes constituted the most common neuropathologic abnormality. Additionally, a number of children had significantly reduced brain weight.

The Pediatric Heart Transplant Study (PHTS) group was founded in 1991 as a voluntary, collaborative effort dedicated to the advancement of the science and treatment of children following listing for heart transplantation. Since 1993, the PHTS has collected data in an international, prospective, event-driven database that examines risk factors for outcome events following listing for transplantation. The events include transplantation, death, rejection, infection, malignancy, graft vasculopathy, and retransplantation. Over its 12 years of existence, the PHTS has made major contributions to the field of pediatric heart transplantation, especially in the areas of outcome analysis and risk factor assessment for death and other major morbidities after listing and after transplantation. The new challenges facing the PHTS include how to implement the practice of evidence-based medicine in the field of pediatric heart transplantation and how to support ongoing data collection and analysis to provide long-term outcomes as the PHTS subjects enter their second decade after transplantation.

Metabolic parameters for coronary allograft vasculopathy (CAV) have not been well defined in children. CAV (by angiography or autopsy) was studied in 337 heart recipients on a cyclosporine-based steroid-sparing regimen. Freedom from CAV for all was 79% at 10 years. Fifty-nine patients (18%) developed CAV at a mean of 6.5 +/- 3 years post-transplant. First year rejections were significantly higher in CAV, mean 2.3 vs. 1.4, P = 0.003, odds ratio (OR) 1.8. Rejection with hemodynamic compromise beyond 1 year post-transplant was associated with CAV, P < 0.001, OR 8.4. There was no significant correlation among human leukocyte antigen DR (HLA DR) mismatch, pacemaker use or homocysteine levels and the development of CAV. Maximum cholesterol and low density lipoprotein (LDL) levels were not significantly different. Neither diabetes nor hypertension was significant predictors of CAV on multivariate logistic regression analysis. In conclusion, frequent and severe rejection episodes may predict pediatric CAV. Neither glucose intolerance nor lipid abnormalities appeared to alter risk for CAV in this population.

Background: There are few published data regarding the long-term outcome of "large" cardiac allografts in children. This study examines the effect of cardiac graft oversizing on the survival of pediatric patients with congenital heart disease (CHD)., Methods: Two hundred ninety-one children, age 1 day to 17 years (median 50 days), with CHD underwent primary cardiac transplantation between 1985 and 2002. Patients were analyzed according to donor-recipient weight ratio (D-R): Group (Gp) I (n = 252) with D-R <2.5 (range 0.59 to 2.49, median 1.4), and Gp II (n = 39) with D-R >/=2.5 (range 2.5 to 4.65, median 2.78). CHD diagnoses included hypoplastic left heart syndrome (138 in Gp I, 13 in Gp II), single ventricle (29 in Gp I, 1 in Gp II) and other (85 in Gp I, 13 in Gp II). Patients with cardiomyopathy were excluded. Pre-transplant cardiac palliation was performed in 36% of Gp I and 15% of Gp II patients. The average graft ischemic times (minutes) were 266 +/- 7.5 and 283 +/- 18.9 for Gp I and Gp II, respectively (p < 0.2)., Results: The operative mortality for Gp I was 10.3% and 10.2% for Gp II (p < 0.99). There was no significant difference between the 2 groups in length of hospital stay (p < 0.15) or duration of ventilator support (p < 0.6) post-transplantation. However, the incidence of open chest was higher (p < 0.003) in Gp II (28%) compared with Gp I (8%). The survival rates for Gp I and Gp II were: 82 +/- 2.4% vs 84 +/- 5.7% at 1 year; 71 +/- 2.9% vs 72 +/- 7.2% at 5 years; and 63 +/- 3.2% vs 65% +/- 7.4 at 10 years., Conclusions: Post-transplant morbidity and short- and long-term survival of pediatric recipients with CHD are not adversely influenced by the use of oversized cardiac allografts.

Background: With improvement in medical outcomes, the current research has shifted toward understanding and enhancing the quality of life after pediatric heart transplantation. Previous research has indicated that infant heart transplant recipients are generally at risk for neurodevelopmental delays; however, no longitudinal studies exploring the patterns of development within this medical population have been performed., Methods: Using the Bayley Scales of Infant Development-II, 39 children (2 to 38 months of age) who underwent heart transplantation in infancy (<1 year) at Loma Linda University Children's Hospital were assessed consecutively over time., Results: Mean Mental Development Index (MDI) scores for all age groups were within normal limits, except for the age ranges of 18 to 23 and 24 to 35 months, which were mildly delayed. Average Psychomoter Development Index (PDI) scores for all age groups reflected mildly delayed performance, except for the 36- to 38-month age group, which was within normal limits. Repeated measures analyses of variance on a sub-set of participants with at least 4 consecutive assessments revealed within-subject effects on MDI scores (F = 5.7, p < 0.01), but not on PDI scores (F = 1.6, p = 0.22). Significant decreases in MDI scores at 18 and 28 to 36 months were noted., Conclusions: Motor development in this population was consistently mildly delayed. Age-dependent variability in cognitive skills was apparent. The delays appeared due to speech/language acquisition (18 months), and abstract reasoning/goal-directed behaviors (28 to 36 months). Possible etiologies for cognitive delays include test artifacts, auditory functioning and effects of immunosuppressive agents. Understanding risk factors in this patient population will allow for early and effective intervention.

We sought to document morbidities and growth for patients with hypoplastic left heart syndrome (HLHS) to inform the initial surgical decision and understand healthcare needs. Data were obtained on 137 patients with HLHS, born between 1989 and 1994, who survived staged surgery ( n = 62) or transplantation ( n = 75) and had follow-up information available from four pediatric cardiac surgical centers. In patients with HLHS older than 1 year of age at follow-up, 93% experienced at least one major postsurgical morbidity. Morbidities depended on the surgery received. Hypertension, renal compromise, and abnormal infections were more common in transplanted patients than staged surgery patients. Staged surgery patients used more anticongestive medications and experienced more morbidities requiring interventional catheterization than did transplanted patients. Rejection was common for transplanted patients. On average these children spent 23 days per year in the hospital. Patients with HLHS were small for their age; 43% of staged surgery patients weighed below the third percentile at last information, compared to 19% of transplanted patients ( p = 0.003). The median height percentile was the 10th in both groups. Normal activity level was reported in more transplanted patients (90%) than staged surgery patients (49%; p < 0.001). Trade-offs between mortality and morbidity outcomes can help inform the initial surgical decision.

The literature regarding organ transplantation has emphasized graft survival in the arena of organ transplantation for life-threatening disease. The concept of "if you can't get it to work .... replace it" has been successful in the adult transplant population and has found its way into the pediatric population. With the improvement in patient and graft survival rates and management of complications, the questions multiply concerning quality-of-life issues. Neurodevelopmental outcome is emerging as one of the focal points for parents, physicians, and education specialists as they request information regarding early intervention and therapies for this growing population of children from the successful era of organ transplantation.

A retrospective analysis of 381 pediatric heart-transplant recipients was performed to determine the frequency, characteristics, and risk factors for post-transplant diabetes. The rate of post-transplant diabetes was 1.8% with antithymocyte globulin, cyclosporine and azathioprine as primary immunosuppressive therapy. Time from transplant to diabetes was 0.25-13 years. Diabetes was characterized by reversibility, and lack of insulinopenia and autoimmunity. The post-transplant diabetes rate in tacrolimus-converted children (n = 45) was 8.8%. In tacrolimus-converted children, age at transplant, mean and maximum tacrolimus blood levels, and first-year rejection episodes were higher in the post-transplant diabetes group, which also consistently had DR-mismatched transplants and HLA DR3/DR4 haplotypes. Body mass index was not different between diabetic and control tacrolimus-converted children. In conclusion, pediatric post-transplant diabetes may be related to reversible insulin resistance. Tacrolimus levels, HLA DR mismatch, and older age at transplant may predispose to post-transplant diabetes.

Seizures are common in infants undergoing cardiac transplant and are usually attributed to a non-specific "post-pump" phenomenon. In this study, we determined which variables were associated with the occurrence of post-transplant seizures in infants with hypoplastic left heart syndrome and the need for continued treatment with antiepileptic medication. Of 127 infants studied over an 11-year period, 27 (21%), ages 9 to 90 days, had post-transplant seizures. These patients were compared to 27 age-matched transplanted infants without seizures. We compared multiple variables before, during, and after transplant including growth parameters, time of diagnosis, cyclosporine levels, maternal variables, circulatory and bypass parameters, laboratory data, neuroimaging and electroencephalographic studies, neurologic examination findings, and peri-operative complications. Post-transplant seizures were associated with total cardiopulmonary bypass time and the presence of post-transplant complications. Deep hypothermic circulatory arrest time was inversely correlated with seizure severity. Pre-transplant electroencephalographic abnormalities and total bypass time were associated with seizures requiring continued use of antiepileptic therapy. Post-transplant electroencephalograms were not associated with the need for continued treatment. Identification of variables associated with the development of post-transplant seizures is essential for early intervention to reduce long-term morbidity and mortality. Future studies to reduce risk of post-transplant seizures are warranted.

Background: Acute rejection commonly occurs within the first year after heart transplantation, and then decreases in frequency with time. Recently, the long-term utility of endomyocardial biopsy during routine annual catheterization has been questioned. The purpose of this study was to retrospectively review the prevalence of biopsy-proven rejection during routine annual catheterization in our patient population, determine whether biopsies late after transplant are useful, and identify factors that correlate with late unsuspected rejection., Methods: Biopsy results from the annual catheterization were evaluated from 1986 to August 2000. The prevalence of moderate rejection was evaluated and compared with the patient's immunosuppressive regimen; the prevalence of late rejection; and how late rejection correlated with recipient age, number of first-year rejections and presence of sub-therapeutic cyclosporine., Results: A total of 1108 biopsies were performed in 269 children with a mean follow-up of 5 +/- 3 years (median 5 years, range 1 to 11 years). Three-drug immunosuppressive therapy, including steroids, was used in 93 patients. There was a persistent 8% to 10% prevalence of moderate rejection at up to 10 years post-transplantation. Moderate rejection was more likely in patients: (1). on 3-drug immunosuppressive therapy; (2). with a recipient age >1 year; and (3). with a relatively lower cyclosporine level., Conclusions: These data suggest that continued surveillance of pediatric transplant patients for acute rejection is indicated for long-term follow-up.

Background: We evaluated the role of total lymphoid irradiation (TLI) in the management of refractory rejection among pediatric heart transplant patients., Methods: Eleven of 298 patients underwent TLI at 6 to 195 months of age and were divided into subgroups: those who survived (group A, n = 7) and those who did not survive beyond 1 year after TLI (group D, n = 4). Non-TLI recipient data were considered as the controls., Results: Six out of 11 patients died eventually (54%). TLI was initiated 3 to 107 months after transplantation with a dosage of 600 to 840 cGy. The pre-TLI rejection rate (0.62 +/- 0.40 per month) was higher (p < 0.0001); however, the post-TLI rejection rate (0.24 +/- 0.65 per month) showed no significant difference from the control rejection rate. The Cox proportional hazard model found significance for TLI as a risk factor for development of posttransplant coronary artery disease (relative risk, 4.8; 95% CI, 1.1 to 21.3) and posttransplant lymphoproliferative disease (relative risk, 47.9; 95% CI, 1.6 to 1,475.3), respectively. Although the rejection rate decreased after TLI in both groups (group A pre/post, 0.51 +/- 0.31/0.06 +/- 0.08 per month; group D pre/post, 0.82 +/- 0.49/0.57 +/- 1.09 per month), significance was obtained only in group A (p = 0.018)., Conclusions: TLI was an effective adjunct for reversal of refractory rejection in pediatric heart transplantation by reducing the rejection rate. Great care must be taken for the risk of development of coronary artery disease or lymphoproliferative disease.

Surgical mortality is high in children with visceral heterotaxy (VH), particularly if atrioventricular valve insufficiency, ventricular dysfunction, or aortic atresia is present. This study reviews the outcome of cardiac transplantation (CT) in infants and children with VH and congenital heart disease who are at high risk for standard palliative or corrective surgery. We reviewed CT outcomes in 29 children with VH, congenital heart disease, atrioventricular valve insufficiency, ventricular dysfunction, and/or aortic atresia. Median age at CT was 3.1 years. Cardiac surgery had been performed in 20 patients (69%) before CT. Follow-up since CT has been 8.5 +/- 2.2 years. Outcomes were compared with 45 children who underwent transplantation for dilated cardiomyopathy. Actuarial graft survival in the VH group at 30 days and 1, 5, and 10 years was 100%, 86%, 68%, and 50%, respectively, compared with 100%, 96%, 83%, and 68% in children who underwent transplantation for dilated cardiomyopathy (p = 0.12). Splenic status, cardiac position, age at CT, number of prior cardiac surgeries, or systemic venous anomalies were not predictors of mortality after CT. Cardiopulmonary bypass and graft ischemic times were longer in the VH group; time on the ventilator after CT, length of hospitalization, and rejection, infection, post-transplant lymphoproliferative disease, and transplant coronary artery disease rates were equal. Thus, CT is a viable alternative therapy for high-risk patients with VH, possibly offering improved survival over standard surgical management.

Objectives: We sought to identify the optimal treatment strategy for hypoplastic left heart syndrome (HLHS)., Background: Surgical treatment of HLHS involves either transplantation (Tx) or staged palliation of the native heart. Identifying the best treatment for HLHS requires integrating individual patient risk factors and center-specific data., Methods: Decision analysis is a modeling technique used to compare six strategies: staged surgery; Tx; stage 1 surgery as an interim to Tx; and listing for transplant for one, two, or three months before performing staged surgery if a donor is unavailable. Probabilities were derived from current literature and a dataset of 231 patients with HLHS born between 1989 and 1994. The goal was to maximize first-year survival., Results: If a donor is available within one month, Tx is the optimal choice, given baseline probabilities; if no donor is found by the end of one month, stage 1 surgery should be performed. When survival and organ donation probabilities were varied, staged surgery was the optimal choice for centers with organ donation rates < 10% in three months and with stage 1 mortality <20%. Waiting one month on the transplant list optimized survival when the three-month organ donation rate was > or =30%. Performing stage 1 surgery before listing, or performing stage 1 surgery after an unsuccessful two- or three-month wait for transplant, were almost never optimal choices., Conclusions: The best strategy for centers that treat patients with HLHS should be guided by local organ availability, stage 1 surgical mortality and patient risk factors.

Background: The survival of recipients of cardiac allografts is limited by rejection, lymphoproliferative disease, and coronary vasculopathy. The purpose of this study in children who had received heart transplants was to evaluate the cardiac allografts for myocardial viral infections and to determine whether the presence of viral genome in the myocardium correlates with rejection, coronary vasculopathy, or graft loss., Methods: We enrolled heart-transplant recipients 1 day to 18 years old who were undergoing evaluation for possible rejection and coronary vasculopathy. Endomyocardial-biopsy specimens were evaluated for evidence of rejection with the use of standard criteria and were analyzed for the presence of virus by the polymerase chain reaction (PCR)., Results: PCR analyses were performed on 553 consecutive biopsy samples from 149 transplant recipients. Viral genome was amplified from 48 samples (8.7 percent) from 34 patients (23 percent); adenovirus was found in 30 samples, enterovirus in 9 samples, parvovirus in 5 samples, cytomegalovirus in 2 samples, herpes simplex virus in 1 sample, and Epstein-Barr virus in 1 sample. In 29 of the 34 patients with positive results on PCR (85 percent), an adverse cardiac event occurred within three months after the positive biopsy, and 9 of the 34 patients had graft loss due to coronary vasculopathy, chronic graft failure, or acute rejection. In 39 of the 115 patients with negative results on PCR (34 percent), an adverse cardiac event occurred within three months of the negative PCR finding; graft loss did not occur in any of the patients in this group. The odds of graft loss were 6.5 times as great among those with positive results on PCR (P=0.006). The detection of adenovirus was associated with considerably reduced graft survival (P=0.002)., Conclusions: Identification of viral genome, particularly adenovirus, in the myocardium of pediatric transplant recipients is predictive of adverse clinical events, including coronary vasculopathy and graft loss.

Objective: The study objectives were to determine posttransplant coronary artery disease (TxCAD) incidence, predisposing factors and optimal timing for retransplantation (re-Tx) in pediatric heart transplantation (Tx) recipients., Background: The TxCAD limits long-term survival following heart Tx, with re-Tx being the primary therapy. Information on risk factors and timing of listing for re-Tx is limited in children., Methods: The records of children who survived >1 year post-Tx at Loma Linda University were reviewed. Nonimmune and immune risk factors were analyzed., Results: TxCAD was documented in 24 of 210 children. Freedom from TxCAD was 92 +/- 2% and 75 +/- 5% at 5 and 10 years' post-Tx, respectively. The TxCAD diagnosis was established at autopsy in 10 asymptomatic patients who died suddenly within nine months following the most recent negative angiograms. The remaining 14 children had angiographic diagnoses of TxCAD and had symptoms and/or graft dysfunction (n = 10) or positive stress studies (n = 4). Three of 14 died within three months after the diagnosis was made. Eleven patients underwent re-Tx within seven months of diagnosis; nine survived. Univariate and multivariate analyses showed that only late rejection (>1 year posttransplant) frequency (p = 0.025) and severity (hemodynamically compromising) (p < 0.01) were independent predictors of TxCAD development. Freedom from TxCAD after severe late rejection was 78 +/- 8% one year postevent and 55 +/- 10% by two years., Conclusions: Late rejection is an independent predictor of TxCAD. Patients suffering severe late rejection develop angiographically apparent TxCAD rapidly and must be monitored aggressively. Both TxCAD mortality and morbidity occur early; therefore, we recommend immediate listing for re-Tx upon diagnosis.

Background: Cardiac retransplantation (re-CTx) in children is a controversial therapy, yet it remains the best treatment option to recipients with failing grafts. Our objective was to determine the incidence of re-CTx in a large pediatric population of recipients and evaluate the outcome of such therapy., Methods: Between November 1985 and November 1999, 347 children underwent cardiac transplantation at the Loma Linda University Medical Center. Of these, 32 children were listed for re-CTx. Ten patients died while waiting, and 22 recipients underwent re-CTx. Median age at re-CTx was 7.1 years (range, 52 days to 20.1 years)., Results: Indications for re-CTx were allograft vasculopathy (n = 16), primary graft failure (n = 5), and acute rejection (n = 1). Two patients with primary graft failure underwent retransplantation within 24 hours of the first transplantation procedure while on extracorporeal membrane oxygenation support. Median time interval to re-CTx for the others was 7.2 years (range, 32 days to 9.4 years). Operative mortality for all cardiac re-CTx procedures was 13.6%. Causes of hospital mortality were pulmonary hypertension with graft failure (n = 2) and multiorgan failure (n = 1). Median hospital stay after re-CTx was 14.1 days (range, 6 to 45 days). There was one late death from severe rejection. Actuarial survival at 3 years for re-CTx was 81.9% +/- 8.9% compared with 77.3% +/- 2.6% for primary cardiac transplantation recipients (p = 0.70)., Conclusions: Elective re-CTx can be performed with acceptable mortality. Although the number of patients undergoing retransplantation in this report is small and their long-term outcome is unknown, the intermediate-term survival after re-CTx is similar to that of children undergoing primary cardiac transplantation.

Objectives: We compared survival in treatment strategies and determined risk factors for one-year mortality for hypoplastic left heart syndrome (HLHS) using intention-to-treat analysis., Background: Staged revision of the native heart and transplantation as treatments for HLHS have been compared in treatment-received analyses, which can bias results., Methods: Data on 231 infants with HLHS, born between 1989 and 1994 and intended for surgery, were collected from four pediatric cardiac surgical centers. Status at last contact for survival analysis and mortality at one year for risk factor analysis were the outcome measures., Results: Survival curves showed improved survival for patients intended for transplantation over patients intended for staged surgery. One-year survival was 61% for transplantation and 42% for staged surgery (p < 0.01); five-year survival was 55% and 38%, respectively (p < 0.01). Survival curves adjusted for preoperative differences were also significantly different (p < 0.001). Waiting-list mortality accounted for 63% of first-year deaths in the transplantation group. Mortality with stage 1 surgery accounted for 86% of that strategy's first-year mortality. Birth weight <3 kg (odds ratio [OR] 2.4), highest creatinine > or =2 mg/dL (OR 4.7), restrictive atrial septal defect (OR 2.7) and, in staged surgery, atresia of one (OR 4.2) or both (OR 11.0) left-sided valves produced a higher risk for one-year mortality., Conclusions: Transplantation produced significantly higher survival at all ages up to seven years. Patients with atresia of one or both valves do poorly in staged surgery and have significantly higher survival with transplantation. This information may be useful in directing patients to the better strategy for them.

Objectives: The study purposes were to determine 1) whether intravascular ultrasound (IVUS) was more sensitive than angiography for the detection of post-transplant coronary artery disease (PTCAD) in pediatric patients; and 2) whether those transplanted as neonates reacted differently than older patients., Background: Experience with IVUS for the diagnosis of PTCAD in children is limited., Methods: Patients were divided into two groups: those transplanted as neonates (early group) and those transplanted in infancy or childhood (late group). Morphometric analysis was performed, including maximal intimal thickness (MIT) and intimal index (II). Stanford classification was used to grade lesion severity. Acute rejection and cytomegalovirus (CMV) status were correlated with MIT and II., Results: Thirty children were studied (early group, n = 13; late group, n = 17). All segments studied were angiographically normal. Mean MIT and mean II were significantly greater in the late group (0.26 +/- 0.14 vs. 0.13 +/- 0.04 mm, p < 0.001 and 0.11 +/- 0.07 vs. 0.07 +/- 0.03 mm, p = 0.04, respectively). There was a significant correlation between MIT and II in those who had acute rejection in the late group. Patients in the late group who were CMV-positive had a significantly higher MIT compared with those in the late group with negative serology (p = 0.04)., Conclusions: Intravascular ultrasound was more sensitive than angiography in detecting PTCAD after pediatric heart transplantation. There is a possible role for acute rejection and CMV in the development of PTCAD.

The feasibility of heart transplantation for infants has now been established. Clinical outcome data is necessary to assist in targeting areas for improvement and for counseling families considering this option. This report describes clinical outcome in 29 infant heart transplant recipients who have survived at least 10 years. A query of the transplant database, referring physicians and parental questionnaire was performed. Patient survival for the overall infant population is 64% at 13 years. Parents of 19/29 (55%) children described them as developmentally normal. Three children have had a severe developmental outcome. Sixteen of 29 children are in mainstream school environments. Four have repeated one grade in school. Speech delay was present in 10/26 (38%). Somatic growth is normal in 88%. All children are NYHA class I. Renal function shows only modest insufficiency with most recent BUN (mean+/-S.D.)=25+/-7 mg/dl and serum creatinine=0.8+/-0.2 mg/dl. Only four children have creatinine levels >1 mg/dl. No child requires dialysis. No children have developed post-transplant lymphoproliferative disease beyond 10 years. Four children have experienced rejection beyond 10 years with one mortality due to rejection and transplant coronary artery disease. Conclusion: Heart transplantation during infancy is technically feasible and results in good survival. Many children have some degree of learning disability but most are mild and the children function well in society. Improvements in surgical techniques may improve developmental outcome. Other side-effects of immunosuppression are manageable and most survivors have a good functional outcome.

Pediatric heart transplantation has become a mainstay in the treatment of end-stage heart disease in infants and children. There is, however, sparse information on post-transplant developmental and cognitive functioning. At Loma Linda University Children's Hospital 223 infants have undergone heart transplantation surgery with a survival rate of 73% (n=165). This article reports on four areas of investigation of this cohort of infants. Infant development: Two studies were done utilizing the Bayley Scales of Infant Development (mean 100, S.D.+/-15). The first study (n=48) showed mean values within the normal range [Mental Development Index (MDI) 87; Psychomotor Developmental Index (PDI) 90]. The second study (n=23) showed developmental scores within normal limits in 4-8 month olds with a tendency for decline in development at 12-24 months (MDI 83, PDI 77). Child development: Ninty-one infant recipients were greater than 5 years old. Forty-five children were excluded because of long distances from the hospital, second transplantation, abnormal karyotype, primary language non-English, or invalid testing. The Wechsler Preschool and Primary Scale of Intelligence-Revised testing of 5-6-year-olds (n=23) showed a Full Scale IQ of 74, Performance IQ of 76, and Verbal IQ of 77. The Wechsler Intelligence Scale for Children-III testing of 7-10-year-olds (n=23) showed a Full Scale IQ of 86, Performance IQ of 89, and Verbal IQ of 86. The Wechsler Individual Achievement Test (mean 100, S.D.+/-15) yielded a Total Composite of 91, Mathematics Composite of 86, Language Composite of 98, and a Reading Composite of 94. Visual spatial skills: Visual motor integration (mean 100, S.D.+/-15) was evaluated in 5-10-year-olds with a mean of 87; however, 52% of the children had scores below 1 S.D. Subtests from the Wechsler scales that assess visual motor and visual spatial skills indicated significant deficits. Behavior: Younger children (n=33) demonstrated behaviors indicative of social isolation. Older children (n=36) showed behavior that was within the normal limits, but depression was noted in a significant number of them. Conclusions: Infant heart transplant recipients demonstrate IQ and achievement levels within the normal range, but there is a significant amount of variability with more children than would be expected scoring in the lower ranges. Children with heart transplantation are at risk for visual spatial skill deficits. Young children are at risk for social isolation while symptoms of depression are noted in older children.

Multiple reports of successful combined heart and kidney transplants adults suggest that this may be a viable option for a small subset of patients with coexisting end-stage heart and kidney failure. A review of the literature, however, reveals that few combined heart and kidney transplants have been reported in children. This article presents the case of a 13-year-old boy who underwent unsuccessful palliative surgery for a congenital heart defect. The patient developed heart failure with subsequent acute renal failure, and ultimately required a combined heart and kidney transplant. The combined procedure was successful in this patient and he is alive and well 27 months postoperatively.

Two hundred thirty-three heart transplantations were performed in infants during their first 6 months of life at Loma Linda University between November, 1985 and June, 1999. Survival has now exceeded 13 years. Nearly 70% of infants are expected to live at least 10 years. Those transplanted during the first 30 days of life have about a 15% survival advantage at 10 years. Scarcity of donors continues to limit the transplantation effort. While acute rejection is the most common cause of late mortality, posttransplant coronary artery disease (PTCAD) is the leading cause of graft loss affecting 22 recipients (9.5%). The majority of patients are asymptomatic prior to diagnosis of PTCAD and are either retransplanted or dead within 6 months. Retransplantation (9 of 11 retransplantations for PTCAD) has been highly successful, with 10 year actuarial survival of 91%. Posttransplant lymphoproliferative disease (PTLD) has been found in only 7 patients (3%), most commonly in lymph nodes. Causes of late mortality include acute rejection (n = 16), PTCAD (n = 9), infection (n = 7), PTLD (n = 2), chronic graft dysfunction (n = 2), arrhythmia (n = 1), recurrent pulmonary vein stenosis (n = 1), and other noncardiac causes (n = 4). Infant psychomotor development is mildly delayed although cognitive development is normal. School-age children are performing at the level of their peers with average achievement and low average intelligence testing. Heart transplantation is durable therapy for newborns and infants with structurally incurable and end-stage myopathic heart disease.

Objectives: The purpose of this study was to determine the feasibility, safety and diagnostic accuracy of dobutamine stress echocardiography (DSE) for evaluating posttransplant coronary artery disease (TxCAD) in children, and to determine the frequency of selected cardiac events after normal or abnormal DSE., Background: Posttransplant coronary artery disease is the most common cause of graft loss (late death or retransplantation) after cardiac transplantation (CTx) in children. Coronary angiography, routinely performed to screen for TxCAD, is an invasive procedure with limited sensitivity. The efficacy of DSE for detecting atherosclerotic coronary artery disease is established, but is unknown in children after CTx., Methods: Of the 78 children (median age 5.7 years, range 3 to 18) entered into the study, 72 (92%) underwent diagnostic DSE by means of a standard protocol, 4.6 +/- 1.9 years after CTx. The results of coronary angiography performed in 70 patients were compared with DSE findings. After DSE, subjects were monitored for TxCAD-related cardiac events, including death, retransplantation and new angiographic diagnosis of TxCAD., Results: No major complications occurred. Minor complications, most often hypertension, occurred in 11% of the 72 subjects. The sensitivity and specificity of DSE were 72% and 80%, respectively, when compared with coronary angiography. At follow-up (21 +/- 8 months), TxCAD-related cardiac events occurred in 2 of 50 children (4%) with negative DSE, versus 6 of 22 children (27%) with positive DSE (p < 0.01)., Conclusions: DSE is a feasible, safe and accurate screening method for TxCAD in children. Positive DSE identifies patients at increased risk of TxCAD-related cardiac events. Negative DSE predicts short-term freedom from such events.