Marti Baum

Transplantation as a primary treatment for hypoplastic left heart syndrome: intermediate-term results.

BACKGROUND Hypoplastic left heart syndrome is a lethal malformation. For the last 10 years, orthotopic cardiac transplantation has been our preferred treatment for infants with hypoplastic left heart syndrome. METHODS One hundred seventy-six infants with hypoplastic left heart syndrome were entered into a cardiac transplant protocol between November 1985 and November 1995. Interventional procedures to stent the ductus arteriosus or enlarge the interatrial communication were performed in 8 and 35 patients, respectively. Thirty-four patients (19%) died during the waiting period, and 142 infants underwent cardiac transplantation. Age at cardiac transplantation ranged from 1.5 hours to 6 months (median, 29 days). The majority of grafts were oversized, and the median graft ischemic time was 273 minutes (range, 60 to 576 minutes). The implantation procedure used a period of hypothermic circulatory arrest ranging from 23 to 110 minutes (median, 53 minutes). Repair of other significant defects included interrupted aortic arch and total or partial anomalous pulmonary venous connection. RESULTS There were 13 early and 22 late deaths. Patient actuarial survival at 1 month and at 1, 5 and 7 years was 91%, 84%, 76%, and 70% respectively. Half of the late deaths were due to rejection. Severe graft vasculopathy was confirmed in 8 patients. Retransplantation was performed in 5 patients for graft vasculopathy 4 and rejection 1. Lymphoblastic leukemia developed in 1 patient 3 years after cardiac transplantation. CONCLUSIONS Cardiac transplantation can be performed in infants with hypoplastic left heart syndrome with good operative and intermediate-term results. Improved survival can be achieved with increased donor availability, better management of rejection, and control of graft vasculopathy.

Neurologic sequelae of deep hypothermic circulatory arrest in cardiac transplant infants

BACKGROUND Considerable controversy exists experimentally and clinically regarding adverse neurologic effects that may follow deep hypothermic circulatory arrest. Moreover, the techniques of DHCA have never been standardized. METHODS We prospectively studies the neurodevelopmental outcome in 38 infants undergoing cardiac transplantation using DHCA before the age of 4 months (mean age, 37.0 days). Neurodevelopmental outcome in the 22 boys and 16 girls was tested up to 2.5 years after transplantation using Bayley scale of infant development. Bayley scores were compared with the rate of core cooling and the length of DHCA in all patients. Deep hypothermic circulatory arrest was accomplished using an asanguineous prime resulting in hematocrits of 5% +/- 5% and ionized Ca2+, 0.4 +/- 0.1 mmol/L. No surface precooling was used, but the head was packed in ice. Mean cooling time was 14.0 +/- 3.5 minutes, resulting in rectal temperatures of 18 degrees +/- 2.5 degrees C. Duration of DHCA ranged from 42 to 70 minutes (mean duration, 56.0 +/- 6.6 minutes). RESULTS Postoperatively, the mean Bayley psychomotor development index was 91 (range, 50 to 130) and mental development index was 88 (range, 50 to 130). No relationship was found between either the rate of cooling or the duration of DHCA and Bayley scores (r = 0.227 and r = 0.322, respectively). CONCLUSIONS These data suggest that neither the rate of cooling nor DHCA times between 42 and 70 minutes using profoundly low hematocrits and low ionized calcium levels has any measurable effect on neurologic outcome up to 2.5 years postoperatively. It is possible that adverse neurologic outcomes from DHCA reflect particular methods of achieving DHCA.

Developmental outcomes and cognitive functioning in infant and child heart transplant recipients

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 Childrens 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.

Clinical outcome 10 years after infant heart transplantation

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.

Emergency department presentation and management of pediatric heart transplant recipients.

The object of this study was to review and delineate the presenting complaints, signs, symptoms, and Emergency Department (ED) management of pediatric heart transplant recipients who presented to Loma Linda University Medical Centers (LLUMC) Emergency Department. A retrospective chart review was made of all of the pediatric heart transplant patients who presented to the ED at LLUMC from January 1986 through February 1993. The department is part of a 600-bed university hospital with an associated 250-bed childrens hospital that includes a pediatric heart transplant center and an ED that sees over 38,000 patients per year. The retrospective review collected information relating to chief complaint, physical findings, laboratory analysis, and diagnoses. Forty-seven patients (23%) presented to the ED for a total of 76 visits. The patients presented a median of 278 days (range 19 days to 6.5 years) after transplantation. The most common chief complaints were related to the respiratory tract, and the most common diagnoses (55%) were related to infectious processes. Fever was present in 21% of the visits. Three of 13 blood cultures obtained were positive. Cardiac symptoms were present in 14% of the visits with two rejection episodes. Hospital admission was required for 22 (29%) of the ED visits. Results showed that pediatric heart transplant recipients are most likely to present to the ED with infections. Although infections from opportunistic organisms and bacteremia must be considered, most infections are similar to those in the nontransplanted child. Life-threatening conditions such as graft rejection are less likely. Nevertheless, the emergency physician should maintain caution in the evaluation of these patients. Close cooperation and consultation with the transplant team will assure the optimal outcome for these patients.

A study of craniofacial growth in infant heart transplant recipients receiving cyclosporine

BACKGROUND Cyclosporine is an effective immunosuppressive drug that has found widespread application in organ transplantation. However, a few studies have implicated cyclosporine as adversely affecting craniofacial growth in the pediatric population. The purpose of this study was to evaluate the possible untoward effects of cyclosporine long-term on craniofacial growth in a group of infant heart transplantation recipients. METHODS A prospective group (n = 28) of 18 Caucasian (white) children (9 female and 9 male, ages 4-10 years) and 10 Hispanic children (3 female and 7 male, ages 4-10 years) were evaluated. No attempt was made for either study group to delineate on individuals specific country of origin. None of the subjects had undergone orthodontic therapy. All subjects had heart transplantations before 6 months of age and followed the Loma Linda University International Pediatric Heart Transplantation Immunosuppression protocol. The primary immunosuppression agent was cyclosporine with azathioprine or methotrexate. Rescue therapy for graft rejection consisted of glucocorticoid and/or polyclonal antibody therapy. None of the subjects received the immunosuppressant tacrolimus (FK506). Using lateral cephalometric radiography, seven skeletal angular measurements (SNA, SNB, ANB, GoGn-SN, NA-Pog, ArGoMe, NPog-AB) were examined and compared to contemporary growth standards. Hand/wrist radiographs were evaluated for bone age. Also, longitudinal height, weight, and head circumference data was obtained and compared to standardized growth and development curves. RESULTS Descriptive statistics were used to summarize the data. Cephalometrically, 86% (N = 24), showed minor deviation from mean normative values. Four of the subjects (14%) exhibited cephalometric measures indicative of individuals with a vertical growth pattern. Analysis of the hand/wrist radiographs showed all but one subject to have normal bone age. Height, weight, and head circumference data revealed a wide range of growth percentiles for the entire group with mean percentiles in the range of 25% to 50%. CONCLUSIONS The findings of this pilot study indicated that, in general, skeletal growth of the craniofacial complex as well as axial skeletal growth was not statistically significantly altered by the immunosuppressive regimen of cyclosporine over the time period evaluated. Further longitudinal data of this studys subjects may shed more light on the possible adverse effects of cyclosporine on craniofacial growth and development in spite of the fact that no untoward correlation was found over the time period studied.

Long-term neuropsychological sequelae of infant cardiac transplant recipients: trends and predictors of outcome

Abstract Studies on long-term neuropsychological sequelae of infant cardiac transplantation are limited as few sites have populations old enough for assessment beyond the infant/toddler years. The intellectual functioning of 63 infant cardiac transplant recipients at Loma Linda University Childrens Hospital (mean age 6.2 years, s.d. 1.3) was assessed using the age appropriate Wechsler Scale of Intelligence - WPPSI-R (N=38) or WISC-III (N=25). Full Scale IQ (FSIQ) scores fell in the below average range (79.2, s.d.18.6). A one-way ANOVA indicated a statistical difference in FSIQ by age (F=3.37, df=6, p=.01); verbal and nonverbal scores markedly improved with increasing age, falling in the average range by ages 7 (86) and 8 (105). Contrary to studies that have examined intellectual abilities as the sole measure of neuropsychological outcome, a stepwise regression was used to predict learning difficulties (≥15 point split between verbal (VIQ) and performance (PIQ) scores). The subset of perinatal and/or perisurgical variables used as predictors of VIQ/PIQ split included: birth and transplant weight, height and head circumference; intubation, PHCA, CPB, & ischemic period; Apgar scores at 1 & 5 minutes; transplant & current age; and number of rejections. Birth head circumference (BHC) explained a significant proportion (51%) of the variance in the VIQ/PIQ split (F=22.6, df=1, p

A longitudinal perspective on neurodevelomental outcome following infant cardiac transplantation

Abstract Few studies have examined the neurodevelopmental sequelae associated with infant heart transplantation. Existing publications have generally reported one-time assessments of developmental status using varying outcome measures. The present study investigated longitudinal patterns of neurodevelopmental outcome in 41 children who were cardiac transplant recipients at Loma Linda University Childrens Hospital. The Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) of the Bayley Scales of Infant Development were used to monitor the performance of each child across four testing sessions (T). A Repeated Measures ANOVA (N=10) was conducted to test overall differences in MDI and PDI scores across the testing sessions. Although no statistically significant changes in PDI scores were apparent (F=2.685, p=.07, df=3), a trend of increased scores with repeated measurements was observed; however, a statistically significant change in MDI scores was noted (F =3.961, p=.020, df=3). Paired samples t-tests on the larger sample (N=41) showed a significant decline in average MDI scores between the first and each subsequent assessment (T1:T2, t=2.6, p=.02, df=21; T1:T3, t=2.3, p=.04, df=12; T1:T4, t=4.0, p=.04, df=9). A significant dip in MDI scores occurred at approximately 18 and 28 months of age, suggesting a notable decrease in performance specifically during these two periods, after which they appeared to increase. Developmental delays such as language difficulties, characteristic of infant heart transplant recipients, were notable factors responsible for the observed change in MDI scores. These findings iterate the importance of longitudinally assessing changes in neurodevelopmental status instead of presenting collective averages across a wide range of age groups. To better identify and potentially remediate such trends in neurodevelopment, future studies should use longitudinal assessments extending beyond the period examined in this study to replicate and confirm these tentative findings.