The Influence of Race and Common Genetic Variations on Outcomes After Pediatric Heart Transplantation.

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.

Comparison of Segmental Versus Longitudinal Intravascular Ultrasound Analysis for Pediatric Cardiac Allograft Vasculopathy.

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.

Late rejection is a predictor of transplant coronary artery disease in children.

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.

The medium-term findings in coronary arteries by intravascular ultrasound in infants and children after heart transplantation.

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.

Survival analysis and risk factors for mortality in transplantation and staged surgery for hypoplastic left heart syndrome.

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.

Dobutamine stress echocardiography for assessing coronary artery disease after transplantation in children.

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.

A comparison of treatment strategies for hypoplastic left heart syndrome using decision analysis.

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.

Posttransplant recoarctation of the aorta: a twelve year experience.

OBJECTIVES: This study was undertaken to investigate the incidence of posttransplant recoarctation of the aorta, delineate the mode of presentation, identify risk factors that predict recoarctation and examine the results of intervention for posttransplant recoarctation. BACKGROUND: Patients with aortic arch hypoplasia require extended arch reconstruction at transplant, with an inherent possibility of subsequent recoarctation of the aorta. METHODS: This was a retrospective review of all children (age <18 years) who underwent cardiac transplantation over a 10-year period. Collected data included pretransplant diagnosis, details of the transplant procedure and posttransplant data including development of recoarctation of the aorta, interventions for recoarctation and the most recent follow-up assessment of the aortic arch. RESULTS: Two hundred eighty-eight transplants were performed on 279 children (follow-up = 1,075 patient-years; range 0 to 133 months, median 43.7). Thirty-two of 152 patients (21%) who underwent extended aortic arch reconstruction subsequently developed recoarctation. All but one patient developed recoarctation within 2 years after transplant; 87% were hypertensive at presentation. Of 30 patients who underwent intervention for recoarctation (balloon angioplasty [n = 26] and surgical repair of recoarctation [n = 4]), 26 (87%) have remained recurrence-free (follow-up = 133 patient-years; range 8 to 106 months, median 47). CONCLUSIONS: The high frequency of recoarctation after cardiac transplantation with extended aortic arch reconstruction mandates serial echocardiographic evaluation of the aortic arch. Patients typically present with systemic hypertension within the first two years after transplantation. Balloon angioplasty is a safe, effective and durable method of treatment.

Ventricular remodeling following infant-pediatric cardiac transplantation. Does age at transplantation or size disparity matter?

Early left ventricular (LV) remodeling following pediatric cardiac transplantation has not been described. To identify patterns and determinants of change in left ventricular mass and volume posttransplant, we studied 125 consecutive children who underwent cardiac transplantation between January 1, 1989 and July 31, 1993. Two-dimensional imaging-directed M-mode echocardiograms were studied weekly until 26 weeks post-transplant. LV mass and volume (indexed to BSA1.5) were measured. LV mass index increased until 3 weeks post-transplant, and then decreased. The mean decrement in LV mass index after 8 weeks post-transplant (relative to baseline) was significantly larger in patients with donor-recipient weight ratio > 1.5 compared with patients with donor-recipient weight ratio < or = 1.5 (-2.2 g/m3 compared with 33.4 g/m3, respectively, P < 0.01). Multiple linear regression was performed employing donor-recipient weight ratio, time since transplantation, ischemic time, and age at transplant as prognostic variables. Donor-recipient weight ratio (P < 0.0001), time since transplant (P < 0.01), and age at transplant (P = 0.02) were identified as independent predictors of change in LV mass index. Donor-recipient weight ratio (P = 0.001) and time since transplantation (P = 0.02) were independent predictors of change in LV volume index. There was an interaction between donor-recipient weight ratio and time since transplantation, suggesting that donor-recipient weight ratio has an independent effect as well as a time-dependent effect on change in LV mass and volume indices. LV mass and volume indices increased early posttransplant and then decreased; this pattern was temporally predictable, and dependent on donor-recipient weight ratio and age at transplant.

Outcome of infants with hypoplastic left heart syndrome who undergo atrial septostomy before heart transplantation.

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.

Rejection management and long-term surveillance of the pediatric heart transplant recipient: the Loma Linda experience.

At Loma Linda University Medical Center, 210 heart transplant procedures have been performed on 207 newborns, infants, and children since 1985. Actuarial survival rate at 5 years is 72% for the entire population and 82% for those receiving a transplant during the first month of life. These patients have been managed with a regimen that minimizes long-term steroid use and emphasizes the noninvasive diagnosis of rejection. This article describes in some detail the mechanics of this process. In addition, the rejection history of 154 children undergoing transplantation from 1989 through 1992 was reviewed. The average number of rejection episodes was 1.67 (standard deviation 1.65; median, 1; mode, 0). The vast majority of rejections occur in the first 3 months after transplantation. Long-term freedom from rejection was 19% for newborn recipients, 42% for infants, 25% for older children. Donor/recipient mismatch for gender, race, blood type, Rh factor, and HLA typing did not correlate with rejection history. Older age at transplantation and cytomegalovirus disease were correlated with more frequent rejection episodes. Five patients had posttransplantation coronary artery disease. This was strongly correlated with greater rejection frequency and death from rejection. In addition, there was a trend toward less posttransplantation coronary artery disease with antibody induction therapy, younger age at transplantation, and absence of cytomegalovirus disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Orthotopic transplantation for total anomalous pulmonary venous connection associated with complex congenital heart disease.

BACKGROUND: When total anomalous pulmonary venous connection is associated with other complex cardiac malformations, early and late postsurgical morbidity and mortality are excessive. METHODS: In an attempt to modify this outcome, twelve children (4 days to 6.8 years of age) with total anomalous pulmonary venous connection and various congenital cardiac defects were treated with orthotopic heart transplantation. Associated cardiac diagnoses included the following: hypoplastic left heart syndrome (n = 2), unbalanced atrioventricular canal with pulmonary atresia (n = 2), and single ventricle with severe pulmonary stenosis (n = 3) or atresia (n = 5). Two patients had situs inversus, and two had dextrocardia with situs ambiguous. Eight patients had asplenia and one had polysplenia. Palliative pretransplantation procedures in five patients included the following: systemic to pulmonary artery shunt (n = 5), atrioventricular valve annuloplasty (n = 1) and classical Glenn shunt (n = 1). The donor left atrium was anastomosed directly to a common pulmonary venous pool in nine patients; whereas three children required complex reconstruction to baffle the pulmonary venous flow to the donor left atrium. RESULTS: There was one operative death related to an oversized heart and vena caval thrombosis. Follow-up ranged from 16 months to 4.5 years (average 3 years). In two patients (18%) pulmonary venous obstruction developed 3 and 4 months after transplantation. Reoperation to relieve the obstruction was successful in one patient. The second patient underwent three such reoperations and died of sepsis 10 months after orthotopic heart transplantation. CONCLUSION: Orthotopic transplantation is a viable option for children with complex total anomalous pulmonary venous connection that precludes a biventricular repair. Transplantation may improve the dismal prognosis of those children, but it does not eliminate the potential for late pulmonary venous obstruction.

Cardiac retransplantation for graft vasculopathy in children: should we continue to do it?

BACKGROUND: Cardiac transplantation (CTx) has been established as an effective therapy for a variety of inoperable cardiac conditions in infants and children. However, graft vasculopathy (GV) has emerged as the main limiting factor to long-term survival of CTx recipients. The only treatment of severe GV is cardiac retransplantation (re-Tx). Controversy exists regarding the use of scarce donor organs for cardiac re-Tx. OBJECTIVE: To compare the outcome of cardiac re-Tx for GV with that of primary CTx in children. DESIGN: A 12-year retrospective cohort review. SETTING: A university-affiliated children's hospital. PATIENTS: All infants and children who underwent CTx (group 1, n = 322) had complete follow-up of 1389.7 patient-years. Graft vasculopathy was confirmed in 32 recipients (1.1-8.2 years after undergoing CTx). Thirteen patients died suddenly, 3 died waiting for cardiac re-Tx (1-17 days after relisting), 4 are pending cardiac re-Tx, and 12 (group 2) underwent cardiac re-Tx. INTERVENTION: Cardiac re-Tx at a mean (+/- SD) interval from the first CTx of 6.3 +/- 1.8 years (range, 2.2-9.4 years). Two patients required additional aortic arch aneurysm repair with cardiac re-Tx. RESULTS: When group 1 was compared with group 2, there was no significant difference in operative mortality (9.0% vs 8.3%; P = .9), rejection rate (0.98 vs 0.86; P = .1), and hospital stay (23.0 +/- 18.8 days vs 20.5 +/- 11.6 days; P = .65). Actuarial survival for groups 1 and 2 at 1 and 4 years was 84.3% vs 83.3% (P = .59) and 74.4% vs 83.3% (P = .85), respectively. CONCLUSIONS: The surgical outcome and intermediate survival of cardiac re-Tx for GV and primary CTx are similar. Children with severe cardiac GV are at risk of sudden death and can benefit from early cardiac re-Tx.

Pediatric cardiac retransplantation: intermediate-term results.

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.

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.

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.

Pediatric heart transplantation at Loma Linda: 1985 to 1996.

Pediatric heart transplantation at Loma Linda is now in its second decade with 299 infants and children having received 309 transplant procedures. Overall survival is 73% with 10 year actuarial survival of 66% for all ages. Newborn recipients have a 77% actuarial survival at 11 years. As expected, acute rejection, infectious disease and technical issues are the most frequent causes of death. Posttransplant coronary artery disease (PTCAD) has been diagnosed in 22 patients, an incidence of 9.5% of those patients surviving at least 1 year after transplantation. Seven children have undergone retransplantation for PTCAD with an actuarial survival at 3 years of 83%. Six children (2%) have been diagnosed with posttransplant lymphoproliferative disease. Long-term renal function is acceptable with average glomerular filtration rate of 79 ml/min/1.73 m2 and average creatinine beyond 5 years of 65 mmol/l (0.7 mg/dl). Most children in this population have heights and weights within the low normal range. Infant recipients who are now at least 6 years old are in an appropriate grade level in 85% of cases. Ten year survival, with good clinical outcome, is achievable in this population.

Heart transplantation among 233 infants during the first six months of life: the Loma Linda experience. Loma Linda Pediatric Heart TransplantGroup.

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.