Outpatient management of intra-corporeal left ventricular assist device system in children: a multi-center experience.

Little is known about the outcomes of children supported on intracorporeal left ventricular assist device (HVAD), and the feasibility of outpatient management. All centers with pediatric patients discharged from the hospital on the device were identified using company database. A total of 14 centers were contacted, with 9 centers, contributing data retrospectively. From 2011 to 2013, 12 pediatric patients (7 females), mean aged 11.9 ± 2.3 years (range 8-15), mean weight 43 ± 19 kg (range 18-81), mean body surface area 1.3 ± 0.3 m(2) (range 0.76-1.96) were identified. Diagnosis included: dilated cardiomyopathy (CMP) (n = 5), noncompaction CMP (n = 4), toxic CMP (n = 2) and viral CMP (n = 1). Indications for support were permanent support (n = 1), bridge to recovery (n = 1) and bridge to transplantation (n = 10). Prior to HVAD implantation, all patients received intravenous inotropes and two patients were on temporary mechanical support. Overall mortality was 0%. Mean duration of inpatient and outpatient support were 56 (range: 19-95 days) and 290 days (range: 42-790), respectively. Mean readmission rate was 0.02 per patient month (2.1 per patient). No adverse events involving emergency department occurred. Eight children resumed local schooling. Home discharge of children supported on HVAD is feasible and safe. School integration can be achieved. There is wide center variability to discharge practice for children.

A multicenter study of primary graft failure after infant heart transplantation: impact of extracorporeal membrane oxygenation on outcomes.

Primary graft failure is the major cause of mortality in infant HTx. The aim of this study was to characterize the indication and outcomes of infants requiring ECMO support due to primary graft failure after HTx. We performed a retrospective review of all infants (<1 yr) who underwent Htx from three institutions. From 1999 to 2008, 92 infants (<1 yr) received Htx. Sixteen children (17%) required ECMO after Htx due to low cardiac output syndrome. Eleven (69%) infants were successfully weaned off ECMO, and 9 (56%) infants were discharged with a mean follow-up of 2.3 ± 2.5 yr. Mean duration of ECMO in survivors was 5.4 days (2-7 days) compared with eight days (2-10 days) in non-survivors (p = NS). The five-yr survival rate for all patients was 75%; however, the five-yr survival rate was 40% in the ECMO cohort vs. 80% in the non-ECMO cohort (p = 0.0001). Graft function within one month post-Htx was similar and normal between ECMO and non-ECMO groups (shortening fraction = 42 ± 3 vs. 40 ± 2, p = NS). For infants, ECMO support for primary graft failure had a lower short-term and long-term survival rate vs. non-ECMO patients. Duration of ECMO did not adversely impact graft function and is an acceptable therapy for infants after HTx for low cardiac output syndrome.

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

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

A risk-prediction model for in-hospital mortality after heart transplantation in US children.

We sought to develop and validate a quantitative risk-prediction model for predicting the risk of posttransplant in-hospital mortality in pediatric heart transplantation (HT). Children <18 years of age who underwent primary HT in the United States during 1999-2008 (n = 2707) were identified using Organ Procurement and Transplant Network data. A risk-prediction model was developed using two-thirds of the cohort (random sample), internally validated in the remaining one-third, and independently validated in a cohort of 338 children transplanted during 2009-2010. The best predictive model had four categorical variables: hemodynamic support (ECMO, ventilator support, VAD support vs. medical therapy), cardiac diagnosis (repaired congenital heart disease [CHD], unrepaired CHD vs. cardiomyopathy), renal dysfunction (severe, mild-moderate vs. normal) and total bilirubin (≥ 2.0, 0.6 to <2.0 vs. <0.6 mg/dL). The C-statistic (0.78) and the Hosmer-Lemeshow goodness-of-fit (p = 0.89) in the model-development cohort were replicated in the internal validation and independent validation cohorts (C-statistic 0.75, 0.81 and the Hosmer-Lemeshow goodness-of-fit p = 0.49, 0.53, respectively) suggesting acceptable prediction for posttransplant in-hospital mortality. We conclude that this risk-prediction model using four factors at the time of transplant has good prediction characteristics for posttransplant in-hospital mortality in children and may be useful to guide decision-making around patient listing for transplant and timing of mechanical support.

Outcome of listing for cardiac transplantation for failed Fontan: a multi-institutional study.

BACKGROUND: The Fontan procedure is a successful palliation for children with single-ventricle physiology; however, many will eventually require heart transplantation. The purpose of this study was to determine risk factors for death awaiting transplantation and to examine results after transplantation in Fontan patients. METHODS AND RESULTS: A retrospective, multi-institutional review was performed of 97 Fontan patients <18 years of age listed at 17 Pediatric Heart Transplant Study centers from 1993 to 2001. Mean age at listing was 9.7 years (0.5 to 17.9 years); 25% were <4 years old; 53% were United Network for Organ Sharing status 1; 18% required ventilator support. Pretransplantation survival was 78% at 6 months and 74% at 12 months and was similar to 243 children with other congenital heart disease (CHD) and 747 children without congenital heart disease (No-CHD), who were also awaiting transplantation. Patients who were younger, status 1, had shorter interval since Fontan, or were on a ventilator were more likely to die while waiting. At 6 months, the probability of receiving a transplant was similar for status 1 and 2 (65% versus 68%); however, the probability of death was higher for status 1 (22% versus 5%). Seventy patients underwent transplantation. Survival was 76% at 1 year, 70% at 3 years, and 68% at 5 years, slightly less than CHD and No-CHD patients. Causes of death included infection (30%), graft failure (17%), rejection (13%), sudden death (13%), and graft coronary artery disease (9%). Protein-losing enteropathy (present in 34 patients) resolved in all who survived >30 days after transplantation. CONCLUSIONS: Heart transplantation is an effective therapy for pediatric patients with a failed Fontan. Although early posttransplantation survival is slightly lower than other patients with CHD, long-term results are encouraging, and protein-losing enteropathy can be expected to resolve.

Hemodynamic data and survival in children with pulmonary hypertension.

OBJECTIVES: Using data from a multi-institutional data base, we sought to determine whether hemodynamic data predict duration of survival in children with primary or secondary pulmonary hypertension. BACKGROUND: Lung transplantation is a therapeutic option for children with pulmonary hypertension. Appropriate timing of lung transplantation requires reliable methods of predicting duration of survival in potential candidates. METHODS: A regional data base was used to obtain cardiac catheterization data on 50 children with mean pulmonary artery pressure (mPAP) > 25 mm Hg and indexed pulmonary resistance (Rp) > 4.5 Wood units. Data on survival were obtained from the participating centers. RESULTS: There were 15 patients without congenital heart disease (group 1) and 35 patients with congenital heart disease (group 2) for analysis. Actuarial survival at 1, 2 and 5 years was 86%, 69% and 69% in group 1 and 88% and 77% in group 2, respectively (p = NS). Hemodynamic variables that predicted survival on univariate analysis were mean right atrial pressure (mRAP) (p < 0.0001), mPAP (p = 0.034), Rp (p < 0.0001) and pulmonary flow (p = 0.003), as well as a variable that we generated-mRAP x Rp (p < 0.0001). On multivariate stepwise logistic regression analysis, mRAP x Rp was independently related to survival. A model using mRAP x Rp allows for the estimation of probability of death at 1 and 2 years after catheterization. CONCLUSIONS: Hemodynamic variables can predict survival in children with pulmonary hypertension in the presence or absence of congenital heart defects. This information can be used to determine the optimal timing of listing for lung transplantation.

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.

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.

Fate of infants with hypoplastic left heart syndrome listed for cardiac transplantation: a multicenter study.

BACKGROUND: Infants with hypoplastic left heart syndrome (HLHS) commonly undergo cardiac transplantation as primary management. METHODS: We examined outcomes of primary transplantation for unpalliated HLHS. We analyzed data from the 20 institutions of the Pediatric Heart Transplant Study Group, from January 1, 1993, through December 31, 1998, using actuarial and parametric survival analysis and competing outcomes analysis. RESULTS: During the 6 years studied, 1,234 patients were listed for cardiac transplantation; 262 patients (21.2%) had unpalliated HLHS. The number (and percentage) of patients with HLHS decreased from 58 (27% of patients listed) in 1993 to 30 (14%) in 1998. Overall, 25% of infants with HLHS died while waiting; primary cause of death was cardiac failure (50%). Of the remaining patients awaiting transplantation, 23 (9%) underwent Norwood/Fontan-type surgeries as interim palliation: 52% died. Ultimately, 175 patients underwent cardiac transplantation (67%); 50% received organs by 2 months after listing. Post-transplant actuarial survival was 72% at 5 years, with 76% of deaths (35/46) occurring within 3 months; early mortality was caused primarily by graft failure within the first 30 days after transplantation (in 54%). Among 1-month survivors, survival at 1 and at 5 years was 92% and 85%, respectively. Of the 262 patients listed with unpalliated HLHS, overall survival, taking into account mortality after listing and after transplantation, was 68% at 3 months and 54% at 5 years. CONCLUSIONS: Cardiac transplantation offers good intermediate survival for infants with unpalliated HLHS.

Extracorporeal life support in cyanotic congenital heart disease before cardiovascular operation.

From July 1988 to March 1991, extracorporeal membrane oxygenation (ECMO) was used in 8 infants (newborn to 16 months old) with unoperated cyanotic congenital heart disease and cardiopulmonary collapse, associated with hypercyanotic spells (4 infants), pulmonary hypertensive crises (3) and sepsis (1). Indications for ECMO support were arterial saturations less than or equal to 60% accompanied by hypotension and metabolic acidosis unresponsive to mechanical ventilation with 100% oxygen, paralysis and sedation, and pharmacologic support with inotropes or vasodilators, or both. Venoarterial bypass by carotid/jugular cannulation with flow rates of 100 to 840 ml/kg/min (mean 460) stabilized all patients. Duration of ECMO support ranged from 15 to 840 hours and was associated with transient seizures (1 patient) and renal failure (1). Seven patients underwent palliative (3 patients) or corrective (4) surgical procedures while on ECMO or within 48 hours of decannulation, including 1 patient bridged to double-lung transplantation with a long (840 hours) duration of ECMO. There was 1 operative and 2 late (greater than 1 month after decannulation) deaths, for an overall survival rate of 62%. These 5 survivors all have normal growth and development, and patent neck vessels at the site of cannulation. These early results indicate that ECMO can be effective mechanical support in cardiovascular crises untreatable with maximal conventional medical therapy and can be used as a bridge to successful surgical palliation or repair.

Comparison of ventricular mass and function in early versus late repair of coarctation of the aorta.

Left ventricular (LV) mass and function in 11 patients (group I) with coarctation of the aorta repaired at a mean age of 35 days were compared with that of 14 patients (group II) who underwent repair at a mean age of 8 years. Each group was compared to age- and sex-matched normal control subjects. All patients were normotensive and had resting arm-leg peak systolic blood pressure gradients < 20 mm Hg. Quantitative M-mode echocardiography was used to determine LV mass index and systolic performance. Magnetic resonance imaging was performed to assess residual narrowing of the descending aorta. LV mass index was increased in both groups when compared with control subjects (group I p = 0.01; group II p = 0.007). Whereas systolic performance in group I was similar to its control group, group II patients had enhanced LV systolic performance as measured by shortening fraction (p = 0.007). Multiple regression analysis of combined group I and II patients demonstrated a significant positive correlation of residual aortic narrowing with LV mass index (p = 0.01). Thus, LV mass remains increased in normotensive patients without major blood pressure gradients after repair of coarctation of the aorta in infancy or childhood. Small degrees of residual aortic narrowing were associated with increased postoperative LV mass regardless of the age at repair.

Early results after pediatric cardiac transplantation with triple immunosuppression therapy.

Pediatric heart transplant recipients were previously reported to have higher early mortality and morbidity than do adult patients treated with triple immunosuppression therapy (steroids, azathioprine and cyclosporine). Nineteen patients (11 infants and 8 older children) underwent orthotopic transplantation using triple immunosuppression therapy. Surveillance for cellular rejection and coronary arteriopathy was performed with endomyocardial biopsy and selective coronary angiography in all patients, with continuous monitoring for hypertension and serious infection. Seventeen of 19 patients (89%; 10 infants and 7 older children) are current survivors, with a median follow-up of 29 months (range 17 to 94). There were 5 and 7 episodes of rejection in the first 12 months after transplantation in the infant and older groups, respectively, for actuarial freedom-from-rejection rates of 65% at 3 months and 54% at 12 months. Severe coronary arteriopathy was detected in 1 infant 11 months after transplantation. In the first 12 months after transplantation, there were 3 hospitalizations for infection, and 2 patients needed treatment for hypertension in the infant group, compared with 1 hospitalization for infection, and 4 patients on antihypertensives in the older group. An increased prevalence of noninfectious complications in the infant group led to significantly longer postoperative stays than in the older group (mean 27.3 vs 19.4 days; p < 0.05). The results indicate that cardiac transplantation using triple immunosuppression therapy in infants, children and adolescents is associated with a high survival rate, and low rates of rejection and serious infection.

Noninvasive diagnosis of right-sided extracardiac conduit obstruction by combined magnetic resonance imaging and continuous-wave Doppler echocardiography.

Right-sided extracardiac conduits are frequently complicated by obstruction over time. We compared the utility of two-dimensional and Doppler echocardiography and magnetic resonance imaging in the diagnosis of postoperative right-sided obstruction with cardiac catheterization and angiography in 10 patients with xenograft or homograft conduits. Correlation (r = 0.95) between continuous-wave Doppler estimates and catheter pullback pressure gradients across the conduits was excellent. Echocardiography could only visualize five of 10 conduits in their entirety. Magnetic resonance imaging visualized all conduits and showed statistically significant (kappa = 0.58) agreement with angiography in the localization and estimation of severity of a variety of right-sided obstructions in these patients. However, flow voids created by the metallic ring around xenograft valves led to a false negative diagnosis of valvular stenosis in four patients when magnetic resonance imaging was used alone. Doppler studies correctly indicated obstruction in these patients. The combination of magnetic resonance imaging studies and continuous-wave Doppler echocardiography can be useful to noninvasively evaluate right-sided obstruction in postoperative patients with right-sided extracardiac conduits.

Increased morbidity and high variability of cyclosporine levels in pediatric heart transplant recipients.

OBJECTIVES: This study analyzed the relationship of variability in routine trough cyclosporine (CSA) levels to morbidity after pediatric cardiac transplantation. BACKGROUND: Due to high interindividual variation between dosage and blood concentrations, trough surveillance CSA levels are routinely performed after cardiac transplantation to adjust dosages. In addition, trough CSA levels have been used as a measure of patient compliance in transplant recipients. Recent investigations have demonstrated a relationship between late rejection and mistimed CSA dosing intervals, which could also lead to CSA levels that are incorrectly presumed to be trough levels. METHODS: Trough surveillance whole-blood CSA levels were retrospectively reviewed in 49 pediatric heart transplant recipients who had a median follow-up of 42 months (range 6 to 138 months). All patients received the same immunosuppression regimen (CSA, azathioprine, and steroids), the same CSA-level surveillance protocol, and the same stabilization of CSA dose and level in the therapeutic range (150 to 300 ng/ml) prior to hospital discharge. CSA levels drawn because of coexisting phenomena (drug interaction, gastroenteritis) that could cause CSA-level fluctuation were excluded from analysis. Cyclosporine variability was measured as the percentage of CSA levels that were considered sub-therapeutic (< or = 100 ng/ml), toxic (> or = 450 ng/ml), or both. Cyclosporine-level variability was then analyzed in respect to demographic and outcome variables. RESULTS: For the group, the median percentage of sub-therapeutic levels was 3% (range, 0% to 16%); the median percentage of toxic levels was 5% (range, 0% to 36%); the median of the combination of sub-therapeutic and toxic levels was 10% (0% to 38%). Eight of the 49 patients (16%) has a high (>20%) percentage of sub-therapeutic + toxic levels or high CSA variability. High CSA variability was significantly associated with recipients > 12 months of age (p = 0.028), and recipients with a history of non-compliance (p < 0.001). Patients with high CSA variability had a significantly higher median number of hospitalized days per year of follow-up (p = 0.036), higher rate of recurrent rejection (> or = 2 episodes; p = 0.0003), and higher death rate more than 6 months after transplant (p = 0.01). CONCLUSIONS: Although this study could not determine cause, high variability in trough CSA levels was a marker for pediatric heart transplant recipients at greater risk for recurrent rejection and hospitalization after transplantation.

Transplant coronary artery disease in pediatric heart transplant recipients.

BACKGROUND: Transplant coronary artery disease (TxCAD) contributes to a large percentage of late morbidity and mortality among adult heart transplant recipients. Intracoronary ultrasound (ICUS) is a sensitive tool in the diagnosis of TxCAD in adult patients and has allowed analysis of factors contributing to disease development. Experience with ICUS in pediatrics, however, has been limited. By using ICUS we sought to determine the overall prevalence of TxCAD in pediatrics and to characterize factors associated with its development in this population. METHODS: Eighty-six studies were performed in 51 pediatric patients a median of 3.4 years after heart transplantation. Evaluation included angiography and ICUS in 83 and angiography alone in 3 studies. Donor and recipient characteristics were obtained. The ICUS images were analyzed for intimal thickening and compared with coronary angiograms. The presence of any intimal thickening on ICUS was considered TxCAD. An intimal index and point of maximal intimal thickening (MIT) were measured. Vessel disease was graded 0 to 4 based on these results. Four patients had evidence of vasculopathy by angiography, whereas 32 patients (63%) had evidence of intimal proliferation by ICUS. Grade 2 or greater disease was present in 19 (37%) patients. A positive correlation was found when comparing time from transplant with intimal index and MIT (p < 0.001). No other factors were found to predict the development of disease. The overall prevalence of disease was 74% in patients studied at least 5 years after transplant. Intracoronary ultrasound can be performed safely in pediatric patients. Transplant coronary artery disease is common in infants and children after heart transplantation, although its prevalence appears to be less than in adult recipients at similar time intervals. We found no factor other than time from transplant was associated with development of disease.

Long-term prostacyclin infusion to reduce pulmonary hypertension in a pediatric cardiac transplant candidate prior to transplantation.

Pulmonary hypertension represents a significant risk factor for peri-operative death in patients undergoing cardiac transplantation. Heart-lung transplantation is generally the only procedure available for patients whose pulmonary hypertension can not be reversed by conventional pharmacologic means. We present a pediatric patient with end-stage cardiac disease and refractory pulmonary hypertension who was treated with long-term intravenous prostacyclin. This resulted in a significant enough improvement in her hemodynamics to allow for successful cardiac transplantation alone.

Infant and donor organ growth after heart transplantation in neonates with hypoplastic left heart syndrome.

BACKGROUND: There is little published data regarding somatic growth and changes in allograft size after heart transplantation in infants with hypoplastic left heart syndrome. METHODS: We evaluated the somatic growth of 26 infants with hypoplastic left heart syndrome who underwent heart transplantation over a 5-year period and measured changes in left ventricular dimensions in 22 of those infants. Age at transplantation was 27 +/- 17 days (mean +/- standard deviation), and the follow-up period was 43 +/- 14 months. Growth and echocardiographic data were converted to standard deviation (Z) scores for comparison with normal populations. RESULTS: Height and weight were always within normal limits (two standard deviations), with a trend toward smaller size throughout the follow-up period. The somatic growth of infants on low-dose maintenance steroids was not significantly different from that of infants withdrawn from chronic steroid regimens. Initial left ventricular posterior wall and septal dimensions were greater than two standard deviations (+4.3 and +6, respectively), probably the result of routine use of oversized donors, but the dimensions decreased to within the normal range during the first year. They then remained within normal limits during follow-up. With one exception at 2 years after transplantation, left ventricular diastolic dimensions were always within two standard deviations of the mean. Left ventricular dimensions of patients with hypertension, rejection, or acute graft failure were not significantly different from patients without these complications. CONCLUSIONS: Neonates with hypoplastic left heart syndrome who undergo heart transplantation can be expected to have somatic growth within normal limits. However, the trend toward growth retardation is worrisome. Left ventricular wall dimensions adjust to smaller recipient size during the first year after transplantation and then remain appropriate for the recipient's size over time.

Lung transplantation in infancy and early childhood.

BACKGROUND: Experience with lung transplantation in infants and young children is limited. Small size, vulnerability to infection, and limited modalities for rehabilitation and surveillance of the transplanted lung make this group particularly challenging. METHODS: We reviewed the course of all children up to the age of 25 months who underwent lung transplantation at two centers between July 1990 and February 1995. RESULTS: Lung transplantation was performed in 17 patients under the age of 25 months, with concurrent cardiac repair in 14. Prior thoracic surgery had been performed in 12; six patients had mechanical ventilation, and three were supported with extracorporeal membrane oxygenation while waiting for lungs. The mean waiting time was 37 days (range 1 to 197 days). Hospital survival was 12 of 17 (71%); there was one late death. Early deaths were due to hemorrhage (two patients), cytomegalovirus and lymphoproliferative disease (one patients), and viral pneumonitis (two patients). The one late death was due to overwhelming gastroenteritis of unknown origin. One additional patient had graft failure caused by viral pneumonitis and underwent successful retransplantation. Bronchial stenosis occurred at 3 of 33 anastomoses. At a mean follow-up of 22 months, surviving patients were well, without supplemental oxygen, and, although small in stature, had normal linear growth. CONCLUSIONS: Lung transplantation is a reasonable therapy for very young patients with limited life expectancy and no other therapeutic alternative, with outcomes comparable with those achieved in older patients. Early recognition of lung transplant candidates and advances in the prevention, diagnosis, and treatment of viral illness may improve survival in these patients.