Extracorporeal Membrane Oxygenation Support After Heart Transplantation in Children-Outcomes of a Single Center Cohort.

OBJECTIVES: Extracorporeal membrane oxygenation is used for postcardiotomy low cardiac output but is less established following heart transplantation. We characterized outcomes for children supported with extracorporeal membrane oxygenation after heart transplantation. DESIGN: Single-center retrospective study. SETTING: Large pediatric cardiac referral center. PATIENTS: All patients who received heart transplantation and were cannulated to extracorporeal membrane oxygenation between 1995 and 2016. INTERVENTIONS: Primary outcome measure was mortality 12 months postextracorporeal membrane oxygenation. Patient characteristics were analyzed for association with outcome according to early graft failure (extracorporeal membrane oxygenation ≤ 7 d after heart transplantation), or late graft failure. MEASUREMENTS AND MAIN RESULTS: There were 246 heart transplants during the study period and 50 extracorporeal membrane oxygenation runs in 44 patients. Median time from transplant to extracorporeal membrane oxygenation was 1 day (range, 0-11.7 yr), with early graft failure in 28 patients (median 1, range 0-2 d) and 22 extracorporeal membrane oxygenation runs in 20 late graft failure patients (median, 0.8 yr; range, 8 d to 11.7 yr), including four patients with prior extracorporeal membrane oxygenation for early graft failure. Twenty-six patients (59%) survived to hospital discharge, and survival 12 months postextracorporeal membrane oxygenation was 24 patients (55%), lower in those with late graft failure (40% vs 67%; p 0.02). Independent risk factors for 12-month mortality were congenital heart disease, higher pulmonary vascular resistance indexed to body surface area (> 2.2 Woods U/m), and higher creatinine. Higher panel reactive antibody levels were associated with 12-month mortality in the late graft failure group only. CONCLUSIONS: Extracorporeal membrane oxygenation can be effectively used to rescue patients with graft dysfunction after heart transplantation but is associated with high early mortality. Factors associated with mortality within 12 months include presence of congenital heart disease, renal dysfunction, elevated pulmonary vascular resistance indexed to body surface area and in those supported with extracorporeal membrane oxygenation late after heart transplantation, significant human leukocyte antigen sensitization.

Impact of a positive crossmatch on pediatric heart transplant outcomes.

BACKGROUND: Pediatric heart transplant (HT) candidates experience high waitlist mortality due to a limited donor pool that is constrained in part by anti-HLA sensitization. We evaluated the impact of CDC and Flow donor-specific crossmatch (XM) results on pediatric HT outcomes. METHODS: All pediatric HTs between 1999 and 2019 in the OPTN database were included. Donor-specific XM results were sub-categorized based on CDC and Flow results. Primary outcomes were treated rejection in the first year and time to death or allograft loss. Propensity scores were utilized to adjust for differences in baseline characteristics. RESULTS: A total of 4,695 pediatric HT patients with T-cell XM data were included. After propensity score adjustment, a positive T-cell CDC-XM was associated with 2 times higher odds of treated rejection (OR 2.29 (1.56, 3.37)) and shorter time to death/allograft loss (HR 1.50 (1.19, 1.88)) compared to a negative Flow-XM. HT recipients who were Flow-XM positive with negative/unknown CDC-XM did not have higher odds of rejection or shorter time to death/allograft loss. An isolated positive B-cell XM was also not associated with worse outcomes. Over the study period XM testing shifted from CDC- to Flow-based assays. CONCLUSIONS: A positive donor-specific T-cell CDC-XM was associated with rejection and death/allograft loss following pediatric HT. This association was not observed with a positive T-cell Flow-XM or B-cell XM result alone. The shift away from performing the CDC-XM may result in loss of important prognostic information unless the clinical relevance of quantitative Flow-XM results on heart transplant outcomes is systematically studied.

Antibody depletion for the treatment of crossmatch-positive pediatric heart transplant recipients.

Sensitization to HLA is a risk factor for adverse outcomes after heart transplantation. Requiring a negative prospective CM results in longer waiting times and increased waitlist mortality. We report outcomes in a cohort of sensitized children who underwent transplant despite a positive CDC CM+ using a protocol of antibody depletion at time of transplant, followed by serial IVIG administration. All patients <21 yrs old who underwent heart transplantation at Boston Children's Hospital from 1/1998 to 1/2011 were included. We compared freedom from allograft loss, allograft rejection, and serious infection between CM+ and CM- recipients. Of 134 patients in the cohort, 33 (25%) were sensitized prior to transplantation and 12 (9%) received a CM+ heart transplant. Serious infection in the first post-transplant year was more prevalent in the CM+ patients compared with CM- patients (50% vs. 16%; p = 0.005), as was HD-AMR (50% vs. 2%; p < 0.001). There was no difference in freedom from allograft loss or any rejection. At our center, children transplanted despite a positive CM had acceptable allograft survival and risk of any rejection, but a higher risk of HD-AMR and serious infection.

Waiting list mortality among children listed for heart transplantation in the United States.

BACKGROUND: Children listed for heart transplantation face the highest waiting list mortality in solid-organ transplantation medicine. We examined waiting list mortality since the pediatric heart allocation system was revised in 1999 to determine whether the revised allocation system is prioritizing patients optimally and to identify specific high-risk populations that may benefit from emerging pediatric cardiac assist devices. METHODS AND RESULTS: We conducted a multicenter cohort study using the US Scientific Registry of Transplant Recipients. All children <18 years of age who were listed for a heart transplant between 1999 and 2006 were included. Among 3098 children, the median age was 2 years (interquartile range 0.3 to 12 years), and median weight was 12.3 kg (interquartile range 5 to 38 kg); 1294 (42%) were nonwhite; and 1874 (60%) were listed as status 1A (of whom 30% were ventilated and 18% were on extracorporeal membrane oxygenation). Overall, 533 (17%) died, 1943 (63%) received transplants, and 252 (8%) recovered; 370 (12%) remained listed. Multivariate predictors of waiting list mortality include extracorporeal membrane oxygenation support (hazard ratio [HR] 3.1, 95% confidence interval [CI] 2.4 to 3.9), ventilator support (HR 1.9, 95% CI 1.6 to 2.4), listing status 1A (HR 2.2, 95% CI 1.7 to 2.7), congenital heart disease (HR 2.2, 95% CI 1.8 to 2.6), dialysis support (HR 1.9, 95% CI 1.2 to 3.0), and nonwhite race/ethnicity (HR 1.7, 95% CI 1.4 to 2.0). CONCLUSIONS: US waiting list mortality for pediatric heart transplantation remains unacceptably high in the current era. Specific high-risk subgroups can be identified that may benefit from emerging pediatric cardiac assist technologies. The current pediatric heart-allocation system captures medical urgency poorly. Further research is needed to define the optimal organ-allocation system for pediatric heart transplantation.

Ventricular assist devices as a bridge to heart transplantation in children.

UNLABELLED: The increase in time waiting for appropriate pediatric allografts for heart transplantation has mandated the use of long-term mechanical assistance in the pediatric population. Extracorporeal membrane oxygenation support has been routinely used but is limited by both its inability to provide support without life-threatening complications for longer than 2 to 3 weeks as well as the inability of patients to achieve mobility. For the past 10 years, pediatric programs have increasing experience with the use of ventricular assist devices (VADs) to bridge patients to heart transplant. This retrospective study analyzed the clinical features and outcomes of 99 pediatric patients who underwent VAD implant as a bridge to heart transplant. METHODS: Between 1993 and 2003, the Pediatric Heart Transplant Study Group enrolled 2,375 patients (age 1 day-17.9 years) listed for heart transplant from 23 participating centers. Four percent (99 patients) of those listed received VAD support as a bridge to transplantation. Seventy-seven (77%) patients survived to transplant with a mean time on support of 57 days. There were 17 deaths on support and 5 bridged to recovery. Overall incidence of adverse events was similar to the adult data with a 19% risk of stroke. There was no difference in 5-year survival after transplant for patients on VAD at time of transplant compared with those (n = 2,293) not requiring VAD (77% vs 73%, P = .8). These data suggest that despite the lack of pediatric specific devices and relatively high adverse event rate, VADs may be used as a bridge to transplant therapy in appropriate-sized children with the expectation of a successful outcome in most patients.

Outcomes of children bridged to heart transplantation with ventricular assist devices: a multi-institutional study.

BACKGROUND: Current ventricular assist devices (VADs) in the United States are designed primarily for adult use. Data on VADs as a bridge to transplantation in children are limited. METHODS AND RESULTS: A multi-institutional, prospectively maintained database of outcomes in children after listing for heart transplantation (n=2375) was used to analyze outcomes of VAD patients (n=99, 4%) listed between January 1993 and December 2003. Median age at VAD implantation was 13.3 years (range, 2 days to 17.9 years); diagnoses were cardiomyopathy (78%) and congenital heart disease (22%). Mean duration of support was 57 days (range, 1 to 465 days). Seventy-three percent were supported with a long-term device, with 39% requiring biventricular support. Seventy-seven patients (77%) survived to transplantation, 5 patients were successfully weaned from support and recovered, and 17 patients (17%) died on support. In the recent era (2000 to 2003), successful bridge to transplantation with VAD was achieved in 86% of patients. Peak hazard for death while waiting was the first 2 weeks after VAD placement. Risk factors for death while awaiting a transplant included earlier era of implantation (P=0.05), female gender (P=0.02), and congenital disease diagnosis (P=0.05). There was no difference in 5-year survival after transplantation for patients on VAD at time of transplantation as compared with those not requiring VAD. CONCLUSIONS: VAD support in children successfully bridged 77% of patients to transplantation, with posttransplantation outcomes comparable to those not requiring VAD. These encouraging results emphasize the need to further understand patient selection and to delineate the impact of VAD technology for children.

Impact of medication non-adherence on survival after pediatric heart transplantation in the U.S.A.

BACKGROUND: Medication non-adherence (NA) can result in life-threatening illness in children after solid-organ transplantation. Little is known about the incidence, risk factors and outcomes of NA in large numbers of pediatric heart transplant (HT) recipients. METHODS: Organ Procurement Transplant Network (OPTN) data were used to identify all children <18 years of age in the U.S.A. who underwent HT from October 1999 to January 2007. Cox proportional hazards analysis was used to identify risk factors for NA and the effect on graft survival. RESULTS: Of 2,070 pediatric heart transplants performed the median age at transplant was 6 years (interquartile range [IQR] 0 to 13 years); 40% had congenital heart disease (CHD), 7% were re-transplants, 42% were non-white and 43% had Medicaid insurance. Overall, 186 (9%) children had a report of NA at a median age of 15 years with more than two-thirds of NA episodes occurring after 12 years of age. Factors independently associated with NA were: adolescent age at transplant (hazard ratio [HR] 7.0, 95% confidence interval [CI] 4.1 to 12, compared with infants); black race (HR 2.3, 95% CI 1.7 to 3.3, compared with white); Medicaid insurance (HR 2.0, 95% CI 1.5 to 2.7, compared with non-Medicaid insurance); and ventilator or ventricular assist device (VAD) support at transplant. The risk of mortality conditional upon report of NA was 26% at 1 year and 33% at 2 years. CONCLUSIONS: Medication NA is an important problem in pediatric HT recipients and is associated with high mortality. Adolescent age, black race, Medicaid insurance and invasive hemodynamic support at transplant were associated with NA, whereas time on the wait list and gender were not. Targeted interventions among at-risk populations may be warranted.

Socioeconomic position and graft failure in pediatric heart transplant recipients.

BACKGROUND: Socioeconomic (SE) position may affect availability of resources, health-related behavior, and outcomes. We assessed whether patient SE position, determined for the block group of patient residence (average population 1000, smallest census unit with SE data), is associated with graft failure in pediatric heart transplant recipients. METHODS AND RESULTS: We used the US Census 2000 database to derive a composite SE score for the block group of residence for all patients who underwent their first heart transplant at Children's Hospital Boston between 1991 and 2005 (n=135). Cox proportional hazards models were used to determine the risk of graft failure (death or retransplant) in the lowest tertile SE group (low SE group) compared with the remaining 2 of 3 patients (controls). The 2 groups were similar with respect to age, gender, diagnosis, and year of transplant. White race was less frequent in low SE group (64% versus 90%, P=0.001). Graft failure occurred in 46 transplant recipients (40 deaths, 6 retransplant). Low SE group (hazard ratio 2.4, 95% CI 1.3 to 4.3) and nonwhite race (hazard ratio 2.7, 95% CI 1.4 to 5.2) were both associated with higher risk of graft failure. In a multivariable model controlling for diagnosis and pretransplant support, race, and low SE position (hazard ratio 2.0, 95% CI 1.0 to 3.7, P=0.04) remained associated with graft failure. Low SE position group had a higher incidence rate of graft rejection and was at a higher risk of late rejection. CONCLUSIONS: Low SE position may be an independent risk factor for graft failure in pediatric heart transplant recipients.