ABSTRACT
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.
Subject(s)
Graft Rejection , Graft Survival , Heart Transplantation , Humans , Child , Male , Female , Graft Rejection/immunology , Graft Rejection/epidemiology , Child, Preschool , Retrospective Studies , Histocompatibility Testing , Adolescent , Infant , Tissue DonorsABSTRACT
BACKGROUND: Newborns with hypoplastic left heart syndrome (HLHS) who are considered at increased risk for death following Norwood/Sano surgery often undergo hybrid palliation (HP) as initial surgery. We aimed to compile the HP experience in HLHS and its variants and assess the rates of, and risk factors for, death and heart transplantation. METHODS: CINAHL, CINAHL PLUS, PubMed/MEDLINE, and SCOPUS were systematically searched for HP outcome studies of death or heart transplantation in HLHS between 1998 and 2022. Pooled incidence was estimated, and potential risk factors were identified using random-effects meta-analysis and reconstructed time-to-event data from Kaplan-Meier curves. RESULTS: Thirty-three publications were included in our review. Overall, of 1,162 patients 417 died and 57 underwent heart transplantation, resulting in a combined outcome of 40.7%, (474/1,162). There was a trend toward decreasing mortality risk across the stages of palliation. Pooled mortality between HP and comprehensive stage 2 palliation was 25%, after stage 2 up to Fontan palliation was 16%, and 6% post-Fontan. The incidence of death or heart transplantation was higher in high-risk patients-43% died and 10% received heart transplantation. CONCLUSION: Our systematic review and meta-analysis found high rates of death or heart transplantation in HP of HLHS patients between HP and Fontan surgeries. All patients should be closely followed during the initial interstage period, which is associated with the highest hazard. Prospective studies on appropriate patient selection, indications, and / or alternatives, as well as refining HP strategies for managing newborns with HLHS are needed to improve outcomes.
Subject(s)
Heart Transplantation , Hypoplastic Left Heart Syndrome , Palliative Care , Humans , Hypoplastic Left Heart Syndrome/surgery , Hypoplastic Left Heart Syndrome/mortality , Heart Transplantation/mortality , Palliative Care/methods , Infant, Newborn , Norwood Procedures/mortality , Risk FactorsABSTRACT
BACKGROUND: Short-term outcomes using steroid avoidance immune suppression are encouraging in pediatric heart transplant (HT) recipients at low risk of antibody-mediated rejection. We assessed medium-term outcomes in pediatric HT recipients initiated on a steroid avoidance protocol at our institution using surveillance biopsies. METHODS: All primary HT recipients during 2006-2020 who did not have a donor-specific antibody were eligible for immune suppression consisting of 5-d Thymoglobulin/steroid induction followed by a tacrolimus-based, steroid-free regimen. We assessed freedom from graft failure (death or retransplant), acute rejection, posttransplant lymphoproliferative disease, and cardiac allograft vasculopathy. RESULTS: Overall, 150 of 181 primary HT recipients were eligible for steroid avoidance regimen. Their median age was 8.7 y, 41% had congenital heart disease, 23% were sensitized, and 35% were on a mechanical support. The median follow-up was 6.1 y. Eleven patients (8%) were on maintenance steroids at discharge and 13% at 1 y. Graft survival was 94% at 1 y and 87% at 5 y. Freedom from rejection was 73% at 1 y and 64% at 5 y. Freedom from posttransplant lymphoproliferative disease was 96% at 1 y and 95% at 5 y. Freedom from moderate cardiac allograft vasculopathy was 94% at 5 y. Eight patients developed diabetes. Estimated glomerular filtration rate was <60 mL/min/1.73 m 2 in 5% of the cohort at 5 y. CONCLUSIONS: Pediatric HT recipients at low risk of antibody-mediated rejection have excellent medium-term survival and relatively low incidence of posttransplant morbidities when managed using a steroid avoidance immune suppression protocol.
Subject(s)
Heart Transplantation , Immunosuppressive Agents , Humans , Child , Immunosuppressive Agents/adverse effects , Immunosuppression Therapy/methods , Steroids , Tacrolimus/adverse effects , Antibodies , Heart Transplantation/adverse effects , Graft Rejection , Graft SurvivalABSTRACT
The aim of this study (CTOTC-09) was to assess the impact of "preformed" (at transplant) donor-specific anti-HLA antibody (DSA) and first year newly detected DSA (ndDSA) on allograft function at 3 years after pediatric heart transplantation (PHTx). We enrolled children listed at 9 North American centers. The primary end point was pulmonary capillary wedge pressure (PCWP) at 3 years posttransplant. Of 407 enrolled subjects, 370 achieved PHTx (mean age, 7.7 years; 57% male). Pre-PHTx sensitization status was nonsensitized (n = 163, 44%), sensitized/no DSA (n = 115, 31%), sensitized/DSA (n = 87, 24%), and insufficient DSA data (n = 5, 1%); 131 (35%) subjects developed ndDSA. Subjects with any DSA had comparable PCWP at 3 years to those with no DSA. There were also no significant differences overall between the 2 groups for other invasive hemodynamic measurements, systolic graft function by echocardiography, and serum brain natriuretic peptide concentration. However, in the multivariable analysis, persistent first-year DSA was a risk factor for 3-year abnormal graft function. Graft and patient survival did not differ between groups. In summary, overall, DSA status was not associated with worse allograft function or inferior patient and graft survival at 3 years, but persistent first-year DSA was a risk factor for late graft dysfunction.
Subject(s)
Heart Transplantation , Isoantibodies , Humans , Child , Male , Female , HLA Antigens , Tissue Donors , Heart Transplantation/adverse effects , Transplantation, Homologous , Antilymphocyte Serum , Graft Survival , Graft Rejection , Retrospective StudiesABSTRACT
BACKGROUND: Black race is associated with worse outcomes across solid organ transplantation. Augmenting immunosuppression through antithymocyte globulin (ATG) induction may mitigate organ rejection and graft loss. We investigated whether racial and socioeconomic outcome disparities persist in children receiving ATG induction. METHODS: Using the Pediatric Heart Transplant Society registry, we compared outcomes in Black and White children who underwent heart transplant with ATG induction between 2000 and 2020. The primary outcomes of treated rejection, rejection with hemodynamic compromise (HC), and graft loss (death or re-transplant). We explored the association of these outcomes with race and socioeconomic disparity, assessed using a neighborhood deprivation index [NDI] score at 1-year post-transplant (high NDI score implies more socioeconomic disadvantage). RESULTS: The study cohort included 1,719 ATG-induced pediatric heart transplant recipients (22% Black, 78% White). There was no difference in first year treated rejection (Black 24.5%, White 28.1%, p = 0.2). During 10 year follow up, the risk of treated rejection was similar; however, Black recipients were at higher risk of HC rejection (p = 0.009) and graft loss (p = 0.02). Black recipients had a higher mean NDI score (p < 0.001). Graft loss conditional on 1-year survival was associated with high NDI score in both White and Black recipients (p < 0.0001). In a multivariable Cox model, both high NDI score (HR 1.97, 95% CI 1.23-3.17) and Black race (HR 2.22, 95% CI 1.40-3.53) were associated with graft loss. CONCLUSION: Black race and socioeconomic disadvantage remain associated with late HC rejection and graft loss in children with ATG induction. These disparities represent important opportunities to improve long term transplant outcomes.
Subject(s)
Antilymphocyte Serum , Heart Transplantation , Humans , Child , Antilymphocyte Serum/therapeutic use , Graft Rejection/epidemiology , Graft Rejection/prevention & control , Immunosuppression Therapy , Retrospective Studies , Socioeconomic Factors , Graft Survival , Immunosuppressive Agents/therapeutic useSubject(s)
Heart Transplantation , Heart-Lung Transplantation , Lung Transplantation , Organ Transplantation , Pulmonary Disease, Chronic Obstructive , Adult , Humans , Lung , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/surgery , Registries , Transplant RecipientsSubject(s)
Heart Transplantation , Heart-Lung Transplantation , Lung Transplantation , Organ Transplantation , Child , Humans , Infant , Registries , Societies, Medical , Survival RateABSTRACT
BACKGROUND: Cardiac allograft vasculopathy (CAV) is a leading cause of long-term morbidity and mortality in pediatric heart transplant (HTx) recipients. Exercise stress echocardiography (ESE) has been shown to be useful in the detection of angiographically confirmed coronary artery disease in children. However, the prognostic utility of ESE for prediction of cardiac events in HTx survivors is unknown. OBJECTIVES: We aim to assess whether an abnormal (positive) ESE is be associated with a higher risk of future cardiovascular (CV) outcomes in pediatric HTx recipients. METHODS: We conducted a retrospective review of CV outcomes in a cohort of 95 pediatric HTx recipients who underwent 188 ESEs over a 10-year period. A composite endpoint for CV events including myocardial infarction, hospitalization for nonrejection heart failure, coronary revascularization, need for repeat transplantation, and death was used. Based on the interpretation of the ESE results, each ESE study was classified for this study as either positive (abnormal) or negative (normal) for ischemia. Results of the coronary angiograms performed near the time of ESE were also assessed and classified for this study as positive (abnormal) or negative (normal) for CAV according to standard HTx criteria for CAV. RESULTS: Fifty-one (27%) ESEs were positive for ischemia. There was a total of 35 CV events in 23 patients. A positive ESE was associated with increased risk of any CV event (hazard ratio = 3.55; 95% CI, 1.52, 8.28), as well as an increased risk of CV death (hazard ratio = 3.19; 95% CI, 1.23, 8.28). Freedom from composite CV outcome at 1, 2, and 3 years following a positive ESE was 89.9% (95% CI = 77.3%, 95.7%), 81.5% (95% CI = 65.9%, 90.5%), and 63.2% (95% CI = 41.9%, 78.5%), respectively. Freedom from composite CV outcome at 1, 2, and 3 years following a negative ESE was 99.3% (94.8, 99.9), 98.4% (93.6, 99.6), and 97.0% (90.6, 99.1), respectively. No patient died within 1 year of a negative ESE. CONCLUSIONS: In this largest study of ESE in pediatric HTx recipients, a positive or abnormal ESE is associated with increased future CV morbidity and mortality. Conversely, a negative ESE can help predict CV event-free survival. Even in the setting of a normal coronary angiogram, our pilot data show that an abnormal ESE may still be clinically important. Use of ESE in follow-up may improve risk stratification and management of pediatric HTx recipients.
Subject(s)
Coronary Artery Disease , Heart Diseases , Heart Transplantation , Humans , Child , Echocardiography, Stress/methods , Prognosis , Heart Transplantation/adverse effects , Coronary Angiography , Coronary Artery Disease/diagnosis , Coronary Artery Disease/etiology , Heart Diseases/etiologyABSTRACT
BACKGROUND: This study aimed to characterize features present at the time of diagnosis and describe outcomes in patients with post-transplant lymphoproliferative disorder (PTLD) following pediatric solid organ transplantation. METHODS: We performed a retrospective review of solid organ transplant patients who developed pathologically confirmed PTLD at our center from 2006 to 2016. RESULTS: Of 594 patients included in this study, 41(6.9%) were diagnosed with PTLD. Median age at transplant was 5.6(IQR 1.7-16.1) years. Proportion of PTLD cases by organ transplanted and median time (IQR) to disease onset were: heart 11/144(7.6%) at 13.6(8.5-55.6) months, lung 7/52(13.5%) at 9.1(4.9-35) months, kidney 8/255(3.1%) at 39.5(13.9-57.1) months, liver 12/125(9.6%) at 7.7(5.5-22) months, intestine 0/4(0%), and multi-visceral 3/14(21.4%) at 5.4(5.4-5.6) months. No significant correlation was seen between recipient EBV status at transplant and timing of development of PTLD. There were six early lesions, 15 polymorphic, 19 monomorphic, and one uncharacterizable PTLD. Following immunosuppression reduction, 30 patients received rituximab, and 14 required chemotherapy. At median 25(IQR 12-53) months follow-up from the onset of PTLD, eight patients died secondary to transplant related complications, three are alive with active disease, and 30 have no evidence of disease. CONCLUSION: PTLD is a significant complication following pediatric solid organ transplantation. EBV levels in conjunction with symptomatic presentation following transplant may assist in detection of PTLD. Most patients can achieve long-term disease-free survival through immunosuppression reduction, anti-CD20 treatment, and chemotherapy in refractory cases.
Subject(s)
Epstein-Barr Virus Infections , Lymphoproliferative Disorders , Organ Transplantation , Antigens, CD20 , Child , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/diagnosis , Epstein-Barr Virus Infections/epidemiology , Humans , Lymphoproliferative Disorders/diagnosis , Lymphoproliferative Disorders/epidemiology , Lymphoproliferative Disorders/etiology , Organ Transplantation/adverse effects , Retrospective Studies , Rituximab/therapeutic useABSTRACT
Previous analyses in pediatric heart transplant (HT) recipients using weight or height have not found donor-recipient size-mismatch to be associated with post-transplant mortality. A recent study in 3,215 normal US children developed an equation for left ventricular (LV) mass using body surface area (BSA). We assessed whether donor-recipient size match using predicted LV mass (PLM) is associated with post-transplant in-hospital mortality or 1-year graft survival. We identified 4,717 children <18 yrs old who received primary HT in the US during 01/2000 to 03/2015 and divided them into five groups [10%, 10%, 60% (reference group), 10% and 10%, respectively] with increasing donor-recipient PLM ratio. In adjusted analysis, group 1 children (PLM ratio ≤.90) were at higher risk of post-transplant in-hospital mortality [Odds Ratio (OR) 1.55, 95% CI 1.04, 2.31]. This association of the most undersized donors with recipient in-hospital mortality was similar when donor-recipient weight ratio<.88 or BSA ratio<.92 (lowest decile) were used instead. There was no difference in 1-year graft survival among groups. Utilizing donors with donor-recipient PLM ratio ≤.90 is associated with higher risk of early post-transplant mortality in pediatric HT recipients. However, this metric is not superior to donor-recipient weight ratio or BSA ratio for assessing size match.
Subject(s)
Heart Transplantation , Tissue and Organ Procurement , Body Size , Child , Graft Survival , Humans , Organ Size , Retrospective Studies , Tissue DonorsSubject(s)
Heart Diseases/surgery , Heart-Lung Transplantation/statistics & numerical data , Lung Diseases/surgery , Pediatrics , Registries , Societies, Medical , Transplant Recipients/statistics & numerical data , Adolescent , Child , Child, Preschool , Female , Global Health , Heart Diseases/mortality , Humans , Infant , Infant, Newborn , Lung Diseases/mortality , Male , Retrospective Studies , Survival Rate/trendsSubject(s)
Heart Diseases/surgery , Heart-Lung Transplantation/statistics & numerical data , Lung Diseases/surgery , Pediatrics , Societies, Medical , Thoracic Surgery , Transplant Recipients/statistics & numerical data , Adolescent , Child , Child, Preschool , Female , Global Health , Heart Diseases/mortality , Humans , Infant , Infant, Newborn , Lung Diseases/mortality , Male , Registries , Survival Rate/trendsABSTRACT
For over 30 years, the International Society for Heart and Lung Transplantation (ISHLT) International Thoracic Organ Transplant (TTX) Registry has gathered data regarding transplant procedures, donor and recipient characteristics, and outcomes from a global community of transplant centers. Almost 70,000 adult lung transplant procedures have been reported to the Registry since its inception, each one providing an opportunity for a recipient with end-stage lung disease to regain quality of life and longevity. With each year's report, we provide more detailed analyses on a particular focus theme important to recipient outcomes. Since 2013, these have been donor and recipient age; retransplantation; early graft failure; indication for transplant; allograft ischemic time; multiorgan transplantation; and donor and recipient size matching.1-7 In response to a changing regulatory environment, the ISHLT TTX Registry is undergoing an update in data acquisition, and the patient cohort examined in this report is therefore derived from the same data source or datasets as that examined in the 2019 annual reports.2,8-10 We refer the reader to the 2019 and prior reports for a detailed description of the baseline characteristics of the cohort, and additional core analyses not directly related to the focus explored in this year's report. To complement the 2020 report which focussed on donor characteristics, the goal of this year's report was to focus entirely on changes in recipient factors over the past 3 decades and to identify important recipient characteristics and transplant processes that may influence post-transplant outcomes. Due to small numbers, heart-lung transplant recipient characteristics and transplant outcomes have not been included. This 38th annual adult lung transplant report is hence based on data submitted to the ISHLT TTX Registry on 67,493 adult recipients of deceased recipient transplants between January 1, 1992 and June 30, 2018.
Subject(s)
Heart Diseases/surgery , Heart-Lung Transplantation/statistics & numerical data , Lung Diseases/surgery , Registries , Societies, Medical , Thoracic Surgery , Transplant Recipients/statistics & numerical data , Adult , Aged , Female , Global Health , Heart Diseases/mortality , Humans , Lung Diseases/mortality , Male , Middle Aged , Survival Rate/trends , Young AdultSubject(s)
Heart Diseases/surgery , Heart-Lung Transplantation/statistics & numerical data , Lung Diseases/surgery , Registries , Societies, Medical , Thoracic Surgery , Transplant Recipients/statistics & numerical data , Adult , Aged , Female , Global Health , Heart Diseases/mortality , Humans , Lung Diseases/mortality , Male , Middle Aged , Survival Rate/trendsABSTRACT
Background Previous studies suggest that infant heart transplant (HT) recipients are at higher risk of developing severe primary graft dysfunction (PGD) than older children. We sought to identify risk factors for developing severe PGD in infant HT recipients. Methods and Results We identified all HT recipients aged <1 year in the United States during 1996 to 2015 using the Organ Procurement and Transplant Network database. We linked their data to ELSO (Extracorporeal Life Support Organization) registry data to identify those with severe PGD, defined by initiation of extracorporeal membrane oxygenation support for PGD within 2 days following HT. We used multivariable logistic regression to assess risk factors for developing severe PGD. Of 1718 infants analyzed, 600 (35%) were <90 days old and 1079 (63%) had congenital heart disease. Overall, 134 (7.8%) developed severe PGD; 95 (71%) were initiated on extracorporeal membrane oxygenation support on the day of HT, 34 (25%) the next day, and 5 (4%) the following day. In adjusted analysis, recipient congenital heart disease, extracorporeal membrane oxygenation, or biventricular assist device support at transplant, recipient blood type AB, donor-recipient weight ratio <0.9, and graft ischemic time ≥4 hours were independently associated with developing severe PGD whereas left ventricular assist device support at HT was not. One-year graft survival was 48% in infants with severe PGD versus 87% without severe PGD. Conclusions Infant HT recipients with severe PGD have poor graft survival. Although some recipient-level risk factors are nonmodifiable, avoiding modifiable risk factors may mitigate further risk in infants at high risk of developing severe PGD.