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The Registry of the International Society for Heart and Lung Transplantation: Twentieth Pediatric Heart Transplantation Report—2017; Focus Theme: Allograft ischemic time
Reprint requests: Josef Stehlik, MD, MPH, Division of Cardiovascular Medicine, University of Utah Health, U.T.A.H. Cardiac Transplant Program, 50 North Medical Drive, 4A100 SOM, Salt Lake City, UT 84132. Tel.: +801 585 2340; fax: +801 581 7735
Pediatric heart transplantation is performed throughout the world and the annual number of transplants has grown dramatically since the first transplant was performed in 1967. The Registry of the International Society for Heart and Lung Transplantation (ISHLT) is the largest source of worldwide heart transplant data with almost 14,000 transplants in children reported. As such, the Registry is able to examine temporal trends in the management and outcomes of pediatric heart transplant recipients.
Statistical methods
Data collection, conventions and statistical methods
National and multinational organ/data exchange organizations and individual centers submit data to the ISHLT Registry. Since its inception, 472 heart transplant centers, 256 lung transplant centers and 180 heart–lung transplant centers have reported data to the Registry. In our estimations, data submitted to the Registry represent approximately three quarters of worldwide transplant activity.
An overview of donor and recipient characteristics and outcomes is presented in this report. The data are supplemented with additional and extended analyses presented in the online slide sets (3 separate slide sets, named “Introduction,” “Heart Overall” and “Heart Pediatric”; see http://ishlt.org/registries/slides.asp?slides=heartLungRegistry/). Slide sets for previous annual reports are also available on this site. The study refers to specific online e-slides when particular data are discussed but not shown in the report due to space limitations; e-slide numbers refer to the online (Pediatric Heart Transplant slide set [eSlide H(p)].
The Registry website (http://ishlt.org/registries/heartLungRegistry.asp/) provides detailed spreadsheets of the data elements collected in the Registry. The Registry requires submission of core donor, recipient and transplant procedure variables at baseline and at yearly follow-up, and therefore these variables have low rates of missingness. Nevertheless, data quality depends on accuracy and completeness of reporting. Rates of missingness may significantly increase for Registry variables that depend on voluntary reporting. The Registry uses various quality control measures to ensure acceptable data quality and completeness before including data for analyses.
Analytical conventions
Unless otherwise specified, heart–lung transplants are not included in analyses of heart transplants or lung transplants. Retransplant includes those with a previously reported transplant of the same organ type, same organ type in combination, or with a retransplant diagnosis. Because identification of all transplants for an individual may not be complete, the number of retransplant events may be slightly underestimated. The Registry does not capture the exact occurrence date for most secondary outcomes (e.g., renal dysfunction), but it does capture the window of occurrence (i.e., the event occurred between the first- and the second-year annual follow-up visits). For the annual report, the mid-point between annual follow-ups is used as a surrogate for the event date. There is some bias in reporting secondary outcomes and other information on the follow-up where a death is reported. To reduce the possibility of underestimating event rates or other outcomes, some analyses are limited to surviving patients. For time-to-event rates and cumulative morbidity rates, follow-up of recipients not experiencing the event of interest was censored at the last time the recipient was reported not to have had the event, either the most recent annual follow-up or the time of retransplantation. Time-to-event graphs (e.g., survival graphs) are truncated when the number of individuals still at risk was <10. Additional information regarding the general statistical methods used for analyses and data interpretation is included in the Supplementary Material available online (www.ishltonline.org).
Focus theme methods: Allograft ischemic time
The Registry Steering Committee selected allograft ischemic time as the theme topic for the 2017 report. Allograft ischemic time was defined as the time elapsed between aortic cross-clamp performed during organ procurement surgery and coronary artery reperfusion during heart transplant surgery.
The reporting of allograft ischemic time significantly varied by geographic region, with high rates of data completeness from North American transplant centers, low rates of completeness from European centers and moderate rates for centers from other regions. Thus, we recommend cautious interpretation of the theme data, especially for analyses that include geographic region and for generalizability to non–North American centers. The inconsistent reporting of different variables from different regions illustrates the trade-offs between worldwide broadly generalizable Registry data versus more internally valid but less generalizable data collected locally or regionally.
Pediatric heart transplant—overview of donor and recipient demographics, survival and morbidity outcomes
Centers and activity
The number of centers reporting pediatric heart transplants (age <18 years old at the time of transplant) has been relatively stable over the last several years, with 120 centers reporting at least 1 transplant in 2015 (Figure 1, eSlide H(p) 4). The majority (>85%) have been reported from Europe and North America. The annual number of transplants reported to the Registry has increased with 414 reported in 2000 and 684 reported in 2015 (eSlide H(p) 10). Most centers are relatively low-volume centers, averaging 1 to 4 pediatric heart transplants per year, whereas the number of centers averaging >10 transplant per year increased from 15 in 2004 to 2008 to 22 in 2009 to June 2016 (eSlide H(p) 5). Centers averaging <10 transplants per year account for the majority of transplants in Europe, whereas centers averaging ≥10 transplants per year account for >60% of the transplants from North America. Outside of Europe and North America, nearly 80% of transplants are performed by centers that average 1 to 4 transplants per year (Figure 2, eSlide H(p) 8).
Figure 1Number of centers reporting pediatric heart transplants.
Consistent with previous reports, infants (age <1 year at transplant) have continued to account for the greatest number of transplants, with >1,600 infant transplants reported to the Registry from 2004 to June 2016 (eSlide H(p) 9). There were geographic differences with proportionally more infants being transplanted in North America and fewer infants being transplanted outside of Europe and North America (eSlide H(p) 11). Congenital heart disease (CHD) was the underlying diagnosis leading to transplant in the majority of infants (55%), whereas cardiomyopathy was the most common diagnosis among adolescents (age 11 to 17 years at transplant) (Figure 3, eSlides H(p) 16 to 19). The percentage of retransplants has been relatively stable over time, comprising 5% of all pediatric heart transplants in 2015 (eSlide H(p) 103). Most retransplants occurred at >60 months from the primary transplant and occurred among patients >5 years old (eSlide H(p) 104). Indication for transplant was the focus theme of the 2016 Registry report and additional details on the underlying diagnoses can be found in that report.
The Registry of the International Society for Heart and Lung Transplantation: nineteenth pediatric heart transplantation report—2016; Focus theme: Primary diagnostic indications for transplant.
The utilization of mechanical circulatory support (MCS) has continued to be common as a bridge to transplant, with ventricular assist devices (VADs) being the primary support modality. The overall utilization differed by age and by underling disease (Figure 4, eSlides H(p) 23 to 25). Among patients with dilated cardiomyopathy (DCM), >50% of non-infants were bridged to transplant on some form of MCS, with most patients being supported with a VAD. Among patients with CHD, the utilization of MCS was less common, especially among infants. Only 12% of infants with CHD were bridged to transplant on some form of MCS, with extracorporeal membrane oxygenation (ECMO) use being more common than VAD use in this group.
Figure 4Percentage of patients bridged with mechanical circulatory support by age group and diagnosis (transplants: January 2009 to June 2016). CHD, congenital heart disease; DCM, dilated cardiomyopathy; ECMO, extracorporeal membrane oxygenation; VAD, ventricular assist device; TAH, total artificial heart.
Sensitization has continued to be an important issue in pediatric heart transplant recipients. Patients with CHD were more likely to have some degree of sensitization compared with DCM, defined as a panel-reactive antibody (PRA) level of ≥10%, approaching nearly 40% in adolescents (Figure 5, eSlide H(p) 26 to 29). A high degree of sensitization, defined as PRA ≥80%, was also more common in CHD patients, occurring in >10% of non-infant transplants and 6% of infant transplants. DCM patients were not free from risk of developing anti-HLA antibodies, although sensitization levels were lower than for patients with CHD.
Figure 5Panel-reactive antibody distribution by age group and diagnosis (transplants: January 2004 to June 2016). CPRA, calculated panel-reactive antibody; PRA, panel-reactive antibody.
Infants have continued to comprise the largest age group of donors (eSlide H(p) 12), driven primarily by transplants in North America and Europe (eSlide H(p) 14). Not surprisingly, hearts from infant donors were more likely to be utilized in infants or young children, whereas adolescent and adult donor hearts were used predominately in adolescent recipients (eSlide H(p) 13). In North America, over 80% of pediatric transplants used hearts from pediatric donors, whereas the use of older adult donors, those ≥ 35 years, occurred in only 1.3% of transplants. This contrasts with Europe and other areas where adult donor hearts were used for 41% and 52% of pediatric transplants, respectively (eSlide H(p) 14). The donor:recipient weight ratio has been relatively stable over time, with nearly 50% of transplants occurring within the ratio of 1.0 to <1.5 (eSlide H(p) 15). Allograft ischemic time is the focus theme of this report and is described in further detail in what follows.
Immunosuppression
Induction therapy has continued to be commonly used in pediatric heart transplant recipients, with 71% receiving some form of induction therapy in the current era (eSlides H(p) 55 and 56). Polyclonal anti-thymocyte globulin was used in 52% of pediatric heart transplant recipients as the most commonly used agent, with interleukin-2 receptor antagonists used in 21% of patients. As in previous reports, the use of induction therapy was not found to be associated with long-term survival, although survival was lower, irrespective of induction therapy, if there was treated rejection in the first year post-transplant (eSlides H(p) 57 and 58).
For maintenance immunosuppression, tacrolimus and myophenolate mofetil or mycophenolic acid (MMF/MPA) have been used in 86% and 92% of patients, respectively, at the time of discharge in the current era (Figure 6, eSlide H(p) 59). Prednisone use at the time of discharge continued to be common at 68%, with sirolimus or everolimus used in <2% of patients. At 1-year post-transplant, the combination of tacrolimus and MMF/MPA was used in the majority of patients, but there was increased use of sirolimus or everolimus in 10% of patients compared with discharge (Figure 7, eSlides H(p) 60 and 61).
Figure 6Maintenance immunosuppression at the time of transplant discharge by era (transplants: January 2004 to June 2016).
Figure 7Maintenance immunosuppressive drug combinations at 1 year follow-up (follow-ups: January 2004 to June 2016). MMF, myophenolate mofetil; MPA, mycophenolic acid.
Functional status, as measured by the Lansky score, has continued to be good among survivors after transplant (eSlide H(p) 52). Over 80% of patients reported either normal activity or minor limitations in strenuous activities at 1, 2 and 3-years post-transplant. Rehospitalizations, however, were relatively common after transplant, although the likelihood of being rehospitalized decreased over time (eSlide H(p) 53).
Rejection
Rejection has continued to be a major morbidity after transplant and, as noted in what follows, early rejection was associated with a decrease in overall survival. Fortunately, there has been a decrease in the percentage of patients treated for rejection between hospital discharge and 1-year post-transplant (eSlide H(p) 73), and this was evident in all age groups and genders. Induction therapy did not decrease the likelihood of treated rejection (eSlides H(p) 74, 75). Conversely, the type of calcineurin inhibitor was associated with rejection, with tacrolimus-treated patients having a lower risk of treated rejection in the first year post-transplant compared with those treated with cyclosporine (Figure 8, eSlides H(p) 76 to 78).
Figure 8Percentage of patients with treated rejection between discharge and 1-year follow-up by calcineurin inhibitor use at discharge (follow-ups: July 2004 to June 2016). Treated rejection—recipient reported to: (1) have at least 1 acute rejection episode that was treated with an anti-rejection agent; or (2) was hospitalized for rejection.
Cardiac allograft vasculopathy (CAV) has continued to be a major limitation to long-term survival for many pediatric heart transplant recipients, although 67% of patients were free from CAV 10 years after transplantation (eSlide H(p) 79). In the univariable analysis, factors associated with the development of CAV included earlier transplant era, no induction therapy, older age at transplant and rejection in the first year post-transplant (Figure 9, eSlides H(p) 80 to 83 and 95). Graft survival after the diagnosis of CAV has remained low and differed by age groups with infants having the poorest graft survival after the diagnosis (median of about 2 years) (eSlide H(p) 86).
Figure 9Freedom from cardiac allograft vasculopathy by age group (transplants: January 2004 to June 2015).
The likelihood of severe renal dysfunction, defined as a serum creatinine >2.5 mg/dl, dialysis or renal transplant, increased over time after transplant. Freedom from severe renal dysfunction was lowest in those patients 6 to 10 years old and in adolescents (83% at 10 years post-transplant) and highest in infants (97% at 10 years post-transplant) (eSlide H(p) 87). Freedom from renal replacement therapy was also associated with age at the time of transplant, with older patients having an increased need for renal replacement therapy (eSlide H(p) 89). The type of calcineurin used was not associated with the development of severe renal dysfunction (eSlide H(p) 88).
Malignancy
The vast majority of malignancies that occur in pediatric heart transplant recipients are lymphomas, with skin cancers being rare (only 3 cases reported among survivors of transplants during 1994 to June 2015) (Table 1, eSlide H(p) 90). The freedom from any malignancy reached 98% at 1 year post-transplant and 89% at 10 years post-transplant, was similar across age groups, and was not associated with type of calcineurin inhibitor or the use of induction therapy for freedom from lymphoma (eSlides H(p) 91, 93 and 94).
Table 1Post-transplant Malignancy: Cumulative Morbidity Rates in Survivors (Transplants: January 1, 1994 to June 30, 2015)
Given the long duration of follow-up available in the Registry, survival rates at 25 years can be assessed (Figure 10, eSlide H(p) 31). The causes of death have varied over time post-transplant, but graft failure has been responsible for a substantial number of deaths at all time-points (Table 2, eSlides H(p) 96 to 101). Early graft failure was the focus theme of the 2015 Registry report.
The Registry of the International Society for Heart and Lung Transplantation: eighteenth official pediatric heart transplantation report—2015; Focus theme: Early graft failure.
Infants showed the longest survival (median 22.3 years), followed by young children (aged 1 to 5 years, median survival 18.4 years), older children (aged 6 to 10 years, median survival 14.4 years) and adolescents (median survival 13.1 years) (Figure 10, eSlide H(p) 31). Given that the great risk of death is in the first-year post-transplant, those who survived the first year had a median survival of >15 years in all age groups (median survival cannot be yet calculated for patients undergoing transplant during infancy as >50% are alive at 25 years post-transplant) (eSlide H(p) 32 and 36). There has continued to be an era effect, with patients transplanted in the recent eras having better survival compared with earlier eras, although the magnitude of this effect may be decreasing and is not evident for all age groups (eSlides H(p) 35, 37 to 40). In contrast to the 2016 Registry report, males and females had similar survival. In addition, there was no difference in survival based on donor/recipient gender match or mismatch (eSlide H(p) 42).
Patients with CHD and those undergoing retransplant had significantly lower intermediate-term survival after transplant compared with patients with DCM for all age groups, with the exception of children 6 to 10 years of age at the time of transplant (eSlides H(p) 43 to 46). As noted previously, retransplant patients had lower survival than those with a primary transplant (eSlide H(p) 105), with retransplantation being the focus theme of the 2014 Registry report.
The Registry of the International Society for Heart and Lung Transplantation: seventeenth official pediatric heart transplantation report—2014; Focus theme: Retransplantation.
In addition, the time interval from the primary transplant was associated with survival after retransplant (Figure 11, eSlide H(p) 106) and was lower when the indication for retransplant was primary graft failure compared with CAV (eSlide H(p) 107). Interestingly, allosensitization, as measured by elevated PRA level, was not associated with long-term survival (Figure 12, eSlides H(p) 47 to 49). Post-transplant survival for patients bridged to transplant with ECMO as a bridge to transplant has continued to be associated with worse survival; however, other forms of MCS resulted in survival similar to that of patients not on MCS (Figure 13, eSlide H(p) 51).
Figure 11Kaplan–Meier survival rates by inter-transplant interval (transplants: January 1994 to June 2015). Only patients <18 years old at the time of retransplant are included.
Figure 13Kaplan–Meier survival by mechanical circulatory support use (transplants: January 2009 to June 2015). ECMO, extracorporeal membrane oxygenation; VAD, ventricular assist device; TAH, total artificial heart.
In patients who survived past 1 year, prednisone use at the time of hospital discharge and at 1 year post-transplant was associated with worse overall survival compared with patients discharged on prednisone but off prednisone at 1 year post-transplant, and compared with patients not on prednisone at either time-point (eSlide H(p) 62). It should be noted that this is a univariable analysis and does not adjust for factors such as rejection episodes that may affect decisions about steroid use. There was no difference in survival conditional on survival to 14 days by type of calcineurin inhibitor used at the time of hospital discharge, or by combination of calcineurin inhibitor and azathioprine vs MMF/MPA (eSlides H(p) 63 and 64). However, cyclosporine use at the time of discharge and tacrolimus use at 1-year post-transplant was associated with worse conditional survival compared to patients treated with cyclosporine at both time-points (eSlide H(p) 65).
Importantly, at least 1 episode of treated rejection has continued to be associated with worse conditional survival compared with no rejection episodes during the first year post-transplant (Figure 14, eSlide H(p) 67), and this association was seen in all age groups except patients 6 to 10 years old at the time of transplant (eSlides H(p) 68 to 71). In addition, the effect of worse 1-year conditional survival among patients with treated rejection in the first year post-transplant did not differ by type of calcineurin inhibitor used at the time of hospital discharge (eSlide H(p) 72).
Figure 14Kaplan–Meier survival based on treated rejection within the first year, conditional on survival to 1 year (1-year follow-ups: July 2004 to June 2015). Treated rejection—recipient was reported to: (1) have at least 1 acute rejection episode that was treated with an anti-rejection agent; or (2) have been hospitalized for rejection. No rejection—recipient had: (1) no acute rejection episodes; and (2) was reported either as not hospitalized for rejection or did not receive anti-rejection agents.
Multivariable analyses were performed to assess for factors independently associated with outcomes. Categorical factors associated with increased 1-year mortality included earlier era, PRA >10%, a diagnosis other than DCM, and being on a ventilator or dialysis at the time of transplant (Figure 15, eSlide H(p) 110). Continuous factors associated with increased 1-year mortality included allograft ischemic time, recipient body mass index (BMI), recipient total bilirubin and center volume of pediatric transplants (Table 3, eSlides H(p) 111 to 118). Risk factors for 1-year mortality were also assessed by age groups. For infants, factors associated with 1-year mortality included diagnosis, inotrope use, dialysis, ECMO, allograft ischemic time and recipient creatinine (eSlides H(p) 119 to 124). For children 1 to 5 years of age at transplant, factors associated with 1-year mortality included cytomegalovirus mismatch, diagnosis, estimated glomerular filtration rate (GFR) and center volume of pediatric transplants (eSlides H(p) 125 to 130). For children 6 to 10 years of age at transplant, diagnosis, estimated GFR and center volume of pediatric transplants were all associated with 1-year mortality (eSlides H(p) 131 to 138), and for adolescents factors associated with 1-year mortality included older era, PRA >10%, ventilator at transplant, dialysis at transplant, mean pulmonary artery pressure and pulmonary capillary wedge pressure (eSlides H(p) 139 to 143). Risk factors for 5-, 10- and 15-year mortality were also determined (Table 3, Figure 16, Figure 17, Figure 18, eSlides H(p) 144 to 164) .
Figure 15Statistically significant categorical risk factors for 1-year mortality with 95% confidence intervals (transplants: January 2004 to June 2015).
Figure 16Statistically significant categorical risk factors for 5-year mortality with 95% confidence intervals (transplants: January 2001 to June 2011).
Figure 17Statistically significant categorical risk factors for 10-year mortality with 95% confidence intervals (transplants: January 1996 to June 2006).
Multivariable analyses were also performed to identify risk factors for development of CAV and severe renal dysfunction. Factors associated with the development of CAV within 5 years included the use of cyclosporine, recipient transfusion, center volume and donor age (eSlides H(p) 165 to 168). Factors associated with the development of CAV within 10 years also included era and underlying diagnosis (eSlides H(p) 169 to 174). Several factors were associated with the development of severe renal dysfunction by 5 and 10 years post-transplant, including retransplantation and dialysis prior to discharge (eSlides H(p) 175 to 183).
Focus theme: Allograft ischemic time
The aim of this focus theme was to determine factors associated with allograft ischemic time and to assess the association between allograft ischemic time and outcomes.
Allograft ischemic time and factors associated with allograft ischemic time
The overall median allograft ischemic time reported over the last decade has been relatively stable, ranging between 3.5 and 3.7 hours (Figure 19, eSlide H(p) 190). There have been differences by diagnosis, with 71% of DCM patients having allograft ischemic time <4 hours compared with 53% of CHD patients (eSlide H(p) 185). Prolonged allograft ischemic time (≥6 hours) was uncommon in all diagnostic groups, ranging from <1% in retransplant patients to 7% in CHD patients. There was a trend for longer allograft ischemic times for patients on ECMO (43% ≥4 hours) compared with VAD/total artificial heart (33% ≥4 hours) or no MCS (34% ≥4 hours), but this did not reach statistical significance (eSlide H(p) 187). Younger patients were more likely to have longer allograft ischemic times, with 43% of infants having allograft ischemic times ≥4 hours vs 32% of adolescents (Figure 20, eSlide H(p) 186). Younger donors also tended to have longer allograft ischemic times (eSlide H(p) 188). There were differences in allograft ischemic time by donor cause of death, with shorter allograft ischemic times seen in donors with head trauma (67% <4 hours) compared with “other” donor cause of death (52% ≥4 hours) (eSlide H(p) 189).
Figure 19Allograft ischemic time distribution by year of transplant.
Allograft ischemic times varied by center volume of pediatric heart transplants. Centers that averaged between 1 and 4 transplants per year reported allograft ischemic times ≥4 hours in 40% of patients, compared with 45% from centers that averaged between 5 and 9 transplants per year and 33% from centers that averaged ≥10 transplants per year (eSlide H(p) 192). There were also geographic differences noted with longer allograft ischemic times reported outside of North America (Figure 21, eSlide H(p) 191). However, reporting of allograft ischemic times was variable in some regions, so caution should be taken in interpretation of these results.
Figure 21Allograft ischemic time distribution by location (transplants: January 2004 to June 2016).
Morbidities and survival by allograft ischemic time
Allograft ischemic time was not associated with most major post-transplant morbidities. There was no association between allograft ischemic time and treated rejection between hospital discharge and 1-year post-transplant (Figure 22, eSlide H(p) 196). Similarly, there was no association of allograft ischemic time with freedom from CAV (Figure 23, eSlide H(p) 197) or the development of severe renal dysfunction (eSlide H(p) 198). Prolonged hospitalizations were more frequent with longer allograft ischemic times, with 35% of patients with ischemic times ≥4 hours a having hospital length of stay ≥29 days compared with 23% of patients with an allograft ischemic time of 0 to <2 hours (eSlide H(p) 199).
Figure 22Percentage of patients with treated rejection between discharge and 1-year follow-up, by allograft ischemic time (transplants: January 2004 to June 2015). (Definition of treated rejection same as in Figure 14).
Differences in unadjusted survival were noted across groups of allograft ischemic times. Thirty-day unadjusted survival was lower for patients with allograft ischemic times ≥4 hours compared to those with allograft ischemic times of <2 hours or 2 to <4 hours (eSlide H(p) 193). In addition, overall unadjusted survival of patients with allograft ischemic times of ≥4 hours was significantly lower than that in patients with allograft ischemic times of 2 to <4 hours (Figure 24, eSlide H(p) 194). Among patients with CHD, allograft ischemic time was not associated with overall survival (Figure 25, eSlide H(p) 195).
Figure 24Kaplan–Meier survival by allograft ischemic time (transplants: January 2004 to June 2015).
As noted earlier, allograft ischemic time was an important factor in a number of multivariable analyses. Allograft ischemic time was independently associated with increased 1-year mortality (overall and in the infant subgroup) and 5-year mortality. In the multivariable analysis, allograft ischemic time was not associated with the development of CAV or severe renal dysfunction at 5 or 10 years post-transplant.
Conclusions
This analysis of the ISHLT Registry has highlighted major findings in the field of pediatric heart transplantation, including the increased use of MCS, especially VAD support in older children with DCM. The focus theme on allograft ischemic time highlights differences in allograft ischemic times based on donor, recipient and center characteristics. Interestingly, although allograft ischemic time was associated with mortality, it was not associated with major post-transplant morbidities.
Disclosure statement
D.C. received travel support from Astellas Pharma, Inc., and serves as a consultant and speaker for Roche, Ltd. L.H.L. received research grant support to his institution from Novartis, Inc., and Abbott, Inc. J.W.R. and J.S. serve as consultants for Medtronic, Inc.
The remaining authors have no conflicts of interest to disclose.
The Registry of the International Society for Heart and Lung Transplantation: nineteenth pediatric heart transplantation report—2016; Focus theme: Primary diagnostic indications for transplant.
The Registry of the International Society for Heart and Lung Transplantation: eighteenth official pediatric heart transplantation report—2015; Focus theme: Early graft failure.
The Registry of the International Society for Heart and Lung Transplantation: seventeenth official pediatric heart transplantation report—2014; Focus theme: Retransplantation.
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