Current state of pediatric cardiac transplantation

Abstract

Pediatric heart transplantation is standard of care for children with end-stage heart failure. The diverse age range, diagnoses, and practice variations continue to challenge the development of evidence-based practices and new technologies. Outcomes in the most recent era are excellent, especially with the more widespread use of ventricular assist devices (VADs). Waitlist mortality remains high and knowledge of risk factors for death while waiting and following transplantation contributes to decision-making around transplant candidacy and timing of listing. The biggest gap impacting both waitlist and overall survival remains mechanical support options for infants and patients with single ventricle physiology. Though acute rejection has decreased progressively, both diagnosis and management of antibody-mediated rejection has become increasingly challenging and complex, as has the ability to understand the implication of anti-HLA antibodies detected both pre- and post-transplantation-including when and how to intervene. Trends in immunosuppression protocols include more use of induction therapy and steroid avoidance or withdrawal protocols. Common long-term morbidities include renal insufficiency, which can be mitigated with surveillance and renal-sparing strategies, and infections. Functional outcomes are excellent, but significant psychosocial challenges exist in relation to neurodevelopment, non-adherence, and transition from child-centered to adult-centered care. Cardiac allograft vasculopathy (CAV) remains a barrier to long-term survival, though it is more apparent that objective evidence of an impact on the allograft is important with regards to impact on outcomes. Retransplantation is rare in pediatric heart transplant recipients. Pediatric heart transplantation continues to evolve in order to address the challenges of the diverse group of patients that reach end-stage heart failure during childhood.

Keywords: Heart transplant; mechanical support; outcomes; sensitization; waitlist.

Figure 1

Total number of pediatric heart transplant recipients by age and year of transplant (from the registry of the International Society of Heart and Lung Transplantation. J Heart Lung Transplant 2016;35:1185-95).

Figure 2

Pediatric heart transplant recipient age distribution January 2004–June 2015 (from the registry of the International Society of Heart and Lung Transplantation. J Heart Lung Transplant 2016;35:1185-95).

Figure 3

Pediatric heart transplant recipient age distribution by geographic location January 2004–June 2015 (from the registry of the International Society of Heart and Lung Transplantation. J Heart Lung Transplant 2016;35:1185-95).

Figure 4

Diagnosis in recipients of pediatric heart transplants aged less than 1 year (from the registry of the International Society of Heart and Lung Transplantation. J Heart Lung Transplant 2016;35:1185-95). CAD, coronary artery disease; CHD, coronary heart disease; DCM, dilated cardiomyopathy.

Figure 5

Diagnosis in recipients of pediatric heart transplants aged from 1 to 5 years (from the registry of the International Society of Heart and Lung Transplantation. J Heart Lung Transplant 2016;35:1185-95). CAD, coronary artery disease; CHD, coronary heart disease; DCM, dilated cardiomyopathy.

Figure 6

Diagnosis in recipients of pediatric heart transplants aged from 6 to 10 years (from the registry of the International Society of Heart and Lung Transplantation. J Heart Lung Transplant 2016;35:1185-95). CAD, coronary artery disease; CHD, coronary heart disease; DCM, dilated cardiomyopathy.

Figure 7

Diagnosis in recipients of pediatric heart transplants aged from 11 to 17 years (from the registry of the International Society of Heart and Lung Transplantation. J Heart Lung Transplant 2016;35:1185-95). CAD, coronary artery disease; CHD, coronary heart disease; DCM, dilated cardiomyopathy.

Figure 8

Diagnosis distribution of recipients of pediatric heart transplants by geographic location (from the registry of the International Society of Heart and Lung Transplantation. J Heart Lung Transplant 2016;35:1185-95). CAD, coronary artery disease; CHD, coronary heart disease; DCM, dilated cardiomyopathy.

Figure 9

Percent of pediatric heart transplant recipients bridged with mechanical circulatory support by age group and diagnosis January 2009 to June 2016 (from the registry of the International Society of Heart and Lung Transplantation. J Heart Lung Transplant 2017;36:1047-59). CHD, congenital heart disease; DCM, dilated cardiomyopathy; ECMO, extracorporeal membrane oxygenation; TAH, total artificial heart; VAD, ventricular assist device; LVAD, left ventricular assist device; RVAD, right ventricular assist device.

Figure 10

Kaplan-Meier survival in pediatric heart transplant recipients by mechanical circulatory support usage January 2009–June 2014 (from the registry of the International Society of Heart and Lung Transplantation. J Heart Lung Transplant 2016;35:1185-95). CHD, congenital heart disease; DCM, dilated cardiomyopathy; ECMO, extracorporeal membrane oxygenation; TAH, total artificial heart; VAD, ventricular assist device; LVAD, left ventricular assist device; RVAD, right ventricular assist device.

Figure 11

Kaplan-Meier survival curve out to 25 years after pediatric heart transplantation stratified by age at the time of transplantation (from the registry of the International Society of Heart and Lung Transplantation. J Heart Lung Transplant 2017;36:1047-59).

Figure 12

Conditional Kaplan-Meier survival conditional on survival to 1 year after pediatric heart transplant for the most recent era from 2004 through 2014 stratified by age at transplantation (from the registry of the International Society of Heart and Lung Transplantation. J Heart Lung Transplant 2016;35:1185-95).

Figure 13

Kaplan-Meier survival for pediatric heart transplant recipients by diagnosis January 2004–June 2014 (from the registry of the International Society of Heart and Lung Transplantation. J Heart Lung Transplant 2016;35:1185-95). CHD, congenital heart disease; DCM, dilated cardiomyopathy.

Figure 14

Relative incidence of the leading causes of death for the most recent era from 2004 to June 2015 following pediatric heart transplant (from the registry of the International Society of Heart and Lung Transplantation. J Heart Lung Transplant 2016;35:1185-95). CMV, cytomegalovirus.

Figure 15

Summary of maintenance immunosuppression in children at 1 and 5 years after heart transplantation (from the registry of the International Society of Heart and Lung Transplantation. J Heart Lung Transplant 2016;35:1185-95). AZA, azathioprine; MMF, mycophenolate mofetil; MPA, mycophenolic acid.

Figure 16

Kaplan-Meier survival by induction group conditional on survival to 14 days in pediatric heart transplant recipients (from the registry of the International Society of Heart and Lung Transplantation. J Heart Lung Transplant 2016;35:1185-95).

Figure 17

Maintenance immunosuppression at time of transplant hospitalization discharge by era in pediatric heart transplant recipients (from the registry of the International Society of Heart and Lung Transplantation. J Heart Lung Transplant 2016;35:1185-95). MMF, mycophenolate mofetil; MPA, mycophenolic acid.

Figure 18

Maintenance immunosuppression at time of 1- and 5-year follow-up in pediatric heart transplant recipients (from the registry of the International Society of Heart and Lung Transplantation. J Heart Lung Transplant 2016;35:1185-95). MMF, mycophenolate mofetil; MPA, mycophenolic acid.

Figure 19

Percentage of pediatric heart transplant recipients experiencing treated rejection between discharge and 1-year follow-up by era (from the registry of the International Society of Heart and Lung Transplantation. J Heart Lung Transplant 2016;35:1185-95).

Figure 20

Kaplan-Meier survival in pediatric heart transplant recipients based on the presence of rejection within the first year after transplantation (conditional on survival to 1 year) (from the registry of the International Society of Heart and Lung Transplantation. J Heart Lung Transplant 2016;35:1185-95).

Figure 21

Freedom from cardiac allograft vasculopathy (CAV) in pediatric heart transplant recipients (from the registry of the International Society of Heart and Lung Transplantation. J Heart Lung Transplant 2016;35:1185-95).

Figure 22

Freedom from cardiac allograft vasculopathy (CAV) in pediatric heart transplant recipients stratified by age group (from the registry of the International Society of Heart and Lung Transplantation. J Heart Lung Transplant 2016;35:1185-95).

Figure 23

Freedom from cardiac allograft vasculopathy (CAV) in pediatric heart transplant recipients stratified by induction (from the registry of the International Society of Heart and Lung Transplantation. J Heart Lung Transplant 2016;35:1185-95).

Figure 24

Kaplan-Meier survival following diagnosis of cardiac allograft vasculopathy (CAV) in pediatric heart transplant recipients stratified by age group (from the registry of the International Society of Heart and Lung Transplantation. J Heart Lung Transplant 2016;35:1185-95).

Figure 25

Kaplan-Meier survival curves for primary and repeat transplants in pediatric heart transplant recipients (from the registry of the International Society of Heart and Lung Transplantation. J Heart Lung Transplant 2016;35:1185-95).

Figure 26

Kaplan-Meier survival for retransplantation in children by intertransplant interval (from the registry of the International Society of Heart and Lung Transplantation. J Heart Lung Transplant 2016;35:1185-95). Tx, transplantation.

Figure 27

Freedom from severe renal dysfunction by age group in pediatric heart transplant recipients (from the registry of the International Society of Heart and Lung Transplantation. J Heart Lung Transplant 2016;35:1185-95).

Video

Current state of pediatric cardiac transplantation.