The first pediatric heart transplant (HTx) was performed by Adrian Kantrowitz at Maimonides Medical Center in Brooklyn, New York, on December 6, 1967 (Fig. 24.1). This was the first human HTx in the United States and followed the first-ever human HTx in only 3 days. The recipient was an 18-day-old male with Ebstein’s

Congenital heart disease remains a common pre-operative diagnosis in the pediatric HTx pop­ulation in the United States. It is the most com­mon indication for transplantation during infancy (Fig. 24.4) [11]. However, cardiac transplanta­tion as a primary therapy is becoming increas­ingly rare with advances and improved outcomes following palliative or corrective surgery. Instead, children are being referred, evaluated, and subsequently listed for end-stage cardiac disease and refractory heart failure without avail­able medical or surgical options. The most com­mon forms of congenital heart disease listed for transplantation are non-HLHS single-ventricle abnormalities (36%), followed by conditions in which the right ventricle functions as the sys­temic pump (20%) [10]. The failing Fontan population is another subset that is referred for transplantation. Primary cardiac transplantation is selectively recommended for severe systemic ventricular dysfunction, severe atrioventricu­lar valve insufficiency, and occlusive coronary artery anomalies, particularly in those patients with pulmonary atresia with an intact ventricular septum. Notably, compared to survival follow­ing transplantation for cardiomyopathy, survival following transplantation for complex congenital heart disease is significantly lower [8].

4 and 5). This chapter will examine consid-

The shortage of donors in the infant population led to ABO-incompatible (ABOi) transplan­tation on the basis that the immune system is underdeveloped in this age group. Infants with isohemagglutinin titers that show absent or low levels of antibodies can receive a heart from an ABOi donor with results comparable to ABO­compatible HTx [14]. Most recipients do not go on to form antibodies later in life despite no enhancements to their immunosuppressive therapy [15]. It has also been observed that post­HTx, these recipients were less likely to develop de novo donor-specific antibodies (particu­larly class II) or acute rejection [16, 17]. Even recipients who do form antibodies still have good outcomes [15]. In 2016 urgent candidates under one year of age were made eligible to be listed for ABOi donors regardless of the isohe­magglutinin titer. In addition, patients between one and two years of age with isohemagglutinin titers less than or equal to 1:16 could be listed for these donors [18]. More recently, in March of 2023, the UNOS policy changed once again. At this time, patients who were status 1a, 1B, or 2 and under the age of 18 years could be listed for ABOi. More recently, older children have been successfully ABOi transplanted [19] All­cause mortality has been noted to be equivalent between ABO compatible and ABOi. One-, 5-, and 10-year survival rates among compatible vs.

Sensitivity to human leukocyte antigen (HLA) and non-HLA donor antigens remains a signifi­cant factor in the already high waitlist mortal­ity for children awaiting HTx. The presence of donor-specific antibodies (DSAs) carries the risk of allograft rejection and/or cardiac allo­graft vasculopathy (CAV) [20]. Sensitization can occur from blood products (especially plate­lets), palliative procedures for congenital heart disease, prior HTx, and the use of mechanical circulatory support devices (MCS) devices. It has also been suggested that preoperative treat­ment of allograft tissue used in congenital heart surgeries could prevent profound sensitiza­tion in patients requiring subsequent HTx [21]. Potential recipients are tested for panel reactive antibodies (PRA). Testing demonstrates pre­formed anti-HLA antibodies. Most centers now use Luminex® solid phase flow beads to detect alloantibodies. Patients with a PRA > 10% are considered sensitized and are at increased risk of graft loss [22]. However, data from the Clinical Trials in Organ Transplant-04 (CTOTC-04) sug­gest comparable 1-year survival among highly sensitized and non-sensitized pediatric HTx recipients [23]. Many centers perform HLA typ­ing so that “virtual” cross-matching can be done once a potential donor is found. In an analysis of the 3914 patients enrolled in the Pediatric Heart Transplant Society Registry database for the years 2010–2021, a shorter time to first rejection was observed in patients with positive crossmatch compared to those with negative crossmatch with no between-group difference in 10 years mortality [24]. Moreover, clinicians should take into consideration that HLA anti­bodies may be high in the first 12–18 months after birth (passively acquired maternally) or be falsely low such as in pediatric patients fol­lowing Fontan surgery who have protein-losing

The number and quality of donor hearts remain significant limiting factors in pediatric HTx. An ISHLT consensus statement noted that potential HTx recipients outnumber the num­ber of donors, and there continues to be sig­nificant waitlist mortality. In spite of this, approximately 40% of organ offers are turned down [34]. Common reasons for declining an organ included the prolonged use of cardiopul­monary resuscitation (CPR), the use of high­dose inotropes, blunt trauma to the chest wall, and prolonged ischemia time [35]. Also, donor size, donor age, cause of death, need for high­dose inotropes, and infection were reasons for declining a potential donor organ [34]. The lack of studies means clinicians rely on experience or data from the adult population. As a result, the donor pool may be unnecessarily narrow. Until recently, vital organ donation from children could only occur after a diagnosis of brain death has been established. There are also additional criteria that vary according to age [36]. In addi­tion, an interval of between 12 and 48 h between two evaluations is required [36]. More recently, in response to a shortage of suitable donors, DCD has become an option for more centers. A review of the UNOS registry from June 2004 to June 2022 demonstrated seven children (<18 y.o.) who underwent HTx from a DCD donor [37]. Donor evaluation should include gender, age, weight, height, the cause of death, a review of any chest trauma, inotrope use, and hemody­namic status. Donor hearts have been declined in the past because of CPR use, but it has been shown to have no impact on outcomes [38]. Survival outcomes were not impacted by factors such as donor cause of death, need for CPR or inotropes [39]. Allograft ischemic time is a risk factor for survival in older children, particularly those 11–17 years old, and has almost no impact on the survival of infants < 1 year old. Longer ischemic times did not have an effect on over­all recipient survival however it did negatively impact one year survival [39]. An echocardio­gram should be done to exclude structural and

dren but is still 30% in the infant age group [3]. Biventricular VAD use now exceeds ECMO use [3]. Transplantation or recovery occurred in 75% of children with the EXCOR®. Mortality was 25% and the leading cause of death was thromboembolic stroke [51]. Decreased renal function, smaller patient size and elevated total bilirubin were additional risk factors for death when on EXOR® VAD therapy [51].

Early extubation should be attempted where possible. Some recipients may have had mechanical ventilation for a prolonged period of time prior to transplantation. These patients need to retrain their respiratory muscles and will require additional support. Pulmonary