Rejection remains an important cause of morbidity and mortality after pediatric heart transplantation (HT). Endomyocardial biopsy (EMB) is the gold standard for rejection diagnosis, but it comes with procedural risk. The frequency of EMB varies significantly across centers. Since April 2018, our center's surveillance EMB schedule is based on a rejection risk prediction score employing age, pre-HT diagnosis, and panel reactive antibodies (PRA). We aimed to evaluate outcomes in the 1st year post-HT before and after risk score implementation.

Patients who underwent HT at our center at ≤ 18 years of age from January 2015 to December 2020 were reviewed. The primary endpoint was rejection-free survival at 1 year-post- HT. Clinical characteristics were compared for patients transplanted in Era 1 (January 2015-April 2018) and Era 2 (April 2018-December 2020). Cumulative 1-year survival free from rejection and from rejection with hemodynamic compromise (RHC) was compared between eras using Kaplan-Meier survival analysis.

115 patients underwent HT during our study period (52 in Era 1 and 63 in Era 2). There was an increase in VAD utilization between eras (19% in Era 1 vs. 40% in Era 2, p = 0.025), but otherwise no significant difference in demographic or clinical variables between the two eras. No statistically significant difference in freedom from rejection or freedom from RHC was identified between the two eras. There was a 60% reduction in the median number of EMB per patient in the first year post-HT after employing the score (5 in Era 1 vs. 2 in Era 2, p < 0.001).

After employing a rejection risk prediction score, our center decreased the frequency of EMB without worsening early post-HT outcomes, thus establishing the clinical applicability of this tool.

Low socioeconomic status (SES) has been associated with higher risk of rejection and graft loss in pediatric heart transplant (HT) recipients. The association of SES with other posttransplant morbidities is unknown.

To assess whether low SES is associated with higher risk of a major adverse transplant event (MATE) among pediatric HT recipients.

Retrospective single-center cohort study at a children's hospital in Boston with consecutive primary HT recipients from 2006 to 2019 and follow-up through 2022. Data were analyzed from June 2023 to March 2024.

Very low or low, moderate, and high or very high Childhood Opportunity Index (COI) for neighborhood (census tract) of patient residence.

Primary outcome was 3-year MATE-6 score assessed in 6-month survivors as cumulative burden of acute cellular rejection, antibody-mediated rejection, coronary vasculopathy, lymphoproliferative disease, kidney dysfunction, and infection, each as an ordinal score from 0 to 4 (24 for death or retransplant). Secondary outcomes were freedom from rejection during first 6 months, freedom from death or retransplant, MATE-3 score for events 1 to 3 (under immune suppression) and events 4 to 6 (chronic immune suppression effects), and each MATE component.

Of 153 children analyzed, the median (IQR) age at HT was 7.2 (1.5-14.8) years, 99 (65%) were male, 16 (10%) were Black, 17 (11%) were Hispanic, and 106 (69%) were White. Fifty patients (33%) lived in very low or low, 17 (11%) in moderate, and 86 (56%) in high or very high COI neighborhoods. There was no significant group difference in mean (SD) 3-year MATE-6 score (very low or low COI, 3.4 [6.5]; moderate COI, 2.4 [6.3]; and high or very high COI, 4.0 [6.9]). Furthermore, there was no group difference in mean (SD) MATE-3 scores for underimmune suppression (very low or low COI, 1.9 [3.5]; moderate COI, 1.2 [3.2]; and high or very high COI, 2.2 [3.6]), chronic immune suppression effects (very low or low COI, 1.6 [3.3]; moderate COI, 1.1 [3.2]; and high or very high COI, 1.8 [3.6]), individual MATE components, rejection during the first 6 months, or death or retransplant.

In this cohort study of pediatric HT recipients, there was no difference in posttransplant outcomes among recipients stratified by SES, a notable improvement from prior studies. These findings may be explained by state-level health reform, standardized posttransplant care, and early awareness of outcome disparities.

Paediatric heart transplant is an established treatment for end stage heart failure in children, however patients have to commit to lifelong medical surveillance and adhere to daily immunosuppressants to minimise the risk of rejection. Compliance with immunosuppressants can be burdensome with their toxic side effects and need for frequent blood monitoring especially in children. Though the incidence of early rejection episodes has significantly improved overtime, the long-term allograft health and survival is determined by Cardiac Allograft Vasculopathy (CAV) which affects a vast number of post-transplant patients. Once CAV has set in, there is no medical or surgical treatment to reverse it and graft survival is significantly compromised across all age groups. Current treatment strategies include novel immunosuppressant agents and drugs to lower blood lipid levels to address the underlying immunological pathophysiology and to manage traditional cardiac risk factors. Translational researchers are seeking novel immunological approaches that can lead to permanent acceptance of the allograft such as using regulatory T cell (Tregs) immunotherapy. Clinical trials in the setting of graft versus host disease, autoimmunity and kidney and liver transplantation using Tregs have shown the feasibility and safety of this strategy. This review will summarise current knowledge of the latest clinical therapies for CAV and pre-clinical evidence in support of Treg therapy for CAV. We will also discuss the different Treg sources and the considerations of translating this into a feasible immunotherapy in clinical practice in the paediatric population.

The late-breaking science presented at the 2023 scientific session of the American Heart Association paves the way for future pragmatic trials and provides meaningful information to guide management strategies in coronary artery disease and heart failure (HF). The dapagliflozin in patient with acute myocardial infarction (DAPA-MI) trial showed that dapagliflozin use among patients with acute MI without a history of diabetes mellitus or chronic HF has better cardiometabolic outcomes compared with placebo, with no difference in cardiovascular outcomes. The MINT trial showed that in patients with acute MI and anemia (Hgb < 10 g/dL), a liberal transfusion goal (Hgb ≥ 10 g/dL) was not superior to a restrictive strategy (Hgb 7-8 g/dL) with respect to 30-day all-cause death and recurrent MI. The ORBITA-2 trial showed that among patients with stable angina and coronary stenoses causing ischemia on little or no antianginal therapy, percutaneous coronary intervention results in greater improvements in anginal frequency and exercise times compared with a sham procedure. The ARIES-HM3 trial showed that in patients with advanced HF who received a HeartMate 3 levitated left ventricular assist device and were anticoagulated with a vitamin K antagonist, placebo was noninferior to daily aspirin with respect to the composite endpoint of bleeding and thrombotic events at 1 year. The TEAMMATE trial showed that everolimus with low-dose tacrolimus is safe in children and young adults when given ≥ 6 months after cardiac transplantation. Providing patients being treated for HF with reduced ejection fraction (HFrEF) with specific out-of-pocket (OOP) costs for multiple medication options at the time of the clinical encounter may reduce 'contingency planning' and increase the extent to which patients are taking the medications decided upon. The primary outcome, which was cost-informed decision-making, defined as the clinician or patient mentioning costs of HFrEF medication, occurred in 49% of encounters with the checklist only control group compared with 68% of encounters in the OOP cost group.

There are limited data evaluating the success of a structured transition plan specifically for pediatric heart transplant (HT) recipients following their transfer of care to an adult specialist. We sought to identify risk factors for poor adherence, graft failure, and mortality following the transfer of care to adult HT care teams.

We retrospectively reviewed all patients who underwent transition from the pediatric to adult HT program at our center between January 2011 and June 2021. Demographic characteristics, comorbid conditions, and psychosocial history were collected at the time of HT, the time of transition, and the most recent follow-up. Adverse events including mortality, graft rejection, infection, and renal function were also captured before and after the transition.

Seventy-two patients were identified (54.1% male, 54.2% Caucasian). Mean age at the time of transition was 23 years after a median of 11.6 years in the pediatric program. The use of calcineurin inhibitors was associated with reduced mortality (HR .04, 95% CI .0-.6, p = .015), while prior psychiatric hospitalization (HR 45.3, 95% CI, 6.144-333.9, p = .0001) was associated with increased mortality following transition. Medication nonadherence and young age at the time of transition were markers for high-risk individuals prior to the transition of care.

Transition of HT recipients from a pediatric program to an adult program occurs during a vulnerable time of emerging adulthood, and we have identified risk factors for mortality following transition. Development of a formalized transition plan with a large multidisciplinary team with focused attention on high-risk patients, including those with psychiatric comorbidities, may favorably influence outcomes.

In the 1980s, heart transplantation was the first successful treatment for infants born with hypoplastic left heart syndrome. Infants who have required heart transplantation benefit from immunologic "advantages," including long-term survival free from cardiac allograft vasculopathy. Currently ∼ 90% of children undergoing a heart transplant are reaching their first-year anniversary and the clinical practices of paediatric heart transplantation have dramatically improved. These successes are largely attributed to research sponsored by the Pediatric Heart Transplant Study Group, the International Society of Heart and Lung Transplantation and, more recently, the Non-profits Enduring Hearts and Additional Ventures. Despite these successes, the field is challenged to increase progress to achieve long-term survival into adulthood. The wait-list mortality, especially among infants, is unacceptably high often leading to palliative measures that can increase post-transplant mortality. Cardiac allograft vasculopathy remains a major cause for progressive graft loss of function and sudden death. The relative tolerance seen in immature recipients has not been translated to modifying older recipients' post-transplant outcomes. The modifiable cause(s) for the increased risks of transplantation in children of different ethnicities and races require definition. Addressing these challenges faces the reality that for-profit research favours funding adult recipients, with ∼ 10-fold greater numbers, and their more modest longevity goals. Advocacy for funding "incentives" such as the Orphan Drug rules in the United States and upholding principles of equity and inclusion are critical to addressing the challenges of paediatric heart transplant recipients worldwide.