The adequacy of graft size is one of the most critical factors when considering a cardiac organ offer, with weight being the most commonly used metric for donor-recipient adjustment. However, studies assessing the impact of weight mismatch on survival have yielded inconsistent results, likely due to the erroneous assumption of a linear correlation with heart size, neglecting other factors. While virtual adjustment using imaging would be ideal, it is rarely feasible in clinical practice due to limited donor imaging availability and the time constraints for accepting offers. To address these limitations, predictive models based on cardiac MRI and/or CT imaging of healthy subjects have been developed in recent years. These models estimate heart size in terms of mass (Predicted Heart Mass, PHM) or volume (Total Cardiac Volume, TCV), incorporating variables such as sex, age, weight, and height. This commentary reviews an article comparing various methods for assessing donor-recipient size mismatch, including these predictive models, in pediatric populations.

This retrospective study uses data from the Pediatric Heart Transplant Society international registry, encompassing over 50 pediatric transplant centers. It includes all pediatric heart transplants (recipient age <18 years) performed between January 1993 and December 2021. Donor and recipient variables were collected to assess mismatch based on weight, height, BMI, body surface area (BSA), PHM, and TCV; the latter two parameters were calculated using published formulas. Cox regression analysis was employed to determine whether mismatch, calculated by each metric, was an independent risk factor for graft loss (death/retransplantation) at 1 and 5 years, adjusting for other risk factors identified in the literature. For significant variables, post-transplant morbidity was assessed by analyzing freedom from rejection and hemodynamically significant rejection at 1 year and graft vasculopathy at 1 and 5 years using the Kaplan-Meier method.

A total of 7,715 donor-recipient pairs were analyzed. Adequate matching (donor/recipient ratio between –20% and +20%) was achieved in 36% of pairs based on weight, 39% on PHM, 50% on BSA, 57% on BMI, 71% on height, and 93% on TCV. Violin plots showed that TCV exhibited greater symmetry and fewer outliers compared to other metrics. Among all mismatch metrics, only height and TCV were independent predictors of graft survival in the adjusted analysis. Both undersized and oversized donors by height were associated with increased graft loss at 1 and 5 years, with a greater effect observed in undersized donors. For TCV, minimally undersized donors (donor/recipient ratio up to –20%) were associated with reduced graft loss, whereas oversized donors up to 25% had no impact on survival. Post-transplant morbidity analysis revealed that recipients of moderately undersized donors by height (donor/recipient ratio <–30%) experienced higher rates of early rejection (p < .0001), with no significant differences observed for hemodynamically significant rejection or graft vasculopathy. No significant differences were found in post-transplant morbidity based on TCV mismatch for any evaluated events.

COMMENTARY

The current shortage of organs for transplantation, especially pronounced in the pediatric population, drives the need for strategies to maximize donor utilization. Identifying a parameter for assessing donor-recipient mismatch that has prognostic implications and avoids discarding potentially suitable hearts based solely on weight mismatch is particularly appealing. This is the main interest of the reviewed article, which is the first to compare different metrics, including TCV and PHM, in children.

A notable finding of the study is the variability in adequate donor-recipient matching percentages depending on the method used, with marked differences such as 93% for TCV versus only 36% for weight. This supports growing evidence that weight, as an isolated measure, likely overestimates mismatch.

Since height and TCV were the only metrics impacting survival, the authors concluded that TCV appears to be the best donor-recipient adjustment measure, citing its symmetrical distribution in violin plots and its direct representation of heart size. However, the model used to calculate TCV was developed by Plasencia et al. in a single-center study of 90 patients, warranting caution until the model or alternatives are validated in larger populations.

Interestingly, PHM mismatch did not independently predict graft loss, as shown in adult studies. This may be due, as the authors acknowledge, to the pediatric PHM model being developed with only 50 subjects (compared to 5,098 for left ventricular mass and 4,204 for right ventricular mass in adult models), making it less robust. Another limitation is the lack of adjusted analysis in post-transplant morbidity evaluation, which showed higher rejection rates in moderately undersized donors by height, likely influenced by other factors such as less frequent induction immunosuppression in this group. Additionally, morbidity outcomes chosen for the study were not primarily related to heart size, whereas primary graft dysfunction—known to correlate with undersized donors in adults—was not analyzed.

Overall, this article underscores the need for a better parameter than weight to assess donor-recipient mismatch in pediatric heart transplantation, to standardize practices across centers and maximize organ utilization. Future directions may involve more direct measures of heart size, either by improving access to donor imaging and streamlining virtual adjustment processes or by refining predictive models for TCV or PHM. In the interim, based on the present study’s findings, height could at least be considered as an additional mismatch measure, especially avoiding undersized donors due to their greater impact on survival.

REFERENCE:

Amdani S, Aljohani OA, Kirklin JK, Cantor R, Koehl D, Schumacher K, et al. Assessing Donor-Recipient Size Mismatch in Pediatric Heart Transplantation: Lessons Learned From Over 7,500 Transplants. JACC Heart Fail. 2023 Aug 21:S2213-1779(23)00391-8. doi: 10.1016/j.jchf.2023.07.005.