Practice variation in the diagnosis of acute rejection among pediatric heart transplant centers: An analysis of the pediatric heart transplant society (PHTS) registry

https://doi.org/10.1016/j.healun.2021.08.002Get rights and content

Background

Freedom from rejection in pediatric heart transplant recipients is highly variable across centers. This study aimed to assess the center variation in methods used to diagnose rejection in the first-year post-transplant and determine the impact of this variation on patient outcomes.

Methods

The PHTS registry was queried for all rejection episodes in the first-year post-transplant (2010-2019). The primary method for rejection diagnosis was determined for each event as surveillance biopsy, echo diagnosis, or clinical. The percentage of first-year rejection events diagnosed by surveillance biopsy was used to approximate the surveillance strategy across centers. Methods of rejection diagnosis were described and patient outcomes were assessed based on surveillance biopsy utilization among centers.

Results

A total of 3985 patients from 56 centers were included. Of this group, 873 (22%) developed rejection within the first-year post-transplant. Surveillance biopsy was the most common method of rejection diagnosis (71.7%), but practices were highly variable across centers. The majority (73.6%) of first rejection events occurred within 3-months of transplantation. Diagnosis modality in the first-year was not independently associated with freedom from rejection, freedom from rejection with hemodynamic compromise, or overall graft survival.

Conclusions

Rejection in the first-year after pediatric heart transplant occurs in 22% of patients and most commonly in the first 3 months post-transplant. Significant variation exists across centers in the methods used to diagnose rejection in pediatric heart transplant recipients, however, these variable strategies are not independently associated with freedom from rejection, rejection with hemodynamic compromise, or overall graft survival.

Section snippets

Methods

This study utilized data from the Pediatric Heart Transplant Society (PHTS), a multi-center, event-driven database of pediatric heart transplant candidates and recipients. Details of PHTS organization and data collection have been previously described (Participating centers are listed in Supplemental Table 1).13 All participating centers are required to maintain institutional review board approval to participate in PHTS and confirmation of institutional review board approval for each

Patient characteristics

A total of 3,985 patients were identified from 56 different centers for inclusion in the analysis. Of the included patients, 873 (21.9%) experienced acute rejection within the first-year post-transplant.

Variability in timing and diagnosis of first rejection

There was significant variability across centers in the freedom from rejection in the first-year post-transplant (Figure 2). A total of 16 (1.8%) rejection events could not be categorized as SBx, echocardiographic, or clinical diagnosis based on the available data (Supplemental Table 2). Of the

Discussion

This analysis provides novel data on the variation in methods used to diagnose rejection across pediatric heart transplant centers. The majority of first-year rejection episodes are diagnosed by SBx and are most common during the first three-months following transplant. Despite considerable variation across centers in overall freedom from rejection and in the methods used to diagnose rejection, we found no difference in freedom from rejection, freedom from rejection with hemodynamic compromise,

Limitations

Our analysis has inherent limitations. Rejection within the PHTS database is defined based on augmentation of immunosuppression. Therefore, we are unable to account for varying thresholds for the treatment of rejection and there are a number of rejection events in our analysis that either did not undergo biopsy or were associated with low-grade histologic rejection. However, detailed information regarding the timing of biopsy in relation to rejection therapies is unavailable in the PHTS

Conclusions

There is significant variation in the methods used to diagnose rejection across pediatric heart transplant centers in the first-year post-transplant. The majority of acute rejection episodes occur within the first 3 months post-transplant and are diagnosed using SBx. There are significant differences in overall freedom from rejection across centers, but varying methods of rejection diagnosis do not appear to contribute significantly to this finding. Minimizing practice variation and creation of

Author contributions

Project conceptualization, data analysis, manuscript preparation: J. Godown, D. Hsu, J. Kirklin, R. Cantor, D. Koehl, E. Cummings, J. Vo.

Participation in working group meeting, critical review and revision of manuscript, acceptance of final submitted version: All authors

Disclosure statement

Dr. Kirklin receives partial salary support from the Society of Thoracic Surgeons. None of the other authors have a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript or other conflicts of interest to disclose.

Funding: none

Acknowledgments

None

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