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The Journal of Heart and Lung Transplantation
International Society for Heart and Lung Transplantation.

Atypical Infiltrates on Endomyocardial Biopsy are Associated with Adverse Outcomes in Pediatric Heart Transplantation

      Purpose

      The significance of atypical infiltrates, defined as eosinophils or plasma cells on endomyocardial biopsy (EMB) after pediatric heart transplant (HTx) is not known. We hypothesized that atypical infiltrates are associated with worse post-HTx outcomes.

      Methods

      We performed a retrospective cohort study of 96 consecutive patients aged <18 years who underwent primary HTx from 2013 to 2017. Patients who underwent heart re-transplant or multi-organ transplant were excluded. The number of EMBs with atypical infiltrates and burden of atypical infiltrates (rare vs predominant on pathologist review) were recorded. Primary outcome was a composite of cardiac allograft vasculopathy, graft failure (defined as re-listing or re-transplant), or death. Groups were compared using Cox regression with time-dependent covariates and mixed effects logistic regression accounting for repeated measures.

      Results

      Atypical infiltrates were seen in 27/96 patients (28%). The presence of atypical infiltrates on EMB was associated with higher likelihood of reaching the composite outcome compared to no atypical infiltrates (HR 5.82, 95% CI 2.5-13.6, p<0.001). This finding persisted when accounting for rejection. Two or more EMBs with atypical infiltrates were associated with greater risk of composite outcome compared to no atypical infiltrates (HR 10.5, 95% CI 2.86-38.5, p=0.001), as was having atypical infiltrates as the predominant feature on EMB (HR 19.1, 95% CI 6.51-56.0, p<0.001). Patients with atypical infiltrates by their 1-year post-transplant biopsy had survival free of primary outcome of 48% at 5 years, compared to 90% if no atypical infiltrates had been seen by the 1-year post-transplant biopsy (log rank = 0.002, Figure).

      Conclusion

      Atypical infiltrates on EMB are associated with poor outcomes following HTx. The risk is higher with increasing frequency and greater extent of atypical infiltrates. Patients with atypical infiltrates are an at-risk population that require close follow up.