Impact of High- vs. Low-Frequency Surveillance Endomyocardial Biopsy Strategy in Pediatric Heart Transplantation

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Routine surveillance biopsy (RSB) is performed to monitor for asymptomatic acute rejection (AR) after heart transplantation (HT). The optimal frequency of RSB in pediatrics is unknown and variation in RSB frequency is high. We hypothesized that higher frequency RSB centers have increased rates of AR and resource utilization, but no difference in graft survival. We utilized a linked database (2002-2016) between Pediatric Health Information System (PHIS) and Scientific Registry of Transplant Recipients (SRTR). We designated centers as high- and low-RSB based on the observed median number of first-year biopsies (from procedural ICD and CPT coding) in recipients assumed to be standard risk: greater than 1 year old without rejection in their first year. The highest tertile of centers were classified as high-RSB and compared to the lowest two-thirds (low-RSB). We then compared outcomes amongst all primary recipients aged 0-21 by center type. Outcomes were HT admission length of stay (LOS), incidence of AR at one year, graft survival, estimated HT admission cost, and total cost in the first year. Regression analysis was used to adjust for potential confounders. We compared 834 patients at 10 high-RSB centers to 2,033 patients at 19 low-RSB centers. Baseline characteristics were similar except high-RSB center recipients had increased use of ventilator or ECMO at HT (23 vs 18%, p=0.039), fewer hispanic/asian/other race (20 vs 24% p=0.005), fewer positive crossmatch (13% vs 17% p=0.007). High-RSB centers had higher first-year incidence of all AR vs low-RSBs (36% vs 29%, p=0.001; OR 1.52 [95% CI 1.24-1.85] p<0.001), but no difference in treated AR (26% vs 24%, p=0.458) or graft survival (adjusted HR 0.96 [95% CI 0.81-1.14] p=0.618; median follow-up 3.9 years). High-RSB centers had longer LOS (median 22 vs 17 days p<0.001), higher median HT admission cost ($349,813 vs $296,511, p<0.001), and first-year total cost of care ($450,708 vs $342,170 p<0.001). Centers with a high-frequency biopsy strategy during the first year diagnose AR more often during the first year after HT but have similar incidence of treated rejection. Early graft survival is unchanged. A low-frequency biopsy strategy is associated with lower cost. To determine the optimal biopsy frequency additional data are needed on long-term graft survival and graft performance.