Impact of routine surveillance biopsy intensity on the diagnosis of moderate to severe cellular rejection and survival after pediatric heart transplantation

Abstract

Data are lacking on RSB intensity and outcomes after pediatric heart transplantation. PHTS centers received a survey on RSB practices from 2005 to present. PHTS data were obtained for 2010-2013 and integrated with center-matched survey responses for analysis. Survey response rate was 82.6% (38/46). Centers were classified as low-, moderate-, and high-intensity programs based on RSB frequency (0-more than 8 RSB/y). RSB intensity decreased with increasing time from HT. Age at HT impacted RSB intensity mostly in year 1, with little to no impact in later years. Most centers have not replaced RSB with non-invasive methods, but many added ECHO and biomarker monitoring. Higher RSB intensity was not associated with decreased 4-year mortality (P=.63) or earlier detection of moderate to severe (ISHLT grade 2R/3R) cellular rejection (RSBMSR) in the first year (P=.87). First-year RSBMSR incidence did not differ with intensity or age at HT. Significant variability exists in RSB intensity, but with no impact on timing and incidence of RSBMSR or 4-year mortality. Reduction in RSB frequency may be safe in certain patients after pediatric HT.

Early findings after integration of donor‐derived cell‐free DNA into clinical care following pediatric heart transplantation

“…1 After the first post-HT year, surveillance EMB is also common with 83% of responding PHTS member-centers performing ≥4 surveillance EMB per year between years 2-5 and 70% performing at least annual surveillance EMB beyond 5 years after HT. 2 Before the integration of dd-cfDNA alternative surveillance assessments, we mandated annual surveillance RHC/EMB ad infinitum, starting 2 years after HT and pairing this with surveillance coronary angiography biennially. This reliance on surveillance EMB, particularly late after HT, can rightfully be criticized as unnecessary.…”

“…Primarily, we used dd-cfDNA with the intent to supplant "per-protocol" surveillance RHC and EMB when the dd-cfDNA result was not elevated. Per this alternative surveillance assessment, we stipulated patients: (1) were at least 12 months post-HT (later lowered to ≥7 months), (2) were well by history and clinical examination, (3) had stable echocardiogram findings, and (4) had no AR on the most recent prior two EMBs. We defined AR as AMR grades pAMR1h, 2, or 3 and/or ACR grade 1B or higher according to the 1990 International Society for Heart and Lung Transplantation grading scheme.…”

“…Surveillance EMB remains a core element of posttransplant care in many pediatric centers, including late after HT. 1,2 However, EMB is costly, invasive, and a source of distress for pediatric HT recipients [3][4][5] ; it is also of relatively low yield late after transplantation. [6][7][8][9][10] These factors have prompted multiple attempts to identify less invasive alternatives to allograft surveillance for AR.…”

Out‐of‐pocket expenses associated with pediatric heart transplantation

“…While the frequency of for‐cause endomyocardial biopsies is unlikely to be directly modifiable, there is enormous variability across centers in the frequency of surveillance endomyocardial biopsies 11,12 . Published data suggest that similar outcomes can be achieved with both invasive and non‐invasive surveillance approaches in pediatric heart transplant recipients 11,13,14 . Therefore, it may be feasible to safely reduce the number of surveillance endomyocardial biopsies.…”

“To biopsy, or not to biopsy”? That is the clinical conundrum

“…Since these cases are elective and likely scheduled surveillance, the question for the practitioner is can non‐invasive markers for rejection largely replace the need for a scheduled surveillance biopsy? Is there precedence in centers performing less surveillance biopsies without inferior outcomes? 2,3 And if the patient has no findings to suggest rejection, not admitted, or the biopsy is not deemed “urgent”, would the practitioner treat for rejection if the histology meets certain pre‐specified pathological criteria? Albeit low, based on the reaffirmed serious complication frequency reported in the study, the practitioner should be prepared to answer these questions before subjecting a patient to biopsy.…”