Rejection surveillance in pediatric heart transplant recipients: Critical reflection on the role of frequent and long‐term routine surveillance endomyocardial biopsies and comprehensive review of non‐invasive rejection screening tools

Abstract

Background Despite significant medical advances in the field of pediatric heart transplantation (HT), acute rejection remains an important cause of morbidity and mortality. Endomyocardial biopsy (EMB) remains the gold‐standard method for diagnosing rejection but is an invasive, expensive, and stressful process. Given the potential adverse consequences of rejection, routine post‐transplant rejection surveillance protocols incorporating EMB are widely employed to detect asymptomatic rejection. Each center employs their own specific routine rejection surveillance protocol, with no consensus on the optimal approach and with high inter‐center variability. The utility of high‐frequency and long‐term routine surveillance biopsies (RSB) in pediatric HT has been called into question. Methods Sources for this comprehensive review were primarily identified through searches in biomedical databases including MEDLINE and Embase. Results The available literature suggests that the diagnostic yield of RSB is low beyond the first year post‐HT and that a reduction in RSB intensity from high‐frequency to low‐frequency can be done safely with no impact on early and mid‐term survival. Though there are emerging non‐invasive methods of detecting asymptomatic rejection, the evidence is not yet strong enough for any test to replace EMB. Conclusion Overall, pediatric HT centers in North America should likely be doing fewer RSB than are currently performed. Risk factors for rejection should be considered when designing the optimal rejection surveillance strategy. Noninvasive testing including emerging biomarkers may have a complementary role to aid in safely reducing the need for RSB.

Elective and non‐elective endomyocardial biopsy in heart transplant patients and procedural outcomes: An IMPACT registry analysis

“…There is some variation in center practices around how frequently biopsies are performed by year post transplant, especially in younger children. 6 Beyond surveillance, biopsies are also performed for clinical suspicion for rejection to diagnose rejection type and grade. Biopsies are further used for post-treatment monitoring to document resolution and response.…”

“…Cardiac catheterization and endomyocardial biopsies are hence performed as a part of routine surveillance. There is some variation in center practices around how frequently biopsies are performed by year post transplant, especially in younger children 6 . Beyond surveillance, biopsies are also performed for clinical suspicion for rejection to diagnose rejection type and grade.…”

Pulmonary hemodynamics before and after pediatric heart transplantation

“…Azeka Even though more subtle techniques including echocardiography, emerging biomarkers, and cardiac magnetic resonance imaging gain importance, routine surveillance biopsies remain the gold standard in detecting rejection. 49 Nevertheless, routine surveillance biopsies after more than 2-3 years are controversial, as studies show a significant decrease in the positivity rate of biopsies. 50 We cannot confirm these findings as the positivity rate of surveillance biopsies before or after 3 years stayed stable in our cohort.…”

Pediatric heart transplantation: Looking forward after five decades of learning

“…The immune cell function assay ImmuKnow® has limited available pediatric data and has not been found to be predictive of rejection. The data in pediatric heart transplant patients for the gene expression profiling test, AlloMap®, are sparse and not yet an alternative in the pediatric age group 83 . The same can be said for Molecular Microscope Diagnostic System (MMDx®) which analyzes RNA transcripts from endomyocardial biopsies to differentiate quiescent tissue from rejection, with abstracts reported from exploratory single‐center experience 84,85 .…”