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.

Keywords: heart transplant; pediatric; rejection; surveillance.