Multi-center study of CMR versus cardiac catheterization with endomyocardial biopsy for pediatric transplant surveillance: study protocol.

Abstract

Notwithstanding advances in post-transplant care, acute allograft rejection (AR) remains the leading cause of mortality in pediatric heart transplant recipients (PHTX). Endomyocardial biopsy (EMB) continues to be the standard of care for AR detection, despite being invasive, costly, and associated with patient discomfort and potential complications. Non-invasive alternatives, including cardiac magnetic resonance imaging (CMR) with T1 and T2 parametric mapping and blood biomarkers (BB) such as cell-free DNA (cfDNA) and microRNA (miRNA), have shown promise in the adult transplant population, but their validation in the pediatric transplant population is lacking. The "Predictive Modeling of Acute Rejection in Pediatric Heart Transplant Recipients" (PEACE) study is a prospective, multicenter trial aiming to assess the diagnostic accuracy of CMR and BB in comparison to EMB. The goal of this manuscript is to describe the purpose and experimental protocol of the PEACE study. The PEACE study's overarching hypothesis is that CMR and BB can consistently and accurately detect myocardial abnormalities, potentially guiding the need for EMB. Secondary objectives include cost-analyses of CMR and BB, as well as a biomarker performance evaluation in biopsy-negative, but symptomatic and suspected AR cases. PEACE will enroll PHTX ages 6-25 years, across approximately 20 U.S. pediatric hospitals. All subjects will undergo EMB for surveillance or suspected AR as standard of care. As part of the research protocol, subjects will undergo blood collection for BB prior to the EMB and CMR within 5 days of EMB. Central core labs will conduct blinded analysis for imaging, pathology, and biomarkers to ensure consistent data interpretation. PEACE represents a critical step in reducing reliance on invasive biopsies in the clinical care of PHTX. By validating non-invasive tools in a large, diverse population, the PEACE study could transform AR detection, resulting in improvement of the patient experience and outcomes in this vulnerable population. (Trial Registration: ClinicalTrials.gov Identifier: NCT07770659, Non-invasive Prediction of EArly Cardiac rEjection (PEACE)).