MINI REVIEW article

Front. Transplant.

Sec. Transplantation Immunology

Volume 4 - 2025 | doi: 10.3389/frtra.2025.1623514

This article is part of the Research TopicPost-Transplant Monitoring for Allograft RejectionView all 3 articles

Diagnostic Approach to Elevated dd-cfDNA with Reassuring EMB in Heart Transplantation

Provisionally accepted
  • Inova Fairfax Hospital, Falls Church, United States

The final, formatted version of the article will be published soon.

Despite significant advances in organ preservation, surgical techniques, and immunosuppressive regimens, rejection continues to pose a major challenge in the care of heart transplant patients. Endomyocardial biopsy (EMB) remains the gold standard test for surveillance and diagnosis of rejection, but is limited by its invasiveness, interobserver variability, procedural risk, and cost thus prompting the widespread use of non-invasive biomarkers such as donorderived cell-free DNA (dd-cfDNA). Due to its high negative predictive value, dd-cfDNA is often routinely used for surveillance of asymptomatic patients. However, it is a non-specific marker of allograft injury and elevated levels in the presence of a reassuring EMB creates a diagnostic dilemma. This review explores the pathophysiological basis and clinical utility of dd-cfDNA in monitoring of heart transplant recipients with particular focus on evaluation and management of discordant findings.

Keywords: biomarkers, Transplantation, rejection, Monitoring, donor-specific antibodies, cell-free DNA, Gene Expression

Received: 06 May 2025; Accepted: 07 Jul 2025.

Copyright: © 2025 Bahniwal, Mehta and Kennedy. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Jamie L.W. Kennedy, Inova Fairfax Hospital, Falls Church, United States

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.