At the intersection of endomyocardial biopsy and dd-cfDNA, where do we go?

Gregory A Fishbein1, Marc K Halushka2

  • 1Pathology and Laboratory Medicine, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA.

Insights

Cardiac allograft rejection is monitored using endomyocardial biopsy (EMB) and donor-derived cell-free DNA (dd-cfDNA) blood tests. This review explores why these methods sometimes disagree and how to improve their alignment for better patient care.

Area of Science:

  • Cardiology
  • Transplant Medicine
  • Molecular Diagnostics

Background:

  • Endomyocardial biopsy (EMB) is the traditional standard for diagnosing cardiac allograft rejection.
  • Blood-based donor-derived cell-free DNA (dd-cfDNA) assays are emerging as a less invasive alternative.
  • Increasing reports indicate discordance between EMB findings and dd-cfDNA levels.

Purpose of the Study:

  • To review current data on the comparison between EMB and dd-cfDNA in assessing cardiac allograft rejection.
  • To investigate the underlying reasons for discrepancies observed between these diagnostic methods.
  • To propose strategies for harmonizing the interpretation and application of EMB and dd-cfDNA.

Main Methods:

  • Literature review of recent studies comparing EMB and dd-cfDNA.
  • Analysis of potential biological and technical factors contributing to discordance.
  • Synthesis of findings to recommend alignment strategies.

Main Results:

  • Discordance between EMB and dd-cfDNA is a recognized clinical challenge.
  • Factors influencing disagreement include rejection severity, timing of sampling, and assay variability.
  • Alignment requires understanding the specific context of each test's performance.

Conclusions:

  • Improved understanding of discordance is crucial for optimizing non-invasive monitoring.
  • Developing standardized protocols for dd-cfDNA testing can enhance its reliability.
  • Integrated approaches combining EMB and dd-cfDNA may offer superior diagnostic accuracy and patient management.