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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.
Abstract:
Cardiac allograft rejection has traditionally been assessed by endomyocardial biopsy (EMB). Blood-based assays such as donor-derived cell-free DNA (dd-cfDNA) are increasingly used, yet emerging data highlight discordance between these approaches. This review evaluates recent data, examines causes of disagreement, and suggests strategies to better align EMB and dd-cfDNA.

