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. 2025 Apr 1;13(4):841.
doi: 10.3390/biomedicines13040841.

Donor-Derived Cell-Free DNA Versus Left Ventricular Longitudinal Strain and Strain-Derived Myocardial Work Indices for Identification of Heart Transplant Injury

Timea Teszak  1 , Timea Barcziova  1 , Csaba Bödör  2 , Lajos Hegyi  2 , Luca Levay  2 , Beata Nagy  2 , Attila Fintha  2 , Adam Szijarto  1 , Attila Kovacs  1   3 , Bela Merkely  1 , Balazs Sax  1
Affiliations

Donor-Derived Cell-Free DNA Versus Left Ventricular Longitudinal Strain and Strain-Derived Myocardial Work Indices for Identification of Heart Transplant Injury

Timea Teszak et al. Biomedicines. .

Abstract

Background/Objectives: Donor-derived cell-free DNA (dd-cfDNA) is a marker of graft injury that increases in acute rejection and has excellent negative predictive value. Left ventricular global longitudinal strain (LVGLS) and strain-derived myocardial work indices are novel echocardiographic parameters with growing applications. Still, they have been poorly investigated in heart transplant (HTx) recipients so far. We sought to examine the diagnostic impact of left ventricular longitudinal strain-derived indices in diagnosing myocardial injury as assessed by dd-cfDNA after HTx. Methods: Since October 2022, HTx recipients have been shifted from our endomyocardial biopsy (EMB)-based rejection surveillance protocol to a monthly dd-cfDNA-led rejection assessment. We analysed the percentage of donor-derived to total cell-free DNA. For echocardiographic analysis, patient selection was restricted to those transplanted ≥ 6 months. We used 2D speckle-tracking echocardiography to assess LVGLS and strain-derived myocardial work parameters. Results: We analysed four hundred and forty-nine dd-cfDNA samples from seventy-one patients until November 2024. The mean dd-cfDNA fraction remained very low (0.13 ± 0.06%). Eighty-eight percent of surveillance EMBs that would have otherwise been performed were avoided. The mean LVGLS was lower than the literature reference values. We found no correlation between dd-cfDNA and LVGLS. Transplanted hearts had different myocardial work indices than the reference values reported in the literature. Conclusions: dd-cfDNA effectively rules out clinically significant acute rejection and decreases the need for invasive surveillance EMBs. LVGLS seems less sensitive than dd-cfDNA for the identification of myocardial injury in the early stages of HTx rejection in patients at low risk for rejection.

Keywords: cardiac allograft rejection; donor-derived cell-free DNA; heart transplantation; left ventricular global longitudinal strain; myocardial work.

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Conflict of interest statement

T.T. and B.S. received a speaker fee from CareDx, Inc. (Brisbane, CA, USA). A.K. and A.S. reported personal fees from Argus Cognitive, Inc. (Budapest, Hungary) unrelated to the content of this paper. The companies had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Distribution of donor-derived cell-free DNA (dd-cfDNA) data points in the function of time after heart transplantation (HTx).
See this image and copyright information in PMC

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