SCIENTIFIC JOURNAL of the Hungarian Society of Cardiology

Noninvasive detection of allograft injury after heart transplantation – Utilization of donor-derived cell-free DNA assay in the management of heart transplant recipients

█ Original article

DOI: 10.26430/CHUNGARICA.2023.53.4.399

Authors:
Teszák Tímea1, Bödör Csaba2, Hegyi Lajos2, Lévay Luca2,
Nagy Ákos2, Fintha Attila2, Pólos Miklós1, Hartyánszky István1, Merkely Béla1, Sax Balázs1
1Semmelweis Egyetem, Városmajori Szív- és Érgyógyászati Klinika, Budapest
2Semmelweis Egyetem, Patológiai és Kísérleti Rákkutató Intézet, Molekuláris Diagnosztika Részleg, Budapest
Levelezési cím:
Dr. Teszák Tímea, 1122 Budapest, Városmajor utca 68. E-mail: teszak.timea@med.semmelweis-univ.hu

Summary

Background: Cardiac allograft rejection is a major etiological factor of graft dysfunction, hospitalisation, and death after heart transplantation (HTx). Endomyocardial biopsy (EMB) is still considered gold standard method of monitoring rejection; however, besides the need for hospitalisation, common concerns are its complications, and high interobserver variability in its interpretation. Noninvasive methods for diagnosing allograft injury are of paramount importance. Donor-derived cell-free DNA (dd-cfDNA) characterizes graft injury and it can be isolated from the recipient’s sera and quantified using next-generation sequencing (NGS). Elevated dd-cfDNA levels precede the diagnosis of rejection on EMB, and possess high negative predictive value.
Purpose: We aimed to present the first Hungarian experience with dd-cfDNA assay for allograft rejection surveillance.
Methods: Analysis was performed on the clinical data of HTx recipients who have undergone dd-cfDNA testing (CareDx AlloSeq) since December 2021. The assay was performed ≥14 days after HTx. The amount of dd-cfDNA is measured relative to the total amount of cfDNA derived from a plasma sample. A dd-cfDNA level of <0.20% is considered negative, while severe injury threshold is at ≥0.35%.
Results: We analysed 107 dd-cfDNA data points of 43 HTx patients in our cross-sectional and longitudinal study. In 27 cases, dd-cfDNA testing was paired with routine EMB, while elevated dd-cfDNA values indicated for-cause EMB in 2 cases. Patients without rejection episodes had low dd-cfDNA values (0.10% [0.03%–0.21%]). For-cause EMBs proved antibody-mediated rejection. Owing to normal dd-cfDNA levels, 60 EMBs, i.e. 92% of routine surveillance EMBs could be avoided.
Conclusions: The noninvasive dd-cfDNA assay safely decreases the rate of invasive surveillance EMBs. Since it has the potential to detect early signs of graft injury, it opens the door to earlier and more personalized titration of immunosuppressive therapy, thus avoiding its toxicities, more severe allograft rejection, and irreversible graft dysfunction.

ISSUE: CARDIOLOGIA HUNGARICA | 2023 | VOLUME 53, ISSUE 4

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