Donor-derived cell-free DNA as a new biomarker for cardiac allograft rejection : A prospective study (FreeDNA-CAR)
Jiménez-Blanco, M. (Centro de Investigación Cardiovascular en Red CIBER)
Crespo-Leiro, Maria Generosa (Complejo Hospitalario Universitario de A Coruña)
García-Cosío Carmena, M.D. (Hospital Universitario 12 de Octubre. Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12))
Gómez Bueno, M. (Hospital Universitario Puerta de Hierro Majadahonda (Madrid))
López-Vilella, R. (Hospital Universitari i Politècnic La Fe (València))
Ortiz-Bautista, C. (Hospital General Universitario Gregorio Marañón)
Farrero, Marta (Hospital Clínic i Provincial de Barcelona)
Zegrí-Reiriz, Isabel (Institut de Recerca Sant Pau)
Díaz-Molina, Beatriz (Hospital Universitario Central de Asturias)
García Romero, Elena (Hospital Universitari de Bellvitge)
Rangel Sousa, Diego (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Salterain, N. (Clínica Universidad de Navarra)
Garrido Bravo, I. (Hospital Universitario Virgen de la Arrixaca (Múrcia))
Segovia, Javier (Hospital Universitario Puerta de Hierro Majadahonda (Madrid))
Universitat Autònoma de Barcelona. Departament de Medicina

Fecha:	2025
Resumen:	Background: There is a long-standing need for a noninvasive biomarker that allows monitoring of cardiac allograft rejection, avoiding the need for periodic endomyocardial biopsies (EMB). Methods: Multicenter, observational, prospective study, performed between 2019 and 2023 (NCT 04973943). All patients underwent 7 per-protocol surveillance EMB during the first postheart transplantation year. Donor-derived cell-free DNA (dd-cfDNA) levels were determined before each EMB, using Next Generation Sequencing Technology (Allonext assay, Eurofins Genome). The primary end-point was the association between dd-cfDNA levels and the presence of acute cellular rejection (ACR) in EMB. Results: The study included 206 patients from 12 centers, with 1,090 pairs of EMB/dd-cfDNA determinations available for analysis. EMB with ACR (n = 49) were associated with dd-cfDNA levels significantly higher than those without, median 0. 189% (interquartilic range 0. 05-0. 70) vs 0. 095% (0. 04-0. 23), p = 0. 013. A dd-cfDNA threshold of 0. 10% showed a negative predictive value for ACR of 97%. A statistically significant association between N-terminal prohormone of brain (NTProBNP) and dd-cfDNA was also found, with an increase of 0. 007% dd-cfDNA (95% confidence interval 0. 003-0. 011) for every 500 units of NTproBNP, p 0. 001. The combination of both biomarkers for diagnosis of ACR showed an area under the receiver operating characteristic (ROC) curve of 0. 681, and this combined approach was significantly better than dd-cfDNA alone (area under the ROC curve 0. 603), p = 0. 016. Using a cut-off point of 0. 10% for dd-cfDNA and 1,000 UI/ml for NTproBNP, negative predictive value increased to 98. 1%. Conclusions: dd-cfDNA may be a useful biomarker to rule out significant ACR in a low-risk population. However, a dd-cfDNA value above normal threshold does not correlate robustly with the presence of disease. The combination with NTproBNP, a readily available biomarker, increased the discrimination power of dd-cfDNA alone. Clinical Trial Notation: Donor-derived Cell-Free DNA as a New Biomarker in Cardiac Acute Rejection, NCT 04973943.
Ayudas:	Instituto de Salud Carlos III PI19/01664
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	NTproBNP ; Acute cardiac rejection ; Biomarkers ; Donor-derived cell-free DNA ; Heart transplantation
Publicado en:	Journal of Heart and Lung Transplantation, Vol. 44 Núm. 4 (april 2025) , p. 560-569, ISSN 1557-3117

DOI: 10.1016/j.healun.2024.11.009
PMID: 39577511

10 p, 2.6 MB

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