Без рубрики

Currently, the issue of chronic heart failure (CHF) is increasingly relevant in Kazakhstan, with a significantly higher mortality rate from the terminal stage of CHF, especially among patients in FC III-IV. Heart transplantation is considered the “gold” standard for surgical treatment of terminal CHF; however, endomyocardial biopsy, used for monitoring the transplanted heart, is an invasive and inconvenient procedure. This study explores the potential of safe and accurate monitoring of acute transplant rejection using circulating donor-derived cell-free DNA (dd-cfDNA). The study involved 40 patients who had undergone heart transplantation. The results revealed that 60% of them had undergone repeat surgery, while 40% had undergone primary transplantation. The primary causes of terminal CHF included various cardiomyopathies, predominantly dilated and ischemic. The dd-cfDNA method shows promise in differentiating T-cell-mediated (ACR) and antibody-mediated (AMR) rejection, with distinct patterns of dd-cfDNA elevation. These differences have high clinical significance for diagnosis and treatment strategies. However, despite the prospects of using dd-cfDNA, further research is needed to establish threshold values and confirm its effectiveness in clinical practice. The study also raises important questions about the cost and accessibility of the method, requiring additional attention in the development of precision medicine methods in the field of heart transplantation.

cardiacsurgeryres

1. Khush, K., Cherikh, W. S., Chambers, D. C., Harhay, M. O., Hayes, D., Hsich, E.,Stehlik, J. (2019). The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-sixth Adult Heart Transplantation Report — 2019; Focus Theme: Donor and Recipient Size Match. The Journal of Heart and Lung Transplantation. doi:10.1016/j.healun.2019.08.0042. Mengel M, Sis B, Kim D, Chang J, Famulski KS, Hidalgo LG, Einecke G, de Freitas DG, Tymchak W, Burton J, Halloran PF. The molecular phenotype of heart transplant biopsies: relationship to histopathological and clinical variables. Am J Transplant. 2010;10:2105–15. [PubMed] [Google Scholar]3. Saraiva F, Matos V, Gonçalves L, Antunes M, Providência LA. Complications of endomyocardial biopsy in heart transplant patients: a retrospective study of 2117 consecutive procedures. Transplant Proc. 2011;43:1908–12. [PubMed] [Google Scholar]].4. Snyder TM, Khush KK, Valantine HA, Quake SR. Universal noninvasive detection of solid organ transplant rejection. Proc Natl Acad Sci U S A. 2011;108:6229–34. [PMC free article] [PubMed] [Google Scholar]5. Austin BA, Taylor DO. Surrogate markers of rejection. Curr Opin Organ Transplant. 2010;15:645–9. [PubMed] [Google Scholar]6. Koestenbauer S, Stiegler P, Stadlbauer V, Mayrhauser U, Leber B, Schweiger M, Wasler A, Prenner G, Sereinigg M, Zelzer S, Stojakovic T, Scarpatetti M, Griesbacher A, Greilberger J, Tscheliessnigg K. Myeloperoxidase and carbonyl proteins: promising markers for non-invasive monitoring of graft rejection after heart transplantation. J Heart Lung Transplant. 2010;29:1352–7. [PubMed] [Google Scholar]7. Morrow T. Blood test can replace invasive heart biopsy. Manag Care. 2010;19:46–7. [PubMed] [Google Scholar]8. Clerkin, K. J., Restaino, S. W., Zorn, E., Vasilescu, E. R., Marboe, C. C., & Mancini, D. M. (2016). The effect of timing and graft dysfunction on survival and cardiac allograft vasculopathy in antibody-mediated rejection. The Journal of Heart and Lung Transplantation, 35(9), 1059–1066. doi:10.1016/j.healun.2016.04.0079. Patel JK, Kobashigawa JA. Should we be doing routine biopsy after heart transplantation in a new era of anti-rejection? Curr Opin Cardiol. 2006;21(2):127-131. doi:10.1097/01.hco.0000210309.71984.3010. F. Saraiva, V. Matos, L. Gonçalves, M. Antunes, L. Providência, Complications of endomyocardial biopsy in heart transplant patients: A retrospective study of 2117 consecutive procedures. Transplant. Proc. 43, 1908–1912 (2011). 11. C. C. Marboe, M. Billingham, H. Eisen, M. C. Deng, H. Baron, M. Mehra, S. Hunt, J. Wohlgemuth, I. Mahmood, J. Prentice, G. Berry, Nodular endocardial infiltrates (Quilty lesions) cause significant variability in diagnosis of ISHLT grade 2 and 3A rejection in cardiac allograft recipients. J. Heart Lung Transplant. 24, S219–S226 (2005).12. Heitzer, E., Auinger, L., & Speicher, M. R. (2020). Cell-Free DNA and Apoptosis: How Dead Cells Inform About the Living. Trends in Molecular Medicine. doi:10.1016/j.molmed.2020.01.01213. Martuszewski, A., Paluszkiewicz, P., Król, M., Banasik, M., & Kepinska, M. (2021). Donor-Derived Cell-Free DNA in Kidney Transplantation as a Potential Rejection Biomarker: A Systematic Literature Review. Journal of Clinical Medicine, 10(2), 193. doi:10.3390/jcm1002019314. Y M Dennis Lo, Diana S C Han, Peiyong Jiang, Rossa W K Chiu. (2021) Epigenetics, fragmentomics, and topology of cell-free DNA in liquid biopsies DOI: 10.1126/science.aaw361615. Sherwood K., Weimer E. T. (2018). Characteristics, properties, and potential applications of circulating cell-free DNA in clinical diagnostics: A focus on transplantation. J. Immunol. Methods 463, 27–38. doi: 10.1016/j.jim.2018.09.01116. Hidestrand, M.; Tomita-Mitchell, A.; Hidestrand, P.M.; Oliphant, A.; Goetsch, M.; Stamm, K.; Liang, H.-L.; Castleberry, C.; Benson, D.W.; Stendahl, G.; et al. Highly Sensitive Noninvasive Cardiac Transplant Rejection Monitoring Using Targeted Quantification of Donor-Specific Cell-Free Deoxyribonucleic Acid. J. Am. Coll. Cardiol. 2014, 63, 1224–1226.17. Lo, Y. D., Tein, M. S., Pang, C. C., Yeung, C. K., Tong, K.-L., & Hjelm, N. M. (1998). Presence of donor-specific DNA in plasma of kidney and liver-transplant recipients. The Lancet, 351(9112), 1329–1330. doi:10.1016/s0140-6736(05)79055-318. Xiaoxiao Qian1, Palak Shah2,3, Sean Agbor-Enoh (2022). Non-invasive Biomarkers in Heart Transplant: 2020-2021 Year in Review. DOI: 10.1097/MOT.000000000000094519. Sorbini M., Togliatto G. M., Simonato E., Boffini M., Cappuccio M., Gambella A., et al. (2021). HLA-DRB1 mismatch-based identification of donor-derived cell free DNA (dd-cfDNA) as a marker of rejection in heart transplant recipients: A single-institution pilot study. J. Heart Lung Transpl. 40, 794–804. 10.1016/j.healun.2021.05.00120. De Vlaminck, I., Valantine, H. A., Snyder, T. M., Strehl, C., Cohen, G., Luikart, H., Khush, K. K. (2014). Circulating Cell-Free DNA Enables Noninvasive Diagnosis of Heart Transplant Rejection. Science Translational Medicine, 6(241), 241ra77–241ra77. doi:10.1126/scitranslmed.3007803