Purpose of Review
Acute rejection is one of the most feared complications of cardiac transplantation. Developing non-invasive methods for detection and surveillance of acute rejection have long been a goal for post-transplant care.
Here, we will review molecular diagnostic tests that are currently in use or under development to diagnose acute cellular rejection after cardiac transplantation.
Gene expression, microRNA, molecular microscope, and cell-free DNA assays offer non-invasive alternatives to the endomyocardial biopsy for acute rejection surveillance.
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Papers of particular interest, published recently, have been highlighted as: • Of importance
Sakakibara S, Konno S. Endomyocardial biopsy. Jpn Heart J. 1962;3:537–43.
Caves P, et al. Transvenous endomyocardial biopsy-application of a method for diagnosing heart disease. Postgrad Med J. 1975;51(595):286–90.
Melvin KR, Mason JW. Endomyocardial biopsy: its history, techniques and current indications. Can Med Assoc J. 1982;126(12):1381–6.
Crespo-Leiro MG, et al. Concordance among pathologists in the second Cardiac Allograft Rejection Gene Expression Observational Study (CARGO II). Transplantation. 2012;94(11):1172–7.
Patel PC, et al. High-sensitivity cardiac troponin I assay to screen for acute rejection in patients with heart transplant. Circulation: HF. 2014;7:463–9.
Horwitz PA, Tsai EJ, Putt ME, et al. Detection of cardiac allograft rejection and response to immunosuppressive therapy with peripheral blood gene expression. Circulation. 2004;110:3815–21.
Schoels M, Dengler TJ, Richter R, Meuer SC, Giese T. Detection of cardiac allograft rejection by real-time PCR analysis of circulating mononuclear cells. Clin Transpl. 2004;18:513–7.
Deng, et al. Noninvasive discrimination of rejection in cardiac allograft recipients using gene expression profiling. Am J Transplant. 2006;6(1):150–60.
Starling RC, et al. Molecular testing in the management of cardiac transplant recipients: initial clinical experience. J Heart Lung Transplant. 2006;25(12):1389–95.
Pham MX, et al. Gene-expression profiling for rejection surveillance after cardiac transplantation. NEJM. 2010;362:1890–900.
• Crespo-Leiro MG, et al. Clinical usefulness of gene-expression profile to rule out acute rejection after heart transplantation: CARGO II. Eur Heart J. 2016;37(33):2591–601. The CARGO II study compared gene expression profiling to standard endomyocardial biopsy for detection of acute cellular rejection
Kobashigawa JA, et al. Randomized pilot trial of gene expression profiling versus heart biopsy in the first year after heart transplant: Early Invasive monitoring attenuation through gene expression trial (EIMAGE). Circ Heart Fail. 2015;8:557–64.
Li L, et al. Identification of common blood gene signatures for the diagnosis of renal and cardiac acute allograft rejection. PLoS One. 2013;8(12):e82153.
• Loupy A, et al. Gene expression profiling for the identification and classification of antibody-mediated heart rejection. Circulation. 2017;135:917–35. Loupy and colleagues demonstrate how gene expression profiling can also be used for surveillance of antibody-mediated rejection
Bodez D, et al. Myocardial gene expression profiling to predict and identify cardiac allograft acute cellular rejection: the GET-study. PLoS One. 2016;11(110):e0167213.
Hollander Z, et al. Predicting acute cardiac rejection from donor heart and pre-transplant recipient blood gene expression. J Heart Lung Transplant. 2013;32(2):259–65.
Huyen V, et al. MicroRNAs as non-invasive biomarkers of heart transplant rejection. Eur Heart J. 2014;35(45):3194–202.
Dewi IS, et al. Association of serum MiR-142-3p and MiR-101-3p levels with acute cellular rejection after heart transplantation. PLoS One. 2017;12(1):e0170842.
Loupy A, et al. Molecular microscope strategy to improve risk stratification in early antibody-mediated kidney allograft rejection. J Am Soc Nephrol. 2014;25(10):2267–77.
Halloran PF et al. Development and validation of a molecular microscope diagnostic system (MMDx) for heart transplant biopsies. [abstract]. Am J Transplant. 2016; 16 (suppl 3). http://atcmeetingabstracts.com/abstract/development-and-validation-of-a-molecular-microscope-diagnostic-system-mmdx-for-heart-transplant-biopsies/. Accessed June 18, 2017.
Snyder TM, et al. Universal noninvasive detection of solid organ transplant rejection. PNAS. 2011;108(15):6229–34.
• De Vlaminck I, et al. Circulating cell-free DNA enables noninvasive diagnosis of heart transplant rejection. Sci Transl Med. 2014;6(241):241ra77. De Vlaminck and colleagues show that cell-free DNA can detect acute cellular and antibody-mediated rejection
Grskovic M, et al. Validation of a clinical-grade assay to measure donor-derived cell-free DNA in solid organ transplant recipients. J Mol Diagn. 2016;18(6):890–902.
Crespo-Leiro MG, et al. Increased plasma levels of donor-derived cell-free DNA correlate with rejection in heart transplant recipients: the CARGO II multicenter trial. JHLT. 2015;34(4):S31032.
Kobashigawa JA, et al. Initial analysis of the donor-derived cell-free DNA-outcomes AlloMap registry (D-OAR) study in heart transplant recipients undergoing surveillance for rejection. JHLT. 2016;35(4):S33.
Conflict of Interest
Kiran Khush reports grants and personal fees from CareDx., Inc., and he has a patent WSGR 47697-703.711 licensed to Karius, Inc.
Shirin Zarafshar declares no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
This article is part of the Topical Collection on Heart Failure
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Khush, K., Zarafshar, S. Molecular Diagnostic Testing in Cardiac Transplantation. Curr Cardiol Rep 19, 118 (2017). https://doi.org/10.1007/s11886-017-0915-1
- Rejection surveillance
- Cellular rejection
- Antibody-mediated rejection
- Gene expression profiling