{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T20:56:29Z","timestamp":1791665789951,"version":"4.3.4"},"reference-count":99,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2023,8,22]]},"abstract":"<jats:p>The number of heart transplants performed annually in the United States and worldwide continues to increase, but there has been little change in graft longevity and patient survival over the past 2 decades. The reference standard for diagnosis of acute cellular and antibody-mediated rejection includes histologic and immunofluorescence evaluation of endomyocardial biopsy samples, despite invasiveness and high interrater variability for grading histologic rejection. Circulating biomarkers and molecular diagnostics have shown substantial predictive value in rejection monitoring, and emerging data support their use in diagnosing other posttransplant complications. The use of genomic (cell-free DNA), transcriptomic (mRNA and microRNA profiling), and proteomic (protein expression quantitation) methodologies in diagnosis of these posttransplant outcomes has been evaluated with varying levels of evidence. In parallel, growing knowledge about the genetically mediated immune response leading to rejection (immunogenetics) has enhanced understanding of antibody-mediated rejection, associated graft dysfunction, and death. Antibodies to donor human leukocyte antigens and the technology available to evaluate these antibodies continues to evolve. This review aims to provide an overview of biomarker and immunologic tests used to diagnose posttransplant complications. This includes a discussion of pediatric heart transplantation and the disparate rates of rejection and death experienced by Black patients receiving a heart transplant. This review describes diagnostic modalities that are available and used after transplant and the landscape of future investigations needed to enhance patient outcomes after heart transplantation.<\/jats:p>","DOI":"10.1161\/circulationaha.123.062847","type":"journal-article","created":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T18:01:01Z","timestamp":1692640861000},"page":"679-694","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":41,"title":["Selection and Interpretation of Molecular Diagnostics in Heart Transplantation"],"prefix":"10.1161","volume":"148","author":[{"given":"Jason F.","family":"Goldberg","sequence":"first","affiliation":[{"name":"Department of Heart Failure and Transplantation, Inova Heart and Vascular Institute, Falls Church, VA (J.F.G., C.R.d., P.S.)."},{"name":"Department of Pediatrics, Inova L.J. Murphy Children\u2019s Hospital, Falls Church, VA (J.F.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren K.","family":"Truby","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Texas Southwestern, Dallas (L.K.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9380-9161","authenticated-orcid":true,"given":"Sean","family":"Agbor-Enoh","sequence":"additional","affiliation":[{"name":"Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD (S.A.-E.)."},{"name":"Applied Precision Genomics, National Heart, Lung and Blood Institute, Bethesda, MD (S.A.-E.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette M.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department of Surgery, Duke University School of Medicine, Durham, NC (A.M.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0660-4943","authenticated-orcid":true,"given":"Christopher R.","family":"deFilippi","sequence":"additional","affiliation":[{"name":"Department of Heart Failure and Transplantation, Inova Heart and Vascular Institute, Falls Church, VA (J.F.G., C.R.d., P.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9697-5926","authenticated-orcid":true,"given":"Kiran K.","family":"Khush","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, CA (K.K.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8175-168X","authenticated-orcid":true,"given":"Palak","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Heart Failure and Transplantation, Inova Heart and Vascular Institute, Falls Church, VA (J.F.G., C.R.d., P.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2019.08.004"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2019.08.002"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0735-1097(99)00452-0"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e31826e19e2"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2022.08.005"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.15339"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.049098"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2005.01175.x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0912965"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajt.2023.02.025"},{"key":"e_1_3_3_12_2","unstructured":"Centers for Medicare and Medicaid Services. Clinical Laboratory Fee Schedule. Published 2023. Accessed May 17 2023. https:\/\/www.cms.gov\/medicare\/medicare-fee-for-service-payment\/clinicallabfeesched\/clinical-laboratory-fee-schedule-files"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2016.04.007"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2011.10.009"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.122.009923"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2019.05.008"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2017.11.003"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.14695"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2021.07.022"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep27859"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3007803"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2019.11.015"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2022.04.002"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2018.09.004"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu346"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvw244"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2020.05.018"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2022.06.019"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2021.12.006"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.114.001658"},{"key":"e_1_3_3_31_2","unstructured":"Food and Drug Administration. FDA Device Classification Cardiac Allograft Gene Expression Profiling Test System. Accessed June 27 2023. https:\/\/www.accessdata.fda.gov\/cdrh_docs\/reviews\/k073482.pdf"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.147610"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/ctr.14258"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/ctr.14699"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2013.03.007"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.247452"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu346"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2017.05.029"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2021.08.004"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.022907"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.17087"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2018.06.010"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1053-2498(03)00190-6"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2003.08.005"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2004.08.018"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000000378"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1097\/MOT.0b013e328364fe23"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000003876"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.102.17.2100"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13422"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.15218"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2017.07.012"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1111\/petr.14264"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1111\/petr.14124"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1111\/petr.13673"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2021.07.017"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.21037\/tp.2019.07.13"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1111\/petr.12706"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.119.006107"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.06.054"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2015.01.987"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2017.02.015"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2015.12.023"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2017.01.003"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2020.04.003"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1111\/tri.12335"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1097\/MOT.0000000000000818"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1111\/ctr.13416"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1111\/ctr.13121"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1111\/ctr.14483"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.14691"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1111\/ctr.12924"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2015.05.001"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.TP.0000436927.08026.a8"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2020.06.010"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e318211d2f4"},{"key":"e_1_3_3_77_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2007.01838.x"},{"key":"e_1_3_3_78_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2020.07.010"},{"key":"e_1_3_3_79_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.tp.0000234837.02126.70"},{"key":"e_1_3_3_80_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2009.12.015"},{"key":"e_1_3_3_81_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2008.10.001"},{"key":"e_1_3_3_82_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(84)90013-9"},{"key":"e_1_3_3_83_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2005.02871.x"},{"key":"e_1_3_3_84_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2019.01.006"},{"key":"e_1_3_3_85_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.10.034"},{"key":"e_1_3_3_86_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2014.02.027"},{"key":"e_1_3_3_87_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2021.07.024"},{"key":"e_1_3_3_88_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2021.07.001"},{"key":"e_1_3_3_89_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.04.033"},{"key":"e_1_3_3_90_2","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000001944"},{"key":"e_1_3_3_91_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.856600"},{"key":"e_1_3_3_92_2","doi-asserted-by":"publisher","DOI":"10.1111\/ctr.13765"},{"key":"e_1_3_3_93_2","unstructured":"Food and Drug Administration. Evidence-based treatment decisions in transplantation: the right dose & regimen for the right patient\/individualized treatment. Published 2018. Accessed June 27 2023. Available from: https:\/\/www.fda.gov\/media\/126472\/download"},{"key":"e_1_3_3_94_2","unstructured":"Food and Drug Administration. Guardant 360 CDx premarket approval order. Published 2020. Accessed June 27 2023. https:\/\/www.accessdata.fda.gov\/cdrh_docs\/pdf20\/P200010A.pdf"},{"key":"e_1_3_3_95_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajt.2023.02.004"},{"key":"e_1_3_3_96_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2021.07.006"},{"key":"e_1_3_3_97_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201207-1160oe"},{"key":"e_1_3_3_98_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40472-021-00331-4"},{"key":"e_1_3_3_99_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13323-015-0022-2"},{"key":"e_1_3_3_100_2","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.10397.1"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCULATIONAHA.123.062847","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T08:18:38Z","timestamp":1738829918000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCULATIONAHA.123.062847"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,22]]},"references-count":99,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2023,8,22]]}},"alternative-id":["10.1161\/CIRCULATIONAHA.123.062847"],"URL":"https:\/\/doi.org\/10.1161\/circulationaha.123.062847","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,22]]},"assertion":[{"value":"2023-08-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}