{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:57:52Z","timestamp":1791215872112,"version":"4.1.0"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Cardiac acute rejection (AR) is a risk factor for poor outcomes; however, there are limited risk prediction models to stratify these patients for death or prolonged left ventricular (LV) dysfunction. We assessed the prognostic utility of percent donor-derived cell-free DNA (%dd-cfDNA) measured at AR diagnosis for predicting adverse outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>The prospective multicenter GRAfT study (Genomic Research Alliance for Transplantation) enrolled heart transplant recipients and collected serial plasma samples to quantitate %dd-cfDNA. AR was defined as acute cellular rejection, antibody-mediated rejection, as well as biopsy-negative antibody-mediated rejection (donor-specific antibody positivity with LV dysfunction). In the primary analyses, AR was stratified by %dd-cfDNA at diagnosis using a data-driven threshold of 0.15%. Cox regression models assessed the associations between the time-dependent covariates of AR and %dd-cfDNA levels at the AR diagnosis and the outcome of prolonged LV ejection fraction decline (\u226450% for \u226590 days) and death.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      The study included 277 patients and 3218 %dd-cfDNA measurements. Over a median follow-up of 4.9 years (interquartile range, 2.5\u20135.0), 53 patients experienced the composite outcome of death or prolonged LV dysfunction, and 75 (27%) patients developed AR, including 43 (15%) patients with acute cellular rejection, 18 (7%) with pathological antibody-mediated rejection, and 14 (5%) with donor-specific antibody+\/LV dysfunction. AR was associated with an increased risk of the primary composite outcome (hazard ratio, 4.47 [95% CI, 2.42\u20138.26];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001). When AR was stratified by %dd-cfDNA at diagnosis, patients with %dd-cfDNA \u22650.15% had higher risks of prolonged LV dysfunction, death, and the composite outcome compared with patients who had not developed AR at the same follow-up time (hazard ratio, 6.28 [95% CI, 3.04\u201313.0];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001 for the composite outcome). In contrast, the risks of death and prolonged LV ejection fraction reduction were not statistically significantly increased among patients who developed AR with %dd-cfDNA &lt;0.15% at diagnosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>AR with elevated %dd-cfDNA levels at diagnosis is associated with an increased risk of adverse outcomes after heart transplant, offering novel prognostic utility.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circheartfailure.125.013718","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T09:00:31Z","timestamp":1781514031000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Donor-Derived Cell-Free DNA at Diagnosis of Cardiac Allograft Rejection Stratifies Risk of Mortality and Graft Dysfunction"],"prefix":"10.1161","volume":"19","author":[{"given":"Zaid N.","family":"Safiullah","sequence":"first","affiliation":[{"name":"Critical Care Medicine Department, National Institutes of Health, Bethesda, MD (Z.N.S.)."},{"name":"Genomic Research Alliance for Transplantation (GRAfT), Bethesda, MD (Z.N.S., H.K., M.K.J., K.S., G.J.B., P.S., H.A.V., S.A.-E.)."},{"name":"Laboratory of Applied Precision Omics (APO), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (Z.N.S., H.K., M.K.J., S.A.-E.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Su","sequence":"additional","affiliation":[{"name":"Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (H.S., X.T.)."},{"name":"George Washington University, Washington, DC (H.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7540-2045","authenticated-orcid":true,"given":"Hyesik","family":"Kong","sequence":"additional","affiliation":[{"name":"Genomic Research Alliance for Transplantation (GRAfT), Bethesda, MD (Z.N.S., H.K., M.K.J., K.S., G.J.B., P.S., H.A.V., S.A.-E.)."},{"name":"Laboratory of Applied Precision Omics (APO), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (Z.N.S., H.K., M.K.J., S.A.-E.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1657-2877","authenticated-orcid":true,"given":"Moon Kyoo","family":"Jang","sequence":"additional","affiliation":[{"name":"Genomic Research Alliance for Transplantation (GRAfT), Bethesda, MD (Z.N.S., H.K., M.K.J., K.S., G.J.B., P.S., H.A.V., S.A.-E.)."},{"name":"Laboratory of Applied Precision Omics (APO), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (Z.N.S., H.K., M.K.J., S.A.-E.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyur","family":"Shah","sequence":"additional","affiliation":[{"name":"Genomic Research Alliance for Transplantation (GRAfT), Bethesda, MD (Z.N.S., H.K., M.K.J., K.S., G.J.B., P.S., H.A.V., S.A.-E.)."},{"name":"Virginia Commonwealth University, Richmond, VA (K.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6176-2629","authenticated-orcid":true,"given":"Gerald J.","family":"Berry","sequence":"additional","affiliation":[{"name":"Genomic Research Alliance for Transplantation (GRAfT), Bethesda, MD (Z.N.S., H.K., M.K.J., K.S., G.J.B., P.S., H.A.V., S.A.-E.)."},{"name":"Stanford University School of Medicine, Stanford, CA (G.J.B., H.A.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8175-168X","authenticated-orcid":true,"given":"Palak","family":"Shah","sequence":"additional","affiliation":[{"name":"Genomic Research Alliance for Transplantation (GRAfT), Bethesda, MD (Z.N.S., H.K., M.K.J., K.S., G.J.B., P.S., H.A.V., S.A.-E.)."},{"name":"Department of Heart Failure and Transplantation, Inova Heart and Vascular Institute, Falls Church, VA (P.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2948-9503","authenticated-orcid":true,"given":"Hannah A.","family":"Valantine","sequence":"additional","affiliation":[{"name":"Genomic Research Alliance for Transplantation (GRAfT), Bethesda, MD (Z.N.S., H.K., M.K.J., K.S., G.J.B., P.S., H.A.V., S.A.-E.)."},{"name":"Stanford University School of Medicine, Stanford, CA (G.J.B., 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