{"doi":"10.1161/circheartfailure.123.011160","title":"Racial Differences in Donor-Derived Cell-Free DNA and Mitochondrial DNA After Heart Transplantation, on Behalf of the GRAfT Investigators","abstract":"BACKGROUND: Black heart transplant patients are at higher risk of acute rejection (AR) and death than White patients. We hypothesized that this risk may be associated with higher levels of donor-derived cell-free DNA (dd-cfDNA) and cell-free mitochondrial DNA. METHODS: The Genomic Research Alliance for Transplantation is a multicenter, prospective, longitudinal cohort study. Sequencing was used to quantitate dd-cfDNA and polymerase chain reaction to quantitate cell-free mitochondrial DNA in plasma. AR was defined as ≥2R cellular rejection or ≥1 antibody-mediated rejection. The primary composite outcome was AR, graft dysfunction (left ventricular ejection fraction <50% and decrease by ≥10%), or death. RESULTS: We included 148 patients (65 Black patients and 83 White patients), median age was 56 years and 30% female sex. The incidence of AR was higher in Black patients compared with White patients (43% versus 19%; P =0.002). Antibody-mediated rejection occurred predominantly in Black patients with a prevalence of 20% versus 2% ( P <0.001). After transplant, Black patients had higher levels of dd-cfDNA, 0.09% (interquartile range, 0.001–0.30) compared with White patients, 0.05% (interquartile range, 0.001–0.23; P =0.003). Beyond 6 months, Black patients showed a persistent rise in dd-cfDNA with higher levels compared with White patients. Cell-free mitochondrial DNA was higher in Black patients (185 788 copies/mL; interquartile range, 101 252–422 133) compared with White patients (133 841 copies/mL; interquartile range, 75 346–337 990; P <0.001). The primary composite outcome occurred in 43% and 55% of Black patients at 1 and 2 years, compared with 23% and 27% in White patients, P <0.001. In a multivariable model, Black patient race (hazard ratio, 2.61 [95% CI, 1.35–5.04]; P =0.004) and %dd-cfDNA (hazard ratio, 1.15 [95% CI, 1.03–1.28]; P =0.010) were associated with the primary composite outcome. CONCLUSIONS: Elevated dd-cfDNA and cell-free mitochondrial DNA after heart transplant may mechanistically be implicated in the higher incidence of AR and worse clinical outcomes in Black transplant recipients. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02423070.","journal":"Circulation Heart Failure","year":2024,"id":431409,"datarank":0.5197232960289572,"base_score":2.833213344056216,"endowment":2.833213344056216,"self_citation_contribution":0.42498200160843247,"citation_network_contribution":0.09474129442052467,"self_endowment_contribution":0.42498200160843247,"citer_contribution":0.09474129442052467,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":10,"citers_with_citation_signal":4,"citers_with_endowment":4,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8365,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02423070"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":246493,"name":"Sean Agbor-Enoh","orcid":"0000-0002-9380-9161","position":1,"is_corresponding":false},{"id":746057,"name":"Ben Seiyon Lee","orcid":"0000-0003-0658-7458","position":2,"is_corresponding":false},{"id":627889,"name":"T. Andargie","orcid":"0000-0003-2888-1316","position":3,"is_corresponding":false},{"id":230587,"name":"Shashank S. Sinha","orcid":"0000-0001-6249-2598","position":4,"is_corresponding":false},{"id":627891,"name":"Hyesik Kong","orcid":"0000-0001-7540-2045","position":5,"is_corresponding":false},{"id":1235726,"name":"Lawrence Henry","orcid":null,"position":6,"is_corresponding":false},{"id":1083840,"name":"Woojin Park","orcid":"0000-0001-9982-0057","position":7,"is_corresponding":false},{"id":1220775,"name":"Erick McNair","orcid":"0000-0003-0931-8560","position":8,"is_corresponding":false},{"id":1220774,"name":"Inna Tchoukina","orcid":"0000-0002-1587-1998","position":9,"is_corresponding":false},{"id":658154,"name":"Keyur B. Shah","orcid":"0000-0002-8329-2963","position":10,"is_corresponding":false},{"id":746056,"name":"Samer S. Najjar","orcid":"0000-0002-9149-416X","position":11,"is_corresponding":false},{"id":683565,"name":"Steven Hsu","orcid":"0000-0002-8384-2638","position":12,"is_corresponding":false},{"id":746610,"name":"M.E. Rodrigo","orcid":null,"position":13,"is_corresponding":false},{"id":246494,"name":"Moon Kyoo Jang","orcid":"0000-0002-1657-2877","position":14,"is_corresponding":false},{"id":332244,"name":"Charles C. Marboe","orcid":"0000-0001-6844-209X","position":15,"is_corresponding":false},{"id":105296,"name":"Gerald J. Berry","orcid":"0000-0002-6176-2629","position":16,"is_corresponding":false},{"id":96109,"name":"Hannah A. Valantine","orcid":"0000-0002-2948-9503","position":17,"is_corresponding":false},{"id":1235727,"name":"on behalf of the GRAfT Investigators","orcid":null,"position":18,"is_corresponding":false},{"id":297886,"name":"Palak Shah","orcid":"0000-0001-8175-168X","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-19T01:59:25.642507Z","pmid":"38375637","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}