Racial Differences in Donor-Derived Cell-Free DNA and Mitochondrial DNA After Heart Transplantation, on Behalf of the GRAfT Investigators.
Citation: Circulation: Heart Failure. 17(4):e011160, 2024 Apr.PMID: 38375637Institution: MedStar Heart & Vascular InstituteForm of publication: Journal ArticleMedline article type(s): Journal Article | Multicenter StudySubject headings: *Cell-Free Nucleic Acids | *Heart Failure | *Heart Transplantation | Biomarkers | Cell-Free Nucleic Acids/ge [Genetics] | DNA, Mitochondrial/ge [Genetics] | Female | Graft Rejection/ge [Genetics] | Heart Failure/ge [Genetics] | Heart Failure/su [Surgery] | Heart Transplantation/ae [Adverse Effects] | Humans | Longitudinal Studies | Male | Middle Aged | Prospective Studies | Race Factors | Stroke Volume | Tissue Donors | Ventricular Function, Left | Year: 2024Local holdings: Available online from MWHC library: 2008 - presentISSN:- 1941-3289
- Najjar, Samer S:
- https://orcid.org/0000-0002-9149-416X
Item type | Current library | Collection | Call number | Status | Date due | Barcode |
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Journal Article | MedStar Authors Catalog | Article | 38375637 | Available | 38375637 |
Available online from MWHC library: 2008 - present
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.
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.
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.
REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02423070.
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.
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