TY  - BOOK
AU  - Najjar, Samer S
AU  - Rodrigo, Maria
TI  - Racial Differences in Donor-Derived Cell-Free DNA and Mitochondrial DNA After Heart Transplantation, on Behalf of the GRAfT Investigators
SN  - 1941-3289
PY  - 2024///
KW  - *Cell-Free Nucleic Acids
KW  - *Heart Failure
KW  - *Heart Transplantation
KW  - Biomarkers
KW  - Cell-Free Nucleic Acids/ge [Genetics]
KW  - DNA, Mitochondrial/ge [Genetics]
KW  - Female
KW  - Graft Rejection/ge [Genetics]
KW  - Heart Failure/ge [Genetics]
KW  - Heart Failure/su [Surgery]
KW  - Heart Transplantation/ae [Adverse Effects]
KW  - Humans
KW  - Longitudinal Studies
KW  - Male
KW  - Middle Aged
KW  - Prospective Studies
KW  - Race Factors
KW  - Stroke Volume
KW  - Tissue Donors
KW  - Ventricular Function, Left
KW  - Automated
KW  - MedStar Heart & Vascular Institute
KW  - Journal Article
KW  - Multicenter Study
N1  - Available online from MWHC library: 2008 - present
N2  - 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
UR  - https://dx.doi.org/10.1161/CIRCHEARTFAILURE.123.011160
ER  -