Racial Differences in Donor-Derived Cell-Free DNA and Mitochondrial DNA After Heart Transplantation, on Behalf of the GRAfT Investigators
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:17 |
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| Enthalten in: |
Circulation. Heart failure - 17(2024), 4 vom: 19. Apr., Seite e011160 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Shah, Palak [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 18.04.2024 Date Revised 27.04.2024 published: Print-Electronic ClinicalTrials.gov: NCT02423070 Citation Status MEDLINE |
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| doi: |
10.1161/CIRCHEARTFAILURE.123.011160 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368656977 |
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| 245 | 1 | 0 | |a Racial Differences in Donor-Derived Cell-Free DNA and Mitochondrial DNA After Heart Transplantation, on Behalf of the GRAfT Investigators |
| 264 | 1 | |c 2024 | |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT02423070 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02423070 | ||
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| 700 | 1 | |a Sinha, Shashank S |e verfasserin |4 aut | |
| 700 | 1 | |a Kong, Hyesik |e verfasserin |4 aut | |
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| 700 | 1 | |a Shah, Keyur B |e verfasserin |4 aut | |
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