Lack of Association Between Donor‐Derived Cell‐Free DNA and Cardiac Allograft Vasculopathy
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Wiley
2024
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| author | Rami Alharethi Stacey Knight Helen I. Luikart Theresa Wolf‐Doty Daniel L. Bride Daniel. T. Kim Kiran K. Khush |
| author_facet | Rami Alharethi Stacey Knight Helen I. Luikart Theresa Wolf‐Doty Daniel L. Bride Daniel. T. Kim Kiran K. Khush Rami Alharethi Stacey Knight Helen I. Luikart Theresa Wolf‐Doty Daniel L. Bride Daniel. T. Kim Kiran K. Khush |
| collection | Wiley Open Access |
| contents | Lack of Association Between Donor‐Derived Cell‐Free DNA and Cardiac Allograft Vasculopathy Rami Alharethi Stacey Knight Helen I. Luikart Theresa Wolf‐Doty Daniel L. Bride Daniel. T. Kim Kiran K. Khush Clinical Transplantation ABSTRACTCardiac allograft vasculopathy (CAV) is a leading cause of death after heart transplantation (HT). We evaluated donor‐derived cell‐free DNA (dd‐cfDNA) as a noninvasive biomarker of CAV development after HT.The INSPIRE registry at the Intermountain Medical Center was queried for stored plasma samples from HT patients with and without CAV. At Stanford University, HT patients with CAV (cases) and without CAV (controls) were enrolled prospectively, and blood samples were collected. All the samples were analyzed for dd‐cfDNA using the AlloSure assay (CareDx, Inc.). CAV was defined per the ISHLT 2010 standardized classification system. Univariate associations between patient demographics and clinical characteristics and their CAV grade were tested using chi‐square and Wilcoxon rank sum tests. Associations between their dd‐cfDNA levels and CAV grades were examined using a nonparametric Kruskal–Wallis test.A total of 69 pts were included, and 101 samples were analyzed for dd‐cfDNA. The mean age at sample collection was 58.6 ± 13.7 years; 66.7% of the patients were male, and 81% were White. CAV 0, 1, 2, and 3 were present in 37.6%, 22.8%, 22.8%, and 16.8% of included samples, respectively. The median dd‐cfDNA level was 0.13% (0.06, 0.33). The median dd‐cfDNA level was not significantly different between CAV (−) and CAV (+): 0.09% (0.05%–0.32%) and 0.15% (0.07%–0.33%), respectively, p = 0.25 and with similar results across all CAV grades.In our study, dd‐cfDNA levels did not correlate with the presence of CAV and did not differ across CAV grades. As such, dd‐cfDNA does not appear to be a reliable noninvasive biomarker for CAV surveillance. 10.1111/ctr.15416 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| doi_str_mv | 10.1111/ctr.15416 |
| format | Artículo Open Access |
| id | wiley_oa_10_1111_ctr_15416 |
| institution | Wiley Open Access |
| license_str_mv | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| publishDate | 2024 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Lack of Association Between Donor‐Derived Cell‐Free DNA and Cardiac Allograft Vasculopathy Rami Alharethi Stacey Knight Helen I. Luikart Theresa Wolf‐Doty Daniel L. Bride Daniel. T. Kim Kiran K. Khush Clinical Transplantation Lack of Association Between Donor‐Derived Cell‐Free DNA and Cardiac Allograft Vasculopathy Rami Alharethi Stacey Knight Helen I. Luikart Theresa Wolf‐Doty Daniel L. Bride Daniel. T. Kim Kiran K. Khush Clinical Transplantation ABSTRACTCardiac allograft vasculopathy (CAV) is a leading cause of death after heart transplantation (HT). We evaluated donor‐derived cell‐free DNA (dd‐cfDNA) as a noninvasive biomarker of CAV development after HT.The INSPIRE registry at the Intermountain Medical Center was queried for stored plasma samples from HT patients with and without CAV. At Stanford University, HT patients with CAV (cases) and without CAV (controls) were enrolled prospectively, and blood samples were collected. All the samples were analyzed for dd‐cfDNA using the AlloSure assay (CareDx, Inc.). CAV was defined per the ISHLT 2010 standardized classification system. Univariate associations between patient demographics and clinical characteristics and their CAV grade were tested using chi‐square and Wilcoxon rank sum tests. Associations between their dd‐cfDNA levels and CAV grades were examined using a nonparametric Kruskal–Wallis test.A total of 69 pts were included, and 101 samples were analyzed for dd‐cfDNA. The mean age at sample collection was 58.6 ± 13.7 years; 66.7% of the patients were male, and 81% were White. CAV 0, 1, 2, and 3 were present in 37.6%, 22.8%, 22.8%, and 16.8% of included samples, respectively. The median dd‐cfDNA level was 0.13% (0.06, 0.33). The median dd‐cfDNA level was not significantly different between CAV (−) and CAV (+): 0.09% (0.05%–0.32%) and 0.15% (0.07%–0.33%), respectively, p = 0.25 and with similar results across all CAV grades.In our study, dd‐cfDNA levels did not correlate with the presence of CAV and did not differ across CAV grades. As such, dd‐cfDNA does not appear to be a reliable noninvasive biomarker for CAV surveillance. 10.1111/ctr.15416 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| title | Lack of Association Between Donor‐Derived Cell‐Free DNA and Cardiac Allograft Vasculopathy |
| topic | Clinical Transplantation |
| url | https://onlinelibrary.wiley.com/doi/10.1111/ctr.15416 |