Journal
JOURNAL OF HEART AND LUNG TRANSPLANTATION
Volume 41, Issue 7, Pages 919-927Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.healun.2022.04.002
Keywords
acute rejection; heart transplant; cell free DNA; endomyocardial biopsy; acute cellular rejection; antibody mediated rejection; graft dysfunction
Funding
- Natera Inc
- American Heart Association [16SFRN31890003, 18CDA34110250]
- Altman Clinical & Translational Research Institute (ACTRI) at UC San Diego Health
- National Center for Advancing Translational Sciences, NIH [KL2TR001444]
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This study aimed to examine the performance characteristics of a novel test for detecting acute rejection (AR) in heart transplant recipients. The results showed that the dd-cfDNA test had good accuracy in detecting AR, indicating its potential as a noninvasive test for AR in heart transplant recipients.
BACKGROUND: Endomyocardial biopsy (EMB), the reference surveillance test for acute rejection (AR) in heart transplant (HTx) recipients, is invasive, costly, and shows significant interobserver variability. Recent studies indicate that donor-derived cell-free DNA (dd-cfDNA), obtained non-invasively from blood, is associated with AR and could reduce the frequency of EMB surveillance. The aim of this study was to examine the performance characteristics of a novel test for detecting AR in adult HTx recipients. METHODS: Plasma samples with contemporaneous EMBs were obtained from HTx recipients. A clinically available SNP-based massively multiplexed-PCR dd-cfDNA assay was used to measure ddcfDNA fraction. dd-cfDNA fractions were compared with EMB-defined rejection status and test performance was assessed by constructing ROC curves and calculating accuracy measures. RESULTS: A total of 811 samples from 223 patients with dd-cfDNA testing and contemporaneous EMB were eligible for the study. dd-cfDNA fraction was significantly higher in AR (median 0.58%, IQR, 0.13%-1.68%) compared to non-AR (median 0.04%, IQR, 0.01%-0.11%, p(c) < 0.001). ROC analysis produced an area under the curve (AUC-ROC) of 0.86 (95% CI, 0.77-0.96). Defining samples with dd-cfDNA fraction >= 0.15% as AR yielded 78.5% sensitivity (95% CI, 60.7%-96.3%) and 76.9% specificity (95% CI, 71.1%-82.7%). Positive and negative predictive values were 25.1% (95% CI, 18.8%-31.5%) and 97.3% (95% CI, 95.1%-99.5%) respectively, calculated using the cohort AR prevalence of 9.0% (95% CI, 5.3%-12.8%) with adjustment for repeat samples. CONCLUSIONS: This novel dd-cfDNA test detects AR in HTx recipients with good accuracy and holds promise as a noninvasive test for AR in HTx recipients. (C) 2022 The Author(s). Published by Elsevier Inc. on behalf of International Society for Heart and Lung Transplantation.
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