Abstract Body (Do not enter title and authors here): Background
After heart transplantation, endomyocardial biopsy (EMBx) is the standard diagnostic modality for acute rejection (AR). However, EMBx is invasive with some limitations to conventional histological interpretation. Non-invasive assessments, such as cardiac magnetic resonance Imaging (MRI) and donor-derived cell-free DNA (dd-cfDNA) assays, have emerged as viable methods for diagnosing acute rejection. This study aims to assess the diagnostic performance of cardiac MRI and dd-cfDNA for evaluating acute cardiac transplant rejection.
Method
PubMed and Web of Science were searched for relevant publications reporting on the use of dd-cfDNA or cardiac MRI for the detection of acute cardiac transplant rejection defined as acute cellular rejection (ACR) and/or antibody-mediated rejection (AMR), with EMBx as the reference standard. Pooled sensitivity, specificity, and hierarchical modeling-based summary receiver-operating characteristic (sROC) curves were calculated.
Results
Out of 725 screened papers, 23 studies were included (10 studies with cardiac MRI and 13 studies with dd-cfDNA). Five studies considered only ACR as a rejection criterion, while eighteen studies included both ACR and AMR. The sensitivity and specificity for detecting acute transplant rejection were 0.68 (95% CI: 0.58-0.77) and 0.82 (95% CI: 0.74-0.88) for dd-cfDNA, and 0.79 (95% CI: 0.66-0.88) and 0.72 (95% CI: 0.62-0.81) for cardiac MRI. The areas under the hierarchical modeling-based sROC curves were 0.82 (95% CI: 0.78-0.85) for dd-cfDNA and 0.82 (95% CI: 0.79-0.85) for cardiac MRI. While there was no significant difference in the sROC between dd-cfDNA and cardiac MRI (p = 0.959), cardiac MRI had significantly higher sensitivity (p < 0.001) and dd-cfDNA had significantly higher specificity (p = 0.001) (Figure)
Conclusion
dd-cfDNA and cardiac MRI demonstrated comparable high diagnostic accuracy for acute cardiac transplant rejection. Given the high sensitivity of cardiac MRI and the high specificity of dd-cfDNA, combining these two non-invasive modalities may provide an effective screening strategy to detect acute cardiac transplant rejection and reduce the need of EMBx.