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Lack of Usefulness of Donor-Derived Cell-Free DNA as a Biomarker for Cardiac Allograft Vasculopathy: A Prospective
Marta Jiménez-Blanco Bravo1,2,3, Laura Pérez-Gómez1,3, Francisco J Hernández-Pérez1
1Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain.
Insights
Donor-derived cell-free DNA (dd-cfDNA) was evaluated as a non-invasive biomarker for cardiac allograft vasculopathy (CAV) in heart transplant recipients. dd-cfDNA did not prove effective in diagnosing CAV or avoiding surveillance coronary angiograms.
Area of Science:
- Cardiology
- Transplantation Immunology
- Biomarker Discovery
Background:
- Cardiac allograft vasculopathy (CAV) is a significant cause of long-term morbidity and mortality in heart transplant recipients.
- Current diagnostic methods, such as surveillance coronary angiograms, are invasive.
- There is a critical need for non-invasive biomarkers to monitor CAV.
Purpose of the Study:
- To assess the efficacy of donor-derived cell-free DNA (dd-cfDNA) as a non-invasive biomarker for diagnosing cardiac allograft vasculopathy (CAV).
- To determine if dd-cfDNA levels can obviate the need for surveillance coronary angiograms in heart transplant patients.
Main Methods:
- Prospective measurement of dd-cfDNA levels in 94 heart transplant recipients more than one year post-transplant.
- Correlation of dd-cfDNA levels with the presence and severity of CAV, as determined by coronary angiography.
- Comparison of dd-cfDNA levels between patients with and without CAV, and between stable and progressive CAV.
Main Results:
- No significant difference in dd-cfDNA levels was observed between patients with and without CAV (p=0.059).
- dd-cfDNA levels did not differentiate between stable and progressive CAV (p=0.76).
- NTproBNP levels showed an association with CAV severity (p=0.017), but dd-cfDNA did not correlate with NTproBNP.
Conclusions:
- Donor-derived cell-free DNA (dd-cfDNA) is not a suitable biomarker for diagnosing cardiac allograft vasculopathy (CAV).
- dd-cfDNA cannot replace surveillance coronary angiograms for CAV detection in heart transplant recipients.
- Further research may explore other biomarkers, such as NTproBNP, for CAV assessment.
Background:
Cardiac allograft vasculopathy (CAV) remains a major cause of morbidity and mortality among long-term heart transplant recipients. There is an unmet need for a non-invasive biomarker of CAV that could obviate the need to perform surveillance coronary angiograms in these patients. Our aim was to evaluate the performance of Donor-derived Cell Free DNA (dd-cfDNA) as a biomarker of CAV.
Methods:
We prospectively measured dd-cfDNA levels in all patients undergoing routine coronary angiography >1 year after heart transplant at a single center. Endpoints included the association between dd-cfDNA levels and the presence CAV, according to several prespecified criteria.
Results:
We included 94 heart transplant recipients, a median of 10.9 years after transplant. Coronary angiogram revealed CAV0, CAV1, CAV2, and CAV3 in 61, 19, 14, and 6% of patients, respectively. Comparison of dd-cfDNA levels in patients with CAV0 and CAV1-2-3 (primary end-point) did not show significant differences (0.92%, IQR 0.46-2.0 vs. 0.46%, IQR 0.075-1.5, p = 0.059), nor did the comparison between patients with stable CAV (no new coronary lesions since previous angiogram, n = 77) and progressive CAV (n = 17); dd-cfDNA values 0.735% (IQR 0.195-2.0) vs. 0.9% (IQR 0.12-1.8), p = 0.76. However, we found an association between NTproBNP levels and CAV degree (p = 0.017). Dd-cfDNA levels did not correlate with NTproBNP (ρ = -0.095).
Conclusion:
In this study, dd-cfDNA did not perform as a useful biomarker to avoid surveillance coronary angiograms for CAV diagnosis.
Clinical Trial Notation:
Potential Role of Donor-derived Cell Free DNA as a Biomarker in Cardiac Allograft Vasculopathy, NCT04791852.
