Elevated Donor-Derived Cell-Free DNA Levels Are Associated With Reduced Myocardial Blood Flow but Not Angiographic
Cathrine M Moeller1, Daniel Oren1, Andrea Fernandez Valledor1
1Milstein Division of Cardiology, Department of Medicine, NewYork-Presbyterian/Columbia University Irving Medical Center (C.M.M., D.O. A.F.V., G.R., E.M. DeFilippis, S.R., Y.M., E.M. Donald, D.L., E.F.L., K.T.O., S.H.L., J.K.R., J.A.F., F.L., G.T.S., N.U., K.J.C.).
Insights
Donor-derived cell-free DNA (dd-cfDNA) levels are not elevated in heart transplant recipients with cardiac allograft vasculopathy (CAV). However, elevated dd-cfDNA is significantly associated with reduced myocardial blood flow (MBF) in these patients.
Area of Science:
- Cardiology
- Transplantation Immunology
- Biomarker Discovery
Background:
- Cardiac allograft vasculopathy (CAV) impairs myocardial blood flow (MBF) and increases mortality in heart transplant (HT) recipients.
- The association between donor-derived cell-free DNA (dd-cfDNA) and CAV, especially without rejection, remains unclear.
- This study investigated the link between dd-cfDNA and CAV with reduced MBF.
Purpose of the Study:
- To test the hypothesis that CAV with reduced MBF (RMBF) is associated with elevated dd-cfDNA.
- To evaluate the utility of dd-cfDNA as a biomarker for CAV and impaired MBF post-HT.
Main Methods:
- Retrospective review of 256 HT recipients undergoing dd-cfDNA testing and CAV screening.
- Patients were categorized by angiographic CAV diagnosis and MBF reserve assessed via cardiac positron emission tomography.
- RMBF was defined as an MBF reserve ≤2; elevated dd-cfDNA was defined as ≥0.12%.
Main Results:
- No significant difference in dd-cfDNA prevalence or levels was found between patients with and without angiographic CAV.
- Patients with RMBF showed significantly higher dd-cfDNA prevalence (51% vs. 27%) and median levels (0.81% vs. 0.25%) compared to those with normal MBF.
- Ischemic etiology of heart failure was more common in the RMBF group.
Conclusions:
- Angiographic CAV in HT recipients is not associated with elevated dd-cfDNA levels.
- Significantly elevated dd-cfDNA levels and prevalence were observed in patients with reduced MBF, suggesting a potential role in detecting functional impairment.
- dd-cfDNA may serve as a non-invasive marker for assessing myocardial blood flow abnormalities in HT recipients.
Background:
Cardiac allograft vasculopathy (CAV) leads to impaired myocardial blood flow (MBF), increasing the risk of cardiovascular death or retransplant among heart transplantation (HT) recipients. Data on elevation in donor-derived cell-free DNA (dd-cfDNA) and CAV in the absence of rejection are mixed. We sought to test the hypothesis that CAV with reduced MBF (RMBF) is associated with elevated dd-cfDNA.
Methods:
A retrospective review was conducted on HT recipients at a high-volume center who underwent dd-cfDNA testing between September 2019 and November 2022. Inclusion criteria included undergoing CAV screening with cardiac positron emission tomography scans and coronary angiograms. Patients were grouped by the presence of angiographic CAV diagnosis and MBF reserve evaluated through cardiac positron emission tomography. The latter was subdivided into normal MBF or RMBF, with RMBF defined as an MBF reserve ≤2. Elevated dd-cfDNA was defined as ≥0.12%.
Results:
Two hundred fifty-six HT recipients were included (median age, 55 years; 27.6% female; median, 8 years [interquartile range (IQR), 5-14] post-HT). Ischemic etiology of heart failure was more prevalent in the RMBF group (36%) compared with the normal MBF group (20%; P=0.02). The prevalence and magnitude of a positive dd-cfDNA test with angiographic CAV (29%; median, 0.26% [IQR, 0.15%-0.62%]) were not significantly different from those without CAV (30%; P=0.94; median, 0.31% [IQR, 0.17%-0.71%]; P=0.38). However, RMBF patients exhibited significantly higher dd-cfDNA prevalence and levels (51%; median, 0.81% [IQR, 0.48%-1.11%]) compared with normal MBF patients (27%; P<0.001; median, 0.25% [IQR, 0.15%-0.52%]; P<0.001).
Conclusions:
HT recipients with angiographic CAV had similar dd-cfDNA levels and rates as those without. Notably, dd-cfDNA levels and rates were significantly elevated in patients with RMBF assessed by positron emission tomography compared with those with normal MBF.
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