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Published on: August 2, 2024
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Multimodal molecular testing provides prognostic value for heart transplant recipients
Jeff Teuteberg1, Snehal Patel2, David A Baran3
1Divison of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA.
Summary
Dual positive gene expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA) testing predicts graft dysfunction and cardiovascular death in heart transplant recipients. This multimodal molecular testing offers prognostic information beyond histology.
Area of Science:
- Cardiology
- Transplant Immunology
- Molecular Diagnostics
Background:
- Multimodal molecular testing, including gene expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA), is increasingly utilized for heart transplant rejection surveillance.
- Limited data exists on the combined predictive capability of GEP and dd-cfDNA for future clinical events post-transplant.
Purpose of the Study:
- To evaluate the joint ability of GEP and dd-cfDNA to predict graft dysfunction (GD) and cardiovascular (CV) death in heart transplant recipients.
- To assess the prognostic value of combined GEP/dd-cfDNA results in predicting clinical outcomes.
Main Methods:
- Analysis of 1934 heart transplant recipients from the Surveillance HeartCare Outcomes Registry.
- Risk assessment based on the most abnormal GEP/dd-cfDNA result between months 2-6 post-transplant for subsequent 12-month GD and CV death incidence.
- Evaluation of 30-day GD and CV death incidence following individual GEP/dd-cfDNA results from 2 months to 5 years post-transplant.
Main Results:
- Patients with dual positive GEP/dd-cfDNA results (GEP+/dd-cfDNA+) showed the highest incidence of GD or CV death (15.5%) in the year following months 2-6 post-transplant (HR 1.59, p=0.017).
- Even without histological evidence of rejection, the GEP+/dd-cfDNA+ group had a higher incidence of GD or CV death (14.6%) compared to other groups (5.1-8.7%, p=0.039).
- A single GEP+/dd-cfDNA+ result increased the 30-day incidence rate of GD or CV death threefold (adjusted IRR 3.12, p=0.007) compared to GEP-/dd-cfDNA- results.
Conclusions:
- Dual positive GEP and dd-cfDNA results identify heart transplant recipients at increased risk for subsequent graft dysfunction and cardiovascular death.
- Circulating multimodal molecular evidence of rejection provides prognostic information that is independent of and not detected by histology.
- These findings support the utility of combined GEP and dd-cfDNA testing for enhanced risk stratification in heart transplant surveillance.
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