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Redefining Cardiac Antibody-Mediated Rejection With Donor-Specific Antibodies and Graft Dysfunction
Jason F Goldberg1,2,3, Xin Tian3,4, Ann Bon5
1Inova Schar Heart and Vascular, Falls Church, VA (J.F.G., P.S.).
Circulation. Heart Failure
|November 25, 2024
Summary
Heart transplant recipients with donor-specific antibodies (DSAs) and graft dysfunction, even without biopsy-confirmed rejection, face increased risks. Identifying these patients early is crucial for better outcomes and survival.
Area of Science:
- Cardiology
- Transplant Immunology
- Biomarker Research
Background:
- Heart transplant recipients with donor-specific antibodies (DSAs) are at higher risk for antibody-mediated rejection.
- Many patients with graft dysfunction and DSAs lack definitive evidence of antibody-mediated rejection on endomyocardial biopsy (EMB).
Purpose of the Study:
- To evaluate the clinical significance of donor-specific antibodies (DSAs) combined with graft dysfunction in heart transplant recipients.
- To assess the association between antibody-mediated rejection categories and long-term clinical outcomes, including death and left ventricular dysfunction.
Main Methods:
- A prospective, multicenter study involving serial endomyocardial biopsies (EMB), echocardiograms, DSA monitoring, and donor-derived cell-free DNA (dd-cfDNA) evaluations.
- Outcomes were defined as positive pathological antibody-mediated rejection (pAMR+) or DSA with left ventricular (LV) dysfunction (LVEF drop ≥10% to ≤50%).
- Cox regression analysis was used to determine the association between rejection categories and adverse clinical outcomes.
Main Results:
- Donor-specific antibodies (DSAs) were present in 40% of patients.
- Median %dd-cfDNA was significantly higher in patients with pAMR+ or DSA+/LV dysfunction compared to those without.
- Both pAMR+ and DSA+/LV dysfunction were significantly associated with increased risk of death or prolonged LV dysfunction, with DSA+/LV dysfunction showing a substantially higher hazard ratio.
Conclusions:
- Expanding the definition of antibody-mediated rejection to include patients with DSAs and concurrent allograft dysfunction is critical.
- Patients with DSAs and graft dysfunction, even without biopsy-proven rejection, are at significant risk for adverse outcomes, including death.
- Early identification of these high-risk patients is essential for improved management and long-term survival in heart transplantation.
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