Introduction

The role of circulating DSA in addition to traditional cardiovascular risk factors, in the development of accelerated CAV have not been demonstrated. We investigated the role of circulating DSA in the development of accelerated CAV in a large prospective observational cohort of heart transplant recipients.

Methods

This was an observational prospective cohort study, including 723 heart transplant patients from 2 centers between 2004 and 2011. Participants were screened for traditional cardiovascular risk factors, circulating anti-HLA antibodies, and their properties (specificity, HLA class, strength). All patients underwent prospective heart allograft biopsies and angiogram with assessment of CAV lesions. We assessed the independent determinants of CAV at 3 years after transplantation.

Results

A total of 145 patients (20.1%) had circulating DSA at the day of transplantation. 170 patients (23.5%) experienced acute rejection in the first 3 years post-transplant with 128 cases (17.7%) of grade 2R ACR and 83 cases (11.5%) of antibody-mediated rejection (ISHLT pAMR+). At 3 years post transplant 29.7% of patients had CAV (20.8%, 7.4% and 1.5% with CAV scores of 1, 2 and 3 respectively). After adjusting on traditional risk factors (recipient age, primary heart disease, gender, hypertension, tobacco use, dyslipidemia, diabetes mellitus, BMI), donor factors (age, gender, BMI, cause of death), transplant characteristics (cold ischemia time, center, emergency heart transplantation), immunological parameters (circulating DSA at the day of transplantation and acute rejection post transplant), and CMV disease occurence post-transplant, the independent determinants of CAV at 3 years were: donor age (RR=1.05; 95%CI=1.03-1.08), recipient dyslipidemia (RR=2.1; 95%CI= 1.02-4.29), presence of circulating DSA at the day of transplantation (RR=2.45 95%CI=1.45-4.12). Occurrence of pAMR2 post-transplant was also a strong and independent factor associated with CAV at 3 years post-transplant (RR=3.51, IC95%=1.84-6.69). This group showed decreased patient survival (HR=1.8 p=0.01).

Conclusion

Circulating DSA are major determinants of severe arteriosclerosis, independent of traditional cardiovascular risk factors. Antibody-mediated CAV is associated with reduced patient survival.

CITATION INFORMATION: Bories M, Varnous S, Lefaucheur C, Rouvier P, Guillemain R, Bruneval P, Duong Van Huyen J, Loupy A. Donor-Specific Antibody Is a Major Independent Predictor of Accelerated Heart Allograft Vasculopathy (CAV). Am J Transplant. 2016;16 (suppl 3).

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