BACKGROUND: Antibody-mediated rejection (AMR) after heart transplantation has recently been defined as a pathological diagnosis. This would include immunopathology which includes C4d staining and histologic findings. The presence of positive C4d staining alone in heart biopsies has been contentious in terms of its clinical relevance. There has been concern that C4d staining alone in asymptomatic patients may impact clinical outcome. Therefore, we chose to review our patients with asymptomatic C4d staining and their clinical outcomes.

METHOD: Between 2001 and 2010, we reviewed 5,390 heart transplant biopsies (in 367 patients who survived 1 year) for C4d staining. Patients with treated AMR were excluded from this study. Patients were divided into 3 groups: No C4d staining (n = 254 patients), isolated C4d group (1 episode of C4d staining) (n = 75 patients), and persistent C4d staining group (>1 episode of C4d staining) (n = 38 patients). Outcomes included 3-year actuarial survival and 3-year freedom from cardiac allograft vasculopathy (CAV: defined as any angiographic stenosis ≥ 30%).

RESULTS: Patients with persistent C4d staining had significantly lower freedom from CAV compared to the no C4d group and isolated C4d groups (76% vs. 89% and 91%, respectively, p = 0.038). 3-Year survival in the persistent C4d group was similar to the no c4d group and isolated C4d groups (84% vs. 93% and 93%, p = 0.120). The average number of C4d staining biopsies in the persistent C4d staining group was 2.7±1.2 biopsies.

CONCLUSION: Persistent asymptomatic C4d staining in the first year after heart transplantation appears to be a marker for CAV at 3 years. Persistent C4d staining may represent a continuing antibody-mediated process leading to an increased development of CAV. Further studies are being pursued.

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