Usefulness of Asymmetric Dimethylarginine to Predict Outcomes After Heart Transplantation

Asymmetric dimethylarginine (ADMA) is a key mediator of vascular homeostasis and an independent predictor of the development of accelerated cardiac allograft vasculopathy after heart transplantation. However, its association with clinical outcomes in heart transplant recipients has not been described. Plasma levels of ADMA were assayed within 8 weeks following transplantation (baseline) using a competitive enzyme-linked immunosorbent assay. The primary end point was the composite of nonfatal myocardial infarction, percutaneous coronary intervention, retransplantation, or death at 5-year follow-up. Kaplan-Meier curves were generated to assess the association between baseline ADMA levels (stratified at 0.70 µM, a previously established cutoff) and cumulative event-free survival. Multivariate Cox regression was performed to adjust for other candidate predictors. In 69 heart transplant recipients at Stanford, the primary end point occurred in 11 patients (16%)-4 percutaneous coronary intervention, 1 retransplant, and 6 deaths-during 5-years follow-up. Patients with baseline ADMA ≥0.70 µM had lower cumulative 5-year event-free survival (77% vs 93%, p = 0.059). In multivariate Cox analysis, baseline ADMA was the only significant predictor of the primary end point (hazard ratio 1.33, 95% confidence interval 1.03 to 1.72 per 0.1 µM; p = 0.031). This association remained significant even after restricting the end point to death or retransplantation (hazard ratio 1.48, 95% confidence interval 1.12 to 1.97 per 0.1 µM; p = 0.006). In conclusion, elevated baseline plasma levels of ADMA independently predicted 5-year clinical outcomes after heart transplantation, suggesting that ADMA has potential prognostic value in the heart transplant arena.