BIOLOGIC AND THERAPEUTIC ADVANCES IN HEART TRANSPLANTATION II

O.V. Orlova¹, A.O. Shevchenko², E.N. Kazakov¹, A.J. Kormer¹, O.P. Shevchenko^1
1Heart Transplantation, Federal V.Shumakov Research Center of Transplantology and Artificial Organs, Moscow/RUSSIAN FEDERATION, ²Cardiology, Russian State Medical University, Moscow/RUSSIAN FEDERATION

Body: Introduction. Long-term survival following heart transplantation is limited by cardiac allograft vasculopathy (CAV). Elevated plasma levels of homocystein (Hcy), anti-cardiolipin antibodies (aCL) and soluble CD40 ligand (sCD40L) are common in heart transplant recipients and have been shown as independent risk factors for ischemic heart disease and thrombosis. The study was aimed to determine the role of Hcy, aCL and sCD40L in development of CAV in heart transplant recipients. Methods. We studied 70 heart transplant recipients from 1 to 16 years after heart transplantation (HTx) (45.5±7.5 years, 61 men and 9 women) and 46 patients awaiting HTx (37.5±9.5 years, 41 men and 5 women). Immunosuppressive therapy included steroids, cyclosporine (or tacrolimus), and mycophenolate mofetil. Plasma levels of Hcy («Axis-Shield», UK), IgG- aCL (IgG-aCL, «Orgentec diagnostika GmbH», Germany), and sCD40L («Bender MedSystems», Austria) were measured by ELISA. Results. Hcy and aCL plasma levels in heart transplant recipient were significantly higher when compared with patients awaiting HTx (20.6+11.5 μmol/l, 28.7+10.7 U/ml vs. 14.8+15.3 μmol/l, 23.5+10.5 U/ml resp., p=0.0016 and p=0.009). sCD40L level did not differ among patients before and after HTx (0.4+0.3 and 0.52+0.4 ng/ml, resp.). Plasma levels of Hcy, IgG-aCL and sCD40L did not correlate with age, sex, total cholesterol, triglycerides, plasma levels of CRP, IL-6, TNF-α, neopterin, and placenta growth factor. Positive significant correlations were found between Hcy and aCl (r=0.65, p=0.0018), sCD40L and Hcy (r=0.55, p=0.0012). In heart transplant recipients Hcy and aCL plasma levels were higher in patients with CAV (22.9+9.8 μmol/l and 34.8+15.5 U/ml) than in those without CAV (11.5±5.0 μmol/l and 15.6±7.0 U/ml resp., p=0.0012). sCD40L level did not differ among patients with CAV (0.52+02 ng/ml) and without CAV (0.4+0.2 ng/ml). The Kaplan-Meier test showed better survival in patients with pretransplant sCD40L levels below median (0.4 ng/ml) (90% vs 16.7%, at 108 months of follow-up, p=0.0018) and\\or low pretransplant aCL levels (<23 U/ml) (100% vs 12.8%, at 108 months of follow-up, p=0.0015), but not in patients with low Hcy level (<15 μmol/l) (67% vs 58% at 108 months of follow-up, p=0.165). Conclusion. These data demonstrate that elevated plasma levels of Hcy and aCL in heart transplant recipients are associated with CAV. High levels of sCD40L and aCL in patient awaiting HTx are risk factors for the development of CAV after HTx.

Disclosure: All authors have declared no conflicts of interest.