473: CD4+ CD25+ Regulatory T-cell Levels Are Associated with Cardiac Allograft Vasculopathy

Abstracts ations, only 55.7% were histolically moderate or severe (2 or 3 R), the other 44.3% were histologically mild (1 R). Surprisingly, during symptomatic 1 R rejections, all TD and 2D strain velocity parameter changes were equivalent to those found during moderate and severe cellular ARs (2 and 3 R). Conclusions: TD and 2D strain imaging can reveal functionally relevant ARs which are underestimated by morphologic grading. The high prevalence of histologically mild ARs accompanied by myocardial dysfunction and the reversibility of LV dysfunction after therapy suggests the usefulness of TD and 2D strain imaging for improvement of therapeutic decisions. 471 Combined Heart Kidney Retransplant Has Lower Survival than De Novo Transplant V. Cotarlan, N. Uriel, G. Stevens, P.C. Colombo, M. Farr, S. Restaino, M.C. Deng, F. Latif, R. Bijou, Y. Naka, U. Jorde, D. Mancini. Columbia Presbiterian Med Ctr, New York, NY. Purpose: Simultaneous heart and kidney (HK) transplantation is an accepted therapeutic option in patients with both end stage heart and kidney disease. Heart transplant patients who develop chronic rejection and renal failure from calcineurin inhibitors are increasingly considered for combined HK rather than cardiac retransplantation alone. Survival in combined HK retransplantation has not been reported. Methods and Materials: Between 1998 and 2008, 1052 patients underwent cardiac transplantation in our center. Retrospective chart review of all patients who underwent combined HK transplantation was performed. Results: Of 15 patients (mean age 52⫾10, 7 on dialysis) who underwent simultaneous combined HK transplantation, 6 (mean age 54⫾10 years, 4 on dialysis) were receiving their second heart transplant and 9(mean age 51⫾10 years, 3 on dialysis) were first time heart and kidney recipients. All 6 retransplant patients had developed transplant coronary artery vasculopathy (TCAV) and renal failure from calcineurin inhibitors (CNI) after a mean time from first transplant of 12.1⫾3.8 years. All 6 patients survived the first year after retransplant (1 year survival of 100%). However, 4 of 6 retransplant recipients died at 14, 19, 30 and 88 months accounting for a 2 and 5 year survival of 64% and 43%. Cause of death was malignancy (n⫽3) and cardiac dysfunction (n⫽1). In the first time heart/kidney recipients, 2 patients died early at 2 months and 16 months with sepsis and multiorgan failure while the remaining 7 are alive and well with 5 year survival of 73%. Conclusions: Simultaneous combined heart and kidney retransplant recipients have worse survival compared to first time heart/kidney recipients. Increased malignancy risk after retransplantation and prolonged immunosuppression appear to be a significant factor limiting long term success. 472 Are There Differences in Gene Expression as Reflected by Molecular Diagnostic Testing between African-American and Non-African American Cardiac Transplant Recipients? A.J. Hicks,1 T. Rowe,2 J. Patel,1 G. Mwandia,1 S.R. Hankins,1 H.J. Eisen.1 1Drexel University College of Medicine, Philadelphia, PA; 2 Hahnemann University Hospital, Philadelphia, PA. Purpose: African American (AA) cardiac transplant recipients have higher post-transplant mortality rates and rates of acute cellular rejection (ACR). While considerable focus has been on socioeconomic and health care disparity causes for the increased rates of mortality in AA patients, assessment of immunologic responses after transplantation have not been as thoroughly studied. Molecular diagnostic testing (MDT) using gene expression profiling of genes whose expression changes with ACR may provide an approach for assessing differences in immune activation in AA vs. non-AA cardiac transplant recipients. Methods and Materials: We obtained MDT scores from 180 cardiac transplant recipients which included 36 AA and 144 non-AA patients. The mean MDT scores and number of ISHLT 2R episodes were compared between the groups. 36 non-AA patients matched to the AA patients by

S155 age, gender and time after cardiac transplant were identified and MDT scores compared to the AA population. Results: The overall non-AA cardiac transplant group had a mean MDT score of 29.27 compared to a mean of 31.04 for the AA cardiac transplant group (p⫽0.025). The age, gender and time post-transplant matched non-AA patient group had a mean MDT score of 29.37 compared to a mean MDT score of 31.04(p⫽0.068) for the AA patient group. 6/36 (16.2%) of AA patients had ISHLT Grade 2R episodes compared to 6/144 (4.1%) non-AA patients(p⫽0.023). Conclusions: AA cardiac transplant patients are known to have higher post-transplant mortality and rates of ACR. The basis of the higher rates of ACR are felt to be immunologic though validation of this is incomplete. Using MDT to assess immune activation, AA cardiac transplant recipients were found to have significantly greater degrees of immune activation and also had more ISHLT 2R episodes compared to the overall non-AA population. Further work will need to be done to identify specific genes responsible for the differences in immune activation. 473 CD4ⴙ CD25ⴙ Regulatory T-cell Levels Are Associated with Cardiac Allograft Vasculopathy S. Aharinejad,1,2 M. Gmeiner,2 S. Rodler,1 A. Thomas,2 T. Lucas,2 G. Laufer,1 A. Zuckermann,1 M. Grimm.1 1Medical University of Vienna, Vienna, Austria; 2Medical University of Vienna, Vienna, Austria. Purpose: Cardiac allograft vasculopathy (CAV) is the major long-term complication in cardiac allograft recipients, triggered by chronic inflammation. A regulatory subpopulation of T cells (Tregs) expressing CD4 and CD25 contributes to immune suppression and inadequate Treg function is associated with acute cellular graft rejection in heart transplant recipients. Whether Tregs play a role in CAV is unknown. Methods and Materials: We included 54 patients (follow up 114⫾64 months) and determined CAV in 34 patients by angiography. Blood samples were stained with CD3, CD4 and CD25 antibodies and analyzed by flow cytometry. CD3⫹ cells were quantified to normalize Treg numbers to total T-cells within the lymphocyte scatter gate. CD4⫹ CD25⫹ cells were subdivided into CD4⫹ CD25low and CD4⫹ CD25high populations. Results: Total CD3⫹ T-cells were comparable in CAV (65⫾22%) and no CAV (63⫾18%) groups. CAV had more Tregs (13.2⫾5.3%) versus no CAV patients (7.5⫾4.9%)(p⬍0.05). Changes were also found between CAV and no CAV groups in the CD4⫹ CD25low (5.16⫾2.6% vs. 3.08⫾1.9%; p⬍0.05) and CD4⫹ CD25high (7.49⫾5.55% vs. 4.25⫾2.51%; p⬍0.05) populations. Analysis of the relationship between CD4⫹ CD25low to CD4⫹ CD25high showed more CD4⫹ CD25high (p⬍0.05) Tregs in the CAV group. Total CD4⫹ CD25⫹ Treg levels correlated with the mean follow-up after transplantation (rs⫽0.51; p⬍0.01). Conclusions: Circulating Treg levels are associated with CAV. A shift towards CD4⫹ CD25high subpopulation indicates their importance in CAV pathophysiology and may indicate an unexpected role for Tregs in chronic allograft rejection. Increased Treg levels may represent a novel, posttransplant immune compensatory mechanism in CAV. 474 Interaction of CMV Prophylaxis and Pre-Emptive Strategies with Immunosuppressive Therapy: Potential Antiviral Effect of Everolimus L. Potena,1 C. d’Agostino,2 D. Abate,4 G. Magnani,1 F. Baccolini,3 T. Ionico,1 F. Grigioni,1 A. Gambino,2 D. Sgarabotto,5 G. Toscano,2 A. Branzi,1 G. Gerosa.2 1University of Bologna, Bologna, Italy; 2 University of Padua, Padua, Italy; 3University of Bologna, Bologna, Italy; 4University of Padua, Padua, Italy; 5University of Padua, Padua, Italy. Purpose: Cytomegalovirus (CMV) infection frequently affects heart transplant (HT) recipients and may reduce long-term graft function. Prophylactic or pre-emptive use of anti-CMV agents and immunosuppressive drugs modulation may prevent acute CMV manifestations. Besides uncertainties about which is the most effective anti-CMV approach, the interaction of CMV prophylaxis or pre-emption with current immunosuppressive strategies is unexplored.