S136 Abstracts Background: New onset diabetes (NOD), a frequent complication after heart, transplantation (HT) has been shown to be related to immunosuppression (IS). The correlation of obesity with NOD, after controlling for immunosuppressive medication dose, is unknown. Objective: To determine the incidence of obesity after HT, its relation with total steroid dose and its correlation with the development of NOD. Patients and Methods: Retrospective analysis of 327 patients with the following characteristics: older than 18 years, ⬎ 1 year survival after HT and diabetes free before HT. We estimate the presence of obesity according to the BMI: 30- 34 Kg/m2 mild obesity (MiO), 35– 40 Kg/m2 moderate obesity (MoO), 40 – 45 Kg/m2 severe obesity (SO), ⬎ 45 Kg/m2 morbid obesity (MorO). We determine the prevalence of NOD at 1, 5 and 10 years after HT. Results: Mean age was 55 years, 83% males. Prevalence of MiO, MoO, SO and MorO at 1year after HT was 19,1%, 3,9%, 0,3%, 0% respectively. At 5 years 25,6%, 5,8%, 1,3% and 1,3% respectively. At 10 years 25,9%, 3,7%, 3,7% and 3,7% respectively. After a mean observation period of 77 months, 24,8% of patients developed NOD. A regression analysis was performed to identify independent predictors of developing NOD at 5 years. The statistical analysis showed BMI as an independent predictor of developing of NOD at 5 years after adjusting for steroid cumulative dose, IS regime, sex and age (OR 1.11; CI 1.03⫺ 1.21; p⫽ 0.01), no other independent predictors were found. Conclusion: In a large cohort of HT recipients, the prevalence of moderate obesity or more (BMI⬎ 30) at 1, 5 and 10 years after HT is 23,4%, 34,0% and 37,0% respectively. An increased BMI is associated with NOD development at 5 years after heart transplantation. 266 INCIDENCE AND POSSIBLE DETERMINANTS OF SURVIVAL BEYOND TWENTY YEARS AFTER ORTHOTOPIC HEART TRANSPLANTATION S.M. Haj-Yahia,1,2,3 A.G. Mitchell,1 E.J. Birks,1,2 J. Mirhossaini,1 J. Smith,2 G. Santisi,1 R. Radley-Smith,1 M.H. Yacoub,2,3 N.R. Banner,1,3 A. Khaghani,1,2,3 1Cardiothoracic Transplantation & Mechanical Circulatory Support, Royal Brompton & Harefield Hospital, London, United Kingdom; 2The Magdi Yacoub Institute, Harefield Heart Science Centre, London, United Kingdom; 3 National Heart & Lung Institute, Imperial College of Science, Technology and Medicine, London, United Kingdom Survival beyond twenty years after heart transplantation has been reported. However, its incidence and possible determinants remain ill defined. We analysed the outcome of 151 patients who underwent orthotopic heart transplantation between 1980 and 1985 at our institution. Detailed records of 107 patients were available. 40 patients (26.4%) lived longer than 20 years, (Gp A), and 67 (44.3%) survived less than 20 years (Gp B). Pre and post transplant patient and donor related factors were analysed. Results: Mean survival rate after transplant was 23.1 (20 –25) yrs for Gp A and 9.03 (0 –17) yrs for Gp B. Mean age at transplant was 40.0 (10 – 60) yrs for Gp A and 44.1 (11–50) yrs for Gp B. 82.5% were males (n ⫽33) in Gp A versus 94 % (n⫽63) in Gp B. Donor mean age was 22.2 (9 – 40) versus 28.36 (11–50) yrs respectively. Male donors accounted for 62.5% and 70.2% in Gp A and B respectively. Ischemia time and indications for transplant were similar in both groups (Ischemic cardiomyopathy 42.5% in Gp A versus 45% in Gp B). Combined immunosupression protocol including cyclosporin was used in 85% and 62% in Gp A and B respectively. Among the longest survivors were 2 of 40 (5%) patients transplanted prior to the introduction of cyclosporin. Post transplant serious infections, end stage renal failure and graft vasculopathy were more frequent in the non survivors (38.8% v. 20%, 23% v. 10% and 73.1% v 32.5% respectively). Non skin malignancy was noted in 2 cases (5%) in The Journal of Heart and Lung Transplantation February 2006 group A and in one case in Gp B (1.4%). Cardiac death was the leading cause of death in Gp B (67.1%). In Gp A, 30 patients (75%) were in NYHA class I and II while only one patient was in class IV (2.5%). Conclusion: It is concluded that a significant number of heart transplant patients can survive beyond twenty years. Cyclosporin treatment, younger age at transplant, younger donor age and lower rate of infections, graft vasculopathy and renal failure may play a role. 267 IMPACT OF CYCLOSPORINE C2 MONITORING ON RENAL FUNCTION IN DE NOVO HEART TRANSPLANT PATIENTS: 10YEAR EXPERIENCE M. Cantarovich, N. Giannetti, M. deB. Edwardes, G. Fontaine, R. Chartier, E. Cyr, R. Cecere, Medicine, Cardiovascular and Thoracic Surgery, Epidemiology and Nursing, McGill University Health Center, Montreal, QC, Canada Purpose: To report the impact of C2 monitoring on renal function in de novo heart transplant (HTx) pts receiving CsA microemulsion. Methods: We included pts who received CsA and who survived 1-yr post-HTx. Pts were divided according to different periods. Period 1 (Jan 88-May 96): 117 pts (52⫾10 yrs) received ATG-induction, steroids, azathioprine, CsA (Sandimmune) and were monitored with CsA trough (C0) levels (ng/ml), 0 –3 months (mo.): 200 – 400, 4 – 6 mo.: 150 –250, 7–12 mo.: 100 –200; Period 2 (June 96-May 97): 13 pts (54⫾8 yrs) received ATG-induction, steroids, mycophenolate mofetil (MMF), CsA microemulsion (Neoral) and were monitored with C2 (0 –3 mo.: 600 – 800, 4 – 6 mo.: 500 –700, 7–12 mo.: 400 – 600); Period 3 (June 97-May 98): 10 pts (51⫾8 yrs) received ATG-induction, steroids, MMF, CsA microemulsion and were monitored with C0 (idem Period 1) and C2 was simultaneously measured; Period 4 (June 98- May 01): 17 pts (51⫾13 yrs) received ATG-induction, steroids, MMF, CsA microemulsion and were monitored with C2 (idem Period 2); Period 5 (June 01-July 04): 9 pts (54⫾15 yrs) received daclizumabinduction, steroids, MMF, CsA microemulsion and were monitoredwith C2 (0 –3 mo.: 1100 –1300, 4 – 6 mo.: 900 –1100, 6 –12 mo.: 600 – 800). CrCl (ml/min) According to Different Strategies Used for CsA Dose Monitoring Period Period Period Period Period 1 2 3 4 5 Pre-Tx 1-month 3-months 12-months Average* % change % change Pre-Tx vs Pre-Tx vs 1-month 12-months 73 ⫾ 28 64 ⫾ 24 74 ⫾ 32 84 ⫾ 43 72 ⫾ 25 74 ⫾ 26 65 ⫾ 18 78 ⫾ 26 98 ⫾ 34 62 ⫾ 13 70 ⫾ 23 70 ⫾ 25 78 ⫾ 27 93 ⫾ 37 63 ⫾ 19 69 ⫾ 24 79 ⫾ 21 79 ⫾ 36 86 ⫾ 34 65 ⫾ 24 70 ⫾ 22 74 ⫾ 20 79 ⫾ 28 90 ⫾ 33 64 ⫾ 18 8% 19% 13% 28%*** ⫺7.3%**** 2% 32%** 14% 18% ⫺7.6%***** ⴱ Weighted average of the CrCl between pre- and 12-months post-HTx, ⴱⴱp ⫽ 0.01, ⴱⴱⴱp ⫽ 0.04 vs Period 1, ⴱⴱⴱp ⫽ 0.02 vs Period 4, ⴱⴱⴱⴱⴱp ⫽ 0.04 vs Period 2. Conclusion: CsA monitoring with C2 contributes to the preservation of renal function during the first year post-HTx. The greatest preservation was observed in Periods 2 and 4 using lower C2 target ranges. Disclosure: The author is a consultant for Hoffman LaRoche, Astellas, Novartis, Wyeth. 268 CARDIOTROPIC VIRUSES AND MICROVASCULOPATHY AFTER HEART TRANSPLANTATION: PRELIMINARY INSIGHTS FROM A PROSPECTIVE STUDY N.E. Hiemann,1 K. Klingel,2 E. Wellnhofer,3 J. Hug,3 S. Dreysse,3 M. Chevallerie,1 H.B. Lehmkuhl,1 C. Knosalla,1 R. Hetzer,1 The Journal of Heart and Lung Transplantation Volume 25, Number 2S R. Kandolf,2 R. Meyer,1 1Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany; 2Molecular Pathology, University Hospital of Tuebingen, Tuebingen, Germany; 3Cardiology, Deutsches Herzzentrum Berlin, Berlin, Germany Purpose: Viral infections have prognostic impact for the development of epicardial graft vessel disease (GVD) after heart transplantation (HTx). However their importance for the development of early microvascular alterations still remains unclear. Material and Methods: Prospective analysis of right ventricular endomyocardial biopsies (Bx) from 58 consecutive patients (mean⫾SEM age 51⫾2 years, 52 males) four weeks after HTx was performed. In Bx stained with hemalaun and eosin, classification of acute cellular rejection ([ACR] ISHLT) and the Quilty phenomenon (invasive vs. non-invasive) and diagnosis of obstructive microvasculopathy were performed (endothelial cell swelling and/or medial thickening). Bx were evaluated for viral infections (HCMV, EBV, HHV6/8, VZV, HSV 1/2, PVB19, entero-/adenovirus) by nested PCR. Results: Obstructive microvasculopathy was caused only by medial thickening in 37% (21/57) of Bx. Mono-viral infections were more frequent in Bx without microvasculopathy and viral double infections were more frequent in Bx with microvasculopathy (p⫽0.005) but in regression analysis this factor was not significant. Bx with evidence of the Quilty phenomenon (7/57) were more frequently positive for PVB19 (71% [5/7] vs. 20% [9/46] p⫽0.005) and showed increased evidence of viral infection (86% [6/7] vs. 59% [27/46], p⫽0.001). Evidence of Quilty and microvasculopathy was independent of ACR (ISHLT 1A 19% [11/57], 1B 4% [2/57], 3B 4% [2/57]). Conclusions: These results do not sustain the hypothesis that microvasculopathy early after HTx is triggered by infections with cardiotropic viruses. Further follow-up will allow us to assess the impact of virus infection on later microvascular alterations. Disclosure: This study was supported by the German Research Foundation. 269 INFLUENCE OF PRETRANSPLANT AMIODARONE ON POSTTRANSPLANT CYCLOSPORINE PHARMACOKINETICS AND HEART RATE J.A. Crompton,1 M.B. Hagan,2 J. Stehlik,2 F. Bader,1 E.M. Gilbert,1 1 Cardiac Transplant, University of Utah Hospital, Salt Lake City, UT; 2Veterans Affairs Medical Center, Salt Lake City, UT Background: Amiodarone (AMIO) is a cytochrome P4503A4 (3A4) inhibitor with a prolonged half-life of approximately 1 month or more following long-term administration. The use of AMIO in end-stage chronic heart failure patients (pts) before heart transplant (tx) is relatively common. Cyclosporine (CsA), a 3A4 substrate, is a routinely used immunosuppressant in heart tx recipients. Because of its long half-life, there is a potential for AMIO to interact with CsA after tx, in addition to having prolonged pharmacodynamic effects. Methods: Pts that received AMIO pre-tx and survived the first 6 months post-tx between 1989 –2004 were included. Post-tx pts on medications known to interact with CsA were excluded. Results: 12 pts met inclusion criteria and were compared to 12 historical controls. Weight-based dose-adjusted CsA level was not significantly different in pts exposed to AMIO pre-tx as compared to pts not treated with AMIO—see table 1. Interestingly, heart rate in pts not receiving concomitant negative chronotropes was lower in the AMIO group in the first post-tx weeks and equalized thereafter. Abstracts S137 Conclusions: Despite its long half-life, pre-tx AMIO does not significantly alter CsA handling in the post-tx population, although its negative chronotropic effect persists early post-tx. The effect of a more rapid first-stage reduction in plasma concentrations, but prior to the more lengthy terminal portion, within amiodarone’s biphasic elimination may explain the lack of significant interaction with CsA. 270 DIMINISHED PRE-OPERATIVE CREATININE CLEARANCE IS NOT A MARKER FOR POST-OPERATIVE RENAL FAILURE OR MORTALITY IN HEART TRANSPLANT RECIPIENTS V.S. Reddy,1 J. Mykytenko,1 A. Smith,2 B. Hott,2 W. Book,2 S.R. Laskar,2 C. D’Amico,2 J.D. Vega,1 1Cardiac Surgery, Emory University, Atlanta, GA; 2Heart Failure Cardiology, Emory University, Atlanta, GA Introduction: Acute and chronic renal failure are markers for increased morbidity and mortality after cardiac transplantation. Preoperative creatinine clearance (CrCl)⬍50 mL/min has been a relative contraindication to transplant. This study reviewed patients with diminished pre-transplant CrCl and normal renal ultrasounds (US) to evaluate rates of postoperative renal impairment and overall outcomes. Methods & Materials: Between 1/2000 and 8/2005, 118 patients underwent primary cardiac transplantation. Among these, 22 patients had a CrCl⬍50 with a normal renal US. All patients received daclizumab induction therapy. Preoperative CrCl, BUN, and creatinine (Cr), postoperative BUN and Cr, the need for transient or permanent dialysis, and major morbidity and mortality were reviewed. One patient was excluded secondary to right ventricular dysfunction and intra-operative death. Results: Among the 21 patients (mean age⫽48), 13 had heart failure due to idiopathic cardiomyopathy (CM), 5 due to ischemic CM, and 3 due to other etiologies. The mean preoperative CrCl was 40 mL/min (range 25– 49). One patient needed temporary dialysis; none required permanent dialysis. Overall survival was 100%. Median follow up was 24 months. Conclusions: Despite a pre-transplant CrCl⬍50 mL/min, indicative of renal dysfunction, no patient required permanent renal replacement therapy. Patients with a normal renal US and diminished CrCl likely have renal dysfunction secondary to low cardiac output and should be considered appropriate candidates for heart transplantation. Avoiding calcineurin inhibitors until renal function normalizes may be an adjunctive strategy in these patients.