472 The Problem of Rejection in Redo Heart Transplant Recipients E. Shao 1 , M. Kawano 1 , J. Patel 1 , M. Kittleson 1 , A. Ankrom 1 , K. Kiyosaki 1 , J. Moriguchi, A. Ardehali 2 , J. Kobashigawa 11 David Geffen School of Medicine at UCLA, Los Angeles, CA; 2 David Geffen School of Medicine at UCLA, Los Angeles, CA Purpose: According to the ISHLT registry, survival after redo heart transplant (HTx) is comparable to survival after de novo HTx. Nevertheless, it is not clear if redo HTx patients have more rejection or cardiac allograft vasculopathy (CAV). We sought to address these questions in a single center study where immunosuppression is standardized. Methods and Materials: Between 1994 and 2008, 48 redo HTx were performed. We compared survival, non-fatal major adverse cardiac events (NF-MACE, heart failure, myocardial infarction, percutaneous intervention, pacemaker, stroke, peripheral vascular disease), CAV (30% stenosis by angiogram) and any treated rejection in the first year post-transplant of the 48 redo HTx patients with that of 821 de novo HTx patients in the same period. Results: 40 (83%) patients required redo HTx due to CAV. Demo- graphics (age, gender, ischemic time, CMV mismatch, reason for transplant) of redo and de novo HTx patients were similar. Redo HTx patients were more likely to have high panel reactive antibodies (defined as 10%) compared to controls (31.3% vs. 10.5%, p0.001). 5-year survival, freedom from NF-MACE, and freedom from CAV were similar between groups (Table). However, freedom from any treated rejection in the first year was significantly lower in the redo HTx compared to de novo HTx patients (79.2% vs. 90.0%, p=0.008). Conclusions: While redo HTx patients have increased incidence of rejection in the first year, this does not affect 5-year survival or freedom from CAV. Therefore, this study suggests that redo HTx appears to be a viable option for HTx patients with severe CAV. Furthermore, an awareness of the increased risk of rejection in redo HTx patients is helpful and may be used to tailor immunsuppressive therapy. Outcomes Redo (N48) Control (N821) P-Value 5-Year Survival 36(75.0%) 628(76.5%) 0.89 5-Year Freedom from CAV 35(72.9%) 655(79.8%) 0.32 5-Year Freedom from NF-MACE 44(91.7%) 767(93.4%) 0.64 1-Year Freedom from Rejection 38(79.2%) 746(90.0%) 0.008 473 Inter-Observer Variability in the Interpretation of Cardiac Biopsies Remains a Challenge: Results of the Cardiac Allograft Rejection Gene Expression Observational (CARGO) II Study M.G. Crespo-Leiro 1 , U. Schulz 2 , J. Vanhaecke 3 , A. Zuckermann 4 , C. Bara 5 , P. Mohacsi 6 , R.C. Bogaev 7 , A. Boyle 8 , H. Ross 9 , J. Parameshwar 10 , M. Zakliczynski 11 , R. Fiocchi 12 , J. Stypmann 13 , D. Hoefer 14 , H. Lehmkuhl 15 , M.C. Deng 16 , P. Leprince 17 , G. Berry 18 , C.C. Marboe 19 , S. Stewart 20 , H.D. Tazelaar 21 , M. Brown 22 H.M. Baron 22 1 Complejo Hospitalario Universitario Juan Canalejo, La Corun ˜a, Spain; 2 Heart and Diabetes Center North Rhine-Westphalia, Ruhr University of Bochum, Bad Oeynhausen, Germany; 3 University Hospital of Leuven, Leuven, Belgium; 4 Medical University of Vienna, Vienna, Austria; 5 Hannover Medical School, Hannover, Germany; 6 University Hospital Bern, Bern, Switzerland; 7 Texas Heart Institute at St. Luke’s Episcopal Hospital, Houston, TX; 8 University of Minnesota, Minneapolis, MN; 9 Toronto General Hospital, Toronto, Canada; 10 Papworth Hospital, Cambridge, United Kingdom; 11 Silesian Center for Heart Disease, Zabrze, Poland, 12 Ospedali Riuniti di Bergamo, Bergamo, Italy; 13 Hospital of the University of Mu ¨nster, Mu ¨nster, Germany; 14 Innsbruck Medical University, Innsbruck, Austria; 15 Deutsches Herzzentrum, Berlin, Germany; 16 Columbia University College of Physicians & Surgeons, New York, NY; 17 Groupe Hospitalier Pitie ´-Salpe ˆtrie `re, Paris, France; 18 Stanford University Medical Center, Stanford, CA; 19 College of Physicians & Surgeons of Columbia University, New York, NY; 20 Papworth Hospital, Cambridge, United Kingdom; 21 Mayo Clinic, Scottsdale, AZ; 22 XDx, Inc., Brisbane, CA Purpose: Endomyocardial biopsy (EMB) is used to guide therapy after heart transplantation. However, EMB is subject to procedural sam- pling error and inter-observer variability. To examine the interpretive variability in an international patient cohort, we performed an analysis using CARGO II biopsy specimens and its core pathology panel. Methods and Materials: For a descriptive analysis of core pathology panel interpretation vs. local pathologist interpretation we randomly selected a subset of 473 biopsies from 279 cardiac transplant recipi- ents at 12 centers. Three core pathologists (CPs) independently reviewed each case for acute cellular rejection (ACR) and were blinded to prior interpretations and any clinical data. A core team assignment of ISHLT Grade 0 required agreement of 3 CPs, while agreement of 2 of 3 CPs was required for assignment of Grades 1A, 1B, 2 (mild rejection, MR) and 3A. Results: CP interpretation of 473 cases, median time post-transplant 178 days (Q1=100,Q3=320), yielded 369 (73 %) cases that satisfied classification criteria. The CPs confirmed 145 of 227 cases (64%) graded 0 by local pathologists and re-assigned 28 cases that were previously graded as MR to Grade 0. Of 24 biopsies graded 3A by local pathologists, the CPs confirmed 9 (37%); 11 (46%) were re-interpreted as MR, and 4 (17%) could not be assigned. 59% of biopsies graded as MR by local pathologists were confirmed by the CPs, while 3.2% were assigned a grade 3A. Conclusions: Comparison of the core team and local pathology results identified substantial inter-reader variability, specifically with regard to grades 3A as the majority were not confirmed and a small number of MR biopsies were also re-assigned to the higher ACR grades. These data 1) substantiate prior studies showing similar pathologic interpretive variability, 2) support the use of core pathol- ogy panels in clinical trials and 3) challenge the reliability of biopsy for post-transplant management. 474 Combinatorial Diagnostic Biomarkers of Acute Cardiac Allograft Rejection Z. Hollander 1 , G. Cohen Freue 2 , D. Lin 3 , A. Ignaszewski 4 , C. Imai 4 , A. Kaan 4 , J. Wilson-McManus 3 , R. Balshaw 2 , R.T. Ng 5 , R.W. McMaster 6 , P. Keown 4 , B.M. McManus 31 The University of British Columbia, Vancouver, BC, Canada; 2 The University of British Columbia, Vancouver, BC, Canada; 3 The University of British Columbia, Vancouver, BC, Canada; 4 The University of British Columbia, Vancouver, BC, Canada; 5 The University of British Columbia, Vancouver, BC, Canada; 6 The University of British Columbia, Vancouver, BC, Canada Purpose: The primary means for “definitive” diagnosis of allograft rejection is the endomycardial biopsy, an invasive and expensive procedure. The BiT initiative aims to identify predictive and diagnos- tic biomarkers of acute and chronic heart, liver and kidney allograft rejection. S230 Abstracts The Journal of Heart and Lung Transplantation February 2009