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520 Improving Results of Adult Congenital Cardiac Transplantation in the Current Era
Abstracts Conclusions: This study illustrates a seasonal variation in AMR, but not ACR, with a higher incidence of AMR in winter mos, whether or not patients received flu vaccine. This phenomenon bears further investigation on potential mechanisms and preventive strategies. 517 Pre-Transplant Strength of Circulating Antibody as Expressed in the Calculated Panel Reactive Antibody Score Predicts AntibodyMediated Rejection after Heart Transplant M. Kittleson,1 J. Patel,1 M. Kawano,1 Z. Goldstein,1 M. Rafiei,1 J. Moriguchi,1 N. Reinsmoen,1 E. Reed,2 A. Hage,1 A. Trento,1 J. Kobashigawa.1 1Cedars-Sinai Heart Institute, Los Angeles, CA; 2 University of California, Los Angeles, Los Angeles, CA. Purpose: Panel reactive antibodies (PRA) describe circulating anti-HLA antibodies and registry studies have shown that a PRA ⬎ 25% is associated with decreased survival after heart transplantation. The calculated PRA (cPRA) is a newer construct that takes into account the specificity and titer of anti-HLA Ab. The cPRA defines the percentage of incompatible donors in a given population to a recipient based on the recipient’s number of high-titer anti-HLA antibodies. The higher the cPRA, the lower the percentage of compatible donors. The purpose of the current study was to determine if a high pre-transplant cPRA, like PRA, is also associated with poor outcomes after heart transplantation. Methods and Materials: We evaluated 71 patients undergoing heart transplantation between 2008 and 2010 at our program with available pretransplant cPRAs. Prior to transplant there were 59 patients with cPRA 0-25% and 12 patients with cPRA⬎25%. We evaluated these patients’ post transplant outcomes in the ensuing 1-year for survival and freedom from cellular and antibody-mediated rejection. All virtual crossmatches were negative at the time of transplant. Patients with cPRA⬎25% were routinely treated with anti-thymocyte globulin in the immediate post transplant period while the cPRA 0-25% group were not. All patients received triple-drug immunosuppression therapy. Results: Patients who had cPRA ⬎25% compared to patients with cPRA 0-25% had significantly lower 1st-year freedom from antibody-mediated rejection (75% vs. 97%, p⫽0.006). Conversely, 1st–year freedom from cellular rejection (98% vs. 100%, p⫽0.62) and 1-year survival (86% vs. 95%, p⫽0.21) was comparable between groups. Conclusions: Patients with high level of circulating antibodies against common antigens as expressed by cPRA are at increased risk for antibodymediated rejection in the first year after heart transplant. Increased surveillance and heightened immunosuppression may be indicated for this highrisk population. 518 Success of Desensitization Protocol in Reducing Calculated Panel Reactive Antibodies in a Large Cohort of Sensitized Heart Transplant Candidates J. Patel,1 J. Moriguchi,1 E. Stimpson,1 N. Reinsmoen,1 E. Reed,2 M. Kawano,1 Z. Goldstein,1 M. Rafiei,1 M. Hamilton,1 E. Schwarz,1 J. Kobashigawa.1 1Cedars-Sinai Heart Institute, Los Angeles, CA; 2 University of California Los Angeles, Los Angeles, CA. Purpose: The presence of circulating anti-HLA antibodies in patients (pts) awaiting heart transplant (HTx) limits the available donor pool. The predicted difficulty in finding a donor heart is based on the calculated panel reactive antibody (cPRA). The cPRA is the percentage of donor hearts in a given population to which a HTx candidate will have anti-HLA antibodies; thus, the higher the cPRA, the harder it is to find a suitable donor. The aim of the current study was to determine if desensitization protocols could successfully reduce cPRA for pts awaiting transplant in a large cohort of sensitized pts. Methods and Materials: Between 2007 and 2010, we assessed 17 pts awaiting HTx with cPRAs⬎50% using a 7500 mean fluorescence intensity (MFI) threshold. A cPRA ⬎50% indicates that more than 50% of donors would be unacceptable because they had HLA antigens to which the HTx candidate expressed HLA antibodies at levels ⬎7500 MFI. These pts were treated with IVIG 2gm/kg on treatment days 1 and 30 and intravenous rituximab 1g on days 7 and 21. The baseline and post treatment cPRAs
S175 were determined. For 6 pts refractory to this therapy, a course of bortezomib (1.3 mg/m2) was given in conjunction with plasmapheresis. Results: For the group, mean baseline cPRA was 65%, which reduced to 40% mean post-treatment, p⫽0.003. 15/17 pts had significant reduction in cPRA. 6 of these 17 patients were additionally given bortezomib with 5 pts responding to therapy. The 2 pts that did not respond to therapy died. To date, 9 pts were able to undergo HTx. 1 patient died of primary graft failure 1 month post HTx with no evidence of rejection at autopsy. 8 patients post-transplant are doing well with no episodes of treated rejection at a mean follow-up of 18⫾16 months. Conclusions: The use of IVIG/rituximab⫾bortezomib significantly decreases cPRA, thus increasing the chances that an acceptable donor heart will be available for the sensitized pt awaiting HTx. 519 Does Immune System Activation from Cellular Rejection Trigger Antibody-Mediated Rejection in Heart Transplantation? S.G. Drakos, D.R. Verma, G.L. Snow, A. Saidi, K. Brunisholz, M.E.H. Hammond, R.A. Alharethi, J. Stehlik, M.D. Everitt, E.M. Gilbert, M.P. Revelo, D. Budge, D.V. Miller, A.G. Kfoury. UTAH Cardiac Transplant Program, Salt Lake City, UT. Purpose: Antibody-mediated Rejection (AMR) is associated with adverse cardiovascular outcomes following heart transplantation. Recognized predisposing factors for AMR have mostly revolved around humoral aspects of the immune response. In this study we investigate whether the activation of the immune system with cellular rejection (CR) is also a trigger for AMR. Methods and Materials: The UTAH Cardiac Transplant Program database was queried for patients transplanted between 1985 and 2010. Routine simultaneous surveillance for AMR and CR was done on all endomyocardial biopsy (EMB) specimens by histologic and immunofluorescence evaluation. A pattern of AMR was defined in patients with ⱖ3 episodes of AMR. Patients were divided into two groups. The “CR group” had at least 1 CR-positive biopsy prior to the diagnosis of AMR pattern while “No CR group” had none. An EMB exhibiting concurrent CR and AMR (mixed rejection) was excluded from analysis if it was the 1st occurrence of CR. Outcomes of interest were 1- and 3-year freedom from AMR pattern. Results: 1001 patients transplanted during the study period qualified for analysis; 862 patients in the “CR group” and 139 in the “No CR” group. Mean age was 46 years, 82% were male. A total of 30,910 EMB were evaluated. At one year, the freedom from AMR pattern for the “CR group” and “No CR group” was 68.5% and 72.4% respectively (p⫽NS). At 3 years, the freedom from AMR pattern was still similar; 68.7% for “No CR group” compared to 61.2% for the “CR group”, p⫽NS. For an added perspective, we additionally found the incidence of CR before AMR occurrence to be similar regardless of whether patients fulfilled AMR pattern criteria or not (88.9% vs. 84.9%, p⫽NS). Conclusions: Our findings suggest that CR does not predispose heart transplant recipients to subsequent AMR. Future exploration is warranted to further elucidate the nature and extent of contribution of the T-cell mediated humoral response in AMR. 520 Improving Results of Adult Congenital Cardiac Transplantation in the Current Era C. Irving,1,2,3 G. Parry,1,2,3 R. Kirk,1,2,3 M. Griselli,1,2,3 A. Hasan.1,2,3 1 Paediatric Cardiothoracic Transplantation, Freeman Hospital, Newcastle upon Tyne, Tyne and Wear, United Kingdom; 2Paediatric Cardiac Intensive Care, Freeman Hospital, Newcastle upon Tyne, Tyne and Wear, United Kingdom; 3Newcastle upon Tyne, United Kingdom Purpose: As the population of adult patients with congenital heart disease is increasing so is the number of these patients referred for cardiac transplantation. In the past, outcomes following transplantation for this group have been poor but there remains little recent data. We describe a single centre experience over 23 years. Methods and Materials: 45 orthotopic cardiac transplants were performed in 44 patients (24 male) ⱖ18 years of age with congenital heart disease
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The Journal of Heart and Lung Transplantation, Vol 30, No 4S, April 2011
(CHD) from 1988 to 2010 in our institution. Outcomes were reviewed using medical records and transplant databases. Results: Mean age at transplant was 33.2 years (range 19.1-59.9 years). Mean follow up time is now 7.3 years (0.1-22.6). 17 patients (39%) had univentricular and 27 (61%) biventricular physiology. The biggest group was transposition of the great arteries following atrial switch in 12 patients (27%). Six (14%) had no previous surgical intervention. Number of transplants has increased substantially in recent years from 19 in 1988-1999 to 26 in 2000-2010. 16 patients (36%) died, 11 within 30 days. The 5 late deaths were at 86 days, 1.8, 2.4, 2.7 and 7 years. Survival was 78% at 30 days, 70% at 1 year, 62% at 5 years, and 50% at 10 and 15 years. There was a significant reduction in 30 day mortality from 44% in 1988-1994 to 10% in 2003-2010. There have been no deaths ⬍30 days post transplant since 2005. Two patients developed post-transplant lymphoproliferative disease. No survivors have required long term renal replacement therapy. One patient was re-transplanted for cardiac allograft vasculopathy. Conclusions: Transplant numbers for adult congenital heart disease continue to rise with increased demand. Operative mortality has been high but this has improved substantially in the recent era with increasing experience. Long term survival is good and comparable to patients without congenital heart disease. 521 Rituximab Improves Survival in Cardiac Allograft Antibody Mediated Rejection: A Single Center Experience A. Ravichandran, G. Ewald, J. Pfeifer, E. Novak, S. Joseph. Cardiovascular Division of Internal Medicine, Washington University Medical Center, Saint Louis, MO. Purpose: Antibody-mediated rejection (AMR) after cardiac transplantation is associated with significant mortality, and represents a theraputic challenge. In small studies, rituximab has been used to treat AMR, but its role remains controversial. Our purpose was to review the outcomes of patients with AMR treated with or without rituximab at our institution. Methods and Materials: We conducted a retrospective analysis of cardiac transplant patients with a diagnosis of AMR seen at our institution from 2001 to the present. Inclusion criteria were clinical suspicion of rejection and absence of cellular rejection with presence of C4D complement staining on biopsy. Patients were divided into rituximab and no-rituximab groups. The primary endpoint was all-cause mortality. Secondary endpoints were infection, change in ejection fraction (EF), and incident rehospitalization. Results: 27 patients meeting inclusion criteria were identified. Ten received rituximab and 17 did not. Baseline characteristics including age, gender, race, and EF on presentation were no different between groups. Kaplan-Meier curves for a 3 year follow-up period demonstrate improved survival in the rituximab group (p⫽0.0279). 4/10 deaths in the no-rituximab group however occurred rapidly (less than 1 week). When these 4 were excluded, there was a trend toward improved survival in the rituximab group, which did not reach statistical significance (p⫽0.1159). There were no differences in secondary endpoints.
Conclusions: We found that rituximab therapy may be associated with improved survival in cardiac allograft AMR. Further studies in larger patient populations are needed to confirm this finding, and to define ideal timing for rituximab initiation.
522 Donor Specific Anti-HLA Antibodies May Not Play a Major Role in Mediating Allograft Dysfunction after Heart Transplantation N. Shankar, M. Gandhi, J. Geske, S. DeGoey, M. Timmons, B. Boilson, J. Schirger, A. Clavell, R. Rodeheffer, J. Wagner, R. Frantz, S. Kushwaha, R. Daly, S. Park, B. Edwards, N. Pereira. Mayo Clinic, Rochester, MN. Purpose: Donor specific antibodies (DSA) have been implicated in the development of allograft dysfunction (AD) following cardiac transplantation (HTX). Single antigen bead assays (SAB) have improved the ability to detect these anti-HLA antibodies. We sought to investigate the role of DSA in the development of AD. Methods and Materials: AD was defined as left ventricular ejection fraction (LVEF) ⱕ50% and a decrement of 10% or more compared to a prior echocardiogram. AD was treated with plasma exchange and high dose steroids. At the time of echocardiography, DSA was measured by SAB and coronary angiography was performed. Cardiac allograft vasculopathy (CAV) was defined as any major branch stenosis ⱖ70%. Results: AD was observed in 10 of 313 patients and were compared to 30 HTX controls with preserved LVEF (mean 63⫾6%) based on gender, age and years since HTX. LVEF during the episode of AD was 33⫾11% increasing in all patients to 48⫾12% after treatment. 6/10 patients and 1/30 controls had antibody mediated rejection on biopsy (p⬍0.0001). There was no significant difference in the number of AD patients with DSA compared to controls with DSA (4/10 vs 15/30, p⫽0.43). Class 1 DSA was more common in AD patients as compared to controls (3/10 vs 2/30, p⫽0.02). There was no difference in class 2 DSA (3/10 vs 15/30, p⫽0.11). Cumulative DSA class 1 titers were significantly higher in patients with AD (3476⫾2269 vs 378⫾263, p⫽0.01) while Class 2 DSA titers were not significantly different from controls (5954⫾5469 vs 2476⫾1175, p⫽0.09). There was no significant difference in the number of patients with CAV between the 2 groups (3/10 vs 4/30, p⫽0.13). Conclusions: This study for the first time demonstrates a divergence between detection of DSA and the presence or absence of AD. Class 1 DSA is more common and titers are higher in patients with AD. However, anti-HLA DSA are absent in 60% of HTX recipients with AD and are present in 50% of controls in whom AD is not observed. The role of DSA in AD needs further study and other non anti-HLA mechanisms may play a role. 523 Post-Transplant Diastolic Dysfunction beyond the First Year: Incidence and Prognostic Significance J. Iturrizaga,1 S.V. Pamboukian,1 J. George,2 R.N. Brown,2 M. Cadeiras,1 M. Smallfield,1 R.C. Bourge,1 J.K. Kirklin,2 D.C. McGiffin,2 M. Hubbard,2 J.A. Tallaj.1, ,3 1Medicine, University of Alabama at Birmingham, Birmingham, AL; 2Surgery, University of Alabama at Birmingham, Birmingham, AL; 3Medicine, Birmingham VA Medical Center, Birmingham, AL. Purpose: We have previously demonstrated that post-transplant (txp) diastolic dysfunction (DD), especially right ventricular (RV) DD, that occurs within the first year of transplantation is associated with worse survival. The purpose of the current study is to evaluate the incidence and clinical significance of DD that occurs beyond the first year post-txp. Methods and Materials: Between Jan 1992 and Dec 2009, 428 patients underwent heart transplantation. The right heart catheterizations and echocardiograms done at the yearly evaluations were analyzed. Patients with significant valvular disease or decreased systolic function were excluded. DD of the RV (RVDD) was defined as right atrial pressure ⬎ 12mmHg. DD of the left ventricle (LVDD) was defined as pulmonary capillary wedge pressure ⬎ 18 mmHg. Results: The incidence of DD has significantly decreased in the recent transplant era, from a 4Y incidence of 20% and 14% for RVDD or LVDD respectively in the patients transplanted between 1992-96 as compared to 4% and 7% in patients transplanted between 2001-08 (p⬍0.05). By multivariable analysis, a higher BMI (RR 3.6 at Y4, p⬍0.001) and number of rejections (RR 2.2 at Y4, p⫽0.04) were predictive of RVDD (table 1). RVDD and the combination of RVDD and LVDD, but not LVDD alone, were associated with an increased subsequent risk of mortality (table 2).
S175 were determined. For 6 pts refractory to this therapy, a course of bortezomib (1.3 mg/m2) was given in conjunction with plasmapheresis. Results: For the group, mean baseline cPRA was 65%, which reduced to 40% mean post-treatment, p⫽0.003. 15/17 pts had significant reduction in cPRA. 6 of these 17 patients were additionally given bortezomib with 5 pts responding to therapy. The 2 pts that did not respond to therapy died. To date, 9 pts were able to undergo HTx. 1 patient died of primary graft failure 1 month post HTx with no evidence of rejection at autopsy. 8 patients post-transplant are doing well with no episodes of treated rejection at a mean follow-up of 18⫾16 months. Conclusions: The use of IVIG/rituximab⫾bortezomib significantly decreases cPRA, thus increasing the chances that an acceptable donor heart will be available for the sensitized pt awaiting HTx. 519 Does Immune System Activation from Cellular Rejection Trigger Antibody-Mediated Rejection in Heart Transplantation? S.G. Drakos, D.R. Verma, G.L. Snow, A. Saidi, K. Brunisholz, M.E.H. Hammond, R.A. Alharethi, J. Stehlik, M.D. Everitt, E.M. Gilbert, M.P. Revelo, D. Budge, D.V. Miller, A.G. Kfoury. UTAH Cardiac Transplant Program, Salt Lake City, UT. Purpose: Antibody-mediated Rejection (AMR) is associated with adverse cardiovascular outcomes following heart transplantation. Recognized predisposing factors for AMR have mostly revolved around humoral aspects of the immune response. In this study we investigate whether the activation of the immune system with cellular rejection (CR) is also a trigger for AMR. Methods and Materials: The UTAH Cardiac Transplant Program database was queried for patients transplanted between 1985 and 2010. Routine simultaneous surveillance for AMR and CR was done on all endomyocardial biopsy (EMB) specimens by histologic and immunofluorescence evaluation. A pattern of AMR was defined in patients with ⱖ3 episodes of AMR. Patients were divided into two groups. The “CR group” had at least 1 CR-positive biopsy prior to the diagnosis of AMR pattern while “No CR group” had none. An EMB exhibiting concurrent CR and AMR (mixed rejection) was excluded from analysis if it was the 1st occurrence of CR. Outcomes of interest were 1- and 3-year freedom from AMR pattern. Results: 1001 patients transplanted during the study period qualified for analysis; 862 patients in the “CR group” and 139 in the “No CR” group. Mean age was 46 years, 82% were male. A total of 30,910 EMB were evaluated. At one year, the freedom from AMR pattern for the “CR group” and “No CR group” was 68.5% and 72.4% respectively (p⫽NS). At 3 years, the freedom from AMR pattern was still similar; 68.7% for “No CR group” compared to 61.2% for the “CR group”, p⫽NS. For an added perspective, we additionally found the incidence of CR before AMR occurrence to be similar regardless of whether patients fulfilled AMR pattern criteria or not (88.9% vs. 84.9%, p⫽NS). Conclusions: Our findings suggest that CR does not predispose heart transplant recipients to subsequent AMR. Future exploration is warranted to further elucidate the nature and extent of contribution of the T-cell mediated humoral response in AMR. 520 Improving Results of Adult Congenital Cardiac Transplantation in the Current Era C. Irving,1,2,3 G. Parry,1,2,3 R. Kirk,1,2,3 M. Griselli,1,2,3 A. Hasan.1,2,3 1 Paediatric Cardiothoracic Transplantation, Freeman Hospital, Newcastle upon Tyne, Tyne and Wear, United Kingdom; 2Paediatric Cardiac Intensive Care, Freeman Hospital, Newcastle upon Tyne, Tyne and Wear, United Kingdom; 3Newcastle upon Tyne, United Kingdom Purpose: As the population of adult patients with congenital heart disease is increasing so is the number of these patients referred for cardiac transplantation. In the past, outcomes following transplantation for this group have been poor but there remains little recent data. We describe a single centre experience over 23 years. Methods and Materials: 45 orthotopic cardiac transplants were performed in 44 patients (24 male) ⱖ18 years of age with congenital heart disease
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The Journal of Heart and Lung Transplantation, Vol 30, No 4S, April 2011
(CHD) from 1988 to 2010 in our institution. Outcomes were reviewed using medical records and transplant databases. Results: Mean age at transplant was 33.2 years (range 19.1-59.9 years). Mean follow up time is now 7.3 years (0.1-22.6). 17 patients (39%) had univentricular and 27 (61%) biventricular physiology. The biggest group was transposition of the great arteries following atrial switch in 12 patients (27%). Six (14%) had no previous surgical intervention. Number of transplants has increased substantially in recent years from 19 in 1988-1999 to 26 in 2000-2010. 16 patients (36%) died, 11 within 30 days. The 5 late deaths were at 86 days, 1.8, 2.4, 2.7 and 7 years. Survival was 78% at 30 days, 70% at 1 year, 62% at 5 years, and 50% at 10 and 15 years. There was a significant reduction in 30 day mortality from 44% in 1988-1994 to 10% in 2003-2010. There have been no deaths ⬍30 days post transplant since 2005. Two patients developed post-transplant lymphoproliferative disease. No survivors have required long term renal replacement therapy. One patient was re-transplanted for cardiac allograft vasculopathy. Conclusions: Transplant numbers for adult congenital heart disease continue to rise with increased demand. Operative mortality has been high but this has improved substantially in the recent era with increasing experience. Long term survival is good and comparable to patients without congenital heart disease. 521 Rituximab Improves Survival in Cardiac Allograft Antibody Mediated Rejection: A Single Center Experience A. Ravichandran, G. Ewald, J. Pfeifer, E. Novak, S. Joseph. Cardiovascular Division of Internal Medicine, Washington University Medical Center, Saint Louis, MO. Purpose: Antibody-mediated rejection (AMR) after cardiac transplantation is associated with significant mortality, and represents a theraputic challenge. In small studies, rituximab has been used to treat AMR, but its role remains controversial. Our purpose was to review the outcomes of patients with AMR treated with or without rituximab at our institution. Methods and Materials: We conducted a retrospective analysis of cardiac transplant patients with a diagnosis of AMR seen at our institution from 2001 to the present. Inclusion criteria were clinical suspicion of rejection and absence of cellular rejection with presence of C4D complement staining on biopsy. Patients were divided into rituximab and no-rituximab groups. The primary endpoint was all-cause mortality. Secondary endpoints were infection, change in ejection fraction (EF), and incident rehospitalization. Results: 27 patients meeting inclusion criteria were identified. Ten received rituximab and 17 did not. Baseline characteristics including age, gender, race, and EF on presentation were no different between groups. Kaplan-Meier curves for a 3 year follow-up period demonstrate improved survival in the rituximab group (p⫽0.0279). 4/10 deaths in the no-rituximab group however occurred rapidly (less than 1 week). When these 4 were excluded, there was a trend toward improved survival in the rituximab group, which did not reach statistical significance (p⫽0.1159). There were no differences in secondary endpoints.
Conclusions: We found that rituximab therapy may be associated with improved survival in cardiac allograft AMR. Further studies in larger patient populations are needed to confirm this finding, and to define ideal timing for rituximab initiation.
522 Donor Specific Anti-HLA Antibodies May Not Play a Major Role in Mediating Allograft Dysfunction after Heart Transplantation N. Shankar, M. Gandhi, J. Geske, S. DeGoey, M. Timmons, B. Boilson, J. Schirger, A. Clavell, R. Rodeheffer, J. Wagner, R. Frantz, S. Kushwaha, R. Daly, S. Park, B. Edwards, N. Pereira. Mayo Clinic, Rochester, MN. Purpose: Donor specific antibodies (DSA) have been implicated in the development of allograft dysfunction (AD) following cardiac transplantation (HTX). Single antigen bead assays (SAB) have improved the ability to detect these anti-HLA antibodies. We sought to investigate the role of DSA in the development of AD. Methods and Materials: AD was defined as left ventricular ejection fraction (LVEF) ⱕ50% and a decrement of 10% or more compared to a prior echocardiogram. AD was treated with plasma exchange and high dose steroids. At the time of echocardiography, DSA was measured by SAB and coronary angiography was performed. Cardiac allograft vasculopathy (CAV) was defined as any major branch stenosis ⱖ70%. Results: AD was observed in 10 of 313 patients and were compared to 30 HTX controls with preserved LVEF (mean 63⫾6%) based on gender, age and years since HTX. LVEF during the episode of AD was 33⫾11% increasing in all patients to 48⫾12% after treatment. 6/10 patients and 1/30 controls had antibody mediated rejection on biopsy (p⬍0.0001). There was no significant difference in the number of AD patients with DSA compared to controls with DSA (4/10 vs 15/30, p⫽0.43). Class 1 DSA was more common in AD patients as compared to controls (3/10 vs 2/30, p⫽0.02). There was no difference in class 2 DSA (3/10 vs 15/30, p⫽0.11). Cumulative DSA class 1 titers were significantly higher in patients with AD (3476⫾2269 vs 378⫾263, p⫽0.01) while Class 2 DSA titers were not significantly different from controls (5954⫾5469 vs 2476⫾1175, p⫽0.09). There was no significant difference in the number of patients with CAV between the 2 groups (3/10 vs 4/30, p⫽0.13). Conclusions: This study for the first time demonstrates a divergence between detection of DSA and the presence or absence of AD. Class 1 DSA is more common and titers are higher in patients with AD. However, anti-HLA DSA are absent in 60% of HTX recipients with AD and are present in 50% of controls in whom AD is not observed. The role of DSA in AD needs further study and other non anti-HLA mechanisms may play a role. 523 Post-Transplant Diastolic Dysfunction beyond the First Year: Incidence and Prognostic Significance J. Iturrizaga,1 S.V. Pamboukian,1 J. George,2 R.N. Brown,2 M. Cadeiras,1 M. Smallfield,1 R.C. Bourge,1 J.K. Kirklin,2 D.C. McGiffin,2 M. Hubbard,2 J.A. Tallaj.1, ,3 1Medicine, University of Alabama at Birmingham, Birmingham, AL; 2Surgery, University of Alabama at Birmingham, Birmingham, AL; 3Medicine, Birmingham VA Medical Center, Birmingham, AL. Purpose: We have previously demonstrated that post-transplant (txp) diastolic dysfunction (DD), especially right ventricular (RV) DD, that occurs within the first year of transplantation is associated with worse survival. The purpose of the current study is to evaluate the incidence and clinical significance of DD that occurs beyond the first year post-txp. Methods and Materials: Between Jan 1992 and Dec 2009, 428 patients underwent heart transplantation. The right heart catheterizations and echocardiograms done at the yearly evaluations were analyzed. Patients with significant valvular disease or decreased systolic function were excluded. DD of the RV (RVDD) was defined as right atrial pressure ⬎ 12mmHg. DD of the left ventricle (LVDD) was defined as pulmonary capillary wedge pressure ⬎ 18 mmHg. Results: The incidence of DD has significantly decreased in the recent transplant era, from a 4Y incidence of 20% and 14% for RVDD or LVDD respectively in the patients transplanted between 1992-96 as compared to 4% and 7% in patients transplanted between 2001-08 (p⬍0.05). By multivariable analysis, a higher BMI (RR 3.6 at Y4, p⬍0.001) and number of rejections (RR 2.2 at Y4, p⫽0.04) were predictive of RVDD (table 1). RVDD and the combination of RVDD and LVDD, but not LVDD alone, were associated with an increased subsequent risk of mortality (table 2).