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245 Wound Healing Events and Effusions with Everolimus Versus MMF Based Regimens in De Novo Heart Transplant Recipients
Abstracts Conclusions: PCE including CT occurred in up to 30% of HTxR within 3 months post HTx. History of DCM and treatment with EVR increased the risk for PCE and PLE. Drainage prolongation may be considered for HTxR treated with EVR. 245 Wound Healing Events and Effusions with Everolimus Versus MMF Based Regimens in De Novo Heart Transplant Recipients A. Zuckermann,1 H. Eisen,2 J. Kobashigawa,3 H. Ross,4 S. Wang,5 H. Lehmkuhl,6 M. Rinaldi,7 G. Torre,8 N. Yonan,9 J. Arizon,10 C. Pellegrini,11 P. Lopez,12 G. Dong,13 C. Panis,13 S. Hirt.14 1Medical University Vienna, Vienna, Austria; 2Division of Cardiology, Drexel University College of Medicine, Philadelphia; 3Heart Transplant Program, Cedars-Sinai Heart Institute, Los Angeles, CA; 4Department of Cardiology/Heart Transplant, University Health Network, Toronto General Hospital, Toronto, Canada; 5Division of Cardiovascular Surgery, National Taiwan University, Taipei, Taiwan; 6Deutsches Herzzentrum Berlin, Berlin, Germany; 7S. Giovanni Battista Hospital, University of Turin, Torino, Italy; 8Methodist Hospital/DeBakey Heart Failure Research Center, Houston; 9Wythenshawe Hospital, Manchester, United Kingdom; 10Department of Cardiology, Reina Sofia University Hospital, Cordoba, Spain; 11Az. Osp.di Bologna Policl.S.OrsolaMalpighi Univ.degli Studi, Bologna, Italy; 12Novartis Pharma AG, Basel, Switzerland; 13Novartis Pharmaceuticals Corporation, East Hanover; 14Universitaetsklinikum Regensburg, Regensburg, Germany. Purpose: The mTOR inhibitors, sirolimus and everolimus (EVR), have potent immunosuppressive and antiproliferative properties. An increased incidence of wound healing events (WHEs) and effusions after heart transplantation has been associated with the use of sirolimus. Here, we compare prospectively collected information on WHEs and effusions between EVR and mycophenolate mofetil (MMF) based immunosuppressive regimens in 547 de novo heart transplant recipients (HTxR). Methods and Materials: De novo HTxR were randomized into the 24month (M), multi-center, open-label A2310 study to receive EVR 1.5 or 3mg/day (C0 3-8ng/mL and C0 6-12ng/mL) with reduced CsA vs 3.0 g/day MMF with standard CsA and steroids. Comparison of event rates at M12 is only presented for EVR 1.5mg and MMF, due to the early termination of the EVR 3mg arm. Detailed information on symptoms, diagnosis and intervention was prospectively collected for WHEs and for effusion events on special case report forms. Results: There was no significant difference in incidence of any WHE (sternal/non-sternal/major WHE) and pleural effusion in EVR 1.5mg vs MMF. Incidence of major WHE was numerically higher with EVR vs MMF. Mediastinitis occurred in ⬍2% and dehiscence in ⬍5% of HTxR. A statistically higher incidence of pericardial effusion events was noted in EVR 1.5mg vs MMF; no patient died due to cardiac tamponade (Table).
S87 246 Circulating Antibody after Heart Transplant and Its Association with Poor Outcome: A Prospective Assessment J. Patel,1 M. Kawano,1 E. Reed,2 Z. Goldstein,1 M. Rafiei,1 N. Reinsmoen,1 B. Azarbal,1 L. Czer,1 A. Trento,1 J. Kobashigawa.1 1 Cedars-Sinai Heart Institute, Los Angeles, CA; 2University of California Los Angeles, Los Angeles, CA. Purpose: Donor-specific antibodies (DSA) after heart transplant are associated with reduced survival and the increased development of cardiac allograft vasculopathy (CAV) in previous cross-sectional studies. The purpose of the current study was to perform a prospective analysis of heart transplant recipients at our center for the development of DSA and subsequent development of CAV. Methods and Materials: We evaluated 130 patients post transplant 20032010 who had routine antibody monitoring by solid-phase assay. Patients on average had 7 ⫾ 3 assays for DSA drawn in the first year after heart transplantation. Patients were divided into three groups: Those that developed DSA (DSA; N⫽20); those with non-DSA antibodies (non-DSA Ab, N⫽46); and those with no antibodies (no Ab, N⫽78). Outcomes assessed included 1st-year freedom from acute cellular rejection (ACR) and antibody-mediated rejection (AMR), 3-year survival and freedom from cardiac allograft vasculopathy (CAV, stenosis ⬎30%). Results: Compared to the no Ab group, the DSA group had significantly lower 3-year survival and lower freedom from CAV (table). In addition, both the DSA and non-DSA Ab groups had significantly lower freedom from 1st-year ACR and AMR compared to the no Ab group. Table
N 1-Year Freedom from Cellular Rejection 1-Year Freedom from Antibody-Mediated Rejection 3-Year Actuarial Survival 3-Year Actuarial Freedom from CAV
DSA
Non-Specific Antibodies Only
No Antibodies
20 80%*
46 87%*
78 99%
65%*
76%*
94%
65%* 70%*
76% 96%
85% 88%
*P⬍0.05, compared to No Antibodies group.
Conclusions: Patients who develop DSA in the first year after transplant have lower survival and greater subsequent development of CAV. Furthermore, antibody production, whether non-specific or DSA, is associated with a greater incidence of first year rejection. Such patients may require more intensive monitoring and augmented immunosuppression to improve their long-term outcomes. 247 Early Versus Late Antibody-Mediated Rejection: Is There a Difference? J. Patel,1 Z. Goldstein,1 M. Kawano,1 M. Rafiei,1 N. Reinsmoen,1 E. Reed,2 D. Luthringer,1 E. Schwarz,1 A. Trento,1 J. Kobashigawa.1 1 Cedars-Sinai Heart Institute, Los Angeles, CA; 2University of California Los Angeles, Los Angeles, CA.
Conclusions: The incidence of WHEs and pleural effusions was comparable between EVR and MMF. Since pericardial effusions were more often seen with EVR, frequent echocardiographic monitoring is recommended.
Purpose: Antibody-mediated rejection (AMR) is associated with increased incidence of transplant coronary artery disease (TCAD) and decreased survival. While it is usually seen early after heart transplantation, late AMR can also occur. The purpose of the current study was to compare the characteristics and outcomes of heart transplant recipients with AMR early vs late after transplant. Methods and Materials: We reviewed 1290 patients transplanted from 1994 to 2010. Patients were divided into groups: treated AMR 1 year after transplant, and two control groups without AMR matched 1:1 for age, sex, and time from transplant. AMR was defined by characteristic histologic and immunologic changes on biopsy. Outcomes were compared, including subsequent 5-year survival and freedom from TCAD (any stenosis ⬎ 30%). Results: There were 112 patients in the early AMR group and 37 patients in the late AMR group. Average time to AMR was 3 ⫾ 7 months in the early group vs.
S87 246 Circulating Antibody after Heart Transplant and Its Association with Poor Outcome: A Prospective Assessment J. Patel,1 M. Kawano,1 E. Reed,2 Z. Goldstein,1 M. Rafiei,1 N. Reinsmoen,1 B. Azarbal,1 L. Czer,1 A. Trento,1 J. Kobashigawa.1 1 Cedars-Sinai Heart Institute, Los Angeles, CA; 2University of California Los Angeles, Los Angeles, CA. Purpose: Donor-specific antibodies (DSA) after heart transplant are associated with reduced survival and the increased development of cardiac allograft vasculopathy (CAV) in previous cross-sectional studies. The purpose of the current study was to perform a prospective analysis of heart transplant recipients at our center for the development of DSA and subsequent development of CAV. Methods and Materials: We evaluated 130 patients post transplant 20032010 who had routine antibody monitoring by solid-phase assay. Patients on average had 7 ⫾ 3 assays for DSA drawn in the first year after heart transplantation. Patients were divided into three groups: Those that developed DSA (DSA; N⫽20); those with non-DSA antibodies (non-DSA Ab, N⫽46); and those with no antibodies (no Ab, N⫽78). Outcomes assessed included 1st-year freedom from acute cellular rejection (ACR) and antibody-mediated rejection (AMR), 3-year survival and freedom from cardiac allograft vasculopathy (CAV, stenosis ⬎30%). Results: Compared to the no Ab group, the DSA group had significantly lower 3-year survival and lower freedom from CAV (table). In addition, both the DSA and non-DSA Ab groups had significantly lower freedom from 1st-year ACR and AMR compared to the no Ab group. Table
N 1-Year Freedom from Cellular Rejection 1-Year Freedom from Antibody-Mediated Rejection 3-Year Actuarial Survival 3-Year Actuarial Freedom from CAV
DSA
Non-Specific Antibodies Only
No Antibodies
20 80%*
46 87%*
78 99%
65%*
76%*
94%
65%* 70%*
76% 96%
85% 88%
*P⬍0.05, compared to No Antibodies group.
Conclusions: Patients who develop DSA in the first year after transplant have lower survival and greater subsequent development of CAV. Furthermore, antibody production, whether non-specific or DSA, is associated with a greater incidence of first year rejection. Such patients may require more intensive monitoring and augmented immunosuppression to improve their long-term outcomes. 247 Early Versus Late Antibody-Mediated Rejection: Is There a Difference? J. Patel,1 Z. Goldstein,1 M. Kawano,1 M. Rafiei,1 N. Reinsmoen,1 E. Reed,2 D. Luthringer,1 E. Schwarz,1 A. Trento,1 J. Kobashigawa.1 1 Cedars-Sinai Heart Institute, Los Angeles, CA; 2University of California Los Angeles, Los Angeles, CA.
Conclusions: The incidence of WHEs and pleural effusions was comparable between EVR and MMF. Since pericardial effusions were more often seen with EVR, frequent echocardiographic monitoring is recommended.
Purpose: Antibody-mediated rejection (AMR) is associated with increased incidence of transplant coronary artery disease (TCAD) and decreased survival. While it is usually seen early after heart transplantation, late AMR can also occur. The purpose of the current study was to compare the characteristics and outcomes of heart transplant recipients with AMR early vs late after transplant. Methods and Materials: We reviewed 1290 patients transplanted from 1994 to 2010. Patients were divided into groups: treated AMR 1 year after transplant, and two control groups without AMR matched 1:1 for age, sex, and time from transplant. AMR was defined by characteristic histologic and immunologic changes on biopsy. Outcomes were compared, including subsequent 5-year survival and freedom from TCAD (any stenosis ⬎ 30%). Results: There were 112 patients in the early AMR group and 37 patients in the late AMR group. Average time to AMR was 3 ⫾ 7 months in the early group vs.