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515 Effect of Gender on Everolimus Treatment for Antibody-Mediated Rejection after Heart Transplantation
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The Journal of Heart and Lung Transplantation, Vol 30, No 4S, April 2011
and compared with heart tissue obtained after heart transplantation (post). In addition, plasma was taken from 18 patients pre and 1, 3, and 6 months after implantation. Plasma was analysed by ACT ELISA and heart tissue was used to investigate the amount of ACT mRNA by q-PCR and localization of ACT protein by immunohistochemistry. Results: ACT plasma levels were significantly elevated in DCM patients compared to healthy controls (p ⬍0.05). After 1 month of LVAD support, the concentration of plasma ACT showed a non-significant increase. However, after 3 months of LVAD support, plasma ACT decreased significantly (p⬍0.05) and ultimately reached the same level as the control. The mRNA expression also decreased significantly in the post myocardial tissue compared to the tissue taken prior implantation (p⬍ 0.02). Immunohistochemistry showed that the ACT-expression in the cardiomyocytes changed from a diffuse pattern towards an alternating pattern of cardiomyocytes expressing strong to no ACT. Conclusions: Plasma levels of ACT decrease to normal during C-LVAD support, which coincides with decreased ACT mRNA in heart tissue. This suggests that the human heart is an important source of ACT production. Whether or not and how ACT contributes to reverse cardiac remodeling requires further research. 513 WITHDRAWN 514 Factors Influencing Early Onset of Coronary Allograft Vasculopathy after Orthotopic Heart Transplantation V. Kösek,1 H. Welp,1 J. Osterhues,1 J. Stypmann,2 H. Scheld,1 J. Sindermann.1 1Thoracic and Cardiovascular Surgery, University Hospital, Muenster, Germany; 2Cardiology and Angiology, University Hospital, Muenster, Germany. Purpose: Heart transplantation is a common surgical procedure for treatment of end stage heart failure. Almost 85.000 operations have been performed worldwide over the past 40 years. However, coronary allograft vasculopathy, which is a phenomenon of chronic rejection, is still a serious problem. The aim of this retrospective study was to identify factors influencing the time point of onset of coronary allograft vasculopathy. Methods and Materials: Medical records of heart transplant recipients transplanted between 1998 and 2008 surviving transplantation for at least one year were screened for 25 factors possibly influencing onset of coronary allograft vasculopathy retrospectively. Annual coronary angiograms were analysed for signs of coronary allograft vasculopathy. Results: Overall 244 patients were included into the study and 1112 coronary angiograms were screened. Median survival in all patients was 185 ⫾ 10 months. Patients with onset of coronary allograft vasculopathy within the first 48 months after transplantation had a significantly shorter long-term-survival than those were coronary allograft vasculopathy occurred later (149 ⫾ 11 vs. 190 ⫾ 7 months; p ⫽ 0.02). Factors significantly associated with early onset of coronary allograft vasculopathy were age over 45 years at transplantation, donor age over 40 years, creatinine clearance under 45 ml/min, gender mismatch between donor and recipient, prolonged ischemia-time and cholesterol levels over 200 mg/dl. Conclusions: Onset of coronary allograft vasculopathy within the first 48 months after transplantation is associated with impaired long-term-survival. Short ischemia-time and strict control of cholesterol levels are factors which might help to delay onset of coronary allograft vasculopathy and thereby improve long-term-survival.
antibody-mediated rejection (AMR) and in immunosuppressive approaches for AMR is unknown. Methods and Materials: We prospectively studied 134 pts (117 men, mean age 50 yrs) who underwent endomyocardial biopsy at 4 weeks (FU1⫽134), 1 yr (FU2⫽107) and 3 yrs (FU3⫽61) after HTx. Acute cellular rejection (ACR, ISHLT grading) was evaluated in H&E stainings. AMR was assessed by immunohistochemistry (CD31-positive capillaries to CD68 and C4d; all x200). Immunosuppression consisted of CsA, everolimus or mycophenolate and steroids. Forty-three pts were continuously on everolimus during the first post-transplant year. Results: ACR grade 1R was found in 21% of pts at FU1, in 11% of pts at FU2 and in 3% of pts at FU3. Grade 3R affected ⬍1% of pts in FU1 and was not detected in FU2 or FU3. AMR was present in 37% of pts at FU1, in 8% of pts at FU2 and in 10% of pts at FU3. Women as compared to men were affected more frequently by ACR of any grade in FU1 (35% vs. 20%; p⫽0.043), FU2 (33% vs. 8%; p⫽0.009) and FU3 (22% vs. 0%; p⫽0.020). Women also presented more often with AMR than men in FU1 (60% vs. 33%; p⫽0.044) and FU2 (21% vs. 6%; p⫽0.073), but there was no difference at FU3 (13% vs. 10%; p⫽0.600). Everolimus suppressed AMR in FU1 (25% vs. 44%, p⫽0.041), and this effect was more pronounced in women (29% vs. 88%; p⫽0.035) than in men (24% vs. 34%; p⫽0.136). However, AMR in FU2 and FU3 was equally frequent in everolimus-treated men and women. Conclusions: Women present more often with AMR than men. Everolimus prevents AMR early after HTx, especially in female HTx recipients. Further study is necessary to determine gender and immunosuppressive effects beyond the first post-transplant year. 516 Seasonal Variations in Cardiac Transplant Antibody-Mediated Rejection L. Piponniau, A. Velleca, M. Kittleson, D. Lockhart, B. Kearney, T. Kao, M. Johnson, M. Kawano, Z. Goldstein, M. Rafiei, F. Esmailian, J. Kobashigawa. Cedars-Sinai Heart Institute, Los Angeles, CA. Purpose: Rejection may be influenced by seasonal factors. In liver transplant recipients, rejection is more common in winter. This may be related to flu vaccines or infections which upregulate the immune system. The purpose of the current study was to determine if there are seasonal variations in acute cellular (ACR) or antibody-mediated rejection (AMR) in heart transplant recipients at our center. Methods and Materials: We evaluated 424 patients transplanted 19942010 to assess for seasonal variations in ACR and AMR. Seasons were defined: winter (December-February), spring (March-May), summer (JuneAugust), and fall (September-November). Rejection episodes were further divided into those that occurred early (⬍ 6 mos) and those that occurred later (⬎ 6 mos) after transplant, since at our center, patients ⬍ 6 mos after transplant do not receive flu vaccines. Results: A significantly higher percent of all AMR episodes occurred in the winter mos compared to the spring, summer and fall mos (32% vs. 23%, 22%, 23% respectively, p⬍0.05). Similarly, those patients with AMR within 6 mos of transplant (no flu vaccine given to these patients per protocol) had significantly higher incidence of AMR in the winter mos compared to the other seasons (33% vs. 23%, 23%, and 21%, p⬍0.05). Conversely, there was no difference in the percent of all ACRs among the winter, spring, summer and fall groups (22% vs. 25%, 26%, and 23% respectively, p⫽NS). The frequency of flu infections was not available, although in general, flu cases are more common in winter. Percent of all Rejection Episodes Occurring in Each Season
515 Effect of Gender on Everolimus Treatment for Antibody-Mediated Rejection after Heart Transplantation N.E. Hiemann,1 E. Wellnhofer,2 S. Kretschmer,1 C. Christan,1 H. Lehmkuhl,1 C. Knosalla,1 R. Hetzer,1 R. Meyer.1 1Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany; 2 Cardiology, Deutsches Herzzentrum Berlin, Berlin, Germany. Purpose: Women are known to present more often with acute cellular rejection after heart transplantation (HTx). However, the role of gender in
Cellular Rejection Antibody-Mediated Rejection (All Times) Antibody-Mediated Rejection (First 6 Months Post Transplant)
Spring
Summer
Fall
Winter
25% 23%
26% 22%
27% 23%
22% 32%*
23%
23%
21%
33%*
*P⬍0.05, compared to Spring, Summer and Fall.
The Journal of Heart and Lung Transplantation, Vol 30, No 4S, April 2011
and compared with heart tissue obtained after heart transplantation (post). In addition, plasma was taken from 18 patients pre and 1, 3, and 6 months after implantation. Plasma was analysed by ACT ELISA and heart tissue was used to investigate the amount of ACT mRNA by q-PCR and localization of ACT protein by immunohistochemistry. Results: ACT plasma levels were significantly elevated in DCM patients compared to healthy controls (p ⬍0.05). After 1 month of LVAD support, the concentration of plasma ACT showed a non-significant increase. However, after 3 months of LVAD support, plasma ACT decreased significantly (p⬍0.05) and ultimately reached the same level as the control. The mRNA expression also decreased significantly in the post myocardial tissue compared to the tissue taken prior implantation (p⬍ 0.02). Immunohistochemistry showed that the ACT-expression in the cardiomyocytes changed from a diffuse pattern towards an alternating pattern of cardiomyocytes expressing strong to no ACT. Conclusions: Plasma levels of ACT decrease to normal during C-LVAD support, which coincides with decreased ACT mRNA in heart tissue. This suggests that the human heart is an important source of ACT production. Whether or not and how ACT contributes to reverse cardiac remodeling requires further research. 513 WITHDRAWN 514 Factors Influencing Early Onset of Coronary Allograft Vasculopathy after Orthotopic Heart Transplantation V. Kösek,1 H. Welp,1 J. Osterhues,1 J. Stypmann,2 H. Scheld,1 J. Sindermann.1 1Thoracic and Cardiovascular Surgery, University Hospital, Muenster, Germany; 2Cardiology and Angiology, University Hospital, Muenster, Germany. Purpose: Heart transplantation is a common surgical procedure for treatment of end stage heart failure. Almost 85.000 operations have been performed worldwide over the past 40 years. However, coronary allograft vasculopathy, which is a phenomenon of chronic rejection, is still a serious problem. The aim of this retrospective study was to identify factors influencing the time point of onset of coronary allograft vasculopathy. Methods and Materials: Medical records of heart transplant recipients transplanted between 1998 and 2008 surviving transplantation for at least one year were screened for 25 factors possibly influencing onset of coronary allograft vasculopathy retrospectively. Annual coronary angiograms were analysed for signs of coronary allograft vasculopathy. Results: Overall 244 patients were included into the study and 1112 coronary angiograms were screened. Median survival in all patients was 185 ⫾ 10 months. Patients with onset of coronary allograft vasculopathy within the first 48 months after transplantation had a significantly shorter long-term-survival than those were coronary allograft vasculopathy occurred later (149 ⫾ 11 vs. 190 ⫾ 7 months; p ⫽ 0.02). Factors significantly associated with early onset of coronary allograft vasculopathy were age over 45 years at transplantation, donor age over 40 years, creatinine clearance under 45 ml/min, gender mismatch between donor and recipient, prolonged ischemia-time and cholesterol levels over 200 mg/dl. Conclusions: Onset of coronary allograft vasculopathy within the first 48 months after transplantation is associated with impaired long-term-survival. Short ischemia-time and strict control of cholesterol levels are factors which might help to delay onset of coronary allograft vasculopathy and thereby improve long-term-survival.
antibody-mediated rejection (AMR) and in immunosuppressive approaches for AMR is unknown. Methods and Materials: We prospectively studied 134 pts (117 men, mean age 50 yrs) who underwent endomyocardial biopsy at 4 weeks (FU1⫽134), 1 yr (FU2⫽107) and 3 yrs (FU3⫽61) after HTx. Acute cellular rejection (ACR, ISHLT grading) was evaluated in H&E stainings. AMR was assessed by immunohistochemistry (CD31-positive capillaries to CD68 and C4d; all x200). Immunosuppression consisted of CsA, everolimus or mycophenolate and steroids. Forty-three pts were continuously on everolimus during the first post-transplant year. Results: ACR grade 1R was found in 21% of pts at FU1, in 11% of pts at FU2 and in 3% of pts at FU3. Grade 3R affected ⬍1% of pts in FU1 and was not detected in FU2 or FU3. AMR was present in 37% of pts at FU1, in 8% of pts at FU2 and in 10% of pts at FU3. Women as compared to men were affected more frequently by ACR of any grade in FU1 (35% vs. 20%; p⫽0.043), FU2 (33% vs. 8%; p⫽0.009) and FU3 (22% vs. 0%; p⫽0.020). Women also presented more often with AMR than men in FU1 (60% vs. 33%; p⫽0.044) and FU2 (21% vs. 6%; p⫽0.073), but there was no difference at FU3 (13% vs. 10%; p⫽0.600). Everolimus suppressed AMR in FU1 (25% vs. 44%, p⫽0.041), and this effect was more pronounced in women (29% vs. 88%; p⫽0.035) than in men (24% vs. 34%; p⫽0.136). However, AMR in FU2 and FU3 was equally frequent in everolimus-treated men and women. Conclusions: Women present more often with AMR than men. Everolimus prevents AMR early after HTx, especially in female HTx recipients. Further study is necessary to determine gender and immunosuppressive effects beyond the first post-transplant year. 516 Seasonal Variations in Cardiac Transplant Antibody-Mediated Rejection L. Piponniau, A. Velleca, M. Kittleson, D. Lockhart, B. Kearney, T. Kao, M. Johnson, M. Kawano, Z. Goldstein, M. Rafiei, F. Esmailian, J. Kobashigawa. Cedars-Sinai Heart Institute, Los Angeles, CA. Purpose: Rejection may be influenced by seasonal factors. In liver transplant recipients, rejection is more common in winter. This may be related to flu vaccines or infections which upregulate the immune system. The purpose of the current study was to determine if there are seasonal variations in acute cellular (ACR) or antibody-mediated rejection (AMR) in heart transplant recipients at our center. Methods and Materials: We evaluated 424 patients transplanted 19942010 to assess for seasonal variations in ACR and AMR. Seasons were defined: winter (December-February), spring (March-May), summer (JuneAugust), and fall (September-November). Rejection episodes were further divided into those that occurred early (⬍ 6 mos) and those that occurred later (⬎ 6 mos) after transplant, since at our center, patients ⬍ 6 mos after transplant do not receive flu vaccines. Results: A significantly higher percent of all AMR episodes occurred in the winter mos compared to the spring, summer and fall mos (32% vs. 23%, 22%, 23% respectively, p⬍0.05). Similarly, those patients with AMR within 6 mos of transplant (no flu vaccine given to these patients per protocol) had significantly higher incidence of AMR in the winter mos compared to the other seasons (33% vs. 23%, 23%, and 21%, p⬍0.05). Conversely, there was no difference in the percent of all ACRs among the winter, spring, summer and fall groups (22% vs. 25%, 26%, and 23% respectively, p⫽NS). The frequency of flu infections was not available, although in general, flu cases are more common in winter. Percent of all Rejection Episodes Occurring in Each Season
515 Effect of Gender on Everolimus Treatment for Antibody-Mediated Rejection after Heart Transplantation N.E. Hiemann,1 E. Wellnhofer,2 S. Kretschmer,1 C. Christan,1 H. Lehmkuhl,1 C. Knosalla,1 R. Hetzer,1 R. Meyer.1 1Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany; 2 Cardiology, Deutsches Herzzentrum Berlin, Berlin, Germany. Purpose: Women are known to present more often with acute cellular rejection after heart transplantation (HTx). However, the role of gender in
Cellular Rejection Antibody-Mediated Rejection (All Times) Antibody-Mediated Rejection (First 6 Months Post Transplant)
Spring
Summer
Fall
Winter
25% 23%
26% 22%
27% 23%
22% 32%*
23%
23%
21%
33%*
*P⬍0.05, compared to Spring, Summer and Fall.