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63: Cardiac Retransplantation: A Valid Option for All Patients?
The Journal of Heart and Lung Transplantation Volume 28, Number 2S
expressed proteins were excised and identified by mass spectrometry (MS). Proteomic profiles of DCM (n⫽3) and IHD (n⫽3) patients were compared with the profile of a pool of proteins isolated from non-failing hearts (n⫽5). Results: In the DCM group, we detected 16 proteins that showed a significant down-regulation (⬎1.5 fold, P⬍0.05) between preand post-LVAD tissue and 13 changed proteins could be identified by MS. In IHD patients, 50 proteomic changes were found, including both up- (n⫽14) and down- (n⫽36) regulated proteins. 29 proteins were identified by MS. The identified proteins in both groups are partially overlapping and include proteins from the cytoskeleton and energy metabolism. The latter changes are paralleled by severe alterations in mitochondrial morphology, as showed by electron microscopy. Post-LVAD proteomes of both DCM and IHD patients to a large extent mimic the protein profiles of non-failing hearts. Conclusions: Unloading of the heart with a LVAD, in both DCM- and IHD-patients is associated with specific atrophic changes in proteins expression profiles, predominantly involved in energy metabolism and cytoskeleton integrity.
62 C-Reactive Protein, Vascular Cell Adhesion Molecule and Neopterin Are Markers of Advanced Cardiac Allograft Vasculopathy Determined by Intravascular Ultrasound S. Arora, P. Aukrust, E. Gude, A. Andreassen, I. Grov, R. Skaardal, T. Ueland, O. Geiran, L. Gullestad Rikshospitalet Medical Center, Oslo, Norway Purpose: A range of inflammatory mediators are likely to be responsible for the development of CAV, but a broad characterization of these markers in relation to different IVUS endpoints has not been performed previously. We evaluated an extensive profile of clinical variables and immune markers to assess the chronic inflammatory milieu associated with advanced cardiac allograft vasculopathy (CAV) assessed by intravascular ultrasound (IVUS). Methods and Materials: In total, 101 heart transplant (HTx) recipients were included and all patients underwent IVUS examination and plasma sampling for measurement of the following immune markers: C-reactive protein (CRP), soluble tumor necrosis factor receptor-1 (sTNFR-1), interleukin-6 (IL-6), osteoprotegerin (OPG), soluble gp130, von Willebrand factor (vWf), vascular cell adhesion molecule-1 (VCAM-1) and neopterin. Results: Mean Percent Atheroma Volume (PAV) was 32.4⫾9.5%. Levels of CRP, sTNFR-1, VCAM-1 and neopterin were significantly higher amongst patients with PAV ⬎32% (n⫽50). Similar significant results were found when using Maximal Intimal Thickness (MIT) ⬎0.5 mm (n⫽47) as an alternative IVUS endpoint. Multivariate regression analysis revealed that CRP ⬎1.5 mg/L [adjusted OR 4.5 (95% CI 1.7-12.4), p⬍0.01], VCAM-1 ⬎391 ng/mL [adjusted OR 3.2 (95% CI 1.1-9.7), p⫽0.04] and neopterin ⬎767 nmol/L [adjusted OR 3.8 (95% CI (1.2-11.7), p⫽0.02] were independently associated with PAV ⬎32%. Conclusions: Advanced CAV quantified by IVUS is associated with an inflammatory signature comprising of elevated CRP, VCAM-1 and neopterin and reflects the multi-faceted immunological activity contributing to CAV development. Forthcoming studies should clarify if measurements of these markers will allow more individualized CAV surveillance and management of HTx recipients.
Abstracts
S87
63 Cardiac Retransplantation: A Valid Option for All Patients? J.M. Barcelo, M. Gomez-Bueno, J. Segovia, R. Burgos, E. Castedo, S. Serrano, J. Ugarte, L. Alonso-Pulpon Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain Purpose: Survival after heart transplantation (HT) has improved significantly over the last years. As a consequence, there are a substantial number of potential candidates for cardiac retransplantation (CR) due to chronic allograft dysfunction. However, CR is controversial due to lower survival rates and shortage of donors. The aim of our study was to retrospectively review short- and long-term outcomes after cardiac retransplantation. Methods and Materials: Between 1984 and 2007, 681 heart transplants have been performed at our institution, and 23 (3.4%) were CR. Indications for retransplantation were primary graft failure (PGF) in 3 patients(13%), acute rejection (AR) in 4 (17.4%), and coronary allograft vasculopathy (CAV) in 16 (69.6%). Results: The median (range) interval between primary transplantation and retransplantation was 1 (0-2) days for PGF, 6 (3-16) months for AR and 10 (2-14) years for EVI group. Baseline characteristic showing significant differences (p⬍0.05) between primary HT and CR were pre-transplant inotrope dependence (39.2% vs 69.6%), mechanical circulatory support (11% vs 26%) and urgent status (26.9% vs 47.6%), respectively. Early mortality after CR was significantly higher compared to first transplantation (43.5% vs 17.2%, p⬍ 0.001). However, a major difference on 30-day mortality was found depending on the indication of retransplantation (early lethality for AR, PGF and EVI patients of 75%, 66.7% and 31%, respectively, p⬍0.001).The 1, 5 and 10-year survival rates were 76%, 65% and 54%, respectively, for primary cardiac transplantation, and 39%, 34% and 27% for cardiac retransplantation (p ⬍0.001). Conclusions: The overall outcomes of CR are significantly worse than those of primary HT, in part due to unequal baseline conditions. However, the short-term and long-term survival after CR for patients with coronary allograft vasculopathy was acceptable. In contrast, patients with acute graft failure due to PGF or AR seem to be inappropriate candidates for cardiac retransplantation. 64 Circulating Anti-Heart Autoantibodies Are Non-Invasive Markers of High Cellular Rejection Burden in Heart Transplantation A.L.P. Caforio1, A. Vinci1, A. Angelini2, F. Tona1, S. Bottaro3, G. Thiene2, G. Gerosa1, S. Iliceto1 1University of Padova, Padova, Italy; 2University of Padova, Padova, Italy; 3University of Padova, Padova, Italy Purpose: Autoimmune response may occur after heart transplantation (HTx). In autoimmune disease autoantibodies provide markers for immune-mediated inflammation in the target organ. We aimed at assessing frequency and potential predictive role of serum anti-heartautoantibodies (AHA) for acute rejection (AR) after HTx.
expressed proteins were excised and identified by mass spectrometry (MS). Proteomic profiles of DCM (n⫽3) and IHD (n⫽3) patients were compared with the profile of a pool of proteins isolated from non-failing hearts (n⫽5). Results: In the DCM group, we detected 16 proteins that showed a significant down-regulation (⬎1.5 fold, P⬍0.05) between preand post-LVAD tissue and 13 changed proteins could be identified by MS. In IHD patients, 50 proteomic changes were found, including both up- (n⫽14) and down- (n⫽36) regulated proteins. 29 proteins were identified by MS. The identified proteins in both groups are partially overlapping and include proteins from the cytoskeleton and energy metabolism. The latter changes are paralleled by severe alterations in mitochondrial morphology, as showed by electron microscopy. Post-LVAD proteomes of both DCM and IHD patients to a large extent mimic the protein profiles of non-failing hearts. Conclusions: Unloading of the heart with a LVAD, in both DCM- and IHD-patients is associated with specific atrophic changes in proteins expression profiles, predominantly involved in energy metabolism and cytoskeleton integrity.
62 C-Reactive Protein, Vascular Cell Adhesion Molecule and Neopterin Are Markers of Advanced Cardiac Allograft Vasculopathy Determined by Intravascular Ultrasound S. Arora, P. Aukrust, E. Gude, A. Andreassen, I. Grov, R. Skaardal, T. Ueland, O. Geiran, L. Gullestad Rikshospitalet Medical Center, Oslo, Norway Purpose: A range of inflammatory mediators are likely to be responsible for the development of CAV, but a broad characterization of these markers in relation to different IVUS endpoints has not been performed previously. We evaluated an extensive profile of clinical variables and immune markers to assess the chronic inflammatory milieu associated with advanced cardiac allograft vasculopathy (CAV) assessed by intravascular ultrasound (IVUS). Methods and Materials: In total, 101 heart transplant (HTx) recipients were included and all patients underwent IVUS examination and plasma sampling for measurement of the following immune markers: C-reactive protein (CRP), soluble tumor necrosis factor receptor-1 (sTNFR-1), interleukin-6 (IL-6), osteoprotegerin (OPG), soluble gp130, von Willebrand factor (vWf), vascular cell adhesion molecule-1 (VCAM-1) and neopterin. Results: Mean Percent Atheroma Volume (PAV) was 32.4⫾9.5%. Levels of CRP, sTNFR-1, VCAM-1 and neopterin were significantly higher amongst patients with PAV ⬎32% (n⫽50). Similar significant results were found when using Maximal Intimal Thickness (MIT) ⬎0.5 mm (n⫽47) as an alternative IVUS endpoint. Multivariate regression analysis revealed that CRP ⬎1.5 mg/L [adjusted OR 4.5 (95% CI 1.7-12.4), p⬍0.01], VCAM-1 ⬎391 ng/mL [adjusted OR 3.2 (95% CI 1.1-9.7), p⫽0.04] and neopterin ⬎767 nmol/L [adjusted OR 3.8 (95% CI (1.2-11.7), p⫽0.02] were independently associated with PAV ⬎32%. Conclusions: Advanced CAV quantified by IVUS is associated with an inflammatory signature comprising of elevated CRP, VCAM-1 and neopterin and reflects the multi-faceted immunological activity contributing to CAV development. Forthcoming studies should clarify if measurements of these markers will allow more individualized CAV surveillance and management of HTx recipients.
Abstracts
S87
63 Cardiac Retransplantation: A Valid Option for All Patients? J.M. Barcelo, M. Gomez-Bueno, J. Segovia, R. Burgos, E. Castedo, S. Serrano, J. Ugarte, L. Alonso-Pulpon Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain Purpose: Survival after heart transplantation (HT) has improved significantly over the last years. As a consequence, there are a substantial number of potential candidates for cardiac retransplantation (CR) due to chronic allograft dysfunction. However, CR is controversial due to lower survival rates and shortage of donors. The aim of our study was to retrospectively review short- and long-term outcomes after cardiac retransplantation. Methods and Materials: Between 1984 and 2007, 681 heart transplants have been performed at our institution, and 23 (3.4%) were CR. Indications for retransplantation were primary graft failure (PGF) in 3 patients(13%), acute rejection (AR) in 4 (17.4%), and coronary allograft vasculopathy (CAV) in 16 (69.6%). Results: The median (range) interval between primary transplantation and retransplantation was 1 (0-2) days for PGF, 6 (3-16) months for AR and 10 (2-14) years for EVI group. Baseline characteristic showing significant differences (p⬍0.05) between primary HT and CR were pre-transplant inotrope dependence (39.2% vs 69.6%), mechanical circulatory support (11% vs 26%) and urgent status (26.9% vs 47.6%), respectively. Early mortality after CR was significantly higher compared to first transplantation (43.5% vs 17.2%, p⬍ 0.001). However, a major difference on 30-day mortality was found depending on the indication of retransplantation (early lethality for AR, PGF and EVI patients of 75%, 66.7% and 31%, respectively, p⬍0.001).The 1, 5 and 10-year survival rates were 76%, 65% and 54%, respectively, for primary cardiac transplantation, and 39%, 34% and 27% for cardiac retransplantation (p ⬍0.001). Conclusions: The overall outcomes of CR are significantly worse than those of primary HT, in part due to unequal baseline conditions. However, the short-term and long-term survival after CR for patients with coronary allograft vasculopathy was acceptable. In contrast, patients with acute graft failure due to PGF or AR seem to be inappropriate candidates for cardiac retransplantation. 64 Circulating Anti-Heart Autoantibodies Are Non-Invasive Markers of High Cellular Rejection Burden in Heart Transplantation A.L.P. Caforio1, A. Vinci1, A. Angelini2, F. Tona1, S. Bottaro3, G. Thiene2, G. Gerosa1, S. Iliceto1 1University of Padova, Padova, Italy; 2University of Padova, Padova, Italy; 3University of Padova, Padova, Italy Purpose: Autoimmune response may occur after heart transplantation (HTx). In autoimmune disease autoantibodies provide markers for immune-mediated inflammation in the target organ. We aimed at assessing frequency and potential predictive role of serum anti-heartautoantibodies (AHA) for acute rejection (AR) after HTx.