Immunoadsorptio in dilated cardiomyopathy a real alternative to the cardiac transplant pr u schulz
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Plus de Clínica Universidad de Navarra
Plus de Clínica Universidad de Navarra (20)
Immunoadsorptio in dilated cardiomyopathy a real alternative to the cardiac transplant pr u schulz
- 1. Klinik für Thorax- und Kardiovas- kularchirurgie Immunoadsorption in DCM: A real alternative to the cardiac transplant (?/!) Uwe Schulz Transplantationsstation und –ambulanz Klinik für Thorax- und Kardiovaskularchirurgie Herz- und Diabeteszentrum NRW Bad Oeynhausen
- 3. Klinik für Thorax- und Kardiovaskular- chirurgie β1- Receptor peptides induce morphological changes control survived died after 9 month saline + adjuvants ß1-Peptide + adjuvants ß1-Peptide + adjuvants Matsui, S et al: J Mol Cell Cardiol 29 (1997) : 641
- 4. Klinik für Thorax- und Kardiovaskular- chirurgie after month 6-9: left ventricular dilation and dysfunction diagnosed by echocardiography & catheterization Sources: 1) Jahns, R et al: 68th Annual Meeting, German Soc. Cardiol. 2002: V235 2) Jahns, R et al:JCI, 2004 transfer of serum into rats Immunisation of rats with β1-adrenergic receptor 15 months : induction of anti-ß1-receptor antibodies after month 9-15: progressive left ventricular dilation and dysfunction serum DCMDCM
- 5. Klinik für Thorax- und Kardiovaskular- chirurgie Spontaneously beating neonatal rat- cardiomyocytes
- 6. Klinik für Thorax- und Kardiovaskular- chirurgie Actin HSP 60 ACh-receptor HSP 70 Aconitate hydratase Vimentin Pyruvate kinase Laminin Dihydrolipoamide DH Myosin Creatin kinase NADD Adenine nucleotide translocator UCR ß1-adrenergic receptor SSA Ca 2+ channel SSB Carnitin ENA Desmin ANCA Myolemma ASA Maisch, B et al: Herz 25 (2000): 200
- 7. Klinik für Thorax- und Kardiovaskular- chirurgie Development of autoimmune-cardiomyopathy ?! Infections viral/ bacterial ?! ?! Ischemia myocardial infarction Heart tissues are damaged by … … resulting in generation of cardiac antibodies Myocyte-antigens are presented to the immune- system … ?! Toxins (alcohol, chemotherapy) Jahns et al., Progr. Inflamm. Res. 2008
- 8. Klinik für Thorax- und Kardiovaskular- chirurgie Cardial targets for autoimmune reactions Cytoskelettal Proteins! Tubulin (Latif 1993)! Laminin (Maisch 1983)! cardial Troponin I (Okazaki, 2003)! cardial Aktin! (Neumann 1990)! cardial α-Myosin (Eriksson 2003)! Sarkomer-Proteins! G-Protein receptors! β1-AR (Magnusson 1994, Jahns 1999,2004)! β2-AR (Sterin-Borda 1988)! α1-AR (Fu 1993, 2004)! muscar. M2-R (Fu 1993; Borda 1996)! AT1-AR (Wallukat 1999, Fu 2000) mitochondrial ADP/ATP-carrier! (Klein 1984; Schultheiss 1986)! GADPH; GPBB; Aconitathydrase! (Buse 2008)! Ion channels (?)! L-Ca2+-channel! T-Ca2+-channel! K+-channels/- ChlPs! K+-ChIP2! (Felix 2002, 2008)!
- 14. Klinik für Thorax- und Kardiovaskular- chirurgie Müller, J; Wallukat, G et al: Circulation 101 (2000): 385
- 15. Klinik für Thorax- und Kardiovaskular- chirurgie Müller, J; Wallukat, G et al: Circulation 101 (2000): 385
- 21. Klinik für Thorax- und Kardiovaskular- chirurgie Hessel F et al.: Eur J Health Economics. 2004 p=0.0071
- 22. Klinik für Thorax- und Kardiovaskular- chirurgie Hessel F et al.: Eur J Health Economics. 2004 p=0.0071 Costs during 5 years: - 128 600 € IA - 75 500 control With regard to survival benefit: - 24900 €/year IA - 28900 €/year control „costs per life year gained“ >> 34 400 €
- 23. Klinik für Thorax- und Kardiovaskular- chirurgie Poster ESC; Stockholm (2.-6. September 2005)
- 33. Klinik für Thorax- und Kardiovaskular- chirurgie Heart transplantation HDZ NRW, Ruhr-University of Bochum Bad Oeynhausen, 3/1989 – 11/2010 2 days - 77 years, mean: 49.9 yrs. 1468 male (81%) / 345 female(19%) Recipients: Donors: 1 day - 72 yrs., mean: 34.7 yrs. 927 male (51,1%) / 886 female (48.9%) n = 1813 Non-VAD: 1431 (78,9%) / VAD: 382 (21,1%)
- 46. Klinik für Thorax- und Kardiovaskular- chirurgie Clinical course: EF (%) TI MI per. Ödeme NYHA Prior to IA: 41 II° I°-II° + III after Rtx: 43 II° I°-II° +/- III after 1 month: 50 I° 0°-I° -- I-II after 2 months: 64 I° 0°-I° -- I after 3 months: 61 I° 0°-I° -- I Successful management of antibody-mediated cardiac allograft rejection with combined immunoadsorption and anti-CD20 monoclonal antibody treatment: case report and literature review. I Kaczmarek, MA Deutsch, S Sadoni, P Brenner, D Schmauss, SH Daebritz, M Weiss, BM Meiser, and B Reichart J Heart Lung Transplant, May 1, 2007; 26(5): 511-5. 37-year old man; CAD; status after myoc. infarction implantation of Novacor-LVAD 12/02; HTX 04/2004 PRA 30%; no induction therapy 01/05 IST switched to SIR/MMF >> 3 months later clinical signs of heart insufficiency
- 47. Klinik für Thorax- und Kardiovaskular- chirurgie Successful management of antibody-mediated cardiac allograft rejection with combined immunoadsorption and anti-CD20 monoclonal antibody treatment: case report and literature review. I Kaczmarek, MA Deutsch, S Sadoni, P Brenner, D Schmauss, SH Daebritz, M Weiss, BM Meiser, and B Reichart J Heart Lung Transplant, May 1, 2007; 26(5): 511-5.
- 48. Klinik für Thorax- und Kardiovaskular- chirurgie Successful management of antibody-mediated cardiac allograft rejection with combined immunoadsorption and anti-CD20 monoclonal antibody treatment: case report and literature review. I Kaczmarek, MA Deutsch, S Sadoni, P Brenner, D Schmauss, SH Daebritz, M Weiss, BM Meiser, and B Reichart J Heart Lung Transplant, May 1, 2007; 26(5): 511-5. „Nevertheless, effective standardized schemes for the treatment of antibody- mediated graft rejection have to be defined. We present a heart transplant recipient with sustained antibody-mediated graft rejection who was successfully managed with a combination treatment consisting of 3 cycles of immunoadsorption and a single-dose administration of the anti-CD20 monoclonal antibody rituximab.“
- 49. Klinik für Thorax- und Kardiovaskular- chirurgie 49 year old man; status after aortic valve replacement; 6 transfusions HTx 2 years later with PRA 80% 11x IA in 35 days Serum IgG 14,2 >> 0.7 g/l // Serum IgM 1,7 >> 0,2 g/l IST: OKT3; CyA; Aza expired pod 28: sepsis (pseudomonas aeruginosa)
- 50. Klinik für Thorax- und Kardiovaskular- chirurgie Case 1: Retransplantation - 39 year old female patient with DCM - First Tx 2003 after 4 weeks of LVAD support (Thoratec) - GVP detected 4/2008 - HU listing 01/2009 due to progression of GVP in combination with increasing number and complexity of rhythm disorders and beginning deterioration of cardiac function (CI 1.9) - PRA 100% (MHC Class I and II positive in ELISA and lymphocyte test) - Prospective cross-match prepared
- 51. Klinik für Thorax- und Kardiovaskular- chirurgie Case 1: Retransplantation - 2 organ offers rejected (positive donor X-match) - further deterioration of clinical situation - Prospective X-match only possible in Germany not in all ET countries (waiting time longer!!) - 2 Immunoadsorptions pre-Tx: 21.02. and 01.03. - intraoperative induction therapy (Thymoglobulin 2,5 mg/kg); Tac/MMF/ Cortison as maintenance IST - 2 Immunoadsorptions post-Tx: on pod 1 and 24 - discharge on pod 28; follow-up 4 weeks after last IA - present PRA ?% (MHC Class I and II weak positive in ELISA and lymphocyte test) - 3rd postop IA next week planned electively
- 52. Klinik für Thorax- und Kardiovaskular- chirurgie Case 2: VAD-use: Total artificial heart (CardioWest) - 36 year old female patient - HNOCM - CardioWest implant in cardiogenic shock 08/2007 - 24.02.2009 HTx - humoral rejection“: antibody treatment (r-ATG); plasmapheresis; catecholamine dependent, renal failure - >>> only marginal improvement - MHC class I and II positive in perioperative X-match: - 1 course of immunoadsorption - slow but progressive improvement - discharge with recovered renal function and myocardial Bx ISHLT grade 0 4 weeks later - follow up 4 weeks after discharge uneventful
- 53. Klinik für Thorax- und Kardiovaskular- chirurgie „immunological“ risk factors - VAD use - excessive use of blood and blood components - post-partum women - homograft use - retransplantation or second transplantation
- 54. Klinik für Thorax- und Kardiovaskular- chirurgie Summary - apheresis can stabilize clinical course of patients with heart insufficiency and dilated cardiomyopathy - removal of autoantibodies is possible - HLA-antibody removal in sensitized patients makes Tx possible - further evaluation needed for both indications
- 55. No se puede mostrar la imagen. Puede que su equipo no tenga suficiente memoria para abrir la imagen o que ésta esté dañada. Reinicie el equipo y, a continuación, abra el archivo de nuevo. Si sigue apareciendo la x roja, puede que tenga que borrar la imagen e insertarla de nuevo. Klinik für Thorax- und Kardiovaskular- chirurgie Der Antikörper-Staubsauger Wer sagt eigentlich, dass bei Herzinsuffizienz nur Pillen und Transplantationschirurgen helfen können? Per Dialyse geht das Wasser jedenfalls auch raus. Jetzt wollen extrakorporal veranlagte Kardiologen auch noch Antikörper absaugen, um dem Wasser den Garaus zu machen.