Successful treatment of cardiogenic shock caused by mixed acute cellular- and antibody-mediated cardiac allograft graft rejection

    Authors

    Keywords

    cellular-mediated rejection, antibody-mediated rejection, heart transplantation

    DOI

    https://doi.org/10.15836/ccar2018.369

    Full Text

    Case report : 18-year-old female was hospitalized for acute heart failure three years after a heart transplant. Echocardiography showed thickened walls and reduced systolic function of both ventricles (left ventricular ejection fraction, LVEF 30%). Pulse steroid therapy was started after urgent cardiac biopsy (Bx). Because of the development of cardiogenic shock, a venous-arterial (VA) ECMO (extracorporeal membrane oxygenation) had to be set up. Bx showed a mixed type of acute rejection: antibody-mediated rejection grade pAMR 1(I+) and cell-mediated rejection grade 3R. Luminex ® confirmed the existence of numerous anti-HLA donor specific antibodies (DSA) class I (A11, A30, B13, B35) and class II (DR3, DR15, DR51, DQ2, DPA1*02) with maximal MFI 13000 for anti-DQ2. Plasmapheresis, intravenous immunoglobulin (IVIg) and antithymocite globulin (ATG) were immediately initiated. On the fourth day, both ventricles had normal wall thickness and improved systolic function (LVEF 40%). The patient was successfully weaned from ECMO. Rituximab was applied at the end of the second week. Control Bx showed no cell-mediated rejection, while immunohistochemistry remained positive. Coronary angiography was normal. Five additional plasmapheresis cycles were performed and IVIg was administered, whereupon echocardiography showed normal left ventricle size and wall thickness, while right ventricle was normal in size but had slightly reduced function. Bx showed no cell- or antibody-mediated rejection. Seven weeks after treatment initiation DSA class I and class II were all negative, except anti-DQ2 (MFI 6100) ( Figure 1 ). 12 months later the patient is stable, without signs of rejection or graft function deterioration. Temporal changes of anti-HLA donor-specific antibodies in response to treatment. MFI = mean fluorescence intensity; class I = class I anti-HLA donor-specific antibodies; class II = class II anti-HLA donor-specific antibodies Conclusion : This case shows the importance of acute mechanical circulatory support in heart transplant patients with critical heart failure and, therefore, gaining additional time to run tests and wait for therapeutic effects (i.e. bridge-to-decision, bridge-to-recovery). By combining steroids, plasmapheresis, IVIg, ATG and rituximab, we interacted with complex immune mechanisms of mixed cell- and antibody-mediated acute graft rejection, and ultimately provided not only survival, but also the complete recovery of the patient. ( 1 )

    Cardiologia Croatica
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    Successful treatment of cardiogenic shock caused by mixed acute cellular- and antibody-mediated cardiac allograft graft rejection

    Extended Abstract
    Issue11-12
    Published
    Pages396-370
    PDF via DOIhttps://doi.org/10.15836/ccar2018.369
    cellular-mediated rejection
    antibody-mediated rejection
    heart transplantation

    Authors

    Vedran PašaraORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Marijan PašalićORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Dora FabijanovićORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Nina JakušORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Ivo PlanincORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Maja ČikešORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Jana Ljubas MačekORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Jure SamardžićORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Hrvoje JurinORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Daniel LovrićORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Renata ŽunecORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Marija Burek KamenarićORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Ivica ŠafradinORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Davor MiličićORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Boško Skorić*ORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia

    Full Text

    Case report : 18-year-old female was hospitalized for acute heart failure three years after a heart transplant. Echocardiography showed thickened walls and reduced systolic function of both ventricles (left ventricular ejection fraction, LVEF 30%). Pulse steroid therapy was started after urgent cardiac biopsy (Bx). Because of the development of cardiogenic shock, a venous-arterial (VA) ECMO (extracorporeal membrane oxygenation) had to be set up. Bx showed a mixed type of acute rejection: antibody-mediated rejection grade pAMR 1(I+) and cell-mediated rejection grade 3R. Luminex ® confirmed the existence of numerous anti-HLA donor specific antibodies (DSA) class I (A11, A30, B13, B35) and class II (DR3, DR15, DR51, DQ2, DPA1*02) with maximal MFI 13000 for anti-DQ2. Plasmapheresis, intravenous immunoglobulin (IVIg) and antithymocite globulin (ATG) were immediately initiated. On the fourth day, both ventricles had normal wall thickness and improved systolic function (LVEF 40%). The patient was successfully weaned from ECMO. Rituximab was applied at the end of the second week. Control Bx showed no cell-mediated rejection, while immunohistochemistry remained positive. Coronary angiography was normal. Five additional plasmapheresis cycles were performed and IVIg was administered, whereupon echocardiography showed normal left ventricle size and wall thickness, while right ventricle was normal in size but had slightly reduced function. Bx showed no cell- or antibody-mediated rejection. Seven weeks after treatment initiation DSA class I and class II were all negative, except anti-DQ2 (MFI 6100) ( Figure 1 ). 12 months later the patient is stable, without signs of rejection or graft function deterioration. Temporal changes of anti-HLA donor-specific antibodies in response to treatment. MFI = mean fluorescence intensity; class I = class I anti-HLA donor-specific antibodies; class II = class II anti-HLA donor-specific antibodies Conclusion : This case shows the importance of acute mechanical circulatory support in heart transplant patients with critical heart failure and, therefore, gaining additional time to run tests and wait for therapeutic effects (i.e. bridge-to-decision, bridge-to-recovery). By combining steroids, plasmapheresis, IVIg, ATG and rituximab, we interacted with complex immune mechanisms of mixed cell- and antibody-mediated acute graft rejection, and ultimately provided not only survival, but also the complete recovery of the patient. ( 1 )