CCCardiol CroatCardiologia CroaticaCardiol. Croat.1848-543X1848-5448Croatian Cardiac SocietyCC_13(11-12)_36910.15836/ccar2018.369Extended AbstractSuccessful treatment of cardiogenic shock caused by mixed acute cellular- and antibody-mediated cardiac allograft graft rejectionUspješno liječenje kardiogenog šoka uzrokovanog miješanim akutnim stanično- i protutijelima-posredovanim odbacivanjem srčanog presatkahttps://orcid.org/0000-0002-6587-2315PašaraVedran1https://orcid.org/0000-0002-3197-2190PašalićMarijan1https://orcid.org/0000-0003-2633-3439FabijanovićDora1https://orcid.org/0000-0001-7304-1127JakušNina1https://orcid.org/0000-0003-0561-6704PlanincIvo1https://orcid.org/0000-0002-4772-5549ČikešMaja12https://orcid.org/0000-0001-7171-2206Ljubas MačekJana1https://orcid.org/0000-0002-9346-6402SamardžićJure1https://orcid.org/0000-0002-2599-553XJurinHrvoje1https://orcid.org/0000-0002-5052-6559LovrićDaniel1https://orcid.org/0000-0003-2607-3059ŽunecRenata1https://orcid.org/0000-0003-2781-4576Burek KamenarićMarija1https://orcid.org/0000-0003-4519-5940ŠafradinIvica1https://orcid.org/0000-0001-9101-1570MiličićDavor12https://orcid.org/0000-0001-5979-2346SkorićBoško12Klinički bolnički centar Zagreb, Zagreb, HrvatskaMedicinski fakultet Sveučilišta u Zagrebu, Zagreb, HrvatskaUniversity Hospital Centre Zagreb, Zagreb, CroatiaUniversity of Zagreb School of Medicine, Zagreb, CroatiaADDRESS FOR CORRESPONDENCE: Boško Skorić, Klinički bolnički centar Zagreb, Kišpatićeva 12, HR-10000 Zagreb, Croatia. / Phone: +385-95-3959-910 / E-mail: bskoric3@yahoo.com1120181311-1239637027102018051120182018Croatian Cardiac SocietyKLJUČNE RIJEČI: odbacivanje presatka posredovano stanicama i protutijelimatransplantacija srcaKEYWORDS: cellular-mediated rejectionantibody-mediated rejectionheart transplantation
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)
LITERATUREColvinMMCookJLChangPFrancisGHsuDTKiernanMSAmerican Heart Association Heart Failure and Transplantation Committee of the Council on Clinical Cardiology; American Heart Association Heart Failure and Transplantation Committee of the Council on Cardiopulmonary Critical Care, Perioperative and Resuscitation; American Heart Association Heart Failure and Transplantation Committee of the Council on Cardiovascular Disease in the Young; American Heart Association Heart Failure and Transplantation Committee of the Council on Clinical Cardiology, Council on Cardiovascular and Stroke Nursing; American Heart Association Heart Failure and Transplantation Committee of the Council on Cardiovascular Radiology and Intervention; American Heart Association Heart Failure and Transplantation Committee of the Council on Cardiovascular Surgery and Anesthesia. Antibody-mediated rejection in cardiac transplantation: emerging knowledge in diagnosis and management: a scientific statement from the American Heart Association. . 2015 May 5;131(18):1608–39. 10.1161/CIR.000000000000009325838326