OBJECTIVES: Antibodies targeting angiotensin II type 1 receptor (AT1R) have been associated with malignant hypertension, autoimmune diseases and acute rejection and graft loss in solid organ transplantation. The aim of our study was to assess the impact of anti-AT1R antibodies on survival and incidence of acute cellular rejection (ACR) and pathology antibody-mediated rejection (pAMR) in a population of heart transplant recipients who were bridged to transplantation with a durable mechanical assist device Heart Mate II. METHODS: Sera of 69 consecutive heart transplant recipients transplanted between October 2008 and August 2014 were tested for the presence of angiotensin II type 1 receptor antibodies before Heart Mate II device implantation and at the time of transplantation. Overall survival and post-transplant rejection-free survival were compared between antibody-negative and antibody-positive recipients using Kaplan-Meier and log-rank tests. RESULTS: Anti-AT1R antibodies were present in 8 patients (11.6%) before Heart Mate II implantation. During the left ventricular assist device (LVAD) bridging, 44 patients (63.8%) who were initially anti-AT1R antibody-negative became positive, leaving 17 (24.6%) anti-AT1R antibody-negative patients at the time of transplantation for all comparisons. One- and 5-year survival was 88 ± 8 and 76 ± 10% for anti-AT1R antibody-negative and 87 ± 5 and 81 ± 7% for anti-AT1R antibody-positive patients, respectively (P = 0.582). Freedom from ACR at 1 year was 68 ± 12% for anti-AT1R-negative and 75 ± 6% for anti-AT1R-positive recipients (P = 0.218). None of the anti-AT1R-negative patients developed AMR 1 year post-transplantation, whereas freedom from pAMR in anti-AT1R-positive recipients was 98 ± 2% (P = 0.198). CONCLUSIONS: Our data showed no difference in the overall post-heart transplant survival and freedom from acute cellular and antibody-mediated rejection between anti-AT1R-negative and anti-AT1R-positive recipients. Further research is needed to assess the role of anti-AT1R antibodies in the risk stratification of LVAD-bridged recipients on the post-heart transplantation outcomes.

Department of Cardiology Institute for Clinical and Experimental Medicine Prague Czech Republic

Department of Cardiovascular Surgery Institute for Clinical and Experimental Medicine Prague Czech Republic

Department of Immunology Institute for Clinical and Experimental Medicine Prague Czech Republic

Zobrazit více v PubMed

Trivedi JR, Cheng A, Singh R, Williams ML, Slaughter MS. Survival on the heart transplant waiting list: impact of continuous flow left ventricular assist device as bridge to transplant. Ann Thorac Surg 2014;98:830–4. PubMed

Long EF, Swain GW, Mangi AA. Comparative survival and cost-effectiveness of advanced therapies for end-stage heart failure. Circ Heart Fail 2014;7:470–8. PubMed

Askar M, Hsich E, Reville P, Daghstani J, Nowacki A, Zhang A et al. . Comparison of HLA & MICA allosensitization patterns among patients supported by ventricular assist devices (VAD) and patients with no devices. J Heart Lung Transplant 2013;32:S74. PubMed

Askar M, Hsich E, Reville P, Nowacki AS, Baldwin W, Bakdash S et al. . HLA and MICA allosensitization patterns among patients supported by ventricular assist devices. J Heart Lung Transplant 2013;32:1241–8. PubMed

Banan B, Phelan D, Medhat A, Ewald G, Mohanakumar T. (47) - Increased sensitization to HLA and to cardiac self-antigens (myosin and vimentin) in patients waiting for cardiac transplantation with left ventricular assisting device (LVAD). J Heart Lung Transplant 2014;33:S25.

Barten MJ, Dragun D, von Salisch S, Dieterlen MT, Garbade J, Klein S et al. . 112 Identification of non-HLA antibodies in ventricular assist device recipients. J Heart Lung Transplant 2012;31:S46.

Dragun D, Muller DN, Brasen JH, Fritsche L, Nieminen-Kehla M, Dechend R et al. . Angiotensin II type 1 receptor activating antibodies in renal-allograft rejection. N Engl J Med 2005;352:558–69. PubMed

Wallukat G, Homuth V, Fischer T, Lindschau C, Horstkamp B, Jupner A et al. . Patients with preeclampsia develop agonistic autoantibodies against the angiotensin AT1 receptor. J Clin Invest 1999;103:945–52. PubMed PMC

Riemekasten G, Philippe A, Nather M, Slowinski T, Muller DN, Heidecke H et al. . Involvement of functional autoantibodies against vascular receptors in systemic sclerosis. Ann Rheum Dis 2011;70:530–6. PubMed

Fu ML, Herltz H, Schulze W, Wallukat G, Micke P, Eftekhari P et al. . Autoantibodies against the angiotensin receptor (AT1) in patients with hypertension. J Hypertens 2000;18:945–53. PubMed

Taniguchi M, Rebellato LM, Cai J, Hopfield J, Briley KP, Haisch CE et al. . Higher risk of kidney graft failure in the presence of anti-angiotensin II type-1 receptor antibodies. Am J Transplant 2013;13:2577–89. PubMed

Giral M, Foucher Y, Dufay A, Van Huyen JP, Renaudin K, Moreau A et al. . Pretransplant sensitization against angiotensin II type 1 receptor is a risk factor for acute rejection and graft loss. Am J Transplant 2013;13:2567–76. PubMed

Banasik M, Boratynska M, Koscielska-Kasprzak K, Kaminska D, Bartoszek D, Zabinska M et al. . The influence of non-HLA antibodies directed against angiotensin II type 1 receptor (AT1R) on early renal transplant outcomes. Transpl Int 2014;27:1029–38. PubMed

Berry GJ, Burke MM, Andersen C, Bruneval P, Fedrigo M, Fishbein MC et al. . The 2013 International Society for Heart and Lung Transplantation Working Formulation for the standardization of nomenclature in the pathologic diagnosis of antibody-mediated rejection in heart transplantation. J Heart Lung Transplant 2013;32:1147–62. PubMed

Stewart S, Winters GL, Fishbein MC, Tazelaar HD, Kobashigawa J, Abrams J et al. . Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of heart rejection. J Heart Lung Transplant 2005;24:1710–20. PubMed

Lund LH, Edwards LB, Kucheryavaya AY, Benden C, Christie JD, Dipchand AI et al. . The Registry of the International Society for Heart and Lung Transplantation: thirty-first official adult heart transplant report—2014; focus theme: retransplantation. J Heart Lung Transplant 2014;33:996–1008. PubMed

Dragun D. Humoral responses directed against non-human leucocyte antigens in solid-organ transplantation. Transplantation 2008;86:1019–25. PubMed

Dragun D, Philippe A, Catar R. Role of non-HLA antibodies in organ transplantation. Transplantation 2012;17:440–5. PubMed

Reinsmoen NL, Lai CH, Heidecke H, Haas M, Cao K, Ong G et al. . Anti-angiotensin type 1 receptor antibodies associated with antibodynmediated rejection in donor HLA antibody negative patients. Transplantation 2010;90:1473–7. PubMed

Hiemann NE, Meyer R, Wellnhofer E, Schoenemann C, Heidecke H, Lachmann N et al. . Non-HLA antibodies targeting vascular receptors enhance alloimmune response and microvasculopathy after heart transplantation. Transplantation 2012;94:919–24. PubMed

Yousufuddin M, Cook DJ, Starling RC, Abdo A, Paul P, Tuzcu EM et al. . Angiotensin II receptors from peritransplantation through first-year-post transplantation and the risk of transplant coronary artery disease. J Am Coll Cardiol 2004;43:1565–73. PubMed

Yamani MH, Cook DJ, Rodrigues ER, Thomas DM, Gupta S, Alster J et al. . Incresed expression of Angiotensin II Type 1 Receptor (AGTR1) in heart transplant recipients with acute rejection. J Heart Lung Transplant 2006;25:1283–9. PubMed