Authors

• Boško Skorić — University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia — ORCID: 0000-0001-5979-2346
• Jana Ljubas Maček — University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia — ORCID: 0000-0001-7171-2206
• Maja Čikeš — University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia — ORCID: 0000-0002-4772-5549
• Hrvoje Jurin — University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia — ORCID: 0000-0002-2599-553X
• Jure Samardžić — University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia — ORCID: 0000-0002-9346-6402
• Daniel Lovrić — University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia — ORCID: 0000-0002-5052-6559
• Ivo Planinc — University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia — ORCID: 0000-0003-0561-6704
• Dora Fabijanović — University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia — ORCID: 0000-0003-2633-3439
• Marijan Pašalić — University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia — ORCID: 0000-0002-3197-2190
• Nina Jakuš — University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia — ORCID: 0000-0001-7304-1127
• Renata Žunec — University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia — ORCID: 0000-0003-2607-3059
• Davor Miličić — University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia — ORCID: 0000-0001-9101-1570

Keywords

antibody-mediated rejection, heart transplantation

DOI

Full Text

**Case report:** On the second year after heart transplantation (HTx), a 25-years-old man was hospitalized for effort intolerance and epigastric pain. Echocardiography showed anterolateral akinesia. Severe cardiac allograft vasculopathy (CAV) with diffuse left anterior descending (LAD) stenoses, occlusion of diagonal branch, diffuse stenoses of obtuse marginal and slow flow in the dominant right coronary artery (RCA) was diagnosed. No signs of cell-mediated rejection (CMR) were present, but swollen endothelial cells as well as positive C3d and C4d capillary staining with immunofluorescence detected antibody-mediated rejection (AMR). The patient was treated with steroids, plasmapheresis and intravenous immunoglobulins. Control biopsies (Bx) were free of AMR and echocardiography showed recovery of systolic function. On the third year he developed inferior ST segment elevation myocardial infarction and primary percutaneous coronary intervention (PCI) of RCA was done. This time left coronary artery was not diffusely ill, and a focal LAD stenosis was electively stented. Neither CMR nor AMR were detected on Bx. On the fourth year, routine angio control revealed CAV progression and we performed PCI of distal left main coronary artery, LAD and intermediate branch (RIM) with double-kissing crush technique. On the fifth year, PCI of RCA restenosis was performed. This time we could measure donor specific antibodies (DSA). Though Bx failed to show AMR, both anti-HLA class I and II were highly elevated and photopheresis was started. On the sixth posttransplant year, despite significant drop in anti-HLA class I, anti-HLA class II antibodies remained high and the patient developed congestive heart failure. An angioplasty with drug-eluting balloon of RIM stenosis was performed. No signs of rejection on Bx were noted. Because of graft failure and advanced CAV, we decided to prepare the patient for re-transplantation. As the calculated panel reactive antibodies (cPRA) were high, we opted for desensitization therapy (plasmapheresis, IVIg, rituximab, bortezomib) to increase the number of potential donors (**Figure 1**). Since cPRA remained >50%, we listed the patient for re-transplantation after the definition of unacceptable HLA antigens. Figure 1. The dynamics of donor specific antibodies (DSA) in serum. **Conclusion:** This case presents difficulties in the management of antibody-mediated rejection. (1) Only a combination of clinical with both pathologic and serologic data, that were not readily available in the past, may prove early effective therapy and prevent progressive graft deterioration.

Literature

1. Colvin MM, Cook JL, Chang P, Francis G, Hsu DT, Kiernan MS, et al. American 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. Circulation. 2015;131(18):1608–39. https://doi.org/10.1161/CIR.0000000000000093