CT Projects



Since 2008 two collaborative projects on cardiac transplant pathology have been carried out/are in progress and a further project is planned.

Using web-based digital histology, the reproducibility of biopsy diagnosis of cardiac allograft rejection using the 2005 and 1990 Working Formulations for Cardiac Allograft Rejection (1; 2) resulted in an abstract presentation at the 2010 meeting of the International Society for Heart and Lung Transplantation (ISHLT) in Chicago. Eighteen pathologists from 15 centres in 7 European countries participated and the results were subsequently published (3)

A questionnaire was devised to investigate current practice across Europe using C4d as an aid to biopsy diagnosis of antibody-mediated rejection (AMR). 35 pathologists from 29 centres in 14 European countries responded. Preliminary results were presented at the 10th Banff Allograft Pathology Conference in 2009. The final results were presented as an abstract during the 2010 Chicago meeting of the International Society for Heart and Lung Transplantation (4) and were summarised in a report of a Consensus Conference held immediately before the meeting and subsequently published by Kobashigawa et al (2011) (5).

Since 2009 the information from these projects has been fed into three ISHLT Pathology Workshops held prior to the 2010, 2011 and 2012 ISHLT Annual Scientific Meetings. These were led by members of ISHLT's Pathology Council with a significant contribution from several members of the AECVP. The outcome of the 2010 workshop led to a paper on the current status of biopsy diagnosis of cardiac AMR and included a provisional pathological grading system (6). In 2011 and 2012 agreed pathological diagnostic criteria were tested by ISHLT Pathology Council members through online surveys of digitized cardiac allograft biopsy slides. The definitive 2013 ISHLT Working Formulation for biopsy diagnosis of AMR has now been accepted for publication. It will be supplemented by an on-line Appendix using digital images to illustrate typical cases of AMR and pitfalls encountered in diagnosis.

A collaborative project between pathologists from 5 European cardiac transplant centres is currently in progress. It investigates the immunophenotype of the myocardial inflammatory burden in endomyocardial biopsies with antibody-mediated rejection. Preliminary results were presented at the 2013 ISHLT meeting in Montreal (7).    

Reference LIst

   1.   Stewart S, Winters GL, Fishbein MC, Tazelaar HD, Kobashigawa J, Abrams J, Andersen CB, Angelini A, Berry GJ, Burke MM, 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.

   2.   Billingham ME, Cary NR, Hammond ME, Kemnitz J, Marboe C, McCallister HA, Snovar DC, Winters GL, Zerbe A. A working formulation for the standardization of nomenclature in the diagnosis of heart and lung rejection: Heart Rejection Study Group. The International Society for Heart Transplantation. J Heart Lung Transplant 1990; 9: 587-93.

   3.   Angelini A, Andersen CB, Bartoloni G, Black F, Bishop P, Doran H, Fedrigo M, Fries JW, Goddard M, Goebel H, et al. A web-based pilot study of inter-pathologist reproducibility using the ISHLT 2004 working formulation for biopsy diagnosis of cardiac allograft rejection: the European experience. J Heart Lung Transplant 2011; 30: 1214-20.

   4.   Burke M, Andersen CB, Ashworth M, et al. C4d methodolody and interpretation in diagnosis of cardiac antibody-mediated rejection: a European survey from the Association for European Cardiovascular Pathology (AECVP). J Heart Lung Transplant 2010; 29: S37-S38.

   5.   Kobashigawa J, Crespo-Leiro MG, Ensminger SM, Reichenspurner H, Angelini A, Berry G, Burke M, Czer L, Hiemann N, Kfoury AG, et al. Report from a consensus conference on antibody-mediated rejection in heart transplantation. J Heart Lung Transplant 2011; 30: 252-69.

   6.   Berry GJ, Angelini A, Burke MM, Bruneval P, Fishbein MC, Hammond E, Miller D, Neil D, Revelo MP, Rodriguez ER, et al. The ISHLT working formulation for pathologic diagnosis of antibody-mediated rejection in heart transplantation: Evolution and current status (2005-2011). J Heart Lung Transplant 2011; 30: 601-11.

   7.   Fedrigo M, Leone O, Burke M, Rice A, Torbenson M, Toquet C, Frigo AC, Guillemain R, Pattier S, Smith J, et al. Inflammatory cell burden and phenotype in endomyocardial biopsies from patients with antibody-mediated rejection (AMR) - An AECVP multicenter study. J Heart Lung Transplant 2013; 32 [4S]: S19.