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Updated: May 16, 2026

An Immunological Model for Heterotopic Heart and Cardiac Muscle Cell Transplantation in Rats
Published on: May 8, 2020
Concordance among pathologists in the second Cardiac Allograft Rejection Gene Expression Observational Study (CARGO
Maria G Crespo-Leiro1, Andreas Zuckermann, Christoph Bara
1Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco, Hospital Universitario A Coruña, La Coruña, Spain. Marisa.Crespo.Leiro@sergas.es
Background:
There has been no large evaluation of the ISHLT 2004 acute cellular rejection grading scheme for heart graft endomyocardial biopsy specimens (EMBs).
Methods:
We evaluated agreement within the CARGO II pathology panel and between the panel (acting by majority) and the collaborating centers (treated as a single entity), regarding the ISHLT grades of 937 EMBs (with all grades ≥2R merged because of small numbers).
Results:
Overall all-grade agreement was almost 71% both within the panel and between the panel and the collaborating centers but, in both cases, was largely because of agreement on grade 0: for the average pair of pathologists, fewer than a third of the EMBs assigned grade ≥2R by at least one were assigned this grade by both.
Conclusion:
The 2004 revision has done little to improve agreement on the higher ISHLT grades. An EMB grade ≥2R is not by itself sufficient as a basis for clinical decisions or as a research criterion. Steps should be taken toward greater uniformity in EMB grading, and efforts should be made to replace the ISHLT classification with diagnostic criteria--EMB based or otherwise--that correspond better with the pathophysiology of the transplanted heart.