Concordance among pathologists in the second Cardiac Allograft Rejection Gene Expression Observational Study (CARGO II)

Transplantation. 2012 Dec 15;94(11):1172-7. doi: 10.1097/TP.0b013e31826e19e2.


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.

Trial registration: NCT00761787.

Publication types

  • Evaluation Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biopsy / standards
  • Coloring Agents
  • Eosine Yellowish-(YS)
  • Europe
  • Gene Expression Regulation
  • Graft Rejection / genetics*
  • Graft Rejection / immunology
  • Graft Rejection / pathology*
  • Heart Transplantation / adverse effects*
  • Hematoxylin
  • Humans
  • Observer Variation
  • Pathology, Clinical / standards*
  • Predictive Value of Tests
  • Reproducibility of Results
  • Severity of Illness Index
  • Staining and Labeling / standards
  • United States


  • Coloring Agents
  • Eosine Yellowish-(YS)
  • Hematoxylin

Associated data