XVIIth BANFF conference on Allograft pathology the BANFF workshop heart report: microvascular inflammatory burden in Heart Transplantation and the impact of non-invasive diagnostic tools.
M. Fedrigo et al
View the full manuscript on the SSRN website
Abstract
The Banff-PITOR joint meeting on Allograft Pathology was held in 2024 in Paris. According to the BANFF policy, heart transplant group discussed two main topics: (a) the microvascular inflammatory burden on endomyocardial biopsy (EMB) exploring new advancements on inflammation-endothelium interactions within the complexity of inflammatory pathways on allograft, and (b) the impact of molecular non-invasive tools in the rejection monitoring. The goal was to discuss the impact of molecular pathology performed on paraffin-embedded tissue in the context of inflammatory burden on EMBs, to explore the new face of endothelium in the microvasculature and its relationship with alloantibodies. The introduction of tissue and blood molecular analysis enhanced the reliability and accuracy of EMBs interpretation by pathologists and also emphasized the complexity of the inflammatory mechanisms occurring in the allograft. The excellent negative predictive value of non-invasive biomarkers and the new imaging modalities foresee the applicability in the clinical practice and potentially changing the follow up of the heart transplanted patients.
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Clinical feasibility and utility of the classification
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The comment period will be open until August 31, 2025. All comments will be reviewed and considered by the Banff meeting report author groups prior to finalizing the manuscripts and submission for formal peer review.
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Dear Marny, thank you for putting this together and homogenizing the different contributions. I have no major comments to raise . I am not in favour of changing ACR and AMR with ABMR and TCMR which are more common in the kidney community, but not in the heart community. The two actual classifications ISHLT are for ACR and AMR. As for the classification to be adopted for reporting , I agree with suggestion for the use of ISHLT 1990 grades side by side by side with the ISHLT 2005 grades. This is actually the policy adopted in our center. The 1990 classification allows the inflammation and injury to be communicated with more granularity.
Annalisa Angelini
This is nice report that I enjoyed reading. Thanks for opening up this report on this blog for public comment. I offer the following suggestions for your consideration:
I suggest that ACR be replaced by TCMR throughout the manuscript. This will promote more clear thinking about the differences between ABMR and TCMR that we all recognize.
Page 7, line 229 makes the very insightful comment that T-cells can recognize HLA antigens expressed on endothelial cells. This means that TCMR must be considered as a potential cause of microvascular inflammation when C4d is negative and DSA is negative. Most such biopsies are indeed T-cell rich if immunohistochemistry is performed. This concept has already been recognized in the kidney and should be a part of this report.
Page 8, section 3: The section on the promise of transcriptomics based quantitation of inflammatory burden should also state its caveats. Many biopsies with histologic TCMR (even with grade 2R) rejection currently get a TCMR score of zero. In biopsies that score positive, the range of scores is in a very narrow range (0-1). Reproducibility of these scores needs to be better defined in terms of mean/medians/SD/IQR. Is a molecular score of 0.5 really different from 0.4, or is that within the range of measurement error. Molecular methods typically do not reliable detect differences of less than 2-3 fold in magnitude.
Page 9: section on ddcfDNA: The last time I checked randomized trials showing the non-inferiority of ddcfDNA to biopsy diagnosis had not been performed. If this is still true we should state that. A high negative predictive value of 99% is quoted. Actual figures for sensitivity and positive predictive value would add to the value of the report. Also it will be nice to have diagnostic performance laid out separately for ABMR and TCMR. If you think it will be worthwhile, I could do a deeper dive into the subject and come up with a more comprehensive tabulation of what is known and what we still do not know.
Figure 1: I would think that ACR refers to Grade 2R and above and ABMR to pAMR 2 and above. It is desirable to clarify the exact definition used.
Page 4: line 108 refers to the wide range of inflammatory infiltrates in endomyocardial biopsies. We should encourage the use of ISHLT 1990 grades side by side by side with the ISHLT 2005 grades. The 1990 classification allows the inflammation and injury to be communicated with more granularity.