Letter to the Editor
Virtual Histology and the Morphologic Assessment of Cardiac Allograft Vasculopathy
Article first published online: 7 FEB 2013
© Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons
American Journal of Transplantation
Volume 13, Issue 4, page 1109, April 2013
How to Cite
Castellani, C., van der Wal, A. C., De Boer, O. J., Fedrigo, M., Thiene, G., Valente, M. and Angelini, A. (2013), Virtual Histology and the Morphologic Assessment of Cardiac Allograft Vasculopathy. American Journal of Transplantation, 13: 1109. doi: 10.1111/ajt.12141
- Issue published online: 30 MAR 2013
- Article first published online: 7 FEB 2013
To the Editor:
We read with great interest the paper by Arora et al. reporting the results of a12-month multicenter Scandinavian study on the qualitative evaluation of the influence of everolimus on cardiac allograft vasculopathy (CAV) morphology among heart transplant (HTx) recipients with a long follow up of >5 years post-HTx. . With the use of virtual histology (VH) [2, 3], the authors revealed a significant increase in calcified and necrotic tissue component in intimal lesions of the everolimus group of HTx patients compared to controls, while the overall plaque volume was not affected at all. Calcified and necrotic components of the plaques were considered by the authors as a result of the inflammatory tissue component of the plaque, and their findings on VH were indeed accompanied by a parallel rise in plasma levels of the markers for endothelial cell activation vWF and VCAM. Intriguing in this study is that the increase in calcified and necrotic components was more prominent in those patients who had a longer time since HTx (>5 years). As recognized also by the authors, CAV lesions are pathologically heterogeneous and can be characterized by a prevalence of fibrous/ fibrocellular pattern or a more atheroma-like pattern. Studies on native atherosclerotic plaques have shown that the cellular microenvironment differs significantly in these two type of lesions and that they can also be affected differently by everolimus .
Here, the question comes up whether the results of this study could have been influenced by the specific morphological types of CAV lesions. These were not classified by the authors, but proliferation signal inhibitors (PSIs) could influence one type of lesion more than the other.
We have recently evaluated pathologically 70 coronary plaques from heart transplanted pts who died because of CAV . With the use of conventional histology and immunohistochemistry, we could identify intraplaque hemorrhages in 60% of CAV lesions, which was even more than the 30.4% of plaque hemorrhages that we observed in the coronary plaques of the same patients in their explanted native heart (p = 0.01). Such intraplaque hemorrhages can be responsible for necrotic core enlargement as was detected in the everolimus treated patients, and this process favors deposition of calcification on the long term. We believe that the lack of reduction of plaque volume in everolimus patients represents not just the inability of the PSI to inhibit the myofibroproliferative response, but can be also attributed to another mechanism of CAV evolution, namely intraplaque hemorrages.
Today, we still need pathological evaluation of plaque morphology in patients with CAV. It will be a challenge for in vivo imaging techniques including IVUS to visualize plaque components like inflammation, angiogenesis and hemorrhages, to further unravel the pathophysiological mechanism of PSI in CAV development.
The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.
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- 4The iatrogenic pathology of percutaneous interventions in coronary arteries. Minerva Medica 2012; 103: 487–502., , .
- 5Intraplaque haemorrhage as a trigger of lesion progression in cardiac allograft vasculopathy. J Heart Lung Transplant 2012; 31: 5275., , , et al.