Virtual Histology Assessment of Cardiac Allograft Vasculopathy Following Introduction of Everolimus-Results of a Multicenter Trial.

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In this 12-month multicenter Scandinavian study, 78 maintenance heart transplant (HTx) recipients randomized to everolimus with reduced calcineurin inhibitor (CNI) exposure or continued standard CNI-therapy underwent matched virtual histology (VH) examination to evaluate morphological progression of cardiac allograft vasculopathy (CAV). Parallel measurement of a range of inflammatory markers was also performed. A similar rate of quantitative CAV progression was observed in the everolimus (n = 30) and standard CNI group (n = 48) (plaque index 1.9 ± 3.8% and 1.6 ± 3.9%, respectively; p = 0.65). However, VH analysis revealed a significant increase in calcified (2.4 ± 4.0 vs. 0.3 ± 3.1%; p = 0.02) and necrotic component (6.5 ± 8.5 vs. 1.1 ± 8.6%; p = 0.01) among everolimus patients compared to controls. The increase in necrotic and calcified components was most prominent in everolimus patients with time since HTx >5.1 years and was accompanied by a significant increase in levels of von Willebrand (vWF) factor (p = 0.04) and vascular cell adhesion molecule (VCAM) (p = 0.03). Conversion to everolimus and reduced CNI is associated with a significant increase in calcified and necrotic intimal components and is more prominent in patients with a longer time since HTx. A significant increase in vWF and VCAM accompanied these qualitative changes and the prognostic implication of these findings requires further investigation.


  • S Arora
  • I Erikstad
  • T Ueland
  • V Sigurdardottir
  • Björn Ekmehag
  • Kristina Jansson
  • H Eiskjaer
  • H E Bøtker
  • S-A Mortensen
  • K Saunamaki
  • E Gude
  • A Ragnarsson
  • D Solbu
  • P Aukrust
  • L Gullestad
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Surgery
Original languageEnglish
Pages (from-to)2700-2709
JournalAmerican Journal of Transplantation
Issue number10
Publication statusPublished - 2012
Publication categoryResearch