title: Virtual histology assessment of cardiac allograft vasculopathy following introduction of everolimus--results of a multicenter trial.
abstract: 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.
authors.affiliation: Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway. satish.arora@medisin.uio.no
authors.forename: S
authors.initials: S
authors.lastname: Arora
authors.forename: I
authors.initials: I
authors.lastname: Erikstad
authors.forename: T
authors.initials: T
authors.lastname: Ueland
authors.forename: V
authors.initials: V
authors.lastname: Sigurdardottir
authors.forename: B
authors.initials: B
authors.lastname: Ekmehag
authors.forename: K
authors.initials: K
authors.lastname: Jansson
authors.forename: H
authors.initials: H
authors.lastname: Eiskjaer
authors.forename: H E
authors.initials: HE
authors.lastname: Bøtker
authors.forename: S-A
authors.initials: SA
authors.lastname: Mortensen
authors.forename: K
authors.initials: K
authors.lastname: Saunamaki
authors.forename: E
authors.initials: E
authors.lastname: Gude
authors.forename: A
authors.initials: A
authors.lastname: Ragnarsson
authors.forename: D
authors.initials: D
authors.lastname: Solbu
authors.forename: P
authors.initials: P
authors.lastname: Aukrust
authors.forename: L
authors.initials: L
authors.lastname: Gullestad
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D000068338:Everolimus; D005260:Female; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014652:Vascular Diseases / Q000209:etiology*
chemical_list: D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus