title: Longitudinal evaluation of microvessel density in survivors vs. nonsurvivors of cardiac pathologic antibody-mediated rejection.
abstract: BACKGROUND
  Antibody-mediated rejection (AMR) of cardiac allografts is associated with reduced long-term graft survival, but not every patient with AMR develops premature graft failure. The tissue level mechanisms leading to graft failure in some patients with antibody-mediated rejection are poorly characterized.
  
  
  METHODS
  We assessed changes in myocardial microvessel density (number of capillaries per unit area) in endomyocardial biopsies over time using whole-slide microscopic imaging of CD34-stained slides and computer-assisted image analysis. Changes were compared among eight heart transplant recipients with multiple episodes of pathologic AMR who died from cardiovascular causes, eight age- and gender-matched patients with pathologic AMR who were still alive at a similar follow-up interval, and six matched controls without AMR or cellular rejection.
  
  
  RESULTS
  Microvessel density decreased in the last biopsies (mean 6.52 years post-transplant) from patients with pathologic AMR and cardiovascular mortality compared to their biopsies at 6 and 12 months post-transplant [respectively, -22% (P=.02) and -25% (P=.02)]. A similar decrease was not seen for the other groups.
  
  
  CONCLUSIONS
  Significantly reduced myocardial microvessel density does occur in a subset of patients with pathologic AMR who have a worse outcome. These data provide insights into the interplay between AMR, microvascular injury, and clinical outcomes.
authors.affiliation: Utah Transplantation Affiliated Hospitals (U.T.A.H.) Cardiac Transplant Program, Salt Lake City, UT, USA. patricia.revelo@path.utah.edu
authors.forename: Monica P
authors.initials: MP
authors.lastname: Revelo
authors.forename: Dylan V
authors.initials: DV
authors.lastname: Miller
authors.forename: Josef
authors.initials: J
authors.lastname: Stehlik
authors.forename: Kim
authors.initials: K
authors.lastname: Brunisholz
authors.forename: Stavros
authors.initials: S
authors.lastname: Drakos
authors.forename: Edward M
authors.initials: EM
authors.lastname: Gilbert
authors.forename: Melanie
authors.initials: M
authors.lastname: Everitt
authors.forename: Deborah
authors.initials: D
authors.lastname: Budge
authors.forename: Rami
authors.initials: R
authors.lastname: Alharethi
authors.forename: Gregory
authors.initials: G
authors.lastname: Snow
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Hammond
authors.forename: Abdallah G
authors.initials: AG
authors.lastname: Kfoury
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000276:immunology; D018952:Antigens, CD34 / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D002196:Capillaries / Q000378:metabolism / Q000473:pathology*; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology*; D004452:Echocardiography; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D006331:Heart Diseases / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D016027:Heart Transplantation / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007111:Immunity, Cellular; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000276:immunology / Q000473:pathology*; D015996:Survival Rate; D014589:Utah / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000906:Antibodies; D018952:Antigens, CD34; D015415:Biomarkers