title: C4d analysis in endomyocardial biopsies of heart transplant patients: is there a correlation with hemodynamic data?
abstract: BACKGROUND
  Endomyocardial biopsy (EMB) is the gold standard for immunologic follow-up to detect acute cellular rejection after cardiac transplantation. Conversely, protocols for the diagnosis and treatment of antibody-mediated rejection (AMR) are not well defined. Histologically, AMR is diagnosed by the presence of capillary damage associated with complement activation. The aim of this study was to correlate C4d expression of activated complement in EMB with hemodynamic compromise upon right heart catheterization.
  
  
  METHODS
  Heart transplant patients underwent hemodynamic and histologic follow-up with EMB and right heart catheterization between January 2008 and December 2009 for a total of 491 procedures. The cardiac biopsy was evaluated for acute cellular and AMR by means of the presence of the C4d complement fraction. The histologic results were compared with hemodynamic data registered during right heart catheterization.
  
  
  RESULTS
  Comparison of the hemodynamic data of subjects with versus without C4d positivity showed no significant difference. Furthermore, there was no significant difference comparing patients with versus without C4d positivity in the absence of significant acute cellular rejection episodes. (C4d-/ACR- vs C4d+/ACR-). The variation of each single hemodynamic parameter from its basal value (defined as the mean value in case of C4d-/ACR-) seemed to not be influenced by the presence of C4d+.
  
  
  CONCLUSIONS
  In our experience, C4d has been routinely evaluated in the majority of EMBs. We could not demonstrate a significant correlation of C4d positivity with hemodynamic compromise. These findings suggest that significant allograft dysfunction is not related to C4d positivity. Therefore, the diagnosis of AMR is difficult to establish, because allograft dysfunction is 1 of the 3 fundamental criteria.
authors.affiliation: Cardiac Surgery Department, San Giovanni Battista University Hospital, Turin, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Boffini
authors.forename: D
authors.initials: D
authors.lastname: Ricci
authors.forename: R
authors.initials: R
authors.lastname: Bonato
authors.forename: M
authors.initials: M
authors.lastname: Ribezzo
authors.forename: E
authors.initials: E
authors.lastname: Simonato
authors.forename: R
authors.initials: R
authors.lastname: Saviolo
authors.forename: L
authors.initials: L
authors.lastname: Checco
authors.forename: C
authors.initials: C
authors.lastname: Comoglio
authors.forename: M
authors.initials: M
authors.lastname: Rinaldi
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D006328:Cardiac Catheterization; D015935:Complement C4b / Q000032:analysis*; D004699:Endocardium / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis* / Q000276:immunology / Q000503:physiopathology; D016027:Heart Transplantation / Q000276:immunology*; D006439:Hemodynamics; D006801:Humans; D007150:Immunohistochemistry; D007558:Italy; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis*; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d