title: ISHLT pathology antibody mediated rejection score correlates with increased risk of cardiovascular mortality: A retrospective validation analysis.
abstract: BACKGROUND
  Antibody-mediated rejection (AMR) in cardiac transplant recipients is a serious form of rejection with adverse patient outcomes. The International Society of Heart and Lung Transplantation (ISHLT) has published a consensus schema for the pathologic diagnosis of various grades of antibody-mediated rejection (pathology antibody-mediated rejection [pAMR]). We sought to determine whether the ISHLT pAMR grading schema correlates with patient outcomes.
  
  
  METHODS
  Using our database, which contains a semi-quantitative scoring of all pathologic descriptors of pAMR, we retrospectively used these descriptors to convert the previous AMR categories to the current ISHLT pAMR categories. Cox proportional hazard models were fit with cardiovascular (CV) death or retransplant as the outcome. The pAMR value was included as a categorical variable, and cellular rejection (CR) values were included in a separate model.
  
  
  RESULTS
  There were 13,812 biopsies from 1,014 patients analyzed. The pAMR grades of pAMR1h, pAMR1i, and pAMR2 conferred comparable increased risk for CV mortality. Significantly increased risk of CV mortality was conferred by biopsies graded as severe AMR (pAMR3).
  
  
  CONCLUSIONS
  The new ISHLT pAMR grading schema identifies patients at increased risk of CV mortality, consistent with risks published from several programs before 2011. The current schema is validated by this analysis in a large biopsy database. Because pAMR1h, pAMR1i, and pAMR2 have similar CV risks associated with them, the threshold for a positive diagnosis of pAMR should be re-evaluated in future iterations of the ISHLT schema.
authors.affiliation: Utah Transplantation Affiliated Hospitals Cardiac Transplant Program, Salt Lake City, Utah; Department of Pathology, Intermountain Medical Center and Intermountain Healthcare, Salt Lake City, Utah; Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah. Electronic address: liz.hammond@hotmail.com.
authors.forename: M Elizabeth H
authors.initials: MEH
authors.lastname: Hammond
authors.affiliation: Department of Pathology, Intermountain Medical Center and Intermountain Healthcare, Salt Lake City, Utah; Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah.
authors.forename: Monica P
authors.initials: MP
authors.lastname: Revelo
authors.affiliation: Utah Transplantation Affiliated Hospitals Cardiac Transplant Program, Salt Lake City, Utah; Department of Pathology, Intermountain Medical Center and Intermountain Healthcare, Salt Lake City, Utah; Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah.
authors.forename: Dylan V
authors.initials: DV
authors.lastname: Miller
authors.affiliation: Statistical Data Center, Intermountain Healthcare, Salt Lake City, Utah.
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Snow
authors.affiliation: Utah Transplantation Affiliated Hospitals Cardiac Transplant Program, Salt Lake City, Utah; Cardiovascular Clinical Program, Intermountain Medical Center and Intermountain Healthcare, Salt Lake City, Utah.
authors.forename: Deborah
authors.initials: D
authors.lastname: Budge
authors.affiliation: Utah Transplantation Affiliated Hospitals Cardiac Transplant Program, Salt Lake City, Utah; Department of Cardiology, University of Utah School of Medicine, Salt Lake City, Utah; Department of Cardiology, George E. Wahlen Veteran Affairs Medical Center, Salt Lake City, Utah.
authors.forename: Josef
authors.initials: J
authors.lastname: Stehlik
authors.affiliation: Utah Transplantation Affiliated Hospitals Cardiac Transplant Program, Salt Lake City, Utah; Department of Cardiology, Primary Childrens Hospital, Salt Lake City, Utah.
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Molina
authors.affiliation: Utah Transplantation Affiliated Hospitals Cardiac Transplant Program, Salt Lake City, Utah; Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah.
authors.forename: Craig H
authors.initials: CH
authors.lastname: Selzman
authors.affiliation: Utah Transplantation Affiliated Hospitals Cardiac Transplant Program, Salt Lake City, Utah; Department of Cardiology, University of Utah School of Medicine, Salt Lake City, Utah.
authors.forename: Stavros G
authors.initials: SG
authors.lastname: Drakos
authors.affiliation: Utah Transplantation Affiliated Hospitals Cardiac Transplant Program, Salt Lake City, Utah; Cardiovascular Clinical Program, Intermountain Medical Center and Intermountain Healthcare, Salt Lake City, Utah.
authors.forename: Alharethi
authors.initials: A
authors.lastname: Rami A
authors.affiliation: Utah Transplantation Affiliated Hospitals Cardiac Transplant Program, Salt Lake City, Utah; Department of Cardiology, University of Utah School of Medicine, Salt Lake City, Utah.
authors.forename: Jose N
authors.initials: JN
authors.lastname: Nativi-Nicolau
authors.affiliation: Utah Transplantation Affiliated Hospitals Cardiac Transplant Program, Salt Lake City, Utah; Cardiovascular Clinical Program, Intermountain Medical Center and Intermountain Healthcare, Salt Lake City, Utah.
authors.forename: Bruce B
authors.initials: BB
authors.lastname: Reid
authors.affiliation: Utah Transplantation Affiliated Hospitals Cardiac Transplant Program, Salt Lake City, Utah; Cardiovascular Clinical Program, Intermountain Medical Center and Intermountain Healthcare, Salt Lake City, Utah.
authors.forename: Abdallah G
authors.initials: AG
authors.lastname: Kfoury
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000276:immunology*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000401:mortality*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006084:Graft Rejection / Q000150:complications / Q000276:immunology*; D016041:Heart-Lung Transplantation; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000209:etiology / Q000401:mortality*; D012189:Retrospective Studies; D018570:Risk Assessment; D055815:Young Adult
chemical_list: D000906:Antibodies
keywords: antibody-mediated rejection; cardiovascular mortality; clinical; heart transplantation; pathology