title: Utility of gene expression profiling score variability to predict clinical events in heart transplant recipients.
abstract: BACKGROUND
  Gene expression profiling test scores have primarily been used to identify heart transplant recipients who have a low probability of rejection at the time of surveillance testing. We hypothesized that the variability of gene expression profiling test scores within a patient may predict risk of future events of allograft dysfunction or death.
  
  
  METHODS
  Patients from the IMAGE study with rejection surveillance gene expression profiling tests performed at 1- to 6-month intervals were selected for this cohort study. Gene expression profiling score variability was defined as the standard deviation of an individual's cumulative test scores. Gene expression profiling ordinal score (range, 0-39), threshold score (binary value=1 if ordinal score ≥ 34), and score variability were studied in multivariate Cox regression models to predict future clinical events.
  
  
  RESULTS
  Race, age at time of transplantation, and time posttransplantation were significantly associated with future events in the univariate analysis. In the multivariate analyses, gene expression profiling score variability, but not ordinal scores or scores over threshold, was independently associated with future clinical events. The regression coefficient P values were <0.001, 0.46, and 0.773, for gene expression profiling variability, ordinal, and threshold scores, respectively. The hazard ratio for a 1 unit increase in variability was 1.76 (95% CI, 1.4-2.3).
  
  
  CONCLUSIONS
  The variability of a heart recipient's gene expression profiling test scores over time may provide prognostic utility. This information is independent of the probability of acute cellular rejection at the time of testing that is rendered from a single ordinal gene-expression profiling test score.
authors.affiliation: 1 University of California, Los Angeles, CA. 2 XDx Inc., Brisbane, CA. 3 Stanford University Medical Center, Stanford, CA. 4 VA Palo Alto Health Care System, Palo Alto, CA. 5 University of Pittsburgh Medical Center, Pittsburgh, PA. 6 Intermountain Medical Center and Intermountain Healthcare, Salt Lake City, UT. 7 Cleveland Clinic, Cleveland, OH. 8 Hospital of the University of Pennsylvania, Philadelphia, PA. 9 Mid America Heart Institute, Saint Luke's Hospital, Kansas City, MO. 10 University of Chicago Medical Center, Chicago, IL. 11 Northwestern University, Chicago, IL. 12 Washington University School of Medicine, St. Louis, MO. 13 Newark Beth Israel Medical Center, Newark, NJ. 14 Texas Heart Institute, Houston, TX. 15 Columbia University, New York City, NY. 16 Address correspondence to: Mario Deng, M.D., F.A.C.C., F.E.S.C., Advanced Heart Failure/Mechanical Support/Heart Transplant, David Geffen School of Medicine at UCLA, Ronald Reagan UCLA Medical Center, 100 Medical Plaza Drive, Suite 630 Los Angeles, CA 90095.
authors.forename: Mario C
authors.initials: MC
authors.lastname: Deng
authors.forename: Barbara
authors.initials: B
authors.lastname: Elashoff
authors.forename: Michael X
authors.initials: MX
authors.lastname: Pham
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Teuteberg
authors.forename: Abdallah G
authors.initials: AG
authors.lastname: Kfoury
authors.forename: Randall C
authors.initials: RC
authors.lastname: Starling
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Cappola
authors.forename: Andrew
authors.initials: A
authors.lastname: Kao
authors.forename: Allen S
authors.initials: AS
authors.lastname: Anderson
authors.forename: William G
authors.initials: WG
authors.lastname: Cotts
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Ewald
authors.forename: David A
authors.initials: DA
authors.lastname: Baran
authors.forename: Roberta C
authors.initials: RC
authors.lastname: Bogaev
authors.forename: Khurram
authors.initials: K
authors.lastname: Shahzad
authors.forename: David
authors.initials: D
authors.lastname: Hiller
authors.forename: James
authors.initials: J
authors.lastname: Yee
authors.forename: Hannah A
authors.initials: HA
authors.lastname: Valantine
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D006084:Graft Rejection / Q000235:genetics* / Q000473:pathology; D016027:Heart Transplantation / Q000009:adverse effects* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States