title: Clinical usefulness of gene-expression profile to rule out acute rejection after heart transplantation: CARGO II.
abstract: A non-invasive gene-expression profiling (GEP) test for rejection surveillance of heart transplant recipients originated in the USA. A European-based study, Cardiac Allograft Rejection Gene Expression Observational II Study (CARGO II), was conducted to further clinically validate the GEP test performance.
  
  
  
  Blood samples for GEP testing (AlloMap(®), CareDx, Brisbane, CA, USA) were collected during post-transplant surveillance. The reference standard for rejection status was based on histopathology grading of tissue from endomyocardial biopsy. The area under the receiver operating characteristic curve (AUC-ROC), negative (NPVs), and positive predictive values (PPVs) for the GEP scores (range 0-39) were computed. Considering the GEP score of 34 as a cut-off (>6 months post-transplantation), 95.5% (381/399) of GEP tests were true negatives, 4.5% (18/399) were false negatives, 10.2% (6/59) were true positives, and 89.8% (53/59) were false positives. Based on 938 paired biopsies, the GEP test score AUC-ROC for distinguishing ≥3A rejection was 0.70 and 0.69 for ≥2-6 and >6 months post-transplantation, respectively. Depending on the chosen threshold score, the NPV and PPV range from 98.1 to 100% and 2.0 to 4.7%, respectively.
  
  
  
  For ≥2-6 and >6 months post-transplantation, CARGO II GEP score performance (AUC-ROC = 0.70 and 0.69) is similar to the CARGO study results (AUC-ROC = 0.71 and 0.67). The low prevalence of ACR contributes to the high NPV and limited PPV of GEP testing. The choice of threshold score for practical use of GEP testing should consider overall clinical assessment of the patient's baseline risk for rejection.
authors.affiliation: Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Universidade da Coruña (UDC), A Coruña, Spain.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Crespo-Leiro
authors.affiliation: Department of Cardiovascular Medicine, University Hospital Muenster, Muenster, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Stypmann
authors.affiliation: Ruhr University of Bochum, Bad Oeynhausen, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Schulz
authors.affiliation: Medical University of Vienna, Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Zuckermann
authors.affiliation: University Hospital Bern, Bern, Switzerland.
authors.forename: Paul
authors.initials: P
authors.lastname: Mohacsi
authors.affiliation: Hannover Medical School, Hannover, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Bara
authors.affiliation: Toronto General Hospital, Toronto, Canada.
authors.forename: Heather
authors.initials: H
authors.lastname: Ross
authors.affiliation: Papworth Hospital, Papworth Everard, Cambridge, UK.
authors.forename: Jayan
authors.initials: J
authors.lastname: Parameshwar
authors.affiliation: Silesian Center for Heart Disease, Zabrze, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Zakliczyński
authors.affiliation: Ospedali Riuniti di Bergamo, Bergamo, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Fiocchi
authors.affiliation: Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hoefer
authors.affiliation: University of Minnesota, Minneapolis, MN, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Colvin
authors.affiliation: David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
authors.forename: Mario C
authors.initials: MC
authors.lastname: Deng
authors.affiliation: Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Leprince
authors.affiliation: CareDx, Brisbane, CA, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Elashoff
authors.affiliation: CareDx, Brisbane, CA, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: Yee
authors.affiliation: Department of Cardiology, University Hospital Gasthuisberg, Leuven, Belgium johan.vanhaecke@uzleuven.be.
authors.forename: Johan
authors.initials: J
authors.lastname: Vanhaecke
mesh_terms: D001706:Biopsy; D020869:Gene Expression Profiling; D006084:Graft Rejection; D016027:Heart Transplantation; D006801:Humans; D046228:Microarray Analysis; D009206:Myocardium; D059467:Transcriptome
keywords: AlloMap; Heart transplant; Molecular diagnostics; Organ rejection; Rejection surveillance; Tests