title: Randomized pilot trial of gene expression profiling versus heart biopsy in the first year after heart transplant: early invasive monitoring attenuation through gene expression trial.
abstract: BACKGROUND
  The endomyocardial biopsy (EMB) is considered the gold standard in rejection surveillance post cardiac transplant, but is invasive, with risk of complications. A previous trial suggested that the gene expression profiling (GEP) blood test was noninferior to EMB between 6 and 60 months post transplant. As most rejections occur in the first 6 months, we conducted a single-center randomized trial of GEP versus EMB starting at 55 days post transplant (when GEP is valid).
  
  
  RESULTS
  Sixty heart transplant patients meeting inclusion criteria were randomized beginning at 55 days post transplant to either GEP or EMB arms. A positive GEP ≥30 between 2 and 6 months, or ≥34 after 6 months, prompted a follow-up biopsy. The primary end point included a composite of death/retransplant, rejection with hemodynamic compromise or graft dysfunction at 18 months post transplant. A coprimary end point included change in first-year maximal intimal thickness by intravascular ultrasound, a recognized surrogate for long-term outcome. Corticosteroid weaning was assessed in both the groups. The composite end point was similar between the GEP and EMB groups (10% versus 17%; log-rank P=0.44). The coprimary end point of first-year intravascular ultrasound change demonstrated no difference in mean maximal intimal thickness (0.35±0.36 versus 0.36±0.26 mm; P=0.944). Steroid weaning was successful in both the groups (91% versus 95%).
  
  
  CONCLUSIONS
  In this pilot study, GEP starting at 55 days post transplant seems comparable with EMB for rejection surveillance in selected heart transplant patients and does not result in increased adverse outcomes. GEP also seems useful to guide corticosteroid weaning. Larger randomized trials are required to confirm these findings.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT014182482377.
authors.affiliation: From the Advanced Heart Disease Section, Cedars-Sinai Heart Institute, Los Angeles, CA. Kobashigawaj@cshs.org.
authors.forename: Jon
authors.initials: J
authors.lastname: Kobashigawa
authors.affiliation: From the Advanced Heart Disease Section, Cedars-Sinai Heart Institute, Los Angeles, CA.
authors.forename: Jignesh
authors.initials: J
authors.lastname: Patel
authors.affiliation: From the Advanced Heart Disease Section, Cedars-Sinai Heart Institute, Los Angeles, CA.
authors.forename: Babak
authors.initials: B
authors.lastname: Azarbal
authors.affiliation: From the Advanced Heart Disease Section, Cedars-Sinai Heart Institute, Los Angeles, CA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Kittleson
authors.affiliation: From the Advanced Heart Disease Section, Cedars-Sinai Heart Institute, Los Angeles, CA.
authors.forename: David
authors.initials: D
authors.lastname: Chang
authors.affiliation: From the Advanced Heart Disease Section, Cedars-Sinai Heart Institute, Los Angeles, CA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Czer
authors.affiliation: From the Advanced Heart Disease Section, Cedars-Sinai Heart Institute, Los Angeles, CA.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Daun
authors.affiliation: From the Advanced Heart Disease Section, Cedars-Sinai Heart Institute, Los Angeles, CA.
authors.forename: Minh
authors.initials: M
authors.lastname: Luu
authors.affiliation: From the Advanced Heart Disease Section, Cedars-Sinai Heart Institute, Los Angeles, CA.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Trento
authors.affiliation: From the Advanced Heart Disease Section, Cedars-Sinai Heart Institute, Los Angeles, CA.
authors.forename: Richard
authors.initials: R
authors.lastname: Cheng
authors.affiliation: From the Advanced Heart Disease Section, Cedars-Sinai Heart Institute, Los Angeles, CA.
authors.forename: Fardad
authors.initials: F
authors.lastname: Esmailian
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D001706:Biopsy; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D005819:Genetic Markers; D006084:Graft Rejection / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics / Q000401:mortality / Q000473:pathology; D016027:Heart Transplantation / Q000009:adverse effects* / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D015141:Los Angeles; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D010865:Pilot Projects; D011237:Predictive Value of Tests; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D018084:Ultrasonography, Interventional
chemical_list: D000305:Adrenal Cortex Hormones; D005819:Genetic Markers; D007166:Immunosuppressive Agents
keywords: cardiac transplantation; gene-expression profiling; graft rejection