title: High-sensitivity cardiac troponin I assay to screen for acute rejection in patients with heart transplant.
abstract: BACKGROUND
  A noninvasive biomarker that could accurately diagnose acute rejection (AR) in heart transplant recipients could obviate the need for surveillance endomyocardial biopsies. We assessed the performance metrics of a novel high-sensitivity cardiac troponin I (cTnI) assay for this purpose.
  
  
  RESULTS
  Stored serum samples were retrospectively matched to endomyocardial biopsies in 98 cardiac transplant recipients, who survived ≥3 months after transplant. AR was defined as International Society for Heart and Lung Transplantation grade 2R or higher cellular rejection, acellular rejection, or allograft dysfunction of uncertain pathogenesis, leading to treatment for presumed rejection. cTnI was measured with a high-sensitivity assay (Abbott Diagnostics, Abbott Park, IL). Cross-sectional analyses determined the association of cTnI concentrations with rejection and International Society for Heart and Lung Transplantation grade and the performance metrics of cTnI for the detection of AR. Among 98 subjects, 37% had ≥1 rejection episode. cTnI was measured in 418 serum samples, including 35 paired to a rejection episode. cTnI concentrations were significantly higher in rejection versus nonrejection samples (median, 57.1 versus 10.2 ng/L; P<0.0001) and increased in a graded manner with higher biopsy scores (P(trend)<0.0001). The c-statistic to discriminate AR was 0.82 (95% confidence interval, 0.76-0.88). Using a cut point of 15 ng/L, sensitivity was 94%, specificity 60%, positive predictive value 18%, and negative predictive value 99%.
  
  
  CONCLUSIONS
  A high-sensitivity cTnI assay seems useful to rule out AR in cardiac transplant recipients. If validated in prospective studies, a strategy of serial monitoring with a high-sensitivity cTnI assay may offer a low-cost noninvasive strategy for rejection surveillance.
authors.affiliation: From the Department of Transplant, Mayo Clinic Florida, Jacksonville (P.C.P.); and Department of Internal Medicine, Division of Cardiology (D.A.H., C.R.A., P.K., J.T.T., J.D.M., P.P.A.M., D.W.M., J.A.d.L., M.H.D.), Department of Internal Medicine, Division of Transplant Immunology (B.L., P.S.), Department of Pediatrics, Division of Pediatric Cardiology (A.K.D., A.P.B.), and Department of Cardiothoracic Surgery (W.S.R.), University of Texas Southwestern Medical Center, Dallas.
authors.forename: Parag C
authors.initials: PC
authors.lastname: Patel
authors.affiliation: From the Department of Transplant, Mayo Clinic Florida, Jacksonville (P.C.P.); and Department of Internal Medicine, Division of Cardiology (D.A.H., C.R.A., P.K., J.T.T., J.D.M., P.P.A.M., D.W.M., J.A.d.L., M.H.D.), Department of Internal Medicine, Division of Transplant Immunology (B.L., P.S.), Department of Pediatrics, Division of Pediatric Cardiology (A.K.D., A.P.B.), and Department of Cardiothoracic Surgery (W.S.R.), University of Texas Southwestern Medical Center, Dallas.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Hill
authors.affiliation: From the Department of Transplant, Mayo Clinic Florida, Jacksonville (P.C.P.); and Department of Internal Medicine, Division of Cardiology (D.A.H., C.R.A., P.K., J.T.T., J.D.M., P.P.A.M., D.W.M., J.A.d.L., M.H.D.), Department of Internal Medicine, Division of Transplant Immunology (B.L., P.S.), Department of Pediatrics, Division of Pediatric Cardiology (A.K.D., A.P.B.), and Department of Cardiothoracic Surgery (W.S.R.), University of Texas Southwestern Medical Center, Dallas.
authors.forename: Colby R
authors.initials: CR
authors.lastname: Ayers
authors.affiliation: From the Department of Transplant, Mayo Clinic Florida, Jacksonville (P.C.P.); and Department of Internal Medicine, Division of Cardiology (D.A.H., C.R.A., P.K., J.T.T., J.D.M., P.P.A.M., D.W.M., J.A.d.L., M.H.D.), Department of Internal Medicine, Division of Transplant Immunology (B.L., P.S.), Department of Pediatrics, Division of Pediatric Cardiology (A.K.D., A.P.B.), and Department of Cardiothoracic Surgery (W.S.R.), University of Texas Southwestern Medical Center, Dallas.
authors.forename: Bhavna
authors.initials: B
authors.lastname: Lavingia
authors.affiliation: From the Department of Transplant, Mayo Clinic Florida, Jacksonville (P.C.P.); and Department of Internal Medicine, Division of Cardiology (D.A.H., C.R.A., P.K., J.T.T., J.D.M., P.P.A.M., D.W.M., J.A.d.L., M.H.D.), Department of Internal Medicine, Division of Transplant Immunology (B.L., P.S.), Department of Pediatrics, Division of Pediatric Cardiology (A.K.D., A.P.B.), and Department of Cardiothoracic Surgery (W.S.R.), University of Texas Southwestern Medical Center, Dallas.
authors.forename: Patricia
authors.initials: P
authors.lastname: Kaiser
authors.affiliation: From the Department of Transplant, Mayo Clinic Florida, Jacksonville (P.C.P.); and Department of Internal Medicine, Division of Cardiology (D.A.H., C.R.A., P.K., J.T.T., J.D.M., P.P.A.M., D.W.M., J.A.d.L., M.H.D.), Department of Internal Medicine, Division of Transplant Immunology (B.L., P.S.), Department of Pediatrics, Division of Pediatric Cardiology (A.K.D., A.P.B.), and Department of Cardiothoracic Surgery (W.S.R.), University of Texas Southwestern Medical Center, Dallas.
authors.forename: Adrian K
authors.initials: AK
authors.lastname: Dyer
authors.affiliation: From the Department of Transplant, Mayo Clinic Florida, Jacksonville (P.C.P.); and Department of Internal Medicine, Division of Cardiology (D.A.H., C.R.A., P.K., J.T.T., J.D.M., P.P.A.M., D.W.M., J.A.d.L., M.H.D.), Department of Internal Medicine, Division of Transplant Immunology (B.L., P.S.), Department of Pediatrics, Division of Pediatric Cardiology (A.K.D., A.P.B.), and Department of Cardiothoracic Surgery (W.S.R.), University of Texas Southwestern Medical Center, Dallas.
authors.forename: Aliessa P
authors.initials: AP
authors.lastname: Barnes
authors.affiliation: From the Department of Transplant, Mayo Clinic Florida, Jacksonville (P.C.P.); and Department of Internal Medicine, Division of Cardiology (D.A.H., C.R.A., P.K., J.T.T., J.D.M., P.P.A.M., D.W.M., J.A.d.L., M.H.D.), Department of Internal Medicine, Division of Transplant Immunology (B.L., P.S.), Department of Pediatrics, Division of Pediatric Cardiology (A.K.D., A.P.B.), and Department of Cardiothoracic Surgery (W.S.R.), University of Texas Southwestern Medical Center, Dallas.
authors.forename: Jennifer T
authors.initials: JT
authors.lastname: Thibodeau
authors.affiliation: From the Department of Transplant, Mayo Clinic Florida, Jacksonville (P.C.P.); and Department of Internal Medicine, Division of Cardiology (D.A.H., C.R.A., P.K., J.T.T., J.D.M., P.P.A.M., D.W.M., J.A.d.L., M.H.D.), Department of Internal Medicine, Division of Transplant Immunology (B.L., P.S.), Department of Pediatrics, Division of Pediatric Cardiology (A.K.D., A.P.B.), and Department of Cardiothoracic Surgery (W.S.R.), University of Texas Southwestern Medical Center, Dallas.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Mishkin
authors.affiliation: From the Department of Transplant, Mayo Clinic Florida, Jacksonville (P.C.P.); and Department of Internal Medicine, Division of Cardiology (D.A.H., C.R.A., P.K., J.T.T., J.D.M., P.P.A.M., D.W.M., J.A.d.L., M.H.D.), Department of Internal Medicine, Division of Transplant Immunology (B.L., P.S.), Department of Pediatrics, Division of Pediatric Cardiology (A.K.D., A.P.B.), and Department of Cardiothoracic Surgery (W.S.R.), University of Texas Southwestern Medical Center, Dallas.
authors.forename: Pradeep P A
authors.initials: PP
authors.lastname: Mammen
authors.affiliation: From the Department of Transplant, Mayo Clinic Florida, Jacksonville (P.C.P.); and Department of Internal Medicine, Division of Cardiology (D.A.H., C.R.A., P.K., J.T.T., J.D.M., P.P.A.M., D.W.M., J.A.d.L., M.H.D.), Department of Internal Medicine, Division of Transplant Immunology (B.L., P.S.), Department of Pediatrics, Division of Pediatric Cardiology (A.K.D., A.P.B.), and Department of Cardiothoracic Surgery (W.S.R.), University of Texas Southwestern Medical Center, Dallas.
authors.forename: David W
authors.initials: DW
authors.lastname: Markham
authors.affiliation: From the Department of Transplant, Mayo Clinic Florida, Jacksonville (P.C.P.); and Department of Internal Medicine, Division of Cardiology (D.A.H., C.R.A., P.K., J.T.T., J.D.M., P.P.A.M., D.W.M., J.A.d.L., M.H.D.), Department of Internal Medicine, Division of Transplant Immunology (B.L., P.S.), Department of Pediatrics, Division of Pediatric Cardiology (A.K.D., A.P.B.), and Department of Cardiothoracic Surgery (W.S.R.), University of Texas Southwestern Medical Center, Dallas.
authors.forename: Peter
authors.initials: P
authors.lastname: Stastny
authors.affiliation: From the Department of Transplant, Mayo Clinic Florida, Jacksonville (P.C.P.); and Department of Internal Medicine, Division of Cardiology (D.A.H., C.R.A., P.K., J.T.T., J.D.M., P.P.A.M., D.W.M., J.A.d.L., M.H.D.), Department of Internal Medicine, Division of Transplant Immunology (B.L., P.S.), Department of Pediatrics, Division of Pediatric Cardiology (A.K.D., A.P.B.), and Department of Cardiothoracic Surgery (W.S.R.), University of Texas Southwestern Medical Center, Dallas.
authors.forename: W Steves
authors.initials: WS
authors.lastname: Ring
authors.affiliation: From the Department of Transplant, Mayo Clinic Florida, Jacksonville (P.C.P.); and Department of Internal Medicine, Division of Cardiology (D.A.H., C.R.A., P.K., J.T.T., J.D.M., P.P.A.M., D.W.M., J.A.d.L., M.H.D.), Department of Internal Medicine, Division of Transplant Immunology (B.L., P.S.), Department of Pediatrics, Division of Pediatric Cardiology (A.K.D., A.P.B.), and Department of Cardiothoracic Surgery (W.S.R.), University of Texas Southwestern Medical Center, Dallas. James.DeLemos@utsouthwestern.edu Mark.Drazner@utsouthwestern.edu.
authors.forename: James A
authors.initials: JA
authors.lastname: de Lemos
authors.affiliation: From the Department of Transplant, Mayo Clinic Florida, Jacksonville (P.C.P.); and Department of Internal Medicine, Division of Cardiology (D.A.H., C.R.A., P.K., J.T.T., J.D.M., P.P.A.M., D.W.M., J.A.d.L., M.H.D.), Department of Internal Medicine, Division of Transplant Immunology (B.L., P.S.), Department of Pediatrics, Division of Pediatric Cardiology (A.K.D., A.P.B.), and Department of Cardiothoracic Surgery (W.S.R.), University of Texas Southwestern Medical Center, Dallas. James.DeLemos@utsouthwestern.edu Mark.Drazner@utsouthwestern.edu.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Drazner
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D016027:Heart Transplantation; D006801:Humans; D008297:Male; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D019210:Troponin I / Q000097:blood*
chemical_list: D015415:Biomarkers; D019210:Troponin I
keywords: biopsy; diagnosis; graft rejection; transplants; troponin