title: Global left ventricular relaxation: A novel tissue Doppler index of acute rejection in pediatric heart transplantation.
abstract: BACKGROUND
  Serial invasive cardiac catheterization with endomyocardial biopsies (EMBs) is the current standard of reference for evaluation after orthotopic heart transplant (OHTx). We developed a novel, non-invasive echocardiographic index of global left ventricular relaxation (LVRI) and assessed its sensitivity, specificity and predictive value for detecting rejection compared with EMB results in a prospective study conducted from September 2012 through May 2014.
  
  
  METHODS
  LVRI was calculated as the sum of diastolic tissue Doppler imaging (TDI) velocities (E') of the left ventricular lateral, septal and posterior walls divided by the percentage of left ventricular posterior wall (LVPW) thinning by M-mode. LVRI was measured in 47 OHTx patients and 50 patients with normal hearts. Of the 33 patients who underwent clinically indicated EMB, 22 patients had Grade 0R EMB, 6 had Grade 1R and 5 had Grade 2R to 3R biopsy results. Sensitivity, specificity and predictive value of LVRI for discriminating Grade 1R to 3R EMB were calculated. The LVRI was compared before and after OHTx rejection treatment and during the early and late post-transplant period. To characterize LVRI, 1-way analysis of variance was used to compare all groups, including non-OHTx patients.
  
  
  RESULTS
  LVRI was lower in patients with Grade 0R EMBs compared with non-OHTx patients. Patients with Grade 1R to 3R EMBs had lower LVRI than those with Grade 0R EMBs. LVRI recovered after treatment for rejection. LVRI appeared to normalize between 40 and 90 days post-transplantation. After 90 days, sensitivity was 100% and specificity was 90.9% for detecting patients with Grade 1R to 3R EMBs using an LVRI of 0.8.
  
  
  CONCLUSIONS
  LVRI, a novel, non-invasive TDI index of global left ventricular diastolic dysfunction, appears to be useful for detecting rejection in children beyond 3 months post-OHTx.
authors.affiliation: Department of Pediatrics, University of Minnesota Children's Hospital, Minneapolis, Minnesota. Electronic address: herna426@umn.edu.
authors.forename: Lazaro E
authors.initials: LE
authors.lastname: Hernandez
authors.affiliation: Department of Pediatrics, University of Minnesota Children's Hospital, Minneapolis, Minnesota.
authors.forename: Charles W
authors.initials: CW
authors.lastname: Shepard
authors.affiliation: Clinical and Translational Science Institute, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Jeremiah
authors.initials: J
authors.lastname: Menk
authors.affiliation: Heart Institute, Joe DiMaggio Children's Hospital, Hollywood, Florida.
authors.forename: Valdes-Cruz
authors.initials: VC
authors.lastname: Lilliam
authors.affiliation: Department of Pediatrics, University of Minnesota Children's Hospital, Minneapolis, Minnesota.
authors.forename: Rebecca K
authors.initials: RK
authors.lastname: Ameduri
mesh_terms: D000293:Adolescent; D001706:Biopsy; D006328:Cardiac Catheterization; D002648:Child; D002675:Child, Preschool; D004452:Echocardiography; D015150:Echocardiography, Doppler / Q000379:methods*; D004699:Endocardium / Q000473:pathology; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis*; D016027:Heart Transplantation; D006352:Heart Ventricles / Q000503:physiopathology; D006801:Humans; D007223:Infant; D008297:Male; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D013997:Time Factors; D018754:Ventricular Dysfunction / Q000175:diagnosis
keywords: acute rejection; heart transplant; pediatrics; tissue Doppler