title: Coronary flow reserve measurement detects transplant coronary artery disease in pediatric heart transplant patients.
abstract: BACKGROUND
  Cardiac allograft vasculopathy (CAV) in patients who have undergone heart transplantation leads to graft dysfunction and is still the major concern for long-term survival. Evaluation of coronary flow velocity reserve (CFR) has been established for diagnosis of CAV. Systemic application of adenosine vs intracoronary testing for CFR has been validated in adults; however, its accuracy in pediatric patients has not yet been proven.
  
  
  METHODS
  CFR was prospectively measured in 33 clinically asymptomatic pediatric heart transplant recipients. CFR measurements were made in the left anterior descending (LAD) artery using a 0.014-inch Doppler FloWire (Cardiometrics). CFR was defined as the ratio of hyperemic (after adenosine injection) to basal (before adenosine) average peak velocity (APV). Adenosine (Adrekar) was administered by intracoronary (15 or 30 mug bolus) and systemic (0.1 mg/kg) injection in each patient. Epicardial CAV was evaluated in coronary angiograms (Stanford criteria) and microvasculopathy was diagnosed in endomyocardial biopsies (evidence of luminal stenosis) blinded to clinical data.
  
  
  RESULTS
  Thirty-three patients were included in this study. Their median age (range) was 11.9 (1.4 to 17) years and median post-transplant time 4.3 (1 to 11.7) years. Seventeen of the 33 patients had epicardial CAV (mainly peripheral obliterations or B1 and B2 lesions) and microvascular CAV. Epicardial CAV only was found in 4 patients and microvasculopathy only was present in only 1 patient. CFR was significantly reduced in patients with epicardial CAV and microvasculopathy when compared with patients without any signs of CAV: 206 +/- 53 vs 276 +/- 39 (p < 0.001) for the systemic application and 213 +/- 50 vs 271 +/- 45 (p = 0.004) for the intracoronary application.
  
  
  CONCLUSIONS
  CFR and coronary vasoreactivity to adenosine are decreased in pediatric patients with CAV and correlate with histopathologic and angiographic evidence of microvascular disease. Measurement of CFR with intracoronary and systemic application of adenosine is comparable, while systemic application is necessary for non-invasive measurement of CFR in pediatric patients.
authors.affiliation: Department of Congenital Heart Defects/Pediatric Cardiology, Deutsches Herzzentrum Berlin, Berlin, Germany. sschubert@dhzb.de
authors.forename: Stephan
authors.initials: S
authors.lastname: Schubert
authors.forename: Hashim
authors.initials: H
authors.lastname: Abdul-Khaliq
authors.forename: Ernst
authors.initials: E
authors.lastname: Wellnhofer
authors.forename: Nicola Erika
authors.initials: NE
authors.lastname: Hiemann
authors.forename: Peter
authors.initials: P
authors.lastname: Ewert
authors.forename: Hans Brendan
authors.initials: HB
authors.lastname: Lehmkuhl
authors.forename: Rudolf
authors.initials: R
authors.lastname: Meyer
authors.forename: Oliver
authors.initials: O
authors.lastname: Miera
authors.forename: Bjoern
authors.initials: B
authors.lastname: Peters
authors.forename: Roland
authors.initials: R
authors.lastname: Hetzer
authors.forename: Felix
authors.initials: F
authors.lastname: Berger
mesh_terms: D000241:Adenosine / Q000008:administration & dosage; D000293:Adolescent; D001707:Biopsy, Needle; D001783:Blood Flow Velocity / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000175:diagnosis* / Q000503:physiopathology*; D003326:Coronary Circulation / Q000187:drug effects; D005260:Female; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D009206:Myocardium / Q000473:pathology*; D014665:Vasodilator Agents / Q000008:administration & dosage
chemical_list: D014665:Vasodilator Agents; D000241:Adenosine