title: Changes in coronary endothelial function predict progression of allograft vasculopathy after heart transplantation.
abstract: OBJECTIVE
  Coronary endothelial dysfunction may be an early marker for cardiac allograft vasculopathy (CAV) in orthotopic heart transplant recipients. We used serial studies to evaluate changes in coronary endothelial function in patients with and without clinically evident CAV.
  
  
  BACKGROUND
  In serial studies with intravascular ultrasound (IVUS) and Doppler flow wire measurements, we previously demonstrated that annual decrements in coronary endothelial function are associated with progressive intimal thickening.
  
  
  METHODS
  We studied 45 patients annually, beginning at transplantation until pre-specified end-points (angiographic CAV or cardiac death) were reached. At each study, we measured coronary endothelial function using intracoronary infusions of adenosine, acetylcholine, and nitroglycerin. We simultaneously recorded IVUS images and Doppler velocities.
  
  
  RESULTS
  Of the 45 patients studied, 9 reached end-points during the study (6 had CAV and 3 died). The mean annual change in area response to acetylcholine was -4.5% +/- 3.0% in patients who reached end-points and -0.9% +/- 1.5% in those who did not (p = 0.04). The mean annual decrement in flow response to acetylcholine was greater in patients who reached end-points (-31% +/- 11% vs -5% +/- 5%, p = 0.08). Responses to adenosine and nitroglycerin did not differ.
  
  
  CONCLUSIONS
  When serial responses were evaluated, patients with end-points had more rapid decreases in endothelial function. The rate of disease progression may be more important than the absolute degree of intimal thickening in early CAV. These data implicate endothelial dysfunction in the development of clinically significant vasculopathy and suggest that serial studies of endothelial function may provide important prognostic information about the development of CAV after heart transplantation.
authors.affiliation: Cardiology Division, Cooper Hospital/University Medical Center, Camden, New Jersey 08103, USA. Hollenberg-Steven@cooperhealth.edu
authors.forename: Steven M
authors.initials: SM
authors.lastname: Hollenberg
authors.forename: Lloyd W
authors.initials: LW
authors.lastname: Klein
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Parrillo
authors.forename: Markus
authors.initials: M
authors.lastname: Scherer
authors.forename: Durand
authors.initials: D
authors.lastname: Burns
authors.forename: Paul
authors.initials: P
authors.lastname: Tamburro
authors.forename: David
authors.initials: D
authors.lastname: Bromet
authors.forename: Aaron
authors.initials: A
authors.lastname: Satran
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Costanzo
mesh_terms: D001783:Blood Flow Velocity; D003326:Coronary Circulation; D003327:Coronary Disease / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology*; D003331:Coronary Vessels / Q000000981:diagnostic imaging* / Q000503:physiopathology; D015150:Echocardiography, Doppler; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology*; D018084:Ultrasonography, Interventional