title: Incidence, progression and functional significance of cardiac allograft vasculopathy after heart transplantation.
abstract: BACKGROUND
  Cardiac allograft vasculopathy after heart transplantation leads to an accelerated form of atherosclerosis with marked and often diffuse vessel wall changes that limit long-term survival. Previous studies showed contradictory results relating vessel wall changes to endothelial vasodilator response.
  
  
  METHODS
  A total of 30 cardiac transplant recipients were studied 3, 12, and 24 months after heart transplantation. Coronary angiography was performed at rest, during supine bicycle ergometry, and after 1.6 mg sublingual nitroglycerin. Coronary cross-sectional area (biplane coronary angiography) and coronary artery wall changes (intravascular ultrasound) were assessed and extent of intimal changes correlated to vasodilator responses to nitroglycerine and bicycle ergometry.
  
  
  RESULTS
  Intravascular ultrasound showed significant intimal thickening in 43, 64, and 58% of patients at 3, 12, and 24 months. Intimal thickening 3 months after transplantation was related to donor age (r=0.70, P<0.01) but did not predict progression of disease that manifested itself angiographically as a decrease in coronary cross-sectional area at 12 and 24 months (P<0.005) and significant coronary stenosis in 12% of patients after 24 months. Endothelium-independent vasodilatation after nitroglycerin (33+/-15, 44+/-20, and 43+/-24%) was normal. Endothelium-dependent, flow-induced vasodilatation during exercise was decreased (14+/-11, 18+/-14, and 16+/-17%) but did not correlate to intimal changes assessed by ultrasound.
  
  
  CONCLUSIONS
  The study confirms the high incidence of intimal thickening after heart transplantation as assessed by intravascular ultrasound. Impaired exercise-induced vasodilatation suggests diminished bioavailability of endothelium-derived nitric oxide to physiological stimulation but the lack of relationship between coronary wall changes and this functional impairment suggests intermittent and presumably reversible endothelial injury in graft atherosclerosis.
authors.affiliation: Division of Cardiology and Cardiovascular Surgery, University Hospital, Zurich, Switzerland.
authors.forename: B K
authors.initials: BK
authors.lastname: Julius
authors.forename: C H
authors.initials: CH
authors.lastname: Attenhofer Jost
authors.forename: G
authors.initials: G
authors.lastname: Sütsch
authors.forename: H P
authors.initials: HP
authors.lastname: Brunner
authors.forename: A
authors.initials: A
authors.lastname: Kuenzli
authors.forename: P R
authors.initials: PR
authors.lastname: Vogt
authors.forename: M
authors.initials: M
authors.lastname: Turina
authors.forename: O M
authors.initials: OM
authors.lastname: Hess
authors.forename: W
authors.initials: W
authors.lastname: Kiowski
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017023:Coronary Angiography; D003331:Coronary Vessels / Q000000981:diagnostic imaging; D018450:Disease Progression; D005260:Female; D016027:Heart Transplantation; D006439:Hemodynamics; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D013557:Switzerland; D017539:Tunica Intima / Q000000981:diagnostic imaging; D018084:Ultrasonography, Interventional; D014652:Vascular Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology* / Q000503:physiopathology