title: Association of periarterial neovascularization with progression of cardiac allograft vasculopathy and long-term clinical outcomes in heart transplant recipients.
abstract: This study investigated the relationship between periarterial neovascularization, development of cardiac allograft vasculopathy (CAV), and long-term clinical outcomes after heart transplantation. Proliferation of the vasa vasorum is associated with arterial inflammation. The contribution of angiogenesis to the development of CAV has been suggested.
  
  
  
  Serial (baseline and 1-year post-transplant) intravascular ultrasound was performed in 102 heart transplant recipients. Periarterial small vessels (PSV) were defined as echolucent luminal structures <1 mm in diameter, located ≤2 mm outside of the external elastic membrane. The signal void structures were excluded when they connected to the coronary lumen (considered as side branches) or could not be followed in ≥3 contiguous frames. The number of PSV was counted at 1-mm intervals throughout the first 50 mm of the left anterior descending artery, and the PSV score was calculated as the sum of cross-sectional values. Patients with a PSV score increase of ≥ 4 between baseline and 1-year post-transplant were classified as the "proliferative" group. Maximum intimal thickness was measured for the entire analysis segment.
  
  
  
  During the first year post-transplant, the proliferative group showed a greater increase in maximum intimal thickness (0.33 ± 0.36 mm vs 0.10 ± 0.28 mm, p < 0.001) and had a higher incidence of acute cellular rejection (50.0% vs 23.9%, p = 0.025) than the non-proliferative group. On Kaplan-Meier analysis, cardiac death-free survival rate over a median of 4.7 years was significantly lower in the proliferative group than in the non-proliferative group (hazard ratio, 3.10; p = 0.036).
  
  
  
  The increase in PSV, potentially representing an angioproliferative response around the coronary arteries, was associated with early CAV progression and reduced survival after heart transplantation.
authors.affiliation: Division of Cardiovascular Medicine, Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California.
authors.forename: Hideki
authors.initials: H
authors.lastname: Kitahara
authors.affiliation: Division of Cardiovascular Medicine, Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California.
authors.forename: Kozo
authors.initials: K
authors.lastname: Okada
authors.affiliation: Division of Cardiovascular Medicine, Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California.
authors.forename: Shigemitsu
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Division of Cardiovascular Medicine, Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California.
authors.forename: Hyoung-Mo
authors.initials: HM
authors.lastname: Yang
authors.affiliation: Division of Cardiovascular Medicine, Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California.
authors.forename: Kojiro
authors.initials: K
authors.lastname: Miki
authors.affiliation: Division of Cardiovascular Medicine, Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California.
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Division of Cardiovascular Medicine, Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California.
authors.forename: Takumi
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Division of Cardiovascular Medicine, Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California.
authors.forename: Helen
authors.initials: H
authors.lastname: Luikart
authors.affiliation: Division of Cardiovascular Medicine, Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Yock
authors.affiliation: Division of Cardiovascular Medicine, Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California.
authors.forename: Alan C
authors.initials: AC
authors.lastname: Yeung
authors.affiliation: Division of Cardiovascular Medicine, Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Fitzgerald
authors.affiliation: Division of Cardiovascular Medicine, Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California.
authors.forename: Kiran K
authors.initials: KK
authors.lastname: Khush
authors.affiliation: Division of Cardiovascular Medicine, Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California.
authors.forename: William F
authors.initials: WF
authors.lastname: Fearon
authors.affiliation: Division of Cardiovascular Medicine, Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California. Electronic address: crci-cvmed@stanford.edu.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Honda
mesh_terms: D064591:Allografts; D003331:Coronary Vessels; D003430:Cross-Sectional Studies; D006084:Graft Rejection; D016027:Heart Transplantation; D006801:Humans; D018084:Ultrasonography, Interventional
keywords: cardiac allograft vasculopathy; heart transplantation; intravascular ultrasound; neovascularization; periarterial small vessels