title: Attenuated-Signal Plaque Progression Predicts Long-Term Mortality After Heart Transplantation: IVUS Assessment of Cardiac Allograft Vasculopathy.
abstract: Although cardiac allograft vasculopathy (CAV) is typically characterized by diffuse coronary intimal thickening with pathological vessel remodeling, plaque instability may also play an important role in CAV. Previous studies of native coronary atherosclerosis have demonstrated associations between attenuated-signal plaque (ASP), plaque instability, and adverse clinical events.
  
  
  
  This study's aim was to characterize the association between ASP and long-term mortality post-heart transplantation.
  
  
  
  In 105 heart transplant recipients, serial (baseline and 1-year post-transplant) intravascular ultrasound was performed in the first 50 mm of the left anterior descending artery. The ASP score was calculated by grading the measured angle of attenuation from grades 0 to 4 (specifically, 0°, 1° to 90°, 91° to 180°, 181° to 270°, and >270°) at 1-mm intervals. The primary endpoint was all-cause death or retransplantation.
  
  
  
  At 1-year post-transplant, 10.5% of patients demonstrated ASP progression (newly developed or increased ASP). Patients with ASP progression had a higher incidence of acute cellular rejection during the first year (63.6% vs. 22.3%; p = 0.006) and tendency for greater intimal growth (percent intimal volume: 9.2 ± 9.3% vs. 4.4 ± 5.3%; p = 0.07) than those without. Over a median follow-up of 4.6 years, there was a significantly lower event-free survival rate in patients with ASP progression at 1-year post-transplant compared with those without. In contrast, maximum intimal thickness did not predict long-term mortality.
  
  
  
  ASP progression appears to reflect chronic inflammation related to acute cellular rejection and is an independent predictor of long-term mortality after heart transplantation. Serial assessments of plaque instability may enhance identification of high-risk patients who may benefit from closer follow-up and targeted medical therapies.
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: William F
authors.initials: WF
authors.lastname: Fearon
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: 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: Kyuhachi
authors.initials: K
authors.lastname: Otagiri
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: 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: 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: 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: 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: Hannah A
authors.initials: HA
authors.lastname: Valantine
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. Electronic address: yshonda@stanford.edu.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Honda
mesh_terms: D000328:Adult; D064591:Allografts; D002140:California / Q000453:epidemiology; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000175:diagnosis* / Q000209:etiology / Q000401:mortality; D003331:Coronary Vessels / Q000000981:diagnostic imaging; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005544:Forecasting; D006084:Graft Rejection / Q000150:complications / Q000175:diagnosis* / Q000401:mortality; D016027:Heart Transplantation / Q000009:adverse effects* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000175:diagnosis* / Q000209:etiology / Q000401:mortality; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D018084:Ultrasonography, Interventional / Q000379:methods*; D066253:Vascular Remodeling; D055815:Young Adult
keywords: acute cellular rejection; intima; intravascular ultrasound; plaque instability; remodeling