title: Prospective Assessment of the Diagnostic Accuracy of Instantaneous Wave-Free Ratio to Assess Coronary Stenosis Relevance: Results of ADVISE II International, Multicenter Study (ADenosine Vasodilator Independent Stenosis Evaluation II).
abstract: OBJECTIVE
  The purpose of this study was to assess the diagnostic accuracy of the instantaneous wave-free ratio (iFR) to characterize, outside of a pre-specified range of values, stenosis severity, as defined by fractional flow reserve (FFR) ≤0.80, in a prospective, independent, controlled, core laboratory-based environment.
  
  
  BACKGROUND
  Studies with methodological heterogeneity have reported some discrepancies in the classification agreement between iFR and FFR. The ADVISE II (ADenosine Vasodilator Independent Stenosis Evaluation II) study was designed to overcome limitations of previous iFR versus FFR comparisons.
  
  
  METHODS
  A total of 919 intermediate coronary stenoses were investigated during baseline and hyperemia. From these, 690 pressure recordings (n = 598 patients) met core laboratory physiology criteria and are included in this report.
  
  
  RESULTS
  The pre-specified iFR cut-off of 0.89 was optimal for the study and correctly classified 82.5% of the stenoses, with a sensitivity of 73.0% and specificity of 87.8% (C statistic: 0.90 [95% confidence interval (CI): 0.88 to 0.92, p < 0.001]). The proportion of stenoses properly classified by iFR outside of the pre-specified treatment (≤0.85) and deferral (≥0.94) values was 91.6% (95% CI: 88.8% to 93.9%). When combined with FFR use within these cut-offs, the percent of stenoses properly classified by such a pre-specified hybrid iFR-FFR approach was 94.2% (95% CI: 92.2% to 95.8%). The hybrid iFR-FFR approach obviated vasodilators from 65.1% (95% CI: 61.1% to 68.9%) of patients and 69.1% (95% CI: 65.5% to 72.6%) of stenoses.
  
  
  CONCLUSIONS
  The ADVISE II study supports, on the basis rigorous methodology, the diagnostic value of iFR in establishing the functional significance of coronary stenoses, and highlights its complementariness with FFR when used in a hybrid iFR-FFR approach. (ADenosine Vasodilator Independent Stenosis Evaluation II-ADVISE II; NCT01740895).
authors.affiliation: Cardiovascular Institute, Hospital Clinico San Carlos and Centro Nacional de Investigaciónes Cardiovasculares Carlos III (CNIC), Madrid, Spain; Faculty of Medicine, Complutense University of Madrid, Spain. Electronic address: escaned@secardiologia.es.
authors.forename: Javier
authors.initials: J
authors.lastname: Escaned
authors.affiliation: Cardiovascular Institute, Hospital Clinico San Carlos and Centro Nacional de Investigaciónes Cardiovasculares Carlos III (CNIC), Madrid, Spain; Erasmus MC, Department of Cardiology, Rotterdam, the Netherlands.
authors.forename: Mauro
authors.initials: M
authors.lastname: Echavarría-Pinto
authors.affiliation: Erasmus MC, Department of Cardiology, Rotterdam, the Netherlands.
authors.forename: Hector M
authors.initials: HM
authors.lastname: Garcia-Garcia
authors.affiliation: AMC Heart Center, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Tim P
authors.initials: TP
authors.lastname: van de Hoef
authors.affiliation: Cardialysis BV, Rotterdam, the Netherlands.
authors.forename: Ton
authors.initials: T
authors.lastname: de Vries
authors.affiliation: University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Prashant
authors.initials: P
authors.lastname: Kaul
authors.affiliation: Cardiovascular Division of the University of Minnesota, Minneapolis, Minnesota.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Raveendran
authors.affiliation: St. Anthony's Heart and Vascular Center and Colorado Heart and Vascular PC, Denver, Colorado.
authors.forename: John D
authors.initials: JD
authors.lastname: Altman
authors.affiliation: Division of Cardiology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Howard I
authors.initials: HI
authors.lastname: Kurz
authors.affiliation: Regions Hospital, Saint Paul, Minnesota.
authors.forename: Johannes
authors.initials: J
authors.lastname: Brechtken
authors.affiliation: Cardiovascular Research of North Florida, Gainesville Florida.
authors.forename: Mark
authors.initials: M
authors.lastname: Tulli
authors.affiliation: Thoraxcentrum Twente, Department of Cardiology, Medisch Spectrum Twente, and Health Technology and Services Research, MIRA, University of Twente, Enschede, the Netherlands.
authors.forename: Clemens
authors.initials: C
authors.lastname: Von Birgelen
authors.affiliation: Wake Heart and Vascular Institute, Raleigh, North Carolina.
authors.forename: Joel E
authors.initials: JE
authors.lastname: Schneider
authors.affiliation: Al Dorrah Heart Care Hospital, Ain Shams University, Cairo, Egypt.
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Khashaba
authors.affiliation: Stony Brook University Medical Center, Stony Brook, New York.
authors.forename: Allen
authors.initials: A
authors.lastname: Jeremias
authors.affiliation: Greenville Memorial Hospital, Grenville, South Carolina.
authors.forename: Jim
authors.initials: J
authors.lastname: Baucum
authors.affiliation: Hospital Universitario la Paz, Madrid, Spain.
authors.forename: Raul
authors.initials: R
authors.lastname: Moreno
authors.affiliation: Department of Cardiology, Amphia Hospital, Breda, the Netherlands.
authors.forename: Martijn
authors.initials: M
authors.lastname: Meuwissen
authors.affiliation: Prairie Heart Institute, St. John's Hospital, Springfield, Illinois.
authors.forename: Gregory
authors.initials: G
authors.lastname: Mishkel
authors.affiliation: Erasmus MC, Department of Cardiology, Rotterdam, the Netherlands.
authors.forename: Robert-Jan
authors.initials: RJ
authors.lastname: van Geuns
authors.affiliation: AtlantiCare Regional Medical Center, Egg Harbor Township, New Jersey.
authors.forename: Howard
authors.initials: H
authors.lastname: Levite
authors.affiliation: Hospital Universitario de San Juan de Alicante, Alicante, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Lopez-Palop
authors.affiliation: Wellmont Holston Valley Medical Center, Kingsport, Tennessee.
authors.forename: Marc
authors.initials: M
authors.lastname: Mayhew
authors.affiliation: Erasmus MC, Department of Cardiology, Rotterdam, the Netherlands.
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Serruys
authors.affiliation: Division of Cardiology, Department of Medicine, Andreas Gruentzig Cardiovascular Center, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Habib
authors.initials: H
authors.lastname: Samady
authors.affiliation: AMC Heart Center, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Piek
authors.affiliation: Center for Coronary Physiology and Imaging, Division of Cardiovascular Diseases, and Department of Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minnesota.
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman
mesh_terms: D000241:Adenosine / Q000008:administration & dosage*; D000368:Aged; D000465:Algorithms; D006328:Cardiac Catheterization; D017023:Coronary Angiography; D023921:Coronary Stenosis / Q000145:classification / Q000175:diagnosis* / Q000503:physiopathology; D004562:Electrocardiography; D005260:Female; D053805:Fractional Flow Reserve, Myocardial; D006439:Hemodynamics; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D012815:Signal Processing, Computer-Assisted; D014665:Vasodilator Agents / Q000008:administration & dosage*
chemical_list: D014665:Vasodilator Agents; D000241:Adenosine
keywords: adenosine; coronary artery disease; fractional flow reserve; instantaneous wave-free ratio; physiology; vasodilation