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)

JACC Cardiovasc Interv. 2015 May;8(6):824-833. doi: 10.1016/j.jcin.2015.01.029.


Objectives: 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).

Keywords: adenosine; coronary artery disease; fractional flow reserve; instantaneous wave-free ratio; physiology; vasodilation.

Publication types

  • Evaluation Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / administration & dosage*
  • Aged
  • Algorithms
  • Cardiac Catheterization*
  • Coronary Angiography
  • Coronary Stenosis / classification
  • Coronary Stenosis / diagnosis*
  • Coronary Stenosis / physiopathology
  • Electrocardiography
  • Female
  • Fractional Flow Reserve, Myocardial*
  • Hemodynamics
  • Humans
  • Hyperemia / physiopathology
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • Reproducibility of Results
  • Severity of Illness Index
  • Signal Processing, Computer-Assisted
  • Vasodilator Agents / administration & dosage*


  • Vasodilator Agents
  • Adenosine

Associated data