Diagnostic classification of the instantaneous wave-free ratio is equivalent to fractional flow reserve and is not improved with adenosine administration. Results of CLARIFY (Classification Accuracy of Pressure-Only Ratios Against Indices Using Flow Study)

J Am Coll Cardiol. 2013 Apr 2;61(13):1409-20. doi: 10.1016/j.jacc.2013.01.034.


Objectives: This study sought to determine if adenosine administration is required for the pressure-only assessment of coronary stenoses.

Background: The instantaneous wave-free ratio (iFR) is a vasodilator-free pressure-only measure of the hemodynamic severity of a coronary stenosis comparable to fractional flow reserve (FFR) in diagnostic categorization. In this study, we used hyperemic stenosis resistance (HSR), a combined pressure-and-flow index, as an arbiter to determine when iFR and FFR disagree which index is most representative of the hemodynamic significance of the stenosis. We then test whether administering adenosine significantly improves diagnostic performance of iFR.

Methods: In 51 vessels, intracoronary pressure and flow velocity was measured distal to the stenosis at rest and during adenosine-mediated hyperemia. The iFR (at rest and during adenosine administration [iFRa]), FFR, HSR, baseline, and hyperemic microvascular resistance were calculated using automated algorithms.

Results: When iFR and FFR disagreed (4 cases, or 7.7% of the study population), HSR agreed with iFR in 50% of cases and with FFR in 50% of cases. Differences in magnitude of microvascular resistance did not influence diagnostic categorization; iFR, iFRa, and FFR had equally good diagnostic agreement with HSR (receiver-operating characteristic area under the curve 0.93 iFR vs. 0.94 iFRa and 0.96 FFR, p = 0.48).

Conclusions: iFR and FFR had equivalent agreement with classification of coronary stenosis severity by HSR. Further reduction in resistance by the administration of adenosine did not improve diagnostic categorization, indicating that iFR can be used as an adenosine-free alternative to FFR.

Trial registration: ClinicalTrials.gov NCT01118481.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / administration & dosage*
  • Aged
  • Blood Flow Velocity / physiology*
  • Coronary Circulation / physiology
  • Coronary Stenosis / diagnosis*
  • Coronary Stenosis / physiopathology
  • Female
  • Fractional Flow Reserve, Myocardial / physiology*
  • Hemodynamics
  • Humans
  • Hyperemia / physiopathology
  • Infusions, Intravenous
  • Male
  • Microcirculation / physiology
  • Middle Aged
  • Myocardial Contraction / physiology
  • Pericardium / pathology
  • ROC Curve
  • Vascular Resistance / physiology
  • Vasodilator Agents / administration & dosage*


  • Vasodilator Agents
  • Adenosine

Associated data

  • ClinicalTrials.gov/NCT01118481