Continuum of Vasodilator Stress From Rest to Contrast Medium to Adenosine Hyperemia for Fractional Flow Reserve Assessment

JACC Cardiovasc Interv. 2016 Apr 25;9(8):757-767. doi: 10.1016/j.jcin.2015.12.273.


Objectives: This study compared the diagnostic performance with adenosine-derived fractional flow reserve (FFR) ≤0.8 of contrast-based FFR (cFFR), resting distal pressure (Pd)/aortic pressure (Pa), and the instantaneous wave-free ratio (iFR).

Background: FFR objectively identifies lesions that benefit from medical therapy versus revascularization. However, FFR requires maximal vasodilation, usually achieved with adenosine. Radiographic contrast injection causes submaximal coronary hyperemia. Therefore, intracoronary contrast could provide an easy and inexpensive tool for predicting FFR.

Methods: We recruited patients undergoing routine FFR assessment and made paired, repeated measurements of all physiology metrics (Pd/Pa, iFR, cFFR, and FFR). Contrast medium and dose were per local practice, as was the dose of intracoronary adenosine. Operators were encouraged to perform both intracoronary and intravenous adenosine assessments and a final drift check to assess wire calibration. A central core lab analyzed blinded pressure tracings in a standardized fashion.

Results: A total of 763 subjects were enrolled from 12 international centers. Contrast volume was 8 ± 2 ml per measurement, and 8 different contrast media were used. Repeated measurements of each metric showed a bias <0.005, but a lower SD (less variability) for cFFR than resting indexes. Although Pd/Pa and iFR demonstrated equivalent performance against FFR ≤0.8 (78.5% vs. 79.9% accuracy; p = 0.78; area under the receiver-operating characteristic curve: 0.875 vs. 0.881; p = 0.35), cFFR improved both metrics (85.8% accuracy and 0.930 area; p < 0.001 for each) with an optimal binary threshold of 0.83. A hybrid decision-making strategy using cFFR required adenosine less often than when based on either Pd/Pa or iFR.

Conclusions: cFFR provides diagnostic performance superior to that of Pd/Pa or iFR for predicting FFR. For clinical scenarios or health care systems in which adenosine is contraindicated or prohibitively expensive, cFFR offers a universal technique to simplify invasive coronary physiological assessments. Yet FFR remains the reference standard for diagnostic certainty as even cFFR reached only ∼85% agreement.

Keywords: adenosine; contrast medium; fractional flow reserve; hyperemia; instantaneous wave-free ratio.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • Adenosine / administration & dosage*
  • Aged
  • Area Under Curve
  • Arterial Pressure
  • Cardiac Catheterization / methods*
  • Contrast Media / administration & dosage*
  • Coronary Artery Disease / diagnostic imaging*
  • Coronary Artery Disease / physiopathology
  • Coronary Artery Disease / therapy
  • Coronary Vessels / diagnostic imaging*
  • Coronary Vessels / physiopathology
  • Female
  • Fractional Flow Reserve, Myocardial*
  • Humans
  • Hyperemia / physiopathology*
  • Injections, Intra-Arterial
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prospective Studies
  • ROC Curve
  • Reproducibility of Results
  • Time Factors
  • Vasodilator Agents / administration & dosage*


  • Contrast Media
  • Vasodilator Agents
  • Adenosine