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The Instantaneous Wave-Free Ratio is Equivalent to Fractional Flow Reserve and does not require adenosine.

Original title: 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. Reference: Sayan Sen et al. J Am Coll Cardiol 2013;61:1409–20.

When considering revascularization, measuring lesion functional compromise is known to improve clinical outcomes and reduce costs. Intracoronary pressure distal to a stenosis reflects not only the severity of the stenosis but also the pressure generated from microcirculation. Fractional Flow Reserve (FFR) calculates the pressure distal to a stenosis and the aorta during a whole cardiac cycle, but in order to separate epicardial lesion values from microcirculation values requires adenosine administration.

The instantaneous wave-free ratio of cardiac cycle (iFR) is an alternative index that does not require adenosine administration or any other vessel dilator, since during this period, microcirculation resistance is naturally constant and minimized. Intracoronary pressure and flow velocity was measured distal to the stenosis at rest and during adenosine administration (ComboWire XT,Volcano Corporation, San Diego, California) in 51 vessels. iFR ratio was calculated as the relationship between mean distal pressure and proximal pressure during the wave-free diastolic period.

Diagnosis matched in 47 of the 51 lesions (92.3%); no significant differences were observed in the area under the ROC curves (p=0.15). iFR ratio showed a trans-stenosis pressure gradient equivalent to that of FFR ratio (iFR 8.2 mmHg vs 12.2 mmHg; p=0.48) with an 0.86 iFR comparable to a 0.75 FFR.

Conclusion: 

iFR and FFR were equivalent when classifying coronary stenosis severity. Adenosine administration did not improve diagnostic categorization, indicating that iFR can be used as an adenosine-free alternative to FFR and that adenosine administration is not required.

Editorial Comment: 

The ADVISE study used different cut-offs, which resulted in a 0.89 iFR, equivalent to a 0.8 FFR. However, although physiology guided revascularization has shown to be effective, it has seen limited practice and perhaps one of the reasons is the need to administer adenosine, which requires the use of a large number of doses to reach the recommended infusion level, increases cost and, in addition, has frequent, though transitory, adverse effects (shortness of breath, chest pain, blushing, AV block). iFR is much more practical but its real value calls for further research to assess clinical end points. 

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