Instantaneous Wave-Free Ratio (iFR) Measures Stenosis Severity Without Adenosine


November 15, 2011

November 15, 2011 — The ADVISE clinical trial concluded that a new measure of stenosis severity — instantaneous wave-free ratio (iFR) — yielded similar results to traditional fractional flow reserve (FFR) without using adenosine to induce maximum hyperemia. Trial results were presented at the 23rd annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium, sponsored by the Cardiovascular Research Foundation.

FFR, while the leading invasive measure of stenosis severity, is only used in 6 percent or fewer of percutaneous coronary intervention (PCI) cases in the United States. One reason is the required use of the drug adenosine, which minimizes and stabilizes coronary resistance during the test but is uncomfortable for patients. FFR is also time-consuming and expensive.

In ADVISE (ADenosine Vasodilation Independent Stenosis Evaluation), 157 stenoses (131 patients) were recruited to this pilot, non–randomized, international, multi-center study. In their investigations, researchers developed a new pressure-based index that does not require adenosine.

Wave intensity analysis was used during the trial. It identified a period during the normal heart rhythm cycle where intracoronary resistance at rest is similar in variability and magnitude (CV: 0.08±0.06 and 284±147mmHg.s/m) to those during FFR (CV: 0.08±0.06 and 302±315mmHg.s/m, p=NS for both).

The resting ratio of the distal-to-proximal pressure during this period, iFR, correlated closely with FFR (r=0.9, p<0.001) with excellent diagnostic efficiency (receiver operating characteristic area under curve of 93 percent, at FFR<0.8), specificity, sensitivity, and negative and positive predictive values of 91 percent, 85 percent, 85 percent and 91 percent, respectively.

“The results of the ADVISE trial indicate that intracoronary resistance is naturally constant and minimized during the wave-free period. The instantaneous wave-free ratio (iFR) calculated over this period produces a drug-free index of stenosis severity that is comparable to FFR,” said principal investigator Justin Davies, MBBS, MRCP, Ph.D. Davies is a clinical academic and interventional cardiologist at the National Heart and Lung Institute at Imperial College London.

“The clinical implications of the trial are that significant barriers to a physiological assessment of stenoses have been removed, and the new technique can potentially improve workflow in the cath lab, leading to a better patient experience and increased adoption,” said Davies.

The ADVISE trial was funded by the National Institute for Health Research, Biomedical Research Council and the Coronary Flow Trust and supported by Volcano Corp. Davies holds licensed patents pertaining to this technology and has acted as a consultant for Volcano.

For more information: