Mixed Results Shown with Adenosine-Free Pressure Measurement vs. FFR

PARIS, France—Two studies showed conflicting results on the accuracy of a new intracoronary resistance measurement that obviates the need for drug administration in estimating coronary stenosis severity. The findings were presented Wednesday, May 16, at EuroPCR 2012.

Previously, Justin E. Davies, MD, PhD, of Imperial College (London, United Kingdom) presented data at the annual Transcatheter Cardiovascular Therapeutics scientific symposium in November 2011 in San Francisco, CA, demonstrating that instantaneous wave-free ratio (iFR) measurement is comparable to fractional flow reserve (FFR) in assessing stenosis severity.

iFR is based on the diastolic ‘wave-free period’ when intracoronary resistance is naturally constant and minimized. Unlike FFR, iFR calculation does not require the administration of adenosine or any other drug.

ADVISE Confirms Usefulness

For the ADVISE (ADenosine Vasodilation Independent Stenosis Evaluation) registry, Dr. Davies and colleagues compared FFR and iFR measurements in 312 patients (339 lesions), most with stable angina (93%) and single-vessel disease (78%). Patients treated under the FFR cutoff of 0.8 had an FFR of 0.73 ± 0.08, while those deferred who were over the cutoff had an FFR of 0.87 ± 0.04.

Most lesions (80%) had an FFR between 0.6 and 0.9, denoting intermediate diameter stenoses (48.5 ± 14%).

In the registry, FFR showed a reproducibility of 85%, lower than in previous studies. Using a cut point of 0.89, iFR had an accuracy of 94% in classifying lesions, with 8% numerically lower on iFR than on FFR. More than 40% of the disagreement between iFR and FFR lay within 0.01 of the FFR cutpoint, and more than 80% within the FFR ‘grey zone’ of 0.75 to 0.80.

These results are similar to those reported in the ADVISE trial presentation from TCT 2011 by Dr. Davies.

“iFR gives an excellent estimate of stenosis severity in an everyday clinical population,” he concluded, adding that “adenosine does not add any significant incremental benefit to diagnostic classification.”

Maximal Hyperemia Not a Concern

Dr. Davies observed that iFR measurement simplifies stenosis assessment and achieves significant time savings with no concern about attaining maximal hyperemia. At the same time, it decreases pressure-wire drift. In addition, iFR provides an improved patient experience and enables rapid documentation of ischemia pre-PCI, especially for patients unsuitable for pharmacological agents, he said.

Audience members, though, wondered why adenosine and iFR would behave differently in humans than in animals, and why iFR would, in fact, change with hyperemia. “We all expect adenosine to act in each patient exactly the same way, and it doesn’t,” Dr. Davies responded, noting that animal studies have largely been in normal circulation while human studies are performed in diseased arteries.

“I think why iFR changes when you induce hyperemia is the fact that you induce more of a response from the myocardium,” he added. “This is not just a problem for iFR, but for FFR, as well.”

Still, he stressed, iFR values have shown almost identical values in 4 human studies to this point. “I think the real focus should be on what happens in humans,” Dr. Davies said. “We all know there are differences between monkeys, pigs, dogs, and humans, and trying to infer too much from a 2-month-old pig compared to a 75-year-old adult human who’s had an infarct is a step too far.”

VERIFY Disagrees

But data from the VERIFY trial presented at the same session contradicted those of the ADVISE registry. “We’re not certain about the diagnostic accuracy of iFR,” maintained Keith G. Oldroyd, MD, of the University of Glasgow (Glasgow, Scotland). Dr. Oldroyd and colleagues prospectively compared FFR and iFR in 206 consecutive stable patients referred for coronary angiography with or without PCI.

Importantly, the researchers used the same methodology as the ADVISE investigators to determine iFR measurements.

Mean pressure readings (Pd/Pa, or the ratio of resting distal pressure to aortic pressure) were taken during the ‘wave-free period’ at rest and during steady state hyperemia. Only weak correlations were shown between iFR and FFR for the whole cohort (r2 = 0.7), and especially for those with FFR values in the key range of 0.6 to 0.9 (r2 = 0.3). In addition, mean iFR values fell significantly in almost all patients after inducing hyperemia (0.82 ± 0.16 to 0.64 ± 0.16). 

iFR showed an area under the curve value of 0.871, with a resting gradiant of 0.875, Pd/Pa of 0.880, and iFR during hyperemia of 0.988. “It’s only when you induce hyperemia that you start to see diagnostic accuracies that we would all be comfortable with,” Dr. Oldroyd said.

He concluded that iFR correlates only weakly with FFR in the clinically relevant range of 0.6 to 0.9, and that the measurement, as well as its diagnostic accuracy, is not independent of adenosine-induced hyperemia. “iFR, at this point in time, cannot be recommended for decision making in clinical practice,” Dr. Oldroyd said.

Dr. Davies responded that “there seems to be an insistence that iFR is hyperemia independent.” In fact, he continued, “hyperemia is not mentioned one time in the ADVISE study. I think it’s a little bit of smoke and mirrors trying to deflect people’s attention.”

Dr. Davies went on to call for “a mindset change that we need to make. It’s not necessarily all about maximizing hyperemia to get the optimal diagnostic results.”


1. Davies J. Results of the ADVISE multicenter clinical registry. Presented at: EuroPCR; May 16, 2012; Paris, France. 

2. Oldroyd KG. VERIFY: A multicenter prospective comparison of FFR vs. iFR for the assessment of coronary artery stenosis severity in everyday practice. Presented at: EuroPCR; May 16, 2012; Paris, France. 



  • Dr. Davies reports receiving research contracts from Medtronic and serving as a consultant for Medtronic and Volcano.
  • Dr. Oldroyd reports no relevant conflicts of interest.


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