Two studies challenge initial findings of iFR vs. FFR

Two studies published in the Journal of the American College of Cardiology have demonstrated that the instantaneous wave-free ratio has a poor correlation with the fractional flow reserve and therefore should not be used interchangeably.

Instantaneous wave-free ratio (iFR), the adenosine-free index of lesion assessment, had been proposed as an index of stenosis severity that is independent of hyperemia. In the ADVISE study, investigators led by Justin Davies, MD, PhD, of the Imperial College, London, reported that iFR had comparable diagnostic efficiency to FFR for the identification of obstructive coronary lesions (ie, FFR <0.8). These two new studies sought to further examine the utility of iFR in comparison with FFR.

VERIFY

The prospective, multicenter, international VERIFY study was initiated by investigators who questioned the theory and validity of the ADVISE results. In the study, 206 consecutive patients referred for PCI were enrolled. Researchers performed a retrospective analysis of 500 archived pressure recordings and measured aortic and distal coronary pressured in duplicate in patients under resting conditions and during intravenous adenosine infusion at 140 mcg/kg/min.

The diagnostic accuracy of the iFR value of ≤0.8 compared with an FFR cut-off value of ≤0.8 was 60% (95% CI, 53%-67%) for all vessels studied and 51% (95% CI, 43%-59%) for patients with FFR in the range of 0.60 to 0.90, the “clinically important range for decision making,” according to the researchers. Additionally, the induction of hyperemia significantly influenced iFR (standard deviation iFR at rest, 0.82 ± 0.16 vs. 0.64 ±0.18 with hyperemia; P<.001).

“iFR, which is by definition a resting parameter and said to be independent of hyperemia, did in fact change markedly during adenosine-induced hyperemia, a finding which challenges the underlying concept and clinical applicability of iFR,” the researchers wrote.

iFR as approximation to FFR

The clinical performance of iFR was tested in another study published by the Journal of the American College of Cardiology, involving 1,129 patients, 120 of whom had combined pressure-flow data; 1,000 Monte Carlo simulations were also performed.

Data indicated iFR was +0.09 higher than FFR on average, with ±0.17 limits of agreement and diastolic resting resistance was 2.5 ± 1.0 times higher than mean hyperemic resistance. Researchers reported that without invoking wave mechanics, classic pressure-flow physiology explained clinical observations well, with a coefficient of determination of >0.9. Their model was supported by the nearly identical scatter of iFR vs. FFR observed between simulation and patient observations.

Although the initial ADVISE trial previously reported iFR to have a comparable diagnostic efficiency to FFR, the researchers of this new paper wrote “iFR provides a biased estimate [of] FFR on average with significant and unpredictable discordance that limits its widespread application, especially when considering the clinical consequences. Such discordance is fundamental to the physiologic basis for iFR itself. Furthermore, diastolic resting myocardial resistance does not equally mean hyperemic resistance, a stipulated condition in the original iFR report.”

For more information:

Berry C. J Am CollCardiol. 2013;doi:10.1016/j.jacc.2012.09.065.

Johnson NP. J Am CollCardiol. 2013;doi:10.1016/j.jacc.2012.09.064.

Disclosure: Berry has received research grant support from St. Jude Medical. Johnson received internal funding from the Weatherhead PET Center for Preventing and Reversing Atherosclerosis, University of Texas Medical School.