iFR Pullback Provides Roadmap for CAD Severity, Predicts Hemodynamics Post-PCI

Instantaneous wave-free ratio (iFR) pullback provides a “physiological map of lesion severity” in patients with coronary artery disease that is difficult to characterize with standard fractional flow reserve (FFR), and this added detail can, in turn, inform the revascularization strategy, new observational data confirm.

Results from the multicenter iFR GRADIENT registry show that calculating iFR in the cath lab changes operators’ planning nearly one-third of the time and accurately predicts the hemodynamic outcome of PCI.

With FFR, measurement of coexisting stenoses is challenging, explain researchers led by Yuetsu Kikuta, MD, and Christopher M. Cook, MBBS (Imperial College London and Hammersmith Hospital NHS Trust, London, England). “In tandem or diffuse disease, fluid dynamic interaction occurs between lesions during maximal hyperemia, such that the FFR of a proximal stenosis is influenced by the presence of a distal stenosis and vice versa,” they write.

As a result of this lesion crosstalk, “the interpretation of one lesion affects the other,” senior author Justin E. Davies, MBBS, PhD (Imperial College London and Hammersmith Hospital NHS Trust), told TCTMD. The only way around that obstacle is to do an FFR pullback, treat one of the multiple lesions, then measure FFR again; all of this requires additional time and adenosine, Davies told TCTMD. “You can imagine that’s not really popular, and people don’t really do it.”

iFR, on the other hand, is measured at rest and does not involve inducing maximal hyperemia, thus avoiding this interplay among lesions, he explained. Davies pointed out that this new analysis is not the first foray into hemodynamic mapping for iFR, referencing a single-center report published back in 2014 in JACC: Cardiovascular Interventions. Details from iFR GRADIENT, a multicenter registry, are being published in the April 23, 2018, issue of the same journal.

Manesh R. Patel, MD (Duke University Medical Center, Durham, NC), who was not involved in the latest research, said it illustrates the “evolution of a mature technology.”

“To date,” Patel noted to TCTMD, “we’ve used coronary physiology to help to determine: should we treat this patient who has some disease in this vessel, yes or no? . . . Now what you’re seeing is the technology is evolving to say: how should we do it? In a vessel that might have some lumpy bumpies and a blockage and then maybe a borderline blockage, what the iFR pullback is allowing us to do is start, with co-registration, determining exactly where the physiologic drop-offs are in that vessel.” This precision enables operators to target the most influential lesions for treatment, he explained. Bina Ahmed, MD (Dartmouth-Hitchcock Medical Center, Lebanon, NH), also commenting on the research, told TCTMD: “It’s commendable how committed this team is to seeing how far they can take this technology. This is sort of the next frontier—not only do we want to treat the right lesions, we want to then identify how well we’ve treated the lesions and the territory [of] the potential disease we were targeting.”

iFR GRADIENT Registry

As part of the iFR GRADIENT registry, operators performed both angiography and iFR pullback ahead of the intended intervention. After each modality, they submitted their plans for revascularization. iFR also was assessed following PCI.

A total of 159 patients with 168 coronary vessels eligible for PCI were enrolled. Most (83%) presented with stable angina, while 8% had unstable angina, 6% NSTEMI, and 3% STEMI.

Decision-making was changed based on the results of iFR compared with angiography in 52 vessels (31%), with fewer lesions treated (-0.18 ± 0.05 lesions per vessel; P = 0.0001) and a shorter total lesion length identified for revascularization (-4.4 ± 1.0 mm per vessel; P < 0.0001). On an artery level, angiography and iFR pullback disagreed on the hemodynamic significance of a vessel 25% of the time.

There were 128 patients with paired values for pre-and post-PCI iFR. Ahead of PCI, the predicted iFR was 0.93 ± 0.05; after PCI, the observed iFR was 0.92 ± 0.06. Overall, iFR pullback predicted the outcome of PCI with a mean error rate of 1.4%.

“To me, that speaks to the fidelity of the method,” Patel commented.

In an accompanying editorial, Morton J. Kern, MD, and Arnold Seto, MD (VA Long Beach Healthcare System, CA), note that a “current point of contention” is whether pressure measured at rest—as in iFR—is as sensitive as pressure measured as maximal hyperemia. This concern makes sense, they agree, but it appears that iFR’s advantage in avoiding lesion crosstalk outweighs its downsides. “The present study suggests that with an error of 1.4%, iFR predicts post-PCI values better than FFR, with reported rates of 4% to 11%,” Kern and Seto say.

‘Stay Tuned for Outcome Data’

The iFR GRADIENT analysis “sets the stage for new thinking about how we should be performing PCI not just in serial lesions but perhaps all coronary interventions,” the editorialists suggest.

“An accurate pressure pullback and prediction of post-PCI physiology could result in more precise and effective procedures that treat all hemodynamically significant lesions with the fewest stents possible,” they observe. “At the same time, such an assessment could distinguish between focal disease that might be amenable to stenting and diffuse disease that might be best treated medically or with bypass surgery. Although it is currently unknown whether the changes in strategy on the basis of iFR pullback will produce better clinical outcomes, this would be the anticipated result. Stay tuned for outcome data.”

I think when we’re talking about treating more complex disease, more diffuse vessels, wanting to know how good a job we’ve done is going to be pretty important. Bina Ahmed

For Patel, having a way to gauge in PCI not only whether or where to treat, but also when enough has been done to optimize outcomes that it’s okay to stop, would be valuable. “Theoretically, physiology might be getting you throughout that entire spectrum in most patients,” he noted.

Davies noted that DEFINE PCI, an observational study of about 500 patients, is further exploring the role of iFR pullback by using it to see which lesions are inadvertently missed during what seems like, on angiography at least, to be successful PCI.

“At the moment what we do is very crude, in terms of we use physiology and we identify whether a [stenosis] is significant or not, then we use that to decide whether to stent or not,” he said. When co-registration is employed, meaning that iFR results are tracked on the angiogram, this allows operators to see exactly where to place stents. “And now,” Davies continued, “you can say, if we put a stent there, this is the improvement we will get.”

iFR pullback is “just making PCI much more straightforward and bringing it into the 21st century,” he concluded.

Ahmed described the idea of measuring post-PCI iFR and seeing how that correlates with clinical outcomes as “intuitive” but cautioned that the field is still a few steps removed from that becoming a reality.

“I think when we’re talking about treating more complex disease, more diffuse vessels, wanting to know how good a job we’ve done is going to be pretty important,” she concluded.