iFR May Help Rule Out Significant Nonculprit Lesions After Primary PCI

“If the iFR study is negative, you can trust it,” Allen Jeremias says. But if it’s positive, there’s a chance it’ll be negative at follow-up.

iFR May Help Rule Out Significant Nonculprit Lesions After Primary PCI

Instantaneous wave-free ratio (iFR) may have a role to play in the acute setting of primary PCI, a new analysis suggests.

Agreement between an acute iFR evaluation of nonculprit arteries and one performed later in patients with STEMI who had undergone successful primary PCI of a culprit lesion was 78%, although the negative predictive value was higher at 89%, researchers led by Troels Thim, MD, PhD (Aarhus University Hospital, Denmark), report in a study published online November 29, 2017, ahead of print JACC: Cardiovascular Interventions.

“Acute iFR evaluation appeared valid for ruling out significant nonculprit stenoses in patients with STEMI undergoing primary percutaneous coronary intervention,” they conclude.

Discussing the potential clinical implications of the findings, the authors say that acute iFR assessment of nonculprit lesions in the setting of STEMI “can be used to defer revascularization or staged follow-up evaluation” and “will most likely reduce the risk, costs, and patient-related concerns associated with staged follow-up procedures.”

In addition, they indicate that acute iFR may help guide complete revascularization: “Our data provide a basis for prospective randomized studies comparing acute full revascularization with functional evaluation of nonculprit stenoses versus staged full revascularization with functional (invasive or noninvasive) evaluation of nonculprit stenoses.”

Commenting for TCTMD, Allen Jeremias, MD (St. Francis Hospital, Roslyn, NY), said that several trials and meta-analysis have established that more complete revascularization in the setting of STEMI improves outcomes. There are remaining questions, however, about how to evaluate nonculprit lesions and when to intervene, either during the index procedure or in a staged fashion.

The idea of using fractional flow reserve (FFR) or iFR to evaluate the lesions at the time of primary PCI makes intuitive sense and might eliminate the need to bring patients back for costly testing at a later time, he said. “If you could eliminate the nuclear scan and if you could eliminate the patients who have nonsignificant lesions, you would save considerable healthcare dollars and also obviously contribute to better healthcare for the patient,” Jeremias explained.

Few studies have examined that approach, however, and the strategy relies on iFR or FFR measurements made in the acute setting being representative of a patient’s baseline state and not being affected by the acute changes at the time of STEMI, he said.


And that’s the area addressed by Thim et al in their study, dubbed iSTEMI. The investigators set out to evaluate the level of agreement between acute iFR measurements taken immediately following primary PCI and iFR or FFR measurements obtained at a staged, follow-up procedure. The study included 120 patients with 157 nonculprit lesions that were assessed after successful primary PCI and left untreated. Follow-up evaluations were performed a median of 16 days later. Lesions were considered hemodynamically significant if iFR values were less than 0.90.

Median iFR values were 0.89 in the acute phase and 0.91 at follow-up. The change over time resulted in the reclassification of 32 lesions—25% of those were upgraded to significant and 75% were downgraded to nonsignificant.

Classification agreement was 78% between acute and follow-up iFR values, with a negative predictive value of 89%. When comparing acute iFR to follow-up FFR with a cutoff of 0.80 or less, the negative predictive value was 77%; lowering the cutoff to less than 0.75 increased the negative predictive value to 91%.

Agreement between acute and follow-up iFR values was highest when the interval between the two time periods was less than 5 days, with agreement worsening as the gap widened, suggesting that “that inherent physiological disarrangements during STEMI may contribute to classification disagreement,” the authors write.

Commenting on the consistency of the iFR results between the two time periods, Jeremias said, “It turns out that it’s not as reliable as one would think.” He pointed out that the acute iFR values essentially overestimated lesion severity because lesions were more likely to go from positive to negative than from negative to positive.

“The obvious conclusion is that if the iFR study is negative, you can trust it,” Jeremias said. “If the iFR study is positive, then there’s still a chance that you might not have to deal with the lesion when the patient comes back more than 2 weeks later.”

Continuum of Risk

Offering a more subtle interpretation of the study, too, Jeremias noted that the median change in iFR between the acute values and the follow-up measurements—from 0.89 to 0.91—was small. “Is there really a clinical difference? I don’t think so, because ischemia is really a continuum of risk,” he said. He added that when patients are so close to the cutoff point, repeated measurements could reclassify patients simply because of biological variation.

When interpreting iFR or FFR values, Jeremias said he likes to think about them as along a continuum and not as a dichotomous positive or negative. Values far above the cutoff indicate that lesions are unlikely to cause any trouble, and those far below the cutoff indicate that revascularization should be performed. “But the ones around the cutoff point, whether you initially treat them medically or choose to revascularize them I don’t think will make a difference in terms of clinical outcomes,” he said.

Noting that 52% of acute iFR measurements in the study indicated a hemodynamically nonsignificant lesion, Jeremias said performing functional tests at the time of the index procedure could avert the need for about half of patients to come back to the cath lab.

“If you acutely do an iFR measurement and it’s negative, you know that patient does not have to return to the lab. You know that patient does not need a nuclear study. So you save a lot of healthcare costs in that patient, and you know you can treat them safely medically,” he said. “If it’s abnormal, I think then it’s fair to bring them back and then you can either treat it with a stent or you can remeasure FFR/iFR depending on what you want to do. But at least you eliminated 50%.”

Using iFR in this way in patients with STEMI is not routine at this point, Jeremias said, adding that larger studies—which look at clinical outcomes in addition to resource use—would be needed to evaluate whether iFR can be valuable in this setting.

iFR During STEMI ‘Reasonable’

In an accompanying editorial, J. Dawn Abbott, MD (Brown University, Providence, RI), notes that the classification agreement was greater when intervals between the acute and follow-up iFR measurements were shorter, which “suggests perturbations in STEMI may be present for a few weeks and influence iFR measurement.”

She adds that it’s not known whether FFR would be more or less likely to be affected the same way in this setting.

 “Until larger, clinically powered studies are available, either assessing iFR noninferiority to FFR or angiographic guidance, adopting iFR to assess nonculprit lesions in STEMI is a reasonable [option],” she says. “For most patients, complete revascularization can be achieved prior to hospital discharge. As always, functional measures such as iFR should not supplant clinical judgement. Lesion vulnerability, patient comorbidities, size of ischemic territory, the ability to comply with dual antiplatelet therapy, and risk of contrast-induced kidney injury are just some of the issues that should be considered when pursuing complete revascularization.”

  • The study was funded by an unrestricted research grant from Volcano Europe.
  • Thim reports no relevant conflicts of interest.
  • Abbott reports performing clinical trial adjudication for Pfizer (antihyperlipidemic therapy) and Recor (renal denervation).
  • Jeremias reports being a consultant for Abbott Vascular, Philips/Volcano, ACIST Medical, Boston Scientific, and Opsens.

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