Moreover, in 82% of DEFINE PCI participants with post-PCI residual ischemia as defined by instantaneous wave-free ratio (iFR) with pullback evaluation of the whole coronary vessel, the impaired physiology was due to an angiographically unrecognized focal stenosis that’s usually potentially treatable, Allen Jeremias, MD, observed in presenting the DEFINE PCI results at the annual meeting of the American College of Cardiology.
“We estimated that if all residual focal lesions could be treated with additional PCI, the rate of significant ischemia could theoretically be reduced from 24% to 5%, said Dr. Jeremias, director of the physiology core laboratory at the Cardiovascular Research Foundation in New York.
Post-PCI ischemia has been associated with recurrent angina and repeat PCI. The 24% prevalence of residual impaired physiology and ischemia despite a successful angiographic result may seem startlingly high to some, but it really shouldn’t be, according to, who is also director of interventional cardiology research and associate director of the cardiac catheterization laboratory at St. Francis Hospital in Roslyn, N.Y.
“There are a lot of physiologic studies looking at FFR [fractional flow reserve] before PCI to determine if we should do it. And we learned how unreliable the angiogram is to make those decisions. So I think obviously we shouldn’t be surprised if the angiogram afterwards is just as unreliable,” he said.
was a prospective observational study of 500 patients who underwent PCI for stable or unstable angina at 27 U.S. and European sites. An iFR was done prior to PCI in all vessels with an angiographic lesion severity of 40% or more. Participating interventionalists performed angiographically guided PCI and confirmed their procedural success with post-PCI angiography before the patient left the cath lab. They also performed an iFR manual pullback interrogation of the entire treated vessel. Although the iFR data are linked to the angiographic images via a technology known as co-registration, the operators were blinded to the iFR results, which along with the angiograms were interpreted in a core laboratory. All patients received guideline-directed medical therapy.
The iFR improved on average from 0.69 pre-PCI to 0.93 post treatment. To put that in perspective, an iFR value of 0.89 or less defines hemodynamically significant ischemia.
Residual physiologic impairment post PCI was deemed due to a missed focal stenosis in 82% of cases and to diffuse atherosclerotic disease in the other 18%. Untreated focal lesions were located within the stent in 38% of cases, proximally in 31%, and distal to the stent in the remainder.
Dr. Jeremias said the investigators looked in vain for possible predictors of post-PCI residual impaired physiology. Post-PCI angiographic results were poorly correlated with iFR. For example, 30% of patients with a residual diameter stenosis of 50% or more had a post-PCI iFR of 0.89 or less, as did 21% of those with a residual diameter stenosis of less than 50%, a nonsignificant difference. Moreover, there were no procedural predictors of poor physiologic outcome.
“I don’t think that the answer is more angiograms or procedural changes guided by the angiogram, but rather guiding of the procedure with physiology and also intravascular imaging,” the cardiologist said.
Session cochair, an interventional cardiologist at Brown University in Providence, R.I., said DEFINE PCI “really brings up the importance of co-registration of iFR, be it with optical coherence tomography or angiography, because we need the information together. If we can’t see these lesions on the angiogram, we need to be doing more complicated combined physiology and anatomy.”
“This is a very interesting study that I think generates a lot of provocative information,” said discussant John J. Warner, MD.
“It certainly challenges, once again, our definition of angiographic success.” The key remaining question is whether additional PCI addressing the residual focal stenoses causing ischemia will result in improved clinical outcomes, added, an interventional cardiologist and CEO of the University of Texas Southwestern Medical Center Hospitals, Dallas.
Dr. Jeremias noted that DEFINE PCI participants are in the process of being followed through 12 months to see the impact of residual ischemia on recurrent angina, major adverse cardiovascular events, and quality of life. Moreover, a large randomized trial known as DEFINE GPS (Guided Physiologic Stenting) will soon get underway. Participants will be randomized to unblinded iFR-guided therapy with pullback in order to optimize the physiologic result or to conventional angiographically guided PCI. This trial will define the clinical value of PCI with iFR pullback and should answer the question of whether the more important iFR number is the magnitude of the iFR gain achieved via revascularization or the absolute iFR number achieved at the end.
DEFINE PCI and DEFINE GPS are funded by Volcano/Philips. Dr. Jeremias reported serving as a consultant to that company and a handful of others.
SOURCE: Jeremias A. ACC 19 .