WASHINGTON – Payers are quite interested in technologies that determine whether a patient really needs an expensive treatment, but fractional flow reserve (FFR) might have to take a back seat to instantaneous wave-free ratio (iFR) for determining the need to revascularize the coronary arteries, according to two presentations at ACC 2017.

Among the companies whose fortunes might be affected by any conclusions drawn from these studies is Heartflow, which reported at the 2016 edition of the American College of Cardiology annual meeting that it had wrapped up a study intended to nudge payers off the sidelines regarding the FFRct system. Heartflow's chief medical officer, Campbell Rogers, told Medical Device Daily that the company's cloud-based software, which employs CT imaging as source data, deferred invasive imaging for nearly a third of patients with no adverse clinical events at one year as a consequence of the deferral. (See Medical Device Daily, April 6, 2016.)

Justin Davies of Imperial College London said iFR avoids the need for adenosine used in FFR as a vasodilator, adding that the Define Flair study randomized the nearly 2,500 patients across almost 50 centers evenly to iFR and FFR. iFR also requires the insertion of a catheter to insert a pressure sensor wire to capture blood flow data, but the avoidance of adenosine sidesteps some serious, albeit rare side effects, depending on the route of administration.

"In total, more patients were deferred in the iFR arm," Davies said, noting that the 652 deferrals in the iFR arm constituted 53 percent of that group, while the 583 deferrals in the FFR arm accounted for only 47 percent of that side of the study. Bypass was performed on 25 patients in the iFR arm, compared to 42 in the FFR arm, while percutaneous intervention was likewise lower in the iFR group (565 total to 625).

"All these numbers are statistically significant," Davies said, noting that the rate of major adverse cardiac events (MACE) was 6.79 on the study article and 7.01 among controls, which Davies remarked was sufficient to demonstrate non-inferiority.

Define Flair is "the largest randomized controlled trial to date" comparing iFR and FFR, Davies continued, noting that this comparison was "performed in a study population reflecting real-world clinical practice."

The Instantaneous Wave-Free Ratio versus Fractional Flow Reserve guided intervention (IFR-SWEDEHEART) study, which enrolled slightly more than 2,000 in three northern European nations, also appeared at ACC 2017. This study also randomized the enrollment roughly equally to iFR and FFR, and disclosed "significant" lesions of the coronary arteries in 29 percent of patients whereas FFR located lesions in 37 percent.

Both studies appeared in the New England Journal of Medicine, which featured an editorial by Deepak Bhatt of Brigham and Women's Hospital in Boston, who remarked that FFR has not attained widespread use despite "strong data in its favor."

Bhatt noted that clinicians are wary of the risk that adenosine might trigger heart block or bradycardia, but patient discomfort and increased treatment times are also a factor (Davies said iFR shaves nearly five minutes off the 45 minutes ordinarily incurred in FFR).

Bhatt concluded that these two studies are not applicable to patients with acute coronary syndrome, but said that while FFR "has been the evidence-based standard for invasive evaluation of such lesions . . . it now appears that iFR may be the new standard."

TAVR LEAFLET THROMBOSIS RESURFACES

Two registry studies dealing with leaflet thrombosis for both transcatheter and surgical aortic valve replacements found their way to the dais at ACC 2017, the Savory and Resolve registries.

Raj Makkar of Cedars Sinai Medical Center in Los Angeles said subclinical leaflet thrombosis has up to now been reported as occurring at between 10 and 15 percent of transcatheter aortic valve replacement (TAVR) cases, although surgical aortic valve replacement (SAVR) is not immune to this problem. The two registries covered more than 930 patients total, more than two thirds of which were in the Cedars' Resolve registry. There was a large difference in mean time to CT, with 58 days elapsing on average for the TAVR enrollees, while the delay for SAVR patients was on average more than 160 days.

Reduced leaflet motion was defined in both registries as a restriction of motion of at least 50 percent, and about 13 percent of the TAVR patients were diagnosed with reduced motion, while the same could be said of only 3.4 percent of the SAVR patients. Reduced motion was actually associated with a lower rate of death in the two studies, although the rate of stroke/transient ischemic attack was significantly higher in the presence of this condition, 3.4 percent for normal leaflet motion compared to 10.4 percent for reduced motion.

The validity of these studies is hampered of course by their observational nature, but Makkar also acknowledged that the longer delay to CT for the SAVR group "makes it difficult to state leaflet thrombosis as the definitive cause" for stroke and TIA. And although the study was not sufficiently populated to contrast the rates of subclinical thrombosis across TAVR types, the Medtronic plc Corevalve incurred the nominally lowest rate at six percent, less than half the rate seen in the Sapien units by Edwards Lifesciences Corp.