NEW ORELANS — The future of the cath lab may involve novel technologies for physiology-guided percutaneous coronary intervention (PCI), with two new studies showing that minimally invasive methods for measuring fractional flow reserve led to outcomes that were on par with those seen with wire-based assessments.

“From these studies, we can conclude that angiography-derived physiology is here to stay,” William Fuller Fearon, MD, an interventional cardiologist at Stanford University in Palo Alto, California, said after results of the ALL-RISE and FAST III trials were presented at American Academy of Cardiology (ACC) Scientific Session 2026.

Both studies, which enrolled about 4000 people combined, found that revascularization guided by the angiography-based techniques achieved cardiovascular outcomes similar to those achieved with PCI guided by pressure wire-based technology, but with shorter procedure times, less radiation exposure, and less fluoroscopy.

Results of the ALL-RISE and FAST III trials have been published simultaneously in The New England Journal of Medicine.

ALL-RISE Results

In the multicenter, international ALL-RISE trial, investigators evaluated the FFRangio system (CathWorks), a computer software-based method that uses AI to analyze coronary angiographic images to estimate FFR. They randomized 1930 patients with at least one intermediate coronary artery stenosis to guidance using the FFRangio system or pressure wire-guided evaluation. Mean age was 68 years and 25% were women.

The primary endpoint was a composite of death, myocardial infarction (MI), or unplanned, clinically indicated coronary revascularization.

Ajay Kirtane, MD, directory of interventional cardiovascular care and a professor of medicine at Columbia University Irving Medical Center, NewYork-Presbyterian Hospital, New York City, reported that 7.1% of patients in the pressure-wire group and 6.9% in the FFRangio group experienced the composite primary endpoint at 1 year (P for noninferiority = .0008).

Secondary clinical endpoints were also similar between groups, Kirtane said. The 1-year rate of death was 2.3% and 2.1% in the FFRangio and pressure wire groups, respectively. For MI, the rates were 2.5% in the pressure wire group and 1.6% in the FFRangio group. The rates of unplanned revascularization were 4.6% in the pressure-wire group and 4.1% in the FFRangio group.

The investigators observed notable differences in the characteristics of each procedure, Kirtane said. Median total procedure time was 39 minutes with the FFRangio system vs 42 minutes with the pressure wire approach. Median total contrast volume was 100 mL vs 105 mL, total fluoroscopy time was 9 vs 12 minutes, and physiological assessment was 6 vs 8 minutes with the FFRangio system compared with pressure wire-based approach.

“And that’s despite the fact that slightly more patients in the FFRangio arm actually had PCI,” he said. PCI was performed in 44.3% of the lesions in the FFRangio group and 35.4% of those in the guide-wire group.

“To me, these data guide the routine use of FFRangio-guided treatment in the cath lab with the simplified workflow over the current standard, and we hope this will help facilitate increased use of coronary physiology concordant with guidelines,” Kirtane said.

Kirtane said one advantage of the FFRangio approach is that it eliminates a number of steps the operator must perform in the wire-guided approach.

“There are very small risks, but they are real,” Kirtane said.

FAST III Results

For the international, multicenter, open-label FAST III trial, Joost Daemen, MD, PhD, a senior interventional cardiologist at Erasmus University Medical Center in Rotterdam, Netherlands, and colleagues evaluated vessel FFR (Pie Medical Imaging). This technique uses computer analysis of three-dimensional (3D) images from a coronary angiogram to calculate the severity of blood flow restriction through an artery.

The trial’s primary outcome was the 1-year composite of death, MI, or revascularization. Daemen, who presented the findings at the ACC Scientific Session 2026, said results showed the vessel FFR-guided revascularization strategy was noninferior to a wire-based approach for intermediate coronary artery lesions.

The trial randomized 2235 participants at 37 centers in Europe to revascularization guided by vessel FFR or standard pressure wire-based FFR. Participants had chronic coronary syndrome, unstable angina, or non-ST-elevated MI, with coronary artery stenosis of 30%-80% in a native vessel larger than 2.5 mm. It excluded patients who had a life expectancy of < 1 year or had severe vessel tortuosity or overlap, among other factors.

A matching rate of 7.5% in each study group experienced the primary composite endpoint of death, MI, or revascularization at 1 year (P =.004), Daemen said.

The trial found similar outcomes between the vessel FFR-guided group and the pressure wire FFR-guided group for study vessel failure (4% vs 4.6%). A full analysis of 10 secondary endpoints, ranging from death from any cause to confirmed or suspected stent thrombosis, found similar rates between the two groups across the board, he said.

Like the ALL-RISE trial, FAST III showed lower procedure times with the angiography-based approach, Daemen said. Mean procedure times were 55.8 minutes for vessel FFR-guided PCI vs 60.9 minutes for pressure wire-guided PCI. More vessel FFR patients underwent revascularization (59.15% vs 51.9%), and more stents were placed per patient (0.92 vs 0.8).

Daemen commented on the differences and similarities between the studies. The techniques both used three-dimensional coronary artery reconstruction based on coronary angiograms to generate a 3D model of coronary anatomy and used different computational algorithms to evaluate pressure gradient, he said.

The studies were “basically overlapping,” he told Medscape Medical News. “We now have data randomized 1:1 between angio-guided physiology or conventional pressure wire-based physiology backing each other up,” he said.

While other platforms and algorithms for angiography-based physiology are in development, these studies’ results cannot be “extrapolated” to those technologies, according to Daemen.

“Noninferiority of those systems to the gold standard needs to be determined, and I think that is something we cannot say based on the results of these trials,” he said.

The Two Trials in Context

Fearon, who was the first author of ALL-RISE but also the discussant for FAST III, said the trials stand out because a previous study of angiography-based physiology, the FAVOR III Europe trial, failed to demonstrate its noninferiority to wire guidance.

The differences observed in procedural characteristics between the angiography-based physiology and pressure wire-guided physiology in both trials are noteworthy, Fearon told Medscape Medical News.

“Cardiologists work on minute-to-minute time frames, so anything that shaves a minute off our procedure is welcome,” he said. “If you can save 2 or 3 minutes, or even 5, that’s even better.”

Other procedure characteristics are critical for improving outcomes, he said. “The amount of contrast used is lower, and that will translate into less kidney dysfunction and less acute kidney injury,” he said. “Also, there was less fluoroscopy used and that’s good news for the patient as well as the physician, and less radiation exposure with that technique compared to the wire, so it’s not only going to improve patient outcomes but also physician outcomes.”

However, despite angiography-based physiology having a Class I indication both in Europe and the US, “it’s still underutilized when you look at registry data,” Fearon said. These trials may help move the needle.

“With these data from ALL-RISE and FAST III, we now have a method that will be easier to apply and will increase utilization in the cath lab as well as streamline workflow,” he said.

“I just think it’s a great day for coronary physiology,” Fearon added. “Many of us have believed that using coronary physiology is critical to improving patient outcomes and had been frustrated by the lack of uptake. We see this as a way to address that shortfall.”

ALL-RISE was funded by Cathworks. FAST III was funded by Pie Medical Imaging and Siemens Healthineers.

Kirtane reported having financial relationships with Abbott Vascular, Amgen, Bolt Medical, Boston Scientific, CathWorks, Concept Medical, Cordis, Idorsia, Janssen, Magenta Medical, Medtronic, Neurotronic, Philips, ReCor Medical, Supira, Teleflex, Edwards Lifesciences, Philips, ReCor Medical, Shockwave, and Supira.

Daemon reported having financial relationships with Abbott Vascular, Boston Scientific, ACIST Medical, Medtronic, Pie Medical, ReCor Medical, Cardialysis, Cardiac Booster, Kaminari Medical, Pulse Medical, Shockwave, and Siemens Healthineers.

Fearon reported having financial relationships with Edwards Lifesciences, Shockwave, Heartflow, Abbott Vascular, CathWorks, and Medtronic.

Richard Mark Kirkner is a medical journalist based in Philadelphia.