Three-Year Survival in CLTI Patients with FFR-Guided Revascularization of Silent Coronary Ischemia

On the first full day of ISET 2022, Professor Emeritus of Surgery at Stanford University and the founder of HeartFlow, Inc., Christopher K. Zarins, MD, presented ISET attendees the 3-year findings from his recently published trial on the benefits of coronary computed-tomography derived fractional flow reserve (FFRct) in the evaluation of critical limb-threatening ischemia (CLTI) patients.

In CLTI patients with no coronary symptoms, the systematic use of FFRct revealed a high prevalence of unsuspected (silent) coronary ischemia (69%), selective revascularization of which (along with lower-extremity revascularization) reduced adverse cardiac events and improved 3-year survival compared with standard cardiac evaluation and care.

To start, Dr. Zarins described the issue: “The 11% annual mortality [in patients with PAD] is extremely high, and that hasn’t changed over the last 40 years. Contrast that to patients who present with coronary artery disease over that period of time; their annual mortality has declined markedly, and it is now 1% to 2% per year—an order of magnitude difference.

“So, what’s the difference in the treatment of these two populations? Well, patients with PAD have their PAD treated and then they’re managed with the best medical therapy and risk factor control. Whereas coronary artery disease patients get treated with coronary revascularization as well as best medical therapy.”

In an observational case-control study, Zarins and colleagues enrolled 223 patients with no cardiac history or symptoms who were undergoing limb-salvage surgery. In one group (n = 103), patients had preoperative FFRct used to detect ischemia-producing coronary stenosis (FFRct ≤ 0.80) with selective postoperative coronary revascularization (the FFRct-guided group). The other group (n = 120) had standard cardiac evaluations.

CT angiography imaging was performed in accordance with current guidelines, and image datasets were sent to HeartFlow via secure web-based interface for computational analysis of FFRct. Dr. Zarins is the founder of HeartFlow.

Both groups were admitted to the hospital and cleared for lower extremity revascularization. Both groups received guideline-directed medical therapy.

In the study arm, an “extremely high and surprising prevalence of silent coronary ischemia” was seen, with 69% of patients having an FFRct 0.80 distal to a stenosis, 58% showing severe ischemia (FFRct 0.75 distal to stenosis), 8% having left main ischemia, and 40% showing multi-vessel ischemia.

All of these patients were free of coronary symptoms and had no known coronary disease in the past,” reported Dr. Zarins.

Elective coronary revascularization (transcatheter and/or surgical) was performed in 47 patients (46%) 1 to 3 months following limb-salvage surgery. Standard-care patients had no coronary revascularization.

During a median follow-up of 36 months, all-cause death was seen in 10.7% of the FFRct arm and 27.5% of the control arm (hazard ratio [HR], 0.32; P<0.01). Cardiovascular death was seen in 2.9% and 17.5%, respectively (HR, 0.14; P<0.01) and myocardial infarction in 3.9% vs. 22.5% (HR, 0.14; P<0.01).

“It’s interesting to note that in the control group, the 28% mortality is actually a favorable number because the mortality rate reported in the literature at 3 years is 35% to 40% for this population of patients,” Zarins told attendees.

“Perhaps this is due to the high prevalence of use of guideline-directed medical therapy, but the mortality rate in the FFRct group was markedly lower at only 11%.”

Referring to the 3-year survival curves (above), Zarins said, “The trajectory of the control group is headed toward the expected 50% 5-year mortality in this group, whereas there’s a flattening of the survival curve in the FFRct group. This is the first demonstration of such a flattening of the survival curve.”

He concluded that prospective randomized trials are indicated to determine the role of FFRct in the management of patients with CLTI.