Exploring Functional Flow Reserve in the SFA

First-time data release from a prospective study of the relationship between functional flow reserve (FFR) evaluation for superficial femoral artery (SFA) treatment was showcased this morning at LINC.

Tatsuya Nakama, MD, from Tokyo Bay Medical Center in Japan, discussed the GRIFFIN study, carving out the salient points for the Main Arena 1 audience. LINC Today caught up with Dr Nakama to find out more about the roots of GRIFFIN, and what we might expect from FFR in the near future.

How does the GRIFFIN study’s approach to FFR measurement in the SFA differ from traditional coronary FFR techniques?

The measurement of FFR in coronary artery disease is conducted to evaluate whether coronary stenosis is causing myocardial ischemia. Typically, FFR measurement is indicated when non-invasive tests (e.g., myocardial scintigraphy or stress echocardiography) fail to confirm ischemia, or when the severity of stenosis cannot be assessed solely by coronary angiography. Nowadays, FFR is an established objective tool for evaluating myocardial ischemia. Many clinical trials and studies have shown that FFR-guided percutaneous coronary intervention (PCI) not only improves clinical outcomes but also reduces unnecessary revascularization and stent placement. In the field of peripheral artery disease (PAD), however, there is little knowledge about the revascularization based on physiological assessments such as FFR. Like PCI, FFR-based revascularization has the potential to offer more appropriate clinical outcomes compared to the current angiographybased approach. Since the treatment targets in PAD are diverse and not as straightforward as coronary arteries, in this study, we focused on the femoropopliteal artery (FPA). The main purpose of this GRIFFIN study was to evaluate whether FFR could be used to optimise the ‘leave nothing behind’ strategy. As in the PCI field, drug-eluting technologies have significantly improved treatment outcomes in this lesion. However, unlike PCI, drug-eluting stents (DES) are not the main devices used in the SFA due to the unique structural features of the FPA. Concerns about stent fractures and thrombotic occlusion have led to the widespread adoption of drug-coated balloons (DCBs) to reduce restenosis without leaving a scaffold behind. For DCB treatments to succeed, adequate lesion preparation is essential before drug application. Lesion preparation is typically assessed angiographically, with attention to avoiding flow-limiting dissections or significant residual stenosis. However, angiographic assessment is often subjective, and it is very difficult to standardise. The DISFORM scoring system is well known but insufficient for scientific and objective evaluations. The GRIFFIN study was initiated to assess the correlation between FFR values post- DCB treatment, and restenosis rates. The study aimed to establish a cutoff FFR value to guide the need for stenting or confirm the adequacy of DCBonly treatment.

What challenges did you encounter in adapting FFR technology for use in the peripheral arteries, particularly the SFA?

One significant challenge was achieving hyperemia. After referencing prior studies using stents, we standardized the study by administering 30 mg of intraarterial papaverine.

Based on the GRIFFIN study results, what FFR threshold values do you propose for guiding treatment decisions in SFA lesions?

There was a clear correlation between FFR values and restenosis rates after DCB treatment. An FFR cutoff value of 0.92 was identified. If the FFR value after lesion preparation exceeds 0.92, DCB-only treatment may suffice. However, if the FFR value is below 0.92, bailout stenting may be necessary to address residual stenosis or dissections effectively.

How might the findings from the GRIFFIN study influence future guidelines for SFA revascularization decision-making?

In patients with intermittent claudication, the goal of treatment is symptom relief rather than stenosis resolution. Given the imperfect patency rates following endovascular therapy, unnecessary treatments (especially stenting) should be avoided. FFR-based treatment can objectively identify areas requiring intervention, potentially reducing treatment length, bailout stent rates, and stent lengths. Establishing clear FFR cutoff values could transform treatment algorithms in the future.

Did the study reveal any limitations or potential pitfalls in using FFR for SFA assessment that clinicians should be aware of?

Cases with clearly severe dissection or significant residual stenosis that made it impossible to complete the treatment with DCB alone were excluded based on the operator’s judgment, and FFR measurements were not performed in such cases. Therefore, it was not possible to evaluate whether severely compromised FFR values in these truly critical cases correlate with poor outcomes, such as restenosis. The absence of data from such cases is a limitation of this study. However, from an ethical standpoint, it is challenging to include ‘obviously poor outcome’ cases in the study. This represents an inherent limitation of this research.

Given the results of the GRIFFIN study, how do you envision FFR technology being integrated into routine clinical practice for peripheral artery disease management?

We used FFR in this study to predict restenosis after DCB treatment. However, in the near future, FFR evaluation could be utilised many situations. For diffuse SFA lesions, FFR may help identify areas requiring intervention, reducing unnecessary treatments and stent placements. While studies involving physiological assessments in PAD are still limited, FFR has the potential to become a guiding tool for optimal revascularization, just like its role in coronary interventions.

How does the cost-effectiveness of FFR-guided SFA treatment compare to traditional angiography-based approaches, based on your findings?

Cost-effectiveness was not evaluated in this study. However, appropriate lesion assessment using FFR could reduce unnecessary interventions and stenting, maximizing treatment efficacy and cost-effectiveness. Future studies will aim to analyse the economic implications of this approach.

Do you have any final comments you would like to share?

I would like to thank Dr Shinsuke Mori (the principal investigator of GRIFFIN study), staff of the participating institutions who contributed to this study, and finally ACIST, the healthcare sponsor of this study.