Fractional Flow Reserve (FFR) Measurement

Fractional flow reserve (FFR) measurement involves determining the ratio between the maximum achievable blood flow in a diseased coronary artery and the theoretical maximum flow in a normal coronary artery. An FFR of 1.0 is widely accepted as normal. An FFR lower than 0.75-0.80 is generally considered to be associated with myocardial ischemia (MI). ^[1]

FFR is easily measured during routine coronary angiography by using a pressure wire to calculate the ratio between coronary pressure distal to a coronary artery stenosis and aortic pressure under conditions of maximum myocardial hyperemia. ^[1] This ratio represents the potential decrease in coronary flow distal to the coronary stenosis. More recently, computed tomography (CT)-based FFR computations have been used to evaluate the functional severity of coronary artery stenoses, with FFRs derived from outflow boundary conditions based on conventional morphology generally agreeing with those based on positron-emission tomography (PET) conditions. ^[2]  However, FFRs measurements based on conventional morphology had a tendency to overestimate functional severity, particularly in the setting of reduced vasodilatory response under hyperemia (and thus abnomal myocardial perfusion). ^[2]

Over the past two decades, FFR measurement has been increasingly used in cardiac catheterization laboratories. It provides a quantitative assessment of the functional severity of a coronary artery stenosis identified during coronary angiography and cardiac catheterization.

A severe coronary artery stenosis can limit myocardial blood flow, resulting in MI. In most cases, the severity of a coronary artery stenosis is judged by visual inspection by the cardiologist during cardiac angiography. A lesion is generally considered severe and flow-limiting if the narrowing of the luminal diameter is estimated to be 70% or greater. ^[3]

During angiography, the cardiologist typically assesses the patient’s symptoms and clinical characteristics, evaluates the angiographic appearance of the coronary tree, and then decides whether revascularization with angioplasty, stenting, or coronary bypass surgery is most appropriate. ^[3]

However, the ability of the cardiologist to discriminate between lesions that can cause MI and lesions that are physiologically insignificant on the basis of coronary angiography alone is limited. ^[4] The use of FFR measurement provides the cardiologist with a straightforward, readily available, quantitative technique for evaluating the physiologic significance of a coronary stenosis.

Indications for FFR measurement are as follows:

• To determine the physiologic and hemodynamic significance of an angiographically intermediate coronary stenosis

• To identify appropriate culprit lesion(s) in multivessel coronary artery disease (CAD)

• To measure the functional importance of stenosis in the presence of distal collateral flow

• To identify the precise location of a coronary lesion when the angiographic image is unclear

Note that this procedure is not intended for use in the setting of a total vessel occlusion.

In a study designed to test the hypothesis that experienced interventional cardiologists could identify patients with FFRs below 0.75 by means of coronary angiography, FFR was measured in 83 angiographically moderate coronary lesions, which were also visually assessed by 3 interventional cardiologists; the reviewers’ classification matched the FFR in only about half of the lesions, and concordance between reviewers was poor. ^[5]  In this study, when visual assessment was compared with FFR, it resulted in good sensitivity (80%) and negative predictive value (91%) but poor specificity (47%) and positive predictive value (25%). ^[5] Angiographic assessment of an angiogram by experienced interventional cardiologists did not predict the significance of most moderate coronary lesions.

In the DEFER study, which assessed patients with single-vessel CAD and angiographically intermediate coronary stenosis, patients with an FFR above 0.75 were randomized to either medical management or stent implantation; at 5-year follow-up, those who did not receive a stent had the same risk of death or acute MI as those who did, which suggests that patients with an FFR higher than 0.75 do not benefit from revascularization of the stenosis. ^[6]

The Fractional Flow Reserve versus Angiography for Multivessel Evaluation (FAME) study, which studied the role of FFR in the evaluation of multivessel CAD, reported results suggesting that a revascularization strategy using FFR yields superior clinical outcomes in patients with multivessel CAD. ^[7]  In this study, patients with multivessel CAD identified by angiography were randomized to undergo either angiography alone or FFR plus angiography. ^[7] Patients in the angiography-only arm underwent stenting of all angiographically severe lesions. Patients in the FFR-plus-angiography arm underwent stenting only if FFR was 0.80 or less. At 2-year follow-up, patients who underwent FFR-driven stenting had fewer stents than those in the angiography-only group, along with reductions in mortality, MI, and repeat revascularization.

More recently, investigators retrospectively (2016-2018) evaluated FFR in 246 German patients with CAD undergoing transcatheter aortic valve implantation (TAVI) who had coronary lesions with a diameter stenosis of at least 50%. ^[8] They found concomitant CAD in 53.3% of TAVI patients. ^[8]  Postprocedure FFR measurements performed in those with a positive FFR up to and including 0.80 did not significantly change 6-8 weeks after TAVI, which the investigators indicated confirmed the validity of FFR for assessing coronary lesions in this specific clinical setting. ^[8]