FFR 2.0: A Calculated Run for Supremacy

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FFR_1343404357.jpg - FFR
(A) Coronary CT angiography indicates obstructive stenosis (white arrow) in the proximal portion of the left anterior descending (LAD) artery. (B) Angiography confirms the LAD stenosis (red arrow) with corresponding hemodynamically significant reductions in coronary pressure in the first diagonal branch (0.78) and distal LAD (0.58) by FFR. (C) Noninvasive computation of FFR from FFRCT of the first diagonal branch (0.79) and distal LAD (0.57), demonstrating lesion-specific ischemia of the proximal LAD stenosis.
Source: J Am Coll Cardiol 2011;58[19]:1989-1997

Fractional flow reserve (FFR) has proven to be a valuable asset in cardiac cath labs for assessing ischemia-causing lesions in patients with coronary artery disease. But it is not without its drawbacks; the procedure is invasive and relies on the use of pharmacologic agents. Two new approaches soon may provide interventional cardiologists with alternatives.  

FFR gives interventionalists an important tool for assessing coronary stenosis before and during PCI. The concept is based on the proportional relationship of coronary blood flow to pressure, with a decrease in pressure across a lesion indicative of decreased flow to the myocardium. But the calculation requires that intracoronary resistance remains constant and minimal. To achieve that, physicians administer vasodilator agents, such as adenosine, to pharmacologically induce hyperemia.

Uptake in the use of FFR in the U.S. has been slow, partly because some patients don’t tolerate adenosine well and some physicians find the FFR process cumbersome and time consuming. For instance, in a poster presentation at ACC.12, Rudzinski et al reported that 26 percent of patients infused with adenosine for FFR measurements developed shortness of breath and flushing. Dattilo et al, in a separate analysis of National Cardiovascular Data Registry CathPCI Registry data presented as a poster at TCT.11, reported that FFR was used in only 7 percent of patients who underwent PCI for intermediate coronary stenoses.

A surrogate for FFR

James K. Min, MD, of Cedars-Sinai Medical Center in Los Angeles, and Justin E. Davies, MBBS, PhD, of Imperial College London, independently have helped develop alternate approaches to FFR. Min and colleagues have borrowed a computational strategy typically used to design aircraft to find a noninvasive method for calculating an FFR measurement while Davies and colleagues are promoting a technique that eliminates the use of adenosine.

“FFR has been widely considered the gold standard but it is an invasive procedure,” says Min. On the other hand, noninvasive coronary CT angiography (CCTA) helps to identify and exclude obstructive coronary stenosis, but it tends to overestimate the presence and severity of occlusions. Min and colleagues sought to meld the benefits of FFR and CCTA by applying the principles of computational fluid dynamics to CCTA scans to model blood flow and pressure data in coronary arteries and calculate lesion-specific FFR measurements. They call the technique FFR CT.

To test their concept, they modeled artery flow based on CCTA data from 103 patients (159 vessels) with suspected or known coronary artery disease who underwent CCTA, invasive angiography and FFR (J Am Coll Cardiol 2011;58[19]:1989-1997). Using FFR as their reference standard, they compared FFR CT with CCTA stenosis, and found that FFR CT had a superior diagnostic accuracy and added to CCTA’s discriminatory capability to identify lesions, mostly by reducing the rate of false positives.

FFRCT showed a good correlation with FFR without the need for additional scans, medications or changes to protocols, prompting the researchers to conclude that computing FFR CT from CCTA scans might provide a noninvasive method for detecting and excluding ischemia-causing lesions.   

“FFRCT has the potential to identify lesions by traditional CT that are potentially ischemic and rule out ischemic-causing lesions,” Min says. “In that manner, the combination of CT plus FFR CT may serve as an effective gatekeeper to the cath lab. The CT is much less expensive than an invasive angiogram and FFR.”

Adieu to adenosine

Davies and colleagues also homed in on the mathematical underpinnings of FFR to find a technique that provides similar value without the need for administering adenosine. They hypothesized that they could identify a time period when intracoronary resistance at rest is naturally constant and minimized, providing a window that is equivalent to hyperemia induced by adenosine. They named this the instantaneous wave-free ratio (iFR), which they argued could be used to derive an index of stenosis severity over time.

“A lot of the FFR pitfalls are associated with administering adenosine,” Davies says. For cath lab personnel and physicians, those issues may include costs, time and variable responses to the drug. While the time and cost per procedure may seem insignificant—in some facilities it may be mere minutes with an incremental cost for adenosine—Davies argues these add up. Additionally,