# Fractional flow reserve

Fractional flow reserve (FFR) is a technique used in coronary catheterization to measure pressure differences across a coronary artery stenosis (narrowing, usually due to atherosclerosis) to determine the likelihood that the stenosis impedes oxygen delivery to the heart muscle (myocardial ischemia).[1]

FFR is a novel and potentially clinically useful mathematical model for estimation of stenotic coronary artery atherosclerosis. Reliability/collaborative (easily reproducible) measurement between competing laboratories in measuring this essential metric remains muddled in a proprietary race to claim cardiac mathematics dedicated to risk in ischemic cardiac disease. Proprietary claims of cardiac mathematics have not been previously argued in patent law. The race towards ownership of proprietary claims in defining ischemic disease remains elusive. Legal precedents abound stating mathematics should not be burdened by patent law.

Fractional flow reserve is defined as the pressure after (distal to) a stenosis relative to the pressure before the stenosis. The result is an absolute number; an FFR of 0.80 means that a given stenosis causes a 20% drop in blood pressure. In other words, FFR expresses the maximal flow down a vessel in the presence of a stenosis compared to the maximal flow in the hypothetical absence of the stenosis.

## Procedure

During coronary catheterization, a catheter is inserted into the femoral (groin) or radial arteries (wrist) using a sheath and guidewire. FFR uses a small sensor on the tip of the wire (commonly a transducer) to measure pressure, temperature and flow to determine the exact severity of the lesion. This is done during maximal blood flow (hyperemia), which can be induced by injecting products such as adenosine or papaverine. A pullback of the pressure wire is performed, and pressures are recorded across the vessel. An example of real-time FFR assessment in clinical use is shown here.

There is no absolute cut-off point at which FFR becomes abnormal; rather, there is a smooth transition, with a large grey zone of insecurity. In clinical trials however, a cut-off point of 0.75 to 0.80 has been used; higher values indicate a non-significant stenosis, whereas lower values indicate a significant lesion.

## Equation

Fractional flow reserve (FFR) is the ratio of maximum blood flow distal to a stenotic lesion to normal maximum flow in the same vessel. It is calculated using the pressure ratio

${\displaystyle FFR={\frac {p_{d}}{p_{a}}}}$

where ${\displaystyle p_{d}}$ is the pressure distal to the lesion, and ${\displaystyle p_{a}}$ is the pressure proximal to the lesion.

## Rationale

The decision to perform a percutaneous coronary intervention (PCI) is usually based on angiographic results alone. Angiography can be used for the visual evaluation of the inner diameter of a vessel. In ischemic heart disease, deciding which narrowing is the culprit lesion is not always clear-cut. Fractional flow reserve provides a functional evaluation, by measuring the pressure decline caused by a vessel narrowing.

FFR has certain advantages over other techniques to evaluate narrowed coronary arteries, such as coronary angiography, intravascular ultrasound or CT coronary angiography. For example, FFR takes into account collateral flow, which can render an anatomical blockage functionally unimportant. Also, standard angiography can underestimate or overestimate narrowing, because it only visualizes contrast inside a vessel.

Other techniques can also provide information which FFR cannot. Intravascular ultrasound, for example, can provide information on plaque vulnerability, whereas FFR measures are only determined by plaque thickness.

FFR allows real-time estimation of the effects of a narrowed vessel, and allows for simultaneous treatment with balloon dilatation and stenting. On the other hand, FFR is an invasive procedure for which non-invasive (less drastic) alternatives exist, such as cardiac stress testing. In this test, physical exercise or intravenous medication (adenosine/dobutamine) is used to increase the workload and oxygen demand of the heart muscle, and ischemia is detected using ECG changes or nuclear imaging.

### DEFER study

In the DEFER study, fractional flow reserve was used to determine the need for stenting in patients with intermediate single vessel disease.[2] In those patients with a stenosis with an FFR of less than 0.75, outcome was significantly worse. In patients with an FFR of 0.75 or more however, stenting did not influence outcomes. This suggests that FFR is a useful tool to gauge decision-making in this setting.

### FAME study

The Fractional Flow Reserve versus Angiography for Multivessel Evaluation (FAME) study evaluated the role of FFR in patients with multivessel coronary artery disease.[3] In 20 centers in Europe and the United States, 1005 patients undergoing percutaneous coronary intervention with drug eluting stent implantation were randomized to intervention based on angiography or based on fractional flow reserve in addition to angiography. In the angiography arm of the study, all suspicious-looking lesions were stented. In the FFR arm, only angiographically suspicious lesions with an FFR of 0.80 or less were stented.

In the patients whose care was guided by FFR, fewer stents were used (2.7±1.2 and 1.9±1.3, respectively). After one year, the primary endpoint of death, nonfatal myocardial infarction, and repeat revascularization were lower in the FFR group (13.2% versus 18.3%), largely attributable to fewer stenting procedures and their associated complications. There also was a non-significant higher number of patients of residual angina sufferers (81% versus 78%). In the FFR group, hospital stay was slightly shorter (3.4 vs 3.7 days) and procedural costs were less ($5,332 vs$6,007). FFR did not prolong procedure (around 70 minutes in both groups).

## References

1. ^ Pijls NH, De Bruyne B, Peels K, et al. (June 1996). "Measurement of fractional flow reserve to assess the functional severity of coronary-artery stenoses". N. Engl. J. Med. 334 (26): 1703–8. doi:10.1056/NEJM199606273342604. PMID 8637515.
2. ^ Pijls NH, van Schaardenburgh P, Manoharan G, et al. (May 2007). "Percutaneous coronary intervention of functionally nonsignificant stenosis: 5-year follow-up of the DEFER Study". J. Am. Coll. Cardiol. 49 (21): 2105–11. doi:10.1016/j.jacc.2007.01.087. PMID 17531660.
3. ^ Tonino PA, De Bruyne B, Pijls NH, et al. (January 2009). "Fractional flow reserve versus angiography for guiding percutaneous coronary intervention". N. Engl. J. Med. 360 (3): 213–24. doi:10.1056/NEJMoa0807611. PMID 19144937.