Fractional flow reserve
Synonyms and Keywords: FFR, coronary fractional flow reserve

# Overview
While coronary angiography assess the extent and the structural severity of fixed coronary stenoses, angiography does not provide functional information regarding flow limitations.  While exercise tolerance testing may provide this functional information, only a quarter to a third of patients undergoing cardiac catheterization may have undergone stress test before cardiac catheterization.  Thus there is the need for diagnostic studies to assess the functional significance of stenoses in the cardiac catheterization laboratory.  While intervention in a critically narrowed lesion is appropriate, a considerable number of lesions are of intermediate severity on coronary angiography. Assessment of fractional flow reserve (FFR) may improve the ability to assess the functinal consequences of such lesions in the cardiac catheterization laboratory .

# Definition
Fractional flow reserve is defined as the fraction of maximal achievable blood flow that can still be maintained to the myocardium despite the presence of a stenosis.
FFR = Pd/Pa ( Pd = pressure distal to the lesion measured by the pressure wire, Pa = pressure at the tip of the guide/catheter)
This measure is a surrogate marker of relative ischemia during exercise.

# Physiologic Basis for FFR Measurements
- During maximal hyperemia the FFR can be calculated by dividing the distal pressure by proximal pressure.
- Pressure drop across a lesion is proportional to:
length of the lesion
flow across the lesion.
- length of the lesion
- flow across the lesion.
- It is inversely related to:
square root of the area of the stenosis.
- square root of the area of the stenosis.

# FFR Vs Coronary flow reserve CFR
The FFR assesse the significance of epicardial stenosis independent of the distal vascular bed, where as the CFR is a measure of the distal vascular bed which may be affected by conditions such as hypertension and diabetes.

# FFR - 0.75 threshold/cut off
Pijls, et al. in a landmark study validated the clinical use of FFR against ischemai on nuclear imaging studies. A threshold of 0.75 is associated with a sensitivity of 90% and a specificity of 100% .

# Setting up the equipment
- Open the Radi wire from the packet and flush it with saline. Do not pull it out of the protective tubing.
- Zero the arterial and distal pressure ports. ( Pa and Pd). (If the pressure tracings need to be displayed in the cardiac cath lab display rather than on the Radi console display, then connect the two connector cables from the Radi console to the cath lab system.)
- Do ACT ( Do not introduce the guide wire in to the coronary artery until the ACT > 200)
- After confirming an ACT > 200 secs, equlize the pressure with the Radi wire at the tip of the guide.
- Cross the lesion with the pre-planned wire. (The Radi wire can be used for lesions that are easy to cross)
- Obsreve the FFR at rest.
- Induced coronary hyperemia.
- Measure FFR
- Could also perform pull back FFR if use the iv route for drugs.

# Inducing maximum coronary hyperemia
This can be done either by delivering one or more of intracoronary boluses of adenosine (20 mcg dose, peaks in 5 seconds), or using 140 mcg/kg/min over two minutes intravenously from the antecubital fossa or up to 180 mcg/kg/min intravenously from the femoral vein.

# Examples of FFR Measurements

# Different types of tracings
As the lesion progresses in severity, the pressure drops first in diastole, and then both in systole and diastole.

# FFR correlation with IVUS
Using FFR as the gold standard for lesion severity, Brigouri et al demonstrated
- Optimal sensitivity (sens) and specificity (spec) of IVUS to discriminate significant from non-significant stenoses when area stenosis was >70% (sen 100%, spec 68%)
- Cut-off values fitted to a FFR of <0.75
MLD <1.8 mm (sen 100%, spec 66%),
MLA <4.0 mm2 (sens 92%, spec 56%)
- MLD <1.8 mm (sen 100%, spec 66%),
- MLA <4.0 mm2 (sens 92%, spec 56%)
- (All lesions with area stenosis 0.75 but 50% of lesions with area stenosis >70% had FFR <0.75) .

# FFR in clinical decision making

## The Outcomes of Lesions that are not Hemodynamically Significant by FFR: The DEFER Trial
The DEFER trial demonstrated that among intermediate lesions that were not hemodynamically significant (i.e. the FFR was greater than 0.75), there was no impact on clinical outcomes (Death or death / MI). Furthermore the risk of adverse events was quite low and mortality attributable to these lesions was under 1% per year.
In the DEFER trial, a total of 325 patients undergoing PCI of an intermediate lesion were randomized to deferral of the PCI if the FFR was > 0.75 (n=91) or performance of a PCI (n=90) even though the lesion was not functionally significant. In other words this trial test what would happen if lesions that are not functionally significant either are or are not dilated. If the FFR was < 0.75, the lesion was dilated.
At 5 years, the survival did not differ between those patients who had a a PCI versus those who did not have a PCI (the deferred group) of a stenosis that was not associated with ischemia.  Likewise there was no difference in the risk of death or MI or the number of patients who were free of chest pain on follow-up between the two groups.  The risk of cardiovascular death was less than 1% per year in vessels that were either treated or untreated and was not affected by stenting.

## The Role of FFR in Selecting Which Lesions to Dilate in the Patient with Multivessel Disease: Results of the FAME Trial
The FAME trial randomized 1005 patients with multivessel disease (excluding those with left main disease or STEMI) who were undergoing intracoronary stent implantation to one of the two following strategies:
- Drug-eluting stent implantation guided by angiography alone in which case all significant lesions were stented versus
- Drug-eluting stent implantation guided by FFR measurements in addition to angiography.  patients who were randomly assigned to the FFR strategy had stents implanted in those lesions with an FFR of 0.80 or less.
Patients in the FFR guided strategy had fewer stents placed than those in the strategy relying upon angiography alone (2.71.2 versus 1.91.3 stents, p<0.001).  At one year, the primary end point of death, nonfatal myocardial infarction, and repeat revascularization was observed in 18.3% of patients in the angiography group versus 13.2% patients) in the angiography plus FFR group (P=0.02). there was no difference in the incidence of survival free from angina at one year: 78% of patients in the angiography group versus 81% of patients in the FFR group (P=0.20).  The risk of death was 3.0% vs 1.8% (p=0.19).  The risk of death or MI was 11.1% in the angiography group versus 7.3% in the FFR group (p=0.04).  The number of patients who were event free and free of angina were 73% in the FFR group and 67.6% in the angiography group (p=0.07).  Procedure costs and the use of contrast was lower in the FFR group as well.  It should be noted that only 63% of lesions that were measured had an FFR less than 0.80.
The authors speculate that the results of COURAGE and SYNTAX might have been different had stenting been performed with FFR guidance in which case only those lesions that were ischemic would have been treated.  THE FFR cutpointis 075 to 0.80 and FAME used the higher end of this range to that fewer lesions were left unrevascularized.
By not dilating and stenting lesions that appear to be severe angiographically but are not associated with ischemia, you avoid the placement of a stent which could result in a risk of thrombosis or restenosis in a lesion that was not associated with ischemia.  The FAME authors concluded that "Routine measurement of FFR in patients with multivessel coronary artery disease who are undergoing PCI with drug-eluting stents significantly reduces the rate of the composite end point of death, nonfatal myocardial infarction, and repeat revascularization at 1 year."

## The Role of FFR in Left Main Coronary Artery Disease (LMCA)
In a small non-randomized study, 30 patients who had a hemodynamically significant FFR of  0.75 were managed medically. There was no difference in clinical outcomes between these two groups.  In this very small study no patients in the medically managed group died or had AMI.
Likewise, in a small study of 51 patients, FFR measurenet was helpful to identify patients with intermediate left main disease in whom deferral of surgical revascularization was associated with excellent survival and low event rates.

## The Role of FFR in Acute Coronary Syndromes
The utility of FFR during the course of an acute coronary syndrome is unclear.
In patients with previous myocardial infarction (defined as > 6 days before FFR is performed), FFR has been closely related to abnormalities on SPECT imaging (sensitivity of 82%, specificity of 87%) .  Patients with a higher LVEF had higher FFRs independent of the lumen diameters.  FFR may be helpful in identifying those patients who may benefit from revascularization > 6 days after an MI.

## The Role of FFR in Serial Lesions
Serial lesions may limit the maximal hyperemia achievable in each of the stenoses.  The interaction and significance of serial stenoses depends upon their sequence, the distance between them, their severity, the length of the stenoses, and the flow down the artery. A pullback can be performed, and the lesion with the greatest gradient can be dilated first. The gradient can then be checked again to determine if any of the remaining lesions need to be dilated as well.

## The Role of FFR in Lesions Involving Bifurcations and Sidebranches
In one small study, measurement of FFR among jailed side branch lesions was shown to be both safe and feasible. This study demonstrated that most of these lesions did not have functional significance, despite morphologic appearance.

## FFR Measurement In Renal Artery Stenosis
Using PressureWire and vasodilatory stimulus, and during diagnositc catheterization, pressure measurement and calculation of Pd/Pa ratio can be used to guide treatment of renal artery stenosis. The cutoff value is found to be a Pd/Pa ratio of 0.90.

# FFR and Procedural Time Saved
Using FFR for decision making was shown to cut down the overall hospital stay with better outcomes when compared to using angiography alone to guide angiographic findings .

# Cost-Effectiveness of FFR
Using FFR for decision making was shown to cut down the overall cost with better outcomes when compared to using angiography alone to guide PCI .

# Precautions
- Ensure that there is no pressure gradient between the pressure wire (placed at the tip of the guide) and the guiding catheter. The pressures should be equalized at the onset.
- The two pressures should be compared and noted before inducing coronary hyperemia.
- Use a standard wire first to cross difficult lesions. The pressure wire may not be the most suitable in complex lesions.
Pressure wire may track under a plaque and cause a dissection.
Repeated attempts in trying to negotiate tortuous anatomy may cause trauma to intact endothelium and promote thrombosis and dissection.
- Pressure wire may track under a plaque and cause a dissection.
- Repeated attempts in trying to negotiate tortuous anatomy may cause trauma to intact endothelium and promote thrombosis and dissection.

# 2011, 2009 and 2005 ACCF/AHA/SCAI Guidelines for Percutaneous Coronary Intervention (DO NOT EDIT)

## Fractional Flow Reserve (DO NOT EDIT)

## Use of Fractional Flow Reserve (DO NOT EDIT)

## Coronary Artery Pressure and Flow:Use of Fractional Flow Reserve and Coronary Vasodilatory Reserve (DO NOT EDIT)