FFR

1. Value of FFR/iFR in cath lab
Mohamad Ashraf Ahmad
Consultant cardiology PSCCH

2. Agenda
• Coronary physiology and concept of FFR/IFR
• Studies support use of FFR and IFR
• Technique
• Pitfalls
• Value of FFR/iFR in cath lab
• FFR/iFR in guidelines
• Clinical cases

3. Coronary physiology
• Coronary circulation can be viewed as a two-compartment
model.
• Large epicardial vessels (> 400 microns), which are also referred to
as ‘conductance vessels’ because they have minimal resistance to
blood flow.
• Arteries smaller than 400 microns, or ‘resistive vessels’.
• Myocardial flow is controlled predominantly by resistive
vessels.

6. Coronary Flow Reserve and auto regulation
• Stenosis in large epicardial
(capacitance) vessel  decreased
perfusion pressure  arterioles
downstream dilate to maintain normal
resting flow
• As stenosis progresses, arteriolar
dilation becomes chronic, decreasing
potential to augment flow and thus
decreasing CFR
• As CFR approaches 1.0 (vasodilatory
capacity “maximum”), any further
decrease in PP or increase in MVO2 
ischemia

7. Concept of FFR
• FFR is defined as a ratio of the maximal myocardial blood
flow in the presence of a stenosis to the theoretical normal
maximal flow in the same distribution.
• FFR is simply calculated by using the distal coronary pressure
of the stenosis divided by the aortic pressure during maximal
hyperemia; Pd/Pa

8. Technique of FFR

10. Pitfalls
• Technical (loose connections, leak in guide connections, improper
zero)
• Mechanical/pharmacological ( guide catheter obstruction,
inadequate hyperemia)
• Hemodynamic artifacts ( Damped pressure wave forms, use of small
guide, guide with side holes)

11. Study Name Year Size Trial Design
Clinical
Presentation FFR Cutoff Outcomes
DEFER11 2001 325 patients at 14
medical centers
Prospective,
randomized
Stable chest pain
and an
intermediate
stenosis without
objective evidence
of ischemia
0.75 No benefit stenting
a non-ischemic
stenosis
FAME4 2009 1,005 patients at 20
medical centers
Prospective,
randomized
Multivessel CAD 0.80 Routine
measurement of
FFR in patients with
multivessel CAD
who are
undergoing PCI
with drug-eluting
stent significantly
reduces MACE at 1
year
FAME 213 2012 888 patients at 28
medical centers
Prospective,
randomized
Stable CAD and
hemodynamically
significant stenoses
0.80 FFR-guided PCI with
DES+ optimal
medical therapy
(OMT) vs. OMT
alone decreased
the rate of urgent
revascularization.

12. Study Name Year Size Trial Design
Clinical
Presentation FFR Cutoff Outcomes
Van Belle et
al.(R3F)23
2014 1,075 patients at 20
centers in France
Prospective
observational study
Angiographically
ambiguous lesion
0.80 FFR during
diagnostic
angiography is safe
and associated with
reclassification of
the
revascularization
decision in about
half of the patients
DANAMI-3-
PRIMULTI20
2015 627 patients at 2
centers in Europe
Prospective
randomized
controlled trial
Patients with STEMI
and multivessel
disease who had
undergone primary
PCI of an infarct-
related coronary
artery
0.80 Complete staged
revascularization
during the index
admission, guided by
FFR reduces the risk of
future events, driven
by fewer repeat
revascularizations
Compare-Acute21 2017 885 at 24 centers in
Europe and Asia
Prospective
randomized
controlled trial
Patients with STEMI
and multivessel
disease who had
undergone primary
PCI of an infarct-
related coronary
artery
0.80 FFR-guided complete
revascularization of
non-infarct-related
arteries in the acute
setting resulted in
lower MACE, driven
by decreased
revascularization

13. iFR (instantenous free wave ratio)
• Adenosin used for hyperemia can produce side effects like
chest pain, bronchospasm and bradycardia
• iFR can assess the physiological assessment without need for
hyperemia or adenosin
• Technique is the same as FFR without the injection of
adenosin

14. Concept of iFR
• iFR is a physiological index used
to assess the severity of
stenosis.
• iFR is calculated by measuring
the resting pressure gradient
across a coronary lesion during
the portion of diastole (wave
free period) when microvascular
resistance is low and stable.

15. IFR versus FFR- guided coronary
intervention
• Enrolled 2042 patients
• 1007 patients underwent FFR
guided revascularization
• 1012 patients underwent iFR
guided revascularization.
• iFR vs FFR for guiding coronary
revascularization
• 1242 patients underwent iFR guided
revascularization
• 1250 patients underwent FFR
guided revascularization
• Justin E Davies et al NEJM 2017M. Gotberg, E.H. et al., NEJM 2017

16. Clinical iFR and FFR cut-points

17. Both studies showed that iFR was non-inferior to FFR regarding death,
MI and unplanned revascularization at 1 year, while iFR was superior to
FFR regarding procedural discomfort.

18. Clinical use of FFR/IFR:
Intermediate lesions
• In patients with angiographically intermediate stenoses, it has been shown
that FFR is more accurate than exercise ECG, MPI and stress
echocardiography for assessing haemodynamic significance.
• In addition, the clinical outcome of patients in whom PCI has been
deferred, because the FFR indicated no haemodynamically significant
stenosis, is very favourable.
• In this population, the risk of death or MI is approximately 1% per year and
this risk is not decreased by PCI.
• These results strongly support the use of FFR measurements as a guide for
decision-making about the need for revascularization in ‘intermediate’
lesions.

19. Multivessel CAD
• FFR measurement has a major implication for the mode of
revascularization strategy (PCI vs CABG).
• Determining which lesion(s) necessitate stenting and which do not
can be difficult in these patients, when using non-invasive imaging
modalities.
• For example, MPI is limited in its ability to accurately localize lesions
responsible for ischaemia in these patients.

20. • FAME 2 study showed that routine measurement of FFR during PCI
with DES in patients with multivessel disease reduced the rate of the
composite endpoint of death, MI, re-PCI and CABG at 1 year by
approximately 30% and reduced mortality and MI at 1 year by
approximately 35%, compared with current angiography-guided
strategy.
• FFR-guided strategy reduces the number of stents used, decreases
the amount of contrast agent used, does not prolong the procedure
and is cost saving

21. Left main stem disease
• The presence of a significant stenosis in the LMCA is of critical
prognostic importance and often determines the type of treatment.
• Assessment using FFR is more challenging in comparison with non-
LMS stenosis due to the requirement for disengagement of the
guiding catheter and an inability to administer intracoronary
adenosine
• Several studies showed that an FFR-guided strategy for equivocal
LMCA lesions is safe and related to a favourable clinical outcome

22. Myocardial infarction
• After a myocardial infarction, previously viable tissue is partially
replaced by scar tissue. Therefore, the total mass of
functional myocardium supplied by a given stenosis in an infarct-
related artery will tend to decrease .
• Assuming that the morphology of the stenosis remains identical, FFR
must therefore increase. This does not mean that FFR underestimates
lesion severity after myocardial infarction.

23. FFR in STEMI
• In the early phase after STEMI, severe microvascular impairment (no
reflow, stunning, inflammation) may be present.
• Low FFR still indicates hemodynamic significance of the residual
stenosis, but high FFR does not necessarily exclude this.
• Therefore, pressure-derived FFR should not be used for the culprit
vessel during the acute phase (less than 5 days) of a STEMI.
• DANAMI-3-PRIMULTI and Compare-Acute studies

24. Bifurcation lesions and
side branch ostial lesion
• Bifurcation lesions are particularly difficult to assess angiographically
because of the overlap orientation relative to parent branch and
radiological artefacts.
• Data supporting the use of FFR in guiding PCI for bifurcation lesions are
limited.
• Two studies by Koo et al. demonstrated: that after stenting, the ostium
of the side branch often looks ‘pinched’ but is often overestimated by
angiography (measurement of FFR identifies a minority of lesions that
are functionally significant); and a favourable outcome for FFR-guided
side branch PCI strategy for bifurcation lesions.

25. Coronary artery bypass graft lesions
• At present, there are no clinical outcome data available regarding the
use of FFR in graft stenosis. Therefore, FFR should be used with
caution in bypass graft stenosis.
• Nevertheless, in patients requiring CABG for multivessel
revascularization, angiographic lesions of uncertain significance would
benefit from FFR, providing prognostic information regarding
potential of future bypass graft patency.

26. FFR/IFR in guidelines

27. • According to the American College of Cardiology (ACC) guidelines on
coronary revascularization, FFR is reasonable for the assessment of
angiographic intermediate coronary lesions (50-70% diameter
stenosis) and can be useful for guiding revascularization decisions in
patients with CAD (Class IIa, Level A)

28. CASE #1

29. CASE # 2

30. Take home message
• Coronary pressure-derived FFR is the current standard of care for the
functional assessment of lesion severity in patients with intermediate-
grade stenosis without evidence of ischemia in non-invasive testing, or in
those with multivessel disease.
• The use of FFR/iFR to guide revascularization has been found to improve
patient outcomes and defer stenting of non ischemic lesions compared
with angiographic assessment.
• In intermediate grey zone lesions, small variations may make a big
difference.
• In grey zone you have to use the grey matter of the brain (clinical
judgment) results in zone 0.81 to 0.79 in a Side branch may lead to more
complex PCI Perhaps better if you avoid it.