1. VALUE OF FFR IN CLINICAL PRACTICE
DEV PAHLAJANI- MD,FACC,FSCAI
HOD INTERVENTIONAL CARDIOLOGY
Breach Candy Hospital, Mumbai

2. Myocardial Fractional Flow Reserve
Pa Pd
Pd
FFR =
Pa
Normal FFR = 1
One of the important characteristics of FFR is that the normal value is
uniformly equal to one whatever the vessel, the myocardial mass,
heart rate, blood pressure… If FFR is not equal to one, there is
something wrong with the conductance of the segment. We don’t
have to refer to a range of normal values.

3. Normal artery at maximum vasodilation:
perfusion pressure ~ aortic pressure Pa
Stenotic artery:
perfusion pressure ~ distal coronary pressure Pd
Because, at maximum vasodilation, blood flow is
proportional to perfusion pressure, the ratio of maximum
stenotic flow to normal maximum flow, can be expressed as a
ratio of perfusion pressures
Therefore: FFR is linearly related to maximum flow

4. Difference between FFRmyo and CFR
P
Q= R
Rs Rm
FFRmyo
(CFR)
It this stage it is important to remind again that CFR accounts for both the resistance due to the
stenosis and the resistance related to the myocardium while FFRmyo mainly accounts for the
epicardial coronary stenosis.
Therefore it is evident that both approaches are complementary.
If CFR is reduced, why is it? It can be due to a resistive vessel dysfunction or it can be due to a
“significant” lesion. Let’s measure an intracoronary pressure: if FFRmyo is low, it means that the
reduction in CFR was due to a severe epicardial lesion. If in contrast FFRmyo is normal, the
decrease in CFR is due to a resistive vessel dysfunction.
IH 2001

5. Nico Pijls, MD PhD, Bernard De Bruyne, MD, PhD
Catharina Hospital, Eindhoven, NL Onze Lieve Vrouw Hospital, Aalst, Belgium
2007 PressureWire® History 2007-Feb

6. PressureWire®
The distal pressure in the coronary artery is measured by a tiny sensor
located 3 cm from the tip of an 0.014” guidewire, called PressureWire®.
6

7. RadiAnalyzer®
PressureWire® is attached to RadiAnalyzer®, an interface which makes
the FFR calculations automatically during the procedure.
It displays both aortic and distal pressure wave forms.
FFR
PressureWire
Cathlab
IBP input
recording
system
AO transducer
7

8. Two-Compartment Model of the
Coronary Circulation
The coronary angiogram detects only
5% of the total coronary tree
As you all know the coronary circulation can be considered a 2
compartment model with an epicardial compartment, the vessels that we
see on the coronary angiogram and a second compartment , often
considered a black box, the microvasculature.

9. Importance of Maximal Vasodilation
Epicardial Microvasculature
= Conductance = Resistance
Arteries > 550 µ Arteries < 550 µ
Nitrates Adenosine
Vasospasm Autoregulation

10. Choice of hyperemic stimuli
1. Intracoronary (IC) versus intravenous (IV)
administration.
2. Hyperemic stimuli
a). Intravenous Adenosine
b.) Intracoronary Adenosine
c.) Intracoronary Papaverine
d.) Adenosine Triphosphate (ATP) (i.v. or i.c.)

11. Intravenous Adenosine
PREPARATION 1mg/ml
1 vial = 30 ml = 90 mg adenosine
1 saline bag = 100 ml NaCl
WITHDRAW 40 ml NaCl from 100 ml saline IV bag and
discard.
WITHDRAW 30 ml (90mg adenosine) from vial/ampules (use 15 x 2 ml vials or 3 x 10 ml vials)
ADD 30 ml (= 90mg adenosine= to saline bag
LABEL and hang V 90 mg in 90 ml normal saline
ADMINISTRATION
I.V.Infusion: 140µg/kg/min
Increase to 180µg/kg/min if FFR 0.75 – 0.80

12. Measurement of Fractional Flow Reserve to assess the functional
severity of coronary artery stenosis.
Pijls NHJ et al. N Eng J Med. 1996;334(no26): 1703-08.

13. Any treatment in health care should be directed
either to
• Releave symptoms ( improve functional class )
or to
• Improve outcome ( prognosis, longevity)
No other justification for any treatment is possible !

14. DEFER study: background
If a stenosis is responsible for reversible
ischemia, revascularization is justified……
……But what if a stenosis or “plaque” is
NOT responsible for reversible ischemia ?
(functionally “non-significant” , “non-culprit”)
PCI is often performed in such lesions,
yet the benefit of such treatment is not clear

15. The DEFER Study: Design
prospective randomized multicentric trial
(14 centers) in 325 patients with stable
chest pain and an intermediate stenosis
without objective evidence of ischemia
Aalst Maastricht
Amsterdam Madrid
Eindhoven Osaka
Essen Rotterdam
Gothenborg Seoul
Hamburg Utrecht
Liège Zwolle
data collection & analysis:
Jan Willem Bech, MD, PhD
Pepijn van Schaardenburgh, MD

16. The DEFER Study: Flow Chart
Patients scheduled for PCI
without Proof of Ischemia
(n=325)
Randomization
deferral of PTCA performance of PTCA
(167) (158)
FFR  0.75 FFR < 0.75 FFR < 0.75 FFR  0.75
(91) (76) (68) (90)
No PTCA PTCA PTCA PTCA
REFERENCE PERFORM
DEFER Group
Group Group

17. Cardiac Death And Acute MI After 5 Years
P< 0.03
20 % P< 0.005
15.7
15
P=0.20
10 7.9
5 3.3
0 DEFER PERFORM REFERENCE
FFR > 0.75 FFR < 0.75

18. Event – free survival (%)
100
75.8
75 64.4
50
FFR 
p=0.03
25 FFR < 0.75
0
0 1 2 3 4 5
Years of Follow-up
No. at risk
FFR ≥ 0.75 178 162 154 143 138 136
FFR < 0.75 135 105 103 96 90 88

19. Event – free survival (%)
100
75 78.8
72.7
64.4
50 Defer
p=0.52
Perform p=0.03
25 p=0.17
Reference
(FFR < 0.75)
0
0 1 2 3 4 5
Years of Follow-up
No. at risk
Defer group 90 85 82 74 73 72
Perform group 88 78 73 70 67 65
Reference gr 135 105 103 96 90 88

20. FAME Overview
FFR vs. Angiography for Multivessel Evaluation1
Goal: To compare safety and cost-effectiveness of PCI
guided by FFR plus angiography with PCI guided by
angiography alone.
– Randomized, prospective study – angiography only or angiography plus FFR
– 20 centers in Europe and U.S.
– 1,005 PCI patients undergoing DES stenting for
multivessel disease
– Only PressureWire from St. Jude Medical was used
in this study
1. FFR vs angiography for guiding PCI in patients with multivessel coronary artery disease. Pijls et al. JACC 2010, 56(3)

21. 2 Year Survival Free of MACE
FFR-Guided
Angio-Guided
730 days
4.5%

22. 2 Year Survival Free of Repeat Revascularization
FFR-Guided
Angio-Guided
730 days
1.9%

23. 2 Year Survival Free of Death/MI
FFR-Guided
Angio-Guided
730 days
4.3%

24. 2 Year Survival Free of MI
FFR-Guided
Angio-Guided 730 days
3.6%

25. Outcome of Deferred Lesions
513 Deferred Lesions in 509
FFR-Guided Patients
2 Years
22
31 Myocardial Infarctions
Peri-procedural
8 Due to a New
9 Late Myocardial Infarctions Lesion or Stent-
Related
1 Myocardial Infarction due to Only 1/513 or 0.2%
an Originally Deferred Lesion of deferred lesions
resulted in a late
myocardial
infarction

26. Outcome of Deferred Lesions
513 Deferred Lesions in
509 FFR-Guided Patients
2 Years
37 in a New
53 Repeat Revascularizations Lesion or in a
Restenotic One
6 Without FFR or
16 Originally Deferred Lesions Despite an FFR >
0.80
Only 10/513 or 1.9%
10 Originally Deferred Lesions of deferred
with Clear Progression lesions clearly
progressed
requiring repeat
revascularization

27. Flow Chart
Stable patients scheduled for 1,2 or 3
vessel DES stenting
FFR in all target lesions
Randomized Registry
Trial
At least 1 stenosis with When all FFR > 0.80
FFR <_ 0.80
Randomisation 1:1 OMT
50%
PCI + randomly
OMT assigned to
OMT
FU
Follow up after 1,6 months,1,2,3,4
and 5 years

28. Rate of Urgent Revascularization

29. Non- Urgent Revascularization (FAME II)

30. Rate of any Revascularization (FAME II)

31. Most Common Pitfalls in doing FFR
Insufficient hyperaemia: Peripheral vs Central line
• Pitfalls related to guiding catheter:
– Large guiding in a small ostium
– Guiding catheter with side-holes
– Sludging of contrast / blood
• Drift
• Introducer needle
• Hydrostatic difference between aortic root and distal coronary artery
(reversed gradient)

32. Wedging of guiding catheter:
Importance of flow

33. Maximum hyperemia is of paramount
importance
Underestimation
Insufficient Underestimation Overestimation
of stenosis
hyperemia of gradient of FFR
severity

35. Discordance between
FFR and IVUS in daily practice
Specificity Sensitivity
FER 1 0.75 100% 88%
IVUS 2 4mm2 56% 92%
Low specificity means:
-Increased rate of false positive results
- Risk of unnecessary stents and CABG

36. When do you use FFR?
- Clinical Guide
Assess stenosis severity and guide treatment
• Intermediate stenosis in one or more coronary arteries, even bypass grafts.
(Evidence of ischemia)
• Serial lesions (Culprit? Cumulative effect?)
• Diffuse disease. (Focal treatable region?)
• Ostial or distal LM and ostial right lesions. (Significant?)
• Sidebranch lesions (Significant?)
• Multivessel Disease.. (Culprit?)
• In-stent restenosis. (Conservative management or revascularization?)
• Prior MI. (A surrogate for non-invasive testing?)
36

37. FFR in ostial lesion
Angiographic severity vs. Functional significance
FFR=0.94
FFR >_ 70% 50%-70%
Angiographic Angiographic
Stenosis Stenosis
>_ 0.75 20 30
< 0.75 5 0
Sensitivity 100%, specificity 55% & test accuracy 60%
Ziaee A, et al. AJC 2004

38. FFR in jailed side branches
Angiographic severity vs. Functional significance
Bellenger, et al. Heart 2007

39. Ostial SB Lesion Severity after SB Jailing
Correlation between FFR and % Stenosis
1.0
.9
Fractional Flow Reserve
r = 0.41
.8 p < 0.001
.7
.6
.5
40 50 60 70 80 90 100
Percent Stenosis (%)
The optimal cutoff value for percent stenosis to predict functionally significant
stenosis was 85%
(Sensitivity: 0.80, Specificity: 0.76) Koo, B.-K. et al. JACC
2005;46:633-637

40. Only FFR and DES = I A

41. FFR Should be Used Before Deciding
on Treatment
For the treating physician, the new
guidelines mean that he should
measure FFR before making a decision
to perform PCI or send the patient to
surgery, in patients who come to the
cath lab without a prior functional test
and with a stenosis(es) 50-90% by
angiography.
This is regardless of whether the patient
has single-vessel disease, multivessel
disease, or if the vessel is especially
important, eg. proximal LAD or LMCA.
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42. THANK YOU!!