VALUE OF FFR IN CLINICAL PRACTICE

DEV PAHLAJANI- MD,FACC,FSCAIHOD INTERVENTIONAL CARDIOLOGY

Breach Candy Hospital, Mumbai

Myocardial Fractional Flow Reserve

Normal FFR = 1

Pa Pd

FFR = Pa

Pd

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.

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

Q = PRRs Rm

FFRmyo

(CFR)

Difference between FFRmyo and CFR

IH 2001

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.

2007 PressureWire® History 2007-Feb

Nico Pijls, MD PhD, Catharina Hospital, Eindhoven, NL

Bernard De Bruyne, MD, PhD Onze Lieve Vrouw Hospital, Aalst, Belgium

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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®.

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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.

Cathlabrecording

system

PressureWire

AO transducer

IBP

inpu

t

FFR

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.

Importance of Maximal Vasodilation

Nitrates Adenosine

Vasospasm Autoregulation

Epicardial= Conductance Arteries > 550 µ

Microvasculature= Resistance

Arteries < 550 µ

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.)

Intravenous AdenosinePREPARATION 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

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.

Any treatment in health care should be directedeither to

• Releave symptoms ( improve functional class )

or to

• Improve outcome ( prognosis, longevity)

No other justification for any treatment is possible !

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

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

AalstAmsterdamEindhoven Essen Gothenborg Hamburg Liège

Maastricht Madrid Osaka Rotterdam Seoul Utrecht Zwolle

data collection & analysis: Jan Willem Bech, MD, PhDPepijn van Schaardenburgh, MD

Patients scheduled for PCI without Proof of Ischemia (n=325)

Randomization

deferral of PTCA (167)

FFR 0.75 (91)

No PTCA DEFER

Group

FFR < 0.75(76)

PTCAREFERENCE Group

performance of PTCA (158)

FFR < 0.75(68)

PTCA

FFR 0.75 (90)

PTCAPERFORM

Group

The DEFER Study: Flow Chart

Cardiac Death And Acute MI After 5 Years

3.3

7.9

15.7

0

5

10

15

20 %

P=0.20

P< 0.03

P< 0.005

DEFER PERFORM REFERENCE

FFR > 0.75 FFR < 0.75

75.8

64.4

0 1 2 3 4 50

25

50

75

100

FFR ³

FFR < 0.75p=0.03

Years of Follow-up

Event – free survival (%)

No. at risk

FFR ≥ 0.75 178 162 154 143 138 136

FFR < 0.75 135 105 103 96 90 88

78.8

72.7

64.4

0

25

50

75

100

Defer

Perform

Reference(FFR < 0.75)

p=0.52

p=0.17p=0.03

0 1 2 3 4 5

Event – free survival (%)

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

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)

2 Year Survival Free of MACE

FFR-Guided

Angio-Guided

730 days4.5%

2 Year Survival Free of Repeat Revascularization

FFR-Guided

Angio-Guided

730 days1.9%

2 Year Survival Free of Death/MI

FFR-Guided

Angio-Guided730 days

4.3%

2 Year Survival Free of MI

FFR-Guided

Angio-Guided 730 days3.6%

513 Deferred Lesions in 509 FFR-Guided Patients

31 Myocardial Infarctions

9 Late Myocardial Infarctions

1 Myocardial Infarction due to an Originally Deferred Lesion

22Peri-procedural

8 Due to a New Lesion or Stent-

Related

Only 1/513 or 0.2% of deferred lesions resulted in a late

myocardial infarction

Outcome of Deferred Lesions

2 Years

513 Deferred Lesions in509 FFR-Guided Patients

10 Originally Deferred Lesions with Clear Progression

37 in a New Lesion or in a

Restenotic One

6 Without FFR or Despite an FFR >

0.80

Only 10/513 or 1.9% of deferred

lesions clearly progressed

requiring repeat revascularization

Outcome of Deferred Lesions

2 Years

Stable patients scheduled for 1,2 or 3 vessel DES stenting

FFR in all target lesions

At least 1 stenosis with FFR <_ 0.80

Randomisation 1:1

PCI + OMT OMT

When all FFR > 0.80

OMT

Follow up after 1,6 months,1,2,3,4 and 5 years

RegistryRandomized Trial

50% randomly assigned to FU

Flow Chart

Rate of Urgent Revascularization

Non- Urgent Revascularization (FAME II)

Rate of any Revascularization (FAME II)

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)

Wedging of guiding catheter: Importance of flow

Maximum hyperemia is of paramount importance

Insufficient hyperemia

Underestimation of gradient

Overestimation of FFR

Underestimation of stenosis

severity

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

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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?)

When do you use FFR?- Clinical Guide

FFR in ostial lesion Angiographic severity vs. Functional significance

FFR=0.94

FFR >_ 70%Angiographic Stenosis

50%-70%Angiographic Stenosis

>_ 0.75 20 30

< 0.75 5 0

Sensitivity 100%, specificity 55% & test accuracy 60%Ziaee A, et al. AJC 2004

FFR in jailed side branches Angiographic severity vs. Functional significance

Bellenger, et al. Heart 2007

Correlation between FFR and % Stenosis

Frac

tiona

l Flo

w R

eser

ve

Percent Stenosis (%)

1.0

.9

.8

.7

.6

.5

40 50 60 70 80 90 100

r = 0.41p < 0.001

Ostial SB Lesion Severity after SB Jailing

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. JACC2005;46:633-637

Only FFR and DES = I A

FFR Should be Used Before Deciding on Treatment

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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.

THANK YOU!!