FFR Cli i l T i l dFFR Clinical Trials and Applications: Changing theApplications: Changing the Practice of PCI

William F Fearon MDWilliam F. Fearon, MDAssociate ProfessorSt f d U i it M di l C tStanford University Medical Center

Disclosure Statement of Financial Interest

Within the past 12 months, I or my spouse/partner have had a financial interest /arrangement or affiliation with the organization(s) listed below

Affiliation/Financial Relationship CompanyGrant/ Research Support: St. Jude MedicalGrant/ Research Support: St. Jude Medical

Consulting Fees/Honoraria: Tryton Medical

Major Stock Shareholder/Equity Interest:Major Stock Shareholder/Equity Interest:

Royalty Income:

Ownership/Founder:Ownership/Founder:

Salary:

Intellectual Property Rights:Intellectual Property Rights:

Other Financial Benefit (minor stock options): HeartFlow

Overview:Validation and application of FFR in single pp gvessel, intermediate CADFFR in specific subsets:FFR in specific subsets:

Diffuse disease, tandem lesionsBifurcation lesionsBifurcation lesionsAfter myocardial infarction

FFR in multivessel CADFFR in multivessel CADOngoing and future studies:

FAME 2FAME 2FAME 3

Validation of FFRFractional Flow Reserve

E iExerciseTest

Thalliuma uScan

Stress E h

0.75

Echo

FFR < 0.75 : Sensitivity = 88%Specificity = 100%

Pijls et al., New Engl J Med 1996;334:1703

Safety of Deferring PCI Based on FFR

P< 0.0035 Year Cardiac Death and Acute MI rate in DEFER trial

15.7

20 % P< 0.00515.7

15P=0.20

7.910

3.3

0

5

0 DEFER PERFORM REFERENCE

FFR ≥ 0.75 FFR < 0.75

Pijls, et al. J Am Coll Cardiol 2007;49:2105-11

FFR and Intermediate Left Main4534 patients

+ “some degree” of LM disease

1352 “≤30% stenosis”

2908 “significant” CABG

274 consecutive pts+“equivocal LM”

FFR

QCAQCA

> 6 mos clinical follow-up

Hamilos, et al., Circulation 2009;120:1505

FFR and Intermediate Left MainSurvival Rate

Hamilos, et al., Circulation 2009;120:1505

FFR and Intermediate Left MainMACE Rate

Hamilos, et al., Circulation 2009;120:1505

Overview:Validation and application of FFR in single pp gvessel, intermediate CADFFR in specific subsets:FFR in specific subsets:

Diffuse disease, tandem lesionsBifurcation lesionsBifurcation lesionsAfter myocardial infarction

FFR in multivessel CADFFR in multivessel CADOngoing and future studies:

FAME 2FAME 2FAME 3

FFR in Diffuse DiseaseFFR in Diffuse DiseaseFFR measured in 37 arteries in 10 patients without CAD and in 107 nonstenotic adjacent arteries in 62 patients with CADj

De Bruyne et al. Circulation 2001;104:2401

FFR Pullback Focal LAD Lesion

Proximal Edge of LAD l i

Distal LAD

LAD lesion

FFR Pullback Pullback in Moderately andPullback in Moderately and

Diffusely Diseased LAD

Distal LAD Proximal LADDistal LAD Proximal LAD

FFR in Tandem Lesions

P llb k f P WiPullback of Pressure WireDuring Maximal Hyperemia

Across Mid LAD Across LM

FFR in Tandem Lesions

P llb k f P WiPullback of Pressure WireDuring Maximal Hyperemia

Across Mid LAD Across LM

FFR in Tandem Lesions

FFR of Left Main = 0 72FFR of Left Main = 0.72(In absence of LAD lesion)

Proximal to LAD t t

Across LMLAD stent

Effect of Tandem Lesions

Myocardium0.84 0.64

Myocardium0.72

Tandem LesionsScientific Aspects

De Bruyne, et al. Circulation 2000;101:1840-7.Pijls, et al. Circulation 2000;102:2371-7.

Bifurcation LesionsFFR in 97 “Jailed” Side Branches

0.75

At 10 month F/U noAt 10 month F/U no Death, MI, or Sidebranch TLR

Koo, et al. J Am Coll Cardiol 2005;46:633-7.

Acute Microvascular Damage and FFRgSTEMI

Variable Degree of Reversible Microvascular

Stunning

Maximum AchievableMaximum Achievable Flow is Less

S ll G di t dSmaller Gradient and Higher FFR across Any Given Stenosis

With time, the microvasculature mayrecover, maximum achievable flow

i d l di tmay increase, and a larger gradient with a lower FFR may be measured across a given stenosis

Chronic Microvascular Damage and FFRgOld Myocardial

Infarction

Irreversible Microvascular Damage

M i A hi blMaximum Achievable Flow is Less

In the setting of chronic microvascular Smaller Gradient and Higher FFR across Any Given Stenosis

gdysfunction, the higher FFR is not falsely elevated, but reflects the smaller amount of viable myocardium ysmaller amount of viable myocardium supplied by the vessel and still provides information about the expected gain in flow after PCIexpected gain in flow after PCI

FFR in Chronic MI (Culprit Vessel)Comparison of FFR in 57 patients with an MI ≥ 6 days old to SPECT imaging before and after PCI

( p )

days old to SPECT imaging before and after PCI

De Bruyne, et al. Circulation 2001;104:157-162

FFR STEMI (Non-Culprit Vessels)( p )• 101 patients with an acute coronary syndrome• 112 non culprit stenoses measured acutely and 35±24 days later

0.90

0.95

1.00

In only 2/112 t th

0.70

0.75

0.80

0.85

stenoses was the FFR >0.80 during the ACS and <0.75 at 0.55

0.60

0.65

follow-up.

0.35

0.40

0.45

0.50

ACUTE FOLLOW-UP0.20

0.25

0.30

0.35

p=NS

Ntalianis, et al. JACC: Cardiovasc Interv 2010;3:1274

Overview:Validation and application of FFR in single pp gvessel, intermediate CADFFR in specific subsets:FFR in specific subsets:

Diffuse disease, tandem lesionsBifurcation lesionsBifurcation lesionsAfter myocardial infarction

FFR in multivessel CADFFR in multivessel CADOngoing and future studies:

FAME 2FAME 2FAME 3

FAME Study: One Year Outcomes

Angio-Guided FFR-Guided%↓

y

18.320% ~30% ↓

8 7 9.511.1

13.2

10

15~35% ↓ ~30% ↓

~35% ↓

3

8.7

5.7 6.5 7.3

5

10~40% ↓

31.8

0Death MI Repeat

RevascDeath/MI MACE

p=0.02p=0.04

New Engl J Med 2009;360:213-24.

FAME Study: Two Year Outcomesy

FFRFFR--GuidedGuided

AngioAngio--GuidedGuided

730 days730 days4.5%4.5%

J Am Coll Cardiol 2010;56:177-184

FAME: Economic EvaluationBootstrap Analysis

FFR-guided PCI saved >$2,000 per patient at one year compared to Angio-guided PCI

Circulation 2010;122:2545-50.

Anatomic vs. Functional CAD

0VD (9%)3VD (14%)

( )

AngiographicAngiographic3 Vessel

1VD (34%) 2VD (43%)Disease

J Am Coll Cardiol 2010;55:2816-21

Overview:Validation and application of FFR in single pp gvessel, intermediate CADFFR in specific subsets:FFR in specific subsets:

Diffuse disease, tandem lesionsBifurcation lesionsBifurcation lesionsAfter myocardial infarction

FFR in multivessel CADFFR in multivessel CADOngoing and future studies:

FAME 2FAME 2FAME 3

FAME 2Death and MI in the COURAGE study

FAME 2

Boden et al., New Engl J Med 2007;356:1503-16.

FAME 2Stable patients scheduled for one‐,two‐ or three vessel DES stenting

FFR in all indicated stenoses

There is at least one Stenosis There is no StenosisThere is at least one  StenosisWith FFR ≤ 0.80

1:1 Randomization

There is no Stenosiswith an FFR ≤ 0.80

1:1 Randomization 

PCI+OMT  OMT  OMT 

Cohort A Cohort BFollow‐up after 1, 6 months, 1, 2, 3, 4, and 5 years

Primary Endpoint: Death, MI, Urgent TVR at 2 yearsPrimary Endpoint: Death, MI, Urgent TVR at 2 years

FAME 3

20%20

19.1 18.4

10 11 213.210 11.2

00SYNTAX FAME

1 year MACE Rates1 year MACE Rates

Overview:Validation and application of FFR in single pp gvessel, intermediate CADFFR in specific subsets:FFR in specific subsets:

Diffuse disease, tandem lesionsBifurcation lesionsBifurcation lesionsAfter myocardial infarction

FFR in multivessel CADFFR in multivessel CADOngoing and future studies:

FAME 2FAME 2FAME 3

Summary:y

The numerous FFR clinical trials and applications have refocused PCI from pp“Anatomic Revascularization” to “Functional Revascularization”Functional Revascularization(i.e. stenting ischemic lesions and

di ll t ti i h i )medically treating nonischemic ones)