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Introduction
• The benefits of PCI in ACS is Clear

• In ACS, non-culprit lesions with angiographic

stenosis were often dilated, without
consideration of objective ischemia

• The benefits of PCI in stable CAD?

• Revascularization treatment based on
ischemia may improve patient outcomes
Introduction
• Guidelines have recommended non-invasive
functional evaluation before revascularization
treatment.
• However : non invasive evaluation are
underutilized
qTopol 1995 : 29% had exerc i s e t e s t i n g b e f o r e
coronary angioplasty.
q Lin 2012 : 44.5% of patients with stable angina
underwent TMT or pharmacological stress testing
and myocardial nuclear imaging within 90 days
before elective PCI.
More lesion-specific alternatives to
exercise stress testing during
coronary angiography or PCI
procedures are needed
 Case

Female, 61 yo.
Chief complaint : chest discomfort
Risk factors : menopause, diabetes melitus
Without history of myocardial infarction
 Trans-Thorax Echocardiography :
Concentric LVH
Normal global and segmental systolic LV function.
Ejection fraction 77%.
E/A < 1
TAPSE 20 mm
Mild Tricuspid regurgitation.
Mild Pulmonary regurgitation
 Cardiac MSCT

LAD : calcified and soft (mixed) LCx : motion artifact at mid with
plaque with severe stenotic at suspicion of soft plaque
proximal
 Cardiac MSCT

RCA : soft plaque with non significant stenotic at mid

 Coronary Angiography

Should we treat the lesion ?

Based on anatomical only
or
Based on functionally (ischemia)
RCA FFR 0.93

LCX FFR 0.73

LAD FFR 0.53

Evaluation after procedure
FFR: Gold Standard for Identifying Ischemia
Proximal
Pressure (Pa)
Distal
Pressure (Pd)
FFR = Pd / Pa
during maximal flow

Pd / Pa = 60 / 100
FFR = 0.60
 Fractional Flow Reserve
• Normal FFR is 1.0

• FFR < 0.75 : ischemia on noninvasive imaging in

a variety of patient populations

• FFR > 0.80 excludes ischemia in 90% of cases.

• FFR between 0.75 and 0.80: the ischemic

potential of the stenosis remains unclear.
 Fractional Flow Reserve
FFR is accurate assessment of the functional
significance of stenosis in individual coronary
arteries :
q sound mathematical basis
q validated
q not affected by hemodynamic conditions
q lesion-specific
q suitable to the assessment of multiple lesions
q easily determined during routine diagnostic
workup
q reproducible
 FAME Study
• The FAME study
(FFR vs. angiography for multi-vessel disease):
patient and lesion selection as well as treatment
decisions based on systematic assessment of FFR,
improve clinical outcomes in CAD and save costs,
particularly in multivessel disease.
FLOW CHART
CONSORT-E CHART
 absolute difference in MACE-free survival

FFR-guided

Angio-guided
30 days
2.9% 90 days
3.8% 180 days
4.9% 360 days
5.3%
 FAME study: Conlusion

Routine measurement of FFR during PCI with DES in

patients with multivessel disease, when compared to
current angiography guided strategy

• reduces the rate of the composite endpoint of death,

myocardial infarction, re-PCI and CABG at 1 year by ~
30%

• reduces mortality and myocardial infarction at 1 year

by ~ 35 %
 Visual-Functional Mismatch
A sub-analysis of the FAME study
(FFR vs Angiography for Multi-vessel Evaluation):

q Of the patients with 3-VD: 14% had 3-VD after FFR ,

whereas 9% had no functionally significant stenosis.

q Of the 1329 target lesions (>50% stenosis by visual

estimation) : only 816 (61%) had FFR < 0.80.

q Of lesions with stenosis of 50%-70%, 71%-90%, and 91%-

99%: only 65%, 20%, and 4%, respectively, were found to
have FFR > 0.80.

qOf 509 patients with angiographically multivessel disease:

only 235 (46%) had functional multivessel disease
(>2 coronary arteries with an FFR <0.80).
 Visual-Functional Mismatch
These findings indicated :
q In the absence of FFR, approximately 40% of
procedures would have been performed in functionally
insignificant stenosis lesions.

q simple visual assessment by coronary angiogram

cannot predict the functional significance of coronary
stenosis

q Coronary lesion with intermediate stenosis should be

evaluated for the functional significance by FFR
 FAME-2 STUDY
Stable CAD patients scheduled for 1, 2 or 3 vessel DES-PCI
N = 1220

FFR in all target lesions

Randomized Trial Registry
At least 1 stenosis When all FFR > 0.80
with FFR ≤ 0.80 (n=888) (n=332)

Randomization 1:1

PCI + MT MT MT
73% 27% 50% randomly
assigned to FU

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

 FAME 2: Design
• Hypothesis:
• The hypothesized that an initial strategy of FFR-guided
PCI plus medical therapy would provide better long-term
outcomes than an initial strategy of medical therapy
alone

De Bruyne, et al. New Engl J Med 2012;367:991-1001

 Baseline Characteristics
Randomized Trial Registry p
Patients, N PCI+MT=447 MT=441 with FU=166
Demographic
Age (y) 63.5±9.3 63.9±9.6 63.6±9.8 0.90
Male sex - (%) 79.6 76.6 68.1 0.005
BMI 28.3±4.3 28.4±4.6 27.8±3.9 0.14

Risk factors for CAD

Positive family history CAD - (%) 48.3 46.9 45.8 0.65
Smoking - (%) 19.9 20.4 21.1 0.79
Hypertension - (%) 77.6 77.8 81.9 0.23
Hypercholesterolemia - (%) 73.9 78.9 71.1 0.15
Diabetes mellitus - (%) 27.5 26.5 25.3 0.65
Insulin requiring diabetes - (%) 8.7 8.8 6.0 0.24

De Bruyne, et al. New Engl J Med 2012;367:991-1001

 Angiographic Characteristics

Patients, N PCI+MT=447 MT=441 with FU=166

Angiographically significant
1.87±1.05 1.73±0.94 1.32±0.59 <0.001
stenoses - no. per patient

No of vessels with ≥ 1 significant

<0.001
stenoses - (%)
1 56.2 59.2 81.9
2 34.9 33.1 15.7
3 8.9 7.7 2.4

Prox- or mid- LAD stenoses - (%) 65.1 62.6 44.6 <0.001

De Bruyne, et al. New Engl J Med 2012;367:991-1001

 Primary Endpoint 1 year:
Death, MI, Urgent Revascularization
30 PCI+MT vs. MT: HR 0.32 (0.19-0.53); p<0.001
PCI+MT vs. Registry: HR 1.29 (0.49-3.39); p=0.61
Cumulative incidence (%)

25 MT vs. Registry: HR 4.32 (1.75-10.7); p<0.001

20

15

10

0
0 1 2 3 4 5 6 7 8 9 10 11 12
Months after randomization
No. at risk
MT 441 414 370 322 283 253 220 192 162 127 100 70 37
PCI+MT 447 414 388 351 308 277 243 212 175 155 117 92 53
Registry 166 156 145 133 117 106 93 74 64 52 41 25 13

De Bruyne, et al. New Engl J Med 2012;367:991-1001

Patients with urgent revascularization

Myocardial
Infarction

Unstable angina
+evidence of
ischemia on ECG
 Patients with urgent revascularization

Myocardial
Urgent revascularization
driven by MI or unstable
Infarction
angina with ECG changes
FFR-Guided MT
PCI + MT

0.9% vs. 5.2%

p<0.001
83% Relative Risk Reduction Unstable angina
+evidence of
ischemia on ECG
Primary Endpoint 5 years:
Death, MI, Urgent Revascularization
Primary Endpoint 5 years:
Death, MI, Urgent Revascularization
Primary Endpoint 5 years:
Death, MI, Urgent Revascularization
Primary Endpoint 5 years:
Death, MI, Urgent Revascularization
Primary Endpoint 5 years:
Death, MI, Urgent Revascularization
 RESUME
- FFR can be used to determine the functional significance
of a stenosis lesion

- FAME 2 Study : 5 years follow up

- Stable CAD with an initial FFR-guided PCI strategy was
associated with a significantly lower rate of the primary
composite end point of death, myocardial infarction, or
urgent revascularization at 5 years than medical
therapy alone.

- Patients without hemodynamically significant stenosis

had a favorable long-term outcome with medical
therapy alone