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FFR Going Beyond Angiography

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Title: FFR Going Beyond Angiography


1
FFR Going Beyond Angiography
  • By
  • Amr El Nagar

2
  • Should this lesion be stented ??

3
Back to the Basic Coronary Physiology
  • Coronary blood flow 3-5 of C.O.
  • Resting myocardial O2 demand is
  • extremely high (20 x skeletal O2 demand)
  • Myocardium extracts maximum O2
  • from blood (80 versus 30-40 skeletal muscle)
  • Myocardium has high capillary density
  • (3000-4000/mm2 versus 500-2000/mm2 skeletal
    muscle)
  • Therefore, only way to meet increasing
  • demand is to increase blood flow

4
Coronary Blood Flow vs Percent Diameter
StenosisAutoregulationAutoregulation
5
Hyperemia
  • Hyperemia is a state of myocardial vasculature
    dilatation
  • Myocardial bed can be pharmacologically dilated
    with an agent egAdenosine
  • occurs naturally in the body in small quantities
    and is produced during exercise to assist in the
    dilatation of the myocardial bed.

6
Physiology to Address Clinical Questions in the
Cath Lab
7
FFR
  • What ??????????????
  • Why???????????????
  • How??????????????
  • When?????????????

8
What is FFR?
It is a Ratio between
Maximum flow down a vessel in the presence of a
stenosis and maximum flow in the hypothetical
absence of the stenosis
9
Derivation of FFR
  • FFR Coronary Flow(Stenosis)
    Coronary Flow (Normal)
  • Coronary Flow Pressure
    Resistance
  • at maximal hyperemia Coronary Flow Pressure
  • So, FFR Coronary Pressure(Stenosis)
    Coronary Pressure (Normal)

10
FFR threshold for ischemia
No ischemia
Yes ischemia
FFR
1.00
0.75
0.00
FFR lt 0.75 ? inducible ischemia (spec. 100
) FFR gt 0.75 ? no inducible ischemia (sens. 90
)
Pijls, De Bruyne et al, NEJM 1996
11
Why FFR(is it superior)????
  • Stenting of non-ischemic stenoses has no benefit
    compared to medical treatment only.
  • Stenting of ischemia-related stenoses improves
    symptoms and outcome.
  • In multivessel coronary disease (MVD),
    identifying which stenoses cause ischemia is
    difficult.
  • Non-invasive tests are often unreliable in MVD
    and coronary angiography often results in both
    under or overestimation of functional stenosis
    severity.

12
Limitations of Anatomic Techniques
- Underestimates diffuse disease - Large Intra-
and inter-observer variability - Not designed to
assesses physiologic lesion significance
13
Limitations of Non-Invasive StudiesSPECT Imaging
  • - SPECT imaging 70 sensitivity for single vessel
    disease
  • - SPECT imaging has 85-90 sensitivity for
    detecting disease in patients with MVD, but only
    50 sensitivity for detecting MVD ischemia pattern

14
But FFR !!!!
  • FFR is not influenced by changes in blood
    pressure,
  • heart rate, or contractility
  • FFR has a unique normal value of 1.0 in every
    patient
  • and every coronary artery
  • FFR incorporates the contribution of collateral
    flow
  • to myocardial perfusion

15
How????Technique!!!!
16
Pressure Wire
Tip
  • Guide wire - 0.014
  • straight or J tip
  • pressure sensor - 3 cm proximal to the end of the
    wire

Pressure sensor
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18
Equipments
RADI ANALYZER
PRESSURE WIRE
19
Myocardium
Aorta
coronary artery
100
0
Qnormal
Pa
Pd
Max. hyperemia
Normal perfusion pressure
100
0
Pd
Pa
Qstenosis
Stenotic perfusion pressure
Qstenosis Stenotic
perfusion press. Pd FFR

Qnormal
Normal perfusion press. Pa
20
  • blood pressure distal to the lesion being
    assessed - Pressure distal (Pd)
  • conventional pressure transducer - measures
    arterial/aortic pressure - Pressure arterial (Pa)

21
  • mean pressures of Pd and Pa are used
  • assuming there is no lesion present no
    difference in pressure
  • The difference between these two pressures taken
    at rest determines if there is a resting gradient
    across a lesion
  • Gradient calculation Pd/Pa.

22
  • no lesion, the pressures will be the same and
    therefore the gradient value will be 1
  •  e.g. Pa 150 mmHg Pd 150mmHg
  •  
  • So, Pd/Pa 1
  •  

23
  • Dilation of micro-vasculature increases oxygen
    demand
  • a flow limiting lesion will cause the blood
    pressure distal to the lesion to fall
  • FFR will fall 
  • The extent of this reduction gives an indication
    as to the degree of flow limitation and hence
    degree of severity of stenosis

24
Vasodilatory Agents for Hyperemia
25
Where to Administer Adenosine?
26
Examples of coronary pressure gradient
27
Coronary pressure measuremnts
28
  • Pitfalls and Artifacts

29
  • Technical
  • loose connection
  • leak in guide connections
  • improper zero
  • Inadequate hyperemia
  • Anatomic/Theoretical
  • Ostial, diffuse disease
  • microvascular disease
  • Extreme tortuosity
  • Serial lesions
  • Mechanical/Hemodynamic

30
Insufficient Hyperemia
  • IV Adenosine-
  • Check infusion, pump system and lines
  • Infuse through central vein
  • Avoid Valsalva maneuver during infusion
  • For Intracoronary route-
  • Guiding catheter failure to seat
  • flow obstruction-incorrect dose mix or dilution
  • incorrect dose mix or dilution

31
Reasons of Non-ischemic FFR Despite an Apparently
Tight Stenosis
  • Physiologic explanations
  • Stenosis hemodynamically nonsignificant despite
    angiographic appearance
  • Small perfusion territory, old MI, little viable
    tissue, small vessel
  • Abundant collaterals
  • Severe microvascular disease (rarely affecting
    FFR)
  • Interpretable explanations
  • Other culprit lesion, diffuse disease not focal
    stenosis
  • Chest pain of noncardiac origin

32
  • Technical explanations
  • Insufficient hyperemia
  • Guiding catheter related pitfall (deep
    engagement, small ostium,sideholes)
  • Electrical drift
  • Actual false negative FFR
  • Acute phase of ST elevation myocardial infarction
  • Severe left ventricular hypertrophy
  • Exercise-induced spasm

33
When FFR???(value)
  • Borderline lesions
  • Evaluation of PCI
  • FFR after coronary intervention should
    preferably be higher than 0.90

34
Multicenter registry Europe-USA-Asia750 pat.
post-STENT FFR
death, infarction, or re-intervention at 6
mnths.
40
37
After stenting Inverse correlation between FFR
and event rate.
28
30
19
20
7
10
4
0
0.96-1.00
0.86-0.90
0.91-0.95
0.81-0.85
0.76-0.80
Post-STENT FFR
35
  • How does FFR works in complex coronary disease?
  • difficult anatomy, poorly visible lesions,
    overlap
  • multiple stenoses within one artery
  • diffuse disease
  • left main disease
  • multivessel disease

36
Male, 67, stable angina, positive exercise test
LCX
D 2
RCA
LAD
D 1
2 intermediate stenoses mid RCA
Complex lesion proximal LAD
37
LAD, hyperemia
Pa
Pa
100
Pd
Pd
FFR 92/98 0.94
0
38
DIAG 2, hyperemia
Pa
Pa
100
Pd
Pd
FFR 87/97 0.89
0
39
DIAG 1, hyperemia
Pa
Pa
Pd
100
Pd
FFR 87/96 0.90
0
40
RCA, hyperemia
Pa
100
Pd
0
FFR 38/92 0.41
41
Balloon 3.0 mm
42
After balloon inflation 3.0 balloon 12 atm
Pa
100
Pd
FFR 55/82 0.67
0
43
Stent 3.5 mm(mid-RCA)
44
Stent 3.5 mm(mid-RCA)
Pa
100
Pd
FFR 76/95 0.80
0
45
Pressure drop
Pull back pressure wire
46
Additional Stent 3.5 mm (prox-RCA)
47
Stent 3.5 mm(mid-RCA) Stent 3.5 mm(prox-RCA)
Pa
100
Pd
FFR 88/94 0.94
0
48
  • In this patient with complex coronary artery
    disease,
  • coronary pressure measurement
  • confirmed the appropriateness of stenting the
    RCA
  • while avoiding a riskful intervention of the
    LAD
  • or bypass surgery
  • Selected the correct spots in the RCA where to
    stent
  • evaluated the result of stenting.

49
  • How does FFR works in complex coronary
    disease?
  • difficult anatomy, poorly visible lesions,
    overlap
  • multiple stenoses within one artery
  • diffuse disease
  • left main disease
  • multi vessel disease

50
A
B
51
Coronary Pressure FFR Pull-Back Curve
Focal disease sudden changes in pressure
52
Coronary Pressure FFR Pull-Back Curve
Diffuse coronary disease gradual increase of
pressure.
53
FFR The Pressure Pull-back Curve
  • By slowly retrieving the pressure wire under
    fluoroscopy and sustained hyperemia
  • the individual contribution of every segment of
    the coronary system to the extent of disease can
    be studied and such spatial information cannot be
    obtained by any other method

54
  • How does FFR works in complex coronary
    disease?
  • difficult anatomy, poorly visible lesions,
    overlap
  • multiple stenoses within one artery
  • diffuse disease
  • long and ostial lesions
  • left main disease
  • multivessel disease

55
Decision making in equivocal left main coronary
artery disease by Fractional Flow Reserve
Bech et al, Heart 2001
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Conclusion
60
  • How does FFR works in complex coronary
    disease?
  • difficult anatomy, poorly visible lesions,
    overlap
  • multiple stenoses within one artery
  • diffuse disease
  • long and ostial lesions
  • left main disease
  • multivessel disease (FAME Study)

61
Evidence Based
  • DEFER STUDY
  • A Multicenter Randomized Study to Compare
    Deferral Versus Performance of PCI of
    Non-Ischemia-Producing Stenoses

62
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 Amsterdam Eindhoven Essen
Gothenborg Hamburg Liège
Maastricht Madrid Osaka
Rotterdam Seoul Utrecht
Zwolle
63
The DEFER Study Objectives
Primary objective
  • to test safety of deferring PCI of stenoses
  • not responsible for inducible ischemia as
  • indicated by FFR gt 0.75 ( outcome )
  • Secondary objective
  • to compare quality of life in such patients,
  • whether or not treated by PCI
  • (CCS-class, need for anti-anginal drugs)
  • (symptoms)

64
The DEFER Study Flow Chart
Patients scheduled for PCI without Proof of
Ischemia (n325)
Randomization
performance of PTCA (158)
performance of PTCA (158)
FFR ? 0.75 (91)
FFR ? 0.75 (90)
FFR lt 0.75 (76)
PTCA
No PTCA
PTCA
PERFORM Group
DEFER Group
REFERENCE Group
65
event free survival ()
100
75
78.8
72.7
64.4
Defer
50
p0.52
p0.03
Perform

p0.17
25
Reference (FFR lt 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
66
Cardiac Death And Acute MI After 5 Years
Plt 0.03

20
Plt 0.005
15.7
15
P0.20
10
7.9
5
3.3
0
DEFER PERFORM REFERENCE

FFR gt 0.75 FFR lt 0.75
67
Freedom From Chest Pain
100



80


60
40
20
0
baseline
1month
1 year
2 year
5 year
FFR gt 0.75 FFR gt 0.75
FFR lt 0.75
68
DEFER Summary
  • In patients with stable chest pain, the most
    important prognostic factor of a given
    coronary artery stenosis, is its ability of
    inducing myocardial ischemia (as reflected by FFR
    lt 0.75)
  • In those patients, clinical outcome of such
    ischemic stenosis, even when treated by PCI,
    is much worse than that of a functionally
    non-significant stenosis.
  • 3. The prognosis of non-ischemic stenosis (FFR
    gt 0.75) is excellent and the risk of such
    non-significant stenosis or plaque to cause
    death or AMI is lt 1 per year, and not decreased
    by stenting

69
DEFER
Conclusion Stenting a
non-ischemic stenosis does not benefit patients
with stable chest pain, neither in
prognostic nor symptomatic respect.
70
FAME study
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Study Population
  • The FAME study was designed to reflect daily
    practice in performing PCI in patients with
    multivessel disease
  • Inclusion criteria
  • ALL patients with multivessel disease
  • Stenoses 50 in 2 or 3 major epicardial
    coronary arteries, which are amenable for
    stenting.
  • Exclusion criteria
  • Left main disease or previous bypass surgery
  • Acute STEMI
  • Extremely tortuous or calcified coronary arteries

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74
PRIMARY ENDPOINT
  • Composite of death, myocardial infarction, or
    repeat revascularization (MACE) at 1 year

75
SECONDARY ENDPOINTS
  • Individual components of MACE at 1 year
  • Functional class
  • Use of anti-anginal drugs
  • Health-related quality of life (EuroQOL-5D)
  • Procedure time
  • Amount of contrast agent used during procedure
  • Cost of the procedure

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CONCLUSIONS (1)
  • 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

84
CONCLUSIONS (2)
  • Routine measurement of FFR during PCI with
    DES in patients with multivessel disease, when
    compared to current angiography guided strategy
  • Is cost-saving and does not prolong the
    procedure.
  • Reduces the number of stents used.
  • Decreases the amount of contrast agent used.
  • Results in a similar, if not better, functional
    status.

85
  • Routine measurement of FFR during PCI with DES
    supports the evolving paradigm of
  • Functionally Complete Revascularization
  • i.e. revascularization of ischemic lesions and
    medical treatment of non-ischemic ones.

86
FFR and Viability
  • Hibernating myocardium is defined as chronic,
    reversible left ventricular dysfunction due to
    CAD.
  • Several animal and human studies have shown that
    hibernating myocardium was characterized by a
    mismatch between flow and function a dyssynergy
    in the presence of a normal (or near normal)
    myocardial flow. Explaining the apparent paradox
    between severe contractile dysfunction in
    presence of normal flow.

87
  • Lee et al,. showed that dyssynergic myocardial
    segments with a contractile reserve had a lower
    flow reserve than normal segments but a
    significantly higher flow reserve than
    dyssynergic segments without contractile reserve.
  • The relationship between hibernating myocardium
    and fraction flow reserve can be summarized as
    follows
  • (a) resting flow is normal,
  • (b) flow reserve is reduced,
  • (c) the higher flow reserve (but within the
    abnormal range), the
    higher the
    likelyhood and the extent of viability.

88
  • Practically, in a patient with an epicardial
    stenosis and a dyssynergy at left ventricular
    angiogram, it is reasonable to state that
  • a high FFR suggest the absence of
    reversible ischemia.

89
Cost-effectiveness issue
  • compare the long-term costs and benefits
    of 3 strategies for treating patients with an
    intermediate coronary lesion and no prior
    functional study
  • 1) deferring the decision for (PCI) to obtain a
    nuclear stress imaging study (NUC strategy)
  • 2) measuring fractional flow reserve (FFR) at
    the time of angiography to help guide the
    decision for PCI (FFR strategy)
  • 3) stenting all intermediate lesions (STENT
    strategy).

90
  • RESULTS
  • The FFR strategy saved 1795 per patient
    compared with the NUC strategy and 3830
    compared with the STENT strategy.
  • Quality-adjusted life expectancy was similar
    among the 3 strategies .

91
  • CONCLUSION
  • In patients with an intermediate coronary
    lesion and no prior functional study,
  • measuring FFR to guide the decision to
    perform PCI may lead to
  • significant cost savings
  • compared with performing nuclear stress imaging
    or with simply stenting lesions in all patients.

92
  • Again.......Should this lesion be stented ??

93
FFR
IVUS
Thank You
If you want to treat a lesion, use IVUS if you
want to treat it correctly, use FFR.
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