FFR Going Beyond Angiography

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FFR Going Beyond Angiography

• By
• Amr El Nagar

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• Should this lesion be stented ??

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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

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Coronary Blood Flow vs Percent Diameter
StenosisAutoregulationAutoregulation
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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.

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Physiology to Address Clinical Questions in the
Cath Lab
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FFR

• What ??????????????
• Why???????????????
• How??????????????
• When?????????????

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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
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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)

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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
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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.

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Limitations of Anatomic Techniques
- Underestimates diffuse disease - Large Intra-
and inter-observer variability - Not designed to
assesses physiologic lesion significance
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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

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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

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How????Technique!!!!
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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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Equipments
RADI ANALYZER
PRESSURE WIRE
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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
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• blood pressure distal to the lesion being
  assessed - Pressure distal (Pd)
• conventional pressure transducer - measures
  arterial/aortic pressure - Pressure arterial (Pa)
  

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• 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.

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• 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
•  

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• 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

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

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

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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

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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

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• 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

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When FFR???(value)

• Borderline lesions
• Evaluation of PCI
• FFR after coronary intervention should
  preferably be higher than 0.90

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Multicenter registry Europe-USA-Asia750 pat.
post-STENT FFR
death, infarction, or re-intervention at 6
mnths.
40
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After stenting Inverse correlation between FFR
and event rate.
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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
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• 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

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Male, 67, stable angina, positive exercise test
LCX
D 2
RCA
LAD
D 1
2 intermediate stenoses mid RCA
Complex lesion proximal LAD
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LAD, hyperemia
Pa
Pa
100
Pd
Pd
FFR 92/98 0.94
0
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DIAG 2, hyperemia
Pa
Pa
100
Pd
Pd
FFR 87/97 0.89
0
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DIAG 1, hyperemia
Pa
Pa
Pd
100
Pd
FFR 87/96 0.90
0
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RCA, hyperemia
Pa
100
Pd
0
FFR 38/92 0.41
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Balloon 3.0 mm
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After balloon inflation 3.0 balloon 12 atm
Pa
100
Pd
FFR 55/82 0.67
0
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Stent 3.5 mm(mid-RCA)
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Stent 3.5 mm(mid-RCA)
Pa
100
Pd
FFR 76/95 0.80
0
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Pressure drop
Pull back pressure wire
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Additional Stent 3.5 mm (prox-RCA)
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Stent 3.5 mm(mid-RCA) Stent 3.5 mm(prox-RCA)
Pa
100
Pd
FFR 88/94 0.94
0
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• 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.

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• 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

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A
B
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Coronary Pressure FFR Pull-Back Curve
Focal disease sudden changes in pressure
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Coronary Pressure FFR Pull-Back Curve
Diffuse coronary disease gradual increase of
pressure.
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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

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• 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

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Decision making in equivocal left main coronary
artery disease by Fractional Flow Reserve
Bech et al, Heart 2001
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Conclusion
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• 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)

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Evidence Based

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

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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
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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)

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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
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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
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Cardiac Death And Acute MI After 5 Years
Plt 0.03

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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
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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
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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

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DEFER
Conclusion Stenting a
non-ischemic stenosis does not benefit patients
with stable chest pain, neither in
prognostic nor symptomatic respect.
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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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PRIMARY ENDPOINT

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

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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

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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.

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• 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.

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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.

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• 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.

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• 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.

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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).

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• 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 .

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• 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.

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

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