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Noninvasive testing:
still needed?
ETP on FFR 2013
European Heart House
Oliver Gaemperli, MDInterventional Cardiology and Cardiac Imaging
University Hospital Zurich
Switzerland
Disclosures
• Speaker honoraria:
- Astra Zeneca, Abbott Vascular, GE Healthcare, Guerbet
• Research grant:
- Abbott Vascular
2013 ETP, European Heart House, Sophia-Antipolis, France, Page 2
Evolution in the concept of ischemia-guided
coronary revascularization:from the early 80’s to the present time
The «patient-based»
approach
Predominant form of revasc:
CABG
The «vessel-based»
approach
0.7 1.0
2.9
4.8
6.76.3
1.8
3.73.3
2.0
0
2
4
6
8
10
0% 1-5% 5-10% 11-20% >20%
Medical Revasc
Predominant form of revasc:
CABG+PCI
The «lesion-based»
approach
Predominant form of revasc:
PCI
2013 ETP, European Heart House, Sophia-Antipolis, France, Page 3
Controversial issues in stable CAD patients
• Which functional technique is better for assessing flow-
limiting coronary artery disease? FFR or noninvasive
imaging?
• Among noninvasive imaging, which technique is the most
accurate? SPECT? CMR? PET? CT? Stress Echo?
• How to implement noninvasive imaging techniques in
diagnostic algorithms with FFR?
• Is noninvasive imaging outdated in the era of FFR?
2013 ETP, European Heart House, Sophia-Antipolis, France, Page 4
Duality of Coronary morphology and function
Two faces of the same disease
White CW. NEJM 1984Intraoperative Doppler flow
Uren NG. NEJM 199415O-H2O PET
Tonino PA et al. JACC 2010Fractional flow reserve
„different techniques... ...same results“
2013 ETP, European Heart House, Sophia-Antipolis, France, Page 7
Coronary Stenosis ≠ Myocardial Ischemia
Lesions-specific factorsFactors that affect
myocardial blood flow
Severity of
diameter
stenosis
Lesion length
Reference vessel
diameter
Lesion
morphologyEccentricity
Plaque burden
and plaque
rupture
Viscous friction,
flow separation,
turbulence and
eddies
Surface
roughness
Collaterals
Microvascular
Resistance
The functional significance of coronary lesions is determined by many factors
2013 ETP, European Heart House, Sophia-Antipolis, France, Page 8
Prognostic role of perfusion imaging (SPECT)
7,4%
0
2
4
6
8
10
SPECT
Normal Abnormal
n>12.000, 14 studies
p<0,001
Iskander, JACC 1998; 32: 57-62
0,6% Follow-Up
2-3 years
2013 ETP, European Heart House, Sophia-Antipolis, France, Page 9
Survival benefit in patients undergoing revascularisation
compared to medical treatment based on the presence
and magnitude of ischemia
Medical
Revasc
0
1
2
3
4
5
6
0 12.5 25 37.5 50
% Total Myocardium Ischemic
log
Ha
za
rd R
ati
op<0.001
10%
10627 pts No Prior MI
Short term Follow up: 1.9 yrs
Hachamovitch et al. Circulation. 2003;107:2900
0.7 1.0
2.9
4.8
6.76.3
1.8
3.73.3
2.0
0
2
4
6
8
10
0% 1-5% 5-10% 11-20% >20%
Medical Revasc
% Total Myocardium Ischemic
Card
iac
dea
th r
ate
(%
)
2013 ETP, European Heart House, Sophia-Antipolis, France, Page 11
The role of coronary morphology and function in
treatment of stable CAD patients
The COURAGE study and COURAGE Nuclear substudy
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
1.5 2 2.5 3 3.5 4 4.5 5
Time to Follow-up (Years)
Cu
mu
lati
ve E
ven
t-fr
ee S
urv
ival
≥5% Ischemia Reduction (n=68)
<5% Ischemia Reduction (n=37)
Unadjusted p=0.001
Risk-Adjusted p=0.082
Years0 1 2 3 4 5 6
0.0
0.5
0.6
0.7
0.8
0.9
1.0
PCI + OMT
Optimal Medical
Therapy (OMT)
Hazard ratio: 1.05
95% CI (0.87-1.27)
P = 0.62
7
Su
rviv
al
free
of
dea
th
Circulation 2008;117
2013 ETP, European Heart House, Sophia-Antipolis, France, Page 12
MPS + selective
angiographyn=1,981
0% 20% 40% 60% 80% 100%
33 4224
2443 34Direct
angiographyn=5,423
Shaw LJ et al.
JACC 1999;33:661-9
Groups matched for pretest likelihood
Economic consequences of Available Diagnostic StrategiesThe Economics of Noninvasive Diagnosis (END) Multicenter study
0
1000
2000
3000
4000
5000
6000
Low Int High Low Int High
Diagnostic Cost Follow-Up Cost
Pretest clinical risk Pretest clinical risk
N= 813 2,928 1,682 816 3,379 1,631
Direct
angiography
MPS +
selective
angiography
US$
$2,900
$4,200$4,800
$2,000$2,400
$2,800
No CAD
1-V-CAD
MVD
2013 ETP, European Heart House, Sophia-Antipolis, France, Page 14
How does FFR compare to noninvasive imaging of perfusion (SPECT)
Concordance between MPI and FFR is quite poor!*
In 42% of patients there was concordance between FFR and MPI
In 36% of patients MPI underestimated the number of ischemic territories
In 22% of patients MPI overestimated the number of ischemic territoris
*Concordance was better if no or only 1
territory were ischemic by FFR
Per patient
Per vessel
Melikian et al. J Am Coll Cardiol Intv 2010;3:307–14
2013 ETP, European Heart House, Sophia-Antipolis, France, Page 15
Validation of FFR
Ref N Population Ref method Threshold
De Bruyne et al.
Circ 1985
60 1-VD Bicycle ECG 0.72*
Pijls et al.
Circ 1995
60 1-VD, pre+post PCI Bicycle ECG 0.74*
Pijls et al.
NEJM 1996
45 1-VD, intermediate
Stenoses
Bicycle ECG + Tl
SPECT + Stress
Echo†
0.75*
Bartunek et al.
JACC 1996
75 1-VD Stress Echo 0.78*
Chalumeau et al.
JACC 2000
127 MVD MIBI SPECT 0.74**
Abe et al.
Circ 2000
46 1-VD Tl SPECT 0.75*
De Bruyne et al.
Circ 2001
57 Post MI MIBI SPECT 0.75 – 0.80*
* 100% specificity; ** Optimal cut-off value, † With reversibility after revasc
2013 ETP, European Heart House, Sophia-Antipolis, France, Page 17
Epicardial arteries
(3.5-1mm)
Perforating branches
(>400μm)
Arterioles
(100-400μm) Capillaries
Epicardial Conduit Microvasculature
FFR
Functional noninvasive imaging
Fundamental differences between FFR and functional noninvasive imaging
2013 ETP, European Heart House, Sophia-Antipolis, France, Page 18
Conceptual Plot of CFR and FFR regions
Johnson & Gould. JACC Cardiovasc Imaging 2012
2013 ETP, European Heart House, Sophia-Antipolis, France, Page 19
Discordant CFR (noninvasive perfusion) and FFR results:
• reflect divergent extremes of focal (epicardial)
versus diffuse (macro +microvascular) disease
• Reflect clinically relevant basic coronary
pathophysiology, not methodology
2013 ETP, European Heart House, Sophia-Antipolis, France, Page 20
Possible algorithm integrating noninvasive imaging and FFR
Patient with suspected or known CAD
Noninvasive (anatomo-)functional Imaging
Ischemia + Ischemia -
Angio + FFR
Ischemia underestimated
by Imaging
Ischemia confirmed by FFR
Ischemia overestimated by
Imaging
«GATEKEEPER» Patient risk
«FINETUNING» »lesion risk»
Treat accordingly; Decide on optimal revasc based
on FFR («functional SYNTAX score?»)
Consider Microvascular
dysfunction
Treat conservatively
*High-risk nonperfusion variables:
High CACSTIDReduced post-stress EFReduced CFR
2013 ETP, European Heart House, Sophia-Antipolis, France, Page 22
The role of cardiac imaging in the FFR era
• Ischemia testing is crucial for the appropriate management of stable
CAD patients
• Cardiac noninvasive functional imaging is a (cost-)effective
gatekeeper of invasive angiography in patients with stable CAD
• Perfusion imaging (ideally with assessment of CFR) and FFR are not
competing techniques, but complementary methodologies to assess
a varying spectrum of focal epicardial versus diffuse (macro- and
microvascular) disease in CAD patients, and to decide on the most
appropriate treatment strategy (medical versus revascularization)
2013 ETP on FFR, European Heart House, Nizza, Page 23
Thank You
PD Dr. med. Oliver GaemperliInterventional Cardiology and Cardiac Imaging
Cardiovascular Center,
University Hospital Zurich,
Switzerland