Dia 1

1


CORONARY PHYSIOLOGY IN THE CATHLAB
LONG-TERM CLINICAL OUTCOME OF MILD CORONARY
STENOSIS
Educational Training Program ESC
European Heart House, Nice, April 19th 21st ,
2007

Nico H.J. Pijls, MD, PhD, Catharina Hospital,
Eindhoven, The Netherlands
2
NOTE

• Any treatment in health care should be directed
• either to
• Releave symptoms ( improve functional class )
• or to
• Improve outcome ( prognosis, longevity)
• No other justification for any treatment is
  possible !

3
DEFER study background (1)

• In patients with coronary artery disease,
• the most important factor with respect to both
• functional class (symptoms)
• and prognosis (outcome)
• Is the presence and extent of inducible ischemia
• (many invasive non-invasive studies in gt
  100,000 patients)

If a stenosis is responsible for reversible
ischemia, revascularization improves
symptoms (if present) and outcome..
4
Is it useful to revascularize hemodynamically
significant stenosis ? (ACIP study)
558 patients , functionally significant
stenosis without symptoms randomization in 3
treatments strategies
8
Cumulative Mortality

6.6
6
No treatment
4
P lt 0.05
2
1.1
Revascularization
0
0 4 8 12
16 20 24 mos
Davies et al, Circulation, 1997
5
DEFER study background (2)
If a stenosis is responsible for reversible
ischemia, revascularization is
justified But what if a stenosis or
plaque is NOT responsible for reversible
ischemia ? (functionally non-significant ,
non-culprit)
PCI is often performed in such lesions, yet the
benefit of such treatment is not clear
6

• female, 58-y-old
• underwent PCI of severe LCX lesion a minute
  before
• 50 stenosis in mid RCA

Should this lesion be stented ??
7
The DEFER Study Background (3)

• The incidence of coronary lesions
• increases with age. About 40 of
• all 60-year-old healthy persons
• have one or more plaques ,
• non-significant , or equivocal stenoses
• (50-70 by angiography) in
• their coronary arteries.

8
Cardiac Death Myocardial Infarction Rates at
9-12 Months after (DES)-stenting
3.8
DES BMS
SIRIUS
3.7
4.9
DES BMS
TAXUS IV
4.9
ENDEAVOR
DES BMS
4.7
4.1
0
2
4
6
8
DES stenting is not harmless !!
9
DEFER study background (4)

• Fractional Flow Reserve, calculated from
• coronary pressure measurement, is an accurate,
  
• invasive, and lesion-specific index to
  demonstrate
• or exclude whether a particular coronary
  stenosis
• can cause reversible ischemia.
• FFR can be determined easily, in the cath-lab,
• immediately prior to a planned intervention

FFR based strategy for PCI in equivocal
stenosis ( DEFER Study)
10
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
data collection analysis Jan Willem Bech, MD,
PhD Pepijn van Schaardenburgh, MD
11
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)

12
The DEFER Study Flow Chart
Patients scheduled for PCI without Proof of
Ischemia (n325)
Randomization
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
13
THE DEFER STUDY RANDOMIZATION
deferral of PCI performance of PCI
1 1 randomization
If FFR lt 0.75 performance anyway
reference group If
FFR gt 0.75 randomization followed
defer PCI
perform PCI
14
The DEFER Study Catheterization

• 6 or 7 F guiding catheter for measurement of
• aortic pressure ( Pa)
• QCA from 2 orthogonal views
• Coronary pressure measurement (Pd ) by
• 0.014 pressure wire (Radi Medical Systems)
• Maximum hyperemia by i.v. adenosine (140
  ug/kg/min)
• Calculation of Fractional Flow Reserve by

FFR Pd / Pa
15
The DEFER Study Base line data
Randomized to Randomized to
Deferral of PTCA Performance of PTCA
N167 N158
Age, (yr) 62?9 63?10 Female sex ()
29 29 Ejection Fraction () 67?10
68?9
16
The DEFER Study Baseline QCA and FFR
All baseline characteristics were identical
between both groups
17
The DEFER Study Diameter Stenosis versus FFR
18
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
19
DEFER Clinical Outcome at 5 Years
FFRlt0.75
FFR 0.75
Reference
Perform
Defer
144
90
91
Number of patients
Lost to follow-up 1
2 10
8 (6.0)
2 (2.3)
3 (3.3)
Cardiac Death()
4 (3.0)
3 (3.4)
3 (3.3)
Non Cardiac Death()
6 (4.5)
4 (4.5)
0
Q wave MI ()
7 (5.2)
1 (1.1)
0
Non-Q wave MI()
14 (10.4)
4 (4.5)
1 (1.1)
CABG()
18 (13.4)
8 (9.1)
8 (8.9)
TLR()
2 (1.5)
1 (1.1)
0
Other ()
70
29
21
Total events
72
58
68
Pts free of angina()
20
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
21
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
22
DEFER Summary and Conclusions (1)

• 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

23
DEFER Summary and Conclusions (2)
Message Stenting an ischemic lesion
makes sense because it improves symptoms and
often also outcome. Stenting a
non-ischemic stenosis has no benefit compared
to medical treatment, neither in prognostic nor
symptomatic respect.
programm of tomorrow
Importance of FFR
24
(No Transcript)
25
Complete vs Incomplete Revascularization
What was wrong the wrong concept in the (mostly
retrospective) studies performed so far ?!
e.g. ARTS-studies 30 incomplete
revascularization, but. arbitrary choice of
no revascularization, or even worse no
revascularization because of technical
difficulties ? considerable number of the
non-revascularized lesions were ischemic
lesions Whereas among the treated lesions, quite
a bit of non-ischemic lesions must have been
stented
26
Complete vs Incomplete Revascularization
What was wrong the wrong concept in the (mostly
retrospective) studies performed so far ?!
e.g. ARTS-studies 30 incomplete
revascularization, but. arbitrary choice of
no revascularization, or even worse no
revascularization because of technical
difficulties ? considerable number of the
non-revascularized lesions were ischemic
lesions Whereas among the treated lesions, quite
a bit of non-ischemic lesions must have been
stented
27
DEFER Summary and Conclusions

• 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 these 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
• Conclusion
• Stenting a non-significant stenosis does not
  benefit patients with
• stable chest pain, neither in prognostic nor
  symptomatic respect

28
event free survival ()
100
75.8
75
64.4
50
³
FFR
0.75
p0.03

FFR lt 0.75
25
0
0
1
2
3
4
5
Years of Follow-up
29
The risk for death or acute myocardial infarction
in the next five years is 20 times higher for an
ischemic lesion compared to a non-ischemic lesion
!!!
8
12000 Patients ( 2 x 6000) similar
stenosis severity by coronary angio
7
7.4
6
5
4
death or Acute MI
3
2
1
0.6
0

no ischemia ischemia

Iskander S, Iskandrian A E JACC 1998
30
The DEFER Study Objectives
Simply stated Ischemia - guided PCI
strategy versus
stent m all strategy In single vessel
disease
With respect to outcome (adeverse events) ,
quality of life
cost-efectiveness
31
(No Transcript)
32
DEFER Clinical Outcome at 5 Years
Cardiac death and Acute Myoc Infarction
FFR lt 0.75
FFR 0.75
Reference
Perform
Defer
3.3 7.9 15.7

P 0.20
P lt 0.003
P lt 0.005
33
Death Myocardial Infarction Rates at 9-12 Months
SIRIUS DES
BMS

3.8
(9 months)
3.7
TAXUS IV DES
BMS

4.9
(9 months)
4.9
ENDEAVOR DES BMS
4.7
(9 months)
4.1
DEFER ALL PCI
(BMS)
5.1
(12 months)
0
2
4
6
8
34
Death Myocardial Infarction Rates at 9-12 Months
SIRIUS DES
BMS

3.8
(9 months)
3.7
TAXUS IV DES
BMS

4.9
(9 months)
4.9
ENDEAVOR DES BMS
4.7
(9 months)
4.1
DEFER FFRlt0.75
7.6
(12 months)
perform
2.7
FFR0.75
defer
1.1
0
2
4
6
8