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Does Myocardial Viability PredictImprovement With Revascularization?
Robert O. Bonow, MD, MS, MACC
No Relationships to Disclose
Northwestern University Feinberg School of MedicineBluhm Cardiovascular Institute
Northwestern Memorial Hospital
Editor-in-Chief, JAMA Cardiology
Does Myocardial Viability PredictImprovement in LV Function?
Improvement in Survival?
Robert O. Bonow, MD, MS, MACC
No Relationships to Disclose
Northwestern University Feinberg School of MedicineBluhm Cardiovascular Institute
Northwestern Memorial Hospital
Editor-in-Chief, JAMA Cardiology
Improvement in Survival?
Have the results of the STICH trialchanged your practice regardingviability assessment?
a. Yesb. No
• LV dysfunction in patients with CAD is notalways an irreversible process, as LV functionmay improve substantially after CABG
BeforeCABGb. No
c. UncertainCABG
Shah et al.JA M A 2013;309:909-918
Have the results of the STICH trialchanged your practice regardingviability assessment?
a. Yesb. No
• LV dysfunction in patients with CAD is notalways an irreversible process, as LV functionmay improve substantially after CABG
BeforeCABGb. No
c. UncertainCABG
AfterCABG
Shah et al.JA M A 2013;309:909-918
CABG in Patients with LV Dysfunction
Bonow and DilsizianA m JC ard iol1995;75:17-25
Elefteriades et al.JA m C ollC ard iol1993;22:1411-1417
Have the results of the STICH trialchanged your practice regardingviability assessment?
a. Yesb. No
• Assessment of myocardial viability is oftenused to predict improvement in LV functionafter CABG and thus select patients for CABG
• SPECT to assess membrane integrity• Dobutamine echo for contractile reserve• PET to assess myocardial metabolism
b. Noc. Uncertain
• PET to assess myocardial metabolism• Cardiac MRI to assess myocardial fibrosis
Have the results of the STICH trialchanged your practice regardingviability assessment?
a. Yesb. No
• Assessment of myocardial viability is oftenused to predict improvement in LV functionafter CABG and thus select patients for CABG
• SPECT to assess membrane integrity• Dobutamine echo for contractile reserve• PET to assess myocardial metabolism
b. Noc. Uncertain
• Numerous studies have suggested thatidentification of viable myocardium alsopredicts im proved su rvivalafter CABG
• PET to assess myocardial metabolism• Cardiac MRI to assess myocardial fibrosis
Myocardial Viability and Improved Survival
10
15
2020
10
Mo
rta
lity
Ra
te(%
/ye
ar)
16.0
7.7
Revas c u larization
M ed ic al
24 studiesn=3088EF=32.9%
15
0
5
1010
5
0
Mo
rta
lity
Ra
te(%
/ye
ar)
Allman et al, JA m C ollC ard iol2002;39:1151-1158
Viable Non-Viable
3.2
7.76.2
n=748 n=557 n=330 n=734
Myocardial Viability and Improved Survival
10
15
2020
15
10
Mo
rta
lity
Ra
te(%
/ye
ar)
16.0
7.7
Revas c u larization
M ed ic al
p<0.001
24 studiesn=3088EF=32.9%
0
5
1010
5
0
Mo
rta
lity
Ra
te(%
/ye
ar)
Viable Non-Viable
3.2
7.76.2
Allman et al, JA m C ollC ard iol2002;39:1151-1158
n=748 n=557 n=330 n=734
Myocardial Viability and Improved Survival
10
15
2020
15
10
Mo
rta
lity
Ra
te(%
/ye
ar)
16.0
7.7
Revas c u larization
M ed ic al
24 studiesn=3088EF=32.9%
p=NS
0
5
1010
5
0
Mo
rta
lity
Ra
te(%
/ye
ar)
Viable Non-Viable
3.2
7.76.2
Allman et al, JA m C ollC ard iol2002;39:1151-1158
n=748 n=557 n=330 n=734
Myocardial Viability and Improved Survival
10
15
2020
15
10
Mo
rta
lity
Ra
te(%
/ye
ar)
10.8
7.7
9.5
Revas c u larization
M ed ic al
28 studiesn=3531EF=31.5%
0
5
1010
5
0
Mo
rta
lity
Ra
te(%
/ye
ar)
from Schinkel et al, C u rrP rob C ard iol2007;32:375-410
Viable Non-Viable
3.5
7.7
n=955 n=854 n=778 n=944
Myocardial Viability and Improved Survival
10
15
2020
15
10
Mo
rta
lity
Ra
te(%
/ye
ar)
10.6
8.5
11.7
Revas c u larization
M ed ic al
13 studiesn=2433EF=29.9%
0
5
1010
5
0
Mo
rta
lity
Ra
te(%
/ye
ar)
from Camici et al, C irc u lation 2008;117:103-114
Viable Non-Viable
3.7
8.5
n=595n=699 n=423 n=500
Limitations of Cohort Studies
• Retrospective
• Heterogeneous methodology
• Decision for CABG may have beeninfluenced by viability statusinfluenced by viability status
• No (or inadequate) adjustment for keybaseline variables (age, comorbidities)
• Cohort studies carried out before modernaggressive medical therapy
• Cleland et al. L anc et2003:362:14-21
• Bello et al. C irc u lation 2003;108:1945-1953Contrast CMR
Medical therapy also improves LV function inpatients with hibernating myocardium…especially beta-blocker therapy
SPECT
• Seghatol et al. A m JC ard iol2004;93:854-859Dobutamine Echo
Surgical Treatment for Ischemic Heart Failure
S TIC H Viability S tu d yS TIC H Viability S tu d y
• 1212 patients with EF <35%
• 601 patients with viability studies
• Primary Endpoint:
All-cause mortality
• Secondary Endpoints:
CV mortality
Death + CV hospitalization
STICH OutcomeMyocardial Viability and Mortality
0.8
0.6
0.4
CV
Mo
rtali
tyR
ate
HR 95% CI
0.63 0.47 0.85
P = 0.002
Without viability
With viability
Without Viability
50%
33%
Bonow et al. N EnglJM ed 2011;364:1617-1635
0.2
0
CV
Mo
rtali
tyR
ate
0 1 2 3 4 5 6
Years After Randomization
With Viability
STICH OutcomeMyocardial Viability and Mortality
0.8
0.6
0.4
CV
Mo
rtali
tyR
ate
HR 95% CI
0.63 0.47 0.85
P = 0.002
Without viability
With viability
Without Viability
50%
33%
Chi-square P
Clinical risk score 33.26 <0.001
LV ejection fraction 24.80 <0.001
LV EDVI 35.36 <0.001
LV ESVI 33.90 <0.001
Myocardial viability 8.54 0.003
Variables associated with mortality
Bonow et al. N EnglJM ed 2011;364:1617-1635
0.2
0
CV
Mo
rtali
tyR
ate
0 1 2 3 4 5 6
Years After Randomization
With Viability
STICH OutcomeMyocardial Viability and Mortality
0.8
0.6
0.4
CV
Mo
rtali
tyR
ate
HR 95% CI
0.63 0.47 0.85
P = 0.002
Without viability
With viability
Without Viability
50%
33%
Chi-square P value
Univariate 8.54 0.003
Multivariable 1.57 0.210
Myocardial viability
Bonow et al. N EnglJM ed 2011;364:1617-1635
0.2
0
CV
Mo
rtali
tyR
ate
0 1 2 3 4 5 6
Years After Randomization
With Viability
STICH OutcomeMyocardial Viability and Mortality
Without Viability With Viability
MED (33 deaths)
CABG (25 deaths)
MED (95 deaths)
CABG (83 deaths)
0.8
0.6
0.4
Mo
rtality
Rate
0.56
0.42
0.35
Bonow et al. N EnglJM ed 2011;364:1617-1635
0.2
00 1 2 3 4 5 6 0 1 2 3 4 5 6
Years Following Randomization Years Following Randomization
0.31
STICH OutcomeMyocardial Viability and Mortality
Without Viability With Viability
MED (33 deaths)
CABG (25 deaths)
MED (95 deaths)
CABG (83 deaths)
0.8
0.6
0.4
Mo
rtality
Rate
0.56
0.42
0.35
38%
Bonow et al. N EnglJM ed 2011;364:1617-1635
0.2
00 1 2 3 4 5 6 0 1 2 3 4 5 6
Years Following Randomization Years Following RandomizationSubgroup
Without viability
With viability
N
114
487
Deaths
58
178
HR
0.70
0.86
95% CI
0.41, 1.18
0.64, 1.16
InteractionP value
0.528
0.25 0.5 1.0 2.0CABGbetter
MEDbetter
0.31
20
25
30
35
40
45
50
LVE
jectio
nF
ractio
n(p
erc
en
t)
50
40
30
20
32.9%31.5%
26.7%29.9%
0
5
10
15
20
LVE
jectio
nF
ractio
n(p
erc
en
t)
Allman
20
1010
0Schinkel Camici STICH
n=3088 n=3531 n=2433 n=601
Allman et al, JA m C ollC ard iol2002;39:1151-1158Schinkel et al. C u rrP rob C ard iol2007;32:375-410
Camici et al. C irc u lation 2008;117:103-114Bonow et al. N Engl J Med 2011;364:1617-1625
10
15
20
Mo
rta
lity
Ra
te(%
/ye
ar)
20
15
10
16%
10.8%
7.1%
10.1%
Medical Therapy in Patients with Viable Myocardium
0
5
Mo
rta
lity
Ra
te(%
/ye
ar)
Allman
5
0Schinkel Camici STICH
7.1%
n=557 n=854 n=595 n=243
Allman et al, JA m C ollC ard iol2002;39:1151-1158Schinkel et al. C u rrP rob C ard iol2007;32:375-410
Camici et al. C irc u lation 2008;117:103-114Bonow et al. N Engl J Med 2011;364:1617-1625
Fang JC. N EnglJM ed 2011;364:1671-1673
STICH Trial in Context
Criticism of STICH:
STICH did not use PET imaging
STICH Trial in Context
Would PET yield different results?
0
-20
--4040
--60
-5.1%
-30.1%
-17.3%
-2.6%
-42.8%
-11.1%
-40.5%
Re
du
ctio
nin
Mo
rta
lity
Ra
te(%
)
Myocardial Viability and Improved Survival
Allman et al, JA m C ollC ard iol2002;39:1151-1158
-80
-100
-120
-98.7%
-77.6%
FDG PET SPECT EchoEF 35% (23-45%) EF 33% (27-46%) EF 30% (25-35%)
Re
du
ctio
nin
Mo
rta
lity
Ra
te(%
)
100
Outcome After PET versus SPECT Imaging
100
Fre
eS
urv
ival(%
)
0
20
40
60
80
0 1 2 3
from Siebelink et al, JA m C ollC ard iol2001;37:81-88
n=49p=NS
80
60
40
20
000
Months After Randomization
Event-
Fre
eS
urv
ival(%
)
PET (n=49)
SPECT (n=54)
355 10 15 20 25 30
100
PARR2: PET-Guided vs Standard Care
p=NS
EF=27±8%100
Fre
e(p
erc
ent)
0
20
40
60
80
0 1 2 3 4
p=NS
from Beanlands et al, JA m C ollC ard iol2007;50:2002-2012
80
60
40
20
00 100 200
Time (days)
Event-
Fre
e(p
erc
ent)
Standard care (n=212)
PET-guided care (n=218)
25015050 300 350
100
Fre
eS
urv
ival(p
erc
en
t)100
90
80
70
60
50
Even
t-F
ree
Su
rviv
al(p
erc
en
t)
MT
ER
ER
MT
A. Hibernating myocardium = 5% B. Hibernating myocardium = 10%
0 200 400 600 800 1000 10008006004002000
Time (days) Time (days)
90
80
70
60
50
Even
t-F
ree
Su
rviv
al(p
erc
en
t)
ER
MT
ER
MT
from Ling et al, C irc C ard iovasc Im aging 2013;6:363-372
D. Hibernating myocardium = 20%C. Hibernating myocardium = 15%
STICH OutcomeMyocardial Viability and Mortality
Without Viability With Viability
MED (33 deaths)
CABG (25 deaths)
MED (95 deaths)
CABG (83 deaths)
0.8
0.6
0.4
Mo
rtality
Rate
0.56
0.42
0.35
Bonow et al. N EnglJM ed 2011;364:1617-1635
0.2
00 1 2 3 4 5 6 0 1 2 3 4 5 6
Years Following Randomization Years Following Randomization
0.31
STICH Trial in Context
Are the STICH Trial results unique?
100
Survival After Coronary Artery Bypass Surgery
100
0
20
40
60
80
0 1 2 3
from Samady et al, C irc u lation 1999;100:1298-1304
n=104p=NS
80
60
40
20
00 2 4
Time After CABG (years)
Surv
ival(p
erc
ent)
Increase EF (n=68)
No increase EF (n=36)
531 6 7
100
Survival After Coronary Artery Bypass Surgery
100
0
20
40
60
80
0 1 2 3
from Samady et al, C irc u lation 1999;100:1298-1304
n=104p=NS
80
60
40
20
00 2 4
Time After CABG (years)
Surv
ival(p
erc
ent)
Increase EF (n=68)
No increase EF (n=36)
531 6 7
39%24%
24% 23%
LVEF
Preop Postop
100
Revascularization vs Medical Therapyin Patients with Myocardial Viability
p=NS
n=138100
0
20
40
60
80
0 1 2 3 4
p=NS
from Cleland et al, Eu rJH eartFail2011;13:227-233
80
60
40
20
00 2 4
Time (years)
Surv
ival(p
erc
ent)
Revascularization (n=69)
Medical therapy (n=69)
531
800
Revascularization vs Medical Therapyin Patients with Left Ventricular Dysfunction
p=NS
n=30680
0
200
400
600
0 1 2 3 4
p=NS
from Tarakji et al, C irc u lation 2006;113:230-237
0 20 40
Amount of Compromised Viable Myocardium (%)
3-Y
ear
Mort
altiy
(%)
503010
60
40
20
0
Medical
Revascularization
STICH Trial in ContextViability Testing: Alive and Well
Viability testing does identify high risk patientsubgroups and is associated with:
• Outcome with evidence-based medical therapy
• Outcome with revascularization• Outcome with revascularization
STICH Trial in ContextViability Testing: Alive and Well
Viability testing does identify high risk patientsubgroups and is associated with:
• Outcome with evidence-based medical therapy
• Outcome with revascularization• Outcome with revascularization
… bu td oes notind epend ently pred ic ts u rvivalbenefitfrom revas c u larization
STICH Trial in ContextViability Testing: Alive and Well
Viability testing does identify high risk patientsubgroups and is associated with:
• Outcome with evidence-based medical therapy
• Outcome with revascularization• Outcome with revascularization
… bu td oes notind epend ently pred ic ts u rvivalbenefitfrom revas c u larization
Viability testing should not be considered aprerequ isite for decisions regarding medicalversus surgical management in patients withischemic LV dysfunction
STICH Primary OutcomeAll-Cause Mortality
0.8
0.6
0.4
Mo
rtali
tyR
ate
Medical therapy
CABG
Medical therapy
1212 patients
EF <35%
Velazquez et al. N EnglJM ed 2011;364:1607-1616
0.2
0
Mo
rtali
tyR
ate
0 2 4 10
Years After Randomization
P = 0.123
6 8
CABG
HR 95% CI
0.86 0.72 1.04
STICH Primary OutcomeAll-Cause Mortality
0.8
0.6
0.4
Mo
rtali
tyR
ate
HR 95% CI
0.86 0.72.1.04
Medical therapy
CABG
1212 patients
EF <35%
Medical therapy
0.2
0
Mo
rtali
tyR
ate
0 2 4 10
Years After Randomization
6 8
CABG
Velazquez et al. N EnglJM ed 2016;374:1511-1520
HR 95% CI
0.84 0.73 0.97
P = 0.020
STICH Trial in Context
Would CMR yield different results?
100
CMR Viability and Survival
p=0.006100
0
20
40
60
80
0 1 2 3 4
from Gerber et al, JA m C ollC ard iol2012;59:825-35
EF=24±7%
80
60
40
20
00
Time (years)
Surv
ival(p
erc
ent)
0.5 1.0 1.5 2.0 2.5 3.0 3.5
n=131
Non-Viable, medical or incomplete revasc
Non-Viable, complete revasc
Viable, complete revasc
Viable, medical or incomplete revasc
100
Propensity-Matched Subsets
p=0.045100
0
20
40
60
80
0 1 2 3 4
from Gerber et al, JA m C ollC ard iol2012;59:825-35
EF=24±7%
80
60
40
20
00
Time (years)
Surv
ival(p
erc
ent)
0.5 1.0 1.5 2.0 2.5 3.0 3.5
n=73
Viable, complete revasc
Viable, medical or incomplete revasc
Non-Viable, complete revasc
Non-Viable, medical or incomplete revasc
Medical therapy?
Patients with ESVI ≤84 ml/m2
Bonow et al, JA C C C ard iovas c Imaging2015;8:1121-1129
Patients with ESVI >84 ml/m2
Patients with ESVI ≤84 ml/m2
Bonow et al, JA C C C ard iovas c Imaging2015;8:1121-1129