does myocardial viability predict improvement with ... · myocardial viability and mortality 0.8...

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


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


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


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


10

15

2020

15

10

Mo

rta

lity

Ra

te(%

/ye

ar)

16.0

7.7


M ed ic al

p<0.001


0

5

1010

5

0

Mo

rta

lity

Ra

te(%

/ye

ar)

Viable Non-Viable

3.2

7.76.2


n=748 n=557 n=330 n=734


10

15

2020

15

10

Mo

rta

lity

Ra

te(%

/ye

ar)

16.0

7.7


M ed ic al


p=NS

0

5

1010

5

0

Mo

rta

lity

Ra

te(%

/ye

ar)

Viable Non-Viable

3.2

7.76.2


n=748 n=557 n=330 n=734


10

15

2020

15

10

Mo

rta

lity

Ra

te(%

/ye

ar)

10.8

7.7

9.5


M ed ic al


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


10

15

2020

15

10

Mo

rta

lity

Ra

te(%

/ye

ar)

10.6

8.5

11.7


M ed ic al


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


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


0.2

0

CV

Mo

rtali

tyR

ate

0 1 2 3 4 5 6


With Viability


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


0.2

0

CV

Mo

rtali

tyR

ate

0 1 2 3 4 5 6


With Viability


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


0.2

00 1 2 3 4 5 6 0 1 2 3 4 5 6

Years Following Randomization Years Following Randomization

0.31



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%


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


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(%

)



-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%



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


0.2

00 1 2 3 4 5 6 0 1 2 3 4 5 6

Years Following Randomization Years Following Randomization

0.31


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





… bu td oes notind epend ently pred ic ts u rvivalbenefitfrom revas c u larization





… 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


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


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


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

does myocardial viability predict improvement with ... · myocardial viability and mortality 0.8...

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