Myocardial Viability and Survival

in Ischemic Left Ventricular Dysfunction

Robert O. Bonow, MD
On behalf of the STICH Trial Investigators

STICH Financial Disclosures

Original Recipient Institution

Principal Investigator

Activity

Duke University Medical Center

Robert H. Jones

Clinical Coordinating Ctr

Duke University Medical Center

Kerry L. Lee

Statistical and Data CC

Northwestern University

Robert O. Bonow

Radionuclide Core Lab

Washington Hospital Center

Julio A. Panza

Dobutamine Echo Core

Mayo Clinic

Jae K. Oh

Echo Core Laboratory

Univ of Alabama-Birmingham

Gerald M. Pohost

CMR Core Laboratory

University of Pittsburgh

Arthur M. Feldman

NCG Core Laboratory

Baylor University Medical Ctr

Paul Grayburn

MR TEE Substudy

Duke University Medical Center

Daniel B. Mark

EQOL Core Laboratory

Funding Sources:
National Heart, Lung and Blood Institute 98%
Abbott Laboratories 2%

Background
LV dysfunction in patients with CAD is not
always an irreversible process, as LV function
may improve substantially after CABG
Assessment of myocardial viability is often
used to predict improvement in LV function after
CABG and thus select patients for CABG
Numerous studies have suggested that
identification of viable myocardium also predicts
improved survival after CABG

Limitations of Cohort Studies

Decision for CABG may have been influenced
by viability status
No (or inadequate) adjustment for key baseline
variables (age, comorbidities)
Cohort studies carried out before modern
aggressive medical therapy

STICH Revascularization Hypothesis

The first prospective randomized trial testing the
hypothesis that CABG improves survival in
patients with ischemic LV dysfunction compared
to outcome with aggressive medical therapy
Provides the first opportunity to assess the
interaction between myocardial viability and
survival in randomized patients who were all
eligible for medical management alone and
also eligible for CABG.

STICH Viability Hypothesis

In this prospective substudy, we tested the
hypothesis that assessment of myocardial
viability identifies patients with CAD and LV
dysfunction who have the greatest survival
benefit with CABG compared to aggressive
medical therapy

STICH Viability Hypothesis

All randomized patients were eligible for
viability testing with SPECT myocardial
perfusion imaging or dobutamine echo.
Viability testing was optional at enrolling
sites and was not a prerequisite for
enrollment.

STICH Viability Hypothesis

SPECT protocols:
Thallium-201 stress-redistribution-reinjection
Thallium-201 rest-redistribution
Nitrate-enhanced Tc-99m perfusion imaging
Dobutamine echo protocols:
Staged increase in dobutamine starting at
5 g/kg/min

STICH Viability Hypothesis

Criteria for myocardial viability were prospective
and pre-specified
SPECT:
17 segment model
11 segments manifesting viability based on
relative tracer activity
Dobutamine echo:
16 segment model
5 segments with dysfunction at rest
manifesting contractile reserve with dobutamine

STICH Viability Hypothesis

Primary endpoint:
All-cause mortality
Secondary endpoints:
Mortality plus cardiovascular hospitalization
Cardiovascular mortality
Intention-to-treat analysis

Patients randomized in STICH

Revascularization Hypothesis

1212

Patients with
myocardial
viability test

618

611

Patients with no
usable myocardial
viability test

Unusable test
Timing
Poor quality

17
Patients with
usable myocardial
viability test

594

Patients with no
myocardial
viability test

601

Patients randomized in STICH

Revascularization Hypothesis

1212

SPECT
n=471

Dobutamine echo
n=280

321 150 130

611
Patients with
usable myocardial
viability test

601
114
487

Viable

Nonviable

Patients with no
usable myocardial
viability test

Baseline Characteristics
Patients With and Without Myocardial Viability

Variable

Viable
(n=487)

Non-Viable
(n=114)

P value

Age

61 10

61 9

NS

Multivessel CAD

73%

73%

NS

Proximal LAD stenosis

64%

70%

NS

Risk score *

12.4 8.7

12.9 9.3

NS

Previous MI

76.6%

94.7%

<0.001

LV ejection fraction (percent)

28 8

23 9

<0.001

LV end-diastolic volume index (ml/m2)

117 37

147 53

<0.001

LV end-systolic volume index (ml/m2)

86 33

116 50

<0.001

* Significant covariates in risk model: Age, renal function, heart failure,

ejection fraction, CAD index, mitral regurgitation, stroke

Myocardial Viability and Mortality

1.0

Without viability

Variables associated with mortality

With viability

Mortality Rate

0.8
HR
0.64

95% CI
P
0.48,0.86 0.003

0.6

Risk score
LV ejection fraction
LV EDVI
LV ESVI
Myocardial viability

Chi-square

33.26
24.80
35.36
33.90
8.54

<0.001
<0.001
<0.001
<0.001
0.003

50%

0.4

33%
0.2

0.0

Without viability
With viability

114
487

99
432

2
3
4
Years from Randomization
85
409

80
371

63
294

36
188

16
102

Myocardial Viability and Mortality

Variable

No.

Univariate
Chi-square
p value

Multivariable
Chi-square
p value

SPECT and/or DE 601

8.54

0.003

1.57

0.210

SPECT alone

471

7.35

0.007

0.58

0.444

DE alone

280

1.18

0.277

0.42

0.518

Myocardial Viability and Cardiovascular Mortality

1.0

Without viability

Cardiovascular Mortality Rate

With viability
Univariate

0.8
HR
0.61

95% CI
P
0.44,0.84 0.003

Chi-square p value
8.81

0.003

Multivariable
Chi-square

p value

0.91

0.339

0.6

43%
0.4
29%

0.2

0.0

Without viability
With viability

114
487

99
432

2
3
4
Years from Randomization
85
409

80
371

63
294

36
188

16
102

Myocardial Viability and Mortality + CV Hospitalization

Mortality and CV Hospitalization Rate

1.0

Without viability
82%

With viability
0.8
HR
0.59

95% CI
P
0.47,0.74 0.001

0.6

63%

0.4

Univariate

Multivariable
HR
95% CI
P
Chi-square p value
Chi-square<0.001
p value
0.59 0.47,0.44

0.2

20.27

<0.001

8.60

0.003

14
94

5
41

0.0

Without viability
With viability

114
487

56
327

2
3
4
Years from Randomization
41
284

34
238

22
166

Patients with
viability tests

601

Patients with
myocardial viability

487

Patients without
myocardial viability

114

243

244

60

54

MED
49.9%

CABG
50.1%

MED
52.6%

CABG
47.4%

Baseline Characteristics
Viable (n=487)

Non-Viable (n=114)

Variable

MED
(n=243)

CABG
Variable P value
(n=244)

MED
(n=60)

CABG
(n=54)

P value

Age

60 10

62 Age
9

62 9

60 9

NS

NS

Gender (% male)

84%

86%Gender (% NS
male)

92%

93%

NS

Previous MI

78%

75%Previous MINS

93%

96%

NS

Multivessel CAD

72%

73%MultivesselNS
CAD

68%

78%

NS

Proximal LAD

65%

63%Proximal LAD
NS

70%

70%

NS

13.7 9.8

12.9 9.3

NS

Risk score *

11.9 8.4

12.8 Risk
903 score NS

*
LV EF (percent)

28 8

27 LV
8 EF (percent)
NS

23 9

23 9

NS

LV EDVI (ml/m2)

118 38

116 LV
35 EDVI (ml/m
NS 2)

151 51

140 54

NS

LV ESVI (ml/m2)

86 34

86 LV
32ESVI (ml/m
NS 2)

121 50

111 51

NS

* Significant covariates in risk model: Age, renal function,

heart failure, ejection fraction, CAD index, MR, stroke

Myocardial Viability and Mortality

Without Viability
1.0

Mortality Rate

0.8

With Viability

MED (33 deaths)

MED (95 deaths)

CABG (25 deaths)

CABG (83 deaths)

56%
0.6

35%

0.4

42%
31%

0.2
0.0
0

2
3
4
5
Years from Randomization

MED

60

51

44

39

29

CABG

54

48

41

41

34

2
3
4
5
Years from Randomization

14

243

219

206

179

146

94

51

22

12

244

213

203

192

148

94

51

Myocardial Viability and Mortality

Without Viability
1.0

Mortality Rate

0.8

With Viability

MED (33 deaths)

MED (95 deaths)

CABG (25 deaths)

CABG (83 deaths)

56%
0.6

35%

0.4

42%
31%

0.2
0.0
0

2
3
4
5
Years from Randomization

2
3
4
5
Years from Randomization

Subgroup

Deaths

HR

95% CI

Interaction
P value

Without viability

114

58

0.70

0.41, 1.18

0.528

With viability

487

178

0.86

0.64, 1.16
0.25
0.5
CABG
better

2
MED
better

Interaction of Viability and Treatment on CV Outcomes

Endpoint
Mortality

Mortality or CV
hospitalization
CV mortality

Events Treatment
236

422

187

p value

As randomized

0.528

As treated

0.962

As randomized

0.390

As treated

0.975

As randomized

0.697

As treated

0.261

STICH Viability Hypothesis

Limitations:
Analysis limited to SPECT and dobutamine
echo, not PET or cardiac MRI
Lack of viability data in all patients; patients
represent a subpopulation of STICH

STICH Viability Hypothesis

This study represents the largest report to date
relating myocardial viability to clinical outcomes
of patients with CAD and LV dysfunction
and is the first to assess these relationships
prospectively among patients who were all
eligible for CABG as well as optimal medical
management alone

STICH Viability Hypothesis

STICH results:
demonstrate a significant association between
myocardial viability and outcome, but this association
is rendered non-significant when subjected to a
multivariable analysis that includes other prognostic
variables.
fail to demonstrate a significant interaction between
myocardial viability and medical versus surgical
treatment with respect to mortality, whether assessed
according to treatment assigned (intention to treat) or
to the treatment actually received.

STICH Viability Hypothesis

Implications:

In patients with CAD and LV dysfunction,

assessment of myocardial viability does not
identify patients who will have the greatest
survival benefit from adding CABG to
aggressive medical therapy

Full report available at www.NEJM.org