Myocardial Viability and Survival in Ischemic Left ...clinicaltrialresults.org/Slides/STICH.viability.10a.pdf · Myocardial Viability and Survival in Ischemic Left Ventricular Dysfunction

Myocardial Viability and Survival

in Ischemic Left Ventricular Dysfunction

Robert O. Bonow, MD

On behalf of the STICH Trial Investigators

STICH Financial Disclosures

Funding Sources:

National Heart, Lung and Blood Institute 98%

Abbott Laboratories 2%

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

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


• 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.


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 μg/kg/min


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


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 no

myocardial

viability test 594

Patients with

myocardial

viability test

611

Patients with

usable myocardial

viability test

Patients with no

usable myocardial

viability test

17

Unusable test

• Timing

• Poor quality

601

618

1212

150321 130

611

SPECT

n=471

Dobutamine echo

n=280

114Nonviable

487Viable

Patients with no

usable myocardial

viability test

Patients with

usable myocardial

viability test

Patients randomized in STICH

Revascularization Hypothesis

601

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

Baseline CharacteristicsPatients With and Without Myocardial Viability

*

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

ejection fraction, CAD index, mitral regurgitation, stroke

Myocardial Viability and Mortality

1.0

0.8

0.6

0.4

0.2

0.0

Mo

rtality

Rate

Years from Randomization

0 1 2 3 4 5 6

Without viability

With viability114 99 85 80 63 36 16

487 432 409 371 294 188 102

HR 95% CI P

0.64 0.48,0.86 0.003

Without viability

With viability

Variables associated with mortality

Chi-square p

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

50%

33%

Variable No.Univariate Multivariable

Chi-square p value 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


1.0

0.8

0.6

0.4

0.2

0.0


0 1 2 3 4 5 6

HR 95% CI P

0.61 0.44,0.84 0.003

Card

iovascu

lar

Mo

rtality

Rate

Without viability

With viability

Without viability

With viability

Myocardial Viability and Cardiovascular Mortality

Univariate Multivariable


8.81 0.003 0.91 0.339

114 99 85 80 63 36 16

487 432 409 371 294 188 102

43%

29%

1.0

0.8

0.6

0.4

0.2

0.0


0 1 2 3 4 5 6

Without viability

With viability

Mo

rtality

an

d C

V H

osp

italizati

on

Rate

114 56 41 34 22 14 5

487 327 284 238 166 94 41

HR 95% CI P

0.59 0.47,0.44 <0.001

Without viability

With viability

Myocardial Viability and Mortality + CV Hospitalization

Univariate Multivariable


20.27 <0.001 8.60 0.003

HR 95% CI P

0.59 0.47,0.74 0.001

82%

63%

Patients with

viability tests

601

Patients without

myocardial viability

Patients with

myocardial viability 487 114

244243

CABG

50.1%

CABG

47.4%

MED

49.9%

54

MED

52.6%

60

Baseline Characteristics

*

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

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

Variable

Non-Viable (n=114)

P valueMED

(n=60)

CABG

(n=54)

Age 62 ± 9 60 ± 9 NS

Gender (% male) 92% 93% NS

Previous MI 93% 96% NS


Proximal LAD 70% 70% NS

Risk score 13.7 ± 9.8 12.9 ± 9.3 NS

LV EF (percent) 23 ± 9 23 ± 9 NS

LV EDVI (ml/m2) 151 ± 51 140 ± 54 NS

LV ESVI (ml/m2) 121 ± 50 111 ± 51 NS

Variable

Viable (n=487)

P valueMED

(n=243)

CABG

(n=244)

Age 60 ± 10 62 ± 9 NS

Gender (% male) 84% 86% NS

Previous MI 78% 75% NS


Proximal LAD 65% 63% NS

Risk score 11.9 ± 8.4 12.8 ± 903 NS

LV EF (percent) 28 ± 8 27± 8 NS

LV EDVI (ml/m2) 118 ± 38 116 ± 35 NS

LV ESVI (ml/m2) 86 ± 34 86 ± 32 NS

*


1.0

0.8

0.6

0.4

0.2

0.0

Mo

rta

lity

Ra

te

Years from Randomization Years from Randomization

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

MED (33 deaths)

CABG (25 deaths)

MED (95 deaths)

CABG (83 deaths)

MED

CABG

60 51 44 39 29 14 4 243 219 206 179 146 94 51

54 48 41 41 34 22 12 244 213 203 192 148 94 51

With ViabilityWithout Viability

56%

42%

35%

31%


1.0

0.8

0.6

0.4

0.2

0.0

Mo

rta

lity

Ra

te

Years from Randomization Years from Randomization

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

MED (33 deaths)

CABG (25 deaths)

MED (95 deaths)

CABG (83 deaths)

Subgroup

Without viability

With viability

N Deaths HR 95% CI

114 58 0.70 0.41, 1.18

487 178 0.86 0.64, 1.16

1 20.50.25

CABG

betterMED

better

Without Viability With Viability

Interaction

P value

0.528

56%

42%

35%

31%

Endpoint Events Treatment p value

Mortality 236As randomized 0.528

As treated 0.962

Mortality or CV

hospitalization422

As randomized 0.390

As treated 0.975

CV mortality 187As randomized 0.697

As treated 0.261

Interaction of Viability and Treatment on CV Outcomes

• 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


Limitations:


• 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


…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 results:


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

Documents

Myocardial Viability and Survival in Ischemic Left ...clinicaltrialresults.org/Slides/STICH.viability.10a.pdf · Myocardial Viability and Survival in Ischemic Left Ventricular Dysfunction