myocardial viability and survival in ischemic left ... · criteria for myocardial viability were...
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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
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 μg/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 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
Myocardial Viability and Mortality
1.0
0.8
0.6
0.4
0.2
0.0
Years from Randomization
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
Chi-square p value Chi-square p value
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
Years from Randomization
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
Chi-square p value Chi-square p value
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
Multivessel CAD 68% 78% 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
Multivessel CAD 72% 73% 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
*
Myocardial Viability and Mortality
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%
Myocardial Viability and Mortality
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
STICH Viability Hypothesis
Limitations:
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
…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:
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