Myocardial Viability and Survival in Ischemic Left Ventricular - - PowerPoint PPT Presentation

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 150 321 130 611

SPECT n=471 Dobutamine echo n=280

114

Nonviable

487

Viable

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 Characteristics

Patients 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 Mortality Rate Years from Randomization 1 2 3 4 5 6

Without viability With viability 114 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 1 2 3 4 5 6

HR 95% CI P 0.61 0.44,0.84 0.003

Cardiovascular Mortality 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 1 2 3 4 5 6

Without viability With viability

Mortality and CV Hospitalization 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

487 114 244 243 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 value MED (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 value MED (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 Mortality Rate Years from Randomization Years from Randomization 1 2 3 4 5 6 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 Viability Without Viability 56% 42% 35% 31%

Myocardial Viability and Mortality

1.0 0.8 0.6 0.4 0.2 0.0 Mortality Rate Years from Randomization Years from Randomization 1 2 3 4 5 6 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 2 0.5 0.25 CABG better MED better

Without Viability With Viability

Interaction P value 0.528

56% 42% 35% 31%

Endpoint Events Treatment p value Mortality 236 As randomized 0.528 As treated 0.962 Mortality or CV hospitalization 422 As randomized 0.390 As treated 0.975 CV mortality 187 As 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

• f 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