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 μ 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 Patients with no 594 myocardial 618 myocardial viability test viability test Unusable test • Timing • Poor quality Patients with no 17 611 usable myocardial viability test Patients with 601 usable myocardial viability test
Patients randomized in STICH Revascularization Hypothesis 1212 SPECT Dobutamine echo n=471 n=280 321 150 130 Patients with no 611 usable myocardial viability test Patients with 601 usable myocardial viability test 114 Nonviable 487 Viable
Baseline Characteristics Patients With and Without Myocardial Viability Viable Non-Viable Variable (n=487) (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/m 2 ) 117 ± 37 147 ± 53 <0.001 LV end-systolic volume index (ml/m 2 ) 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 Variables associated with mortality Without viability Chi-square p With viability Risk score 33.26 <0.001 0.8 LV ejection fraction 24.80 <0.001 HR 95% CI P LV EDVI 35.36 <0.001 0.64 0.48,0.86 0.003 LV ESVI 33.90 <0.001 Mortality Rate Myocardial viability 8.54 0.003 0.6 50% 0.4 33% 0.2 0.0 0 1 2 3 4 5 6 Years from Randomization Without viability 114 99 85 80 63 36 16 With viability 487 432 409 371 294 188 102
Myocardial Viability and Mortality Univariate Multivariable Variable No. Chi-square p value Chi-square p value 601 8.54 0.003 1.57 0.210 SPECT and/or DE 471 7.35 0.007 0.58 0.444 SPECT alone 280 1.18 0.277 0.42 0.518 DE alone
Myocardial Viability and Cardiovascular Mortality 1.0 Without viability With viability Univariate Multivariable Cardiovascular Mortality Rate 0.8 Chi-square p value Chi-square p value HR 95% CI P 0.61 0.44,0.84 0.003 8.81 0.003 0.91 0.339 0.6 43% 0.4 29% 0.2 0.0 0 1 2 3 4 5 6 Years from Randomization Without viability 114 99 85 80 63 36 16 With viability 487 432 409 371 294 188 102
Myocardial Viability and Mortality + CV Hospitalization 1.0 Without viability Mortality and CV Hospitalization Rate 82% With viability 0.8 HR 95% CI P 0.59 0.47,0.74 0.001 0.6 63% 0.4 Univariate Multivariable HR 95% CI P Chi-square p value Chi-square p value 0.59 0.47,0.44 <0.001 0.2 20.27 <0.001 8.60 0.003 0.0 0 1 2 3 4 5 6 Years from Randomization Without viability 114 56 41 34 22 14 5 With viability 487 327 284 238 166 94 41
Patients with viability tests 601 Patients with Patients without 487 114 myocardial viability myocardial viability 243 244 60 54 MED CABG CABG MED 49.9% 47.4% 50.1% 52.6%
Baseline Characteristics Viable (n=487) Non-Viable (n=114) MED CABG MED CABG Variable Variable P value P value (n=243) (n=244) (n=60) (n=54) Age 60 ± 10 62 ± 9 Age NS 62 ± 9 60 ± 9 NS Gender (% male) 84% 86% Gender (% male) NS 92% 93% NS Previous MI 78% 75% Previous MI NS 93% 96% NS Multivessel CAD 72% 73% Multivessel CAD NS 68% 78% NS Proximal LAD 65% 63% Proximal LAD NS 70% 70% NS * Risk score 11.9 ± 8.4 12.8 ± 903 Risk score NS 13.7 ± 9.8 12.9 ± 9.3 NS * LV EF (percent) 28 ± 8 27± 8 LV EF (percent) NS 23 ± 9 23 ± 9 NS LV EDVI (ml/m 2 ) LV EDVI (ml/m 2 ) 118 ± 38 116 ± 35 NS 151 ± 51 140 ± 54 NS LV ESVI (ml/m 2 ) LV ESVI (ml/m 2 ) 86 ± 34 86 ± 32 NS 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 With Viability 1.0 MED (95 deaths) MED (33 deaths) CABG (83 deaths) CABG (25 deaths) 0.8 Mortality Rate 56% 0.6 35% 0.4 42% 31% 0.2 0.0 0 1 2 3 4 5 6 0 1 2 3 4 5 6 Years from Randomization Years from Randomization MED 60 51 44 39 29 14 4 243 219 206 179 146 94 51 CABG 54 48 41 41 34 22 12 244 213 203 192 148 94 51
Myocardial Viability and Mortality Without Viability With Viability 1.0 MED (95 deaths) MED (33 deaths) CABG (83 deaths) CABG (25 deaths) 0.8 Mortality Rate 56% 0.6 35% 0.4 42% 31% 0.2 0.0 0 1 2 3 4 5 6 0 1 2 3 4 5 6 Years from Randomization Years from Randomization Interaction Subgroup N Deaths HR 95% CI 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 1 2 CABG MED better better
Interaction of Viability and Treatment on CV Outcomes Endpoint Events Treatment p value As randomized 0.528 Mortality 236 As treated 0.962 As randomized 0.390 Mortality or CV 422 hospitalization As treated 0.975 As randomized 0.697 CV mortality 187 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
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