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Myocardial Viability - the STICH Trial NEJM May 2011

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    • 1. Original ArticleMyocardial Viability and Survival inIschemic Left Ventricular Dysfunction Robert O. Bonow, M.D., Gerald Maurer, M.D., Kerry L. Lee, Ph.D., Thomas A. Holly, M.D., Philip F. Binkley, M.D., Patrice Desvigne-Nickens, M.D., Jaroslaw Drozdz, M.D., Ph.D., Pedro S. Farsky, M.D., Arthur M. Feldman, M.D., Torsten Doenst, M.D., Ph.D., Robert E. Michler, M.D., Daniel S. Berman, M.D., Jose C. Nicolau, M.D., Ph.D., Patricia A. Pellikka, M.D., Krzysztof Wrobel, M.D., Nasri Alotti, M.D., Ph.D., Federico M. Asch, M.D., Liliana E. Favaloro, M.D., Lilin She, Ph.D., Eric J. Velazquez, M.D., Robert H. Jones, M.D., and Julio A. Panza, M.D. for the STICH Trial Investigators
    • 2. BackgroundLeft ventricular dysfunction secondary in patients withcoronary artery disease is not always an irreversibleprocess LV function can improve substantially in patients after CABGIdentifying this subgroup of patients remains the holygrail of viability researchThe common clinical practice of not offering CABG topatients with LV dysfunction and nonviable scar onnoninvasive studies in not justified by published data
    • 3. ObjectiveIn this substudy of the STICH trial, we report theoutcome of patients who were randomlyassigned to receive medical therapy alone ormedical therapy + CABG who also underwentassessment of myocardial viability
    • 4. Viability HypothesisIn this prospective substudy, we tested thehypothesis that assessment of myocardialviability identifies patients with CAD and LVdysfunction who have the greatest survivalbenefit with CABG compared to aggressivemedical therapy
    • 5. Study PatientsPatients with angiographic documentation of coronary arterydisease amenable to surgical revascularization and with LVsystolic dysfunction (EF < 35%).Exclusion criteria - left main coronary artery stenosis fo morethan 50%, cardiogenic shock, myocardial infarction within 3months, and a need for aortic-valve surgery.Patients were randomly assigned to receive medical therapyalone or medical therapy plus CABG.A risk at randomization (RAR) score was calculated for eachpatient with the use of an equation derived in an independentdata set that predicts 5-year risk of death without CABG
    • 6. Study ProceduresInitial design of the STICH trial, viability testing with SPECT wasrequired for the enrollment of patients This was eventually expanded to make viability testing optional and allow the use of either SPECT or dobutamine echocardiographyInvestigators at all study centers were strongly encouraged to performviability testing in every patient, but the decision to perform the testwas left up to the recruiting investigatorsFor SPECT, patients with viability were degined as those with 11 ormore viable segments on the basis of relative tracer activityFor dobutamine echo, patients with viability were defined as those with5 or more segments with abnormal resting systolic function butmanifesting contractile reserve during dobutamine administration
    • 7. Viability StudySPECT protocols Thallium-201 stress-redistribution-reinjection Thallium 201 rest-redistribution Nitrate-enhanced Tc99m perfusion imagingDobutamine echo protocols Stages increase in dobutamine starting at 5 µg/ kg/min
    • 8. Patient Follow-up andOutcomesPatients were followed every 4 months for the first yearand every 6 months thereafterPrimary outcome was death from any causeSecondary end points Death from cardiovascular cause Composite of death from any cause Hospitalization for cardiovascular causesIntention-to-treat analysis
    • 9. ResultsOf 1212 patient enrolled in the hypothesis 1 comparison, 601 whounderwent assessment of viability were included in the analysisDifferences between two groups Higher percentage of white patients and lower patients of Asian patients underwent viability study Patient in the viability study were more likely To have hyperlipidemia, To be on optimal medical therapy, Have lower LVEF and higher LVEDV and LVESV Have lower blood pressure
    • 10. Study Design
    • 11. Black 31 (2.6) 18 (3.0) 13 (2.1) Asian 209 (17.2) 29 (4.8) 180 (29.5) Other 141 (11.6) 54 (9.0) 87 (14.2) Multiracial 4 (0.3) 4 (0.7) 0 (0.0) Prior myocardial infarction, no. (%) 934 (77.1) 481 (80.0) 453 (74.1) 0.015 Baseline Characteristics of Patients With and Without Diabetes, no. (%) 478 (39.4) 224 (37.3) 254 (41.6) 0.126 Stroke, no. (%) 92 (7.6) 53 (8.8) 39 (6.4) 0.109 Hypertension, no. (%) 728 (60.1) 363 (60.4) 365 (59.7) 0.814 Hyperlipidemia, no. (%) 730 (60.3) 403 (67.3) 327 (53.5) <0.001 Viability Test Current smoker, no. (%) 252 (20.8) 126 (21.0) 126 (20.7) 0.895 Chronic renal insufficiency, no. (%) 94 (7.8) 43 (7.2) 51 (8.3) 0.443 Atrial flutter/fibrillation, no. (%) 153 (12.6) 90 (15.0) 63 (10.3) 0.015 Peripheral vascular disease,no. (%) 184 (15.2) 91 (15.1) 93 (15.2) 0.969 RAR score, mean ± SD 12.7 ± 8.8 12.5 ± 8.8 12.9 ± 8.8 0.311 !"# Previous CABG, no. (%) 36 (3.0) 16 (2.7) 20 (3.3) 0.531# Bypass graft status, no. (%)Table S2. Baseline characteristics of patients with and without testing of myocardial viability !"#$%&($&)#(*#(++,-)&) 35 (97.2) 15 (93.8) 20 (100) 0.444 !"#(++,-)&) 29 (80.6) 14 (87.5) 15 (75.0) 0.426 Previous PCI, no. (%) 156 (12.9) 104 (17.3) 52 (8.5) <0.001 Patients with Patients without Previous ICD, no. (%) 29 (2.4) 16 (2.7) 13 (2.1) 0.543 All patients CAD distribution, no. (%) !"# Characteristic a viability test a viability test P value # (n=1212) No. of disease)#.&$$&,$#!/01 0.416 (n=601) (n=611) Table S2. Baseline characteristics of patients with and without testing of 13 (2.1) myocardial viability None* 25 (2.1) 12 (2.0) Age, mean ± SD 60.3 ± 9.3 60.7 ± 9.4 59.9 ± 9.2 0.113 One-vessel 282 (23.2) 152 (25.3) 130 (21.3) Male, no. (%) 1064 (87.7) 521 (86.7) 543 (88.9) 0.246 Two-vessel 462 (38.2) 221 (36.8) 241 (39.4) Race, no. (%) <0.001 Three-vessel 442 (36.5) Patients with Patients without 215 (35.8) 227 (37.2) All patients White 827 (68.2) 496 (82.5) 331 (54.2) Characteristic 2*(3456,#789#$%&($4$#!/01##### 826 (68.2) a viability test 389 (64.8) a viability test 437 (71.5) P0.012 value (n=1212) Black 31 (2.6) 18 (3.0) 13 (2.1) 7&:%#564#$%&($4$#;!0<1= 32 (2.6) (n=601) 14 (2.3) (n=611) 18 (2.9)) 0.506 Asian 209 (17.2) 29 (4.8) 180 (29.5) Age, mean ± SD Current CCS angina class, no. (%) 60.3 ± 9.3 60.7 ± 9.4 59.9 ± 9.2 0.113 0.023 Other 141 (11.6) 54 (9.0) 87 (14.2) Male, no. (%) No angina 1064 (87.7) 442 (36.5) 521 (39.3) 236 (86.7) 543 (33.7) 206 (88.9) 0.246 Multiracial 4 (0.3) 4 (0.7) 0 (0.0) Race, no. (%) I 187 (15.4) 94 (15.6) 93 (15.2) <0.001 Prior myocardial infarction, no. (%) 934 (77.1) 481 (80.0) 453 (74.1) 0.015 II White 827 (43.3) 525 (68.2) 496 (42.1) 253 (82.5) 331 (44.5) 272 (54.2) Diabetes, no. (%) 478 (39.4) 224 (37.3) 254 (41.6) 0.126 IIIBlack 31 (2.6) 48 (4.0) 18 (3.0) 14 (2.3) 13 (2.1) 34 (5.6) IV Asian 209 (0.8) 10 (17.2) 29 (4.8) 4 (0.7)) 180(1.0) 6 (29.5) Stroke, no. (%) 92 (7.6) 53 (8.8) 39 (6.4) 0.109 Other 141 (11.6) 54 (9.0) 87 (14.2) Hypertension, no. (%) 728 (60.1) 363 (60.4) 365 (59.7) 0.814 Highest NYHA functional class Hyperlipidemia, no. (%) 730 (60.3) 403 (67.3) 327 (53.5) <0.001 withinMultiracial no. (%) 3 months, 4 (0.3) 4 (0.7) 0 (0.0) 0.231 Prior myocardial infarction, no. (%) I 934 (5.7) 69 (77.1) 481 (4.5) 27 (80.0) 453 (6.9) 42 (74.1) 0.015 Current smoker, no. (%) 252 (20.8) 126 (21.0) 126 (20.7) 0.895 Diabetes, no. (%) II 478 (39.4) 438 (36.1) 224 (37.3) 212 (35.3) 254 (41.6) 226 (37.0) 0.126 Chronic renal insufficiency, no. (%) 94 (7.8) 43 (7.2) 51 (8.3) 0.443 Stroke, no. (%) III 92 (7.6) 540 (44.6) 53 (8.8) 275 (45.8) 39 (6.4) 265 (43.4) 0.109 !"# Atrial flutter/fibrillation, no. (%) 153 (12.6) 90 (15.0) 63 (10.3) 0.015 # Hypertension, no. (%) IV 728 (13.6) 165 (60.1) 363(14.5) 87 (60.4) 365(12.8) 78 (59.7) 0.814 Peripheral vascular disease,no. (%) 184 (15.2) 91 (15.1) 93 (15.2) 0.969 Hyperlipidemia,baseline, no. (%) Medications at no. (%) 730 (60.3) 403 (67.3) 327 (53.5) <0.001 RAR score, mean ± SD 12.7 ± 8.8 12.5 ± 8.8 12.9 ± 8.8 0.311 Current smoker, no. (%) Beta blocker 252 (20.8) 1036 (85.5) 126 (21.0) 534 (88.9) 126 (20.7) 502 (82.2) 0.895 <0.001 Previous CABG, no. (%) 36 (3.0) 16 (2.7) 20 (3.3) 0.531 Chronic renal insufficiency, no. (%) ACE inhibitor 94 (7.8) 996 (82.2) 43 (7.2) 514 (85.5) 51 (8.3) 482 (78.9) 0.443 0.002 Bypass graft status, no. (%) Atrial flutter/fibrillation, no. (%) Angiotensin receptor blocker 153 (12.6) 115 (9.5) 90 (15.0) 46 (7.7) 63 (10.3) 69 (11.3) 0.015 0.031 !"#$%&($&)#(*#(++,-)&) 35 (97.2) 15 (93.8) 20 (100) 0.444 Peripheral vascular disease,no. (%) ACE inhibitor or ARB 184 (15.2) 1085 (89.5) 91 (15.1) 554 (92.2) 93 (15.2) 531 (86.9) 0.969 0.003 !"#(++,-)&) 29 (80.6) 14 (87.5) 15 (75.0) 0.426 RAR score, mean ± SD Statin 12.7 (81.1) 983 ± 8.8 12.5 ± 8.8 508 (84.5) 12.9 ± 8.8 475 (77.7) 0.311 0.003 Previous PCI, no. (%) 156 (12.9) 104 (17.3) 52 (8.5) <0.001 Previous CABG, no. (%) Aspirin 36 (3.0) 1002 (82.7) 513(2.7) 16 (85.4) 489(3.3) 20 (80.0) 0.531 0.014 Bypass graft status, no. (%) Digoxin 245 (20.2) 109 (18.1) 136 (22.3) 0.074 Previous ICD, no. (%) 29 (2.4) 16 (2.7) 13 (2.1) 0.543 !"#$%&($&)#(*#(++,-)&) Blood pressure, mean ± SD# 35 (97.2) 15 (93.8) 20 (100) 0.444 CAD distribution, no. (%) !"#(++,-)&) 29 (80.6) 14 (87.5) 15 (75.0) 0.426 Systolic (mmHg) 121.2 ± 17.5 119.8 ± 17.3 122.5 ± 17.7 0.003 No. of disease)#.&$$&,$#!/01 0.416 Previous PCI, no. (%) Diastolic (mmHg) 156 (12.9) 75.5 ± 11.0 104 (17.3) 74.7 ± 10.7 52 (8.5) 76.3 ± 11.3 <0.001 0.022 None* 25 (2.1) 12 (2.0) 13 (2.1) Previous ICD, no. ± SD# Heart rate, mean (%) 74.9(2.4) 29 ± 14.7 73.3(2.7) 16 ± 12.9 13 (2.1) 76.4 ± 16.1 0.543 <0.001 One-vessel 282 (23.2) 152 (25.3) 130 (21.3) CAD distribution, no. mean ± SD LV ejection fraction, (%) 0.279 ± 0.087 0.267 ± 0.086 0.290 ± 0.086 <0.001 Two-vessel 462 (38.2) 221 (36.8) 241 (39.4) LVEDVIof disease)#.&$$&,$#!/01 No. (ml/m2), mean ± SD 117.6 ± 39.2 122.8 ± 41.9 110.4 ± 33.9 0.416 <0.001 Three-vessel 442 (36.5) 215 (35.8) 227 (37.2) None* LVESVI (ml/m2), mean ± SD 85.5(2.1) 25 ± 36.2 91.7(2.0) 12 ± 38.9 13 (2.1) 78.6 ± 31.6 <0.001 2*(3456,#789#$%&($4$#!/01##### 826 (68.2) 389 (64.8) 437 (71.5) 0.012 One-vessel mean ± SD Hemoglobin (g/dL), 282 (23.2) 13.8 ± 1.7 152 (25.3) 13.9 ± 1.7 130 (21.3) 13.6 ± 1.8 0.005 7&:%#564#$%&($4$#;!0<1= 32 (2.6) 14 (2.3) 18 (2.9)) 0.506 Two-vessel Creatinine (mg/dL), mean ± SD 462 (38.2) 1.2 ± 0.6 221 (36.8) 1.2 ± 0.7 241 (39.4) 1.2 ± 0.5 0.004 Current CCS angina class, no. (%) 0.023 Three-vessel BUN (mg/dL), mean ± SD 442 (36.5) 29.3 ± 21.2 215 (35.8) 29.2 ± 19.7 227 (37.2) 29.5 ± 22.3 0.980 No angina 442 (36.5) 236 (39.3) 206 (33.7) 2*(3456,#789#$%&($4$#!/01##### 826 (68.2) 389 (64.8) 437 (71.5) 0.012 7&:%#564#$%&($4$#;!0<1= 32 (2.6) 14 (2.3) 18 (2.9)) 0.506 I 187 (15.4) 94 (15.6) 93 (15.2) *Although some patients had no coronary artery stenosis !75%, all patients had a coronary artery II 525 (43.3) 253 (42.1) 272 (44.5) Current CCS!50%. class, no. (%) with stenosis angina 0.023 No angina 442 (36.5) 236 (39.3) 206 (33.7)
    • 12. Baseline CharacteristicsPatients with and without myocardial viability
    • 13. !"# #Table S5. Baseline characteristics of patients with and without evidence of viable myocardium All patients Patients with Patients without with viability myocardial myocardial Characteristic P value testing viability* viability* (n=601) (n=487) (n=114) Age, mean ± SD 60.7 ± 9.4 60.7 ± 9.5 60.8 ± 8.8 0.891 Male, no. (%) 521 (86.7) 416 (85.4)# 105 (92.1) 0.059 Race, no. (%)# 0.209 White 496 (82.5) 393 (80.7) 103 (90.4) Black 18 (3.0) 17 (3.5) 1 (0.9) Asian 29 (4.8) 26 (5.3) 3 (2.6) Other 54 (9.0) 47 (9.7) 7 (6.1) !"# Multi-racial# 4 (0.7) 4 (0.8) 0 (0.0) # Prior myocardial infarction, no. (%) 481 (80.0) 373 (76.6) 108 (94.7) <0.001 # Diabetes, no. (%) 224 (37.3) 198 (40.7) 26 (22.8) <0.001 Medications at baseline, no. (%) Stroke, no. (%) 53 (8.8) 42 (8.6) 11 (9.6) 0.728 Beta blocker 534 (88.9) 437 (89.7) 96 (85.0) 0.156 Hypertension, no. (%) 363 (60.4) 312 (64.1) 50 (44.7) <0.001 ACE inhibitor 514 (85.5) 412 (84.6) 102 (89.5) 0.183 Hyperlipidemia, no. (%) 403 (67.3) 326 (67.1) 77 (68.1) 0.828 Angiotensin receptor blocker 46 (7.7) 40 (8.2) 6 (5.3) 0.286 Current smoker, no. (%) 126 (21.0) 108 (22.2) 18 (15.8) 0.131 Chronic renal insufficiency, no. (%) 43 (7.2) 33 (6.8) 10 (8.8) 0.460 ACE inhibitor or ARB 554 (92.2) 446 (91.6) 108 (94.7) 0.259 Atrial flutter/fibrillation, no. (%) 90 (15.0) 74 (15.2) 16 (14.0) 0.755 Statin 508 (84.5) 405 (83.2) 103 (90.4) 0.056 Peripheral vascular disease,no. (%) 91 (15.1) 75 (15.4) 16 (14.0) 0.714 Aspirin 513 (85.4) 414 (85.0) 99 (86.8) 0.618 RAR score, mean ± SD 12.5 ± 8.8 12.4 ± 8.7 12.9 ± 9.3 0.753 Digoxin 109 (18.1) 80 (16.4) 29 (25.4) 0.025 Previous CABG, no. (%) 16 (2.7) 12 (2.5) 4 (3.5) 0.520 Blood pressure, mean ± SD Bypass graft status, no. (%) Systolic (mmHg) 119.8 ± 17.3 121.1 ± 17.7 114.4 ± 14.3 <0.001 !"#$%&($&)#(*#(++,-)&) 15 (93.8) 11 (91.7) 4 (100) 1.000 Diastolic (mmHg) 74.7 ± 10.7 74.9 ± 10.9 73.7 ± 9.3 0.447 !"#(++,-)&) 14 (87.5) 10 (83.3) 4 (100) 1.000 Heart rate, mean ± SD# 73.3 ± 12.9 73.3 ± 12.4 73.5 ± 14.7 0.839 Previous PCI, no. (%) 104 (17.3) 77 (15.8) 27 (23.7) 0.045 LV ejection fraction, mean ± SD 0.267 ± 0.086 0.275 ± 0.083 0.229 ± 0.088 <0.001 Previous ICD, no. (%) 16 (2.7) 10 (2.1) 6 (5.3) 0.096 LVEDVI (ml/m2), mean ± SD 122.8 ± 41.9 116.9 ± 36.5 146.5 ± 52.6 <0.001 CAD distribution, no. (%) LVESVI (ml/m2), mean ± SD 91.7 ± 38.9 85.9 ± 33.2 116.3 ± 50.2 <0.001 No. of diseased vessels !75% 0.957 None 12 (2.0) 9 (1.9) 3 (2.6) Hemoglobin (g/dL), mean ± SD 13.9 ± 1.7 13.9 ± 1.7 14.1 ± 1.6 0.426 One-vessel 152 (25.3) 124 (25.5) 28 (24.6) Creatinine (mg/dL), mean ± SD 1.2 ± 0.7 1.2 ± 0.8 1.2 ± 0.4 0.123 Two-vessel 221 (36.8) 179 (36.8) 42 (36.8) BUN (mg/dL), mean ± SD 29.2 ± 19.7 29.5 ± 20.0 27.3 ± 18.0 0.485 Three-vessel 215 (35.8) 174 (35.8) 41 (36.0) Proximal LAD stenosis !75% 389 (64.8) 309 (63.6) 80 (70.2) 0.184 ACE = angiotensin converting enzyme; ARB = angiotensin receptor blocker; BUN = blood urea Left main stenosis .!/012 14 (2.3) 12 (2.5) 2 (1.8) 1.000 nitrogen; CABG = coronary artery bypass graft surgery; CAD = coronary artery disease; CCS = Current CCS angina class, no. (%) 0.061 Canadian Cardiac Society; EDVI = end-diastolic volume index; ESVI = end-systolic volume index; No angina 236 (39.3) 202 (41.5) 34 (29.8) ICD = implantable cardioverter defibrillator; LV= left ventricular; NYHA = New York Heart I 94 (15.6) 68 (14.0) 26 (22.8) Association; RAR = risk at randomization# II 253 (42.1) 203 (41.7) 50 (43.9) III 14 (2.3) 11 (2.3) 3 (2.6) IV 4 (0.7)) 3 (0.6) 1 (0.9) Highest NYHA functional class 0.055 within 3 months, no. (%) I 27 (4.5) 24 (4.9) 3 (2.6) II 212 (35.3) 182 (37.4) 30 (26.3) III 275 (45.8) 211 (43.3) 64 (56.1) IV 87 (14.5) 70 (14.4) 17 (14.9)
    • 14. Viability and MortalityDuring a median of 5.1 years of followup 39% of the total population died 51% of deaths occurred in patients without myocardial viability 37% of deaths occurred in patients with viabilityHowever, after adjustment for othersignificant baseline prognosticvariables in a multivariate, viabilitystatus was no longer significantlyassociated with the rate of death(p=0.21)
    • 15. Multivariate Analysis
    • 16. Secondary endpointsPatients with viability also had lower rates ofsecondary endpts Death from CV causes (hazard ratio, 0.61; 95% CI, 0.44 to 0.84; P=0.003) Not significant on multivariate analysis Composite of death or hospitlization for CV causes (hazard ratio, 0.59; 95% CI, 0.47 to 0.74; P<0.001) Significant on multivariate analysis
    • 17. Viability and treatment arm
    • 18. CABG versus medical therapy
    • 19. Study LimitationsViability study was not performed in enrolledpatients in STICHViability studies were limited to dobutamine andSPECT, while MRI and PET studies wereexcluded
    • 20. ConclusionsStudy demonstrated a significant associationbetween myocardial viability and outcome, butthis association was non-siginificant whensubjected to a multivariate analysisStudy failed to demonstrate a significantinteraction between myocardial viability andmedical versus surgical treatment

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