Severe Left Ventricular Dysfunction: Evolving Revascularization Strategies Robert O. Bonow, MD, MS, MACC Northwestern University Feinberg School of Medicine Bluhm Cardiovascular Institute Northwestern Memorial Hospital No Relationships to Disclose
1 Year Survival Rate (%) Prognosis in Chronic CAD Influence of LV Ejection Fraction 88 74% 6 6 65% 5% 62% 56% 4 4 27% 2 2 Medical Surgical Medical Surgical Medical Surgical EF >5% EF 35-5% EF <35% from Muhlbaier et al, Circulation 1992;86:II-198
Increase in Survival (%) Prognosis in Ischemic LV Dysfunction Increase in Survival by Revascularization 6 55% 57% 5 4 37% 41% 44% 3 3% 2 1 1%
Increase in Survival (%) Prognosis in Ischemic LV Dysfunction Increase in Survival by Medical Therapy 1 9 8 8 7 77% [43,91] 9% [7,96] 6 6 5 4 4 3 2 2 38% [2,68] 1 ACEi / ARB ACEi / ARB + β blocker ACEi / ARB + β blocker + ICD / CRT from Yancy CW, J Am Heart Assoc 212;1:16-26
Surgical Treatment for Ischemic Heart Failure
STICH Trial 1212 patients with EF <35% 99 sites in 22 countries Primary Endpoint: All-cause mortality Secondary Endpoints: CV mortality Death + CV hospitalization Death + HF hospitalization
Mortality Rate STICH Primary Outcome All-Cause Mortality.8 Medical therapy 1212 patients EF <35%.6 HR 95% CI.86.72.1.4.4 P =.123 Medical therapy.2 1 2 3 4 5 6 Years After Randomization Velazquez et al. N Engl J Med 211;364:167-1616
CV Mortality Rate STICH Secondary Outcome Cardiovascular Mortality.8 Medical therapy.6 HR 95% CI.81.66.1..4 P =.5 Medical therapy.2 1 2 3 4 5 6 Years After Randomization Velazquez et al. N Engl J Med 211;364:167-1616
Death or CV Hospitalization STICH Secondary Outcome Death + CV Hospitalization.8 Medical therapy Medical therapy.6.4.2 HR 95% CI.74.64..85 P <.1 1 2 3 4 5 6 Years After Randomization Velazquez et al. N Engl J Med 211;364:167-1616
Mortality Rate STICH Secondary Outcome All-Cause Mortality Treatment Received.8 Medical therapy.6.4 HR 95% CI.7.58,.84 P <.1 Medical therapy.2 1 2 3 4 5 6 Years After Randomization Velazquez et al. N Engl J Med 211;364:167-1616 Doenst et al. Circ Heart Fail 213;6:443-45
Mortality Rate STICH Secondary Outcome All-Cause Mortality Per Protocol.8 Medical therapy.6.4 HR 95% CI.76.62,.92 P =.5 Medical therapy.2 1 2 3 4 5 6 Years After Randomization Velazquez et al. N Engl J Med 211;364:167-1616 Doenst et al. Circ Heart Fail 213;6:443-45
STICH Quality of LIfe KCCQ: Overall Summary KCCQ Overall Summary 8 8 75 75 7 7 + Medical Medical alone Medical 65 65 6 6 Is STICH a negative trial or a positive trial? 55 Baseline 4 mo 12 mo 24 mo 36 mo 1 2 3 Mark et al, Ann Intern Med 214;161:392-399
Myocardial Revascularization in Patients with LV Dysfunction The STICH Trial: Are there subsets who benefit from? Myocardial viability
Mortality Rate Myocardial Revascularization in Patients with LV Dysfunction The STICH Trial: Are there subsets who benefit from? Myocardial viability.8 Without Viability With Viability.6 MED (33 deaths) (25 deaths).56 MED (95 deaths) (83 deaths).4.2.42 1 2 3 4 5 6 1 2 3 4 5 6 Years Following Randomization Interaction P value.528.35.31 Years Following Randomization Bonow et al. N Engl J Med 211;364:1617-1635
Mortality Rate Myocardial Revascularization in Patients with LV Dysfunction The STICH Trial: Are there subsets who benefit from? Myocardial viability The Heart Trial.8 8 With Viability With Viability.6 6 Medical therapy (n=69) Revascularization (n=69) MED (95 deaths) (83 deaths).4 4.2 2 n=138 p=ns.35.31 1 1 2 23 4 3 4 5 6 Years Following Randomization 1 2 3 4 5 6 Years Following Randomization from Cleland et al, Eur J Heart Fail 211;13:227-233 Bonow et al. N Engl J Med 211;364:1617-1635
Patients with ESVI 84 ml/m 2 Bonow et al, JACC Cardiovasc Imaging 215;8:1121-1129
Patients with ESVI 84 ml/m 2 Patients with ESVI >84 ml/m 2 Bonow et al, JACC Cardiovasc Imaging 215;8:1121-1129
3-Year Mortaltiy (%) Revascularization vs Medical Therapy in Patients with Left Ventricular Dysfunction 8 6 n=36 Medical p=ns 4 4 2 2 Revascularization 1 2 3 4 5 1 2 3 4 Amount of Compromised Viable Myocardium (%) from Tarakji et al, Circulation 26;113:23-237
Myocardial Revascularization in Patients with LV Dysfunction The STICH Trial: Are there subsets who benefit from? Myocardial ischemia
Mortality Rate Myocardial Revascularization in Patients with LV Dysfunction The STICH Trial: Are there subsets who benefit from? Myocardial ischemia No Ischemia Ischemia.6.4 MED (31 deaths) (22 deaths).39 MED (56 deaths) (47 deaths).39.2.33.35 1 2 3 4 5 6 1 2 3 4 5 6 Years Following Randomization Years Following Randomization Panza et al. J Am Coll Cardiol 213;61:186-187
Log hazard ratio Impact of Ischemia and Scar on Therapeutic Benefit of Coronary Revascularization 1.5 1. N=13,555 Medical therapy.5. P<.1 Revascularization -.5. 12.5 25. Magnitude of ischemic myocardium associated 37.5 5. with survival benefit with revascularization Total myocardium in ischemic (%) patients without prior MI No such benefit in patients with prior MI Role of ischemia not significant in patients with >1% myocardial scar Hachamovich et al, Eur Heart J 211;32:112-124
Mortality Rate Myocardial Revascularization in Patients with LV Dysfunction The STICH Trial: Are there subsets who benefit from? Biomarkers.8.6 BNP Tertile 1 Tertile 2 Tertile 3.39 BNP Tertile 1 Tertile 2 Tertile 3 Medicine Tertile HR 95% CI Tertile HR 95% CI T2 : T1 2.2 1.23,3.34 T3 : T1 3.5 1.87,4.5 T2 : T1 1.94 1.21,3.9 T3 : T1 2.43 1.52,3.87.39.4.33.35.2 1 2 3 4 5 6 1 2 3 4 5 6 Years Following Randomization Years Following Randomization Feldman et al. Circ Heart Fail 213;6:461-472
Mortality Rate Myocardial Revascularization in Patients with LV Dysfunction The STICH Trial: Are there subsets who benefit from? Functional capacity PAS >55 + 6MW 3m PAS 55 + 6MW <3m.6.4 MED HR 95% CI P value.71.52,.97.33.39 MED HR 95% CI P value.95.75,1.19.626.2 P=.33.33 P=.626 1 2 3 4 5 6 1 2 3 4 5 6 Years Following Randomization Years Following Randomization Stewart et al. JACC Heart Fail 214;2:335-343
Mortality Rate Myocardial Revascularization in Patients with LV Dysfunction The STICH Trial: Are there subsets who benefit from? CAD severity, EF, ESV.8 2 3 Factors 1 Factor.6.4.2 MED (31 deaths) (22 deaths) HR 95% CI P value.71.36,.89.33 P=.4.51.39.39.33 MED (56 deaths) (47 deaths) HR 95% CI P value 1.8.81,1.44.626 P=.591.39.3.35.3 1 2 3 4 5 6 1 2 3 4 5 6 Years Following Randomization Years Following Randomization Panza et al. J Am Coll Cardiol 214;64:553-561
Myocardial Revascularization in Patients with LV Dysfunction Factors to consider: More important Severity of LV dysfunction Severity of LV remodeling Angiographic severity of CAD Functional capacity Less important Extent of myocardial viability Severity of myocardial ischemia Biomarkers Velazquez and Bonow. J Am Coll Cardiol 215;65:615-624