Coronary Revascularization in Patients witj Severe LV Dysfunction.: Implications of the STICH trial Is the concept of viability still viable? Banff 2016 3041435-1
Prognosis of Patients With LV Dysfunction and CAD Major determinants Pt with CAD Pt with LV dysfunction Severity of LV dysfunction Results of revascularization a paradox and a window of opportunity Periprocedural risk Severity of CAD/ischemia Late mortality 2016 MFMER 3507142-10
Probability of death from any cause STICH Trial Outcomes 1,212 pt 2002-2007 EF <0.35 CCS angina 2 (95%) NYHA 3 (97%) 1.0 0.8 0.6 0.4 0.2 All Cause Mortality H Ratio- 0.86 95% CI 0.72-1.04 P=0.12 MED CABG 0.0 0 2 4 6 Years since randomization Velasquez: NEJM, 2011 2013 MFMER 3309958-3
Probability of death from CV causes Probability of death from any cause or hospitalization for CV causes CV Mortality and CHF Hospitalization 1.0 0.8 CV Mortality H.R 0.81 95% CI 0.66-1.00 P=0.05 1.0 0.8 All-Cause Mortality and CHF Hospitalization H.R.0.74 95% CI 0.64-0.85 P<0.001 0.6 0.6 MED 0.4 MED 0.4 CABG 0.2 CABG 0.2 0.0 0 1 2 3 4 5 6 0.0 0 1 2 3 4 5 6 Years since randomization Years since randomization Velasquez: NEJM, 2011 2013 MFMER 3309958-4
Definition of Viable Myocardium Myocardium that is dysfunctional at rest and not scarred and has the potential for functional recovery Hibernation should be used retrospectively only to describe those segments which actually improve following revascularization Shah: EHJ, 2013 2015 MFMER 3432359-5
Viability and Prognosis in Patients with LV Dysfunction Different Substrates Hibernation (resting ischemia) Repetitive stunning (inducible ischemia) Extent of scar Extent of remodeling Duration of hibernation How much is enough not an all or none issue Need for combined imaging approaches to characterize substrates and reversibility 2015 MFMER 3432775-9
% Viable/total myocardium Quantity of Viable Myocardial Required to Improve Survival With Revascularization in Patients With Ischemic Cardiomyopathy 29 studies 4,167 patients Meta-analysis 50 40 30 20 10 Optimal Threshold for Presence of Viability 25.8 35.9 38.7 0 PET Stress Echo SPECT Inaba: J NuclCardiol, 2010 2014 MFMER 3362090-4
Clinical Indications for Viability Testing Severe CAD and no history of MI Absent Q waves on ECG Significant angina or stressinduced ischemia Patients with CAD and severe LV dysfunction (EF 0.35) Flash pulmonary edema with subsequent improvement Angiography Subtotal occlusions Collaterals Clinical EF? 2015 MFMER 3471328-3
Weighted average annual mortality (%) Viability Testing and Mortality After Treatment 14 nonrandomized studies 1998-2006 15 10 10.6 11.7 8.5 5 3.7 Medical therapy Revascularization 0 Viability present Viability absent Camici: Circ, 2008 2013 MFMER 3307194-19
Probability of death STICH Myocardial Viability and Survival 601 pt viability testing SPECT DSE 1.0 0.8 0.6 Hazard ratio 0.64 95% CI 0.48-0.86 P=0.003 Without viability (114 pt) 0.4 0.2 With viability (487 pt) 0.0 0 1 2 3 4 5 6 Years since randomization Bonow: NEJM, 2011 2013 MFMER 3309958-10
STICH Myocardial Viability and Survival Subgroup No. Deaths HR (95% CI) P Without 114 58 0.70 (0.41-1.18) 0.53 viability With 487 178 0.86 (0.64-1.16) viability 0.25 0.50 1.0 2.0 CABG better Medical therapy better Mortality Variable Chi-square P RAR score 33.26 <0.001 LVEF 24.80 <0.001 LVED volume index 35.36 <0.001 LVES volume index 33.90 <0.001 Myocardial viability 8.54 0.003 Bonow: NEJM, 2011 2016 MFMER 3507142-11
Patients Randomized in STICH Revascularization Hypothesis 1,212 SPECT n=471 Dobutamine echo n=280 Patients with usable myocardial viability test 321 150 130 601 487 114 Viable Nonviable 611 Patients with no usable myocardial viability test Bonow et al: NEJM, 2011 2015 MFMER 3477336-05
STICH Viability Study Limitations Study is underpowered Non-randomized viability performed at physician discretion and unblinded Baseline differences between pt with/without viability testing comorbidities Generalizability to contemporary population ICD 50% CRT 20% 85% of patients in substudy non-usa 3 VD only present in approximately one third Viability determined in a binary fashion PET and CMRI greater accuracy and provide additional information Does not distinguish between dysfunctioning viable myocardium and reversibility 2016 MFMER 3507142-12
Role of Viability Testing in Clinical Decision Making in Patients With LV Dysfunction Not Essential Significant angina Good distal vessels ECG No Q waves Preserved voltage Reasonable surgical risk Helpful Severe LV dysfunction Extensive LV remodeling Multiple comorbidities Incomplete revascularization is likely Angina less severe 2016 MFMER 3507142-13
Mortality rate Inducible Myocardial Ischemia and Outcomes of Revascularization STICH Trial EF <0.35 Stress testing Inducible ischemia 64% % ischemic myocardium (18±11%) 1.0 0.8 No Ischemia Mortality Ischemia 0.6 0.4 MED (31 events) MED (56 events) 0.2 0.0 CABG (22 events) 0 1 2 3 4 5 6 Years following randomization CABG (47 events) 0 1 2 3 4 5 6 Years following randomization Panza: JACC, 2012 2013 MFMER 3267767-3
Log hazard ratio Impact of Ischemia and Scar on Therapeutic Benefit from Coronary Revascularization 13,969 pt Adenosine or exercise SPECT Role of ischemia in pt with >10% fixed myocardial defect % ischemic myocardium = P=0.089 Ischemia treatment interaction = P=0.489 1.5 1.0 0.5 0.0 P<0.001-0.5 0.0 12.5 25.0 37.5 50.0 Total myocardium ischemic (%) Medical therapy Early revascularization Hachamovich: EHJ, 2011 2014 MFMER 3357109-17
Log hazard ratio Impact of Ischemia and Scar on Therapeutic Benefit from Coronary Revascularization 13,969 pt Adenosine or exercise SPECT Role of ischemia on benefit of revascularization was nullified by presence of extensive infarction/scar 1.5 1.0 0.5 0.0 P<0.001-0.5 0.0 12.5 25.0 37.5 50.0 Total myocardium ischemic (%) Medical therapy Early revascularization Hachamovich: EHJ, 2011 2014 MFMER 3391078-6
Jolicover et al Presence of angina does not confer markedly worse prognosis or a greater benefit from revascularization by CABG But CABG does improve angina symptoms compared with medical therapy alone 2015 MFMER 3485852-8
Is There a Role for Viability and Ischemia Testing? Is the Concept Still Valid and Rational? STICH patients Other patient subgroups No No effect of viability, inducible ischemia and angina on surgical outcomes remodeling with non-viability but no effect on surgical outcomes Bonow: NEJM, 2011; Panza: JACC, 2012 Jolicover: JACC, 2015; Bonow: JACC, 2015 Yes 2015 MFMER 3485205-06
Role of Viability Testing- Conclusions Ongoing trials may be pivotal : (AIMI HF) May predict response to revascularization in selected pts with CAD and LV dysfunction Marker of prognosis May influence response to medical therapy Impact of viability and residual ischemia may be overwhelmed by extensive scar and remodeling. Should not be a routine determinant of decision to revascularize 2015 MFMER 3493400-10