Dr Nithin P G
Viability assessment and its role in Revascularization
Review of evidence
Dr. Nithin P G
Dr Nithin P G
Overview
• Introduction
• Viability assessment by various investigations
• Comparisons
• Clinical correlations
• Benefits of viability assessment in clinical scenario
• Conclusion
Dr Nithin P G
Introduction
TERMS
– ‘Stunning’
– ‘C/C Stunning’
– ‘Hibernation’
– ‘Ischemic cardiomyopathy’
– Viability???
Dr Nithin P G
Introduction
Viable vs Non- viable
Heart 2004;90(Suppl V):v26–v33
Dr Nithin P G
Introduction
Contractile reserve vs. Metabolic parameters
52% 59% 59%
33%
Heart 2004;90(Suppl V):v26–v33
Dr Nithin P G
Introduction
What to look for in viable tissues? [endpoints used in viability studies]
– Improvement in regional LV function (segments)
– Improvement in global LV function (LVEF)
– Improvement in symptoms (NYHA functional class)
– Improvement in exercise capacity (metabolic equivalents)
– Reverse LV remodeling (LV volumes)
– Prevention of sudden death (ventricular arrhythmias)
– Long-term prognosis (survival)
Dr Nithin P G
Introduction
– Segmental LV function
– LVEF
– LV volumes
– Long-term prognosis (survival)
Pooled data-105 studies (n= 3,003) [Nucl. Im., DSE]15,045 dysfunctional segments analyzed; 7,941 (53%) showed improvement in function after revasc. [84% detected prior as viable]
Curr Probl Cardiol. 2001;26:142–18620%–30% of LV viable to allow improvement in the LVEFTrials use criteria of >5% increase in EF
J Nucl Med 2007; 48:1135–1146
ESV ≥140 mL low improvement in LVEF post-revascularization [sens 68%; spec 65% to predict absence of global recovery]
EDV 70% of patients with EDV 140-180 ml & 35% with EDV>180 ml improved LVEF by 5%
J Thorac Cardiovasc Surg 2004;127:385-390
Eur Heart J 2000;21:125-136
Dr Nithin P G
Viability assessment by different investigations
Dr Nithin P G
Viability assessment
Nuclear imaging with PET
• 18F-FDG tracer with oral glucose loading protocol most commonly used.
European Heart Journal (2010) 31, 2984–2995
Dr Nithin P G
Viability assessment
% sensitivity % specificity % NPV %PPV20 studies [N= 598] 93 58 85 77[without flow tracer] 88 74
J Nucl Med 2007; 48:1135–1146
Curr Probl Cardiol. 2001;26:142–186
Ability to predict improvement in LVEF
Ability to predict improvement in LVEF
Viability present Viability absent
% LVEF pre % LVEF post % LVEF pre % LVEF post
12 studies [N=33] 37 47 39 40
J Nucl Med 2007; 48:1135–1146J Nucl Med. 1994;35:707–715
Dr Nithin P G
Viability assessment
% event rates
Viability present Viability absent
Revascularization Medical trt. Revascularization Medical trt.7 studies (N= 619) 7 29 12 12
Viability, Trt. type & Event Rates in Pts with LVD and c/c CAD
J Nucl Med 2007; 48:1135–1146
Dr Nithin P G
Viability assessment
Nuclear imaging with SPECT• Tracers- 201Tl-Chloride & 99mTc-Labeled Agents [sestamibi]
Viability assessment• Stress -Normal perfusion
• Stress- defects with redistribution on delayed images
• Delayed rest images or reinjection- fixed defect showing redistribution
• Delayed rest images or reinjection- more than 50% tracer uptake
Dr Nithin P G
Viability assessment% sensitivity % specificity % NPV %PPV
201Tl-Chloride 33 trials[N=858] 87 55 81 64
99mTc-Labeled Agents 20 trials[N=488] 81 66 77 71
J Nucl Med 2007; 48:1135–1146
Curr Probl Cardiol. 2001;26:142–186
Ability to predict improvement in LVEF
Ability to predict improvement in LVEF
Viability present Viability absent
% LVEF pre % LVEF post % LVEF pre % LVEF post
201Tl 5 trials [N=96] 30 38 29 3199mTc 4 trials [N=75] 47 53 40 39
J Nucl Med 2007; 48:1135–1146J Nucl Med. 1994;35:707–715
Dr Nithin P G
Viability assessment
DSE• Low dose- High dose dobutamine infusion best
Viability assessment• Biphasic response- viability with superimposed ischemia
• Worsening-severe ischemia with critical stenosis
• Sustained improvement- subendocardial necrosis
• No change- transmural scar
Dr Nithin P G
Viability assessment
% sensitivity % specificity % NPV %PPV32 studies [N= 1090] 81 80 85 77
J Nucl Med 2007; 48:1135–1146
Curr Probl Cardiol. 2001;26:142–186
Ability to predict improvement in LVEF
Ability to predict improvement in LVEF
Viability present Viability absent
% LVEF pre % LVEF post % LVEF pre % LVEF post
8 studies [N=254] 35 43 35 36
J Nucl Med 2007; 48:1135–1146J Nucl Med. 1994;35:707–715
Dr Nithin P G
Viability assessment
% event rates
Viability present Viability absent
Revascularization Medical trt. Revascularization Medical trt.6 studies (N= 686) 6 22 16 28
Viability, Trt. type & Event Rates in Pts with LVD and c/c CAD
J Nucl Med 2007; 48:1135–1146
Dr Nithin P G
Viability Assessment
• Contrast echocardiography– Myocardial perfusion correlate positively with microvascular density and
capillary area and inversely with the extent of fibrosis– DSE, 201Tl imaging, and contrast echo [N=18], pts undergoing
revascularization[contrast echo 89% sens., 51% spec.]
• TDI- strain rate imaging– Augmentation of strain and strain rate with dobutamine is a marker of
myocardial viability– PET detected viable segments compared with strain rate imaging during
low-dose dobutamine stress test [N=37]. An increase in the longitudinal strain rate of more than -0.23 S-1 identified viable tissue [83% sens., 84% spec.]
J Am Coll Cardiol. 1997;29:985–993
J Am Coll Cardiol 2002;39:443-449
Dr Nithin P G
Viability Assessment
CMR
Viability criteria– End-diastolic wall thickening > 5.5 mm
– Contrast enhanced CMR- delayed hyperenhancement
For predicting functional recovery % sensitivity % specificity
3 studies [N= 100] 95 41
For predicting functional recovery % sensitivity % specificity
4 studies [N= 132] 95 45
Heart 2005;91:1359–1365
Heart 2005;91:1359–1365 Addl. information on LVEF, LV volumes, ischaemic MR & LV shape
Dr Nithin P G
Viability Assessment
DE CMR
Viability criteria– Increase in End-diastolic wall thickening > 2 mm
For predicting functional recovery % sensitivity % specificity
9 studies [N= 252] 73(50-89) 83(70-95)
Heart 2005;91:1359–1365
Dr Nithin P G
Viability Assessment
Contrast CT
Studies Compared with Results
Hyperenhancement [subendocardial if <50% wall thickness &transmural if >50%]J Am Coll Cardiol. 2007;49:1178-1185.
DSE Agreement in 560 of 576 (97%) segments.
2 weeks of STEMI [N=28]J Am Coll Cardiol. 2005;45:2042-2047 CE-CMR Agreement in 415 of 448
(93%) segmentsA/c or c/c MI [first-pass MDCT, first-pass CMR, DE-MDCT, and DE-CMR] Circulation. 2006;113:823-833
b/w DE-MDCT & DE-CMR
Good agreement (82%) in delayed hyperenhanced regions on a segmental basisSlightly better concordance for a/c than c/c pts.
Dr Nithin P G
Comparison b/w different investigations
Dr Nithin P G
Comparison Ability to predict improvement in LVEF
DSE vs. SPECT•Agreement b/w 60.8% - 72%
•Segments with viability but no contractile reserve [rarely < 50% uptake but with contractile reserve]
•72% agreement [N=114]- 92% of segments without perfusion no contractile reserve, but 47% with perfusion also without contractile reserve
J Nucl Med 2007; 48:1135–1146JACC 1996;28:530-535
Circulation. 2002;106(suppl 1):14–18
DSE vs. MRI•Agreement around 79%
•More severe LV dysfunction [mean EF ~25%] and NYHA class > III have higher false negative rates with DSE
Heart 1999;82;684-688J Am Coll Cardiol 1990;15:1021-1031
Curr Probl Cardiol. 2001;26:142–186
Dr Nithin P G
Comparison
DE-CMR vs 201Tl redistribution vs DSE• Ischemic cardiomyopathy 3 days before transplantation• Number of viable segments detected similar in DSE & DE CMR, but less
than 201Tl, confirmed by HPE
Am J Cardiol 2002;90:455-459
% necrosis +LR -LR
DSE 31 5.5 7.7
DE-CMR 33 5.2 5.5201Tl 40 2.2 3.6
Dr Nithin P G
Comparison
European Heart Journal (2010) 31, 2984–2995
Dr Nithin P G
Clinical correlation
Dr Nithin P G
How much viable tissue?
J Teh Univ Heart Ctr 1 (2009) 5-15
Dr Nithin P G
How much viable tissue?
EF- 27%33%NYHA-3.21.6
Non viable revasc- 17%
Non viable revasc- 50%
J Teh Univ Heart Ctr 1 (2009) 5-15
Dr Nithin P G
Timing of revascularization
Circulation. 2003;108(suppl 1):II39–II42
N=4020+12 days
2 yr mort. 5%
N=4587+47 days
2 yr mort. 20%
Dr Nithin P G
Viability and coronary circulationStudy Imaging Findings[N=41] previous Q wave infarction and SV-CAD [compared viability with angiographic variables, including the degree of patency & collateralization]. Rev Port Cardiol 1996;15:313-320
201Tl SPECT•No association b/w TIMI grade and reversibility •Collateral circulation associated with viability, but absence did not exclude viability.
[N=64]CAD & LV dysfunction [whether coronary patency could help in assessing viability]
Clin Cardiol 2003;26:60-66PET
Patent arteries more likely to be viable Akinetic segments by occluded arteries (56 vs. 23, 72%) Dyskinetic segmentsnon-viable (86%) and supplied by occluded arteries (77%).
[N=47] total occlusion. good coronary collaterals had a high sensitivity (75%) and specificity (65.7%) as well as high positive predictive (75%) and negative predictive values (79%)
Angiology 2007;58:550-555
DSE
18 (38.3%) viable 29 (61.7%) non-viablesignificant coronary collateral circulation in viable [66.7% (12 patients)] and non viable [20.7% (6 patients]. Good coronary collaterals sens. (75%) & spec. (65.7%)
Dr Nithin P G
Benefits of Viability Assessment
Dr Nithin P G
Meta-analysis
J Am Coll Cardiol 2002;39:1151– 8
•Late survival with revasc. vs. medical therapy after myocardial viability testing in pts with severe CAD & LV dysfunction
• 24 studies Thallium, PET & DSE
• N= 3,088 (2,228 men), EF 32+8%, followed for 25+10 months
Dr Nithin P G
Meta-analysis
Dr Nithin P G
Meta-analysis
Dr Nithin P G
Meta-analysis
Drawbacks
• Most studies very small (n < 100) Not randomized and highly selected
• Most patients had angina; few had overt symptoms of heart failure
• Most had only mild LV dysfunction
• Most reported from imaging labs and surgical services
• 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
Dr Nithin P G
PARR2•[N=430]; EF ≤ 35% considered for revascularization, transplant, or HF work‐ up with high suspicion of CAD.• Randomized patients to a PET‐guided therapy or “standard care” (no PET).• Imaging physicians issued a therapy recommendation based on PET findings and treating physicians then made a decision regarding revascularization.• Patients in the standard care arm had no PET, but could have another viability test, which was performed in 138 of 209 (66%) patients.• Primary outcome: composite of cardiac death, myocardial infarction, or recurrent cardiac hospitalization within 1 year.
J Am Coll Cardiol 2007;50:2002-2012
Dr Nithin P G
PARR2
Hazard ratio 0.78 [95% CI –(0.58 to1.1)] [p= 0.15]
Dr Nithin P G
PARR2
Hazard ratio 0.62 [95% CI- (0.42 to 0.93)][p=0.019]
Dr Nithin P G
HEART Trial
•RCT [N=800] symptomatic HF, EF ≤ 35%, and evidence of substantial myocardial viability to conservative vs. CAG with the intention of revascularization.• Stopped early -138 pts enrolled, 69 randomized to revascularization, but only 45 underwent a procedure.
Eur J Heart Fail 2011;13:227-33
Dr Nithin P G
HEART Trial
A conservative management strategy may not be inferior to one of coronary arteriography with the intent to revascularize in patients with HF, LV systolic dysfunction, and extensive myocardial viability
Dr Nithin P G
•The first prospective randomized trial testing the hypothesis that CABG improves survival in patients with ischemic LV dysfunction [EF-26.7%±8.6] compared to outcome with aggressive medical therapy
•Myocardial viability identifies patients with CAD and LV dysfunction who have the greatest survival benefit with CABG compared to aggressive medical therapy
N Engl J Med 2011;364:1617-25
Dr Nithin P G
STICH Trial- substudy
• All pts eligible for viability testing with SPECT [Tl or Tc] or DSE
– Viability testing optional
– Criteria for myocardial viability were prospective and pre- specified [SPECT (11/17); DSE (5/16)]
• Primary endpoint: – All cause mortality
• Secondary endpoints:– Mortality plus cardiovascular hospitalization – Cardiovascular mortality
Dr Nithin P G
321 150 130
SPECT 471
DSE471
1212
618 594
17
611
601
Patients with viability test
Patients with usable viability
test
Pateints with no usable viability
test
Patients with no viability test
Unusable test
487 114
243 244 60 54
MED49.9%
MED52.6%
CABG 50.1%
CABG 47.4%
Viable Non-Viable
Dr Nithin P G
STICH Trial- substudy
After multivariate analysis p=0.21
Dr Nithin P G
STICH Trial- substudy
Dr Nithin P G
STICH Trial- substudy• Substudy of a major trial
• Viability study according to the judgement of physician
• Small number of non viable group for comparison
• Sx influenced by timing and results of viability test
• Two types of viability tests-SPECT & DSE
• Better medical therapy available
• Combined procedure [CABG + SVR] done probably not optimum
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
Dr Nithin P G
Conclusions
Dr Nithin P G
Conclusions
• Limitations in study design and test inaccuracies -prevented the detection of a true interaction b/w viability & benefit of revascularization
• Advances in medical therapy markedly reduced the added benefit of revascularization
• The critical information may not lie in the presence but rather in the absence of viability.
• The benefit of CABG may only be related to revascularization of potentially ischemic segments.
• The greatest benefit of CABG may be limited to those patients with more advanced forms of the disease[those with relatively small amount of viable myocardium]
Dr Nithin P G
Conclusions
• Currently available evidence does not support the use of viability testing as the arbitrator in the decision making process regarding revascularization in ischemic cardiomyopathy
• Ischemic cardiomyopathy [heterogeneous population] multiple factors play important prognostic role. Viability alone cannot provide an unequivocal answer
• Prospective trials demystify the emphasis previously placed – without appropriate evidence‐‐ in the significance of myocardial viability
• These observations urge physicians to consider the multiplicity of factors involved in the decision making process in this complex population of patients.
Dr Nithin P G
Thank you
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