Insights into Viability- Function and Contractile Reserve

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1 Insights into Viability- Function and Contractile Reserve Tom Marwick Cleveland Clinic Conflicts research grants and consulting with GE, Philips, Siemens Off-label use of Definity for assessment of myocardial perfusion

2 Pathophysiologic targets 1. Contractile reserve 2. Ischemia 3. Fibrosis/cellular viability 4. Flow-metabolism mismatch 5. Microcirculation Rahimtoola SH. JACC-CVI 2008;1:536

3 Is CR supported by evidence/appropriate? ACC/AHA Echo guidelines Recommendations for Echocardiography in Diagnosis and Prognosis of Chronic Ischemic Heart Disease Assessment of myocardial viability (hibernating myocardium) for planning revascularization. Class I Armstrong W. Circulation 2003 Stress Echocardiography Appropriateness Criteria (Table 8) Assessment of Viability/Ischemia Appropriateness Score (1 9) Known CAD on catheterization A (8) Patient eligible for revascularization Douglas P. JACC 2008;51:1133

4 What does the clinician need to know? 1.Resting echocardiogram - Are there sufficient clues about viability to proceed to revasc? 2.Will regional function recover? 3. Importance of ischemia 4.Global: Will the LV improve?

6 Markers of viability from resting echo LV volumes and ejection fraction Wall thinning Deceleration time Transmural extent

7 Volume and LV scar vs EF improvement >5% Pre-op LVEDV (ml) p=0.05 # echo scar segments p= pts with severe LV impairment, followed 10 weeks postop Pasquet A, Eur Heart J 2000

8 3D assessment of LV volume

10 Prediction of recovery from preserved thickness 45 pts with LV impairment, followed 2 months postop Cwaig J Zoghbi W, J Am Coll Cardiol 2000

11 Prediction of recovery from deceleration time 40 pts with severe LVD Db echo and thallium SPECT Follow-up 3 months postop Yong Y, Circulation 2001

12 Implications of scar size for remodeling 57 pts (EF 49±13%) studied 4.4±0.4 years after MI (OPTIMAAL study) Strong linear relation between scar size and LVEDVI (r = 0.81, p <0.0001), LVESVI (r = 0.86, p <0.0001), and LVEF (r = 0.74, p <0.0001) Scar size was the strongest independent predictor of EF and volumes independent of scar site and transmurality Orn S, Am J Cardiol 2007

13 Radial strain and transmural extent Becker M. EHJ 2006

14 Sensitivity/specificity Sensitivity/specificity FUNCTION AND CONTRACTILE RESERVE Radial deformation and transmural extent C/S (17%) C/SR (1.4) R/S (27%) R/SR (1.35) C/S (11%) C/SR (1.0) R/S (17%) R/SR (1.1) Stunning (0%) vs nontransmural (1-50%) Nontransm (1-50%) vs transmural (>50%) Sensitivity Specificity Becker M. EHJ 2006

15 What does the clinician need to know? 1. Clues from resting echocardiogram 2.Will regional function recover? 3. Importance of ischemia 4.Global: Will the LV improve?

16 Prediction of LV remodeling

17 Comparison of techniques for diagnosis of viable myocardium 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Sensitivity Specificity Tl RR (n<150) Tl SRR (n<250) MIBI (n<200) FDG PET (n<300) LDDE (n<450) Db-MRI (n<100) C-MRI (n<100) Bax J + others

18 Strain rate for prediction of viability (PET) Green-yellow changes with Db=viable Hoffmann R, J Am Coll Cardiol 2002 Strain rate at rest (solid line) and during dobutamine stimulation (dotted line) in a viable segt by 18 FDG PET. Peak SR increases from 1.1 /s at rest to 2.0 /s

19 Baseline and follow-up Rest Baseline SR 9 Month Follow-up SR Low Dose Dobutamine * * ΔSR * 0 ESS 0 ESS Hanekom L, Circulation * * ΔESS -15 *

20 Optimal cut-offs WM vs SRI Sensitivity Specificity % WMS Lowdose SR SR increment Lowdose ESS ESS increment -0.7/s -0.25/s -9-3 Model ** p=0.015 vs WMS 55 pts (age 64±10 y, EF 36±8%) with past MI Hanekom L, Circulation 2005

25 Rest Low dose Peak dose Strain SR

27 Structural change and negative DE 22 segts that improved after CABG (effectively removed fibrotic segts) Tested pre-cabg with PET and DbEcho Designed to address whether lack of Db response correlated with ultrastructural damage p<0.001 Damaged myofibrils p<0.03 Glycogenrich cells No Db response Db response p=ns Interstitial fibrosis Pagano.. Camici. Heart 2000;83:456

28 Implications of extent for management Chronic LVD Db Echo UGLY Very dilated LV Lots of thinned segts Non-recoverable LV BAD Lots of RWMA No or small DbE response How much is there left? GOOD Lots of RWMA Extensive biphasic resp Recoverable LV Transmural ext of scar MRI/Tissue Doppler No intervention Poor outcome Level of absolute flow PET,?MCE Metabolism FDG PET Revascularize Prognostic benefit

29 What does the clinician need to know? 1. Clues from resting echocardiogram 2.Will regional function recover? 3. Is there ischemia? 4.Global: Will the LV improve?

30 Regional contractile reserve

Pts with biphasic response (ischemia and viability) had the best recovery of function after revascularization, emphasizing the need to continue dobutamine infusion until

31 Pts with biphasic response (ischemia and viability) had the best recovery of function after revascularization, emphasizing the need to continue dobutamine infusion until the end point is reached for assessment of viability. Cornel JH. J Am Coll Cardiol 31: , 1998 FUNCTION AND CONTRACTILE RESERVE Biphasic response and functional recovery

32 Outcomes and DbE findings Follow-up to 9 yrs (mean 3.5±2.0 yrs) Follow-up 98.7% complete Revascularization in 332 pts (CABG 184, PTCA 184 pts) - censored from follow-up Endpoints; Cardiac death in 259 pts (8%) Infarction in 151 pts (5%)

33 What does the clinician need to know? 1. Clues from resting echocardiogram 2.Will regional function recover? 3. Is there ischemia? 4.Global function: Will the LV improve?

Extent of viability and recovery of LV function 100 80 60 40 20 P=NS LVEF <35% LVEF >35% P=NS 0 Sensitivity Specificity 61 pts; viable = 4 segts with biphasic response for prediction EF improvt >5%

34 Extent of viability and recovery of LV function P=NS LVEF <35% LVEF >35% P=NS 0 Sensitivity Specificity 61 pts; viable = 4 segts with biphasic response for prediction EF improvt >5% Cornel Fioretti, J Am Coll Cardiol 1998 In pts with severe LVD, predictive accuracy of DSE for functional recovery after revasc was maintained in pts with or without severe LVD Cusick DA. J Heart Lung Transpl 15:186S, 1997

35 Lowdose EF response predicts response to CABG Viable pts (D EF post op >5%) Non viable pts (D EF post op <5%) EF (%) < NS EF (%) NS NS < EF pre EF low DbE EF post NS EF pre EF low DbE EF post Pasquet, Am J Cardiol 1999

36 Extent of viability and outcome LDDE in LVD n=274 Revascularized n=133 Medical therapy n=141 None (n=44) No viable segts C. EF 36±4% Small (n=60) <6 viable segts B. EF 34±4% Extensive (n=29) >6 viable segts A. EF 35±5% Death Postop EF 37±6% Postop EF 40±5% Postop EF 47±6% Meluzin J, J Am Coll Cardiol 1998 All events (incl UAP, CHF)

37 Functional markers of viability Resting echocardiogram LV volumes deceleration time wall thinning Interpretation of the stress response uniphasic vs biphasic volume responses New developments quantitative approaches

39 Hibernation and ischemia are not rare #pts LVEF Method %viab Auerbach Circ 99 Cleland Lancet 03 Schinkel AJC ±8 PET 55% ±11 SPECT 58% ±12 DSE 58% Nonviab V 1 segt V 2 segts V 3 segts V 4 segts 408 pts with EF <40%, stable CHF >3 months CHRISTMAS study

Viability Testing Using Dynamic Echocardiography

Viability Testing Using Dynamic Echocardiography Theodora A Zaglavara, MD, PhD Director of Echocardiography EUROMEDICA KYANOUS STAVROS HOSPITAL Thessaloniki GREECE Goals of Cardiac Imaging in Coronary