Myocardial viability testing. What we knew and what is new

Transcription

1 Myocardial viability testing. What we knew and what is new Dr B K S Sastry, MD, DM. CARE Hospitals, Hyderabad

2 What is Viability Viability Dysfunctional myocardium subtended by diseased coronary arteries Limited or absent scarring Potential for functional recovery Prospective definition Reversible ischemic contractile dysfunction Myocardial stunning Myocardial hibernation

3 meta-analysis of 24 studies that included 3,088 patients WCC&IVUS2015

4 meta-analysis of 24 studies that included 3,088 patients WCC&IVUS2015

5 Problems with Earlier Studies All studies were small, not randomized, observational, and retrospective. There was potential patient selection bias. The methodology and criteria for defining viability as well as the treatment regimens were not standardized among the different studies

6 Techniques for assessment of viability Contractile reserve-dob.echo and dob.mri Cell membrane integrity-spect Thallium Intact mitochondria-spect Tc Myocardial glucose utilization-pet FDG Scar tissue-demri,msct Fractional Flow Reserve, Strain Rate imaging etc.

7 Dobutamine stress echo Low-dose dobutamine (5 10 μg/kg/min) Increase contractility in viable myocardium High-dose dobutamine(upto 40 μg/kg/min) Biphasic response initial improvement F/B worsening underperfused but viable tissue-most specific sign of improvement after revasc. Uniphasic response-sustained improvement-myocardial damage with subsequent reperfusion-less predictive of improvement after revasc. Deterioration of wall motion without initial improvement-severe ischemia No change in wall motion-scar Sensitivity(84%),specificity(81%)for recovery of function

8 Strengths and Limitations of DSE Strengths- Higher specificity Viability&ischemia assessed MR can be detected Good spatial resolution Widely available Lower cost Predictive of clinical outcomes Limitations Poor window in 30% Lower sensitivity Viable regions with absent flow reserve will not show thickening Reliance on visual assessment

9 Myocardial perfusion SPECT Thallium or Tc. Labelled radio isotopes may be used. Uptake depends on viability &regional perfusion Redistribution-gradual accumulation of tracer in hypoperfused areas, rapid washout from normally perfused areas Segments with tracer uptake >60%-viable Subendocardial scar tissue may be labelled as viable-lower specificity

10 Stress Thallium Protocols Rest redistribution protocols- Defects in initial images that improve in 4 hour image-viable myocardium Additional 24 hr image if fixed defects in 4 hr image S/L NTG prior to injection Less sensitive-86%,specificity 47%

11 Stress MIBI Strengths and Limitations Strengths High sensitivity Quantitative objective criteria LVEF FDG with special collimator Predictive of outcomes Limitations Reduced spatial resolution &sensitivity compared to PET Attenuation artefacts Cannot differentiate endocardial viability Less quantitative than PET

12 PET Positron emitting isotopes releasing 2 photons at angle180,detected by camera by coincidence counting to give a higher resolution Perfusion tracers-n13 ammonia, Rb 82,O15 water Metabolic tracers- F18DG,C11acetate,C11 palmitate FDG taken up by viable cells, phoshorylated & trapped inside Poor uptake in diabetics

13 PET Scan Interpretation Normal perfusion-viability Flow metabolism mismatch-reduced perfusion with intact metabolism-hibernating viable myocardium Flow metabolism match-impaired FDG uptake with reduced perfusion-scar Gold standard for assessment of viability

14 Strengths and Limitations of PET Strengths- Perfusion &metabolism More sensitive No attenuation Absolute blood flow can be measured Predictive of outcomes Limitations Lower specificity to dob.echo & MRI Cannot differentiate b/w endocardial and epicardial viability High cost Limited availability

15 Contrast Enhanced MRI DEMRI using Gadolinium based agents (i.v.0.2 mmol/kg) Extracellular space Infarcted or scarred tissue-interstitial spaces larger-delayed wash in &delayed wash out Hyperenhanced area of myocardium on images taken 10 to 20 min after contrast Size and shape of infarct correlate with histology

16 Short-axis DE-MRI images in three patients with acute myocardial infarction. WCC&IVUS2015

17 End Diastolic thickness of more than 6 mm suggests viable myocardium WCC&IVUS2015

18 DE MRI pictures in patient with Reversible and irreversible LV dysfunction WCC&IVUS2015

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21 Shah DJ, Kim HW, JAMA Mar. WCC&IVUS2015

22 Strengths and Limitations of MRI Strengths Accurate assessment of extent of scar Superior spatial resolution Wall thickness correctly measured Simultaneous assessment of perfusion, function and viability Good imaging windows Limitations High cost Limited availability Longer time Contra.with implanted ferromagnetic objects Gadolinium contra.in CKD with GFR<30ml/min Claustrophobia Irregular rhythems Breathholding required

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25 DSE Vs nuclear imaging Sensitivity 90% for nuclear imaging,74% for DSE Specificity 57% for nuclear imaging,78% for DSE Bax JJ et al;2002 Integration of both may be useful

26 STITCH Trial A randomized, multi center, non blinded trial patients with CAD and LVEF < 35% without severe AP / LMCA disease were randomized to CABG with intensive medical therapy or intensive medical therapy alone. The primary endpoint of all cause mortality after a median follow up of 56 months occurred in 41% of patients randomized to medical therapy alone compared with 36% randomized to CABG. This difference did not reach statistical significance (HR with CABG, 0.86; 95% CI, ; P=.12).

27 STITCH Trial protocol Post-randomization myocardial viability testing by dobutamine stress echocardiography and/or radionuclide imaging was recommended. In the 601 patients who received a viability study, there was a significant association between viability and outcome on univariate analysis but not on multivariate analysis. Assessment of myocardial viability did not identify patients with a differential survival benefit from CABG as compared with medical therapy alone.

28 Limitations of STICH Trial Slightly less than half of the 1212 enrolled patients enrolled underwent viability testing. Patients were not randomized to viability testing. Selection/enrolment bias can not be eliminated. Only 19% of the patients were deemed not to have viable myocardium,which limited the power of the analysis to detect a differential effect of CABG. Viability analyses were limited to SPECT and DSE imaging. Caution should be taken to not extrapolate these results to DE-MRI.

29 Conclusions of STITCH trial There was no significant interaction between myocardial viability and medical versus surgical treatment with reference to primary end point. This was true whether patients were grouped according to the assigned treatment (i.e., intentionto-treat analysis) or to the treatment actually received. Other variables could have influenced the outcome. Assessment of myocardial viability alone should not be the deciding factor in selecting the best therapy.

30 Other Trials Similar to STICH trial, Heart Failure Revascularization trial, an RCT of Conservative Vs Revascularization strategy did not show benefit with revascularization in patients with proven viable myocardium. Adding surgical ventricular reconstruction to surgical revascularization would not improve the outcomes in patients with non viable myocardium

31 Functionality Vs Viability A viable tissue may not be functional. Even when it is contractile, it may not increase LV regional function if it is trapped within a scar. Prognosis may improve even if the functionality is restored. Peri procedurural or Peri op MI, may lead to a negative result. Late vessel patency also has implications.

32 In Conclusion Retrospective studies showed benefit of Viability testing. Prospective studies failed to show the benefit. Further studies with better techniques and methodology need to be done. Till then make decision based on many factors.