assessment of myocardial viabilitysummitmd.com/pdf/pdf/10_6_jamesmin.pdf · stich‐viability trial...
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Assessment Of Myocardial Viability
James K. Min, MD FACCPresident Society of Cardiovascular Computed TomographyPresident, Society of Cardiovascular Computed TomographyAssociate Professor of Medicine, UCLA School of Medicine
Associate Professor of Medicine and Imaging Cedars-Sinai Medical CenterAssociate Professor of Medicine and Imaging, Cedars Sinai Medical CenterCo-Director, Cardiac Imaging, Cedars-Sinai Heart Institute
Director, Cardiac Imaging Research, Cedars-Sinai Medical Center
Disclosures: Research support (NHLBI; Qatar National Research Fund; GE Healthcare; Philips Medical, Vital Images, Infinitt/Xelis); Medical Advisory Board (GE Healthcare); Medical Consultant (Edwards Life Sciences); Equity Interest (TC3 Cardiovascular Core Laboratories; Cedars-Sinai Medical Center)
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Typical Viability Scenarioyp y• 55 year-old male with severe y
chest pain; dragged into hospital by wife after 1 dayhospital by wife after 1 day
• Cath: occluded LAD, low BP balloon pump balloon pump
• Bedside echo: EF 20%
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Management DilemnaManagement DilemnaB ll d ll d b t• Balloon pump gradually weaned, but ongoing low-output symptomsg g p y p
• Bypass surgery (CABG) is being considered to improve blood flow toconsidered to improve blood flow to hypocontractile myocardiumyp y
CMR ordered to assess viabilityCMR ordered to assess viability . . .
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Questions We Really Want AnsweredQuestions We Really Want Answered
Will thi ti t d b tt ith• Will this patient do better with coronary revascularization?
R li i t ?– Relieving symptoms?– Do better with an ICD?
E i i d l t i l?– Experience improved long-term survival?
Will thi ti t i ( i d• Will this patient improve (prognosis and therapeutic benefit)?
Impro e LV f nction? Not ha e orsening LV– Improve LV function? Not have worsening LV function?Respond to medical therapy?– Respond to medical therapy?
– Do better with an ICD?
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Premise for Viability ImagingPremise for Viability Imaging
Si k di i b t t f• Sick myocardium is substrate for -–Heart failure–Arrhythmias
Cardiovascular death–Cardiovascular death• If myocardium can be restored to y
health (i.e. if viable), then outcomes should improveshould improve
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What is myocardial viability?What is myocardial viability?• Absence of scar: LGE-CMRAbsence of scar: LGE CMR• Integrity of cell membranes: LGE-CMR, thallium
scintigraphyscintigraphy• Metabolic activity: FDG-PET• Demonstration of inotropic reserve:Demonstration of inotropic reserve:
dobutamine stress echo or CMR
• Intact generation of high-energy phosphates: P-MRSP MRS
• Lack of sodium accumulation: Na-MRS
*Evaluated in STICH Viability study
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(1) CMR is validated against a pathologic reference standard
2 months2 months 2 months2 months
Circulation 1999;100:1992-2002 JACC 2000; 36:1985-1991
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(2) CMR LGE depicts a logical t i th h i l istepwise pathophysiologic process
Normal myocardiumNa NaGdd
Acute infarctionNaNa
Gd
ScarGd
Gd
Na
GdGdGd
Na
Gd Na
GdGd Gd
N
K K
KK
K Na
Na Na
GdGd
Na Gd
GdGdNa
Gd Na
NaGd Gd
GdK K
KK
K
NaGd
Na
GdGd
GdNaNa
NaGd
Na Gd
NaGd
GdNa
Na
KKK
Intact cell Ruptured cellNa NaGd
NaGd
C ll t i
Na
GdGd
GdGdNa
Intact cell membrane
Ruptured cell membrane
Collagen matrix
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(3) Infarct Transmurality Predicts (3) Infarct Transmurality Predicts ( ) yRevascularization Response
( ) yRevascularization Response
50 pts with LV dysfunction d iundergoing coronary
revascularization (NEJM 2000;343:1445-53)
Wall Motion Improvement Predicted by MRI?
( ; )
MRI #1MRI #1Cine MRI
for wall motion Cine MRIPCI (32%) orMRI #2MRI #2
for wall motion
DE-MRI for viability
Cine MRIfor wall motion
12 5W18 25D
PCI (32%) or CABG (68%)
viability 12 5W 18 25D
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Prediction of Regional & Global ImprovementGlobal Improvement
256/32
Likelihood of
9
109/183
p < 0.0001 for trend
Likelihood of Wall Motion
Improvement
46/110
Improvement13/124 1/58
Transmural Extent of HyperenhancementTransmural Extent of Hyperenhancement
N Eng J Med 2000;343:1445-1453
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(4) Infarct Transmurality Predicts(4) Infarct Transmurality Predicts(4) Infarct Transmurality Predicts Therapeutic Response
(4) Infarct Transmurality Predicts Therapeutic Response
35 pts with LV dysfunction undergoing initiation of beta blocker therapy (62%initiation of beta blocker therapy (62% CAD, NYHA II – III) Circ 2003; 108:1945-53
Wall Motion Improvement Predicted by MRI?
MRI #1MRI #1Cine MRIfor wall motion Cine MRIBeta blocker
MRI #2MRI #2for wall motion
DE-MRI for viability
Cine MRIfor wall motion
6 months
Beta blocker
viability 6 months
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Relation Between Transmural Extent of Scar and Contractile Improvement after
Beta-Blocker TherapyBeta-Blocker Therapy
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(5) Infarct Surface Area by CMR Better Predicts VT Inducibility than LVEF
Bello D et al. JACC 2005.Stevenson WG. JCE 1995.
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(6) Scar is Substrate for Adverse Post-MI Remodeling
acute MI (hours)infarct expansion(hrs to days)
global remodeling(days to months)acute MI (hours)
infarct expansion(hrs to days)
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(7) CMR Evaluates Effects on Coronary Microcirculation
• Essential for delivery of substrates/O & washout of• Essential for delivery of substrates/O2 & washout of metabolites
Scar (white)
MO (black)Pericardial effusion
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MO and Recovery of Function Post-MI
No MO
norm
al MO
roving
to
ments im
pr% of segm
transmural extent of infarction, LGE
%
Nijveldt R et al. JACC 2008.
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(8) Does Viability Imaging Improve Outcomes?
p=0.02adjHRadjHR0.62
(.42 - .93)
Significant reduction in cardiac events w/FDG-PET ifmanagement adhered to PET recommendations
Beanlands R et al. JACC 2007.
management adhered to PET recommendations
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Who Got a Viability Study in STICH?Who Got a Viability Study in STICH?
• Caucasians (82% vs. 54%) [Fewer Asians (5% vs 30%)]Asians (5% vs. 30%)]
• Atrial fib / flutter (15% vs. 10%)( )• Better Med Tx (higher rates of beta-
bl k ACEI t ti ASA )blocker, ACEI, statin, ASA use)• No CMR viability data availableNo CMR viability data available
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Back to Our PatientBack to Our Patient…
55 / l ith t MI l d d LAD• 55 y/o male with recent MI; occluded LAD• LGE-CMR ordered for viability assessment
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Our Patient…
N i bilit i LAD t itNo viability in LAD territory Left ventricular assist device transplantation
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Utility of CMR for Viability Imaging• Direct relation with pathology• Accurate imaging of infarct size/ viability• Predicts functional response toPredicts functional response to
revascularizationI l ili PET/ SPECT• Incremental utility vs. PET/ SPECT
• Targets therapeutic approaches to CMTargets therapeutic approaches to CM• Identifies at-risk arrhythmogenic
ti tpatients• Examines effects of MI on coronary y
microcirculation
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Thank youThank you.
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The Reports of Viability Imaging’s Death are Greatly Exaggerated…
• Randomization is key• Randomization is key• Multiple modalities need to
be comparedbe compared• Management decisions
based on viability should bebased on viability should be standardized
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Clinical Definition of ViabilitClinical Definition of Viability
Ideal Imaging Method
QUESTION:Is the anterior wallIs the anterior wall viable or not viable?
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Definition of ViabilityDefinition of Viability
InfarctInfarctMRI: aMRI: a
a+caa cc
S C aSPECT: abbb
RemoteRemote
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Limited Spatial Resolution (P ti l l ff t )(Partial volume effects)
•If <50% of counts ofIf 50% of counts of remote region Fixed (Infarct) byFixed (Infarct) by SPECT
•If <50% myocardium involved No Infarctinvolved No Infarct by SPECT
Lancet 2003; 361:374 - 9
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Infarct Morphology is ImportanInfarct Morphology is Importan
Transmural extent of infarct predicts functional presponse
DE‐MRI is uniquely capable of imaging p g gtransmural extent of infarctinfarct
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Microvascular Obstruction by LGE‐CMR
SAX
Microvascular Obstruction by LGE‐CMR
SAXHLA
(bl k)
Scar (white)
Pericardial
VLA
MO (black) effusion
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You’re worse off without viabilityYou re worse off without viability
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Case: 46 y/o Caucasian Man• Chest pain: Atypical chest pain prompted CT
angiogram at OSHangiogram at OSH• Reported to have left main dissection• High grade stenosis in LAD• High-grade stenosis in LAD• Other coronaries reported as “moderate”• Now CP free• Now CP-free
• Self refers to 2 cardiologists for 2nd and 3rd• Self-refers to 2 cardiologists for 2nd and 3rd
opinion• Coronary CT angiogram re reviewed• Coronary CT angiogram re-reviewed
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STICH‐Viability TrialSTICH‐Viability Trial
• 1 212 patients underwent physician directed• 1,212 patients underwent physician‐directed viability testing with SPECT or dobutamine echo
• 601 with usable test results• 601 with usable test results
Bonow RO et al. NEJM 2011.
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Relation Between Transmural Extent of Scar and Contractile Improvement
ft B t Bl k Thafter Beta-Blocker Therapy
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Prediction of Global ImprovementPrediction of Global Improvement
r = 0.75p < 0 0001r = 0.75p < 0 0001p < 0.0001p < 0.0001
N Engl J Med N Engl J Med 2000;343:14452000;343:1445--14531453
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• 5 dogs with CMR and SPECT prior toSPECT prior to sacrifice
• Pathology infarctPathology infarct verification
LancetLancet 2003; 361:374 2003; 361:374 -- 99
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Dog B
D B
TTC MRI SPECTHISTOLOGYinfarct
DE‐CMRinfarct
SPECTinfarct
Dog B
L tL t 2003 361 3742003 361 374 7979LancetLancet 2003;361:3742003;361:374‐‐7979
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HISTOLOGYDE‐CMRSPECTinfarctInfarctNo infarct
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MyocyteMyocyte Necrosis = Necrosis = HyperenhancementHyperenhancement
TTCTTC
UV
JACC JACC 2000; 36:1985 2000; 36:1985 -- 9191MRI
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Late Gadolinium Enhancement (LGE)( )
Kim RJ et al. Circ 1999.
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Thank youThank you.
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(4) Understanding of Atherosclerotic Adaptive Mechanisms 1980s to Present
• Plaque localization
Mechanisms, 1980s to Present
Plaque localization• Artery wall adaptive responses• Shear stress regulation of artery size
Ath l ti l l ti• Atherosclerotic plaque evolution• Autoregulation
Circ Res 53:502-514 1983Circ Res 53:502 514, 1983
NEJM 1987
“ i ll ” l i hi“Function Follows Form” Relationships
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Vulnerable PlaqueVulnerable Plaque
Çç√ç√
Figure 1. Prototype high-risk plaque at risk of rupture. (Narula and Strauss. Nature Medicine 2007.)
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Most Myocardial Infarctions Are Caused by Low Grade StenosesLow-Grade Stenoses
• In >50% of victims, the first symptom of asymptomatic atherosclerosis is
Source: Pooled data from 4 studies: Ambrose et al, 1988; Little et al, 1988; Nobuyoshi et al, 1991; and Giroud et al, 1992. (Adapted from Falk et al.)
sudden cardiac death or acute MI
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Mild Plaques Cause Adverse Events2,583 patients undergoing CCTA with <50% stenosis followed for 3.1 years
14
16HR 1.93 HR 2.74 HR 6.09
10
12
14
4
6
8
0
2
1VD 2VD 3VD1VD 2VD 3VD
• >6-fold higher mortality for patients with 3-vessel mild CAD
Source: Lin et al., J Am Coll Cardiol 2011
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Where do weWhere do we go from here?g
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Increased hazards for ACM evident for those with low FRS and no medically modifiable risk factorslow FRS and no medically modifiable risk factors
HR 4 40 HR 3 20
8
10HR 4.40
(95% CI 2.68-7.22)P<0.0001
HR 3.20(95% CI 1.57-6.50)
p=0.001
6
8 P 0.0001 p 0.001
2
4
0
2
Low FRS No Tx CAD RFLow FRS No Tx CAD RF
Hazards Ratio28.6%56.5%
Medically Modifiable CAD RF = diabetes, dyslipidemia, hypertension
Source: Min et al. ACC 2011 Scientific Sessions 2011; Chow et al. AHA 2011