Download CMR Viability

A major teaching
hospital of Harvard
Medical School
Myocardial Viability: CMR
Thomas H. Hauser
MD, MMSc, MPH, FACC
Director of Nuclear Cardiology
Beth Israel Deaconess Medical Center
Assistant Professor of Medicine
Harvard Medical School
Boston, MA
Case
A 79-year-old man with a history of “heart attacks”
in 1978 and 1979 presented with increasing
dyspnea on exertion over several months. He also
noted increasing fatigue over the same time
period. He otherwise felt well.
Physical examination revealed a HR of 60 with a BP
of 115/65. His lungs were clear. His heart sounds
were normal. There was no peripheral edema.
He was referred for a nuclear myocardial perfusion
study to further evaluate his symptoms.
Imaging Protocol
• Stress: Prone 99mTc-Sestamibi
• Rest: Prone 201Tl
Nuclear Myocardial Perfusion: Slices
Nuclear Myocardial Perfusion: Gated
Nuclear Myocardial Perfusion: LVEF
Case
The nuclear myocardial perfusion study was
interpreted as having a large, severe fixed defect
involving the LAD territory. The left ventricular
cavity size was increased with severe systolic
dysfunction due to akinesis in the territory of the
defect.
He was referred for cardiac catheterization.
Cardiac Catheterization
Coronary angiography demonstrated left main and 3
vessel disease in a left dominant system. The left
main had a discrete, distal 60% stenosis. The LAD
was occluded proximally and filled via left to left
collaterals. The large ramus branch had a 80%
stenosis. The OM branch of the LCX had a tubular
70-80% stenosis. The RCA had a proximal
smooth, 70% stenosis and a 70% distal stenosis.
Case
Should the patient be revascularized?
Dysfunctional but Viable Myocardium
LVEF 32%
LVEF 54%
Horn HR, Teichholz LE, Cohn PF, Herman MV, Gorlin R. Augmentation of left ventricular
contraction pattern in coronary artery disease by an inotropic catecholamine: the epinephrine
ventriculogram. Circulation 1974;49:1063-1071
Dysfunctional but Viable Myocardium
• Hibernating
– Chronic ischemia or repetitive stunning
– Ultrastructural changes that result in
• Disassembly of contractile apparatus
– Recovery in weeks or months after revascularization
• Stunned
– Acute ischemia
– No ultrastructural changes
– Recovery in minutes to days after revascularization
CABG in Patients with LV Dysfunction
Chareonthaitawee et al, JACC 2005;46:567
Importance of Viable Myocardium
J Am Coll Cardiol 2002;39:1151
Prevalence of Myocardial Viability
Schinkel et al, J Nucl Med 2007; 48:1135
Evaluation of Viability
Chareonthaitawee et al, JACC 2005;46:567
Evaluation of Viability
• SPECT
–
–
201Tl
–
–
123I
99mTc
Fatty Acids
PET Agents
• PET
–
18FDG
–
11C
Acetate
• Echocardiography
– Dobutamine
• CMR
– Late gadolinium enhancement (hyperenhancement, delayed
enhancement)
– Dobutamine CMR
SPECT
•
201Tl
most commonly used
– Several protocols for use
• Stress – redistribution
• Rest – redistribution
– Usually imaged 4 to 24 hours after initial injection
– With or without reinjection
» Usually at 4 hours
– Perfusion tracer initially
• Ischemia is a sign of viability
– Membrane integrity tracer in the late phase
• K analog
– Assesses integrity of membrane and Na-K-ATPase
SPECT
•
99mTc
also helpful
– Stress – rest protocol
– Perfusion tracer
– Ischemia is a sign of viability
– Membrane integrity tracer
• Trapped by active mitochondria
201Tl
Uptake and Recovery of Function
Perrone-Filardi P, Pace L, Pratarto M, et al. Dobutamine echocardiography predicts improvement
of hypoperfused dysfunctional myocardium after revascularization in patients with coronary
artery disease. Circulation. 1995;91:2556-2565.
Comparison of 201Tl and 99mTc
Udelson JE, Coleman PS, Metherall J, et al. Predicting recovery of severe regional ventricular
dysfunction. Comparison of resting scintigraphy with 201Tl and 99mTc-sestamibi. Circulation.
1994;89:2552-2561.
Nuclear Myocardial Perfusion: Slices
Case
Based on the nuclear myocardial perfusion images,
revascularization would not be predicted to
improve his left ventricular systolic function.
Because he was otherwise a good operative
candidate, further evaluation of viability was
pursued
PET
• All PET agents (18FDG, 11C acetate) assess cardiac
energy metabolism.
–
18FDG
imaging assesses glucose metabolism
• Ischemic myocardium generally favors glucose utilization
–
11C
acetate imaging assesses lipid metabolism
Importance of Good Patient Preparation
• In the assessment of myocardial viability, the
quality and utility of the images is highly
dependent on appropriate patient preparation
– Inadequate patient preparation can lead to spurious
results or images with no diagnostic value
Myocardial Energy Metabolism
• Cardiac myocytes are continuously active
– Require efficient use of energy resources
– Require continual repletion of energy substrates
• Faced with varying levels in supply
– Flexibility in substrate use
» Glucose
» Free fatty acids
» Amino acids
FDG Uptake and Retention
glycogen
Insulin
glut
FDG
FDG – 6 – P
Aerobic Metabolism
Acipimox
• Potent inhibitor of peripheral lypolysis
– Drastically reduces FFA in blood
• As FFA are the principal alternative energy source
for the myocardium, glucose utilization increases
– Relatively independent of insulin and glucose levels
• Not FDA approved
– Used in Europe
Hyperinsulinemic/Euglycemic Clamp
• Simultaneous infusions of insulin and glucose to
increase the insulin level while keeping the
glucose level from falling
– High insulin
– Normal glucose
– Low FFA
• High myocardial glucose utilization
Glucose Loading
• Provide a large dose of oral or IV glucose
• Endogenous production of insulin
–
–
–
–
Supplemented with exogenous insulin if needed
Moderately high insulin
Normal glucose
Low FFA
• High myocardial glucose utilization
PET: 18FDG
Srinivasan G, Kitsiou AN, Bacharach SL, et al. [18F]Fluorodeoxyglucose Single Photon Emission
Computed Tomography : Can It Replace PET and Thallium SPECT for the Assessment of Myocardial
Viability? Circulation. 1998;97:843 - 850.
Dobutamine Echocardiography
Dobutamine Echocardiography
• Low dose dobutamine
– Typically paired with high dose dobutamine
– Four typical responses
•
•
•
•
Biphasic response
Progressive dysfunction
Sustained improvement
No change
Dobutamine Echocardiograpy
Afridi et al, JACC 1998. Group I (n = 85) consisted of patients who had evidence of myocardial viability and subsequently underwent revascularization. Group II (n = 119) consisted of patients with myocardial
viability who did not undergo revascularization. Group III (n = 30) consisted of patients who did not have myocardial viability and underwent revascularization. Finally, group IV (n = 84) patients lacked myocardial
viability and did not undergo revascularization.
Comparison of Techniques
Chareonthaitawee et al, JACC 2005;46:567
Gd Contrast Kinetics in Myocardium
Circulation, Dec 1996; 94: 3318 - 3326
Delayed
Contrast
Enhancement:
Bright is Dead
Circulation, Nov 1999; 100: 1992 - 2002
Normal Myocardium
Anterior/Apical Scar
Ischemic CM with Viable Myocardium
Prediction of Recovery of Function
• 41 patients imaged
before and ~80 days
after revasc.
• 78% of segments with
no LGE had recovery
of function
• 92% of segments with
>50% transmural
LGE did not recover
• 36% of all segments
had an intermediate
probability of
recovery
Kim et al, N Engl J Med 2000; 343:1445-1453
Dobutamine CMR
Wellnhofer et al, Circulation 2004;109:2172-2174
Dobutamine CMR
Wellnhofer et al, Circulation 2004;109:2172-2174
Solid = DCMR, dashed both, hatched LGE. Scar cutoff 25%
Case
The patient was referred for CMR.
SSFP Gated Images
Late Gadolinium Enhancement
Case
The CMR study was interpreted as showing a
severely increased cavity size and severe systolic
dysfunction with transmural/near transmural late
gadolinium enhancement of the mid and distal
anterior wall, the distal septum, the distal inferior
wall and the apex.
He was treated medically and died one year later of
complications from a lung mass and progressive
congestive heart failure.
Which is Better?: CMR vs. PET
•
•
•
•
Cost
Safety
Ease of implementation
Accuracy
Cost
• Cost
– Medicare payment (rough estimate of cost to society)
• CMR ~$750
• PET ~$1400
– Hospital margins/physician payments
• PET > CMR
• Conclusion: CMR is superior (… if you are the
payer)
Safety
• Safety
– PET
• Radiation
• Hypoglycemia
– CMR
• NSF
• Conclusion: CMR and PET are both generally safe
in this patient population
Ease of Implementation
• Patient preparation for FDG PET is arduous
5. If the initial BS is >250, then give IV regular insulin according to the protocol below. If oral
glucose is given, recheck BS in 30 minutes and then give IV regular insulin according to the
same protocol.
Give IV regular insulin
BS ? 140
None
BS 141 to 160
1 units
BS 161 to 180
2 units
BS 181 to 200
3 units
BS 201 to 220
4 units
BS 221 to 240
5 units
BS 241 to 260
6 units
BS 261 to 280
7 units
BS 281 to 300
8 units
BS >300
Notify Physician
6. Check BS every 15 minutes.
 If BS is <140, inject FDG
 If BS continues to rise, give IV regular insulin according to the protocol above and
continue to check BS every 15 minutes
 If BS is falling but remains elevated, give IV regular insulin at half the dose according
to the protocol above and continue to check BS every 15 minutes
 If BS remains elevated after 90 minutes, contact the imaging physician
7. Have the patient eat a light meal 15 minutes after injection of FDG.
8. Continue to check BS every 30 minutes after injection of FDG to monitor for hypoglycemia.
9. Begin imaging 60-90 minutes after injection of FDG.
10. After imaging, monitor patient for 30 minutes and obtain BS. If BS >70 then the patient can
be discharged.
11. Upon discharge instruct the patient to:
 Beware of hypoglycemia. Encourage the patient to have a meal soon after discharge.
 Resume all prior medications.
If at any time during the protocol there is a question about how to proceed,
contact the imaging physician immediately.
CMR: Exellent Spatial Resolution
Wagner et al. Lancet. 2003;361:374
PET: Scar is More Important than Mismatch
• Beanlands et al evaluated
70 patients before and
after revasc.
• “Scar” score was the most
important predictor of
recovery of function
– Superior to mismatch score
in both univariate and
multivariate analyses
Beanlands et al (PARR-1) JACC 2002;40:1735– 43
PET Only Images Myocardium, Not Scar
Knuesel et al. Circulation. 2003;108:1095
CMR Multicenter Trial
• Lenge et al imaged 183 patients
before and ~6 months after
revasc.
• 72% of segments with no LGE
had recovery of function
• 83% of segments with >50%
transmural LGE did not recover
• 21% of all segments had an
intermediate probability of
recovery
Lenge et al, SCMR 2008
PET Multicenter Trial
• Gerber et al imaged
178 patients before
and 2 to 6 months
after revasc.
• Endpoint was >5%
improvement in LVEF
– RVG, echo, LV gram
Gerber et al, Eur Heart J 2001; 22, 1691–1701
PET: Poor Specificity
• Gerber et al also assessed
myocardial glucose uptake
during hyperinsulinemiceuglycemic clamping
• Large overlap of normal
and dysfunctional
segments with wide intraand inter-patient variation
• Probable overlap large
overlap of segments that
recover and do not recover
(data not reported)
Gerber et al, Eur Heart J 2001; 22, 1691–1701
Comparison of FDG and DE-CMR
Knuesel et al. Circulation. 2003;108:1095
Direct Comparison of FDG PET and CMR
• Wu et al imaged 28 patients
before and ~20 days after
revasc.
• CMR (>50% transmural)
– Sensitivity 92%
– Specificity 45%
• PET/SPECT (>50% normalized
uptake)
– Sensitivity 99%
– Specificity 60%
• ROC analysis showed no
significant difference
Wu et al, JNM Vol. 48 No. 7 1096-1103
PET: Fails to Improve Clinical Outcomes
• Beanlands et al randomized
430 patients to FDG PET
guided revascularization or
standard care
• Primary endpoint was a
composite of cardiac death,
MI or hospital stay for a
cardiac cause at 1 year
• No significant difference in
the primary endpoint or
survival
– Minor effects found in
subgroups
Comprehensive CMR Evaluation
• Structure
• Function
– With or without stress
• Flows
• Perfusion
– With or without stress
• Scar/Viability
• Coronary Anatomy
FDG and MR for Scar/Viability
•
•
•
•
FDG
Directly assesses metabolism
Images viable myocardium
Established gold standard for
determining recovery of
function after revascularization
Clinical trial suggests lack of
effect on outcomes
•
•
•
•
•
•
•
DE-CMR
Directly assesses anatomy
Images both scar and viable
myocardium
Clinically established
established
Superior spatial resolution
compared to FDG
Lower cost
Easier to implement
Part of a comprehensive CMR
evaluation
Summary
• Clinical relevance of evaluating myocardial viability
• SPECT
– Tl-201
– Tc-99m
• PET
– FDG
• Echocardiography
– Dobutamine
• CMR
– Late gadolinium enhancement
– Dobutamine
• Compared CMR and PET