Presentation on theme: "Myocardial Viability: CMR Thomas H. Hauser MD, MMSc, MPH, FACC Director of Nuclear Cardiology Beth Israel Deaconess Medical Center Assistant Professor."— Presentation transcript:
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 A major teaching hospital of Harvard Medical School
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.
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 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 LVEF 32% LVEF 54%
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 – 201 Tl – 99m Tc – 123 I Fatty Acids –PET Agents PET – 18 FDG – 11 C Acetate Echocardiography –Dobutamine CMR –Late gadolinium enhancement (hyperenhancement, delayed enhancement) –Dobutamine CMR
201 Tl 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
99m Tc also helpful –Stress – rest protocol –Perfusion tracer –Ischemia is a sign of viability –Membrane integrity tracer Trapped by active mitochondria SPECT
201 Tl 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 201 Tl and 99m Tc-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 ( 18 FDG, 11 C acetate) assess cardiac energy metabolism. – 18 FDG imaging assesses glucose metabolism Ischemic myocardium generally favors glucose utilization – 11 C 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 glut FDG FDG – 6 – P glycogen Aerobic Metabolism Insulin
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
Srinivasan G, Kitsiou AN, Bacharach SL, et al. [ 18 F]Fluorodeoxyglucose Single Photon Emission Computed Tomography : Can It Replace PET and Thallium SPECT for the Assessment of Myocardial Viability? Circulation. 1998;97:843 - 850. PET: 18 FDG
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
Ischemic CM with Viable Myocardium
Kim et al, N Engl J Med 2000; 343:1445-1453 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
Dobutamine CMR Wellnhofer et al, Circulation 2004;109:2172-2174
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 –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 –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
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 hyperinsulinemic- euglycemic clamping Large overlap of normal and dysfunctional segments with wide intra- and 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