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© 2007 Cardinal Health. All rights reserved. PET In Cardiology; Metabolic Imaging with 18-FDG.

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1 © 2007 Cardinal Health. All rights reserved. PET In Cardiology; Metabolic Imaging with 18-FDG

2 © 2007 Cardinal Health. All rights reserved. Introduction to Metabolic Cardiac Imaging Patients with severe left ventricular dysfunction and heart failure may have reduced cardiac performance due to irreversible (myocardial infarction or scarring), or reversible causes. Definitions: Infarction – artery blocked - heart attack Stenosis – narrowing of the blood vessel Ischemia – restriction in blood supply Perfusion – blood flow Akinesis – lack of wall motion in a myocardial segment Tachycardia – abnormal, rapid heart beat CABG – coronary artery bypass graft CHF – congestive heart failure

3 © 2007 Cardinal Health. All rights reserved. Myocardial Metabolism Resting aerobic conditions: myocardium predominantly utilizes free fatty acids (FFA) as energy substrate. Glucose loading: insulin released by glucose loading downregulates FFA use, and increases glucose utilization. Chronic ischemia: FFA utilization suppressed; anaerobic glycolysis preferred. glucose utilization normal. Acute ischemia: FFA suppressed, enhanced glucose utilization to supranormal levels.

4 © 2007 Cardinal Health. All rights reserved. Reversible Causes of Global and Regional Myocardial Dysfunction Stunned myocardium: episode of severe ischemia causes acute cell injury, disruption of architecture, and transient myocardial dysfunction. Residual severe stenosis with patent artery. Hibernating myocardium: severe stenosis causes chronically ischemic myocardium. Contractility sacrificed for cell integrity.

5 © 2007 Cardinal Health. All rights reserved. Myocardial Viability and PET Imaging Viable Myocardium> myocardium which exhibits regional dysfunction due to injury or ischemia and severely reduced blood flow (perfusion), but which is intact metabolically, and can achieve normal or near-normal contractility with revascularization. Goal of PET Imaging > Identify myocardial segments with poor contractility and severely reduced perfusion, which are intact metabolically (viable).

6 © 2007 Cardinal Health. All rights reserved. Why 18-Fluorodeoxyglucose Is A Good Cardiac Tracer Glucose analogue with Fl-18 substituting for hydroxyl group. Trapped in glucose-pyruvate anaerobic glycolysis. On site synthesis not required. With a 110 min. half-life, off- site synthesis and delivery available. Studies performed in the non-fasting state, with oral glucose loading and insulin injection.

7 © 2007 Cardinal Health. All rights reserved. FDG Protocols Resting perfusion imaging performed as previously described. 18-FDG administered intravenously Oral glucose loading One hour given for equilibration Fingerstick glucose assessed Insulin administered if necessary 20 minute static acquisition

8 © 2007 Cardinal Health. All rights reserved. Analysis of Perfusion/Metabolism PET Images Compare perfusion (Rb-82) with metabolic activity (18-FDG) in each myocardial segment. Evaluate for regions of mismatch between perfusion and metabolism, relate to wall motion.

9 © 2007 Cardinal Health. All rights reserved. Perfusion/Metabolism Pattern I Perfusion metabolism match: severely reduced perfusion, with matching reduction in FDG uptake. This is consistent with low probability of viable myocardium The following slide shows a severe perfusion defect of the lateral and inferolateral walls (upper panels), with a matching severe metabolic defect in the lower panels. This is consistent with a low probability of viable myocardium in those regions. This patient would not benefit from an invasive revascularization procedure and would be treated medically.

10 © 2007 Cardinal Health. All rights reserved. Perfusion Metabolism Match Rb-82 FDG Severe perfusion defect of the lateral and inferolateral walls (upper panels), with a matching severe metabolic defect in the lower panels

11 © 2007 Cardinal Health. All rights reserved. Perfusion/Metabolism Pattern II Perfusion metabolism mismatch: severely reduced perfusion. FDG uptake normal or near normal. Consistent with high probability of viable myocardium. The following slide shows a patient with a severe perfusion defect of the lateral wall (RB-82, upper panel). Metabolic study shows intact 18-FDG uptake in the lateral wall (lower panel), indicative of viable myocardium. Therefore, this patient would benefit from revascularization.

12 © 2007 Cardinal Health. All rights reserved. Perfusion Metabolism Mismatch Rb-82 FDG Severe perfusion defect of the lateral wall (RB- 82, upper panel). Metabolic study shows intact 18- FDG uptake in the lateral wall (lower panel),

13 © 2007 Cardinal Health. All rights reserved. Perfusion/Metabolism Pattern III Enhanced FDG uptake: severely reduced perfusion. FDG uptake increased, with downscaling of FDG uptake in other segments. Consistent with viable myocardium and resting silent ischemia. The following slide shows a patient with a severe perfusion defect of the lateral and inferolateral walls (upper two panels, NH3). Metabolic imaging (lower panel) shows hyper intense uptake of 18-FDG in the lateral and inferolateral walls, with relative downscaling of FDG uptake in other segments. This pattern is consistent with viable myocardium, and resting ischemia. Therefore, the patient would be treated??????

14 © 2007 Cardinal Health. All rights reserved. Enhanced 18-FDG Uptake (ML Goris, Bretille J. Colour Atlas of Nuclear Cardiology. Chapman and Hall Medical. London. 1992. p. 216) Severe perfusion defect of the lateral and inferolateral walls Hyper intense uptake of 18- FDG in the lateral and inferolateral walls Viable Myocardium and Resting Ischemia

15 © 2007 Cardinal Health. All rights reserved. Use of PET Metabolic Imaging to Guide Revascularization Revascularization of segments shown viable on PET has a high likelihood of improving cardiac function. Revascularization of nonviable segments is unlikely to improve function.

16 © 2007 Cardinal Health. All rights reserved. Results of Revascularization in Viable vs. Nonviable Segments Likelihood of improved wall motion: Mismatch82% Match:17% Tillsch J. NEJM (1986) 314: 884-8. Tamaki N. Am J Cardiol (1989) 64: 860-5 Von Dahl A. J Nuc Med (1993) 34:23

17 © 2007 Cardinal Health. All rights reserved. Improvement in LV function with Revascularization Based on PET Metabolic Imaging The following table lists studies in which PET perfusion and metabolic imaging is used to identify viable myocardium and dictate coronary bypass surgery or angioplasty. In 109 total patients studied, mean LV ejection fraction rose from 34% to 47% post revascularization. Schelbert H. Card Clin 1994; 12: 303-316

18 © 2007 Cardinal Health. All rights reserved. PET Viability with 18-FDG Superior to SPECT: 30% of nonviable segments on Tl-201 are viable by PET FDG Extent of viability on PET FDG predicts extent of improvement in left ventricular function post- CABG Prognosis: Patients with viable myocardium and revascularization < 10% event rate Patients with viable myocardium, no revascularization > 27% event rate

19 © 2007 Cardinal Health. All rights reserved. Pitfalls of PET Perfusion/Metabolic Imaging Early Post-Myocardial Infarction, there is a increased incidence of: False (+) Positive Studies: (Positive mismatch, but no viable myocardium). Due to increased anaerobic glycolytic uptake by remodeling WBCs (white blood cells) and macrophages. False (--) Negative Studies: (Viable myocardium, but local metabolic factors, such as acidosis and lactate, impair glucose and FDG uptake by myocardium). Gropler R. JACC (1992) 19:989 JACC (1993) 22: 1587. Range Effects: ß(+) energy F-18 (0.64 MeV) vs. Rb-82 (3.35 MeV)

20 © 2007 Cardinal Health. All rights reserved. Case Study #1 Anterior Wall Viability? Rb-82FDG History 66 YOM H/O anterior MI and CHF Angiogram: 99% stenosis mid- LAD; 50% stenosis LCX; akinesis anterior and apical walls. PET Findings Matched severe perfusion and metabolic defects in the mid-distal anterior wall and apex Low prob. of viable myocardium Outcome No indications for revascularization of LAD Intensive medical treatment.

21 © 2007 Cardinal Health. All rights reserved. Case Study #2; Interior and/or Exterior Wall Viability? Rest Rb-82 FDG History 50 YOM with unstable angina, cardiogenic shock, sustained ventricular tachycardia. Angiogram: 100% LAD; 80% RCA. Stenoses. LVEF 25% with severe diffuse hypokinesis. IABP placed PET Findings Perfusion/metabolism mismatch in the anterior, apical and inferior wall regions. Indicates viable, hibernating myocardium in the LAD and RCA distributions Outcome PCI successfully performed to LAD and RCA. IABP weaned. Patient discharged.

22 © 2007 Cardinal Health. All rights reserved. Case Study #3 Site of Resting Ischemia and Wall Viability? Rb-82 FDG History 68 YOF DM: S/P CABG: recurrent angina SPECT MPI: severe intensity, slightly reversible lateral defect Angiogram: Patent LIMA. Grafts to LADD and LCX 100%; 100% RCA. Diffuse LV hypokinesis, LVEF 38%. PET Findings PET: mod-severe perfusion defect of lateral and inferolateral walls with hyper-intense lateral wall FDG uptake. Resting lateral wall ischemia Outcome PCI of native LCX

23 © 2007 Cardinal Health. All rights reserved. Case Study #4 Evidence of viable myocardium in the anterior wall to justify catheterization and PCI? History 77 YOF H/O of CHF. ECG reveals delayed R-wave progression suggestive of anterior MI. Echocardiogram: severe hypokinesis to akinesis of the anterior, septal and apical walls. PET Findings Severe perfusion defect of the anterior, apical, septal and inferoapical walls, with matched decrease in 18-FDG uptake in these regions. Low prob. of viable myocardium Outcome Continued medical therapy Rest Rb-82 FDG

24 © 2007 Cardinal Health. All rights reserved. Case Study #5 Jeopardized or Viable Myocardium? History 68 YOM H/O anterior MI, S/P CABG, now with unstable angina. Angiogram: patent LIMA, and patent grafts to RCA and OM. Significant CAD proximal to grafts. LV gram: severe anterior wall hypokinesis PET Findings Anterior wall severe matched defect of perfusion and metabolism Low probability of viable myocardium. Moderate defect in the anteroseptum with slightly greater 18-FDG uptake vs. Rb-82 (mild mismatch). Outcome Continued medical therapy Rb-82 FDG NOTE: Rb-82 uptake in lateral wall is >> 18-FDG. This indicates viable myocardium

25 © 2007 Cardinal Health. All rights reserved. Case Study #6 Viable myocardium sufficient to justify revascularization and mitral valve replacement? Rb-82FDG History Pt. with history of MI. Admitted with CHF and found to have mitral regurgitation. LVF severely reduced on echocardiogram. PET Findings Anteroapical perfusion/metabolism mismatch - viable myocardium Inferior wall severe perfusion defect with matched FDG uptake - low prob. of viable myocardium Outcome CABG + MVR

26 © 2007 Cardinal Health. All rights reserved. Case Study #7 Is LAD viable? Rb-82 FDG History 66YOM S/P anterior MI and stent to the LCX. Now admitted with unstable angina. Angiogram: 100% stenosis of proximal LAD. 100% stenosis of LCX stent. LV gram: Severely reduced LVF with anteroapical akinesis. LVEF 25%. PET Findings Severe perfusion defect of the anterior, anterolateral and apical walls, with matched 18-FDG uptake in those regions. FDG uptake and perfusion intact in the lateral wall. Low probability of anterior wall viable myocardium Outcome PCI LCX

27 © 2007 Cardinal Health. All rights reserved. Case Study #8 Viable myocardium in the LAD? Rb-82 FDG History 71YOM with abnormal ECG Angiogram: 100% stenosis of LAD LV gram: akinesis of the distal anteroapex PET Findings Severe perfusion defect in the distal anterior and apical walls, with intact metabolic 18-FDG uptake. Perfusion/metabolism mismatch - viable myocardium Outcome PCI of LAD

28 © 2007 Cardinal Health. All rights reserved. Case Study #9 Is Anterior Wall Viable? Rb-82 FDG History 81YOF with abnormal ECG H/O stents to the RCA and LCX. Recurrent angina Angiogram: Patent stents of the LCX. Occluded stent of the RCA. 100% occlusion of the mid LAD Ventriculogram: moderately reduced LV function with anteroapical akinesis PET Findings Perfusion/Metabolism mismatch in the anteroapical, anterolateral and lateral walls, consistent with hibernating, viable myocardium Outcome CABG

29 © 2007 Cardinal Health. All rights reserved. Case Study #10 Is there viable myocardium in the anterior and lateral walls to justify attempts at revascularization? Rb-82FDG History 64 yo male with anterolateral MI, CHF Angiography: 100% occlusion mid LAD. 100% occlusion mid LCX. RCA nonobstructive Echocardiogram: severely reduced LV function.. Akinesis of the distal septum and apex. Severe hypokinesis of the lateral wall. PET Findings Rb-82 perfusion: Severe perfusion defects distal anterior, apical, lateral walls. 18-FDG Metabolic study: severe defects matching rubidium perfusion uptake. Consistent with low probability of viable myocardium Outcome Medical management

30 © 2007 Cardinal Health. All rights reserved. Case Study #11 Is there viable myocardium in the anterior wall? Rb-82FDG History 79 y.o. male with acute myocardial infarction and cardiogenic shock Coronary Angiography revealed 100% occlusion of the proximal LAD, and 90% stenosis of the LCX. RCA was non- dominant Echo revealed severely reduced LV function with anterior, septal and apical akinesis. PET Findings PET study shows severe matching perfusion defects in the LAD distribution. Viable myocardium present in the lateral and inferior walls (which was jeopardized on angiogram). Outcome PCI LCX

31 © 2007 Cardinal Health. All rights reserved. ACC/ASNC Guidelines for PET Imaging Class I Adenosine or dipyridamole myocardial perfusion PET in patients in whom an appropriately indicated myocardial perfusion SPECT study has been found to be equivocal for diagnostic or risk stratification purposes. (Level of Evidence: B)

32 © 2007 Cardinal Health. All rights reserved. ACC/ASNC Guidelines for PET Imaging Class IIa 1.Adenosine or dipyridamole myocardial perfusion PET to identify the extent, severity, and location of ischemia as the initial diagnostic test in patients who are unable to exercise. (Level of Evidence: B) 2.Adenosine or dipyridamole myocardial perfusion PET to identify the extent, severity, and location of ischemia as the initial diagnostic test in patients who are able to exercise but have LBBB or an electronically-paced rhythm. (Level of Evidence: B)

33 © 2007 Cardinal Health. All rights reserved. ACC/ASNC Guidelines for Viability Imaging

34 © 2007 Cardinal Health. All rights reserved. Summary PET MPI: Due to higher energy isotopes, higher resolution and established attenuation correction, PET has superior sensitivity, specificity and accuracy for detecting, and evaluating the significance of CAD. PET has a unique and central role in diagnosing CAD in patients with prior equivocal or non-diagnostic non-invasive studies. PET metabolic imaging, with 18-FDG allows identification of high risk CAD patients who may benefit from revascularization.

35 © 2007 Cardinal Health. All rights reserved. Andrew Van Tosh, M.D. Associate Professor of Medicine Albert Einstein College of Medicine Lab Director, Nuclear Cardiology Beth Israel Medical Center, New York


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