2Introduction 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 attackStenosis – narrowing of the blood vesselIschemia – restriction in blood supplyPerfusion – blood flowAkinesis – lack of wall motion in a myocardial segmentTachycardia – abnormal, rapid heart beatCABG – coronary artery bypass graftCHF – congestive heart failure
3Myocardial 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.
4Reversible 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.
5Myocardial 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).
6Why 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.
7FDG ProtocolsResting perfusion imaging performed as previously described.18-FDG administered intravenouslyOral glucose loadingOne hour given for equilibrationFingerstick glucose assessedInsulin administered if necessary20 minute static acquisition
8Analysis 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.
9Perfusion/Metabolism Pattern I Perfusion metabolism match: severely reduced perfusion, with matching reduction in FDG uptake. This is consistent with low probability of viable myocardiumThe 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.
10Perfusion Metabolism Match Rb-82Severe perfusion defect of the lateral and inferolateral walls (upper panels), with a matching severe metabolic defect in the lower panelsFDG
11Perfusion/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.
12Perfusion Metabolism Mismatch Rb-82Severe perfusion defect of the lateral wall (RB-82, upper panel).Metabolic study shows intact 18-FDG uptake in the lateral wall (lower panel),FDG
13Perfusion/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??????
14Enhanced 18-FDG UptakeSevere perfusion defect of the lateral and inferolateral wallsHyper intense uptake of 18-FDG in the lateral and inferolateral wallsViable Myocardium and Resting Ischemia(ML Goris, Bretille J. Colour Atlas of Nuclear Cardiology. Chapman and Hall Medical. London p. 216)
15Use 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.
16Results of Revascularization in Viable vs. Nonviable Segments Likelihood of improved wall motion:Mismatch 82%Match: 17%Tillsch J. NEJM (1986) 314:Tamaki N. Am J Cardiol (1989) 64: 860-5Von Dahl A. J Nuc Med (1993) 34:23
17Improvement 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:
18PET Viability with 18-FDG Superior to SPECT: 30% of nonviable segments on Tl-201 are viable by PET FDGExtent of viability on PET FDG predicts extent of improvement in left ventricular function post- CABGPrognosis:Patients with viable myocardium and revascularization < 10% event ratePatients with viable myocardium, no revascularization > 27% event rate
19Pitfalls 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 WBC’s (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: Range Effects: ß(+) energy F-18 (0.64 MeV) vs. Rb-82 (3.35 MeV)
20Case Study #1 Anterior Wall Viability? History66 YOMH/O anterior MI and CHFAngiogram: 99% stenosis mid-LAD; 50% stenosis LCX; akinesis anterior and apical walls.PET FindingsMatched severe perfusion and metabolic defects in the mid-distal anterior wall and apexLow prob. of viable myocardiumOutcomeNo indications for revascularization of LADIntensive medical treatment.Rb-82FDG
21Case Study #2; Interior and/or Exterior Wall Viability? History50 YOM with unstable angina, cardiogenic shock, sustained ventricular tachycardia.Angiogram: 100% LAD; 80% RCA. Stenoses. LVEF 25% with severe diffuse hypokinesis. IABP placedPET FindingsPerfusion/metabolism mismatch in the anterior, apical and inferior wall regions.Indicates viable, hibernating myocardium in the LAD and RCA distributionsOutcomePCI successfully performed to LAD and RCA. IABP weaned. Patient discharged.RestRb-82FDG
22Case Study #3 Site of Resting Ischemia and Wall Viability? History68 YOFDM: S/P CABG: recurrent anginaSPECT MPI: severe intensity, slightly reversible lateral defectAngiogram: Patent LIMA. Grafts to LADD and LCX 100%; 100% RCA. Diffuse LV hypokinesis, LVEF 38%.PET FindingsPET: mod-severe perfusion defect of lateral and inferolateral walls with hyper-intense lateral wall FDG uptake.Resting lateral wall ischemiaOutcomePCI of native LCXRb-82FDG
23Case Study #4 Evidence of viable myocardium in the anterior wall to justify catheterization and PCI? History77 YOFH/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 FindingsSevere perfusion defect of the anterior, apical, septal and inferoapical walls, with matched decrease in 18-FDG uptake in these regions.Low prob. of viable myocardiumOutcomeContinued medical therapyRestRb-82FDG
24Case Study #5 Jeopardized or Viable Myocardium? History68 YOMH/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 hypokinesisPET FindingsAnterior wall severe matched defect of perfusion and metabolismLow probability of viable myocardium.Moderate defect in the anteroseptum with slightly greater 18-FDG uptake vs. Rb-82 (mild mismatch).OutcomeContinued medical therapyRb-82FDGNOTE: Rb-82 uptake in lateral wall is >> 18-FDG. This indicates viable myocardium
25Case Study #6 Viable myocardium sufficient to justify revascularization and mitral valve replacement?HistoryPt. with history of MI. Admitted with CHF and found to have mitral regurgitation. LVF severely reduced on echocardiogram.PET FindingsAnteroapical perfusion/metabolism mismatch - viable myocardiumInferior wall severe perfusion defect with matched FDG uptake - low prob. of viable myocardiumOutcomeCABG + MVRRb-82FDG
26Case Study #7 Is LAD viable? History66YOMS/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 FindingsSevere 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 myocardiumOutcomePCI LCXRb-82FDG
27Case Study #8 Viable myocardium in the LAD? History71YOM with abnormal ECGAngiogram: 100% stenosis of LADLV gram: akinesis of the distal anteroapexPET FindingsSevere perfusion defect in the distal anterior and apical walls, with intact metabolic 18-FDG uptake.Perfusion/metabolism mismatch - viable myocardiumOutcomePCI of LADRb-82FDG
28Case Study #9 Is Anterior Wall Viable? History81YOF with abnormal ECGH/O stents to the RCA and LCX. Recurrent anginaAngiogram: Patent stents of the LCX. Occluded stent of the RCA. 100% occlusion of the mid LADVentriculogram: moderately reduced LV function with anteroapical akinesisPET FindingsPerfusion/Metabolism mismatch in the anteroapical, anterolateral and lateral walls, consistent with hibernating, viable myocardiumOutcomeCABGRb-82FDG
29Case Study #10 Is there viable myocardium in the anterior and lateral walls to justify attempts at revascularization?History64 yo male with anterolateral MI, CHFAngiography: 100% occlusion mid LAD. 100% occlusion mid LCX. RCA nonobstructiveEchocardiogram: severely reduced LV function.. Akinesis of the distal septum and apex. Severe hypokinesis of the lateral wall.PET FindingsRb-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 myocardiumOutcomeMedical managementRb-82FDG
30Case Study #11 Is there viable myocardium in the anterior wall? History79 y.o. male with acute myocardial infarction and cardiogenic shockCoronary Angiography revealed 100% occlusion of the proximal LAD, and 90% stenosis of the LCX. RCA was non-dominantEcho revealed severely reduced LV function with anterior, septal and apical akinesis.PET FindingsPET study shows severe matching perfusion defects in the LAD distribution. Viable myocardium present in the lateral and inferior walls (which was jeopardized on angiogram).OutcomePCI LCXRb-82FDG
31ACC/ASNC Guidelines for PET Imaging Class IAdenosine 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)
32ACC/ASNC Guidelines for PET Imaging Class IIaAdenosine 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)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)
34SummaryPET 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.
35Andrew Van Tosh, M.D. Associate Professor of Medicine Albert Einstein College of MedicineLab Director, Nuclear CardiologyBeth Israel Medical Center, New York