CT or PET/CT for coronary artery disease Rotterdam 2012 Juhani Knuuti, MD, PhD, FESC Turku PET Centre University of Turku Turku, Finland Juhani.knuuti@utu.fi Turku PET Centre University of Turku Åbo Akademi University Turku University Hospital
Disclosure: Juhani Knuuti, M.D. Juhani Knuuti, M.D. has financial interests to disclose. Potential conflicts of interest have been resolved. Research Support / Grants Stock/Equity (any amount) Consulting Employment Speakers Bureau / Honoraria None None Lantheus None Philips Research contracts (institutional): Orion Pharma, Turku Imanet Ltd, GE Healthcare, GSK, Merck, Bayer-Schering, Novartis, Lundbeck, Roche; Lantheus Turku PET Centre University of Turku Åbo Akademi University Turku University Hospital 2
Imaging and CAD Current main trends From ischemic cascade to CAD cascade From diagnosis of CAD to guidance of therapy Novel imaging applications Quantification Imaging of vulnerable plaque Turku PET Centre University of Turku Åbo Akademi University Turku University Hospital
Paradigm shift 1: From ischemic to CAD cascade Preclinical atherosclerosis Non-obstructive CAD hypoperfusion Myocardial perfusion metabolic alterations diastolic dysfunction systolic dysfunction ECG-Changes angina Signs of ischaemia Turku PET Centre University of Turku Åbo Akademi University Turku University Hospital
Multislice CT vs. Myocardial Perfusion Regional comparison in 140 patients Data from Schuijf et al. 2006, Di Carli et al. 2006, Hacker et al. 2005, and Rispler et al. 2006
MDCT findings in patients with normal SPECT perfusion imaging result Werkhoven JM, et al Am J Cardiol. 2008 Jan 1;101(1):40-5. Turku PET Centre University of Turku Åbo Akademi University Turku University Hospital
CT angiography Curved MPR reconstructions of the major coronary vessels Case LP LAD >50% LCX RCA 30-40% >50% CT Acquisition: Premedication: Metoprolol 10 mg i.v. HR 46/min Acquisition: Prospective step-and-shoot protocol, ma 650, 120 kv Contrast: Iomeron 400mg/ml 68 ml Radiation dose 7.4 msv Case:LP
PET perfusion imaging during stress Displayed as fused volume rendered images scaled to absolute scale 0-3.5 ml/g/min Normal perfusion: above 2.5 ml/g/min: yellow or red 3.5 ml/g/min 0.0 ml/g/min PET Acquisition: Injected Dose: 1100 MBq O-15-water Stress: Adenosine 140 µg/min/kg for 6.5 min Acquisition time: dynamic 4.5 min Radiation dose 0.9 msv Case:LP
Invasive angiography + FFR Case LP Right 48% FFR: 0.86 (normal) Left 46% FFR:? 60% FFR: 0.92 (normal) FFR = Fractional flow reserve invasive measurement of the stenosis functional gradient during adenosine infusion Case:LP
Prognostic Value of Myocardial Perfusion SPECT n = 12 000 pts 10 8 6 P < 0.001 7,4 4 2 0,6 0 normal abnormal Iskander S et al. JACC 1998;32:57
Additional prognostic value of CT and perfusion imaging N=541 Van Verkhoven et al J Am Coll Cardiol 2009;53: 623 32
Imaging and CAD Current main trends From ischemic cascade to CAD cascade From diagnosis of CAD to guidance of therapy Novel imaging applications Quantification Imaging of vulnerable plaque Turku PET Centre University of Turku Åbo Akademi University Turku University Hospital
Paradigm shift 2: From diagnosis to guidance of therapy Anatomy (Obstructive CAD) Flow-Limiting (Perfusion, FFR) Optimal Medical Treatment Complete Functional Revascularization and optimal medical treatment Noninvasive function: Perfusion, WMA Hachamovitch Circulation 2003;107:2900 COURAGE NEJM 2007;356:1503 COURAGE Circulation 2008;117:1283 Invasive function: FFR DEFER JACC 2007;49:2105 FAME NEJM 2009;360:213 FAME JACC 2010;56:177 Turku PET Centre University of Turku Åbo Akademi University Turku University Hospital
Functional consequences of stenoses LAD D1 LAD D1 Turku PET Centre, Finland
Invasive Anatomy vs. Functional Consequences 1.0 Pressure-derived erived FFR 0.8 0.6 0.4 0.2 N = 2334 0.0 0 20 40 60 80 100 Angiographic Diameter Stenosis (%) Wijns, de Bruyne, Vanhoenacker, JNC 2007;93:856-61
Tonino et al. FAME
CT angiography Curved MPR reconstructions of the major coronary vessels Case LP LAD >50% LCX RCA 30-40% >50% CT Acquisition: Premedication: Metoprolol 10 mg i.v. HR 46/min Acquisition: Prospective step-and-shoot protocol, ma 650, 120 kv Contrast: Iomeron 400mg/ml 68 ml Radiation dose 7.4 msv Case:LP
PET perfusion imaging during stress Displayed as fused volume rendered images scaled to absolute scale 0-3.5 ml/g/min Normal perfusion: above 2.5 ml/g/min: yellow or red 3.5 ml/g/min 0.0 ml/g/min PET Acquisition: Injected Dose: 1100 MBq O-15-water Stress: Adenosine 140 µg/min/kg for 6.5 min Acquisition time: dynamic 4.5 min Radiation dose 0.9 msv Case:LP
Multivessel disease: What is the culprit lesion? LAD RCA C E FFR=0.94 FFR=0.54 D F 3.5 FFR=0.63 0 ml/g/min D1 Turku PET Centre University of Turku Åbo Akademi University Turku University Hospital
Multivessel disease: What is the culprit lesion? Case: stenoses in all major vessels; RCA is culprit RCA LCX LAD Turku PET Centre University of Turku Åbo Akademi University Turku University Hospital
Microvascular disease Absolute perfusion decreased but no epicardial disease Relative perfusion Absolute perfusion Turku PET Centre University of Turku Åbo Akademi University Turku University Hospital
Hybrid noninvasive (PET/CT) vs. Hybrid invasive (ICA + FFR) Sensitivity Specificity PPV (%) NPV (%) Accuracy (%) MDCT 75 95 76 94 91 PET 94 93 77 98 93 MDCT-PET hybrid 95 99 96 99 98 100 Vessel analysis in patients Figure 3: Vessel with Analysis intermediate against ICA likelihood +FFR of CAD, N=107 percen ntage 90 80 70 60 MDCT 50 PET 40 MDCT-PET hybrid 30 20 10 0 PPV (%) NPV (%) Accuracy (%) MDCT 76 94 91 PET 77 98 93 MDCT-PET hybrid 96 99 98 Kajander et al Circulation 2010 Turku PET Centre University of Turku Åbo Akademi University Turku University Hospital
Challenges and solutions of perfusion imaging Challenge Solution LM disease? Balanced 3 vessel disease? Multivessel disease? Anatomical location? Non-ischemic CAD? Microvascular disease? Turku PET Centre University of Turku Åbo Akademi University Turku University Hospital
Challenges and solutions of ischemia imaging Challenge LM disease Balanced 3 vessel disease Multivessel disease Anatomical location Non-ischemic CAD Solution Hybrid Hybrid Hybrid Microvascular disease / Hybrid Turku PET Centre University of Turku Åbo Akademi University Turku University Hospital
Impact of hybrid imaging on downstream resource utilization 100% p<0.001 96% 86% 80% Revasculari isations 60% 40% 20% 45% 39% NEJM 2010 USA N=400 000 36% GER N=840 000 0% CATH rate CAD yield Per CATH REVASC Per CATH Eur Heart J 2011 Jul 30. Turku PET Centre University of Turku Åbo Akademi University Turku University Hospital
Imaging and CAD Current main trends From ischemic cascade to CAD cascade From diagnosis of CAD to guidance of therapy Novel imaging applications Quantification Imaging of vulnerable plaque Turku PET Centre University of Turku Åbo Akademi University Turku University Hospital
Challenges and solutions of CAD/ishchemia imaging Challenge LM disease Balanced 3 vessel disease Multivessel disease Anatomical location Non-ischemic CAD Microvascular disease Solution Hybrid Quantification Quantification Hybrid Hybrid Quantification/ Hybrid Turku PET Centre University of Turku Åbo Akademi University Turku University Hospital
Quantification of myocardial perfusion Which patients will benefit? Balanced 3 vessel or multivessel disease Culprit lesion vs. non-culprit lesion in multi vessel disease Early changes in coronary dysfunction Turku PET Centre University of Turku Åbo Akademi University Turku University Hospital
Absolute flow vs Relative flow Kajander et al Circ Cardiovasc Imaging. 2011 Turku PET Centre University of Turku Åbo Akademi University Turku University Hospital
Absolute flow is as good as flow reserve! Joutsiniemi et al (Circ Imaging) University of Turku Åbo Akademi University Turku University Hospital
Imaging and CAD Current main trends From ischemic cascade to CAD cascade From diagnosis of CAD to guidance of therapy Novel imaging applications Quantification Imaging of vulnerable plaque Turku PET Centre University of Turku Åbo Akademi University Turku University Hospital
MDCT Characterization of Coronary Plaques Motoyama J Am Coll Cardiol 2009 LAD LAD LCX Left main
Plaque characterization using CT vs. Myocardial Perfusion SPECT Van Verkhoven et al J Am Coll Cardiol 2009;53: 623 32 N=541
MDCT Characterization of Coronary Plaques - Prognosis Large low attenuation plaque area Positive remodeling Spotty calcification 15 ACS in 1059 patients Motoyama J Am Coll Cardiol 2009
Dual gated 18 F-FDG PET/CT of coronary arteries in ACS patients CTA CTA-PET Fusion Acute LAD plaque rupture Myocardial FDG uptake supressed by low carbohydrate, high fat diet Lankinen at Turku al PET ICNC Centre, 2011 Finland
Dual gated 18 F-FDG FDG PET/CT of coronary arteries in ACS patients 39 year old man Risk factors of CAD: Smoking Family history + 5 days of UAP ECG: lateral T-inversion TNT + LCX subtotal occlusion stented TBR ratio 4.2 Turku PET Centre, Finland Lankinen EHJ 2011 (abstract) Turku PET Centre, Finland
Dual gated 18 F-FDG FDG PET/CT of coronary arteries in ACS patients 20 ACS (non-stemi or UAP) patients Dual-gated 18 F FDG PET/CT (3d after onset of symptoms) High-fat diet intervention to suppress myocardial uptake (Williams AJR 2008) Visual coronary FDG uptake in 80% of patients (3 prior to intervention) TBR 3.2±1.3 (range 1.8-5.4) Lankinen EHJ 2011 (abstract) Turku Turku PET PET Centre, Centre, Finland Finland
Concerns on sequential / hybrid imaging for CAD Complicated for patients (sequential) Logistic challenges (hybrid) Higher work load Non-standardized image analysis Radiation burden Lacking evidence and indications Costs and cost-effectivenes
Comparison of risks for fatal event 1000 1000 800 600 400 The risk per 10 000 200 0 140 119 2 16 9 0,5 15 1 1 12 5 6 1 23 Since upper limit of lifetime risk of any imaging test was 23 per 10 000 only 2.3% of the events need to be prevented to completely cancel Risk of fatal cardiac event (10-years) Aspirin, lifetime risk of fatal bleeding Motor vehicle accident Pedestrian accident Drowning Bicycling Calcium score CT angiography Dobutamine stress echocardiography (CE) Dobutamine stress CMR Adenosine contrast enhanced CMR Exercise SPECT perfusion imaging Dipyridamole SPECT perfusion imaging Adenosine PET perfusion imaging Invasive angiography the risk of imaging.