Myocardial Perfusion: Positron Emission Tomography

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1 Myocardial Perfusion: Positron Emission Tomography TH. Schindler, MD University Hospitals of Geneva, Cardiovascular Center, Geneva, Switzerland ESC 2010 Stockholm

2 Personal Disclosure Research Grant support by the: - Suisse National Research Foundation (SNF) - University Hospitals of Geneva, Department of Internal Medicine (DPI) and Clinical Research Center (CRC) - ESC and Italien Cardiology Society (Research Fellowship : Dr. GM Vincenti) - Novartis Foundation and University of Genoa (Italy) (Research Fellowship: Dr. A. Quercioli)

3 PET Perfusion and Flow Measurements Comprehensive Identification and Characterization of the Clinically-Manifest and Subclinical CAD Process Provides Predictive Information on Future Coronary Events Contribute to Explore Coronary Pathophysiology Allow Monitoring of Beneficial Effects of Therapeutic Risk Factor Modification that may Improve the Longterm Cardiovascular Outcome

4 Positron-Emitting Tracers of Myocardial Blood Flow Tracer Abbreviation Physical Halflife Oxygen-15 Water H 2 15 O 2.4 min Nitrogen-13 Ammonia Rubidium-82 Chloride 13 NH min 82 Rb + 78 sec

5 Compartment Models for Tracers of MBF Estimates in ml/g/min Serially Acquired Images of a Bolus Transit of N-13 Ammonia 2-Compartment Model for N-13 Ammonia (Schelbert HR et al., Circulation 1981)

6 Arterial Radiotracer Input Function and Myocardial Tissue Response Through fitting of the time activity curves with the operational equation formulated by the 2-compartment tracer kinetic model, estimates of MBF in ml/g/min are obtained

7 15O-water and PET Determined MBF Images (Short axis resting MBF images with (CTAC) and without (NAC) attenuation correction) Stress-rest MBF quantification with 15O-water 0.8 msv! (Lubberink M et al. J Nucl Med 2010)

8 3D Hybrid Volume Rendered Image: CTA and Stress-Induced MBF (Kajander S. et al. Circulation 2010)

9 CT-Angiogram derived from a PET/CT System (Kajander S. et al. Circulation 2010)

10 Detection of Obstructive CAD (N-13 Ammonia PET/CT Perfusion Images)

11 Left Coronary Angiography

12 82Rubidium PET/CT images: 56 years old obese patient (BMI 33kg/m2) In obese individuals and women: Sensitivity: 95% Specifity: 90% Optimal attenuation correction with CT! (Di Carli MF Circulation 2007)

13 Sensitivity and Specifity of PET (-CT) for Detecting Obstructive CAD Year Author Radiotracer Prior MI (%) Sensitivity (%) Specificity (%) 2006 Bateman 82 Rubidium Sampson 82 Rubidium None Marwick 82 Rubidium Grover- McKay 82 Rubidium Stewart 82 Rubidium Go 82 Rubidium Demer 82 Rubidium, 13 N-ammonia Tamaki 13 N-ammonia Gould 82 Rubidium, 13 N-ammonia Not reported Schelbert 13 N-ammonia Total 92 91

14 Abnormal Longitudinal Decrease in MBF (Gradient): Non-Invasive Probe of Epicardial Functional and/or Structural Disease? (Schindler TH. et al, Eur J Nucl Med Mol Imaging 2006) (Hernandez-Pampaloni M et al. Circulation 2001) (Gould KL Circulation 2000)

15 - Subclinical CAD - Prognostic Role of Myocardial Flow Reserve 13N-Ammonia PET/CT Perfusion Images MBF (ml/g/min) STRESS 1.47 REST 0.81 Myocardial Flow Reserve (MFR): 1.81

16 Coronary Angiography Right Coronary Artery Left Coronary Artery

17 Acute Coronary Syndrome 13 Months Later v1 v2 v3 v4 v5 v6

18 Coronary Flow Reserve and Long-Term Prediction of Cardiovascular Events 120 patients with intra-coronary flow velocity measurements % Event Free > p=0.08 <2.9 p= months (Britten et al. Cor Art Dis 2004)

19 Stenosis Severity in Infarct Vessel Four Investigations in 196 Patients Time from Angiography to AMI 24.2 Months 80 < 50% 50-70% > 70% Percent of Patients after S. C. Smith, Circulation, 1996

20 Non - obstructive CAD 3.1 mm 3.1 mm Angiography IVUS Courtesy J Tobis, UCLA

21 Event Free Survival PET determined Coronary Endothelial Vasoreactivity and Prognosis 1.0 % MBF 40% % MBF>0% and <40% Log rank 7.42 p = % MBF 0% (Schindler TH, J Am Coll Cardiol 2005) Follow-up (months)

22 Ischemic Heart Disease and Cardiac Death Free Survival (Tio RA et al, J Nucl Med 2009)

23 Myocardial Perfusion, Flow Reserve and Prognosis (Herzog B et al, J Am Coll Cardiol 2009)

24 Identification and Characterization of Multivessel Disease

25 N-13 Ammonia PET Fusioned with CT: Stress-Induced Perfusion Defect Antero-Apical

26 Regional MFR (Munich Heart Software, S. Nekolla) Coronary Angiography Three vessel disease LAD: 100% stenosis LCX: 85% stenosis RCA: 50% stenosis

27 Coronary Angiography Left Coronary Artery Right Coronary Artery

28 Clinical Utility of Quantification of Myocardial Blood Flow with PET 1. Identification of subclinical CAD 2. Improved characterization of CAD burden 3. Identification of balanced reduction of MBF in all vascular territories (Schindler TH et al. JACC Img 2010)

29 Algorithm for the Integration of PET Perfusion and Flow Measurements (Schindler TH et al. JACC Img 2010)

30 Coronary Vasodilator Reserve in Relation to Percentage Coronary Artery Diameter Stenosis (Uren NG et al. N Engl J Med 1994) Interpretation of MFR only context with coronary anatomy or Perfusion imaging!

31 MBF to CPT (ml/g/min) Effect of Hormone Replacement Therapy (HRT) on Endothelium-Related MBF Response to CPT 0.6 p=0.45 p<0.02 p< HRT NO HRT HRT at Base but not FU Base FU Base FU Base FU (Schindler TH et al. Eur Heart J 2009)

32 Coronary Calcium Score (CCS) Coronary Artery Calcification (CAC) after Glucose- Lowering Treatment with Metformin and/or Glyburide 200 p < p = ns 50 0 Controls Diabetes Mellitus Base Follow-up Base Follow-up (Schindler TH et al. Eur Heart J 2009)

33 MBF (ml/g/min) from rest to CPT Endothelium-Related MBF Responses to CPT after Glucose- Lowering Treatment p= ns 0,6 p = ns p<0.05 0,4 0,2 0,0 Controls Diabetes Mellitus Base Follow-up Base Follow-up (Schindler TH et al. Eur Heart J 2009)

34 Difference in endothelium-related MBF to CPT Relationship between Improvement in Coronary Endothelial Function and CAC Progression in Type 2 Diabetes Mellitus y= 0.68x r = 0.53, p< Difference in log CCS (Schindler TH et al. Eur Heart J 2009)

35 PET Perfusion and Flow Measurements Comprehensive Identification and Characterization of the Clinically-Manifest and Subclinical CAD Process Provides Predictive Information on Future Coronary Events Contribute to Explore Coronary Pathophysiology Allow Monitoring of Beneficial Effects of Therapeutic Risk Factor Modification that may Improve the Longterm Cardiovascular Outcome

36 Conclusion The aim of image-guided and individualized cardiovascular therapy may be attained in the near future by PET technology.

37 Reserve Slides

38 Coronary Artery Calcification (CAC) and Hyperemic MBFs (Curillova et al. Eur J Nucl Med Mol Imaging 2009)

39 PET Perfusion Imaging (Schindler TH et al. JACC Img 2010)

40 Hyperemic MBF Increases to Adenosine Stimulation (4 mg L-NAME / kg BW i.v.) p < ,5 Baseline -21% L-NAME MBF (ml/min / g) 2 1,5 1 0,5 0 NS endotheliumrelated smooth muscle cell relaxation to adenosine Rest MBF Adenosine MBF Measure of Integrated Coronary Circulatory Function (Buus et al, Circulation 2001)

41 Hypertrophic Cardiomyopathy, MBF and Prognosis (Cecchi F et al, New Engl J Med 2003)

42 Cardiomyopathy, MBF and Prognosis (Neglia D et al. Circulation 2002)

43 Gated Rest-Stress 82-Rb Myocardial Perfusion PET Multivessel CAD with stenoses > 70 % Unmasked with gated PET Gated PET at Peak Stress! (Dorbala S. J Nucl Med 2007)

44 Myocardial Perfusion, MFR and Prognosis (Herzog B et al, J Am Coll Cardiol 2009)

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