personalized medicine? Pierre-Yves MARIE Department of Nuclear - PowerPoint PPT Presentation

Is myocardial-SPECT still a reference technique for CAD patients in the era of personalized medicine? Pierre-Yves MARIE Department of Nuclear Medicine CHU-Nancy, FRANCE.

Is myocardial-SPECT still a reference technique for CAD patients in the era of personalized medicine? I - A remaining need of a personalized functional information II - The future: - new cameras and new tracers - combining functional and anatomic information.

Is myocardial-SPECT still a reference technique for CAD patients in the era of personalized medicine? I - A remaining need of a personalized functional information II - The future: - new cameras and new tracers - combining functional and anatomic information.

I - A remaining need of a personalized functional information Anatomical information: is not enough for assessing CAD, coronary atherosclerosis remains frequently: - without ischemia, - uncomplicated. Coronary Multidetector CT angiography

Autopsy studies have determined What is this rate in > 65 the rates of high grade coronary years-old north-american atherosclerosis in patients : male subjects? (i) who were without any 1. less than 25% history of CAD 2. from 25 to 50% (ii) who died because of a 3. more than 50% non-cardiac cause. Coronary Multidetector CT angiography

Coronary atherosclerosis in diabetes mellitus A population-based autopsy study. Tauqir Y. Goraya et al. J Am Coll Cardiol. 2002;40(5):946-53. Prevalence of high-grade coronary atherosclerosis at autopsy by diabetes and clinical coronary disease status. No CAD history CAD history D- D+ D- D+ D- D+ D- D+

I - A remaining need of a personalized functional information Exercise 99m Tc-sestamibi Severe coronary stenoses are not Short-axis always associated with severe apical perfusion abnormalities at exercise median Mechanisms: - collaterals, - antianginal medications. basal Long-axis horizontal Patient with a total occlusion of the right coronary artery, but with a normal exercise-SPECT under beta-blockers vertical

I - A remaining need of a personalized functional information Exercise Survival of 442 patients who had 99m Tc-sestamibi exercise SPECT under beta-blockers Short-axis 40% and their anti-anginal treatment apical Survival Neither ischemia P<0.001 30% median nor large necrosis 1.0 .9 Ischemia .8 Large necrosis 20% basal (> 20% LV) .7 Long-axis .6 10% horizontal .5 0 1 2 3 4 5 Years J Nucl Cardiol. 2003;10(4): 361-8. 0% vertical J Nucl Cardiol 2003; 10:361-8.

I - A remaining need of a personalized functional information Severe coronary stenoses are not always associated with severe perfusion abnormalities at exercise Coronary flow insufficiency may occur in the absence of any > 50% stenosis at coronary angiography: -abnormal flow reserve, -exercise vasoconstriction.

In intermediate stenoses, exercise ischemia may involves both : - a limitation of coronary flow reserve , - vasoconstriction of stenotic coronary segments. Gage JE. Circulation. 1986;73:865

40 patients with: [1] proven CAD (> 50% stenosis at angiography) and [2] positive exercise test Eur J Nucl Med 2000 ;27(7):788-99.

Exercise SPECT-defects are larger than dipyridamole SPECT- defects when ischemic areas are related to < 70% stenoses (Eur J Nucl Med 2000 ;27(7):788-99). Vertical Tl-201 Short-axis long-axis apical mid-vent. basal Exercise Rest- reinjection Dipyridamole . 72-year old man, angina and ST depression at exercise . 60 % stenosis on RCA

Dipyridamole SPECT-defects are larger than exercise ones in patients with low exercise-increase in heart rate ( β -blockers) Eur J Nucl Med 2000 ;27(7):788-99. Tl-201 Vertical Short-axis long-axis apical mid-vent. basal Exercise Rest- reinjection Dipyridamole . Exercise: angina, ST depression and 73% of maximal heart rate . Coronary angiography: dominant LCx: 80 %, intermediate branch: 90 % .

Prognostic stratification using exercise MPI Perfusion Function Main parameters: Exercise Rest Exercise Rest  Exercise testing parameters Short-axis (maximal work load and heart apical rate, positive test)  Normal stress-SPECT median  Extent of stress defects  Extent of reversible stress basal defects Long-axis  Post-stress LV ejection fraction horizontal (<45%) and end-systolic volume (>70 mL)  Reversible wall motion vertical abnormalities

Help in therapeutic decision according to the amount of ischemic area Cardiac death rate (% per year) Hachamovitch R, Circulation, 2003

Help in therapeutic decision according to the amount of ischemic area Hachamovitch R, et al. Eur Heart J 2011;32:1012-1024: 1 3 969 patients followed at >7 years for all-cause death after stress SPECT (65% exercise) Hazard ratio for revascularization vs. medical therapy as a function of %myocardium ischaemic Patients with prior MI Patients with <10% MI (n=3,216) (n=11,880) Hazard ratio Hazard ratio % total myocardium ischemic % total myocardium ischemic

Help in therapeutic decision according to the amount of ischemic area Hachamovitch R, et al. Eur Heart J 2011;32:1012-1024: 1 3 969 patients followed at >7 years for all-cause death after stress SPECT (65% exercise) Log hazard ratio for revascularization vs. for medical therapy as a function of %myocardium ischaemic in patients with <10% necrotic myocardium Medical therapy Log Hazard ratio Early revascularization % total myocardium ischemic

I - A remaining need of a personalized functional information: is MRI a better choice than SPECT? -No radiation -Highly accurate assessments of contractility and of MI areas -Perfusion assessment with pharmacologic tests Perfusion Cine-MRI Septal ischemia

I - A remaining need of a personalized functional information: is MRI a better choice than SPECT? Klem I. et al. Improved detection of CAD by stress perfusion cardiovascular MR with the use of delayed enhancement infarction imaging. J Am Coll Cardiol. 2006;47:1630-8. Delayed Stress Rest Coronary enhancement perfusion perfusion angiography + Delayed-enhancement imaging for increasing: + -sensitivity (84% → 89%) - -specificity (58% → 87%)

Detection of CAD by perfusion-MRI with DCE analysis Stress perfusion Abnormal Rest perfusion Abnormal Normal DCE analysis Normal Abnormal No CAD Ischemia Infarction (artifact)

Detection of CAD by perfusion-SPECT with G.SPECT Stress perfusion Abnormal Rest perfusion Abnormal Normal Function Normal Abnormal (G.SPECT) No CAD Ischemia Infarction (artifact)

Viability SPECT-tr trac acers rs MRI : assessment delayed retention ± nitrates Tra ransmura ral e exte tent % of of u upta take < 25% > 60% Viab Vi able (> 80% of further improvement) 25-50% 40-60% In Inte term rmediat ate ( ≈ 50% of further improvement ) >50% < 40% Non vi viab able (< 20% of further improvement ) 0% 50% 100%

I - A remaining need of a personalized functional information: is MRI a better choice than SPECT? - No radiation - Highly accurate assessments of contractility and of MI areas - Perfusion assessment with pharmacologic tests But MRI < SPECT for assessing stress ischemia: - no assessment at exercise - less safe - more complex to perform and to analyze

Is myocardial-SPECT still a reference technique for CAD patients in the era of personalized medicine? I - A remaining need of a personalized functional information Physiological information on myocardial ischemia at exercise. Help in therapeutic decision. II - The future: - new cameras and new tracers - combining functional and anatomic information. -...

Is myocardial-SPECT still a reference technique for CAD patients in the era of personalized medicine? I - A remaining need of a personalized functional information Physiological information on myocardial ischemia at exercise. Help in therapeutic decision. II - The future: - new cameras and new tracers - combining functional and anatomic information. -...

II - The future: solid-state detectors Cadmium zinc telluride (CZT) solid-state detectors ++++ • - much higher myocardial count rate ++ • - much higher energy resolution ++ • - higher spatial resolution + Spectrum Dynamics • - smaller size GE Medical Systems

II - The future: solid-state detectors Performances of High-Sensitivity Cameras Imbert L. et al. 2012 Comparison:  between Discovery-NM530c and DSPECT CZT-cameras, and Anger cameras with astigmatic or parallel-hole collimator,  on SPECT images from phantoms and from normal subjects. Phantom study Clinical study Horizontal Median Long-axis Short-axis long-axis short-axis Discovery - NM 530c DSPECT IQSPECT Conventional -SPECT

II - The future: solid-state detectors Performances of High-Sensitivity Cameras Imbert L. et al. 2012 Comparison:  between Discovery-NM530c and DSPECT CZT-cameras, and Anger cameras with astigmatic or parallel-hole collimator,  on SPECT images from phantoms and from normal subjects. Spatial resolution Phantom study Clinical study Spatial resolution (mm) Sharpness index (cm -1 ) * * * c r t c r t c r t c r t NM DSP IQ Conv NM DSP IQ Conv