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					Nuclear cardiology methods in routine clinical practice Materials for medical students Lang O., Kamínek M. Dept Nucl Med, School of Medicine, Praha, Olomouc Nuclear cardiology  Set of non-invasive mostly imaging diagnostic methods of the cardiovascular system  Huge expansion during last 30 years, in Czech rep. during last 10 years  Examination of venous system of lower extremities and lung perfusion are included Seminar includes        Imaging in nuclear cardiology (NC) NC methods Myocardial perfusion Myocardial viability Heart function Examination of pulmonary embolism New trends Ways of imaging in NC  Detectors of ionizing radiation – gamma cameras  Source of radiation inside the patient body radiopharmaceutical, tracer  Ways of distribution - perfusion, metabolic process, receptors, etc.  Source of information - ionizing photon (gamma)  Digital images - processing, archiving, transfer  planar, tomographic • SPECT (transversal), PET (coincidence) Data collection by gamma cameras PET camera Way of tomography - SA slices Other tomographic slices Parts of left ventricle myocardium Legenda: 1 - apex 2 - anterior wall VLA SA 3 - lateral wall 4 - inferior wall 5 – septum HLA Pollar map Heart examination  Myocardium imaging    perfusion during stress and rest (80%) viability necrosis, innervation, ischemia  Mechanical function assessment    steady-state ventriculography (multigated - MUGA) Angiocardiography (first-pass) non-imaging systems Myocardial perfusion rate of NC examinations number/1000 inhabitants./year 12 10 8 6 4 2 0 CR 1999 EU 1994 EU 1998 USA 1994 Why stress? Pathophysiology of CAD Hemodynamic effect of coronary stenoses Collaterals Ischemic cascade Rest myocardial perfusion in CAD  Physiological compensatory arteriolar dilatation in the region supplied by narrowed artery  Blood flow remains the same as in the region supplied by normal artery  Radiopharmaceutical distribution remains homogenous Stress myocardial perfusion in CAD  Arteriolar dilatation in the bed of normal artery for blood flow increase  Blood flow through the normal artery increases  Arteriolae in the bed of narrowed artery are already dilated - no further dilatation can occure, so blood flow remains as in the resting state  Non-homogenous perfusion (radiopharmaceutical distribution) as a result Ischemic cascade Type of stress  Mechanical dynamic stress  ergometer (bicycle), tread-mill  Pharmacological stress    vasodilators - adenosine, dipyridamole positively inotropic drugs - dobutamine, arbutamine atropine  Combined of all mentioned above Ergometer  Goal is to achieve at least 85% of maximal heart rate (220-age) or double-product more than 25000  Increase by 50 (25) W after every 3 (2) minutes  Rate of pedalling 40 to 60 per minute  Radiopharmaceutical injection at peak stress  distribution proportional to blood flow at the time of injection  Maintain this stress for at least 1 to 2 minutes  Withdraw betablockers (BB), patient fasting Dipyridamole stress  Acts indirectly via the adenosin (block its removal)  Dilates coronary resistant arteries - it makes possible to assess coronary flow reserve  Maximal effect is achieved 3 to 4 minutes after stopping the 4 minutes infusion  Its effect can be stopped with theophyllines  withdraw them before the test  Usually used in patients using BB, unable to exercise, with LBBB Contraindications to perform dipyridamole stress  Patients with chronic obstructive pulmonary disease treated by theophyllines (dobutamine can be used)  Patients should avoid tee, cofee, cola before the test to prevent false negative results (insuficient or no vasodilation) Dipyridamole stress Side effects of dipyridamole  They occures in approximately 30% of patients       headache neck tension warm feeling dizziness nausea, hypotension chest pain (very seldom) Performance of dipy stress  Dipyridamole applied by intravenous infusion  Usual dosage is 0.56 (0.75; 0.84) mg/kg  Dose is diluted with saline to 50 ml  to prevent local side effects (arm pain)  Duration of infusion is 4 minutes  If the patient is unable of any physical stress, tracer is injected 3-5 min. after stopping infusion Combined stress  Dipyridamole is infused according to previous rules to sitting or lying patient  3 to 6 min. bicycle stress follows    better image quality lower frequency of side effects can be performed even in patients with hypotension  1 to 2 min. before stopping bicycle stress radiopharmaceutical is injected Test arrangement  Right arm - tourniquet of tonometer  Left arm - infusion through the cannula  Saline is connected after stopping dipyridamole for venous link for the case of any complication  Patient is sitting on the ergometer, ECG electrodes according to Mason and Likar Dobutamine stress  If dipyridamole is contraindicated  Dobutamine intravenously in the dose of 5 to 10 g/kg/min., increase every 3 min. up to dose of 40 g/kg/min.  Monitore ECG, HR and BP, if 85% of maximal HR is not achieved, add Atropine  Radiopharmaceutical is injected 1 to 2 min. before stopping stress  Contraindications: ventricular tachycardia, severe hypertension, hypertrophic cardiomyopathy Myocardial perfusion protocols        One-day (Tl, Tc, FDG) - two-days (Tc, FDG, Tl) Stress - rest or rest - stress (Tc, Tl-Tc) Stress - (redistribution) - reinjection (Tl) Stress - metabolism (Tc - FDG) Stress - rest - metabolism (Tc, FDG) Rest - redistribution - (late redistribution) (Tl) Rest - metabolism (Tc - FDG) Radiopharmaceuticals for perfusion Tl-201 chlorid or Tc-99m MIBI for SPECT, N-13H3 or H2O-15 for PET Distribution in the myocardium rely on cells perfusion Tl-201 has redistribution Tc-99m MIBI does not have redistribution Data processing  Quantitative analysis of myocadial perfusion distribution  CEqual™ - uses pollar maps for standardization and comparison with „normals“  Gated (synchronized) tomography (QGSPECT)   divides cardiac cycle into 8 periods makes possible to evaluate mechanical function of the heart (ejection fraction - EF) Quantification of perfusion QGSPECT Basic patterns of myocardial perfusion imaging (MPI)  Normal finding  homogenous perfusion during stress as well as rest  Sign of ischemia  perfusion defect during stress which disappears on rest (reversible defect)  Sign of scar  perfusion defect on stress and rest (fixed defect)  Sign of ischemia and scar  combination of both mentioned above Main clinical indication of MPI         Detection of ischemic heart disease Hemodynamic effect of coronary stenoses Prognosis of patients with konwn CAD Evaluation of revascularization effect and detection of restenosis Risk stratification of patients after MI Myocardial viability Acute coronary syndromes Cardiac risk in non-cardiac surgery Detection of CAD 66y old pt, atypical chest pain, ECHO difuse wall motion abnormality, Ao+mi reg, sci isch. of inferior wall, EF 40% Detection of CAD basic parameters  Planar Tl-201 scintigraphy - qualitative evaluatioin  Group of 4.678 pts - sens. 82%, spec. 88%      pts without MI - sens. 85% pts after MI - sens. 99% one-vessel disease - sens. 79% two-vessel disease - sens. 88% three vessel disease - sens. 92% Detection of CAD basic parameters  Referral bias    only patients with positive scintigraphy are referred to coronarography patients with normal scintigraphy are not catheterized higher sensitivity but decline of specificity  Normalcy rate (used instead of specificity)  negative scintigraphy in patients with very low pretest probabilty of CAD based on history, symptoms, stress ECG Detection of CAD basic parameters  SPECT Tl-201 scintigraphy  Group of 1.527 pts - sens. 90%, spec. 70% (more false positives due to artefacts), normalcy rate 89%      pts without MI - sens. 85% pts after MI - sens. 99% one-vessel disease - sens. 83% two-vessel disease - sens. 93% three-vessel disease - sens. 95% Detection of CAD basic parameters  SPECT Tl-201 scintigraphy  Group of 704 pts   stenosis of 50 to 70% - sens. 63% stenosis of 75 to 100% - sens. 88%  Dipyridamole stress (1.272 pts)   sens. 87% spec. 81% Detection of CAD basic parameters  SPECT Tl-201 scintigraphy  Asymptomatic pts    5.000 coronarograms normal scintigraphy exclude CAD positive scintigrapy has positive predictive value (PPV) of 50% - does not confirm CAD Detection of CAD basic parameters  SPECT Tl-201 scintigraphy  Individual arteries (1.200 pts)  SPECT is better than planar scintigraphy (better localisation)    LAD - sens. 80%, spec. 83% LCx - sens. 72%, spec. 84% RCA - sens. 83%, spec. 84% Detection of CAD basic parameters  SPECT Tc-99m MIBI scintigraphy  Sensitivity 87%  Specificity 73% (less artefacts using GSPECT)  Normalcy rate 92%  Optimal indication for detection of CAD   pretest probability 0.15 to 0.50 + pos. stress ECG pretest probability 0.50 to 0.85 Detection of CAD basic parameters  Difference was not confirmed     Tl-201 vs Tc-99m MIBI MIBI vs Myoview physical vs pharmacological stress men vs women  Improvement of accuracy was confirmed   SPECT vs planar scintigraphy GSPECT, quantification, prone projection Pts prognosis Prognosis of pts with known CAD basic parameters  Good prognosis - normal scintigraphy  2.825 pts without MI • annual increment of death 0.24% • annual increment of MI 0.53%  Signs of poor prognosis    more perfusion defects in more arterial territories increased uptake in lungs and transient LV dilatation reversible defects, large and severe defects Pts after revascularization detection of culprit lesion 56 y old pt, typical AP, positive stress ECG SCG arteries stenoses, way of treatmen: 1. CABG RIA, RMS I, III a IV 2. PTCA RMS III a IV Pts after revascularization assessment of the result moderate ischemia of the lateral wall, after PTCA LCx: perfusion and wall motion improvement, EF from 56% to 63%, stress ECG positive in both Pts after revascularization prognosis chi - square = 26.76 p = 0.00000023 RR = 3.15 40 30 20 25 40 8 10 0 no 9 positive negative MPI yes Cardiac events Pts after revascularization summary  Early after the procedure   negative scintigraphy - good prognosis positive scintigraphy - no predictive value  Ability of long-term prognosis  Restenosis detection   in symptomatic patients in asymptomatic patients with positive stress ECG Pts after MI  Definition of infarct size  Assessment of salvaged myocardium thanks to different ways of therapy  Evaluation of myocardial viability in location of wall motion abnormality  Risk stratification using stress perfusion scintigraphy Pts after MI scintigrapnic findings  Group of 55 pts  pos 38 (69%), borderline 3 (5%), neg 14 (26%)  Group after QMI (32 pts)  pos 23 (72%), borderline 2 (6%), neg 7 (22%)  Group after nQMI (23 pts)  pos 15 (65%), borderline 1 (4%), neg 7 (31%)  Group with positive enzymes kinetics (35 pts)  pos 25 (71%), borderline 3 (9%), neg 7 (20%) Pts after MI with positive scinti types of impairment  Group of 41 pts  scar 6 (15%), scar + ischemia 9 (22%), isch 26 (63%)  Group after QMI (25 pts)  scar 5 (20%), scar + ischemia 7 (28%), isch 13 (52%)  Group after nQMI (16 pts)  scar 1 (6%), scar + ischemia 2 (13%), isch 13 (81%)  Group with positive enzymes kinetics (25 pts)  scar 4 (16%), scar + ischemia 8 (32%), isch 13 (52%) 74y old pt, nQIM 9/98, left - scinti before PTCA 2.11.98, then PTCA LAD and OM with stents, right - scinti after PTCA 17.12.98 Pts after MI summary  High risk pts (shock, failure, persistent AP, previous MI) - coronarography  Without failure with EF < 40% - scintigraphy  viability and residual ischemia  Moderate risk - stress scintigraphy  conservative vs invasive therapy  Low risk - stress ECG Myocardial viability clinical significance  Important before revascularization  prediction of cardiac function improvement (> 25% of myocardium should be viable)  Patients with cardiac failure   decline of mortality but increase of cardiac failure due to CAD nowadays high prevalence of viable myocardium among pts in waiting list for heart transplantation Myocardial viability characteristics  Defined by perfusion, metabolism and function  Stunned myocardium  wall motion abnormality but normal perfusion and preserved metabolism  Hibernating myocardium  wall motion and perfusion abnormality but preserved metabolism  Scar  abnormality of all characteristics Myocardial viability PET examination (mismatch = hibernation) Myocardial viability principle of the assessment  Preserved function of ATP-ase  late accumulation of Tl-201  Preserved glucose metabolism  accumulation of F-18 FDG  Preserved mitochondrial function  accumulation of Tc-99m MIBI  Preserved answer to dobutamine  dobutamine echocardiography 50y old woman, QMI of anterior wall treated by rescue PTCA LAD with stent implant. 6/99, ECHO anterior wall motion abnorm., stress scinti 7/99 apico-antero-septal scar, examination by Tl-201 9/99, F-18 FDG 10/99 201Tl rest redistribution VLA 99mTc MIBI rest 18F FDG rest VLA 50y old woman, QMI antero-septal 1995, after PTCA LAD 1997, recurrent AP, stress scinti 11/98 antero-septal scar, Tl201 1/99, F-18 FDG 2/99, ECHO unable to evaluate 99mTc MIBI rest 201Tl redistribution VLA 99mTc MIBI rest 18F FDG rest VLA 72y old woman, MI 4/00, PTCA LAD 5/00, exam. 7/00, viab. 8/00, PTCA LAD 9/00, follow up exam. 10/00 – perfusion improv. about 7% of myocardium of LV, EF as well as wall motion the same Myocardial viability accuracy of different methods Acute coronary syndromes  Imaging of jeopardized myocardium    injection on admission, imaging after stabilization PPV of perfusion defect 90% NPV of no defect 100%  Infarction size measurement  examination before leaving (correlates with histology)  Viability  Risk stratification Acute coronary syndromes  Examination  rest SPECT perfusion with Tc-99m MIBI  Indication  non-diagnostic ECG  Limitation  availability  Benefit  cost Cardiac risk assessment in noncoronary surgery  Separates group of pts with higher risk  Group of 2020 pts   perfusion defect - perioperative events in 20% of pts no perfusion defect - perioperative events in 2% of pts Radionuclide ventriculography (MUGA)  Information about regional and global ventricular function  Excellent reproducibility of the results  Indications   cardiotoxicity of cytostatics alternative in pts non-evaluable with ECHO Radionuclide angiocardiography  First-pass   evaluation of right ventricle function quantification of central circulation shunts  Non-imaging devices   can monitore EF on CCU can be used for ambulatory EF monitoring Non-imaging devices Post-stress ventriculography Imaging of myocardial sympathetic receptor density I-123 MIBG  Tracer accumulates in postganglionic praesynaptic vesicules  Non-invasive assessment of myocardial sympathetic tone  prognosis of pts with cardiac failure  Rational treatment of cardiac failure with beta-blockers New trends  New tracers for myocardial perfusion imaging  Imaging of myocardial ischemia  Imaging of myocardial necrosis  Imaging of cells apoptosis  Imaging of endothellin receptors  Imaging of gene expression Conclusion  Nuclear cardiology tests can display noninvasively myocardial perfusion distribution during different pathophysiological conditions above all  They contribute to myocardial viability assessment in acute and chronic forms of CAD  Cooperation of cardiologists with nuclear medicine physicians is essential for proper use of this methods in favour of our patients Radionuclide venography and lung scintigraphy  Main clinical indication is suspicion of pulmonary embolism  Main clinical significance is negative finding - can exclude embolism  Widely available is perfusion scintigraphy  Correlation with chest radiograph is essential  Ventilation scintigraphy is useful in embolism of less than 50% of pulmonary circulation Lung perfusion scintigraphy  Tc-99m MAA as a tracer        capillary microembolism display pulmonary blood flow distribution It does not increase pulmonary pressure Injection in supine position Planar or SPECT imaging Procedure takes approximately 30 min. Interpretation is visual - PIOPED criteria Lung perfusion scintigraphy patient imaging Lung perfusion scintigraphy planar images - normal Lung perfusion scintigraphy planar and SPECT slices - embolism Lung perfusion and ventilation pulmonary embolism anterior view, left - perfusion, right - ventilation Lung perfusion and ventilation pulmonary embolism ANT POST RPO LPO perfusion ventilation Radionuclide venography  Displays patency/abrupt cutoff of lower limbs deep venous system  Displays abnormal collateralization  Displays irregular or asymmetric filling  Does not display thrombus  Injection of Tc-99m MAA into dorsal pedal veins - lung perfusion scintigraphy follows  Procedure takes approx. 40 to 60 minutes Radionuclide venography injection and imaging Radionuclide venography left without, right with tourniquets Radionuclide venography pathological findings New trends  Thrombi imaging  Labeled thrombocytes  not readily available  Receptors imaging  Acutect - not registered in the Czech rep. • peptide binding to receptors of activated thrombocytes labelled with Tc-99m  Result available in the order of 4 to 6 hours