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