Nuclear Medicine in Cardiology

1. Nuclear Medicine in Cardiology A. Hussein S. Kartamihardja Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

2. What does the heart do ? • The heart is a powerful muscle consisting of two pumps side by side. • Its steady beating maintains flow of blood to all parts of the body throughout life. Diagnostic modalities in heart disease • ECG/ Treadmill • Radiography • Echocardiography • CT scan • MRI • Angiography • Radionuclide imaging Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

3. Cardiac Nuclear Medicine Radiopharmaceutical Physician Instrumentation Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

4. History of nuclear cardiology • Blumgard and Weiss (1927) : the first use of radioactivity in the study of the cardiovascular system • Wilson : measurement of the circulation times • Tl-201 (1971) • The development and improvement of SPECT • The development and established Tc-labeled agents • Alternative stress than physical exercise • Gate-spect allows simultaneous assessment both of myocardial perfusion, function and assessment of myocardial viability • Gamma camera coincidence imaging system • Myocardial metabolic imaging Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

5. The ideal perfusion radiopharmaceutical • Distribution in the myocardium in linier proportional to blood flow. • Efficient myocardial extraction from blood on the first passage through the heart • Stable retention within myocardium during data acquisition • Rapid elimination allowing repeat studies under different conditions • Good imaging characteristics (short half life, low radiation burden to the patient) • Ready availability • Competitive pricing • No current tracer possesses all of these properties. • Thallium-201 • Tc-99m Teboroxim • Tc-99m MIBI • Tc-99m Tetrofosmin Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

6. Thallium –201 Basic Properties • A metallic element which behaves chemically in a similar manner to potassium and is given as thallous chloride • Photon energy is low, and 88% of its emissions are x-ray with photon energy of 60-80keV • Gamma photons of 135 and 167 keV (12%) • Enter myocyte by • 60% active transport via Na+/K+ ATPase pump • 40% passively along the electrochemical gradient • Distribution within the myocardium is proportional to blood flow • The half life of elimination within the heart is approximately 7 hrs Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

7. Tc-99m MIBI (methoxyisobutylisonitrile)Tc-99m TETROFOSMIN (Basic Properties) • It is lipophilic • Distribution within the myocardium is proportional to blood flow • Diffuses out of the capillary into cardiac myocytes and is associated with mitochondria within the cell. • Cardiac uptake is depend on normal mitochondrial function. • Liver uptake of tetrofosmin is not as prominent as with Tc-99m MIBI • No redistribution Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

8. Correlation between Tl-201 and Tc-99m tetrofosmin imaging Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

9. Clinical application of Nuclear Cardiology • CAD • Acute and post MI • Cardiomyopathy • Valvular disease and Shunts • Cardiotoxicity • Aneurysms • Transplants • Diagnosis & prognosis • Risk stratification • Medical vs. surgical treatment • Efficiency of management Stress-rest Tl-201 and Tc-99m labeled agents has been widely used in the diagnosis and assessment of coronary artery disease MPI still an important position in clinical practiceonly 1/3 of symptom-free men with exercise induced ST segment depression had coronary angiographic lesions > 50% diameter stenosis MPI has been proposed to improve the accuracy and risk assessment of exercise testing in patients with suspected CAD Sensitivity 74% - 96%, specificity 65% -97% Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

10. Principles of myocardial perfusion imaging ? Imaging at 24 hrs is sometimes performed when the question of underestimation of myocardial mass in the redistribution images is clinically important • What is coronary artery disease ? • A condition where there is progressive damage to the vessel wall supplying the coronary arteries. • Unbalance between demand and supply O2 to myocardium Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

11. Cardiac stress test Physical exercises Exercise has to be adequate to produced the heterogenity in blood flow to achieve high detection sensitivity • Treadmil • Ergocycle Pharmacological • Pharmacological stress test become important, since many patients are unable to exercise • Pharmacological stress agents largely remove the need for patient cooperation and motivation, and enable a confident assessment of cardiac function in virtually all cases • Dipyridamole • Dobutamine • Adenosine Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

12. Dipyridamole • Coronary artery dilator • The effects of dipyridamole include a mild decrease in systolic BP, slight increase HR. • The side effects include flushing, abdominal pain, nausea, vomiting, transient AV block and bronchospasm • Infusion dose of 0.56 mg/kg over four minutes (0.14 ml/kg/min) Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

13. Dobutamine • The ß-agonists increase myocardial oxygen demand through a combined inotropic and chronotropic action • It dilates the distal coronary vessels, which leads to an increase in coronary flow • Dose up to 40 ug/kg/min (commence at 10 ug/kg/min and proceed in 10 ug/kg/min step every 3 min) • Non-cardiac symptoms cause by dobutamine include tingling, flushing, nausea, headache, shaking and lightheadedness Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

14. Adenosine • Is a naturally occurring purine which mediates the cellular action of dipyridamole • No significant difference between the coronary hyperemic response to adenosine and dipyridamol • Has very short half life of between 2 – 10 seconds • Maximal coronary vasodilatation is achieved in 85% of patients with intravenous dose of 140ugr/kg/min • Side effect are similar to those with dipyridamol Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

15. Spect imaging In SPECT imaging, the heart is viewed in 3 planes : • The horizontal long axis, which is parallel to the long axis of the heart from base to apex. It begins at the inferior aspect of the heart and progresses superiorly • The vertical long axis, which is perpendicular to the horizontal long axis. It begins at the lateral aspect of left ventricle and proceeds medially through the septum • The short axis of the heart which is perpendicular to both of the long axes. It begins at the base of the heart and progress through the mid plane to the apex Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

16. Image interpretation I. Defects • Location • Extent • Severity • Reversible or fixed • Quantitative or semi quantitative analysis II. Other information • Transient ischemic dilation • Lung uptake Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

17. Normal perfusion scan • There is a wide variety of normal appearances arising from variation in size and position of the heart, body size and quality of tomographic acquisition • Knowledge of these variation and confidence in their identification is vital to prevent the reporting of defects as normal variant • An important issue to bear in mind if difficulty arise in distinguishing normal variants from true defects Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

18. Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

19. G 2121-00 PRE-PTCA POST-PTCA Differences between stress and rest/redistribution imaging indicates reversibility (ischemia) Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

20. M724499 PATIENT NO : M724499 SEX : MALE AGE : 53 YRS CLINICAL INDICATION : TWO ACUTE CORONARY EPISODES ANGIOGRAM: A STENOSIS AT THE PROXIMAL AND MIDDLE THIRDS OF THE LAD ARTERY Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

21. REST MPI SPECT GATED BLOOD POOL NO : S 0585/01SEX : MALEAGE : 60 YRSECG : NON Q-WAVE MYOCARDIAL INFARCTION S 0585/01 Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

22. Comparison between SPECT and Treadmill exercise test Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

23. Risk Stratification Outcome following non-fatal MI : Low risk group 50% - 66% of the patients Can be managed with medical treatment High risk group 34% - 50% of the patients Prone to future complications with 3 months death, re-infarction, CHF and unstable angina • Separation of high and low risk groups : • Clinical evaluation • Rest and stress ECG* • Rest and stress RNA* • Rest and stress MPI* • Rest and stress echo • Angiography • Recommended by ACC & AHA • Task Force • Nuclear cardiology separates high risk patient who need invasive and expensive procedures and low risk patient who do not. • Acts as a ”Gate - Keeper” for referral to angiography. Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

24. Myocardial perfusion scan findings associated with increased risk for cardiac events after acute myocardial infarction • Perfusion defects induced by exercise or pharmacological • Reversible perfusion defects in multiple coronary vascular territories • Large perfusion defect size • Improved reperfusion after Tl-201 reinjection • Increased lung uptake • Left ventricular cavity dilatation • Left ventricular dysfunction on gated myocardial perfusion scan • Abnormal right ventricular uptake Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

25. Myocardial Viability / Hibernation • Persistently impaired myocardial and left ventricular function at rest, due to reduced coronary blood flow. (Rahimtola) • The functional abnormality can be partially or completely restored to normal by reducing myocardial oxygen demand and/or increasing coronary blood flow • Myocardial dysfunction is expected to be irreversible in regions with myocardial scar, but can be improved in region with ischemic but viable or hibernating myocardium. • The determination of myocardium viability in patients with CAD and the LV dysfunction has become a frequent issue since interventional cardiology is growing rapidly. • The differentiation of scar from hibernating myocardium is important. • Up to now, radionuclide myocardial imaging holds the most important promise in this field. • Metabolic measurement by PET may be the most sensitive non-invasive approach for the evaluation of myocardial viability. Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

26. Myocardial Viability Why separate viable from scar tissue ? • Surgical treatment for viable myocardium results in 11.5% event rate compared to 50% after medical treatment • Surgical treatment for poor viability and scar have survival rate of 79% compared to 97% with viable tissue • LVD due to viable tissue have worse prognostic than scars with annual survival of 50% compared with 92% (PET data) Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

27. Techniques for assessing myocardial viability Regional wall motion evaluation • Ventriculography (gated spect) • Echocardiography (dobutamine) • Radionuclide angiography • Magnetic resonance imaging Perfusion and cell membrane integrity • Tl-201protocols • Tc-99m sestamibi • Tc-99m tetrofosmin • Nitrate-augmented perfusionimaging Assessment of metabolism • Well established for predicting functional recovery after revisualization • F-18 FDG • I-123 fatty acids (IPPA, BMIPP) Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

28. Cost Effectiveness of Nuclear Cardiology Historical Background • Nuclear Cardiology as “ a better stress test ” • Detection of CAD as a benchmark for success • Gold standard : coronary angiography • Misconceptions • Expensive stress test • Sensitivity < 100% • False positive • Imperfect correlation with angiography • The changing paradigm • Angiography provides information on anatomy • Nuclear cardiology provides information on function/physiology • Physiology is as important as anatomy, and perhaps more important • Functional testing with nuclear imaging provide comparable prognostic information at lower cost than angiography, non-invasive • Information provided by nuclear cardiology can reduce cost and optimize treatment Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

29. Summary MPI has been widely used and an important position in the diagnosis and assessment of CAD Sensitivity 74% - 96%, specificity 65% -97% Nuclear cardiology separates persistent defect with LV dysfunction but viable myocardium from scar tissue • Nuclear cardiology separates high risk patient who need invasive and expensive procedures from low risk patient who do not. • Acts as a ”Gate - Keeper” for referral to angiography. Cost of management strategies using MPI are cheaper and equally effective when compared with strategies without MPI with same outcome. Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

30. Thank you ! Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital