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

What does the heart do ? Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital 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. ECG/ Treadmill Radiography Echocardiography CT scan MRI Angiography Radionuclide imaging Diagnostic modalities in heart disease

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

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

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. 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. Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital Thallium-201 Tc-99m Teboroxim Tc-99m MIBI Tc-99m Tetrofosmin

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

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

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

Diagnosis & prognosis Risk stratification Medical vs. surgical treatment Efficiency of management Clinical application of Nuclear Cardiology Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital CAD Acute and post MI Cardiomyopathy Valvular disease and Shunts Cardiotoxicity Aneurysms Transplants 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 practice only 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%

Principles of myocardial perfusion imaging ? Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital What is coronary artery disease ?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 O 2 to myocardium Imaging at 24 hrs is sometimes performed when the question of underestimation of myocardial mass in the redistribution images is clinically important

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

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

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

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

Spect imaging In SPECT imaging, the heart is viewed in 3 planes : 1. 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 2. 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 3. 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

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

Normal perfusion scan Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital 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

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

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

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

Comparison between SPECT and Treadmill exercise test VariableSPECTTreadmill Availability Cost Familiarity Accuracy ++++ Localization Extent of disease Viable myocardium Left ventricular function Risk assessment Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

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

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

Myocardial Viability / Hibernation Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital 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.

Myocardial Viability Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital 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)

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 perfusion imaging 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

Historical Background Nuclear Cardiology as “ a better stress test ” Detection of CAD as a benchmark for success Gold standard : coronary angiography Cost Effectiveness of Nuclear Cardiology Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital 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

MPI has been widely used and an important position in the diagnosis and assessment of CAD Sensitivity 74% - 96%, specificity 65% -97% Summary Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital 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. Nuclear cardiology separates persistent defect with LV dysfunction but viable myocardium from scar tissue

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