Update in Cardiac Stress Testing and Nuclear Cardiology Matthew Schumaecker, MD, FACC, FASNC Medical Director, Nuclear Cardiology Division of Cardiology, Carilion Clinic Assistant Professor of Medicine VTC School of Medicine

Objectives After 50 minutes, the awake audience member should have: A renewed conceptual framework of cardiac stress testing A better understanding of the epidemiology behind stress testing, particularly nuclear cardiac testing An introduction to novel technologies in nuclear cardiology with emphasis on low-radiation techniques

Part I: What is Cardiac Stress Testing

Overview of Stress Modalities Stress Modality Imaging Modality Exercise Treadmill Bicycle Pharmacological Dobutamine Atropine Adenosine Dipyridamole Surface electrocardiography Echocardiography Myocardial Perfusion Imaging: SPECT PET

Stress Modality: Exercise Disadvantages: Cannot perform in patients with significant functional limitations ECG uninterpretable in LBBB, LVH, resting ST abnormalities, WPW, PPM and SPECT can be false positive in LBBB and patients with PPM Advantages: Least expensive stress modality Lowest concern for adverse reaction Produces physiologic ischemia in CAD Threshold of reproduction of ischemic symptoms Derived functional data is strongly predictive of cardiac mortality

Stress Modality: Exercise-Treadmill Treadmill is most commonly used for exercise Bicycle is used mostly in echo lab for valve cases (i.e., mitral stenosis) and to assess for exercise-induced pulmonary hypertension. Patients are put on a standardized protocol which can predict performance based on age and gender (i.e., Bruce, Cornell, Naughton)

Stress Modality: Exercise-Treadmill Bruce Protocol - Treadmill Most commonly used protocol. Very well-studied and validated with good prognostic data. Each stage lasts three minutes Patient exercises to symptomatic maximum Stage Speed (mph) Gradient (%) I 1.7 10 II 2.5 12 III 3.4 14 IV 4.2 16 V 5.0 18 VI 5.5 20

Stress Modality: Exercise MET = Metabolic equivalent 1 MET = amount of energy expended at supine rest 1 MET ≈ (kcal/hour)/kg 1 MET ≈ 3.5 ml/kg/min VO2 Average maximum exercise threshold in healthy middle-aged male ~ 10 METS

Stress Modality: Exercise-Treadmill

Stress Modality: Exercise-Treadmill

Stress Modality: Exercise - Bicycle Can obtain respiratory data if equipped Advantages More direct measurement of work (i.e., watts) Disadvantages Can be cumbersome to set up. Echocardiographic images obtained during exercise Takes longer to reach MPHR Not widely used in US for cardiac stress testing Useful for evaluating mitral stenosis and exercise induced pulmonary hypertension Can complement vasodilator stress by producing better images and minimizing symptoms

Stress Modality: Dobutamine Beta agonist Simulates exercise by positive chronotropy and inotropy. Can be difficult to achieve 85% MPHR with dobutamine alone May need to augment chronotropic response with atropine up to 1 mg. Can cause SAM and LVOT obstruction in patients with significant septal hypertrophy.

Stress Modality: Vasodilator Slide by Dr. Robert Hendel. ASNC 7/07

Stress Modality: Vasodilator Slide by Dr. Robert Hendel. ASNC 7/07

Stress Modality: Adenosine Causes coronary arteriolar vasodilation Extremely short half life Given in a four or six minute infusion Tracer is injected halfway through the protocol Can cause flushing, diaphoresis, chest pain. Usually resolves within minutes after infusion

Stress Modality: Regadenoson Four Types of Adenosine Receptors A1 – AV Block A2A – Vasodilate small coronary vessels A2B – Mast cell degranulation A3 - Bronchoconstriction

ADVANCE MPI-2 Mahmarian et al. JACC Imaging; Aug 2009

Stress Modality: Dipyridamole Trade Name: Persantine Acts by blocking the cellular uptake of adenosine Four to ten times less expensive than adenosine Comparable to adenosine with respect to sensitivity; specificity may be lower Much longer half life so adverse reactions tend to be more severe Not used very much in clinical practice

Imaging Modalities Slide by Dr. Robert Hendel. ASNC 7/07

Surface ECG Obtained during every stress modality. Determine underlying rhythm Assess for arrhythmic response to stress Assess for ischemic response to stress ST segment is monitored during all phases of stress to look for significant deviation. Sensitivity and specificity alone are lower than other modalities (especially in women) but can be complementary to other modalities.

ECG Positivity Tak and Gutierrez. Postgraduate Medicine Online June 2004

Stress Echo Pro Con No radiation Higher specificity Can assess other cardiac chambers and valves. Can assess valve disease Can assess pulmonary hypertension Operator-dependent Lower sensitivity No vasodilator option Non-quantitative

Stress Nuclear Pro Con Higher sensitivity Vasodilator option Quantitative support Less inter-operator and inter-reader variability Radiation concern Does not evaluate valves or other cardiac processes other than myocardial perfusion

Part II: Why Do We Stress Test?

Part II: Why Do We Stress Test? Rule out CAD? Reassure patients? Reassure ourselves? Avoid lawsuits?

Imaging Modalities: Sensitivity and Specificity

Why Do We Stress Test? To provide a physiologically-based risk assessment in selected individuals which is adjunctive and additive to traditional risk assessment from H&P and models such as Framingham or Reynold’s Risk Score

Cardiac Death and MI by SPECT Degree of Normalcy Hachamovitch R, Berman DS, Shaw LJ, et al. Circulation. 1998 Feb 17;97(6):535-43. Black boxes– Cardiac death White boxes – Myocardial infarction

Cardiac Death Rate Stratified by Revascularization vs Cardiac Death Rate Stratified by Revascularization vs. Medical Therapy and by SPECT Degree of Normalcy Hachamovitch R, Berman DS, Shaw LJ, et al. Circulation. 1998 Feb 17;97(6):535-43. Black boxes – Medical Therapy White boxes – Revascularization

Part III: Which Patients Do We Stress Test?

Part III: Which Patients Do We Stress Test? Patients at high risk for CAD? Abnormal ECG Hyperlipidemia Hypertensives Smokers

Why Detecting (asymptomatic) CAD Might Not Matter

Why Detecting (Asymptomatic) CAD Might Not Matter

Is there any role to stress testing asymptomatic individuals? NOT USUALLY

“Special” Asymptomatic Indications Consideration for class Ic antiarrhythmic Newly diagnosed cardiomyopathy CT calcium score > 400 Agatston units Chemotherapy MAYBE – high risk (>20%/10 year) diabetics

Appropriate Use Criteria

Appropriate Use Criteria

Part IV: Radiation Safety and Advances in Nuclear Imaging Technology

Danger of increased radiation “ Myocardial perfusion imaging … now accounts for more than 10% of the entire cumulative effective (radiation) dose to the US population from all sources except radiotherapy.” Einstein AJ. Effect of radiation exposure from cardiac imaging. J Am Coll Cardiol 2012; 59:553-565.

Society Mandate for Lower Radiation Exposure The American Society of Nuclear Cardiology has set a goal that accredited nuclear cardiology laboratories should reduce radiation levels to 9 mSv in half of patients by 2014 Journal Nuclear Cardiology 2010; 17:709-718

82,861 patients studied after MI. 77% had cardiac imaging or procedure For every 10 mSv of low-dose ionizing radiation, there was a 3% increase in the risk of age- and sex-adjusted cancer over a mean follow-up period of five years (hazard ratio 1.003 per mSv, 95% confidence interval 1.002–1.004).

At Carilion, closer to 15.2 mSv Imaging procedures and their approximate effective radiation doses* Procedure Average effective dose (mSv) Range reported in the literature (mSv) Bone density test+ 0.001 0.00–0.035 X-ray, arm or leg 0.0002–0.1 X-ray, panoramic dental 0.01 0.007–0.09 X-ray, chest 0.1 0.05–0.24 X-ray, abdominal 0.7 0.04–1.1 Mammogram 0.4 0.10–0.6 X-ray, lumbar spine 1.5 0.5–1.8 CT, head 2 0.9–4 CT, cardiac for calcium scoring 3 1.0–12 Nuclear imaging, bone scan 6.3 � CT, spine 6 1.5–10 CT, pelvis 3.3–10 CT, chest 7 4.0–18 CT, abdomen 8 3.5–25 CT, colonoscopy 10 4.0–13.2 CT, angiogram 16 5.0–32 CT, whole body variable 20 or more Nuclear imaging, cardiac stress test 40.7 Source: Mettler FA, et al. "Effective Doses in Radiology and Diagnostic Nuclear Medicine: A Catalog,"Radiology (July 2008), Vol. 248, pp. 254–63. At Carilion, closer to 15.2 mSv

Spectrum Dyamics D-SPECT Uses CZT (Cadmium Zinc Telluride) crystal instead of tradition NaI This makes it much more sensitive to photon emissions Analagous to taking a picture with very high speed film – you need less “light” to get a picture This allow us to get clear pictures: More quickly With less radiation On more obese patients (weight limit 531 lbs)

Solid State SPECT Imaging: Low Dose Recent data shows that an excellent quality scan could be accomplished with 5 mCi of Technetium. This would provide about 1.6 mSv of radiation per scan

Stress First/Only 60-70% nuclear studies normal If stress images are normal, rest images are not clinically valuable In lower risk patients, we could do stress imaging and only if abnormal bring back for rest

Radiation Exposure Normal BMI Procedure Radiation Exposure Dual Isotope Imaging traditional SPECT 24mSv Same Isotope (Tc-Tc) Imaging/ traditional SPECT 12mSV Same Isotope (Tc-Tc) Imaging / D-SPECT 4 mSv Stress Only (Tc) / D-SPECT 1 mSv

Questions Matthew Schumaecker Blackberry: 540-494-2411