February Saurabh Malhotra MD, MPH Clinical Instructor UPMC Heart and Vascular Institute

Transcription

1 February Broward County Convention Center 195 Eisenhower Blvd Fort Lauderdale, FL Prem Soman MD, PhD, FRCP (UK), FACC Associate Professor of Medicine (Cardiology), Clinical & Translational Science Director, Nuclear Cardiology Director, Advanced Cardiac Imaging Fellowship UPMC Heart and Vascular Institute Pittsburgh, PA Saurabh Malhotra MD, MPH Clinical Instructor UPMC Heart and Vascular Institute Pittsburgh, PA

2 Session 1: The Role of Non-Invasive Cardiac Imaging in Primary Care: When and How To Use It Learning Objectives 1. Identify patients who are appropriate candidates for noninvasive cardiac imaging and cardiology referral 2. Recognize current guideline recommended indications for noninvasive cardiac imaging tests and apply them in the selection of appropriate tests for CV risk assessment 3. Describe the value and limitations of various noninvasive cardiac imaging techniques for cardiovascular risk stratification in patients with known or suspected coronary artery disease 4. Outline the differences between the pharmacologic stress agents used in conjunction with non-invasive cardiac imaging Faculty Prem Soman, MD, PhD, FRCP (UK), FACC Associate Professor of Medicine (Cardiology) Director, Nuclear Cardiology Labs Director, Advanced Cardiac Imaging Fellowship Program UPMC Heart and Vascular Institute Pittsburgh, Pennsylvania Dr Prem Soman is associate professor of medicine (cardiology) and director of nuclear cardiology at the Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA. Dr Soman is internationally recognized for his research contributions to the field and for numerous original research papers, editorials, and text book chapters. He is chair of the 213 annual scientific sessions of the American Society of Nuclear Cardiology (ASNC), serves on the editorial board of the Journal of Nuclear Cardiology, and on the board of directors of ASNC and the cardiovascular council of the Society of Nuclear Medicine and Molecular Imaging. Saurabh Malhotra MD, MPH Clinical Instructor UPMC Heart and Vascular Institute Pittsburgh, Pennsylvania Dr Saurabh Malhotra is a clinical instructor at the Heart and Vascular Institute at University of Pittsburgh Medical Center. Dr Malhotra s clinical interest is in multimodality noninvasive cardiovascular imaging. He is an emerging leader in the field of cardiac imaging with special emphasis on nuclear cardiology. He has received the highest level of training in various imaging modalities. He is board certified in general cardiology, echocardiography, nuclear cardiology, and cardiac computed tomography (CT). Dr Malhotra also received a Masters in public health degree from the Bloomberg School of Public Health at Johns Hopkins University with a focus on epidemiology and biostatistics. His academic focus is on identifying novel imaging predictors of ventricular arrhythmias among patients with cardiomyopathy. Dr Malhotra holds leadership positions in the American Society of Nuclear Cardiology and the cardiovascular council of the Society of Nuclear Medicine and Molecular Imaging. He is a fellow of the American Society of Nuclear Cardiology and serves on the editorial board of the Journal of Nuclear Medicine. Faculty Financial Disclosure Statements The presenting faculty reported the following: Dr Soman serves as a consultant for GE Healthcare and Astellas and is a grant recipient for GE Healthcare. Dr Malhotra has no financial relationships to disclose. Education Partner Financial Disclosure Statement The content collaborators at Horizon CME have reported the following: Brian Lee, PharmD, Elizabeth Wilkerson, CHES, and Cara Williams, PharmD have no relationships to disclose. Acronym List Acronym Definition AMI acute myocardial infarction

3 CA CABG CACS CCTA CMR CTA ECHO EST coronary angiography coronary artery bypass graft coronary artery calcium score cardiac computed tomography angiography cardiac magnetic resonance computed tomography angiography echo cardiogram exercise stress test LBBB MACE MPI NPV PCI RBBB SPECT WMA WPW left bundle branch block major adverse cardiac event myocardial perfusion imaging negative predictive value percutaneous coronary intervention right bundle branch block single photon emission computed tomography wall motion abnormality Wolfe-Parkinson-White Syndrome Suggested Reading List American College of Cardiology Foundation Appropriate Use Criteria Task Force, American Society of Echocardiography, American Heart Association, et al. ACCF/ASE/AHA/ASNC/HFSA/HRS/SCAI/SCCM/SCCT/SCMR 211 Appropriate Use Criteria for Echocardiography. A Report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, American Society of Echocardiography, American Heart Association, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Critical Care Medicine, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Resonance Endorsed by the American College of Chest Physicians. J Am Coll Cardiol. 211;57(9): Diamond GA, Forrester JS. Analysis of probability as an aid in the clinical diagnosis of coronary-artery disease. N Engl J Med. 1979;3(24): Gibbons RJ, Balady GJ, Beasley JW, et al. ACC/AHA Guidelines for Exercise Testing. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Exercise Testing). J Am Coll Cardiol. 1997;3(1): Gould KL, Lipscomb K, Hamilton GW. Physiologic basis for assessing critical coronary stenosis. Instantaneous flow response and regional distribution during coronary hyperemia as measures of coronary flow reserve. Am J Cardiol. 1974;33(1): Greenland P, Alpert JS, Beller GA, et al. 21 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 21;122(25):e Greenwood JP, Maredia N, Younger JF, et al. Cardiovascular magnetic resonance and single-photon emission computed tomography for diagnosis of coronary heart disease (CE-MARC): a prospective trial. Lancet. 212;379(9814): Hachamovitch R, Berman DS, Kiat H, et al. Exercise myocardial perfusion SPECT in patients without known coronary artery disease: incremental prognostic value and use in risk stratification. Circulation. 1996;93(5): Hachamovitch R, Berman DS, Shaw LJ, et al. Incremental prognostic value of myocardial perfusion single photon emission computed tomography for the prediction of cardiac death: differential stratification for risk of cardiac death and myocardial infarction. Circulation. 1998;97(6): Hendel RC, Cerqueira M, Douglas PS, et al. A multicenter assessment of the use of single-photon emission computed tomography myocardial perfusion imaging with appropriateness criteria. J Am Coll Cardiol. 21;55(2): Hendel RC, Berman DS, Di Carli MF, et al. ACCF/ASNC/ACR/AHA/ASE/SCCT/SCMR/SNM 29 Appropriate Use Criteria for Cardiac Radionuclide Imaging: A Report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the American Society of Nuclear Cardiology, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the Society of Cardiovascular Computed Tomography, the Society for

4 Cardiovascular Magnetic Resonance, and the Society of Nuclear Medicine Endorsed by the American College of Emergency Physicians. J Am Coll Cardiol. 29;53(23): Hulten EA, Carbonaro S, Petrillo SP, Mitchell JD, Villines TC. Prognostic value of cardiac computed tomography angiography: a systematic review and meta-analysis. J Am Coll Cardiol. 211;57(1): Hundley WG, Bluemke DA, Finn JP, et al. ACCF/ACR/AHA/NASCI/SCMR 21 expert consensus document on cardiovascular magnetic resonance: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents. J Am Coll Cardiol. 21;55(23): Jahnke C, Nagel E, Gebker R, et al. Prognostic value of cardiac magnetic resonance stress tests: adenosine stress perfusion and dobutamine stress wall motion imaging. Circulation. 27;115(13): Klocke FJ, Baird MG, Lorell BH, et al. ACC/AHA/ASNC guidelines for the clinical use of cardiac radionuclide imaging-- executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASNC Committee to Revise the 1995 Guidelines for the Clinical Use of Cardiac Radionuclide Imaging). Circulation. 23;18(11): Lee TH, Boucher CA. Noninvasive tests in patients with stable coronary artery disease. N Engl J Med. 21; 344(24): Mark DB, Berman DS, Budoff MJ, et al. ACCF/ACR/AHA/NASCI/SAIP/SCAI/SCCT 21 expert consensus document on coronary computed tomographic angiography: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents. J Am Coll Cardiol. 21;55(23): Min JK, Dunning A, Lin FY, et al. Age- and sex-related differences in all-cause mortality risk based on coronary computed tomography angiography findings results from the International Multicenter CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry) of 23,854 patients without known coronary artery disease. J Am Coll Cardiol. 211;58(8): Morise AP, Haddad WJ, Beckner D. Development and validation of a clinical score to estimate the probability of coronary artery disease in men and women presenting with suspected coronary disease. Am J Med. 1997;12(4): Olmos, LI, Dakik H, Gordon R, et al. Long-term prognostic value of exercise echocardiography compared with exercise 21 Tl, ECG, and clinical variables in patients evaluated for coronary artery disease. Circulation 1998;98(24): Prenner BM, Bukofzer S, Behm S, Feaheny K, McNutt BE. A randomized, double-blind, placebo-controlled study assessing the safety and tolerability of regadenoson in subjects with asthma or chronic obstructive pulmonary disease. J Nucl Cardiol. 212;19(4): Weiner DA, Ryan TJ, McCabe CH, et al. Prognostic importance of a clinical profile and exercise test in medically treated patients with coronary artery disease. J Am Coll Cardiol. 1984;3(3):

5 SESSION 1 7:45 9:15am The Role of Non-Invasive Cardiac Imaging in Primary Care: When and How To Use It SPEAKERS Prem Soman, MD, PhD Saurabh Malhotra, MD, MPH Presenter Disclosure Information The following relationships exist related to this presentation: Dr. Soman serves as a consultant for GE Healthcare, and Astellas, has research support from GE Healthcare. Dr. Malhotra has no financial relationships to disclose. Off-Label/Investigational Discussion In accordance with pmicme policy, faculty have been asked to disclose discussion of unlabeled or unapproved use(s) of drugs or devices during the course of their presentations. The Role of Non-Invasive Cardiac Imaging in Primary Care: When and How to Use It? Faculty Prem Soman, MD, PhD Associate Professor of Medicine (Cardiology) Director of Nuclear Cardiology University of Pittsburgh Medical Center Pittsburgh, PA Saurabh Malhotra, MD, MPH Instructor in Medicine (Cardiology) University of Pittsburgh Medical Center Pittsburgh, PA Generic Drug Name adenosine dipyridamole dobutamine Ibuprofen regadenoson Drug List US Trade Name Adenocard, Adenoscan Persantine Dobutrex Advil, Motrin Lexiscan Learning Objectives Identify patients who are appropriate candidates for non-invasive cardiac imaging and cardiology referral Recognize current guideline recommended indications for non-invasive cardiac imaging tests and apply them in the selection of appropriate tests for CV risk assessment Describe the value and limitations of various noninvasive cardiac imaging techniques for cardiovascular risk stratification in patients with known or suspected coronary artery disease Outline the differences between the pharmacologic stress agents used in conjunction with non-invasive cardiac imaging 1

6 Prevalence and Impact of CHD in the US Why Stress Test to Diagnose CAD? High Prevalence 16.3 Million 1.2 Million Hospitalizations Commonest Killer 1:6 deaths Very Costly $44 Billion Coronary Blood Flow (ml/min/g) Coronary Flow Reserve Hyperaemia Rest Percent Diameter Narrowing Coronary Artery STRESS REST Stenosis Stenosis CHD = coronary heart disease. Roger VL, et al. Circulation. 212;125(1):e2-e22. Adapted from Braunwald s Heart Disease, 8th Ed. Chapter 16. Gould K L. Am J Cardiol. 1978;41: Ischemic Cascade Objectives of Stress Testing MPI Perfusion Abnormalities Flow Heterogeneity ECHO Wall Thickening Abnormalities Diastolic Dysfunction ECG ECG Changes Regional Systolic Dysfunction SYMPTOMS Angina Chest Pain Electrical Transit Abnormalities Diagnosis of CAD Estimating the probability of obstructive CAD Risk Stratification in known or suspected CAD (Estimating the risk of death or non-fatal MI) Low risk <1% per year Intermediate risk 1-3% per year High risk >3% per year INCREASING DURATION OF ISCHEMIA Hauser AM. J Am Coll Cardiol. 1985;5(2 Pt 1): Nesto RW. Amer J Card. 1987;59(7):23C-3C. CAD = coronary artery disease. Gibbons RJ, et al. J Am Coll Cardiol. 1997;3: Who to Test?: Asymptomatic Patients Stress testing is generally not indicated May consider in high risk patients e.g., >2% annual risk, CACS >4 and diabetes Who to Test?: Symptomatic Patients Test based on pre-test probability of CAD Low probability: No testing Intermediate probability Highest yield of testing High probability May test for risk stratification or management planning (not diagnosis) CACS = coronary artery calcium score. Greenland P, et al. Circulation. 21;122:e Diamond GA and Forrester JS. NEJM. 1979; 3:

7 Impact of Pre-Test Probability on Test Results Posttest Likelihood of CAD (%) 1 Hypothetical Test with 7% Sensitivity and Specificity Low Likelihood Intermediate Likelihood High Likelihood Pretest Likelihood of CAD (%) Adapted from Diamond GA and Forrester JS. NEJM. 1979;3: Positive Test Result Negative Test Result Determination of Pre-Test Probability Age Group Typical Angina Atypical Angina Non-anginal Chest pain 3-39 Intermediate Intermediate Low 4-49 High Intermediate Low 5-59 High Intermediate Intermediate 6-69 High Intermediate Intermediate Age Group Typical Angina Atypical Angina Non-anginal Chest pain 3-39 Intermediate Very low Very low 4-49 Intermediate Low Very low 5-59 Intermediate Intermediate Low 6-69 High Intermediate Intermediate High >9%, Intermediate 1-9% Low < 1%, Very low < 5% Adapted from Diamond GA and Forrester JS NEJM.1979;3(24): Typical vs. Atypical Angina Who to Refer to Cardiology Typical angina Substernal chest pain or discomfort Provoked by exertion or emotional stress Relieved by rest and/or nitroglycerin Atypical angina Meets 2 of the above criteria Nonanginal chest pain Meets 1 or none of the above criteria Typical angina particularly if new onset of severe symptoms, rest pain or unstable symptoms CAD = coronary artery disease Herman LK, et al. Am J Cardiol. 21;15(11): Fox K, J, Sechtem U, et al. Eur Heart J. 26; 27(11): Mieres JH, et al. Am Fam Physician. 27;75: Appropriate Use Criteria Appropriate Use Criteria Appropriate diagnostic or therapeutic procedure: Expected benefits survival or health outcomes (symptoms, functional status, QOL) exceed the expected negative consequences (AE + downstream testing) Based on Available evidence + collective expert (broad) judgment Not intended to adjudicate individual cases, but rather define patterns of care Original Rating Appropriate Uncertain Inappropriate 213 Rating Appropriate May be appropriate Rarely appropriate Hendel et al., ACCF Appropriate Use of Cardiovascular Technology, J Am Coll Cardiol., 213;61(12): Hendel et al., ACCF Appropriate Use of Cardiovascular Technology, J Am Coll Cardiol., 213;61(12):

8 The Anatomy of a Stress Test The Anatomy of a Stress Test Stressor Agent Imaging Modality Stressor Exercise Pharmacologic vasodilator Adenosine Regadenoson Dipyridamole Pharmacologic inotrope Dobutamine Imaging ECG MPI (Nuclear) Echocardiogram MRI ECG = electrocardiogram; MPI = myocardial perfusion imaging; MRI = magnetic resonance imaging. The Anatomy of a Stress Test Exercise ECG, Nuclear, Echocardiogram Pharmacologic vasodilator Nuclear, MRI Dobutamine Nuclear, Echocardiogram, MRI Noninvasive Diagnosis of CAD without Stress Testing CT Coronary Angiography ECG = electrocardiogram; MPI = myocardial perfusion imaging; MRI = magnetic resonance imaging. CT = computed tomography. Exercise Testing Exercise Stress Testing (EST) Most physiological stressor A good functional capacity indicates excellent prognosis and overall health Use exercise stress preferentially Safety: 1:1, deaths, 2:1, cardiac arrests Gibbons L, et al. Circulation. 1989;8: Gibbons RJ, et al. J Am Coll Cardiol.1997;3:

9 Indications for EST Class I Adult patients (including those with complete RBBB or less than 1 mm of resting ST ) with an intermediate pretest probability of CAD, based on gender, age, and symptoms Sensitivity and Specificity of Exercise ECG for CAD *Compared to Observed CAD with Cardiac Catheterization Exercise ECG Appropriate in patients able to exercise, with an interpretable ECG and intermediate probability of CAD Not appropriate: Low probability and High probability >1mm ST depression at baseline, LBBB, paced, pre-excitation (OK in RBBB, <1mm ST) EST = exercise stress test; RBBB = right bundle branch block; CAD = coronary artery disease. Gibbons RJ, et al. J Am Coll Cardiol. 1997;3: % Sensitivity* *Compared to observed CAD with cardiac catheterization. CAD = coronary artery disease. Lee TH, et al. N Engl J Med. 21;344: Specificity/Normalcy* Prognostic Value of Exercise ECG CASS Study Medical Treatment Limb 4 patients with EST Only Stage I with >1. mm ST 12% of patients 5% mortality/year Stage III or higher with <1. mm ST 34% of patients <1% mortality/year Pts with excellent exercise tolerance (>1 METs) have good prognosis regardless of coronary anatomy EST = exercise stress test; MET = metabolic equivalent (unit of measurement). Weiner DA, et al. J Am Coll Cardiol. 1984;3: EST Indicators of Adverse Prognosis <6 METs of exercise Failure to increase SBP to 12 mm Hg Decrease in BP of 1 mm Hg during exercise Downsloping ST segment 2 mm at <6 METs involving 5 leads, persisting 5 min into recovery ST segment elevation Angina at low exercise workloads Sustained (>3 sec) or symptomatic VT MET = metabolic equivalent (unit of measurement); VT = ventricular tachycardia. Morrow K, et al. Ann Intern Med. 1993:118(9): Key Point Exercise stress test: Best physiologic testing Good prognostic data Myocardial Perfusion Imaging (MPI) 5

10 MPI Nuclear Stress Testing IV injection of a radioactive compound (tracer) that is taken up by cardiac muscle in proportion to coronary blood flow. Produces a 3-D map of myocardial perfusion Myocardial Perfusion Imaging (MPI) Stress Modalities Exercise Pharmacologic: Vasodilators (dipyridamole, adenosine, regadenoson) Dobutamine Tracers Tc-99m-based tracers (Tc-99m sestamibi and Tc-99m tetrofosmin) Thallium-21 Beller GA. Adv Intern Med. 1997;42: MIBI = Methoxy-IsoButyl-Isonitrile. Beller GA. Adv Intern Med. 1997;42: Indications for MPI Indications for MPI Diagnosis of CAD Patients who cannot exercise or have confounding changes on the baseline ECG (LBBB, LVH, digitalis, preexcitation, >1mm ST depression at baseline) Risk stratification in symptomatic patients with known or suspected CAD Assessment of myocardial viability Detecting post PCI or CABG ischemia Assessing the functional significance of coronary stenosis MPI = myocardial perfusion imaging; LBBB = left bundle branch block; LVH = left ventricular hypertrophy; PPM = permanent pacemaker;pci = percutaneous coronary intervention; CABG = coronary artery bypass graft. Klocke FJ, et al. Circulation. 23;18: When to refer for Pharmacological Stress? Inability to achieve 85% maximal predicted heart rate with treadmill exercise Inability to exercise: Orthopedic, peripheral vascular, neurologic, neuromuscular conditions Baseline abnormal ECG: LBBB, pre-excitation (WPW), ventricular pacing, >1mm ST depression Early post-mi In contemporary practice, about 6% of patients referred for MPI have pharmacological stress ECG = electrocardiogram; LBBB = left bundle branch block; WPW = Wolfe-Parkinson-White Syndrome; MI = myocardial infarction. Klocke FJ, et al. Circulation. 23;18: Pharmacologic Stress Agents for Nuclear MPI Agent Dipyridamole Adenosine Regadenoson Dobutamine Half-life Infusion Time Contraindications Vasodilators min 1-15 min Severe lung disease or <1 sec 4-6 min asthma, 2 nd or 3 rd degree AV block, sinus node disease, asthma (dipyridamole, adenosine only) Adverse Effects Chest pain, headache, tachycardia, flushing, hypotension, bronchospasm, dyspnea, heart block 2-4 min 1 sec No bronchospasm Catecholamines 2 min 2-3 min Arrhythmias, recent MI ( 3 days), severe HTN, severe HOCM, aortic aneurysm or dissection Ischemia, arrhythmia, hypotension, headache, chest pain, palpitations, SOB HOCM = Hypertrophic Obstructive Cardiomyopathy; SOB = shortness of breath. Elhendy, et al. Nucl Med. 22;43: Patel RN, et al. SMJ. 27;1: Botvinick EH. J Nucl Med Technol. 29;37: Accessed Aug. 2, Accessed Aug. 2, 212. Safety and Appropriate Use of Adenosine & Regadenoson Rare but serious risk of myocardial infarction and death following the administration of regadenoson and adenosine have occurred. Avoid using these drugs in patients with signs or symptoms of acute myocardial ischemia such as unstable angina or cardiovascular instability, as these patients may be at greater risk for serious cardiovascular adverse reactions. Cardiac resuscitation equipment and trained staff should be available before administration of these agents. Accessed January 18,

11 Patient Preparation NPO 6 hours prior to injection of radiotracer Nausea common with vasodilators To prevent gastric uptake for false positives Need empty stomach with any emergency No caffeine 24 hours prior to vasodilator study Antagonizes vasodilator stress agents Hold beta blockers or antianginal agents if attempting to diagnose ischemia NPO = nothing by mouth. % Sensitivity and Specificity of Nuclear MPI for CAD Exercise Pharm Stress 91 Combined Sensitivity Specificity Normalcy Exercise ECG MPI = myocardial perfusion imaging; CAD = coronary artery disease. *Compared to observed CAD with cardiac catheterization. Adapted from Klocke FJ, et al. Circulation. 23;18(11): Lee TH, et al. N Engl J Med. 21;344: % Sensitivity * 77 Specificity/ Normalcy * Strengths of Nuclear Myocardial Perfusion Imaging (MPI) Widely available Few contraindications: almost anyone can get an MPI! Quantitative data: Particular strength is risk stratification Prognostic Value of Normal MPI Risk of Major Cardiac Events when MPI Is Normal No. of Studies No. of Patients Mean Follow-up (Mo) Events Per Year 16 > 27, % Courtesy of P. Soman, MD. MPI = myocardial perfusion imaging. Klocke FJ, et al. Circulation. 23;18: Prognostic Value of Normal MPI Slightly higher adverse event rate (1-2%) despite normal MPI Pharmacological stress Diabetics Elderly (>85 years) Chronic kidney disease Prognostic Value of Abnormal Myocardial Perfusion Imaging (MPI) MPI Provides Incremental Benefit for Further Risk Stratification Event Rate / Year (%) Rates of Cardiac Death and MI as a Function of Extent and Severity of Perfusion Defects.3 Cardiac Death MI Normal Mildly Abnormal Moderately Abnormal Clinical Implications of Nuclear Testing Severely Abnormal Scan Results Risk of Cardiac Death Risk of Nonfatal MI Management Strategy Mildly abnormal Low Intermediate Medical therapy Moderately / severely abnormal High High Assessment for revascularization MPI = myocardial perfusion imaging. Hachamovitch R, et al. Circulation.1996;93:95-914; Hachamovitch R, et al. Circulation. 1998;97:

12 Use of MPI to Plan Therapy Mortality Risk (Log Hazard Ratio) ,627 Patients 146 Cardiac Death 492 All Cause Mortality P < Total Myocardium Ischemic (%) Medical Therapy Revascularization Non Nuclear Imaging Techniques for Diagnosing CAD Saurabh Malhotra, MD, MPH Instructor in Medicine (Cardiology) University of Pittsburgh Medical Center Pittsburgh, PA MPI = myocardial perfusion imaging. Hachamovitch R, et al. Circulation. 23;17(23): CAD = coronary artery disease. Stress Echocardiography Based on principle that ischemic myocardium becomes hypokinetic Baseline echo to identify regional wall motion Immediate post-stress echo to look for changes in wall motion Exercise or pharmacologic (dobutamine) stress % Sensitivity and Specificity of Non-Invasive Tests for CAD Compared to Observed CAD with Cardiac Catheterization Exercise ECG Exercise SPECT TI Exercise SPECT Tc Exercise Echo 2 Ischemia = change in wall motion with stress Sensitivity Specificity/Normalcy Douglas PS, et al. J Am Coll Cardiol. 211;57: ECG = electrocardiogram; SPECT = single-photon emission computed tomography; CAD = coronary artery disease. Lee TH, et al. N Engl J Med. 21;344: Event-Free Survival (Total Cardiac Events) Event-Free Survival Curves for Total Cardiac Events Exercise TL 21 SPECT N = Normal Ischemia P <.1 Fixed Defect P =.1 Mixed Defect P < Time (years) Similar prognostic data for nuclear MPI and stress ECHO TL 21 = thallium 21; SPECT = single-photon emission computed tomography; ECHO = echocardiogram; WMA = wall motion abnormality. Olmos LI, et al. Circulation. 1998;98: Exercise ECHO N = 248 Normal Ischemia P <.1 Fixed WMA P <.1 Mixed WMA P < Time (years) Prognostic Value of Stress Echo vs Stress MPI Exercise echo and MPI improve diagnostic and prognostic power of clinical variables including stress ECG Comparable prognostic information Choice of echo or MPI depends on several factors, including availability, feasibility, expertise, and cost considerations CAD = coronary artery disease; SPECT = single-photon emission compound tomography; ECG = electrocardiogram. Olmos LI, et al. Circulation. 1998;98:

13 Key Points Use exercise with stress MPI or echocardiography, when possible Prepare patient no caffeine, anti-anginal Similar diagnostic and prognostic data with MPI and echo, but incremental to clinical data alone Choice between MPI and ECHO? Use what your Center does best Cardiac CT MPI = myocardial perfusion imaging. CCTA and Invasive Angiography: Meta-Analysis 28 studies, N=224 patients 16 and CCTA 64 can slice rule CT compared out CAD with to coronary high sensitivity angiography and negative predictive value 5% coronary stenosis is positive Sens Spec Slice PPV NPV (95% CI) (95% CI) Key Statement: CT Coronary angiography is reasonable for 97% 9% the Patient assessment 64 of obstructive disease in symptomatic 93% patients 96% (97,1) (89, 98) (Class IIa, Level of Evidence: B) 88% 96% Segment 64 79% 98% (88, 97) (96, 97) CCTA = cardiac computed tomography angiography; PPV = positive predictive value; NPV = negative predictive value; CI = confidence interval. Hamon M, et al. Radiology 27;245: % Sensitivity and Specificity of Non-Invasive Tests for CAD Compared to Observed CAD with Cardiac Catheterization Sensitivity Specificity/Normalcy Exercise ECG Exercise SPECT TI Exercise SPECT Tc Exercise Echo CCTA ECG = electrocardiogram; SPECT = single-photon emission computed tomography; CAD = coronary artery disease; CCTA = Coronary CT angiography. Adapted from Zaret & Beller, Clinical Nuclear Cardiology, 2nd edtiion 1999; Hamon M, et al. Radiology. 27;245: Limitations of Coronary CTA Calcification blooming Rapid heart rate motion Stents Distal / small vessels CTA = computed tomography angiography Nissen SE. J Am Coll Cardiol. 28;52: major limitations CCTA Prognosis: Meta-Analysis Events per 1 Patients per Year Annual Event Rates Stratified by Degree of CAD* N=9, No CAD Non-Obstructive CAD Obstructive CAD MACE Death MI Revascularization CCTA = coronary CT angiography; CAD = coronary artery disease; MACE = major adverse cardiac events. *All groups were significantly different by analysis of variance (p.5). Hulten EA, et al. J Am Coll Cardiol. 211;57:

14 CONFIRM A Large International Multicenter Registry All-Cause 3-year Survival in 23,854 Patients without Known CAD Survival Probability Normal Non-Obstructive P <.1 1-Vessel CAD P <.1 2-Vessel CAD P =.1 3-Vessel CAD P < Survival Time (years) Almost zero event rate with a negative CTA in a symptomatic patient CAD = coronary artery disease. Min JK, et al. J Am Coll Cardiol. 211;58: Incremental Prognostic Value of CCTA Sensitivity AUC =.81 AUC =.72 Clinical + CAD Clinical.1 P = Specificity CCTA = cardiac computed tomographic angiography; AUC = area under the curve; CAD = coronary artery disease. Chow BJW, et al. J Am Coll Cardiol. 21;55(1): ~2 patients w/o known CAD Follow up: 2 years Outcomes: Death or non-fatal MI Annual Event Rates No CAD:.13% Non-obstructive CAD:.5% Obstructive CAD: 3-6% Key Points Coronary CTA has high sensitivity and negative predictive value to rule out CAD Can use in Emergency Department or Urgent Care for CAD evaluation Coronary CT has incremental prognostic value compared to clinical data Need slow regular heart rate Calcium can interfere with imaging, but has prognostic value Need for iodinated contrast limits the use in patients with renal insufficiency. Cardiac Magnetic Resonance Imaging Stress CMR Pharmacologic: dobutamine or vasodilator Treadmill exercise: very few centers Components of stress CMR: Wall motion Myocardial perfusion Administration of non-iodinated, gadolinium based extracellular contrast agent Ischemia: early hypo perfusion Infarct: late gadolinium enhancement (LGE) CE-MARC study Performance of CMR for Detecting CAD 676 patients: largest study to date CAD: 7% anatomical stenosis on angiography Sensitivity: 87% Specificity: 83% Positive predictive value: 77% Negative predictive value: 91% CMR = cardiac magnetic resonance. CMR = cardiac magnetic resonance. Greenwood JP, et al. Lancet. 212;379(9814):

15 CMR: Prognostic Value Key Points Event-Free Survival (%) Normal DSMR Abormal DSMR Event-Free Survival (%) Event free survival with normal DSMR and MRP.2.2 P <.1 P < Time (years) Time (years) 461 symptomatic patients; CMR for perfusion (adenosine) and WM (dobutamine); Outcomes: cardiac death or non-fatal MI; median follow-up 2.3 years at 3 years ~ 99%.4 Normal MR Perfusion Abnormal MR Perfusion High spatial resolution providing good structural data Cannot use with exercise, renal insufficiency, or metallic implant Limited availability and expertise CMR = cardiac magnetic resonance; WM = wall motion; MI = myocardial infarction; MRP = magnetic resonance perfusion; DSMR = dobutamine stress magnetic resonance. Jahnke C, et al., Circulation, 27; 115(13): Which Test to Choose? Appropriate indication? Know the contraindications No single test is superior All the tests have a very high NPV Local expertise in test performance and interpretation 1 NPV = negative predictive value. 1 Fihn et al., ACCF/AHA Guidelines, J Am Coll Cardiol. 212;6(24):e44-e164 Which Test To Use?: Comparative Effectiveness Nuclear Echo CT MRI Wide Availability + + ± Exercise + + n/a Dobutamine + + n/a + Vasodilator + n/a + Independent of body habitus Metal implants Renal failure + + Atrial fibrillation + ± ± Structural Information Case 1 Patient Cases 52-year-old man who has never seen a physician before Persuaded by wife to seek medical attention for recent onset of chest pain (few months) Left precordial pain, 2-3 times/month, and not always exertional. He is limited by severe left knee arthritis. No other medical history. Medications: Ibuprofen as needed BP 17/93 mm Hg, HR 68 bpm, irregular Other physical exam: normal ECG: Atrial fibrillation with LBBB LBBB = left bundle branch block. 11

16 Determination of Pre-Test Probability Age Group Typical Angina Atypical Angina Non-anginal Chest pain 3-39 Intermediate Intermediate Low 4-49 High Intermediate Low 5-59 High Intermediate Intermediate 6-69 High Intermediate Intermediate Case 1: MPI Result There is a large, severe, mostly reversible perfusion defect in the lateral wall which occupies approximately 35% of the LV myocardium. High >9%, Intermediate 1-9% Low < 1%, Very low < 5% Adapted from Diamond GA and Forrester JS NEJM.1979;3(24): Case 2 Case 2 68 year old female patient, very active lifestyle, no medical problems/medications Family history of premature coronary artery disease: Mother had an MI aged 52. Presents with atypical chest pain Baseline ECG is normal She exercised for 9 min 2 sec on the Bruce protocol, peak heart rate was 136 beats per min (9% of maximum predicted) and peak blood pressure was 18/92 mm Hg. She had mild chest discomfort at a low work load which resolved with continued exercise. Case 2 Summary for Optimal Stress Testing Treadmill Echo Optimal patient selection Appropriate indication She exercised for 1m 15s on the Bruce protocol with a normal wall motion response to stress response Optimal choice of test Availability, expertise and contraindications Right test, right patient, right time 12